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1.
  • Li, Hao, et al. (författare)
  • Regeneration in the Auditory Organ in Cuban and African Dwarf Crocodiles (Crocodylus rhombifer and Osteolaemus tetraspis) Can We Learn From the Crocodile How to Restore Our Hearing?
  • 2022
  • Ingår i: Frontiers in Cell and Developmental Biology. - : Frontiers Media S.A.. - 2296-634X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In several non-mammalian species, auditory receptors undergo cell renewal after damage. This has raised hope of finding new options to treat human sensorineural deafness. Uncertainty remains as to the triggering mechanisms and whether hair cells are regenerated even under normal conditions. In the present investigation, we explored the auditory organ in the crocodile to validate possible ongoing natural hair cell regeneration. Materials and Methods: Two male Cuban crocodiles (Crocodylus rhombifer) and an adult male African Dwarf crocodile (Osteolaemus tetraspis) were analyzed using transmission electron microscopy and immunohistochemistry using confocal microscopy. The crocodile ears were fixed in formaldehyde and glutaraldehyde and underwent micro-computed tomography (micro-CT) and 3D reconstruction. The temporal bones were drilled out and decalcified. Results: The crocodile papilla basilaris contained tall (inner) and short (outer) hair cells surrounded by a mosaic of tightly connected supporting cells coupled with gap junctions. Afferent neurons with and without ribbon synapses innervated both hair cell types. Supporting cells occasionally showed signs of trans-differentiation into hair cells. They expressed the MAFA and SOX2 transcription factors. Supporting cells contained organelles that may transfer genetic information between cells, including the efferent nerve fibers during the regeneration process. The tectorial membrane showed signs of being replenished and its architecture being sculpted by extracellular exosome-like proteolysis. Discussion: Crocodilians seem to produce new hair cells during their life span from a range of supporting cells. Imposing efferent nerve fibers may play a role in regeneration and re-innervation of the auditory receptors, possibly triggered by apoptotic signals from wasted hair cells. Intercellular signaling may be accomplished by elaborate gap junction and organelle systems, including neural emperipolesis. Crocodilians seem to restore and sculpt their tectorial membranes throughout their lives.
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2.
  • Sundfeldt, Karin, 1962, et al. (författare)
  • Higher levels of soluble E-cadherin in cyst fluid from malignant ovarian tumours than in benign cysts.
  • 2001
  • Ingår i: Anticancer research. - 0250-7005. ; 21:1A, s. 65-70
  • Tidskriftsartikel (refereegranskat)abstract
    • A major diagnostic dilemma in the clinical gynaecological oncology setting is to preoperatively determine whether a complex ovarian mass is benign or malignant. The cell-cell adhesion molecule E-cadherin has previously been localised in biopsies from both benign and malignant epithelial ovarian tumours. In this study, soluble E-cadherin levels was measured with ELISA-technique in peripheral blood, ascites and cystic fluids from patients (n = 33) undergoing surgery for ovarian cystic masses. The levels of soluble E-cadherin were significantly higher in cystic fluid from cystadenocarcinomas (p < 0.001) and borderline tumours (p < 0.05) as compared to cystic fluid from cystadenomas. In ascites fluid and peripheral blood no significant differences were seen. However, ratios of cystic fluid/peripheral blood levels were significantly higher in cystadenocarcinoma (p < 0.001) and borderline tumours (p < 0.05) as compared to benign tumours. In conclusion, measurements of soluble E-cadherin in cystic fluid from patients presenting with complex ovarian masses may be beneficial in increasing the accuracy of preoperative diagnosis.
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3.
  • Alme, Tomas Nordheim, et al. (författare)
  • Chronic fatigue syndromes: real illnesses that people can recover from
  • 2023
  • Ingår i: Scandinavian Journal of Primary Health Care. - : TAYLOR & FRANCIS LTD. - 0281-3432 .- 1502-7724. ; 41:4, s. 372-376
  • Tidskriftsartikel (refereegranskat)abstract
    • The Oslo Chronic Fatigue Consortium consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brains response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation.Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them.
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4.
  • Andersson, Christina, et al. (författare)
  • The effectiveness of smartphone compassion training on stress among Swedish university students : A pilot randomized trial
  • 2021
  • Ingår i: Journal of Clinical Psychology. - : John Wiley & Sons. - 0021-9762 .- 1097-4679. ; 77:4, s. 927-945
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate the effects of a 6-week smartphone compassion training intervention on mental health.Method: Fifty-seven Swedish university students (mean age = 25, SD = 5) reporting high levels of stress were randomized to compassion training (n = 23), mindfulness (n = 19), or waitlist (n = 15).Result: Multilevel models indicated that both compassion and mindfulness training increased self-compassion compared to the waitlist, while only compassion significantly reduced stress. Between-group effect sizes for compassion compared to waitlist were large for both self-compassion (d = 1.61) and stress (d = 0.94). Compassion and mindfulness did not differ significantly, but effect sizes were in favor of compassion. Secondary outcomes indicated positive effects on emotional awareness, while no effect was found for global psychological distress.Conclusions: Our results suggest that compassion training via a smartphone application can improve self-compassion and reduce stress among university students. Future studies in larger clinical samples are warranted.
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5.
  • Azour, Farivar, et al. (författare)
  • Invasion rate and population characteristics of the round goby Neogobius melanostomus: effects of density and invasion history
  • 2015
  • Ingår i: Aquatic Biology. - : Inter-Research Science Center. - 1864-7782 .- 1864-7790. ; 24:1, s. 41-52
  • Tidskriftsartikel (refereegranskat)abstract
    • Round goby Neogobius melanostomus is currently one of the most wide-ranging invasive fish species in Europe and North America. The present study demonstrates how the distribution of round goby has expanded from 2008 to 2013 at a rate of about 30 km yr(-1) along the Danish coastline in the western Baltic Sea. Further analyses showed that fish from an established high-density round goby population were slow-growing and displayed poorer condition (weight at age and hepatosomatic index) compared to fish sampled from recently invaded locations (i.e. at the forefront of the distribution range). The established population revealed a broad age distribution and a 1:1 gender ratio, while fish from a recently invaded site were primarily of intermediate ages with a male-biased gender ratio. Otolith analyses suggested that the oldest individuals from the recently invaded area experienced superior growth conditions only in the most recent years, suggesting immigration into the area as adults. Our results suggest that intraspecific competition for food may cause continued dispersal of the species and that population demographics likely relate to invasion history.
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6.
  • Edfeldt, Lennart, 1950-, et al. (författare)
  • Non-echo planar diffusion-weighted MRI increases follow-up accuracy after one-step step canal wall-down obliteration surgery for cholesteatoma
  • 2013
  • Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 133:6, s. 574-583
  • Tidskriftsartikel (refereegranskat)abstract
    • Conclusion: Non-echo planar (non-EPI) diffusion-weighted (DW) magnetic resonance imaging (MRI) increases the number of detected cholesteatoma after one-step canal-wall down (CWD) obliteration surgery for cholesteatoma compared with clinical evaluation alone.Objective: To evaluate the use of DW-MRI for detection of cholesteatoma after surgical treatment using CWD obliteration technique.Methods: Thirty-eight adult patients (41 ears) treated with identical one-step canal-wall down obliteration surgical technique were included in a prospective and blinded study. All patients were investigated with non-EPI and EPI DW-MRI 1-9 months after the clinical examination. Follow-up time after primary surgery varied between 10 and 234 months. DW-MRI were assessed by two neuroradiologists and compared with clinical results. Inter-rater agreement was calculated. Positive non-EPI DW-MRI cases underwent revision surgery within 18-159 days after imaging.Results: Out of 41 cases seven were evaluated as positive for cholesteatoma on non-EPI DW-MRI. Since one patient refused surgery six of these seven cases underwent surgical revision and all were verified. There was agreement between clinical and non-EPI findings in five of eight cases. EPI findings correlated poorly with non-EPI and clinical findings. Inter-rater agreement (Cohen´s kappa) was 0.91 for non-EPIDW-MRI (p<0.001) and -0.062 for EPI DW-MRI (p=0.43) 
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7.
  • Edfeldt, Lennart, et al. (författare)
  • Surgical treatment of adult cholesteatoma : long-term follow-up using total reconstruction procedure without staging
  • 2013
  • Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 133:1, s. 28-34
  • Tidskriftsartikel (refereegranskat)abstract
    • Conclusions:A total of 330 cases of adult cholesteatoma were operated with canal-wall down (CWD) and total reconstruction procedure (TRP) without staging. Independent of preoperative middle ear conditions, cholesteatoma extent and localization, long-term improvement of hearing with a low incidence of residual and recurrent disease were achieved.Objectives:To evaluate long-term surgical and hearing results using a well-defined surgical technique without staging in adult cholesteatoma.Methods:The same CWD surgical technique, including obliteration of the mastoid cavity, reconstruction of the canal wall, and ossiculoplasty with autologous bone, was used by three senior surgeons (1982-2004). Preoperative and postoperative pure tone average (PTA) for air conduction (AC), bone conduction (BC), and air-bone gap (ABG) were assessed and compared 1, 3, and 6 years after surgery. Various prognostic factors with potential influence on long-term hearing outcome were evaluated.Results:Recurrence of AC occurred in 10%, residual disease in 3%. Six years after surgery all patients except one had a dry ear and over 92% of all cases were water resistant. Three patients developed complete deafness. Long-lasting improvement and/or preservation of hearing, with maintenance of PTA-ABG closure in 68% of all cases within 20 dB, were obtained. Sixty-four (19%) ossicular revisions were performed.
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8.
  • Edfeldt, Lennart, et al. (författare)
  • Surgical treatment of paediatric cholesteatoma : Long-term follow up in comparison with adults
  • 2012
  • Ingår i: International Journal of Pediatric Otorhinolaryngology. - : Elsevier BV. - 0165-5876 .- 1872-8464. ; 76:8, s. 1091-1097
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: This study was designed to analyse long-term results after surgery of acquired (ACH) and congenital cholesteatoma (CCH) of the middle ear in children and compare these with adults.Methods: Computer-based analysis of consecutively operated paediatric patients for ACH and CCH in a tertiary referral centre was made in 57 cases under the age of 12 operated 1983-2004 by three surgeons using identical technique. A canal wall down and total reconstruction procedure (TRP) with obliteration of the mastoid cavity, canal wall reconstruction, ossiculoplasty with consistent use of autologous bone and an "aeration enhancement procedure" (AEP) with silicon sheet in selected cases were used. Pre- and post-operative PTA (0.5-3 kHz) and pure-tone average air-bone gap (PTA-ABG) together with surgical parameters were assessed 1, 3 and 6 years following surgery.Results: Results showed stable hearing over 6 years with low incidence of persistent and recurrent disease comparable with results from adult patients. In nearly half of the cases, silastic sheeting was used. In 21 cases, stapes was eroded. Bone conduction thresholds levels remained unaffected 6 years after surgery. No deaf ears, postoperative facial dysfunction or other lesions related to surgery were observed. Six years after surgery every evaluated ear was found to be water-resistant and infection-free.Conclusion: Our results suggest that one-stage eradication of ACH and CCH in children using total reconstruction procedure (TRP) provide long-term improvement or preservation of hearing, with a low incidence of persistent or recurrent disease. No difference in surgical outcome between children and adults was found.
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9.
  • Enghag, Sara, et al. (författare)
  • Incus Necrosis and Blood Supply : A Micro-CT and Synchrotron Imaging Study
  • 2019
  • Ingår i: Otology and Neurotology. - : LIPPINCOTT WILLIAMS & WILKINS. - 1531-7129 .- 1537-4505. ; 40:7, s. E713-E722
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Incus necrosis is a common complication following stapes surgery and is associated with impaired microcirculation. The objective of this study was to investigate the vascular anatomy of the human incus by using light microscopy, micro-computed tomography (micro-CT), and synchrotron phase-contrast imaging (SR-PCI) for a novel three-dimensional (3D) analysis of the middle ear, mucosal folds, major vascular pathways, and intraosseous vascular bone channels. Methods: One-hundred-and-fifty temporal bones from the Uppsala collection were analyzed under light microscopy. Twenty temporal bones underwent high-resolution micro-CT scanning, and an additional seven specimens underwent SR-PCI at the Canadian Lightsource in Saskatoon, Canada. One of these specimens was from an individual who had undergone stapes surgery. Data were processed with volume-rendering software to create 3D reconstructions using scalar opacity mapping for bone transparency, cropping, and soft tissue analyses. Results: Micro-CT and SR-PCI with 3D rendering revealed the extensive vascular plexus within the un-decalcified incus bone communicating with the exterior surface. The relationship between the vessels, lenticular process, and incudostape-dial joint were clearly observed. SR-PCI allowed for histologic-level detail while preserving the specimen and its 3D relationships. Conclusion: SR-PCI with 3D reconstructions confirmed the main vascular supply to the lenticular process along the intraosseous lenticular vessels. This is the first synchrotron analysis of a patient having undergone stapes surgery, and it suggests that incus necrosis associated with stapes surgery may be caused by a disruption of the lenticular blood flow induced by the prosthesis loop, and not by strangulation of mucosal vessels as has been previously described.
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10.
  • Erixon, Elsa, et al. (författare)
  • Variational anatomy of the human cochlea : implications for cochlear implantation
  • 2009
  • Ingår i: Otology and Neurotology. - 1531-7129 .- 1537-4505. ; 30:1, s. 14-22
  • Tidskriftsartikel (refereegranskat)abstract
    • HYPOTHESIS: To study variations in human cochlea anatomy with potential implications for cochlear implantation surgery. BACKGROUND: A comprehension of the anatomic variations of the human cochlea is essential for understanding the degree of surgical trauma induced by inserting various electrode arrays in cochlear implantation surgery. Variations in anatomy may also limit the potential for performing hearing preservation. METHODS: We studied 73 archival, nonselected, adult, corrosion casts of human inner ears. Anatomic reference points were constructed from photographic reproductions taken at different angles, and various dimensions were assessed using planimetry. Anatomic variants with particular clinical/surgical interests were pinpointed. RESULTS: Results showed that the human cochlea is individually shaped, varying greatly in dimensions ("fingerprint"). The outer cochlear wall length ranged from 38.6 to 45.6 mm with a mean length of 42.0 mm. The first turn represented 53% of the total length and ranged from 20.3 to 24.3 mm. The number of quadrants varied from slightly more than 8 to 12. The facial nerve canal ran in close proximity to the upper first turn explaining facial nerve excitement during stimulation of electrodes in this region in some instances. The internal diameter (height) of the cochlear tube in the first turn varied broadly (1.6-2.6 mm), occasionally with limited space for conventional implants. CONCLUSION: The human cochlea exhibits extensive anatomic variations. These variations will influence the location of cochlear implant arrays and affect the potential of hearing preservation surgery. Our results may explain the surgeon's difficulties sometimes to insert electrode arrays even in so-called "normal" cochleae.
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11.
  • Fängström, Karin, et al. (författare)
  • Is the Strengths and Difficulties Questionnaire with a Trauma Supplement a Valuable Tool in Screening Refugee Children for Mental Health Problems?
  • 2019
  • Ingår i: The Journal of Refugee Studies. - : Oxford University Press (OUP). - 0951-6328 .- 1471-6925. ; 32:Special issue 1, s. 122-140
  • Tidskriftsartikel (refereegranskat)abstract
    • The high number of asylum seekers in Sweden has highlighted the need to develop and evaluate structured assessment tools for children. In this study, we aimed to explore the utility of the Strengths and Difficulties Questionnaire (SDQ) with a trauma supplement of six items for preschool children in routine care. Parents of two- to six-year-olds (N = 61) were asked to complete the questionnaire during the routine health check-up offered to all refugees upon their arrival to Sweden. Focus-group interviews were conducted with the nurses who used the SDQ. The nurses found the SDQ valuable once they established a routine and felt that the SDQ contributed to a more structured and informative conversation about the child’s mental health. The SDQ total difficulties showed good internal consistency (alpha = 0.82). A significant proportion of children scored above the clinical cut-off and SDQ scores correlated significantly with the number of post-traumatic stress disorder symptoms measured using the supplement (rho = 0.29). The findings suggest that the SDQ with the trauma supplement is a useful tool in this clinical setting.
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14.
  • Hallin, Karin, 1977-, et al. (författare)
  • Auditory brainstem implant pitch discrimination and auditory outcome
  • 2022
  • Ingår i: ACTA OTO-LARYNGOLOGICA CASE REPORTS. - : Taylor & Francis. - 2377-2484. ; 7:1, s. 39-43
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a pitch discrimination test performed by five experienced adult auditory brainstem implant (ABI) users with neurofibromatosis type 2 (NF2). The ability to discriminate frequency/pitch from different channels on the implant may be an important factor in improving speech performance. The pitch discrimination ability was evaluated by using a triangle test compared to adjacent contacts and the speech perception was measured by the Swedish three-digit test. The test was easy to perform, and all patients were able to answer reliably, even though it cannot be ruled out that patients used attributes other than pitch to differentiate between sounds. Due to the limited number of patients and small variation in results, no conclusive correlations could be made regarding pitch discrimination and auditory outcome. There was a tendency for poorer ability to discriminate pitch (discrimination of tonotopically adjacent electrodes) at testing to result in poorer speech results.
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15.
  • Hultgård-Ekwall, Anna-Karin, et al. (författare)
  • An interstitial network of podoplanin-expressing cells in the human endolymphatic duct
  • 2006
  • Ingår i: Journal of the Association for Research in Otolaryngology. - : Springer Science and Business Media LLC. - 1525-3961 .- 1438-7573. ; 7:1, s. 38-47
  • Tidskriftsartikel (refereegranskat)abstract
    • The human endolymphatic duct (ED) with encompassing interstitial connective tissue (CT) is believed to be important for endolymph resorption and fluid pressure regulation of the inner ear. The periductal CT cells are interconnected via numerous cellular extensions, but do not form vessel structures. Here we report that the periductal CT is populated by two distinct cell phenotypes; one expressing podoplanin, a protein otherwise found on lymph endothelia and on epithelia involved in fluid fluxes, and a second expressing a fibroblast marker. A majority of the interstitial cells expressed podoplanin but not the lymphatic endothelial cell markers hyaluronan receptor (LYVE-1) or vascular endothelial growth factor receptor-3 (VEGFR-3). The fibroblast marker positive cells were found close to the ED epithelium. In the mid- and distal parts of the ED, these cells were enriched under folded epithelia. Furthermore, subepithelial CT cells were found to express activated platelet derived growth factor (PDGF)-beta receptors. Cultured CT cells from human inner ear periductal and perisaccular explant tissues were identified as fibroblasts. These cells compacted a three-dimensional collagen lattice by a process that could be promoted by PDGF-BB, a factor involved in interstitial fluid pressure regulation. Our results are compatible with the notion that the periductal CT cells are involved in the regulation of inner ear fluid pressure. By active compaction of the periductal CT and by the formation of villous structures, the CT cells could modulate fluid fluxes over the ED epithelium as well as the longitudinal flow of endolymph in the ED.
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16.
  • Hultgård Ekwall, Anna-Karin, 1967- (författare)
  • Fibroblast Contractility in vivo and in vitro : Effects of Prostaglandins and Potential Role for Inner Ear Fluid Homeostasis
  • 2005
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Fibroblasts continuously strive to organize and compact the surrounding extracellular matrix (ECM). Recent data suggest that this cellular contractility controls interstitial fluid homeostasis in loose connective tissues (CT). The aim of this thesis was to study the effects of prostaglandins on fibroblast contractility and to investigate whether fibroblasts in the interstitial CT surrounding the human endolymphatic duct (ED) can modulate inner ear fluid pressure and endolymph resorption.Paper I shows that prostaglandin E1 (PGE1) and prostacyclin inhibit fibroblast-mediated collagen matrix compaction in vitro and lower the interstitial fluid pressure in vivo in rat dermis. Paper II demonstrates that the inhibition of collagen matrix compaction by PGE1 is protein kinase A-dependent. Furthermore, PGE1 induces a complete but reversible actin depolymerization in human dermal fibroblasts by affecting the phosphorylation state of regulatory actin-binding proteins. Paper III describes that the cells of the interstitial CT encompassing the human ED are organized in a network based on intercellular- and cell-ECM contacts. Paper IV shows that two distinct cell phenotypes populate this interstitial CT: one expressing the lymph endothelial marker podoplanin and the other a fibroblast marker. Furthermore, CT cells isolated from human ED tissues exhibited the same tissue compacting properties in vitro as dermal fibroblasts.In conclusion, PGE1 inhibits fibroblast contractility by interfering with the stability and dynamics of the actin cytoskeleton, which leads to a loss of integrin-mediated adhesion to the ECM. These mechanisms are supposedly involved in edema formation in skin during inflammation and might be involved in the formation of endolymphatic hydrops in the inner ear of patients with Ménière’s disease.
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17.
  • Hultgård-Ekwall, Anna-Karin H, et al. (författare)
  • Network organization of interstitial connective tissue cells in the human endolymphatic duct
  • 2003
  • Ingår i: Journal of Histochemistry and Cytochemistry. - : SAGE Publications. - 0022-1554 .- 1551-5044. ; 51:11, s. 1491-500
  • Tidskriftsartikel (refereegranskat)abstract
    • The human endolymphatic duct (ED) and sac of the inner ear have been suggested to control endolymph volume and pressure. However, the physiological mechanisms for these processes remain obscure. We investigated the organization of the periductal interstitial connective tissue cells and extracellular matrix (ECM) in four freshly fixed human EDs by transmission electron microscopy and by immunohistochemistry. The unique surgical material allowed a greatly improved structural and epitopic preservation of tissue. Periductal connective tissue cells formed frequent intercellular contacts and focally occurring electron-dense contacts to ECM structures, creating a complex tissue network. The connective tissue cells also formed contacts with the basal lamina of the ED epithelium and the bone matrix, connecting the ED with the surrounding bone of the vestibular aqueduct. The interstitial connective tissue cells were non-endothelial and non-smooth muscle fibroblastoid cells. We suggest that the ED tissue network forms a functional mechanical entity that takes part in the control of inner ear fluid pressure and endolymph resorption.
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19.
  • Jerkeman, Mats, et al. (författare)
  • MRD-driven treatment with venetoclax-R2 in mantle cell lymphoma : the Nordic Lymphoma Group MCL7 VALERIA trial
  • 2024
  • Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 8:2, s. 407-415
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite improvements in treatment of mantle cell lymphoma (MCL), most patients eventually relapse. In this multicenter phase 1b/2 trial, we evaluated safety and efficacy of minimal residual disease (MRD)-driven venetoclax, lenalidomide, and rituximab (venetoclax-R2) in relapsed/refractory (R/R) MCL and explored the feasibility of stopping treatment in molecular remission. The primary end point was overall response rate (ORR) at 6 months. After dose escalation, the recommended phase 2 dose was lenalidomide 20 mg daily, days 1 to 21; venetoclax 600 mg daily after ramp-up; and rituximab 375 mg/m(2) weekly for 4 weeks, then every 8 weeks. MRD monitoring by RQ-PCR was performed every 3 months. When MRD-negativity in the blood was reached, treatment was continued for another 3 months; if MRD-negativity was then confirmed, treatment was stopped. In total, 59 patients were enrolled, with a median age of 73 years. At 6 months, the ORR was 63% (29 complete remission [CR], 8 partial remission [PR]), and 40% (4 CR, 2 PR) for patients previously failing a Bruton tyrosine kinase (BTK) inhibitor. Median progression-free survival (PFS) was 21 months, with median overall survival of 31 months. TP53 mutation was associated with inferior PFS (P < .01). Overall, 28 patients (48%) discontinued treatment in molecular remission, and 25 remain MRD negative after a median of 17.4 months. Hematological toxicity was frequent, with 52 of 59 (88%) patients with G3-4 neutropenia and 21 of 59 (36%) patients with G3-4 thrombocytopenia. To conclude, MRD-driven venetoclax-R2 is feasible and tolerable and shows efficacy in R/R MCL, also after BTK inhibitor failure.
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20.
  • Jorgensen, Rasmus Rask Kragh, et al. (författare)
  • Machine Learning-Based Survival Prediction Models for Progression-Free and Overall Survival in Advanced-Stage Hodgkin Lymphoma
  • 2024
  • Ingår i: JCO Clinical Cancer Informatics. - : Lippincott Williams & Wilkins. - 2473-4276. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • PurposePatients diagnosed with advanced-stage Hodgkin lymphoma (aHL) have historically been risk-stratified using the International Prognostic Score (IPS). This study investigated if a machine learning (ML) approach could outperform existing models when it comes to predicting overall survival (OS) and progression-free survival (PFS).Patients and MethodsThis study used patient data from the Danish National Lymphoma Register for model development (development cohort). The ML model was developed using stacking, which combines several predictive survival models (Cox proportional hazard, flexible parametric model, IPS, principal component, penalized regression) into a single model, and was compared with two versions of IPS (IPS-3 and IPS-7) and the newly developed aHL international prognostic index (A-HIPI). Internal model validation was performed using nested cross-validation, and external validation was performed using patient data from the Swedish Lymphoma Register and Cancer Registry of Norway (validation cohort).ResultsIn total, 707 and 760 patients with aHL were included in the development and validation cohorts, respectively. Examining model performance for OS in the development cohort, the concordance index (C-index) for the ML model, IPS-7, IPS-3, and A-HIPI was found to be 0.789, 0.608, 0.650, and 0.768, respectively. The corresponding estimates in the validation cohort were 0.749, 0.700, 0.663, and 0.741. For PFS, the ML model achieved the highest C-index in both cohorts (0.665 in the development cohort and 0.691 in the validation cohort). The time-varying AUCs for both the ML model and the A-HIPI were consistently higher in both cohorts compared with the IPS models within the first 5 years after diagnosis.ConclusionThe new prognostic model for aHL on the basis of ML techniques demonstrated a substantial improvement compared with the IPS models, but yielded a limited improvement in predictive performance compared with the A-HIPI.
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21.
  • Kisiel, Marta, 1984-, et al. (författare)
  • Medical students' self-reported gender discrimination and sexual harassment over time
  • 2020
  • Ingår i: BMC Medical Education. - : Springer Science and Business Media LLC. - 1472-6920. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Gender discrimination (GD) and sexual harassment (SH) occur at all academic institutions worldwide. Medical students report high prevalence of GD and SH, which may negatively affect their education and health. There are indications that policies and reforms on reducing GD/SH are insufficient. Swedish medical students' experiences of GD/SH are monitored by course-evaluations and bi-annual student union evaluations; however, the response rate is usually low. The aim of this study was to compare the exposure to and context of self-reported GD/SH over an 11-year period amongst medical students at a Swedish university.METHODS: In 2002, a questionnaire (n = 622) was mailed to medical students' home addresses. It was repeated in 2013 and then distributed during mandatory lectures (n = 856). The questions used a behavioristic approach and asked about specific GH/SH experiences. Participation was voluntary and anonymous. The changes in prevalence over time were calculated by sampling weights in order to obtain comparable estimates, representative of both cohorts.RESULTS: The response frequency was 55% (62% women) in 2002 and 81% (59% women) in 2013. The prevalence of GD tended to decrease for male and clinical students in comparison to female and pre-clinical peers. However, the prevalence of SH increased for female compared to male students. The ratio of SH for female pre-clinical students doubled in many instances; most often, the mistreatment occurred in the clinic. Medical doctors were indicated as perpetrators up to five times more often by all students in 2013.CONCLUSION: Our results show a disproportional change in exposure to GD/SH between female and male medical students, resulting in a widening of the gender gap regarding prevalence of GD and SH between 2002 and 2013. In particular, personal experiences of SH increased for both sexes. It is proof that institutional efforts to fight mistreatment might be ineffective.
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22.
  • Li, Hao, 1984-, et al. (författare)
  • The ultrastructure of a stria vascularis in the auditory organ of the cuban crocodile (Crocodylus rhombifer)
  • 2023
  • Ingår i: Frontiers in Cell and Developmental Biology. - : Frontiers Media S.A.. - 2296-634X. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: An endocochlear potential (EP) exists in the mammalian cochlea generated by the stria vascularis and an associated fibrocyte network. It plays an essential role for sensory cell function and hearing sensitivity. In non-mammalian ectothermic animals the endocochlear potential is low and its origin somewhat unclear. In this study, we explored the crocodilian auditory organ and describe the fine structure of a stria vascularis epithelium that has not been verified in birds.Material and Methods: Three Cuban crocodiles (Crocodylus rhombifer) were analyzed with light and transmission electron microscopy. The ears were fixed in glutaraldehyde The temporal bones were drilled out and decalcified. The ears were dehydrated, and embedded and was followed by semi-thin and thin sectioning.Results: The fine structure of the crocodile auditory organ including the papilla basilaris and endolymph system was outlined. The upper roof of the endolymph compartment was specialized into a Reissner membrane and tegmentum vasculosum. At the lateral limbus an organized, multilayered, vascularized epithelium or stria vascularis was identified.Discussion: Electron microscopy demonstrates that the auditory organ in Crocodylus rhombifer, unlike in birds, contains a stria vascularis epithelium separate from the tegmentum vasculosum. It is believed to secrete endolymph and to generate a low grade endocochlear potential. It may regulate endolymph composition and optimize hearing sensitivity alongside the tegmentum vasculosum. It could represent a parallel evolution essential for the adaptation of crocodiles to their diverse habitats.
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23.
  • Loiske, Karin, 1978-, et al. (författare)
  • Left and right ventricular systolic long-axis function and diastolic function in patients with takotsubo cardiomyopathy
  • 2011
  • Ingår i: Clinical Physiology and Functional Imaging. - Oxford : Wiley. - 1475-0961 .- 1475-097X. ; 31:3, s. 203-208
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Takotsubo cardiomyopathy is characterized by apical wall motion abnormalities without coronary stenosis. Limited information is available on the genesis of the underlying reversible contractile disorder. Our objective in this prospective study was to investigate biventricular changes in systolic long-axis function and diastolic parameters in the acute phase and after recovery.Methods and results: Thirteen consecutive patients were examined by echocardiography and coronary angiography at admission and again by echocardiography after 3 months. Amplitudes, systolic and diastolic velocities of the mitral and tricuspid annuli and conventional diastolic parameters were measured. Systolic long-axis shortening of the left ventricle (LV) and right ventricle (RV) improved from 9·6 ± 2·2 mm to 11·2 ± 1·9 mm (P = 0·02) and from 21·3 ± 3·6 mm to 24·1 ± 2·8 mm (P = 0·02), respectively. LV systolic, early and late diastolic velocities measured by pulsed-wave tissue Doppler also improved, while additional conventional diastolic parameters of the LV and RV diastolic function were unchanged.Conclusions: Takotsubo cardiomyopathy temporarily affects systolic LV and RV function, while most diastolic parameters remain unchanged
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24.
  • Lundin, Karin, et al. (författare)
  • Cochlear implantation in the elderly
  • 2013
  • Ingår i: Cochlear Implants International. - 1467-0100 .- 1754-7628. ; 14:2, s. 92-97
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To analyse complications and outcome of cochlear implant (CI) treatment in seniors receiving CIs during a 10-year period.METHODS:A total of 28 patients, 79 years or older (mean age 81.6 years), were evaluated and compared with a younger group of 76 patients, 20-60 years old (mean age 48.9 years). A retrospective study of the patients' records was performed. Data on per- and post-operative complications, pre- and post-operative speech perception, estimated cognitive skills, and social situation was extracted. A subjective score was assessed and correlated with post-operative performance.RESULTS: No severe per- or post-operative surgical complications were noted. Speech perception improved significantly after surgery (P < 0.001). The younger age group showed better results post-operatively for monosyllabic words (P < 0.01) compared with the older group with no difference seen for bi-syllabic words. In both the groups, there were no significant differences between patients living with or without social support.DISCUSSION:CI surgery for patients 79 years or older was well tolerated. Patients benefited greatly from the device with improved hearing. CI should not be denied older individuals who are otherwise in good health. Non-use in the elderly was associated with post-operative vertigo and tinnitus, severe disease and limited social support.
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25.
  • Lundin, Karin, et al. (författare)
  • Experiences and Results from Cochlear Implantation in Patients with Long Duration of Deafness
  • 2014
  • Ingår i: Audiology & Neurotology Extra. - : S. Karger AG. - 1664-5537. ; 4:2, s. 46-55
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective:The aim of the present study was to gauge factors that influence the outcome of cochlear implants (CI) in patients who have been deaf for an extended period.Patients and Methods:Twelve adult cases (13 ears) were operated on at the CI unit in Uppsala during the period of 2002-2013. These patients had a deafness duration ranging between 20 and 72 years in the implanted ear and severe to profound hearing loss or deafness in the other ear. Data concerning pre- and postoperative speech perception, deafness duration, hearing/deafness duration in the contralateral ear, age at implantation, intraoperative electrophysiological measurements, cause of deafness, and user status were collected.Results:Eleven of 12 patients (13 ears) benefitted from CI treatment.Conclusion: The overall hearing experience, deafness duration, and age at onset of deafness are important issues to consider prior to CI.
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26.
  • Lundin, Karin, et al. (författare)
  • Experiences from Auditory Brainstem Implantation (ABI) in four Paediatric Patients
  • 2016
  • Ingår i: Cochlear Implants International. - : Taylor & Francis. - 1467-0100 .- 1754-7628. ; 17:2, s. 109-115
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Indications for auditory brainstem implants (ABIs) have been widened from patients with neurofibromatosis type 2 (NF2) to paediatric patients with congenital cochlear malformations, cochlear nerve hypoplasia/aplasia, or cochlear ossification after meningitis. We present four ABI surgeries performed in children at Uppsala University Hospital in Sweden since 2009.Methods: Three children were implanted with implants from Cochlear Ltd. (Lane Cove, Australia) and one child with an implant from MedEl GMBH (Innsbruck, Austria). A boy with Goldenhar syndrome was implanted with a Cochlear Nucleus ABI24M at age 2 years (patient 1). Another boy with CHARGE syndrome was implanted with a Cochlear Nucleus ABI541 at age 2.5 years (patient 2). Another boy with post-ossification meningitis was implanted with a Cochlear Nucleus ABI24M at age 4 years (patient 3). A girl with cochlear aplasia was implanted with a MedEl Synchrony ABI at age 3 years (patient 4). In patients 1, 2, and 3, the trans-labyrinthine approach was used, and in patient 4 the retro-sigmoid approach was used.Results: Three of the four children benefited from their ABIs and use it full time. Two of the full time users had categories of auditory performance (CAP) score of 4 at their last follow up visit (6 and 2.5 years postoperative) which means they can discriminate consistently any combination of two of Ling's sounds. One child has not been fully evaluated yet, but is a full time user and had CAP 2 (responds to speech sounds) after 3 months of ABI use. No severe side or unpleasant stimulation effects have been observed so far. There was one case of immediate electrode migration and one case of implant device failure after 6.5 years.Conclusion: ABI should be considered as an option in the rehabilitation of children with similar diagnoses.
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27.
  • Lundin, Karin, 1977- (författare)
  • Experiences from Cochlear Implantation and Auditory Brainstem Implantation in Adults and Children : Electrophysiological Measurements, Hearing Outcomes and Patient Satisfaction
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Cochlear implants (CIs) and auditory brainstem implants (ABIs) are prostheses for hearing used in patients with profound hearing impairment. A CI requires an operational cochlear nerve to function in contrast to an ABI. ABIs were initially designed for adult patients with neurofibromatosis type 2 (NF2), suffering from bilateral vestibular schwannomas. Now ABIs are also used for patients, both adults and children, with congenital cochlear malformations, cochlear nerve hypoplasia/aplasia, and cochlear ossification. The aims of this thesis are to evaluate hearing outcome in patients implanted with a CI after long-term deafness. An extended period of deafness has earlier been considered as a contraindication for CI surgery. Further, we analyzed if electrically evoked auditory brainstem responses (eABRs) can predict CI outcome and pinpoint the optimal selection of treatment such as CI or ABI. We also disclose our experiences from ABI surgery in Uppsala, such as implant use, hearing outcome, complications, and satisfaction among the patients. Finally, we evaluated the results and benefits of ABIs in non-NF2 pediatric patients.Results show that patients with an extended deafness period and durations over 20 years can achieve speech understanding and benefit from CIs. Patients with long-term deafness and limited years of hearing before deafness did not perform as well as those with shorter deafness duration and longer hearing experience did. eABR seems to have a definite role in the diagnostic armamentarium, to better consider alternative surgical strategies such as ABI. No eABR waveform predicted a poor CI outcome. There was no correlation between speech perception and eABR waveform latencies or eABR waveform quality. A majority of the ABI patients used their ABIs and benefited from them for at least some period. ABI assisted voice control in a majority of the full-time users and they reported improved understanding of speech with the implant switched on. No severe complications from ABI surgery or ABI stimulation were noted. The patients were generally satisfied, even if their hearing remained very limited. All pediatric patients but one used the implant continuously and benefited from it.
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28.
  • Lundin, Karin, et al. (författare)
  • Prognostic Value of Electrically Evoked Auditory Brainstem Responses in Cochlear Implantation
  • 2015
  • Ingår i: Cochlear Implants International. - 1467-0100 .- 1754-7628. ; 16:5, s. 254-261
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesThe aim of this study was to investigate whether electrical auditory brainstem responses (eABRs) obtained during cochlear implantation (CI) can predict CI outcomes. We also aimed to assess whether eABR can be used to select patients for auditory brainstem implantation (ABI).MethodsThis was a retrospective study. The latencies and quality of the eABR waveforms from adult patients implanted with CI in Uppsala from 2011 to 2013 (n = 74) and four children with severe cochlear abnormalities were analyzed. Speech perception was assessed through postoperative monosyllabic word (MS-word) recognition. A score was constructed for each patient based on wave II, III, and V patency.ResultseABR latencies increased towards base stimulation of the cochlea. Wave V for the mid- and low-frequency regions was the most robust. Significant latency shifts occurred in wave V from the low- to high-frequency regions (**P < 0.01) and from the mid- to high-frequency regions (**P < 0.01). No correlations were found between waveform score, wave V–III interval, wave V latency, and MS-word scores. A negative eABR always predicted a negative outcome. Among the patients with negative outcomes, 75% had eABRs.DiscussionImplant electrical stimulation and brain stem recordings can be used (eABRs wave V) to predict a negative functional outcome. Low-frequency waves V were observed in all patients with successful CI outcomes. Patients for whom eABR waveforms were completely absent had unsuccessful CI outcomes.
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29.
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30.
  • Lundin, Karin, 1977-, et al. (författare)
  • Re-implantation of an auditory brainstem implant (ABI) in a child : A case report
  • 2017
  • Ingår i: Acta oto-laryngologica case reports. - : Taylor & Francis Group. - 2377-2484. ; 2:1, s. 119-124
  • Tidskriftsartikel (refereegranskat)abstract
    • The study aimed at describing a case of auditory brainstem implant (ABI) paediatric re-implantation performed at the Akademiska University Hospital, Sweden. The patient was a boy with Goldenhar syndrome with absent vestibular-cochlear nerves and was first implanted with an ABI in 2009 at the age of two years. A technical device failure in 2015 led to a re-implantation at the age of nine years. The ABI was successfully re-implanted although the implant was closely attached to the surrounding tissue and difficult to remove. The intraoperative electrical auditory brainstem measures (eABRs) gave unclear responses after re-implantation. After 12 months, the patient's hearing thresholds was not as good as it was after the primary implant, but it is still developing. The child is a full-time user. ABI re-implantation is possible even after many years, although there is a risk that the implant might be fixed to the brainstem and difficult to remove.
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31.
  • Lundin, Karin, et al. (författare)
  • Self-Reported Benefit, Sound Perception, and Quality-of-Life in Patients with Auditory Brainstem Implants (ABIs)
  • 2016
  • Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 136:1, s. 62-67
  • Tidskriftsartikel (refereegranskat)abstract
    • CONCLUSION:The majority of the patients used their auditory brainstem implants (ABIs) all the time, reporting that he/she would make the decision to receive an implant again if the decision were reconsidered. The findings support that the ABI is a valuable treatment in patients with type 2 neurofibromatosis (NF2) and in children with congenital inner ear and nerve anomalies or cochlear ossification.OBJECTIVE:To evaluate the patients who underwent ABI implantation in Uppsala during 1993-2013. This study analyzed patients' implant use, perception of environmental sounds, perceived benefit from the implant, and quality-of-life (QoL).METHOD:The NF2-patients (n = 20) comprised the majority of the patients, and there were a few non-NF2 pediatric patients (n = 4). The exclusion criteria included deceased patients (n = 4) and patients with no hearing sensations from the implant, or those with an inactivated ABI (n = 2). The data were collected from a questionnaire survey.RESULTS:Eleven adult patients and two pediatric patients answered the questionnaires. Eight of the adult patients used their implants 'always'. The two children always used their implants. Hearing problems had the largest negative effect on the QoL. The non-users and the users scored equally on the NFTI-QoL.
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32.
  • Mei, Xueshuang, et al. (författare)
  • Human inner ear blood supply revisited : the Uppsala collection of temporal bone - an international resource of education and collaboration
  • 2018
  • Ingår i: Upsala Journal of Medical Sciences. - : TAYLOR & FRANCIS LTD. - 0300-9734 .- 2000-1967. ; 123:3, s. 131-142
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The Uppsala collection of human temporal bones and molds is a unique resource for education and international research collaboration. Micro-computerized tomography (micro-CT) and synchrotron imaging are used to investigate the complex anatomy of the inner ear. Impaired microcirculation is etiologically linked to various inner ear disorders, and recent developments in inner ear surgery promote examination of the vascular system. Here, for the first time, we present three-dimensional (3D) data from investigations of the major vascular pathways and corresponding bone channels.Methods: We used the archival Uppsala collection of temporal bones and molds consisting of 324 inner ear casts and 113 macerated temporal bones. Micro-CT was used to investigate vascular bone channels, and 26 fresh human temporal bones underwent synchrotron radiation phase contrast imaging (SR-PCI). Data were processed by volume-rendering software to create 3D reconstructions allowing orthogonal sectioning, cropping, and soft tissue analyses.Results: Micro-CT with 3D rendering was superior in reproducing the anatomy of the vascular bone channels, while SR-PCI replicated soft tissues. Arterial bone channels were traced from scala vestibuli (SV) arterioles to the fundus, cochlea, and vestibular apparatus. Drainage routes along the aqueducts were examined.Conclusion: Human inner ear vessels are difficult to study due to the adjoining hard bone. Micro-CT and SR-PCI with 3D reconstructions revealed large portions of the micro-vascular system in un-decalcified specimens. The results increase our understanding of the organization of the vascular system in humans and how altered microcirculation may relate to inner ear disorders. The findings may also have surgical implications.
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33.
  • Rask-Andersen, Helge, et al. (författare)
  • Special Anatomic Considerations in Otosclerosis Surgery
  • 2018
  • Ingår i: Otolaryngologic clinics of North America. - : Saunders Elsevier. - 0030-6665 .- 1557-8259. ; 51:2, s. 357-
  • Tidskriftsartikel (refereegranskat)abstract
    • The anatomy of the vestibular organs together with considerations of the middle and inner ear anatomy relevant to stapes surgery is discussed. An archival collection of macerated and freshly frozen human temporal bones underwent micro computed tomography (CT) with subsequent volume rendering. Three-dimensional (3D) reconstructions and the topographic anatomy of the oval window were considered. Micro-CT and 3D rendering revealed the relationship between the otolith organs and the oval window. Anatomic variations were extensive and included the distance between the footplate and the reconstructed macula margins. A "no-go" zone is suggested for the surgeon to avoid injury during stapes surgery.
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34.
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35.
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36.
  • Rask, Katarina, 1966, et al. (författare)
  • Increased expression of the transcription factors CCAAT-enhancer binding protein-beta (C/EBBeta) and C/EBzeta (CHOP) correlate with invasiveness of human colorectal cancer.
  • 2000
  • Ingår i: International journal of cancer. Journal international du cancer. - 0020-7136. ; 86:3, s. 337-43
  • Tidskriftsartikel (refereegranskat)abstract
    • Regulation of cell differentiation is most often impaired in malignant tumors and may represent a key mechanism for the progression of the disease. CCAAT-enhancer binding protein (C/EBP) is a family of transcription factors involved in the regulation of embryonic gut development in rodents, which has also been detected in various malignancies, e.g., liposarcomas and breast and ovarian epithelial tumors. We studied the relationship between C/EBP and tumor histology (Duke's invasive stage and pathological grade) in colorectal cancer. Immunoblotting techniques were used on microdissected fresh frozen tumor specimens, and expression of C/EBPalpha, C/EBPbeta and C/EBPzeta (CHOP) was analyzed in addition to that of the cell-cycle regulator p53 and the proliferation marker PCNA. Expression of C/EBPbeta (LAP isoforms) was markedly increased in all tumors compared with normal colon mucosa. Although the inter-patient variability was large, we found that LIP, the isoform of C/EBPbeta known to inhibit transcription, was expressed at higher levels in Duke's stage B tumors compared with Duke's stage A, whereas Duke's C tumors had the lowest LIP expression. A similar relationship was seen for CHOP. The cell-cycle regulator gene p53 was the only factor that clearly correlated with pathological grade: a decrease in p53 expression was demonstrated. Our data suggest that genetic and cellular events involving C/EBPbeta and CHOP are important for tumor invasion and that these events do not appear to be related to the pathological grade of the tumor.
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37.
  • Rask, Katarina, 1966, et al. (författare)
  • Ovarian epithelial cancer: a role for PGE2-synthesis and signalling in malignant transformation and progression
  • 2006
  • Ingår i: Mol Cancer. - : Springer Science and Business Media LLC. ; 15:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The involvement of the cyclooxygenases (COX), in particular COX-2, is well documented for many tumours, e.g. colon, breast and prostate cancer, by both experimental and clinical studies. There are epidemiological data from subjects using NSAIDs, and experimental evidence supporting the hypothesis of prostaglandins (PGs) as regulators of tumourigenesis in the ovary. One of the end products of PG-synthesis, PGE2, regulates several key-processes, which are characteristic for tumour growth, e.g. angiogenesis, proliferation and apoptosisis. The present study investigated the pathway for PGE2 – synthesis and signalling in ovarian tumourigenesis by analysing specimen from normal ovaries (n = 18), benign (B) (n = 8), borderline type (BL) (n = 6) and malignant tumours (AC) (n = 22). The expression and cell-specific localization of COX-1, COX-2, microsomal prostaglandin E synthase-1 (mPGES-1) and two of the receptors for PGE2, EP1 and EP2, were examined by immunoblotting (IB) and immunohistochemistry (IHC). Results The results are in line with earlier studies demonstrating an increase of COX-2 in AC compared to the normal ovary, B and BL tumours. Increased expressions were also observed for COX-1, mPGES-1 and EP-1 which all were significantly (p < 0.05) augmented in less differentiated AC (grades: moderately-, poorly- and undifferentiated). The increase of COX-2 was also correlated to stage (FIGO classification) with significant elevations in stages II and III. EP1 was increased in stage III while no significant alterations were demonstrated for COX-1, mPGES-1 or EP2 for stage. IHC revealed staining of the tumour cells, but also increase of COX-1, COX-2, mPGES-1 and EP1–2 in the stromal compartment of AC (grades: moderately-, poorly- and undifferentiated). This observation suggests interactions between tumour cells and stromal cells (fibroblasts, immune cells), e.g. paracrine signalling mediated by growth factors, cytokines and possibly PGs. Conclusion The increases of COX-1, COX-2, mPGES-1 and EP1–2 in epithelial ovarian cancer, supports the hypothesis that PGE2-synthesis and signalling are of importance for malignant transformation and progression. The observed augmentations of COX-1, COX-2 and mPGES-1 have implications for future therapeutic strategies.
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38.
  • Rask, Katarina, 1966, et al. (författare)
  • Wnt-signalling pathway in ovarian epithelial tumours: increased expression of beta-catenin and GSK3 beta
  • 2003
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:7, s. 1298-1304
  • Tidskriftsartikel (refereegranskat)abstract
    • Beta-catenin is involved in both cell-cell adhesion and in transcriptional regulation by the Wingless/Wnt signalling pathway. Alterations of components of this pathway have been suggested to play a central role in tumorigenesis. The present study investigated, by immunohistochemistry and immunoblotting, the protein expression and localisation of beta-catenin, adenomatous polyposis coli (APC), glycogen synthase kinase 3beta (GSK3beta) and lymphocyte enhancer factor-1 (Lef-1) in normal human ovaries and in epithelial ovarian tumours in vivo and in vitro. Immortalised human ovarian surface epithelium and ovarian cancer cell cells (OVCAR-3) expressed beta-catenin, APC, GSK3beta and Lef-1. Nuclear staining of beta-catenin and Lef-1 were demonstrated only in OVCAR-3 cells. There were significant increases of beta-catenin and GSK3beta, while APC was reduced in ovarian cancer compared to the normal ovary. Beta-catenin and Lef-1 were coimmunoprecipitated in ovarian tumours, but not in the normal ovary. Nuclear localisation of beta-catenin or Lef-1 could not be demonstrated in the normal ovary or in the ovarian tumours. The absence of nuclear localisation of beta-catenin could be due to an increased binding to the cadherin-alpha-catenin cell adhesion complex. In fact, we have earlier reported an increased expression of E-cadherin in ovarian adenocarcinomas. In summary, this study demonstrates an increase in the expression of components of the Wingless/Wnt pathway in malignant ovarian tumours. The increase suggests a role for this signalling pathway in cell transformation and in tumour progression. However, it remains to be demonstrated whether it is an increased participation of beta-catenin in transcriptional regulation, or in the stabilisation of cellular integrity, or both, that is the crucial event in ovarian tumorigenesis.
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39.
  • Rask, Marie (författare)
  • Women receiving notification of an abnormal Pap smear result : experiences and impact on health-related quality of life
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Aim: The aim of this thesis was to investigate experiences of receiving notification of an abnormal Pap smear result and its impact on women’s health-related quality of life as well as to investigate women’s awareness of human papillomavirus.Methods: In total, 176 women and 20 healthcare professionals participated. Data were collected through individual interviews (I, II) and a questionnaire (IV) including the instrument Functional Assessment of Chronic Illness Therapy – Cervical Dysplasia (FACIT-CD) and Hospital Anxiety and Depression Scale (HADS). For the translation and cross-cultural adaptation of the FACIT-CD, and for evaluation of its linguistic validity and reliability, cognitive debriefing interviews and a questionnaire consisting of the Swedish instrument FACIT-CD was used. Data were analysed by content analysis (I, II) and by using statistical analysis (III, IV), while one part (III) was analysed according to FACIT translation methodology.  Results: Women receiving notification of an abnormal Pap smear result have good overall HRQoL; they become anxious but not depressed. Reasons for anxiety were mainly that women misinterpreted the result as cancer, which could lead to lower attendance for further investigation, treatment and follow-up. To cope with the anxiety, women sought emotional support and information. They primarily used the Internet for information but also turned to healthcare professionals for information needs. Moreover, women had low awareness of HPV, its sexually transmitted nature, and its relationship to abnormal Pap smear results and cervical cancer. An awareness of HPV as a sexually transmitted infection did not lead to higher level of anxiety or more depression symptoms or worse HRQoL, compared to not being aware. Finally, the Swedish FACIT-CD is equivalent to the English version and linguistically valid and exhibited good internal consistency reliability.Conclusion: Women have low awareness of HPV and abnormal Pap smear results, whereupon they misinterpret their test result as cancer. It is of importance that women understand their test result, in order to minimise anxiety as well as to maintain high attendance for investigation, treatment and follow-up of abnormalities.
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40.
  • Rask, Olof, et al. (författare)
  • Lower incidence of procoagulant abnormalities during follow-up after creation of the Fontan circulation in children.
  • 2009
  • Ingår i: Cardiology in the Young. - 1467-1107. ; 19, s. 152-158
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Children who undergo surgery for complex congenital cardiac disease are reported to be at increased thrombotic risk. Our aim was to evaluate long-term changes in the haemostatic system after surgery, to compare markers of activated coagulation in children having surgery with those in a healthy control population, and to relate them to adverse clinical outcome.Patients and methodsWe studied, prior to surgery, the coagulation profiles of a cohort of 28 children admitted for a modified Fontan operation, studying them again after a period of mean follow-up of 9.6 years. Median age at the time of final surgery was 18.5 months, with a range from 12 to 76 months. We compared generation of thrombin, and levels of the activated protein C-protein C inhibitor complex to controls at follow-up. Thrombophilia and clinical outcome were evaluated. RESULTS: At long-term follow-up, a lower incidence of procoagulant abnormalities was observed compared to that before surgery. Of 27 patients, 3 (11%), but none of 45 controls, had levels of activated protein C-protein C inhibitor complex above the reference range. There were no significant differences in generation of thrombin between patients and controls. No thrombotic events were recorded, and the patients were generally in good clinical condition. CONCLUSIONS: Overall, haemostasis appeared to be in balance, and less prothrombotic, after surgery. A subset of the cohort did show indications of activated coagulation. The current therapeutic approach seems to be sufficient to protect the majority of patient. New tests of global coagulation, nonetheless, may be helpful in improving identification of individuals at increased thrombotic risk.
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41.
  • Schart-Moren, Nadine, et al. (författare)
  • Peri-operative electrically evoked auditory brainstem response assessment of facial nerve/cochlea interaction at cochlear implantation
  • 2018
  • Ingår i: Cochlear Implants International. - : Informa UK Limited. - 1467-0100 .- 1754-7628. ; 19:6, s. 324-329
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Dehiscence between the cochlear otic capsule and the facial nerve canal is a rare and relatively newly described pathology. In cochlear implantation (CI), this dehiscence may lead to adverse electric facial nerve stimulation (FNS) already at low levels, rendering its use impossible. Here, we describe an assessment technique to foresee this complication.METHODS: Pre- and postoperative computed tomography (CT) scans and intraoperative electrically evoked auditory brainstem response (e-ABR) measurements were analyzed in two patients with cochlear-facial dehiscence (CFD).RESULTS: Because of the relatively low resolution, the confirmation of CFD with a clinical CT was difficult. The e-ABR displayed a large potential with 6 and 7.5 ms latency, respectively, which did not occur otherwise.DISCUSSION: Potential strategies to resolve and manage FNS are described.CONCLUSION: Prediction of FNS by assessing the distance between the labyrinthine portion of the facial nerve and the cochlea is difficult using conventional CT scans. A large evoked late myogenic potential at low stimulation levels during intraoperative e-ABR measurement may foresee FNS at CI activation.
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42.
  • Siegbahn, Malin, et al. (författare)
  • Auditory Brainstem Implants (ABIs) : 20 Years of Clinical Experience in Uppsala, Sweden
  • 2014
  • Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 134:10, s. 1052-1061
  • Tidskriftsartikel (refereegranskat)abstract
    • CONCLUSIONS:Even though sound perception may be limited after treatment with an auditory brainstem implant (ABI), it provides benefits and should be selectively offered to patients. Importantly the patients must be motivated, given reasonable expectations of outcome and offered long-term rehabilitation with a considerable 'learn to listen' period with the implant device.OBJECTIVES:To describe the clinical experiences and results of 24 ABI surgeries performed in Uppsala University Hospital between 1993 and 2013.METHODS:Most patients (n = 20) suffered from neurofibromatosis type 2 (NF2); a few patients (n = 4) were paediatric non-NF2 patients. The files were searched for information on the presurgery size of the vestibular schwannoma, whether the patient had undergone gamma knife treatment, the surgical approach, the side effects of the surgery and of the use of the implant, the electrode activation pattern and implant use, and categories of auditory performance (CAP) score.RESULTS:Our results show that many patients greatly benefited from an ABI, and most of the patients used their implants even though the hearing improvements usually consisted of awareness of surrounding sounds and improved lip-reading. No severe side effects were observed from implant stimulation.
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43.
  • Strömbäck, Karin, et al. (författare)
  • High frequency hearing following stapes surgery
  • 2012
  • Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 132:9, s. 944-950
  • Tidskriftsartikel (refereegranskat)abstract
    • Conclusion:Our results indicate that a pre-existing sensorineural hearing loss (SNHL) is not a potential risk factor for further hearing loss in stapes surgery.Objective:The study evaluated whether pre-existing SNHL in otosclerosis constitutes a risk factor for further hearing loss in stapedotomy.Methods:Preoperative and postoperative audiometric evaluation including air (AC) and bone conduction (BC) hearing levels were assessed together with collection of surgical records from 338 consecutively operated cases for primary otosclerosis using a database. Patients were operated by the same surgeon between 2000 and 2006. In all, 291 patients were operated on 1 side and 47 patients were operated on both sides. Ages ranged from 16 to 76 years. Stapedotomy was performed in all cases except five (stapedectomy). Cases were separated into four different groups based on preoperative AC hearing levels at 4, 6, and 8 kHz: group I, <30 dB HL; group II, 30-50 dB HL; group III, 51-70 dB HL; group IV, >70 dB HL).Results:Hearing deterioration at 4, 6, and 8 kHz (>10 dB) was observed in 6.5% of all cases. Patients with normal preoperative hearing were found to be more prone to further SNHL 4, 6, and 8 kHz (range 13-25 dB) at surgery, while patients in group IV, with preoperative SNHL impairment, remained unaffected.
  •  
44.
  • Säll-Hansson, Karin, et al. (författare)
  • The meaning of the experiences of persons with chronic pain in their encounters with the health service
  • 2011
  • Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 25:3, s. 444-450
  • Tidskriftsartikel (refereegranskat)abstract
    • The meaning of the experiences of persons with chronic pain in their encounters with the health service Chronic pain causes great suffering for those affected and treating it is one of the most common assignments in the health service. The aim of the study was to investigate the meaning of the experiences of persons with chronic pain in their encounters with health service staff. The study had a descriptive design with a phenomenological approach based on the perspective of caring science. Interviews were carried out with eight patients. The study showed that patients experienced a positive approach and that the staff had understood the serious nature of the situation. A positive approach can communicate hope and help to strengthen the patient. It is important to ask the patient about how he/she experiences his/her situation and thus gain an insight into this person's lifeworld. Participation entailed being active oneself and calling attention to one's needs and wishes for treatment. The study also showed that a negative approach by the staff played a prominent part in their experiences and appeared to be engraved in their memories. A negative approach is felt as being insulting and belittling. Patients with chronic pain felt that they were discredited and that their experience of their situation was called into question. They had to fight to get care and had to suggest treatments and examinations. There were also patients who had neither been asked about their pain experience nor had the opportunity to assess their pain with an assessment scale. Some of the phases in Travelbee's relationship model could be seen in several of the encounters but not all. The participants did not always feel that the manner of the nursing staff was empathetic or sympathetic, which led to greater suffering.
  •  
45.
  • Wendin, Karin, 1963-, et al. (författare)
  • Insects as food : a pilot study for industrial production
  • 2019
  • Ingår i: 13th Pangborn Sensory Science Symposium.
  • Konferensbidrag (refereegranskat)abstract
    • Despite the many papers reporting on disgust factors of eating insects in Western cultures, the interest of insects as food is increasing, not least because they are nutritious, sustainable and tasty! The time has come to take the next step by making insects available not only as delicious restaurant food, but also for industrial production of foods and meals based on insects. The sensory attributes are of greatest importance to increase understanding of insects as a main ingredient in production and shelf life. By the use of factorial designs with mealworms as main ingredient, the aim was to evaluate the sensory impact of additions such as salt, oil/water and antioxidant agent. Also the impact of particle size of the mealworms was evaluated.Cooked fresh mealworms cut or ground into different particle sizes, oil, water, salt and rosemary were blended according to a factorial design. The resulting products were evaluated by descriptive sensory analysis in addition to instrumental measurements of viscosity and colour. Nutritional contents were calculated. Results showed that particle size of the mealworms had a great impact, ie an increased particle size increased the yellowness and the perceived coarseness. Further, both viscosity and crispiness increased. An increased particle size also meant a decreased odour, probably due to decreased exposure of particle surface. Increased salt content did, as expected, increase saltiness. It also increased the nutty flavour, probably due to the polarity of Sodium Chloride. Different ratios of oil/water did not seem to impact the sensory properties. With reference to the anti-oxidative effects of carnosic acid and carnosol, addition of rosemary had a significant impact on shelf life in terms of decreased rancidity and colour changes. All samples were high in protein content. All factors, but especially particle size of the mealworm fraction, influenced the sensory attributes.
  •  
46.
  • Wendin, Karin, et al. (författare)
  • Insects as food : a pilot study for industrial production
  • 2019
  • Ingår i: Book of Abstracts of the EAAP 70<sup>th</sup> Annual  Meeting of the European Federation of Animal Science. - Ghent. - 9789086863396 ; , s. -161
  • Konferensbidrag (refereegranskat)abstract
    • Despite the many papers reporting on disgust factors of eating insects in Western cultures, the interest of insects as food is increasing, not least because they are nutritious, sustainable and tasty! The time has come to take the next step by making insects available not only as delicious restaurant food, but also for industrial production of foods and meals based on insects. The sensory attributes are of greatest importance to increase understanding of insects as a main ingredient in production and shelf life. By the use of factorial designs with mealworms as main ingredient, the aim was to evaluate the sensory impact of additions such as salt, oil/water and antioxidant agent. Also the impact of particle size of the mealworms was evaluated.Cooked fresh mealworms cut or ground into different particle sizes, oil, water, salt and rosemary were blended according to a factorial design. The resulting products were evaluated by descriptive sensory analysis in addition to instrumental measurements of viscosity and colour. Nutritional contents were calculated. Results showed that particle size of the mealworms had a great impact, ie an increased particle size increased the yellowness and the perceived coarseness. Further, both viscosity and crispiness increased. An increased particle size also meant a decreased odour, probably due to decreased exposure of particle surface. Increased salt content did, as expected, increase saltiness. It also increased the nutty flavour, probably due to the polarity of Sodium Chloride. Different ratios of oil/water did not seem to impact the sensory properties. With reference to the anti-oxidative effects of carnosic acid and carnosol, addition of rosemary had a significant impact on shelf life in terms of decreased rancidity and colour changes. All samples were high in protein content. All factors, but especially particle size of the mealworm fraction, influenced the sensory attributes.
  •  
47.
  • Wendin, Karin, et al. (författare)
  • Insects as food : a pilot study for industrial production
  • 2019
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Despite the many papers reporting on disgust factors of eating insects in Western cultures, the interest of insects as food is increasing, not least because they are nutritious, sustainable and tasty! The time has come to take the next step by making insects available not only as delicious restaurant food, but also for industrial production of foods and meals based on insects. The sensory attributes are of greatest importance to increase understanding of insects as a main ingredient in production and shelf life.   By the use of factorial designs with mealworms as main ingredient, the aim was to evaluate the sensory impact of additions such as salt, oil/water and antioxidant agent. Also the impact of particle size of the mealworms was evaluated. Cooked fresh mealworms cut or ground into different particle sizes, oil, water, salt and rosemary were blended according to a factorial design. The resulting products were evaluated by descriptive sensory analysis in addition to instrumental measurements of viscosity and colour. Nutritional contents were calculated.  Results showed that particle size of the mealworms had a great impact, ie an increased particle size increased the yellowness and the perceived coarseness. Further, both viscosity and crispiness increased. An increased particle size also meant a decreased odour, probably due to decreased exposure of particle surface. Increased salt content did, as expected, increase saltiness. It also increased the nutty flavour, probably due to the polarity of Sodium Chloride. Different ratios of oil/water did not seem to impact the sensory properties. With reference to the anti-oxidative effects of carnosic acid and carnosol, addition of rosemary had a significant impact on shelf life in terms of decreased rancidity and colour changes. All samples were high in protein content.   All factors, but especially particle size of the mealworm fraction, influenced the sensory attributes.
  •  
48.
  • Wendin, Karin, 1963-, et al. (författare)
  • Introducing mealworm as an ingredient in crisps and pâtés – sensory characterization and consumer liking
  • 2021
  • Ingår i: Future Foods. - : Elsevier. - 2666-8335. ; 4, s. 1-8
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this study was to evaluate sensory perception and consumers’ attitude and liking of products with different textures, crisps and pâtés, with added mealworm ingredient in different amounts. By addition of mealworm ( Tenebrio molitor L. ) in the crisps, the brittleness increased. However, an increase in mealworm also increased the darkness. Adding mealworms to pâté reduced the odour and flavour of vegetable and increased the flavour of cinnamon and pepper as well as the oily texture. There was no significant difference in total liking between 10 and 30% addition of mealworm, nor between 0 and 10% addition, in any of the two products. The crisps received higher liking score than the pâtés. Thus, there is also a much higher probability that a customer would buy insect crisps than insect pâté. Environmental sustainability and sensory properties were shown to be the main reasons for buying foods with added insect ingredients.
  •  
49.
  • Wendin, Karin, et al. (författare)
  • Introducing mealworm as an ingredient in crisps and pâtés – sensory characterization and consumer liking
  • 2021
  • Ingår i: Future Foods. - : Elsevier B.V.. - 2666-8335. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this study was to evaluate sensory perception and consumers’ attitude and liking of products with different textures, crisps and pâtés, with added mealworm ingredient in different amounts. By addition of mealworm (Tenebrio molitor L.) in the crisps, the brittleness increased. However, an increase in mealworm also increased the darkness. Adding mealworms to pâté reduced the odour and flavour of vegetable and increased the flavour of cinnamon and pepper as well as the oily texture. There was no significant difference in total liking between 10 and 30% addition of mealworm, nor between 0 and 10% addition, in any of the two products. The crisps received higher liking score than the pâtés. Thus, there is also a much higher probability that a customer would buy insect crisps than insect pâté. Environmental sustainability and sensory properties were shown to be the main reasons for buying foods with added insect ingredients. © 2021 The Authors
  •  
50.
  • Wendin, Karin, 1963-, et al. (författare)
  • Mealworm (Tenebrio molitor) as a sustainable ingredient in crisps and pâtes. Sensory characterisation and consumer liking
  • 2021
  • Ingår i: 14th Pangborn Sensory Science Symposium ‘Sustainable Sensory Science’.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Sustainable food with low environmental impact is of great importance. Insects are highly nutritious and has low effect on the environment. However, in western countries, insects as foods have a low acceptance. It is therefore of importance to process the insects into foods with familiar flavour and texture. To understand consumers’ perception, different types of common food products should be examined. Thus, in this study two widely different products are included, crisps and pâtés with added mealworm ingredient.The aim of this study was to evaluate sensory perception and consumers’ attitude and liking of products with different textures, crisps and pâtés, with added mealworm ingredient.Two types of products differing largely in texture properties were produced: crisps (crispy) and pâtés (soft). Three varieties of each product type were produced, containing mealworm flour in the amounts of 0%, 10% and 30%, respectively. Adding mealworms in the crisps increased brittleness and darkness. Adding mealworms to pâté increased flavours of cinnamon and pepper as well as oily texture. There was no significant difference in total liking between 10 and 30% addition of mealworm, nor between 0 and 10%, in any of the two products. The crisps received higher liking score than the pâtés. 85% of the consumers indicated their interest in buying food products based on insects. However, a large majority, 90%, were interested in buying crisps, while only 30% showed interest in buying the pâté. This clearly points out the importance of sensory aspects in liking and consideration of buying products with added mealworms. In conclusion: Mealworm ingredient could be used in products differing in textures, addition of mealworm had different impact on the sensory attributes in each of the product types. It was shown that environmental sustainability and sensory properties were the main reasons for buying foods with added insect ingredient.
  •  
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