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1.
  • Kwon, David H., et al. (författare)
  • Bone tissue response following local drug delivery of bisphosphonate through titanium oxide nanotube implants in a rabbit model
  • 2017
  • Ingår i: Journal of Clinical Periodontology. - : Wiley. - 0303-6979. ; 44:9, s. 941-949
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The objective of this study was to evaluate whether surface chemistry-controlled TiO2 nanotube structures may serve as a local drug delivery system for zoledronic acid improving implant-bone support. Methods: Twenty-four screw-shaped Ti implants with surface chemistry-controlled TiO2 nanotube structures were prepared and divided into a zoledronic acid-formatted test and a native control group. The implants were inserted into contra-lateral femoral condyles in 12 New Zealand White rabbits. Bone support was evaluated using resonance frequency analysis (RFA) and removal torque (RTQ), as well as histometric analysis following a 3-weeks healing interval. Results: Zoledronic acid-formatted TiO2 nanotube test implants showed significantly improved implant stability and osseointegration measured using RFA and RTQ compared with control (p<0.05), and showed significantly enhanced new bone formation within the root of the threads compared with control (p<0.05). Conclusions: TiO2 nanotube implants may prove to be a significant delivery system for drugs or biologic agents aimed at supporting local bone formation. Additional study of candidate drugs/agents, optimized dosage and release kinetics is needed prior to evaluation in clinical settings. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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  • Lundberg, J., et al. (författare)
  • Access to the brain parenchyma using endovascular techniques and a micro-working channel
  • 2017
  • Ingår i: Journal of Neurosurgery. - : Journal of Neurosurgery Publishing Group (JNSPG). - 0022-3085 .- 1933-0693. ; 126:2, s. 511-517
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE Several older studies report a low risk for parenchymal access to the CNS by surgical techniques. In more recent studies, including those with post-puncture CT scans, there are indications that the risk of bleeding might approach 8%. New therapies, such as those that use viral vectors, modified mRNA, or cell transplantation, will probably warrant more parenchymal access to the CNS. Other minimally invasive routes might then be tempting to explore. This study was designed in 2 parts to address the possibility of using the endovascular route. The first aim was to test the ability to create a parenchymal micro-working channel to the CNS in macaque monkeys through the vessel wall. Second, the biocompatibility of a device-associated, detached, distal securing plug that was made of nitinol was investigated in swine for 1 year. METHODS Trans-vessel wall intervention in the middle cerebral artery and associated cerebral parenchyma was performed in 4 rhesus macaque monkeys using a full clinical angiography suite. A contrast agent and methylene blue were injected to test the working channel and then detached at the distal end to act as a securing plug through the vessel wall. One-year follow-ups were also performed using angiography and histological analysis in 10 swine with 24 implants that were distributed in the external carotid artery tree. RESULTS The cerebral interventions were performed without acute bleeding. Both the contrast agent and methylene blue were infused into the brain parenchyma and subarachnoidal space via the endovascular micro-working channel (7 injections in 4 animals). In the 1-year follow-up period, the implant that was left in the external carotid vessel wall in the swine was covered by the endothelium, which was followed by dislodgement just outside the blood vessel with thin capsule formation. No stenosis in the artery was detected on 1-year angiography. The animals showed normal behavior and blood sample results during the follow-up period. This is the first histological demonstration of nitinol biocompatibility when the implant is positioned through an arterial wall and indicates that the trans-vessel wall technique is not comparable with stent placement and its ability to induce intimal hyperplasia and restenosis. CONCLUSIONS This study demonstrates that the trans-vessel wall technique is applicable to brain intervention in macaque monkeys, providing a micro-working channel for delivery or sampling. The long-term follow-up study of the detached device in swine showed no clinical or biochemical complications and a normal angiography appearance.
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  • Barkarmo, Sargon, et al. (författare)
  • Biofilm formation on polyetheretherketone and titanium surfaces
  • 2019
  • Ingår i: Clinical and Experimental Dental Research. - : Wiley. - 2057-4347. ; 5:4, s. 427-437
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Polyetheretherketone (PEEK) is a polymer used in devices in orthopedic and dental rehabilitation. The aim of this in vitro study was to compare biofilm formation by a range of important oral bacterial species on PEEK, blasted PEEK, commercially pure titanium (cp-Ti), and titanium-6 aluminium-4 vanadium (Ti6Al4V). Material and methods: Coin-shaped samples were manufactured, and the surfaces were characterized using optical interferometry, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and contact angle measurements. Bacterial species of Streptococcus sanguinis, Streptococcus oralis, Enterococcus faecalis, and Streptococcus gordonii were cultured on the four material surfaces for varying amounts of time. Biofilms were quantified following staining with crystal violet. Results: Roughness and contact angle results showed blasted PEEK>PEEK>cp-Ti=Ti6Al4V. There was increased biofilm formation on blasted PEEK by S. sanguinis, S. oralis, and S. gordonii, whereas the bacterial adhesion was similar on PEEK, cp-Ti, and Ti6Al4V. The bacterial growth of E. faecalis was significantly higher on cp-Ti compared with the other three groups. Conclusion: The results, taking into consideration the biofilm formation, suggest that PEEK should perform as well as cp-Ti or TiAl6V4 when used as a dental restorative material. © 2019 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.
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  • Bratt, Anna S., 1969-, et al. (författare)
  • An internet-based compassion course for healthcare professionals : Rationale and protocol for a randomised controlled trial
  • 2022
  • Ingår i: Internet Interventions. - : Elsevier BV. - 2214-7829. ; 28
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Severe stress is one of the most common causes of sick leave in Sweden. Previous research has shown that compassion interventions for healthcare professionals can decrease work-related stress through the introduction of self-care, self-awareness, and emotion regulation abilities when experiencing difficult situations. Internet-based stress management interventions have hitherto shown promising results in reducing stress. However, further research is needed to examine the effectiveness of internet-based compassion interventions for healthcare professionals. Objective: In the present study protocol, a randomised controlled trial is described, aiming to examine the effects of an internet-based compassion course for healthcare professionals on work-related stress and stress of conscience. Method: Healthcare professionals will be offered an internet-based stress management course of five modules across a period of five weeks. The design is a randomised controlled study consisting of three groups enrolled in one of the following: a compassion course (n = 120), a cognitive behavioural stress management course (n = 120), or placed on a waitlist followed by either the compassion course or the cognitive behavioural stress management course (n = 36). We hypothesise that the internet-based compassion course would reduce the participants' stress of conscience to a greater degree compared to the other two groups. The secondary hypothesis is that the compassion course would increase the participants' professional quality of life (i.e., higher job satisfaction and lower empathy fatigue) and self-compassion. In addition, the internet-based compassion course is expected to reduce the participants' work-related stress and sick leave rates to the same degree (non-inferiority) as the cognitive behavioural stress management course and to a higher degree when compared to the waitlist condition. The primary outcome measure is the Stress of Conscience Questionnaire (SCQ) and the secondary outcome measures are the Professional Quality of Life Scale (PROQOL), the Work-related Stress Copenhagen Psychosocial Questionnaire (COPSOQ), and the Self-compassion Scale (SCS). Assessments will be performed at baseline, four weekly assessments during treatment, post-treatment (5 weeks), and follow-ups at 10 weeks, 15 weeks, and 6 months. The repeated measures data will be analysed using a generalised estimating equation for repeated measurements to examine whether changes over time differ between the groups and whether the improvements persist over time. Discussion: The clinical trial is expected to provide novel data on the effects of compassion interventions and add to the existing knowledge of internet-based interventions for stress management in healthcare professionals.
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  • Crescitelli, Rossella, 1985, et al. (författare)
  • Subpopulations of extracellular vesicles from human metastatic melanoma tissue identified by quantitative proteomics after optimized isolation
  • 2020
  • Ingår i: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The majority of extracellular vesicle (EV) studies conducted to date have been performed on cell lines with little knowledge on how well these represent the characteristics of EVs in vivo. The aim of this study was to establish a method to isolate and categorize subpopulations of EVs isolated directly from tumour tissue. First we established an isolation protocol for subpopulations of EVs from metastatic melanoma tissue, which included enzymatic treatment (collagenase D and DNase). Small and large EVs were isolated with differential ultracentrifugation, and these were further separated into high and low-density (HD and LD) fractions. All EV subpopulations were then analysed in depth using electron microscopy, Bioanalyzer (R), nanoparticle tracking analysis, and quantitative mass spectrometry analysis. Subpopulations of EVs with distinct size, morphology, and RNA and protein cargo could be isolated from the metastatic melanoma tissue. LD EVs showed an RNA profile with the presence of 18S and 28S ribosomal subunits. In contrast, HD EVs had RNA profiles with small or no peaks for ribosomal RNA subunits. Quantitative proteomics showed that several proteins such as flotillin-1 were enriched in both large and small LD EVs, while ADAM10 were exclusively enriched in small LD EVs. In contrast, mitofilin was enriched only in the large EVs. We conclude that enzymatic treatments improve EV isolation from dense fibrotic tissue without any apparent effect on molecular or morphological characteristics. By providing a detailed categorization of several subpopulations of EVs isolated directly from tumour tissues, we might better understand the function of EVs in tumour biology and their possible use in biomarker discovery.
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  • Franke-Stenport, Victoria, et al. (författare)
  • Titanium implants and BMP-7 in bone : an experimental model in the rabbit
  • 2003
  • Ingår i: Journal of materials science. Materials in medicine. - 0957-4530 .- 1573-4838. ; 14:3, s. 247-254
  • Tidskriftsartikel (refereegranskat)abstract
    • This study evaluates the effect of rhBMP-7/OP-1 on the osseointegration of commercially pure titanium implants in an experimental implant model in rabbits. Threaded titanium implants with two transverse parallel canals were inserted in the femur and tibia of rabbits. The canals were filled with, 10 microg of BMP-7/collagen carrier, pure collagen carrier or were left empty as a control. The stiffness of the implant fixation was evaluated by Resonance Frequency Analysis (RFA) at baseline and four weeks postoperatively. Percentage of bone ingrowth in the canals was measured on microradiographs. Histomorphometry along the threaded part of the implants was performed on 15 microm thin sections. The results from the RFA demonstrated a higher mean value for the BMP-7 treated implants in the tibia than the carrier treated implants but not compared to the control implants. The control implants in the tibia demonstrated more bone ingrowth in the upper canal than to the carrier or the BMP-7 treated implants. Apart from these differences there were no significant effects of BMP. In this study BMP-7 did not contribute to any substantially improved bone anchorage of titanium implants.
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  • Jansson, Saga, et al. (författare)
  • Incidence of acute myocardial injury and its association with left and right ventricular systolic dysfunction in critically ill COVID-19 patients
  • 2022
  • Ingår i: Annals of Intensive Care. - Heidelberg, Germany : Springer. - 2110-5820. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Previous studies have found an increase in cardiac troponins (cTns) and echocardiographic abnormalities in patients with COVID-19 and reported their association with poor clinical outcomes. Whether acute injury occurs during the course of critical care and if it is associated with cardiac function is unknown.The purpose of this study was to document the incidence of acute myocardial injury (AMInj) and echocardiographically defined left ventricular (LV) and right ventricular (RV) systolic dysfunction in consecutive patients admitted to an intensive care unit (ICU) for COVID-19. The relationship between AMInj and echocardiographic abnormalities during the first 14 days of ICU admission was studied. Finally, the association between echocardiographic findings, AMInj and clinical outcome was evaluated.Methods: Seventy-four consecutive patients (≥18 years) admitted to the ICU at Linköping University Hospital between 19 Mar 2020 and 31 Dec 2020 for COVID-19 were included. High-sensitivity troponin-T (hsTnT) was measured daily for up to 14 days. Transthoracic echocardiography was conducted within 72 h of ICU admission. Acute myocardial injury was defined as an increased hsTnT > 14ng/l and a > 20% absolute change with or without ischaemic symptoms. LV and RV systolic dysfunction was defined as at least 2 abnormal indicators of systolic function specified by consensus guidelines.Results: Increased hsTnT was observed in 59% of patients at ICU admission, and 82% developed AMInj with peak levels at 8 (3–13) days after ICU admission. AMInj was not statistically significantly associated with 30-day mortality but was associated with an increased duration of invasive mechanical ventilation (10 (3–13) vs. 5 days (0–9), p=0.001) as well as ICU length of stay (LOS) (19.5 (11–28) vs. 7 days (5–13), p=0.015). After adjustment for SAPS-3 and admission SOFA score, the effect of AMInj was significant only for the duration of mechanical ventilation (p=0.030).The incidence of LV and RV dysfunction was 28% and 22%, respectively. Only indices of LV and RV longitudinal contractility (mitral and tricuspid annular plane systolic excursion) were associated with AMInj. Echocardiographic parameters were not associated with clinical outcome.Conclusions: Myocardial injury is common in critically ill patients with COVID-19, with AMInj developing in more than 80% after ICU admission. In contrast, LV and RV dysfunction occurred in approximately one-quarter of patients. AMInj was associated with an increased need for mechanical ventilation and ICU LOS but neither AMInj nor ventricular dysfunction was significantly associated with mortality.
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  • Johansson, Carina S. (författare)
  • Development and aging of nerve fibres in the rat inferior alveolar nerve
  • 1996
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Structural and functional properties of nerve fibres in the rat inferior alveolar nerve (IAN) were examined during development and aging.Rat molar pulpal expllints influence neurite outgrowth from perinatal rat trigeminal ganglion explants, eo-cultured in vitro. Three patterns were found: The A-pattern, where neurites grew in all directions, predominated. In some cultures, the highest density of neurites grew towards the pulpal explant (the B-pattern) or grew in the opposite direction (the C-pattern). The 3 patterns might reflect actions of different neurite-promoting or -repelling factors.Shortly after entering the mandibular canal, the IAN of the adult rat divides into the mental nerve (MN, 70% of all axons) projecting to muco-cutaneous domains of the chin and the lower lip, and the inferior dental nerve (IDN, 30% of all axons) projecting to the teeth and adjacent tissues. The IAN has achieved the adult number of axons (8,000-10,000) by 1 week. De novo myelination commences at birth and ends by three weeks. In the adult IAN 70% of all axons are myelinated. A mature bimodal size distribution of the myelinated IAN axons has been established by 2 months.During postnatal development, the IAN grows 3x in length, as indicated by the elongation of the mandibular canal. Measurements of the nodal spacing in deveoping and adult IANs shows that the largest intemodes elongate more than the nerve. This mis-match can be explained by the presence of very short internodes (VS!s, L<150 f!m) during the first few postnatal weeks. The VSis reflect a myelin sheath remodelling, through which some proportion of the newly formed internodes are eliminated. In young adult animals VSis are absent, the L/D relation is regular, and the internodes grow in size. During aging, the regular relation between L and D in the IAN breaks down due to reappearance of VSis and the emergence of unusually long intern odes.The sural nerve (SN), which shows little myelin sheath remodelling, and the MN, in which myelin sheath remodelling is frequent, are equally sensitive to K+-channel blockade with 4-aminopyridine (4-AP) during early development. While the adult SN is relatively insensitive to 4-AP, the adult MN remains sensitive. This difference can not be explained in terms of a non-uniform adult nodal structure in the two nerves.The MN component of the IAN exhibits less marked age-related changes than the IDN component. This might be related to the fact that the mucocutaneous targe! of the MN is grossly intact in old rats, while the lower jaw dentition shows marked changes.
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  • Ramires, P. A., et al. (författare)
  • Biological behavior of sol-gel coated dental implants
  • 2003
  • Ingår i: Journal of materials science. Materials in medicine. - 0957-4530 .- 1573-4838. ; 14:6, s. 539-545
  • Tidskriftsartikel (refereegranskat)abstract
    • The biocompatibility of dental implants coated with titania/hydroxyapatite (HA) and titania/bioactive glass (BG) composites obtained via sol-gel process was investigated using an in vitro and in vivo model. A device for the in vitro testing of screw-shaped dental implants was developed, in order to well compare the two experimental models studying the behavior of human MG63 osteoblast-like cells seeded onto a particular geometry. The expression of some biochemical parameters of osteoblastic phenotype (alkaline phosphatase specific activity, collagen and osteocalcin production) and some indications on cells morphology obtained by scanning electron microscopy were evaluated. The in vitro and in vivo models were compared after implants insertion in rabbit tibia and femur. The removal torque and histomorphometric parameters (percentage of bone in contact with implant surface and the amount of bone inside the threaded area) were examined. A good agreement was found between the in vitro and in vivo models. These experiments showed better performances of HA and BG sol-gel coated dental implants with respect to uncoated titanium; in particular, it was found that in vitro the HA coating stimulates osteoblastic cells in producing higher level of ALP and collagen, whereas in vivo this surface modification resulted in a higher removal torque and a larger bone-implant contact area. This behavior could be ascribed to the morphology and the chemical composition of the implants with rough and bioactive surfaces.
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  • Sul, Young-Taeg, 1960, et al. (författare)
  • Optimum surface properties of oxidized implants for reinforcement of osseointegration: surface chemistry, oxide thickness, porosity, roughness, and crystal structure
  • 2005
  • Ingår i: International Journal of Oral & Maxillofacial Implants. - Chicago, Ill. : Quintessence Pub. Co.. - 0882-2786 .- 1942-4434. ; 20:3, s. 349-59
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To investigate detailed surface characterization of oxidized implants in a newly invented electrolyte system and to determine optimal surface oxide properties to enhance the bone response in rabbits. MATERIALS AND METHODS: A total of 100 screw-type titanium implants were prepared and divided into 1 control group (machine-turned implants) and 4 test groups (magnesium ion-incorporated oxidized implants). Forty implants were used for surface analyses. A total of 60 implants, 12 implants from each group, were placed in the tibiae of 10 New Zealand white rabbits and measured with a removal torque test after a healing period of 6 weeks. RESULTS: For the test groups, the oxide thicknesses ranged from about 1,000 to 5,800 nm; for the control group, mean oxide thickness was about 17 nm. The surface morphology showed porous structures for test groups and nonporous barrier film for the control group. Pore diameter ranged from < or = 0.5 microm to < or = 3.0 microm. In regard to surface roughness, arithmetic average height deviation (Sa) values varied from 0.68 to 0.98 microm for test implants and 0.55 microm for control implants; developed surface ratio (Sdr) values ranged from 10.6% to 46% for the test groups and were about 10.6% for the control group. A mixture of anatase and rutile-type crystals were observed in the test groups; amorphous-type crystals were observed in the control group. After a healing period of 6 weeks, removal torque measurements in all 4 test groups demonstrated significantly greater implant integration as compared to machine-turned control implants (P < or = .033). DISCUSSION: Determinant oxide properties of oxidized implants are discussed in association with bone responses. Of all surface properties, RTVs were linearly increased as relative atomic concentrations of magnesium ion increase. CONCLUSIONS: Surface properties of the oxidized implants in the present study, especially surface chemistry, influenced bone responses. The surface chemistry of the optimal oxidized implant should be composed of approximately 9% magnesium at relative atomic concentration in titanium oxide matrix and have an oxide thickness of approximately 1,000 to 5,000 nm, a porosity of about 24%, and a surface roughness of about 0.8 microm in Sa and 27% to 46% in Sdr; its oxide crystal structure should be a mixture of anatase- and rutile-phase crystals.
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  • Sul, Young-Taeg, et al. (författare)
  • Resonance frequency measurements in vivo and related surface properties of magnesium-incorporated, micropatterned and magnesium-incorporated TiUnite, Osseotite, SLA and TioBlast implants
  • 2009
  • Ingår i: Clinical Oral Implants Research. - Oxford : Wiley-Blackwell. - 0905-7161 .- 1600-0501. ; 20:10, s. 1146-1155
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To investigate implant stability using resonance frequency measurements of topographically changed and/or surface chemistry-modified implants in rabbit bone.MATERIAL AND METHODS: Six groups of microstructured, screw-shaped titanium implants: two oxidized, cation-incorporated experimental implants [Mg implants and MgMp implants with micropatterned thread flanges (80-150 microm wide and 60-70 microm deep)] and four commercially available clinical implants (TiUnite((R)), Osseotite((R)), SLA((R)), and TiOblast((R))) were installed in 10 rabbit tibia for 6 weeks. The surface properties of the implants were characterized in detail using several analytical techniques. Implant stability was measured using a resonance frequency analyzer (Osstell(TM)). RESULTS: Surface characterization of the implants revealed microstructured, moderately rough implant surfaces varying 0.7-1.4 mum in S(a) (mean height deviation), but with clear differences in surface chemistry. After 6 weeks, all implants showed statistically significantly higher increases in implant stability. When compared with one another, MgMp implants showed the most significant mean implant stability quotient (ISQ) value relative to the others (PCONCLUSION: The present study found that implant surface properties influence RFA measurements of implant stability. Surface chemistry-modified titanium implants showed higher mean ISQ values than did topographically changed implants. In particular, cation (magnesium)-incorporated micropatterns in MgMp implants may play a primary role in DeltaISQ.
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  • Vyas, N., et al. (författare)
  • The effect of standoff distance and surface roughness on biofilm disruption using cavitation
  • 2020
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Effective biofilm removal from surfaces in the mouth is a clinical challenge. Cavitation bubbles generated around a dental ultrasonic scaler are being investigated as a method to remove biofilms effectively. It is not known how parameters such as surface roughness and instrument distance from biofilm affect the removal. We grewStrepotococcus sanguinisbiofilms on coverslips and titanium discs with varying surface roughness (between 0.02-3.15 mu m). Experimental studies were carried out for the biofilm removal using high speed imaging and image analysis to calculate the area of biofilm removed at varying ultrasonic scaler standoff distances from the biofilm. We found that surface roughness up to 2 mu m does not adversely affect biofilm removal but a surface roughness of 3 mu m caused less biofilm removal. The standoff distance also has different effects depending on the surface roughness but overall a distance of 1 mm is just as effective as a distance of 0.5 mm. The results show significant biofilm removal due to an ultrasonic scaler tip operating for only 2s versus 15-60s in previous studies. The technique developed for high speed imaging and image analysis of biofilm removal can be used to investigate physical biofilm disruption from biomaterial surfaces in other fields.
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