| 1. |
- Koziolek, M., et al.
(författare)
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Challenges in Permeability Assessment for Oral Drug Product Development
- 2023
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Ingår i: Pharmaceutics. - : MDPI. - 1999-4923. ; 15:10
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Tidskriftsartikel (refereegranskat)abstract
- Drug permeation across the intestinal epithelium is a prerequisite for successful oral drug delivery. The increased interest in oral administration of peptides, as well as poorly soluble and poorly permeable compounds such as drugs for targeted protein degradation, have made permeability a key parameter in oral drug product development. This review describes the various in vitro, in silico and in vivo methodologies that are applied to determine drug permeability in the human gastrointestinal tract and identifies how they are applied in the different stages of drug development. The various methods used to predict, estimate or measure permeability values, ranging from in silico and in vitro methods all the way to studies in animals and humans, are discussed with regard to their advantages, limitations and applications. A special focus is put on novel techniques such as computational approaches, gut-on-chip models and human tissue-based models, where significant progress has been made in the last few years. In addition, the impact of permeability estimations on PK predictions in PBPK modeling, the degree to which excipients can affect drug permeability in clinical studies and the requirements for colonic drug absorption are addressed.
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| 2. |
- Niessen, Laura, et al.
(författare)
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Sufficiency as trend or tradition?—Uncovering business pathways to sufficiency through historical advertisements
- 2023
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Ingår i: Frontiers in Sustainability. - 2673-4524. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Climate change and dwindling resources underline that we need to bring production and consumption levels in line with planetary boundaries. Consumption, particularly in high-income communities, needs to be reduced and stabilized at sustainable levels. Businesses can play a key role as suppliers of goods and services and creators of demand. Some companies are rising to the challenge and promoting less consumption or “sufficiency” through long product lifetimes, repair services or rental offers, but they remain niche actors in the economic system. Similarly, while circular initiatives gain traction across sectors, firms focus primarily on recycling and efficiency improvements rather than supporting more radical “Reduce” strategies. To engage companies in promoting sustainable levels of consumption, it can be helpful to understand pathways of established businesses who currently promote sufficiency. What can we learn from companies that currently promote sufficiency in their communications? Have they always advocated sufficient consumption, or have they changed recently? Through a historical perspective, we provide insights on the pathway of sufficiency for three companies. A document analysis of historical advertisements shines light on the messaging to potential customers over time. It is combined with an analysis of contemporary communications to connect the companies' past and present sufficiency approaches. Understanding different pathways to sufficiency can help modern-day businesses to reconsider their own business models and orientation. It can also point out levers for policy to support a transformation toward sustainable and circular business models that promote living within planetary boundaries.
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| 3. |
- Niessen, Laura, et al.
(författare)
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The impact of business sufficiency strategies on consumer practices : The case of bicycle subscription
- 2023
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Ingår i: Sustainable Production and Consumption. - : Elsevier BV. - 2352-5509. ; 35, s. 576-591
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Tidskriftsartikel (refereegranskat)abstract
- To stay within planetary boundaries, we need to move into sustainable levels of resource consumption, or sufficiency. Businesses can play a key role in driving sufficiency as they satisfy and also create demand. This article investigates how a bicycle subscription company can promote sufficiency among its users, with a focus on modal shift and product care. It aims to fill the research gap on how business sufficiency strategies impact actual consumption, while also providing insights into the less studied business model of bicycle subscription. User mobility patterns and care behaviour are analysed through the lens of social practice theory. Using the subscription, many users experience a modal shift towards cycling, mostly replacing public transport, walking and car journeys. Around half of the respondents also cycle longer distances and more frequently than before the subscription. Yet, users might stop cycling after the subscription, often due to moving to areas with a poor cycling infrastructure. Concerning product longevity, subscribers differ, with some taking good care of the vehicle and others being less careful. The research shows some advances towards sufficiency but also highlights the limits of one company's actions and the importance of structural changes to promote sufficient consumption.
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| 4. |
- Niessen, Laura, et al.
(författare)
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How can businesses drive sufficiency? The business for sufficiency framework
- 2021
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Ingår i: Sustainable Production and Consumption. - : Elsevier BV. - 2352-5509. ; 28, s. 1090-1103
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Tidskriftsartikel (refereegranskat)abstract
- The breaching of planetary boundaries and excessive extraction of natural resources requires a revisited approach to consumption and production. The concept of sufficiency, which advocates meeting human needs within the planetary limits by curbing excessive consumption levels, is gaining increasing attention. Businesses are drivers of consumption, yet they have been largely overlooked as potential leaders towards a sufficiency-based economy and research on businesses driving sustainable consumption strategically is still a niche. The methods applied here are a literature and practice review and interviews to understand the state-of-the-art in sufficiency-orientated business strategies and develop a framework for future research and practice. Merging English- and German-language research, a base matrix of the waste hierarchy and the four lessens is presented. This matrix is populated with business sufficiency strategies, condensing existing work and creating the ‘Business for Sufficiency’ (BfS) framework. Empirical research with businesses already employing sufficiency strategies refines and validates the framework and sheds light on the viability, desirability, feasibility and sustainability of such offers, highlighting barriers and opportunities. The most prevalent strategies fall into the Rethink framework dimension which require the least radical changes. In addition, interviewees highlighted obstacles in reconciling more radical strategies such as Moderating sales with their financial sustainability. Yet, all interviewees stressed the need for reduced consumption and the role that business should play in enabling sufficiency, demonstrating the relevance of this topic for future research and practice.
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| 5. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 6. |
- Rycroft-Malone, J., et al.
(författare)
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A realist process evaluation within the Facilitating Implementation of Research Evidence (FIRE) cluster randomised controlled international trial: An exemplar
- 2018
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Ingår i: Implementation Science. - : Springer Science and Business Media LLC. - 1748-5908. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Facilitation is a promising implementation intervention, which requires theory-informed evaluation. This paper presents an exemplar of a multi-country realist process evaluation that was embedded in the first international randomised controlled trial evaluating two types of facilitation for implementing urinary continence care recommendations. We aimed to uncover what worked (and did not work), for whom, how, why and in what circumstances during the process of implementing the facilitation interventions in practice. Methods: This realist process evaluation included theory formulation, theory testing and refining. Data were collected in 24 care home sites across four European countries. Data were collected over four time points using multiple qualitative methods: observation (372h), interviews with staff (n=357), residents (n=152), next of kin (n=109) and other stakeholders (n=128), supplemented by facilitator activity logs. A combined inductive and deductive data analysis process focused on realist theory refinement and testing. Results: The content and approach of the two facilitation programmes prompted variable opportunities to align and realign support with the needs and expectations of facilitators and homes. This influenced their level of confidence in fulfilling the facilitator role and ability to deliver the intervention as planned. The success of intervention implementation was largely dependent on whether sites prioritised their involvement in both the study and the facilitation programme. In contexts where the study was prioritised (including release of resources) and where managers and staff support was sustained, this prompted collective engagement (as an attitude and action). Internal facilitators' (IF) personal characteristics and abilities, including personal and formal authority, in combination with a supportive environment prompted by managers triggered the potential for learning over time. Learning over time resulted in a sense of confidence and personal growth, and enactment of the facilitation role, which resulted in practice changes. Conclusion: The scale and multi-country nature of this study provided a novel context to conduct one of the few trial embedded realist-informed process evaluations. In addition to providing an explanatory account of implementation processes, a conceptual platform for future facilitation research is presented. Finally, a realist-informed process evaluation framework is outlined, which could inform future research of this nature. © 2018 The Author(s).
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| 7. |
- Seers, K., et al.
(författare)
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Facilitating Implementation of Research Evidence (FIRE): An international cluster randomised controlled trial to evaluate two models of facilitation informed by the Promoting Action on Research Implementation in Health Services (PARIHS) framework
- 2018
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Ingår i: Implementation Science. - : Springer Science and Business Media LLC. - 1748-5908. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Health care practice needs to be underpinned by high quality research evidence, so that the best possible care can be delivered. However, evidence from research is not always utilised in practice. This study used the Promoting Action on Research Implementation in Health Services (PARIHS) framework as its theoretical underpinning to test whether two different approaches to facilitating implementation could affect the use of research evidence in practice. Methods: A pragmatic clustered randomised controlled trial with embedded process and economic evaluation was used. The study took place in four European countries across 24 long-term nursing care sites, for people aged 60years or more with documented urinary incontinence. In each country, sites were randomly allocated to standard dissemination, or one of two different types of facilitation. The primary outcome was the documented percentage compliance with the continence recommendations, assessed at baseline, then at 6, 12, 18, and 24months after the intervention. Data were analysed using STATA15, multi-level mixed-effects linear regression models were fitted to scores for compliance with the continence recommendations, adjusting for clustering. Results: Quantitative data were obtained from reviews of 2313 records. There were no significant differences in the primary outcome (documented compliance with continence recommendations) between study arms and all study arms improved over time. Conclusions: This was the first cross European randomised controlled trial with embedded process evaluation that sought to test different methods of facilitation. There were no statistically significant differences in compliance with continence recommendations between the groups. It was not possible to identify whether different types and "doses" of facilitation were influential within very diverse contextual conditions. The process evaluation (Rycroft-Malone et al., Implementation Science. doi: 10.1186/s13012-018-0811-0) revealed the models of facilitation used were limited in their ability to overcome the influence of contextual factors. © 2018 The Author(s).
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| 8. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 9. |
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| 10. |
- Abbasi, R., et al.
(författare)
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IceTop : The surface component of IceCube
- 2013
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 700, s. 188-220
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Tidskriftsartikel (refereegranskat)abstract
- IceTop, the surface component of the IceCube Neutrino Observatory at the South Pole, is an air shower array with an area of 1 km(2). The detector allows a detailed exploration of the mass composition of primary cosmic rays in the energy range from about 100 TeV to 1 EeV by exploiting the correlation between the shower energy measured in IceTop and the energy deposited by muons in the deep ice. In this paper we report on the technical design, construction and installation, the trigger and data acquisition systems as well as the software framework for calibration, reconstruction and simulation. Finally the first experience from commissioning and operating the detector and the performance as an air shower detector will be discussed.
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