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  • Aggestam, Lena, et al. (författare)
  • Evaluation criteria to increase information quality in electronic knowledge repositories
  • 2008
  • Ingår i: Proceedings of the 16th European Conference on Information Systems (ECIS). - Association for Information Systems. - 978-0-9553159-2-3 ; s. 1814-1825
  • Konferensbidrag (refereegranskat)abstract
    • Knowledge forms an important asset in modern organisations. In order to gain and sustain competitive advantage knowledge has to be managed. One aspect of this is to use Electronic Knowledge Repositories (EKRs) in order to enhance knowledge sharing, reuse and learning. The success of an EKR is dependent on the quality of its content. For knowledge to be stored in an EKR, it has to be captured. One crucial part of the capture process is to evaluate whether the identified knowledge should be incorporated in the EKR or not. Therefore, to increase information quality in an EKR, the evaluation stage of the capture process must be successfully performed. This paper characterizes Critical Success Factors (CSF) for knowledge evaluation and presents six evaluation criteria to guide the evaluation stage in order to increase information quality in EKR:s. In particular we highlight the importance of performing evaluation addressing correctness, relevance, protection and redundancy. 
  • Aggestam, Lena, et al. (författare)
  • Strategic Knowledge Management Issues when Designing Knowledge Repositories
  • 2007
  • Ingår i: Proceedings of the 15th European Conference on Information Systems, ECIS 2007. - Association for Information Systems. ; s. 528-539
  • Konferensbidrag (refereegranskat)abstract
    • Knowledge forms an important asset in modern organisations. In order to gain and sustain competitive advantage knowledge has to be managed. One aspect of doing this is to build knowledge repositories. In this paper we extend the strategic knowledge management framework to betters suit the process of constructing knowledge repositories. The extended framework highlights, for example, the impact of organizational culture and the importance of distinguishing between the individual and organizational knowledge processes and relating them to each other. The application of the extended framework to analyze a case in the public health care sector revealed a number of important aspects in the preparation and implementation of a knowledge management project. In particular we highlight the importance of having a strategic vision and making the dual relationship between usage and design explicit when implementing a knowledge repository.
  • Aggestam, Lena, et al. (författare)
  • Supporting Knowledge Evaluation to Increase Quality in Electronic Knowledge Repositories
  • 2010
  • Ingår i: International Journal of Knowledge Management. - IGI Global. - 1548-0666. ; 6:1, s. 23-43
  • Tidskriftsartikel (refereegranskat)abstract
    • Knowledge forms an important asset in modern organizations. In order to gain and sustain competitive advantage knowledge has to be managed. One aspect of this is to use Electronic Knowledge Repositories (EKR) to enhance knowledge sharing, reuse and learning. The success of an EKR is dependent on the quality of its content. For knowledge to be stored in an EKR, it has to be captured. One crucial part of the capture process is to evaluate whether the identified knowledge should be incorporated in the EKR or not. Therefore, to increase quality in an EKR, the evaluation stage of the capture process must be successfully carried out. Based on an interpretive field study and an extensive literature review, this paper identifies and characterizes Critical Success Factors (CSF) in the evaluation stage and presents guidance aiming to support implementation of the evaluation stage with the purpose to increase the quality of an EKR. In particular, the guidance supports the decision whether identified knowledge should be stored or not and it highlights the importance of performing evaluation addressing correctness, relevance, protection and redundancy. The characterization of the capture process contributes mainly to KM theory, and the guidance to KM practice.
  • Amare, Azmeraw T, et al. (författare)
  • Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.
  • 2017
  • Ingår i: JAMA psychiatry. - 2168-6238. ; 75:1, s. 65-74
  • Tidskriftsartikel (refereegranskat)abstract
    • Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association.A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36 989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017.Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained.Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P < 5 × 10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
  • Backlund, Lena, et al. (författare)
  • Cognitive manic symptoms associated with the P2RX7 gene in bipolar disorder.
  • 2011
  • Ingår i: Bipolar disorders. - 1399-5618. ; 13:5-6, s. 500-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Several genetic loci have been suggested to be associated with bipolar disorder but results have been inconsistent. Studying associations between bipolar symptoms and candidate genes may better expose this relationship. Here we investigate the association between bipolar key symptoms and the P2RX7 gene. Methods: Key symptoms of mania were rated in two sets of medicated bipolar disorder patients (n = 171 and n = 475) at two specialized outpatient clinics for affective disorders and three regular psychiatric outpatient units in Sweden. The relationships between all manic symptoms according to DSM-IV were entered in a principal component analysis. We used a case-case model to reduce the genetic heterogeneity and tested associations between four factors related to manic symptoms and their association to four single nucleotide polymorphisms in the P2RX7 gene. Results: The combination of the cognitive symptoms, distractibility, talkativeness, and thought disorder was significantly associated with rs1718119 in the P2RX7 gene in Set 1 [odds ratio (OR) = 1.78; p = 0.011]. The association was re-tested in the second set (OR = 1.42; p = 0.009). In the total sample, the association was even stronger (OR = 1.49; p < 0.001). None of the other factors was associated with the P2RX7 gene. Within the first factor, the distractibility symptom accounted for a significant portion of the association to rs1718119 (p = 0.016). Conclusion: There is an association between specific symptoms of bipolar disorder and the P2RX7 gene. This finding may open up new approaches to elucidating the neurobiology behind bipolar symptoms.
  • Backlund, Lena (författare)
  • Determinants of long term course in Bipolar disorder
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Introduction: Bipolar disorder (BP) is a common and severe psychiatric illness with a high variability. An early treatment is often crucial for a good prognosis, but it is difficult for clinicians to define high risk patients in order to predict a more severe course. Our aim was to investigate factors predicting the long-term course of BP. Methods: We have retrospectively investigated the course of illness in 100 BP patients, using a life-charting program. Predictors and their impact on the outcome of lithium treatment were analyzed (Paper I). We then used the Swedish in-patient registry to study the annual incidence rate of BP patients hospitalized for the first time during 1997-2005. We also monitored the readmission rates during five years of patients who had their first admission for bipolar episodes during year 2000 (Paper II). Two groups of BP patients were recruited from a number of psychiatric outpatient clinics for molecular genetic studies. Manic symptoms were assessed and phenotype variations such as mixed episodes (ME), rapid cycling (RC), and the age at onset were defined. Using association analysis, patients with specific symptoms/phenotypes were compared to the other bipolar patients for genetic markers in one small sample. Positive associations identified were then searched for in a larger second sample (Papers III and IV). Results: The number of episodes decreased after the introduction of lithium. An early onset was associated with a longer time until treatment (18.1 vs.10.7 years). The most important predictors for a poor outcome during treatment were RC (OR=10.7), comorbidity (OR=3.8), and ME (OR=2.8) (Paper I). The average length of stay during the first hospitalization was 42 days for ME compared to 30 days for other episodes. Of the 874 participants who had had their first admission for a bipolar episode in 2000, 44% had at least one readmission during the 5-year follow-up. A small group (15%) accounted for more than one half of the readmissions during the same period (Paper II). Utilizing molecular genetics, cognitive symptoms in mania were found to be associated with the SNP rs1718119 (p<0.0006; Paper III), and RC with the SNP rs2230912 (p<0.004; paper IV), both SNPs being located in the P2RX7 gene. Combining the SNP rs2230912 in the P2RX7 gene and the previously associated rs10838524 in the CRY2 gene in an epistasis analysis yielded evidence of a strong association with RC (p=0.000005; OR=7.4). Conclusions: The life-charting methodology can be useful in studying the long-term course of BP. A limitation is that the multitude of data on each studied patient limits the possibility of dealing with large samples. Our findings support the results of previous studies suggesting that RC, ME and comorbidity for other Axis I disorders are important predictors for a more severe course of illness. Most of the first admitted BP patients were not readmitted in the subsequent 5-year period. The genetic findings suggest that different symptoms in BP are associated with specific genes, making the biological pathways behind BP more transparent. The finding that BP patients with a specific combination of variations in the P2RX7 and CRY 2 genes run a 7-fold greater risk of developing RC that those patients not having this combination, is a new contribution to the research field, which increase the possibility of identifying patients who risk developing a more severe course of BP.
  • Backlund, Lena, et al. (författare)
  • Identifying predictors for good lithium response - A retrospective analysis of 100 patients with bipolar disorder using a life-charting method.
  • 2009
  • Ingår i: European psychiatry : the journal of the Association of European Psychiatrists. - 0924-9338. ; 24:3, s. 171-7
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Our aim was to investigate bipolar patients in order to test the validity of various outcome measures and to identify prognostic predictors for pharmacological treatment. MATERIAL AND METHOD: One hundred patients were interviewed using a computerized life-charting program in a descriptive, retrospective analysis. The concept "Burden of illness" was defined as a combination of severity and duration of episodes. Response to treatment was defined as the difference in burden before and after treatment, a low burden during treatment, and freedom of episodes for at least 3 years after insertion of treatment. RESULTS: The absence of mixed episodes and a high initial burden predicted a good response measured as the difference in burden. If remission for 3 years or a low burden during lithium treatment was used, the absence of rapid cycling and of mixed episodes were the most important predictors. The severity of illness before treatment had no impact. DISCUSSION AND CONCLUSION: We suggest the use of absolute measures of severity during treatment as the most appropriate measure of the outcome. Furthermore, our data provide corroboration that treatment with lithium ameliorates the prognosis of the illness, but that mixed episodes and rapid cycling predict a poorer response to lithium.
  • Backlund, Lena, et al. (författare)
  • P2RX7: Expression Responds to Sleep Deprivation and Associates with Rapid Cycling in Bipolar Disorder Type 1
  • 2012
  • Ingår i: Plos One. - 1932-6203. ; 7:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Rapid cycling is a severe form of bipolar disorder with an increased rate of episodes that is particularly treatment-responsive to chronotherapy and stable sleep-wake cycles. We hypothesized that the P2RX7 gene would be affected by sleep deprivation and be implicated in rapid cycling. Objectives: To assess whether P2RX7 expression is affected by total sleep deprivation and if variation in P2RX7 is associated with rapid cycling in bipolar patients. Design: Gene expression analysis in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and case-case and case-control SNP/haplotype association analyses in patients. Participants: Healthy volunteers at the sleep research center, University of California, Irvine Medical Center (UCIMC), USA (n = 8) and Swedish outpatients recruited from specialized psychiatric clinics for bipolar disorder, diagnosed with bipolar disorder type 1 (n = 569; rapid cycling: n = 121) and anonymous blood donor controls (n = 1,044). Results: P2RX7 RNA levels were significantly increased during sleep deprivation in PBMCs from healthy volunteers (p = 2.3*10(-9)). The P2RX7 rs2230912_A allele was more common (OR = 2.2, p = 0.002) and the ACGTTT haplotype in P2RX7 (rs1718119 to rs1621388) containing the protective rs2230912_G allele (OR = 0.45-0.49, p = 0.003-0.005) was less common, among rapid cycling cases compared to non-rapid cycling bipolar patients and blood donor controls. Conclusions: Sleep deprivation increased P2RX7 expression in healthy persons and the putatively low-activity P2RX7 rs2230912 allele A variant was associated with rapid cycling in bipolar disorder. This supports earlier findings of P2RX7 associations to affective disorder and is in agreement with that particularly rapid cycling patients have a more vulnerable diurnal system.
  • Charney, Alexander W, et al. (författare)
  • Contribution of Rare Copy Number Variants to Bipolar Disorder Risk Is Limited to Schizoaffective Cases.
  • 2018
  • Ingår i: Biological psychiatry. - 1873-2402.
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. Subtypes of BD including schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I), and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania, and depression. The genetic factors contributing to the combination of symptoms among these subtypes are poorly understood.Rare large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis, and 307 with unknown psychosis history], 1436 BD II, 579 SAB, and 505 BD not otherwise specified) and 8656 controls. CNV burden and a polygenic risk score (PRS) for schizophrenia were used to evaluate the relative contributions of rare and common variants to risk of BD, BD subtypes, and psychosis.CNV burden did not differ between BD and controls when treated as a single diagnostic entity. However, burden in SAB was increased relative to controls (p = .001), BD I (p = .0003), and BD II (p = .0007). Burden and schizophrenia PRSs were increased in SAB compared with BD I with psychosis (CNV p = .0007, PRS p = .004), and BD I without psychosis (CNV p = .0004, PRS p = 3.9 × 10-5). Within BD I, psychosis was associated with increased schizophrenia PRSs (p = .005) but not CNV burden.CNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.
  • de Jong, Simone, et al. (författare)
  • Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
  • 2018
  • Ingår i: Communications Biology. - Nature Publishing Group. - 2399-3642. ; 1
  • Tidskriftsartikel (refereegranskat)abstract
    • Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
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