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1.	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.
2.	Gad, Helge, et al. (författare) MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool 2014 Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221 Tidskriftsartikel (refereegranskat)abstract Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
3.	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.
4.	Svensson, Ann, 1962-, et al. (författare) Assessing the business value of electronic order-to-payment cycle 2009 Ingår i: ECIS 2009 Proceedings. Konferensbidrag (refereegranskat)abstract In this paper, we build an evaluation tool for assessing the business impacts of an electronic order-topayment cycle. Based on a literature review and expert interviews, we formulate a three-stage model which includes performance indicators for electronic order, electronic invoice, and electronic payment processes. In addition, we pinpoint the inter-process linkages. We test the proposed evaluation tool in a business context and find that the impacts of automating the order-to-payment cycle relate closely to cost avoidance. However, a strong emphasis on asset utilization can be observed as well â€“ better use of IT could enhance utilization of existing human resources and capital, affecting company profitability.
5.	Svensson, Ann, 1962-, et al. (författare) Attitudes to Information Technology Among Health Care Professions 2009 Ingår i: the 17<sup>th</sup> European Conference on Information Systems, Verona, Italy, June 8-10. Konferensbidrag (refereegranskat)
6.	Svensson, Ann, 1962-, et al. (författare) Attitudes to information technology in health care professions 2009 Ingår i: The 17th European Conference on Information Systems, Verona, june 8-10, 2009.. Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract The purpose of this paper is to explore attitudes towards IT among various categories of health care staff; health care professions. We will identify problem areas that may be the reasons for why different attitudes among different professions at a healthcare organisation exist, and subsequently we will analyse how this may have impact on how to make sense of IT use. The research question is: What factors may explain differences regarding attitudes to IT among different professions in a health care organisation?The paper reports from a particular study of the “NU” healthcare organisation in west Sweden. The results reveal two main problem areas: i) the infrastructural and; ii) the socio-organisational. These are discussed as analytical implications for bridging the gaps between different professions in health care organisations.
7.	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.
8.	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.
9.	Ahlbeck Bergendahl, Ida, et al. (författare) Fisk- och skaldjursbestånd i hav och sötvatten 2016 : Resursöversikt 2016 Rapport (övrigt vetenskapligt/konstnärligt)abstract I rapporten kan du ta del av bedömningen som görs av situationen för bestånd som regleras inom ramen för EU:s gemensamma fiskeripolitik (GFP). Bedömningarna baseras på det forskningssamarbete och den rådgivning som sker inom det Internationella Havsforskningsrådet (ICES).De bestånd som förvaltas nationellt baseras på de biologiska underlagen, och rådgivningen i huvudsak på den forskning och övervakning samt analys som bedrivs av Institutionen för akvatiska resurser vid Sveriges lantbruksuniversitet (SLU Aqua) samt yrkesfiskets rapportering.Rapporten omfattar 41 fiskarter uppdelade i olika bestånd, samt sju skal- och blötdjursarter.Nytt för årets upplaga är kapitlet om ekosystemtjänster. Avsnittet beskriver de fördelar människan får genom ekosystemen, till exempel hur fisk och skaldjur kommer till nytta för människan genom föda, rekreation och biologisk mångfald. Nytt för i år är också att rapportens diagram och figurer anpassats för läsare med defekt färgseende.Översikten är utarbetad av SLU Aqua på uppdrag av Havs- och vattenmyndigheten.
10.	Ahlbeck Bergendahl, Ida, et al. (författare) Fisk- och skaldjursbestånd i hav och sötvatten 2017 : resursöversikt 2018 Rapport (övrigt vetenskapligt/konstnärligt)
11.	Ahlbeck Bergendahl, Ida, et al. (författare) Fisk- och skaldjursbestånd i hav och sötvatten 2017 : Resursöversikt 2017 Rapport (övrigt vetenskapligt/konstnärligt)abstract I rapporten kan du ta del av bedömningen som görs av situationen för bestånd som regleras inom ramen för EU:s gemensamma fiskeripolitik (GFP). Bedömningarna baseras på det forskningssamarbete och den rådgivning som sker inom det Internationella Havsforskningsrådet (ICES).De bestånd som förvaltas nationellt baseras på de biologiska underlagen, och rådgivningen i huvudsak på den forskning och övervakning samt analys som bedrivs av Institutionen för akvatiska resurser vid Sveriges lantbruksuniversitet (SLU Aqua) samt yrkesfiskets rapportering.Rapporten omfattar 41 fiskarter och sju skaldjursarter.Nytt för i år är att vi även beskriver fritidsfisket mer utförligt. Det fisket får allt större betydelse för utvecklingen av många av Sveriges bestånd av fisk- och skaldjur, till exempel sötvattens- och kustlevande arter som abborre, gädda, gös, lax, röding och öring, liksom marina arter som torsk och hummerÖversikten är utarbetad av SLU Aqua på uppdrag av Havs- och vattenmyndigheten.
12.	Alhadi Alhasani, Huda, et al. (författare) ’Vi’ och ’dom’ – Sociopolitiska dimensionerav matematikutbildning där olika språkoch kulturer möts 2022 Ingår i: Matematikundervisningenssociopolitiska utmaningar. - Stockholm : Stockholm University Press. - 9789176351994 - 9789176351987 ; , s. 299-321 Bokkapitel (refereegranskat)abstract Bokens kapitel utgör viktiga bidrag i en kritisk granskning av svenskmatematikutbildning utifrån sociopolitiska samhällsperspektiv. Motbakgrund av bokens olika kapitel belyser vi upplevelser och konsekvenser av att konstrueras som den andre i svensk matematikutbildning.Med hjälp av begreppet andrafiering synliggör vi författare till dettakapitel tillsammans ’dom andra’ och deras erfarenheter i relation tillmigration och matematikutbildning. Vi som författat detta kapitel, tvånyutexaminerade lärare och två forskare, har därför ingått en så kalladallians. Vårt kapitel visar hur matematikutbildning bidrar till processerav andrafiering och skapandet av den andra och hur dessa processerpåverkar flerspråkiga elevers och lärarstudenters identitetsskapandeoch därmed även deras möjligheter att lära matematik. Flerspråkighetbehöver synliggöras och normaliseras. Alla elevers och lärarstudentersspråk och kulturer måste få ta plats, inte som exotiska inslag av kulturella uttryck utan som en del av den ordinarie matematikutbildningen.
13.	Allenström, Björn, et al. (författare) The interaction of large and high-speed vessels with the environment in archipelagos - Final report.” SSPA Research Report No 122 2003 Rapport (övrigt vetenskapligt/konstnärligt)
14.	Alm Bergvall, Ulrika, et al. (författare) Vigilance adjustments in relation to long- and short term risk in wild fallow deer (Dama dama) 2016 Ingår i: Behavioural Processes. - : Elsevier BV. - 0376-6357 .- 1872-8308. ; 128, s. 58-63 Tidskriftsartikel (refereegranskat)abstract The risk allocation hypothesis predicts that vigilance should be adjusted to the temporal variation in risk. We test this hypothesis in wild fallow deer exposed to short term (disturbance) and long term (presence of a fawn after parturition) changes in risk. We recorded the proportion, frequency and type of vigilance and size of used area before and after parturition, in GPS-collared wild female fallow deer. Vigilance was divided in two main groups: non-grazing vigilance and grazing vigilance. The latter group was divided into grazing vigilance while chewing and a grazing vigilance when chewing was interrupted. By recording external disturbance in form of passing cars, we were able to investigate if this altered the amount, and type of vigilance. We found that females increased the proportion and frequency of grazing vigilance stop chewing after parturition. The grazing vigilance chewing was unaffected, but non-grazing vigilance decreased. Disturbance increased the proportion grazing vigilance stop chewing to the same extent before and after parturition. We found a clear decrease in female home range size after parturition as a possible behavioural adjustment. The increase in grazing vigilance stop chewing after parturition is a rarely described but expected cost of reproduction.
15.	Alopaeus, Tea, et al. (författare) Med de nya svenska klimatmålen i sikte : Gapanalys samt strategier och förutsättningar för att nå etappmålen 2030 med utblick mot 2045 2017 Rapport (övrigt vetenskapligt/konstnärligt)abstract Under våren 2017 presenterade Naturvårdsverket scenarier för hur växthusgasutsläppen i Sverige skulle kunna utvecklas till 2035. Sedan Naturvårdsverket presenterade scenarierna har ett nytt klimatpolitiskt ramverk för Sverige beslutats av riksdagen med nya klimatmål till 2030, 2040 och 2045. Regeringen har även presenterat ett antal nya styrmedel i budgetpropositionen.Naturvårdsverket ska inom miljömålssystemet löpande och strategiskt analysera och utvärdera styrmedel och åtgärder. Naturvårdsverket har mellan maj och november 2017 gjort en första uppföljning mot de nya klimatmålen. I denna rapport presenteras hur beslutade och planerade styrmedel kan komma att falla ut givet olika antagande. En översiktlig analys av styrmedel görs också.Arbetsgruppens sammansättning har varierat över tid. Sammantaget har följande personer på Naturvårdsverket deltagit i arbetsgruppen: Tea Alopaeus (projektledare), Björn Boström, Mats Björsell, Martin Boije, Joanna Dickinson, Dag Henning, Daniel Engström Stenson, Eva Jernbäcker (projektledare till september), Julien Morel, Miriam Münnich Vass, Karl-Anders Stigzelius, Ulrika Svensson, Per Wollin.Stockholm 29 november 2017Björn RisingerGeneraldirektör
16.	Andersson, Ulrika, et al. (författare) Våld mot kvinnor och straffrätt 2011 Ingår i: På vei: kjønn og rett i Norden. Bokkapitel (refereegranskat)
17.	Anzén, Ulrika, et al. (författare) Årsbok 2016 : Socialhögskolan, Lunds universitet 2017 Rapport (övrigt vetenskapligt/konstnärligt)abstract Denna årsbok presenterar Socialhögskolans verksamhet för 2016och in mot 2017.
18.	Ashton, M, et al. (författare) Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat 1999 Ingår i: Xenobiotica. - : Informa UK Limited. - 0049-8254 .- 1366-5928. ; 29:2, s. 195-204 Tidskriftsartikel (refereegranskat)abstract 1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg(-1)) or i.p. (50 mg.kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95 % confidence interval: 10.4, 13.0) l.h(-1).kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) I.h(-1).kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was similar to 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8+/-2.0%) compared with the female rat (11.7+/-2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.
19.	Axling, Ulrika, et al. (författare) The Effect of Lactobacillus plantarum299v on Iron Status and Physical Performance in Female Iron-Deficient Athletes : A Randomized Controlled Trial 2020 Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 12:5 Tidskriftsartikel (refereegranskat)abstract Iron is an essential micronutrient for oxygen transport and mitochondrial metabolism and is critical for physical performance. Compromised iron stores are more commonly found among athletes, and females are especially at risk. Iron deficiency is generally treated using oral iron supplements. However, only a small proportion of ingested iron is absorbed, necessitating higher intakes, which may result in adverse side effects, reduced compliance, and inefficient repletion of iron stores. The probiotic strainLactobacillus plantarum299v (Lp299v) significantly increases intestinal iron absorption in meal studies. The present study was conducted to explore the effects of 20 mg of iron with or without Lp299v on iron status, mood state, and physical performance. Fifty-three healthy non-anemic female athletes with low iron stores (ferritin < 30 mu g/L) were randomized, and 39 completed the study. Intake of Lp299v with iron for four weeks increased ferritin levels more than iron alone (13.6 vs. 8.2 mu g/L), but the difference between the groups was not significant (p= 0.056). The mean reticulocyte hemoglobin content increased after intake of Lp299v compared to control (1.5 vs. 0.82 pg) after 12 weeks, but the difference between the group was not significant (p= 0.083). The Profile of Mood States (POMS) questionnaire showed increased vigor with Lp299v vs. iron alone after 12 weeks (3.5 vs. 0.1,p= 0.015). No conclusive effects on physical performance were observed. In conclusion, Lp299v, together with 20 mg of iron, could result in a more substantial and rapid improvement in iron status and improved vigor compared to 20 mg of iron alone. A larger clinical trial is needed to further explore these findings as well as the impact of Lp299v on physical performance.
20.	Bejerholm, Ulrika, et al. (författare) From national incentives of implementing Individual Placement and Support to the impact on the service users' quality of life, and view on support 2015 Ingår i: ENMESH 2015 : Eleventh International Conference of the European Network For Mental Health Service Research; Closing the gap between research and policy in mental health. - : ENMESH. ; , s. 153-154 Konferensbidrag (refereegranskat)abstract Introduction: It is a challenge to translate evidence-based-research into practice in a way that meets the needs of the service users. The effectiveness of the IPS vocational rehabilitation approach in terms of gaining competitive employment is well known. During the last three years, IPS has been widely implemented in Community Mental Health Service in Sweden, with financial support from the government. Within this context, we aimed to investigate the benefits of IPS as experienced by some of the serviceusers in addition to them increasing their job opportunities.Methods: Based on a one group pre-test and post-test design (one year), we administered instruments targeting activity and community integration (POES-S) and quality of life (MANSA) among 117 service users from four sites. We also addressed their satisfactionwith the IPS service (MY VIEW) and therapeutic relationship with the IPS-employment specialist (STAR) after one year. Descriptive and comparative statistics were applied.Results: Significant differences and increase of scores were found between measurement points with regard to both activity and community integration and quality of life. Satisfaction with service and therapeutic relationships were scored well above the midpoint of the scales after one year.Conclusions: The results indicate that national incentives to implement IPSbenefits the way of life of the users and is a valued service.
21.	Benetou, V, et al. (författare) Mediterranean diet and incidence of hip fractures in a European cohort 2013 Ingår i: Osteoporosis International. - : Springer London. - 0937-941X .- 1433-2965. ; 24:5, s. 1587-1598 Tidskriftsartikel (refereegranskat)abstract Prevention of hip fractures is of critical public health importance. In a cohort of adults from eight European countries, evidence was found that increased adherence to Mediterranean diet, measured by a 10-unit dietary score, is associated with reduced hip fracture incidence, particularly among men. INTRODUCTION: Evidence on the role of dietary patterns on hip fracture incidence is scarce. We explored the association of adherence to Mediterranean diet (MD) with hip fracture incidence in a cohort from eight European countries. METHODS: A total of 188,795 eligible participants (48,814 men and 139,981 women) in the European Prospective Investigation into Cancer and nutrition study with mean age 48.6 years (±10.8) were followed for a median of 9 years, and 802 incident hip fractures were recorded. Diet was assessed at baseline through validated dietary instruments. Adherence to MD was evaluated by a MD score (MDs), on a 10-point scale, in which monounsaturated were substituted with unsaturated lipids. Association with hip fracture incidence was assessed through Cox regression with adjustment for potential confounders. RESULTS: Increased adherence to MD was associated with a 7 % decrease in hip fracture incidence [hazard ratio (HR) per 1-unit increase in the MDs 0.93; 95 % confidence interval (95 % CI) = 0.89-0.98]. This association was more evident among men and somewhat stronger among older individuals. Using increments close to one standard deviation of daily intake, in the overall sample, high vegetable (HR = 0.86; 95 % CI = 0.79-0.94) and high fruit (HR = 0.89; 95 % CI = 0.82-0.97) intake was associated with decreased hip fracture incidence, whereas high meat intake (HR = 1.18; 95 % CI = 1.06-1.31) with increased incidence. Excessive ethanol consumption (HR high versus moderate = 1.74; 95 % CI = 1.32-2.31) was also a risk factor. CONCLUSIONS: In a prospective study of adults, increased adherence to MD appears to protect against hip fracture occurrence, particularly among men.
22.	Bergkvist, Linda, et al. (författare) Motivationsfaktorer i projekt 2003 Rapport (refereegranskat)abstract Uppsatsen syftar till att undersöka vilka motivationsfaktorer som projektmedlemmen upplever i projektarbetsformen. Vårt intresse för forskningsområdet grundar sig i att projektdeltagarnas motivation anses vara en viktig drivkraft vid projektarbete (Jansson & Ljung, 2002) och vi såg det därför som viktigt att belysa ämnet utifrån projektmedlemmens perspektiv. Vi inriktade oss på kundorderprojekt i IT-branschen och fokuserade undersökningen på de operativa deltagarna i projektarbetsformen. Vår forskningsfråga lyder: Vad, specifikt för projekt-arbetsformen, blir projektmedlemmen motiverad av i sitt projektarbete? För att besvara denna fråga genomförde vi en kvalitativ studie med en abduktiv ansats. Vår undersökning påbörjades genom litteraturstudier i etablerade motivationsteorier som vi sedan kopplade till projektarbetsformens karakteristika. Detta ledde oss fram till nio motivations-faktorer som vi ansåg specifika för projektarbetsformen. Relevansen för dessa undersöktes sedan genom intervjuer med respondenter från två olika IT-företag i Karlstad. Utifrån analysen av vår empiriska undersökning samt vår litteraturstudie kom vi fram till att av de ursprungliga motivationsfaktorerna är följande fem specifika för projektarbetsformen: projektmål, arbetsuppgifter, personliga mål, självförverkligande och samhörighet. Projektmål är motiverande då de är nära relaterade till projektmedlemmen, framtagna genom diskussioner inom projektgruppen samt accepterade av projektmedlemmarna. Projektmedlemmen blir motiverad av att få nya arbetsuppgifter som leder till utveckling inom eget kompetens- och intresseområde. Dessutom är det motiverande att få ta eget ansvar för hur uppgiften ska lösas. Personliga mål är motiverande i projekt då de är kopplade till den enskilde projekt-medlemmens kompetensutveckling. Projektmedlemmen uppnår självförverkligande i projekt genom att få lagom svåra arbets-uppgifter, personlig kompetensutveckling och bekräftelse. Samhörighet gynnar mer projektet som helhet än den enskilde projektmedlemmens motivation. Trots detta uppger majoriteten av respondenterna samhörighet som den viktigaste motivationsfaktorn i projektarbetsformen. Vår slutsats är därmed att då projektmedlemmen känner ett stort personligt ansvar för projektet bidrar det till att det som gynnar projektet som helhet också gynnar den personliga motivationen.
23.	Bergmark, Magnus, et al. (författare) Complex Interventions and Interorganisational Relationships : Examining Core Implementation Components of Assertive Community Treatment 2018 Ingår i: International Journal of Integrated Care. - : Ubiquity Press. - 1568-4156 .- 1568-4156. ; 18:4, s. 1-11 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Introduction: There is increasing interest in implementing evidence-based integrated models of care in community-based mental health service systems. Assertive Community Treatment (ACT) is seen as an attractive, and at the same time challenging, model to implement in sectored service settings. This study investigates the implementation process of such an initiative.Methods: Interviews were conducted with ACT team members, the process leader, steering group members, and collaboration partners. The “Sustainable Implementation Scale” helped to identify critical implementation components, and these were further explored using the qualitative interview data. The “Tool for Measuring Assertive Community Treatment” addressed programme fidelity, and the initiative’s sustainability was assessed.Results: High-fidelity implementation of ACT in a sectored service setting is possible. Prominent components that facilitated implementation were careful preparations, team members’ characteristics, and efforts by the process leader and the steering group to improve networking. Implementation was hampered by conflicting goals among the involved authorities and a mismatch between the ACT model’s characteristics and existing organisational traditions and regulations.Discussion and Conclusions: Reducing the uncertainty caused by conflicting goals is an important step in improving the implementation of ACT. In order to facilitate implementation, the goals, regulations, and availability of resources should be aligned horizontally and vertically through the involved organisations.
24.	Bergmark, Magnus, et al. (författare) Facilitators and Barriers for Sustainable Implementation of Integrated Support in a Sectored Community Mental Health Service System : Experiences from a Swedish Project 2017 Ingår i: ENMESH - The context of mental health care. ; , s. 134- Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Aim: The present research project, reported in several published articles, have studied the implementation of integrated support models (IPS and ACT). Implementation strategies used at several levels have been analyzed, including the national political level, organizational level and team level. This presentation aims to discuss the main findings of barriers and facilitators for sustainable implementation of these interventions in a sectored community mental health service system.Method: Qualitative content analysis was used to analyze political steering strategies. The Sustainable Implementation Scale, based on findings from implementation science, was used to assess effectiveness of implementation. The Supported Employment Fidelity Scale and Tool for Assessment of Assertive Community Treatment was used to assess program fidelity of 15 programs. Data of the selected programs’ target groups and sustainability was used in order to assess the programs establishment in the welfare system’s regular services.Results: Sustainable implementation of the selected models is possible, but several barriers in and between different organizational levels exist. Preparations and collaboration strategies are crucial for teams and organizations. The system level includes several inconsistencies that hamper effective implementation.Conclusions: Political steering, involved agencies’ organizations and the models supposed to be implemented has to be better aligned. A more holistic approach is needed in order to promote supportive horizontal and vertical inter-organizational relationships.
25.	Bergmark, Magnus, et al. (författare) Incorporation of evidence-based programs in local contexts : Components of importance for implementation, fidelity and sustainability 2015 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract The trend toward evidence-based practice has lead to an increased use of internationally tested programs. This development has been questioned because of translation problems, including the lack of fit with national welfare systems and local organizations. This study has followed the implementation process of 14 Individual Placement and Support (IPS) programs that have received national stimulus startup grants. The overarching aim was to explore whether a high fidelity implementation of IPS in a real life Swedish context is possible. The study’s focus was directed towards implementation components at different organizational levels, program fidelity, and the sustainability of the initiatives. Fourteen IPS programs that started during 2012 were selected. Based on research findings that described essential implementation components, an interview protocol and an analysis scale were developed and used. The Sustainable Implementation Scale (SIS) includes components at organizational level, team level, and continuous support. Representatives from the IPS programs were interviewed at baseline, after 12 and 24 months. The 24-month follow-up was conducted 6 months after the disbursement of stimulus grants had ended; therefore questions about the programs sustainability were included. The Supported Employment Fidelity Scale (SEFS) was used to monitor program fidelity after 12 and 24 months. Five of the municipalities with IPS programs had shut them down, while 3 municipalities had partly integrated IPS in regular programs.Six of the programs were fully integrated in the organizations’ regular activities. These 6 programs were characterized by high scores in SIS, primarily on the components concerning recruitment of staff, management, education and access to support structures. There was a significant correlation between the scores on SEFS, SIS, and the sustainability of the program. Collaboration between authorities was a challenge for the programs. An engaged, joint steering group and strategies for local financing were important for the survival of the initiatives. A high fidelity, real-life implementation of IPS in Sweden is possible, but requires a strong focus on essential implementation components and strategies that address contextual barriers. The SIS is a promising tool for monitoring implementation.
26.	Bergström, Ulrica, 1970-, et al. (författare) The hip fracture incidence curve is shifting to the right : a forecast of the age-quake 2009 Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 80:5, s. 520-524 Tidskriftsartikel (refereegranskat)abstract Background The number of hip fractures has doubled in the last 30–40 years in many countries. Age-adjusted incidence has been reported to be decreasing in Europe and North America, but is there a decreasing trend in all age groups? Patients and methods This population-based study included all hip-fracture patients over 50 years of age (a total of 2,919 individuals, 31% of whom were men) admitted to Umeå University Hospital, Sweden, from 1993 through 2005. Results The incidence of hip fracture declined between the periods 1993–1996 and 2001–2005: from 706 to 625 hip fractures per 105 women and from 390 to 317 hip fractures per 105 men. However, there was a 114% increase in the number of fractures in women aged 90 or older (12 and 25 hip fractures/year, respectively, in the two time periods). For the period 2001–05, women ≥ 90 years of age accounted for almost the same numbers of hip fractures as women aged 75–79 (27 fractures/year). The rate increased during this period, from 2,700 per 105 women to 3,900 per 105 women > 90 years. In men there were declining trends for both relative and absolute numbers. Interpretation Although age-adjusted incidence declined in the population > 50 years of age, absolute fracture rate and incidence increased in the very old. Women over 90 now have the same absolute number of hip fractures every year as women aged 75–79 years. There was a right-shift in hip fracture distribution towards the oldest old, probably due to an increased number of octo/nonagenarians, a new population of particularly frail old people that hardly existed earlier. Better health among septuagenarians may also have delayed the age at which fractures occurred. This changing pattern will strain orthopedic and geriatric resources even more.
27.	Bernhard, Iréne, 1953-, et al. (författare) Collaboration Model for Work-Integrated Learning in Higher Education 3rd Cycle 2018 Ingår i: INTED 2018. - : INTED. - 9788469794807 ; , s. 5509-5515 Konferensbidrag (refereegranskat)abstract Universities need to constantly accommodate new forms of collaboration with society. Interaction with and impacts on society and practice are of crucial importance. University West (UW) in Sweden has a profile area in work-integrated learning (WIL), which generally aims to address issues on integrating theory and practice in a coherent and sustainable way. In this paper we base our arguments on a research education (3rd cycle) in informatics with specialization in work-integrated learning. The aim with the paper is to evaluate UW’s research education and research environment from a WIL perspective. We will adopt an informing science model in order to conduct a current state analysis, in which we identify and visualize collaboration activities within and between the research education/environment and the UWs key stakeholders; society/practices, research community and PhD students. Concrete implications show how collaboration and informing flows are connected and how they can be improved. General reflections are given on the model as a useful means for quality development and assurance beyond learning outcomes, including aspects of collaboration and interaction that can be regarded as paths of societal and practical impacts.
28.	Bernhard, Iréne, 1953-, et al. (författare) Samverkansmodell för Arbetsintegrerat Lärande i Forskarutbildning : En ökad samhällsrelevans genom interaktiva flöden 2020 Rapport (övrigt vetenskapligt/konstnärligt)abstract Universiteten i Sverige och övriga världen måste ständigt se över former för förbättrat utbyte med det omgivande samhället. Strategier för samverkan behöver kunna följas upp, mätas och förbättras. På Högskolan Väst (HV) har vi vårt profilområde inom arbetsintegrerat lärande (AIL), som generellt syftar till att integrera såväl teori som praktik i både utbildning, forskning och samverkan - på ett systematiskt och hållbart sätt. I denna rapport kartläggs samverkanseffekter i forskarutbildningen i informatik med inriktning mot arbetsintegrerat lärande. Syftet med rapporten är att utvärdera forskarutbildningen och forskningsmiljön från ett AIL-perspektiv. Vi har utgått från en informativ vetenskapsmodell (Informing Flows Framework) för att genomföra en nulägesanalys där vi identifierar och visualiserar samarbetstyper inom och mellan forskar-utbildningen/forskningsmiljön och Högskolan Västs nyckelaktörer: praktiken, forskarsamhället och doktorander. Konkreta implikationer visar hur samverkan och informationsflöden är kopplade och hur de kan förbättras. Allmänna reflektioner ges på modellen som ett användbart sätt för kvalitetsutveckling som går bortom de traditionella lärandemålen. Vi ser klara utvecklingsvägar för att kunna inkludera fler och djupare aspekter av samarbete och interaktion, som kan ge förbättrat utbyte och tydligare mått och strategier för vad och hur vi ska betrakta ”societal impact” för forskarutbildningen.
29.	Biendicho, Jordi Jacas, et al. (författare) In situ investigation of commercial Ni(OH)(2) and LaNi5-based electrodes by neutron powder diffraction 2015 Ingår i: Journal of Materials Research. - : Springer Science and Business Media LLC. - 0884-2914 .- 2044-5326. ; 30:3, s. 407-416 Tidskriftsartikel (refereegranskat)abstract Electrochemical reactions at both positive and negative electrodes in a nickel metal hydride (Ni-MH) battery during charge have been investigated by in situ neutron powder diffraction. Commercially available beta-Ni(OH)(2) and LaNi5-based powders were used in this experiment as positive and negative electrodes, respectively. Exchange of hydrogen by deuterium for the beta-Ni(OH)(2) electrode was achieved by ex situ cycling of the cell prior to in situ measurements. Neutron diffraction data collected in situ show that the largest amount of deuterium contained at the positive electrode is de-intercalated from the electrode with no phase transformation involved up to similar to 100 mA h/g and, in addition, the 110 peak width for the positive electrode increases on charge. The negative electrode of composition MmNi(3.6)Al(0.4)Mn(0.3)Co(0.7), where Mm = Mischmetal, exhibits a phase transformation to an intermediate hydride gamma phase first and then to the beta phase on charge. Unit cell dimensions and phase fractions have been investigated by Rietveld refinement of the crystal structure.
30.	Boman, Ulrika, et al. (författare) Alkoholkonsumtionen i Sverige fram till 2006 2007 Rapport (övrigt vetenskapligt/konstnärligt)
31.	Bonagas, Nadilly, et al. (författare) Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress 2022 Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156- Tidskriftsartikel (refereegranskat)abstract The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
32.	Borhade, Sanjay R, et al. (författare) Inhibition of Insulin-Regulated Aminopeptidase (IRAP) by Arylsulfonamides 2014 Ingår i: ChemistryOpen. - : Wiley. - 2191-1363. ; 3:6, s. 256-263 Tidskriftsartikel (refereegranskat)abstract The inhibition of insulin-regulated aminopeptidase (IRAP, EC 3.4.11.3) by angiotenesin IV is known to improve memory and learning in rats. Screening 10 500 low-molecular-weight compounds in an enzyme inhibition assay with IRAP from Chinese Hamster Ovary (CHO) cells provided an arylsulfonamide (N-(3-(1H-tetrazol-5-yl)phenyl)-4-bromo-5-chlorothiophene-2-sulfonamide), comprising a tetrazole in the meta position of the aromatic ring, as a hit. Analogues of this hit were synthesized, and their inhibitory capacities were determined. A small structure-activity relationship study revealed that the sulfonamide function and the tetrazole ring are crucial for IRAP inhibition. The inhibitors exhibited a moderate inhibitory potency with an IC50=1.1±0.5 μm for the best inhibitor in the series. Further optimization of this new class of IRAP inhibitors is required to make them attractive as research tools and as potential cognitive enhancers.
33.	Bruce, Barbro, et al. (författare) Språklig sårbarhet i förskola och skola : barnet, språket och pedagogiken 2016 Bok (övrigt vetenskapligt/konstnärligt)abstract För att lyfta fram betydelsen av lärandemiljön, språket och pedagogiken, och för att komma bort från ett ensidigt fokus på barnets/elevens språkliga förmåga, presenterar författarna i den här boken ett i sammanhanget helt nytt begrepp: språklig sårbarhet. Den språkliga sårbarheten uppstår som en obalans mellan barnets/elevens språkliga förutsättningar och de förväntningar som ställs på språklig förståelse och uttrycksförmåga i kunskapsutveckling och kamratrelationer. Det innebär att sårbarheten ökar i takt med att de språkliga kraven i skolan blir högre. Samtidigt blir den mer dold i kraft av att den inte längre gör sig påmind i uttalet. Boken presenterar både typisk språkutveckling och olika typer av hinder och utmaningar med fokus på pedagogiska möjligheter. Ett centralt inslag är lärares språkliga medvetenhet i syfte att möjliggöra och främja samverkan och samsyn mellan olika professioner. Språklig sårbarhet i förskola och skola vänder sig till lärare, specialpedagoger, speciallärare och logopeder – verksamma såväl som studerande – samt till alla inom elevhälsa och med ledaransvar.
34.	Bruce, Barbro, et al. (författare) Språklig sårbarhet i förskola och skola : barnet, språket och pedagogiken 2016 Bok (övrigt vetenskapligt/konstnärligt)abstract För att lyfta fram betydelsen av lärandemiljön, språket och pedagogiken, och för att komma bort från ett ensidigt fokus på barnets/elevens språkliga förmåga, presenterar författarna i den här boken ett i sammanhanget helt nytt begrepp: språklig sårbarhet. Den språkliga sårbarheten uppstår som en obalans mellan barnets/elevens språkliga förutsättningar och de förväntningar som ställs på språklig förståelse och uttrycksförmåga i kunskapsutveckling och kamratrelationer. Det innebär att sårbarheten ökar i takt med att de språkliga kraven i skolan blir högre. Samtidigt blir den mer dold i kraft av att den inte längre gör sig påmind i uttalet. Boken presenterar både typisk språkutveckling och olika typer av hinder och utmaningar med fokus på pedagogiska möjligheter. Ett centralt inslag är lärares språkliga medvetenhet i syfte att möjliggöra och främja samverkan och samsyn mellan olika professioner. Språklig sårbarhet i förskola och skola vänder sig till lärare, specialpedagoger, speciallärare och logopeder –verksamma såväl som studerande – samt till alla inom elevhälsa och med ledaransvar.
35.	Bäckman, Ulrika, et al. (författare) Importance of Vascular Endothelial Growth Factor A in the Progression of Experimental Neuroblastoma 2002 Ingår i: Angiogenesis. - 0969-6970 .- 1573-7209. ; 5:4, s. 267-274 Tidskriftsartikel (refereegranskat)abstract Vascular endothelial growth factor A (VEGF-A) and its receptor tyrosine kinases located on endothelial cells seem to play an important role in the multistep pathway of angiogenesis. SU5416 is a small molecule which inhibits angiogenesis by acting as an inhibitor of VEGF receptor-2 tyrosine kinase. We have developed a reproducible murine model for neuroblastoma, a childhood cancer, based on s.c. xenotransplantation of SH-SY5Y neuroblastoma cells. We found that SH-SY5Y cells expressed VEGF-A on both the mRNA and protein levels, that plasma concentrations of VEGF-A were significantly elevated in animals with neuroblastoma with a volume > 1.4 ml, and that there was a correlation between VEGF-A levels in plasma and tumor size in untreated tumor-bearing animals. Treatment with SU5416 reduced the growth of neuroblastoma tumors by 65% without apparent toxicity. SU5416 treatment also suppressed tumor angiogenesis, despite an increase in plasma VEGF-A levels per ml tumor volume during therapy. Our experimental data suggest that the angiogenesis inhibitor SU5416 may be beneficial in the treatment of solid tumors of childhood such as neuroblastoma.
36.	Bäckman, Ulrika, et al. (författare) The Bisphosphonate Zoledronic Acid Reduces Experimental Neuroblastoma Growth by Interference with Tumor Angiogenesis 2008 Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 28:3A, s. 1551-1557 Tidskriftsartikel (refereegranskat)abstract Background: Zoledronic acid is a new member of the bisphosphonate (BP) class of compounds, a family of closely related synthetic molecules originally derived from the naturally occurring pyrophosphate. These compounds that are potent inhibitors of bone resorption, have been shown to reduce the growth of several cancer cell lines in vitro, and can act as inhibitors of angiogenesis. The angiogenesis inhibitor TNP-470, a synthetic analogue of the fungal antibiotic fumagillin, has been shown to inhibit the growth of multiple tumors in vivo, and is currently in Phase H clinical trials for cancer. Materials and Methods: The effects of daily subcutaneous (s.c.) administration of zoledronic acid (0.1 mg/kg) were compared with those of TNP-470 (15 mg/kg/day and 30 mg/kg every other day, s.c.) in a nude mouse xenograft model for the childhood cancer, neuroblastoma (NB). Results: Zoledronic acid reduced the tumor growth by 33% whereas TNP-470 was less effective and reduced the tumor growth by 26% and 11% for animals treated with 15 mg/kg/day and 30 mg/kg every other day, respectively. Analysis of angiogenesis showed a significant reduction of the number of vessels per grid and in vessel length in all the treatment groups. Conclusion: Zoledronic acid shows tumoristatic and angiostatic properties that might be beneficial in the treatment of solid tumors such as neuroblastoma.
37.	Chankeaw, Wiruntita, et al. (författare) Non-esterified fatty acids affect the survival and increase lipid accumulation of bovine endometrial epithelial cells 2016 Ingår i: Reproduction in Domestic Animals. - : Wiley. - 0936-6768 .- 1439-0531. ; 51, s. 82-82 Konferensbidrag (refereegranskat)
38.	Chen, Chunli, et al. (författare) The multistate tuberculosis pharmacometric model : a semi-mechanistic pharmacokinetic-pharmacodynamic model for studying drug effects in an acute tuberculosis mouse model 2017 Ingår i: Journal of Pharmacokinetics and Pharmacodynamics. - : Springer Science and Business Media LLC. - 1567-567X .- 1573-8744. ; 44:2, s. 133-141 Tidskriftsartikel (refereegranskat)abstract The Multistate Tuberculosis Pharmacometric (MTP) model, a pharmacokinetic-pharmacodynamic disease model, has been used to describe the effects of rifampicin on Mycobacterium tuberculosis (M. tuberculosis) in vitro. The aim of this work was to investigate if the MTP model could be used to describe the rifampicin treatment response in an acute tuberculosis mouse model. Sixty C57BL/6 mice were intratracheally infected with M. tuberculosis H37Rv strain on Day 0. Fifteen mice received no treatment and were sacrificed on Days 1, 9 and 18 (5 each day). Twenty-five mice received oral rifampicin (1, 3, 9, 26 or 98 mg·kg-1·day-1; Days 1–8; 5 each dose level) and were sacrificed on Day 9. Twenty mice received oral rifampicin (30 mg·kg-1·day-1; up to 8 days) and were sacrificed on Days 2, 3, 4 and 9 (5 each day). The MTP model was linked to a rifampicin population pharmacokinetic model to describe the change in colony forming units (CFU) in the lungs over time. The transfer rates between the different bacterial states were fixed to estimates from in vitro data. The MTP model described well the change in CFU over time after different exposure levels of rifampicin in an acute tuberculosis mouse model. Rifampicin significantly inhibited the growth of fast-multiplying bacteria and stimulated the death of fast- and slow-multiplying bacteria. The data did not support an effect of rifampicin on non-multiplying bacteria possibly due to the short duration of the study. The pharmacometric modelling framework using the MTP model can be used to perform investigations and predictions of the efficacy of anti-tubercular drugs against different bacterial states.
39.	Conaway, H Herschel, et al. (författare) Retinoids inhibit differentiation of hematopoietic osteoclast progenitors. 2009 Ingår i: The FASEB journal. - Bethesda, Md. : Wiley. - 1530-6860 .- 0892-6638. ; 23:10, s. 3526-38 Tidskriftsartikel (refereegranskat)abstract Whether vitamin A promotes skeletal fragility, has no effect on fracture rate, or protects against bone loss is unclear. In the present study, effects of retinoids on osteoclast differentiation in cultured mouse bone marrow cells (BMCs), bone marrow macrophages (BMMs), spleen cells, and RAW264.7 cells were evaluated by analyzing osteoclast formation and expression of genes important in signal transduction and osteoclast function. All-trans-retinoic acid (ATRA) did not stimulate osteoclastogenesis in BMCs, but inhibited hormone and RANKL-induced gene expression and formation of osteoclasts. In BMMs, spleen cells, and RAW264.7 cells, osteoclast differentiation and formation stimulated by M-CSF/RANKL were inhibited (IC(50) = 0.3 nM) by ATRA. The effect was exerted at an early step of RANKL-induced differentiation. ATRA also abolished increases of the transcription factors c-Fos and NFAT2 stimulated by RANKL and suppressed down-regulation of the antiosteoclastogenic transcription factor MafB. By comparing effects of several compounds structurally related to ATRA, as well as by using receptor antagonists, evaluation pointed to inhibition being mediated by RARalpha, with no involvement of PPARbeta/delta. The results suggest that activation of RARalpha by retinoids in myeloid hematopoietic precursor cells decreases osteoclast formation by altering expression of the transcription factors c-Fos, NFAT2, and MafB.
40.	Conaway, H Herschel, et al. (författare) Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL, a response inhibited by monomeric glucocorticoid receptor. 2011 Ingår i: The Journal of biological chemistry. - 1083-351X .- 0021-9258. ; 286:36, s. 31425-36 Tidskriftsartikel (refereegranskat)abstract Increased vitamin A (retinol) intake has been suggested to increase bone fragility. In the present study, we investigated effects of retinoids on bone resorption in cultured neonatal mouse calvarial bones and their interaction with glucocorticoids (GC). All-trans-retinoic acid (ATRA), retinol, retinalaldehyde, and 9-cis-retinoic acid stimulated release of (45)Ca from calvarial bones. The resorptive effect of ATRA was characterized by mRNA expression of genes associated with osteoclast differentiation, enhanced osteoclast number, and bone matrix degradation. In addition, the RANKL/OPG ratio was increased by ATRA, release of (45)Ca stimulated by ATRA was blocked by exogenous OPG, and mRNA expression of genes associated with bone formation was decreased by ATRA. All retinoid acid receptors (RARα/β/γ) were expressed in calvarial bones. Agonists with affinity to all receptor subtypes or specifically to RARα enhanced the release of (45)Ca and mRNA expression of Rankl, whereas agonists with affinity to RARβ/γ or RARγ had no effects. Stimulation of Rankl mRNA by ATRA was competitively inhibited by the RARα antagonist GR110. Exposure of calvarial bones to GC inhibited the stimulatory effects of ATRA on (45)Ca release and Rankl mRNA and protein expression. This inhibitory effect was reversed by the glucocorticoid receptor (GR) antagonist RU 486. Increased Rankl mRNA stimulated by ATRA was also blocked by GC in calvarial bones from mice with a GR mutation that blocks dimerization (GR(dim) mice). The data suggest that ATRA enhances periosteal bone resorption by increasing the RANKL/OPG ratio via RARα receptors, a response that can be inhibited by monomeric GR.
41.	De Jager, Veronique, et al. (författare) Early Bactericidal Activity of Meropenem plus Clavulanate (with or without Rifampin) for Tuberculosis : The COMRADE Randomized, Phase 2A Clinical Trial 2022 Ingår i: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 205:10, s. 1228-1235 Tidskriftsartikel (refereegranskat)abstract Rationale: Carbapenems are recommended for treatment of drug-resistant tuberculosis. Optimal dosing remains uncertain.Objectives: To evaluate the 14-day bactericidal activity of meropenem, at different doses, with or without rifampin.Methods: Individuals with drug-sensitive pulmonary tuberculosis were randomized to one of four intravenous meropenem-based arms: 2 g every 8 hours (TID) (arm C), 2 g TID plus rifampin at 20 mg/kg once daily (arm D), 1 g TID (arm E), or 3 g once daily (arm F). All participants received amoxicillin/clavulanate with each meropenem dose. Serial overnight sputum samples were collected from baseline and throughout treatment. Median daily fall in colony-forming unit (CFU) counts per milliliter of sputum (solid culture) (EBA(CFU0-14)) and increase in time to positive culture (TTP) in liquid media were estimated with mixed-effects modeling. Serial blood samples were collected for pharmacokinetic analysis on Day 13.Measurements and Main Results: Sixty participants enrolled. Median EBA(CFU0-14) counts (2.5th-97.5th percentiles) were 0.22 (0.12-0.33), 0.12 (0.057-0.21), 0.059 (0.033-0.097), and 0.053 (0.035-0.081); TTP increased by 0.34 (0.21-0.75), 0.11 (0.052-037), 0.094 (0.034-0.23), and 0.12 (0.04-0.41) (log(10) h), for arms C-F, respectively. Meropenem pharmacokinetics were not affected by rifampin coadministration. Twelve participants withdrew early, many of whom cited gastrointestinal adverse events.Conclusions: Bactericidal activity was greater with the World Health Organization-recommended total daily dose of 6 g daily than with a lower dose of 3 g daily. This difference was only detectable with solid culture. Tolerability of intravenous meropenem, with amoxicillin/clavulanate, though, was poor at all doses, calling into question the utility of this drug in second-line regimens.
42.	Derneryd, Anders, et al. (författare) A 23 GHz sector antenna for point-to-multipoint communications 2005 Ingår i: 18th International Conference on Applied Electromagnetics and Communications, Conference Proceedings. - ZAGREB : KOREMA. ; , s. 297-300 Konferensbidrag (refereegranskat)abstract A broadband and compact antenna concept for a point-to-multipoint communication system at millimeter-wave frequencies is presented. The antenna consists of a rectangular feed waveguide, an H-plane parallel plate horn, an enclosed parabolic reflector section, a radiation slot aperture, and corrugated external baffles. The bandwidth is 2.9 GHz corresponding to a relative bandwidth of 12.6 % at 23 GHz for a return loss better than 10 dB of a prototype. The overall dimensions of the manufactured antenna are 200 mm by 14 7 mm by 50 mm.
43.	Diwakarla, Shanti, et al. (författare) Aryl Sulfonamide Inhibitors of Insulin-Regulated Aminopeptidase Enhance Spine Density in Primary Hippocampal Neuron Cultures 2016 Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 7:10, s. 1383-1392 Tidskriftsartikel (refereegranskat)abstract The zinc metallopeptidase insulin regulated aminopeptidase (IRAP), which is highly expressed in the hippocampus and other brain regions associated with cognitive function, has been identified as a high-affinity binding site of the hexapeptide angiotensin IV (Ang IV). This hexapeptide is thought to facilitate learning and memory by binding to the catalytic site of IRAP to inhibit its enzymatic activity. In support of this hypothesis, low molecular weight, nonpeptide specific inhibitors of TRAP have been shown to enhance memory in rodent models. Recently, it was demonstrated that linear and macrocyclic Ang IV-derived peptides can alter the shape and increase the number of dendritic spines in hippocampal cultures, properties associated with enhanced cognitive performance. After screening a library of 10 500 drug like substances for their ability to inhibit IRAP, we identified a series of low molecular weight aryl sulfonamides, which exhibit no structural similarity to Ang IV, as moderately potent IRAP inhibitors:A structural and biological characterization of three of these aryl sulfonamides was performed. Their binding modes to human IRAP were explored by docking calculations combined with molecular dynamics simulations and binding affinity estimations using the linear interaction energy method. Two alternative binding modes emerged from this analysis, both of which correctly rank the ligands according to their experimental binding affinities for this series of compounds. Finally, we show that two of these drug-like IRAP inhibitors can alter dendritic spine morphology and increase spine density in primary cultures of hippocampal neurons.
44.	Ejlertsson, Jörgen, et al. (författare) Anaerobic degradation of xenobiotics by organisms from munical solid waste under landfilling conditions 1995 Ingår i: Antonie van Leeuwenhoek. International Journal of General and Molecular Microbiology. - 0003-6072 .- 1572-9699. ; 69:1, s. 67-74 Tidskriftsartikel (refereegranskat)abstract The potential for biological transformation of 23 xenobiotic compounds by microorganisms in municipal solid waste (MSW) samples from a laboratory scale landfill reactor was studied. In addition the influence of these xenobiotic compounds on methanogenesis was investigated. All R11, 1,1 dichloroethylene, 2,4,6 trichlorophenol, dimethyl phthalate, phenol, benzoate and phthalic acid added were completely transformed during the period of incubation (> 100 days). Parts of the initially added perchloroethylene, trichloroethylene, R12, R114, diethyl phthalate, dibutyl phthalate and benzylbutyl phthalate were transformed. Methanogenesis from acetate was completely inhibited in the presence of 2,5 dichlorophenol, whereas 2,4,6 trichlorophenol and R11 showed an initial inhibition, whenafter methane formation recovered. No transformation or effect on the anaerobic microflora occurred for R13, R22, R114, 3 chlorobenzoate, 2,4,6 trichlorobenzoate, bis(2 ethyl)hexyl phthalate, diisodecyl phthalate and dinonyl phthalate. The results indicate a limited potential for degradation, of the compounds tested, by microorganisms developing in a methanogenic landfill environment as compared with other anaerobic habitats such as sewage digestor sludge and sediments.
45.	Englund, Undis, 1957-, et al. (författare) Active commuting reduces the risk of wrist fractures in middle-aged women : the UFO study 2013 Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 24:2, s. 533-540 Tidskriftsartikel (refereegranskat)abstract Middle-aged women with active commuting had significantly lower risk for wrist fracture than women commuting by car/bus.INTRODUCTION: Our purpose was to investigate whether a physically active lifestyle in middle-aged women was associated with a reduced risk of later sustaining a low-trauma wrist fracture.METHODS: The Umeå Fracture and Osteoporosis (UFO) study is a population-based nested case-control study investigating associations between lifestyle and fragility fractures. From a cohort of ~35,000 subjects, we identified 376 female wrist fracture cases who had reported data regarding their commuting habits, occupational, and leisure physical activity, before they sustained their fracture. Each fracture case was compared with at least one control drawn from the same cohort and matched for age and week of reporting data, yielding a total of 778 subjects. Mean age at baseline was 54.3 ± 5.8 years, and mean age at fracture was 60.3 ± 5.8 years.RESULTS: Conditional logistic regression analysis with adjustments for height, body mass index, smoking, and menopausal status showed that subjects with active commuting (especially walking) were at significantly lower risk of sustaining a wrist fracture (OR 0.48; 95 % CI 0.27-0.88) compared with those who commuted by car or bus. Leisure time activities such as dancing and snow shoveling were also associated with a lower fracture risk, whereas occupational activity, training, and leisure walking or cycling were unrelated to fracture risk.CONCLUSION: This study suggests that active commuting is associated with a lower wrist fracture risk, in middle-aged women.
46.	Englund, Undis, 1957-, et al. (författare) Physical activity in middle-aged women and hip fracture risk : the UFO study 2011 Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 22:2, s. 499-505 Tidskriftsartikel (refereegranskat)abstract Summary: In a population-based case-control study, we demonstrate that middle-aged women who were active with walking or in different physical spare time activities were at lower risk of later sustaining a hip fracture compared to more sedentary women.Introduction: In middle-aged women participating in the Umeå Fracture and Osteoporosis (UFO) study, we investigated whether physical activity is associated with a subsequent decreased risk of sustaining a hip fracture.Methods: The UFO study is a nested case-control study investigating associations between bone markers, lifestyle, and osteoporotic fractures. We identified 81 female hip fracture cases that had reported lifestyle data before they sustained their fracture. Each case was compared with two female controls who were identified from the same cohort and matched for age and week of reporting data, yielding a total cohort of 237 subjects. Mean age at baseline was 57.2 ± 5.0 years, and mean age at fracture was 65.4 ± 6.4 years.Results: Conditional logistic regression analysis with adjustments for height, weight, smoking, and menopausal status showed that subjects who were regularly active with walking or had a moderate or high frequency of physical spare time activities (i.e. berry/mushroom picking and snow shovelling) were at reduced risk of sustaining a hip fracture (OR 0.14; 95% CI; 0.05–0.53 for walking and OR 0.19; 95% CI; 0.08–0.46, OR 0.17, 95% CI; 0.05–0.64 for moderate and high frequency of spare time activities, respectively) compared to more sedentary women.Conclusion: An active lifestyle in middle age seems to reduce the risk of future hip fracture. Possible mechanisms may include improved muscle strength, coordination, and balance resulting in a decreased risk of falling and perhaps also direct skeletal benefits.
47.	Estrada, Karol, et al. (författare) Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. 2012 Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501 Tidskriftsartikel (refereegranskat)abstract Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
48.	Fagman, Erika, et al. (författare) 18F-FDG PET/CT in the diagnosis of prosthetic valve endocarditis 2016 Ingår i: The International Journal of Cardiovascular Imaging. - : Springer Science and Business Media LLC. - 1569-5794 .- 1573-0743. ; 32:4, s. 679-686 Tidskriftsartikel (refereegranskat)abstract Recent studies have shown promising results using 18F-fluorodeoxyglucose positron emission tomography/ computed tomography (18F-FDG PET/CT) in the diagnosis of prosthetic valve endocarditis (PVE). However, previous studies did not include negative controls. The aim of this study was to compare 18F-FDG-uptake around prosthetic aortic valves in patients with and without PVE and to determine the diagnostic performance of 18F-FDG PET/CT in the diagnosis of PVE. 18F-FDG PET/CT examinations in patients with a prosthetic aortic valve performed 2008–2014 were retrieved. Eight patients with a final diagnosis of definite PVE were included in the analysis of the diagnostic performance of 18F-FDG PET/CT. Examinations performed on suspicion of malignancy in patients without PVE (n = 19) were used as negative controls. Visual and semi-quantitative analysis was performed. Maximal standardized uptake value (SUVmax) in the valve area was measured and SUVratio was calculated by dividing valve SUVmax by SUVmax in the descending aorta. The sensitivity was 75 %, specificity 84 %, positive likelihood ratio [LR(+)] 4.8 and negative likelihood ratio [LR(-)] 0.3 on visual analysis. Both SUVmax and SUVratio were significantly higher in PVE patients [5.8 (IQR 3.5–6.5) and 2.4 (IQR 1.7–3.0)] compared to non-PVE patients [3.2 (IQR 2.8–3.8) and 1.5 (IQR 1.3–1.6)] (p<0.001). ROC-curve analysis of SUVratio yielded an area under the curve of 0.90 (95 % CI 0.74–1.0). 18F-FDG-uptake around non-infected aortic prosthetic valves was low. The level of 18F-FDG-uptake in the prosthetic valve area showed a good diagnostic performance in the diagnosis of PVE.
49.	Fagman, Erika, et al. (författare) Surgical decision-making in aortic prosthetic valve endocarditis: the influence of electrocardiogram-gated computed tomography. 2016 Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - : Oxford University Press (OUP). - 1873-734X. ; 50:6, s. 1165-1171 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to investigate the value of electrocardiogram (ECG)-gated computed tomography (CT) in the surgical decision-making and preoperative evaluation in patients with aortic prosthetic valve endocarditis (PVE).
50.	Faraj, Alan, et al. (författare) Difference in persistent tuberculosis bacteria between in vitro and sputum from patients : implications for translational predictions 2020 Ingår i: Scientific Reports. - : NATURE RESEARCH. - 2045-2322. ; 10:1 Tidskriftsartikel (refereegranskat)abstract This study aimed to investigate the number of persistent bacteria in sputum from tuberculosis patients compared to in vitro and to suggest a model-based approach for accounting for the potential difference. Sputum smear positive patients (n=25) provided sputum samples prior to onset of chemotherapy. The number of cells detected by conventional agar colony forming unit (CFU) and most probable number (MPN) with Rpf supplementation were quantified. Persistent bacteria was assumed to be the difference between MPNrpf and CFU. The difference in persistent bacteria between in vitro and human sputum prior to chemotherapy was quantified using different model-based approaches. The persistent bacteria in sputum was 17% of the in vitro levels, suggesting a difference in phenotypic resistance, whereas no difference was found for multiplying bacterial subpopulations. Clinical trial simulations showed that the predicted time to 2 log fall in MPNrpf in a Phase 2a setting using in vitro pre-clinical efficacy information, would be almost 3 days longer if drug response was predicted ignoring the difference in phenotypic resistance. The discovered phenotypic differences between in vitro and humans prior to chemotherapy could have implications on translational efforts but can be accounted for using a model-based approach for translating in vitro to human drug response.

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