| 1. |
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| 2. |
- Lilienberg, Elsa, et al.
(författare)
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Investigation of Hepatobiliary Disposition of Doxorubicin Following Intrahepatic Delivery of Different Dosage Forms
- 2014
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 11:1, s. 131-144
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Tidskriftsartikel (refereegranskat)abstract
- Unresectable, intermediate stage hepatocellular carcinoma (HCC) is often treated palliatively in humans by doxorubicin (DOX). The drug is administered either as a drug-emulsified-in-Lipiodol (DLIP) or as drug loaded into drug eluting beads (DEB), and both formulations are administered intrahepatically. However, several aspects of their in vivo performance in the liver are still not well-understood. In this study, DLIP and DEB were investigated regarding the local and systemic pharmacokinetics (PK) of DOX and its primary metabolite doxorubicinol (DOXol). An advanced PK-multisampling site acute in vivo pig model was used for simultaneous sampling in the portal, hepatic, and femoral veins and the bile duct. The study had a randomized, parallel design with four treatment groups (TI–TIV). TI (n = 4) was used as control and received an intravenous (i.v.) infusion of DOX as a solution. TII and TIII were given a local injection in the hepatic artery with DLIP (n = 4) or DEB (n = 4), respectively. TIV (n = 2) received local injections of DLIP in the hepatic artery and bile duct simultaneously. All samples were analyzed for concentrations of DOX and DOXol with UPLC-MS/MS. Compared to DLIP, the systemic exposure for DOX with DEB was reduced (p < 0.05), in agreement with a slower in vivo release. The approximated intracellular bioavailability of DOX during 6 h appeared to be lower for DEB than DLIP. Following i.v. infusion (55 min), DOX had a liver extraction of 41 (28–53)%, and the fraction of the dose eliminated in bile of DOX and DOXol was 20 (15–22)% and 4.2 (3.2–5.2)%, respectively. The AUCbile/AUCVP for DOX and DOXol was 640 (580–660) and 5000 (3900–5400), respectively. In conclusion, DLIP might initially deliver a higher hepatocellular concentration of DOX than DEB as a consequence of its higher in vivo release rate. Thus, DLIP delivery results in higher intracellular peak concentrations that might correlate with better anticancer effects, but also higher systemic drug exposure and safety issues.
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| 3. |
- Magnusson, Patrik K. E., et al.
(författare)
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The Swedish Twin Registry : establishment of a biobank and other recent developments
- 2013
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Ingår i: Twin Research and Human Genetics. - Cambridge, United Kingdom : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 16:1, s. 317-329
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish Twin Registry (STR) today contains more than 194,000 twins and more than 75,000 pairs have zygosity determined by an intra-pair similarity algorithm, DNA, or by being of opposite sex. Of these, approximately 20,000, 25,000, and 30,000 pairs are monozygotic, same-sex dizygotic, and opposite-sex dizygotic pairs, respectively. Since its establishment in the late 1950s, the STR has been an important epidemiological resource for the study of genetic and environmental influences on a multitude of traits, behaviors, and diseases. Following large investments in the collection of biological specimens in the past 10 years we have now established a Swedish twin biobank with DNA from 45,000 twins and blood serum from 15,000 twins, which effectively has also transformed the registry into a powerful resource for molecular studies. We here describe the main projects within which the new collections of both biological samples as well as phenotypic measures have been collected. Coverage by year of birth, zygosity determination, ethnic heterogeneity, and influences of in vitro fertilization are also described.
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| 4. |
- Nordanstig, Joakim, et al.
(författare)
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Mortality with Paclitaxel-Coated Devices in Peripheral Artery Disease.
- 2020
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Ingår i: The New England journal of medicine. - : Massachusetts Medical Society. - 1533-4406 .- 0028-4793. ; 383, s. 2538-46
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Tidskriftsartikel (refereegranskat)abstract
- The results of a recent meta-analysis aroused concern about an increased risk of death associated with the use of paclitaxel-coated angioplasty balloons and stents in lower-limb endovascular interventions for symptomatic peripheral artery disease.We conducted an unplanned interim analysis of data from a multicenter, randomized, open-label, registry-based clinical trial. At the time of the analysis, 2289 patients had been randomly assigned to treatment with drug-coated devices (the drug-coated-device group, 1149 patients) or treatment with uncoated devices (the uncoated-device group, 1140 patients). Randomization was stratified according to disease severity on the basis of whether patients had chronic limb-threatening ischemia (1480 patients) or intermittent claudication (809 patients). The single end point for this interim analysis was all-cause mortality.No patients were lost to follow-up. Paclitaxel was used as the coating agent for all the drug-coated devices. During a mean follow-up of 2.49 years, 574 patients died, including 293 patients (25.5%) in the drug-coated-device group and 281 patients (24.6%) in the uncoated-device group (hazard ratio, 1.06; 95% confidence interval, 0.92 to 1.22). At 1 year, all-cause mortality was 10.2% (117 patients) in the drug-coated-device group and 9.9% (113 patients) in the uncoated-device group. During the entire follow-up period, there was no significant difference in the incidence of death between the treatment groups among patients with chronic limb-threatening ischemia (33.4% [249 patients] in the drug-coated-device group and 33.1% [243 patients] in the uncoated-device group) or among those with intermittent claudication (10.9% [44 patients] and 9.4% [38 patients], respectively).In this randomized trial in which patients with peripheral artery disease received treatment with paclitaxel-coated or uncoated endovascular devices, the results of an unplanned interim analysis of all-cause mortality did not show a difference between the groups in the incidence of death during 1 to 4 years of follow-up. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT02051088.).
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| 5. |
- Nylin, Sören, et al.
(författare)
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Embracing Colonizations : A New Paradigm for Species Association Dynamics
- 2018
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Ingår i: Trends in Ecology and Evolution. - Elsevier : Elsevier BV. - 0169-5347 .- 1872-8383. ; 33:1, s. 4-14
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Tidskriftsartikel (refereegranskat)abstract
- Parasite-host and insect-plant research have divergent traditions despite the fact that most phytophagous insects live parasitically on their host plants. In parasitology it is a traditional assumption that parasites are typically highly specialized; cospeciation between parasites and hosts is a frequently expressed default expectation. Insect-plant theory has been more concerned with host shifts than with cospeciation, and more with hierarchies among hosts than with extreme specialization. We suggest that the divergent assumptions in the respective fields have hidden a fundamental similarity with an important role for potential as well as actual hosts, and hence for host colonizations via ecological fitting. A common research program is proposed which better prepares us for the challenges from introduced species and global change. Parasites are typically assumed to be highly specialized on their hosts and well adapted to them, yet they frequently colonize new hosts - including humans, causing EIDs.This parasite paradox has caused a growing unease with the traditional assumptions in parasitology, which differ markedly from those in the field of insect-plant studies.We report the results of a workshop where parasitologists and insect-plant researchers met to explore the possibility that the two systems may be more similar than the divergent research traditions suggest, so that a common research program can be developed to better prepare us for future challenges.
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| 6. |
- Nyman Iliadou, Anastasia, et al.
(författare)
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Familial factors confound the associationbetween maternal smoking during pregnancyand young adult offspring overweight
- 2010
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 39:5, s. 1193-1202
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Tidskriftsartikel (refereegranskat)abstract
- Background Smoking during pregnancy has been shown to increase the risks of several adverse birth outcomes. Associations with overweight and/or obesity in the offspring have also been suggested. We aim to investigate whether familial factors confound the association between maternal smoking during pregnancy and overweight in early adulthood in young Swedish males born 1983–88. Methods In a population-based Swedish cohort comprising 124 203 singleton males born to Nordic mothers between 1983 and 1988, we examined the association between maternal smoking during pregnancy and the risk of overweight in the offspring at age ∼18 years. We also investigated the association within siblings, controlling for common genes and shared environment. Results In the cohort analyses, the risk of overweight was increased in sons of smoking mothers compared with sons of non-smokers: adjusted odds ratios 1.41, 95% confidence interval (CI) 1.34–1.49, and 1.56, 95% CI 1.46–1.66, for one to nine cigarettes per day, and >10 cigarettes per day, respectively. Stratifying for maternal smoking habits across two subsequent male pregnancies, there was an increased risk of overweight for the second son only if the mother was smoking in both male pregnancies. The effect of smoking during pregnancy on the offspring’s body mass index was not present when the association was evaluated within full and half sibling pairs. Conclusion The association between maternal smoking during pregnancy and offspring’s risk of overweight appears to be confounded by familial factors.
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| 7. |
- Nyman, Johan, 1992-
(författare)
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Cathodic arc deposition of metal-rich Cr-based coatings
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Wood and wood-based products have always been key components in the development of human civilization. Nowadays most wood harvesting is done using chainsaws, and their efficient operation helps promote worker safety and reduce emissions. An important factor for efficient operation is the sharpness of the chain – a sharper chain requires less energy for cutting and reduces the risk of dangerous kickback. To reduce the rate of wear and prolong the life of the chains, they are protected by a hard chrome coating. The production of this coating involves compounds in which Cr atoms are in the toxic and carcinogenic hexavalent state. The deposited coatings contain no toxic compounds, however. Consequently, there is a need to develop replacement processes which can produce equally well-performing coatings.In this thesis I investigate the process of cathodic arc deposition of coatings for this purpose. Cathodic arc deposition is a well-established technique for tool coatings, free of toxic compounds. Specifically, elemental Cr coatings, and Cr-rich Cr-N, Cr-C, and Cr-C-N coatings are studied.For the study on elemental Cr, focus is put on the impact of substrate bias on the growth and coating properties. This is important in cathodic arc deposition as the evaporated species are ionized to a high degree. I show that an increasing substrate bias increases the temperature of the substrate and compressive stress of the coatings while decreasing the growth rate because of resputtering. The texture also changes from a preferential [110]- to [100]-orientation, and the hardness is lower than for typical hard chrome coatings.For alloying with N or C, using N2 and C2H2, respectively, the N-/Ccontent is shown to decrease with increasing bias. This process is attributed to preferential resputtering, and ceases at a critical partial pressure, different for N and C, at which point there is no observed difference in N- or C- content at different bias. The incorporation strongly affects the microstructure of the coatings. For N, there is a transition from a columnar structure to a featureless appearance at high N-content, while for C a mixed amorphous/crystalline structure appears at high C-content. For both C and N, the change in microstructure is accompanied by a large increase in hardness, which almost doubles when the alloying concentration reaches ~7 at.%.In a fourth study, combined C- and N-alloying is investigated. Here it is seen that the preferential resputtering persists for N, but for C there is a linear increase in content with partial pressure of C2H2 for all bias levels. This results in the coatings containing more C than N, with a structure like that of Cr-C. At the highest alloying level, a new structure appears which is not seen for the Cr-N and Cr-C studies, consisting of small, elongated grains and columns.In a fifth study, synchrotron-based X-ray adsorption spectroscopy is used to provide structural information about the coatings that is difficult to access with X-ray diffraction. The measurements show that Cr2N and Cr3C2 are the predominant phases forming alongside bcc Cr and reveal changes in bond orientations and strengths at differing alloying concentrations.
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| 8. |
- Nyman, Johan, et al.
(författare)
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Composition, structure, and mechanical properties of cathodic arc deposited Cr-rich Cr-N coatings
- 2023
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Ingår i: Journal of Vacuum Science & Technology. A. Vacuum, Surfaces, and Films. - : A V S AMER INST PHYSICS. - 0734-2101 .- 1520-8559. ; 41:2
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Tidskriftsartikel (refereegranskat)abstract
- We arc deposit Cr-rich Cr-N coatings and show that these coatings are a promising alternative to electrodeposited hard chrome. We find that the substrate bias is of importance for controlling the N content in the grown coatings as it determines the degree of preferential resputtering of N. The substrate bias also affects the substrate temperature and film growth rate. Higher bias results in higher temperatures due to higher energy transfer to the substrate, while the growth rate decreases due to an increased re-sputtering. The N content affects the morphology, microstructure, hardness, and resistivity of the coatings. The hardness increases from 10 GPa with 0.5 at. % N to 17 GPa with 7.5 at. % N, after which no further increase in hardness is seen. At the same time, the grain structure changes from columnar to more featureless and the resistivity rises from 15 to 45 mu omega cm.
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| 9. |
- Nyman, Johan, 1992-, et al.
(författare)
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Substrate bias effects on cathodic arc deposited Cr coatings
- 2023
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Ingår i: Results in Materials. - 2590-048X. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the effects of substrate bias on cathodic arc deposition of Cr coatings without external substrate heating at four different substrate bias levels, floating, −30, −50, and −70 V. After 10 min of deposition, the substrate temperature reaches 180, 210, 230, and 260 °C for floating potential, −30, −50, and −70 V, respectively. Time-of-flight energy elastic recoil detection analysis shows that all grown coatings are of high purity, with no coating containing more than 0.2 at.% of C and/or O. Increasing the substrate bias also reduces the number of macroparticles, steers the texture from preferred [110]- to [100]-orientation and induces a residual compressive stress of ∼450 MPa in the coatings. The hardness of the coatings remains at a constant 7.5 GPa irrespective of the substrate bias. The four-point probe resistivity of the grown coatings is 15–17 μΩcm regardless of substrate bias, close to the 12.9 μΩcm of bulk Cr.
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| 10. |
- Nyman, T., et al.
(författare)
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The early wasp plucks the flower: disparate extant diversity of sawfly superfamilies (Hymenoptera: "Symphyta') may reflect asynchronous switching to angiosperm hosts
- 2019
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Ingår i: Biological Journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4066 .- 1095-8312. ; 128:1, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- The insect order Hymenoptera originated during the Permian nearly 300 Mya. Ancestrally herbivorous hymenopteran lineages today make up the paraphyletic suborder Symphyta', which encompasses c. 8200 species with very diverse host-plant associations. We use phylogeny-based statistical analyses to explore the drivers of diversity dynamics within the Symphyta', with a particular focus on the hypothesis that diversification of herbivorous insects has been driven by the explosive radiation of angiosperms during and after the Cretaceous. Our ancestral-state estimates reveal that the first symphytans fed on gymnosperms, and that shifts onto angiosperms and pteridophytes - and back - have occurred at different time intervals in different groups. Trait-dependent analyses indicate that average net diversification rates do not differ between symphytan lineages feeding on angiosperms, gymnosperms or pteridophytes, but trait-independent models show that the highest diversification rates are found in a few angiosperm-feeding lineages that may have been favoured by the radiations of their host taxa during the Cenozoic. Intriguingly, lineages-through-time plots show signs of an early Cretaceous mass extinction, with a recovery starting first in angiosperm-associated clades. Hence, the oft-invoked assumption of herbivore diversification driven by the rise of flowering plants may overlook a Cretaceous global turnover in insect herbivore communities during the rapid displacement of gymnosperm- and pteridophyte-dominated floras by angiosperms.
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