| 1. |
- Barjesteh van Waalwijk van Doorn-Khosrovani, Sahar, et al.
(författare)
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PCM4EU and PRIME-ROSE : Collaboration for implementation of precision cancer medicine in Europe
- 2024
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Ingår i: Acta Oncologica. - 1651-226X .- 1651-226X. ; 63, s. 385-391
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the two European Union (EU)-funded projects, PCM4EU (Personalized Cancer Medicine for all EU citizens) and PRIME-ROSE (Precision Cancer Medicine Repurposing System Using Pragmatic Clinical Trials), we aim to facilitate implementation of precision cancer medicine (PCM) in Europe by leveraging the experience from ongoing national initiatives that have already been particularly successful. PATIENTS AND METHODS: PCM4EU and PRIME-ROSE gather 17 and 24 partners, respectively, from 19 European countries. The projects are based on a network of Drug Rediscovery Protocol (DRUP)-like clinical trials that are currently ongoing or soon to start in 11 different countries, and with more trials expected to be established soon. The main aims of both the projects are to improve implementation pathways from molecular diagnostics to treatment, and reimbursement of diagnostics and tumour-tailored therapies to provide examples of best practices for PCM in Europe. RESULTS: PCM4EU and PRIME-ROSE were launched in January and July 2023, respectively. Educational materials, including a podcast series, are already available from the PCM4EU website (http://www.pcm4eu.eu). The first reports, including an overview of requirements for the reimbursement systems in participating countries and a guide on patient involvement, are expected to be published in 2024. CONCLUSION: European collaboration can facilitate the implementation of PCM and thereby provide affordable and equitable access to precision diagnostics and matched therapies for more patients. ble from the PCM4EU website (http://www.pcm4eu.eu). The first reports, including an overview of requirements for the reimbursement systems in participating countries and a guide on patient involvement, are expected to be published in 2024. CONCLUSION: European collaboration can facilitate the implementation of PCM and thereby provide affordable and equitable access to precision diagnostics and matched therapies for more patients.
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| 2. |
- Edsjö, Anders, et al.
(författare)
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Precision cancer medicine : Concepts, current practice, and future developments
- 2023
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Ingår i: Journal of Internal Medicine. - 0954-6820 .- 1365-2796. ; 294:4, s. 455-481
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Forskningsöversikt (refereegranskat)abstract
- Precision cancer medicine is a multidisciplinary team effort that requires involvement and commitment of many stakeholders including the society at large. Building on the success of significant advances in precision therapy for oncological patients over the last two decades, future developments will be significantly shaped by improvements in scalable molecular diagnostics in which increasingly complex multilayered datasets require transformation into clinically useful information guiding patient management at fast turnaround times. Adaptive profiling strategies involving tissue- and liquid-based testing that account for the immense plasticity of cancer during the patient's journey and also include early detection approaches are already finding their way into clinical routine and will become paramount. A second major driver is the development of smart clinical trials and trial concepts which, complemented by real-world evidence, rapidly broaden the spectrum of therapeutic options. Tight coordination with regulatory agencies and health technology assessment bodies is crucial in this context. Multicentric networks operating nationally and internationally are key in implementing precision oncology in clinical practice and support developing and improving the ecosystem and framework needed to turn invocation into benefits for patients. The review provides an overview of the diagnostic tools, innovative clinical studies, and collaborative efforts needed to realize precision cancer medicine.
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| 3. |
- Engstrøm, Thomas, et al.
(författare)
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Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients : A phase 2 randomised clinical trial
- 2018
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 104:19, s. 1593-1599
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Reperfusion immediately after reopening of the infarct-related artery in ST-segment elevation myocardial infarction (STEMI) may cause myocardial damage in addition to the ischaemic insult (reperfusion injury). The gap junction modulating peptide danegaptide has in animal models reduced this injury. We evaluated the effect of danegaptide on myocardial salvage in patients with STEMI. Methods: In addition to primary percutaneous coronary intervention in STEMI patients with thrombolysis in myocardial infarction flow 0-1, single vessel disease and ischaemia time less than 6 hours, we tested, in a clinical proof-of-concept study, the therapeutic potential of danegaptide at two-dose levels. Primary outcome was myocardial salvage evaluated by cardiac MRI after 3 months. Results: From November 2013 to August 2015, a total of 585 patients were randomly enrolled in the trial. Imaging criteria were fulfilled for 79 (high dose), 80 (low dose) and 84 (placebo) patients eligible for the per-protocol analysis. Danegaptide did not affect the myocardial salvage index (danegaptide high (63.9±14.9), danegaptide low (65.6±15.6) and control (66.7±11.7), P=0.40), final infarct size (danegaptide high (19.6±11.4 g), danegaptide low (18.6±9.6 g) and control (21.4±15.0 g), P=0.88) or left ventricular ejection fraction (danegaptide high (53.9%±9.5%), danegaptide low (52.7%±10.3%) and control (52.1%±10.9%), P=0.64). There was no difference between groups with regard to clinical outcome. Conclusions: Administration of danegaptide to patients with STEMI did not improve myocardial salvage. Trial registration number: NCT01977755; Pre-results.
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| 4. |
- Lassen, Ulrik Hjort, 1979
(författare)
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Craftmen's Practice of Timber Framing Methods
- 2009
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Ingår i: Proceedings of the International Symposium on Timber Structures, 25-27 June, Istanbul, Turkey. "Timber Structures from Antiquity to the Present" - Edited by: John CHILTON and Ihsan MUNGAN. - 9789758574254 ; , s. 101-112
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Konferensbidrag (refereegranskat)abstract
- In this paper I have surveyed and classified the different transferring methods used for adjusting irregularly sized timber. In contrary to the research that exists in this field that has mostly focused on buildings and construction types, I have tried to classify and explain the methods that I have identified keeping the focus on what actually happens in the practical situation. It can be seen as an attempt to re-establish the craftsman’s know-how in hands on restoration and reconstruction. The empirical material constists of my own carpentry experience and of participation in practical restoration and reconstruction projects in Danish, Norwegian, French, English, Japanese and American timber-frame traditions. I have also used historical and contemporary literature and handbooks for carpenters that involve methods of scribing irregularly sized timber. The preliminary classification of the transferring methods is followed by a visual description of each identified procedure and a short analysis of effi ciency, workplace arrangements, context of tradition, tools and markings for the different methods. Despite advanced power tools, CAD-drawings and prefabrication, every experienced timber framer has undoubtedly found himself in a situation when the transferring methods are effi cient and therefore needed. Even today there will always be situations that require a craftsman’s practice of timber framing methods.
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| 5. |
- Lassen, Ulrik Hjort, 1979
(författare)
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Hantverk på Japanska? Om att mötas och utbildas i handling
- 2011
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Ingår i: Bygnadskultur. - 0348-6885. ; :2:2011, s. 26-30
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Vad skiljer en japansk stolpverkskonstruktion från en norsk? Vilka timringstraditioner förekommer på den engelska landsbygden? Och hur gör man för att lära av varandra när man samtidigt ska bygga ett hus? Det är frågor som hantverksdoktoranden Ulrik Hjort Lassen numera kan besvara. I den här artikeln berättar han om tre internationella arbetsseminarier för hantverkare som han har haft chansen att delta i.
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| 6. |
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| 7. |
- Lassen, Ulrik Hjort, 1979
(författare)
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Piquer au Plomb
- 2014
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Ingår i: Hantverkslaboratoriets filmkanal på Youtube.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Piquer au Plomb - "at tilridse med loddet". En film av Ulrik Hjort Lassen. Filmen är en undervisningsinriktad beskrivning av en fransk metod för påmärkning av timmer och en del av Ulrik Hjort Lassens forskningsarbete i stolpverkskonstruktioner.
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| 8. |
- Lassen, Ulrik Hjort, 1979
(författare)
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Piquer au plomb - En undersögelse af en gammel byggeteknik
- 2007
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- An analytic study of the French timber framed three-aisled barn in Aclou, built in the 15th century, has shown that it is possible to reconstruct the original building process by means of knowledge of workmanship, of recise measuring and of digital documentation. This reconstruction has been an attempt to regard historical buildings as a result of a building process and not just as a historical monument. The focus of this study has been to find and to use the still existing traces and markings from the original building process as argumentation for a reconstruction, a description of the workmanship that lies behind the timber frame construction. It has been an attempt to make a scientific research of the intellectual part of the craft to show and to revive some of the simple but very efficient techniques and tools which were developed throughout the past thousand years, and which today mistakenly have slipped out of use.
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| 9. |
- Lassen, Ulrik Hjort, 1979, et al.
(författare)
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'Plumb Line scribe': Using multimedia to preserve traditional craft skills
- 2013
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Ingår i: Craft Research. - : Intellect. - 2040-4689 .- 2040-4697. ; 4:1, s. 31-52
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Tidskriftsartikel (refereegranskat)abstract
- The skills required in craft practice involve a high degree of tacit knowledge which is internalised and frequently difficult for the craft expert to articulate. Wood, a multimedia designer, has undertaken extensive research over the last 10 years seeking to understand the knowledge of skilled craftsmen and find methods of capturing it and passing it on. She has developed an elicitation strategy that employs an expert learner to uncover the skilled knowledge of master craftsmen, and a transmission strategy based on the concept of bridges to assist the design of learning resources for novices. The aim of this research was to investigate the possibility of combining the two roles defined in Wood’s research as an expert learner and designer. Lassen has used the techniques developed by Wood to record and transmit the skilled knowledge needed to make timber-framed buildings, knowledge that today is in danger of being lost. The focus of the study has been the procedure for scribing timbers which is a central part of the building process. Being a skilled carpenter, Lassen has acted as an expert learner, learning the skills of scribing through a combination of researching existing documentation, working with master craftsmen, and his own experimentation. He developed and tested a multimedia learning resource to provide ‘bridges’ for new learners to this knowledge. The outcome of the application of Wood’s elicitation and transmission strategy to plumb line scribing is a demonstration of the transferability of Wood’s methods within this new context. This is important because it reveals the potential for other craft practitioners to apply Wood’s methods to their own learning and teaching, and produce learning resources to provide bridges to their craft knowledge and preserve their unique skills.
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| 10. |
- Lassen, Ulrik Hjort, 1979
(författare)
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Practice-led research in timber framing methods
- 2012
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Ingår i: Hantverkslaboratoriet.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- My research lies within the area of timber-framed constructions. As a carpenter I am interested in the working procedures involved in the practical building situation, and I focus on the part of the building process, situated between the idea of a construction and the cutting of the joinery. In this study it is called the ‘scribing’ process. This construction is a case study in my practice-led research, where it has been possible to apply working procedures in practical craft laborations. The aim of the study has been to test and compare different methods and solutions in the same construction, and to identify and analyse different parts of the building process that have an influence on the scribing process. It has been a way to take in the knowledge I have learned and found in different contexts, to improve my own skill level and to support the results of my research. The leading questions throughout the study have been: •Which parts of the building process have a direct influence on the scribing procedures? •Which principles form the basis of the scribing of timbers, when focusing on what is happening in the practical situation? •Which tools, skills and theoretical knowledge are necessary to be able to scribe a timber-framed construction?
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| 11. |
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| 12. |
- Lassen, Ulrik Hjort, 1979, et al.
(författare)
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Stolpverket i logen i Maglö
- 2011
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Ingår i: Bebyggelsehistorisk tidskrift. - 0349-2834. ; 60/2010, s. 58-77
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Tidskriftsartikel (refereegranskat)abstract
- The timber-framed parts of buildings and the technical aspects of how the buildings were constructed are rarely addressed in scientific papers on the history of built environments. In Scandinavia architects, art historians, archaeologists and ethnologists have the preferential right to carry out the documentation procedures concerning historic buildings. In this study the 250-year-old barn in Maglö has been the subject of a survey on a historical and technical basis. The aim has been to describe timber framing as a traditional Swedish building method, and to put forward the barn as a unique representative of a forgotten historic building tradition in Southern Sweden. During 2009−2010 a documentation of the barn was carried out which involved measuring and analysing the structure, studying the structural details and the still-existing traces and markings from the original building process. The documentation was performed by carpenters experienced in historic building techniques. Therefore the focus has been to understand the workmanship behind the timber-frame structure, thereby creating a dialogue between the modern and the historic carpenter, which is of great value when the aim of the documentation is to reconstruct the original building process or to make deliberate judgements during restoration. The article firstly gives a review of the history of built environments in Maglö, drawing parallels to Danish barns of the same time, since the inner structure of all similar barns of Southern Sweden has been removed because of the modern use of the buildings for industrialised agriculture. This states that the barn of Maglö is rather unique in Sweden, although only one-third of the building has survived. The second part is a short description of timber framing in a technical and historical context, which states that today there are many regional terms for different timber-framed structures. The Swedish word stolpverk has been suggested as the Swedish parallel to timber framing, and general aspects of the building method are described shortly. The main part of the article is a tour through the timber frames of the barn, describing and analysing structural details that are not obvious to people unfamiliar with the craft and historic working methods. This involves the joinery, the different parts and materials, the traces of the tools, the bracing of the structure and the scribing and marking of the frames. This technical description of the building has shown that a lot of information about how to build timber-framed structures can be obtained from one single building. In order to find out in a broader perspective which methods were used to build timber framing in Sweden, there is a huge amount of practical knowledge hidden in the old buildings. The documentation procedure using exact measurement and a carpenter’s eye to find and analyse the interesting parts and details helps to garner this knowledge.
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| 13. |
- Lassen, Ulrik Hjort, 1979
(författare)
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The Invisible Tools of a Timber Framer - A survey of principles, situations and procedures for marking
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- My thesis focuses on the marking procedures when building timber frames, from the idea of a construction to the cutting of the timbers. The marking procedures are essential parts of the building process, and without markings you don’t know where to cut. Markings can be very different from one region to the other, from one carpenter to another and dependent on the material and the purpose of the construction. It is a highly skilled process demanding a three-dimensional capacity of the carpenter and involving a general craft knowledge in every decision process. Knowledge of how to handle irregular materials, how to transfer a shape from one place to another, how to establish and work with reference planes, reference lines and reference points and how to use practical geometry and developed drawing in the layout. The thesis is a survey of the marking procedures from the timber framing traditions in northwestern Europe and Scandinavia, and the aim is to provide a greater understanding of the basic principles and applications of the marking procedures. I have taken a practice-led approach undertaking the dual role of being both practitioner and researcher, and this has been a way to enter the executional level of the craft. Procedural descriptions have been used as a method to verbalize the actions involved in the marking procedures, and they have been useful in studies of written sources and literature. They have been applied when recording my own experiences from working seminars and experiments and in the dialogues with carpenters as a basis for the mutual understanding of the situations. In the survey the general principles are outlined, the possible situations are defined and a number of procedures are analysed and explained. The extent of the survey is embodied in a ‘map’ which demonstrates the complexity of marking situations and procedures and how they are interconnected. The thesis provides a platform for understanding the application of the skilled but often not verbalized knowledge which is internalized in the craftsmen and only brought forward in the execution of their work.
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| 14. |
- Lassen, Ulrik, 1979, et al.
(författare)
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Stolpverket i logen på Maglö
- 2010
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Ingår i: Bebyggelsehistorisk tidskrift. - : Föreningen Bebyggelsehistorisk tidskrift. - 0349-2834 .- 2002-3812. ; :60, s. 58-77
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Tidskriftsartikel (refereegranskat)
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| 15. |
- Lokhorst, Henk M, et al.
(författare)
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Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma.
- 2015
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 373:13, s. 1207-1219
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Tidskriftsartikel (refereegranskat)abstract
- Background Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy. Methods In part 1, the dose-escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per kilogram of body weight. In part 2, the dose-expansion phase, 30 patients received 8 mg per kilogram of daratumumab and 42 received 16 mg per kilogram, administered once weekly (8 doses), twice monthly (8 doses), and monthly for up to 24 months. End points included safety, efficacy, and pharmacokinetics. Results No maximum tolerated dose was identified in part 1. In part 2, the median time since diagnosis was 5.7 years. Patients had received a median of four prior treatments; 79% of the patients had disease that was refractory to the last therapy received (64% had disease refractory to proteasome inhibitors and immunomodulatory drugs and 64% had disease refractory to bortezomib and lenalidomide), and 76% had received autologous stem-cell transplants. Infusion-related reactions in part 2 were mild (71% of patients had an event of any grade, and 1% had an event of grade 3), with no dose-dependent adverse events. The most common adverse events of grade 3 or 4 (in ≥5% of patients) were pneumonia and thrombocytopenia. The overall response rate was 36% in the cohort that received 16 mg per kilogram (15 patients had a partial response or better, including 2 with a complete response and 2 with a very good partial response) and 10% in the cohort that received 8 mg per kilogram (3 had a partial response). In the cohort that received 16 mg per kilogram, the median progression-free survival was 5.6 months (95% confidence interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months. Conclusions Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma. (Funded by Janssen Research and Development and Genmab; ClinicalTrials.gov number, NCT00574288 .).
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| 16. |
- Mirza, Mansoor Raza, et al.
(författare)
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A phase I study of the PARP inhibitor niraparib in combination with bevacizumab in platinum-sensitive epithelial ovarian cancer: NSGO AVANOVA1/ENGOT-OV24
- 2019
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Ingår i: Cancer Chemotherapy and Pharmacology. - : SPRINGER. - 0344-5704 .- 1432-0843. ; 84:4, s. 791-798
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Tidskriftsartikel (refereegranskat)abstract
- Background Combining poly(ADP-ribose) polymerase (PARP) inhibitors with antiangiogenic agents appeared to enhance activity vs PARP inhibitors alone in a randomized phase II trial. Materials and methods In AVANOVA (NCT02354131) part 1, patients with measurable/evaluable high-grade serous/endometrioid platinum-sensitive ovarian cancer received bevacizumab 15 mg/kg every 21 days with escalating doses of niraparib capsules (100, 200, or 300 mg daily) in a 3 + 3 dose-escalation design. Primary objectives were to evaluate safety and tolerability and to determine the recommended phase II dose (RP2D). Results Three of 12 enrolled patients had germline BRCA2 mutations. In cycle 1, nine patients experienced grade 3 toxicities: five with hypertension, three with anemia, and one with thrombocytopenia. There was one dose-limiting toxicity (grade 4 thrombocytopenia with niraparib 300 mg), thus the RP2D was bevacizumab 15 mg/kg with niraparib 300 mg. The response rate was 50%; disease was stabilized in a further 42%. Median progression-free survival was 11.6 (95% confidence interval 8.4-20.1) months. Niraparib pharmacokinetics were consistent with historical single-agent data. Overlapping exposure was observed across the dose ranges tested on days 1 and 21. Conclusions There was one dose-limiting toxicity; other adverse events were typical PARP inhibitor and antiangiogenic class effects. Niraparib-bevacizumab showed promising activity; Part 2 (vs bevacizumab) was recently reported and phase III comparison with standard-of-care therapy is planned.
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| 17. |
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| 18. |
- Rafaeva, Maria, et al.
(författare)
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Modeling Metastatic Colonization in a Decellularized Organ Scaffold-Based Perfusion Bioreactor
- 2022
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Ingår i: Advanced healthcare materials. - : Wiley. - 2192-2640 .- 2192-2659. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Metastatic cancer spread is responsible for most cancer-related deaths. To colonize a new organ, invading cells adapt to, and remodel, the local extracellular matrix (ECM), a network of proteins and proteoglycans underpinning all tissues, and a critical regulator of homeostasis and disease. However, there is a major lack in tools to study cancer cell behavior within native 3D ECM. Here, an in-house designed bioreactor, where mouse organ ECM scaffolds are perfused and populated with cells that are challenged to colonize it, is presented. Using a specialized bioreactor chamber, it is possible to monitor cell behavior microscopically (e.g., proliferation, migration) within the organ scaffold. Cancer cells in this system recapitulate cell signaling observed in vivo and remodel complex native ECM. Moreover, the bioreactors are compatible with co-culturing cell types of different genetic origin comprising the normal and tumor microenvironment. This degree of experimental flexibility in an organ-specific and 3D context, opens new possibilities to study cell–cell and cell–ECM interplay and to model diseases in a controllable organ-specific system ex vivo.
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| 19. |
- Riba, Michela, et al.
(författare)
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The 1+Million Genomes Minimal Dataset for Cancer
- 2024
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Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 56:5, s. 733-736
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Tidskriftsartikel (refereegranskat)abstract
- Defining minimal standards for data collection is key to creating interoperative, searchable genomic and clinical databases. We highlight here the 1+Million Genomes Minimal Dataset for Cancer, encompassing 140 items in 8 domains to foster the collection of cancer data, inform transnational cooperation and advance precision cancer medicine.
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| 20. |
- Taskén, Kjetil, et al.
(författare)
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Single point of entry to the European precision cancer medicine trial network PRIME-ROSE
- 2024
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 1527-7755 .- 0732-183X. ; 42:16
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Konferensbidrag (refereegranskat)abstract
- Background: Over the last decades, there has been a surge in the development and approval of targeted drugs and immunotherapies for treating cancer patients, as seen by the 757 % increase in approvals by the FDA for new cancer treatments since 2000 (1). This has significantly impacted cancer care and contributed to improving overall survival in various cancer subgroups. However, access to these new treatments is constrained by the market access strategy of the patent-owning company and available knowledge of treatment effects. Only a few treatments have received pan-cancer approval from EMA or FDA, and most drugs receive market authorization per indication. As a result, there is a widening access gap between patients with different cancer types (2). Methods: Exploring the effect of biomarker-driven treatments in new cancer subtypes requires the ability to find patients with rare biomarkers. PRIME-ROSE is a European precision medicine network comprising 11 ongoing or soon-to-start national DRUP-like clinical trials testing registered drugs outside their current label (www.prime-rose.eu). Patients with relevant tumor biomarkers are identified and treated with matched drugs available in each trial’s drug portfolio. The ambition is to swiftly and systematically evaluate the effectiveness of approved precision cancer medicines in new indications through pragmatic trial designs and with RWE control cohorts, ensuring expansion into all relevant patient groups to maximize societal benefit. This is particularly relevant for rare cancers, which are enriched in precision medicine trials (3). Results: In PRIME-ROSE, the trials now share and aggregate data to build evidence faster and more effectively impact patient care by addressing key challenges in precision cancer medicine implementation (increasing the recruitment area to 71 million inhabitants). This will significantly reduce the time for filling treatment cohorts and contribute to closing the indication/drug-specific knowledge gap. In fact, several pharmaceutical companies have already shown their interest in and commitment to participating in PRIME-ROSE, as it offers the unique advantage of entering the trials in the network simultaneously (single point of entry) and with a floating allocation of treatment slots between trials, increasing efficiency in finding patients with specific biomarkers to fill treatment cohorts. Conclusions: A unified entry point to the PRIME-ROSE network is feasible and can facilitate building the knowledge base faster for label expansion and/or country-specific approvals/ reimbursement. National multi-stakeholder ecosystems that include pragmatic, RWE-controlled DRUP-like clinical trials may advance precision medicine implementation.
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