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| 2. |
- Tyrberg, Erika, et al.
(författare)
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The effect of vitamin B supplementation on neuronal injury in people living with HIV: a randomized controlled trial
- 2022
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Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 4:6
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Tidskriftsartikel (refereegranskat)abstract
- Effective antiretroviral therapy has radically changed the course of the HIV pandemic. However, despite efficient therapy, milder forms of neurocognitive symptoms are still present in people living with HIV. Plasma homocysteine is a marker of vitamin B deficiency and has been associated with cognitive impairment. People living with HIV have higher homocysteine concentrations than HIV-negative controls, and we have previously found an association between plasma homocysteine concentration and CSF concentration of neurofilament light protein, a sensitive marker for ongoing neuronal injury in HIV. This prompted us to perform this randomized controlled trial, to evaluate the effect of vitamin B supplementation on neuronal injury in a cohort of people living with HIV on stable antiretroviral therapy. At the Department of Infectious Diseases at Sahlgrenska University Hospital in Gothenburg, Sweden, 124 virally suppressed people living with HIV were screened to determine eligibility for this study. Sixty-one fulfilled the inclusion criteria by having plasma homocysteine levels at or above 12 mu mol/l. They were randomized (1:1) to either active treatment (with cyanocobalamin 0.5 mg, folic acid 0.8 mg and pyridoxine 3.0 mg) q.d. or to a control arm with a cross over to active treatment after 12 months. Cognitive function was measured repeatedly during the trial, which ran for 24 months. We found a significant correlation between plasma neurofilament light protein and plasma homocysteine at screening (n = 124, r = 0.35, P < 0.0001). Plasma homocysteine levels decreased by 35% from a geometric mean of 15.7 mu mol/l (95% confidence interval 14.7-16.7) to 10.3 mu mol/l (95% confidence interval 9.3-11.3) in the active treatment arm between baseline and Month 12. No significant change was detected in the control arm during the same time period [geometric mean 15.2 (95% confidence interval 14.3-16.2) versus geometric mean 16.5 mu mol/l (95% confidence interval 14.7-18.6)]. A significant difference in change in plasma homocysteine levels was seen between arms at 12 months [-40% (95% confidence interval -48 to -30%), P < 0.001]. However, no difference between arms was seen in either plasma neurofilament light protein levels [-6.5% (-20 to 9%), P = 0.39], or cognitive measures [-0.08 (-0.33 to 0.17), P = 0.53]. Our results do not support a vitamin B-dependent cause of the correlation between neurofilament light protein and homocysteine. Additional studies are needed to further elucidate this matter. Tyrberg et al. report the results of a randomized controlled trial investigating the effect of vitamin B supplementation on neuronal injury in people living with HIV with effective antiretroviral therapy. Supplementation decreased levels of homocysteine but not neuronal injury measured by neurofilament light protein.
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- Ahlgren, Erika, et al.
(författare)
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Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the role of homocysteine in neuronal injury in HIV infection. Methods Using a cross-sectional design and archived samples, we compared concentrations of plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL), a sensitive marker of neuronal injury, in 83 HIV-1-infected subjects without antiretroviral treatment. We also analyzed plasma vitamin B12, serum folate, CSF, and plasma HIV RNA, the immune activation marker neopterin in CSF and serum, and albumin ratio as a marker of blood-brain barrier integrity. Twenty-two subjects provided a second sample median of 12.5 months after antiretroviral treatment initiation. Results A significant correlation was found between plasma homocysteine and CSF NFL concentrations in untreated individuals (r = 0.52, p < 0.0001). As expected, there was a significant inverse correlation between homocysteine and B12 (r = -0.41, p < 0.001) and folate (r = -0.40, p = < 0.001) levels. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1-infected individuals. The correlation of plasma homocysteine and CSF NFL was also present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016). Conclusion A correlation between plasma homocysteine and axonal injury, as measured by CSF NFL, was found in both untreated and treated HIV. While this study is not able to prove a causal link, homocysteine and functional B12/folate deficiency appear to play a role in neural injury in HIV-infected individuals.
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- DAWODY, JAZAER, 1959, et al.
(författare)
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An integrated system for energy-efficient exhaust aftertreatment for heavy-duty vehicles
- 2015
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Ingår i: Renewable Energy in the Service of Mankind. - Cham : Springer International Publishing. - 9783319177779 - 9783319177762 ; 1, s. 133-143
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- © Springer International Publishing Switzerland 2015. This chapter presents a unique system approach applied in a joint academic- industrial research programme, E4 Mistra, to attain the goals of high energy efficiency and low emissions in an exhaust aftertreatment system for heavy-duty vehicles. The high energy efficiency is achieved by heat recuperation, onboard hydrogen production for NOx reduction, and by finding new solutions for making the aftertreatment system active at low exhaust temperatures. To reach low particulate emissions, a mechanical filter using a sintered metal powder is developed and coated with catalytic material to improve the soot oxidation efficiency. Low NOx emissions are achieved by an efficient NOx reduction catalyst. The integrated E4 Mistra system comprises four technological advances: thermoelectric (TE) materials for heat recuperation, catalytic reduction of NOx over innovative catalyst substrates using either the onboard diesel or biodiesel, H2 from a high-efficiency fuel reformer, and particulate filtration over a porous metal filter. The TE materials are used in a TE generator (TEG) which converts thermal energy into electricity. The TEG is used to recuperate heat from the exhaust-gas recirculation (EGR) circuit of heavy-duty trucks and is expected to generate ~1 kW electric power from 20 kW heat in the exhaust gas. The TEG is integrated in a plate heat exchanger (HEX) designed particularly for this application. Apart from the knowledge and experiences in TEG and heat exchange technologies, a thorough fluid dynamics and TE analysis are performed in this project to understand the governing processes and optimize the system accordingly. The components of the E4 Mistra system are explained in the chapter in addition to test results, which show the system's capacity for H2 production, NOx conversion, particulate matter filtration and soot oxidation, and finally electric power generation via heat recuperation from the exhaust gas using the developed TEG-HEX system.
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- DAWODY, JAZAER, 1959, et al.
(författare)
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E4-Mistra, a research program for the development of an energy efficient low emission exhaust aftertreatment system for heavy duty vehicles
- 2012
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Ingår i: World Renewable Energy Forum, WREF 2012, Including World Renewable Energy Congress XII and Colorado Renewable Energy Society (CRES) Annual Conference. - : American Solar Energy Society. - 9781622760923 ; , s. 4530-4536
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Konferensbidrag (refereegranskat)abstract
- This paper presents a unique system approach applied in a joint academic - industrial research program, E4 Mistra, to reach the goals of energy efficiency and low emissions exhaust aftertreatment system for heavy duty vehicles. The high energy efficiency is achieved by heat recuperation, on-board hydrogen production for use in both an auxiliary power unit and for NOx reduction and by finding new solutions for making the after-treatment system active at low exhaust temperatures. To reach low particulate emissions a mechanical filter using a sintered metal filter is developed. Low NOx emissions are achieved by an efficient NOx reduction catalyst. The system is based on four technological advances: Thermoelectric material s for heat recuperation, catalytic reduction of NOx over innovative catalyst substrates using hydrocarbons from the fuel and H2 from a high efficiency fuel reformer, and particulate filtration over a porous metal filter.
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| 7. |
- Edén, Arvid, 1975, et al.
(författare)
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CSF biomarkers in patients with COVID-19 and neurological symptoms: A case series.
- 2021
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Ingår i: Neurology. - 1526-632X. ; 96:2
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Tidskriftsartikel (refereegranskat)abstract
- To explore whether hospitalized patients with SARS-CoV-2 and neurologic symptoms have evidence of CNS infection, inflammation and injury using CSF biomarker measurements.We assessed CSF SARS-CoV-2 RNA along with CSF biomarkers of intrathecal inflammation (CSF white blood cell count, neopterin, β2-microglobulin (β2M) and immunoglobulin G-index), blood-brain-barrier (BBB) integrity (albumin ratio), and axonal injury (CSF neurofilament light chain protein [NfL]) in 6 patients with moderate to severe COVID-19 and neurologic symptoms who had undergone a diagnostic lumbar puncture. Neurologic symptoms and signs included features of encephalopathies (4/6), suspected meningitis (1/6) and dysgeusia (1/6). SARS-CoV-2 infection was confirmed by rtPCR analysis of nasopharyngeal swabs.SARS-CoV-2 RNA was detected in the plasma of 2 patients (Cycle threshold [Ct] value 35.0-37.0) and in CSF at low levels (Ct 37.2, 38.0, 39.0) in 3 patients in one but not in a second rtPCR assay. CSF neopterin (median, 43.0 nmol/L) and β2-microglobulin (median, 3.1 mg/L) were increased in all. Median IgG-index (0.39), albumin ratio (5.35) and CSF white blood cell count (<3 cells/µL) were normal in all, while CSF NfL was elevated in 2 patients.Our results on patients with COVID-19 and neurologic symptoms suggest an unusual pattern of marked CSF inflammation in which soluble markers were increased but white cell response and other immunologic features typical of CNS viral infections were absent. While our initial hypothesis centered on CNS SARS-CoV-2 invasion, we could not convincingly detect SARS-CoV-2 as the underlying driver of CNS inflammation. These features distinguish COVID-19 CSF from other viral CNS infections, and raise fundamental questions about the CNS pathobiology of SARS-CoV-2 infection.
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- Ennab Vogel, Nicklas, 1981-
(författare)
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Optimizing prehospital acute stroke care in the presence of economic constraints
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mechanical thrombectomy (MT) has become standard of care for acute anterior circulation ischaemic stroke due to large vessel occlusion since the launch of second-generation stent retrievers for clinical use nearly a decade ago. Up until recently, the treatment was exclusively performed at university hospitals in Sweden. Sundsvall Regional Hospital joined as the eighth treatment facility in late 2023. Scarce resources of healthcare systems across the world hamper the complete implementation of MT in acute stroke care. Hence, efforts to improve patients’ accessibility to and healthcare providers’ utilization of MT remain prioritized. Methods for determining the optimal number and locations of treatment facilities for MT in economically constrained healthcare systems remain unstudied. The optimal number and locations of ambulance helicopters for prehospital transportation of patients with presumed acute stroke too. The aim of the thesis is to solve constrained optimization problems within the framework of cost-effectiveness analysis for prehospital acute stroke care management of patients with AIS. To fill these knowledge gaps, this thesis takes on an interdisciplinary research approach, and combines health economics, operations research, and medicine to identify cost-effective solutions for location problems with respect to the implementation of MT in the Swedish healthcare system. A comprehensive set of consolidated data based on anonymized, patient-level, nation-wide registry data for a study period of six years underlies analyses. This thesis employs predictive modelling, geographic network analysis, optimization, and decision modelling for economic evaluation within the framework of cost-effectiveness analysis to identify the most cost-effective solutions to implement. The fitting of predictive generalized linear models to four treatment modalities in acute stroke care for patients with acute ischaemic stroke established the linear associations in absolute effect measures between the modified Rankin Scale score at 90 days post-stroke and the time from symptom onset to treatment start with intravenous thrombolysis only, MT only and intravenous thrombolysis plus MT, respectively. With imposed economic constraints, the analysis identified the optimal number and locations of thrombectomy centres for the Swedish healthcare system. Furthermore, it identified the optimal number and locations of ambulance helicopters too. Finally, it was possible to determine the combination of optimally located thrombectomy centres and ambulance helicopters that comprises the most cost-effective solution to implement into the Swedish stroke system of care. This thesis demonstrates that economically constrained optimization of thrombectomy centres and ambulance helicopters in acute stroke systems of care comprises highly cost-effective solutions that entail immense health gains in patients with acute ischaemic stroke. Health economics, operational research and medicine can be combined to create a powerful decision-modelling tool in the evaluation of implementation strategies for prehospital acute stroke systems of care.
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| 9. |
- Enroth, Helena, et al.
(författare)
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Evaluation of QuickFISH and maldi Sepsityper for identification of bacteria in bloodstream infection
- 2019
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Ingår i: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 51:4, s. 249-258
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of bacteria and their antibiotic susceptibility patterns are critical to guide therapeutic decision-making for optimal care of septic patients. The current gold standard, blood culturing followed by subculture on agar plates for subsequent identification, is too slow leading to excessive use of broad-spectrum antibiotic with harmful consequences for the patient and, in the long run, the public health. The aim of the present study was to assess the performance of two commercial assays, QuickFISH® (OpGen) and Maldi Sepsityper™ (Bruker Daltonics) for early and accurate identification of microorganisms directly from positive blood cultures.Materials and methods: During two substudies of positive blood cultures, the two commercial assays were assessed against the routine method used at the clinical microbiology laboratory, Unilabs AB, at Skaraborg Hospital, Sweden.Results: The Maldi Sepsityper™ assay enabled earlier microorganism identification. Using the cut-off for definite species identification according to the reference method (>2.0), sufficiently accurate species identification was achieved, but only among Gram-negative bacteria. The QuickFISH®assay was time-saving and showed high concordance with the reference method, 94.8% (95% CI 88.4–98.3), when the causative agent was covered by the QuickFISH® assay.Conclusions: The use of the commercial assays may shorten the time to identification of causative agents in bloodstream infections and can be a good complement to the current clinical routine diagnostics. Nevertheless, the performance of the commercial assays is considerably affected by the characteristics of the causative agents.
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| 10. |
- Forslund, Sofia K., et al.
(författare)
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Combinatorial, additive and dose-dependent drug–microbiome associations
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505
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Tidskriftsartikel (refereegranskat)abstract
- During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1–5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease.
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