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1.
  • Prendergast, Virginia, et al. (författare)
  • Effects of a standard versus comprehensive oral care protocol among intubated neuroscience ICU patients : results of a randomized controlled trial
  • 2012
  • Ingår i: Journal of Neuroscience Nursing. - : Lippincott Williams & Wilkins. - 0888-0395 .- 1945-2810. ; 44:3, s. 134-146
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of the study was to compare changes in oral health during intubation until 48 hours after extubation in neuroscience intensive care unit (ICU) patients enrolled in a standard or a comprehensive oral care protocol. The effects of manual toothbrushing (standard group, n = 31) were compared with those of tongue scraping, electric toothbrushing, and moisturizing (comprehensive group, n = 25) in intubated patients in a neuroscience ICU in a 2-year randomized clinical trial. Oral health was evaluated based on the Oral Assessment Guide (OAG) on enrollment, the day of extubation, and 48 hours after extubation. There were no significant differences in the frequency of the oral care protocol. Protocol compliance exceeded 91% in both groups. The total OAG score and all eight categories significantly deteriorated (Friedman test, p < .001, Bonferroni corrected) in the standard oral care group and did not return to baseline after extubation. Large effect sizes were present at all three points in this group. The total OAG score deteriorated during intubation within the comprehensive protocol group (Friedman test, p < .004) but returned to baseline status after extubation. In four categories, the ratings on tongue, mucous membranes, gingiva, and teeth did not deteriorate significantly over time. Published oral care protocols are substandard in promoting and maintaining oral health in intubated patients. A comprehensive oral care protocol, using a tongue scraper, an electrical toothbrush, and pharmacological moisturizers, was more effective for oral hygiene throughout intubation and after extubation than manual toothbrushing alone.
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2.
  • Andersson, Pia, et al. (författare)
  • Oral health problems in elderly rehabilitation patients
  • 2004
  • Ingår i: International Journal of Dental Hygiene. - : Wiley-Blackwell. - 1601-5029 .- 1601-5037. ; 2:2, s. 70-77
  • Tidskriftsartikel (refereegranskat)abstract
    • A combination of poor oral hygiene and dry mouth may be hazardous to the oral health status. However, systematic assessments in order to detect oral health problems are seldom performed in the nursing care of the elderly. The aims of this study were to investigate the occurrence of oral health problems measured using the Revised Oral Assessment Guide (ROAG) and to analyse associations between oral health problems and age, gender, living conditions, cohabitation, reason for admission, number of drugs, and functional and nutritional status. One registered nurse performed oral health assessments using ROAG in 161 newly admitted elderly patients in rehabilitation care. Oral health problems were found in 71% of the patients. Thirty per cent of these patients had between four and eight problems. Low saliva flow and problems related to lips were the most frequent oral health problems. Problems in oral health status were significantly associated with presence of respiratory diseases (problems with gums, lips, alterations on the tongue and mucous membranes), living in special accommodation (low saliva flow, problems with teeth/dentures and alterations on the tongue), being undernourished (alterations on the tongue and low saliva flow) and being a woman (low saliva flow). The highest Odds ratio (OR) was found in problems with gums in relation with prevalence of respiratory diseases (OR 8.9; confidence interval (CI) 2.8–27.8; P < 0.0005). This study indicates the importance of standardised oral health assessments in order to detect oral health problems which can otherwise be hidden when the patients are admitted to the hospital ward.
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3.
  • Adrian Meredith, Jenny, 1971-, et al. (författare)
  • Design and synthesis of novel P2 substituents in diol-based HIV protease inhibitors
  • 2010
  • Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 45:1, s. 160-170
  • Tidskriftsartikel (refereegranskat)abstract
    • The synthesis and SAR of HIV-1 protease inhibitors containing novel P2 structural elements are presented. The inhibitors were designed having hydrogen bond accepting P2 substituents to probe potential favorable interactions to Asp-29/Asp-30 of the HIV-1 protease backbone utilizing inhibitor 3 as a model template. Several inhibitors were synthesized from an L-Val methyl amide P2 motif by appending hydrogen bonding moieties from either the isopropyl side-chain or from the methyl amide portion. The most promising inhibitors 4a and 4e displayed K-i values of 1.0 nM and 0.7 nM respectively and EC50 values in the MT4 cell-based assay of 0.17 mu M and 0.33 mu M respectively, a slight loss in potency compared to lead inhibitor 3. These inhibitors were also tested against an HIV protease inhibitor resistant strain carrying the M461, V82F, and 184V mutations. Inhibitors 4a and 4e displayed a 3 and 4 fold change respectively compared with HIV wild type, whereas lead inhibitor 3 showed a higher 9 fold change. This study further demonstrate the chemical tractability of the approach where various P2 substituents can be introduced in just one chemical step from lactone 21 enabling facile modifications of the overall properties in this inhibitor class.
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4.
  • Alterman, Mathias, et al. (författare)
  • P1/P1' modified HIV protease inhibitors as tools in two new sensitive surface plasmon resonance biosensor screening assays
  • 2001
  • Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 13:2, s. 203-212
  • Tidskriftsartikel (refereegranskat)abstract
    • The commonly used HIV-1 protease assays rely on measurements of the effect of inhibitions on the hydrolysis rate of synthetic peptides. Recently an assay based on surface plasmon resonance (SPR) was introduced. We have taken advantage of the fact that the SPR signal is proportional to the mass of the analyte interacting with the immobilised molecule and developed two new improved efficient competition assay methods. Thus, high molecular weight binders were used as amplifiers of the surface plasmon resonance signal. Linkers were attached by a Heck reaction to the para-positions of the P1/P1′ benzyloxy groups of a linear C2-symmetric C-terminal duplicated inhibitor to enable (a) biotin labelling or (b) direct immobilisation of the inhibitor to the biosensor surface matrix. The interaction properties of a series of 17 structurally diverse inhibitors was assessed and compared to previously reported data. The most sensitive assay was obtained by immobilising the enzyme and amplifying the signal with an antibody, giving a detection range between 0.1 nM and 10 μM. Immobilisation of the inhibitor resulted in a stable and durable surface but a narrower detection range (1–100 nM). The two competition assays are anticipated to be very suitable for fast screening of potential HIV inhibitors.
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5.
  • Andersson, Pia, et al. (författare)
  • Comparison of oral health status on admission and at discharge in a group of geriatric rehabilitation patients
  • 2003
  • Ingår i: Oral health & preventive dentistry. - 1757-9996 .- 1602-1622. ; 1:3, s. 221-228
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: The aim of this study was to compare oral health status on a geriatric rehabilitation ward among patients who were assessed using the Revised Oral Assessment Guide (ROAG) on admission and at discharge; and to investigate in what respect the oral health procedures (OHP) suggested in ROAG were applied when oral health problems were detected. MATERIALS AND METHODS: Registered nurses on the ward performed oral health assessments using ROAG with 107 patients on admission and at discharge. When oral health problems were detected measures to be taken were suggested using ROAG. RESULTS: Oral health problems were common among the patients on admission (86%), as well as at discharge (51%). The frequency of the problems was significantly lower at discharge compared to admission. The OHP that were recommended in ROAG were completely followed when saliva flow-related problems were detected. Regarding other oral health problems, measures other than the recommended ones were often performed. CONCLUSION: This study demonstrated that the oral health was better at the end of the hospital stay compared to admission.
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6.
  • Andersson, Pia, et al. (författare)
  • Comparison of oral health status on admission and discharge in a group of geriatric rehabilitation patients
  • 2003
  • Ingår i: Oral Health and Preventive Dentistry. ; 1:3, s. 221-228
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to compare oral health status on a geriatric rehabilitation ward among patients who were assessed using the Revised Oral Assessment Guide (ROAG) on admission and at discharge; and to investigate in what respect the oral health procedures (OHP) suggested in ROAG were applied when oral health problems were detected. MATERIALS AND METHODS: Registered nurses on the ward performed oral health assessments using ROAG with 107 patients on admission and at discharge. When oral health problems were detected measures to be taken were suggested using ROAG. RESULTS: Oral health problems were common among the patients on admission (86%), as well as at discharge (51%). The frequency of the problems was significantly lower at discharge compared to admission. The OHP that were recommended in ROAG were completely followed when saliva flow-related problems were detected. Regarding other oral health problems, measures other than the recommended ones were often performed. CONCLUSION: This study demonstrated that the oral health was better at the end of the hospital stay compared to admission.
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7.
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8.
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9.
  • Andersson, Pia, et al. (författare)
  • Inter-rater reliability of an oral assessment guide for elderly patients residing in a rehabilitation ward
  • 2002
  • Ingår i: Special Care in Dentistry. - : Wiley. - 0275-1879 .- 1754-4505. ; 22:5, s. 181-186
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to test the inter-rater reliability of a revised oral assessment guide (ROAG) for patients residing in a geriatric rehabilitation ward. A consecutive sample of 140 patients was recruited for the study. Oral assessments were performed for 133 newly admitted patients by one registered nurse (RN) during a period of six months. A dental hygienist (DH) carried out 103 oral assessments during the same half-year. For 66 patients, the RN and the DH performed independent assessments. There was an agreement between the RN and the DH in the majority of the independent assessments, except for tongue and teeth/dentures. The percentage agreement exceeded 80 percent. Inter-rater agreement measured by Cohen's Kappa coefficient ranged from moderate to very good and percentage agreement had a range of 58 to 91 percent. The agreement was highest in assessment of voice and swallowing (91%). Assessments of teeth and dentures seemed to be most difficult for the RN to evaluate. ROAG was found to be a clinically useful assessment tool. Additional education and training is needed to improve the reliability of the oral assessments and should include continuous support from a dental hygienist as well as a pictorial manual on how to use the ROAG.
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10.
  • Andersson, Pia, et al. (författare)
  • Inter-rater reliability of an oral assessment guide för elderly patients residing in a rehabilitation ward
  • 2002
  • Ingår i: Special Care in Dentistry. - 0275-1879. ; 22:5, s. 181-186
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to test the inter-rater reliability of a revised oral assessment guide (ROAG) for patients residing in a geriatric rehabilitation ward. A consecutive sample of 140 patients was recruited for the study. Oral assessments were performed for 133 newly admitted patients by one registered nurse (RN) during a period of six months. A dental hygienist (DH) carried out 103 oral assessments during the same half-year. For 66 patients, the RN and the DH performed independent assessments. There was an agreement between the RN and the DH in the majority of the independent assessments, except for tongue and teeth/dentures. The percentage agreement exceeded 80 percent. Inter-rater agreement measured by Cohen's Kappa coefficient ranged from moderate to very good and percentage agreement had a range of 58 to 91 percent. The agreement was highest in assessment of voice and swallowing (91%). Assessments of teeth and dentures seemed to be most difficult for the RN to evaluate. ROAG was found to be a clinically useful assessment tool. Additional education and training is needed to improve the reliability of the oral assessments and should include continuous support from a dental hygienist as well as a pictorial manual on how to use the ROAG.
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11.
  • Andersson, Pia, et al. (författare)
  • Oral health and nutritional status in a group of geriatric rehabilitation patients
  • 2002
  • Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley-Blackwell. - 0283-9318 .- 1471-6712. ; 16:3, s. 311-318
  • Tidskriftsartikel (refereegranskat)abstract
    • The aims of this study were to evaluate the oral health status and nutritional status in a group of geriatric rehabilitation patients, and to analyse the relationship between these two parameters. Nurses at the ward performed structured assessments of oral and nutritional status using the Revised Oral Assessment Guide and the Subjective Global Assessment form in 223 newly admitted patients. Most oral health problems were found among patients who stayed longer at the hospital and were more dependent on help as compared with the healthier patients. Thirty-four per cent of the patients were either severely undernourished, at risk or suspected to be undernourished (UN). Oral health problems were more common among UN patients (p < 0.0005) compared with well-nourished patients. The most frequent oral health problem was found on teeth or dentures (48%). Problems related to the tongue and lips were also common among UN patients (56 and 44%, respectively). Oral health status was correlated (r = 0.32) to nutritional status. Problems with swallowing had the strongest association to the nutritional status (OR 6.05; 95% CI 2.41-15.18). This study demonstrated that poor oral health status was related to undernourishment.
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12.
  • Andersson, P, et al. (författare)
  • Oral health and nutritional status in a group of geriatric rehabilitation patients
  • 2002
  • Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 1471-6712 .- 0283-9318. ; 16:3, s. 311-318
  • Tidskriftsartikel (refereegranskat)abstract
    • The aims of this study were to evaluate the oral health status and nutritional status in a group of geriatric rehabilitation patients, and to analyse the relationship between these two parameters. Nurses at the ward performed structured assessments of oral and nutritional status using the Revised Oral Assessment Guide and the Subjective Global Assessment form in 223 newly admitted patients. Most oral health problems were found among patients who stayed longer at the hospital and were more dependent on help as compared with the healthier patients. Thirty-four per cent of the patients were either severely undernourished, at risk or suspected to be undernourished (UN). Oral health problems were more common among UN patients (p < 0.0005) compared with well-nourished patients. The most frequent oral health problem was found on teeth or dentures (48%). Problems related to the tongue and lips were also common among UN patients (56 and 44%, respectively). Oral health status was correlated (r = 0.32) to nutritional status. Problems with swallowing had the strongest association to the nutritional status (OR 6.05; 95% CI 2.41-15.18). This study demonstrated that poor oral health status was related to undernourishment.
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13.
  • Andersson, P, et al. (författare)
  • Oral health problems in elderly rehabilitation patients
  • 2004
  • Ingår i: International Journal of Dental Hygiene. - : Wiley. - 1601-5029 .- 1601-5037. ; 2:2, s. 70-77
  • Tidskriftsartikel (refereegranskat)abstract
    • A combination of poor oral hygiene and dry mouth may be hazardous to the oral health status. However, systematic assessments in order to detect oral health problems are seldom performed in the nursing care of the elderly. The aims of this study were to investigate the occurrence of oral health problems measured using the Revised Oral Assessment Guide (ROAG) and to analyse associations between oral health problems and age, gender, living conditions, cohabitation, reason for admission, number of drugs, and functional and nutritional status. One registered nurse performed oral health assessments using ROAG in 161 newly admitted elderly patients in rehabilitation care. Oral health problems were found in 71% of the patients. Thirty per cent of these patients had between four and eight problems. Low saliva flow and problems related to lips were the most frequent oral health problems. Problems in oral health status were significantly associated with presence of respiratory diseases (problems with gums, lips, alterations on the tongue and mucous membranes), living in special accommodation (low saliva flow, problems with teeth/dentures and alterations on the tongue), being undernourished (alterations on the tongue and low saliva flow) and being a woman (low saliva flow). The highest Odds ratio (OR) was found in problems with gums in relation with prevalence of respiratory diseases (OR 8.9; confidence interval (CI) 2.8-27.8; P < 0.0005). This study indicates the importance of standardised oral health assessments in order to detect oral health problems which can otherwise be hidden when the patients are admitted to the hospital ward.
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14.
  • Andersson, Pia, 1955-, et al. (författare)
  • Testing an oral assessment guide during chemotherapy treatmen in a Swedish care setting : a pilot study
  • 1999
  • Ingår i: Journal of Clinical Nursing. - 0962-1067 .- 1365-2702. ; 8:2, s. 150-158
  • Tidskriftsartikel (refereegranskat)abstract
    • Oral complications are common in patients with haematological malignancies who undergo chemotherapy treatment. A pilot study including 16 haematological patients was carried out to evaluate the oral status using an Oral Assessment Guide (OAG) and to test the reliability of the OAG. The oral assessments were made daily by registered nurses at a Department of Internal Medicine in Sweden. Once a week a dental hygienist made the oral assessments independent of the registered nurses in order to provide data for calculations of inter-rater reliability. All patients had varying degrees of alterations in the oral cavity, especially in the mucous membranes, teeth/dentures and gums. The inter-rater agreement between the nurses and the dental hygienist was good for saliva and swallow, and moderate for voice and gums. Assessments to detect alterations in the oral cavity afford the opportunity for early and individualized interventions and may decrease the risk of oral infections. It is necessary to train the nurses to ensure high levels of reliability in the oral assessments. The OAG seems to be a reliable and clinical useful tool for assessing the oral cavity status and determining changes.
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15.
  • Andersson, P, et al. (författare)
  • Testing an oral assessment guide during chemotherapy treatment in a Swedish care setting: a pilot study
  • 1999
  • Ingår i: Journal of Clinical Nursing. - : Wiley. - 1365-2702 .- 0962-1067. ; 8:2, s. 150-158
  • Tidskriftsartikel (refereegranskat)abstract
    • Oral complications are common in patients with haematological malignancies who undergo chemotherapy treatment. A pilot study including 16 haematological patients was carried out to evaluate the oral status using an Oral Assessment Guide (OAG) and to test the reliability of the OAG. The oral assessments were made daily by registered nurses at a Department of Internal Medicine in Sweden. Once a week a dental hygienist made the oral assessments independent of the registered nurses in order to provide data for calculations of inter-rater reliability. All patients had varying degrees of alterations in the oral cavity, especially in the mucous membranes, teeth/dentures and gums. The inter-rater agreement between the nurses and the dental hygienist was good for saliva and swallow, and moderate for voice and gums. Assessments to detect alterations in the oral cavity afford the opportunity for early and individualized interventions and may decrease the risk of oral infections. It is necessary to train the nurses to ensure high levels of reliability in the oral assessments. The OAG seems to be a reliable and clinical useful tool for assessing the oral cavity status and determining changes.
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16.
  • Balciunas, Darius, et al. (författare)
  • Functional interactions within yeast mediator and evidence of differential subunit modifications
  • 2003
  • Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 278:6, s. 3831-3839
  • Tidskriftsartikel (refereegranskat)abstract
    • It is possible to recruit RNA polymerase II to a target promoter and, thus, activate transcription by fusing Mediator subunits to a DNA binding domain. To investigate functional interactions within Mediator, we have tested such fusions of the lexA DNA binding domain to Med1, Med2, Gal11, Srb7, and Srb10 in wild type, med1, med2, gal11, sin4, srb8, srb10, and srb11 strains. We found that lexA-Med2 and lexA-Gal11 are strong activators that are independent of all Mediator subunits tested. lexA-Srb10 is a weak activator that depends on Srb8 and Srb11. lexA-Med1 and lexA-Srb7 are both cryptic activators that become active in the absence of Srb8, Srb10, Srb11, or Sin4. An unexpected finding was that lexA-VP16 differs from Gal4-VP16 in that it is independent of the activator binding Mediator module. Both lexA-Med1 and lexA-Srb7 are stably associated with Med4 and Med8, which suggests that they are incorporated into Mediator. Med4 and Med8 exist in two mobility forms that differ in their association with lexA-Med1 and lexA-Srb7. Within purified Mediator, Med4 is present as a phosphorylated lower mobility form. Taken together, these results suggest that assembly of Mediator is a multistep process that involves conversion of both Med4 and Med8 to their low mobility forms.
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17.
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18.
  • Bengtsson, Stefan L., 1978-, et al. (författare)
  • Immersion and ritual in Object-Oriented Didactics and Sensuous Learning
  • 2021
  • Konferensbidrag (refereegranskat)abstract
    • Environmental and sustainability education (ESE) that wants to address existing environmental and sustainability challenges is basically critical, that is if it wants to change through education and learning contemporary ways of being in the world (cf Hart & Nolan 1999). This change is often framed in terms of transformation, where something is changed into something else, yet, that change of that something (van Poeck, König & Wals 2018; Lundegård & Wickman 2009), for example the process, is partially a retainment of something (Mezirow 2000). For example, it is still the social, learner, knowledge or custom that was transformed, highlighting its continuity. This focus on retainment and continuity has recently been challenged through the concept of transgressive learning (e.g. Lotz-Sisitka et al. 2015), where the focus is rather of abandonment and discontinuity of ways of being through learning (Bengtsson 2019). Transgression is by the presenting authors seen as a means of potentially subverting the reproduction of coloniality of Western thought (Chaves et al. 2015), pertaining anthropocentrism (Kopnina 2012) and capitalism/neoliberalism (Hursh, Henderson & Greenwood 2015) in and through ESE.This paper aims to contribute to a theoretical and practical development of didactical means for transgression, particularly by providing alternative pedagogical and didactical entry points for understanding learning as not primarily rational but by highlighting aesthetics and the sensuous learner. In this effort, the paper combines the theoretical outlooks of sensuous learning (Hallberg 2015, 2017, 2018) and object-oriented learning (Bengtsson 2018) in order to develop further a object-oriented didactics of ESE (Bengtsson, Lysgaard, Jordt-Joergensen 2019). The effort is here to provide theoretical and practical means for engaging with withdrawn and uncanny objects of education through sensuous learning. Drawing on the initial considerations of object-oriented didactics (Bengtsson, Lysgaard, Jordt-Joergensen 2019) holding that the real object of education is not congruent with the content of education and that the educative substance (Bildungsgehalt) of the object of education is indeterminate (located in an open future) and infinite (given that the qualities of the object of education are always larger than any attempts to reduce it to a content of education), sensuous learning is here to provide entry points for understanding how the indeterminate and infinite qualities of the object of education can be rendered sensible.The paper will address the following research questions:How can didactic intervention engage with the surplus of the educative substance (Bildungssubstanz) of the object of education? (Practical question)How can senouse learning sensitize the learner and teacher to the indeterminate potential of the educative substance of the object as that substance is according to the axioms of object-oriented learning located in a future still to come? (Practical and theoretical question)How can we understand the contribution of object-oriented didactics to the production of a Sensuous Society (Hallberg 2017) and Ecological Bildung (Bengtsson, Lysgaard, Jordt-Joergensen 2019). How is this link actualized in didactical intervention and in learning? (Theoretical question)MethodThe paper represents a theoretical development of existing conceptions of a) transgressive learning, b) dark pedagogy and c) sensuous learning. In particular, it induces insights and perspectives from theory and methods in performance art and arts-based research into pedagogical and didactical research. Findings and models developed in Sisters Academy ́s school takeovers and boarding schools formats offer rich and innovative approaches to facilitating sensuous learning that are taken as inspiration for the development of object-oriented didactics. The Takeover format is meant to immerse the entire school into the sensuous and poetic and thus 'leave no one behind' in an attempt to democratize' the aesthetic. It is this all-embracing immersion that allows such democratization. However, the modes of participation can largely differ and is never forced and thus based on individual navigation within the overall educational experiment. This paper will in particular focus on two aspects of sensuous learning: immersion and the ritual. By engaging with approaches and models to immersion and the ritual, this paper is to explore in an open and creative manner how immersion and the ritual could be integrated into didactical interventions. Immersion, refers here also to the possibility of an immersion of the whole sensory spectrum, where the ritual might address different senses. The ritual is in this sense open and not already focused on particular senses or what is to be sensed.Expected OutcomesBy rendering partially sensible the object of education through didactic intervention, sensuous learning is resensitizing the learner to what in sensuous learning is called “Poetic Self” (Hallberg 2017, 2018) and in dark pedagogy is called “Future Self of Essence” (Bengtsson 2019b). Accordingly, educational substance (Bildungsgehalt) of the object of education to be engaged with in sensuous learning is not strictly speaking that of the object or “for me”. Instead, sensuous learning can be seen to lead to a transgression where the learner loses or ruins “its self”/”itself” (Bataille 1988). The poetic self is in this sense not engaging in the process of autopoiesis, i.e. self-reproduction and self-maintenance, finds itself caught up in “some thing”/”something”. The openness of the ritual and the process of object-oriented didactic gesture points here also the uncanny/unhomely (unheimlich) aspect of learning that is resensitizing to the Poetic Self/Future Self. The uncanniness refers here to a conception of self that is not strictly “in place”, but alienated and hence a self sensing self that is both itself and not-itself. Accordingly, the paper is to provide a reconception of understanding the positionality and limit of the self at the core of our understanding of learning. The combination of sensuous learning and object oriented didactics is in the context above to provide ecologically oriented entry points for ESE and for developing further transgressive learning.
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19.
  • Bhatt, Deepak L., et al. (författare)
  • Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study
  • 2019
  • Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 42:5, s. 498-505
  • Tidskriftsartikel (refereegranskat)abstract
    • In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients >= 50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of >= 50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.
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20.
  • Björklund, Catarina, 1981-, et al. (författare)
  • Design and synthesis of potent and selective BACE-1 inhibitors
  • 2010
  • Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society. - 0022-2623 .- 1520-4804. ; 53:4, s. 1458-1464
  • Tidskriftsartikel (refereegranskat)abstract
    • Several highly potent BACE-1 protease inhibitors have been developed from an inhibitor series containing a novel hydroxyethylene (HE) core structure displaying aryloxymethyl or benzyloxymethyl P1 side chains and a methoxy P1’ side chain. The target molecules were readily synthesized from chiral carbohydrate starting materials, furnishing the inhibitor compounds in good overall yields. The inhibitors show both high BACE-1 potency and good selectivity against cathepsin D, where the most potent inhibitor furnish a BACE-1 IC50 value of 0.32 nM and displays > 3000 fold selectivity over cathepsin D.
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21.
  • Buch, Charlotta, et al. (författare)
  • Localization of peroxisomal matrix proteins by photobleaching
  • 2009
  • Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 388:2, s. 355-359
  • Tidskriftsartikel (refereegranskat)abstract
    • The distribution of some enzymes between peroxisomes and cytosol, or a dual localization in both these compartments, can be difficult to reconcile. We have used photobleaching in live cells expressing green fluorescent protein (GFP)-fusion proteins to show that imported bona fide peroxisomal matrix proteins are retained in the peroxisome. The high mobility of the GFP-fusion proteins in the cytosol and absence of peroxisomal escape makes it possible to eliminate the cytosolic fluorescence by photobleaching, to distinguish between exclusively cytosolic proteins and proteins that are also present at low levels in peroxisomes. Using this technique we found that GFP tagged bile acid-CoA:amino acid N-acyltransferase (BAAT) was exclusively localized in the cytosol in HeLa cells. We conclude that the cytosolic localization was due to its carboxyterminal non-consensus peroxisomal targeting signal (-SQL) since mutation of the -SQL to -SKL resulted in BAAT being efficiently imported into peroxisomes.
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22.
  • Bäck, Marcus, et al. (författare)
  • Novel potent macrocyclic inhibitors of the hepatitis C virus NS3 protease : use of cyclopentane and cyclopentene P2-motifs
  • 2007
  • Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 15:22, s. 7184-7202
  • Tidskriftsartikel (refereegranskat)abstract
    • Several highly potent novel HCV NS3 protease inhibitors have been developed from two inhibitor series containing either a P2 trisubstituted macrocyclic cyclopentane- or a P2 cyclopentene dicarboxylic acid moiety as surrogates for the widely used N-acyl-(4R)-hydroxyproline in the P2 position. These inhibitors were optimized for anti HCV activities through examination of different ring sizes in the macrocyclic systems and further by exploring the effect of P4 substituent removal on potency. The target molecules were synthesized from readily available starting materials, furnishing the inhibitor compounds in good overall yields. It was found that the 14-membered ring system was the most potent in these two series and that the corresponding 13-, 15-, and 16-membered macrocyclic rings delivered less potent inhibitors. Moreover, the corresponding P1 acylsulfonamides had superior potencies over the corresponding P1 carboxylic acids. It is noteworthy that it has been possible to develop highly potent HCV protease inhibitors that altogether lack the P4 substituent. Thus the most potent inhibitor described in this work, inhibitor 20, displays a Ki value of 0.41 nM and an EC50 value of 9 nM in the subgenomic HCV replicon cell model on genotype 1b. To the best of our knowledge this is the first example described in the literature of a HCV protease inhibitor displaying high potency in the replicon assay and lacking the P4 substituent, a finding which should facilitate the development of orally active small molecule inhibitors against the HCV protease.
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23.
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24.
  • Candefjord, Stefan, et al. (författare)
  • Combining scanning haptic microscopy and fibre optic Raman spectroscopy for tissue characterization
  • 2012
  • Ingår i: Journal of Medical Engineering & Technology. - : Taylor & Francis. - 0309-1902 .- 1464-522X. ; 36:6, s. 319-327
  • Tidskriftsartikel (refereegranskat)abstract
    • The tactile resonance method (TRM) and Raman spectroscopy (RS) are promising for tissue characterization in vivo. Our goal is to combine these techniques into one instrument, to use TRM for swift scanning, and RS for increasing the diagnostic power. The aim of this study was to determine the classification accuracy, using support vector machines, for measurements on porcine tissue and also produce preliminary data on human prostate tissue. This was done by developing a new experimental set-up combining micro-scale TRMscanning haptic microscopy (SHM)for assessing stiffness on a micro-scale, with fibre optic RS measurements for assessing biochemical content. We compared the accuracy using SHM alone versus SHM combined with RS, for different degrees of tissue homogeneity. The cross-validation classification accuracy for healthy porcine tissue types using SHM alone was 6581%, and when RS was added it increased to 8187%. The accuracy for healthy and cancerous human tissue was 6770% when only SHM was used, and increased to 7277% for the combined measurements. This shows that the potential for swift and accurate classification of healthy and cancerous prostate tissue is high. This is promising for developing a tool for probing the surgical margins during prostate cancer surgery. 
  •  
25.
  • Chatzittofis, Andreas, et al. (författare)
  • HPA axis dysregulation in men with hypersexual disorder
  • 2016
  • Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 63, s. 247-253
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypersexual disorder integrating pathophysiological aspects such as sexual desire deregulation, sexual addiction, impulsivity and compulsivity was suggested as a diagnosis for the DSM-5. However, little is known about the neurobiology behind this disorder. A dysregulation of the hypothalamic pituitary adrenal (HPA) axis has been shown in psychiatric disorders but has not been investigated in hypersexual disorder. The aim of this study was to investigate the function of the HPA axis in hypersexual disorder. The study includes 67 male patients with hypersexual disorder and 39 healthy male volunteers. Basal morning plasma levels of cortisol and ACTH were assessed and low dose (0.5 mg) dexamethasone suppression test was performed with cortisol and ACTH measured post dexamethasone administration. Non-suppression status was defined with DST-cortisol levels >= 138 nmol/l. The Sexual Compulsive scale (SCS), Hypersexual disorder current assessment scale (HD:CAS), Montgomery-Asberg Depression Scale-self rating (MADRS-S) and Childhood trauma questionnaire (CTQ), were used for assessing hypersexual behavior, depression severity and early life adversity. Patients with hypersexual disorder were significantly more often DST non-suppressors and had significantly higher DST-ACTH levels compared to healthy volunteers. The patients reported significantly more childhood trauma and depression symptoms compared to healthy volunteers. CTQ scores showed a significant negative correlation with DST-ACTH whereas SCS and HD:CAS scores showed a negative correlation with baseline cortisol in patients. The diagnosis of hypersexual disorder was significantly associated DST non-suppression and higher plasma DST-ACTH even when adjusted for childhood trauma. The results suggest HPA axis dysregulation in male patients with hypersexual disorder.
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26.
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27.
  • Chatzittofis, Andreas, et al. (författare)
  • Interpersonal violence, early life adversity, and suicidal behavior in hypersexual men
  • 2017
  • Ingår i: Journal of Behavioral Addictions. - : Akademiai Kiado. - 2062-5871 .- 2063-5303. ; 6:2, s. 187-193
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: There are significant gaps in knowledge regarding the role of childhood adversity, interpersonal violence, and suicidal behavior in hypersexual disorder (HD). The aim of this study was to investigate interpersonal violence in hypersexual men compared with healthy volunteers and the experience of violence in relation to suicidal behavior. Methods: This case-control study includes 67 male patients with HD and 40 healthy male volunteers. The Childhood Trauma Questionnaire-Short Form (CTQ-SF) and the Karolinska Interpersonal Violence Scale (KIVS) were used for assessing early life adversity and interpersonal violence in childhood and in adult life. Suicidal behavior (attempts and ideation) was assessed with the Mini-International Neuropsychiatric Interview (version 6.0) and the Montgomery-Asberg Depression Rating Scale - Self-rating. Results: Hypersexual men reported more exposure to violence in childhood and more violent behavior as adults compared with healthy volunteers. Suicide attempters (n = 8, 12%) reported higher KIVS total score, more used violence as a child, more exposure to violence as an adult as well as higher score on CTQ-SF subscale measuring sexual abuse (SA) compared with hypersexual men without suicide attempt. Discussion: Hypersexuality was associated with interpersonal violence with higher total scores in patients with a history of suicide attempt. The KIVS subscale exposure to interpersonal violence as a child was validated using the CTQ-SF but can be complemented with questions focusing on SA for full assessment of early life adversity. Conclusion: Childhood adversity is an important factor in HD and interpersonal violence might be related to suicidal behavior in hypersexual men.
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28.
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29.
  • Claeson, Magdalena, 1976, et al. (författare)
  • Modelling the Future: System Dynamics in the Cutaneous Malignant Melanoma Care Pathway
  • 2016
  • Ingår i: Acta dermato-venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 96:2, s. 181-185
  • Tidskriftsartikel (refereegranskat)abstract
    • Incidence rates for cutaneous malignant melanoma are increasing worldwide. Estimates of the future number of melanoma cases are important for strategic planning of the care pathway. The aim of this study was to use system dynamics modelling to evaluate the long-term effects of changes in incidence, population growth and preventive interventions. Historical data on invasive melanoma cases in Western Sweden from 1990 to 2006 were obtained. Using computer simulation software, a model estimating the accumulated number of melanoma cases for 2014 to 2023 was developed. Five future scenarios were designed: stable incidence, business-as-usual, 25% reduced patient's delay, 50% reduced doctor's delay, and a combination of the last 2, called improved overall secondary prevention. After 10 years, improved overall secondary prevention would have resulted in a 42% decrease in melanomas >4 mm and a 10% increase in melanomas ≤1 mm, compared with business-as-usual. System dynamics is a valuable tool, which can help policymakers choose the preventive interventions with the greatest impact.
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30.
  • Claeson, Magdalena, 1976, et al. (författare)
  • Multiple primary melanomas in Western Sweden; 1990-2013
  • 2016
  • Ingår i: 3rd International Conference on UV and Skin Cancer Prevention, Melbourne.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • IntroductionIn Sweden, the incidence of cutaneous malignant melanoma rises yearly with 5.5% for men and 5.2% for women and has now reached world standard rates of 17.6 for men and 18.8 for women per 100,000 population. Over the past decades, the incidence of melanoma has been higher in Western Sweden than the national average. Previous international studies have shown that melanoma patients have an elevated risk of developing a new separate primary melanoma. This study aimed at describing multiple primary melanomas (MPMs) in Western Sweden with focus on the number of tumours detected, tumour characteristics and the time to diagnosis of a subsequent melanoma.MethodsData was extracted retrospectively from the Swedish Melanoma Registry and provided information on all invasive and in situ melanoma cases in Western Sweden (1.6 million inhabitants) from 1990 to 2013. Results Within the studied period, 12,152 patients developed 13,291 melanomas. 11,254 of the patients developed only a single primary melanoma. In total, 898 patients (7.4% of all melanoma patients) developed 2,037 MPMs. Preliminary results show that the median Breslow thickness for all invasive melanomas was below 1 mm. The median Breslow thickness for the MPMs was slightly thinner for the second and third invasive melanoma as compared to the first invasive melanoma. Further, there was a higher percentage of in situ tumours among the subsequent melanomas. The median time to diagnosis of a subsequent melanoma was approximately 3 years. DiscussionSubsequent primary melanomas in Western Sweden are most commonly diagnosed with a somewhat thinner Breslow thickness than the first primary melanoma. The comparatively high percentage of melanoma survivors developing MPMs and the short median time to diagnosis of a subsequent melanoma stresses the importance of follow-up for melanoma patients, particularly during the first years.
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31.
  • Claeson, Magdalena, 1976, et al. (författare)
  • MultiplePrimary Melanomas: A Common Occurrencein Western Sweden.
  • 2017
  • Ingår i: Acta dermato-venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 97:6, s. 715-719
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients diagnosed with a single primary cutaneous melanoma are at increased risk of developing multiple primary melanomas. The aim of this study is to describe the epidemiology of multiple primary melanomas (invasive and in situ) in Western Sweden. Data from the Swedish Melanoma Registry from 1990 to 2013 revealed that 898 patients (7.4%) developed 2,037 multiple primary lesions and 11,254 patients developed single lesions. The proportion of subsequent lesions that were melanoma in situ was 47%, compared with 26% of first melanomas (p<0.0001). The median time to diagnosis of a subsequent melanoma was 38 months (95% confidence interval (CI), 53-62 months). In total, 49% of subsequent melanomas were detected within 3 years. Patients and physicians should be aware of the high proportion of multiple primary melanomas in Western Sweden, especially during the first years of follow-up.
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32.
  • Flanagan, John, et al. (författare)
  • High plasma oxytocin levels in men with hypersexual disorder
  • 2022
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 107:5, s. e1816-e1822
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Hypersexual disorder (HD) involves excessive, persistent sexual behaviors related to various mood states and the diagnosis compulsive sexual behavior disorder is included as an impulse control disorder in the 11th revision of the International Classification of Diseases. Although the neurobiology behind the disorder is not clear, some studies suggest dysregulated hypothalamic-pituitary-adrenal axis. Oxytocin acts as counterregulatory neuroendocrine hormone to cortisol and is also involved in sexual behavior.Objective: We hypothesized that oxytocin may play a role in the pathophysiology of HD with compensatory actions to cortisol.Design: Longitudinal.Setting: ANOVA clinic (Karolinska University Hospital).Patients or other participants: 64 males with HD and 38 age-matched healthy volunteers.Main Outcome Measures: Plasma oxytocin levels, measured with radioimmunoassay; Hypersexual Disorder Screening Inventory; and Hypersexual Disorder: Current Assessment Scale for assessing hypersexual symptoms.Interventions: A patient subgroup (n=30) completed the manual-based group-administered cognitive-behavioral therapy (CBT) program for HD, and posttreatment oxytocin levels were measured.Results: Hypersexual men (n=64) exhibited significantly higher oxytocin plasma levels (mean±SD: 31.0±9.9 pM) compared with healthy volunteers (16.9±3.9 pM; P<0.001). There were significant positive correlations between oxytocin levels and the rating scales measuring hypersexual behavior. Patients who completed CBT treatment (n=30) had a significant reduction of oxytocin plasma levels from pretreatment (30.5±10.1 pM) to posttreatment (20.2±8.0 pM; P<0.001).Conclusions: The results suggest that the hyperactive oxytocinergic system in hypersexual men may be a compensatory mechanism to attenuate hyperactive stress.
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33.
  • Geschwindner, Stefan, et al. (författare)
  • Characterisation of de novo mutations in the C-terminal domain of proprotein convertase subtilisin/kexin type 9.
  • 2015
  • Ingår i: Protein Engineering Design & Selection. - : Oxford University Press (OUP). - 1741-0126 .- 1741-0134.
  • Tidskriftsartikel (refereegranskat)abstract
    • Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the hepatic low-density lipoprotein receptor (LDL-R) and is therefore a prominent therapeutic target for reducing LDL-cholesterol. The C-terminal domain of PCSK9 is unlikely to be involved in a direct extracellular interaction with the LDL-R. We probed the importance of the C-terminus for the degradation of the LDL-R by designing seven de novo mutants of PCSK9 that fill potential druggable cavities. The mutants were tested for their ability to diminish LDL uptake in human HepG2 cells and for affinity towards a calcium independent mutant of the EGF(A) domain of the human LDL-R. The later was done by a newly developed surface plasmon resonance-based assay format. We identified three mutant proteins (G517R, V610R and V644R) with decreased ability to block LDL uptake into HepG2 cells. These mutations define areas outside the direct interaction area between PCSK9 and the LDL-R that could be targeted to inhibit the PCSK9 triggered degradation of the LDL-R. We also describe the mechanistic rationalisation of the affinity changes seen with the natural occurring human D374Y (gain of function) mutation causing severe hypercholesterolaemia. The action of this mutant is due to a significantly decreased dissociation rate constant, whereas the mutation does not affect the association rate constant.
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34.
  • Görts Öberg, Katarina, et al. (författare)
  • Hypersexual Disorder According to the Hypersexual Disorder Screening Inventory in Help-Seeking Swedish Men and Women With Self-Identified Hypersexual Behavior
  • 2017
  • Ingår i: Sexual Medicine. - : Elsevier. - 2050-1161. ; 5:4, s. E229-E236
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The Hypersexual Disorder Screening Inventory (HDSI) was developed by the American Psychiatric Association for clinical screening of hypersexual disorder (HD). Aims: To examine the distribution of the proposed diagnostic entity HD according to the HDSI in a sample of men and women seeking help for problematic hypersexuality and evaluate some psychometric properties. Methods: Data on sociodemographics, the HDSI, the Sexual Compulsivity Scale (SCS), and the Cognitive and Behavioral Outcomes of Sexual Behavior were collected online from 16 women and 64 men who self-identified as hypersexual. Respondents were recruited by advertisements offering psychological treatment for hypersexual behavior. Main Outcome Measures: The HDSI, covering the proposed criteria for HD. Results: Of the entire sample, 50% fulfilled the criteria for HD. Compared with men, women scored higher on the HDSI, engaged more often in risky sexual behavior, and worried more about physical injuries and pain. Men primarily used pornography, whereas women had sexual encounters. The HD group reported a larger number of sexual specifiers, higher scores on the SCS, more negative effects of sexual behavior, and more concerns about consequences compared with the non-HD group. Sociodemographics had no influence on HD. The HDSI's core diagnostic criteria showed high internal reliability for men (a = 0.80) and women (a = 0.81). A moderate correlation between the HDSI and the SCS was found (0.51). The vast majority of the entire sample (76 of 80, 95%) fulfilled the criteria for sexual compulsivity according to the SCS. Conclusion: The HDSI could be used as a screening tool for HD, although further explorations of the empirical implications regarding criteria are needed, as are refinements of cutoff scores and specific sexual behaviors. Hypersexual problematic behavior causes distress and impairment and, although not included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, HD should be endorsed as a diagnosis to develop evidence-based treatment and future studies on its etiology. Copyright (C) 2017, The Authors. Published by Elsevier Inc. on behalf of the International Society for Sexual Medicine. This is an open access article under the CC BY-NC-ND license.
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35.
  • Hallberg, Ida, et al. (författare)
  • Perfluorononanoic acid (PFNA) alters lipid accumulation in bovine blastocysts after oocyte exposure during in vitro maturation
  • 2019
  • Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 84, s. 1-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Perfluorononanoic acid (PFNA) is one of the perfluoroalkyl acids present in human tissues. In this study, effects on early embryo development after PFNA exposure were investigated using the bovine in vitro production system. Oocytes were exposed to PFNA during maturation in vitro (10 μg mL-1 and 0.1 μg mL-1), and then fertilized and cultured in parallel with control groups. Developmental parameters (cleavage, blastocyst formation) were followed and embryo quality evaluated (stage, grade). Embryos developed after exposure to 0.1 μg mL-1 were stained to distinguish nuclei, active mitochondria and neutral lipids. 10 μg mL-1 of PFNA had a severe negative effect on blastocyst formation (OR: 0.27 p < 0.05), an effect not observed at 0.1 μg mL-1. However, lipid droplet distribution was significantly altered in embryos exposed to 0.1 μg mL-1, suggesting a disturbance of lipid metabolism after exposure to sublethal levels of PFNA during oocyte maturation in vitro.
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36.
  • Hallberg, Inger, 1956, et al. (författare)
  • Phases in development of an interactive mobile phone-based system to support self-management of hypertension
  • 2014
  • Ingår i: Integrated blood pressure control. - : Dove Medical Press. - 1178-7104. ; 7, s. 19-28
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypertension is a significant risk factor for heart disease and stroke worldwide. Effective treatment regimens exist; however, treatment adherence rates are poor (30%–50%). Improving self-management may be a way to increase adherence to treatment. The purpose of this paper is to describe the phases in the development and preliminary evaluation of an interactive mobile phone-based system aimed at supporting patients in self-managing their hypertension. A person-centered and participatory framework emphasizing patient involvement was used. An interdisciplinary group of researchers, patients with hypertension, and health care professionals who were specialized in hypertension care designed and developed a set of questions and motivational messages for use in an interactive mobile phone-based system. Guided by the US Food and Drug Administration framework for the development of patient-reported outcome measures, the development and evaluation process comprised three major development phases (1, defining; 2, adjusting; 3, confirming the conceptual framework and delivery system) and two evaluation and refinement phases (4, collecting, analyzing, interpreting data; 5, evaluating the self-management system in clinical practice). Evaluation of new mobile health systems in a structured manner is important to understand how various factors affect the development process from both a technical and human perspective. Forthcoming analyses will evaluate the effectiveness and utility of the mobile phone-based system in supporting the self-management of hypertension.
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37.
  • Hallberg, Jonas, et al. (författare)
  • A Cognitive-Behavioral Therapy Group Intervention for Hypersexual Disorder : A Feasibility Study
  • 2017
  • Ingår i: Journal of Sexual Medicine. - : Elsevier. - 1743-6095 .- 1743-6109. ; 14:7, s. 950-958
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The proposed criteria of the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition for hypersexual disorder (HD) included symptoms reported by patients seeking help for excessive and out-of-control non-paraphilic sexual behavior, including sexual behaviors in response to dysphoric mood states, impulsivity, and risk taking. Although no prior studies of cognitive-behavioral therapy (CBT) for the treatment of HD have been performed, CBT has been found effective for dysphoric mood states and impulsivity. Aim: To investigate the feasibility of a CBT manual developed for HD explored through symptom decrease, treatment attendance, and clients' treatment satisfaction. Methods: Ten men with a diagnosis of HD took part in the CBT group program. Measurements were taken before, during, and at the end of treatment and 3 and 6 months after treatment. Outcomes: The primary outcome was the Hypersexual Disorder: Current Assessment Scale (HD: CAS) score that measured the severity of problematic hypersexual symptoms and secondary outcomes were the Hypersexual Disorder Screening Inventory (HDSI) score, the proportion of attended sessions, and the Client Satisfaction Questionnaire (CSQ-8) score. Results: Main results were significant decreases of HD symptoms from before to after treatment on HD: CAS and HDSI scores and a decrease in the number of problematic sexual behaviors during the course of therapy. A high attendance rate of 93% and a high treatment satisfaction score on CSQ-8 also were found. Clinical Implications: The CBT program seemed to ameliorate the symptoms of HD and therefore might be a feasible treatment option. Strengths and Limitations: This study provides data from a CBT program for the treatment of the specific proposed criteria of HD. Because of the small sample and lack of a control group, the results can be considered only preliminary. Conclusion: Although participants reported decreased HD symptoms after attending the CBT program, future studies should evaluate the treatment program with a larger sample and a randomized controlled procedure to ensure treatment effectiveness. Copyright (C) 2017, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
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38.
  • Hallberg, Jonas, et al. (författare)
  • A Randomized Controlled Study of Group-Administered Cognitive Behavioral Therapy for Hypersexual Disorder in Men
  • 2019
  • Ingår i: Journal of Sexual Medicine. - : Elsevier. - 1743-6095 .- 1743-6109. ; 16:5, s. 733-745
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Hypersexual disorder (HD) is defined as a condition in which the individual loses control over engagement in sexual behaviors, leading to distress and negative effects on key life areas. Cognitive behavioral therapy (CBT) has been proven to reduce symptoms of hypersexual behavior; however, no randomized controlled study of CBT interventions for HD has been reported previously. Aim: To investigate the efficacy of group-administered CBT for HD. Methods: Male participants (n = 137) diagnosed with HD, were randomized between 7 weeks of group-administered CBT (n = 70) and a waitlist control receiving the intervention after 8 weeks (n = 67). Measurements were administered at pre-, mid-, and posttreatment, with follow-up after 3 and 6 months. Outcomes: The primary outcome was the Hypersexual Disorder: Current Assessment Scale (HD: CAS), and secondary outcomes were the Sexual Compulsivity Scale (SCS) and measures of depression (Montgomery-Asberg Depression Rating Scale (MADRS-S), psychological distress (Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), and treatment satisfaction (CSQ-8). Results: A significantly greater decrease in HD symptoms and sexual compulsivity, as well as significantly greater improvements in psychiatric well-being, were found for the treatment condition compared with the waitlist. These effects remained stable at 3 and 6 months after treatment. Clinical Implications: CBT can ameliorate HD symptoms and psychiatric distress, suggesting that the CBT program may serve as a first-line treatment in clinical settings. Strengths & Limitations: This is the first randomized controlled study evaluating the efficacy of a CBT programin a rather large sample of HD-specific diagnosed men. The long-termtreatment effects are vague due to the low response rate on follow-up measurements, and the efficacy of this program for hypersexual women remains unknown. Conclusion: This study supports the efficacy of a group-administered CBT program as a treatment option for HD; however, future studies should include women, comprise dismantling analysis of the constituting interventions, and evaluate other treatment formats, for example, administration via the Internet. Copyright (C) 2019, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
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39.
  • Hallberg, Jonas, et al. (författare)
  • Internet-Administered Cognitive Behavioral Therapy for Hypersexual Disorder, With or Without Paraphilia(s) or Paraphilic Disorder(s) in Men : A Pilot Study
  • 2020
  • Ingår i: Journal of Sexual Medicine. - : Elsevier. - 1743-6095 .- 1743-6109. ; 17:10, s. 2039-2054
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Hypersexual disorder (HD) is a condition in which the individual experiences loss of control over engagement in sexual behaviors, leading to negative effects on various areas of life. Paraphilias often present concomitantly with HD, and although cognitive behavioral therapy (CBT) has been proven to reduce engagement in hypersexual behavior, no studies have investigated the effects of Internet-administered CBT (ICBT) on HD, with or without paraphilia(s) or paraphilic disorder(s). Aim: To investigate the effects of Internet-administered CBT on HD, with or without paraphilia(s) or paraphilic disorder(s). Methods: Male participants (n = 36) evaluated positive according to the proposed diagnostic HD criteria, with or without paraphilia(s) or paraphilic disorder(s), received 12 weeks of ICBT. Measures were administered weekly over the treatment period, with an additional follow-up measurement 3 months after completion of treatment. An assessment interview was performed 2 weeks after treatment. Outcomes: The primary outcome was the Hypersexual Behavior Inventory (HBI-19), and secondary outcomes were the Hypersexual Disorder: Current Assessment Scale (HD:CAS), the Sexual Compulsivity Scale (SCS), as well as a tentative composite of 6 Severity Self-rating Measures, for Paraphilic Disorders and depression (Montgomery-Asberg Depression Rating Scale [MADRS-S]), psychological distress (Clinical Outcomes in Routine Evaluation Outcome Measure [CORE-OM]), and treatment satisfaction (CSQ-8). Results: Large, significant decreases in HD symptoms and sexual compulsivity were found, as well as moderate improvements in psychiatric well-being and paraphilic symptoms. These effects remained stable 3 months after treatment. Clinical Implications: ICBT can ameliorate HD symptoms, psychiatric distress, and paraphilic symptoms, which suggests that the ICBT for HD, with or without paraphilia(s) or paraphilic disorder(s), may constitute a valuable addition of treatment options in clinical settings. Strengths and Limitations: This is the first study evaluating the efficacy ofICBT on a sample of men suffering from HD. In addition, a proportion of the sample reported concomitant paraphilic interests and disorders, thus mirroring an everyday clinical practice in the field of sexual medicine. No control group was assigned, and some of the outcome measures are still to be validated. The long-term effects of ICBT and its efficacy in hypersexual women are unknown. Conclusions: This study gives support for ICBT as an effective treatment option for HD. Future evaluations of the treatment program should include women and larger samples in randomized controlled procedures and investigate the long-term effects. Copyright (C) 2020, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
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40.
  • Hallberg, Josef, et al. (författare)
  • Reminiscence processes using life-log entities for persons with mild dementia
  • 2009
  • Ingår i: Proceedings of the First International Workshop on Reminiscence Systems (RSW-2009). ; , s. 16-21
  • Konferensbidrag (refereegranskat)abstract
    • In this paper we present the reminiscence process in a prototype memory support tool for persons with mild dementia. The purpose is to promote autonomy for persons with mild dementia by supporting actualization and maintenance of episodic memories, and real-time access to a context-annotated life log.  The main research challenges are defined with a user scenario, Suitable reminiscence methods and memory entitities to reperesent life logs are described, and a preliminary architecture is presented. Finally an early design of a concrete ReviewClient is shown, to solicit feedback on the reminiscence methods, entitites chosen, architecture and the usability of the proposed interface.
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41.
  • Hallberg, Lillemor R.-M. 1942-, et al. (författare)
  • Minimizing the dysfunctional interplay between activity and recovery : A grounded theory on living with fibromyalgia
  • 2011
  • Ingår i: International Journal of Qualitative Studies on Health and Well-being. - Abingdon : Taylor & Francis. - 1748-2623 .- 1748-2631. ; 6:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to generate a substantive theory, based on interviews with women with fibromyalgia, explaining how they manage their main concerns in daily life. The study has an inductive approach in line with classic grounded theory (Glaser, 1992). Twenty-three women living in the southwest region of Sweden were interviewed in-depth about their daily living with fibromyalgia and problems related to this. Probing and follow-up questions were asked by the interviewers when relevant. The interviews were transcribed verbatim and consecutively analysed in line with guidelines for grounded theory. The results showed that the main concern for women with fibromyalgia was to reach a balance in daily life. This concern was resolved by them using different strategies aimed at minimizing the dysfunctional interplay between activity and recovery (core category). This imbalance includes that the women are forcing themselves to live a fast-paced life and thereby tax or exceed their physical and psychological abilities and limits. Generally, the fibromyalgia symptoms vary and are most often unpredictable to the women. Pain and fatigue are the most prominent symptoms. However, pain-free periods occur, often related to intense engagement in some activity, relaxation or joy, but mainly the "pain gaps" are unpredictable. To reach a balance in daily life and manage the dysfunctional interplay between activity and recovery the women use several strategies. They are avoiding unnecessary stress, utilizing good days, paying the price for allowing oneself too much activity, planning activities in advance, distracting oneself from the pain, engaging in alleviating physical activities, and ignoring pain sensations. Distracting from the pain seems to be an especially helpful strategy as it may lead to "pain gaps". This strategy, meaning to divert attention from the pain, is possible to learn, or improve, in health promoting courses based on principles of cognitive behavioural therapy (CBT). We suggest that such courses are offered in primary care for patients with fibromyalgia or other types of longstanding pain. The courses should be led by registered nurses or psychologists, who are experienced in CBT and have extensive knowledge about theories on longstanding pain, stress and coping. Such courses would increase well-being and quality of life in women suffering from fibromyalgia. © 2011 L. R.-M. Hallberg & S. Bergman.
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42.
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43.
  • Hallberg, Magnus, et al. (författare)
  • Functional and physical interactions within the middle domain of the yeast mediator
  • 2006
  • Ingår i: Molecular Genetics and Genomics. - : Springer Science and Business Media LLC. - 1617-4615 .- 1617-4623. ; 276:2, s. 197-210
  • Tidskriftsartikel (refereegranskat)abstract
    • Med21 (Srb7) is a small essential subunit of the middle domain of the Mediator, which is conserved in all eukaryotes. It is thought to play an important role in both transcriptional activation and repression. In the yeast Saccharomyces cerevisiae, Med21 is known to interact both with the Mediator subunit Med6 and the global co-repressor Tup1. We have made a temperature-sensitive med21-ts mutant, which we used in a high copy number suppressor screen. We found ten yeast genes that can suppress the med21-ts mutation in high copy number. The three strongest suppressors were MED7 and MED10 (NUT2), which encode other Mediator subunits, and ASH1, which encodes a repressor of the HO gene. 2-Hybrid experiments confirmed multiple interactions between Med21, Med10, Med7 and Med4, and also revealed a Med21 self-interaction. The interactions of Med21 with Med7 and Med10 were verified by co-immunoprecipitation of tagged proteins produced in insect cells and E. coli, where both interactions were found to depend strongly on the amino acid residues 2-8 of Med21. These interactions, and the interactions of Med21 with Med6 and Tup1, suggest that Med21 may serve as a molecular switchboard that integrates different signals before they reach the core polymerase.
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44.
  •  
45.
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46.
  • Hallberg, Magnus, 1974- (författare)
  • Studies of Functional Interactions within Yeast Mediator and a Proposed Novel Mechanism for Regulation of Gene Expression
  • 2004
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The yeast Mediator complex is required for transcriptional regulation both in vivo and in vitro and the identification of similar complexes from metazoans indicates that its function is conserved through evolution. Mediator subunit composition and structure is well characterized both by biochemical, genetic and biophysical methods. In contrast, little is known about the mechanisms by which Mediator operates and how the complex is regulated. The aim of my thesis was to elucidate how Mediator functions at the molecular level and to investigate functional interactions within Mediator. It is possible to recruit RNA polymerase II to a target promoter and thus to activate transcription by fusing Mediator subunits to a DNA binding domain. In order to investigate functional interactions within Mediator, we made such fusion proteins where different Mediator subunits were fused to the DNA binding domain of lexA. The expression of a reporter gene containing binding sites for lexA was subsequently measured in both a wild type strain and in strains where genes encoding specific Mediator subunits had been disrupted. We found that lexA-Med2 and lexA-Gal11 are strong activators that function independently of all Mediator subunits tested. On the other hand, lexA-Srb10 is a weak activator that depends on Srb8 and Srb11 and lexA-Med1 and lexA-Srb7 are both cryptic activators that become active in the absence of Srb8, Srb10, Srb11, or Sin4. Both lexA-Med1 and lexA-Srb7 proteins showed a stable association with the Mediator subunits Med4 and Med8 in wild type cells and in all deletion strains tested, indicating that they were functionally incorporated into the Mediator complex. We also showed that both Med4 and Med8 exist in two forms that differed in electrophoretic mobility and that these forms differed in their ability to associate with Mediator immuno-purified from the LEXA-SRB7 and LEXA-MED1 strains. Dephosphorylation assays of purified Mediator indicated that the two mobility forms of Med4 corresponded to the phosphorylated and unphosphorylated forms of the Med4 protein respectively. Some of the data presented in this study as well as previous genetic and biochemical data obtained in our lab suggested a functional link between the Med1, Med2, Srb10 and Srb11 proteins. We extended these findings by showing that the Srb10 kinase phosphorylates the Med2 protein at residue serine 208, both in vitro and in vivo. We also showed that a point mutation of the single phosphorylation site to an alanine or to an aspartic acid residue altered the gene expression of a specific set of genes. Taken together, these data indicate that posttranslational modification of Mediator subunits is a so far uncharacterized mechanism for regulation of gene expression. In order to study the function of the Srb7 subunit of Mediator, we isolated a temperature sensitive strain where the amino acids 2 to 8 of srb7 were deleted. The Mediator subunits Nut2 and Med7 were isolated as high copy suppressor of srb7-∆(2-8) and we were also able to show that Srb7 interacted with Nut2 and Med7 both in a 2-hybrid system and in co-immuno precipitation experiments using recombinantly expressed proteins. Interestingly, a deletion of amino acids 2 to 8 of Srb7 abolishes its interaction with both Med7 and Nut2 in vitro. Med4 also interacted with Srb7 in the 2-hybrid system and surprisingly, the first eight amino acids of Srb7 were shown to be sufficient for this interaction.
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47.
  • Hallberg, Stefan, 1955, et al. (författare)
  • Developing a simulation model for the patient pathway of cutaneous malignant melanoma
  • 2015
  • Ingår i: Operations Research for Health Care. - : Elsevier BV. - 2211-6923. ; 6, s. 23-30
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, a system dynamic simulation model for a part of the patient pathway of cutaneous malignant melanoma was developed. A model was built that produced quantified out-put of diagnosed patients staged by severity, using System dynamic simulation. Data from the Swedish Melanoma Registry were combined with current scientific results and used in this analytical tool. Solutions to how these results are adapted into a simulation are described. The simulation model has the ability to generate alternative quantitative output of patient health in a population corresponding to realistic interventions in health care programmes as well as population and incidence development.
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48.
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49.
  • Holmström, Paul, 1948, et al. (författare)
  • A System Dynamics 'Flight Simulator‛ for the Evaluation of Policy Interventions in Patient Pathways for Cutaneous Malignant Melanoma
  • 2012
  • Ingår i: Operations Research Society Conference, OR54.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • A system dynamics simulation model was developed as part of building improved long-time planning and policy evaluation in the patient pathways for Cutaneous Malignant Melanoma. An “incidence generator” was used to create patient output sets dependent on different patient delays in seeking treatment. A “flight simulator” was built to test the scenarios against incidence rates, follow-up programmes etc, assessing the trajectories of healthcare costs over time. It is shown that costs escalate significantly unless patient delays addressed and follow-up programmes reviewed.
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50.
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