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1.	Svensson, Marina, et al. (författare) Agency, Autonomy and Voice among Chinese Investigative Journalists : Rethinking the Role of Journalism 2013 Ingår i: Chinese Investigative Journalists’ Dreams : Agency, Autonomy, Voice - Agency, Autonomy, Voice. - 9780739189870 ; , s. 1-16 Bokkapitel (refereegranskat)
2.	Andersson, Lars, et al. (författare) Framtidsberättelser från lantbruket år 2030 2016 Rapport (populärvet., debatt m.m.)
3.	Ayoun Alsoud, Rami, et al. (författare) Combined quantitative tuberculosis biomarker model for time-to-positivity and colony forming unit to support tuberculosis drug development 2023 Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 14 Tidskriftsartikel (refereegranskat)abstract Biomarkers are quantifiable characteristics of biological processes. In Mycobacterium tuberculosis, common biomarkers used in clinical drug development are colony forming unit (CFU) and time-to-positivity (TTP) from sputum samples. This analysis aimed to develop a combined quantitative tuberculosis biomarker model for CFU and TTP biomarkers for assessing drug efficacy in early bactericidal activity studies. Daily CFU and TTP observations in 83 previously patients with uncomplicated pulmonary tuberculosis after 7 days of different rifampicin monotherapy treatments (10-40 mg/kg) from the HIGHRIF1 study were included in this analysis. The combined quantitative tuberculosis biomarker model employed the Multistate Tuberculosis Pharmacometric model linked to a rifampicin pharmacokinetic model in order to determine drug exposure-response relationships on three bacterial sub-states using both the CFU and TTP data simultaneously. CFU was predicted from the MTP model and TTP was predicted through a time-to-event approach from the TTP model, which was linked to the MTP model through the transfer of all bacterial sub-states in the MTP model to a one bacterial TTP model. The non-linear CFU-TTP relationship over time was well predicted by the final model. The combined quantitative tuberculosis biomarker model provides an efficient approach for assessing drug efficacy informed by both CFU and TTP data in early bactericidal activity studies and to describe the relationship between CFU and TTP over time.
4.	Chorell, Elin, et al. (författare) A Multivariate Screening Strategy for Investigating Metabolic Effects of Strenuous Physical Exercise in Human Serum 2007 Ingår i: Journal of Proteome Research. - : American Chemical Society. - 1535-3893 .- 1535-3907. ; 6:6, s. 2113-2120 Tidskriftsartikel (refereegranskat)abstract A novel hypothesis-free multivariate screening methodology for the study of human exercise metabolism in blood serum is presented. Serum gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) data was processed using hierarchical multivariate curve resolution (H-MCR), and orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to model the systematic variation related to the acute effect of strenuous exercise. Potential metabolic biomarkers were identified using data base comparisons. Extensive validation was carried out including predictive H-MCR, 7-fold full cross-validation, and predictions for the OPLS-DA model, variable permutation for highlighting interesting metabolites, and pairwise t tests for examining the significance of metabolites. The concentration changes of potential biomarkers were verified in the raw GC/TOFMS data. In total, 420 potential metabolites were resolved in the serum samples. On the basis of the relative concentrations of the 420 resolved metabolites, a valid multivariate model for the difference between pre- and post-exercise subjects was obtained. A total of 34 metabolites were highlighted as potential biomarkers, all statistically significant (p < 8.1E-05). As an example, two potential markers were identified as glycerol and asparagine. The concentration changes for these two metabolites were also verified in the raw GC/TOFMS data.The strategy was shown to facilitate interpretation and validation of metabolic interactions in human serum as well as revealing the identity of potential markers for known or novel mechanisms of human exercise physiology. The multivariate way of addressing metabolism studies can help to increase the understanding of the integrative biology behind, as well as unravel new mechanistic explanations in relation to, exercise physiology.
5.	Funck, Elin, et al. (författare) Det medicinska professionella fältet 2019. - 1 Ingår i: Ett professionellt landskap i förvandling. - Lund : Studentlitteratur AB. - 9789144122274 ; , s. 271-306 Bokkapitel (refereegranskat)
6.	Johansson, Kerstin, bitr. professor, 1963-, et al. (författare) Samverkan för högre övergångstal : Om logiker hos Norrköpings kommun och Linköpings universitet 2019 Rapport (övrigt vetenskapligt/konstnärligt)abstract Denna rapport har sin grund i det samverkansavtal som finns mellan Linköpings universitet och Norrköpings kommun. Med detta avtal som utgångspunkt genomfördes en kunskaps och forskningsöversikt våren 2019som utvecklas och diskuteras i föreliggande rapport.1 Rapporten beskriver och diskuterar det som här benämns Norrköpings kommun och Linköpings universitets logiker kopplade till högre utbildning. Dessa logiker jämförs även med en grupp ungas utbildningsstrategier.Statistik sammanställd av Norrköpings kommun (2018) visar att utbildningsnivån bland kommunens invånare är något lägre i Norrköping i förhållande till de kommuner man jämfört med samt till riket i stort. Enligt denna statistik är även övergångstalen från gymnasieskola till universitet och högskola lägre i Norrköpings kommun. Bland Norrköpings politiker och kommunstyrelse finns en uttalad stark ambition att höja dessa siffror och arbetet för att höja utbildningsnivån är ett prioriterat område inom flera av kommunens verksamheter (Vision 2035; Utbildningskontorets uppdragsplan 2019). Detta finns även med som en målsättning i det strategiska samverkansavtalet mellan Norrköpings kommun och Linköpings universitet. En ytterligare målsättning som finns formulerat i detta avtal är att antalet studenter på Campus Norrköping ska öka. I enlighet med avtalet ska de två aktörerna tillsammans arbeta för nå dessa mål. I den sammantagna bilden av kommunens logiker ryms idéer om livslångt lärande, jämlikhet och kompensatoriska insatser, vilka kopplas till en idé om bildning. Samtidigt uttrycks även logiker som refererar till att universitetsverksamheten är en möjliggörande kraft och grundläggande resurs som bidrar till kommunens välgång och utveckling.Den sammantagna bilden av universitetets logiker å sin sida kan utifrån denna studies fokus tolkas som vilande på en marknadsföringslogik. Studentrekrytering till universitetet konstrueras (eller med ett mer vardagligt begrepp synliggöras) som synonymt med marknadsföring, och utbildningar beskrivs som varor som ska säljas. Marknadsföringslogiken förgrenas även i en slags ekonomisk logik, eftersom marknadsföringen grundar sig på – och måste förhålla sig till – de ekonomiska förutsättningarna.Här framträder alltså en konflikt mellan kommunens och universitetets logiker, som kan exemplifieras med den nationellt, men även lokalt i Norrköpings kommun, rådande lärarbristen. Kommunen har ett stort behov av utbildade lärare och tycks ha vissa förväntningar på, eller åtminstone förhoppningar om, att Linköpings universitet kan fylla en viktig funktion i utbildandet av de lärare som kommunen behöver. Ett sätt att förstå detta är utifrån marknadsföringslogiken och dess konsekvenser: när studentrekryteringen sker baserat på en tanke om att ”sälja” mest och bäst, så är lärarutbildningarna inte de som anses vara ”häftigast” eller mest säljbara. Ett annat betydande resultat i studien, vilket diskuteras i kapitel 6, handlar om hur Norrköpings kommun resonerar utifrån den uttalade målsättningen om ett behov av att höja utbildningsnivån i kommunen. Tanken om att vara en ”bra” kommun knyts samman med tanken om att ha hög utbildningsnivå. Med andra ord är det föreställningarna om och bilderna av vad en bra kommun är som utgör grund för kommunens mål och visioner om höjd utbildningsnivå.Idén om universitetsutbildning som ett ideal är centralt även i ungas sätt att förstå och prata om högre utbildning. Ungdomarnas logik refererar på ett tydligt sätt till ett framtidsperspektiv. Nästan samtliga informanter vill plugga vidare efter studenten, och det motiveras av en föreställning om att det innebär bättre framtidsutsikter. På så vis framträder ungdomarnas logik som att utbildning är synonymt med ett gott framtida liv. I speglingen mot universitetsutbildningens möjliggörande funktioner konstrueras också deras yrkesexamen som barnskötare som ett ”sämre alternativ” och barnskötarprofessionen betraktas som något de kan ägna sig åt tillfälligt, i väntan på att de ska få lust att börja plugga.Vidare utgör samverkan och komplexiteter i samverkan också ett huvudresultat. Samverkan är en självklarhet och utgör en central och gemensam (mellan LiU och Norrköpings kommun) tydligt uttalad ambition. Dock menar vi att på flera punkter finns oklarhet och parternas samverkan i frågor om utbildning och bildning kan behöva definieras mer specifikt avseende tex. parterna uppdrag och mål. Dessa frågor är kopplade till kommunens utveckling avseende tex. sysselsättning och arbetsmarknadspolitik, välfärd samt forskningspolitik.Med denna rapport vill vi uppmärksamma några avgränsade aspekter av en komplex helhet. Vi är medvetna om att de skillnaderna i logik mellan aktörerna som rapporten belyser bland annat handlar om universitets domäner och kommunens lokala ansvar, men vi menar att denna rapport kan bidra med kunskap om samverkan mellan två viktiga samhällsaktörer.
7.	Susanto, Budi Octasari, et al. (författare) Rifampicin can be given as flat-dosing instead of weight-band dosing 2020 Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 71:12, s. 3055-3060 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The weight-band dosing in tuberculosis treatment regimen has been implemented in clinical practice for decades. Patients will receive different number of fixed dose combination (FDC) tablets according to their weight-band. However, some analysis have shown that weight was not the best covariate to explain variability of rifampicin exposure. Furthermore, the rationale for using weight-band dosing instead of flat-dosing becomes questionable. Therefore, this study aimed to compare the average and the variability of rifampicin exposure after weight-band dosing and flat-dosing.METHODS: Rifampicin exposure were simulated using previously published population pharmacokinetics model at dose 10-40 mg/kg for weight-band dosing and dose 600-2400 mg for flat-dosing. The median AUC0-24h after day 7 and 14 were compared as well as the variability of each dose group between weight-band and flat-dosing.RESULTS: The difference of median AUC0-24h of all dose groups between flat-dosing and weight-band dosing were considered low (< 20%) except for the lowest dose. At the dose of 10 mg/kg (600 mg for flat-dosing), flat-dosing resulted in higher median AUC0-24h compared to the weight-band dosing. A marginal decrease in between-patient variability was predicted for weight-band dosing compared to flat-dosing.CONCLUSIONS: Weight-band dosing yields a small and non-clinically relevant decrease in variability of AUC0-24h.
8.	Svensson, Elin M., 1985-, et al. (författare) The Potential for Treatment Shortening With Higher Rifampicin Doses : Relating Drug Exposure to Treatment Response in Patients With Pulmonary Tuberculosis 2018 Ingår i: Clinical Infectious Diseases. - : OXFORD UNIV PRESS INC. - 1058-4838 .- 1537-6591. ; 67:1, s. 34-41 Tidskriftsartikel (refereegranskat)abstract Background. Tuberculosis remains a huge public health problem and the prolonged treatment duration obstructs effective tuberculosis control. Higher rifampicin doses have been associated with better bactericidal activity, but optimal dosing is uncertain. This analysis aimed to characterize the relationship between rifampicin plasma exposure and treatment response over 6 months in a recent study investigating the potential for treatment shortening with high-dose rifampicin. Methods. Data were analyzed from 336 patients with pulmonary tuberculosis (97 with pharmacokinetic data) treated with rifampicin doses of 10, 20, or 35 mg/kg. The response measure was time to stable sputum culture conversion (TSCC). We derived individual exposure metrics with a previously developed population pharmacokinetic model of rifampicin. TSCC was modeled using a parametric time-to-event approach, and a sequential exposure-response analysis was performed. Results. Higher rifampicin exposures increased the probability of early culture conversion. No maximal limit of the effect was detected within the observed range. The expected proportion of patients with stable culture conversion on liquid medium at week 8 was predicted to increase from 39% (95% confidence interval, 37%-41%) to 55% (49%-61%), with the rifampicin area under the curve increasing from 20 to 175 mg/L.h (representative for 10 and 35 mg/kg, respectively). Other predictors of TSCC were baseline bacterial load, proportion of culture results unavailable, and substitution of ethambutol for either moxifloxacin or SQ109. Conclusions. Increasing rifampicin exposure shortened TSCC, and the effect did not plateau, indicating that doses >35 mg/kg could be yet more effective. Optimizing rifampicin dosage while preventing toxicity is a clinical priority.
9.	Svensson, Marina, et al. (författare) Gendering Investigative Journalism: Norms and Practices Inside and Outside of the Newsroom 2013 Ingår i: Chinese Investigative Journalists’ Dreams: Agency, Autonomy, Voice. - 9780739189870 ; , s. 91-110 Bokkapitel (refereegranskat)
10.	Svensson, Marina, et al. (författare) Reporting Law and Injustices: Investigative Journalists and the Legal System 2013 Ingår i: Chinese Investigative Journalists’ Dreams: Agency, Autonomy, Voice. - 9780739189870 ; , s. 157-177 Bokkapitel (refereegranskat)
11.	Svensson, Robin J., et al. (författare) Greater Early Bactericidal Activity at Higher Rifampicin Doses Revealed by Modeling and Clinical Trial Simulations 2018 Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 218:6, s. 991-999 Tidskriftsartikel (refereegranskat)abstract Background. The currently recommended rifampicin dose (10 mg/kg) for treating tuberculosis is suboptimal. The PanACEA HIGHRIF1 trial evaluated the pharmacokinetics and early bactericidal activity of rifampicin doses of up to 40 mg/kg. Conventional statistical analyses revealed no significant exposure-response relationship. Our objectives were to explore the exposure-response relationship for high-dose rifampicin by using pharmacokinetic-pharmacodynamic modeling and to predict the early bactericidal activity of 50 mg/kg rifampicin.Methods. Data included time to Mycobacterium tuberculosis positivity of liquid cultures of sputum specimens from 83 patients with tuberculosis who were treated with 10 mg/kg rifampicin (n = 8; reference arm) or 20, 25, 30, 35, or 40 mg/kg rifampicin (n = 15/arm) for 7 days. We used a semimechanistic time-to-event approach to model the time-to-positivity data. Rifampicin exposure and baseline time to culture positivity were explored as covariates.Results. The baseline time to culture positivity was a significant covariate on the predicted initial bacterial load, and rifampicin exposure was a significant covariate on the bacterial kill rate in sputum resulting in increased early bactericidal activity. The 90% prediction interval for the predicted median day 7 increase in time to positivity for 50 mg/kg rifampicin was 7.25-10.3 days.Conclusions. A significant exposure-response relationship was found between rifampicin exposure and early bactericidal activity. Clinical trial simulations showed greater early bactericidal activity for 50 mg/kg rifampicin.
12.	Thysell, Elin, et al. (författare) Processing of mass spectrometry based metabolomics data for large scale screening studies and diagnostics Annan publikation (övrigt vetenskapligt/konstnärligt)abstract In mass spectrometry based metabolomics predictive data processing and sample classification based on representative sample subsets makes it possible to screen large sample banks or data sets in an efficient fashion regarding both data quality and processing time. This is a requirement for making use of high sensitivity and complexity metabolite data and to turn the metabolomics field into a competitive omics platform for biological interpretation and diagnostics. Predictive metabolomics by means of hierarchical multivariate curve resolution (H-MCR) followed by orthogonal partial least squares discriminant analysis (OPLS-DA) was used for the processing and classification of gas chromatography/time of flight mass spectrometry (GC/TOFMS) data characterizing human blood serum samples collected in a study of strenuous physical exercise. The efficiency of the predictive processing as a high throughput tool for generating high quality data is clearly proven and stated as a main benefit of the method. Extensive model validation schemes by means of cross validation and external predictions verified the robustness of the extracted systematic patterns in the data. Comparisons regarding the extracted metabolite patterns between models emphasized the reliability of the methodology in a biological information context. Furthermore, the high predictive power concerning longitudinal predictions provided proof for the diagnostic potential of the methodology. Finally, the predictive metabolite pattern was interpreted physiologically as well as verified in the literature, highlighting the biological relevance of the diagnostic pattern. The suggested approach makes it feasible to screen large data or sample sets with retained data quality and interpretation and to do this in a high throughput fashion. The method could be of value for sample bank mining, metabolome-wide association studies, verification of marker patterns and development of diagnostic systems.
13.	Thysell, Elin, et al. (författare) Validated and predictive processing of gas chromatography-mass spectra screening studies, diagnostics and metabolite pattern verification 2012 Ingår i: Metabolites. - : M D P I AG. - 2218-1989 .- 2218-1989. ; 2:4, s. 796-817 Tidskriftsartikel (refereegranskat)abstract The suggested approach makes it feasible to screen large metabolomics data, sample sets with retained data quality or to retrieve significant metabolic information from small sample sets that can be verified over multiple studies. Hierarchical multivariate curve resolution (H-MCR), followed by orthogonal partial least squares discriminant analysis (OPLS-DA) was used for processing and classification of gas chromatography/time of flight mass spectrometry (GC/TOFMS) data characterizing human serum samples collected in a study of strenuous physical exercise. The efficiency of predictive H-MCR processing of representative sample subsets, selected by chemometric approaches, for generating high quality data was proven. Extensive model validation by means of cross-validation and external predictions verified the robustness of the extracted metabolite patterns in the data. Comparisons of extracted metabolite patterns between models emphasized the reliability of the methodology in a biological information context. Furthermore, the high predictive power in longitudinal data provided proof for the potential use in clinical diagnosis. Finally, the predictive metabolite pattern was interpreted physiologically, highlighting the biological relevance of the diagnostic pattern.
14.	Thysell, Elin, et al. (författare) Validated and Predictive Processing of Gas Chromatography-Mass Spectrometry Based Metabolomics Data for Large Scale Screening Studies, Diagnostics and Metabolite Pattern Verification 2012 Ingår i: Metabolites. - Basel : MDPI. - 2218-1989. ; 2, s. 796-817 Tidskriftsartikel (refereegranskat)abstract The suggested approach makes it feasible to screen large metabolomics data, sample sets with retained data quality or to retrieve significant metabolic information from small sample sets that can be verified over multiple studies. Hierarchical multivariate curve resolution (H-MCR), followed by orthogonal partial least squares discriminant analysis (OPLS-DA) was used for processing and classification of gas chromatography/time of flight mass spectrometry (GC/TOFMS) data characterizing human serum samples collected in a study of strenuous physical exercise. The efficiency of predictive H-MCR processing of representative sample subsets, selected by chemometric approaches, for generating high quality data was proven. Extensive model validation by means of cross-validation and external predictions verified the robustness of the extracted metabolite patterns in the data. Comparisons of extracted metabolite patterns between models emphasized the reliability of the methodology in a biological information context. Furthermore, the high predictive power in longitudinal data provided proof for the potential use in clinical diagnosis. Finally, the predictive metabolite pattern was interpreted physiologically, highlighting the biological relevance of the diagnostic pattern. The suggested approach makes it feasible to screen large metabolomics data, sample sets with retained data quality or to retrieve significant metabolic information from small sample sets that can be verified over multiple studies. Hierarchical multivariate curve resolution (H-MCR), followed by orthogonal partial least squares discriminant analysis (OPLS-DA) was used for processing and classification of gas chromatography/time of flight mass spectrometry (GC/TOFMS) data characterizing human serum samples collected in a study of strenuous physical exercise. The efficiency of predictive H-MCR processing of representative sample subsets, selected by chemometric approaches, for generating high quality data was proven. Extensive model validation by means of cross-validation and external predictions verified the robustness of the extracted metabolite patterns in the data. Comparisons of extracted metabolite patterns between models emphasized the reliability of the methodology in a biological information context. Furthermore, the high predictive power in longitudinal data provided proof for the potential use in clinical diagnosis. Finally, the predictive metabolite pattern was interpreted physiologically, highlighting the biological relevance of the diagnostic pattern.
15.	Zidar, Josefina, et al. (författare) Group and Single Housing of Male Mice : Collected Experiences from Research Facilities in Sweden 2019 Ingår i: Animals. - : MDPI AG. - 2076-2615. ; 9:12 Tidskriftsartikel (refereegranskat)abstract Animals used for scientific purposes are protected by EU legislation. Social animals should be kept in stable groups that enable species-typical social behavior and provide individuals with social comfort. However, when group-housing male mice, aggression within the homecage is a common husbandry and welfare problem. Excessive fighting and injuries due to aggression can cause pain and stress, resulting in individuals being euthanized or housed individually. In addition, stress can alter physiological parameters, risking scientific validity and generating larger sample sizes. Mouse aggression, and the consequences thereof, thus opposes the 3R goals of Refining the methods to minimize potential pain and suffering and Reducing the number of animals used. Animal technicians, veterinarians, and scientists using animals have valuable information on how these problems are experienced and handled in practice. We assembled these experiences from laboratory animal facilities in Sweden, mapping problems observed and identifying strategies used to prevent mouse aggression. In line with current literature, less aggression was perceived if mice were grouped before sexual maturity, re-grouping avoided and nesting material transferred at cage cleaning. Preventing aggression will minimize pain and suffering and enable housing of stable groups, leading to more reliable scientific outcomes and is thus of high 3Rs relevance.
16.	Abdelwahab, Mahmoud Tareq, et al. (författare) Clofazimine pharmacokinetics in patients with TB : dosing implications 2020 Ingår i: Journal of Antimicrobial Chemotherapy. - : OXFORD UNIV PRESS. - 0305-7453 .- 1460-2091. ; 75:11, s. 3269-3277 Tidskriftsartikel (refereegranskat)abstract Background: Clofazimine is in widespread use as a key component of drug-resistant TB regimens, but the recommended dose is not evidence based. Pharmacokinetic data from relevant patient populations are needed to inform dose optimization. Objectives: To determine clofazimine exposure, evaluate covariate effects on variability, and simulate exposures for different dosing strategies in South African TB patients. Patients and methods: Clinical and pharmacokinetic data were obtained from participants with pulmonary TB enrolled in two studies with intensive and sparse sampling for up to 6 months. Plasma concentrations were measured by LC-MS/MS and interpreted with non-Linear mixed-effects modelling. Body size descriptors and other potential covariates were tested on pharmacokinetic parameters. We simulated different dosing regimens to safely shorten time to average daily concentration above a putative target concentration of 0.25 mg/L. Results: We analysed 1570 clofazimine concentrations from 139 participants; 79 (57%) had drug-resistant TB and 54 (39%) were HIV infected. Clofazimine pharmacokinetics were well characterized by a three-compartment model. Clearance was 11.5 L/h and peripheral volume 10500 L for a typical participant. Lower plasma exposures were observed in women during the first few months of treatment, explained by higher body fat fraction. Model-based simulations estimated that a Loading dose of 200 mg daily for 2 weeks would achieve average daily concentrations above a target efficacy concentration 37 days earlier in a typical TB participant. Conclusions: Clofazimine was widely distributed with a Long elimination half-Life. Disposition was strongly influenced by body fat content, with potential dosing implications for women with TB.
17.	Abdelwahab, Mahmoud Tareq, et al. (författare) Effect of Clofazimine Concentration on QT Prolongation in Patients Treated for Tuberculosis 2021 Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 65:7 Tidskriftsartikel (refereegranskat)abstract Clofazimine is classified as a WHO group B drug for the treatment of rifampin-resistant tuberculosis. QT prolongation, which is associated with fatal cardiac arrhythmias, is caused by several antitubercular drugs, including clofazimine, but there are no data quantifying the effect of clofazimine concentration on QT prolongation. Our objective was to describe the effect of clofazimine exposure on QT prolongation. Fifteen adults drug-susceptible tuberculosis patients received clofazimine monotherapy as 300mg daily for 3 days, followed by 100mg daily in one arm of a 2-week, multiarm early bactericidal activity trial in South Africa. Pretreatment Fridericia-corrected QT (QTcF) (105 patients, 524 electrocardiograms [ECGs]) and QTcFs from the clofazimine monotherapy arm matched with clofazimine plasma concentrations (199 ECGs) were interpreted with a nonlinear mixed-effects model. Clofazimine was associated with significant QT prolongation described by a maximum effect (Emax) function. We predicted clofazimine exposures using 100-mg daily doses and 2 weeks of loading with 200 and 300mg daily, respectively. The expected proportions of patients with QTcF change from baseline above 30 ms (DQTcF. 30) were 2.52%, 11.6%, and 23.0% for 100-, 200-, and 300-mg daily doses, respectively. At steady state, the expected proportion with Delta QTcF of >30 ms was 23.7% and with absolute QTcF of >450 ms was 3.42% for all simulated regimens. The use of loading doses of 200 and 300mg is not predicted to expose patients to an increased risk of QT prolongation, compared with the current standard treatment, and is, therefore, an alternative option for more quickly achieving therapeutic concentrations.
18.	Abulfathi, Ahmed Aliyu, et al. (författare) Clinical Pharmacokinetics and Pharmacodynamics of Rifampicin in Human Tuberculosis 2019 Ingår i: Clinical Pharmacokinetics. - : Springer Science and Business Media LLC. - 0312-5963 .- 1179-1926. ; 58:9, s. 1103-1129 Forskningsöversikt (refereegranskat)abstract The introduction of rifampicin (rifampin) into tuberculosis (TB) treatment five decades ago was critical for shortening the treatment duration for patients with pulmonary TB to 6months when combined with pyrazinamide in the first 2months. Resistance or hypersensitivity to rifampicin effectively condemns a patient to prolonged, less effective, more toxic, and expensive regimens. Because of cost and fears of toxicity, rifampicin was introduced at an oral daily dose of 600mg (8-12mg/kg body weight). At this dose, clinical trials in 1970s found cure rates of >= 95% and relapse rates of < 5%. However, recent papers report lower cure rates that might be the consequence of increased emergence of resistance. Several lines of evidence suggest that higher rifampicin doses, if tolerated and safe, could shorten treatment duration even further. We conducted a narrative review of rifampicin pharmacokinetics and pharmacodynamics in adults across a range of doses and highlight variables that influence its pharmacokinetics/pharmacodynamics. Rifampicin exposure has considerable inter- and intra-individual variability that could be reduced by administration during fasting. Several factors including malnutrition, HIV infection, diabetes mellitus, dose size, pharmacogenetic polymorphisms, hepatic cirrhosis, and substandard medicinal products alter rifampicin exposure and/or efficacy. Renal impairment has no influence on rifampicin pharmacokinetics when dosed at 600mg. Rifampicin maximum (peak) concentration (C-max) > 8.2 mu g/mL is an independent predictor of sterilizing activity and therapeutic drug monitoring at 2, 4, and 6h post-dose may aid in optimizing dosing to achieve the recommended rifampicin concentration of >= 8 mu g/mL. A higher rifampicin C-max is required for severe forms TB such as TB meningitis, with C-max >= 22 mu g/mL and area under the concentration-time curve (AUC) from time zero to 6h (AUC(6)) >= 70 mu g.h/mL associated with reduced mortality. More studies are needed to confirm whether doses achieving exposures higher than the current standard dosage could translate into faster sputum conversion, higher cure rates, lower relapse rates, and less mortality. It is encouraging that daily rifampicin doses up to 35mg/kg were found to be safe and well-tolerated over a period of 12weeks. High-dose rifampicin should thus be considered in future studies when constructing potentially shorter regimens. The studies should be adequately powered to determine treatment outcomes and should include surrogate markers of efficacy such as C-max/MIC (minimum inhibitory concentration) and AUC/MIC.
19.	Abulfathi, Ahmed A., et al. (författare) Pharmacometrics - tools to assure optimal medicine use in low- and middle-income countries : Editorial 2022 Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 13 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
20.	Abulfathi, Ahmed A., et al. (författare) Probability of mycobactericidal activity of para-aminosalicylic acid with novel dosing regimens 2020 Ingår i: European Journal of Clinical Pharmacology. - : Springer Nature. - 0031-6970 .- 1432-1041. ; 76:11, s. 1557-1565 Tidskriftsartikel (refereegranskat)abstract Purpose Para-aminosalicylic acid (PAS) is currently one of the add-on group C medicines recommended by the World Health Organization for multidrug-resistant tuberculosis treatment. At the recommended doses (8-12 g per day in two to three divided doses) of the widely available slow-release PAS formulation, studies suggest PAS exposures are lower than those reached with older PAS salt formulations and do not generate bactericidal activity. Understanding the PASER dose-exposure-response relationship is crucial for dose optimization. The objective of our study was to establish a representative population pharmacokinetics model for PASER and evaluate the probability of bactericidal and bacteriostatic target attainment with different dosing regimens.Methods To this end, we validated and optimized a previously published population pharmacokinetic model on an extended dataset. The probability of target attainment was evaluated for once-daily doses of 12 g, 14 g, 16 g and 20 g PASER. Results The final optimized model included the addition of variability in bioavailability and allometric scaling with body weight on disposition parameters. Peak PAS concentrations over minimum inhibitory concentration of 100, which is required for bactericidal activity are achieved in 53%, 65%, 72% and 84% of patients administered 12, 14, 16 and 20 g once-daily PASER, respectively, when MIC is 1 mg/L. For the typical individual, the exposure remained above 1 mg/L for >= 98% of the dosing interval in all the evaluated PASER regimens.Conclusion The pharmacokinetic/pharmacodynamic parameters linked to bactericidal activity should be determined for 14 g, 16 g and 20 g once-daily doses of PASER.
21.	Abulfathi, Ahmed A., et al. (författare) The pharmacokinetics of para-aminosalicylic acid and its relationship to efficacy and intolerance 2020 Ingår i: British Journal of Clinical Pharmacology. - : WILEY. - 0306-5251 .- 1365-2125. ; 86:11, s. 2123-2132 Forskningsöversikt (refereegranskat)abstract Following its introduction as an antituberculosis agent close to 75 years ago, the use of para-aminosalicylic acid (PAS) has been limited by gastrointestinal intolerance and multiple formulations were produced in attempts to reduce its occurrence. More recently, an enteric-coated, granular, slow-release PAS formulation (PASER) was introduced and is now in wide-spread use for the treatment of drug-resistant tuberculosis. The current PASER dosing regimen is based on recommendations derived from older studies using a variety of different PAS formulations and relegate PAS to a role as an exclusively bacteriostatic agent. However, there is ample evidence that if sufficiently high serum concentrations are reached, PAS can be bactericidal and that intolerance following once daily dosing, that aids the achievement of such concentrations, is no worse than that following intermittent daily dosing. In particular, prevention of resistance to companion drugs appears to be dependent on the size of the single dose, and hence the peak concentrations, and not on maintaining serum levels consistently above minimum inhibitory concentration. We present a narrative review of the development of PAS formulations, dosing practices, and published data regarding pharmacokinetics and pharmacodynamics and the relationship of PAS dosage to intolerance and efficacy. Our conclusions suggests that we are at present not using PAS to its maximum ability to contribute to regimen efficacy and protect companion drugs.
22.	Abulfathi, Ahmed A., et al. (författare) The Population Pharmacokinetics of Meropenem in Adult Patients With Rifampicin-Sensitive Pulmonary Tuberculosis 2021 Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 12 Tidskriftsartikel (refereegranskat)abstract Background: Meropenem is being investigated for repurposing as an anti-tuberculosis drug. This study aimed to develop a meropenem population pharmacokinetics model in patients with pulmonary tuberculosis and identify covariates explaining inter-individual variability.Methods: Patients were randomized to one of four treatment groups: meropenem 2 g three times daily plus oral rifampicin 20 mg/kg once daily, meropenem 2 g three times daily, meropenem 1 g three times daily, and meropenem 3 g once daily. Meropenem was administered by intravenous infusion over 0.5-1 h. All patients also received oral amoxicillin/clavulanate together with each meropenem dose, and treatments continued daily for 14 days. Intensive plasma pharmacokinetics sampling over 8 h was conducted on the 14th day of the study. Nonlinear mixed-effects modeling was used for data analysis. The best model was chosen based on likelihood metrics, goodness-of-fit plots, and parsimony. Covariates were tested stepwise.Results: A total of 404 concentration measurements from 49 patients were included in the analysis. A two-compartment model parameterized with clearance (CL), inter-compartmental clearance (Q), and central (V1) and peripheral (V2) volumes of distribution fitted the data well. Typical values of CL, Q, V1, and V2 were 11.8 L/h, 3.26 L/h, 14.2 L, and 3.12 L, respectively. The relative standard errors of the parameter estimates ranged from 3.8 to 35.4%. The covariate relations included in the final model were creatinine clearance on CL and allometric scaling with body weight on all disposition parameters. An effect of age on CL as previously reported could not be identified.Conclusion: A two-compartment model described meropenem population pharmacokinetics in patients with pulmonary tuberculosis well. Covariates found to improve model fit were creatinine clearance and body weight but not rifampicin treatment. The final model will be used for an integrated pharmacokinetics/pharmacodynamics analysis linking meropenem exposure to early bactericidal activity.
23.	Aevarsson, Arnthór, et al. (författare) Going to extremes - a metagenomic journey into the dark matter of life 2021 Ingår i: FEMS Microbiology Letters. - : Oxford University Press (OUP). - 1574-6968. ; 368:12 Forskningsöversikt (refereegranskat)abstract The Virus-X-Viral Metagenomics for Innovation Value-project was a scientific expedition to explore and exploit uncharted territory of genetic diversity in extreme natural environments such as geothermal hot springs and deep-sea ocean ecosystems. Specifically, the project was set to analyse and exploit viral metagenomes with the ultimate goal of developing new gene products with high innovation value for applications in biotechnology, pharmaceutical, medical, and the life science sectors. Viral gene pool analysis is also essential to obtain fundamental insight into ecosystem dynamics and to investigate how viruses influence the evolution of microbes and multicellular organisms. The Virus-X Consortium, established in 2016, included experts from eight European countries. The unique approach based on high throughput bioinformatics technologies combined with structural and functional studies resulted in the development of a biodiscovery pipeline of significant capacity and scale. The activities within the Virus-X consortium cover the entire range from bioprospecting and methods development in bioinformatics to protein production and characterisation, with the final goal of translating our results into new products for the bioeconomy. The significant impact the consortium made in all of these areas was possible due to the successful cooperation between expert teams that worked together to solve a complex scientific problem using state-of-the-art technologies as well as developing novel tools to explore the virosphere, widely considered as the last great frontier of life.
24.	Aldrin, Emilia, 1982-, et al. (författare) Nordisk namnforskning 2017 : 2.6 Sverige 2018 Ingår i: Namn och bygd. - Uppsala : Kungl. Gustav Adolfs akademien för svensk folkkultur. - 0077-2704. ; 106, s. 150-158 Forskningsöversikt (övrigt vetenskapligt/konstnärligt)
25.	Alffenaar, J. W. C., et al. (författare) Clinical standards for the dosing and management of TB drugs 2022 Ingår i: The International Journal of Tuberculosis and Lung Disease. - Paris, France : International Union Against Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 26:6, s. 483- Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Background: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice' for dosing and management of TB drugs.Methods: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.Results: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.Conclusion: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.
26.	Anand, Aseem, et al. (författare) Assessing Radiographic Response to 223Ra with an Automated Bone Scan Index in Metastatic Castration-Resistant Prostate Cancer Patients 2020 Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X .- 1535-5667. ; 61:5, s. 671-675 Tidskriftsartikel (refereegranskat)abstract For effective clinical management of patients being treated with 223Ra, there is a need for radiographic response biomarkers to minimize disease progression and to stratify patients for subsequent treatment options. The objective of this study was to evaluate an automated bone scan index (aBSI) as a quantitative assessment of bone scans for radiographic response in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: In a multicenter retrospective study, bone scans from patients with mCRPC treated with monthly injections of 223Ra were collected from 7 hospitals in Sweden. Patients with available bone scans before treatment with 223Ra and at treatment discontinuation were eligible for the study. The aBSI was generated at baseline and at treatment discontinuation. The Spearman rank correlation was used to correlate aBSI with the baseline covariates: alkaline phosphatase (ALP) and prostate-specific antigen (PSA). The Cox proportional-hazards model and Kaplan-Meier curve were used to evaluate the association of covariates at baseline and their change at treatment discontinuation with overall survival (OS). The concordance index (C-index) was used to evaluate the discriminating strength of covariates in predicting OS. Results: Bone scan images at baseline were available from 156 patients, and 67 patients had both a baseline and a treatment discontinuation bone scan (median, 5 doses; interquartile range, 3-6 doses). Baseline aBSI (median, 4.5; interquartile range, 2.4-6.5) was moderately correlated with ALP (r = 0.60, P < 0.0001) and with PSA (r = 0.38, P = 0.003). Among baseline covariates, aBSI (P = 0.01) and ALP (P = 0.001) were significantly associated with OS, whereas PSA values were not (P = 0.059). After treatment discontinuation, 36% (24/67), 80% (54/67), and 13% (9/67) of patients demonstrated a decline in aBSI, ALP, and PSA, respectively. As a continuous variable, the relative change in aBSI after treatment, compared with baseline, was significantly associated with OS (P < 0.0001), with a C-index of 0.67. Median OS in patients with both aBSI and ALP decline (median, 134 wk) was significantly longer than in patients with ALP decline only (median, 77 wk; P = 0.029). Conclusion: Both aBSI at baseline and its change at treatment discontinuation were significant parameters associated with OS. The study warrants prospective validation of aBSI as a quantitative imaging response biomarker to predict OS in patients with mCRPC treated with 223Ra.
27.	Avango, Dag, et al. (författare) Kulturarvet som strategisk resurs i den gröna omställningen i norr: målkonflikt eller möjlighet? 2024 Ingår i: Bebyggelseshistorisk tidskrift. - 0349-2834. ; 86, s. 8-29 Tidskriftsartikel (refereegranskat)abstract Artikeln diskuterar kulturarvet i ljuset av den ’gröna omställning’ som svarar på EU:s mål och riktade finansiella satsningar för industriomvandlingen i norra Sverige. Det kan jämföras med den stora industriella omställningen vid 1900-talets början såväl genom att skapa nya möjligheter men också genom de målkonflikter som uppstår mellan nya och befintliga värden, både vad gäller naturförhållanden och ekonomi som kulturvärden och historiska lämningar av mänsklig verksamhet. Omställningen berör platser med en lång historia av mänskligt liv och arbete och som spelar en viktig roll för de som idag bor där och potentiellt för de som söker sig dit för att driva verksamhet eller för att bo, leva och arbeta. I många fall visar det sig svårt att ta denna potential tillvara av skäl som är strukturella, juridiska och politiska snarare än knutna till enskilda aktörer. Artikeln är författad av en multidisciplinär forskargrupp som använder ett praktikbaserat förhållningssätt och samskapande dialog för att undersöka hur förbättrade planeringsprocesser som tidigt involverar olika aktörer, intressen och expertis i förändringsprojekt kan bidra till att lösa målkonflikter och skapa möjligheter. Målkonflikter mellan exploatering och bevarandeintressen i samband med myndigheters och privata aktörers hantering av natur- och kulturmiljöer har länge varit i fokus för forskningen och artikeln syftar till att komplettera dessa perspektiv utifrån exempel som illustrerar möjligheter för att det fysiska kulturarvet ska ses som en strategisk historisk resurs i samhällsutvecklingen. En utgångspunkt är att kulturarv inte är statiskt utan värderas och omvärderas i en process där olika kulturvärden kan associeras med byggnader, platser och miljöer. Dessa kulturvärden förändras alltså över tid, och olika aktörer förhåller sig till dem på skiftande sätt. Genom processer som inbegriper förhandling med andra intressen kan landskap, platser, byggnader, föremål och deras användning förvandlas till kulturarv. Ett samskapande arbetssätt har möjliggjorts genom ett forsknings- och innovationsprojekt, finansierat av Vinnova, vilket genomförts genom en kombinerad metodansats med fallstudier, i projektet kallade lärcase, som ram för empiriska undersökningar och praktiskt genomförande. De lärcase som lyfts i denna artikel är dels Nautanen, en tidigare gruvmiljö i Norrbotten där nyetablering planeras av Boliden AB, dels Kvarnsvedens tidigare pappersbruk i Borlänge, där Northvolt etablerar en fabrik för produktion av bilbatterier vilket medfört rivning av en byggnad med konstaterade kulturhistoriska värden, den så kallade Bobergshallen. Med förslag till fortsatt forskning genom begreppsutveckling i en multidisciplinär och praktiknära kontext problematiserar artikeln begreppet cirkulär ekonomi i relation till kulturarvsfrågor och möjliggör att kulturarvet nyttjas som strategisk resurs i den gröna omställningen med förhoppning att realisera förväntningarna om grön nyindustralisering och attraktiva livsmiljöer.
28.	Avango, Dag, et al. (författare) Kulturarvet som strategisk resurs i den gröna omställningen i norr: målkonflikt eller möjlighet? 2024 Ingår i: Bebyggelsehistorisk tidskrift. - 0349-2834 .- 2002-3812. ; 86, s. 8-29 Tidskriftsartikel (refereegranskat)abstract Artikeln diskuterar kulturarvet i ljuset av den ’gröna omställning’ som svarar på EU:s mål och riktade finansiella satsningar för industriomvandlingen i norra Sverige. Det kan jämföras med den stora industriella omställningen vid 1900-talets början såväl genom att skapa nya möjligheter men också genom de målkonflikter som uppstår mellan nya och befintliga värden, både vad gäller naturförhållanden och ekonomi som kulturvärden och historiska lämningar av mänsklig verksamhet. Omställningen berör platser med en lång historia av mänskligt liv och arbete och som spelar en viktig roll för de som idag bor där och potentiellt för de som söker sig dit för att driva verksamhet eller för att bo, leva och arbeta. I många fall visar det sig svårt att ta denna potential tillvara av skäl som är strukturella, juridiska och politiska snarare än knutna till enskilda aktörer. Artikeln är författad av en multidisciplinär forskargrupp som använder ett praktikbaserat förhållningssätt och samskapande dialog för att undersöka hur förbättrade planeringsprocesser som tidigt involverar olika aktörer, intressen och expertis i förändringsprojekt kan bidra till att lösa målkonflikter och skapa möjligheter. Målkonflikter mellan exploatering och bevarandeintressen i samband med myndigheters och privata aktörers hantering av natur- och kulturmiljöer har länge varit i fokus för forskningen och artikeln syftar till att komplettera dessa perspektiv utifrån exempel som illustrerar möjligheter för att det fysiska kulturarvet ska ses som en strategisk historisk resurs i samhällsutvecklingen. En utgångspunkt är att kulturarv inte är statiskt utan värderas och omvärderas i en process där olika kulturvärden kan associeras med byggnader, platser och miljöer. Dessa kulturvärden förändras alltså över tid, och olika aktörer förhåller sig till dem på skiftande sätt. Genom processer som inbegriper förhandling med andra intressen kan landskap, platser, byggnader, föremål och deras användning förvandlas till kulturarv. Ett samskapande arbetssätt har möjliggjorts genom ett forsknings- och innovationsprojekt, finansierat av Vinnova, vilket genomförts genom en kombinerad metodansats med fallstudier, i projektet kallade lärcase, som ram för empiriska undersökningar och praktiskt genomförande. De lärcase som lyfts i denna artikel är dels Nautanen, en tidigare gruvmiljö i Norrbotten där nyetablering planeras av Boliden AB, dels Kvarnsvedens tidigare pappersbruk i Borlänge, där Northvolt etablerar en fabrik för produktion av bilbatterier vilket medfört rivning av en byggnad med konstaterade kulturhistoriska värden, den så kallade Bobergshallen. Med förslag till fortsatt forskning genom begreppsutveckling i en multidisciplinär och praktiknära kontext problematiserar artikeln begreppet cirkulär ekonomi i relation till kulturarvsfrågor och möjliggör att kulturarvet nyttjas som strategisk resurs i den gröna omställningen med förhoppning att realisera förväntningarna om grön nyindustralisering och attraktiva livsmiljöer.
29.	Axelsson Andrén, Elin, 1988, et al. (författare) Low serum HDL-cholesterol is associated with increased risk of the subcortical small vessel type of dementia 2024 Ingår i: Cerebral Circulation - Cognition and Behavior. - 2666-2450. ; 6 Tidskriftsartikel (refereegranskat)abstract Background: There are conflicting results whether serum lipid pattern is related to the amount of white matter hyperintensities (WMHs) on magnetic resonance imaging. Little is known of the associations between lipid concentrations and the subsequent risk of the subcortical small vessel type of dementia (SSVD), in which WMHs are a prominent manifestation. Here, we determined whether lipid levels are associated with the risk of SSVD, Alzheimer's disease (AD), or mixed dementia (combined AD and SSVD). Methods: This was a longitudinal, prospective study of 329 patients with subjective or objective mild cognitive impairment at baseline. The statistical analyses included Cox proportional hazards regression with adjustments for age, gender, education, body mass index, current smoking, hypertension, diabetes mellitus, and APOE ε4 genotype. Results: During the follow-up (mean 4.1 years), 80 patients converted to dementia [SSVD, n = 15 (5 %); AD, n = 39 (12 %); and mixed dementia, n = 26 (8 %)]. Serum high-density lipoprotein cholesterol (HDL, per SD increase) was inversely associated with the risk of SSVD, whereas triglycerides (TG), low-density lipoprotein cholesterol (LDL)/HDL ratio, and TG/HDL ratio were positively associated with SSVD risk. Furthermore, the lowest HDL tertile was associated with a sevenfold, and the highest tertile of TG/HDL ratio with a threefold, increase in SSVD risk. There were no associations with the risk of AD or mixed dementia after adjustment for covariates. Conclusion: In a memory clinic population, low HDL and high TG/HDL ratio were independent risk factors of SSVD, but not of AD or mixed dementia.
30.	Axelsson, Elin, et al. (författare) Diagnostic Performance of Cerebrospinal Fluid Neurofilament Light Chain and Soluble Amyloid-β Protein Precursor β in the Subcortical Small Vessel Type of Dementia. 2023 Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 96:4, s. 1515-1528 Tidskriftsartikel (refereegranskat)abstract The subcortical small vessel type of dementia (SSVD) is a common subtype of vascular dementia, but there is a lack of disease-specific cerebrospinal fluid (CSF) biomarkers.We investigated whether CSF concentrations of neurofilament light chain (NFL), soluble amyloid-β protein precursor α (sAβPPα), sAβPPβ, and CSF/serum albumin ratio could separate SSVD from healthy controls, Alzheimer's disease (AD), and mixed dementia (combined AD and SSVD).This was a mono-center study of patients with SSVD (n=38), AD (n=121), mixed dementia (n=62), and controls (n=96). The CSF biomarkers were measured using immunoassays, and their independent contribution to the separation between groups were evaluated using the Wald test. Then, the area under the receiver operating characteristics curve (AUROC) and 95% confidence intervals (CIs) were calculated.Elevated neurofilament light chain (NFL) and decreased sAβPPβ independently separated SSVD from controls, and sAβPPβ also distinguished SSVD from AD and mixed dementia. The combination of NFL and sAβPPβ discriminated SSVD from controls with high accuracy (AUROC 0.903, 95% CI: 0.834-0.972). Additionally, sAβPPβ combined with the core AD biomarkers (amyloid-β42, total tau, and phosphorylated tau181) had a high ability to separate SSVD from AD (AUROC 0.886, 95% CI: 0.830-0.942) and mixed dementia (AUROC 0.903, 95% CI: 0.838-0.968).The high accuracy of NFL and sAβPPβ to separate SSVD from controls supports that SSVD is a specific diagnostic entity. Moreover, SSVD was distinguished from AD and mixed dementia using sAβPPβ in combination with the core AD biomarkers.
31.	Axelsson, Elin, et al. (författare) Patients with the Subcortical Small Vessel Type of Dementia Have Disturbed Cardiometabolic Risk Profile 2020 Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 73:4, s. 1373-1383 Tidskriftsartikel (refereegranskat)abstract Background: Population-based studies have shown that cardiometabolic status is associated with the amount of white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI). However, little is known of cardiometabolic risk factors in the subcortical small vessel type of dementia (SSVD), in which WMHs are one of the most prominent manifestations. Objective: To determine whether the profile of cardiometabolic risk factors differed between SSVD, Alzheimer's disease (AD), mixed dementia (combined AD and SSVD), and healthy controls. Methods: This was a mono-center, cross-sectional study of SSVD (n = 40), AD (n = 113), mixed dementia (n = 62), and healthy controls (n = 94). In the statistical analyses, we adjusted for covariates using ANCOVA and binary logistic regression. Results: The prevalence of hypertension was increased in SSVD and mixed dementia (p < 0.001 and p < 0.05 versus controls, respectively). Diabetes was more prevalent in SSVD patients, and body mass index was lower in AD and mixed dementia, compared to the controls (all p < 0.05). Serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) were reduced in the SSVD group (both p < 0.05 versus control). These differences remained after adjustment for covariates. In the SSVD group, Trail Making Test A score correlated positively with systolic blood pressure, mean arterial pressure, and pulse pressure. Conclusion: All dementia groups had an altered cardiometabolic risk profile compared to the controls. The SSVD patients showed increased prevalence of hypertension and diabetes, and in line with previous population-based data, TC and LDL-C in serum were reduced.
32.	Axelsson, Michael, 1958, et al. (författare) Hållning av zebrafisk i försöksdjursanläggningar 2016 Rapport (övrigt vetenskapligt/konstnärligt)
33.	Badr, Sara, 1985, et al. (författare) Combined basic and fine chemical biorefinery concepts with integration of processes at different technology readiness levels 2018 Ingår i: Computer Aided Chemical Engineering. - 1570-7946. ; 43, s. 1577-1582 Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract Biorefineries offer promising alternatives to the use of fossil fuels to produce energy and chemicals. This work describes the development of a biorefinery concept to produce adipic acid from Swedish forest residues and lutein from micro-algae. A description is provided for each process line available, its technology readiness level (TRL) and the tools available to model it. Scenarios of the integrated concept are built with associated material flow analysis. Key results of the material inventory of the base case scenario are presented as well as insights into the development of further scenarios. Material flow inventories can then be further used for economic and environmental assessment. Major challenges of integration are discussed in terms of uncertainties and data gaps for processes with low TRL such as scaling up lab experiments, understanding the restrictions of material recycling and its impact on process performance. The feedback given through these scenarios can help guide further experimental efforts.
34.	Badr, Sara, 1985, et al. (författare) Prospective analysis of an intergrated biorefinery concept for the production of balk and fine chemicals 2018 Ingår i: 23rd International Congress of Chemical and Process Engineering, CHISA 2018 and 21st Conference on Process Integration, Modelling and Optimisation for Energy Saving and Pollution Reduction, PRES 2018. ; 2, s. 737- Konferensbidrag (refereegranskat)
35.	Beiron, Johanna, 1992, et al. (författare) The role of BECCS in providing negative emissions in Sweden under competing interests for forest-based biomass 2022 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Negative emissions are needed to meet climate mitigation targets and can be achieved through the capture and storage of biogenic CO2 emissions (BECCS). Sweden holds a large potential for BECCS from the industry and heat and power sectors. This work provides a first assessment of how the conditions for BECCS in Sweden are impacted by competition for forest-based biomass from other sectors, in this work represented by production of transportation fuels. An optimization model is applied to study how demand levels for negative emissions and biofuels, and availability of forestry resources, influence the optimal system design considering the electricity, district heating and biomass sectors. BECCS and direct air capture technologies are available for investments in the model. The results show that biomass availability and biofuel demand have a large impact on the choice of negative emission technology, where high competition for biomass favours DACCS rather than BECCS. The available biomass is prioritized for use in fuel production and sets the upper limit for BECCS. In this work, CHP plants are more competitive for BECCS implementation than pulp mills, due to the energy penalty for CHP plants having a smaller impact on the overall energy system performance. The findings indicate that in addition to considering techno-economic assessments of individual technologies, it is important to take into account the system context in which they operate.
36.	Bengtsson, Fredrik, 1989, et al. (författare) A new method of scaling the gramian based input-output pairing methods for improved results 2018 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract A key problem in the application of process control systems is to decide which inputs should control which outputs. There are multiple ways to solve this problem, among them using gramian based measures, which include the Hankel interaction index array, the participation matrix and the Σ2 method. These methods take into account system dynamics as opposed to many other methods which only consider the steady-state system. However, the gramian based methods have issues with input and output scaling. Generally, this is resolved by scaling all inputs and outputs to have equal range. We will, however, demonstrate how this can result in an incorrect pairing. Further, we examine scaling of the gramian based measures, using either row or column sums, or by utilizing the Sinkhorn-Knopp algorithm instead. Then, to more systematically analyze the benefits of the scaling schemes, a multiple input multiple output model generator is used to test the different schemes on a large number of systems. This, along with implementation of automatic controller tuning, allows for a statistical comparison of the scaling methods. This assessment shows considerable benefits to be gained from the alternative scaling of the gramian based measures, especially when using the Sinkhorn-Knopp algorithm. The use of this method also has the advantage that the results are completely independent of the original scaling of the inputs and outputs.
37.	Bengtsson, Fredrik, 1989, et al. (författare) Assessing the Controllability of Heat Exchanger Networks 2016 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
38.	Bengtsson, Fredrik, 1989, et al. (författare) Resolving Issues of Scaling for Gramian Based Input-Output Pairing Methods 2018 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
39.	Bengtsson, Fredrik, 1989, et al. (författare) Resolving issues of scaling for gramian-based input–output pairing methods 2022 Ingår i: International Journal of Control. - : Informa UK Limited. - 0020-7179 .- 1366-5820. ; 95:3, s. 679-691 Tidskriftsartikel (refereegranskat)abstract A key problem in process control is to decide which inputs should control which outputs. There are multiple ways to solve this problem, among them using gramian-based measures, which include the Hankel interaction index array, the participation matrix and the (Formula presented.) method. The gramian-based measures, however, have issues with input and output scaling. Generally, this is resolved by scaling all inputs and outputs to have equal range. However, we demonstrate how this can result in an incorrect pairing and examine alternative methods of scaling the gramian-based measures, using either row or column sums or by utilising the Sinkhorn-Knopp algorithm. To systematically analyse the benefits of the scaling schemes, a multiple-input multiple-output model generator is used to test the different schemes on a large number of systems. This assessment shows considerable benefits to be gained from the alternative scaling of the gramian-based measures, especially when using the Sinkhorn-Knopp algorithm.
40.	Bergman, Elin, et al. (författare) Dabigatran in clinical practice - One-year experience at Skåne University Hospital. 2013 Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 132:2, s. 316-317 Tidskriftsartikel (refereegranskat)
41.	Beyer, Luisa I., et al. (författare) Mimicking Nonribosomal Peptides from the Marine Actinomycete Streptomyces sp. H-KF8 Leads to Antimicrobial Peptides 2023 Ingår i: ACS Infectious Diseases. - 2373-8227. ; 10:1, s. 79-92 Tidskriftsartikel (refereegranskat)abstract Microorganisms within the marine environment have been shown to be very effective sources of naturally produced antimicrobial peptides (AMPs). Several nonribosomal peptides were identified based on genome mining predictions of Streptomyces sp. H-KF8, a marine Actinomycetota isolated from a remote Northern Chilean Patagonian fjord. Based on these predictions, a series of eight peptides, including cyclic peptides, were designed and chemically synthesized. Six of these peptides showed antimicrobial activity. Mode of action studies suggest that two of these peptides potentially act on the cell membrane via a novel mechanism allowing the passage of small ions, resulting in the dissipation of the membrane potential. This study shows that though structurally similar peptides, determined by NMR spectroscopy, the incorporation of small sequence mutations results in a dramatic influence on their bioactivity including mode of action. The qualified hit sequence can serve as a basis for more potent AMPs in future studies.
42.	Blomquist, Caroline, 1966- (författare) Metabolic consequences of a Paleolithic diet in obese postmenopausal women 2017 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract BackgroundObesity, in particular abdominal adiposity, is associated with elevated fatty acids and pro-inflammatory adipokines, which are linked to ectopic fat storage and insulin resistance. During menopause, there is a redistribution of fat from the peripheral to abdominal depots. This transition is associated with an increased risk of type 2 diabetes and cardiovascular diseases. We hypothesized that a Paleolithic diet, with high proportions of lean meat, fish, vegetables, fruits, and oils, but devoid of dairy products and cereals, might have long-term beneficial effects on inflammation, fat metabolism, and circulating fatty acids. These effects might potentially reduce the risk of metabolic complications in postmenopausal women that are obese. MethodsPostmenopausal women with obesity were studied before, after six months, and after 24 months of one of two specified ad libitum diets. One diet was a Paleolithic diet, in which approximately 30% of the total energy (E%) was protein, 30 E% was fat, and 40 E% was carbohydrate. The other diet was a prudent control diet, consistent with Nordic Nutrition recommendations of 15 E% protein, 25 E% fat, and 55 E% carbohydrate. Dietary intakes of polyunsaturated fatty acids and protein were validated objectively by measuring circulating and urinary biomarkers. Anthropometrics and diet reports were analyzed, and abdominal subcutaneous fat samples were evaluated for the expression of proteins key in inflammation and fat metabolism and for lipoprotein lipase mass and activity. In addition, blood samples were analyzed to determine concentrations of specific serum proteins, serum lipids, and the fatty acids carried in cholesterol esters.ResultsThe Paleolithic diet group reported reduced intakes of saturated fatty acids and carbohydrates and elevated intakes of protein and unsaturated fatty acids, compared to baseline. The elevated intakes of polyunsaturated fatty acids and protein were objectively verified for this group. After 24 months, both diets were found to have beneficial effects on the expression of inflammation-related genes in adipose tissue and pro-inflammatory factors in the circulation. Compared to the control group, the Paleolithic diet group exhibited more pronounced reductions of circulating cardiometabolic risk factors, including the ratio of triglycerides to high density lipoprotein, lipogenic index, specific fatty acids, and indices of desaturase activities. After six months, the Paleolithic group also exhibited more pronounced reductions in lipogenesis-promoting factors, including the expression of key proteins in fat synthesis, the activity of lipoprotein lipase, and the activity of stearoyl-CoA desaturase 1, compared to the control group.ConclusionLong-term weight loss in postmenopausal obese women was accompanied by reductions in low-grade inflammation in adipose tissue and in the circulation. In addition, a Paleolithic diet, with a high content of unsaturated fatty acids and a low content of refined carbohydrates, appeared to provide greater reductions in cardiometabolic risk factors associated with insulin resistance and lipogenesis, compared to a prudent control diet.
43.	Bokinge, Pontus, et al. (författare) Effects of process decarbonisation on future targets for excess heat delivery from an industrial process plant 2020 Ingår i: Eceee Industrial Summer Study Proceedings. - 2001-7987 .- 2001-7979. - 9789198387865 ; 2020-September, s. 233-242 Konferensbidrag (refereegranskat)abstract The use of industrial excess heat for purposes such as district heating has the potential to contribute to societal targets for energy efficiency and greenhouse gas emissions reduction. However, to meet the ambitious national and international climate targets set for 2050, a breadth of different decarbonisation pathways are required, not least in the industrial sector. These include a transition to bio-based and recycled feedstock and fuels, carbon capture and storage, and electrification. Such profound changes of industrial processes and energy systems are likely to affect the availability of excess heat from these plants, and a better understanding of how the excess heat potentials might change is needed in order to utilise excess heat in ways that can be resource-efficient also in the long-term. In this paper, we present a systematic approach which can be used to analyse how different decarbonisation options may affect the potential future availability of excess heat at a specific plant site. The approach is based on the use of consistent, energy targeting methods based on pinch analysis tools, and therefore relies on comprehensive data about process heating and cooling demands. To illustrate the approach, we demonstrate results from two industrial case studies in which different decarbonisation measures are assumed to be implemented. The case studies were selected from a case study portfolio, which includes relevant and site-specific process and energy data for a large share of Swedish industrial process sites. The results show that deep decarbonisation can have significant impact on the availability and temperature profile of industrial excess heat, illustrating the importance of accounting for future process development when estimating excess heat potentials.
44.	Bonhivers, Jean-Christophe, et al. (författare) Comparison between pinch analysis and bridge analysis to retrofit the heat exchanger network of a kraft pulp mill 2014 Ingår i: Applied Thermal Engineering. - : Elsevier BV. - 1359-4311. ; 70:1, s. 369-379 Tidskriftsartikel (refereegranskat)abstract Pinch analysis is based on the hot, cold and grand composite curves and is the most commonly-used approach to identify strategies for reducing energy consumption by heat exchanger network retrofit. This method was originally developed for the synthesis of new networks, and there remain certain difficulties for its application to improve existing networks. The advanced composite curves have been developed for retrofit situations specifically, and use data about existing heat exchangers to provide more information about the modifications necessary to achieve heat savings. Bridge analysis, which is based on the energy transfer diagram, is a new method and enumerates the sets of heat transfer modifications necessary to save energy. In this paper, the grand composite curve, the advanced composite curves and the energy transfer diagram have been constructed for analysis of the heat exchanger network of a kraft pulp mill. Links between these methods are made explicit; then results are discussed and compared. It is shown that the information provided by these approaches is consistent; however, the level of detail progressively increases from the grand composite curve to the advanced composite curves until the energy transfer diagram. Fundamentally, reducing the energy consumption implies decreasing the flow rate of heat cascaded through the network from the hot utility until the environment. As a consequence, any heat savings solution includes network modifications bridging coolers to heaters. Traditional pinch analysis does not provide information about the network modifications required after removal of cross-pinch transfers, while the advanced composite curves indicate the heat savings potential attainable through modifications of few existing heat exchanger units. Bridge analysis provides more detail about heat savings modifications, which bridge existing heaters and coolers, than traditional pinch analysis and the advanced composite curves do.
45.	Bonhivers, Jean-Christophe, et al. (författare) Comparison between the grand composite curve, advanced composite curves and energy transfer diagram for heat exchanger network retrofit 2014 Ingår i: 21st International Congress of Chemical and Process Engineering, CHISA 2014 and 17th Conference on Process Integration, Modelling and Optimisation for Energy Saving and Pollution Reduction, PRES 2014. - 9781510828131 ; 4, s. 2180-2180 Konferensbidrag (refereegranskat)
46.	Bonhivers, Jean-Christophe, et al. (författare) Energy Transfer Diagram for Site-Wide Analysis and Application to a Kraft Pulp Mill 2015 Ingår i: Applied Thermal Engineering. - : Elsevier BV. - 1359-4311. ; 75, s. 547-560 Tidskriftsartikel (refereegranskat)abstract In industrial processes, heat is transferred from the heating utilities to the environment or converted to another form of energy. Process operations and heat exchanges decrease the level of energy quality; i.e., heat is cascaded to lower temperatures. The energy transfer diagram (ETD), which has been recently developed, indicates the flow rate of heat transferred from the utilities to the environment through each process operation and each heat exchanger as a function of temperature. This tool can be used to identify heat savings projects by modification of the process units and the heat-exchanger network (HEN). However, in a larger sense the diagram indicates the flow rate of energy transferred through any system as a function of the level of energy quality, and can be used for the analysis of a complete plant, including the thermal, chemical, mechanical and electrical transformations. This paper presents new developments to consider energy conversion with the ETD, the application to an entire kraft pulp mill, including the HEN, the process operations, and the utility system, and results from site-wide analysis.
47.	Brill, Margreke JE, et al. (författare) Confirming model-predicted pharmacokinetic interactions between bedaquiline and lopinavir/ritonavir or nevirapine in patients with HIV and drug resistant tuberculosis 2017 Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 0924-8579 .- 1872-7913. ; 49, s. 212-217 Tidskriftsartikel (refereegranskat)abstract Bedaquiline and its metabolite M2 are metabolised by CYP3A4. The antiretrovirals ritonavir-boosted lopinavir (LPV/r) and nevirapine inhibit and induce CYP3A4, respectively. Here we aimed to quantify nevirapine and LPV/r drug–drug interaction effects on bedaquiline and M2 in patients co-infected with HIV and multidrug-resistant tuberculosis (MDR-TB) using population pharmacokinetic (PK) analysis and compare these with model-based predictions from single-dose studies in subjects without TB. An observational PK study was performed in three groups of MDR-TB patients during bedaquiline maintenance dosing: HIV-seronegative patients (n = 17); and HIV-infected patients using antiretroviral therapy including nevirapine (n = 17) or LPV/r (n = 14). Bedaquiline and M2 samples were collected over 48 h post-dose. A previously developed PK model of MDR-TB patients was used as prior information to inform parameter estimation using NONMEM. The model was able to describe bedaquiline and M2 concentrations well, with estimates close to their priors and earlier model-based interaction effects from single-dose studies. Nevirapine changed bedaquiline clearance to 82% (95% CI 67–99%) and M2 clearance to 119% (92–156%) of their original values, indicating no clinically significant interaction. LPV/r substantially reduced bedaquiline clearance to 25% (17–35%) and M2 clearance to 59% (44–69%) of original values. This work confirms earlier model-based predictions of nevirapine and LPV/r interaction effects on bedaquiline and M2 clearance from subjects without TB in single-dose studies, in MDR-TB/HIV co-infected patients studied here. To normalise bedaquiline exposure in patients with concomitant LPV/r therapy, an adjusted bedaquiline dosing regimen is proposed for further study.
48.	Bucardo, Filemon, et al. (författare) Genetic susceptibility to symptomatic norovirus infection in Nicaragua. : norovirus susceptibility in Nicaragua 2009 Ingår i: Journal of medical virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 81:4, s. 728-35 Tidskriftsartikel (refereegranskat)abstract Host genetic resistance to Norovirus (NoV) has been observed in challenge and outbreak studies in populations from Europe, Asia, and USA. In this study, we have investigated if histo-blood group antigens can predict susceptibility to diarrhea caused by NoV in Nicaragua, Central America, and if this can be reflected in antibody-prevalence and titer to NoV among individuals with different histo-blood group antigen phenotypes. Investigation of 28 individuals infected with NoV and 131 population controls revealed 6% of non-secretors in the population and nil non-secretors among patients infected with NoV, suggesting that non-secretors may be protected against NoV disease in Nicaragua. Surprisingly, 25% of the population was Lewis negative (Le(a-b-)). NoV infections with genogroup I (GI) and GII occurred irrespective of Lewis genotype, but none of the Lewis a positive (Le(a + b-)) were infected. The globally dominating GII.4 virus infected individuals of all blood groups except AB (n = 5), while the GI viruses (n = 4) infected only blood type O individuals. Furthermore, O blood types were susceptible to infections with GI.4, GII.4, GII.7, GII.17, and GII.18-Nica viruses, suggesting that secretors with blood type O are susceptible (OR = 1.52) and non-secretors resistant. The overall antibody-prevalence to NoV GII.3 VLP was 62% with the highest prevalence among blood type B carriers (70%) followed by A (68%) and O (62%). All four investigated individuals carrying blood type AB were antibody-negative. Among secretors, 63% were antibody-positive compared to 33% among non-secretors (P = 0.151). This study extends previous knowledge about the histo-blood group antigens role in NoV disease in a population with different genetic background than North American and European.
49.	Bucardo, Filemon, et al. (författare) Genetic susceptibility to symptomatic norovirus infection in Nicaragua 2009 Ingår i: Journal of Medical Virology. - : John Wiley & Sons. - 0146-6615 .- 1096-9071. ; 81:4, s. 728-735 Tidskriftsartikel (refereegranskat)abstract Host genetic resistance to Norovirus (NoV) has been observed in challenge and outbreak studies in populations from Europe, Asia, and USA. In this study, we have investigated if histo-blood group antigens can predict susceptibility to diarrhea caused by NoV in Nicaragua, Central America, and if this can be reflected in antibody-prevalence and titer to NoV among individuals with different histo-blood group antigen phenotypes. Investigation of 28 individuals infected with NoV and 131 population controls revealed 6% of non-secretors in the population and nil non-secretors among patients infected with NoV, suggesting that non-secretors may be protected against NoV disease in Nicaragua. Surprisingly, 25% of the population was Lewis negative (Le(a-b-)). NoV infections with genogroup I (GI) and GII occurred irrespective of Lewis genotype, but none of the Lewis a positive (Le(a + b-)) were infected. The globally dominating GII.4 virus infected individuals of all blood groups except AB (n = 5), while the GI viruses (n = 4) infected only blood type O individuals. Furthermore, O blood types were susceptible to infections with GI.4, GII.4, GII.7, GII.17, and GII.18-Nica viruses, suggesting that secretors with blood type O are susceptible (OR = 1.52) and non-secretors resistant. The overall antibody-prevalence to NoV GII.3 VLP was 62% with the highest prevalence among blood type B carriers (70%) followed by A (68%) and O (62%). All four investigated individuals carrying blood type AB were antibody-negative. Among secretors, 63% were antibody-positive compared to 33% among non-secretors (P = 0.151). This study extends previous knowledge about the histo-blood group antigens role in NoV disease in a population with different genetic background than North American and European.
50.	Bukkems, Vera E., et al. (författare) A population pharmacokinetics analysis assessing the exposure of raltegravir once-daily 1200 mg in pregnant women living with HIV 2021 Ingår i: CPT. - : John Wiley & Sons. - 2163-8306. ; 10:2, s. 161-172 Tidskriftsartikel (refereegranskat)abstract Once-daily two 600 mg tablets (1200 mg q.d.) raltegravir offers an easier treatment option compared to the twice-daily regimen of one 400 mg tablet. No pharmacokinetic, efficacy, or safety data of the 1200 mg q.d. regimen have been reported in pregnant women to date as it is challenging to collect these clinical data. This study aimed to develop a population pharmacokinetic (PopPK) model to predict the pharmacokinetic profile of raltegravir 1200 mg q.d. in pregnant women and to discuss the expected pharmacodynamic properties of raltegravir 1200 mg q.d. during pregnancy based on previously reported concentration-effect relationships. Data from 11 pharmacokinetic studies were pooled (n = 221). A two-compartment model with first-order elimination and absorption through three sequential transit compartments best described the data. We assessed that the bio-availability of the 600 mg tablets was 21% higher as the 400 mg tablets, and the bio-availability in pregnant women was 49% lower. Monte-Carlo simulations were performed to predict the pharmacokinetic profile of 1200 mg q.d. in pregnant and nonpregnant women. The primary criteria for efficacy were that the lower bound of the 90% confidence interval (CI) of the concentration before next dose administration (C-trough) geometric mean ratio (GMR) of simulated pregnant/nonpregnant women had to be greater than 0.75. The simulated raltegravir C-trough GMR (90% CI) was 0.51 (0.41-0.63), hence not meeting the primary target for efficacy. Clinical data from two pregnant women using 1200 mg q.d. raltegravir showed a similar C-trough ratio pregnant/nonpregnant. Our pharmacokinetic results support the current recommendation of not using the raltegravir 1200 mg q.d. regimen during pregnancy until more data on the exposure-response relationship becomes available.

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