| 1. |
- Amare, Azmeraw T, et al.
(författare)
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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.
- 2018
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 65-74
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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 36989 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.
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| 3. |
- Emmelkamp, Paul M.G., et al.
(författare)
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Advancing psychotherapy and evidence-based psychological interventions
- 2014
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Ingår i: International Journal of Methods in Psychiatric Research. - : John Wiley & Sons. - 1049-8931 .- 1557-0657. ; 23:S1, s. 58-91
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Tidskriftsartikel (refereegranskat)abstract
- Psychological models of mental disorders guide research into psychological and environmental factors that elicit and maintain mental disorders as well as interventions to reduce them. This paper addresses four areas. (1) Psychological models of mental disorders have become increasingly transdiagnostic, focusing on core cognitive endophenotypes of psychopathology from an integrative cognitive psychology perspective rather than offering explanations for unitary mental disorders. It is argued that psychological interventions for mental disorders will increasingly target specific cognitive dysfunctions rather than symptom-based mental disorders as a result. (2) Psychotherapy research still lacks a comprehensive conceptual framework that brings together the wide variety of findings, models and perspectives. Analysing the state-of-the-art in psychotherapy treatment research, “component analyses” aiming at an optimal identification of core ingredients and the mechanisms of change is highlighted as the core need towards improved efficacy and effectiveness of psychotherapy, and improved translation to routine care. (3) In order to provide more effective psychological interventions to children and adolescents, there is a need to develop new and/or improved psychotherapeutic interventions on the basis of developmental psychopathology research taking into account knowledge of mediators and moderators. Developmental neuroscience research might be instrumental to uncover associated aberrant brain processes in children and adolescents with mental health problems and to better examine mechanisms of their correction by means of psychotherapy and psychological interventions. (4) Psychotherapy research needs to broaden in terms of adoption of large-scale public health strategies and treatments that can be applied to more patients in a simpler and cost-effective way. Increased research on efficacy and moderators of Internet-based treatments and e-mental health tools (e.g. to support “real time” clinical decision-making to prevent treatment failure or relapse) might be one promising way forward.
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| 4. |
- Forslund, Helena, et al.
(författare)
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Logistics Performance Management Challenges in Dyadic Relationships
- 2006
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Ingår i: Conference proceedings from the 18th International NOFOMA conference.
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Konferensbidrag (refereegranskat)abstract
- Supply chain management is about having an end-customer perspective and creating value through integration of business processes and optimization of the entire supply chain. The performance management (defining metrics, target setting, measurement and analysis) should be important for succeeding in the supply chain management ambitions. This paper focuses on logistics performance management in inter-organizational business processes, i.e. in the inter-linked purchasing, order to delivery and distribution processes, of manufacturing companies. The objective of this paper is to describe the logistics performance management process in dyads of supplying and buying companies and to identify research needs related to supply chain integration of the performance management process. The analysis is mainly empirical and is based on case studies of four dyads of supplying and buying manufacturing companies. The analysis focuses on describing and comparing the four phases of the performance management process in the four studied dyads. The defining metrics activity was based on few metrics but found to be problematic as no dyads operate with joint metric definitions. The target setting activity was executed in all dyads but joint targets were only found in some dyads. Not all companies measured performance, due to priorities and technical problems. The analysis activity was often conducted together in the dyads in the shape of meetings. The analysis also studies the levels of supply chain integration of the performance management process. The studied dyads have very low level of supply chain integration of the activities. The section is ended with some performance management integration challenges in supply chains.
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| 5. |
- Forslund, Helena, et al.
(författare)
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Mätsystemsamverkan i försörjningskedjor
- 2006
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Ingår i: Konferensproceedings från PLANs forsknings- och tillämpningskonferens.
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Konferensbidrag (refereegranskat)abstract
- Mätning och styrning av logistikprestationer kan beskrivas som en process med fem aktiviteter – välja prestationsvariabler, definiera mått, sätta mål, mäta och analysera/agera. Detta paper fokuserar på logistikprestationer i inter-organisatoriska affärsprocesser, de länkade inköps-, order-till-leverans- och distributionsprocesserna mellan tillverkande företag. Syftet med papret är att beskriva samverkan kring mätsystemen i par av levererande och köpande företag, s k dyader samt att identifiera framtida forskningsbehov i anslutning till detta. Analysen är huvudsakligen empirisk och fallstudiebaserad, och jämför aktiviteterna i mätsystemprocessen i sju dyader. Aktiviteten välja prestationsvariabler visade sig resultera i krav på leveransprecision i samtliga dyader. Definiera mått utgick från samma mått men var problematisk eftersom inga dyader arbetade med gemensamma definitioner. Samtliga företag satte mål för logistikmått men gemensamma mål fanns bara i några dyader. Alla företag mätte inte logistikmått, p g a bristande prioriteter och tekniska svårigheter. Aktiviteten analysera/agera visade svagheter men genomfördes ofta i form av gemensamma möten i dyaderna. Flera förslag till fortsatt forskning föreslås.
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| 6. |
- Fullager, Daniel B., et al.
(författare)
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Metalized Poly-methacrylate Off-Axis Parabolic Mirrors for Terahertz Imaging Fabricated by Additive Manufacturing
- 2019
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Ingår i: Journal of Infrared, Millimeter and Terahertz Waves. - : SPRINGER. - 1866-6892 .- 1866-6906. ; 40:3, s. 269-275
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Tidskriftsartikel (refereegranskat)abstract
- Terahertz radiation sources are currently one of the most widely used non-ionizing illumination mechanisms for security applications and also find increasing utilization in quality control of commercial products. Presently, a majority of these applications rely on scanning rather than direct imaging and implicitly suffer from temporal latency due to post processing. The monetary and temporal cost associated with procuring commercially manufactured optics that are suitable for imaging leads to fundamental limitations in the ability to rapidly develop application-specific imaging modalities using terahertz sources. Herein, we show a novel method for the rapid prototyping of metallic coated poly-methacrylate parabolic reflectors fabricated by stereolithographic 3D printing. Images comparing the performance of a commercially available off-axis parabolic reflector to our metalized poly-methacrylate prototype, which was designed to be identical to the commercially available mirror, are subsequently presented. The images show that at 530 GHz it is possible to produce a metalized poly-methacrylate off-axis paraboloid whose spatial beam profile is nearly identical to that of a commercially available equivalent.
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| 7. |
- Groenewold, Nynke A., et al.
(författare)
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Volume of subcortical brain regions in social anxiety disorder : mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group
- 2023
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 28:3, s. 1079-1089
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Tidskriftsartikel (refereegranskat)abstract
- There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = −0.077, pFWE = 0.037; right: d = −0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = −0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = −0.141, pFWE < 0.001; right: d = −0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.
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| 8. |
- Hoffmann, Jean-Marc, et al.
(författare)
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Differences in Expansion Potential of Naive Chimeric Antigen Receptor T Cells from Healthy Donors and Untreated Chronic Lymphocytic Leukemia Patients
- 2018
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Therapy with chimeric antigen receptor T (CART) cells for hematological malignancies has shown promising results. Effectiveness of CART cells may depend on the ratio of naive (T-N) vs. effector (T-E) T cells, TN cells being responsible for an enduring antitumor activity through maturation. Therefore, we investigated factors influencing the T-N/T-E ratio of CART cells.Materials and methods: CART cells were generated upon transduction of peripheral blood mononuclear cells with a CD19.CAR-CD28-CD137zeta third generation retroviral vector under two different stimulating culture conditions: anti-CD3/anti-CD28 antibodies adding either interleukin (IL)-7/1L-15 or IL-2. CART cells were maintained in culture for 20 days. We evaluated 24 healthy donors (HDs) and 11 patients with chronic lymphocytic leukemia (CLL) for the composition of cell subsets and produced CART cells. Phenotype and functionality were tested using flow cytometry and chromium release assays.Results: IL -7/1L-15 preferentially induced differentiation into T-N, stem cell memory (T-SCM: naive CD27+ CD95+), CD4+ and CXCR3+ CART cells, while IL-2 increased effector memory (T-EM), CD56+ and CD4+ T regulatory (T-Reg) CART cells. The net amplification of different CART subpopulations derived from HDs and untreated CLL patients was compared. Particularly the expansion of CD4+ CART(N) cells differed significantly between the two groups. For HDs, this subtype expanded >60-fold, whereas CD4+ CART(N) cells of untreated CLL patients expanded less than 10-fold. Expression of exhaustion marker programmed cell death 1 on CART(N) cells on day 10 of culture was significantly higher in patient samples compared to HD samples. As the percentage of malignant B cells was expectedly higher within patient samples, an excessive amount of B cells during culture could account for the reduced expansion potential of CART(N) cells in untreated CLL patients. Final T-N/T-E ratio stayed <0.3 despite stimulation condition for patients, whereas this ratio was >2 in samples from HDs stimulated with IL-7/1L-15, thus demonstrating efficient CART(N) expansion.Conclusion: Untreated CLL patients might constitute a challenge for long-lasting CART effects in vivo since only a low number of T-N among the CART product could be generated. Depletion of malignant B cells before starting CART production might be considered to increase the T-N/T-E ratio within the CART product.
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