| 11. |
- Albayaty, Muna, et al.
(författare)
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Pharmacokinetic Evaluation of Once-Weekly and Once-Monthly Buprenorphine Subcutaneous Injection Depots (CAM2038) Versus Intravenous and Sublingual Buprenorphine in Healthy Volunteers Under Naltrexone Blockade : An Open-Label Phase 1 Study
- 2017
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Ingår i: Advances in Therapy. - : Springer Science and Business Media LLC. - 0741-238X .- 1865-8652. ; 34:2, s. 560-575
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: CAM2038 q1w (once weekly) and q4w (once monthly) are investigational buprenorphine subcutaneous (SC) formulations based on FluidCrystal® injection depot technology. These two drug products are being developed for opioid dependence treatment, with a target for once-weekly and once-monthly SC dosing. The rationale for developing two products with different dosing frequencies is that treatment strategies/routines, and hence different treatment preferences, can vary between patients, different stages of opioid maintenance treatment, and countries. This study evaluated the pharmacokinetics and safety of buprenorphine and norbuprenorphine following administration of CAM2038 q1w or q4w versus active controls. Methods: Healthy volunteers were randomized to five treatment groups. All received a single intravenous dose of buprenorphine 600 µg, followed post-washout by a single dose of CAM2038 q4w 96 mg, a single dose of CAM2038 q4w 192 mg, or sublingual buprenorphine 8, 16, or 24 mg daily for 7 days, followed post-washout by a single dose of CAM2038 q4w 64 or 128 mg or four repeated weekly doses of CAM2038 q1w 16 mg. All subjects received daily naltrexone. Results: Eighty-seven subjects were randomized. Median buprenorphine tmax after CAM2038 q4w was 4–10 h (24 h for CAM2038 q1w); mean terminal half-life was 19–25 days (5 days for CAM2038 q1w). CAM2038 q4w showed dose-proportional buprenorphine release, with similar exposure to repeat-dose CAM2038 q1w at comparable monthly dose level. Both CAM2038 formulations showed complete absolute bioavailability of buprenorphine and 5.7- to 7.7-fold greater buprenorphine bioavailability versus sublingual buprenorphine. CAM2038 q1w and q4w were well tolerated; subjects’ acceptance was higher for CAM2038 than for sublingual buprenorphine 1 h post-dose. Conclusions: The pharmacokinetic profiles of CAM2038 q1w and q4w versus sublingual buprenorphine support expected treatment efficacy with once-weekly and once-monthly dosing, respectively. CAM2038 formulations were safe and showed good local tolerability. Trial registration: ISRCTN24987553. Funding: Camurus AB.
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| 12. |
- Allen, N, et al.
(författare)
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Endometrial cancer and oral contraceptives : an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies
- 2015
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Ingår i: The Lancet. Oncology. - 1474-5488. ; 16:9, s. 1061-1070
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Oral contraceptives are known to reduce the incidence rate of endometrial cancer, but it is uncertain how long this effect lasts after use ceases, or whether it is modified by other factors.METHODS: Individual participant datasets were sought from principal investigators and provided centrally for 27 276 women with endometrial cancer (cases) and 115 743 without endometrial cancer (controls) from 36 epidemiological studies. The relative risks (RRs) of endometrial cancer associated with oral contraceptive use were estimated using logistic regression, stratified by study, age, parity, body-mass index, smoking, and use of menopausal hormone therapy.FINDINGS: The median age of cases was 63 years (IQR 57-68) and the median year of cancer diagnosis was 2001 (IQR 1994-2005). 9459 (35%) of 27 276 cases and 45 625 (39%) of 115 743 controls had ever used oral contraceptives, for median durations of 3·0 years (IQR 1-7) and 4·4 years (IQR 2-9), respectively. The longer that women had used oral contraceptives, the greater the reduction in risk of endometrial cancer; every 5 years of use was associated with a risk ratio of 0·76 (95% CI 0·73-0·78; p<0·0001). This reduction in risk persisted for more than 30 years after oral contraceptive use had ceased, with no apparent decrease between the RRs for use during the 1960s, 1970s, and 1980s, despite higher oestrogen doses in pills used in the early years. However, the reduction in risk associated with ever having used oral contraceptives differed by tumour type, being stronger for carcinomas (RR 0·69, 95% CI 0·66-0·71) than sarcomas (0·83, 0·67-1·04; case-case comparison: p=0·02). In high-income countries, 10 years use of oral contraceptives was estimated to reduce the absolute risk of endometrial cancer arising before age 75 years from 2·3 to 1·3 per 100 women.INTERPRETATION: Use of oral contraceptives confers long-term protection against endometrial cancer. These results suggest that, in developed countries, about 400 000 cases of endometrial cancer before the age of 75 years have been prevented over the past 50 years (1965-2014) by oral contraceptives, including 200 000 in the past decade (2005-14).FUNDING: Medical Research Council, Cancer Research UK.
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| 13. |
- Aoude, Lauren G, et al.
(författare)
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Nonsense Mutations in the Shelterin Complex Genes ACD and TERF2IP in Familial Melanoma.
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 107:2, s. 408-408
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Tidskriftsartikel (refereegranskat)abstract
- The shelterin complex protects chromosomal ends by regulating how the telomerase complex interacts with telomeres. Following the recent finding in familial melanoma of inactivating germline mutations in POT1, encoding a member of the shelterin complex, we searched for mutations in the other five components of the shelterin complex in melanoma families.
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| 14. |
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| 15. |
- Augustinsson, Annelie, et al.
(författare)
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Accuracy of self-reported family history of cancer, mutation status and tumor characteristics in patients with early onset breast cancer
- 2018
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Ingår i: Acta Oncologica. - 0284-186X. ; 57:5, s. 595-603
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Tidskriftsartikel (refereegranskat)abstract
- Background: The main objectives of this study were to evaluate the concordance between self-reported and registry-reported information regarding family history of breast cancer (BC), ovarian cancer (OvC) and other types of cancer in first-degree relatives of patients with early onset BC, and to determine the frequency of mutation carriers and non-mutation carriers. The secondary objective was to describe tumor characteristics for each mutation group. Material and methods: Between 1993 and 2013, 231 women who were ≤35 years old when diagnosed with BC were registered at the Oncogenetic Clinic at Skåne University Hospital in Lund, Sweden. Self-reported and registry-reported information regarding first-degree family history of cancer was collected together with information regarding tumor characteristics. Results: Almost perfect agreement was observed between self-reported and registry-reported information regarding first-degree family history of BC (κ = 0.92) and OvC (κ = 0.86). Lesser agreement was observed between reports regarding family history of other types of cancer (κ = 0.51). Mutation screening revealed pathogenic germline mutations in 30.4%; 18.8% in BRCA1, 7.1% in BRCA2 and 4.5% in other genes. Compared with other mutation groups, BRCA1 mutation carriers were more likely to be diagnosed with high-grade, ER-, PR- and triple-negative tumors. Conclusions: Our results demonstrate that physicians and genetic counselors can rely on self-reported information regarding BC and OvC in first-degree relatives. However, self-reported information regarding other types of cancer is not communicated as effectively, and there should be more focus on retrieving the correct information regarding family history of all tumor types. Furthermore, we observed that even though all BC patients fulfilled the criteria for genetic counseling and testing, a large number of patients diagnosed at ≤35 years of age did not receive genetic counseling at the Oncogenetic Clinic. This finding merits further elucidation.
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| 16. |
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| 17. |
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| 18. |
- Axelsson, Arvid, et al.
(författare)
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Exploring Multispectral ALS Data for Tree Species Classification
- 2018
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Ingår i: Remote Sensing. - : MDPI AG. - 2072-4292. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Multispectral Airborne Laser Scanning (ALS) is a new technology and its output data have not been fully explored for tree species classification purposes. The objective of this study was to investigate what type of features from multispectral ALS data (wavelengths of 1550 nm, 1064 nm and 532 nm) are best suited for tree species classification. Remote sensing data were gathered over hemi-boreal forest in southern Sweden (58 degrees 2718.35N, 13 degrees 398.03E) on 21 July 2016. The field data consisted of 179 solitary trees from nine genera and ten species. Two new methods for feature extraction were tested and compared to features of height and intensity distributions. The features that were most important for tree species classification were intensity distribution features. Features from the upper part of the upper and outer parts of the crown were better for classification purposes than others. The best classification model was created using distribution features of both intensity and height in multispectral data, with a leave-one-out cross-validated accuracy of 76.5%. As a comparison, only structural features resulted in an highest accuracy of 43.0%. Picea abies and Pinus sylvestris had high user's and producer's accuracies and were not confused with any deciduous species. Tilia cordata was the deciduous species with a large sample that was most frequently confused with many other deciduous species. The results, although based on a small and special data set, suggest that multispectral ALS is a technology with great potential for tree species classification.
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| 19. |
- Barrett, Jennifer H., et al.
(författare)
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Fine mapping of genetic susceptibility loci for melanoma reveals a mixture of single variant and multiple variant regions
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:6, s. 1351-1360
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Tidskriftsartikel (refereegranskat)abstract
- At least 17 genomic regions are established as harboring melanoma susceptibility variants, in most instances with genome-wide levels of significance and replication in independent samples. Based on genome-wide single nucleotide polymorphism (SNP) data augmented by imputation to the 1,000 Genomes reference panel, we have fine mapped these regions in over 5,000 individuals with melanoma (mainly from the GenoMEL consortium) and over 7,000 ethnically matched controls. A penalized regression approach was used to discover those SNP markers that most parsimoniously explain the observed association in each genomic region. For the majority of the regions, the signal is best explained by a single SNP, which sometimes, as in the tyrosinase region, is a known functional variant. However in five regions the explanation is more complex. At the CDKN2A locus, for example, there is strong evidence that not only multiple SNPs but also multiple genes are involved. Our results illustrate the variability in the biology underlying genome-wide susceptibility loci and make steps toward accounting for some of the missing heritability. What's new? In genome-wide association studies, researchers identify genetic variants that frequently associate with a particular disease, though the variants identified may not contribute to the molecular cause of the disease. This study took a closer look at 17 regions associated with melanoma, fine mapping the regions both in people with melanoma and in healthy controls. Though single SNPs account for the association in some regions, they found that in a few regions, several SNPs - and possibly multiple genes - contributed to the association signal. These findings illustrate the importance of not overlooking the interaction between multiple genetic markers when conducting such studies.
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| 20. |
- Bergström, Ulf, et al.
(författare)
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Stickleback increase in the Baltic Sea - A thorny issue for coastal predatory fish
- 2015
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Ingår i: Estuarine, Coastal and Shelf Science. - : Elsevier BV. - 0272-7714 .- 1096-0015. ; 163, s. 134-142
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Tidskriftsartikel (refereegranskat)abstract
- In the Baltic Sea, the mesopredator three-spined stickleback (Gasterosteus aculeatus) spends a large part of its life cycle in the open sea, but reproduces in shallow coastal habitats. In coastal waters, it may occur in high abundances, is a potent predator on eggs and larvae of fish, and has been shown to induce trophic cascades with resulting eutrophication symptoms through regulation of invertebrate grazers. Despite its potential significance for the coastal food web, little is known about its life history and population ecology. This paper provides a description of life history traits, migration patterns and spatiotemporal development of the species in the Baltic Sea during the past decades, and tests the hypothesis that stickleback may have a negative impact on populations of coastal predatory fish. Offshore and coastal data during the last 30 years show that stickleback has increased fourfold in the Bothnian Sea, 45-fold in the Central Baltic Sea and sevenfold in the Southern Baltic Sea. The abundances are similar in the two northern basins, and two orders of magnitude lower in the Southern Baltic Sea. The coastward spawning migration of sticklebacks from offshore areas peaks in early May, with most spawners being two years of age at a mean length of 65 mm. The early juvenile stage is spent at the coast, whereafter sticklebacks perform a seaward feeding migration in early autumn at a size of around 35 mm. A negative spatial relation between the abundance of stickleback and early life stages of perch and pike at coastal spawning areas was observed in spatial survey data, indicating strong interactions between the species. A negative temporal relationship was observed also between adult perch and stickleback in coastal fish monitoring programmes supporting the hypothesis that stickleback may have negative population level effects on coastal fish predators. The recent increase in stickleback populations in different basins of the Baltic Sea in combination with negative spatiotemporal patterns and previously observed interactions between stickleback and coastal predatory fish suggests that this species may have gained a key role in the coastal food webs of the Baltic Sea. Through its migrations, stickleback may also constitute an important vector linking coastal and open sea ecosystem dynamics. (c) 2015 Elsevier Ltd. All rights reserved.
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