| 11. |
- Sou, Tomás, et al.
(författare)
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Model-Informed Drug Development for Antimicrobials : Translational PK and PK/PD Modeling to Predict an Efficacious Human Dose for Apramycin
- 2021
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Ingår i: Clinical Pharmacology and Therapeutics. - : John Wiley & Sons. - 0009-9236 .- 1532-6535. ; 109:4, s. 1063-1073
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Tidskriftsartikel (refereegranskat)abstract
- Apramycin represents a subclass of aminoglycoside antibiotics that has been shown to evade almost all mechanisms of clinically relevant aminoglycoside resistance. Model-informed drug development may facilitate its transition from preclinical to clinical phase. This study explored the potential of pharmacokinetic/pharmacodynamic (PK/PD) modeling to maximize the use of in vitro time-kill and in vivo preclinical data for prediction of a human efficacious dose (HED) for apramycin. PK model parameters of apramycin from four different species (mouse, rat, guinea pig, and dog) were allometrically scaled to humans. A semimechanistic PK/PD model was developed from the rich in vitro data on four Escherichia coli strains and subsequently the sparse in vivo efficacy data on the same strains were integrated. An efficacious human dose was predicted from the PK/PD model and compared with the classical PK/PD index methodology and the aminoglycoside dose similarity. One-compartment models described the PK data and human values for clearance and volume of distribution were predicted to 7.07 L/hour and 26.8 L, respectively. The required fAUC/MIC (area under the unbound drug concentration-time curve over MIC ratio) targets for stasis and 1-log kill in the thigh model were 34.5 and 76.2, respectively. The developed PK/PD model predicted the efficacy data well with strain-specific differences in susceptibility, maximum bacterial load, and resistance development. All three dose prediction approaches supported an apramycin daily dose of 30 mg/kg for a typical adult patient. The results indicate that the mechanistic PK/PD modeling approach can be suitable for HED prediction and serves to efficiently integrate all available efficacy data with potential to improve predictive capacity.
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| 12. |
- Mattias, Lindh, et al.
(författare)
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Handbok för nordlig solel
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Solen är en för människan evig energikälla och solel har en given plats i ett framtida hållbart och förnybart energisystem – globalt och i Sverige. Kostnaden för en solelanläggning har sjunkit drastiskt de senaste åren och tillgängligheten har ökat. Det gör solel relevant utanför de regioner som har störst solinstrålning; även i norra Skandinavien är det en långsiktigt hållbar investering ur både ett energi- och ekonomiskt perspektiv.Nordlig solel har goda men annorlunda förutsättningar jämfört med de i södra Sverige och Centraleuropa. Solens position på himlen och den instrålade energin per år är lägre, det är en stor andel diffust ljus och man kan förvänta sig mer reflektioner från en snötäckt mark på vintern. På sommaren är soltimmarna fler och solens bana längre. Medeltemperaturen är betydligt lägre på årsbasis men skillnaden mot sydligare breddgrader är mindre under sommaren då instrålningen är stor. En annan avgörande faktor är snö som under stora delar av året i norr täcker marken och potentiellt solelanläggningar. Om snötäckningen kan begränsas till de mörkaste månaderna blir årseffekterna på energiproduktionen små, men snölaster ställer höga krav på solelanläggningars kvalitet, både ur installations- och komponentperspektiv.Genom att beakta följande fem rekommendationer kan man minska risken för problem:1. Undersök snöförhållandena på platsen innan installation. Anläggningsägaren vet ofta bäst var snön brukar ansamlas och när den smälter bort eller glider av.2. Säkerställ att installationen är genomtänkt ur ett snöperspektiv. En noggrann kontroll av att installationen följer leverantörernas anvisningar är extra viktigt när förhållandena är krävande.3. Välj robusta moduler och fästanordningar – en solelanläggning ska hålla i många år och bör utformas för att klara lokala snöförhållanden.4. Utforma om möjligt anläggningen så att snöröjning inte krävs. Röj (varsamt) undan snö från anläggningen om det trots det blir nödvändigt: för att undvika takras, skydda solelanläggningen mot tryck- och glidskador från ett tjockt snötäcke och för att möjliggöra elproduktion från tidig vår.5. Montera modulerna med rätt orientering. Söderläge och så hög lutning som möjligt upp till om kring 50° (i Piteå) är generellt bäst. Ofta är man begränsad av takets utformning men även avvikelser från söder mot öst eller väst och mindre lutningar kan ge ett acceptabelt energiutbyte.Huvudregeln bör vara att: Montera solceller där solinstrålningen är stor men snö inte ansamlas!
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| 13. |
- Petersson, Anna, et al.
(författare)
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Interior design dilemmas in a shared room of silence.
- 2020
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Ingår i: Material Religion: the journal of objects, art and belief. - : Informa UK Limited. - 1743-2200. ; 16:2, s. 213-235
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Tidskriftsartikel (refereegranskat)abstract
- This text sheds light on the delicate practice of including different religious as well as nonreligious expressions in a shared room. The effects of design decisions in a “room of silence” at a Swedish hospital are studied over a transitional period of renovation of the space. We observe the impact of materiality in the room’s establishment, renovation, and usage, and show how the room’s interior design, its decor and objects, are conditioned by ritual acts as well by practical and spontaneous place-making processes. By following how the negotiations of the interior space relate to presupposed separations of aesthetic and religious ideals, we see how the design of a room of silence can allow several religious groups to comfortably use one common room; but also how design can cause clashes between different interests and how materiality is forced in the end to advice a clear spatial distinction between different types of usage in the room.
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| 14. |
- Petersson, Anna, et al.
(författare)
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The concept of hyperenculturation : An example from a Swedish research school
- 2020
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Ingår i: Högre utbildning. - : Cappelen Damm AS - Cappelen Damm Akademisk. - 2000-7558. ; 10:2, s. 24-36
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this paper is to discuss how research schools with a structured programme and targeted profile may make it difficult for doctoral students to expand the academic role. Our paper is based on material collected in a questionnaire given to doctoral students enrolled at a Swedish research school in architecture. In this questionnaire we found three areas – openness to other disciplines and practices; support for different communicational channels; andvarious research approaches and methodologies – where a certain divergence could be observed between what the students perceived was important for their educational development, and how well their needs and wishes were met by the research school and its extended learning environment. We also found that the doctoral students valued the teaching experience they gained, and wished they had been able to teach more. In order to shed light on a process of enculturation that we see as potentially leading to a narrowing learning culture, we introduce and discuss the concept of what we call ‘hyperenculturation.’
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| 15. |
- Granlund, Alexander, et al.
(författare)
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The Influence of Module Tilt on Snow Shadowing of Frameless Bifacial Modules
- 2019
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In this study, frameless bifacial modules’ performance in a boreal climate is examined, with a focus on snow coverage and snow clearance for different module tilt angles. A group of ten bifacial modules at different tilt angles located in northern Sweden at latitude 65°N were studied during the first months of 2019. It was shown that modules mounted at 0 and 15° tilt was covered the most by snow and 80 and 90° the least. All other modules, mounted at 25-70° tilt, showed mostly similar results in snow coverage and removal. All modules were subjected to snow coverage from January to March. In January no considerable energy output was observed for any module. In February and March modules with tilt angles of 0 and 15° had a lower energy output than the other modules, for which no considerable differences were observed. In April, when no snow coverage occurred, the module mounted at 45° had the largest energy output and in May, 25-35° performed the best. For the entire period of January-May the modules at 35-45° output the most energy.
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| 16. |
- Juhas, Mario, et al.
(författare)
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In vitro activity of apramycin against multidrug-, carbapenem- and aminoglycoside-resistant Enterobacteriaceae and Acinetobacter baumannii
- 2019
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Ingår i: Journal of Antimicrobial Chemotherapy. - : OXFORD UNIV PRESS. - 0305-7453 .- 1460-2091. ; 74:4, s. 944-952
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Widespread antimicrobial resistance often limits the availability of therapeutic options to only a few last-resort drugs that are themselves challenged by emerging resistance and adverse side effects. Apramycin, an aminoglycoside antibiotic, has a unique chemical structure that evades almost all resistance mechanisms including the RNA methyltransferases frequently encountered in carbapenemase-producing clinical isolates. This study evaluates the in vitro activity of apramycin against multidrug-, carbapenem- and aminoglycoside-resistant Enterobacteriaceae and Acinetobacter baumannii, and provides a rationale for its superior antibacterial activity in the presence of aminoglycoside resistance determinants.Methods: A thorough antibacterial assessment of apramycin with 1232 clinical isolates from Europe, Asia, Africa and South America was performed by standard CLSI broth microdilution testing. WGS and susceptibility testing with an engineered panel of aminoglycoside resistance-conferring determinants were used to provide a mechanistic rationale for the breadth of apramycin activity.Results: MIC distributions and MIC90 values demonstrated broad antibacterial activity of apramycin against Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Morganella morganii, Citrobacter freundii, Providencia spp., Proteus mirabilis, Serratia marcescens and A. baumannii. Genotypic analysis revealed the variety of aminoglycoside-modifying enzymes and rRNA methyltransferases that rendered a remarkable proportion of clinical isolates resistant to standard-of-care aminoglycosides, but not to apramycin. Screening a panel of engineered strains each with a single well-defined resistance mechanism further demonstrated a lack of cross-resistance to gentamicin, amikacin, tobramycin and plazomicin.Conclusions: Its superior breadth of activity renders apramycin a promising drug candidate for the treatment of systemic Gram-negative infections that are resistant to treatment with other aminoglycoside antibiotics.
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| 17. |
- Petersson, Anna Malou, et al.
(författare)
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Developing an ideation method to be used in cross-functional inter-organizational teams by means of action design research
- 2018
-
Ingår i: Research in Engineering Design. - : Springer. - 0934-9839 .- 1435-6066. ; 29:3, s. 433-457
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Tidskriftsartikel (refereegranskat)abstract
- Using ideation methods in an optimal way has a great potential to increase the number of ideas which a team can contribute during the conceptual phase of product development in industry. Previous studies on ideation methods have been mainly statistical studies in a laboratory setting. In the present study, however, the aim was to develop tailor-made ideation methods in a specific context, among actors on a deregulated railway market, through close interaction between researchers and engineers in a real-world context. Considering previous relevant research on ideation methods, associative memory models and the findings from tests of established ideation methods performed in the same group, a number of preliminary design principles were formulated and implemented in an ideation method that combines individual phases of rotational and gallery viewing with phases of verbal group interaction. The method was tested and refined in a cross-functional inter-organizational group comprising participants from different actors in the railway sector. Besides its provision of qualitative and quantitative test results, the present study has considered the opinions of the participants in detail, which can give important insights into the factors determining whether such a method will be implemented in industry. The participants found the method to be more useful and to generate more ideas that could be used in practice compared to the established ideation methods which they had tried. The learning derived from the specific case was formalized into a number of design principles for ideation methods to be used in cross-functional inter-organizational groups.
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| 18. |
- Björnsson Hallgren, Hanna C, et al.
(författare)
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Specific exercises for subacromial pain : Good results maintained for 5 years
- 2017
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Ingår i: Acta Orthopaedica. - : Taylor & Francis. - 1745-3674 .- 1745-3682. ; 88:6, s. 600-605
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose — We have previously shown that specific exercises reduced the need for surgery in subacromial painpatients at 1-year follow-up. We have now investigated whetherthis result was maintained after 5 years and compared the outcomesof surgery and non-surgical treatment.Patients and methods — 97 patients were included in the previouslyreported randomized study of patients on a waiting list forsurgery. These patients were randomized to specifi c or unspecifi cexercises. After 3 months of exercises the patients were asked ifthey still wanted surgery and this was also assessed at the present5-year follow-up. The 1-year assessment included Constant–Murley score, DASH, VAS at night, rest and activity, EQ-5D, andEQ-VAS. All these outcome assessments were repeated after 5years in 91 of the patients.Results — At the 5-year follow-up more patients in the specifi cexercise group had declined surgery, 33 of 47 as compared with16 of 44 (p = 0.001) in the unspecifi c exercise group. The meanConstant–Murley score continued to improve between the 1- and5-year follow-ups in both surgically and non-surgically treatedgroups. On a group level there was no clinically relevant changebetween 1 and 5 years in any of the other outcome measuresregardless of treatment.Interpretation — This 5-year follow-up of a previously publishedrandomized controlled trial found that specifi c exercisesreduced the need for surgery in patients with subacromial pain.Patients not responding to specifi c exercises may achieve similargood results with surgery. These fi ndings emphasize that a specifi cexercise program may serve as a selection tool for surgery.
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| 19. |
- Petersson, Anna Malou
(författare)
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Collaborative conceptual design methods in the context of the Swedish deregulated railway market : From the perspectives of maintenance, infrastructure management, product provision, and research
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- As a result of the deregulation of the Swedish railway market, the differentfunctions involved during the life cycle of railway products have been spreadout over different actors. The trigger for the work presented in this thesis wasthe insight that, since function-specific knowledge of the railway in Swedenbelongs to different organizations, special efforts would be needed to achieve aholistic picture of a railway product during the conceptual design phase. However,there is a lack of methods developed for groups with participants fromdifferent organizations possessing different functional knowledge about a product.The overall aim of the research for this thesis was therefore to develop anideation method and a concept selection method specifically for groups actingin the context of the Swedish deregulated railway market, with members fromdifferent organizations with different functional knowledge. By means of actiondesign research, the methods were developed within the scope of a researchproject involving four different actors on the Swedish railway market.The project group tested Method 635, the gallery method and the SIL method.Overall, the gallery method was most popular and the SIL method leastpopular among the participants. Method 635 was found to have a considerablyhigher idea and concept generation rate than the gallery and SIL methods.The developed ideation method combines the rotational viewing of generatedideas in the group and gallery viewing with steps of verbal interaction wherethe group members take turns to present and comment on generated ideas. Theproject group regarded the developed method as the best method of all themethods which they had tried, and it outperformed the other methods with regardto the total number of generated concepts and ideas. The views of the projectgroup on the method correlated positively to the views of participants takingpart in field tests of the method.The developed concept selection method combines refined versions of theprocedures for topic clarification, goal specification, requirement specificationand concept screening developed by Pahl and Beitz with a concept scoring procedurebased on the life cycle and societal costs associated with each conceptthat fulfils the stated requirements.The most important effect of the composition of the group was found to bethe wide range of viewpoints on the topic at hand that the representative groupof different relevant actors was able to provide.
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| 20. |
- Petersson, Anna Malou, et al.
(författare)
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Ideation methods applied in a cross-functional inter-organizational group : an exploratory case study from the railway sector
- 2017
-
Ingår i: Research in Engineering Design. - : Springer. - 0934-9839 .- 1435-6066. ; 28:1, s. 71-97
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Tidskriftsartikel (refereegranskat)abstract
- The conceptual design phase is a critical step, since it influences the subsequent steps during product development with regard to cost, quality and performance. Previous research has focused on cross-functional teams within an organization. However, many product development projects benefit from the participation of members from different organizations, not least during the conceptual design phase of technical products, where it is essential to consider different aspects of the product-to-be. Therefore, we conducted an in-depth case study of a cross-functional inter-organizational group testing ideation methods in a real-life setting within a development project in the railway sector. The group comprised participants from an infrastructure manager, a supplier, a maintenance contractor and research bodies. The tested ideation methods were Method 635, the gallery method and the SIL method. The participants found working in a cross-functional inter-organizational group to be beneficial both during the group-analysis of the topics and during the generation of ideas on how to address the ideation topic. Applying the ideation methods to the ideation topics facilitated the sharing of information between participants, and the diversity of the group manifested itself in several ways during ideation. Overall, the gallery method was most popular, and the SIL method was least popular among the participants.
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