| 1. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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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. |
- 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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| 4. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 5. |
- 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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| 6. |
- Lu, Yingchang, et al.
(författare)
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A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk.
- 2018
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 78:18, s. 5419-5430
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Tidskriftsartikel (refereegranskat)abstract
- .AbstractLarge-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 × 10−6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10−7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 × 10−3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis.Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419–30. ©2018 AACR.
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| 7. |
- Bellm, Eric C., et al.
(författare)
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The Zwicky Transient Facility : System Overview, Performance, and First Results
- 2019
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:995
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Tidskriftsartikel (refereegranskat)abstract
- The Zwicky Transient Facility (ZTF) is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope. A custom-built wide-field camera provides a 47 deg(2) field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey, the Palomar Transient Factory. We describe the design and implementation of the camera and observing system. The ZTF data system at the Infrared Processing and Analysis Center provides near-real-time reduction to identify moving and varying objects. We outline the analysis pipelines, data products, and associated archive. Finally, we present on-sky performance analysis and first scientific results from commissioning and the early survey. ZTF's public alert stream will serve as a useful precursor for that of the Large Synoptic Survey Telescope.
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| 8. |
- Bengtsson, Fia, 1986-, et al.
(författare)
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Environmental drivers of Sphagnum growth in peatlands across the Holarctic region
- 2021
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Ingår i: Journal of Ecology. - : John Wiley & Sons. - 0022-0477 .- 1365-2745. ; 109:1, s. 417-431
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Tidskriftsartikel (refereegranskat)abstract
- The relative importance of global versus local environmental factors for growth and thus carbon uptake of the bryophyte genusSphagnum-the main peat-former and ecosystem engineer in northern peatlands-remains unclear. We measured length growth and net primary production (NPP) of two abundantSphagnumspecies across 99 Holarctic peatlands. We tested the importance of previously proposed abiotic and biotic drivers for peatland carbon uptake (climate, N deposition, water table depth and vascular plant cover) on these two responses. Employing structural equation models (SEMs), we explored both indirect and direct effects of drivers onSphagnumgrowth. Variation in growth was large, but similar within and between peatlands. Length growth showed a stronger response to predictors than NPP. Moreover, the smaller and denserSphagnum fuscumgrowing on hummocks had weaker responses to climatic variation than the larger and looserSphagnum magellanicumgrowing in the wetter conditions. Growth decreased with increasing vascular plant cover within a site. Between sites, precipitation and temperature increased growth forS. magellanicum. The SEMs indicate that indirect effects are important. For example, vascular plant cover increased with a deeper water table, increased nitrogen deposition, precipitation and temperature. These factors also influencedSphagnumgrowth indirectly by affecting moss shoot density. Synthesis. Our results imply that in a warmer climate,S. magellanicumwill increase length growth as long as precipitation is not reduced, whileS. fuscumis more resistant to decreased precipitation, but also less able to take advantage of increased precipitation and temperature. Such species-specific sensitivity to climate may affect competitive outcomes in a changing environment, and potentially the future carbon sink function of peatlands.
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| 9. |
- Boudi, Zoubir, et al.
(författare)
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Association between boarding in the emergency department and in-hospital mortality : A systematic review
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:4
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Forskningsöversikt (refereegranskat)abstract
- Importance: Boarding in the emergency department (ED) is a critical indicator of quality of care for hospitals. It is defined as the time between the admission decision and departure from the ED. As a result of boarding, patients stay in the ED until inpatient beds are available; moreover, boarding is associated with various adverse events.Study objective: The objective of our systematic review was to determine whether ED boarding (EDB) time is associated with in-hospital mortality (IHM).Methods: A systematic search was conducted in academic databases to identify relevant studies. Medline, PubMed, Scopus, Embase, Cochrane, Web of Science, Cochrane, CINAHL and PsychInfo were searched. We included all peer-reviewed published studies from all previous years until November 2018. Studies performed in the ED and focused on the association between EDB and IHM as the primary objective were included. Extracted data included study characteristics, prognostic factors, outcomes, and IHM. A search update in PubMed was performed in May 2019 to ensure the inclusion of recent studies before publishing.Results: From the initial 4,321 references found through the systematic search, the manual screening of reference lists and the updated search in PubMed, a total of 12 studies were identified as eligible for a descriptive analysis. Overall, six studies found an association between EDB and IHM, while five studies showed no association. The last remaining study included both ICU and non-ICU subgroups and showed conflicting results, with a positive association for non-ICU patients but no association for ICU patients. Overall, a tendency toward an association between EDB and IHM using the pool random effect was observed.Conclusion: Our systematic review did not find a strong evidence for the association between ED boarding and IHM but there is a tendency toward this association. Further well-controlled, international multicenter studies are needed to demonstrate whether this association exists and whether there is a specific EDB time cut-off that results in increased IHM.
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| 10. |
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| 11. |
- Fridström Montoya, Therése, 1973-
(författare)
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Leva som andra genom ställföreträdare : en rättslig och faktisk paradox
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the past, people with intellectual disabilities have been treated as objects, rather than subjects, of law. Today, Swedish law purports to recognize that such persons have the same rights and freedoms as anyone else. To achieve this goal, Sweden’s social welfare law provides persons with intellectual disabilities a right to the support and service they need to “be able to live like others do”. For persons who lack the capability to apply for these measures because they lack the capabilities or do not meet the prerequisites to be a legal actor, a legal representative is needed.This dissertation examines the problem reflected in the constructed expression “ability to live like others do through legal representation”, first through traditional legal analysis of its implementation in Swedish law, followed by a critical theoretical analysis of that law. The dissertation shows how Swedish law does not resolve the conflict between legal capacity and actual capabilities for people with intellectual disabilities, as it ratifies dependence on others for access to social welfare rights for people with intellectual disabilities in order for them to be taken seriously as legal actors and subjects before the law. The dissertation proposes a rethinking of the law from a Crip Theory perspective, which questions the able-mindedness norm of the legal subject. The dissertation argues that Swedish law exemplifies this norm as a reflection of power that produces and reproduces a certain kind of legal subject through normalization mechanisms. This dissertation shows that barriers still remain to the realization of full legal capacity for persons with intellectual disabilities, and to the possibilities for such persons to be recognized as self-determinate subjects in law.
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| 12. |
- 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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| 13. |
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| 14. |
- Lauque, Dominique, et al.
(författare)
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Length-of-Stay in the Emergency Department and In-Hospital Mortality : A Systematic Review and Meta-Analysis
- 2022
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 12:1
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Forskningsöversikt (refereegranskat)abstract
- The effect of emergency department (ED) length of stay (EDLOS) on in-hospital mortality (IHM) remains unclear. The aim of this systematic review and meta-analysis was to determine the association between EDLOS and IHM. We searched the PubMed, Medline, Embase, Web of Science, Cochrane Controlled Register of Trials, CINAHL, PsycInfo, and Scopus databases from their inception until 14-15 January 2022. We included studies reporting the association between EDLOS and IHM. A total of 11,337 references were identified, and 52 studies (total of 1,718,518 ED patients) were included in the systematic review and 33 in the meta-analysis. A statistically significant association between EDLOS and IHM was observed for EDLOS over 24 h in patients admitted to an intensive care unit (ICU) (OR = 1.396, 95% confidence interval [CI]: 1.147 to 1.701; p < 0.001, I2 = 0%) and for low EDLOS in non-ICU-admitted patients (OR = 0.583, 95% CI: 0.453 to 0.745; p < 0.001, I2 = 0%). No associations were detected for the other cut-offs. Our findings suggest that there is an association between IHM low EDLOS and EDLOS exceeding 24 h and IHM. Long stays in the ED should not be allowed and special attention should be given to patients admitted after a short stay in the ED.
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| 15. |
- Litins'ka, Yana, et al.
(författare)
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An Ounce of Prevention for a Pound of Cure? Infection Disease Testing at the Border
- 2023
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Ingår i: Festskrift till Elisabeth Rynning: Integritet och rättssäkerhet inom och bortom den medicinska rätten. - 9789177372356 ; , s. 251-263
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Bokkapitel (refereegranskat)abstract
- On 5 January 2023, the Swedish Government announced the decision to introduce new restrictions to enter Sweden: due to the spread of Covid-19 in China, travellers from this direction need to show negative Covid-test results. In cases when there is no possibility of showing the results, the travellers are not allowed to enter Sweden. Governmental Ordinance (2023:2) was temporary and lasted from 7 January until 19 February 2023.Although the Ordinance is no longer in force, the fact of its enaction raises several public law concerns. Firstly, the concerns about the rule of law and the legal nature of such testing within the Swedish legal order must be addressed. Chapter 2 Article 6 of the Instrument of Government (hereinafter – IoG) prohibits forced bodily interventions; the right can be limited only by Parliament and, if necessary, in a democratic society. Governmental Ordinance 2023:2 raises the question of whether it limits the freedom from bodily interventions in the constitutional meaning. Secondly, if it will be concluded that the decisions about testing for infectious disease are the exclusive competence of Parliament, the central questions of legislative preparedness to prevent epidemic outbreaks in Sweden via testing those who arrive from the countries where such outbreaks occur must be raised. This contribution analyses the possibilities and hindrances for introducing compulsory testing to enter Sweden, such as the one established under Ordinance 2023:2. The analysis focuses on national constitutional and administrative law norms.
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| 16. |
- Osorio, Ana, et al.
(författare)
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DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
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| 17. |
- Shrine, Nick, et al.
(författare)
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New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 481-493
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Tidskriftsartikel (refereegranskat)abstract
- Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
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| 18. |
- Wu, Lijuan, et al.
(författare)
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The Association between Emergency Department Length of Stay and In-Hospital Mortality in Older Patients Using Machine Learning : An Observational Cohort Study
- 2023
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 12:14
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Tidskriftsartikel (refereegranskat)abstract
- The association between emergency department (ED) length of stay (EDLOS) with in-hospital mortality (IHM) in older patients remains unclear. This retrospective study aims to delineate the relationship between EDLOS and IHM in elderly patients. From the ED patients (n = 383,586) who visited an urban academic tertiary care medical center from January 2010 to December 2016, 78,478 older patients (age ≥60 years) were identified and stratified into three age subgroups: 60-74 (early elderly), 75-89 (late elderly), and ≥90 years (longevous elderly). We applied multiple machine learning approaches to identify the risk correlation trends between EDLOS and IHM, as well as boarding time (BT) and IHM. The incidence of IHM increased with age: 60-74 (2.7%), 75-89 (4.5%), and ≥90 years (6.3%). The best area under the receiver operating characteristic curve was obtained by Light Gradient Boosting Machine model for age groups 60-74, 75-89, and ≥90 years, which were 0.892 (95% CI, 0.870-0.916), 0.886 (95% CI, 0.861-0.911), and 0.838 (95% CI, 0.782-0.887), respectively. Our study showed that EDLOS and BT were statistically correlated with IHM (p < 0.001), and a significantly higher risk of IHM was found in low EDLOS and high BT. The flagged rate of quality assurance issues was higher in lower EDLOS ≤1 h (9.96%) vs. higher EDLOS 7 h
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| 19. |
- Agell, Anders, et al.
(författare)
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Underhåll till barn
- 2004
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Ingår i: Nordisk borneret I. - 9289308656 ; , s. 235-430
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 20. |
- Ahumada, Tomas, et al.
(författare)
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In Search of Short Gamma-Ray Burst Optical Counterparts with the Zwicky Transient Facility
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 932:1
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Tidskriftsartikel (refereegranskat)abstract
- The Fermi Gamma-ray Burst Monitor (GBM) triggers on-board in response to ∼40 short gamma-ray bursts (SGRBs) per year; however, their large localization regions have made the search for optical counterparts a challenging endeavour. We have developed and executed an extensive program with the wide field of view of the Zwicky Transient Facility (ZTF) camera, mounted on the Palomar 48 inch Oschin telescope (P48), to perform target-of-opportunity (ToO) observations on 10 Fermi-GBM SGRBs during 2018 and 2020–2021. Bridging the large sky areas with small field-of-view optical telescopes in order to track the evolution of potential candidates, we look for the elusive SGRB afterglows and kilonovae (KNe) associated with these high-energy events. No counterpart has yet been found, even though more than 10 ground-based telescopes, part of the Global Relay of Observatories Watching Transients Happen (GROWTH) network, have taken part in these efforts. The candidate selection procedure and the follow-up strategy have shown that ZTF is an efficient instrument for searching for poorly localized SGRBs, retrieving a reasonable number of candidates to follow up and showing promising capabilities as the community approaches the multi-messenger era. Based on the median limiting magnitude of ZTF, our searches would have been able to retrieve a GW170817-like event up to ∼200 Mpc and SGRB afterglows to z = 0.16 or 0.4, depending on the assumed underlying energy model. Future ToOs will expand the horizon to z = 0.2 and 0.7, respectively.
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| 21. |
- Alsabri, Mohamed, et al.
(författare)
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Impact of Teamwork and Communication Training Interventions on Safety Culture and Patient Safety in Emergency Departments : A Systematic Review
- 2022
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Ingår i: Journal of patient safety. - : Lippincott Williams & Wilkins. - 1549-8417 .- 1549-8425. ; 18:1, s. E351-E361
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Forskningsöversikt (refereegranskat)abstract
- Objectives: This study aimed to narratively summarize the literature reporting on the effect of teamwork and communication training interventions on culture and patient safety in emergency department (ED) settings.Methods: We searched PubMed, EMBASE, Psych Info CINAHL, Cochrane, Science Citation Inc, the Web of Science, and Educational Resources Information Centre for peer-reviewed journal articles published from January 1, 1988, to June 8, 2018, that assessed teamwork and communication interventions focusing on how they influence patient safety in the ED. One additional search update was performed in July 2019.Results: Sixteen studies were included from 8700 screened publications. The studies' design, interventions, and evaluation methods varied widely. The most impactful ED training interventions were End-of-Course Critique, Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS), and crisis resource management (CRM)-based training. Crisis resource management and TeamSTEPPS CRM-based training curriculum were used in most of the studies. Multiple tools, including the Kirkpatrick evaluation model, the Agency for Healthcare Research and Quality Hospital Survey on Patient Safety Culture, the TeamSTEPPS Teamwork Attitudes Questionnaire, the Safety Attitudes Questionnaire, and the Communication and Teamwork Skills Assessment, were used to assess the impact of such interventions. Improvements in one of the domains of safety culture and related domains were found in all studies. Four empirical studies established improvements in patient health outcomes that occurred after simulation CRM training (Kirkpatrick 4), but there was no effect on mortality.Conclusions: Overall, teamwork and communication training interventions improve the safety culture in ED settings and may positively affect patient outcome. The implementation of safety culture programs may be considered to reduce incidence of medical errors and adverse events.
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| 22. |
- Alsand, John, et al.
(författare)
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Nordic Cohabitation Law
- 2015. - 1
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- The book describes and analyses the different legal approaches and policy discussion regarding cohabitation in the Nordic countries (Denmark, Finland, Iceland, Norway and Sweden). It looks at historical developments, general private law principles, division of property on separation or death of one cohabitant, inheritance, and the regulations concerning children born to cohabitants. In concludes by proposing principles for the regulation of the financial circumstances of cohabitants.
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| 23. |
- Andreoni, Igor, et al.
(författare)
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Fast-transient Searches in Real Time with ZTFReST : Identification of Three Optically Discovered Gamma-Ray Burst Afterglows and New Constraints on the Kilonova Rate
- 2021
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 918:2
-
Tidskriftsartikel (refereegranskat)abstract
- The most common way to discover extragalactic fast transients, which fade within a few nights in the optical, is via follow-up of gamma-ray burst and gravitational-wave triggers. However, wide-field surveys have the potential to identify rapidly fading transients independently of such external triggers. The volumetric survey speed of the Zwicky Transient Facility (ZTF) makes it sensitive to objects as faint and fast fading as kilonovae, the optical counterparts to binary neutron star mergers, out to almost 200 Mpc. We introduce an open-source software infrastructure, the ZTF REaltime Search and Triggering, ZTFReST, designed to identify kilonovae and fast transients in ZTF data. Using the ZTF alert stream combined with forced point-spread-function photometry, we have implemented automated candidate ranking based on their photometric evolution and fitting to kilonova models. Automated triggering, with a human in the loop for monitoring, of follow-up systems has also been implemented. In 13 months of science validation, we found several extragalactic fast transients independently of any external trigger, including two supernovae with post-shock cooling emission, two known afterglows with an associated gamma-ray burst (ZTF20abbiixp, ZTF20abwysqy), two known afterglows without any known gamma-ray counterpart (ZTF20aajnksq, ZTF21aaeyldq), and three new fast-declining sources (ZTF20abtxwfx, ZTF20acozryr, ZTF21aagwbjr) that are likely associated with GRB200817A, GRB201103B, and GRB210204A. However, we have not found any objects that appear to be kilonovae. We constrain the rate of GW170817-like kilonovae to R < 900 Gpc(-3) yr(-1) (95% confidence). A framework such as ZTFReST could become a prime tool for kilonova and fast-transient discovery with the Vera Rubin Observatory.
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| 24. |
- Antoniou, Antonis C., et al.
(författare)
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A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:10, s. 885-892
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Tidskriftsartikel (refereegranskat)abstract
- Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P-trend = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P-trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P-trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P-trend = 1.1 x 10(-7)).
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| 25. |
- Antoniou, Antonis C., et al.
(författare)
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Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2011
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
-
Tidskriftsartikel (refereegranskat)abstract
- Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
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| 26. |
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| 27. |
- Asland, John, 1976-, et al.
(författare)
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Nordisk samboerrett
- 2014. - 1
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Bok (övrigt vetenskapligt/konstnärligt)
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| 28. |
- Asland, John, et al.
(författare)
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Nordisk samboerrett
- 2014
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- Denne utviklingen har nok forledet noen samboere til å tro at de har en rettslig beskyttelse på lignende vis som ektefeller, men slik er det ikke. Med unntak av Sverige er samboerretten i Norden i stor grad preget av ulovfestet rett og skjønnsmessige kompensasjonsregler. Rettssaker i kjølvannet av oppløste samboerforhold vitner om en uoversiktlig og til dels uklar rettsstilling, hvor noen samboere også risikerer å gå tomhendt ut selv av langvarige forhold.Denne boken gir en samlet fremstilling av reglene om samboerforhold i alle de fem nordiske landene – både de eiendomsrettslige reglene under samlivet og reglene om økonomisk oppgjør etter endt samliv samt rettsutviklingen frem mot dagens rettstilstand. Dessuten redegjøres det for hovedtrekkene i det arverettslige og barnerettslige regelverket.
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| 29. |
- Brattström, Margareta, 1966-, et al.
(författare)
-
Fullmakt för framtiden
- 2022
-
Ingår i: Festskrift till Maarit Jänterä-Jareborg. - Uppsala : Iustus förlag. - 9789177371694 ; , s. 37-52
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 30. |
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| 31. |
- Brattström, Margareta, 1966-, et al.
(författare)
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Preskription av äktenskapets rättsverkningar?
- 2010
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Ett äktenskap medför flera rättsverkningar. Av stor praktisk betydelse är giftorätten, som innebär att nettovärdet av det sammanlagda giftorättsgodset delas lika mellan makarna vid äktenskapets upplösning. Äktenskapsbalkens regler ger därtill en make med störst behov rätt att vid äktenskapets upplösning överta den gemensamma bostaden. Det finns dock inga regler om frister inom vilken tid efter upplösningen av ett äktenskap som ett anspråk på bodelning eller övertagande av bostad ska framställas. Rättigheter av ekonomisk respektive social karaktär grundade av äktenskap träffas inte heller av reglerna om tioårig preskription av fordringar. På senare tid har det visat sig att faktumet att några av de rättigheter som ett äktenskap grundar inte preskriberas kan ge upphov till problem, dels på grund av den tid som kan förflyta från det att rättigheten uppstått till dess att den utkrävs, dels på grund av den okunnighet som förefaller finnas såväl bland folk i gemen som hos jurister rörande dessa rättigheters innebörd och bestånd. Med utgångspunkt i tre rättsfall analyseras och utvärderas rättsläget. Sammantaget finner vi att det finns goda skäl för att införa en preskriptionstid.
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| 32. |
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| 33. |
- Brattström, Margareta, 1966-, et al.
(författare)
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Rätt arv : Fördelning av kvarlåtenskap
- 2011. - 3
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Rätt arv handlar om hur en avliden persons kvarlåtenskap skall fördelas; en fråga som i alla tider har tilldragit sig uppmärksamhet. Många har intresse, berättigat eller inte, av att få del av den efterlämnade egendomen. Reglerna om arv och testamente anger hur man skall gå tillväga i denna situation. De ger uttryck för en avvägning mellan olika intressen; arvingarna och i synnerhet barnens intresse av kvarlåtenskapen, en efterlevande makes eller sambos intresse av att få behålla det gemensamma hemmet intakt samt arvlåtarens intresse av att genom testamente få förfoga över sin egendom efter eget huvud.I boken beskrivs bl.a. arvsordningen och förutsättningar för arv samt skyddet för en efterlevande make, både genom giftorätt och arvsrätt. Vidare behandlas efterarvsrätt, testamentsrätten samt förmånstagarförordnanden i försäkring. Boken innehåller en genomgång av de frågor som ett arvskifte aktualiserar samt en grundläggande redogörelse för den internationellt privaträttsliga regleringen rörande arv och testamente. I ett avslutande kapitel uppmärksammas några successionsrättsliga frågor av rättspolitiskt intresse - är reglerna om arv och testamente avpassade för vår tid?
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| 34. |
- Brattström, Margareta, 1966-, et al.
(författare)
-
Rätt arv : Fördelning av kvarlåtenskap
- 2020. - 5
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- Rätt arv handlar om hur en avliden persons kvarlåtenskap skall fördelas; en fråga som i alla tider har tilldragit sig uppmärksamhet. Många har intresse, berättigat eller inte, av att få del av den efterlämnade egendomen. Reglerna om arv och testamente anger hur man skall gå tillväga i denna situation. De ger uttryck för en avvägning mellan olika intressen; arvingarna och i synnerhet barnens intresse av kvarlåtenskapen, en efterlevande makes eller sambos intresse av att få behålla det gemensamma hemmet intakt samt arvlåtarens intresse av att genom testamente få förfoga över sin egendom efter eget huvud.I boken beskrivs bl.a. arvsordningen och förutsättningar för arv samt skyddet för en efterlevande make, både genom giftorätt och arvsrätt. Vidare behandlas efterarvsrätt, testamentsrätten samt förmånstagarförordnanden i försäkring. Boken innehåller en genomgång av de frågor som ett arvskifte aktualiserar. I ett avslutande kapitel uppmärksammas några successionsrättsliga frågor av rättspolitiskt intresse - är reglerna om arv och testamente avpassade för vår tid?
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| 35. |
- Brattström, Margareta, 1966-, et al.
(författare)
-
Rätt arv : fördelning av kvarlåtenskap
- 2023. - 6
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- Rätt arv handlar om hur en avliden persons kvarlåtenskap skall fördelas; en fråga som i alla tider har tilldragit sig uppmärksamhet. Många har intresse, berättigat eller inte, av att få del av den efterlämnade egendomen. Reglerna om arv och testamente anger hur man skall gå tillväga i denna situation. De ger uttryck för en avvägning mellan olika intressen; arvingarna och i synnerhet barnens intresse av kvarlåtenskapen, en efterlevande makes eller sambos intresse av att få behålla det gemensamma hemmet intakt samt arvlåtarens intresse av att genom testamente få förfoga över sin egendom efter eget huvud.I boken beskrivs bl.a. arvsordningen och förutsättningar för arv samt skyddet för en efterlevande make, både genom giftorätt och arvsrätt. Vidare behandlas efterarvsrätt, testamentsrätten samt förmånstagarförordnanden i försäkring. Boken innehåller en genomgång av de frågor som ett arvskifte aktualiserar. I ett avslutande kapitel uppmärksammas några successionsrättsliga frågor av rättspolitiskt intresse - är reglerna om arv och testamente avpassade för vår tid?
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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Brattström, Margareta, 1966-, et al.
(författare)
-
Underåriga styrelseledamöter - ett problem?
- 2009
-
Ingår i: Familieret og engagement. - Köpenhamn : Thomsson Reuters. - 9788761925626 ; , s. 39-72
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 40. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 41. |
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| 42. |
- Cataldi, Gianni, et al.
(författare)
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Searching for Biosignatures in Exoplanetary Impact Ejecta
- 2017
-
Ingår i: Astrobiology. - : Mary Ann Liebert Inc. - 1531-1074 .- 1557-8070. ; 17:8, s. 721-746
-
Tidskriftsartikel (refereegranskat)abstract
- With the number of confirmed rocky exoplanets increasing steadily, their characterization and the search for exoplanetary biospheres are becoming increasingly urgent issues in astrobiology. To date, most efforts have concentrated on the study of exoplanetary atmospheres. Instead, we aim to investigate the possibility of characterizing an exoplanet (in terms of habitability, geology, presence of life, etc.) by studying material ejected from the surface during an impact event. For a number of impact scenarios, we estimate the escaping mass and assess its subsequent collisional evolution in a circumstellar orbit, assuming a Sun-like host star. We calculate the fractional luminosity of the dust as a function of time after the impact event and study its detectability with current and future instrumentation. We consider the possibility to constrain the dust composition, giving information on the geology or the presence of a biosphere. As examples, we investigate whether calcite, silica, or ejected microorganisms could be detected. For a 20km diameter impactor, we find that the dust mass escaping the exoplanet is roughly comparable to the zodiacal dust, depending on the exoplanet's size. The collisional evolution is best modeled by considering two independent dust populations, a spalled population consisting of nonmelted ejecta evolving on timescales of millions of years, and dust recondensed from melt or vapor evolving on much shorter timescales. While the presence of dust can potentially be inferred with current telescopes, studying its composition requires advanced instrumentation not yet available. The direct detection of biological matter turns out to be extremely challenging. Despite considerable difficulties (small dust masses, noise such as exozodiacal dust, etc.), studying dusty material ejected from an exoplanetary surface might become an interesting complement to atmospheric studies in the future.
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| 43. |
- Coughlin, Michael W., et al.
(författare)
-
GROWTH on S190425z : Searching Thousands of Square Degrees to Identify an Optical or Infrared Counterpart to a Binary Neutron Star Merger with the Zwicky Transient Facility and Palomar Gattini-IR
- 2019
-
Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 885:1
-
Tidskriftsartikel (refereegranskat)abstract
- The third observing run by LVC has brought the discovery of many compact binary coalescences. Following the detection of the first binary neutron star merger in this run (LIGO/Virgo S190425z), we performed a dedicated follow-up campaign with the Zwicky Transient Facility (ZTF) and Palomar Gattini-IR telescopes. The initial skymap of this single-detector gravitational wave (GW) trigger spanned most of the sky observable from Palomar Observatory. Covering 8000 deg(2) of the initial skymap over the next two nights, corresponding to 46% integrated probability, ZTF system achieved a depth of 21 m(AB) in g- and r-bands. Palomar Gattini-IR covered 2200 square degrees in J-band to a depth of 15.5 mag, including 32% integrated probability based on the initial skymap. The revised skymap issued the following day reduced these numbers to 21% for the ZTF and 19% for Palomar Gattini-IR. We narrowed 338,646 ZTF transient ?alerts? over the first two nights of observations to 15 candidate counterparts. Two candidates, ZTF19aarykkb and ZTF19aarzaod, were particularly compelling given that their location, distance, and age were consistent with the GW event, and their early optical light curves were photometrically consistent with that of kilonovae. These two candidates were spectroscopically classified as young core-collapse supernovae. The remaining candidates were ruled out as supernovae. Palomar Gattini-IR did not identify any viable candidates with multiple detections only after merger time. We demonstrate that even with single-detector GW events localized to thousands of square degrees, systematic kilonova discovery is feasible.
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| 44. |
- Ding, Yuan C, et al.
(författare)
-
A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Granath, Gustaf, et al.
(författare)
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Environmental and taxonomic controls of carbon and oxygen stable isotope composition in Sphagnum across broad climatic and geographic ranges
- 2018
-
Ingår i: Biogeosciences. - : Copernicus Publications. - 1726-4170 .- 1726-4189. ; 15:16, s. 5189-5202
-
Tidskriftsartikel (refereegranskat)abstract
- Rain-fed peatlands are dominated by peat mosses (Sphagnum sp.), which for their growth depend on nutrients, water and CO2 uptake from the atmosphere. As the isotopic composition of carbon (C-12(,)13) and oxygen (O-16(,)18) of these Sphagnum mosses are affected by environmental conditions, Sphagnum tissue accumulated in peat constitutes a potential long-term archive that can be used for climate reconstruction. However, there is inadequate understanding of how isotope values are influenced by environmental conditions, which restricts their current use as environmental and palaeoenvironmental indicators. Here we tested (i) to what extent C and O isotopic variation in living tissue of Sphagnum is speciesspecific and associated with local hydrological gradients, climatic gradients (evapotranspiration, temperature, precipitation) and elevation; (ii) whether the C isotopic signature can be a proxy for net primary productivity (NPP) of Sphagnum; and (iii) to what extent Sphagnum tissue delta O-18 tracks the delta O-18 isotope signature of precipitation. In total, we analysed 337 samples from 93 sites across North America and Eurasia us ing two important peat-forming Sphagnum species (S. magellanicum, S. fuscum) common to the Holarctic realm. There were differences in delta C-13 values between species. For S. magellanicum delta C-13 decreased with increasing height above the water table (HWT, R-2 = 17 %) and was positively correlated to productivity (R-2 = 7 %). Together these two variables explained 46 % of the between-site variation in delta C-13 values. For S. fuscum, productivity was the only significant predictor of delta C-13 but had low explanatory power (total R-2 = 6 %). For delta O-18 values, approximately 90 % of the variation was found between sites. Globally modelled annual delta O-18 values in precipitation explained 69 % of the between-site variation in tissue delta O-18. S. magellanicum showed lower delta O-18 enrichment than S. fuscum (-0.83 %0 lower). Elevation and climatic variables were weak predictors of tissue delta O-18 values after controlling for delta O-18 values of the precipitation. To summarize, our study provides evidence for (a) good predictability of tissue delta O-18 values from modelled annual delta O-18 values in precipitation, and (b) the possibility of relating tissue delta C-13 values to HWT and NPP, but this appears to be species-dependent. These results suggest that isotope composition can be used on a large scale for climatic reconstructions but that such models should be species-specific.
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| 49. |
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| 50. |
- Ho, Anna Y. Q., et al.
(författare)
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ZTF20aajnksq (AT 2020blt) : A Fast Optical Transient at z ≈ 2.9 with No Detected Gamma-Ray Burst Counterpart
- 2020
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 905:2
-
Tidskriftsartikel (refereegranskat)abstract
- We present ZTF20aajnksq (AT 2020blt), a fast-fading (Delta r = 2.3 mag in Delta t = 1.3 days) red (g - r 0.6 mag) and luminous (M-1626 A = -25.9 mag) optical transient at z = 2.9 discovered by the Zwicky Transient Facility (ZTF). AT 2020blt shares several features in common with afterglows to long-duration gamma-ray bursts (GRBs): (1) an optical light curve well-described by a broken power law with a break at t(j) = 1 d (observer frame); (2) a luminous (L0.3-10 KeV = 10(46) erg s(-1)) X-ray counterpart; and (3) luminous (L-10 GHz = 4 x 10(31) erg s(-1) Hz(-1)) radio emission. However, no GRB was detected in the 0.74 days between the last ZTF nondetection (r > 21.36 mag) and the first ZTF detection (r = 19.60 mag), with an upper limit on the isotropic-equivalent gamma-ray energy release of E-gamma,E-iso < 7 x 10(52) erg. AT 2020blt is thus the third afterglow-like transient discovered without a detected GRB counterpart (after PTF11agg and ZTF19abvizsw) and the second (after ZTF19abvizsw) with a redshift measurement. We conclude that the properties of AT 2020blt are consistent with a classical (initial Lorentz factor Gamma(0) greater than or similar to 100) on-axis GRB that was missed by high-energy satellites. Furthermore, by estimating the rate of transients with light curves similar to that of AT 2020blt in ZTF high-cadence data, we agree with previous results that there is no evidence for an afterglow-like phenomenon that is significantly more common than classical GRBs, such as dirty fireballs. We conclude by discussing the status and future of fast-transient searches in wide-field high-cadence optical surveys.
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