| 1. |
- Augustsson, Anna, et al.
(author)
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High metal reactivity and environmental risks at a site contaminated by glass waste
- 2016
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In: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 154, s. 434-443
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Journal article (peer-reviewed)abstract
- This study addresses the reactivity and risks of metals (Ba, Cd, Co, Cr, Cu, Ni, Pb, Zn, As and Sb) at a Swedish site with large glass waste deposits. Old glassworks sites typically have high total metal concentrations, but as the metals are mainly bound within the glass waste and considered relatively inert, environmental investigations at these kinds of sites are limited. In this study, soil and landfill samples were subjected to a sequential chemical extraction procedure. Data from batch leaching tests and groundwater upstream and downstream of the waste deposits were also interpreted. The sequential extraction revealed that metals in <2 mm soil/waste samples were largely associated with geochemically active fractions, indicating that metals are released from pristine glass and subsequently largely retained in the surrounding soil and/or on secondary mineral coatings on fine glass particles. From the approximately 12,000 m(3) of coarse glass waste at the site, almost 4000 kg of Pb is estimated to have been lost through corrosion, which, however, corresponds to only a small portion of the total amount of Pb in the waste. Metal sorption within the waste deposits or in underlying soil layers is supported by fairly low metal concentrations in groundwater. However, elevated concentrations in downstream groundwater and in leachates of batch leaching tests were observed for several metals, indicating on-going leaching. Taken together, the high metal concentrations in geochemically active forms and the high amounts of as yet uncorroded metal-rich glass, indicate considerable risks to human health and the environment.
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| 2. |
- Brauner, Hanna, et al.
(author)
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Distinct phenotype and function of NK cells in the pancreas of nonobese diabetic mice.
- 2010
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In: Journal of Immunology. - : American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 184:5, s. 2272-2280
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Journal article (peer-reviewed)abstract
- Little is known about target organ-infiltrating NK cells in type 1 diabetes and other autoimmune diseases. In this study, we identified NK cells with a unique phenotype in the pancreas of NOD mice. Pancreatic NK cells, localized to the endocrine and exocrine parts, were present before T cells during disease development and did not require T cells for their infiltration. Furthermore, NK cells, or NK cell precursors, from the spleen could traffic to the pancreas, where they displayed the pancreatic phenotype. Pancreatic NK cells from other mouse strains shared phenotypic characteristics with pancreatic NK cells from NOD mice, but displayed less surface killer cell lectin-like receptor G1, a marker for mature NK cells that have undergone proliferation, and also did not proliferate to the same extent. A subset of NOD mouse pancreatic NK cells produced IFN-gamma spontaneously, suggesting ongoing effector responses. However, most NOD mouse pancreatic NK cells were hyporesponsive compared with spleen NK cells, as reflected by diminished cytokine secretion and a lower capacity to degranulate. Interestingly, such hyporesponsiveness was not seen in pancreatic NK cells from the nonautoimmune strain C57BL/6, suggesting that this feature is not a general property of pancreatic NK cells. Based on our data, we propose that NK cells are sentinel cells in a normal pancreas. We further speculate that during inflammation, pancreatic NK cells initially mediate proinflammatory effector functions, potentially contributing to organ-specific autoimmunity, but later become hyporesponsive because of exhaustion or regulation.
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| 3. |
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| 4. |
- Henneberger, P K, et al.
(author)
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The occupational contribution to severe exacerbation of asthma.
- 2010
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In: The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 36:4, s. 743-50
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Journal article (peer-reviewed)abstract
- The goal of this study was to identify occupational risk factors for severe exacerbation of asthma and estimate the extent to which occupation contributes to these events. The 966 participants were working adults with current asthma who participated in the follow-up phase of the European Community Respiratory Health Survey. Severe exacerbation of asthma was defined as self-reported unplanned care for asthma in the past 12 months. Occupations held in the same period were combined with a general population job-exposure matrix to assess occupational exposures. 74 participants reported having had at least one severe exacerbation event, for a 1-yr cumulative incidence of 7.7%. From regression models that controlled for confounders, the relative risk (RR) was statistically significant for low (RR 1.7, 95% CI 1.1-2.6) and high (RR 3.6, 95% CI 2.2-5.8) biological dust exposure, high mineral dust exposure (RR 1.8, 95% CI 1.02-3.2), and high gas and fumes exposure (RR 2.5, 95% CI 1.2-5.5). The summary category of high dust, gas, or fumes exposure had RR 3.1 (95% CI 1.9-5.1). Based on this RR, the population attributable risk was 14.7% among workers with current asthma. These results suggest occupation contributes to approximately one in seven cases of severe exacerbation of asthma in a working population, and various agents play a role.
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| 5. |
- Herold, Nikolas, et al.
(author)
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Targeting SAMHD1 with the Vpx protein to improve cytarabine therapy for hematological malignancies
- 2017
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 23:2, s. 256-263
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Journal article (peer-reviewed)abstract
- The cytostatic deoxycytidine analog cytarabine (ara-C) is the most active agent available against acute myelogenous leukemia (AML). Together with anthracyclines, ara-C forms the backbone of AML treatment for children and adults'. In AML, both the cytotoxicity of ara-C in vitro and the clinical response to ara-C therapy are correlated with the ability of AML blasts to accumulate the active metabolite ara-C triphosphate (ara-CTP)(2-5), which causes DNA damage through perturbation of DNA synthesis(6). Differences in expression levels of known transporters or metabolic enzymes relevant to ara-C only partially account for patient-specific differential ara-CTP accumulation in AML blasts and response to ara-C treatment(7-9). Here we demonstrate that the deoxynucleoside triphosphate (dNTP) triphosphohydrolase SAM domain and HD domain 1 (SAMHD1) promotes the detoxification of intracellular ara-CTP pools. Recombinant SAMHD1 exhibited ara-CTPase activity in vitro, and cells in which SAMHD1 expression was transiently reduced by treatment with the simian immunodeficiency virus (SIV) protein Vpx were dramatically more sensitive to ara-C-induced cytotoxicity. CRISPR-Cas9-mediated disruption of the gene encoding SAMHD1 sensitized cells to ara-C, and this sensitivity could be abrogated by ectopic expression of wild-type (WT), but not dNTPase-deficient, SAMHD1. Mouse models of AML lacking SAMHD1 were hypersensitive to ara-C, and treatment ex vivo with Vpx sensitized primary patient derived AML blasts to ara-C. Finally, we identified SAMHD1 as a risk factor in cohorts of both pediatric and adult patients with de novo AML who received ara-C treatment. Thus, SAMHD1 expression levels dictate patient sensitivity to ara-C, providing proof-of-concept that the targeting of SAMHD1 by Vpx could be an attractive therapeutic strategy for potentiating ara-C efficacy in hematological malignancies.
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| 6. |
- Höglund, Henrik, et al.
(author)
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Prodromal symptoms and health care consumption prior to out-of-hospital cardiac arrest in patients without previously known ischaemic heart disease
- 2014
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In: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 85:7, s. 864-868
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Journal article (peer-reviewed)abstract
- Aims: To describe prodromal symptoms and health care consumption prior to an out-of-hospital cardiac arrest (OHCA) in patients without previously known ischaemic heart disease (IHD). Background: The most common lethal event of cardiovascular disease is sudden cardiac death, and the majority occur outside hospital. Little is known about prodromal symptoms and health care consumption associated with OHCAs. Design: Case-crossover study. Methods: Medical records of 403 OHCA cases without previously known IHD, age 25-74 years in the MONICA myocardial registry in Norrbotten County 2000-2008, were reviewed. Presenting symptoms and emergency visits at public primary care facilities and internal medicine clinics in Norrbotten County were analyzed from the week prior to the OHCA and from the same week one year previously, which served as a control week. Unlike most studies we included unwitnessed arrests and those where no cardiopulmonary resuscitation (CPR) was attempted. Results: Emergency visits were more common during the week prior to the OHCA than during the control week, both for visits to primary care (29 vs. 6, p < 0.001) and to internal medicine clinics (16 vs. 0, p < 0.001). Symptoms were more prevalent during the week prior to the OHCA (36.7 vs. 6.7%, p < 0.001). The most prevalent symptoms were chest pain (14.6 vs. 0%, p < 0.001), gastrointestinal symptoms (7.7 vs. 1.2%, p < 0.001) and dyspnoea/peripheral oedema (6.9 vs. 0.2%, p < 0.001). Conclusions: Patients who suffer an OHCA seek health care and present prodromal symptoms significantly more often the week prior to the event than the same week one year earlier.
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| 7. |
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| 8. |
- Kisiel, Marta, 1984-, et al.
(author)
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The risk of respiratory tract infections and antibiotic use in a general population and among people with asthma
- 2021
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In: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 7:4
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Journal article (peer-reviewed)abstract
- Aim The aim of this study was to investigate occupational, environmental, early life and other risk factors associated with respiratory infections and antibiotics use in a general population and among asthmatic individuals. Method This study included 15842 participants of the Respiratory Health in Northern Europe (RHINE) study aged 25–54 years from five Nordic countries, who answered a questionnaire covering respiratory outcomes, exposures, demographic characteristics and numbers of infections and courses of antibiotics in the last 12 months. Multiple logistic regression with and without adjustment for age, sex, smoking status, body mass index and centre were used to study the risk of infection and antibiotics in relation to asthma, and also the association between infection and antibiotics and occupations. Results In the whole population, 11.6% reported having three or more respiratory infections, and 14.7% had used antibiotics because of respiratory tract infections within the last year. Asthmatic participants reported tripled odds for such infections (adjusted OR 2.98, 95% CI 2.53–3.52) and antibiotics use (adjusted OR 3.67, 95% CI 3.18–4.24) as compared to non-asthmatic participants. Both in the general and the asthmatic population, female sex, obesity and exposure to building dampness were associated with respiratory infections. Female sex and current smoking and living in Tartu were associated with antibiotic use. The use of antibiotics was doubled in people hospitalised for severe respiratory infection in childhood. Conclusion In this study we identified several factors associated with increased respiratory infections and use of antibiotics in a general population and among asthmatic individuals. The frequency of respiratory infections and subsequent antibiotic treatment were increased among those with asthma. © The authors 2021.
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| 9. |
- Kogevinas, Manolis, et al.
(author)
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Exposure to substances in the workplace and new-onset asthma : an international prospective population-based study (ECRHS-II)
- 2007
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 370:9584, s. 336-341
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Journal article (peer-reviewed)abstract
- Background The role of exposure to substances in the workplace in new-onset asthma is not well characterised in population-based studies. We therefore aimed to estimate the relative and attributable risks of new-onset asthma in relation to occupations, work-related exposures, and inhalation accidents. Methods We studied prospectively 6837 participants from 13 countries who previously took part in the European Community Respiratory Health Survey (1990-95) and did not report respiratory symptoms or a history of asthma at the time of the first study. Asthma was assessed by methacholine challenge test and by questionnaire data on asthma symptoms. Exposures were defined by high-risk occupations, an asthma-specific job exposure matrix with additional expert judgment, and through self-report of acute inhalation events. Relative risks for new onset asthma were calculated with log-binomial models adjusted for age, sex, smoking, and study Centre. Findings A significant excess asthma risk was seen after exposure to substances known to cause occupational asthma (Relative risk=1.6, 95% CI 1.1-2.3, p=0.017). Risks were highest for asthma defined by bronchial hyper-reactivity in addition to symptoms (2.4,1.3-4.6, p=0.008). Of common occupations, a significant excess risk of asthma was seen for nursing (2.2,1.3-4.0, p=0.007). Asthma risk was also increased in participants who reported an acute symptomatic inhalation event such as fire, mixing cleaning products, or chemical spills (RR=3.3, 95% CI 1.0-11.1, p=0.051). The population-attributable risk for adult asthma due to occupational exposures ranged from 10% to 25%, equivalent to an incidence of new-onset occupational asthma of 250-300 cases per million people per year. Interpretation Occupational exposures account for a substantial proportion of adult asthma incidence. The increased risk of asthma after inhalation accidents suggests that workers who have such accidents should be monitored closely.
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| 10. |
- Medvedeva, Anna, 1981-, et al.
(author)
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Stress relaxation resistance for improved fatigue performance of shot peened tool components
- 2008
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In: Proceedings of the 10<sup>th</sup> International Conference on Shot Peening, 15-18 September, Tokyo, Japan, 2008. - Tokyo : Academy Common Meiji University. ; , s. 286-295
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Conference paper (peer-reviewed)abstract
- Shot peening is an extensively used process in the production of mechanical components to improve their fatigue strength at ambient temperature. At higher working temperatures of some mechanical components, e.g. from 300 to 600°C, the influence and behaviour of the compressive residual stresses are more uncertain, since they tend to relieve at higher temperatures. The response to shot peening induced residual stresses of low alloyed and hot work tool steels was evaluated with respect to stress relief heat treatments and isothermal high temperature fatigue testing. Not only the residual stresses, but also the material substructure and its dislocation characteristics are of importance. Dislocation structures were determined using X-ray diffraction to explain the preference of the different steel grades. Also, results obtained from bending fatigue testing at ambient temperature of tool components after shot peening and stress relief heat treatments demonstrated the different ability of retaining the fatigue strength.
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