| 1. |
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| 2. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 3. |
- Couch, Fergus J., et al.
(författare)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 4. |
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| 5. |
- Ahmed, M., et al.
(författare)
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Search for the lepton-family-number nonconserving decay μ +→e +γ
- 2002
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Ingår i: Physical Review D. - : American Physical Society. - 1550-7998 .- 1550-2368. ; 65:11
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Tidskriftsartikel (refereegranskat)abstract
- The MEGA experiment, which searched for the muon- and electron-number violating decay μ +→e + γ, is described. The spectrometer system, the calibrations, the data taking procedures, the data analysis, and the sensitivity of the experiment are discussed. The most stringent upper limit on the branching ratio, B(μ + →e + γ)<1.2×10 -11 with 90% confidence, is derived from a likelihood analysis.
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| 8. |
- Drlica-Wagner, A., et al.
(författare)
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SEARCH FOR GAMMA-RAY EMISSION FROM DES DWARF SPHEROIDAL GALAXY CANDIDATES WITH FERMI-LAT DATA
- 2015
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 809:1
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Tidskriftsartikel (refereegranskat)abstract
- Due to their proximity, high dark-matter (DM) content, and apparent absence of non-thermal processes, Milky Way dwarf spheroidal satellite galaxies (dSphs) are excellent targets for the indirect detection of DM. Recently, eight new dSph candidates were discovered using the first year of data from the Dark Energy Survey (DES). We searched for gamma-ray emission coincident with the positions of these new objects in six years of Fermi Large Area Telescope data. We found no significant excesses of gamma-ray emission. Under the assumption that the DES candidates are dSphs with DM halo properties similar to the known dSphs, we computed individual and combined limits on the velocity-averaged DM annihilation cross section for these new targets. If the estimated DM content of these dSph candidates is confirmed, they will constrain the annihilation cross section to lie below the thermal relic cross section for DM particles with masses less than or similar to 20 GeV annihilating via the b (b) over bar or pi(+)pi(-) channels.
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| 9. |
- Mavaddat, Nasim, et al.
(författare)
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Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 107:5, s. 036-036
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.
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| 10. |
- Albert, A., et al.
(författare)
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SEARCHING FOR DARK MATTER ANNIHILATION IN RECENTLY DISCOVERED MILKY WAY SATELLITES WITH FERMI-LAT
- 2017
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 834:2
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Tidskriftsartikel (refereegranskat)abstract
- We search for excess gamma-ray emission coincident with the positions of confirmed and candidate Milky Way satellite galaxies using six years of data from the Fermi Large Area Telescope (LAT). Our sample of 45 stellar systems includes 28 kinematically confirmed dark-matter-dominated dwarf spheroidal galaxies (dSphs) and 17 recently discovered systems that have photometric characteristics consistent with the population of known dSphs. For each of these targets, the relative predicted gamma-ray flux due to dark matter annihilation is taken from kinematic analysis if available, and estimated from a distance-based scaling relation otherwise, assuming that the stellar systems are DM-dominated dSphs. LAT data coincident with four of the newly discovered targets show a slight preference (each similar to 2 sigma local) for gamma-ray emission in excess of the background. However, the ensemble of derived gamma-ray flux upper limits for individual targets is consistent with the expectation from analyzing random blank-sky regions, and a combined analysis of the population of stellar systems yields no globally significant excess (global significance < 1 sigma). Our analysis has increased sensitivity compared to the analysis of 15 confirmed dSphs by Ackermann et al. The observed constraints on the DM annihilation cross section are statistically consistent with the background expectation, improving by a factor of similar to 2 for large DM masses (m(DM, b<(b)over bar>) greater than or similar to 1 TeV and m(DM, tau+tau-) greater than or similar to 70 GeV) and weakening by a factor of similar to 1.5 at lower masses relative to previously observed limits.
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| 11. |
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| 14. |
- Zeng, Chenjie, et al.
(författare)
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Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
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| 17. |
- Hamdi, Yosr, et al.
(författare)
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Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
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| 18. |
- Hetland, M. L., et al.
(författare)
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Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial
- 2020
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 371
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis. DESIGN Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study. SETTING Twenty nine rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland between 2012 and 2018. PARTICIPANTS Patients aged 18 years and older with treatment naive rheumatoid arthritis, symptom duration less than 24 months, moderate to severe disease activity, and rheumatoid factor or anti-citrullinated protein antibody positivity, or increased C reactive protein. INTERVENTIONS Randomised 1:1:1:1, stratified by country, sex, and anti-citrullinated protein antibody status. All participants started methotrexate combined with (a) active conventional treatment (either prednisolone tapered to 5 mg/day, or sulfasalazine combined with hydroxychloroquine and intraarticular corticosteroids), (b) certolizumab pegol, (c) abatacept, or (d) tocilizumab. MAIN OUTCOME MEASURES The primary outcome was adjusted clinical disease activity index remission (CDAI <= 2.8) at 24 weeks with active conventional treatment as the reference. Key secondary outcomes and analyses included CDAI remission at 12 weeks and over time, other remission criteria, a non-inferiority analysis, and harms. RESULTS 812 patients underwent randomisation. The mean age was 54.3 years (standard deviation 14.7) and 68.8% were women. Baseline disease activity score of 28 joints was 5.0 (standard deviation 1.1). Adjusted 24 week CDAI remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (39.9% to 53.1%) for certolizumab pegol, 52.0% (45.5% to 58.6%) for abatacept, and 42.1% (35.3% to 48.8%) for tocilizumab. Corresponding absolute differences were 3.9% (95% confidence interval -5.5% to 13.2%) for certolizumab pegol, 9.4% (0.1% to 18.7%) for abatacept, and -0.6% (-10.1% to 8.9%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms. CONCLUSIONS All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Abazajian, Kevork, et al.
(författare)
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CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
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Tidskriftsartikel (refereegranskat)abstract
- CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
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| 23. |
- Darabi, H, et al.
(författare)
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Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)
- 2016
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 32512-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90–0.94; P = 8.96 × 10−15)) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10−09, r2 = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10−11, r2 = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.
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| 24. |
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| 28. |
- Laaksonen, T., et al.
(författare)
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Sympatric divergence and clinal variation in multiple coloration traits of Ficedula flycatchers
- 2015
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Ingår i: Journal of Evolutionary Biology. - : Wiley. - 1010-061X .- 1420-9101. ; 28:4, s. 779-790
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Tidskriftsartikel (refereegranskat)abstract
- Geographic variation in phenotypes plays a key role in fundamental evolutionary processes such as local adaptation, population differentiation and speciation, but the selective forces behind it are rarely known. We found support for the hypothesis that geographic variation in plumage traits of the pied flycatcher Ficedula hypoleuca is explained by character displacement with the collared flycatcher Ficedula albicollis in the contact zone. The plumage traits of the pied flycatcher differed strongly from the more conspicuous collared flycatcher in a sympatric area but increased in conspicuousness with increasing distance to there. Phenotypic differentiation (P-ST) was higher than that in neutral genetic markers (F-ST), and the effect of geographic distance remained when statistically controlling for neutral genetic differentiation. This suggests that a cline created by character displacement and gene flow explains phenotypic variation across the distribution of this species. The different plumage traits of the pied flycatcher are strongly to moderately correlated, indicating that they evolve non-independently from each other. The flycatchers provide an example of plumage patterns diverging in two species that differ in several aspects of appearance. The divergence in sympatry and convergence in allopatry in these birds provide a possibility to study the evolutionary mechanisms behind the highly divergent avian plumage patterns.
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| 29. |
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| 33. |
- Watanabe, A, et al.
(författare)
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Gunnar Fant 60 years
- 1979
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Ingår i: TMH-QPSR. ; 20:2, s. 1-45
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Tidskriftsartikel (refereegranskat)
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| 34. |
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| 35. |
- Claesson, A., et al.
(författare)
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Incidence and characteristics of drowning in Sweden during a 15-year period
- 2021
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Ingår i: Resuscitation. - : ELSEVIER IRELAND LTD. - 0300-9572 .- 1873-1570. ; 162, s. 11-19
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Drowning is a global health problem and deeper knowledge about the extent and causes is of utmost importance for implementing preventative actions. The aim of this study was to describe the incidence and characteristics of drowning in Sweden over time, including both non-fatal and fatal cases. Methods: All cases identified as drowning (ICD-10 coding) at a national level in Sweden between 2003-2017 were collected. Three sources of data from the Swedish National Board of Health and Welfare were extracted via the Cause of Death Register and the National Patient Register. Results: Over 15 years, a total of 6609 cases occurred, resulting in an annual incidence of 4.66 per 100 000. The median age was 49 years (IQR 23-67) and 67% were males. Non-fatal drownings represented 51% (n = 3363), with an overall non-fatal to fatal ratio of 1:1, this being 8:1 for children (0-17 years of age). Non-fatal cases were more often female (36% vs. 30%; p < 0.001), younger 30 (IQR 10-56) vs. 60 (IQR: 45-72) (p < 0.001) and of unintentional nature (81% vs. 55%; p < 0.001). The overall incidence decreased over time from 5.6 to 4.1 per 100 000 (p < 0.001). The highest rate of 30-day survival was found in females 0-17 years (94%, 95% CI 91.1-95.5) and the lowest in males >66 years (28.7%, 95% CI 26.2-31.2). Although the incidence in children 0-4 years increased from 7.4 to 8.1 per 100 000 (p < 0.001), they demonstrated the highest non-fatal to fatal ratio (13:1). Conclusion: Drowning is declining but remains a consistent and underestimated public-health problem. Non-fatal drowning cases represent about half of the burden and characteristics differ from fatal drowning cases, being younger, more often female and of unintentional nature. Keywords: Drowning, Non-fatal, OHCA
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| 36. |
- Cooper, M. D., et al.
(författare)
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Construction and performance of MEGA's low-mass, high-rate cylindrical MWPCs
- 1998
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 417:1, s. 24-49
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Tidskriftsartikel (refereegranskat)abstract
- A design for extremely low mass, high-resolution multiwire proportional chambers (MWPC) was achieved by the MEGA collaboration in its experiment to search for the lepton family number violating decay μ → eγ. To extend the present branching ratio limit by over an order of magnitude, these MWPCs were operated in high particle fluxes. They showed minimal effects of aging, and evidenced spatial and energy resolutions for the orbiting positrons from muon decay which were consistent with our design parameters. The unique features of these chambers, their assembly into the MEGA positron spectrometer, and their performance during the experiment are described in this paper.
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| 37. |
- Jassi, A, et al.
(författare)
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The Work and Social Adjustment Scale, Youth and Parent Versions: Psychometric Evaluation of a Brief Measure of Functional Impairment in Young People
- 2020
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Ingår i: Child psychiatry and human development. - : Springer Science and Business Media LLC. - 1573-3327 .- 0009-398X. ; 51:3, s. 453-460
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Tidskriftsartikel (refereegranskat)abstract
- The Work and Social Adjustment Scale (WSAS) is a brief global measure of functional impairment that is widely used in adult health. We have adapted the WSAS for its use in youth, the WSAS-Youth version (WSAS-Y) and WSAS-Parent version (WSAS-P). This study evaluated the psychometric properties of the scale. The internal consistency, factor structure, convergent and divergent validity, test–retest reliability and sensitivity to change of the WSAS-Y/P were studied in 525 children and adolescents with obsessive–compulsive disorder and related disorders receiving treatment. The internal consistency of the WSAS-Y/P was excellent across diagnostic groups and time-points. Exploratory factor analysis extracted a single-factor of functional impairment, explaining in excess of 85% of the variance. The test–retest reliability was adequate. The WSAS-Y/P correlated more strongly with other measures of functional impairment than with measures of symptom severity, indicating good convergent/divergent validity. Finally, the WSAS-Y/P was highly sensitive to change after treatment.
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| 38. |
- Johansson, Henrik J., et al.
(författare)
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Breast cancer quantitative proteome and proteogenomic landscape
- 2019
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.
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| 39. |
- Kristiansson, M., et al.
(författare)
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Drones can be used to provide dispatch centres with on-site photos before arrival of EMS in time critical incidents
- 2024
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Ingår i: Resuscitation. - 0300-9572 .- 1873-1570. ; , s. 110312-110312
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDrones are able to deliver automated external defibrillators in cases of out-of-hospital cardiac arrest (OHCA) but can be deployed for other purposes. Our aim was to evaluate the feasibility of sending live photos to dispatch centres before arrival of other units during time-critical incidents.MethodsIn this retrospective observational study, the regional dispatch centre implemented a new service using five existing AED-drone systems covering an estimated 200 000 inhabitants in Sweden. Drones were deployed automatically over a 4-month study period (December 2022–April 2023) in emergency calls involving suspected OHCAs, traffic accidents and fires in buildings. Upon arrival at the scene, an overhead photo was taken and transmitted to the dispatch centre. Feasibility of providing photos in real time, and time delays intervals were examined.ResultsOverall, drones were deployed in 59/440 (13%) of all emergency calls: 26/59 (44%) of suspected OHCAs, 20/59 (34%) of traffic accidents, and 13/59 (22%) of fires in buildings.The main reasons for non-deployment were closed airspace and unfavourable weather conditions (68%). Drones arrived safely at the exact location in 58/59 cases (98%). Their overall median response time was 3:49 min, (IQR 3:18–4:26) vs. emergency medical services (EMS), 05:51 (IQR: 04:29–08:04) p-value for time difference between drone and EMS = 0,05. Drones arrived first on scene in 47/52 cases (90%) and the largest median time difference was found in suspected OHCAs 4:10 min, (IQR: 02:57–05:28). The time difference in the 5/52 (10%) cases when EMS arrived first the time difference was 5:18 min (IQR 2:19–7:38), p = NA. Photos were transmitted correctly in all 59 alerts. No adverse events occurred.ConclusionIn a newly implemented drone dispatch service, drones were dispatched to 13% of relevant EMS calls. When drones were dispatched, they arrived at scene earlier than EMS services in 90% of cases. Drones were able to relay photos to the dispatch centre in all cases.Although severely affected by closed airspace and weather conditions, this novel method may facilitate additional decision-making information during time-critical incidents.
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- Tangen, A, et al.
(författare)
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Associations Between Cognition and Serotonin 1B Receptor Availability in Healthy Volunteers: A [11C]AZ10419369 Positron Emission Tomography Study
- 2023
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Ingår i: The international journal of neuropsychopharmacology. - : Oxford University Press (OUP). - 1469-5111 .- 1461-1457. ; 26:4, s. 241-248
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe serotonin system has been implicated in several psychiatric disorders. All major psychiatric disorders are associated with cognitive impairment, but treatment improving cognitive deficits is lacking, partly due to limited understanding of the neurobiology of cognitive functioning. Several markers for the serotonin system have been associated with cognitive functions. Our research group previously has reported a positive correlation between serotonin (5-HT1B) receptor availability in the dorsal brainstem and visuospatial memory in a pilot study of healthy individuals. Here, we aim to replicate our previous finding in a larger group of healthy volunteers as well as to investigate putative associations between 5-HT1B receptor availability and other cognitive domains.MethodsForty-three healthy individuals were examined with positron emission tomography using the 5-HT1B receptor radioligand [11C]AZ10419369 and a visuospatial memory test to replicate our previous finding as well as tests of verbal fluency, cognitive flexibility, reaction time, and planning ability to explore other domains potentially associated with the serotonin system.ResultsReplication analysis revealed no statistically significant association between 5-HT1B receptor availability in the dorsal brainstem and visuospatial memory performance. Exploratory analyses showed age-adjusted correlations between 5-HT1B receptor availability in whole brain gray matter and specific brain regions, and number of commission errors, reaction time, and planning ability.ConclusionsHigher 5-HT1B receptor availability was associated with more false-positive responses and faster reaction time but lower performance in planning and problem-solving. These results corroborate previous research supporting an important role of the serotonin system in impulsive behavior and planning ability.
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