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| 2. |
- Larsson, D. G. Joakim, 1969, et al.
(författare)
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Critical knowledge gaps and research needs related to the environmental dimensions of antibiotic resistance
- 2018
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 117, s. 132-138
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Forskningsöversikt (refereegranskat)abstract
- There is growing understanding that the environment plays an important role both in the transmission of antibiotic resistant pathogens and in their evolution. Accordingly, researchers and stakeholders world-wide seek to further explore the mechanisms and drivers involved, quantify risks and identify suitable interventions. There is a clear value in establishing research needs and coordinating efforts within and across nations in order to best tackle this global challenge. At an international workshop in late September 2017, scientists from 14 countries with expertise on the environmental dimensions of antibiotic resistance gathered to define critical knowledge gaps. Four key areas were identified where research is urgently needed: 1) the relative contributions of different sources of antibiotics and antibiotic resistant bacteria into the environment; 2) the role of the environment, and particularly anthropogenic inputs, in the evolution of resistance; 3) the overall human and animal health impacts caused by exposure to environmental resistant bacteria; and 4) the efficacy and feasibility of different technological, social, economic and behavioral interventions to mitigate environmental antibiotic resistance.(1)
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| 4. |
- Mcelhinney, L. M., et al.
(författare)
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High prevalence of Seoul hantavirus in a breeding colony of pet rats
- 2017
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Ingår i: Epidemiology and Infection. - 0950-2688 .- 1469-4409. ; 145:15, s. 3115-3124
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Tidskriftsartikel (refereegranskat)abstract
- As part of further investigations into three linked haemorrhagic fever with renal syndrome (HFRS) cases in Wales and England, 21 rats from a breeding colony in Cherwell, and three rats from a household in Cheltenham were screened for hantavirus. Hantavirus RNA was detected in either the lungs and/or kidney of 17/21 (81%) of the Cherwell rats tested, higher than previously detected by blood testing alone (7/21, 33%), and in the kidneys of all three Cheltenham rats. The partial L gene sequences obtained from 10 of the Cherwell rats and the three Cheltenham rats were identical to each other and the previously reported UK Cherwell strain. Seoul hantavirus (SEOV) RNA was detected in the heart, kidney, lung, salivary gland and spleen (but not in the liver) of an individual rat from the Cherwell colony suspected of being the source of SEOV. Serum from 20/20 of the Cherwell rats and two associated HFRS cases had high levels of SEOV-specific antibodies (by virus neutralisation). The high prevalence of SEOV in both sites and the moderately severe disease in the pet rat owners suggest that SEOV in pet rats poses a greater public health risk than previously considered.
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| 5. |
- Verner, E., et al.
(författare)
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Fe II Diagnostic Tools for Quasars
- 2004
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 611:2, s. 780-785
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Tidskriftsartikel (refereegranskat)abstract
- The enrichment of Fe relative to α-elements such as O and Mgrepresents a potential means to determine the age of quasars and probethe galaxy formation epoch. To explore how Fe II emission in quasars islinked to physical conditions and abundance, we have constructed an 830level Fe II model atom and investigated through photoionizationcalculations how Fe II emission strengths depend on nonabundancefactors. We have split Fe II emission into three major wavelength bands,Fe II (UV), Fe II (Opt1), and Fe II (Opt2), and explore how the Fe II(UV)/Mg II, Fe II (UV)/Fe II (Opt1), and Fe II (UV)/Fe II (Opt2)emission ratios depend on hydrogen density and ionizing flux in thebroad-line regions (BLRs) of quasars. Our calculations show that (1)similar Fe II (UV)/Mg II ratios can exist over a wide range of physicalconditions, (2) the Fe II (UV)/Fe II (Opt1) and Fe II (UV)/Fe II (Opt2)ratios serve to constrain ionizing luminosity and hydrogen density, and(3) flux measurements of Fe II bands and knowledge of the ionizing fluxprovide tools to derive distances to BLRs in quasars. To derive all BLRphysical parameters with uncertainties, comparisons of our model withobservations of a large quasar sample at low redshift (z<1) aredesirable. The STIS and NICMOS instruments aboard the Hubble SpaceTelescope offer the best means to provide such observations.
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| 6. |
- Verner, E., et al.
(författare)
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Revisited Abundance Diagnostics in Quasars: Fe II/Mg II Ratios
- 2003
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 592:2, s. 59-62
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Tidskriftsartikel (refereegranskat)abstract
- Both the Fe II UV emission in the 2000-3000 Å region [Fe II(UV)]and resonance emission line complex of Mg II at 2800 Å areprominent features in quasar spectra. The observed Fe II(UV)/Mg IIemission ratios have been proposed as means to measure the buildup ofthe Fe abundance relative to that of the alpha-elements C, N, O, Ne,and Mg as a function of redshift. The current observed ratios show largescatter and no obvious dependence on redshift. Thus, it remainsunresolved whether a dependence on redshift exists and whether theobserved Fe II(UV)/Mg II ratios represent a real nucleosynthesisdiagnostic. We have used our new 830 level model atom for Fe+in photoionization calculations, reproducing the physical conditions inthe broad-line regions of quasars. This modeling reveals thatinterpretations of high values of Fe II(UV)/Mg II are sensitive not onlyto Fe and Mg abundance, but also to other factors such asmicroturbulence, density, and properties of the radiation field. We findthat the Fe II(UV)/Mg II ratio combined with Fe II(UV)/Fe II(optical)emission ratio, where Fe II(optical) denotes Fe II emission in 4000-6000Å band, can be used as a reliable nucleosynthesis diagnostic forthe Fe/Mg abundance ratios for the physical conditions relevant to thebroad-line regions of quasars. This has extreme importance for quasarobservations with the Hubble Space Telescope and also with the futureJames Webb Space Telescope.
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- Goeijenbier, M., et al.
(författare)
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The hanta hunting study : underdiagnosis of Puumala hantavirus infections in symptomatic non-travelling leptospirosis-suspected patients in the Netherlands, in 2010 and April to November 2011
- 2014
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Ingår i: Eurosurveillance. - 1025-496X .- 1560-7917. ; 19:32, s. 27-36
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Tidskriftsartikel (refereegranskat)abstract
- Leptospirosis and haemorrhagic fever with renal syndrome (HFRS) are hard to distinguish clinically since these two important rodent-borne zoonoses share hallmark symptoms such as renal failure and haemorrhage. Leptospirosis is caused by infection with a spirochete while HFRS is the result of an infection with certain hantaviruses. Both diseases are relatively rare in the Netherlands. Increased incidence of HFRS has been observed since 2007 in countries that border the Netherlands. Since a similar rise in incidence has not been registered in the Netherlands, we hypothesise that due to overlapping clinical manifestations, hantavirus infections may be confused with leptospirosis, leading to underdiagnosis. Therefore, we tested a cohort of non-travelling Dutch patients with symptoms compatible with leptospirosis, but with a negative diagnosis, during 2010 and from April to November 2011. Sera were screened with pan-hantavirus IgG and IgM enzyme-linked immunosorbent assays (ELISAs). Sera with IgM reactivity were tested by immunofluorescence assay (IFA). ELISA (IgM positive) and IFA results were confirmed using focus reduction neutralisation tests (FRNTs). We found hantavirus-specific IgG and/or IgM antibodies in 4.3% (11/255) of samples taken in 2010 and in 4.1% (6/146) of the samples during the 2011 period. After FRNT confirmation, seven patients were classed as having acute Puumala virus infections. A review of hantavirus diagnostic requests revealed that at least three of the seven confirmed acute cases as well as seven probable acute cases of hantavirus infection were missed in the Netherlands during the study period.
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| 8. |
- Ling, Jiaxin, et al.
(författare)
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Genetic analyses of Seoul hantavirus genome recovered from rats (Rattus norvegicus) in the Netherlands unveils diverse routes of spread into Europe
- 2019
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Ingår i: Journal of Medical Virology. - : WILEY. - 0146-6615 .- 1096-9071. ; 91:5, s. 724-730
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Tidskriftsartikel (refereegranskat)abstract
- Seoul virus (SEOV) is the etiologic agent of hemorrhagic fever with renal syndrome. It is carried by brown rats (Rattus norvegicus), a commensal rodent that closely cohabitates with humans in urban environments. SEOV has a worldwide distribution, and in Europe, it has been found in rats in UK, France, Sweden, and Belgium, and human cases of SEOV infection have been reported in Germany, UK, France, and Belgium. In the search of hantaviruses in brown rats from the Netherlands, we found both serological and genetic evidence for the presence of SEOV in the local wild rat population. To further decipher the relationship with other SEOV variants globally, the complete genome of SEOV in the Netherlands was recovered. SEOV sequences obtained from three positive rats (captured at close trapping locations at the same time) were found highly similar. Phylogenetic analyses demonstrated that two lineages of SEOV circulate in Europe. Strains from the Netherlands and UK, together with the Baxter strain from US, constitute one of these two, while the second includes strains from Europe and Asia. Our results support a hypothesis of diverse routes of SEOV spread into Europe. These findings, combined with other indications on the expansion of the spatial European range of SEOV, suggest an increased risk of this virus for the public health, highlighting the need for increased surveillance.
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| 9. |
- Michelsen, Verner, et al.
(författare)
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The Pegomya maculata species group (Diptera Anthomyiidae) in Europe, with description of a new species
- 2009
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Ingår i: Zootaxa. - 1175-5334. ; :2315, s. 51-65
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Tidskriftsartikel (refereegranskat)abstract
- The number of species in the Pegomya maculata species group is raised from three to four with the description of a new, Holarctic species, P. grahami sp. nov. The other species, P. maculata Stein, P. atricauda Ringdahl and P. macrophthalma Griffiths, are redescribed. The number of species in Europe is raised from two to four. Two species, P. grahami (previously recorded as P. maculata) and P. macrophthalma, are also Nearctic. Pegomya maculata is the only species known from the female, but descriptions are given of 2-3 unidentified female morphospecies matching the species group. A lectotype is designated for Pegomyia maculata Stein, 1906.
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| 11. |
- Pavelin, Jon, et al.
(författare)
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The nedd-8 activating enzyme gene underlies genetic resistance to infectious pancreatic necrosis virus in Atlantic salmon
- 2021
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Ingår i: Genomics. - : Elsevier. - 0888-7543 .- 1089-8646. ; 113:6, s. 3842-3850
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Tidskriftsartikel (refereegranskat)abstract
- Genetic resistance to infectious pancreatic necrosis virus (IPNV) in Atlantic salmon is a rare example of a trait where a single locus (QTL) explains almost all of the genetic variation. Genetic marker tests based on this QTL on salmon chromosome 26 have been widely applied in selective breeding to markedly reduce the incidence of the disease. In the current study, whole genome sequencing and functional annotation approaches were applied to characterise genes and variants in the QTL region. This was complemented by an analysis of differential expression between salmon fry of homozygous resistant and homozygous susceptible genotypes challenged with IPNV. These analyses pointed to the NEDD-8 activating enzyme 1 (nae1) gene as a putative functional candidate underlying the QTL effect. The role of nae1 in IPN resistance was further assessed via CRISPR-Cas9 knockout of the nae1 gene and chemical inhibition of the nae1 protein activity in Atlantic salmon cell lines, both of which resulted in highly significant reduction in productive IPNV replication. In contrast, CRISPR-Cas9 knockout of a candidate gene previously purported to be a cellular receptor for the virus (cdh1) did not have a major impact on productive IPNV replication. These results suggest that nae1 is the causative gene underlying the major QTL affecting resistance to IPNV in salmon, provide further evidence for the critical role of neddylation in hostpathogen interactions, and highlight the value in combining high-throughput genomics approaches with targeted genome editing to understand the genetic basis of disease resistance.
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| 13. |
- Tam, CS, et al.
(författare)
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Zanubrutinib monotherapy for patients with treatment naïve chronic lymphocytic leukemia and 17p deletion
- 2021
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 106:9, s. 2354-2363
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic lymphocytic leukemia or small lymphocytic lymphoma whose tumors carry deletion of chromosome 17p13.1 [del(17p)] have an unfavorable prognosis and respond poorly to standard chemoimmunotherapy. Zanubrutinib is a selective next-generation Bruton tyrosine kinase inhibitor. We evaluated the safety and efficacy of zanubrutinib 160 mg twice daily in treatment-naïve patients with del(17p) disease enrolled in a dedicated, nonrandomized cohort (Arm C) of the phase 3 SEQUOIA trial. A total of 109 patients (median age, 70 years; range, 42 – 86) with centrally confirmed del(17p) were enrolled and treated. After a median of 18.2 months (range, 5.0 – 26.3), seven patients had discontinued study treatment due to progressive disease, four due to an adverse event, and one due to withdrawal of consent. The overall response rate was 94.5% with 3.7% of patients achieving complete response with or without incomplete hematologic recovery. The estimated 18-month progression-free survival rate was 88.6% (95% CI, 79.0 – 94.0) and the estimated 18-month overall survival rate was 95.1% (95% CI, 88.4 – 98.0). Most common all-grade adverse events included contusion (20.2%), upper respiratory tract infection (19.3%), neutropenia/neutrophil count decreased (17.4%), and diarrhea (16.5%). Grade ≥ 3 adverse events were reported in 53 patients (48.6%), most commonly neutropenia (12.9%) and pneumonia (3.7%). An adverse event of atrial fibrillation was reported in three patients (2.8%). Zanubrutinib was active and well tolerated in this large, prospectively enrolled treatment cohort of previously untreated patients with del(17p) chronic lymphocytic leukemia/small lymphocytic lymphoma. This trial was registered at ClinicalTrials.gov as #NCT03336333.
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