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Sökning: WFRF:(Armitage S)

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1.
  • Schael, S, et al. (författare)
  • Precision electroweak measurements on the Z resonance
  • 2006
  • Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
  • Forskningsöversikt (refereegranskat)abstract
    • We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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2.
  • Arndt, D. S., et al. (författare)
  • STATE OF THE CLIMATE IN 2017
  • 2018
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
  • Forskningsöversikt (refereegranskat)
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3.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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4.
  • Figlioli, G, et al. (författare)
  • The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
  • 2019
  • Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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8.
  • Sumaila, U. Rashid, et al. (författare)
  • WTO must ban harmful fisheries subsidies
  • 2021
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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9.
  • Peden, John F., et al. (författare)
  • A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease
  • 2011
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:4, s. 339-344
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)(1-7), a modest number considering the apparent heritability of CAD(8). All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with similar to 575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 x 10(-8) in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.
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10.
  • Ring, A., et al. (författare)
  • Bridging The Age Gap: observational cohort study of effects of chemotherapy and trastuzumab on recurrence, survival and quality of life in older women with early breast cancer
  • 2021
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 125, s. 209-219
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk disease who may benefit from chemotherapy. Methods: A multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years. Propensity score-matching adjusted for variation in baseline age, fitness and tumour stage. Results: Three thousands four hundred sixteen women were recruited from 56 UK centres between 2013 and 2018. Two thousands eight hundred eleven (82%) had surgery. 1520/2811 (54%) had high-risk EBC and 2059/2811 (73%) were fit. Chemotherapy was given to 306/1100 (27.8%) fit patients with high-risk EBC. Unmatched comparison of chemotherapy versus no chemotherapy demonstrated reduced metastatic recurrence risk in high-risk patients(hazard ratio [HR] 0.36 [95% CI 0.19–0.68]) and in 541 age, stage and fitness-matched patients(adjusted HR 0.43 [95% CI 0.20–0.92]) but no benefit to overall survival (OS) or breast cancer-specific survival (BCSS) in either group. Chemotherapy improved survival in women with oestrogen receptor (ER)-negative cancer (OS: HR 0.20 [95% CI 0.08–0.49];BCSS: HR 0.12 [95% CI 0.03–0.44]).Transient negative quality-of-life impacts were observed. Conclusions: Chemotherapy was associated with reduced risk of metastatic recurrence, but survival benefits were only seen in patients with ER-negative cancer. Quality-of-life impacts were significant but transient. Trial Registration: ISRCTN 46099296. © 2021, The Author(s).
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11.
  • Caton, J. G., et al. (författare)
  • A new classification scheme for periodontal and peri-implant diseases and conditions - Introduction and key changes from the 1999 classification
  • 2018
  • Ingår i: Journal of Periodontology. - : Wiley. - 0022-3492. ; 89
  • Tidskriftsartikel (refereegranskat)abstract
    • A classification scheme for periodontal and peri-implant diseases and conditions is necessary for clinicians to properly diagnose and treat patients as well as for scientists to investigate etiology, pathogenesis, natural history, and treatment of the diseases and conditions. This paper summarizes the proceedings of the World Workshop on the Classification of Periodontal and Peri-implant Diseases and Conditions. The workshop was co-sponsored by the American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP) and included expert participants from all over the world. Planning for the conference, which was held in Chicago on November 9 to 11, 2017, began in early 2015. An organizing committee from the AAP and EFP commissioned 19 review papers and four consensus reports covering relevant areas in periodontology and implant dentistry. The authors were charged with updating the 1999 classification of periodontal diseases and conditions and developing a similar scheme for peri-implant diseases and conditions. Reviewers and workgroups were also asked to establish pertinent case definitions and to provide diagnostic criteria to aid clinicians in the use of the new classification. All findings and recommendations of the workshop were agreed to by consensus. This introductory paper presents an overview for the new classification of periodontal and peri-implant diseases and conditions, along with a condensed scheme for each of four workgroup sections, but readers are directed to the pertinent consensus reports and review papers for a thorough discussion of the rationale, criteria, and interpretation of the proposed classification. Changes to the 1999 classification are highlighted and discussed. Although the intent of the workshop was to base classification on the strongest available scientific evidence, lower level evidence and expert opinion were inevitably used whenever sufficient research data were unavailable. The scope of this workshop was to align and update the classification scheme to the current understanding of periodontal and peri-implant diseases and conditions. This introductory overview presents the schematic tables for the new classification of periodontal and peri-implant diseases and conditions and briefly highlights changes made to the 1999 classification. It cannot present the wealth of information included in the reviews, case definition papers, and consensus reports that has guided the development of the new classification, and reference to the consensus and case definition papers is necessary to provide a thorough understanding of its use for either case management or scientific investigation. Therefore, it is strongly recommended that the reader use this overview as an introduction to these subjects. Accessing this publication online will allow the reader to use the links in this overview and the tables to view the source papers (Table1).
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12.
  • Berglundh, Tord, 1954, et al. (författare)
  • Peri-implant diseases and conditions: Consensus report of workgroup 4 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions
  • 2018
  • Ingår i: Journal of Periodontology. - : Wiley. - 0022-3492. ; 89
  • Tidskriftsartikel (refereegranskat)abstract
    • A classification for peri-implant diseases and conditions was presented. Focused questions on the characteristics of peri-implant health, peri-implant mucositis, peri-implantitis, and soft- and hard-tissue deficiencies were addressed. Peri-implant health is characterized by the absence of erythema, bleeding on probing, swelling, and suppuration. It is not possible to define a range of probing depths compatible with health; Peri-implant health can exist around implants with reduced bone support. The main clinical characteristic of peri-implant mucositis is bleeding on gentle probing. Erythema, swelling, and/or suppuration may also be present. An increase in probing depth is often observed in the presence of peri-implant mucositis due to swelling or decrease in probing resistance. There is strong evidence from animal and human experimental studies that plaque is the etiological factor for peri-implant mucositis. Peri-implantitis is a plaque-associated pathological condition occurring in tissues around dental implants, characterized by inflammation in the peri-implant mucosa and subsequent progressive loss of supporting bone. Peri-implantitis sites exhibit clinical signs of inflammation, bleeding on probing, and/or suppuration, increased probing depths and/or recession of the mucosal margin in addition to radiographic bone loss. The evidence is equivocal regarding the effect of keratinized mucosa on the long-term health of the peri-implant tissue. It appears, however, that keratinized mucosa may have advantages regarding patient comfort and ease of plaque removal. Case definitions in day-to-day clinical practice and in epidemiological or disease-surveillance studies for peri-implant health, peri-implant mucositis, and peri-implantitis were introduced. The proposed case definitions should be viewed within the context that there is no generic implant and that there are numerous implant designs with different surface characteristics, surgical and loading protocols. It is recommended that the clinician obtain baseline radiographic and probing measurements following the completion of the implant-supported prosthesis.
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13.
  • Clarke, R., et al. (författare)
  • Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals
  • 2014
  • Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165. ; 100:2, s. 657-666
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Elevated plasma homocysteine is a risk factor for Alzheimer disease, but the relevance of homocysteine lowering to slow the rate of cognitive aging is uncertain. Objective: The aim was to assess the effects of treatment with B vitamins compared with placebo, when administered for several years, on composite domains of cognitive function, global cognitive function, and cognitive aging. Design: A meta-analysis was conducted by using data combined from 11 large trials in 22,000 participants. Domain-based z scores (for memory, speed, and executive function and a domain-composite score for global cognitive function) were available before and after treatment (mean duration: 2.3 y) in the 4 cognitive-domain trials (1340 individuals); Mini-Mental State Examination (MMSE) type tests were available at the end of treatment (mean duration: 5 y) in the 7 global cognition trials (20,431 individuals). Results: The domain-composite and MMSE-type global cognitive function z scores both decreased with age (mean SE: 0.054 0.004 and 0.036 0.001/y, respectively). Allocation to B vitamins lowered homocysteine concentrations by 28% in the cognitive-domain trials but had no significant effects on the z score differences from baseline for individual domains or for global cognitive function (z score difference: 0.00; 95% CI: 0.05, 0.06). Likewise, allocation to B vitamins lowered homocysteine by 26% in the global cognition trials but also had no significant effect on end-treatment MMSE-type global cognitive function (z score difference: 0.01; 95% CI: 0.03, 0.02). Overall, the effect of a 25% reduction in homocysteine equated to 0.02 y (95% CI: 0.10, 0.13 y) of cognitive aging per year and excluded reductions of >1 mo per year of treatment. Conclusion: Homocysteine lowering by using B vitamins had no significant effect on individual cognitive domains or global cognitive function or on cognitive aging.
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14.
  • Shipton, Ceri, et al. (författare)
  • 78,000-year-old record of Middle and Later stone age innovation in an East African tropical forest
  • 2018
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The Middle to Later Stone Age transition in Africa has been debated as a significant shift in human technological, cultural, and cognitive evolution. However, the majority of research on this transition is currently focused on southern Africa due to a lack of long-term, stratified sites across much of the African continent. Here, we report a 78,000-year-long archeological record from Panga ya Saidi, a cave in the humid coastal forest of Kenya. Following a shift in toolkits ~67,000 years ago, novel symbolic and technological behaviors assemble in a non-unilinear manner. Against a backdrop of a persistent tropical forest-grassland ecotone, localized innovations better characterize the Late Pleistocene of this part of East Africa than alternative emphases on dramatic revolutions or migrations.
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15.
  • Wilhelmsen, Lars, 1932, et al. (författare)
  • SLCO1B1 variants and statin-induced myopathy--a genomewide study.
  • 2008
  • Ingår i: The New England journal of medicine. - 1533-4406. ; 359:8, s. 789-99
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Lowering low-density lipoprotein cholesterol with statin therapy results in substantial reductions in cardiovascular events, and larger reductions in cholesterol may produce larger benefits. In rare cases, myopathy occurs in association with statin therapy, especially when the statins are administered at higher doses and with certain other medications. METHODS: We carried out a genomewide association study using approximately 300,000 markers (and additional fine-mapping) in 85 subjects with definite or incipient myopathy and 90 controls, all of whom were taking 80 mg of simvastatin daily as part of a trial involving 12,000 participants. Replication was tested in a trial of 40 mg of simvastatin daily involving 20,000 participants. RESULTS: The genomewide scan yielded a single strong association of myopathy with the rs4363657 single-nucleotide polymorphism (SNP) located within SLCO1B1 on chromosome 12 (P=4x10(-9)). SLCO1B1 encodes the organic anion-transporting polypeptide OATP1B1, which has been shown to regulate the hepatic uptake of statins. The noncoding rs4363657 SNP was in nearly complete linkage disequilibrium with the nonsynonymous rs4149056 SNP (r(2)=0.97), which has been linked to statin metabolism. The prevalence of the rs4149056 C allele in the population was 15%. The odds ratio for myopathy was 4.5 (95% confidence interval [CI], 2.6 to 7.7) per copy of the C allele, and 16.9 (95% CI, 4.7 to 61.1) in CC as compared with TT homozygotes. More than 60% of these myopathy cases could be attributed to the C variant. The association of rs4149056 with myopathy was replicated in the trial of 40 mg of simvastatin daily, which also showed an association between rs4149056 and the cholesterol-lowering effects of simvastatin. No SNPs in any other region were clearly associated with myopathy. CONCLUSIONS: We have identified common variants in SLCO1B1 that are strongly associated with an increased risk of statin-induced myopathy. Genotyping these variants may help to achieve the benefits of statin therapy more safely and effectively. (Current Controlled Trials number, ISRCTN74348595.)
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16.
  • Wyld, L., et al. (författare)
  • Bridging the age gap in breast cancer: cluster randomized trial of two decision support interventions for older women with operable breast cancer on quality of life, survival, decision quality, and treatment choices
  • 2021
  • Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 108:5, s. 499-510
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Rates of surgery and adjuvant therapy for breast cancer vary widely between breast units. This may contribute to differences in survival. This cluster RCT evaluated the impact of decision support interventions (DESIs) for older women with breast cancer, to ascertain whether DESIs influenced quality of life, survival, decision quality, and treatment choice. METHODS: A multicentre cluster RCT compared the use of two DESIs against usual care in treatment decision-making in older women (aged at least ≥70 years) with breast cancer. Each DESI comprised an online algorithm, booklet, and brief decision aid to inform choices between surgery plus adjuvant endocrine therapy versus primary endocrine therapy, and adjuvant chemotherapy versus no chemotherapy. The primary outcome was quality of life. Secondary outcomes included decision quality measures, survival, and treatment choice. RESULTS: A total of 46 breast units were randomized (21 intervention, 25 usual care), recruiting 1339 women (670 intervention, 669 usual care). There was no significant difference in global quality of life at 6 months after the baseline assessment on intention-to-treat analysis (difference -0.20, 95 per cent confidence interval (C.I.) -2.69 to 2.29; P=0.900). In women offered a choice of primary endocrine therapy versus surgery plus endocrine therapy, knowledge about treatments was greater in the intervention arm (94 versus 74 per cent; P=0.003). Treatment choice was altered, with a primary endocrine therapy rate among women with oestrogen receptor-positive disease of 21.0 per cent in the intervention versus 15.4 per cent in usual-care sites (difference 5.5 (95 per cent C.I. 1.1 to 10.0) per cent; P=0.029). The chemotherapy rate was 10.3 per cent at intervention versus 14.8 per cent at usual-care sites (difference -4.5 (C.I. -8.0 to 0) per cent; P=0.013). Survival was similar in both arms. CONCLUSION: The use of DESIs in older women increases knowledge of breast cancer treatment options, facilitates shared decision-making, and alters treatment selection. Trial registration numbers: EudraCT 2015-004220-61 (https://eudract.ema.europa.eu/), ISRCTN46099296 (http://www.controlled-trials.com). © The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.
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17.
  • Wyld, L., et al. (författare)
  • Improving outcomes for women aged 70 years or above with early breast cancer: Research programme including a cluster RCT
  • 2022
  • Ingår i: Programme Grants for Applied Research. - 2050-4322. ; 10:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In breast cancer management, age-related practice variation is widespread, with older women having lower rates of surgery and chemotherapy than younger women, based on the premise of reduced treatment tolerance and benefit. This may contribute to inferior outcomes. There are currently no age-and fitness-stratified guidelines on which to base treatment recommendations. Aim: We aimed to optimise treatment choice and outcomes for older women (aged > 70 years) with operable breast cancer. Objectives: Our objectives were to (1) determine the age, comorbidity, frailty, disease stage and biology thresholds for endocrine therapy alone versus surgery plus adjuvant endocrine therapy, or adjuvant chemotherapy versus no chemotherapy, for older women with breast cancer; (2) optimise survival outcomes for older women by improving the quality of treatment decision-making; (3) develop and evaluate a decision support intervention to enhance shared decision-making; and (4) determine the degree and causes of treatment variation between UK breast units. Design: A prospective cohort study was used to determine age and fitness thresholds for treatment allocation. Mixed-methods research was used to determine the information needs of older women to develop a decision support intervention. A cluster-randomised trial was used to evaluate the impact of this decision support intervention on treatment choices and outcomes. Health economic analysis was used to evaluate the cost-benefit ratio of different treatment strategies according to age and fitness criteria. A mixed-methods study was used to determine the degree and causes of variation in treatment allocation. Main outcome measures: The main outcome measures were enhanced age-and fitness-specific decision support leading to improved quality-of-life outcomes in older women (aged > 70 years) with early breast cancer. Results: (1) Cohort study: The study recruited 3416 UK women aged > 70 years (median age 77 years). Follow-up was 52 months. (a) The surgery plus adjuvant endocrine therapy versus endocrine therapy alone comparison: 2854 out of 3416 (88%) women had oestrogen-receptor-positive breast cancer, 2354 of whom received surgery plus adjuvant endocrine therapy and 500 received endocrine therapy alone. Patients treated with endocrine therapy alone were older and frailer than patients treated with surgery plus adjuvant endocrine therapy. Unmatched overall survival and breast-cancer-specific survival were higher in the surgery plus adjuvant endocrine therapy group (overall survival: Hazard ratio 0.27, 95% confidence interval 0.23 to 0.33; p < 0.001; breast-cancer-specific survival: Hazard ratio 0.41, 95% confidence interval 0.29 to 0.58; p < 0.001) than in the endocrine therapy alone group. In matched analysis, surgery plus adjuvant endocrine therapy was still associated with better overall survival (hazard ratio 0.72, 95% confidence interval 0.53 to 0.98; p = 0.04) than endocrine therapy alone, but not with better breast-cancer-specific survival (hazard ratio 0.74, 95% confidence interval 0.40 to 1.37; p = 0.34) or progression-free-survival (hazard ratio 1.11, 95% confidence interval 0.55 to 2.26; p = 0.78). (b) The adjuvant chemotherapy versus no chemotherapy comparison: 2811 out of 3416 (82%) women received surgery plus adjuvant endocrine therapy, of whom 1520 (54%) had high-recurrence-risk breast cancer [grade 3, node positive, oestrogen receptor negative or human epidermal growth factor receptor-2 positive, or a high Oncotype DX® (Genomic Health, Inc., Redwood City, CA, USA) score of > 25]. In this high-risk population, there were no differences according to adjuvant chemotherapy use in overall survival or breast-cancer-specific survival after propensity matching. Adjuvant chemotherapy was associated with a lower risk of metastatic recurrence than no chemotherapy in the unmatched (adjusted hazard ratio 0.36, 95% confidence interval 0.19 to 0.68; p = 0.002) and propensity-matched patients (adjusted hazard ratio 0.43, 95% confidence interval 0.20 to 0.92; p = 0.03). Adjuva t chemotherapy improved the overall survival and breast-cancer-specific survival of patients with oestrogen-receptor-negative disease. (2) Mixed-methods research to develop a decision support intervention: An iterative process was used to develop two decision support interventions (each comprising a brief decision aid, a booklet and an online tool) specifically for older women facing treatment choices (endocrine therapy alone or surgery plus adjuvant endocrine therapy, and adjuvant chemotherapy or no chemotherapy) using several evidence sources (expert opinion, literature and patient interviews). The online tool was based on models developed using registry data from 23,842 patients and validated on an external data set of 14,526 patients. Mortality rates at 2 and 5 years differed by < 1% between predicted and observed values. (3) Cluster-randomised clinical trial of decision support tools: 46 UK breast units were randomised (intervention, n = 21; usual care, n = 25), recruiting 1339 women (intervention, n = 670; usual care, n = 669). There was no significant difference in global quality of life at 6 months post baseline (difference-0.20, 95% confidence interval-2.7 to 2.3; p = 0.90). In women offered a choice of endocrine therapy alone or surgery plus adjuvant endocrine therapy, knowledge about treatments was greater in the intervention arm than the usual care arm (94% vs. 74%; p = 0.003). Treatment choice was altered, with higher rates of endocrine therapy alone than of surgery in the intervention arm. Similarly, chemotherapy rates were lower in the intervention arm (endocrine therapy alone rate: Intervention sites 21% vs. usual-care sites 15%, difference 5.5%, 95% confidence interval 1.1% to 10.0%; p = 0.02; adjuvant chemotherapy rate: Intervention sites 10% vs. usual-care site 15%, difference 4.5%, 95% confidence interval 0.0% to 8.0%; p = 0.013). Survival was similar in both arms. (4) Health economic analysis: A probabilistic economic model was developed using registry and cohort study data. For most health and fitness strata, surgery plus adjuvant endocrine therapy had lower costs and returned more quality-adjusted life-years than endocrine therapy alone. However, for some women aged > 90 years, surgery plus adjuvant endocrine therapy was no longer cost-effective and generated fewer quality-adjusted life-years than endocrine therapy alone. The incremental benefit of surgery plus adjuvant endocrine therapy reduced with age and comorbidities. (5) Variation in practice: analysis of rates of surgery plus adjuvant endocrine therapy or endocrine therapy alone between the 56 breast units in the cohort study demonstrated significant variation in rates of endocrine therapy alone that persisted after adjustment for age, fitness and stage. Clinician preference was an important determinant of treatment choice. Conclusions: This study demonstrates that, for older women with oestrogen-receptor-positive breast cancer, there is a cohort of women with a life expectancy of < 4 years for whom surgery plus adjuvant endocrine therapy may offer little benefit and simply have a negative impact on quality of life. The Age Gap decision tool may help make this shared decision. Similarly, although adjuvant chemotherapy offers little benefit and has a negative impact on quality of life for the majority of older women with oestrogen-receptor-positive breast cancer, for women with oestrogen-receptor-negative breast cancer, adjuvant chemotherapy is beneficial. The negative impacts of adjuvant chemotherapy on quality of life, although significant, are transient. This implies that, for the majority of fitter women aged > 70 years, standard care should be offered. Limitations: As with any observational study, despite detailed propensity score matching, residual bias cannot be excluded. Follow-up was at median 52 months for the cohort analysis. Longer-term follow-up will be required to validate these findings owing to the slow time course of oestrogen-receptor-positive breast cancer. Future work: The online algorithm is now available (URL: Https://ag gap.shef.ac.uk/; accessed May 2022). There are plans to validate the tool and incorprate quality-of-life and 10-year survival outcomes.
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18.
  • Aarestrup, FM, et al. (författare)
  • Towards a European health research and innovation cloud (HRIC)
  • 2020
  • Ingår i: Genome medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 12:1, s. 18-
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Union (EU) initiative on the Digital Transformation of Health and Care (Digicare) aims to provide the conditions necessary for building a secure, flexible, and decentralized digital health infrastructure. Creating a European Health Research and Innovation Cloud (HRIC) within this environment should enable data sharing and analysis for health research across the EU, in compliance with data protection legislation while preserving the full trust of the participants. Such a HRIC should learn from and build on existing data infrastructures, integrate best practices, and focus on the concrete needs of the community in terms of technologies, governance, management, regulation, and ethics requirements. Here, we describe the vision and expected benefits of digital data sharing in health research activities and present a roadmap that fosters the opportunities while answering the challenges of implementing a HRIC. For this, we put forward five specific recommendations and action points to ensure that a European HRIC: i) is built on established standards and guidelines, providing cloud technologies through an open and decentralized infrastructure; ii) is developed and certified to the highest standards of interoperability and data security that can be trusted by all stakeholders; iii) is supported by a robust ethical and legal framework that is compliant with the EU General Data Protection Regulation (GDPR); iv) establishes a proper environment for the training of new generations of data and medical scientists; and v) stimulates research and innovation in transnational collaborations through public and private initiatives and partnerships funded by the EU through Horizon 2020 and Horizon Europe.
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19.
  • Armitage, James M, et al. (författare)
  • A model assessment of polychlorinated dibenzo-p-dioxin and dibenzofuran sources and fate in the Baltic Sea.
  • 2009
  • Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 407:12, s. 3784-3792
  • Tidskriftsartikel (refereegranskat)abstract
    • The contamination of the Baltic Sea with polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) has resulted in restrictions on the marketing and consumption of Baltic Sea fish, making this a priority environmental issue in the European Union. To date there is no consensus on the relative importance of different sources of PCDD/Fs to the Baltic Sea, and hence no consensus on how to address this issue. In this work we synthesized the available information to create a PCDD/F budget for the Baltic Sea, focusing on the two largest basins, the Bothnian Sea and the Baltic Proper. The non-steady state multimedia fate and transport model POPCYCLING-Baltic was employed, using recent data for PCDD/F concentrations in air and sediment as boundary conditions. The PCDD/F concentrations in water predicted by the model were in good agreement with recent measurements. The budget demonstrated that atmospheric deposition was the dominant source of PCDD/Fs to the basins as a whole. This conclusion was supported by a statistical comparison of the PCDD/F congener patterns in surface sediments from accumulation bottoms with the patterns in ambient air, bulk atmospheric deposition, and a range of potential industrial sources. Prospective model simulations indicated that the PCDD/F concentrations in the water column will continue to decrease in the coming years due to the slow response of the Baltic Sea system to falling PCDD/F inputs in the last decades, but that the decrease would be more pronounced if ambient air concentrations were to drop further in the future, for instance as a result of reduced emissions. The study illustrates the usefulness of using monitoring data and multimedia models in an integrated fashion to address complex organic contaminant issues.
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20.
  • Armitage, James M., 1974- (författare)
  • Modeling the global fate and transport of perfluoroalkylated substances (PFAS)
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Perfluoroalkylated substances (PFAS) are persistent contaminants that are widely distributed in the global environment. Despite the fact that these chemicals have been manufactured and used for over 50 years, there has been little scientific and regulatory interest until very recently. An important research priority over the past decade has been to gain a better understanding of the mechanisms and pathways explaining the presence of these compounds in remote regions. One explanation is related to the use and release of volatile precursor compounds which undergo atmospheric transport and are also susceptible to degradation to PFAS through gas phase reactions with radical species. The main purpose of this doctoral thesis was to investigate an alternative explanation, namely the long-range transport (LRT) of PFAS themselves, which have been released into the environment in substantial quantities during manufacturing and product use. Papers I – III explore the LRT potential of perfluorocarboxylic acids and perfluorocarboxylates and demonstrate that both oceanic and atmospheric transport are efficient pathways of dispersion from source to remote regions of the Northern Hemisphere. Oceanic transport of perfluorooctane sulfonate (PFOS) was shown to be an important process in Paper IV as well. The role of precursor transport and degradation to PFOS was also examined in this paper. The most interesting aspect of the fate and transport of PFOS precursors is the rapid response in ambient concentrations exhibited by these compounds in the model simulations following production phase-out. Since precursor compounds are known to degrade to PFOS in vivo, the modeling results demonstrate that this exposure pathway is a plausible explanation for the declining trends in PFOS concentrations reported for marine mammals in some remote environments.
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21.
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22.
  • Arnot, Jon A., et al. (författare)
  • Toward a Consistent Evaluative Framework for POP Risk Characterization
  • 2011
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 45:1, s. 97-103
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of Annex E in the Stockholm Convention (SC) on Persistent Organic Pollutants (POPs) is to assess whether a chemical is likely, as a result of its long-range environmental transport, to lead to significant adverse human health or environmental effects, such that global action is warranted. To date, risk profiles for nominated POPs have not consistently selected assessment endpoints or completed mandated risk characterizations. An assessment endpoint hierarchy is proposed to facilitate risk characterization for the implementation of the SC. The framework is illustrated for a nominated POP, hexabromocyclododecane (HBCD), using three risk estimation methods. Based on current monitoring and toxicity data, the screening-level results indicate that humans and ecological receptors in remote regions such as the Arctic are unlikely to experience significant adverse effects (i.e., low risk) due to long-range environmental transport of HBCD. The results for birds are more uncertain than the results for fish and mammals due to the paucity of avian toxicity data. Risk characterization results for HBCD and for some listed POPs are compared to illustrate how the proposed methods can further assist decision-making and chemical management.
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23.
  • Berglundh, Tord, 1954, et al. (författare)
  • Peri-implant diseases and conditions: Consensus report of workgroup 4 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions
  • 2018
  • Ingår i: J Clin Periodontol. - : Wiley. - 0303-6979 .- 1600-051X. ; 45
  • Tidskriftsartikel (refereegranskat)abstract
    • A classification for peri-implant diseases and conditions was presented. Focused questions on the characteristics of peri-implant health, peri-implant mucositis, peri-implantitis, and soft- and hard-tissue deficiencies were addressed. Peri-implant health is characterized by the absence of erythema, bleeding on probing, swelling, and suppuration. It is not possible to define a range of probing depths compatible with health; Peri-implant health can exist around implants with reduced bone support. The main clinical characteristic of peri-implant mucositis is bleeding on gentle probing. Erythema, swelling, and/or suppuration may also be present. An increase in probing depth is often observed in the presence of peri-implant mucositis due to swelling or decrease in probing resistance. There is strong evidence from animal and human experimental studies that plaque is the etiological factor for peri-implant mucositis. Peri-implantitis is a plaque-associated pathological condition occurring in tissues around dental implants, characterized by inflammation in the peri-implant mucosa and subsequent progressive loss of supporting bone. Peri-implantitis sites exhibit clinical signs of inflammation, bleeding on probing, and/or suppuration, increased probing depths and/or recession of the mucosal margin in addition to radiographic bone loss. The evidence is equivocal regarding the effect of keratinized mucosa on the long-term health of the peri-implant tissue. It appears, however, that keratinized mucosa may have advantages regarding patient comfort and ease of plaque removal. Case definitions in day-to-day clinical practice and in epidemiological or disease-surveillance studies for peri-implant health, peri-implant mucositis, and peri-implantitis were introduced. The proposed case definitions should be viewed within the context that there is no generic implant and that there are numerous implant designs with different surface characteristics, surgical and loading protocols. It is recommended that the clinician obtain baseline radiographic and probing measurements following the completion of the implant-supported prosthesis.
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24.
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26.
  • Droge, Steven T. J., et al. (författare)
  • Screening the baseline fish bioconcentration factor of various types of surfactants using phospholipid binding data
  • 2021
  • Ingår i: Environmental Science. - : Royal Society of Chemistry (RSC). - 2050-7887 .- 2050-7895. ; 23:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Fish bioconcentration factors (BCFs) are commonly used in chemical hazard and risk assessment. For neutral organic chemicals BCFs are positively correlated with the octanol-water partition ratio (K-OW), but K-OW is not a reliable parameter for surfactants. Membrane lipid-water distribution ratios (D-MLW) can be accurately measured for all kinds of surfactants, using phospholipid-based sorbents. This study first demonstrates that D-MLW values for ionic surfactants are more than 100 000 times higher than the partition ratio to fish-oil, representing neutral storage lipid. A non-ionic alcohol ethoxylate surfactant showed almost equal affinity for both lipid types. Accordingly, a baseline screening BCF value for surfactants (BCFbaseline) can be approximated for ionic surfactants by multiplying D-MLW by the phospholipid fraction in tissue, and for non-ionic surfactants by multiplying D-MLW by the total lipid fraction. We measured D-MLW values for surfactant structures, including linear and branched alkylbenzenesulfonates, an alkylsulfoacetate and an alkylethersulfate, bis(2-ethylhexyl)-surfactants (e.g., docusate), zwitterionic alkylbetaines and alkylamine-oxides, and a polyprotic diamine. Together with sixty previously published D-MLW values for surfactants, structure-activity relationships were derived to elucidate the influence of surfactant specific molecular features on D-MLW. For 23 surfactant types, we established the alkyl chain length at which BCFbaseline would exceed the EU REACH bioaccumulation (B) threshold of 2000 L kg(-1), and would therefore require higher tier assessments to further refine the BCF estimate. Finally, the derived BCFbaseline are compared with measured literature in vivo BCF data where available, suggesting that refinements, most notably reliable estimates of biotransformation rates, are needed for most surfactant types.
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27.
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28.
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29.
  • Fletcher, John S., et al. (författare)
  • Evaluating the challenges associated with time-of-fight secondary ion mass spectrometry for metabolomics using pure and mixed metabolites
  • 2013
  • Ingår i: Metabolomics. - : Springer Science and Business Media LLC. - 1573-3882 .- 1573-3890. ; 9:3, s. 535-544
  • Tidskriftsartikel (refereegranskat)abstract
    • Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is potentially well placed to contribute to metabolomic analysis while bringing the added benefit of high resolution, label free imaging. The focused ion beams used to desorb species from the sample can be focused below 1 μm allowing chemical imaging on a sub-cellular scale. In this study we test the capability of ToF-SIMS to generate mass spectrometry and MSMS spectra from a set of standard metabolites that can be compared with open access metabolite databases containing ESI-CID MSMS spectra. The influence of the chemical environment, the matrix effect, on the observed mass spectra is assessed using a mixed metabolite sample and the data discussed in terms of compound identification and quantification. Radical ions and small fragment ions seem to be less sensitive to ion suppression or enhancement and may provide a route to quantification. Understanding such parameters will be key for the successful application of the technique for in situ metabolomics with ToF-SIMS.
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30.
  • Jones, Owen R., et al. (författare)
  • Senescence rates are determined by ranking on the fast-slow life-history continuum
  • 2008
  • Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 11:7, s. 664-673
  • Tidskriftsartikel (refereegranskat)abstract
    • Comparative analyses of survival senescence by using life tables have identified generalizations including the observation that mammals senesce faster than similar-sized birds. These generalizations have been challenged because of limitations of life-table approaches and the growing appreciation that senescence is more than an increasing probability of death. Without using life tables, we examine senescence rates in annual individual fitness using 20 individual-based data sets of terrestrial vertebrates with contrasting life histories and body size. We find that senescence is widespread in the wild and equally likely to occur in survival and reproduction. Additionally, mammals senesce faster than birds because they have a faster life history for a given body size. By allowing us to disentangle the effects of two major fitness components our methods allow an assessment of the robustness of the prevalent life-table approach. Focusing on one aspect of life history - survival or recruitment - can provide reliable information on overall senescence.
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31.
  • Kierkegaard, Amelie, et al. (författare)
  • Bioconcentration of Several Series of Cationic Surfactants in Rainbow Trout
  • 2021
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 55:13, s. 8888-8897
  • Tidskriftsartikel (refereegranskat)abstract
    • Cationic surfactants have a strong affinity to sorb to phospholipid membranes and thus possess an inherent potential to bioaccumulate, but there are few measurements of bioconcentration in fish. We measured the bioconcentration of 10 alkylamines plus two quaternary ammonium compounds in juvenile rainbow trout at pH 7.6, and repeated the measurements at pH 6.2 for 6 of these surfactants. The BCF of the amines with chain lengths <= C-14 was positively correlated with chain length, increasing similar to 0.5 log units per carbon. Their BCF was also pH dependent and approximately proportional to the neutral fraction of the amine in the water. The BCFs of the quaternary ammonium compounds showed no pH dependence and were >2 orders of magnitude less than for amines of the same chain length at pH 7.6. This indicates that systemic uptake of permanently charged cationic surfactants is limited. The behavior of the quaternary ammonium compounds and the two C-16 amines studied was consistent with previous observations that these surfactants accumulate primarily to the gills and external surfaces of the fish. At pH 7.6 the BCF exceeded 2000 L kg(-1) for 4 amines with chains >= C-13, showing that bioconcentration can be considerable for some longer chained cationic surfactants.
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32.
  • Kierkegaard, Amelie, et al. (författare)
  • Tissue Distribution of Several Series of Cationic Surfactants in Rainbow Trout (Oncorhynchus mykiss) Following Exposure via Water
  • 2020
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 54:7, s. 4190-4199
  • Tidskriftsartikel (refereegranskat)abstract
    • Bioaccumulation assessment is important for cationic surfactants in light of their use in a wide variety of consumer products and industrial processes. Because they sorb strongly to natural surfaces and to cell membranes, their bioaccumulation behavior is expected to differ from other classes of chemicals. Divided over two mixtures, we exposed rainbow trout to water containing 10 alkyl amines and 2 quaternary alkylammonium surfactants for 7 days, analyzed different fish tissues for surfactant residues, and calculated the tissues' contribution to fish body burden. Mucus, skin, gills, liver, and muscle each contributed at least 10% of body burden for the majority of the test chemicals. This indicates that both sorption to external surfaces and systemic uptake contribute to bioaccumulation. In contrast to the analogue alkylamine bases, the permanently charged quaternary ammonium compounds accumulated mostly in the gills and were nearly absent in internal tissues, indicating that systemic uptake of the charged form of cationic surfactants is very slow. Muscle-blood distribution coefficients were close to 1 for all alkyl amines, whereas liver-blood distribution coefficients ranged from 13 to 90, suggesting that the dominant considerations for sorption in liver are different from those in blood and muscle. The significant fraction of body burden on external surfaces can have consequences for bioaccumulation assessment.
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33.
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34.
  • Li, Y, et al. (författare)
  • Alluvial fan aggradation/incision history of the eastern Tibetan plateau margin and implications for debris flow/debris-charged flood hazard
  • 2018
  • Ingår i: Geomorphology. - : Elsevier BV. - 0169-555X .- 1872-695X. ; 318, s. 203-216
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper reconstructs the Quaternary aggradation and incision history of a debris flow/debris-charged flood-affected valley in order to detect the impact of climate on alluvial fan dynamics. We used optically stimulated luminescence (OSL) dating of quartz to determine the ages of alluvial fan terraces. Comparison between the aggradation and incision history and regional climatic records suggests that aggradation occurred in cold and/or dry climates, whereas incision is a feature of warm and wet climates. Cold climates lead to enhanced frost shattering, and dry climates cause deteriorated vegetation. Both effects caused surplus sediment which was transported by infrequent flood discharges to form alluvial fan/terrace deposits. Incision during wet and warm climates is due to increased vegetation cover and an increase in the frequency of flood discharges. This relationship between climate and valley evolution is applied to assess future changes in the present active channel by considering recent climatic records. The results show that the valley channel is expected to experience net incision if the average temperature continues increasing while precipitation maintains at a constant level.
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35.
  • McLachlan, Michael S., et al. (författare)
  • A framework for understanding the bioconcentration of surfactants in fish
  • 2023
  • Ingår i: Environmental Science. - 2050-7887 .- 2050-7895. ; 25:7, s. 1238-1251
  • Tidskriftsartikel (refereegranskat)abstract
    • Surfactants are a class of chemicals released in large quantities to water, and therefore bioconcentration in fish is an important component of their safety assessment. Their structural diversity, which encompasses nonionic, anionic, cationic and zwitterionic molecules with a broad range of lipophilicity, makes their evaluation challenging. A strong influence of environmental pH adds a further layer of complexity to their bioconcentration assessment. Here we present a framework that penetrates this complexity. Using simple equations derived from current understanding of the relevant underlying processes, we plot the key bioconcentration parameters (uptake rate constant, elimination rate constant and bioconcentration factor) as a function of its membrane lipid/water distribution ratio and the neutral fraction of the chemical in water at pH 8.1 and at pH 6.1. On this chemical space plot, we indicate boundaries at which four resistance terms (perfusion with water, transcellular, paracellular, and perfusion with blood) limit transport of surfactants across the gills. We then show that the bioconcentration parameters predicted by this framework align well with in vivo measurements of anionic, cationic and nonionic surfactants in fish. In doing so, we demonstrate how the framework can be used to explore expected differences in bioconcentration behavior within a given sub-class of surfactants, to assess how pH will influence bioconcentration, to identify the underlying processes governing bioconcentration of a particular surfactant, and to discover knowledge gaps that require further research. This framework for amphiphilic chemicals may function as a template for improved understanding of the accumulation potential of other ionizable chemicals of environmental concern, such as pharmaceuticals or dyes.
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36.
  • Nyberg, Roger G. (författare)
  • Automating condition monitoring of vegetation on railway trackbeds and embankments
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Vegetation growing on railway trackbeds and embankments present potential problems. The presence of vegetation threatens the safety of personnel inspecting the railway infrastructure. In addition vegetation growth clogs the ballast and results in inadequate track drainage which in turn could lead to the collapse of the railway embankment.Assessing vegetation within the realm of railway maintenance is mainly carried out manually by making visual inspections along the track. This is done either on-site or by watching videos recorded by maintenance vehicles mainly operated by the national railway administrative body.A need for the automated detection and characterisation of vegetation on railways (a subset of vegetation control/management) has been identified in collaboration with local railway maintenance subcontractors and Trafikverket, the Swedish Transport Administration (STA). The latter is responsible for long-term planning of the transport system for all types of traffic, as well as for the building, operation and maintenance of public roads and railways.The purpose of this research project was to investigate how vegetation can be measured and quantified by human raters and how machine vision can automate the same process.Data were acquired at railway trackbeds and embankments during field measurement experiments. All field data (such as images) in this thesis work was acquired on operational, lightly trafficked railway tracks, mostly trafficked by goods trains. Data were also generated by letting (human) raters conduct visual estimates of plant cover and/or count the number of plants, either on-site or in-house by making visual estimates of the images acquired from the field experiments. Later, the degree of reliability of(human) raters’ visual estimates were investigated and compared against machine vision algorithms.The overall results of the investigations involving human raters showed inconsistency in their estimates, and are therefore unreliable. As a result of the exploration of machine vision, computational methods and algorithms enabling automatic detection and characterisation of vegetation along railways were developed. The results achieved in the current work have shown that the use of image data for detecting vegetation is indeed possible and that such results could form the base for decisions regarding vegetation control. The performance of the machine vision algorithm which quantifies the vegetation cover was able to process 98% of the im-age data. Investigations of classifying plants from images were conducted in in order to recognise the specie. The classification rate accuracy was 95%.Objective measurements such as the ones proposed in thesis offers easy access to the measurements to all the involved parties and makes the subcontracting process easier i.e., both the subcontractors and the national railway administration are given the same reference framework concerning vegetation before signing a contract, which can then be crosschecked post maintenance.A very important issue which comes with an increasing ability to recognise species is the maintenance of biological diversity. Biological diversity along the trackbeds and embankments can be mapped, and maintained, through better and robust monitoring procedures. Continuously monitoring the state of vegetation along railways is highly recommended in order to identify a need for maintenance actions, and in addition to keep track of biodiversity. The computational methods or algorithms developed form the foundation of an automatic inspection system capable of objectively supporting manual inspections, or replacing manual inspections.
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37.
  • Ribbenstedt, Anton, 1986-, et al. (författare)
  • In Vivo Bioconcentration of 10 Anionic Surfactants in Rainbow Trout Explained by In Vitro Data on Partitioning and S9 Clearance
  • 2022
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:10, s. 6305-6314
  • Tidskriftsartikel (refereegranskat)abstract
    • Bioconcentration factors (BCFs) in rainbow trout were measured for 10 anionic surfactants with a range of alkyl chain lengths and different polar head groups. The BCFs ranged from 0.04 L kg–1 ww (for C10SO3) to 1370 L kg–1 ww (C16SO3). There was a strong correlation between the log BCF and log membrane lipid–water distribution ratio (DMLW, r2 = 0.96), and biotransformation was identified as the dominant elimination mechanism. The strong positive influence of DMLW on BCF was attributed to two phenomena: (i) increased partitioning from water into the epithelial membrane of the gill, leading to more rapid diffusion across this barrier and more rapid uptake, and (ii) increased sequestration of the surfactant body burden into membranes and other body tissues, resulting in lower freely dissolved concentrations available for biotransformation. Estimated whole-body in vivo biotransformation rate constants kB-BCF are within a factor three of rate constants estimated from S9 in vitro assays for six of the eight test chemicals for which kB-BCF could be determined. A model-based assessment indicated that the hepatic clearance rate of freely dissolved chemicals was similar for the studied surfactants. The dataset will be useful for evaluation of in silico and in vitro methods to assess bioaccumulation. 
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38.
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41.
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42.
  • Thompson, Luke R., et al. (författare)
  • A communal catalogue reveals Earth's multiscale microbial diversity
  • 2017
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 551:7681, s. 457-463
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.
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43.
  • Timmis, Kenneth, et al. (författare)
  • A concept for international societally relevant microbiology education and microbiology knowledge promulgation in society
  • 2024
  • Ingår i: Microbial Biotechnology. - 1751-7907. ; 17:5
  • Tidskriftsartikel (refereegranskat)abstract
    • EXECUTIVE SUMMARY: Microbes are all pervasive in their distribution and influence on the functioning and well-being of humans, life in general and the planet. Microbially-based technologies contribute hugely to the supply of important goods and services we depend upon, such as the provision of food, medicines and clean water. They also offer mechanisms and strategies to mitigate and solve a wide range of problems and crises facing humanity at all levels, including those encapsulated in the sustainable development goals (SDGs) formulated by the United Nations. For example, microbial technologies can contribute in multiple ways to decarbonisation and hence confronting global warming, provide sanitation and clean water to the billions of people lacking them, improve soil fertility and hence food production and develop vaccines and other medicines to reduce and in some cases eliminate deadly infections. They are the foundation of biotechnology, an increasingly important and growing business sector and source of employment, and the centre of the bioeconomy, Green Deal, etc. But, because microbes are largely invisible, they are not familiar to most people, so opportunities they offer to effectively prevent and solve problems are often missed by decision-makers, with the negative consequences this entrains. To correct this lack of vital knowledge, the International Microbiology Literacy Initiative-the IMiLI-is recruiting from the global microbiology community and making freely available, teaching resources for a curriculum in societally relevant microbiology that can be used at all levels of learning. Its goal is the development of a society that is literate in relevant microbiology and, as a consequence, able to take full advantage of the potential of microbes and minimise the consequences of their negative activities. In addition to teaching about microbes, almost every lesson discusses the influence they have on sustainability and the SDGs and their ability to solve pressing problems of societal inequalities. The curriculum thus teaches about sustainability, societal needs and global citizenship. The lessons also reveal the impacts microbes and their activities have on our daily lives at the personal, family, community, national and global levels and their relevance for decisions at all levels. And, because effective, evidence-based decisions require not only relevant information but also critical and systems thinking, the resources also teach about these key generic aspects of deliberation. The IMiLI teaching resources are learner-centric, not academic microbiology-centric and deal with the microbiology of everyday issues. These span topics as diverse as owning and caring for a companion animal, the vast range of everyday foods that are produced via microbial processes, impressive geological formations created by microbes, childhood illnesses and how they are managed and how to reduce waste and pollution. They also leverage the exceptional excitement of exploration and discovery that typifies much progress in microbiology to capture the interest, inspire and motivate educators and learners alike. The IMiLI is establishing Regional Centres to translate the teaching resources into regional languages and adapt them to regional cultures, and to promote their use and assist educators employing them. Two of these are now operational. The Regional Centres constitute the interface between resource creators and educators-learners. As such, they will collect and analyse feedback from the end-users and transmit this to the resource creators so that teaching materials can be improved and refined, and new resources added in response to demand: educators and learners will thereby be directly involved in evolution of the teaching resources. The interactions between educators-learners and resource creators mediated by the Regional Centres will establish dynamic and synergistic relationships-a global societally relevant microbiology education ecosystem-in which creators also become learners, teaching resources are optimised and all players/stakeholders are empowered and their motivation increased. The IMiLI concept thus embraces the principle of teaching societally relevant microbiology embedded in the wider context of societal, biosphere and planetary needs, inequalities, the range of crises that confront us and the need for improved decisioning, which should ultimately lead to better citizenship and a humanity that is more sustainable and resilient.ABSTRACT: The biosphere of planet Earth is a microbial world: a vast reactor of countless microbially driven chemical transformations and energy transfers that push and pull many planetary geochemical processes, including the cycling of the elements of life, mitigate or amplify climate change (e.g., Nature Reviews Microbiology, 2019, 17, 569) and impact the well-being and activities of all organisms, including humans. Microbes are both our ancestors and creators of the planetary chemistry that allowed us to evolve (e.g., Life's engines: How microbes made earth habitable, 2023). To understand how the biosphere functions, how humans can influence its development and live more sustainably with the other organisms sharing it, we need to understand the microbes. In a recent editorial (Environmental Microbiology, 2019, 21, 1513), we advocated for improved microbiology literacy in society. Our concept of microbiology literacy is not based on knowledge of the academic subject of microbiology, with its multitude of component topics, plus the growing number of additional topics from other disciplines that become vitally important elements of current microbiology. Rather it is focused on microbial activities that impact us-individuals/communities/nations/the human world-and the biosphere and that are key to reaching informed decisions on a multitude of issues that regularly confront us, ranging from personal issues to crises of global importance. In other words, it is knowledge and understanding essential for adulthood and the transition to it, knowledge and understanding that must be acquired early in life in school. The 2019 Editorial marked the launch of the International Microbiology Literacy Initiative, the IMiLI. HERE, WE PRESENT: our concept of how microbiology literacy may be achieved and the rationale underpinning it; the type of teaching resources being created to realise the concept and the framing of microbial activities treated in these resources in the context of sustainability, societal needs and responsibilities and decision-making; and the key role of Regional Centres that will translate the teaching resources into local languages, adapt them according to local cultural needs, interface with regional educators and develop and serve as hubs of microbiology literacy education networks. The topics featuring in teaching resources are learner-centric and have been selected for their inherent relevance, interest and ability to excite and engage. Importantly, the resources coherently integrate and emphasise the overarching issues of sustainability, stewardship and critical thinking and the pervasive interdependencies of processes. More broadly, the concept emphasises how the multifarious applications of microbial activities can be leveraged to promote human/animal, plant, environmental and planetary health, improve social equity, alleviate humanitarian deficits and causes of conflicts among peoples and increase understanding between peoples (Microbial Biotechnology, 2023, 16(6), 1091-1111). Importantly, although the primary target of the freely available (CC BY-NC 4.0) IMiLI teaching resources is schoolchildren and their educators, they and the teaching philosophy are intended for all ages, abilities and cultural spectra of learners worldwide: in university education, lifelong learning, curiosity-driven, web-based knowledge acquisition and public outreach. The IMiLI teaching resources aim to promote development of a global microbiology education ecosystem that democratises microbiology knowledge.
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