| 1. |
- Ahmad, Amais, et al.
(författare)
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IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 4 : Prediction accuracy and software comparisons with improved data and modelling strategies
- 2020
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 156, s. 50-63
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Tidskriftsartikel (refereegranskat)abstract
- Oral drug absorption is a complex process depending on many factors, including the physicochemical properties of the drug, formulation characteristics and their interplay with gastrointestinal physiology and biology. Physiological-based pharmacokinetic (PBPK) models integrate all available information on gastro-intestinal system with drug and formulation data to predict oral drug absorption. The latter together with in vitro-in vivo extrapolation and other preclinical data on drug disposition can be used to predict plasma concentration-time profiles in silico. Despite recent successes of PBPK in many areas of drug development, an improvement in their utility for evaluating oral absorption is much needed. Current status of predictive performance, within the confinement of commonly available in vitro data on drugs and formulations alongside systems information, were tested using 3 PBPK software packages (GI-Sim (ver.4.1), Simcyp® Simulator (ver.15.0.86.0), and GastroPlusTM (ver.9.0.00xx)). This was part of the Innovative Medicines Initiative (IMI) Oral Biopharmaceutics Tools (OrBiTo) project.Fifty eight active pharmaceutical ingredients (APIs) were qualified from the OrBiTo database to be part of the investigation based on a priori set criteria on availability of minimum necessary information to allow modelling exercise. The set entailed over 200 human clinical studies with over 700 study arms. These were simulated using input parameters which had been harmonised by a panel of experts across different software packages prior to conduct of any simulation. Overall prediction performance and software packages comparison were evaluated based on performance indicators (Fold error (FE), Average fold error (AFE) and absolute average fold error (AAFE)) of pharmacokinetic (PK) parameters.On average, PK parameters (Area Under the Concentration-time curve (AUC0-tlast), Maximal concentration (Cmax), half-life (t1/2)) were predicted with AFE values between 1.11 and 1.97. Variability in FEs of these PK parameters was relatively high with AAFE values ranging from 2.08 to 2.74. Around half of the simulations were within the 2-fold error for AUC0-tlast and around 90% of the simulations were within 10-fold error for AUC0-tlast. Oral bioavailability (Foral) predictions, which were limited to 19 APIs having intravenous (i.v.) human data, showed AFE and AAFE of values 1.37 and 1.75 respectively. Across different APIs, AFE of AUC0-tlast predictions were between 0.22 and 22.76 with 70% of the APIs showing an AFE > 1. When compared across different formulations and routes of administration, AUC0-tlast for oral controlled release and i.v. administration were better predicted than that for oral immediate release formulations. Average predictive performance did not clearly differ between software packages but some APIs showed a high level of variability in predictive performance across different software packages. This variability could be related to several factors such as compound specific properties, the quality and availability of information, and errors in scaling from in vitro and preclinical in vivo data to human in vivo behaviour which will be explored further. Results were compared with previous similar exercise when the input data selection was carried by the modeller rather than a panel of experts on each in vitro test. Overall, average predictive performance was increased as reflected in smaller AAFE value of 2.8 as compared to AAFE value of 3.8 in case of previous exercise.
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| 2. |
- Ederle, Joerg, et al.
(författare)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Tidskriftsartikel (refereegranskat)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 3. |
- Wendin, Karin, 1963-, et al.
(författare)
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Introducing mealworm as an ingredient in crisps and pâtés – sensory characterization and consumer liking
- 2021
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Ingår i: Future Foods. - : Elsevier. - 2666-8335. ; 4, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to evaluate sensory perception and consumers’ attitude and liking of products with different textures, crisps and pâtés, with added mealworm ingredient in different amounts. By addition of mealworm ( Tenebrio molitor L. ) in the crisps, the brittleness increased. However, an increase in mealworm also increased the darkness. Adding mealworms to pâté reduced the odour and flavour of vegetable and increased the flavour of cinnamon and pepper as well as the oily texture. There was no significant difference in total liking between 10 and 30% addition of mealworm, nor between 0 and 10% addition, in any of the two products. The crisps received higher liking score than the pâtés. Thus, there is also a much higher probability that a customer would buy insect crisps than insect pâté. Environmental sustainability and sensory properties were shown to be the main reasons for buying foods with added insect ingredients.
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| 4. |
- Ahnström, Johan, et al.
(författare)
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Farmers' Interest in Nature and Its Relation to Biodiversity in Arable Fields
- 2013
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Ingår i: International Journal of Ecology. - : Hindawi Publishing Corporation. - 1687-9708 .- 1687-9716.
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Tidskriftsartikel (refereegranskat)abstract
- Biodiversity declines in farmland have been attributed to intensification of farming at the field level and loss of heterogeneity at the landscape level. However, farmers are not solely optimizing production; their actions are also influenced by social factors, tradition and interest in nature, which indirectly influence biodiversity but rarely are incorporated in studies of farmland biodiversity. We used social science methods to quantify farmers’ interest in nature on 16 farms with winter wheat fields in central Sweden, and combined this with biodiversity inventories of five organism groups (weeds, carabid beetles, bumblebees, solitary bees, and birds) and estimates of landscape composition andmanagement intensity at the field level.Agricultural intensity,measured as crop density, and farmers’ interest in nature explained variation in biodiversity, measured as the proportion of the regional species richness found on single fields. Interest in nature seemed to incorporate many actions taken by farmers and appeared to be influenced by both physical factors, for example, the surrounding landscape, and social factors, for example, social motivations.This study indicates that conservation of biodiversity in farmland, and design of new agri-environmental subsidy systems, would profit from taking farmers’ interest in nature and its relation to agricultural practices into account.
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| 5. |
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| 6. |
- Alkan Olsson, Johanna, et al.
(författare)
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Local stakeholders acceptance of model-generated data used as a communication tool in water management: The Ronnea study
- 2005
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Ingår i: Ambio. - : Royal Swedish Academy of Sciences. - 0044-7447 .- 1654-7209. ; 34:7, s. 507-512
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to increase the knowledge of local stakeholders acceptance of model-generated data when used as a communication tool in water quality management. The Ronnea catchment in the southwest of Sweden was chosen as the study area. The results indicate the model-generated data served as a uniting factor. Simultaneously, the stakeholders were concerned with presented data, the main problems being sources of pollution, which were not accounted for, lack of trustworthiness when measuring pollution, and the uncertainty of the impact of natural variation and delayed effects. Four clusters of factors were identified as influencing stakeholders acceptance of the model-generated data: confidence in its practical applications, confidence in the people involved in or providing material for the dialog (such as experts, decision-makers, and media), the social characteristics of the participants (such as age and profession), and the way of communicating the data (such as tone of communication, group composition, duration, and geographical scope of the dialog). The perception of the fairness of the practical application of given model-generated data was also an important factor for acceptance.
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| 7. |
- André, Malin, et al.
(författare)
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A survey of public knowledge and awareness related to antibiotic use and resistance in Sweden
- 2010
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 65:6, s. 1292-1296
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Tidskriftsartikel (refereegranskat)abstract
- To examine the level of knowledge about antibiotic treatment and awareness of antibiotic resistance among the general public in Sweden. A quantitative, cross-sectional interview study based on a structured questionnaire used during telephone interviews. The sample comprised 1000 randomly selected individuals aged 21-80 years throughout Sweden. Demographic data as well as level of agreement with various statements concerning antibiotics and antibiotic use were provided by the respondents. The response rate was 74.7%. Of the respondents, 19.1% agreed that antibiotics cure common colds more quickly; this belief was higher in those who had not previously received antibiotics. A high proportion, 80.7%, agreed that bacteria could become resistant to antibiotics. Trust in doctors was high, and significantly more respondents reported trusting the doctor not prescribing an antibiotic, 87.0%, than the doctor prescribing an antibiotic, 81.0%. The respondents showed some confusion surrounding the terms 'bacteria' and 'viruses', and the meaning of these in relation to the prescribing decision. The high level of trust in restrictive prescribing as well as the awareness of antibiotic resistance expressed by the Swedish public should be recognized by health professionals and utilized in future campaigns.
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| 8. |
- Bacchus, Philip, et al.
(författare)
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Civil-military collaboration to facilitate rapid deployment of a mobile laboratory in early response to covid-19 : A high-readiness exercise
- 2021
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Ingår i: HEALTH SECURITY. - : Mary Ann Liebert. - 2326-5094 .- 2326-5108. ; 19:5, s. 488-497
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Tidskriftsartikel (refereegranskat)abstract
- Rapid and adaptable diagnostic capabilities are of great importance in the face of emerging infectious diseases. In an outbreak, timely establishment of diagnostic routines is crucial to identifying cases and preventing the spread of the disease, especially when faced with high-consequence pathogens. In this article, we describe a multiagency exercise including the rapid deployment and diagnostic adaptation of the Swedish Armed Forces mobile laboratory (biological field analysis laboratory) in the context of COVID-19. This deployment was initiated as a high-readiness exercise at the end of January 2020, when the global development of the outbreak was still uncertain. Through collaboration with the Public Health Agency of Sweden and a civilian hospital, a real-time reverse transcriptase polymerase chain reaction method specific to SARS-CoV-2 was made available and adapted to the mobile laboratory, and the team established and evaluated a functional and efficient diagnostic asset along with a logistical support chain. We also organized and evaluated mobile testing teams, and the method was later used in large-scale, national, cross-sectional COVID-19 surveys in several regions of Sweden. In this article, we focus on the challenges of overbridging the civil-military interface in this context and identifying lessons learned and added values to the response during the early pandemic. We propose that the experiences from this exercise and governmental agency collaboration are valuable in preparation for future outbreaks.
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| 9. |
- Bean, Christopher, 1990-, et al.
(författare)
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Short sleep, psychosocial work stressors, and measures of obesity: results from an Australian cohort study
- 2019
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Konferensbidrag (refereegranskat)abstract
- Introduction: Short sleep and workplace stress are both established risk factors for overweight and obesity, yet few studies have considered how these two factors may intersect. The aim of this study was to establish the associations between these two exposures and their relative associations with body mass index (kg/m2 ) and waist circumference (cm).Methods: A cross-sectional design sampled current employees (N=423) from an Australian cohort using a computer-assisted telephone interview and clinic-measured height, weight, and waist circumference. Short sleep (≤6h/ night) was reported by 25.8% of the participants. Psychosocial work stressors were defined using the Job Demand-ControlSupport (JDCS) model and calculated at the subscale level (psychological demands; skill discretion; decision authority; coworker support; supervisor support). General linear models were used to assess associations between short sleep, the JDCS subscales (split at median), and BMI and waist circumference.Results: Separate analyses identified short sleep and a lack of skill discretion at work as predictors of both BMI and waist circumference. Furthermore, when both predictors were entered in the same model, each was associated with elevated BMI (b=1.79, p=.003; b=1.08, p=.045) and waist circumference (b=4.20, p=.005; b=2.97, p=.028). Short sleep was also associated with high perceived psychological demands at work (b=1.81, p=.003). All models were adjusted for gender, age, work hours, blue vs. white collar job, and household income.Discussion: These findings indicate the importance of considering the interplay between short sleep and psychosocial work stressors, and their respective associations with measures of overweight Sleep Sci. 2019;12(Supl.3):1-75 26 and obesity. Further research using longitudinal data is needed to model potential mechanisms (e.g., behavioral and physiological). A novel feature was the subscale consideration of the prominent JDCS model of work stress. Advocacy for both improved habitual sleep (e.g., ≥7h/night) and job redesign to increase skill discretion at work may promote lower levels of overweight and obesity for employees.
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| 10. |
- Berg, Anne, et al.
(författare)
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Expanding Political Capital : Why Social Democratic Women Participated in Middle-Class Feminist Educational Organisations in Sweden c.1890–1910
- 2024
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Ingår i: History of Education. - 0046-760X .- 1464-5130.
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Tidskriftsartikel (refereegranskat)abstract
- This article seeks to introduce a new historical explanation as to why left-wing working-class women engaged in liberal, middle-class organisations during the first wave of feminism. The article specifically deals with middle-class associations and clubs that had educational purposes. Instead of focusing on the larger explanatory scheme of the power of patriarchal societal structures or bourgeois feminisms as a hegemonic force, the account revolves around the political educational functions of liberal feminist engagement for some politically active social democratic women in Sweden. The case of social democratic women who entered the liberal middle class educational organisation Tolfterna (the Dozen) is the point of departure for a micro-historical analysis of the political capital accumulation practices that class collaboration entailed. Finally, the article explores how working-class women’s choices and actions can be considered a group-specific strategy to expand their political resources to attain what is called feminist liberal political capital.
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