| 1. |
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| 2. |
- Adcox, K, et al.
(author)
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PHENIX detector overview
- 2003
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In: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 469-479
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Journal article (peer-reviewed)abstract
- The PHENIX detector is designed to perform a broad study of A-A, p-A, and p-p collisions to investigate nuclear matter under extreme conditions. A wide variety of probes, sensitive to all timescales, are used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon. Designing for the needs of the heavy-ion and polarized-proton programs has produced a detector with unparalleled capabilities. PHENIX measures electron and muon pairs, photons, and hadrons with excellent energy and momentum resolution. The detector consists of a large number of subsystems that are discussed in other papers in this volume. The overall design parameters of the detector are presented. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 3. |
- Sliz, E., et al.
(author)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 4. |
- Tabassum, R, et al.
(author)
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Genetic architecture of human plasma lipidome and its link to cardiovascular disease
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
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Journal article (peer-reviewed)abstract
- Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
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| 5. |
- Rajewsky, N., et al.
(author)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Journal article (peer-reviewed)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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| 6. |
- Das, A., et al.
(author)
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Genomic predictors of response to PD-1 inhibition in children with germline DNA replication repair deficiency
- 2022
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28:1, s. 125-135
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Journal article (peer-reviewed)abstract
- Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading deficiency (MMRD and PPD) in children harbour the highest mutational and microsatellite insertion–deletion (MS-indel) burden in humans. MMRD and PPD cancers are commonly lethal due to the inherent resistance to chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed to benefit children in previous studies, we hypothesized that hypermutation caused by MMRD and PPD will improve outcomes following ICI treatment in these patients. Using an international consortium registry study, we report on the ICI treatment of 45 progressive or recurrent tumors from 38 patients. Durable objective responses were observed in most patients, culminating in a 3 year survival of 41.4%. High mutation burden predicted response for ultra-hypermutant cancers (>100 mutations per Mb) enriched for combined MMRD + PPD, while MS-indels predicted response in MMRD tumors with lower mutation burden (10–100 mutations per Mb). Furthermore, both mechanisms were associated with increased immune infiltration even in ‘immunologically cold’ tumors such as gliomas, contributing to the favorable response. Pseudo-progression (flare) was common and was associated with immune activation in the tumor microenvironment and systemically. Furthermore, patients with flare who continued ICI treatment achieved durable responses. This study demonstrates improved survival for patients with tumors not previously known to respond to ICI treatment, including central nervous system and synchronous cancers, and identifies the dual roles of mutation burden and MS-indels in predicting sustained response to immunotherapy. © 2022, The Author(s).
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| 7. |
- Waszak, S. M., et al.
(author)
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Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort
- 2018
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In: Lancet Oncology. - : Elsevier BV. - 1470-2045. ; 19:6, s. 785-798
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Journal article (peer-reviewed)abstract
- Background Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. Methods In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. Findings We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 4069) and 5-year overall survival was 65% (95% CI 5281); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. Interpretation Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. Copyright (c) 2018 The Author(s). Published by Elsevier Ltd.
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| 8. |
- Waszak, S. M., et al.
(author)
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Germline Elongator mutations in Sonic Hedgehog medulloblastoma
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 580:7803
-
Journal article (peer-reviewed)abstract
- Cancer genomics has revealed many genes and core molecular processes that contribute to human malignancies, but the genetic and molecular bases of many rare cancers remains unclear. Genetic predisposition accounts for 5 to 10% of cancer diagnoses in children(1,2), and genetic events that cooperate with known somatic driver events are poorly understood. Pathogenic germline variants in established cancer predisposition genes have been recently identified in 5% of patients with the malignant brain tumour medulloblastoma(3). Here, by analysing all protein-coding genes, we identify and replicate rare germline loss-of-function variants across ELP1 in 14% of paediatric patients with the medulloblastoma subgroup Sonic Hedgehog (MBSHH). ELP1 was the most common medulloblastoma predisposition gene and increased the prevalence of genetic predisposition to 40% among paediatric patients with MBSHH. Parent-offspring and pedigree analyses identified two families with a history of paediatric medulloblastoma. ELP1-associated medulloblastomas were restricted to the molecular SHH alpha subtype(4) and characterized by universal biallelic inactivation of ELP1 owing to somatic loss of chromosome arm 9q. Most ELP1-associated medulloblastomas also exhibited somatic alterations in PTCH1, which suggests that germline ELP1 loss-of-function variants predispose individuals to tumour development in combination with constitutive activation of SHH signalling. ELP1 is the largest subunit of the evolutionarily conserved Elongator complex, which catalyses translational elongation through tRNA modifications at the wobble (U-34) position(5,6). Tumours from patients with ELP1-associated MBSHH were characterized by a destabilized Elongator complex, loss of Elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response, consistent with loss of protein homeostasis due to Elongator deficiency in model systems(7-9). Thus, genetic predisposition to proteome instability may be a determinant in the pathogenesis of paediatric brain cancers. These results support investigation of the role of protein homeostasis in other cancer types and potential for therapeutic interference.
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| 9. |
- Müller, T D, et al.
(author)
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Ghrelin.
- 2015
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In: Molecular metabolism. - : Elsevier BV. - 2212-8778. ; 4:6, s. 437-60
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Journal article (peer-reviewed)abstract
- The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism.
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| 10. |
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| 11. |
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| 12. |
- Campbell, Brittany B., et al.
(author)
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Comprehensive Analysis of Hypermutation in Human Cancer
- 2017
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In: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 171:5
-
Journal article (peer-reviewed)abstract
- © 2017 Elsevier Inc. We present an extensive assessment of mutation burden through sequencing analysis of > 81,000 tumors from pediatric and adult patients, including tumors with hypermutation caused by chemotherapy, carcinogens, or germline alterations. Hypermutation was detected in tumor types not previously associated with high mutation burden. Replication repair deficiency was a major contributing factor. We uncovered new driver mutations in the replication-repair-associated DNA polymerases and a distinct impact of microsatellite instability and replication repair deficiency on the scale of mutation load. Unbiased clustering, based on mutational context, revealed clinically relevant subgroups regardless of the tumors' tissue of origin, highlighting similarities in evolutionary dynamics leading to hypermutation. Mutagens, such as UV light, were implicated in unexpected cancers, including sarcomas and lung tumors. The order of mutational signatures identified previous treatment and germline replication repair deficiency, which improved management of patients and families. These data will inform tumor classification, genetic testing, and clinical trial design. A large-scale analysis of hypermutation in human cancers provides insights into tumor evolution dynamics and identifies clinically actionable mutation signatures.
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| 13. |
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| 14. |
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| 15. |
- Adermark, Louise, 1974, et al.
(author)
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Disentangling the Role of Astrocytes in Alcohol Use Disorder
- 2016
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In: Alcoholism-Clinical and Experimental Research. - : Wiley. - 0145-6008. ; 40:9
-
Journal article (peer-reviewed)abstract
- Several laboratories recently identified that astrocytes are critical regulators of addiction machinery. It is now known that astrocyte pathology is a common feature of ethanol (EtOH) exposure in both humans and animal models, as even brief EtOH exposure is sufficient to elicit long-lasting perturbations in astrocyte gene expression, activity, and proliferation. Astrocytes were also recently shown to modulate the motivational properties of EtOH and other strongly reinforcing stimuli. Given the role of astrocytes in regulating glutamate homeostasis, a crucial component of alcohol use disorder (AUD), astrocytes might be an important target for the development of next-generation alcoholism treatments. This review will outline some of the more prominent features displayed by astrocytes, how these properties are influenced by acute and long-term EtOH exposure, and future directions that may help to disentangle astrocytic from neuronal functions in the etiology of AUD.
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| 16. |
- Agrell, Erik, 1965, et al.
(author)
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Roadmap of optical communications
- 2016
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In: Journal of Optics. - : IOP Publishing. - 2040-8978 .- 2040-8986. ; 18:6
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Journal article (peer-reviewed)abstract
- Lightwave communications is a necessity for the information age. Optical links provide enormous bandwidth, and the optical fiber is the only medium that can meet the modern society's needs for transporting massive amounts of data over long distances. Applications range from global high-capacity networks, which constitute the backbone of the internet, to the massively parallel interconnects that provide data connectivity inside datacenters and supercomputers. Optical communications is a diverse and rapidly changing field, where experts in photonics, communications, electronics, and signal processing work side by side to meet the ever-increasing demands for higher capacity, lower cost, and lower energy consumption, while adapting the system design to novel services and technologies. Due to the interdisciplinary nature of this rich research field, Journal of Optics has invited 16 researchers, each a world-leading expert in their respective subfields, to contribute a section to this invited review article, summarizing their views on state-of-the-art and future developments in optical communications.
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| 17. |
- Bannon, L., et al.
(author)
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Hybrid design creates innovative, museum experiences
- 2005
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In: Communications of the ACM. - : Association for Computing Machinery (ACM). - 0001-0782 .- 1557-7317. ; 48:3, s. 62-65
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Journal article (peer-reviewed)abstract
- Museums which rely on simple text panels for providing information to visitors about museum artifacts are discussed. The study involved extensive fieldwork, audio-visual recording, interviews and discussion with curators, museum, educators and exhibit designers. The radio frequency identification (RFID)-tagged paper enabled visitors to assemble a coherent experience from their interactions with different installations. It is suggested that ubiquitous technologies should be assembled and combined with other media to form a interactive and collaborative systems in the museum.
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| 18. |
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| 19. |
- Bowers, Mark S., et al.
(author)
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Feature issue introduction : advanced solid-state lasers
- 2022
-
In: Optical Materials Express. - : Optica Publishing Group. - 2159-3930 .- 2159-3930. ; 12:6, s. 2283-2287
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Journal article (peer-reviewed)abstract
- This Joint Issue of Optics Express and Optical Materials Express features 36 state of-the art articles written by authors who participated in the international conference Advanced Solid State Lasers held online from October 3-7, 2021. This review provides a summary of these articles covering a wide spectrum of topics around solid-state lasers from materials research to sources and from design innovation to applications.
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| 20. |
- Bowers, Mark S., et al.
(author)
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Feature issue introduction : advanced solid-state lasers
- 2022
-
In: Optics Express. - : Optica Publishing Group. - 1094-4087. ; 30:12, s. 20762-20766
-
Journal article (peer-reviewed)abstract
- This joint issue of Optics Express and Optical Materials Express features 36 state-of-the art articles written by authors who participated in the international conference advanced solid state lasers held online from October 3-7, 2021. This review provides a summary of these articles covering a wide spectrum of topics around solid-state lasers from materials research to sources and from design innovation to applications.
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| 21. |
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| 22. |
- Corazzini, Kirsten N., et al.
(author)
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Toward Common Data Elements for International Research in Long-term Care Homes : Advancing Person-Centered Care
- 2019
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In: Journal of the American Medical Directors Association. - : Elsevier. - 1525-8610 .- 1538-9375. ; 20:5, s. 598-603
-
Journal article (peer-reviewed)abstract
- To support person-centered, residential long-term care internationally, a consortium of researchers in medicine, nursing, behavioral, and social sciences from 21 geographically and economically diverse countries have launched the WE-THRIVE consortium to develop a common data infrastructure. WE-THRIVE aims to identify measurement domains that are internationally relevant, including in low-, middle-, and high-income countries, prioritize concepts to operationalize domains, and specify a set of data elements to measure concepts that can be used across studies for data sharing and comparisons. This article reports findings from consortium meetings at the 2016 meeting of the Gerontological Society of America and the 2017 meeting of the International Association of Gerontology and Geriatrics, to identify domains and prioritize concepts, following best practices to identify common data elements (CDEs) that were developed through the US National Institutes of Health/National Institute of Nursing Research's CDEs initiative. Four domains were identified, including organizational context, workforce and staffing, person-centered care, and care outcomes. Using a nominal group process, WE-THRIVE prioritized 21 concepts across the 4 domains. Several concepts showed similarity to existing measurement structures, whereas others differed. Conceptual similarity (convergence; eg, concepts in the care outcomes domain of functional level and harm-free care) provides further support of the critical foundational work in LTC measurement endorsed and implemented by regulatory bodies. Different concepts (divergence; eg, concepts in the person-centered care domain of knowing the person and what matters most to the person) highlights current gaps in measurement efforts and is consistent with WE-THRIVE's focus on supporting resilience and thriving for residents, family, and staff. In alignment with the World Health Organization's call for comparative measurement work for health systems change, WE-THRIVE's work to date highlights the benefits of engaging with diverse LTC researchers, including those in low-, middle-, and high-income countries, to develop a measurement infrastructure that integrates the aspirations of person-centered LTC.
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| 23. |
- Gaver, W. W., et al.
(author)
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The Drift Table : Designing for ludic engagement
- 2004
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In: Conf Hum Fact Comput Syst Proc. - New York, NY, USA : ACM. - 1581137036 - 9781581137033 ; , s. 885-900
-
Conference paper (peer-reviewed)abstract
- The Drift Table is an electronic coffee table that displays slowly moving aerial photography controlled by the distribution of weight on its surface. It was designed to investigate our ideas about how technologies for the home could support ludic activities-that is, activities motivated by curiosity, exploration, and reflection rather than externally-defined tasks. The many design choices we made, for example to block or disguise utilitarian functionality, helped to articulate our emerging understanding of ludic design. Observations of the Drift Table being used in volunteers' homes over several weeks gave greater insight into how playful exploration is practically achieved and the issues involved in designing for ludic engagement.
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| 24. |
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| 25. |
- Henningsson, A. J., et al.
(author)
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Rapid diagnosis of acute norovirus-associated gastroenteritis: evaluation of the Xpert Norovirus assay and its implementation as a 24/7 service in three hospitals in Jonkoping County, Sweden
- 2017
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In: European Journal of Clinical Microbiology and Infectious Diseases. - : SPRINGER. - 0934-9723 .- 1435-4373. ; 36:10, s. 1867-1871
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Journal article (peer-reviewed)abstract
- Noroviruses are a leading cause of epidemic and sporadic cases of acute gastroenteritis worldwide. The rapid diagnosis of norovirus infection is important for prompt infection control measures and may reduce the need for additional diagnostic testing. Here we evaluated the performance of the rapid Xpert Norovirus assay, and assessed the turn-around time (TAT) before and after the implementation of the analysis as a 24/7 service at all the three hospitals in Jonkoping County, Sweden. We describe the implementation process which was performed in two steps during 2014. A total number of 276 clinical samples (stool and vomitus) from patients with symptoms of acute gastroenteritis were included in 2014-2015. The samples were analysed with the Xpert Norovirus assay and the already existing routine method: an in-house reverse transcription real-time PCR. Samples showing discrepant results with the two assays were further analysed by a third PCR method. The Xpert Norovirus assay performed well with a sensitivity of 100% and a specificity of 93% compared to the gold standard (defined as the result obtained by at least two of the three PCR methods). The median TAT decreased from 22 hours in 2013 to 2.4 hours in 2015 (p amp;lt; 0.001). We conclude that the performance of the Xpert Norovirus assay was excellent, and that the implementation of the analysis as a 24/7 service at all three hospitals in the county has greatly reduced the time to diagnosis which is beneficial for both patients and healthcare providers.
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