| 61. |
- Häggström, Ida, 1982-
(författare)
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Quantitative methods for tumor imaging with dynamic PET
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is always a need and drive to improve modern cancer care. Dynamic positron emission tomography (PET) offers the advantage of in vivo functional imaging, combined with the ability to follow the physiological processes over time. In addition, by applying tracer kinetic modeling to the dynamic PET data, thus estimating pharmacokinetic parameters associated to e.g. glucose metabolism, cell proliferation etc., more information about the tissue's underlying biology and physiology can be determined. This supplementary information can potentially be a considerable aid when it comes to the segmentation, diagnosis, staging, treatment planning, early treatment response monitoring and follow-up of cancerous tumors.We have found it feasible to use kinetic parameters for semi-automatic tumor segmentation, and found parametric images to have higher contrast compared to static PET uptake images. There are however many possible sources of errors and uncertainties in kinetic parameters obtained through compartment modeling of dynamic PET data. The variation in the number of detected photons caused by the random nature of radioactive decay, is of course always a major source. Other sources may include: the choice of an appropriate model that is suitable for the radiotracer in question, camera detectors and electronics, image acquisition protocol, image reconstruction algorithm with corrections (attenuation, random and scattered coincidences, detector uniformity, decay) and so on. We have found the early frame sampling scheme in dynamic PET to affect the bias and uncertainty in calculated kinetic parameters, and that scatter corrections are necessary for most but not all parameter estimates. Furthermore, analytical image reconstruction algorithms seem more suited for compartment modeling applications compared to iterative algorithms.This thesis and included papers show potential applications and tools for quantitative pharmacokinetic parameters in oncology, and help understand errors and uncertainties associated with them. The aim is to contribute to the long-term goal of enabling the use of dynamic PET and pharmacokinetic parameters for improvements of today's cancer care.
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| 62. |
- Häggström, Ida, 1982-, et al.
(författare)
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Semi-automatic tumour segmentation by selective navigation in a three-parameter volume, obtained by voxel-wise kinetic modelling of C-11-acetate
- 2010
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Ingår i: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 139:1-3, s. 214-218
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Tidskriftsartikel (refereegranskat)abstract
- Positron emission tomography (PET) is increasingly used for delineation of tumour tissue in, for example, radiotherapy treatment planning. The most common method used is to outline volumes with a certain per cent uptake over background in a static image. However, PET data can also be collected dynamically and analysed by kinetic models, which potentially represent the underlying biology better. In the present study, a three-parameter kinetic model was used for voxel-wise evaluation of C-11-acetate data of head/neck tumours. These parameters which represent the tumour blood volume, the uptake rate and the clearance rate of the tissue were derived for each voxel using a linear regression method and used for segmentation of active tumour tissue. This feasibility study shows that it is possible to segment images based on derived model parameters. There is, however, room for improvements concerning the PET data acquisition, noise reduction and the kinetic modelling. In conclusion, this early study indicates a strong potential of the method even though no 'true' tumour volume was available for validation.
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| 63. |
- Häggström, Ida, et al.
(författare)
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The influence of time sampling scheme on kinetic parameters obtained from compartmental modeling of a dynamic PET study : a Monte Carlo study
- 2012
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Ingår i: IEEE Nuclear Science Symposium Conference Record. - Anaheim : IEEE conference proceedings. - 9781467320306 ; , s. 3101-3107
-
Konferensbidrag (refereegranskat)abstract
- Compartmental modeling of dynamic PET data enables quantification of tracer kinetics in vivo, through the obtained model parameters. The dynamic data is sorted into frames during or after the acquisition, with a sampling interval usually ranging from 10 s to 300 s. In this study we wanted to investigate the effect of the chosen sampling interval on kinetic parameters obtained from a 2-tissue model, in terms of bias and standard deviation, using a complete Monte Carlo simulated dynamic F-18-FLT PET study. The results show that the bias and standard deviation in parameter K-1 is small regardless of sampling scheme or noise in the time-activity curves (TACs), and that the bias and standard deviation in k(4) is large for all cases. The bias in V-a is clearly dependent on sampling scheme, increasing for increased sampling interval. In general, a too short sampling interval results in very noisy images and a large bias of the parameter estimate, and a too long sampling interval also increases bias. Noise in the TACs is the largest source of bias.
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| 64. |
- Höijer, Ida, et al.
(författare)
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Amplification-free long-read sequencing reveals unforeseen CRISPR-Cas9 off-target activity
- 2020
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: One ongoing concern about CRISPR-Cas9 genome editing is that unspecific guide RNA (gRNA) binding may induce off-target mutations. However, accurate prediction of CRISPR-Cas9 off-target activity is challenging. Here, we present SMRT-OTS and Nano-OTS, two novel, amplification-free, long-read sequencing protocols for detection of gRNA-driven digestion of genomic DNA by Cas9 in vitro.RESULTS: The methods are assessed using the human cell line HEK293, re-sequenced at 18x coverage using highly accurate HiFi SMRT reads. SMRT-OTS and Nano-OTS are first applied to three different gRNAs targeting HEK293 genomic DNA, resulting in a set of 55 high-confidence gRNA cleavage sites identified by both methods. Twenty-five of these sites are not reported by off-target prediction software, either because they contain four or more single nucleotide mismatches or insertion/deletion mismatches, as compared with the human reference. Additional experiments reveal that 85% of Cas9 cleavage sites are also found by other in vitro-based methods and that on- and off-target sites are detectable in gene bodies where short-reads fail to uniquely align. Even though SMRT-OTS and Nano-OTS identify several sites with previously validated off-target editing activity in cells, our own CRISPR-Cas9 editing experiments in human fibroblasts do not give rise to detectable off-target mutations at the in vitro-predicted sites. However, indel and structural variation events are enriched at the on-target sites.CONCLUSIONS: Amplification-free long-read sequencing reveals Cas9 cleavage sites in vitro that would have been difficult to predict using computational tools, including in dark genomic regions inaccessible by short-read sequencing.
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| 65. |
- I Siponen, Marina, et al.
(författare)
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Structural Determination of Functional Domains in Early B-cell Factor (EBF) Family of Transcription Factors Reveals Similarities to Rel DNA-binding Proteins and a Novel Dimerization Motif
- 2010
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Ingår i: JOURNAL OF BIOLOGICAL CHEMISTRY. - : The American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 285:34, s. 25875-25879
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Tidskriftsartikel (refereegranskat)abstract
- The early B-cell factor (EBF) transcription factors are central regulators of development in several organs and tissues. This protein family shows low sequence similarity to other protein families, which is why structural information for the functional domains of these proteins is crucial to understand their biochemical features. We have used a modular approach to determine the crystal structures of the structured domains in the EBF family. The DNA binding domain reveals a striking resemblance to the DNA binding domains of the Rel homology superfamily of transcription factors but contains a unique zinc binding structure, termed zinc knuckle. Further the EBF proteins contain an IPT/TIG domain and an atypical helix-loop-helix domain with a novel type of dimerization motif. The data presented here provide insights into unique structural features of the EBF proteins and open possibilities for detailed molecular investigations of this important transcription factor family.
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| 66. |
- Jalkanen, Jukka-Pekka, et al.
(författare)
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Modelling of discharges from Baltic Sea shipping
- 2021
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Ingår i: Ocean Science. - : Copernicus GmbH. - 1812-0784 .- 1812-0792.
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the new developments of the Ship Traffic Emission Assessment Model (STEAM) which enable the modelling of pollutant discharges to water from ships. These include nutrients from black/grey water discharges as well as from food waste. Further, the modelling of contaminants in ballast, black, grey and scrubber water, bilge discharges, and stern tube oil leaks are also described as well as releases of contaminants from antifouling paints.Each of the discharges is regulated by different sections of the IMO MARPOL convention, and emission patterns of different pollution releases vary significantly. The discharge patterns and total amounts for the year 2012 in the Baltic Sea area are reported and open-loop SOx scrubbing effluent was found to be the second-largest pollutant stream by volume. The scrubber discharges have increased significantly in recent years, and their environmental impacts need to be investigated in detail.
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| 67. |
- Jalo, Noor, et al.
(författare)
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Barriers to and drivers of energy management in Swedish SMEs
- 2021
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Ingår i: Energies. - : MDPI. - 1996-1073. ; 14:21
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Tidskriftsartikel (refereegranskat)abstract
- The energy efficiency gap is known as the difference between optimal level of energy efficiency and the actual level of achieved energy efficiency. Energy management has proven to further close the energy efficiency gap. Energy management may differ depending on whether it concerns a large, energy-intensive company or small and medium-sized enterprises (SMEs). SMEs are of high interest since they form a large share of the economy today. For SMEs, a lighter form of energy management, in the form of energy efficiency network participation, has proven to deliver sound energy efficiency impact, while for larger, energy-intensive firms, a certified energy management system may be more suitable. However, various barriers inhibit adoption of energy efficiency measures. While there is an array of research on barriers to and driving forces for energy efficiency in general, research on barriers to, and driving forces for, energy management is rare, one exception being a study of energy-intensive pulp and paper mills. This holds even more so for industrial SMEs. This paper aims to identify the barriers to, and drivers for, energy management in manufacturing SMEs. Results of this explorative study show that the top four barriers to energy management are lack of time/other priorities, non-energy-related working tasks are prioritized higher, slim organization, and lack of internal expert competences, i.e., mainly organizational barriers. The top four drivers for energy management are to reduce production waste, participation in energy efficiency networks, cost reduction from lower energy use, and commitment from top management. Furthermore, results show that energy management among the studied SMEs seems to not be as mature, even though the companies participated in an energy management capacity building program in the form of energy efficiency networks, which, in turn, shows a still largely untapped potential in the societal aim to reduce the energy efficiency and management gaps. The main contribution of this paper is a first novel attempt to explore barriers to, and drivers for, energy management among SMEs.
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| 68. |
- Jalo, Noor, et al.
(författare)
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Do energy efficiency networks help reduce barriers to energy efficiency? : A case study of a regional Swedish policy program for industrial SMEs
- 2021
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Ingår i: Renewable & sustainable energy reviews. - : Elsevier. - 1364-0321 .- 1879-0690. ; 151
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Tidskriftsartikel (refereegranskat)abstract
- Improved energy efficiency is one of the key elements to decouple energy-related emissions from economic growth. Since the energy management practices in small and medium-sized enterprises are underdeveloped, most of the energy efficiency potential is left untapped. Studies show that several barriers pertaining to economic, technological, and organizational systems lead to poor implementation rates of energy efficiency measures. An energy efficiency network is considered effective in overcoming these barriers and promoting energy management practices in small and medium-sized enterprises. This paper explores the role of energy efficiency networks, and specifically the role of its functions in overcoming the identified barriers from literature. This study was carried out as a multiple case study including 13 industrial small and medium-sized enterprises using semi-structured interviews with participants from companies in a Swedish regional energy efficiency network program. Results show that energy efficiency networks are effective in overcoming some of the barriers to energy efficiency implementation and that the present functions are effective in addressing some barriers faced by small and medium-sized enterprises, e.g., energy efficiency implementation barriers such as lack of time and resources. However, some barriers still remain as constraints for energy efficiency implementation, even after energy efficiency network participation.
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| 69. |
- James, Stefan, 1964-, et al.
(författare)
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Rationale and design of the DAPA-MI trial : Dapagliflozin in patients without diabetes mellitus with acute myocardial infarction
- 2023
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 266, s. 188-197
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Tidskriftsartikel (refereegranskat)abstract
- Background Therapies that could further prevent the development of heart failure (HF) and other cardiovascular and metabolic events in patients with recent myocardial infarction (MI) represent a large and unmet medical need. Methods DAPA-MI is a multicenter, parallel-group, registry-based, randomized, double-blind, placebo-controlled phase 3 trial in patients without known diabetes or established HF, presenting with MI and impaired left ventricular systolic function or Q-wave MI. The trial evaluated the effect of dapagliflozin 10 mg vs placebo, given once daily in addition to standard of care therapy, on death, hospitalization for HF (HHF), and other cardiometabolic outcomes. The primary objective of the trial was to determine, using the win-ratio method, if dapagliflozin is superior to placebo by comparing the hierarchical composite outcome of death, HHF, nonfatal MI, atrial fibrillation/flutter, new onset of type 2 diabetes mellitus, HF symptoms as measured by New York Heart Association Functional Classification at last visit, and body weight decrease >= 5% at last visit. Assuming a true win-ratio of 1.20 between dapagliflozin and placebo, 4,000 patients provide a statistical power of 80% for the test of the primary composite outcome. A registry-based randomized controlled trial framework allowed for recruitment, randomization, blinding, and pragmatic data collection of baseline demographics, medications, and clinical outcomes using existing national clinical registries (in Sweden and the UK) integrated with the trial database. Conclusions The trial explores opportunities to improve further the outcome of patients with impaired LV function after MI. The innovative trial design of DAPA-MI, incorporating national clinical registry data, has facilitated efficient patient recruitment as well as outcome ascertainment.
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| 70. |
- Johansson, Anna-Karin, et al.
(författare)
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Kustnära förorenade områden som kan utgöra källor till dioxin i Bottenhavet
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Länsstyrelsen i Gävleborg tilldelades medel från Naturvårdsverket för ett projekt med syfte att få enbättre förståelse för vilka förorenade områden och/eller vilka branscher som kan vara en källa tilldioxin i Bottenhavet. Grannlänen Västernorrland och Uppsala bjöds in att delta i projektet eftersomäven deras kuststräckor gränsar till Bottenhavet. Bakgrunden till projektet är de fortsatt höga halterna av dioxin i fet fisk från Östersjön med speciellthöga halter längs Bottenhavets kust. Orsakerna till de höga halterna är ännu inte helt klarlagda, men idet nationella projektet, Baltic POPs, har man dragit slutsatsen att den största källan till dioxin iÖstersjön är atmosfäriskt nedfall från Europa. Man drar dock även slutsatsen att regionala källor kanha en lokal påverkan på arter som lever kustnära. Kunskap inhämtades från aktuella projekt och litteratur om ämnet. Utifrån litteraturgenomgångenidentifierades några branscher som skulle kunna vara intressanta att titta på ur dioxinsynpunkt inomebh-arbetet. Dessa branscher är främst sågverk med doppning, massa- och pappersindustri, järn- ochstål industri, textilindustri och verkstadsindustri, samt deponier med avfall från dessa branscher. Parallellt med detta arbete gjordes en genomgång av länens identifierade objekt i ebh-stödet för att sevilka objekt som utgör eller skulle kunna utgöra en källa till dioxin. Resultatet av detta finnspresenterat i ett antal kartor som illustrerar var kunskapsluckorna finns när det gäller dioxinförorenadeområden. Baserat på undersökningar av några dioxinförorenade sågverksområden i Sverige gjordes även en grovuppskattning av hur mycket de 45 kustnära sågverken i våra tre län skulle kunna bidra tilldioxinföroreningar längs Bottenhavets kust.
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