| 1. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 4. |
- Emile-Geay, J., et al.
(författare)
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Data Descriptor: A global multiproxy database for temperature reconstructions of the Common Era
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Reproducible climate reconstructions of the Common Era (1 CE to present) are key to placing industrial-era warming into the context of natural climatic variability. Here we present a community-sourced database of temperature-sensitive proxy records from the PAGES2k initiative. The database gathers 692 records from 648 locations, including all continental regions and major ocean basins. The records are from trees, ice, sediment, corals, speleothems, documentary evidence, and other archives. They range in length from 50 to 2000 years, with a median of 547 years, while temporal resolution ranges from biweekly to centennial. Nearly half of the proxy time series are significantly correlated with HadCRUT4.2 surface temperature over the period 1850-2014. Global temperature composites show a remarkable degree of coherence between high-and low-resolution archives, with broadly similar patterns across archive types, terrestrial versus marine locations, and screening criteria. The database is suited to investigations of global and regional temperature variability over the Common Era, and is shared in the Linked Paleo Data (LiPD) format, including serializations in Matlab, R and Python. Since the pioneering work of D'Arrigo and Jacoby1-3, as well as Mann et al. 4,5, temperature reconstructions of the Common Era have become a key component of climate assessments6-9. Such reconstructions depend strongly on the composition of the underlying network of climate proxies10, and it is therefore critical for the climate community to have access to a community-vetted, quality-controlled database of temperature-sensitive records stored in a self-describing format. The Past Global Changes (PAGES) 2k consortium, a self-organized, international group of experts, recently assembled such a database, and used it to reconstruct surface temperature over continental-scale regions11 (hereafter, ` PAGES2k-2013'). This data descriptor presents version 2.0.0 of the PAGES2k proxy temperature database (Data Citation 1). It augments the PAGES2k-2013 collection of terrestrial records with marine records assembled by the Ocean2k working group at centennial12 and annual13 time scales. In addition to these previously published data compilations, this version includes substantially more records, extensive new metadata, and validation. Furthermore, the selection criteria for records included in this version are applied more uniformly and transparently across regions, resulting in a more cohesive data product. This data descriptor describes the contents of the database, the criteria for inclusion, and quantifies the relation of each record with instrumental temperature. In addition, the paleotemperature time series are summarized as composites to highlight the most salient decadal-to centennial-scale behaviour of the dataset and check mutual consistency between paleoclimate archives. We provide extensive Matlab code to probe the database-processing, filtering and aggregating it in various ways to investigate temperature variability over the Common Era. The unique approach to data stewardship and code-sharing employed here is designed to enable an unprecedented scale of investigation of the temperature history of the Common Era, by the scientific community and citizen-scientists alike.
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| 5. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Yang, Wen-Yi, et al.
(författare)
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Association of Office and Ambulatory Blood Pressure With Mortality and Cardiovascular Outcomes
- 2019
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Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 322:5, s. 409-420
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Tidskriftsartikel (refereegranskat)abstract
- ImportanceBlood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes. ObjectiveTo evaluate the association of BP indexes with death and a composite CV event. Design, Setting, and ParticipantsLongitudinal population-based cohort study of 11135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016). ExposuresBlood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or the night; and the dipping ratio (nighttime divided by daytime readings). Main Outcomes and MeasuresMultivariable-adjusted hazard ratios (HRs) expressed the risk of death or a CV event associated with BP increments of 20/10 mm Hg. Cardiovascular events included CV mortality combined with nonfatal coronary events, heart failure, and stroke. Improvement in model performance was assessed by the change in the area under the curve (AUC). ResultsAmong 11135 participants (median age, 54.7 years, 49.3% women), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a CV event over a median of 13.8 years of follow-up. Both end points were significantly associated with all single systolic BP indexes (P<.001). For nighttime systolic BP level, the HR for total mortality was 1.23 (95% CI, 1.17-1.28) and for CV events, 1.36 (95% CI, 1.30-1.43). For the 24-hour systolic BP level, the HR for total mortality was 1.22 (95% CI, 1.16-1.28) and for CV events, 1.45 (95% CI, 1.37-1.54). With adjustment for any of the other systolic BP indexes, the associations of nighttime and 24-hour systolic BP with the primary outcomes remained statistically significant (HRs ranging from 1.17 [95% CI, 1.10-1.25] to 1.87 [95% CI, 1.62-2.16]). Base models that included single systolic BP indexes yielded an AUC of 0.83 for mortality and 0.84 for the CV outcomes. Adding 24-hour or nighttime systolic BP to base models that included other BP indexes resulted in incremental improvements in the AUC of 0.0013 to 0.0027 for mortality and 0.0031 to 0.0075 for the composite CV outcome. Adding any systolic BP index to models already including nighttime or 24-hour systolic BP did not significantly improve model performance. These findings were consistent for diastolic BP. Conclusions and RelevanceIn this population-based cohort study, higher 24-hour and nighttime blood pressure measurements were significantly associated with greater risks of death and a composite CV outcome, even after adjusting for other office-based or ambulatory blood pressure measurements. Thus, 24-hour and nighttime blood pressure may be considered optimal measurements for estimating CV risk, although statistically, model improvement compared with other blood pressure indexes was small.
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| 7. |
- Horne, A., et al.
(författare)
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Efficacy of Moderately Dosed Etoposide in Macrophage Activation Syndrome-Hemophagocytic Lymphohistiocytosis
- 2021
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 48:10, s. 1596-1602
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Macrophage activation syndrome (MAS) constitutes 1 subtype of the hyperinflammatory syndrome hemophagocytic lymphohistiocytosis (HLH), and the term MAS-HLH was recently proposed for HLH with underlying autoimmune/autoinflammatory conditions. The mortality of MAS-HLH has been estimated at 5-10%. Here we report our experiences with moderately dosed etoposide in severe MAS-HLH; the objective was to effectively reduce severe hyperinflammatory activity with limited side effects. Methods. In addition to conventional antiinflammatory treatment, moderately dosed etoposide was administered to 7 children affected by rapidly progressing MAS-HLH with central nervous system (n = 5) and/ or pulmonary (n = 5) involvement. Three had underlying systemic juvenile idiopathic arthritis (sJIA), 2 had atypical sJIA (no arthritis at diagnosis), and 2 had systemic lupus erythematosus. We performed lymphocyte cytotoxicity analyses in all 7 and genetic analyses in 6. Results. All children promptly responded to moderately dosed etoposide (50-100 mg/m(2Y) once weekly), added to conventional MAS-HLH treatment that was considered insufficient. The mean accumulated etoposide dose was 671 mg/m(2) (range 300-1050 mg/m(2)) as compared to 1500 mg/m(2) recommended in the first 8 weeks of the HLH-94/HLH-2004 protocols. One child developed neutropenic fever and another neutropenic sepsis (neutrophils 0.3 x 10(9)/L at therapy onset). Five of 7 children had low percentages (< 5%) of circulating natural killer (NK) cells prior to or in association with diagnosis; NK cell activity was pathologically low in 2 of 5 children studied. Disease-causing variants in HLH-associated genes were not found. All children were alive at latest follow-up (2-9 yrs after onset); neurological symptoms had normalized in 4 of 5 affected children. Conclusion. Moderately dosed etoposide may be beneficial in severe and/or refractory MAS-HLH.
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| 13. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 15. |
- Asplund, Anna, et al.
(författare)
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Expression profiling of microdissected cell populations selected from basal cells in normal epidermis and basal cell carcinoma
- 2008
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 158:3, s. 527-538
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Tidskriftsartikel (refereegranskat)abstract
- Background Basal cell carcinomas (BCCs) are prevalent tumours with uniform histology that develop without any known precursor lesion. Alterations in the sonic hedgehog-patched1 signalling pathway are accepted as necessary events for tumorigenesis, and mutations in the patched1 gene are frequently present in tumours. Objectives To analyse transcript profiles in BCC. Methods We used laser-assisted microdissection to isolate and collect cell populations defined under the microscope. Peripheral cells from nests of BCC were selected to represent tumour cells, and normal keratinocytes from epidermis basal layer were used as control. Extracted RNA was amplified and hybridized on to a cDNA microarray. Results Our results show that BCC cells express a transcript signature that is significantly different from that of normal keratinocytes, and over 350 genes with various functions were identified as differentially expressed. The compiled data suggest an upregulation of the Wnt signalling pathway as a major event in BCC cells. Furthermore, tumour cells appear to have an increased sensitivity to oxygen radicals and dysregulated genes involved in antigen presentation. Results were validated at both the transcriptional level using real-time polymerase chain reaction and at the protein level using immunohistochemistry. Conclusions We show that microdissection in combination with robust strategies for RNA extraction, amplification and cDNA microarray analysis allow for reliable transcript profiling and that antibody-based proteomics provides an advantageous strategy for the analysis of corresponding differentially expressed proteins. We found that expression patterns were significantly altered in BCC cells compared with basal keratinocytes and that the Wnt signalling pathway was upregulated in tumour cells.
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| 18. |
- Bischof, J, et al.
(författare)
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A versatile platform for creating a comprehensive UAS-ORFeome library in Drosophila
- 2013
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Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 140:11, s. 2434-2442
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Tidskriftsartikel (refereegranskat)abstract
- Overexpression screens are used to explore gene functions in Drosophila, but this strategy suffers from the lack of comprehensive and systematic fly strain collections and efficient methods for generating such collections. Here, we present a strategy that could be used efficiently to generate large numbers of transgenic Drosophila strains, and a collection of 1149 UAS-ORF fly lines that were created with the site-specific ΦC31 integrase method. For this collection, we used a set of 655 genes that were cloned as two variants, either as an open reading frame (ORF) with a native stop codon or with a C-terminal 3xHA tag. To streamline the procedure for transgenic fly generation, we demonstrate the utility of injecting pools of plasmids into embryos, each plasmid containing a randomised sequence (barcode) that serves as a unique identifier for plasmids and, subsequently, fly strains. We also developed a swapping technique that facilitates the rapid exchange of promoters and epitope tags in vivo, expanding the versatility of the ORF collection. The work described here serves as the basis of a systematic library of Gal4/UAS-regulated transgenes.
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| 25. |
- Bjorklund, J., et al.
(författare)
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Cell size and wall dimensions drive distinct variability of earlywood and latewood density in Northern Hemisphere conifers
- 2017
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 216:3, s. 728-740
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Tidskriftsartikel (refereegranskat)abstract
- Interannual variability of wood density - an important plant functional trait and environmental proxy - in conifers is poorly understood. We therefore explored the anatomical basis of density. We hypothesized that earlywood density is determined by tracheid size and latewood density by wall dimensions, reflecting their different functional tasks. To determine general patterns of variability, density parameters from 27 species and 349 sites across the Northern Hemisphere were correlated to tree-ring width parameters and local climate. We performed the same analyses with density and width derived from anatomical data comprising two species and eight sites. The contributions of tracheid size and wall dimensions to density were disentangled with sensitivity analyses. Notably, correlations between density and width shifted from negative to positive moving from earlywood to latewood. Temperature responses of density varied intraseasonally in strength and sign. The sensitivity analyses revealed tracheid size as the main determinant of earlywood density, while wall dimensions become more influential for latewood density. Our novel approach of integrating detailed anatomical data with large-scale tree-ring data allowed us to contribute to an improved understanding of interannual variations of conifer growth and to illustrate how conifers balance investments in the competing xylem functions of hydraulics and mechanical support.
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| 29. |
- Bjorklund, Robert, et al.
(författare)
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Continuous monitoring of yoghurt fermentation using a noble metal electrode array
- 2009
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Ingår i: International Journal of Food Science and Technology. - : Wiley. - 0950-5423 .- 1365-2621. ; 44:3, s. 635-640
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Tidskriftsartikel (refereegranskat)abstract
- An electrochemical probe containing gold, platinum and rhodium working electrodes was used to monitor yoghurt production in a pilot facility. Three commercial starting cultures at 40, 42 and 44 C transformed milk having 1.5% fat content to mild yoghurt products. The electrochemical changes in the broth during fermentation were recorded as current responses from pulse voltammetry over the electrodes. Principal component analysis of the responses generated two-dimensional score plots describing the qualitative fermentation progressions. Two distinct fermentation pathways were observed leading to similar final products. The pH was recorded during the fermentations and the data was used as reference values for creating a partial least squares model for prediction of pH as an example of a quantitative application for the sensor. The relative mean squared error for validation of the model using four probes interchangeably was about 2%. The probe was constructed of materials approved for use in the food industry and did not require a standard glass reference electrode.
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| 33. |
- Fransson, Susanne, 1975, et al.
(författare)
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Whole-genome sequencing of recurrent neuroblastoma reveals somatic mutations that affect key players in cancer progression and telomere maintenance
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Neuroblastoma is the most common and deadly childhood tumor. Relapsed or refractory neuroblastoma has a very poor prognosis despite recent treatment advances. To investigate genomic alterations associated with relapse and therapy resistance, whole-genome sequencing was performed on diagnostic and relapsed lesions together with constitutional DNA from seven children. Sequencing of relapsed tumors indicates somatic alterations in diverse genes, including those involved in RAS-MAPK signaling, promoting cell cycle progression or function in telomere maintenance and immortalization. Among recurrent alterations, CCND1-gain, TERT-rearrangements, and point mutations in POLR2A, CDK5RAP, and MUC16 were shown in >= 2 individuals. Our cohort contained examples of converging genomic alterations in primary-relapse tumor pairs, indicating dependencies related to specific genetic lesions. We also detected rare genetic germline variants in DNA repair genes (e.g., BARD1, BRCA2, CHEK2, and WRN) that might cooperate with somatically acquired variants in these patients with highly aggressive recurrent neuroblastoma. Our data indicate the importance of monitoring recurrent neuroblastoma through sequential genomic characterization and that new therapeutic approaches combining the targeting of MAPK signaling, cell cycle progression, and telomere activity are required for this challenging patient group.
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| 36. |
- Goroshchuk, O, et al.
(författare)
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Targeting Plk1 with siRNNs in primary cells from pediatric B-cell acute lymphoblastic leukemia patients
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 2688-
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Tidskriftsartikel (refereegranskat)abstract
- B-cell acute lymphoblastic leukemia (B-ALL) accounts for nearly one fifth of all childhood cancers and current challenges in B-ALL treatment include resistance, relapse and late-onset side effects due to the chemotherapy. To overcome these hurdles, novel therapies need to be investigated. One promising target is Polo-like kinase 1 (Plk1), a key regulator of the cell cycle. In this study, the Plk family expression is investigated in primary peripheral blood and bone marrow mononuclear cells from ten pediatric B-ALL patients. For the first time, short interfering RiboNucleic Neutrals (siRNNs) that enter cells without a transfection reagent are used to target Plk1 mRNA in primary cells from pediatric B-ALL patients. Our results show that the expression of Plk1 and Plk4 is significantly higher in pediatric B-ALL patients compared to healthy donors. Moreover, treatment of primary peripheral blood and bone marrow mononuclear cells from pediatric B-ALL patients, cultured ex vivo, with Plk1-targeting siRNNs results in cleavage of Plk1 mRNA. Importantly, the Plk1 knockdown is specific and does not affect other Plk members in contrast to many small molecule Plk1 inhibitors. Thus, Plk1 is a potential therapeutic target in pediatric B-ALL and selective targeting of Plk1 can be achieved by the use of siRNNs.
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| 37. |
- Grander, D, et al.
(författare)
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Factors influencing the response to interferon therapy in chronic hepatitis C. Studies on viral genotype and induction of 2',5'-oligoadenylate synthetase in the liver and peripheral blood cells
- 1996
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 31:6, s. 604-611
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The mechanism behind the antiviral action of interferon (IFN) therapy in chronic hepatitis C virus (HCV) infection is not well understood, and, furthermore, few factors have been shown to be good predictors of a favourable response to IFN treatment in chronic HCV infection. METHODS: Freshly explanted liver cells and peripheral blood mononuclear cells (PBMC) from 80 patients with chronic HCV infection were used to study the capacity of IFN to induce the enzyme 2',5'-oligoadenylate synthetase (2'5'-AS) in vitro. The HCV genotype was determined in 53 patients. The induction of 2'5'-AS was correlated to the results of IFN-alpha treatment in 36 patients. RESULTS: Normalization of transaminases during IFN treatment was significantly associated with 2'5'-AS levels in liver cells cultured in the absence of IFN. A similar tendency, although not statistically significant, was found for IFN-induced levels of 2'5'-AS in liver cells. No such associations were found when PBMC were analysed. Six patients showed a sustained biochemical response. These six did not deviate significantly from the remaining patients with regard to base-line or IFN-induced levels of 2'5'-AS in liver cells or PBMC. Eradication of HCV RNA during IFN treatment did not correlate with 2'5'-AS levels in liver cells. Comparison of HCV genotype and clinical response showed that patients with genotype 3a had the most favourable outcome. No association was found between liver histology and treatment outcome. CONCLUSION: These data imply that direct effects of IFN on liver cells are of importance for the response to IFN treatment.
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| 38. |
- Hagey, DW, et al.
(författare)
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Myeloid cells from Langerhans cell histiocytosis patients exhibit increased vesicle trafficking and an altered secretome capable of activating NK cells
- 2023
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 108:9, s. 2422-2434
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Tidskriftsartikel (refereegranskat)abstract
- Langerhans cell histiocytosis (LCH) is a potentially life-threatening inflammatory myeloid neoplasia linked to paediatric neurodegeneration, whereby transformed LCH cells form agglomerated lesions in various organs. Although MAP-kinase pathway mutations have been identified in LCH cells, the functional consequences of these mutations and the mechanisms that cause the pathogenic behaviour of LCH cells are not well understood. In our study, we used an in vitro differentiation system and RNA-sequencing to compare monocyte-derived dendritic cells from LCH patients to those derived from healthy controls or patients with Crohn’s disease, a non-histiocytic inflammatory disease. We observed that Interferon-γ treatment exacerbated intrinsic differences between LCH patient and control cells, including strikingly increased endoand exocytosis gene activity in LCH patients. We validated these transcriptional patterns in lesions and functionally confirmed that LCH cells exhibited increased endo- and exocytosis. Furthermore, RNA-sequencing of extracellular vesicles (EV) revealed the enrichment of pathological transcripts involved in cell adhesion, MAP-kinase pathway, vesicle trafficking and T-cell activation in LCH patients. Thus, we tested the effect of the LCH secretome on lymphocyte activity and found significant activation of NK cells. These findings implicate EVs in the pathology of LCH for the first time, in line with their established roles in the formation of various other tumour niches. Thus, we describe novel traits of LCH patient cells and suggest a pathogenic mechanism of potential therapeutic and diagnostic importance.
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| 39. |
- Hellstrom-Lindberg, E, et al.
(författare)
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Lead poisoning from souvenir earthenware
- 2006
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Ingår i: International archives of occupational and environmental health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 79:2, s. 165-168
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Tidskriftsartikel (refereegranskat)
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| 42. |
- Jensen, I, et al.
(författare)
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An overlooked key to excellence in research : a longitudinal cohort study on the association between the psycho-social work environment and research performance
- 2021
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Ingår i: Studies in Higher Education. - : Taylor & Francis Group. - 0307-5079 .- 1470-174X. ; 46:12, s. 2610-2628
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Tidskriftsartikel (refereegranskat)abstract
- Theories of what determines research performance have evolved from political and economic science, amongst other disciplines. Contemporary research shows that universities have a problematic work environment characterized by bullying, insecure jobs, and dysfunctional leadership. In this study, we explore the relationship between the psycho-social work environment (PSWE) and research performance. The study consists of longitudinal data from a medical university in Sweden. PSWE was assessed by employee surveys and the outcome was register data from 8 years of bibliometrics and external funding. SEM-analyses were applied building on theoretical and empirical models. Results show that PSWE explained future research performance, with the highest impact on the quality of publications. The most important PSWE factors for good performance were fair, considerate leaders and a supportive social climate. The results suggest that improving the psycho-social work environment at the universities could be one strategy to improve research performance.
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