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Sökning: WFRF:(Håkansson Claes)

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1.
  • Andersson, Claes, et al. (författare)
  • Associations between risk factors in late adolescence and problem behaviors in young adulthood : A six-year follow-up of substance related and behavioral addictions in swedish high school seniors
  • 2021
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:23
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Risk factors of traditional substance use related problems in young adults are more well-known than for behavioral addictions such as gambling and gaming problems. The present study aims to provide knowledge about the longitudinal patters of substance use related and behavioral addictions in early adulthood. Methods: Using self-report surveys, substance-related, psychiatric, and demographic predictors were assessed in Swedish high school seniors and re-assessed six years later along with gambling and gaming problems, n = 800. Associations (Risk Ratios) between risk factors in late adolescence and problem behaviors in young adulthood were analyzed. Results: Tobacco use, illicit drug use, and hazardous drinking in young adulthood were associated with tobacco use, illicit drug use, alcohol use, conduct problems, and impaired impulse control in late adolescence. Gambling problems in young adulthood were only associated with heredity of alcohol problems, while gaming was not associated to any problem behavior in late adolescence. Conclusion: It is concluded that predictors for traditional substance-related addictions differ from predictors for behavioral addictions, and that this difference is more pronounced for gaming problems than for gambling problems.
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  • Andersson, Claes, et al. (författare)
  • ATLAS-SPEL : Prediktion av spelproblem hos unga
  • 2016
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Trots att vi vet att problematiskt spelbeteende ofta utvecklas ofta i yngre vuxenålder, saknas kunskap om faktorer som i åldersgruppen predicerar spelproblem och spelberoende.
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3.
  • Andersson, Claes, et al. (författare)
  • Interactive voice response with feedback intervention in out-patient treatment of substance use problems in adolescents: a randomized controlled trial on substance use, stress and psychiatric symptoms.
  • 2017
  • Ingår i: International Journal of Behavioral Medicine. - : Springer Science and Business Media LLC. - 1070-5503 .- 1532-7558. ; 24:5, s. 789-797
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Substance use disorders and problematic substance use are common problems in adolescence and young adulthood. Brief personalized feedback has been suggested for treatment of alcohol and drug problems and poor mental health. This repeated measurement randomized controlled trial examines the effect of an interactive voice response (IVR) system for assessing stress, depression, anxiety and substance use. Methods: The IVR system was used twice weekly over 3 months after treatment initiation, with or without addition of a personalized feedback intervention on stress and mental health symptoms. Both IVR assessment only (control group) and IVR assessment including feedback (intervention group) were provided as an add-on to treatment-as-usual procedures (TAU) in outpatient treatment of substance use problems in adolescents and young adults (N = 73). Results: By using a mixed models approach, differences in change scores were analyzed over the three-month assessment period. Compared to the control group, the intervention group demonstrated significantly greater improvement in the Arnetz and Hasson stress score (AHSS, p = 0.019), the total Symptoms Checklist 8 score (SCL-8D, p = 0.037), the SCL-8D anxiety sub-score (p = 0.017), and on a summarized feedback score (p = 0.026), but not on the depression subscale. There were no differences in global substance use scores between the intervention group (feedback on mental health symptoms) and the control group. Conclusion: In conclusion, IVR may be useful for follow-up and repeated interventions as an add-on to regular treatment, and personalized feedback could potentially improve mental health in adolescents and young adults with problematic substance use.
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4.
  • Andersson, Claes, et al. (författare)
  • Interactive Voice Response with Feedback Intervention in Outpatient Treatment of Substance Use Problems in Adolescents and Young Adults : A Randomized Controlled Trial
  • 2017
  • Ingår i: International Journal of Behavioral Medicine. - : Springer. - 1070-5503 .- 1532-7558. ; 24:5, s. 789-797
  • Tidskriftsartikel (refereegranskat)abstract
    • Substance use disorders and problematic substance use are common problems in adolescence and young adulthood. Brief personalized feedback has been suggested for treatment of alcohol and drug problems and poor mental health. This repeated measurement randomized controlled trial examines the effect of an Interactive Voice Response (IVR) system for assessing stress, depression, anxiety and substance use. The IVR system was used twice weekly over three months after treatment initiation, with or without addition of a personalized feedback intervention on stress and mental health symptoms. Both IVR assessment only (control group) and IVR assessment including feedback (intervention group) were provided as an add-on to treatment-as-usual procedures (TAU) in outpatient treatment of substance use problems in adolescents and young adults (N=73). By using a mixed models approach, differences in change scores were analyzed over the three-month assessment period. Compared to the control group, the intervention group demonstrated significantly greater improvement in the Arnetz and Hasson stress score (AHSS, p=0.019), the total Symptoms Checklist 8 score (SCL-8D, p=0.037), the SCL-8D anxiety sub-score (p=0.017), and on a summarized feedback score (p=0.026), but not on the depression subscale. There were no differences in global substance use scores between the intervention group (feedback on mental health symptoms) and the control group. In conclusion, IVR may be useful for follow-up and repeated interventions as an add-on to regular treatment, and personalized feedback could potentially improve mental health in adolescents and young adults with problematic substance use.
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5.
  • Arvidsson, Inger, et al. (författare)
  • Should I Stay or Should I Go? : Associations between Occupational Factors, Signs of Exhaustion, and the Intention to Change Workplace among Swedish Principals
  • 2023
  • Ingår i: Sustainable Healthy Working Life for All Ages. - : MDPI Books. ; , s. 139-158
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • A high turnover among principals may disrupt the continuity of leadership and negativelyaffect teachers and, by extension, the students. The aim was to investigate to what extent variouswork environment factors and signs of exhaustion were associated with reported intentions tochange workplace among principals working in compulsory schools. A web-based questionnaire wasadministered twice, in 2018 and in 2019. Part I of the study involved cross-sectional analyses of theassociations 2018 (n = 984) and 2019 (n = 884) between occupational factors, signs of exhaustion, andthe intention to change workplace, using Generalized Estimating Equations models. Part II involved631 principals who participated in both surveys. The patterns of intended and actual changes ofworkplace across two years were described, together with associated changes of occupational factorsand signs of exhaustion. Supportive management was associated with an intention to stay, whiledemanding role conflicts and the feeling of being squeezed between management and co-workers(buffer-function) were associated with the intention to change workplace. The principals whointended to change their workplace reported more signs of exhaustion. To increase retention amongprincipals, systematic efforts are probably needed at the national, municipal, and local level, in orderto improve their working conditions
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6.
  • Baenas, Isabel, et al. (författare)
  • Impact of COVID-19 Lockdown in Eating Disorders : A Multicentre Collaborative International Study
  • 2022
  • Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. The COVID-19 lockdown has had a significant impact on mental health. Patients with eating disorders (ED) have been particularly vulnerable. Aims. (1) To explore changes in eating-related symptoms and general psychopathology during lockdown in patients with an ED from various European and Asian countries; and (2) to assess differences related to diagnostic ED subtypes, age, and geography. Methods. The sample comprised 829 participants, diagnosed with an ED according to DSM-5 criteria from specialized ED units in Europe and Asia. Participants were assessed using the COVID-19 Isolation Scale (CIES). Results. Patients with binge eating disorder (BED) experienced the highest impact on weight and ED symptoms in comparison with other ED subtypes during lockdown, whereas individuals with other specified feeding and eating disorders (OFSED) had greater deterioration in general psychological functioning than subjects with other ED subtypes. Finally, Asian and younger individuals appeared to be more resilient. Conclusions. The psychopathological changes in ED patients during the COVID-19 lockdown varied by cultural context and individual variation in age and ED diagnosis. Clinical services may need to target preventive measures and adapt therapeutic approaches for the most vulnerable patients.
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7.
  • Düringer, Caroline, et al. (författare)
  • Agonist-specific patterns of beta(2)-adrenoceptor responses in human airway cells during prolonged exposure.
  • 2009
  • Ingår i: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 158, s. 169-179
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: beta(2)-Adrenoceptor agonists (beta(2)-agonists) are important bronchodilators used in the treatment of asthma and chronic obstructive pulmonary disease. At the molecular level, beta(2)-adrenergic agonist stimulation induces desensitization of the beta(2)-adrenoceptor. In this study, we have examined the relationships between initial effect and subsequent reduction of responsiveness to restimulation for a panel of beta(2)-agonists in cellular and in vitro tissue models. Experimental approach: beta(2)-Adrenoceptor-induced responses and subsequent loss of receptor responsiveness were studied in primary human airway smooth muscle cells and bronchial epithelial cells by measuring cAMP production. Receptor responsiveness was compared at equi-effective concentrations, either after continuous incubation for 24 h or after a 1 h pulse exposure followed by a 23 h washout. Key findings were confirmed in guinea pig tracheal preparations in vitro. Key results: There were differences in the reduction of receptor responsiveness in human airway cells and in vitro guinea pig trachea by a panel of beta(2)-agonists. When restimulation occurred immediately after continuous incubation, loss of responsiveness correlated with initial effect for all agonists. After the 1 h pulse exposure, differences between agonists emerged, for example isoprenaline and formoterol induced the least reduction of responsiveness. High lipophilicity was, to some extent, predictive of loss of responsiveness, but other factors appeared to be involved in determining the relationships between effect and subsequent loss of responsiveness for individual agonists. Conclusions and implications: There were clear differences in the ability of different beta(2) agonists to induce loss of receptor responsiveness at equi-effective concentrations.
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  • Fernández-Aranda, Fernando, et al. (författare)
  • COVID Isolation Eating Scale (CIES) : Analysis of the impact of confinement in eating disorders and obesity—A collaborative international study
  • 2020
  • Ingår i: European Eating Disorders Review. - : Wiley. - 1072-4133 .- 1099-0968. ; 28:6, s. 871-883
  • Tidskriftsartikel (refereegranskat)abstract
    • Confinement during the COVID-19 pandemic is expected to have a serious and complex impact on the mental health of patients with an eating disorder (ED) and of patients with obesity. The present manuscript has the following aims: (1) to analyse the psychometric properties of the COVID Isolation Eating Scale (CIES), (2) to explore changes that occurred due to confinement in eating symptomatology; and (3) to explore the general acceptation of the use of telemedicine during confinement. The sample comprised 121 participants (87 ED patients and 34 patients with obesity) recruited from six different centres. Confirmatory Factor Analyses (CFA) tested the rational-theoretical structure of the CIES. Adequate goodness-of-fit was obtained for the confirmatory factor analysis, and Cronbach alpha values ranged from good to excellent. Regarding the effects of confinement, positive and negative impacts of the confinement depends of the eating disorder subtype. Patients with anorexia nervosa (AN) and with obesity endorsed a positive response to treatment during confinement, no significant changes were found in bulimia nervosa (BN) patients, whereas Other Specified Feeding or Eating Disorder (OSFED) patients endorsed an increase in eating symptomatology and in psychopathology. Furthermore, AN patients expressed the greatest dissatisfaction and accommodation difficulty with remote therapy when compared with the previously provided face-to-face therapy. The present study provides empirical evidence on the psychometric robustness of the CIES tool and shows that a negative confinement impact was associated with ED subtype, whereas OSFED patients showed the highest impairment in eating symptomatology and in psychopathology.
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  • Håkansson, Claes, et al. (författare)
  • Inter-modality assessment of medial temporal lobe atrophy in a non-demented population: application of a visual rating scale template across radiologists with varying clinical experience
  • 2022
  • Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 32, s. 1127-1134
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To assess inter-modality agreement and accuracy for medial temporal lobe atrophy (MTA) ratings across radiologists with varying clinical experience in a non-demented population. Methods Four raters (two junior radiologists and two senior neuroradiologists) rated MTA on CT and MRI scans using Scheltens' MTA scale. Ratings were compared to a consensus rating by two experienced neuroradiologists for estimation of true positive and negative rates (TPR and TNR) and over- and underestimation of MTA. Inter-modality agreement expressed as Cohen's kappa (dichotomized data), Cohen's kappa(w), and two-way mixed, single measures, consistency ICC (ordinal data) were determined. Adequate agreement was defined as kappa/kappa(w) >= 0.80 and ICC >= 0.80 (significance level at 95% CI >= 0.65). Results Forty-nine subjects (median age 72 years, 27% abnormal MTA) with cognitive impairment were included. Only junior radiologists achieved adequate agreement expressed as Cohen's kappa. All raters achieved adequate agreement expressed as Cohen's kappa(w) and ICC. True positive rates varied from 69 to 100% and TNR varied from 85 to 100%. No under- or overestimation of MTA was observed. Ratings did not differ between radiologists. Conclusion We conclude that radiologists with varying experience achieve adequate inter-modality agreement and similar accuracy when Scheltens' MTA scale is used to rate MTA on a non-demented population. However, TPR varied between radiologists which could be attributed to rating style differences.
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17.
  • Håkansson, Claes, et al. (författare)
  • Reporting frequency of radiology findings increases after introducing visual rating scales in the primary care diagnostic work up of subjective and mild cognitive impairment
  • 2021
  • Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 31:2, s. 666-673
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Study the effect of introducing a template for radiological reporting of non-enhanced computed tomography (NECT) in the primary care diagnostic work up of cognitive impairment using visual rating scales (VRS). Methods Radiology reports were assessed regarding compliance with a contextual report template and the reporting of the parameters medial temporal lobe atrophy (MTA), white matter changes (WMC), global cortical atrophy (GCA), and width of lateral ventricles (WLV) using established VRS in two age-matched groups examined with NECT before (n= 111) and after (n= 125) the introduction of contextual reporting at our department. True positive rate (TPR) and true negative rate (TNR) before and after were compared. Results We observed a significant increase in the percentage of radiology reports with mentioning of MTA from 29 to 76% (p< 0.001), WMC from 69 to 86% (p< 0.01), and GCA from 54 to 82% (p< 0.001). We observed a significant increase in the percentages of reports where all of the parameters were mentioned, from 6 to 29% (p< 0.001). There was a significant increase in TPR from 10 to 55% for MTA. Conclusion This study suggests that contextual radiological assessment using VRS could increase the reporting frequency of radiology findings in the diagnostic work up of cognitive impairment but compliance with templates may be difficult to endorse.
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18.
  • Håkansson, Claes, et al. (författare)
  • Structural imaging findings on non-enhanced computed tomography are severely underreported in the primary care diagnostic work-up of subjective cognitive decline
  • 2019
  • Ingår i: Neuroradiology. - : Springer Science and Business Media LLC. - 0028-3940 .- 1432-1920. ; 61:4, s. 397-404
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The purpose of this study was to investigate how structural imaging findings of medial temporal lobe atrophy (MTA), posterior cortical atrophy (PCA), global cortical atrophy (GCA), white matter changes (WMC), and Evans’ index/width of lateral ventricles (EI/WLV) are reported in the primary care diagnostic work-up of patients with subjective cognitive decline or mild cognitive impairment. Methods: We included 197 patients referred to a non-enhanced computed tomography (NECT) as part of the diagnostic work-up. We compared the frequencies of reported findings in radiology reports written by neuroradiologists and general radiologists with actual pathological findings in a second view done by a single neuroradiologist using the MTA, PCA, GCA, WMC, and EI/WLV visual rating scales. Structural findings were also compared to cognitive tests. Results: We found that MTA and PCA were clearly underreported by both neuroradiologists and general radiologists. The presence of GCA and WMC was also underreported among general radiologists. Only MTA showed a clear association with cognitive test results. Conclusions: We believe that the use of visual rating scales should be put into clinical practice to increase the yield of clinical NECT exams in the investigation of cognitive impairment. Special emphasis should be put on reporting MTA.
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  • Håkansson, Pelle, 1973- (författare)
  • Ribonucleotide reductase and DNA damage
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • A prerequisite for a multicellular organism to survive is the ability to correctly replicate and repair DNA while minimizing the number of heritable mutations. To achieve this, cells need a balanced supply of deoxyribonucleoside triphosphates (dNTPs), the precursors for DNA synthesis. The rate-limiting step in de novo biosynthesis of dNTPs is catalyzed by the enzyme ribonucleotide reductase (RNR). The classic eukaryotic RNR enzyme consists of a large and a small subunit. Together, these subunits form a heterotetrameric RNR complex. The larger subunit harbours active sites whereas the smaller subunit contains a stable tyrosyl free radical. Both subunits are required for RNR activity. Since failure to correctly regulate de novo dNTP biosynthesis can lead to misincorporation of nucleotides into DNA, genetic abnormalities and cell death, RNR activity is tightly regulated. The regulation of RNR activity involves cell cycle-specific expression and degradation of the RNR proteins, as well as binding of allosteric effectors to the large RNR subunit. In this thesis, in vitro assays based on purified recombinant RNR proteins, in combination with in vivo assays, have been used successfully to study the regulation of RNR activity in response to DNA damage. I present new findings regarding the function of an alternative mammalian RNR small subunit, and on the role of a small RNR inhibitor protein of fission yeast, during normal growth and after DNA damage. I also show conclusively that there are fundamental differences in the regulation of dNTP biosynthesis between the cells of higher and lower eukaryotes after DNA damage.
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  • Ilinca, Andreea, et al. (författare)
  • MAP3K6 Mutations in a Neurovascular Disease Causing Stroke, Cognitive Impairment, and Tremor
  • 2021
  • Ingår i: Neurology: Genetics. - 2376-7839. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To describe a possible novel genetic mechanism for cerebral small vessel disease (cSVD) and stroke.Methods: We studied a Swedish kindred with ischemic stroke and intracerebral hemorrhage, tremor, dysautonomia, and mild cognitive decline. Members were examined clinically, radiologically, and by histopathology. Genetic workup included whole-exome sequencing (WES) and whole-genome sequencing (WGS) and intrafamilial cosegregation analyses.Results: Fifteen family members were examined clinically. Twelve affected individuals had white matter hyperintensities and 1 or more of (1) stroke episodes, (2) clinically silent lacunar ischemic lesions, and (3) cognitive dysfunction. All affected individuals had tremor and/or atactic gait disturbance. Mild symmetric basal ganglia calcifications were seen in 3 affected members. Postmortem examination of 1 affected member showed pathologic alterations in both small and large arteries the brain. Skin biopsies of 3 affected members showed extracellular amorphous deposits within the subepidermal zone, which may represent degenerated arterioles. WES or WGS did not reveal any potentially disease-causing variants in known genes for cSVDs or idiopathic basal ganglia calcification, but identified 1 heterozygous variant, NM_004672.4 MAP3K6 c.322G>A p.(Asp108Asn), that cosegregated with the disease in this large family. MAP3K6 has known functions in angiogenesis and affects vascular endothelial growth factor expression, which may be implicated in cerebrovascular disease.Conclusions: Our data strongly suggest the MAP3K6 variant to be causative for this novel disease phenotype, but the absence of functional data and the present lack of additional families with this disease and MAP3K6 mutations still limit the formal evidence for the variant's pathogenicity.
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  • Jochems, Caroline, 1973, et al. (författare)
  • Long-term anti-arthritic and anti-osteoporotic effects of raloxifene in established experimental postmenopausal polyarthritis.
  • 2008
  • Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 1365-2249 .- 0009-9104. ; 152:3, s. 593-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Both oestrogen deficiency and the inflammatory disease contribute to the generalized bone loss seen in postmenopausal rheumatoid arthritis (RA). Oestradiol and the selective oestrogen receptor modulator raloxifene have been shown to ameliorate the disease in collagen-induced arthritis (CIA), a well-established animal model for human RA. The aim of this study was to investigate whether raloxifene-treatment would be beneficial in long-term treatment of established CIA, both regarding anti-arthritic and anti-osteoporotic properties. Female dilute brown agouti mice were ovariectomized and CIA was induced. Raloxifene or vehicle treatment was administered 5 days per week, and the clinical arthritis score was evaluated continuously. At termination, bone mineral density was analysed, paws were collected for histological examination and sera were analysed for markers of bone and cartilage turnover, as well as antibodies to type II collagen and levels of interleukin (IL)-6. Treatment with raloxifene is beneficial in long-term treatment of established CIA. It hampers the disease severity and frequency, protects the joints from destruction and protects against the development of osteoporosis. The proinflammatory cytokine IL-6 was down-regulated in raloxifene-treated mice compared with controls. The serum levels of antibodies to collagen were not affected by raloxifene-treatment. Long-term treatment with raloxifene has both anti-arthritic and anti-osteoporotic effects in established experimental postmenopausal polyarthritis.
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22.
  • Lie, Anders, 1959, et al. (författare)
  • Automated vehicles: How do they relate to vision zero
  • 2022
  • Ingår i: The Vision Zero Handbook: Theory, Technology and Management for a Zero Casualty Policy. - Cham : Springer International Publishing. ; , s. 1057-1071
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • The Swedish Transport Administration (STA) work to reduce the number of suicides in the transport system. Fatalities, i.e., on roads, railways, and bridges, originate from either accidents or suicides, natural death excluded. Knowing the correct manner of death is needed to work with optimal prevention strategies. The aims are to separate fatalities due to suicides, follow the development, and implement measures for suicide prevention. Methods are developed for suicide classification and criteria for the selection in which suicides were suspected. Fatalities in level one and two of five were classified as suicides. Data from the STA's databases are used and so are data from the psychosocial investigations done by a trained investigator in the topic and with clinical experience from counselling at hospitals. 2129 persons died on the roads in Sweden, 10% (206 persons) were classified as suicides. 336 persons died after being hit by trains, 85% (284 persons) were suicides. 130 persons died by jumping from bridges. The number of suicides increases with population density. Suicide in the transport system is a major problem; firstly personal tragedies, it is also a work environment problem for truck and train drivers and for the emergency staff. It generates delays and costs for passenger and cargo transport. By analyzing the results of countermeasures in the form of obstructive barriers, the physical environment can be improved and high-risk areas can be accentuated. Restricting access to the means of suicide is important in suicide prevention. Strategies for the STA include suicide prevention in the design of new roads, railways, and bridges, as well as by identifying and reducing existing high-risk locations. Sharing the results with other authorities and organizations and cooperation within suicide prevention missions are vital for the enhancement of the overall suicide prevention work in society.
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  • Mårtensson, Gustav, et al. (författare)
  • Medial temporal atrophy in preclinical dementia : Visual and automated assessment during six year follow-up
  • 2020
  • Ingår i: NeuroImage: Clinical. - : Elsevier BV. - 2213-1582. ; 27
  • Tidskriftsartikel (refereegranskat)abstract
    • Medial temporal lobe (MTL) atrophy is an important morphological marker of many dementias and is closely related to cognitive decline. In this study we aimed to characterize longitudinal progression of MTL atrophy in 93 individuals with subjective cognitive decline and mild cognitive impairment followed up over six years, and to assess if clinical rating scales are able to detect these changes. All MRI images were visually rated according to Scheltens’ scale of medial temporal atrophy (MTA) by two neuroradiologists and AVRA, a software for automated MTA ratings. The images were also segmented using FreeSurfer's longitudinal pipeline in order to compare the MTA ratings to volumes of the hippocampi and inferior lateral ventricles. We found that MTL atrophy rates increased with CSF biomarker abnormality, used to define preclinical stages of Alzheimer's Disease. Both AVRA's and the radiologists’ MTA ratings showed similar longitudinal trends as the subcortical volumes, suggesting that visual rating scales provide a valid alternative to automatic segmentations. Our results further showed that it took more than 8 years on average for individuals with mild cognitive impairment, and an Alzheimer's disease biomarker profile, to increase the MTA score by one. This suggests that discrete MTA ratings are too coarse for tracking individual MTL atrophy in short time spans. While the MTA scores from each radiologist showed strong correlations to subcortical volumes, the inter-rater agreement was low. We conclude that the main limitation of quantifying MTL atrophy with visual ratings in clinics is the subjectiveness of the assessment.
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  • Orsmark-Pietras, Christina, et al. (författare)
  • Precision Diagnostics in Myeloid Malignancies : Development and Validation of a National Capture-Based Gene Panel
  • 2024
  • Ingår i: Genes Chromosomes and Cancer. - : John Wiley and Sons Inc. - 1045-2257 .- 1098-2264. ; 63:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Gene panel sequencing has become a common diagnostic tool for detecting somatically acquired mutations in myeloid neoplasms. However, many panels have restricted content, provide insufficient sensitivity levels, or lack clinically validated workflows. We here describe the development and validation of the Genomic Medicine Sweden myeloid gene panel (GMS-MGP), a capture-based 191 gene panel including mandatory genes in contemporary guidelines as well as emerging candidates. The GMS-MGP displayed uniform coverage across all targets, including recognized difficult GC-rich areas. The validation of 117 previously described somatic variants showed a 100% concordance with a limit-of-detection of a 0.5% variant allele frequency (VAF), achieved by utilizing error correction and filtering against a panel-of-normals. A national interlaboratory comparison investigating 56 somatic variants demonstrated highly concordant results in both detection rate and reported VAFs. In addition, prospective analysis of 323 patients analyzed with the GMS-MGP as part of standard-of-care identified clinically significant genes as well as recurrent mutations in less well-studied genes. In conclusion, the GMS-MGP workflow supports sensitive detection of all clinically relevant genes, facilitates novel findings, and is, based on the capture-based design, easy to update once new guidelines become available. The GMS-MGP provides an important step toward nationally harmonized precision diagnostics of myeloid malignancies.
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32.
  • Simark-Mattsson, Charlotte, 1955, et al. (författare)
  • Lactobacillus-mediated interference of mutans streptococci in caries-free vs. caries-active subjects.
  • 2007
  • Ingår i: European journal of oral sciences. - : Wiley. - 0909-8836 .- 1600-0722. ; 115:4, s. 308-14
  • Tidskriftsartikel (refereegranskat)abstract
    • In order to assess whether naturally occurring oral lactobacilli have probiotic properties, lactobacilli were isolated from saliva and plaque from children and adolescents, with or without caries lesions. The interference capacities of these lactobacilli were investigated against a panel of 13 clinical isolates and reference strains of Streptococcus mutans and Streptococcus sobrinus, as well as against the subject's autologous mutans streptococci, using the agar-overlay technique. Lactobacillus-mediated inhibition differed significantly between the three subject groups (no caries, arrested caries, or active caries), demonstrating increased inhibition in subjects without present or previous caries experience compared to subjects with arrested caries or subjects presenting with frank lesions. Lactobacilli from subjects lacking S. mutans inhibited the growth of the test panel of mutans streptococci significantly better than lactobacilli from subjects who were colonized. Furthermore, subjects without caries experience harbored lactobacilli that more effectively repressed the growth of their autologous mutans streptococci. Twenty-three Lactobacillus spp. completely inhibited the growth of all mutans streptococci tested. Species with maximum interference capacity against mutans streptococci included Lactobacillus paracasei, Lactobacillus plantarum, and Lactobacillus rhamnosus. Naturally occurring oral lactobacilli significantly inhibited the growth of both test strains of mutans streptococci and the subject's autologous mutans streptococci in vitro, and this effect was more pronounced in caries-free subjects.
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  • Truong, My, et al. (författare)
  • The potential role of T2*-weighted multi-echo data image combination as an imaging marker for intraplaque hemorrhage in carotid plaque imaging
  • 2021
  • Ingår i: BMC Medical Imaging. - : Springer Science and Business Media LLC. - 1471-2342. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Carotid atherosclerotic plaques with intraplaque hemorrhage (IPH) are associated with elevated stroke risk. IPH is predominantly imaged based on paramagnetic properties of the upstream hemoglobin degradation product methemoglobin. This is an explorative observational study to test the feasibility of a spoiled gradient echo based T2* weighted MRI sequence (3D MEDIC) for carotid plaque imaging, and to compare signs suggestive of the downstream degradation product hemosiderin on 3D MEDIC with signs of methemoglobin on a T1wBB sequence. Methods: Patients with recent TIA or stroke were selected based on the presence on non-calcified plaque components on CTA to promote an enriched prevalence of IPH in the material. Patients (n = 42) underwent 3T MRI with 3D MEDIC and 2D turbo spin echo T1w black blood (T1wBB). Images were independently evaluated by two neuroradiologists and Cohens Kappa was used for inter-reader agreement for each sequence. Results: The technical feasibility for 3D MEDIC, was 34/42 patients (81%). Non-calcified plaque components with susceptibility effect without simultaneous T1-shortening—a combination suggestive of hemosiderin, was seen in 13/34 of the plaques. An equally large group display elevated T1w signal in combination with signal loss on 3D MEDIC, a combination suggestive of both hemosiderin and methemoglobin. Cohen’s kappa for inter-reader agreement was 0.64 (CI 0.345–0.925) for 3D MEDIC and 0.94 (CI 0.81–1.00) for T1wBB. Conclusions: 3D MEDIC shows signal loss, without elevated T1w signal on T1wBB, in non-calcified tissue in many plaques in this group of patients. If further studies, including histological verification, confirm that the 3D MEDIC susceptibility effect is indeed caused by hemosiderin, 3D MEDIC could aid in the detection of IPH, beyond elevation of T1w signal.
  •  
34.
  • Windahl, Sara H, 1971, et al. (författare)
  • Identification of Target Cells for the Genomic Effects of Estrogens in Bone
  • 2007
  • Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 148:12, s. 5688-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Estrogen has bone protective effects, but the exact mechanism behind these effects remains unclear. The aim of the present study was to identify the primary target cells in bone for the classical genomic effects of estrogens in vivo. For this purpose we have used reporter mice with a luciferase gene under the control of three estrogen-responsive elements (EREs), enabling detection of in vivo activation of gene transcription. Three-month-old ovariectomized mice were treated with a single dose (50microg/kg) 17beta-estradiol (E2). Luciferase activity was analysed in several tissues and in different bone marrow-derived lymphocyte enriched/depleted preparations using MacsMouse CD19 (for B lymphocytes) or CD90 (for T lymphocytes) MicroBeads. Histological characterization of cells with high luciferase content was performed using immunohistochemistry. Both cortical bone and bone marrow displayed a rapid (within 1h) and pronounced E2-induced increase in luciferase activity. The luciferase activity in total bone marrow and in bone marrow depleted of lymphocytes was increased 6-8 times more than in either B lymphocyte and T lymphocyte enriched cell fractions 4h after the E2-injection, demonstrating that mature lymphocytes are not major direct targets for the genomic effect of estrogens in bone. Immunohistochemistry identified clear luciferase staining in hypertrophic growth plate chondrocytes, megakaryocytes, osteoblasts and lining cells, while no staining was seen in proliferative chondrocyte. Although most of the osteocytes did not display any detectable luciferase staining, a subpopulation of osteocytes both in cortical and trabecular bone stained positive for luciferase. In conclusion, hypertrophic growth plate chondrocytes, megakaryocytes, osteoblasts, lining cells and a subpopulation of osteocytes were identified to respond to estrogen via the classical ERE-mediated genomic pathway in bone. Furthermore, our findings indicate that possible direct estrogenic effects on the majority of osteocytes, not staining positive for luciferase, on proliferative chondrocytes and on mature lymphocytes are mediated by non-ERE actions.
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