| 1. |
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Ahearn, Thomas U., et al.
(författare)
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Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
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Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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| 4. |
- Haiman, Christopher A., et al.
(författare)
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A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:12, s. 61-1210
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 x 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 x 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 x 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.
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| 5. |
- Horn, Lars-Christian, et al.
(författare)
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Immunostaining for p16(INK4a) used as a conjunctive tool improves interobserver agreement of the histologic diagnosis of cervical intraepithelial neoplasia
- 2008
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Ingår i: American Journal of Surgical Pathology. - 1532-0979. ; 32:4, s. 502-512
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Tidskriftsartikel (refereegranskat)abstract
- The quality of cervical histopathology is critical to cervical cancer prevention, cancer treatment, and research programs. On the basis of the histology results further patient management is determined. However, the diagnostic interpretation of histologic hematoxylin-eosin (H&E)-stained slides is affected by substantial rates of discordance among pathologists. Overexpression of the cyclin-dependent kinase inhibitor p16(INK4a), a cell cycle regulating protein, has been shown to be strongly correlated with dysplastic lesions of the cervix uteri. In this study.. we assessed whether p16(INK4a) immunohistochemistry may increase the performance of pathologists in diagnosing squamous lesions in cervical punch and cone biopsies. When using a consecutive p 16(INK4a)-stained slide in conjunction to the H&E-stained slide, interobserver agreement between 6 pathologists improved significantly for both cervical punch and cone biopsies (P < 0.001). For punch biopsies (n = 247), K value increased from 0.49 (moderate agreement) to 0.64 indicating substantial agreement, and interobserver agreement for cone biopsies (n = 249) improved from 0.63 (conventional H&E slide reading) to 0.70 when H&E-stained slides were read conjunctively with p16(INK4a)-stained slides. In comparison to a common consensus diagnosis established by 3 independent experts, 4 pathologists reached an improvement with the conjunctive p16(INK4a) test, 2 of them showing significantly better agreement (P < 0.001 and P = 0.002, respectively). P-16INK4a immunohistochemistry as an adjunct to conventional H&E-stained specimens thus contributes to a more reproducible diagnosis of cervical intraepithelial neoplasia, and may be a valuable aid for the interpretation of cervical histology.
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| 6. |
- Stevens, Kristen N., et al.
(författare)
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Common Breast Cancer Susceptibility Loci Are Associated with Triple-Negative Breast Cancer
- 2011
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Ingår i: Cancer Research. - 1538-7445. ; 71:19, s. 6240-6249
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Tidskriftsartikel (refereegranskat)abstract
- Triple-negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiologic factors that promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome-wide association studies display heterogeneity of effect among breast cancer subtypes as defined by the status of estrogen and progesterone receptors. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple-negative breast cancer and 4,978 healthy controls. We identified six single-nucleotide polymorphisms, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.1), and rs8100241 (19p13.1), significantly associated with the risk of triple-negative breast cancer. Together, our results provide convincing evidence of genetic susceptibility for triple-negative breast cancer. Cancer Res; 71(19); 6240-9. (C)2011 AACR.
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| 7. |
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- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Tidskriftsartikel (refereegranskat)
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| 8. |
- 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
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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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| 9. |
- Engert, Andreas, et al.
(författare)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 10. |
- Pivarcsi, Andor, et al.
(författare)
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Tumor immune escape by the loss of homeostatic chemokine expression.
- 2007
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:48, s. 19055-60
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Tidskriftsartikel (refereegranskat)abstract
- The novel keratinocyte-specific chemokine CCL27 plays a critical role in the organization of skin-associated immune responses by regulating T cell homing under homeostatic and inflammatory conditions. Here we demonstrate that human keratinocyte-derived skin tumors may evade T cell-mediated antitumor immune responses by down-regulating the expression of CCL27 through the activation of epidermal growth factor receptor (EGFR)-Ras-MAPK-signaling pathways. Compared with healthy skin, CCL27 mRNA and protein expression was progressively lost in transformed keratinocytes of actinic keratoses and basal and squamous cell carcinomas. In vivo, precancerous skin lesions as well as cutaneous carcinomas showed significantly elevated levels of phosphorylated ERK compared with normal skin, suggesting the activation of EGFR-Ras signaling pathways in keratinocyte-derived malignancies. In vitro, exogenous stimulation of the EGFR-Ras signaling pathway through EGF or transfection of the dominant-active form of the Ras oncogene (H-RasV12) suppressed whereas an EGFR tyrosine kinase inhibitor increased CCL27 mRNA and protein production in keratinocytes. In mice, neutralization of CCL27 led to decreased leukocyte recruitment to cutaneous tumor sites and significantly enhanced primary tumor growth. Collectively, our data identify a mechanism of skin tumors to evade host antitumor immune responses.
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| 11. |
- Scheer, Monika, et al.
(författare)
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Desmoplastic small round cell tumors : Multimodality treatment and new risk factors
- 2019
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Ingår i: Cancer Medicine. - : WILEY. - 2045-7634. ; 8:2, s. 527-542
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Tidskriftsartikel (refereegranskat)abstract
- Background: To evaluate optimal therapy and potential risk factors.Methods: Data of DSRCT patients <40 years treated in prospective CWS trials 1997‐2015 were analyzed.Results: Median age of 60 patients was 14.5 years. Male:female ratio was 4:1. Tumors were abdominal/retroperitoneal in 56/60 (93%). 6/60 (10%) presented with a localized mass, 16/60 (27%) regionally disseminated nodes, and 38/60 (63%) with extraperitoneal metastases. At diagnosis, 23/60 (38%) patients had effusions, 4/60 (7%) a thrombosis, and 37/54 (69%) elevated CRP. 40/60 (67%) patients underwent tumor resection, 21/60 (35%) macroscopically complete. 37/60 (62%) received chemotherapy according to CEVAIE (ifosfamide, vincristine, actinomycin D, carboplatin, epirubicin, etoposide), 15/60 (25%) VAIA (ifosfamide, vincristine, adriamycin, actinomycin D) and, 5/60 (8%) P6 (cyclophosphamide, doxorubicin, vincristine, ifosfamide, etoposide). Nine received high‐dose chemotherapy, 6 received regional hyperthermia, and 20 received radiotherapy. Among 25 patients achieving complete remission, 18 (72%) received metronomic therapies. Three‐year event‐free (EFS) and overall survival (OS) were 11% (±8 confidence interval [CI] 95%) and 30% (±12 CI 95%), respectively, for all patients and 26.7% (±18.0 CI 95%) and 56.9% (±20.4 CI 95%) for 25 patients achieving remission. Extra‐abdominal site, localized disease, no effusion or ascites only, absence of thrombosis, normal CRP, complete tumor resection, and chemotherapy with VAIA correlated with EFS in univariate analysis. In multivariate analysis, significant factors were no thrombosis and chemotherapy with VAIA. In patients achieving complete remission, metronomic therapy with cyclophosphamide/vinblastine correlated with prolonged time to relapse.Conclusion: Pleural effusions, venous thrombosis, and CRP elevation were identified as potential risk factors. The VAIA scheme showed best outcome. Maintenance therapy should be investigated further.
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| 12. |
- Aasi, J., et al.
(författare)
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Einstein@Home all-sky search for periodic gravitational waves in LIGO S5 data
- 2013
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 87:4
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents results of an all-sky search for periodic gravitational waves in the frequency range [50, 1190] Hz and with frequency derivative range of similar to[-20, 1.1] x 10(-10) Hz s(-1) for the fifth LIGO science run (S5). The search uses a noncoherent Hough-transform method to combine the information from coherent searches on time scales of about one day. Because these searches are very computationally intensive, they have been carried out with the Einstein@Home volunteer distributed computing project. Postprocessing identifies eight candidate signals; deeper follow-up studies rule them out. Hence, since no gravitational wave signals have been found, we report upper limits on the intrinsic gravitational wave strain amplitude h(0). For example, in the 0.5 Hz-wide band at 152.5 Hz, we can exclude the presence of signals with h(0) greater than 7.6 x 10(-25) at a 90% confidence level. This search is about a factor 3 more sensitive than the previous Einstein@Home search of early S5 LIGO data.
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| 13. |
- Aasi, J., et al.
(författare)
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Parameter estimation for compact binary coalescence signals with the first generation gravitational-wave detector network
- 2013
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 88:6
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Tidskriftsartikel (refereegranskat)abstract
- Compact binary systems with neutron stars or black holes are one of the most promising sources for ground-based gravitational-wave detectors. Gravitational radiation encodes rich information about source physics; thus parameter estimation and model selection are crucial analysis steps for any detection candidate events. Detailed models of the anticipated waveforms enable inference on several parameters, such as component masses, spins, sky location and distance, that are essential for new astrophysical studies of these sources. However, accurate measurements of these parameters and discrimination of models describing the underlying physics are complicated by artifacts in the data, uncertainties in the waveform models and in the calibration of the detectors. Here we report such measurements on a selection of simulated signals added either in hardware or software to the data collected by the two LIGO instruments and the Virgo detector during their most recent joint science run, including a "blind injection'' where the signal was not initially revealed to the collaboration. We exemplify the ability to extract information about the source physics on signals that cover the neutron-star and black-hole binary parameter space over the component mass range 1M(circle dot)-25M(circle dot) and the full range of spin parameters. The cases reported in this study provide a snapshot of the status of parameter estimation in preparation for the operation of advanced detectors.
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| 14. |
- Aasi, J., et al.
(författare)
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Search for gravitational waves from binary black hole inspiral, merger, and ringdown in LIGO-Virgo data from 2009-2010
- 2013
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 87:2
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Tidskriftsartikel (refereegranskat)abstract
- We report a search for gravitational waves from the inspiral, merger and ringdown of binary black holes (BBH) with total mass between 25 and 100 solar masses, in data taken at the LIGO and Virgo observatories between July 7, 2009 and October 20, 2010. The maximum sensitive distance of the detectors over this period for a (20, 20)M-circle dot coalescence was 300 Mpc. No gravitational wave signals were found. We thus report upper limits on the astrophysical coalescence rates of BBH as a function of the component masses for nonspinning components, and also evaluate the dependence of the search sensitivity on component spins aligned with the orbital angular momentum. We find an upper limit at 90% confidence on the coalescence rate of BBH with nonspinning components of mass between 19 and 28M(circle dot) of 3:3 x 10(-7) mergers Mpc(-3) yr(-1).
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| 15. |
- Aasi, J., et al.
(författare)
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The characterization of Virgo data and its impact on gravitational-wave searches
- 2012
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Ingår i: Classical and Quantum Gravity. - : IOP Publishing. - 1361-6382 .- 0264-9381. ; 29:15
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Tidskriftsartikel (refereegranskat)abstract
- Between 2007 and 2010 Virgo collected data in coincidence with the LIGO and GEO gravitational-wave (GW) detectors. These data have been searched for GWs emitted by cataclysmic phenomena in the universe, by non-axisymmetric rotating neutron stars or from a stochastic background in the frequency band of the detectors. The sensitivity of GW searches is limited by noise produced by the detector or its environment. It is therefore crucial to characterize the various noise sources in a GW detector. This paper reviews the Virgo detector noise sources, noise propagation, and conversion mechanisms which were identified in the three first Virgo observing runs. In many cases, these investigations allowed us to mitigate noise sources in the detector, or to selectively flag noise events and discard them from the data. We present examples from the joint LIGO-GEO-Virgo GW searches to show how well noise transients and narrow spectral lines have been identified and excluded from the Virgo data. We also discuss how detector characterization can improve the astrophysical reach of GW searches.
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| 16. |
- Abadie, J., et al.
(författare)
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All-sky search for gravitational-wave bursts in the second joint LIGO-Virgo run
- 2012
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:12
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Tidskriftsartikel (refereegranskat)abstract
- We present results from a search for gravitational-wave bursts in the data collected by the LIGO and Virgo detectors between July 7, 2009 and October 20, 2010: data are analyzed when at least two of the three LIGO-Virgo detectors are in coincident operation, with a total observation time of 207 days. The analysis searches for transients of duration less than or similar to 1 s over the frequency band 64-5000 Hz, without other assumptions on the signal waveform, polarization, direction or occurrence time. All identified events are consistent with the expected accidental background. We set frequentist upper limits on the rate of gravitational-wave bursts by combining this search with the previous LIGO-Virgo search on the data collected between November 2005 and October 2007. The upper limit on the rate of strong gravitational-wave bursts at the Earth is 1.3 events per year at 90% confidence. We also present upper limits on source rate density per year and Mpc(3) for sample populations of standard-candle sources. As in the previous joint run, typical sensitivities of the search in terms of the root-sum-squared strain amplitude for these waveforms lie in the range similar to 5 x 10(-22) Hz(-1/2) to similar to 1 x 10(-20) Hz(-1/2). The combination of the two joint runs entails the most sensitive all-sky search for generic gravitational-wave bursts and synthesizes the results achieved by the initial generation of interferometric detectors.
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| 17. |
- Abadie, J., et al.
(författare)
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All-sky search for periodic gravitational waves in the full S5 LIGO data
- 2012
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:2
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Tidskriftsartikel (refereegranskat)abstract
- We report on an all-sky search for periodic gravitational waves in the frequency band 50-800 Hz and with the frequency time derivative in the range of 0 through -6 x 10(-9) Hz/s. Such a signal could be produced by a nearby spinning and slightly nonaxisymmetric isolated neutron star in our Galaxy. After recent improvements in the search program that yielded a 10x increase in computational efficiency, we have searched in two years of data collected during LIGO's fifth science run and have obtained the most sensitive all-sky upper limits on gravitational-wave strain to date. Near 150 Hz our upper limit on worst-case linearly polarized strain amplitude h(0) is 1 x 10(-24), while at the high end of our frequency range we achieve a worst-case upper limit of 3.8 x 10(-24) for all polarizations and sky locations. These results constitute a factor of 2 improvement upon previously published data. A new detection pipeline utilizing a loosely coherent algorithm was able to follow up weaker outliers, increasing the volume of space where signals can be detected by a factor of 10, but has not revealed any gravitational-wave signals. The pipeline has been tested for robustness with respect to deviations from the model of an isolated neutron star, such as caused by a low-mass or long-period binary companion.
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| 18. |
- Abadie, J., et al.
(författare)
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First low-latency LIGO plus Virgo search for binary inspirals and their electromagnetic counterparts
- 2012
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 541
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Tidskriftsartikel (refereegranskat)abstract
- Aims. The detection and measurement of gravitational-waves from coalescing neutron-star binary systems is an important science goal for ground-based gravitational-wave detectors. In addition to emitting gravitational-waves at frequencies that span the most sensitive bands of the LIGO and Virgo detectors, these sources are also amongst the most likely to produce an electromagnetic counterpart to the gravitational-wave emission. A joint detection of the gravitational-wave and electromagnetic signals would provide a powerful new probe for astronomy. Methods. During the period between September 19 and October 20, 2010, the first low-latency search for gravitational-waves from binary inspirals in LIGO and Virgo data was conducted. The resulting triggers were sent to electromagnetic observatories for followup. We describe the generation and processing of the low-latency gravitational-wave triggers. The results of the electromagnetic image analysis will be described elsewhere. Results. Over the course of the science run, three gravitational-wave triggers passed all of the low-latency selection cuts. Of these, one was followed up by several of our observational partners. Analysis of the gravitational-wave data leads to an estimated false alarm rate of once every 6.4 days, falling far short of the requirement for a detection based solely on gravitational-wave data.
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| 19. |
- Abadie, J., et al.
(författare)
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Implementation and testing of the first prompt search for gravitational wave transients with electromagnetic counterparts
- 2012
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 539
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Tidskriftsartikel (refereegranskat)abstract
- Aims. A transient astrophysical event observed in both gravitational wave (GW) and electromagnetic (EM) channels would yield rich scientific rewards. A first program initiating EM follow-ups to possible transient GW events has been developed and exercised by the LIGO and Virgo community in association with several partners. In this paper, we describe and evaluate the methods used to promptly identify and localize GW event candidates and to request images of targeted sky locations. Methods. During two observing periods (Dec. 17, 2009 to Jan. 8, 2010 and Sep. 2 to Oct. 20, 2010), a low-latency analysis pipeline was used to identify GW event candidates and to reconstruct maps of possible sky locations. A catalog of nearby galaxies and Milky Way globular clusters was used to select the most promising sky positions to be imaged, and this directional information was delivered to EM observatories with time lags of about thirty minutes. A Monte Carlo simulation has been used to evaluate the low-latency GW pipeline's ability to reconstruct source positions correctly. Results. For signals near the detection threshold, our low-latency algorithms often localized simulated GW burst signals to tens of square degrees, while neutron star/neutron star inspirals and neutron star/black hole inspirals were localized to a few hundred square degrees. Localization precision improves for moderately stronger signals. The correct sky location of signals well above threshold and originating from nearby galaxies may be observed with similar to 50% or better probability with a few pointings of wide-field telescopes.
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| 20. |
- Abadie, J., et al.
(författare)
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Search for Gravitational Waves Associated with Gamma-Ray Bursts during LIGO Science Run 6 and Virgo Science Runs 2 and 3
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X. ; 760:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of a search for gravitational waves associated with 154 gamma-ray bursts (GRBs) that were detected by satellite-based gamma-ray experiments in 2009-2010, during the sixth LIGO science run and the second and third Virgo science runs. We perform two distinct searches: a modeled search for coalescences of either two neutron stars or a neutron star and black hole, and a search for generic, unmodeled gravitational-wave bursts. We find no evidence for gravitational-wave counterparts, either with any individual GRB in this sample or with the population as a whole. For all GRBs we place lower bounds on the distance to the progenitor, under the optimistic assumption of a gravitational-wave emission energy of 10(-2) M-circle dot c(2) at 150 Hz, with a median limit of 17 Mpc. For short-hard GRBs we place exclusion distances on binary neutron star and neutron-star-black-hole progenitors, using astrophysically motivated priors on the source parameters, with median values of 16 Mpc and 28 Mpc, respectively. These distance limits, while significantly larger than for a search that is not aided by GRB satellite observations, are not large enough to expect a coincidence with a GRB. However, projecting these exclusions to the sensitivities of Advanced LIGO and Virgo, which should begin operation in 2015, we find that the detection of gravitational waves associated with GRBs will become quite possible.
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| 21. |
- Abadie, J., et al.
(författare)
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Search for gravitational waves from intermediate mass binary black holes
- 2012
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:10
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of a weakly modeled burst search for gravitational waves from mergers of nonspinning intermediate mass black holes in the total mass range 100-450 M-circle dot and with the component mass ratios between 1: and 4:1. The search was conducted on data collected by the LIGO and Virgo detectors between November of 2005 and October of 2007. No plausible signals were observed by the search which constrains the astrophysical rates of the intermediate mass black holes mergers as a function of the component masses. In the most efficiently detected bin centered on 88 + 88 M-circle dot, for nonspinning sources, the rate density upper limit is 0.13 per Mpc(3) per Myr at the 90% confidence level.
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| 22. |
- Abadie, J., et al.
(författare)
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Search for gravitational waves from low mass compact binary coalescence in LIGO's sixth science run and Virgo's science runs 2 and 3
- 2012
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:8
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Tidskriftsartikel (refereegranskat)abstract
- We report on a search for gravitational waves from coalescing compact binaries using LIGO and Virgo observations between July 7, 2009, and October 20, 2010. We searched for signals from binaries with total mass between 2 and 25M(circle dot); this includes binary neutron stars, binary black holes, and binaries consisting of a black hole and neutron star. The detectors were sensitive to systems up to 40 Mpc distant for binary neutron stars, and further for higher mass systems. No gravitational-wave signals were detected. We report upper limits on the rate of compact binary coalescence as a function of total mass, including the results from previous LIGO and Virgo observations. The cumulative 90% confidence rate upper limits of the binary coalescence of binary neutron star, neutron star-black hole, and binary black hole systems are 1.3 x 10(-4), 3.1 x 10(-5), and 6.4 x 10(-6) Mpc(-3) yr(-1), respectively. These upper limits are up to a factor 1.4 lower than previously derived limits. We also report on results from a blind injection challenge.
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| 23. |
- Abadie, J., et al.
(författare)
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Upper limits on a stochastic gravitational-wave background using LIGO and Virgo interferometers at 600-1000 Hz
- 2012
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:12
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Tidskriftsartikel (refereegranskat)abstract
- A stochastic background of gravitational waves is expected to arise from a superposition of many incoherent sources of gravitational waves, of either cosmological or astrophysical origin. This background is a target for the current generation of ground-based detectors. In this article we present the first joint search for a stochastic background using data from the LIGO and Virgo interferometers. In a frequency band of 600-1000 Hz, we obtained a 95% upper limit on the amplitude of Omega(GW)(f) = Omega(3)(f/900 Hz)(3), of Omega(3) < 0.32, assuming a value of the Hubble parameter of h(100) = 0.71. These new limits are a factor of seven better than the previous best in this frequency band.
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| 24. |
- Adrian-Martinez, S., et al.
(författare)
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A first search for coincident gravitational waves and high energy neutrinos using LIGO, Virgo and ANTARES data from 2007
- 2013
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :6
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.
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| 25. |
- Albert, Christian, et al.
(författare)
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Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy : A Systematic Review and Meta-analysis
- 2020
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Ingår i: American Journal of Kidney Diseases. - : Elsevier BV. - 0272-6386 .- 1523-6838. ; 76:6, s. 826-
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Forskningsöversikt (refereegranskat)abstract
- Rationale & Objective: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction.Study Design: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines.Setting & Study Populations: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms.Selection Criteria for Studies: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI.Data Extraction: Individual-study-data meta analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis.Analytical Approach: Individual-study-data meta analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses.Results: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.790.81) and 0.86 (95% CI, 0.84-0.8 6). Cutoff concentrations at 95% specificity for urinary NGAL were >580 ng/mL with 27% sensitivity for severe AKI and >589 ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were >364 ng/mL with 44% sensitivity and >546 ng/mL with 26% sensitivity, respectively.Limitations: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies. Conclusions: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.
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| 26. |
- Barkhordarian, Gagik, et al.
(författare)
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Formation of Ca(BH4)(2) from hydrogenation of CaH2+MgB2 composite
- 2008
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 112:7, s. 2743-2749
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Tidskriftsartikel (refereegranskat)abstract
- The hydrogenation of the CaH2+MgB2 Composite and the dehydrogenation of the resulting products are investigated in detail by in situ time-resolved synchrotron radiation powder X-ray diffraction, high-pressure differential scanning calorimetry, infrared, and thermovolumetric measurements. It is demonstrated that a Ca(BH4)(2)+MgH2 composite is formed by hydrogenating a CaH2+MgB2 composite, at 350 degrees C and 140 bar of hydrogen. Two phases of Ca(BH4)(2) were characterized: alpha- and beta-Ca(BH4)(2). alpha-Ca(BH4)(2) transforms to beta-Ca(BH4)(2) at about 130 degrees C. Under the conditions used in the present study, beta-Ca(BH4)(2) decomposes first to CaH2, Ca3Mg4H14, Mg, B (or MgB2 depending on experimental conditions), and hydrogen at 360 degrees C, before complete decomposition to CaH2, Mg, B (or MgB2), and hydrogen at 400 degrees C. During hydrogenation under 140 bar of hydrogen, beta-Ca(BH4)(2) is formed at 250 degrees C, and alpha-Ca(BH4)(2) is formed when the sample is cooled to less than 130 degrees C. Ti isopropoxide improves the kinetics of the reactions, during both hydrogenation and dehydrogenation. The dehydrogenation temperature decreases to 250 degrees C, with 1 wt % of this additive, and hydrogenation starts already at 200 degrees C. We propose that the improved kinetics of the above reactions with MgB2 (compared to pure boron) can be explained by the different boron bonding within the crystal structure of MgB2 and pure boron.
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| 27. |
- Boesenberg, Ulrike, et al.
(författare)
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Hydrogen sorption properties of MgH2-LiBH4 composites
- 2007
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Ingår i: Acta Materialia. - : Elsevier BV. - 1873-2453 .- 1359-6454. ; 55:11, s. 3951-3958
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Tidskriftsartikel (refereegranskat)abstract
- A detailed analysis of the reaction mechanism of the reactive hydride composite (RHC) MgH2 + 2LiBH(4) <-> MgB2 + 2LiH + 4H(2) was performed using high-pressure differential scanning calorimetry (HP-DSC) measurements and in situ synchrotron powder X-ray diffraction (XRD) measurements along with kinetic investigations using a Sievert-type apparatus. For the desorption the following two-step reaction has been observed: MgH2 + 2LiBH(4) <-> Mg + 2LiBH(4) + H-2 <-> MgB2 + 2LiH + 4H(2). However, this reaction is kinetically restricted and proceeds only at elevated temperatures. In contrast to the desorption reaction, LiBH4 and MgH2 are found to form simultaneously under fairly moderate conditions of 50 bar hydrogen pressure in the temperature range of 250-300 degrees C. As found in pure light metal hydrides, significant improvement of sorption kinetics is possible if suitable additives are used. (c) 2007 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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| 28. |
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| 29. |
- Dantonello, Tobias M, et al.
(författare)
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Challenges in the Local Treatment of Large Abdominal Embryonal Rhabdomyosarcoma
- 2014
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Ingår i: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1068-9265 .- 1534-4681. ; 21:11, s. 3579-3586
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Embryonal rhabdomyosarcoma is the most common pediatric soft tissue sarcoma. The best local treatment in large, nonmetastatic primary unresected nongenitourinary embryonal rhabdomyosarcoma of the abdomen (LARME) is however unclear.METHODS:We analyzed patients with LARME treated in four consecutive CWS trials. All diagnoses were confirmed by reference reviews. Treatment included multiagent chemotherapy and local treatment of the primary tumor with surgery and/or radiotherapy. The impact of primary debulking surgery (PDS) also was studied.RESULTS:One hundred patients <21 years with a median age of 4 years had LARME. Sixty-one of them had a tumor >10 cm in diameter at diagnosis. PDS was performed in 19 of 100 children. The outcomes of patients with PDS were similar to those of the other patients. In 36 children, the tumor was resected after induction chemotherapy; 60 RME were irradiated. The toxic effects of radiochemotherapy were not significantly increased compared with the nonirradiated patients. With a median follow-up of 10 years, the 5-year EFS and OS were 52 ± 10 and 65 ± 9 %, respectively. Significant risk factors in multivariate analysis were age >10 years; no achievement of complete remission; and inadequate secondary local treatment, defined as incomplete secondary resection or no radiation.CONCLUSIONS:Children with LARME have a fair prognosis, despite an often huge tumor size and unfavorable primary site, if the tumors can either be resected or irradiated following induction chemotherapy. PDS was only performed in a small subgroup. Radiation performed concomitantly with chemotherapy did not increase the acute toxicity significantly.
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| 30. |
- Evans, P. A., et al.
(författare)
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Swift Follow-up Observations of Candidate Gravitational-wave Transient Events
- 2012
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Ingår i: The Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 203:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the first multi-wavelength follow-up observations of two candidate gravitational-wave (GW) transient events recorded by LIGO and Virgo in their 2009-2010 science run. The events were selected with low latency by the network of GW detectors (within less than 10 minutes) and their candidate sky locations were observed by the Swift observatory (within 12 hr). Image transient detection was used to analyze the collected electromagnetic data, which were found to be consistent with background. Off-line analysis of the GW data alone has also established that the selected GW events show no evidence of an astrophysical origin; one of them is consistent with background and the other one was a test, part of a "blind injection challenge." With this work we demonstrate the feasibility of rapid follow-ups of GW transients and establish the sensitivity improvement joint electromagnetic and GW observations could bring. This is a first step toward an electromagnetic follow-up program in the regime of routine detections with the advanced GW instruments expected within this decade. In that regime, multi-wavelength observations will play a significant role in completing the astrophysical identification of GW sources. We present the methods and results from this first combined analysis and discuss its implications in terms of sensitivity for the present and future instruments.
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| 31. |
- Filosa, Alessandro, et al.
(författare)
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Neuron-glia communication via EphA4/ephrin-A3 modulates LTP through glial glutamate transport
- 2009
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 12:10, s. 1285-1292
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Tidskriftsartikel (refereegranskat)abstract
- Astrocytes are critical participants in synapse development and function, but their role in synaptic plasticity is unclear. Eph receptors and their ephrin ligands have been suggested to regulate neuron-glia interactions, and EphA4-mediated ephrin reverse signaling is required for synaptic plasticity in the hippocampus. Here we show that long-term potentiation (LTP) at the CA3-CA1 synapse is modulated by EphA4 in the postsynaptic CA1 cell and by ephrin-A3, a ligand of EphA4 that is found in astrocytes. Lack of EphA4 increased the abundance of glial glutamate transporters, and ephrin-A3 modulated transporter currents in astrocytes. Pharmacological inhibition of glial glutamate transporters rescued the LTP defects in EphA4 (Epha4) and ephrin-A3 (Efna3) mutant mice. Transgenic overexpression of ephrin-A3 in astrocytes reduces glutamate transporter levels and produces focal dendritic swellings possibly caused by glutamate excitotoxicity. These results suggest that EphA4/ephrin-A3 signaling is a critical mechanism for astrocytes to regulate synaptic function and plasticity.
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| 32. |
- Gosalawit-Utke, Rapee, et al.
(författare)
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Ca(BH4)(2)-MgF2 Reversible Hydrogen Storage: Reaction Mechanisms and Kinetic Properties
- 2011
-
Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 115:9, s. 3762-3768
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Tidskriftsartikel (refereegranskat)abstract
- A composite of Ca(BH4)(2)-MgF2 is proposed as a reversible hydrogen storage system. The dehydrogenation and rehydrogenation reaction mechanisms are investigated by in situ time-resolved synchrotron radiation powder X-ray diffraction (SR-PXD) and Raman spectroscopy. The formation of an intermediate phase (CaF2-xHx) is observed during rehydrogenation. The hydrogen content of 4.3 wt % is obtained within 4 h during the first dehydrogenation at isothermal and isobaric conditions of 330 degrees C and 0.5 bar H-2, respectively. The cycling efficiency is evaluated by three release and uptake cycles together with absorbed hydrogen content in the range 5.1-5.8 wt % after 2.5 h (T = 330 degrees C and p(H-2) = 130 bar). The kinetic properties on the basis of hydrogen absorption are comparable for all cycles. As compared to pure Ca(BH4)(2) and Ca(BH4)(2)-MgH2 composite, Ca(BH4)(2)-MgF2 composite reveals the kinetic destabilization and the reproducibility of hydrogen storage capacities during cycling, respectively.
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| 33. |
- Hehlmann, Ruediger, et al.
(författare)
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The European LeukemiaNet : achievements and perspectives
- 2011
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 96:1, s. 156-162
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Tidskriftsartikel (refereegranskat)abstract
- The only way to cure leukemia is by cooperative research. To optimize research, the European Leukemia Net integrates 105 national leukemia trial groups and networks, 105 interdisciplinary partner groups and about 1,000 leukemia specialists from 175 institutions. They care for tens of thousands of leukemia patients in 33 countries across Europe. Their ultimate goal is to cure leukemia. Since its inception in 2002, the European Leukemia Net has steadily expanded and has unified leukemia research across Europe. The European Leukemia Net grew from two major roots: 1) the German Competence Network on Acute and Chronic Leukemias; and 2) the collaboration of European Investigators on Chronic Myeloid Leukemia. The European Leukemia Net has improved leukemia research and management across Europe. Its concept has led to funding by the European Commission as a network of excellence. Other sources (European Science Foundation; European Leukemia Net-Foundation) will take over when the support of the European Commission ends.
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| 34. |
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| 35. |
- Hunkeler, Priska A., et al.
(författare)
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A glimpse beneath Antarctic sea ice : Platelet layer volume from multifrequency electromagnetic induction sounding
- 2016
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 43:1, s. 222-231
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Tidskriftsartikel (refereegranskat)abstract
- In Antarctica, ice crystals emerge from ice-shelf cavities and accumulate in unconsolidated layers beneath nearby sea ice. Such sub-ice platelet layers form a unique habitat, and serve as an indicator for the state of an ice shelf. However, the lack of a suitable methodology impedes an efficient quantification of this phenomenon on scales beyond point measurements. In this study, we inverted multi-frequency electromagnetic (EM) induction soundings of > 100 km length, obtained on fast ice with an underlying platelet layer in the eastern Weddell Sea. EM-derived platelet-layer thickness and conductivity are consistent with other field observations. Our results further suggest that platelet-layer volume is higher than previously thought in this region, and that platelet-layer ice-volume fraction is proportional to its thickness. We conclude that multi-frequency EM is a suitable tool to determine platelet-layer volume, with the potential to obtain crucial knowledge of associated processes in otherwise inaccessible ice-shelf cavities.
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| 36. |
- Koscielniak, Ewa, et al.
(författare)
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Long-Term Clinical Outcome and Prognostic Factors of Children and Adolescents with Localized Rhabdomyosarcoma Treated on the CWS-2002P Protocol
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- Simple SummaryThe major challenge in pediatric oncology is the optimal adaptation of therapy burden to risk profile, aiming to achieve the best outcome with minimum toxicities. The CWS-2002P study in patients <= 21 years with localized rhabdomyosarcoma was developed with this goal by reducing or intensifying the chemotherapy depending on the risk group. An important additional aim was to investigate the use of low-dose maintenance chemotherapy. The risk stratification system was effective in predicting outcomes in the four risk groups with very good long-term results. Neither the reduction nor the intensification of chemotherapy influenced the outcome in comparison to previous studies showing that further de-escalation of chemotherapy should be investigated. The weighting of risk factors used for therapy stratification needs to be reevaluated. Maintenance therapy seemed to have an impact on prognosis.We report here the results of the prospective, non-randomized, historically controlled CWS-2002P study in patients <= 21 years with localized RMS developed with the aim to improve the long-term outcome by adapting the burden of therapy to risk profile and to investigate the feasibility and relation to the outcome of maintenance therapy (MT) in the high-risk groups. Patients were allocated into low-risk (LR), standard-risk (SR), high-risk (HR), and very high-risk (VHR) groups. Chemotherapy consisted of vincristine (VCR) and dactinomycin (ACTO-D) for all patients with the addition of ifosfamide (IFO) in the SR, HR, and VHR and doxorubicin (DOX) in the HR and VHR groups. Low-dose cyclophosphamide and vinblastine maintenance therapy (MT) over 6 months was recommended in the HR and VHR groups. A total of 444 patients have been included in this analysis. With a median follow-up of 9 center dot 6 years (IQR 7 center dot 6-10 center dot 9) for patients alive, the 5-year EFS and OS for the whole group was 73% (95% CI 69-77) and 80% (95% CI 76-84), respectively. The 5-year EFS by risk group was 100% in the LR, 79% (95% CI 72-84) in the SR, 69% (95% CI 63-75) in the HR, and 42% (95% CI 23-61) in the VHR (log-rank p = 0.000). The 5-year EFS was 77% (95% CI 70-84) for 155 patients in the HR group who received MT as compared to 63% (95% CI 50-76) for 49 patients who did not (log-rank p = 0.015). Neither the reduction in the IFO dose in the SR nor the increased dose intensity of DOX in HR groups influenced the outcome when compared to the previous CWS and other European studies. MT was feasible, seemed to have an impact on prognosis, and should be studied in a well-controlled prospective trial in this patient population. The weighting of risk factors used for therapy stratification needs to be reevaluated.
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| 37. |
- Minella, Christian Bonatto, et al.
(författare)
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Effect of Transition Metal Fluorides on the Sorption Properties and Reversible Formation of Ca(BH4)(2)
- 2011
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 115:5, s. 2497-2504
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Tidskriftsartikel (refereegranskat)abstract
- Light metal borohydrides are considered as promising materials for solid state hydrogen storage. Because of the high hydrogen content of 11.5 wt % and the rather low dehydrogenation enthalpy of 32 kJ mol(-1)H(2), Ca(BH4)(2) is considered to be one of the most interesting compounds in this class of materials. In the present work, the effect of selected TM-fluoride (TM = transition metal) additives on the reversible formation of Ca(BH4)(2) was investigated by means of thermovolumetric, calorimetric, Fourier transform infrared spectroscopy, and ex situ, and in situ synchrotron radiation powder X-ray diffraction (SR-PXD) measurements. Furthermore, selected desorbed samples were analyzed by B-11{H-1} solid state magic angle spinning nuclear magnetic resonance (MAS NMR). Under the conditions used in this study (145 bar H-2 pressure and 350 degrees C), TiF4 and NbF5 were the only additives causing partial reversibility. In these two cases, B-11{H-1} MAS NMR analyses detected CaB6 and likely CaB12H12 in the dehydrogenation products. Elemental boron was found in the decomposition products of Ca(BH4)(2) samples with VF4, TiF3, and VF3. The results indicate an important role of CaB6 for the reversible formation of Ca(BH4)(2).
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| 38. |
- Nieters, Alexandra, et al.
(författare)
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Smoking and lymphoma risk in the european prospective investigation into cancer and nutrition
- 2008
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 167:9, s. 1081-1089
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Tidskriftsartikel (refereegranskat)abstract
- Lymphomas are one of the few cancers that have been increasing in incidence over the past decades. So far, only a few established risk factors have been identified, including immunosuppression and viral infections. Recent evidence suggests etiologic heterogeneity of different lymphoma subtypes. Smoking may affect risk differently, depending on the lymphoma entity. The European Prospective Investigation into Cancer and Nutrition was used to study the role of smoking in the etiology of lymphomas and individual subtypes within a prospective study. Information on baseline and lifetime tobacco smoking by 478,590 participants was collected between 1992 and 2000. Cox proportional hazards regression was used to calculate multivariate-adjusted hazard ratios and 95% confidence intervals. During 3,567,410 person-years of follow-up, 1,371 lymphoma cases (1,304 non-Hodgkin's lymphomas and 67 Hodgkin's lymphomas) were identified. Relative risk for smokers at recruitment was more than twofold higher for Hodgkin's lymphoma (hazard ratio = 2.14, 95% confidence interval: 1.18, 3.87) but was not elevated for non-Hodgkin's lymphoma (hazard ratio = 1.06, 95% confidence interval: 0.94, 1.19) and individual B-cell non-Hodgkin's lymphoma subtypes. In this prospective study, smoking appeared to increase Hodgkin's lymphoma risk consistently in both genders, whereas B-cell non-Hodgkin's lymphoma risk was not associated. Future analysis should involve viral biomarkers and genetic susceptibility markers to elucidate potential mechanisms of smoking-induced carcinogenesis, particularly for Hodgkin's lymphoma.
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| 39. |
- Pranzas, P. Klaus, et al.
(författare)
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Characterization of Hydrogen Storage Materials and Systems with Photons and Neutrons
- 2011
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Ingår i: Advanced Engineering Materials. - : Wiley. - 1527-2648 .- 1438-1656. ; 13:8, s. 730-736
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Tidskriftsartikel (refereegranskat)abstract
- Complex hydrides are very promising candidates for future light-weight solid state hydrogen storage materials. The present work illustrates detailed characterization of such novel hydride materials on different size scales by the use of synchrotron radiation and neutrons. The comprehensive analysis of such data leads to a deep understanding of the ongoing processes and mechanisms. The reaction pathways during hydrogen desorption and absorption are identified by in situ X-ray diffraction (XRD). Function and size of additive phases are estimated using X-ray absorption spectroscopy (XAS) and anomalous small-angle X-ray scattering (ASAXS). The structure of the metal hydride matrix is characterized using (ultra) small-angle neutron scattering (SANS/USANS). The hydrogen distribution in tanks filled with metal hydride material is studied with neutron computerized tomography (NCT). The results obtained by the different analysis methods are summarized in a final structural model. The complementary information obtained by these different methods is essential for the understanding of the various sorption processes in light metal hydrides and hydrogen storage tanks.
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| 40. |
- Purrington, Kristen S., et al.
(författare)
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Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer
- 2014
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 35:5, s. 1012-1019
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Tidskriftsartikel (refereegranskat)abstract
- In a genome-wide scan, we show that 30 variants in 25 genomic regions are associated with risk of TN breast cancer. Women carrying many of the risk variants may have 4-fold increased risk relative to women with few variants.Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 x 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 x 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 x 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 x 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.
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| 41. |
- Selyuzhenok, Valeria, et al.
(författare)
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The bimodality of the East Siberian fast ice extent: mechanisms and changes
- 2023
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Ingår i: Annals of Glaciology. - 0260-3055. ; In Press
-
Tidskriftsartikel (refereegranskat)abstract
- Using operational sea-ice maps, we provide first insight into the seasonal evolution of fast ice in the East Siberian Sea for the period between 1999 and 2021. The fast ice season tends to start later by 4.7 d per decade and to end earlier by 9.7 d per decade. As a result, there is a trend towards a shorter length of fast ice season by 2 weeks per decade. The analysis of air temperatures indicates that onset and end of the fast ice season are largely driven by thermodynamic processes. Two spatial modes (large, L-mode and small, S-mode) of East Siberian fast ice cover which have significant areal differences were distinguished. The occurrence of L- and S-modes was linked to the polarity of the Arctic Oscillation (AO) index. Negative AO phase leads to increased sea-ice convergence in the region, which in turn favours sea-ice grounding and promotes the development of large fast ice extent (L-mode). Lower deformation rates in the region during positive AO phase does not allow the formation of grounded features which results in small fast ice extent (S-mode). An analysis of sea-ice divergence confirms that L-mode seasons are characterised by higher on-shore convergence compared with S-mode seasons.
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| 42. |
- Tobisch, Alexandra, et al.
(författare)
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Comparison of basis functions and q-space sampling schemes for robust compressed sensing reconstruction accelerating diffusion spectrum imaging
- 2019
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Ingår i: NMR in Biomedicine. - : WILEY. - 0952-3480 .- 1099-1492. ; 32:3
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Tidskriftsartikel (refereegranskat)abstract
- Time constraints placed on magnetic resonance imaging often restrict the application of advanced diffusion MRI (dMRI) protocols in clinical practice and in high throughput research studies. Therefore, acquisition strategies for accelerated dMRI have been investigated to allow for the collection of versatile and high quality imaging data, even if stringent scan time limits are imposed. Diffusion spectrum imaging (DSI), an advanced acquisition strategy that allows for a high resolution of intra-voxel microstructure, can be sufficiently accelerated by means of compressed sensing (CS) theory. CS theory describes a framework for the efficient collection of fewer samples of a data set than conventionally required followed by robust reconstruction to recover the full data set from sparse measurements. For an accurate recovery of DSI data, a suitable acquisition scheme for sparse q-space sampling and the sensing and sparsifying bases for CS reconstruction need to be selected. In this work we explore three different types of q-space undersampling schemes and two frameworks for CS reconstruction based on either Fourier or SHORE basis functions. After CS recovery, diffusion and microstructural parameters and orientational information are estimated from the reconstructed data by means of state-of-the-art processing techniques for dMRI analysis. By means of simulation, diffusion phantom and in vivo DSI data, an isotropic distribution of q-space samples was found to be optimal for sparse DSI. The CS reconstruction results indicate superior performance of Fourier-based CS-DSI compared to the SHORE-based approach. Based on these findings we outline an experimental design for accelerated DSI and robust CS reconstruction of the sparse measurements that is suitable for the application within time-limited studies.
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| 43. |
- Wetter, Oliver, et al.
(författare)
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The year-long unprecedented European heat and drought of 1540-a worst case
- 2014
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Ingår i: Climatic Change. - : Springer Science and Business Media LLC. - 0165-0009 .- 1573-1480. ; 125:3-4, s. 349-363
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Tidskriftsartikel (refereegranskat)abstract
- The heat waves of 2003 in Western Europe and 2010 in Russia, commonly labelled as rare climatic anomalies outside of previous experience, are often taken as harbingers of more frequent extremes in the global warming-influenced future. However, a recent reconstruction of spring-summer temperatures for WE resulted in the likelihood of significantly higher temperatures in 1540. In order to check the plausibility of this result we investigated the severity of the 1540 drought by putting forward the argument of the known soil desiccation-temperature feedback. Based on more than 300 first-hand documentary weather report sources originating from an area of 2 to 3 million km(2), we show that Europe was affected by an unprecedented 11-month-long Megadrought. The estimated number of precipitation days and precipitation amount for Central and Western Europe in 1540 is significantly lower than the 100-year minima of the instrumental measurement period for spring, summer and autumn. This result is supported by independent documentary evidence about extremely low river flows and Europe-wide wild-, forest- and settlement fires. We found that an event of this severity cannot be simulated by state-of-the-art climate models.
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