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1.
  • Al-Saadi, Jonathan, et al. (author)
  • Endovascular transplantation of mRNA-enhanced mesenchymal stromal cells results in superior therapeutic protein expression in swine heart
  • 2024
  • In: Molecular therapy. Methods & clinical development. - : Elsevier BV. - 2399-6951 .- 2329-0501. ; 32:2
  • Journal article (peer-reviewed)abstract
    • Heart failure has a poor prognosis and no curative treatment exists. Clinical trials are investigating gene- and cell-based therapies to improve cardiac function. The safe and efficient delivery of these therapies to solid organs is challenging. Herein, we demonstrate the feasibility of using an endovascular intramyocardial delivery approach to safely administer mRNA drug products and perform cell transplantation procedures in swine. Using a trans-vessel wall (TW) device, we delivered chemically modified mRNAs (modRNA) and mRNA-enhanced mesenchymal stromal cells expressing vascular endothelial growth factor A (VEGF-A) directly to the heart. We monitored and mapped the cellular distribution, protein expression, and safety tolerability of such an approach. The delivery of modRNA-enhanced cells via the TW device with different flow rates and cell concentrations marginally affect cell viability and protein expression in situ. Implanted cells were found within the myocardium for at least 3 days following administration, without the use of immunomodulation and minimal impact on tissue integrity. Finally, we could increase the protein expression of VEGF-A over 500-fold in the heart using a cell-mediated modRNA delivery system compared with modRNA delivered in saline solution. Ultimately, this method paves the way for future research to pioneer new treatments for cardiac disease.
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2.
  • Chireh, Arvin, et al. (author)
  • Micro-biopsy for detection of gene expression changes in ischemic swine myocardium : A pilot study
  • 2021
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:4, s. e0250582-
  • Journal article (peer-reviewed)abstract
    • Micro-endomyocardial biopsy (micro-EMB) is a novel catheter-based biopsy technique, aiming to increase flexibility and safety compared to conventional EMB. The technique was developed and evaluated in healthy swine. Therefore, the ability to detect disease related tissue changes could not be evaluated. The aim of the present pilot study was to investigate the ability to detect disease related gene expression changes using micro-EMB. Myocardial infarction was induced in three swine by coronary artery balloon occlusion. Micro-EMB samples (n = 164) were collected before, during, and after occlusion. RNA-sequencing was performed on 85 samples, and 53 of these were selected for bioinformatic analysis. A large number of responding genes was detected from the infarcted area (n = 1911). The early responding genes (n = 1268) were mostly related to apoptosis and inflammation. There were fewer responding genes two days after infarction (n = 6), which were related to extra-cellular matrix changes, and none after 14 days. In contrast to the infarcted area, samples harvested from a non-infarcted myocardial region showed considerably fewer regulated genes (n = 33). Deconvolution analysis, to estimate the proportion of different cell types, revealed a higher proportion of fibroblasts and a reduced proportion of cardiomyocytes two days after occlusion compared to baseline (p < 0.02 and p < 0.01, respectively. S5 File). In conclusion, this pilot study demonstrates the capabilities of micro-EMB to detect local gene expression responses at an early stage after ischemia, but not at later timepoints.
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4.
  • Chireh, A., et al. (author)
  • Safety evaluation of high-risk myocardial micro-biopsy in a swine model
  • 2022
  • In: Heart and Vessels. - : Springer Nature. - 0910-8327 .- 1615-2573. ; 37:4, s. 697-704
  • Journal article (peer-reviewed)abstract
    • The objective of the study was to investigate the safety profile of high-risk micro-endomyocardial biopsy (micro-EMB) compared to conventional EMB in a large animal model. Twenty pigs were subjected to a maximum of 30 consecutive biopsies, including sampling from the free ventricular wall, with either micro-EMB (n = 10) or conventional EMB (n = 10). There were no major complications in the micro-EMB group (0/10), compared to six major complications in the EMB group (6/10; p = 0.003). Survival analysis further highlighted these differences (p = 0.004). There were significantly higher volumes of pericardial effusion in the EMB group (p = 0.01). The study shows a safety advantage of micro-EMB compared to standard EMB in the experimental high-risk circumstances investigated in this animal study. These results indicate enhanced possibilities to collect samples from sensitive areas by using the micro-EMB technique instead of standard EMB. 
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5.
  • Gedeon, Charlotte, et al. (author)
  • Standards for opioid use disorder care : An assessment of Nordic approaches
  • 2019
  • In: Nordic Studies on Alcohol and Drugs. - : Sage Publications. - 1455-0725 .- 1458-6126. ; 36:3, s. 286-298
  • Journal article (peer-reviewed)abstract
    • Aims: Outcomes in opioid use disorder (OUD) in Nordic countries have improved with integrated treatment and harm-reduction programmes. Approaches and the standard of care are different across the region. Evidence of treatment needs and current approaches are defined from evidence to inform development of a common standard.Method: Evidence of population sizes and treatment approach collected. Common standards for care (harm reduction, pharmacotherapy, psychology/social therapy) defined for each country.Results: Evidence defines number in treatment; potential population needing treatment not defined for all countries. Populations sizes, treatment access (ratio in treatment programme compared to total country population) defined: Sweden 4,000 in OUD care (access ratio 40); Finland 3,000 (55); Norway 8,000 (154); Denmark 7,500 (132). Approach to treatment similar: integrated treatment programmes standard. Care provided by specialists in outpatient clinics/primary care; secondary care/inpatient services are available. Harm reduction is limited in Sweden but available and more accessible elsewhere. Treatment entry criteria: access relatively unlimited in Norway and Denmark, more limited in Finland and Sweden. Standards of care defined: easy access to high-quality services, individual planning, care not limited by time, management of relapse, education for patients, continuous engagement, holistic approach including management of comorbidities, needle equipment programmes without limit, treatment in prisons as community.Conclusion: There are opportunities to improve OUD care in the Nordics. Policy makers and clinicians can advance OUD care and share common success factors. Collaborative work across the Nordic countries is valuable. Further research in clinical practice development can yield important results for the benefit of patients with OUD.
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6.
  • Grankvist, R, et al. (author)
  • Myocardial micro-biopsy procedure for molecular characterization with increased precision and reduced trauma
  • 2020
  • In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 8029-
  • Journal article (peer-reviewed)abstract
    • Endomyocardial biopsy is a valuable tool in cardiac diagnostics but is limited by low diagnostic yield and significant complication risks. Meanwhile, recent developments in transcriptomic and proteomic technologies promise a wealth of biological data from minimal tissue samples. To take advantage of the minimal tissue amount needed for molecular analyses, we have developed a sub-millimeter endovascular biopsy device, considerably smaller than current clinical equipment, and devised a low-input RNA-sequencing protocol for analyzing small tissue samples. In in vivo evaluation in swine, 81% of biopsy attempts (n = 157) were successful. High quality RNA-sequencing data was generated from 91% of the sequenced cardiac micro-biopsy samples (n = 32). Gene expression signatures of samples taken with the novel device were comparable with a conventional device. No major complications were detected either during procedures or during 7 days’ follow-up, despite acquiring a relatively large number of biopsies (median 30) in each animal. In conclusion, the novel device coupled with RNA-sequencing provides a feasible method to obtain molecular data from the myocardium. The method is less traumatic and has a higher flexibility compared to conventional methods, enabling safer and more targeted sampling from different parts of the myocardium.
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7.
  • Grehk, Mikael, et al. (author)
  • Initial stages of metal-organic chemical-vapor deposition of ZrO2 on a FeCrAl alloy
  • 2008
  • In: Thin Solid Films. - Amsterdam : Elsevier BV. - 0040-6090 .- 1879-2731. ; 516:6, s. 875-879
  • Journal article (peer-reviewed)abstract
    • The initial stages of metal-organic chemical-vapor deposition of ZrO2 on a model FeCrAl alloy was investigated using synchrotron radiation photoelectron spectroscopy, X-ray absorption spectroscopy, scanning Auger microprobe, and time of flight secondary mass spectrometry. The coatings were grown in ultra-high vacuum at 400 degrees C and 800 degrees C using the single source precursor zirconium tetra-tert-butoxide. At 400 degrees C the coatings mainly consist of tetragonal ZrO2 and at 800 degrees C a mixed ZrO2/Al2O3 layer is formed. The Al metal diffuses from the FeCrAl bulk to the metal/coating interface at 400 degrees C and to the surface of the coating at 800 degrees C. The result indicates that the reaction mechanism of the growth process is different at the two investigated temperatures.
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8.
  • Isaksson, Mikael, et al. (author)
  • Zipper : a duplex scheme for VDSL based on DMT
  • 1997
  • Reports (other academic/artistic)abstract
    • A duplex scheme for DMT-based VDSL systems is presented here. It offers a solution to the problem with NEXT and near-echoes in broadband communications. The scheme has high duplex efficiency, low latency, and attractive transmit power features. However, hardware verification remains.
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9.
  • Jaff, Nasren, et al. (author)
  • Transcriptomic analysis of the harvested endothelial cells in a swine model of mechanical thrombectomy
  • 2018
  • In: Neuroradiology. - : SPRINGER. - 0028-3940 .- 1432-1920. ; 60:7, s. 759-768
  • Journal article (peer-reviewed)abstract
    • In mechanical thrombectomy (MT) for ischemic stroke, endothelial cells (ECs) from intracranial blood vessels adhere to the stent retriever device and can be harvested. However, understanding the molecular biology and the role of the endothelium in different pathological conditions remains insufficient. The purpose of the study was to characterize and analyze the molecular aspect of harvested ECs using cell culture and transcriptomic techniques in an MT swine model relevant to clinical ischemic stroke. In swine, preformed thrombi were injected into the external carotid and subclavian arteries to occlude their branches. MT was performed according to clinical routine. The stent retriever device and thrombus were treated with cell dissociation buffer. The resulting cell suspension was analyzed by immunohistochemistry and was cultured. Cultured cells were analyzed using single-cell RNA sequencing (scRNA-seq) after fluorescence-activated cell sorting (FACS). A total number of 37 samples were obtained containing CD31-positive cells. Cell culture was successful in 90% of samples, and the cells expressed multiple typical EC protein markers. Eighty-nine percent of the sorted cells yielded high-quality transcriptomes, and single-cell transcriptomes from cultured cells showed that they expressed typical endothelial gene patterns. Gene expression analysis of ECs from an occluded artery did not show distinctive clustering into subtypes. ECs harvested during MT can be cultured and analyzed using single-cell transcriptomic techniques. This analysis can be implemented in clinical practice to study the EC gene expression of comorbidities, such as hypertension, diabetes mellitus, and metabolic syndrome, in patients suffering from acute ischemic stroke.
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10.
  • Kakko, Johan, et al. (author)
  • Principles for managing OUD related to chronic pain in the Nordic countries based on a structured assessment of current practice
  • 2018
  • In: Substance Abuse Treatment, Prevention, and Policy. - : BioMed Central. - 1747-597X. ; 13
  • Research review (peer-reviewed)abstract
    • Background: Long-term use of opioid analgesics (OA) for chronic pain may result in opioid use disorder (OUD). This is associated with adverse outcomes for individuals, families and society. Treatment needs of people with OUD related to chronic pain are different compared to dependence related to use, and also injection, of illicit opioids. In Nordic countries, day-to-day practical advice to assist clinical decision-making is insufficient.Aim: To develop principles based on expert clinical insights for treatment of OUD related to the long-term use of OA in the context of chronic pain.Methods: Current status including an assessment of barriers to effective treatment in Finland, Denmark, Iceland, Norway, Sweden was defined using a patient pathway model. Evidence to describe best practice was identified from published literature, clinical guidelines and expert recommendations from practice experience.Results: Availability of national treatment guidelines for OUD related to chronic pain is limited across the Nordics. Important barriers to effective care identified: patients unlikely to present for help, healthcare system set up limits success, diagnosis tools not used, referral pathways unclear and treatment choices not elucidated. Principles include the development of a specific treatment pathway, awareness/education programs for teams in primary care, guidance on use of diagnostic tools and a flexible treatment plan to encourage best practice in referral, treatment assessment, choice and ongoing management via an integrated care pathway. Healthcare systems and registries in Nordic countries offer an opportunity to further research and identify population risks and solutions.Conclusions: There is an opportunity to improve outcomes for patients with OUD related to chronic pain by developing and introducing care pathways tailored to specific needs of the population.
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11.
  • Karlsson, P. G., et al. (author)
  • Metal organic chemical vapor deposition of ultrathin ZrO2 films on Si(1 0 0) and Si(1 1 1) studied by electron spectroscopy
  • 2007
  • In: Surface Science. - 0039-6028 .- 1879-2758. ; 601:4, s. 1008-1018
  • Journal article (peer-reviewed)abstract
    • The growth of ultrathin ZrO2 films on Si(100)-(2x1) and Si(111)-(7x7) has been studied with core level photoelectron spectroscopy and X-ray absorption spectroscopy. The films were deposited sequentially by chemical vapor deposition in ultra-high vacuum using zirconium tetra-tert-butoxide as precursor. Deposition of a > 50Å thick film leads in both cases to tetragonal ZrO2 (t-ZrO2), whereas significant differences are found for thinner films. On Si(111)-(7x7) the local structure of t-ZrO2 is not observed until a film thickness of 51Å is reached. On Si(100)-(2x1) the local geometric structure of t-ZrO2 is formed already at a film thickness of 11Å. The higher tendency for the formation of t-ZrO2 on Si(100) is discussed in terms of Zr–O valence electron matching to the number of dangling bonds per surface Si atom. The Zr–O hybridization within the ZrO2 unit depends furthermore on the chemical composition of the surrounding. The precursor t-butoxy ligands undergo efficient C–O scission on Si(100), leaving carbonaceous fragments embedded in the interfacial layer. In contrast, after small deposits on Si(111) stable t-butoxy groups are found. These are consumed upon further deposition. Stable methyl and, possibly, also hydroxyl groups are found on both surfaces within a wide film thickness range.
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13.
  • Nilsson, Johan O., et al. (author)
  • Modeling Kinetics of Water Adsorption on the Rutile TiO2 (110) Surface: Influence of Exchange-Correlation Functional
  • 2018
  • In: Physica Status Solidi (B): Basic Research. - : Wiley. - 1521-3951 .- 0370-1972. ; 255:3
  • Journal article (peer-reviewed)abstract
    • The accuracy of the theoretical description of materials properties in the framework of density functional theory (DFT) inherently depends on the exchange-correlation (XC) functional used in the calculations. Here we investigate the influence of the choice of a XC functional (PBE, RPBE, PW91, and PBE0) on the kinetics of the adsorption, diffusion and dissociation of water on the rutile TiO2(110) surface using a combined Kinetic Monte Carlo (KMC) - DFT approach, where the KMC simulations are based on the barriers for the aforementioned processes calculated with DFT. We also test how the adsorption energy of intact and dissociated water molecules changes when dispersion interactions are included into the calculations. We consider the beginning of the water layer formation varying coverage up to 0.2 monolayer (ML) at temperatures up to 180K. We demonstrate that the dynamics of the simulated water-titania system is extremely sensitive to the choice of the XC functional.
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14.
  • Ottosson, Mikael, et al. (author)
  • Arbetsrehabilitering och myndighetssamverkan : Utvärdering av Samordningsförbundet i Svedala
  • 2010
  • Reports (other academic/artistic)abstract
    • Ett i den politiska debatten centralt område är arbetsrehabilitering. Inom detta område går det att se en ökad politisk aktivitet som många gånger mynnar ut i begreppet ”samverkan”. Ropet på samverkan beror möjligen på att det blir allt svårare för enskilda myndigheter att såväl överblicka som hantera sitt verksamhetsfält i takt med att omvärlden ter sig allt mer komplex. Föreliggande rapport bygger på en utvärdering av Samordningsförbundet i Svedala utförd av Mikael Ottosson och Niklas Sandell. Mikael Ottosson är historiker och verksam på Centrum för tillämpad arbetslivsforskning (CTA) vid Malmö högskola och Niklas Sandell är företagsekonom och verksam på Rådet för KommunalEkonomisk Forskning och Utbildning (KEFU) vid Lunds universitet. Utvärderingens primära syfte är att belysa Samordningsförbundet i Svedala som det såg ut vid slutet av 2009. Utvärderingen fokuserar fyra områden: syfte och mål, organisation, innehåll och effektivitet.
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16.
  • Sandell, Anders, et al. (author)
  • Growth of ultrathin ZrO2 films on Si(100) : film-thickness-dependent band alignment
  • 2007
  • In: Applied Physics Letters. - : American Institute of Physics. - 0003-6951 .- 1077-3118. ; 88:13
  • Journal article (peer-reviewed)abstract
    • The band alignment of ultrathin ZrO2 films of different thickness formed on Si(100) have been monitored with synchrotron radiation photoelectron spectroscopy and x-ray absorption spectroscopy. The films were deposited sequentially by way of metal-organic chemical-vapor deposition in ultrahigh vacuum. A significant decrease in the conduction band offset is found for increasing film thickness. It is accompanied by a corresponding increase of the valence band offset. The variations originate in the formation of an interfacial layer characterized by a lower degree of Zr-O interaction than in bulk ZrO2 but with no clear evidence for partially occupied Zr 4d dangling bonds.
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17.
  • Sandell, A, et al. (author)
  • Metalorganic Chemical Vapor Deposition of Anatase Titanium Dioxide on Si: Modifying the Interface by Pre-Oxidation.
  • 2003
  • In: Surface Science. - 0039-6028 .- 1879-2758. ; 530:1-2, s. 63-70
  • Journal article (peer-reviewed)abstract
    • The formation of TiO2 films on clean and pre-oxidized Si(1 1 1) through chemical vapor deposition of titanium(IV) isopropoxide (TTIP) in ultra-high vacuum has been examined by synchrotron radiation photoelectron spectroscopy, X-ray absorption spectroscopy (XAS) and scanning tunneling microscopy. In both cases, TTIP deposition at 500 °C eventually results in an anatase TiO2 film with a carbon-free surface and the surface morphology of the anatase films is very similar. By using a novel way of combining photoemission and XAS data, it is demonstrated that the two situations have substantially different interfacial properties. Pre-oxidation of the surface at 500 °C passivates the surface so that the thickness of the amorphous TiSixOy interface layer decreases from 30–35 to 15–25 Å and eliminates the formation of interfacial carbon completely.
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18.
  • Sandell, Mikael, et al. (author)
  • 3 D-printed micrograters for sampling of the blood vessel wall
  • 2021
  • In: 2021 34th IEEE international conference on micro electro mechanical systems (MEMS 2021). - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 548-550
  • Conference paper (peer-reviewed)abstract
    • Endothelial cells lining blood vessels have phenotypic variations that indicate the health/disease status for a variety of conditions, including atherosclerosis and hypertension. Current sampling strategies lead to a high variation in the sampled amount, and we are not aware of sampling tools specifically targeting endothelial cells. Here, we present a new type of endovascular catheter for sampling of the blood vessel wall. The catheter is a 380 mu m nitinol tube over which 3D printed graters are threaded. The catheter is designed to be non-invasive during the axial motion and to interact with the blood vessel wall when rotated. Initial results indicate successful in-vivo sampling - with minimal blood contamination - of the wall of blood vessels less than 0.5 mm in diameter.
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19.
  • Sandell, Mikael, et al. (author)
  • A novel noble metal stent coating reduces in vitro platelet activation and acute in vivo thrombosis formation : a blinded study
  • Other publication (other academic/artistic)abstract
    • Inherent to any stenting procedure is the prescription of dual antiplatelet therapy (DAPT) to reduce the platelet response. Clinical guidelines recommend 6 - 12 months of DAPT, depending on stent type, clinical picture and patient factors. Our hypothesis is that a nanostructured noble metal coating has the potential to reduce protein deposition and platelet activation, which in turn could reduce the need for DAPT. Here, a noble metal nanostructure coating on stents is investigated. Twelve pigs underwent endovascular implantation of coated and non-coated stents for paired comparisons in a double-blinded study design. The non-coated control stent was placed at the contralateral corresponding artery. Volumetric analysis of angiographic data, performed by a treatment blinded assessor, demonstrated a significant thrombus reduction for one of the coatings compared to control. This effect was already seen one hour after implantation. This finding was supported by in vitro data showing a significant reduction of coagulation activation in the coated group. This novel coating shows promise as an implant material addition and could potentially decrease the need for DAPT in the acute clinical setting.
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20.
  • Sandell, Mikael, et al. (author)
  • A novel noble metal stent coating reduces in vitro platelet activation and acute in vivo thrombosis formation : a blinded study
  • 2023
  • In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
  • Journal article (peer-reviewed)abstract
    • Inherent to any stenting procedure is the prescription of dual antiplatelet therapy (DAPT) to reduce the platelet response. Clinical guidelines recommend 6–12 months of DAPT, depending on stent type, clinical picture and patient factors. Our hypothesis is that a nanostructured noble metal coating has the potential to reduce protein deposition and platelet activation. These effects would reduce subsequent thrombo-inflammatory reactions, potentially mitigating the need for an extensive DAPT in the acute phase. Here, a noble metal nanostructure coating on stents is investigated. Twelve pigs underwent endovascular implantation of coated and non-coated stents for paired comparisons in a blinded study design. The non-coated control stent was placed at the contralateral corresponding artery. Volumetric analysis of angiographic data, performed by a treatment blinded assessor, demonstrated a significant thrombus reduction for one of the coatings compared to control. This effect was already seen one hour after implantation. This finding was supported by in vitro data showing a significant reduction of coagulation activation in the coated group. This novel coating shows promise as an implant material addition and could potentially decrease the need for DAPT in the early phases of stent implementation.
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21.
  • Sandell, Mikael, et al. (author)
  • An Ultraminiaturized MEMS Microbiopsy Tool for Trans Blood Vessel Wall Biopsies
  • 2020
  • In: Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS). - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 10-12
  • Conference paper (peer-reviewed)abstract
    • We present a new type of microbiopsy tool (MBT) an order of magnitude smaller than commercially available biopsy catheters that, together with a trans-vessel wall catheter (Extroducer) successfully samples soft tissues with significantly less trauma to the tissue than commercial catheters. The MBT is mounted on a Nitinol wire. It features a gripping action that is actuated by the relative motion inside the Extroducer and has demonstrated repeated successful tissue sampling of approximately 500-1000 cells in ex-vivo tissue. This new catheter system can potentially allow super-selective, minimally invasive tissue sampling and transcriptomic analysis from hard to reach areas. 
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22.
  • Sandell, Mikael, et al. (author)
  • Endovascular Device for Endothelial Cell Sampling
  • 2022
  • In: Advanced NanoBiomed Research. - : Wiley. - 2699-9307 .- 2699-9307. ; 2:10, s. 2200023-2200023
  • Journal article (peer-reviewed)abstract
    • Endothelial cells play an important role in several vascular diseases, and molecular analysis of these cells could provide valuable information on underlying tissue status. However, no clinically established procedure for harvesting endothelial cells exists. A micro-3D-printed device adapted for endovascular techniques to harvest endothelial cells for transcriptomic analysis is presented. In vivo evaluation in swine (n = 6) yielded tissue samples in 60 out of 65 cases, of which 80% show a substantial amount of tissue. The cytological evaluation indicates high selectivity towards endothelial cells, and RNA-sequencing shows gene expression signatures consistent with vascular tissue. It is found that there are no short-term safety risks compared to operation with a control wire of equal dimensions and acute complications are not detected. If translated to clinical use, the device could enable increased understanding of early-stage endothelial cell-mediated disease progression and earlier diagnosis of diseases such as atherosclerosis.
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  • Sandell, Mikael, et al. (author)
  • Hydraulic micropistons enable high-force operations through miniaturized catheters
  • Other publication (other academic/artistic)abstract
    • Objective: As catheter sizes decrease, traditional navigation techniques for endovascular catheter-based devices within small working channels may fail due to mechanical scaling laws. This study evaluates a novel solution employing micropistons mounted on an intraluminal device in a miniaturized catheter to increase force generation at the distal end. Methods: The force exerted by a wire at the distal end of a catheter was measured under various degrees of bending and in an artificial vascular path. Our micropiston solution was benchmarked against conventional flushing techniques and manual pushing. Results: Incorporating micropistons to the internal wire consistently increased the generated force across all measured instances. This effect was more pronounced at higher degrees of bending, where manual pushing was deemed unfeasible. Conclusion: Our findings demonstrate that micropistons can effectively augment the delivery and operation of small wires, potentially overcoming the problems associated with extremely downscaled intraluminal devices. Significance: This advancement may enable the use of catheter systems much smaller than what is currently used.  
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24.
  • Sandell, Mikael (author)
  • Minimally Invasive Catheter-Based Technologies
  • 2023
  • Doctoral thesis (other academic/artistic)abstract
    • A simple incision procedure in a blood vessel makes the entire vascular system accessible. Through contrast injection and X-ray visualization, the vascular tree can be mapped and navigated through manual manipulation of thin tubes and wires. This utilization of the vasculature as internal pathways is commonly referred to as the endovascular technique. This technique can be used to deliver implants and drugs, retrieve problematic lesions or objects from the vasculature, or take tissue samples. Compared to open surgery, the advantage of this technique lies in the reduced invasiveness, ideally only leaving a small incision scar at the point of entry. Some interventions, however, are still associated with certain risks, requiring medication or complicating further interventions. The development of sequencing technologies presents an opportunity to improve and miniaturize devices, reducing invasiveness. This thesis aims to mitigate these risks and capitalize on the potential of next generation sequencing through microfabrication technologies, producing devices that are less invasive than current methods or that enable a new procedure.Initially, the aspect of endovascular heart biopsy is covered. The first work presents the fabrication and in vivo evaluation of a nitinol-based catheter device designed for extracting myocardial tissue. The device is fabricated through picosecond laser machining of nitinol tubes and wires, producing a device that is substantially smaller than what is currently used. The samples are evaluated and compared to samples extracted with conventional devices through RNA-Sequencing, verifying the proof of concept. The second work further emphasizes the device's functionality by evaluating it in a disease model of endomyocardial infarction. Tissue that is affected by the infarct and surrounding healthy tissue is extracted and compared in terms of its genetic expression. This comparison reveals a genetic discrepancy between the sick and healthy tissue, verifying the potential of using the device with RNA-sequencing for diagnostic purposes. The third work evaluates the safety aspects of the novel device in a head-to-head comparison with a conventional device. The study reveals a clear benefit of using the smaller device in terms of the complication rate during the procedure.The fourth work presents the fabrication and in vivo evaluation of another nitinol based catheter device designed for endothelial cell sampling. The device is fabricated through two-photon polymerization technologies, producing sub-mm brush structures mounted on a nitinol wire. Currently, there are no devices in clinical use that are capable of exclusively extracting endothelial cells. The novel device presents a solution for selective interaction with the innermost layer of the blood vessel. It represents an important step toward sampling endothelial cells for diagnostic and research purposes.The fifth and sixth works collectively present two different aspects of a third nitinol based catheter device designed to sample tissue from soft organs anywhere in the body. The device is fabricated using laser micromachining, grinding, and two-photon polymerization. The work is separated in terms of the in vivo evaluation and the technical solution. The technical aspects of the device are examined in terms of force generation in miniaturized catheter systems and the problems that arise in terms of mechanical scaling. These problems are solved by attaching pistons along the wire surface coupled with applied pressure to increase the force generated. The sampling with this device is realized, similar to the fourth work, with sub-mm brushes mountedon the wire. In vivo evaluation of this device reveals successful sampling of minute tissue quantities from the liver and kidney, in the size range of 10-100 cells per sample.The seventh work presents the in vivo and in vitro performance of a nanostructure coating on nitinol-based stents. Patients with a stent implant are prescribed an extensive medication regimen to counteract the metal implant's effects on the blood and surrounding tissue. This issue is being continuously targeted by new stent platforms, either with a drug-eluting polymer layer or by being resorbable by the body or through various other means. These implants all have a transient behavior, resulting in different issues over time. Paper VII presents an alternative approach to this problem by instead applying a nanostructure coating that is designed to interact with the blood to a much lesser degree, as demonstrated by CT-angiography and the measurement of multiple biomarkers.
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25.
  • Sandell, Mikael, et al. (author)
  • Sampling through a transvascular working channel
  • Other publication (other academic/artistic)abstract
    • Endovascular biopsies are widely utilized for many organs, either as standard practice or when there are contraindications to the percutaneous route. Depending on the target site, currently used devices for sampling through the endovascular route is either not possible to use, such as in the brain, or present certain risks due to their size, such as in the heart or liver. A recent development in catheter technology has opened up new possibilities for parenchymal access through a microscopic working channel. Through this method essentially all organs can be accessed safely without causing hemorrhagic complications. Here, an endovascular sampling device designed to be used through this channel is presented. The device contains 3D-printed brush structures and is tested in the liver and kidney. Cytological data reveals the presence of the tissue in question. 
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26.
  • Sandell, Niklas, et al. (author)
  • Berättelserna i "VD har ordet" - i dialog med omvärlden
  • 2018
  • In: Balans Fördjupning. ; :1, s. 14-17
  • Journal article (pop. science, debate, etc.)abstract
    • ”Vd har ordet” är det avsnitt i årsredovisningen som många anser vara allra viktigast och mest läst. Men vilken berättelse, eller snarare vilka berättelser, om företaget är det som lämnas under rubriken ”Vd har ordet”? I en studie av 30 årsredovisningar har olika berättelser identifierats, såsom exempelvis den kamerala berättelsen och den strategiska berättelsen. I denna artikel beskrivs och utvecklas dessa berättelser utifrån dess förankring i samtiden och i kulturellt förankrade idealbilder av företaget.
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28.
  • Siikanen, Jonathan, et al. (author)
  • A Peristaltic Pump Driven Zr-89 Separation Module
  • 2012
  • In: 14th International Workshop on Targetry and Target Chemistry. - : AIP. - 1551-7616 .- 0094-243X. ; 1509, s. 206-210
  • Conference paper (peer-reviewed)abstract
    • To facilitate the separation of Zr-89 produced in yttrium foils, an automated separation module was designed and assembled. The module separates more than 85% of produced Zr-89 - activity in 3 g foils in less than 90 min. About 10 % remains in the dissolving vial. The quality of the separated Zr-89 activity was investigated for labeling of the HER2-binding monoclonal antibody fragment, trastuzumab-Fab.
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29.
  • van de Beek, Jaap, et al. (author)
  • Low-complex frame synchronization in OFDM systems
  • 1995
  • In: Gateway to the 21st century : record. - Piscataway, NJ : IEEE Communications Society. - 0780329554 ; , s. 982-986, s. 982-986
  • Conference paper (peer-reviewed)abstract
    • Orthogonal frequency-division multiplexing (OFDM) systems have gained an increased interest due to their use in wireless applications such as mobile communication systems. A novel data-based frame synchronization method for OFDM-systems is presented. OFDM frames are shown to contain sufficient information to synchronize a system without the use of pilots. The cyclic extension, preceding OFDM frames, is of decisive importance for this method. Based on only the sign bits of the in-phase and the quadrature components of the received OFDM signal, the maximum likelihood solution is derived. This solution basically consists of a correlator, a moving sum and a peak detector. The stability of the generated frame-clock is improved significantly by averaging over a few number of frames. Simulations show that this low-complex, averaging method can be used to synchronize an OFDM system on twisted pair copper wires and in slowly fading radio channels
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30.
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