| 1. |
- Gillman, Anna, et al.
(författare)
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Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards
- 2015
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Ingår i: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 81:7, s. 2378-2383
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Tidskriftsartikel (refereegranskat)abstract
- Influenza A virus (IAV) has its natural reservoir in wild waterfowl and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate (OC)), stockpiled as Tamiflu® for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may there exert evolutionary pressure on avian IAV in waterfowl, resulting in development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo Mallard (Anas platyrhynchos) study we tested if an OC-resistant avian IAV strain (A(H1N1)/NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected Mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission in 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV, induced by OC exposure of the natural host, can persist in absence of the drug. Thus, there is a risk that human pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir resistant pandemic IAV would be a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment and resistance surveillance of IAV in wild birds.
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| 2. |
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| 3. |
- Backlund, Per, et al.
(författare)
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Pre-hospital training and simulation initiative
- 2014
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Konferensbidrag (refereegranskat)abstract
- Background The pre-hospital process is a complex one involving aspects such as medical skills as well as care taking, team performance, inter-organizational cooperation and communication. This calls for novel training methods and technology support. Our review of literature (covering the areas of pre-hospital care, training simulator technologies and methods and process modelling) indicates that the different aspects are typically trained in isolation, e.g. medical skills using patient simulators.Objective The pre-hospital training center project addresses the overall complexity of the pre-hospital process by taking all of the aspects into account when designing scenarios and technology support for training the complete prehospital process (covering alarm, on-scene activities, transportation and hand-over). This is indeed a challenging task as we need to develop both training methods and technology support for a very complex training situation.Methods The project will develop a prototype scenario along with technology support to enact it. The training scenario will involve many of the aspects listed above and will be tested in a field experiment with ambulance personnel. Results The expected outcome of the project is a platform for establishing a pre-hospital simulation and training center. The initial technologies, research results and experiences will be used to form a consortium for further work and development. Conclusions We have identified a need for a pre-hospital training center with the unique and ambitious idea of covering the entire pre-hospital process as well as its many interacting aspects. To the best of our knowledge this approach is not at all common and we expect the complexity to be so high that it is a challenging enough research area that can only be addressed if we have a well-designed simulation and training center in place with all the different areas of knowledge represented, i.e. pre-hospital medicine as well as simulation and visualization technology.
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| 4. |
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| 5. |
- Blom, Kerstin, et al.
(författare)
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Internet-vs. group-delivered cognitive behavior therapy for insomnia : A randomized controlled non-inferiority trial
- 2015
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Ingår i: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 70, s. 47-55
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare guided Internet-delivered to group-delivered cognitive behavioral therapy (CBT) for insomnia. We conducted an 8-week randomized controlled non-inferiority trial with 6-months follow-up. Participants were forty-eight adults with insomnia, recruited via media. Interventions were guided Internet-delivered CBT (ICBT) and group-delivered CBT (GCBT) for insomnia. Primary outcome measure was the Insomnia Severity Index (ISI), secondary outcome measures were sleep diary data, depressive symptoms, response- and remission rates. Both treatment groups showed significant improvements and large effect sizes for ISI (Within Cohen's d: ICBT post = 1.8, 6-months follow-up = 2.1; GCBT post = 2.1, 6-months follow-up = 2.2). Confidence interval of the difference between groups posttreatment and at FU6 indicated non-inferiority of ICBT compared to GCBT. At post-treatment, two thirds of patients in both groups were considered responders (ISI-reduction > 7p). Using diagnostic criteria, 63% (ICBT) and 75% (GCBT) were in remission. Sleep diary data showed moderate to large effect sizes. We conclude that both guided Internet-CBT and group-CBT in this study were efficacious with regard to insomnia severity, sleep parameters and depressive symptoms. The results are in line with previous research, and strengthen the evidence for guided Internet-CBT for insomnia. Trial registration: The study protocol was approved by, and registered with, the regional ethics review board in Linkoping, Sweden, registration number 2010/385-31. (C) 2015 The Authors. Published by Elsevier Ltd.
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| 6. |
- Blum, Kristin M., et al.
(författare)
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Removal of 30 active pharmaceutical ingredients in surface water under long-term artificial UV irradiation
- 2017
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 176, s. 175-182
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the i) kinetics, and ii) proportion of photolysis of 30 relatively stable active pharmaceutical ingredients (APIs) during artificial UV irradiation for 28 d in ammonium acetate buffer, filtered and unfiltered river water. Buffer was included to control removal kinetics under stable pH conditions and without particulate matter. Dark controls were used to determine removal due to other processes than photolysis and calculate the proportion of photolysis of the total removal. The removal of each API in each matrix was determined using online solid phase extraction/liquid chromatography tandem mass spectrometry (online SPE/LC-MS/MS). Most APIs transformed during the 28 d of UV irradiation and the dark controls showed that photolysis was the major removal process for the majority of the APIs studied. The half-lives ranged from 6 h (amitriptyline) in unfiltered river water to 884 h (37 d, carbamazepine) in buffer. In unfiltered river water, the proportion of APIs with short half-lives (<48 h) was much higher (29%) than in the other matrices (4%), probably due to additional organic carbon, which could have promoted indirect photolysis. Furthermore, two APIs, memantine and fluconazole, were stable in all three matrices, while alprazolam was stable in buffer and unfiltered river water and four additional APIs were stable in buffer. Considering the relatively long-term UV-exposure, this study enabled the investigation of environmentally relevant half-lives in natural waters. Many APIs showed high persistence, which is environmentally concerning and emphasizes the importance of further studies on their environmental fate and effects.
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| 7. |
- Bröjer, Caroline, et al.
(författare)
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Pathobiology and virus shedding of low-pathogenic avian influenza virus (A/H1N1) infection in mallards exposed to oseltamivir
- 2013
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Ingår i: Journal of Wildlife Diseases. - : Wildlife Disease Association. - 0090-3558 .- 1943-3700. ; 49:1, s. 103-113
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Tidskriftsartikel (refereegranskat)abstract
- Low-pathogenic avian influenza (LPAI) viruses in wild birds are important as they can constitute the basis for the development of highly pathogenic avian influenza viruses or form part of human-adapted strains with pandemic potential. However, the pathogenesis of LPAI viruses is not well characterized in dabbling ducks, one of the natural reservoirs of LPAI viruses. Between 21 September 2009 and 21 December 2009, we used real-time reverse transcriptase polymerase chain reaction (q-PCR), histopathology, and immunohistochemistry (IHC) to study Mallards (Anas platyrhynchos) infected with an influenza A/H1N1 virus isolated from a wild Mallard in Sweden. The ducks were either inoculated intraesophageally ("artificial infection") or infected by virus shed by other ducks in the experiment ("contact infection"). The ducks were subjected to three low concentrations (80 ng/L, 1 mu g/L, and 80 mu g/L) of the active metabolite of oseltamivir (Tamiflu (R)), oseltamivir carboxylate (OC), which resulted in the development of the viral resistance mutation H274Y at 1 and 80 mu g/L. The LPAI virus infection was localized to the intestinal tract and cloacal bursa except in one Mallard. The exception was a duck euthanized 1 day postinoculation, whose infection was located solely in the lung, possibly due to intratracheal deposition of virus. The intestinal infection was characterized by occasional degenerating cells in the lamina propria and presence of viral antigen as detected by IHC, as well as positive q-PCR performed on samples from feces and intestinal contents. Histopathologic changes, IHC positivity, and viral shedding all indicated that the infection peaked early, around 2 days postinfection. Furthermore, more viral antigen and viral RNA were detected with IHC and q-PCR in the proximal parts early in the infection. There was no obvious difference in the course of the infection in artificial versus contact infection, when the level of OC was increased from 80 ng/L to 1 mu g/L (based on IHC and q-PCR), when the level of OC was increased to 80 mu/L, or when the resistance mutation H274Y developed (based on q-PCR).
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| 8. |
- Bybrant, Mara Cerqueiro, et al.
(författare)
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The prevalence of having coeliac disease in children with type 1 diabetes was not significantly higher during the Swedish coeliac epidemic
- 2023
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Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 112:10, s. 2175-2181
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Tidskriftsartikel (refereegranskat)abstract
- Aim: From 1986 to 1996, there was a four-fold increase in coeliac disease among young Swedish children, known as the Swedish coeliac epidemic. Children with type 1 diabetes have an increased risk of developing coeliac disease. We studied whether the prevalence of coeliac disease differed in children with type 1 diabetes born during and after this epidemic.Methods: We compared national birth cohorts of 240 844 children born in 1992–1993 during the coeliac disease epidemic and 179 530 children born in 1997–1998 after the epidemic. Children diagnosed with both type 1 diabetes and coeliac disease were identified by merging information from five national registers.Results: There was no statistically significant difference in the prevalence of coeliac disease among children with type 1 diabetes between the two cohorts: 176/1642 (10.7%, 95% confidence interval 9.2%–12.2%) in the cohort born during the coeliac disease epidemic versus 161/1380 (11.7%, 95% confidence interval 10.0%–13.5%) in the post-epidemic cohort.Conclusion: The prevalence of having both coeliac disease and type 1 diabetes was not significantly higher in children born during, than after, the Swedish coeliac epidemic. This may support a stronger genetic disposition in children who develop both conditions.
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| 9. |
- Fedorova, Ganna, et al.
(författare)
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Fate of three anti-influenza drugs during ozonation of wastewater effluents : degradation and formation of transformation products
- 2016
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 150, s. 723-730
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Tidskriftsartikel (refereegranskat)abstract
- Anti-influenza drugs constitute a key component of pandemic preparedness plans against influenza. However, the occurrence of such drugs in water environments, the potential of resistance development in the natural hosts, and the risk for transmission of antiviral resistance to humans call for measures to increase removal in wastewater treatment plants (WWTPs). In this study, removal of three anti-influenza drugs; amantadine (AM), oseltamivir carboxylate (OC) and zanamivir (ZA), and formation/removal of their transformation products during ozonation of wastewater effluents from two Swedish WWTPs in Uppsala and Stockholm were studied. The removal profile of target antivirals and formation/removal of their transformation products were studied by liquid chromatography/high resolution mass spectrometry. 3.5 h of ozone exposure (total dose of ozone 5.95 g) led to complete removal of the three anti-influenza drugs with a degradation in the following order ZA > OC > AM. Two, five and one transformation products were identified and semi-quantified for AM, OC and ZA, respectively. Increasing and later decreasing transformation products concentration followed the decrease in concentration of target compounds. All transformation products detected, except one of AM in wastewater from Stockholm WWTP, were removed at the end of the experiment. The removal efficiency was higher for all studied compounds in wastewater from Uppsala WWTP, which had lower TOC and COD values, less phosphorus, and also higher pH in the water. Ozonation thus offers multiple benefits through its potential to degrade influenza antivirals, hence decrease the risk of environmental resistance development, in addition to degrading other pharmaceuticals and resistant microorganisms.
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| 10. |
- Fick, Jerker, et al.
(författare)
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Contamination of surface, ground, and drinking water from pharmaceutical production
- 2009
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Ingår i: Environmental Toxicology and Chemistry. - : SETAC Journals. - 0730-7268 .- 1552-8618. ; 28:12, s. 2522-2527
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Tidskriftsartikel (refereegranskat)abstract
- Low levels of pharmaceuticals are detected in surface, ground, and drinking water worldwide. Usage and incorrect disposal have been considered the major environmental sources of these micro-contaminants. Recent publications, however, suggest that wastewater from drug production can potentially be a source of much higher concentrations in certain locations. We investigated the environmental fate of active pharmaceutical ingredients in a major production area for the global bulk-drug market. Water samples were taken from a common effluent treatment plant near Hyderabad, India, which receives process water from about 90 bulk drug manufacturers. Surface water was analyzed from the recipient stream and from two lakes that are not contaminated by the treatment plant. Water samples were also taken from wells in six nearby villages. The samples were analyzed for the presence of twelve pharmaceuticals with LC-MS/MS. All wells were determined to be contaminated with drugs. Ciprofloxacin, enoxacin, cetirizine, terbinafine and citalopram were detected at >1microg l-1 in several wells. Very high concentrations of ciprofloxacin (up to 14 mg L-1) and other pharmaceuticals (up to 2 mg L-1) were found in the effluent of the treatment plant and in the two lakes (up to 6.5 mg L-1). Thus, insufficient wastewater treatment in one of the world's largest centers for bulk drug production leads to unprecedented drug contamination of surface, ground, and drinking water. This raises serious concerns regarding the development of antibiotic resistance, and it creates a major challenge for producers and regulatory agencies to improve the situation.
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| 11. |
- Gillman, Anna, et al.
(författare)
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Influenza A(H7N9) Virus Acquires Resistance-Related Neuraminidase I222T Substitution When Infected Mallards Are Exposed to Low Levels of Oseltamivir in Water
- 2015
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Biochemistry and Molecular Biology. - 0066-4804 .- 1098-6596. ; 59:9, s. 5196-5202
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Tidskriftsartikel (refereegranskat)abstract
- Influenza A virus (IAV) has its natural reservoir in wild waterfowl, and new human IAVs often contain gene segments originating from avian IAVs. Treatment options for severe human influenza are principally restricted to neuraminidase inhibitors (NAIs), among which oseltamivir is stockpiled in preparedness for influenza pandemics. There is evolutionary pressure in the environment for resistance development to oseltamivir in avian IAVs, as the active metabolite oseltamivir carboxylate (OC) passes largely undegraded through sewage treatment to river water where waterfowl reside. In an in vivo mallard (Anas platyrhynchos) model, we tested if low-pathogenic avian influenza A(H7N9) virus might become resistant if the host was exposed to low levels of OC. Ducks were experimentally infected, and OC was added to their water, after which infection and transmission were maintained by successive introductions of uninfected birds. Daily fecal samples were tested for IAV excretion, genotype, and phenotype. Following mallard exposure to 2.5 mu g/liter OC, the resistance-related neuraminidase (NA) I222T substitution, was detected within 2 days during the first passage and was found in all viruses sequenced from subsequently introduced ducks. The substitution generated 8-fold and 2.4-fold increases in the 50% inhibitory concentration (IC50) for OC (P < 0.001) and zanamivir (P = 0.016), respectively. We conclude that OC exposure of IAV hosts, in the same concentration magnitude as found in the environment, may result in amino acid substitutions, leading to changed antiviral sensitivity in an IAV subtype that can be highly pathogenic to humans. Prudent use of oseltamivir and resistance surveillance of IAVs in wild birds are warranted.
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| 12. |
- Gillman, Anna, et al.
(författare)
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Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards
- 2015
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Ingår i: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 81:7, s. 2378-2383
-
Tidskriftsartikel (refereegranskat)abstract
- Influenza A virus (IAV) has its natural reservoir in wild waterfowl, and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate [OC]), stockpiled as Tamiflu for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may exert evolutionary pressure on avian IAV in waterfowl, resulting in the development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo mallard (Anas platyrhynchos) study, we tested whether an OC-resistant avian IAV (H1N1) strain with an H274Y mutation in the neuraminidase (NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for the neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission among 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV that is induced by exposure of the natural host to OC can persist in the absence of the drug. Thus, there is a risk that human-pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir-resistant pandemic IAV would pose a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment, and surveillance for resistant IAVs in wild birds.
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| 13. |
- Gillman, Anna, et al.
(författare)
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Resistance Mutation R292K Is Induced in Influenza A(H6N2) Virus by Exposure of Infected Mallards to Low Levels of Oseltamivir
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Resistance to neuraminidase inhibitors (NAIs) is problematic as these drugs constitute the major treatment option for severe influenza. Extensive use of the NAI oseltamivir (Tamiflu(R)) results in up to 865 ng/L of its active metabolite oseltamivir carboxylate (OC) in river water. There one of the natural reservoirs of influenza A, dabbling ducks, can be exposed. We previously demonstrated that an influenza A(H1N1) virus in mallards (Anas platyrhynchos) exposed to 1 mu g/L of OC developed oseltamivir resistance through the mutation H274Y (N2-numbering). In this study, we assessed the resistance development in an A(H6N2) virus, which belongs to the phylogenetic N2 group of neuraminidases with distinct functional and resistance characteristics. Mallards were infected with A(H6N2) while exposed to 120 ng/L, 1.2 mu g/L or 12 mu g/L of OC in their sole water source. After 4 days with 12 mu g/L of OC exposure, the resistance mutation R292K emerged and then persisted. Drug sensitivity was decreased approximate to 13,000-fold for OC and approximate to 7.8-fold for zanamivir. Viral shedding was similar when comparing R292K and wild-type virus indicating sustained replication and transmission. Reduced neuraminidase activity and decrease in recovered virus after propagation in embryonated hen eggs was observed in R292K viruses. The initial, but not the later R292K isolates reverted to wild-type during egg-propagation, suggesting a stabilization of the mutation, possibly through additional mutations in the neuraminidase (D113N or D141N) or hemagglutinin (E216K). Our results indicate a risk for OC resistance development also in a N2 group influenza virus and that exposure to one NAI can result in a decreased sensitivity to other NAIs as well. If established in influenza viruses circulating among wild birds, the resistance could spread to humans via re-assortment or direct transmission. This could potentially cause an oseltamivir-resistant pandemic; a serious health concern as preparedness plans rely heavily on oseltamivir before vaccines can be mass-produced.
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| 14. |
- Jansson, Stina, et al.
(författare)
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Implementation of Problem-Based Learning in Environmental Chemistry
- 2015
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Ingår i: Journal of Chemical Education. - : American Chemical Society (ACS). - 0021-9584 .- 1938-1328. ; 92:12, s. 2080-2086
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Tidskriftsartikel (refereegranskat)abstract
- Environmental Chemistry covers a range of topics within the discipline of chemistry, from toxicology to legislation, which warrants interdisciplinary study. Consequently, problem-based learning (PBL), a style of student-centered learning which facilitates the integration of multiple subjects, was investigated to determine if it would be a more appropriate instructional method for teaching Environmental Chemistry than the traditional teacher-centered education model. This article describes the practical aspects of course development and implementation of PBL in a master’s level course in Environmental Chemistry. Overall, the results, which were collected from the initial two years of the course, indicated that the students were pleased and found PBL to be an efficient methodology for not only learning, but also acquiring an in-depth understanding of Environmental Chemistry. This is intended as a case-study with the target audience consisting primarily of high school and undergraduate chemistry teachers, but may also be useful for teachers in other subject areas with an interest in student-centered education.
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| 15. |
- Järhult, Josef D., et al.
(författare)
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Environmental levels of the antiviral oseltamivir induce development of resistance mutation H274Y in influenza A/H1N1 virus in mallards
- 2011
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Ingår i: PLOS ONE. - San Francisco, CA : Public Library of Science (PLoS). - 1932-6203. ; 6:9
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Tidskriftsartikel (refereegranskat)abstract
- Oseltamivir (Tamiflu®) is the most widely used drug against influenza infections and is extensively stockpiled worldwide as part of pandemic preparedness plans. However, resistance is a growing problem and in 2008-2009, seasonal human influenza A/H1N1 virus strains in most parts of the world carried the mutation H274Y in the neuraminidase gene which causes resistance to the drug. The active metabolite of oseltamivir, oseltamivir carboxylate (OC), is poorly degraded in sewage treatment plants and surface water and has been detected in aquatic environments where the natural influenza reservoir, dabbling ducks, can be exposed to the substance. To assess if resistance can develop under these circumstances, we infected mallards with influenza A/H1N1 virus and exposed the birds to 80 ng/L, 1 µg/L and 80 µg/L of OC through their sole water source. By sequencing the neuraminidase gene from fecal samples, we found that H274Y occurred at 1 µg/L of OC and rapidly dominated the viral population at 80 µg/L. IC₅₀ for OC was increased from 2-4 nM in wild-type viruses to 400-700 nM in H274Y mutants as measured by a neuraminidase inhibition assay. This is consistent with the decrease in sensitivity to OC that has been noted among human clinical isolates carrying H274Y. Environmental OC levels have been measured to 58-293 ng/L during seasonal outbreaks and are expected to reach µg/L-levels during pandemics. Thus, resistance could be induced in influenza viruses circulating among wild ducks. As influenza viruses can cross species barriers, oseltamivir resistance could spread to human-adapted strains with pandemic potential disabling oseltamivir, a cornerstone in pandemic preparedness planning. We propose surveillance in wild birds as a measure to understand the resistance situation in nature and to monitor it over time. Strategies to lower environmental levels of OC include improved sewage treatment and, more importantly, a prudent use of antivirals.
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| 16. |
- Järhult, Josef D., 1975-
(författare)
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Tamiflu® - Use It and Lose It?
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Influenza A viruses cause seasonal and pandemic outbreaks that range from mild infections to the disastrous Spanish Flu. Resistance to neuraminidase inhibitors (NAIs) is a growing problem as these drugs constitute a vital part of treatment strategies and pandemic preparedness plans worldwide. Oseltamivir (Tamiflu®) is the mostly used NAI. Its active metabolite, oseltamivir carboxylate (OC), is excreted from treated patients and degrades poorly in sewage treatment plants and surface water. Thus, OC can enter aquatic environments where the natural influenza reservoir, dabbling ducks, can be exposed to the substance and resistance could develop. If NAI resistance is established in influenza viruses circulating among wild birds, the resistance can form part of a virus re-entering the human population either by reassortment or by direct transmission. In this thesis, evidence is presented that OC is present in the waterways during a seasonal influenza outbreak in Japan, a country in which oseltamivir is liberally used. Furthermore, when mallards were infected with an influenza A/H1N1 virus and subjected to low, environmental-like concentrations of OC, resistance developed through acquisition of the well-known resistance mutation H274Y. The influenza infection in the mallards was mainly intestinal, had a rapid onset and was progressing in a longitudinal fashion in the intestine. Finally, influenza A viruses isolated from wild mallards in Sweden and containing resistance-related mutations were examined by a neuraminidase inhibition assay. The viruses did not have a decreased sensitivity to NAIs, but had mutations with a resistance-enhancing potential. Thus, OC is present in the environment and environmental-like concentrations of OC induce resistance in influenza viruses of dabbling ducks. The present resistance situation among wild birds is not well understood but the existence of H274Y among wild birds, though rare, and the spread of the former seasonal A/H1N1 virus containing H274Y among humans indicate that resistance mutations could establish themselves also among wild birds. An oseltamivir-resistant pandemic or a human-adapted highly-pathogenic avian influenza virus are frightening scenarios as oseltamivir is a cornerstone in the defense in those situations. There is a need for further studies, surveillance in wild birds and for a prudent use of antivirals.
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| 17. |
- Järhult, Josef, et al.
(författare)
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Environmental levels of oseltamivir induce development of resistance mutation H274Y in influenza A/H1N1 virus in mallards – implications for the risk of an oseltamivir resistant influenza pandemic
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Resistance in influenza is a growing problem. Oseltamivir carboxylate (OC), the active substance of the most widely used antiviral drug oseltamivir (Tamiflu ®), is poorly degraded in sewage treatment plants and surface water. OC has been detected in aquatic environments where the natural influenza reservoir, dabbling ducks, can be exposed to it. To test if resistance can occur in this situation, we infected mallards with influenza A/H1N1 virus and exposed the birds to 0.08 μg /L, 1.00 μg/L and 80.00 μg/L of OC. The resistance mutation H274Y occurred at 1 μg/L and rapidly dominated the viral population at 80 μg/L. The environmental levels of OC are expected to reach this magnitude. IC50 for OC was increased from 1-4 nM to 400-700 nM in H274Y-positive isolates, confirming a resistant phenotype. As influenza viruses can cross the species barrier, resistance to oseltamivir can spread to human-adapted strains with pandemic potential disabling one of the cornerstones in pandemic preparedness planning.
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| 18. |
- Kristiansson, Erik, 1978, et al.
(författare)
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Pyrosequencing of Antibiotic-Contaminated River Sediments Reveals High Levels of Resistance and Gene Transfer Elements
- 2011
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- The high and sometimes inappropriate use of antibiotics has accelerated the development of antibiotic resistance, creating a major challenge for the sustainable treatment of infections world-wide. Bacterial communities often respond to antibiotic selection pressure by acquiring resistance genes, i.e. mobile genetic elements that can be shared horizontally between species. Environmental microbial communities maintain diverse collections of resistance genes, which can be mobilized into pathogenic bacteria. Recently, exceptional environmental releases of antibiotics have been documented, but the effects on the promotion of resistance genes and the potential for horizontal gene transfer have yet received limited attention. In this study, we have used culture-independent shotgun metagenomics to investigate microbial communities in river sediments exposed to waste water from the production of antibiotics in India. Our analysis identified very high levels of several classes of resistance genes as well as elements for horizontal gene transfer, including integrons, transposons and plasmids. In addition, two abundant previously uncharacterized resistance plasmids were identified. The results suggest that antibiotic contamination plays a role in the promotion of resistance genes and their mobilization from environmental microbes to other species and eventually to human pathogens. The entire life-cycle of antibiotic substances, both before, under and after usage, should therefore be considered to fully evaluate their role in the promotion of resistance.
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| 19. |
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| 20. |
- Lindberg, Richard H., et al.
(författare)
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Online solid phase extraction liquid chromatography using bonded zwitterionic stationary phases and tandem mass spectrometry for rapid environmental trace analysis of highly polar hydrophilic compounds – Application for the antiviral drug Zanamivir
- 2015
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Ingår i: Talanta. - : Elsevier. - 0039-9140 .- 1873-3573. ; 141, s. 164-169
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Zanamivir (Za) is a highly polar and hydrophilic antiviral drug used for the treatment of influenza A viruses. Za has been detected in rivers of Japan and it's environmental occurrence has the risk of inducing antiviral resistant avian influenza viruses. In this study, a rapid automated online solid phase extraction liquid chromatography method using bonded zwitterionic stationary phases and tandem mass spectrometry (SPE/LC–MS/MS) for trace analysis of Za was developed. Furthermore, an internal standard (IS) calibration method capable of quantifying Za in Milli-Q, surface water, sewage effluent and sewage influent was evaluated. Optimum pre-extraction sample composition was found to be 95/5 v/v acetonitrile/water sample and 1% formic acid. The developed method showed acceptable linearities (r2≥0.994), filtration recovery (≥91%), and intra-day precisions (RSD≤16%), and acceptable and environmentally relevant LOQs (≤20 ng L−1). Storage tests showed no significant losses of Za during 20 days and +4/−20 °C (≤12%) with the exception of influent samples, which should be kept at −20 °C to avoid significant Za losses. The applicability of the method was demonstrated in a study on phototransformation of Za in unfiltered and filtered surface water during 28 days of artificial UV irradiation exposure. No significant (≤12%) phototransformation was found in surface water after 28 days suggesting a relatively high photostability of Za and that Za should be of environmental concern.
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| 21. |
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| 22. |
- Nykvist, Marie, et al.
(författare)
-
In vivo mallard experiments indicate that zanamivir has less potential for environmental influenza A virus resistance development than oseltamivir
- 2017
-
Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 98, s. 2937-2949
-
Tidskriftsartikel (refereegranskat)abstract
- Neuraminidase inhibitors are a cornerstone of influenza pandemic preparedness before vaccines can be mass-produced and thus a neuraminidase inhibitor-resistant pandemic is a serious threat to public health. Earlier work has demonstrated the potential for development and persistence of oseltamivir resistance in influenza A viruses exposed to environmentally relevant water concentrations of the drug when infecting mallards, the natural influenza reservoir that serves as the genetic base for human pandemics. As zanamivir is the major second-line neuraminidase inhibitor treatment, this study aimed to assess the potential for development and persistence of zanamivir resistance in an in vivo mallard model; especially important as zanamivir will probably be increasingly used. Our results indicate less potential for development and persistence of resistance due to zanamivir than oseltamivir in an environmental setting. This conclusion is based on: (1) the lower increase in zanamivir IC50 conferred by the mutations caused by zanamivir exposure (2-17-fold); (2) the higher zanamivir water concentration needed to induce resistance (at least 10 µg l-1); (3) the lack of zanamivir resistance persistence without drug pressure; and (4) the multiple resistance-related substitutions seen during zanamivir exposure (V116A, A138V, R152K, T157I and D199G) suggesting lack of one straight-forward evolutionary path to resistance. Our study also adds further evidence regarding the stability of the oseltamivir-induced substitution H275Y without drug pressure, and demonstrates the ability of a H275Y-carrying virus to acquire secondary mutations, further boosting oseltamivir resistance when exposed to zanamivir. Similar studies using influenza A viruses of the N2-phylogenetic group of neuraminidases are recommended.
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| 23. |
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| 24. |
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| 25. |
- Singer, Andrew C., et al.
(författare)
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Compliance to Oseltamivir among Two Populations in Oxfordshire, United Kingdom Affected by Influenza A(H1N1)pdm09, November 2009 : A Waste Water Epidemiology Study
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:4
-
Tidskriftsartikel (refereegranskat)abstract
- Antiviral provision remains the focus of many pandemic preparedness plans, however, there is considerable uncertainty regarding antiviral compliance rates. Here we employ a waste water epidemiology approach to estimate oseltamivir (Tamiflu (R)) compliance. Oseltamivir carboxylate (oseltamivir's active metabolite) was recovered from two waste water treatment plant (WWTP) catchments within the United Kingdom at the peak of the autumnal wave of the 2009 Influenza A (H1N1)pdm09 pandemic. Predictions of oseltamivir consumption from detected levels were compared with two sources of national government statistics to derive compliance rates. Scenario and sensitivity analysis indicated between 3-4 and 120-154 people were using oseltamivir during the study period in the two WWTP catchments and a compliance rate between 45-60%. With approximately half the collected antivirals going unused, there is a clear need to alter public health messages to improve compliance. We argue that a near real-time understanding of drug compliance at the scale of the waste water treatment plant (hundreds to millions of people) can potentially help public health messages become more timely, targeted, and demographically sensitive, while potentially leading to less mis- and un-used antiviral, less wastage and ultimately a more robust and efficacious pandemic preparedness plan.
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| 26. |
- Singer, Andrew C., et al.
(författare)
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Intra- and inter-pandemic variations of antiviral, antibiotics and decongestants in wastewater treatment plants and receiving rivers
- 2014
-
Ingår i: PLOS ONE. - : Public library of science. - 1932-6203. ; 9:9
-
Tidskriftsartikel (refereegranskat)abstract
- The concentration of eleven antibiotics (trimethoprim, oxytetracycline, ciprofloxacin, azithromycin, cefotaxime, doxycycline, sulfamethoxazole, erythromycin, clarithromycin, ofloxacin, norfloxacin), three decongestants (naphazoline, oxymetazoline, xylometazoline) and the antiviral drug oseltamivir's active metabolite, oseltamivir carboxylate (OC), were measured weekly at 21 locations within the River Thames catchment in England during the month of November 2009, the autumnal peak of the influenza A[H1N1]pdm09 pandemic. The aim was to quantify the pharmaceutical response to the pandemic and compare this to drug use during the late pandemic (March 2010) and the inter-pandemic periods (May 2011). A large and small wastewater treatment plant (WWTP) were sampled in November 2009 to understand the differential fate of the analytes in the two WWTPs prior to their entry in the receiving river and to estimate drug users using a wastewater epidemiology approach. Mean hourly OC concentrations in the small and large WWTP's influent were 208 and 350 ng/L (max, 2070 and 550 ng/L, respectively). Erythromycin was the most concentrated antibiotic measured in Benson and Oxford WWTPs influent (max = 6,870 and 2,930 ng/L, respectively). Napthazoline and oxymetazoline were the most frequently detected and concentrated decongestant in the Benson WWTP influent (1650 and 67 ng/L) and effluent (696 and 307 ng/L), respectively, but were below detection in the Oxford WWTP. OC was found in 73% of November 2009's weekly river samples (max = 193 ng/L), but only in 5% and 0% of the late-and inter-pandemic river samples, respectively. The mean river concentration of each antibiotic during the pandemic largely fell between 17-74 ng/L, with clarithromycin (max = 292 ng/L) and erythromycin (max = 448 ng/L) yielding the highest single measure. In general, the concentration and frequency of detecting antibiotics in the river increased during the pandemic. OC was uniquely well-suited for the wastewater epidemiology approach owing to its nature as a prodrug, recalcitrance and temporally-and spatially-resolved prescription statistics.
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| 27. |
- Singer, Andrew C., et al.
(författare)
-
Intra- and inter-pandemic variations of antiviral, antibiotics and decongestants in wastewater treatment plants and receiving rivers
- 2015. - 1
-
Ingår i: Water treatment in developed and developing nations. - Oakville, ON : Apple Academic Press. - 9781771882453 - 9781771882415 - 9780429154713 ; , s. 155-186
-
Bokkapitel (refereegranskat)abstract
- Pandemics are unique public health emergencies that can result in a large sudden increase in the use of a restricted set of pharmaceuticals within a short time period. In the case of an influenza pandemic, antiviral use will greatly exceed inter-pandemic use in most countries by several orders of magnitude, as few countries maintain significant inter-pandemic usage-Japan being a notable exception [1]. Depending on the severity of the pandemic, antibiotics have the potential to significantly exceed inter-pandemic usage for the treatment of secondary bacterial respiratory infections [2]. Decongestant usage is also predicted to increase with an increase in upper-and lower-respiratory tract infections [3].
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| 28. |
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| 29. |
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| 30. |
- Strandberg, Bo, et al.
(författare)
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The use of semipermeable membrane devices as passive samplers to determine persistent organic compounds in indoor air
- 2006
-
Ingår i: Journal of Environmental Monitoring. - : RSC Publishing. - 1464-0325 .- 1464-0333. ; 8:2, s. 257-62
-
Tidskriftsartikel (refereegranskat)abstract
- In the study reported here semipermeable membrane devices (SPMDs) were used to sample 28 PAHs and 19 PCBs in the gas phase in 15 single-family houses located in an area where domestic wood burning is widespread. Eight of the households used wood burning appliances whereas the others used other systems for residential heating. Most of the studied compounds were found in the houses: the PAHs at levels that were similar to or slightly higher than published SPMD-sampled levels for background or urban sites in Sweden, and the PCBs at levels that were somewhat lower than those recently found in both indoor and outdoor urban locations. A principal component analysis revealed that wood-burning heating systems may contribute to PAHs in indoor air. The sources may be emissions indoors or penetration from outdoors. The convenience of SPMD technology facilitates its use for semi-quantitative screening and monitoring of various persistent organic compounds indoors in dwellings and working environments.
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| 31. |
- Svebrant, Sofia, et al.
(författare)
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On-site pilot testing of hospital wastewater ozonation to reduce pharmaceutical residues and antibiotic-resistant bacteria
- 2021
-
Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 10:6
-
Tidskriftsartikel (refereegranskat)abstract
- Hospital sewage constitutes an important point source for antibiotics and antibiotic-resistant bacteria due to the high antibiotic use. Antibiotic resistance can develop and cause problems in sewage systems within hospitals and municipal wastewater treatment plants, thus, interventions to treat hospital sewage on-site are important. Ozonation has proven effective in treating relatively clean wastewater, but the effect on untreated wastewater is unclear. Therefore, we piloted implementation of ozonation to treat wastewater in a tertiary hospital in Uppsala, Sweden. We measured active pharmaceutical ingredients (APIs) using liquid chromatography-mass spectrometry and antibiotic-resistant Enterobacteriaceae using selective culturing pre-and post-ozonation. Comparing low (1 m3 /h) and high (2 m3 /h) flow, we obtained a 'dose-dependent' effect of API reduction (significant reduction of 12/29 APIs using low and 2/29 APIs using high flow, and a mean reduction of antibiotics of 41% using low vs. 6% using high flow, 25% vs. 6% for all APIs). There was no significant difference in the amount of antibiotic-resistant Enterobacteiaceae pre-and post-ozonation. Our results demonstrate that ozonation of untreated wastewater can reduce API content. However, due to the moderate API decrease and numerous practical challenges in the on-site setting, this specific ozonation system is not suitable to implement at full scale in our hospital.
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| 32. |
- Svebrant, Sofia, et al.
(författare)
-
The enzyme toilet rim block 'pCure' does not efficiently remove drug residues in a hospital setting : exemplifying the importance of on-site implementation testing
- 2018
-
Ingår i: Infection Ecology & Epidemiology. - : Taylor & Francis Group. - 2000-8686. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Negative environmental effects of active pharmaceutical ingredients (APIs) are increasingly recognized, especially concerning antibiotics, and hospitals are important point sources. "pCure" is a toilet rim block containing API-degrading enzymes; the producing company claims positive in vitro results but no implementation studies have been performed.Materials and methods: In a university hospital setting, 16 weeks were randomized to installation or no installation of pCure in all 261 toilets connected to the same cesspit where sewage water was sampled daily. Ninety-six samples were analyzed for 102 APIs using liquid chromatography/tandem mass spectrometry.Results and Discussion: Fifty-one APIs were detected with a large variation in levels but no significant differences in the initial statistical analysis. More statistical testing of API level ratios (pCure installed/not installed) yielded some cases of significant decrease. Differences were small and not consistent when comparing means and medians. We cannot exclude a small pCure effect but clearly pCure has no effect of biological importance. Conclusion: pCure is not useful to reduce drug residue discharge in a hospital setting. In a bigger perspective, our study exemplifies that products claiming to reduce an environmental problem need to be tested in on-site implementation studies by independent researchers before reaching the market.
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| 33. |
- Söderström, Eva, et al.
(författare)
-
Combining work process models to identify training needs in the prehospital care process
- 2014
-
Ingår i: Perspectives in Business Informatics Research. - Cham : Springer. - 9783319113692 - 9783319113708 ; , s. 375-389
-
Konferensbidrag (refereegranskat)abstract
- The prehospital process is complex and covers a wide range of locations, healthcare personnel, technologies and competences. Enabling high quality holistic training is hence a challenge. Process models are efficient tools for representing reality, but no single modeling approach can cover the complexity of prehospital care. In our research, we have investigated the possibility to combine various process modeling techniques in order to identify training components and as many perspectives of the prehospital process as possible. Results show that combining different approaches and adapting them based on the need at hand is a successful strategy for enabling an of the prehospital care process from multiple perspectives, including identification of holistic, realistic and engaging training components. Future work can utilize our results to build training scenarios that can be implemented in training using for example simulation.
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| 34. |
- Söderström-Fiscella, Hanna, et al.
(författare)
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Vaginal bleeding in prepubertal girls - etiology and clinical management.
- 2015
-
Ingår i: Journal of Pediatric and Adolescent Gynecology. - : Elsevier BV. - 1873-4332 .- 1083-3188.
-
Tidskriftsartikel (refereegranskat)abstract
- We aimed to investigate the etiology and clinical management of vaginal bleeding in girls aged 0-9 years and to compare our results with previous publications.
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| 35. |
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| 36. |
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| 37. |
- Söderström, Hanna, et al.
(författare)
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Compliance to a Gluten-Free Diet in Swedish Children with Type 1 Diabetes and Celiac Disease
- 2021
-
Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:12
-
Tidskriftsartikel (refereegranskat)abstract
- Children with type 1 diabetes (T1D) are at increased risk of celiac disease (CD). The replacement of insulin in T1D, and the exclusion of gluten in CD, are lifelong, burdensome treatments. Compliance to a gluten-free diet (GFD) in children with CD is reported to be high, while compliance in children with both diseases has scarcely been studied. To examine compliance to a GFD in children with both T1D and CD, we analyzed tissue transglutaminase IgA-antibodies (tTGA). Moreover, associations between compliance and age, sex, glycemic control, ketoacidosis (DKA), body mass index (BMI), and time of CD diagnosis were investigated. Of the 743 children diagnosed with T1D in southern Sweden between 2005 and 2012, 9% were also diagnosed with CD. Of these, 68% showed good compliance to a GFD, 18% showed intermediate compliance, and 14% were classified as non-compliant. Higher age, poorer HbA1c, and more DKAs were significantly (p < 0.05) associated with poorer compliance. In conclusion, we found that compliance to a GFD in children with T1D and CD is likely be lower than in children with CD only. Our results indicate that children with both T1D and CD could need intensified dietary support and that older children and children with poor metabolic control are especially vulnerable subgroups.
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| 38. |
- Söderström, Hanna, et al.
(författare)
-
Detection of the antiviral drug oseltamivir in aquatic environments
- 2009
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:6, s. e6064-
-
Tidskriftsartikel (refereegranskat)abstract
- Oseltamivir (Tamiflu) is the most important antiviral drug available and a cornerstone in the defence against a future influenza pandemic. Recent publications have shown that the active metabolite, oseltamivir carboxylate (OC), is not degraded in sewage treatment plants and is also persistent in aquatic environments. This implies that OC will be present in aquatic environments in areas where oseltamivir is prescribed to patients for therapeutic use. The country where oseltamivir is used most is Japan, where it is used to treat seasonal flu. We measured the levels of OC in water samples from the Yodo River system in the Kyoto and Osaka prefectures, Japan, taken before and during the flu-season 2007/8. No OC was detected before the flu-season but 2-58 ng L(-1) was detected in the samples taken during the flu season. This study shows, for the first time, that low levels of oseltamivir can be found in the aquatic environment. Therefore the natural reservoir of influenza virus, dabbling ducks, is exposed to oseltamivir, which could promote the evolution of viral resistance.
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| 39. |
- Söderström, Hanna, et al.
(författare)
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Does a gluten-free diet lead to better glycemic control in children with type 1 diabetes? : Results from a feasibility study and recommendations for future trials
- 2022
-
Ingår i: Contemporary Clinical Trials Communications. - : Elsevier. - 2451-8654. ; 26
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Increasing evidence suggests a link between type 1 diabetes (T1D) and intake of gluten, but no controlled trials have examined whether a gluten-free diet (GFD) has positive effects on glycemic control in children with T1D. Methods: We conducted a non-randomized feasibility study. Twenty-three children with newly diagnosed T1D were included and either followed a GFD (n = 14) or a normal diet (n = 9) for 12 months. Effects of diet on glycemic control were examined by measuring insulin production (c-peptide), hemoglobine A1c (HbA1c) and insulin dose adjusted A1c (IDAA1c). Degree of adherence to the GFD and effects on quality of life were also examined. Results: Children on a GFD showed a statistically significantly lower HbA1c at six months (P = 0.042) compared with children on a normal diet and point estimate differences indicated better glycemic control in the GFD group at 6 and 12 months. Adherence to a GFD varied but was satisfactory for a majority of children. The GFD group reported poorer quality of life at inclusion and there was a non-significant difference for quality of life between groups throughout the study. Conclusions: A strict GFD can be maintained by children with newly diagnosed T1D and may have positive effects on glycemic control. Our findings should be interpreted carefully because of small samples and possible confounding. We provide recommendations for future trials and suggest using a randomized-controlled design with 30–40 participants in each arm.
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| 40. |
- Söderström, Hanna, et al.
(författare)
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PAHs and nitrated PAHs in air of five European countries determined using SPMDs as passive samplers
- 2005
-
Ingår i: Atmospheric Environment. - : Elsevier. - 1352-2310 .- 1873-2844. ; 39:9, s. 1627-1640
-
Tidskriftsartikel (refereegranskat)abstract
- The gas phase polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs in the atmosphere of five European countries (Austria, the Czech Republic, Poland, Slovakia and Sweden) were measured simultaneously during two 21-day passive sampling campaigns using semipermeable membrane devices (SPMDs). SPMD samplers, consisting of a pair of SPMDs covered by a metal umbrella, were deployed at 40 locations ranging from remote and rural to urban and industrial, at a similar time during each of the two sampling campaigns (autumn 1999, except in Poland, winter 1999, and summer 2000). The total amounts of PAHs and nitro-PAHs found in the SPMDs ranged between 5.0–1.2×103 and 1.1×10−3–4.0 ng SPMD−1 day−1, respectively. The measured environmental sampling conditions were similar between sites and, thus, the variations in the SPMD data reflected the spatial differences in gas phase concentrations of nitro-PAHs and PAHs within and between countries. The gas phase concentrations of nitro-PAHs and PAHs found in East Europe (Slovakia, the Czech Republic and Poland 1999) were 10 times higher than those measured in Sweden, Austria and Poland in 2000. In each country, the levels of PAHs and nitro-PAHs differed by one–three orders of magnitudes amongst sampling sites. The highest within-country spatial differences were found in Poland where levels of PAHs and nitro-PAHs were about one and two orders of magnitudes, respectively, higher in winter 1999 than in summer 2000, probably due to increasing emissions of coal combustion for residential heating. Differences in PAH-patterns between sites were visualized by the multivariate projection method, principal component analysis (PCA). However, no specific source patterns were found, probably since imissions rather than emissions were measured, so the PAHs detected at many sites originated from multiple sources.
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| 41. |
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| 42. |
- Söderström, Hanna S., et al.
(författare)
-
Passive air sampling using semipermeable membrane devices at different wind-speeds in situ calibrated by performance reference compounds
- 2004
-
Ingår i: Environmental Science and Technology. - Washington : American Chemical Society. - 0013-936X .- 1520-5851. ; 38:18, s. 4828-4834
-
Tidskriftsartikel (refereegranskat)abstract
- Semipermeable membrane devices (SPMDs) are passive samplers used to measure the vapor phase of organic pollutants in air. This study tested whether extremely high wind-speeds during a 21-day sampling increased the sampling rates of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), and whether the release of performance reference compounds (PRCs) was related to the uptakes at different wind-speeds. Five samplers were deployed in an indoor, unheated, and dark wind tunnel with different wind-speeds at each site (6−50 m s-1). In addition, one sampler was deployed outside the wind tunnel and one outside the building. To test whether a sampler, designed to reduce the wind-speeds, decreased the uptake and release rates, each sampler in the wind tunnel included two SPMDs positioned inside a protective device and one unprotected SPMD outside the device. The highest amounts of PAHs and PCBs were found in the SPMDs exposed to the assumed highest wind-speeds. Thus, the SPMD sampling rates increased with increasing wind-speeds, indicating that the uptake was largely controlled by the boundary layer at the membrane−air interface. The coefficient of variance (introduced by the 21-day sampling and the chemical analysis) for the air concentrations of three PAHs and three PCBs, calculated using the PRC data, was 28−46%. Thus, the PRCs had a high ability to predict site effects of wind and assess the actual sampling situation. Comparison between protected and unprotected SPMDs showed that the sampler design reduced the wind-speed inside the devices and thereby the uptake and release rates.
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| 43. |
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| 44. |
- Söderström, Hanna S, et al.
(författare)
-
Polycyclic aromatic hydrocarbons in a semiaquatic plant and semipermeable membrane devices exposed to air in Thailand
- 2003
-
Ingår i: Environmental Science and Technology. - 0013-936X .- 1520-5851. ; 37:1, s. 47-52
-
Tidskriftsartikel (refereegranskat)abstract
- Semipermeable membrane devices (SPMDs) were deployed at six sites in the Bangkok region, Thailand, to investigate spatial variations in atmospheric concentrations of polycyclic aromatic hydrocarbons (PAHs). Sampling sites affected by various levels of traffic intensity were studied. In addition, PAH levels were determined in a common human food plant (water spinach) harvested from canals and ponds in the sampling areas. Significant differences in atmospheric PAH concentrations between sites were found, with 10 times higher PAH levels in the urban areas compared to the rural areas. Increasing concentrations of 1-methylphenanthrene relative to phenanthrene were found in the urban air close to the city center, indicating that traffic probably contributed to the higher PAH concentrations detected. Due to SPMD's passive sampling technique, their long-term operation and high ability to detect spatial differences, they proved to be suitable for semiquantitative field studies of PAHs. The PAH compounds sampled with SPMDs were mainly associated with gaseous PAHs, while both gas phase and particle-bound PAHs were detected in the plant samples. The relative abundance ratios of some PAHs in the plants were not well correlated with the ratios detected in the SPMDs, indicating that gas-phase exposure made low contribution to the PAH concentrations in the plants. However, similarities in the profiles of 3-ring PAHs between the SPMD and plant samples indicate that gas-phase exchange occurs between the atmosphere and the plants.
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| 45. |
- Söderström, Hanna, 1974-
(författare)
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Semipermeable membrane devices as integrative tools for monitoring nonpolar aromatic compounds in air
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Air pollutants pose a high risk for humans, and the environment, and this pollution is one of the major environmental problems facing modern society. Active air sampling is the technique that has been traditionally used to monitor nonpolar aromatic air pollutants. However, active high volume samplers (HiVols) require a power supply, maintenance and specialist operators, and the equipment is often expensive. Thus, there is a need to develop new, less complicated sampling techniques that can increase the monitoring frequency, the geographical distribution of the measurements, and the number of sites used in air monitoring programs. In the work underlying this thesis, the use of semipermeable membrane devices (SPMDs) as tools for monitoring gas phase concentrations of nonpolar aromatic compound was evaluated using the compound classes polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), alkylated PAHs (alkyl-PAHs) and nitrated PAHs (nitro-PAHs) as test compounds. High wind-speeds increased the uptake and release in SPMDs of PAHs and PCBs with log KOA values > 7.9, demonstrating that the uptake of most nonpolar aromatic compounds is controlled by the boundary layer at the membrane-air interface. The use of a metal umbrella to shelter the SPMDs decreased the uptake of PAHs and PCBs by 38 and 55 percent, respectively, at high wind/turbulence, and thus reduced the wind effect. Further, the use of performance reference compounds (PRCs) to assess the site effect of wind on the uptake in SPMDs reduced the between-site differences to less than 50 percent from as much as three times differences in uptake of PCBs and PAHs. However, analytical interferences reduced the precision of some PRCs, showing the importance of using robust analytical quality control. SPMDs were shown to be efficient samplers of gas phase nonpolar aromatic compounds, and were able to determine local, continental and indoor spatial distributions of PAHs, alkyl- PAHs and nitro-PAHs. In addition, the use of the SPMDs, which do not require electricity, made sampling possible at remote/rural areas where the infrastructure was limited. SPMDs were also used to determine the source of PAH pollution, and different approaches were discussed. Finally, SPMDs were used to estimate the importance of the gas phase exposure route to the uptake of PAHs in plants. The results demonstrate that SPMDs have several advantages compared with HiVols, including integrative capacity over long times, reduced costs, and no need of special operators, maintenance or power supply for sampling. However, calibration data of SPMDs in air are limited, and spatial differences are often only semi-quantitatively determined by comparing amounts and profiles in the SPMDs, which have limited their use in air monitoring programs. In future work, it is therefore important that SPMDs are properly sheltered, PRCs are used in the sampling protocols, and that calibrated sampling rate data, or the SPMD-air partition data, of specific compounds are further developed to make determination of time weighted average (TWA) concentrations possible.
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| 46. |
- Söderström, Hanna, et al.
(författare)
-
Strategies for monitoring the emerging polar organic contaminants in water with emphasis on integrative passive sampling
- 2009
-
Ingår i: Journal of Chromatography A. - Amsterdam : Elsevier. - 0021-9673 .- 1873-3778. ; 1216:3, s. 623-630
-
Tidskriftsartikel (refereegranskat)abstract
- Although polar organic contaminants (POCs) such as pharmaceuticals are considered as some of today's most emerging contaminants few of them are regulated or included in on-going monitoring programs. However, the growing concern among the public and researchers together with the new legislature within the European Union, the registration, evaluation and authorisation of chemicals (REACH) system will increase the future need of simple, low cost strategies for monitoring and risk assessment of POCs in aquatic environments. In this article, we overview the advantages and shortcomings of traditional and novel sampling techniques available for monitoring the emerging POCs in water. The benefits and drawbacks of using active and biological sampling were discussed and the principles of organic passive samplers (PS) presented. A detailed overview of type of polar organic PS available, and their classes of target compounds and field of applications were given, and the considerations involved in using them such as environmental effects and quality control were discussed. The usefulness of biological sampling of POCs in water was found to be limited. Polar organic PS was considered to be the only available, but nevertheless, an efficient alternative to active water sampling due to its simplicity, low cost, no need of power supply or maintenance, and the ability of collecting time-integrative samples with one sample collection. However, the polar organic PS need to be further developed before they can be used as standard in water quality monitoring programs.
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| 47. |
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| 48. |
- Söderström, Lisa, 1982-, et al.
(författare)
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Dietary advice and oral nutritional supplements do not increase survival in older malnourished adults : a multicentre randomised controlled trial
- 2020
-
Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 125:3, s. 240-249
-
Forskningsöversikt (refereegranskat)abstract
- Objectives: The study aimed to investigate the effect on survival after 6 months of treatment involving individual dietary advice and oral nutritional supplements in older malnourished adults after discharge from hospital. Methods: This multicentre randomised controlled trial included 671 patients aged 65 years who were malnourished or at risk of malnutrition when admitted to hospital between 2010 and 2014, and followed up after 8.2 years (median 4.1 years). Patients were randomised to receive dietary advice or oral nutritional supplements, separate or in combination, or routine care. The intervention started at discharge from the hospital and continued for 6 months, with survival being the main outcome measure. Results: During the follow-up period 398 (59.3%) participants died. At follow-up, the survival rates were 36.9% for dietary advice, 42.4% for oral nutritional supplements, 40.2% for dietary advice combined with oral nutritional supplements, and 43.3% for the control group (log-rank test p = 0.762). After stratifying the participants according to nutritional status, survival still did not differ significantly between the treatment arms (log-rank test p = 0.480 and p = 0.298 for the 506 participants at risk of malnutrition and the 165 malnourished participants, respectively). Conclusions: Oral nutritional supplements with or without dietary advice, or dietary advice alone, do not improve the survival of malnourished older adults. These results do not support the routine use of supplements in older malnourished adults, provided that survival is the aim of the treatment.
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| 49. |
- Söderström, Lisa, 1982-, et al.
(författare)
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Mealtime habits and meal provision are associated with malnutrition among elderly patients admitted to hospital
- 2013
-
Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 32:2, s. 281-288
-
Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Large-scale studies performed in hospitals with the validated Mini Nutritional Assessment tool (MNA) are scarce. However, factors associated with malnutrition are important for identifying individuals at risk. The aims of the present study were to estimate the prevalence of malnutrition and to examine the association between mealtime habits, meal provision, and malnutrition among elderly patients admitted to hospital.Methods: This cross-sectional study included patients aged ≥ 65 years admitted to internal medicine, surgical or orthopaedic wards. The MNA was used for their nutritional assessment, and factors potentially associated with malnutrition were recorded.Results: Of 1771 patients (mean age 78 years), 35.5% were well-nourished, 55.1% were at risk of malnutrition and 9.4% were malnourished. Overnight fasts exceeding 11 hours, fewer than four eating episodes a day, and not cooking independently were associated with both malnutrition and risk of malnutrition.Conclusions: The risk of malnutrition was high among elderly patients admitted to hospital, whereas the proportion with fully developed malnutrition was lower than expected. A long overnight fast, few eating episodes, and not cooking independently were associated with an increased risk of malnutrition. Knowledge of these factors when providing care to the elderly may assist health-care professionals to prevent malnutrition.
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| 50. |
- Tepper, Viktoria, et al.
(författare)
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Influenza A/H4N2 mallard infection experiments further indicate zanamivir as less prone to induce environmental resistance development than oseltamivir
- 2020
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 101:8, s. 816-824
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Tidskriftsartikel (refereegranskat)abstract
- Neuraminidase inhibitors (NAIs) are the gold standard treatment for influenza A virus (IAV). Oseltamivir is mostly used, followed by zanamivir (ZA). NAIs are not readily degraded in conventional wastewater treatment plants and can be detected in aquatic environments. Waterfowl are natural IAV hosts and replicating IAVs could thus be exposed to NAIs in the environment and develop resistance. Avian IAVs form the genetic basis for new human IAVs, and a resistant IAV with pandemic potential poses a serious public health threat, as NAIs constitute a pandemic preparedness cornerstone. Resistance development in waterfowl IAVs exposed to NAIs in the water environment has previously been investigated in an in vivo mallard model and resistance development was demonstrated in several avian IAVs after the exposure of infected ducks to oseltamivir, and in an H1N1 IAV after exposure to ZA. The N1 and N2 types of IAVs have different characteristics and resistance mutations, and so the present study investigated the exposure of an N2-type IAV (H4N2) in infected mallards to 1, 10 and 100 µg l−1 of ZA in the water environment. Two neuraminidase substitutions emerged, H274N (ZA IC50 increased 5.5-fold) and E119G (ZA IC50 increased 110-fold) at 10 and 100 µg l−1 of ZA, respectively. Reversion towards wild-type was observed for both substitutions in experiments with removed drug pressure, indicating reduced fitness of both resistant viruses. These results corroborate previous findings that the development of resistance to ZA in the environment seems less likely to occur than the development of resistance to oseltamivir, adding information that is useful in planning for prudent drug use and pandemic preparedness.
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