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1.
  • Semb, G, et al. (author)
  • Erratum
  • 2017
  • In: Journal of plastic surgery and hand surgery. - 2000-6764. ; 51:2, s. 158-158
  • Journal article (peer-reviewed)
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2.
  • Hopkins, H., et al. (author)
  • Impact of introduction of rapid diagnostic tests for malaria on antibiotic prescribing: analysis of observational and randomised studies in public and private healthcare settings
  • 2017
  • In: Bmj-British Medical Journal. - : BMJ. - 1756-1833 .- 0959-8138. ; 356
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES To examine the impact of use of rapid diagnostic tests for malaria on prescribing of antimicrobials, specifically antibiotics, for acute febrile illness in Africa and Asia. Analysis of nine preselected linked and codesigned observational and randomised studies (eight cluster or individually randomised trials and one observational study). Public and private healthcare settings, 2007-13, in Afghanistan, Cameroon, Ghana, Nigeria, Tanzania, and Uganda. Proportions of patients for whom an antibiotic was prescribed in trial groups who had undergone rapid diagnostic testing compared with controls and in patients with negative test results compared with patients with positive results. A secondary aim compared classes of antibiotics prescribed in different settings. Antibiotics were prescribed to 127 052/238 797 (53%) patients in control groups and 167 714/283 683 (59%) patients in intervention groups. Antibiotics were prescribed to 40% (35 505/89 719) of patients with a positive test result for malaria and to 69% (39 400/57 080) of those with a negative result. All but one study showed a trend toward more antibiotic prescribing in groups who underwent rapid diagnostic tests. Random effects meta-analysis of the trials showed that the overall risk of antibiotic prescription was 21% higher (95% confidence interval 7% to 36%) in intervention settings. In most intervention settings, patients with negative test results received more antibiotic prescriptions than patients with positive results for all the most commonly used classes: penicillins, trimethoprim-sulfamethoxazole (one exception), tetracyclines, and metronidazole. Introduction of rapid diagnostic tests for malaria to reduce unnecessary use of antimalarials-a beneficial public health outcome-could drive up untargeted use of antibiotics. That 69% of patients were prescribed antibiotics when test results were negative probably represents overprescription. This included antibiotics from several classes, including those like metronidazole that are seldom appropriate for febrile illness, across varied clinical, health system, and epidemiological settings. It is often assumed that better disease specific diagnostics will reduce antimicrobial overuse, but they might simply shift it from one antimicrobial class to another. Current global implementation of malaria testing might increase untargeted antibiotic use and must be examined.
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  • Bruxvoort, K. J., et al. (author)
  • The Impact of Introducing Malaria Rapid Diagnostic Tests on Fever Case Management: A Synthesis of Ten Studies from the ACT Consortium
  • 2017
  • In: Am J Trop Med Hyg. - : American Society of Tropical Medicine and Hygiene. - 0002-9637 .- 1476-1645. ; 97:4, s. 1170-1179
  • Journal article (peer-reviewed)abstract
    • Since 2010, the World Health Organization has been recommending that all suspected cases of malaria be confirmed with parasite-based diagnosis before treatment. These guidelines represent a paradigm shift away from presumptive antimalarial treatment of fever. Malaria rapid diagnostic tests (mRDTs) are central to implementing this policy, intended to target artemisinin-based combination therapies (ACT) to patients with confirmed malaria and to improve management of patients with nonmalarial fevers. The ACT Consortium conducted ten linked studies, eight in sub-Saharan Africa and two in Afghanistan, to evaluate the impact of mRDT introduction on case management across settings that vary in malaria endemicity and healthcare provider type. This synthesis includes 562,368 outpatient encounters (study size range 2,400-432,513). mRDTs were associated with significantly lower ACT prescription (range 8-69% versus 20-100%). Prescribing did not always adhere to malaria test results; in several settings, ACTs were prescribed to more than 30% of test-negative patients or to fewer than 80% of test-positive patients. Either an antimalarial or an antibiotic was prescribed for more than 75% of patients across most settings; lower antimalarial prescription for malaria test-negative patients was partly offset by higher antibiotic prescription. Symptomatic management with antipyretics alone was prescribed for fewer than 25% of patients across all scenarios. In community health worker and private retailer settings, mRDTs increased referral of patients to other providers. This synthesis provides an overview of shifts in case management that may be expected with mRDT introduction and highlights areas of focus to improve design and implementation of future case management programs.
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5.
  • Ardalan, Maryam, 1979, et al. (author)
  • Rapid effects of S-ketamine on the morphology of hippocampal astrocytes and BDNF serum levels in a sex-dependent manner
  • 2020
  • In: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 32, s. 94-103
  • Journal article (peer-reviewed)abstract
    • The prevalence of major depressive disorder (MDD) is higher in women than men. Importantly, a differential behavioral response by sex to the antidepressant response to ketamine in rodents has been reported. Mechanistically, male depressed-like animals showed an increased spine density after ketamine treatment via restoration of synaptic protein levels while those proteins were not altered in female rats. In addition, preclinical studies indicate that the impairment of astrocytic plasticity is one of the contributing mechanisms in the pathophysiology of MDD. Accordingly, in this study, we determined the effect of sex on the rapid morphological alteration of hippocampal astrocytes and the serum level of BDNF one hour after S-ketamine injection. A single intraperitoneal dose of S-ketamine (15 mg/kg) or saline was injected to the male and female Flinders Sensitive Line (FSL) rats, a genetic animal model of depression and their brains were perfused one hour after treatment. The size of the GFAP positive astrocytes in the hippocampal subregions was measured. The volume of different hippocampal subregions was assessed using the Cavalieri estimator. Moreover, serum levels of BDNF were measured with enzyme-linked immunosorbent assay (ELISA) kits. The volume of hippocampal subregions significantly increased one hour after S-ketamine in both male and female FSL animals. However, a substantial alteration in the morphology of the hippocampal astrocytes was observed only in the female rats. Additionally, significantly increased serum BDNF levels in the female depressed rats were observed one hour after S-ketamine treatment. Our results indicate that the rapid effects of S-ketamine on the morphology of the hippocampal astrocytes and the serum level of BDNF are sex-dependent.
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6.
  • Beer, Netta, et al. (author)
  • High effective coverage of vector control interventions in children after achieving low malaria transmission in Zanzibar, Tanzania.
  • 2013
  • In: Malaria journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 12
  • Journal article (peer-reviewed)abstract
    • ABSTRACT: Background: Formerly a high malaria transmission area, Zanzibar is now targeting malaria elimination. A major challenge is to avoid resurgence of malaria, the success of which includes maintaining high effective coverage of vector control interventions such as bed nets and indoor residual spraying (IRS). In this study, caretakers' continued use of preventive measures for their children is evaluated, following a sharp reduction in malaria transmission. Methods: A cross-sectional community-based survey was conducted in June 2009 in North A and Micheweni districts in Zanzibar. Households were randomly selected using two-stage cluster sampling. Interviews were conducted with 560 caretakers of under-five-year old children, who were asked about perceptions on the malaria situation, vector control, household assets, and intention for continued use of vector control as malaria burden further decreases. Results: Effective coverage of vector control interventions for under-five children remains high, although most caretakers (65%; 363/560) did not perceive malaria as presently being a major health issue. Seventy percent (447/643) of the under-five children slept under a long-lasting insecticidal net (LLIN) and 94% (607/643) were living in houses targeted with IRS. In total, 98% (628/643) of the children were covered by at least one of the vector control interventions. Seasonal bed-net use for children was reported by 25% (125/508) of caretakers of children who used bed nets. A high proportion of caretakers (95%; 500/524) stated that they intended to continue using preventive measures for their under-five children as malaria burden further reduces. Malaria risk perceptions and different perceptions of vector control were not found to be significantly associated with LLIN effective coverage. Conclusions: While the majority of caretakers felt that malaria had been reduced in Zanzibar, effective coverage of vector control interventions remained high. Caretakers appreciated the interventions and recognized the value of sustaining their use. Thus, sustaining high effective coverage of vector control interventions, which is crucial for reaching malaria elimination in Zanzibar, can be achieved by maintaining effective delivery of these interventions.
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  • Chen, Yin Huai, et al. (author)
  • Absence of GP130 cytokine receptor signaling causes extended Stüve-Wiedemann syndrome
  • 2020
  • In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 217:3
  • Journal article (peer-reviewed)abstract
    • The gene IL6ST encodes GP130, the common signal transducer of the IL-6 cytokine family consisting of 10 cytokines. Previous studies have identified cytokine-selective IL6ST defects that preserve LIF signaling. We describe three unrelated families with at least five affected individuals who presented with lethal Stüve-Wiedemann-like syndrome characterized by skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. We identified essential loss-of-function variants in IL6ST (a homozygous nonsense variant and a homozygous intronic splice variant with exon skipping). Functional tests showed absent cellular responses to GP130-dependent cytokines including IL-6, IL-11, IL-27, oncostatin M (OSM), and leukemia inhibitory factor (LIF). Genetic reconstitution of GP130 by lentiviral transduction in patient-derived cells reversed the signaling defect. This study identifies a new genetic syndrome caused by the complete lack of signaling of a whole family of GP130-dependent cytokines in humans and highlights the importance of the LIF signaling pathway in pre- and perinatal development.
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10.
  • Elfving, Andreas, et al. (author)
  • An explorative study on proteomic analyses related to inflammation and pain in children with juvenile idiopathic arthritis
  • 2023
  • In: BMC Pediatrics. - : Springer Nature. - 1471-2431. ; 23:1
  • Journal article (peer-reviewed)abstract
    • Background: Our aim was attempting to find proteins involved in the pain process and correlating with pain but not degree of inflammation in children with juvenile idiopathic arthritis (JIA), using a proteomics panel.Methods: A total of 87 plasma samples were collected from 51 children with JIA (51 at diagnosis in a higher disease activity state, 18 at follow-up in a lower disease activity state) and 18 healthy controls. Relative levels of 92 proteins related to a wide range of biological processes in inflammation were obtained using a proximity extension assay panel. Comparisons between children with and without JIA, in different disease categories, by juvenile disease activity score (JADAS27) and degree of pain on a visual analogue scale (VAS), were performed using parametric and non-parametric statistical methods.Results: Nineteen proteins involved in arthritic inflammation, such as interleukin 6 (IL-6) and S100 protein A12, were higher in patients with JIA than controls, seven decreased significantly during treatment, and 18 correlated significantly with JADAS27. Three proteins correlated with pain VAS scores in unadjusted analyses: the glial cell line-derived neurotrophic factor (GDNF), transforming growth factor beta, and IL-18R1. Levels of GDNF correlated significantly with pain VAS scores but not with JADAS27.Conclusions: Plasma levels of 18 of 92 tested proteins correlated with degree of disease activity. Levels of three proteins correlated with pain, and levels of one, GDNF, originating from neural cells, correlated with pain without correlating with inflammatory degree, suggesting that it may play a role in pain in JIA. Further studies in larger cohorts are warranted.
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11.
  • Elfving, Maria, et al. (author)
  • Maternal enterovirus infection during pregnancy as a risk factor in Offspring Diagnosed with Type 1 Diabetes between 15 and 30 years of age
  • 2008
  • In: Experimental Diabetes Research. - : Hindawi Limited. - 1687-5214 .- 1687-5303. ; , s. 271958-
  • Journal article (peer-reviewed)abstract
    • Maternal enterovirus infections during pregnancy may increase the risk of offspring developing type 1 diabetes during childhood. The aim of this study was to investigate whether gestational enterovirus infections increase the offspring's risk of type 1 diabetes later in life. Serum samples from 30 mothers without diabetes whose offspring developed type 1 diabetes between 15 and 25 years of age were analyzed for enterovirus-specific immunoglobulin M (IgM) antibodies and enterovirus genome (RNA), and compared to a control group. Among the index mothers, 9/30 (30%) were enterovirus IgM-positive, and none was positive for enterovirus RNA. In the control group, 14/90 (16%) were enterovirus IgM-positive, and 4/90 (4%) were positive for enterovirus RNA (n.s.). Boys of enterovirus IgM-positive mothers had approximately 5 times greater risk of developing diabetes (OR 4.63; 95% CI 1.22-17.6), as compared to boys of IgM-negative mothers (P < .025). These results suggest that gestational enterovirus infections may be related to the risk of offspring developing type 1 diabetes in adolescence and young adulthood.
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12.
  • Engelmark, O., et al. (author)
  • Ecological effects and management aspects of an exotic tree species : the case of lodgepole pine in Sweden
  • 2001
  • In: Forest Ecology and Management. - 0378-1127 .- 1872-7042. ; 141:02-jan, s. 3-13
  • Journal article (peer-reviewed)abstract
    • The North American tree Pinus contorta var, latifolia was experimentally introduced in Sweden already in the 1920s, and has been used in Swedish forestry on a large scale since the 1970s. These plantations now cover 565,000 ha, mainly in the northern area. In this paper we summarize and discuss existing ecological knowledge of this species introduction. With regard to longterm sustainability we suggest management means to minimize harmful effects of the introduction on ecosystems. These include aspects of self dispersal, pests, ecosystem and landscape structures, and also ecological processes and biodiversity. We also focus on observed and possible interactions in the ecosystems. As Pinus contorta seeds are disseminated and trees regenerated outside initial plantations, this may have future bearings on biodiversity. We suggest a strategy which takes account of the uncertainty in predicting future ecological effects. The strategy includes areal restrictions and zones without Pinus contorta, but also to set up a monitoring program. Observations of adverse effects from the plantations would then give the possibility to adjust P. contorta management.
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  • Salomonsson, S., et al. (author)
  • A Population-based Investigation of the Autoantibody Profile in Mothers of Children with Atrioventricular Block
  • 2011
  • In: Scandinavian Journal of Immunology. - Oxford : Blackwell Publishing. - 0300-9475 .- 1365-3083. ; 74:5, s. 511-517
  • Journal article (peer-reviewed)abstract
    • The objective of the study was to investigate the antigen specificity and occurrence of individual autoantibodies in mothers of children diagnosed with atrioventricular (AV) block in a nation-wide setting. Patients with AV block detected before 15 years of age were identified using national quality registries as well as a network of pediatric and adult cardiologists and rheumatologists at the six university hospitals in Sweden. Patients with gross heart malformations, surgically or infectiously induced blocks were excluded. Blood samples were obtained from the mothers and maternal autoantibody profile, including the occurrence of antibodies against Ro52, Ro60, La, SmB, SmD, RNP-70k, RNP-A, RNP-C, CENP-C, Scl-70, Jo-1, ribosomal RNP and histones was investigated in 193 mothers of children with AV block by immunoblotting and ELISA. Autoantibody reactivity was detected in 48% (93/193) of the mothers of children with AV block. In autoantibody-positive mothers, the vast majority, 95% (88/93), had antibodies against Ro52, while 63% (59/93) had autoantibodies to Ro60 and 58% (54/93) had autoantibodies to La. In addition, 13% (12/93) of the autoantibody-positive mothers had antibodies to other investigated antigens besides Ro52, Ro60 and La, and of these anti-histone antibodies were most commonly represented, detected in 8% (7/93) of the mothers. In conclusion, this Swedish population-based study confirms that maternal autoantibodies may associate with heart block in the child. Further, our data demonstrate a dominant role of Ro52 antibodies in association with AV block.
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  • Wu, Y.-H., et al. (author)
  • Surface diffusion limited nucleation of Ge dots on the Si(001) surface
  • 2002
  • Conference paper (peer-reviewed)abstract
    • The formation of Ge islands during MBE growth is a spontaneous process and these islands, i.e. dots, are usually randomly arranged. In order to implement these nanoscaled islands into device applications, ordering of epitaxial dots is a crucial step. We report a study on the MBE growth of Ge islands on Si(001) substrates, containing <110>-oriented square and long stripe type patterns defined by anisotropic wet etching of Si, in order to provide more understanding of how surface diffusion of Ge atoms would influence the formation of Ge islands on various types of surfaces. It has been found that there were preferential nucleation sites for Ge islands along the bottom edges of the Si ridges. The Ge islands at the edge positions were larger than those formed on the free surface and they could be regularly spaced. Due to the consumption of Ge at the bottom edges of ridge patterns, the density of Ge dots on the free surface varied between ˜ 3 × 108 and ˜ 1 × 109 cm-2 when changing the spatial separation between two adjacent Si ridges (2-100 µm). A Ge mean diffusion length of ˜ 7.5 µm has been determined for Ge growth at 700 °C. © 2002 Elsevier Science B.V. All rights reserved.
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