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Sökning: WFRF:(Johnston Peter)

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1.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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2.
  • Su, Zhan, et al. (författare)
  • Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
  • 2012
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
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3.
  • Jenniskens, Peter, et al. (författare)
  • Fall, recovery, and characterization of the Novato L6 chondrite breccia
  • 2014
  • Ingår i: Meteoritics and Planetary Science. - : Wiley. - 1086-9379. ; 49:8, s. 1388-1425
  • Tidskriftsartikel (refereegranskat)abstract
    • The Novato L6 chondrite fragmental breccia fell in California on 17 October 2012, and was recovered after the Cameras for Allsky Meteor Surveillance (CAMS) project determined the meteor's trajectory between 95 and 46 km altitude. The final fragmentation from 42 to 22 km altitude was exceptionally well documented by digital photographs. The first sample was recovered before rain hit the area. First results from a consortium study of the meteorite's characterization, cosmogenic and radiogenic nuclides, origin, and conditions of the fall are presented. Some meteorites did not retain fusion crust and show evidence of spallation. Before entry, the meteoroid was 35 +/- 5 cm in diameter (mass 80 +/- 35 kg) with a cosmic-ray exposure age of 9 +/- 1 Ma, if it had a one-stage exposure history. A two-stage exposure history is more likely, with lower shielding in the last few Ma. Thermoluminescence data suggest a collision event within the last similar to 0.1 Ma. Novato probably belonged to the class of shocked L chondrites that have a common shock age of 470 Ma, based on the U, Th-He age of 420 +/- 220 Ma. The measured orbits of Novato, Jesenice, and Innisfree are consistent with a proposed origin of these shocked L chondrites in the Gefion asteroid family, perhaps directly via the 5: 2 mean-motion resonance with Jupiter. Novato experienced a stronger compaction than did other L6 chondrites of shock-stage S4. Despite this, a freshly broken surface shows a wide range of organic compounds.
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4.
  • Escott-Price, Valentina, et al. (författare)
  • Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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5.
  • Jones, Lesley, et al. (författare)
  • Convergent genetic and expression data implicate immunity in Alzheimer's disease
  • 2015
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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6.
  • Lawler, Mark, et al. (författare)
  • A Catalyst for Change: The European Cancer Patient's Bill of Rights.
  • 2014
  • Ingår i: The Oncologist. - : Oxford University Press (OUP). - 1549-490X .- 1083-7159.
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Cancer Concord is a unique patient-centered partnership that will act as a catalyst to achieve improved access to an optimal standard of cancer care and research for European citizens. In order to provide tangible benefits for European cancer patients, the partnership proposes the creation of a “European Cancer Patient's Bill of Rights,” a patient charter that will underpin equitable access to an optimal standard of care for Europe's citizens.
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7.
  • Thompson, Paul M., et al. (författare)
  • The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
  • 2014
  • Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
  • Tidskriftsartikel (refereegranskat)abstract
    • The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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8.
  • Bass, Gary Alan, 1979-, et al. (författare)
  • Techniques for mesoappendix transection and appendix resection: insights from the ESTES SnapAppy study
  • 2023
  • Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer Science and Business Media LLC. - 1863-9933 .- 1615-3146 .- 1863-9941. ; 49, s. 17-32
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Surgically managed appendicitis exhibits great heterogeneity in techniques for mesoappendix transection and appendix amputation from its base. It is unclear whether a particular surgical technique provides outcome benefit or reduces complications. Material and methods: We undertook a pre-specified subgroup analysis of all patients who underwent laparoscopic appendectomy at index admission during SnapAppy (ClinicalTrials.gov Registration: NCT04365491). We collected routine, anonymized observational data regarding surgical technique, patient demographics and indices of disease severity, without change to clinical care pathway or usual surgeon preference. Outcome measures of interest were the incidence of complications, unplanned reoperation, readmission, admission to the ICU, death, hospital length of stay, and procedure duration. We used Poisson regression models with robust standard errors to calculate incident rate ratios (IRRs) and 95% confidence intervals (CIs). Results: Three-thousand seven hundred sixty-eight consecutive adult patients, included from 71 centers in 14 countries, were followed up from date of admission for 90days. The mesoappendix was divided hemostatically using electrocautery in 1564(69.4%) and an energy device in 688(30.5%). The appendix was amputated by division of its base between looped ligatures in 1379(37.0%), with a stapler in 1421(38.1%) and between clips in 929(24.9%). The technique for securely dividing the appendix at its base in acutely inflamed (AAST Grade 1) appendicitis was equally divided between division between looped ligatures, clips and stapled transection. However, the technique used differed in complicated appendicitis (AAST Grade 2 +) compared with uncomplicated (Grade 1), with a shift toward transection of the appendix base by stapler (58% vs. 38%; p < 0.001). While no statistical difference in outcomes could be detected between different techniques for division of appendix base, decreased risk of any [adjusted IRR (95% CI): 0.58 (0.41–0.82), p = 0.002] and severe [adjusted IRR (95% CI): 0.33 (0.11–0.96), p = 0.045] complications could be detected when using energy devices. Conclusions: Safe mesoappendix transection and appendix resection are accomplished using heterogeneous techniques. Technique selection for both mesoappendix transection and appendix resection correlates with AAST grade. Higher grade led to more ultrasonic tissue transection and stapled appendix resection. Higher AAST appendicitis grade also correlated with infection-related complication occurrence. Despite the overall well-tolerated heterogeneity of approaches to acute appendicitis, increasing disease acuity or complexity appears to encourage homogeneity of intraoperative surgical technique toward advanced adjuncts.
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9.
  • Bousquet, Jean, et al. (författare)
  • Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
  • Tidskriftsartikel (refereegranskat)abstract
    • Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
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10.
  • Butler, Peter, et al. (författare)
  • Coulomb excitation of pear-shaped nuclei
  • 2019
  • Ingår i: - : EDP Sciences. ; , s. 01007-01007
  • Konferensbidrag (refereegranskat)abstract
    • There is a large body of evidence that atomic nuclei can undergo octupole distortion and assume the shape of a pear. This phenomenon is important for measurements of electric-dipole moments of atoms, which would indicate CP violation and hence probe physics beyond the Standard Model of particle physics. Isotopes of both radon and radium have been identified as candidates for such measurements. Here, we have observed the low-lying quantum states in 224Rn and 226Rn by accelerating beams of these radioactive nuclei. We show that radon isotopes undergo octupole vibrations but do not possess static pear-shapes in their ground states. We conclude that radon atoms provide less favourable conditions for the enhancement of a measurable atomic electric-dipole moment.
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11.
  • Forssten, Maximilian Peter, 1996-, et al. (författare)
  • Surgical management of acute appendicitis during the European COVID-19 second wave: safe and effective
  • 2023
  • Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer Science and Business Media LLC. - 1863-9933 .- 1615-3146 .- 1863-9941. ; 49, s. 57-67
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The COVID-19 (SARS-CoV-2) pandemic drove acute care surgeons to pivot from long established practice patterns. Early safety concerns regarding increased postoperative complication risk in those with active COVID infection promoted antibiotic-driven non-operative therapy for select conditions ahead of an evidence-base. Our study assesses whether active or recent SARS-CoV-2 positivity increases hospital length of stay (LOS) or postoperative complications following appendectomy. Methods: Data were derived from the prospective multi-institutional observational SnapAppy cohort study. This preplanned data analysis assessed consecutive patients aged ≥ 15years who underwent appendectomy for appendicitis (November 2020–May 2021). Patients were categorized based on SARS-CoV-2 seropositivity: no infection, active infection, and prior infection. Appendectomy method, LOS, and complications were abstracted. The association between SARS-CoV-2 seropositivity and complications was determined using Poisson regression, while the association with LOS was calculated using a quantile regression model. Results: Appendectomy for acute appendicitis was performed in 4047 patients during the second and third European COVID waves. The majority were SARS-CoV-2 uninfected (3861, 95.4%), while 70 (1.7%) were acutely SARS-CoV-2 positive, and 116 (2.8%) reported prior SARS-CoV-2 infection. After confounder adjustment, there was no statistically significant association between SARS-CoV-2 seropositivity and LOS, any complication, or severe complications. Conclusion: During sequential SARS-CoV-2 infection waves, neither active nor prior SARS-CoV-2 infection was associated with prolonged hospital LOS or postoperative complication. Despite early concerns regarding postoperative safety and outcome during active SARS-CoV-2 infection, no such association was noted for those with appendicitis who underwent operative management.
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12.
  • Menditto, Enrica, et al. (författare)
  • Adherence to treatment in allergic rhinitis using mobile technology : The MASK Study
  • 2019
  • Ingår i: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 49:4, s. 442-460
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC <= 1.25), 51 (4.23%) were partly adherent (MPR >= 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.
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13.
  • Nene, Vishvanath, et al. (författare)
  • Genome sequence of Aedes aegypti, a major arbovirus vector.
  • 2007
  • Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5832, s. 1718-23
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at approximately 1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae. Nearly 50% of the Ae. aegypti genome consists of transposable elements. These contribute to a factor of approximately 4 to 6 increase in average gene length and in sizes of intergenic regions relative to An. gambiae and Drosophila melanogaster. Nonetheless, chromosomal synteny is generally maintained among all three insects, although conservation of orthologous gene order is higher (by a factor of approximately 2) between the mosquito species than between either of them and the fruit fly. An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species.
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14.
  • Pasupathy, Sivabaskari, et al. (författare)
  • Survival in Patients With Suspected Myocardial Infarction With Nonobstructive Coronary Arteries : A Comprehensive Systematic Review and Meta-Analysis From the MINOCA Global Collaboration
  • 2021
  • Ingår i: Circulation. Cardiovascular Quality and Outcomes. - : Lippincott Williams & Wilkins. - 1941-7713 .- 1941-7705. ; 14:11
  • Forskningsöversikt (refereegranskat)abstract
    • BACKGROUND: Suspected myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) occurs in ≈5% to 10% of patients with MI referred for coronary angiography. The prognosis of these patients may differ to those with MI and obstructive coronary artery disease (MI-CAD) and those without a MI (patients without known history of MI [No-MI]). The primary objective of this study is to evaluate the 12-month all-cause mortality of patients with MINOCA.METHODS: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the terms "MI," "nonobstructive," "angiography," and "prognosis" were searched in PubMed and Embase databases from inception to December 2018, including original, English language MINOCA studies with >100 consecutive patients. Publications with a heterogeneous cohort, unreported coronary stenosis, or exclusively focusing on MINOCA-mimicking conditions, were excluded. Unpublished data were obtained from the MINOCA Global Collaboration. Data were pooled and analyzed using Paule-Mandel, Hartung, Knapp, Sidik & Jonkman, or restricted maximum-likelihood random-effects meta-analysis methodology. Heterogeneity was assessed using Cochran's Q and I2 statistics. The primary outcome was 12-month all-cause mortality in patients with MINOCA, with secondary comparisons to MI-CAD and No-MI.RESULTS: The 23 eligible studies yielded 55 369 suspected MINOCA, 485 382 MI-CAD, and 33 074 No-MI. Pooled meta-analysis of 14 MINOCA studies accounting for 30 733 patients revealed an unadjusted 12-month all-cause mortality rate of 3.4% (95% CI, 2.6%-4.2%) and reinfarction (n=27 605; 10 studies) in 2.6% (95% CI, 1.7%-3.5%). MINOCA had a lower 12-month all-cause mortality than those with MI-CAD (3.3% [95% CI, 2.5%-4.1%] versus 5.6% [95% CI, 4.1%-7.0%]; odds ratio, 0.60 [95% CI, 0.52-0.70], P<0.001). In contrast, there was a statistically nonsignificant trend towards increased 12-month all-cause mortality in patients with MINOCA (2.6% [95% CI, 0%-5.9%]) compared with No-MI (0.7% [95% CI, 0.1%-1.3%]; odds ratio, 3.71 [95% CI, 0.58-23.61], P=0.09).CONCLUSIONS: In the largest contemporary MINOCA meta-analysis to date, patients with suspected MINOCA had a favorable prognosis compared with MI-CAD, but statistically nonsignificant trend toward worse outcomes compared to those with No-MI. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42020145356.
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15.
  • Schoch, Conrad L., et al. (författare)
  • Finding needles in haystacks: linking scientific names, reference specimens and molecular data for Fungi
  • 2014
  • Ingår i: Database: The Journal of Biological Databases and Curation. - : Oxford University Press (OUP). - 1758-0463. ; 2014:bau061, s. 1-21
  • Tidskriftsartikel (refereegranskat)abstract
    • DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi.
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16.
  • Thompson, Rachel, et al. (författare)
  • RD-Connect : An Integrated Platform Connecting Databases, Registries, Biobanks and Clinical Bioinformatics for Rare Disease Research
  • 2014
  • Ingår i: Journal of general internal medicine. - : Springer Science and Business Media LLC. - 0884-8734 .- 1525-1497. ; 29:S3, s. S780-S787
  • Forskningsöversikt (refereegranskat)abstract
    • Research into rare diseases is typically fragmented by data type and disease. Individual efforts often have poor interoperability and do not systematically connect data across clinical phenotype, genomic data, biomaterial availability, and research/trial data sets. Such data must be linked at both an individual-patient and whole-cohort level to enable researchers to gain a complete view of their disease and patient population of interest. Data access and authorization procedures are required to allow researchers in multiple institutions to securely compare results and gain new insights. Funded by the European Union's Seventh Framework Programme under the International Rare Diseases Research Consortium (IRDiRC), RD-Connect is a global infrastructure project initiated in November 2012 that links genomic data with registries, biobanks, and clinical bioinformatics tools to produce a central research resource for rare diseases.
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17.
  • Torchia, Jonathon, et al. (författare)
  • Molecular subgroups of atypical teratoid rhabdoid tumours in children : an integrated genomic and clinicopathological analysis
  • 2015
  • Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 16:5, s. 569-582
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5. Lack of biological understanding of the substantial clinical heterogeneity of these tumours restricts therapeutic advances. We integrated genomic and clinicopathological analyses of a cohort of patients with atypical teratoid rhabdoid tumours to find out the molecular basis for clinical heterogeneity in these tumours. Methods We obtained 259 rhabdoid tumours from 37 international institutions and assessed transcriptional profiles in 43 primary tumours and copy number profiles in 38 primary tumours to discover molecular subgroups of atypical teratoid rhabdoid tumours. We used gene and pathway enrichment analyses to discover group-specific molecular markers and did immunohistochemical analyses on 125 primary tumours to evaluate clinicopathological significance of molecular subgroup and ASCL1-NOTCH signalling. Findings Transcriptional analyses identified two atypical teratoid rhabdoid tumour subgroups with differential enrichment of genetic pathways, and distinct clinicopathological and survival features. Expression of ASCL1, a regulator of NOTCH signalling, correlated with supratentorial location (p=0.004) and superior 5-year overall survival (35%, 95% CI 13-57, and 20%, 6-34, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0.033) in 70 patients who received multimodal treatment. ASCL1 expression also correlated with superior 5-year overall survival (34%, 7-61, and 9%, 0-21, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0.001) in 39 patients who received only chemotherapy without radiation. Cox hazard ratios for overall survival in patients with differential ASCL1 enrichment treated with chemotherapy with or without radiation were 2.02 (95% CI 1.04-3.85; p=0.038) and 3.98 (1.71-9.26; p=0.001). Integrated analyses of molecular subgroupings with clinical prognostic factors showed three distinct clinical risk groups of tumours with different therapeutic outcomes. Interpretation An integration of clinical risk factors and tumour molecular groups can be used to identify patients who are likely to have improved long-term radiation-free survival and might help therapeutic stratification of patients with atypical teratoid rhabdoid tumours.
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18.
  • Zamora, Juan Carlos, et al. (författare)
  • Considerations and consequences of allowing DNA sequence data as types of fungal taxa
  • 2018
  • Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
  • Tidskriftsartikel (refereegranskat)abstract
    • Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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19.
  • Barone, Giovanni Davide, et al. (författare)
  • Harnessing photosynthetic microorganisms for enhanced bioremediation of microplastics : A comprehensive review
  • 2024
  • Ingår i: ENVIRONMENTAL SCIENCE AND ECOTECHNOLOGY. - : Elsevier. - 2666-4984. ; 20
  • Forskningsöversikt (refereegranskat)abstract
    • Mismanaged plastics, upon entering the environment, undergo degradation through physicochemical and/or biological processes. This process often results in the formation of microplastics (MPs), the most prevalent form of plastic debris (<1 mm). MPs pose severe threats to aquatic and terrestrial ecosystems, necessitating innovative strategies for effective remediation. Some photosynthetic microorganisms can degrade MPs but there lacks a comprehensive review. Here we examine the specific role of photoautotrophic microorganisms in water and soil environments for the biodegradation of plastics, focussing on their unique ability to grow persistently on diverse polymers under sunlight. Notably, these cells utilise light and CO2 to produce valuable compounds such as carbohydrates, lipids, and proteins, showcasing their multifaceted environmental benefits. We address key scientific questions surrounding the utilisation of photosynthetic microorganisms for MPs and nanoplastics (NPs) bioremediation, discussing potential engineering strategies for enhanced efficacy. Our review highlights the significance of alternative biomaterials and the exploration of strains expressing enzymes, such as polyethylene terephthalate (PET) hydrolases, in conjunction with microalgal and/or cyanobacterial metabolisms. Furthermore, we delve into the promising potential of photo-biocatalytic approaches, emphasising the coupling of plastic debris degradation with sunlight exposure. The integration of microalgal-bacterial consortia is explored for biotechnological applications against MPs and NPs pollution, showcasing the synergistic effects in wastewater treatment through the absorption of nitrogen, heavy metals, phosphorous, and carbon. In conclusion, this review provides a comprehensive overview of the current state of research on the use of photoautotrophic cells for plastic bioremediation. It underscores the need for continued investigation into the engineering of these microorganisms and the development of innovative approaches to tackle the global issue of plastic pollution in aquatic and terrestrial ecosystems. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Chinese Society for Environmental Sciences, Harbin Institute of Technology, Chinese Research Academy of Environmental Sciences.
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20.
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21.
  • Cleland, Jennifer, et al. (författare)
  • Using paradox theory to understand responses to tensions between service and training in general surgery
  • 2018
  • Ingår i: Medical Education. - : Wiley. - 0308-0110. ; 52:3, s. 288-301
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: The tension between service and training in pressured health care environments can have a detrimental impact on training quality and job satisfaction. Yet the management literature proposes that competing demands are inherent in organisational settings: it is not the demands as such that lead to negative outcomes but how people and organisations react to opposing tensions. We explored how key stakeholders responded to competing service-training demands in a surgical setting that had recently gone through a highly-publicised organisational crisis.METHODS: This was an explanatory case study of a general surgery unit. Public documents informed the research questions and the data were triangulated with semi-structured interviews (n = 14) with key stakeholders. Data coding and analysis were initially inductive but, after the themes emerged, we used a paradox lens to group themes into four contextual dimensions: performing, organising, belonging and learning.RESULTS: Tensions were apparent in the data, with managers, surgeons and trainees or residents in conflict with each other because of different goals or priorities and divergent perspectives on the same issue of balancing service and training (performing). This adversely impacted on relationships across and within groups (belonging, learning) and led to individuals prioritising their own goals rather than working for the 'greater good' (performing, belonging). Yet although relationships and communication improved, the approach to getting a better balance maintained the 'compartmentalisation' of training (organising) rather than acknowledging that training and service cannot be separated.DISCUSSION: Stakeholder responses to the tensions provided temporary relief but were unlikely to lead to real change if the tension between service and training was considered to be an interdependent and persistent paradox. Reframing the service-training paradox in this way may encourage adjusting responses to create effective working partnerships. Our findings add to the body of knowledge on this topic, and will resonate with all those engaged in surgical and other postgraduate training.
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22.
  • Damineli, Augusto, et al. (författare)
  • The Long-term Spectral Changes of Eta Carinae : Are they Caused by a Dissipating Occulter as Indicated by CMFGEN Models?
  • 2023
  • Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 954
  • Tidskriftsartikel (refereegranskat)abstract
    • Eta Carinae (η Car) exhibits a unique set of P Cygni profiles with both broad and narrow components. Over many decades, the spectrum has changed-there has been an increase in observed continuum fluxes and a decrease in Fe II and H I emission-line equivalent widths. The spectrum is evolving toward that of a P Cygni star such as P Cygni itself and HDE 316285. The spectral evolution has been attributed to intrinsic variations such as a decrease in the mass-loss rate of the primary star or differential evolution in a latitudinal-dependent stellar wind. However, intrinsic wind changes conflict with three observational results: the steady long-term bolometric luminosity; the repeating X-ray light curve over the binary period; and the constancy of the dust-scattered spectrum from the Homunculus. We extend previous work that showed a secular strengthening of P Cygni absorptions by adding more orbital cycles to overcome temporary instabilities and by examining more atomic transitions. CMFGEN modeling of the primary wind shows that a time-decreasing mass-loss rate is not the best explanation for the observations. However, models with a small dissipating absorber in our line of sight can explain both the increase in brightness and changes in the emission and P Cygni absorption profiles. If the spectral evolution is caused by the dissipating circumstellar medium, and not by intrinsic changes in the binary, the dynamical timescale to recover from the Great Eruption is much less than a century, different from previous suggestions.
  •  
23.
  • Gärdenfors, Peter, et al. (författare)
  • Event boards as tools for holistic AI
  • 2019
  • Ingår i: CEUR Workshop Proceedings : 6th International Workshop on Artificial Intelligence and Cognition - 6th International Workshop on Artificial Intelligence and Cognition. ; 2418, s. 1-10
  • Konferensbidrag (refereegranskat)
  •  
24.
  • Gärdenfors, Peter, et al. (författare)
  • Interpreting Robot Pointing Behavior
  • 2013
  • Ingår i: Social Robotics : 5th International Conference, ICSR 2013, Bristol, UK, October 27-29, 2013, Proceedings - 5th International Conference, ICSR 2013, Bristol, UK, October 27-29, 2013, Proceedings. - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. - 9783319026749 - 9783319026756 ; 8239, s. 148-159
  • Konferensbidrag (refereegranskat)abstract
    • The ability to draw other agents’ attention to objects and events is an important skill on the critical path to effective human-robot collaboration. People use the act of pointing to draw other people’s attention to objects and events for a wide range of purposes. While there is significant work that aims to understand people’s pointing behavior, there is little work analyzing how people interpret robot pointing. Since robots have a wide range of physical bodies and cognitive architectures, interpreting pointing will be determined by a specific robot’s morphology and behavior. Humanoids and robots whose heads, torso and arms resemble humans that point may be easier for people to interpret, however if such robots have different perceptual capabilities to people then misinterpretation may occur. In this paper we investigate how ordinary people interpret the pointing behavior of a leading state-of-the-art service robot that has been designed to work closely with people. We tested three hypotheses about how robot pointing is interpreted. The most surprising finding was that the direction and pitch of the robot’s head was important in some conditions.
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25.
  • Herrera, Miguel F., et al. (författare)
  • AACE/ACE DISEASE STATE CLINICAL REVIEW : PANCREATIC NEUROENDOCRINE INCIDENTALOMAS
  • 2015
  • Ingår i: Endocrine Practice. - 1530-891X .- 1934-2403. ; 21:5, s. 546-553
  • Forskningsöversikt (refereegranskat)abstract
    • Incidental detection of pancreatic neuroendocrine tumors (PNETs) has substantially increased over the last decade due to widespread use of advanced imaging studies. Reliable initial imaging-based characterization is crucial for the differential diagnosis from other exocrine neoplasms and to determine the appropriate management plan. Measurements of chromogranin A, pancreatic polypeptide, and calcitonin are recommended for the biochemical evaluation. A thorough medical history needs to be performed to rule out multiple endocrine neoplasia (MEN) type 1. The European Neuroendocrine Tumor Society (ENETS)/Tumor Node Metastasis (TNM) staging system together with a grading based on the Ki-67 proliferation index and mitotic counts has proven to give more appropriate prognostic information than the World Health Organization (WHO)/American Joint Committee on Cancer (AJCC) TNM staging but may still fail to safely differentiate benign from malignant lesions. Poorly differentiated PNETs generally present with metastases and are rarely amenable for resection. Well-or intermediately differentiated tumors >= 2 cm with imaging evidence of malignancy or with a Ki-67 > 2% should be resected. It has been suggested that non-MEN related, nonfunctioning, and asymptomatic PNETs < 2 cm with a Ki-67 index >= 2% carry a low risk of metastasis and may be observed in the absence of clinical or radiologic criteria of malignancy or progression, especially in older patients. However, because metastases may occur with long delay with smaller PNETS, physicians should consider patient age, lesion location, and the risks of operation, and patients not undergoing surgery need to be closely followed closely.
  •  
26.
  • Hilton, Emma N, et al. (författare)
  • Left-sided embryonic expression of the BCL-6 corepressor, BCOR, is required for vertebrate laterality determination.
  • 2007
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 16:14, s. 1773-1782
  • Tidskriftsartikel (refereegranskat)abstract
    • Oculofaciocardiodental (OFCD) syndrome is an X-linked male lethal condition encompassing cardiac septal defects, as well as ocular and dental anomalies. The gene mutated in OFCD syndrome, the BCL-6 corepressor (BCOR), is part of a transcriptional repression complex whose transcriptional targets remain largely unknown. We reviewed cases of OFCD syndrome and identified patients exhibiting defective lateralization including dextrocardia, asplenia and intestinal malrotation, suggesting that BCOR is required in normal laterality determination. To study the function of BCOR, we used morpholino oligonucleotides (MOs) to knockdown expression of xtBcor in Xenopus tropicalis, thus creating an animal model for OFCD syndrome. The resulting tadpoles had cardiac and ocular features characteristic of OFCD syndrome. Reversed cardiac orientation and disorganized gut patterning were seen when MOs were injected into the left side of embryos, demonstrating a left-sided requirement for xtBcor in lateral determination in Xenopus. Ocular defects displayed no left-right bias and included anterior and posterior segment disorders such as microphthalmia and coloboma. Expression of xtPitx2c was shown to be downregulated when xtBcor was depleted. This identifies a pathway in which xtBcor is required for lateral specification, a process intrinsically linked to correct cardiac septal development.
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27.
  • Hyde, K. D., et al. (författare)
  • Global consortium for the classification of fungi and fungus-like taxa
  • 2023
  • Ingår i: MYCOSPHERE. - : Mushroom Research Foundation. - 2077-7000 .- 2077-7019. ; 14:1, s. 1960-2012
  • Tidskriftsartikel (refereegranskat)abstract
    • The Global Consortium for the Classification of Fungi and fungus-like taxa is an international initiative of more than 550 mycologists to develop an electronic structure for the classification of these organisms. The members of the Consortium originate from 55 countries/regions worldwide, from a wide range of disciplines, and include senior, mid-career and early-career mycologists and plant pathologists. The Consortium will publish a biannual update of the Outline of Fungi and fungus-like taxa, to act as an international scheme for other scientists. Notes on all newly published taxa at or above the level of species will be prepared and published online on the Outline of Fungi website (https://www.outlineoffungi.org/), and these will be finally published in the biannual edition of the Outline of Fungi and fungus-like taxa. Comments on recent important taxonomic opinions on controversial topics will be included in the biannual outline. For example, 'to promote a more stable taxonomy in Fusarium given the divergences over its generic delimitation', or 'are there too many genera in the Boletales?' and even more importantly, 'what should be done with the tremendously diverse 'dark fungal taxa?' There are undeniable differences in mycologists' perceptions and opinions regarding species classification as well as the establishment of new species. Given the pluralistic nature of fungal taxonomy and its implications for species concepts and the nature of species, this consortium aims to provide a platform to better refine and stabilise fungal classification, taking into consideration views from different parties. In the future, a confidential voting system will be set up to gauge the opinions of all mycologists in the Consortium on important topics. The results of such surveys will be presented to the International Commission on the Taxonomy of Fungi (ICTF) and the Nomenclature Committee for Fungi (NCF) with opinions and percentages of votes for and against. Criticisms based on scientific evidence with regards to nomenclature, classifications, and taxonomic concepts will be welcomed, and any recommendations on specific taxonomic issues will also be encouraged; however, we will encourage professionally and ethically responsible criticisms of others' work. This biannual ongoing project will provide an outlet for advances in various topics of fungal classification, nomenclature, and taxonomic concepts and lead to a community-agreed classification scheme for the fungi and fungus-like taxa. Interested parties should contact the lead author if they would like to be involved in future outlines.
  •  
28.
  • Ibrahem, Ismail, et al. (författare)
  • Copper Nanoparticles on Controlled Pore Glass and TEMPO for the Aerobic Oxidation of Alcohols
  • 2018
  • Ingår i: ChemNanoMat. - : Wiley. - 2199-692X. ; 4:1, s. 71-75
  • Tidskriftsartikel (refereegranskat)abstract
    • Herein, we report on the facile synthesis of a heterogeneous copper nanocatalyst and its combination with 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) for the aerobic oxidation of alcohols to their corresponding carbonyl compounds. This low cost copper nanocatalyst was found to exhibit excellent recyclability, making it a highly attractive catalytic system from an economical and environmental point of view. Extensive characterization of the catalyst by a number of techniques revealed that it was comprised of well-dispersed Cu(I/II) nanoparticles with an average size of around 6nm.
  •  
29.
  • Iqbal, M. Naeem, et al. (författare)
  • Mesoporous Ruthenium Oxide : A Heterogeneous Catalyst for Water Oxidation
  • 2017
  • Ingår i: ACS Sustainable Chemistry and Engineering. - : American Chemical Society (ACS). - 2168-0485. ; 5:11, s. 9651-9656
  • Tidskriftsartikel (refereegranskat)abstract
    • Herein we report the synthesis of mesoporous ruthenium oxide (MP-RuO2) using a template-based approach. The catalytic efficiency of the prepared MP-RuO2 was compared to commercially available ruthenium oxide nanoparticles (C-RuO2) as heterogeneous catalysts for water oxidation. The results demonstrated superior performance of MP-RuO2 for oxygen evolution compared to the C-RuO2 with respect to recyclability, amount of generated oxygen, and stability over several catalytic runs.
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30.
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31.
  • Johnston, Alice S.A., et al. (författare)
  • Temperature thresholds of ecosystem respiration at a global scale
  • 2021
  • Ingår i: Nature Ecology and Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 5:4, s. 487-494
  • Tidskriftsartikel (refereegranskat)abstract
    • Ecosystem respiration is a major component of the global terrestrial carbon cycle and is strongly influenced by temperature. The global extent of the temperature–ecosystem respiration relationship, however, has not been fully explored. Here, we test linear and threshold models of ecosystem respiration across 210 globally distributed eddy covariance sites over an extensive temperature range. We find thresholds to the global temperature–ecosystem respiration relationship at high and low air temperatures and mid soil temperatures, which represent transitions in the temperature dependence and sensitivity of ecosystem respiration. Annual ecosystem respiration rates show a markedly reduced temperature dependence and sensitivity compared to half-hourly rates, and a single mid-temperature threshold for both air and soil temperature. Our study indicates a distinction in the influence of environmental factors, including temperature, on ecosystem respiration between latitudinal and climate gradients at short (half-hourly) and long (annual) timescales. Such climatological differences in the temperature sensitivity of ecosystem respiration have important consequences for the terrestrial net carbon sink under ongoing climate change.
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32.
  • Johnston, Jennifer J., et al. (författare)
  • Molecular Analysis Expands the Spectrum of Phenotypes Associated with GLI3 Mutations
  • 2010
  • Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794. ; 31:10, s. 1142-1154
  • Tidskriftsartikel (refereegranskat)abstract
    • A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with typical GCPS or PHS were previously reported, and we report the remaining 93 probands here. This includes 19 probands (12 mutations) who fulfilled clinical criteria for GCPS or PHS, 48 probands (16 mutations) with features of GCPS or PHS but who did not meet the clinical criteria (sub-GCPS and sub-PHS), 21 probands (6 mutations) with features of PHS or GCPS and oral-facial- digital syndrome, and 5 probands (1 mutation) with nonsyndromic polydactyly. These data support previously identified genotype-phenotype correlations and demonstrate a more variable degree of severity than previously recognized. The finding of GLI3 mutations in patients with features of oral-facial-digital syndrome supports the observation that GLI3 interacts with cilia. We conclude that the phenotypic spectrum of GLI3 mutations is broader than that encompassed by the clinical diagnostic criteria, but the genotype-phenotype correlation persists. Individuals with features of either GCPS or PHS should be screened for mutations in GLI3 even if they do not fulfill clinical criteria. Hum Mutat 31:1142-1154, 2010. (C) 2010 Wiley-Liss, Inc.
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33.
  • Johnston, Nina, 1961-, et al. (författare)
  • Systematic reviews : causes of non-adherence to P2Y12 inhibitors in acute coronary syndromes and response to intervention
  • 2016
  • Ingår i: Open heart. - : BMJ. - 2053-3624. ; 3:2
  • Forskningsöversikt (refereegranskat)abstract
    • To understand the factors associated with non-adherence to oral antiplatelet (OAP) therapy in acute coronary syndromes (ACS), and where interventions have modified these factors. Linked systematic reviews were undertaken in accordance with the Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines, using CINAHL Plus, MEDLINE, PsycINFO and PubMed databases. The searches were limited to studies available in English and published from 2000 onwards; last run in June 2015. Review 1: factors. Fifteen articles were identified that reported 25 different factors associated with OAP non-adherence. Factors were categorised into: Demographic, Treatment, Healthcare System Processes, Clinical, Opportunity (ie, factors outside the patients, such as cost and healthcare access) and Psychosocial. It was not possible to determine if any of these factors were more impactful than others, either overall or temporally. Review 2: interventions. Six articles were identified that described interventions targeting adherence in patients with acute coronary syndromes (ACS)/coronary artery disease (CAD). Four broad categories of intervention were identified: treatment counselling and education, educational materials, SMS reminders and telephone monitoring and reinforcement delivered different practitioners. Only reminder-based interventions had a consistently successful impact on adherence outcomes at both 3 and 12 months. A number of factors are associated with OAP non-adherence, and encouragingly, there is some evidence of the effectiveness of intervention to modify treatment adherence in patients with ACS/CAD. Future evaluations ensuring a better cohesion between the factors studied as associated with non-adherence and those targeted by intervention would further increase understanding and lead to improved results.
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34.
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35.
  • Kempf, Tibor, et al. (författare)
  • Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay
  • 2007
  • Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 53:2, s. 284-291
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Growth-differentiation factor 15 (GDF15) is a member of the transforming growth factor beta (TGF-beta) cytokine superfamily. There has been increasing interest in using circulating GDF15 as a biomarker in patients, for example those with cardiovascular disease. METHODS: We developed an IRMA that uses a polyclonal, affinity chromatography-purified goat antihuman GDF15 IgG antibody, assessed the preanalytic characteristics of GDF15, and determined circulating GDF15 concentrations in 429 apparently healthy elderly individuals and 153 patients with chronic heart failure (CHF). RESULTS: The assay had a detection limit of 20 ng/L, an intraassay imprecision of < or =10.6%, and an interassay imprecision of < or =12.2%. Specificity was demonstrated with size-exclusion chromatography, parallel measurements with polyclonal and monoclonal anti-GDF15 antibody, and lack of cross-reactivity with TGF-beta. The assay was not appreciably influenced by the anticoagulant matrix or unrelated biological substances. GDF15 was stable at room temperature for 48 h and resistant to 4 freeze-thaw cycles. Apparently healthy, elderly individuals presented with a median GDF15 concentration of 762 ng/L (25th-75th percentiles, 600-959 ng/L). GDF15 concentrations were associated with age and with cystatin C and C-reactive protein concentrations. CHF patients had increased GDF15 concentrations that were closely related to disease severity. CONCLUSION: The IRMA can detect GDF15 in human serum and plasma with excellent sensitivity and specificity. The reference limits and confounding variables defined for apparently healthy elderly individuals and the favorable preanalytic characteristics of GDF15 are expected to facilitate future studies of GDF15 as a biomarker in various disease settings, including CHF.
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36.
  • Koelle, D. M., et al. (författare)
  • Worldwide circulation of HSV-2 x HSV-1 recombinant strains
  • 2017
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Homo sapiens harbor two distinct, medically significant species of simplexviruses, herpes simplex virus (HSV)-1 and HSV-2, with estimated divergence 6-8 million years ago (MYA). Unexpectedly, we found that circulating HSV-2 strains can contain HSV-1 DNA segments in three distinct genes. Using over 150 genital swabs from North and South America and Africa, we detected recombinantsworldwide. Common, widely distributed gene UL39 genotypes are parsimoniously explained by an initial >457 basepair (bp) HSV-1 x HSV-2 crossover followed by back-recombination to HSV-2. Blocks of >244 and >539 bp of HSV-1 DNA within genes UL29 and UL30, respectively, have reached near fixation, with a minority of strains retaining sequences we posit as ancestral HSV-2. Our data add to previous in vitroand animal work, implying that in vivo cellular co-infection with HSV-1 and HSV-2 yields viable interspecies recombinants in the natural human host.
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37.
  • Kunadian, Vijay, et al. (författare)
  • Gender Differences in Outcomes and Predictors of All-Cause Mortality After Percutaneous Coronary Intervention (Data from United Kingdom and Sweden)
  • 2017
  • Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 119:2, s. 210-216
  • Tidskriftsartikel (refereegranskat)abstract
    • To determine gender differences and predictors of all-cause mortality (30 days and 1 year) after percutaneous coronary intervention (PCI) in patients with stable angina pectoris and acute coronary syndrome (non ST-elevation myocardial infarction/unstable angina pectoris and ST-elevation myocardial infarction) in the British Cardiovascular Intervention Society (BCIS) and Swedish Coronary Angiography and Angioplasty Registry (SCAAR) data sets, an analysis of prospectively collected data from 2007 to 2011 was performed. In total, 458,261 patients (BCIS: n = 368,492 [25.9% women]; Sweden: n = 89,769 [27.2% women]) who underwent PCI were included in this analysis. Using multiple regression analysis, in the BCIS registry, female gender was an independent predictor of all-cause mortality at 30 days (odds ratio [OR] 1.15, 95% CI 1.10 to 1.22, p <0.0001) and at 1 year (OR 1.08, 95% CI 1.04 to 1.12, p <0.0001) after PCI for all patients. Likewise, in the SCAAR registry, female gender was an independent predictor of all-cause mortality at 30 days (OR 1.15, 95% CI 1.05 to 1.26, p = 0.002) and 1 year (OR 1.09, 95% CI 1.03 to 1.17, p = 0.006) after PCI for all patients. In both data sets, there was no statistically significant interaction between age and gender for all-cause mortality at 30 days (BCIS, p = 0.59; SCAAR, p = 0.40) and at 1 year (BCIS, p = 0.11; SCAAR, p = 0.83). In conclusion, despite advances in care, women compared with men continue to experience higher all cause mortality after PCI for coronary artery disease. The patient's age at the time of PCI remains a strong predictive factor of mortality in this population. Strategies and further research are warranted to better address the management of coronary artery disease in women with possibly earlier diagnosis and more tailored treatments.
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38.
  • Lawler, M., et al. (författare)
  • The European Cancer Patient's Bill of Rights, update and implementation 2016
  • 2016
  • Ingår i: Esmo Open. - : Elsevier BV. - 2059-7029. ; 1:6
  • Tidskriftsartikel (refereegranskat)abstract
    • In this implementation phase of the European Cancer Patient's Bill of Rights (BoR), we confirm the following three patient-centred principles that underpin this initiative: 1. The right of every European citizen to receive the most accurate information and to be proactively involved in his/her care. 2. The right of every European citizen to optimal and timely access to a diagnosis and to appropriate specialised care, underpinned by research and innovation. 3. The right of every European citizen to receive care in health systems that ensure the best possible cancer prevention, the earliest possible diagnosis of their cancer, improved outcomes, patient rehabilitation, best quality of life and affordable health care. Agree our high-level goal. The vision of 70% longterm survival for patients with cancer in 2035, promoting cancer prevention and cancer control and the associated progress in ensuring good patient experience and quality of life. Establish the major mechanisms to underpin its delivery. (1) The systematic and rigorous sharing of best practice between and across European cancer healthcare systems and (2) the active promotion of Research and Innovation focused on improving outcomes; (3) Improving access to new and established cancer care by sharing best practice in the development, approval, procurement and reimbursement of cancer diagnostic tests and treatments. Work with other organisations to bring into being a Europe based centre that will (1) systematically identify, evaluate and validate and disseminate best practice in cancer management for the different countries and regions and (2) promote Research and Innovation and its translation to maximise its impact to improve outcomes.
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39.
  • Mangerel, Joshua, et al. (författare)
  • Alternative lengthening of telomerases is enriched in, and impacts survival of TP53 mutant pediatric malignant brain tumors
  • 2014
  • Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 128:6, s. 853-862
  • Tidskriftsartikel (refereegranskat)abstract
    • Although telomeres are maintained in most cancers by telomerase activation, a subset of tumors utilize alternative lengthening of telomeres (ALT) to sustain self-renewal capacity. In order to study the prevalence and significance of ALT in childhood brain tumors we screened 517 pediatric brain tumors using the novel C-circle assay. We examined the association of ALT with alterations in genes found to segregate with specific histological phenotypes and with clinical outcome. ALT was detected almost exclusively in malignant tumors (p = 0.001). ALT was highly enriched in primitive neuroectodermal tumors (12 %), choroid plexus carcinomas (23 %) and high-grade gliomas (22 %). Furthermore, in contrast to adult gliomas, pediatric low grade gliomas which progressed to high-grade tumors did not exhibit the ALT phenotype. Somatic but not germline TP53 mutations were highly associated with ALT (p = 1.01 × 10(-8)). Of the other alterations examined, only ATRX point mutations and reduced expression were associated with the ALT phenotype (p = 0.0005). Interestingly, ALT attenuated the poor outcome conferred by TP53 mutations in specific pediatric brain tumors. Due to very poor prognosis, one year overall survival was quantified in malignant gliomas, while in children with choroid plexus carcinoma, five year overall survival was investigated. For children with TP53 mutant malignant gliomas, one year overall survival was 63 ± 12 and 23 ± 10 % for ALT positive and negative tumors, respectively (p = 0.03), while for children with TP53 mutant choroid plexus carcinomas, 5 years overall survival was 67 ± 19 and 27 ± 13 % for ALT positive and negative tumors, respectively (p = 0.07). These observations suggest that the presence of ALT is limited to a specific group of childhood brain cancers which harbor somatic TP53 mutations and may influence the outcome of these patients. Analysis of ALT may contribute to risk stratification and targeted therapies to improve outcome for these children.
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40.
  • Maskell, Peter D., et al. (författare)
  • Total body water is the preferred method to use in forensic blood-alcohol calculations rather than ethanols volume of distribution
  • 2020
  • Ingår i: Forensic Science International. - : ELSEVIER IRELAND LTD. - 0379-0738 .- 1872-6283. ; 316
  • Tidskriftsartikel (refereegranskat)abstract
    • During the prosecution and defence of drink-driving cases, forensic practitioners are often required to engage in various blood-alcohol calculations, such as whether or not the statutory limit was exceeded (e.g. 80 mg/100 mL, 0.08 g/100 mL or 0.80 g/L). For this purpose, most forensic scientists utilize the Widmark equation, or some modification thereof, to calculate a persons blood alcohol concentration (BAC) based on information about the amount of ethanol consumed and the pattern of drinking. This equation comes in two main forms; one of which incorporates the apparent volume of distribution of ethanol (V) and the other a persons total body water (TBW). In this study, we utilised two independent data sets, one involving the determination of V for ethanol in 173 men and 63 women, and the other TBW determined for 582 men and 884 women. Those subjects included in the TBW group represented various racial groups (Caucasians, African Americans, Hispanics, Asians and Puerto Ricans), with body mass index (BMI) ranging from 17 to 80 kg/m(2). Both versions of the Widmark equation were evaluated in relation to their accuracy and precision in predicting TBW and/or V using the two most common anthropometric equations; those of Watson et al. and Forrest. Both anthropometric equations exhibited good accuracy (<4.3%) for the prediction of both TBW and V. However, the root mean square error was lower TBW was used for prediction (9.09-12.84%) rather than V (11.72-15.08%). Overall, this study has demonstrated (a) that blood-alcohol calculations are more reliable using TBW rather than V (b) that both equations (Watson et al. and Forrest) are applicable to ethnic groups other than Caucasians and (c) the Forrest equation predicts TBW in men and women with BMI from 17 to 35 kg/m(2) and that the Watson et al. equation works for those with more extreme BMI; females (17-80 kg/m(2)) and males (17-67 kg/m(2)). (C) 2020 Elsevier B.V. All rights reserved.
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41.
  • McGuckian, Thomas B., et al. (författare)
  • Development of complex executive function over childhood : Longitudinal growth curve modeling of performance on the Groton Maze Learning Task
  • 2023
  • Ingår i: Child Development. - : John Wiley & Sons. - 0009-3920 .- 1467-8624. ; 94:3, s. 648-658
  • Tidskriftsartikel (refereegranskat)abstract
    • This longitudinal study modeled children's complex executive function (EF) development using the Groton Maze Learning Task (GMLT). Using a cohort-sequential design, 147 children (61 males, 5.5–11 years) were recruited from six multicultural primary schools in Melbourne and Perth, Australia. Race/ethnicity data were not available. Children were assessed on the GMLT at 6-month intervals over 2-years between 2010 and 2012. Growth curve models describe age-related change from 5.5 to 12.5 years old. Results showed a quadratic growth trajectory on each measure of error—that is, those that reflect visuospatial memory, executive control (or the ability to apply rules for action), and complex EF. The ability to apply rules for action, while a rate-limiting factor in complex EF, develops rapidly over early-to-mid childhood.
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42.
  • Mikus, MS, et al. (författare)
  • Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation
  • 2022
  • Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 59:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Asthma phenotyping requires novel biomarker discovery.ObjectivesTo identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs).MethodsAn antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED.ResultsIn U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-β and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation.ConclusionsThe plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA.
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43.
  • Ng, Eunice, et al. (författare)
  • Factors Associated With Work Ability in Patients Undergoing Surgery for Cervical Radiculopathy
  • 2015
  • Ingår i: Spine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0362-2436 .- 1528-1159. ; 40:16, s. 1270-1276
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Design. Cross-sectional study. Objective. To investigate the factors associated with work ability in patients undergoing surgery for cervical radiculopathy. Summary of Background Data. Surgery is a common treatment of cervical radiculopathy in people of working age. However, few studies have investigated the impact on the work ability of these patients. Methods. Patients undergoing surgery for cervical radiculopathy (n = 201) were recruited from spine centers in Sweden to complete a battery of questionnaires and physical measures the day before surgery. The associations between various individual, psychological, and work-related factors and self-reported work ability were investigated by Spearman rank correlation coefficient, multivariate linear regression, and forward stepwise regression analyses. Factors that were significant (P < 0.05) in each statistical analysis were entered into the successive analysis to reveal the factors most related to work ability. Work ability was assessed using the Work Ability Index. Results. The mean Work Ability Index score was 28 (SD, 9.0). The forward stepwise regression analysis revealed 6 factors significantly associated with work ability, which explained 62% of the variance in the Work Ability Index. Factors highly correlated with greater work ability included greater self-efficacy in performing self-cares, lower physical load on the neck at work, greater self-reported chance of being able to work in 6 months time, greater use of active coping strategies, lower frequency of hand weakness, and higher health-related quality of life. Conclusion. Psychological, work-related and individual factors were significantly associated with work ability in patients undergoing surgery for cervical radiculopathy. High self-efficacy was most associated with greater work ability. Consideration of these factors by surgeons preoperatively may provide optimal return to work outcomes after surgery.
  •  
44.
  • Novianto, Rony, et al. (författare)
  • Classical conditioning in social robots
  • 2014
  • Ingår i: Social Robotics : 6th International Conference, ICSR 2014, Proceedings - 6th International Conference, ICSR 2014, Proceedings. - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. - 9783319119724 ; 8755, s. 279-289
  • Konferensbidrag (refereegranskat)abstract
    • Classical conditioning is important in humans to learn and predict events in terms of associations between stimuli and to produce responses based on these associations. Social robots that have a classical conditioning skill like humans will have an advantage to interact with people more naturally, socially and effectively. In this paper, we present a novel classical conditioning mechanism and describe its implementation in ASMO cognitive architecture. The capability of this mechanism is demonstrated in the Smokey robot companion experiment. Results show that Smokey can associate stimuli and predict events in its surroundings. ASMO’s classical conditioning mechanism can be used in social robots to adapt to the environment and to improve the robots’ performances.
  •  
45.
  • Olsen, Peter, et al. (författare)
  • Cyclic allylic carbonates as a renewable platform for protecting chemistry in water
  • 2018
  • Ingår i: Green Chemistry. - : Royal Society of Chemistry (RSC). - 1463-9262 .- 1463-9270. ; 20:14, s. 3186-3190
  • Tidskriftsartikel (refereegranskat)abstract
    • The present work explores different cyclic allylic carbonates as a potential class of allylcarbamate precursors. The 5-membered carbonate formed a carbamate with very good thermal and pH stability, which could be cleanly deprotected in aqueous solution, in just 30 min with 2 mol% Pd(OAc)(2) as catalyst. The polar nature of the installed motif made it possible to deprotect highly unpolar substrates in water as solvent.
  •  
46.
  • Olsen, Peter, et al. (författare)
  • Synthesis of highly functional carbamates through ring-opening of cyclic carbonates with unprotected α-amino acids in water
  • 2018
  • Ingår i: Green Chemistry. - : Royal Society of Chemistry (RSC). - 1463-9262 .- 1463-9270. ; 20:2, s. 469-475
  • Tidskriftsartikel (refereegranskat)abstract
    • The present work shows that it is possible to ring-open cyclic carbonates with unprotected amino acids in water. Fine tuning of the reaction parameters made it possible to suppress the degree of hydrolysis in relation to aminolysis. This enabled the synthesis of functionally dense carbamates containing alkenes, carboxylic acids, alcohols and thiols after short reaction times at room temperature. When Glycine was used as the nucleophile in the ring-opening with four different five membered cyclic carbonates, containing a plethora of functional groups, the corresponding carbamates could be obtained in excellent yields (>90%) without the need for any further purification. Furthermore, the orthogonality of the transformation was explored through ring-opening of divinylenecarbonate with unprotected amino acids equipped with nucleophilic side chains, such as serine and cysteine. In these cases the reaction selectively produced the desired carbamate, in 70 and 50% yield respectively. The synthetic design provides an inexpensive and scalable protocol towards highly functionalized building blocks that are envisioned to find applications in both the small and macromolecular arena. 
  •  
47.
  • Peng, Y. Y., et al. (författare)
  • Doping dependence of the electron-phonon coupling in two families of bilayer superconducting cuprates
  • 2022
  • Ingår i: Physical Review B. - 2469-9969 .- 2469-9950. ; 105:11
  • Tidskriftsartikel (refereegranskat)abstract
    • While electron-phonon coupling (EPC) is crucial for Cooper pairing in conventional superconductors, its role in high-Tc superconducting cuprates is debated. Using resonant inelastic x-ray scattering at the oxygen K edge, we study the EPC in Bi2Sr2CaCu2O8+δ (Bi2212) and Nd1+xBa2-xCu3O7-δ (NBCO) at different doping levels ranging from heavily underdoped (p=0.07) to overdoped (p=0.21). We analyze the data with a localized Lang-Firsov model that allows for the coherent excitations of two phonon modes. While electronic band dispersion effects are non-negligible, we are able to perform a study of the relative values of EPC matrix elements in these cuprate families. In the case of NBCO, the choice of the excitation energy allows us to disentangle modes related to the CuO chains and the CuO2 planes. Combining the results from the two families, we find the EPC strength decreases with doping at q∥=(-0.25,0) r.l.u., but has a nonmonotonic trend as a function of doping at smaller momenta. This behavior is attributed to the screening effect of charge carriers. We also find that the phonon intensity is enhanced in the vicinity of the charge-density-wave excitations while the extracted EPC strength appears to be less sensitive to their proximity. By performing a comparative study of two cuprate families, we are able to identify general trends in the EPC for the cuprates and provide experimental input to theories invoking a synergistic role for this interaction in d-wave pairing.
  •  
48.
  • Roberts, Ruby, et al. (författare)
  • Medical students’ views of clinical environments
  • 2018
  • Ingår i: The Clinical Teacher. - : Wiley. - 1743-498X .- 1743-4971. ; 15:4, s. 325-330
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Monitoring the quality of clinical learning environments (CLEs) is immensely important in medical education. Objective indicators of the quality of the CLE can be used to measure learner perceptions and to inform educational improvements; however, many established tools were not designed for use in clinical settings and are not theoretically grounded. Our aim was to apply a new tool to the new context of a UK setting to explore the perceptions of senior medical students in a number of different CLEs. Methods: The four-factor Undergraduate Clinical Education Environment Measure (UCEEM) was translated into English, and used to gather final-year medical students’ perceptions of four different specialties they had rotated through: Emergency Medicine (EM), General Surgery (GS), Medicine for the Elderly (ME), and Obstetrics and Gynaecology (O&G). The UCEEMwas distributed in paper form. Students were asked to complete it in relation to two of the four specialties. Results/findings: Year-5 medical students (n = 132) returned a completed UCEEM. For opportunities to learn in and through work experience EM was reported the most positively. ME was perceived to be the most prepared for student entry. Students reported being well received by staff and made to feel part of the team within GS, EM and ME, but less so in O&G. Discussion: UCEEM appears to be a useful tool for evaluating medical student perceptions of CLEs. Theoretically robust, UCEEM is straightforward to administer and to score. It has the potential to be used by time-pressured educators to collect baseline and comparative data for evaluation and improvement purposes.
  •  
49.
  • Soultan, Alaaeldin, et al. (författare)
  • The future distribution of wetland birds breeding in Europe validated against observed changes in distribution
  • 2022
  • Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9318 .- 1748-9326. ; 17:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Wetland bird species have been declining in population size worldwide as climate warming and land-use change affect their suitable habitats. We used species distribution models (SDMs) to predict changes in range dynamics for 64 non-passerine wetland birds breeding in Europe, including range size, position of centroid, and margins. We fitted the SDMs with data collected for the first European Breeding Bird Atlas and climate and land-use data to predict distributional changes over a century (the 1970s-2070s). The predicted annual changes were then compared to observed annual changes in range size and range centroid over a time period of 30 years using data from the second European Breeding Bird Atlas. Our models successfully predicted ca. 75% of the 64 bird species to contract their breeding range in the future, while the remaining species (mostly southerly breeding species) were predicted to expand their breeding ranges northward. The northern margins of southerly species and southern margins of northerly species, both, predicted to shift northward. Predicted changes in range size and shifts in range centroids were broadly positively associated with the observed changes, although some species deviated markedly from the predictions. The predicted average shift in core distributions was ca. 5 km yr-1 towards the north (5% northeast, 45% north, and 40% northwest), compared to a slower observed average shift of ca. 3.9 km yr-1. Predicted changes in range centroids were generally larger than observed changes, which suggests that bird distribution changes may lag behind environmental changes leading to 'climate debt'. We suggest that predictions of SDMs should be viewed as qualitative rather than quantitative outcomes, indicating that care should be taken concerning single species. Still, our results highlight the urgent need for management actions such as wetland creation and restoration to improve wetland birds' resilience to the expected environmental changes in the future.
  •  
50.
  • Stone, Vicki, et al. (författare)
  • The Essential Elements of a Risk Governance Framework for Current and Future Nanotechnologies
  • 2018
  • Ingår i: Risk Analysis. - : Wiley. - 0272-4332 .- 1539-6924. ; 38:7, s. 1321-1331
  • Tidskriftsartikel (refereegranskat)abstract
    • Societies worldwide are investing considerable resources into the safe development and use of nanomaterials. Although each of these protective efforts is crucial for governing the risks of nanomaterials, they are insufficient in isolation. What is missing is a more integrative governance approach that goes beyond legislation. Development of this approach must be evidence based and involve key stakeholders to ensure acceptance by end users. The challenge is to develop a framework that coordinates the variety of actors involved in nanotechnology and civil society to facilitate consideration of the complex issues that occur in this rapidly evolving research and development area. Here, we propose three sets of essential elements required to generate an effective risk governance framework for nanomaterials. (1) Advanced tools to facilitate risk-based decision making, including an assessment of the needs of users regarding risk assessment, mitigation, and transfer. (2) An integrated model of predicted human behavior and decision making concerning nanomaterial risks. (3) Legal and other (nano-specific and general) regulatory requirements to ensure compliance and to stimulate proactive approaches to safety. The implementation of such an approach should facilitate and motivate good practice for the various stakeholders to allow the safe and sustainable future development of nanotechnology.
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