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1.
  • Azevedo, Flavio, et al. (författare)
  • Social and moral psychology of COVID-19 across 69 countries
  • 2023
  • Ingår i: Scientific Data. - : NATURE PORTFOLIO. - 2052-4463. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.
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2.
  • Van Bavel, Jay J., et al. (författare)
  • National identity predicts public health support during a global pandemic
  • 2022
  • Ingår i: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic. Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.
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3.
  • Ahearn, Thomas U., et al. (författare)
  • Common variants in breast cancer risk loci predispose to distinct tumor subtypes
  • 2022
  • Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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4.
  • Kapoor, Pooja Middha, et al. (författare)
  • Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
  • 2021
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
  • Tidskriftsartikel (refereegranskat)abstract
    • We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer. 
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5.
  • Dareng, EO, et al. (författare)
  • Polygenic risk modeling for prediction of epithelial ovarian cancer risk
  • 2022
  • Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 30:3, s. 349-362
  • Tidskriftsartikel (refereegranskat)abstract
    • Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28–1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08–1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21–1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29–1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35–1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
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6.
  • Dixon-Suen, Suzanne C, et al. (författare)
  • Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
  • 2022
  • Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.METHODS: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.RESULTS: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).CONCLUSION: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
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7.
  • Escala-Garcia, Maria, et al. (författare)
  • A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
  • 2020
  • Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
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8.
  • Fazey, Ioan, et al. (författare)
  • Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
  • 2020
  • Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
  • Tidskriftsartikel (refereegranskat)abstract
    • Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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9.
  • Mueller, Stefanie H., et al. (författare)
  • Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry
  • 2023
  • Ingår i: Genome Medicine. - : BioMed Central (BMC). - 1756-994X. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 x 10(-6)) and AC058822.1 (P = 1.47 x 10(-4)), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C.Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 x 10(-5)), demonstrating the importance of diversifying study cohorts.
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10.
  • Schwartz, Gregory G., et al. (författare)
  • Dalcetrapib Reduces Risk of New-Onset Diabetes in Patients With Coronary Heart Disease
  • 2020
  • Ingår i: Diabetes Care. - : AMER DIABETES ASSOC. - 0149-5992 .- 1935-5548. ; 43:5, s. 1077-1084
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE Incident type 2 diabetes is common among patients with recent acute coronary syndrome and is associated with an adverse prognosis. Some data suggest that cholesteryl ester transfer protein (CETP) inhibitors reduce incident type 2 diabetes. We compared the effect of treatment with the CETP inhibitor dalcetrapib or placebo on incident diabetes in patients with recent acute coronary syndrome. RESEARCH DESIGN AND METHODS In the dal-OUTCOMES trial, 15,871 patients were randomly assigned to treatment with dalcetrapib 600 mg daily or placebo, beginning 4-12 weeks after an acute coronary syndrome. Absence of diabetes at baseline was based on medical history, no use of antihyperglycemic medication, and hemoglobin A(1c) and serum glucose levels below diagnostic thresholds. Among these patients, incident diabetes after randomization was defined by any diabetes-related adverse event, new use of antihyperglycemic medication, hemoglobin A(1c) >= 6.5%, or a combination of at least two measurements of serum glucose >= 7.0 mmol/L (fasting) or >= 11.1 mmol/L (random). RESULTS At baseline, 10,645 patients (67% of the trial cohort) did not have diabetes. During a median follow-up of 30 months, incident diabetes was identified in 403 of 5,326 patients (7.6%) assigned to dalcetrapib and in 516 of 5,319 (9.7%) assigned to placebo, corresponding to absolute risk reduction of 2.1%, hazard ratio of 0.77 (95% CI 0.68-0.88; P < 0.001), and a need to treat 40 patients for 3 years to prevent 1 incident case of diabetes. Considering only those with prediabetes at baseline, the number needed to treat for 3 years to prevent 1 incident case of diabetes was 25. Dalcetrapib also decreased the number of patients who progressed from normoglycemia to prediabetes and increased the number who regressed from diabetes to no diabetes. CONCLUSIONS In patients with a recent acute coronary syndrome, incident diabetes is common and is reduced substantially by treatment with dalcetrapib.
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11.
  • Ahme, Antonia, et al. (författare)
  • Warming increases the compositional and functional variability of a temperate protist community
  • 2024
  • Ingår i: Science of the Total Environment. - 0048-9697 .- 1879-1026. ; 926
  • Tidskriftsartikel (refereegranskat)abstract
    • Phototrophic protists are a fundamental component of the world's oceans by serving as the primary source of energy, oxygen, and organic nutrients for the entire ecosystem. Due to the high thermal seasonality of their habitat, temperate protists could harbour many well-adapted species that tolerate ocean warming. However, these species may not sustain ecosystem functions equally well. To address these uncertainties, we conducted a 30-day mesocosm experiment to investigate how moderate (12 °C) and substantial (18 °C) warming compared to ambient conditions (6 °C) affect the composition (18S rRNA metabarcoding) and ecosystem functions (biomass, gross oxygen productivity, nutritional quality – C:N and C:P ratio) of a North Sea spring bloom community. Our results revealed warming-driven shifts in dominant protist groups, with haptophytes thriving at 12 °C and diatoms at 18 °C. Species responses primarily depended on the species' thermal traits, with indirect temperature effects on grazing being less relevant and phosphorus acting as a critical modulator. The species Phaeocystis globosa showed highest biomass on low phosphate concentrations and relatively increased in some replicates of both warming treatments. In line with this, the C:P ratio varied more with the presence of P. globosa than with temperature. Examining further ecosystem responses under warming, our study revealed lowered gross oxygen productivity but increased biomass accumulation whereas the C:N ratio remained unaltered. Although North Sea species exhibited resilience to elevated temperatures, a diminished functional similarity and heightened compositional variability indicate potential ecosystem repercussions for higher trophic levels. In conclusion, our research stresses the multifaceted nature of temperature effects on protist communities, emphasising the need for a holistic understanding that encompasses trait-based responses, indirect effects, and functional dynamics in the face of exacerbating temperature changes.
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12.
  • Ariens, Robert, et al. (författare)
  • Illustrated State-of-the-Art Capsules of the ISTH 2020 Congress
  • 2020
  • Ingår i: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS. - : Wiley. - 2475-0379. ; 4:5, s. 680-713
  • Forskningsöversikt (refereegranskat)abstract
    • The 2020 Congress of the International Society of Thrombosis and Haemostasis (ISTH) was held virtually July 12-15, 2019, due to the coronavirus disease 2019 pandemic. The congress convenes annually to discuss clinical and basic topics in hemostasis and thrombosis. Each year, the program includes State of Art (SOA) lectures given by prominent scientists. Presenters are asked to create Illustrated Capsules of their talks, which are concise illustrations with minimal explanatory text. Capsules cover major themes of the presentation, and these undergo formal peer review for inclusion in this article. Owing to the shift to a virtual congress this year, organizers reduced the program size. There were 39 SOA lectures virtually presented, and 29 capsules (9 from talks omitted from the virtual congress) were both submitted and successful in peer review, and are included in this article. Topics include the roles of the hemostatic system in inflammation, infection, immunity, and cancer, platelet function and signaling, platelet function disorders, megakaryocyte biology, hemophilia including gene therapy, phenotype tests in hemostasis, von Willebrand factor, anticoagulant factor V, computational driven discovery, endothelium, clinical and basic aspects of thrombotic microangiopathies, fibrinolysis and thrombolysis, antithrombotics in pediatrics, direct oral anticoagulant management, and thrombosis and hemostasis in pregnancy. Capsule authors invite virtual congress attendees to refer to these capsules during the live presentations and participate on Twitter in discussion. Research and Practice in Haemostasis and Thrombosis will release 2 tweets from @RPTHJournal during each presentation, using #IllustratedReview, #CoagCapsule and #ISTH2020. Readers are also welcome to utilize capsules for teaching and ongoing education.
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13.
  • Arshamian, Artin, et al. (författare)
  • Human sickness detection is not dependent on cultural experience
  • 2021
  • Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 288:1954
  • Tidskriftsartikel (refereegranskat)abstract
    • Animals across phyla can detect early cues of infection in conspecifics, thereby reducing the risk of contamination. It is unknown, however, if humans can detect cues of sickness in people belonging to communities with whom they have limited or no experience. To test this, we presented Western faces photographed 2 h after the experimental induction of an acute immune response to one Western and five non-Western communities, including small-scale hunter-gatherer and large urban-dwelling communities. All communities could detect sick individuals. There were group differences in performance but Western participants, who observed faces from their own community, were not systematically better than all non-Western participants. At odds with the common belief that sickness detection of an out-group member should be biased to err on the side of caution, the majority of non-Western communities were unbiased. Our results show that subtle cues of a general immune response are recognized across cultures and may aid in detecting infectious threats.
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14.
  • Axfors, Cathrine, et al. (författare)
  • Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
  • 2021
  • Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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15.
  • Balter, Leonie J. T., et al. (författare)
  • Lipopolysaccharide-induced changes in the kynurenine pathway and symptoms of sickness behavior in humans
  • 2023
  • Ingår i: Psychoneuroendocrinology. - 0306-4530 .- 1873-3360. ; 153
  • Tidskriftsartikel (refereegranskat)abstract
    • Metabolites of the kynurenine pathway are hypothesized to be implicated in inflammation-associated depression, but there is a lack of experimental studies in humans assessing the kinetics of kynurenine metabolites in relation to experimentally-induced sickness. The aim of the present study was to assess changes in the kynurenine pathway and to explore its relation to symptoms of sickness behavior during an acute experimental immune challenge.This double-blind placebo-controlled randomized cross-over study included 22 healthy human participants (n = 21 both sessions, Mage = 23.4, SD = 3.6, nine women) who received an intravenous injection of 2.0 ng/kg lipopolysaccharide (LPS) and saline (placebo) on two different occasions in a randomized order. Blood samples (0 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 7 h post-injection) were analyzed for kynurenine metabolites and inflammatory cytokines. The intensity of symptoms of sickness behavior was assessed using the 10-item Sickness Questionnaire at 0 h, 1.5 h, 3 h, 5 h, and 7 h post-injection.LPS induced significantly lower concentrations of plasma tryptophan (at 2 h, 4 h, 5 h, and 7 h post-injection), kynurenine (at 2 h, 3 h, 4 h, and 5 h post-injection), nicotinamide (at 4 h, 5 h, and 7 h post-injection), and higher levels for quinolinic acid at 5 h post-injection as compared to placebo. LPS did not affect kynurenic acid, 3-hydroxykynurenine, and picolinic acid. The development of the sickness symptoms was largely similar across items, with the highest levels around 1.5–3 h post-injection. Changes in plasma levels of kynurenine metabolites seem to coincide rather than precede or follow changes in subjective sickness. Exploratory analyses indicate that higher Sickness Questionnaire total scores at 1.5–5 h post-injection were correlated with lower kynurenic acid and nicotinamide levels.These results lend further support for LPS-induced changes in the kynurenine pathway, but may not, as interpreted from blood levels, causally link to LPS-induced acute symptoms of sickness behavior. Future research may consider a larger sample to further scrutinize the role of the kynurenine pathway in the sickness response.
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16.
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17.
  • Bryhn, Andreas, et al. (författare)
  • Fisk- och skaldjursbestånd i hav och sötvatten 2019 : Resursöversikt
  • 2020
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Fisken i havet är en resurs som rör sig fritt över nationella gränser. EU har därför en gemensam fiskeripolitik (GFP). Många arter som är viktiga för Sverige regleras inte i GFP och förvaltas därför nationellt.Denna rapport syftar till att:beskriva utvecklingen av fiskeripolitikenförklara den nuvarande politikens mål och regelverk och dess relation till mål och regler på miljöområdetförklara politikens nationella genomförande och det nationella handlingsutrymmetexemplifiera hur Havs- och vattenmyndigheten arbetat med att reglera fisket.
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18.
  • Buchbinder, David, et al. (författare)
  • Predictors of Loss to Follow-Up Among Pediatric and Adult Hematopoietic Cell Transplantation Survivors : A Report from the Center for International Blood and Marrow Transplant Research
  • 2020
  • Ingår i: Biology of blood and marrow transplantation. - : Elsevier. - 1083-8791 .- 1523-6536. ; 26:3, s. 553-561
  • Tidskriftsartikel (refereegranskat)abstract
    • Follow-up is integral for hematopoietic cell transplantation (HCT) care to ensure surveillance and intervention for complications. We characterized the incidence of and predictors for being lost to follow-up. Two-year survivors of first allogeneic HCT (10,367 adults and 3865 children) or autologous HCT (7291 adults and 467 children) for malignant/nonmalignant disorders between 2002 and 2013 reported to the Center for International Blood and Marrow Transplant Research were selected. The cumulative incidence of being lost to follow-up (defined as having missed 2 consecutive follow-up reporting periods) was calculated. Marginal Cox models (adjusted for center effect) were fit to evaluate predictors. The 10-year cumulative incidence of being lost to follow-up was 13% (95% confidence interval [CI], 12% to 14%) in adult allogeneic HCT survivors, 15% (95% CI, 14% to 16%) in adult autologous HCT survivors, 25% (95% CI, 24% to 27%) in pediatric allogeneic HCT survivors, and 24% (95% CI, 20% to 29%) in pediatric autologous HCT survivors. Factors associated with being lost to follow-up include younger age, nonmalignant disease, public/no insurance (reference: private), residence farther from the tranplantation center, and being unmarried in adult allogeneic HCT survivors; older age and testicular/germ cell tumor (reference: non-Hodgkin lymphoma) in adult autologous HCT survivors; older age, public/no insurance (reference: private), and nonmalignant disease in pediatric allogeneic HCT survivors; and older age in pediatric autologous HCT survivors. Follow-up focusing on minimizing attrition in high-risk groups is needed to ensure surveillance for late effects.
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19.
  • Coignard, J, et al. (författare)
  • A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers
  • 2021
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1078-
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
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21.
  • Cornell, Robert F., et al. (författare)
  • Bortezomib-Based Induction Is Associated with Superior Outcomes in Light Chain Amyloidosis Patients Treated with Autologous Hematopoietic Cell Transplantation Regardless of Plasma Cell Burden
  • 2021
  • Ingår i: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 27:3, s. 264.e1-264.e7
  • Tidskriftsartikel (refereegranskat)abstract
    • The benefits of pre-transplant induction chemotherapy in light chain (AL) amyloidosis, a low burden plasma cell (PC) neoplasm associated with multiorgan dysfunction, is debatable, although with the availability of bortezomib, this approach is being increasingly pursued. We analyzed the outcomes of AL amyloidosis patients undergoing autologous hematopoietic cell transplant between 2014 and 2018 that were reported to the Center for International Blood and Marrow Transplant Research database. Of 440 patients, 294 received bortezomib-based induction, and 146 received no induction. Patients receiving induction had greater PC burden compared to no induction (PC 10% or more, 39% versus 11%; P < .01). At 2 years, the induction group compared to no induction had lower relapse/progression: 13% (9% to 18%) versus 23% (16% to 32%) (P = .02); better progression-free survival (PFS): 82% (77% to 87%) versus 69% (61% to 77%) (P < .01); and similar overall survival (OS): 92% (88% to 95%) versus 89% (84% to 94%) (P = .22), findings that were confirmed on multivariate analysis. A subset analysis limited to patientswith <10% PC also showed superior relapse/progression (hazard ratio [HR],.43; 95% confidence interval [CI],.24 to.78; P < .01) and PFS (HR,.43; 95% CI,.26 to .72; P < .01) for induction compared to no induction. Thus, we conclude that pre-transplant bortezomib-based induction was associated with improved relapse/progression and PFS in AL amyloidosis. Longer survival follow-up is warranted, as OS was excellent in both cohorts at 2 years.
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22.
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23.
  • Dennis, J, et al. (författare)
  • Rare germline copy number variants (CNVs) and breast cancer risk
  • 2022
  • Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 65-
  • Tidskriftsartikel (refereegranskat)abstract
    • Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E−18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.
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24.
  • Escala-Garcia, M, et al. (författare)
  • Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis
  • 2021
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 19787-
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10−8 and 4.42 × 10−8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.
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25.
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26.
  • Farhadfar, Nosha, et al. (författare)
  • Impact of autologous blood transfusion after bone marrow harvest on unrelated donor's health and outcome : a CIBMTR analysis
  • 2020
  • Ingår i: Bone Marrow Transplantation. - : SPRINGERNATURE. - 0268-3369 .- 1476-5365. ; 55:11, s. 2121-2131
  • Tidskriftsartikel (refereegranskat)abstract
    • Pre-harvest autologous blood collection from bone marrow (BM) donors is performed to meet potential post-operative transfusion needs. This study examines the impact of autologous blood transfusion on BM donor's health and safety. The study included first-time unrelated BM donors from the United States whose BM harvest was facilitated by the National Marrow Donor Program (NMDP) centers between 2006 and 2017. Examination of 7024 BM donors revealed that 60% received at least one unit of autologous blood. The donors who received autologous blood were older, had lower hemoglobin pre-harvest, underwent longer duration of anesthesia, and higher volume BM harvest. Only donors who underwent high-volume BM harvest, defined as a BM harvest volume >27% of donor's blood volume, benefited from autologous transfusion. After a high-volume BM harvest, autologous blood transfusion was shown to decrease grade 2 to 4 collection-associated toxicities within 48 h of BM donation (p = 0.010) and shorten the time to donor-reported "complete" recovery from donation-associated symptoms (p < 0.001). Therefore, autologous transfusion could be avoided as support of marrow donation in the majority of unrelated BM donors and should be limited to cases where the planned BM harvest volume is expected to exceed 27% of donor's blood volume.
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27.
  • Farhadfar, Nosha, et al. (författare)
  • Impact of Pretransplantation Renal Dysfunction on Outcomes after Allogeneic Hematopoietic Cell Transplantation
  • 2021
  • Ingår i: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 27:5, s. 410-422
  • Tidskriftsartikel (refereegranskat)abstract
    • Renal dysfunction is a recognized risk factor for mortality after allogeneic hematopoietic cell transplantation (alloHCT), yet our understanding of the effect of different levels of renal dysfunction at time of transplantation on outcomes remains limited. This study explores the impact of different degrees of renal dysfunction on HCT outcomes and examines whether the utilization of incremental degrees of renal dysfunction based on estimated glomerular filtration rate (eGFR) improve the predictability of the hematopoietic cell transplantation comorbidity index (HCT-CI). The study population included 2 cohorts: cohort 1, comprising patients age >= 40 years who under went alloHCT for treatment of hematologic malignancies between 2008 and 2016 (n = 13,505; cohort selected given a very low incidence of renal dysfunction in individuals age <40 years), and cohort 2, comprising patients on dialysis at the time of HCT (n = 46). eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method. The patients in cohort 1 were assigned into 4 categories-eGFR >= 90 mL/min (n = 7062), eGFR 60 to 89 mL/min (n = 5264), eGFR 45 to 59 mL/min (n = 897), and eGFR <45 mL/min (n=282)-to assess the impact of degree of renal dysfunction on transplantation outcomes. Transplantation outcomes in patients on dialysis at the time of alloHCT were analyzed separately. eGFR <60 mL/min was associated with an increased risk for nonrelapse mortality (NRM) and requirement for dialysis post-HCT. Compared with the eGFR >= 90 group, the hazard ratio (HR) for NRM was 1.46 (P = .0001) for the eGFR 45 to 59 mL/min group and 1.74 (P = .004) for the eGFR <45 mL/min group. Compared with the eGFR >= 90 mL/min group, the eGFR 45 to 59 mL/min group (HR, 2.45; P < .0001) and the eGFR <45 mL/min group (HR, 3.09; P < .0001) had a higher risk of renal failure necessitating dialysis after alloHCT. In addition, eGFR <45 mL/min was associated with an increased overall mortality (HR, 1.63; P < .0001). An eGFR-based revised HCT-CI was also developed and shown to be predictive of overall survival (OS) and NRM, with predictive performance similar to the original HCT-CI. Among 46 patients on dialysis at alloHCT, the 1-year probability of OS was 20%, and that of NRM was 67%. The degree of pretransplantation renal dysfunction is an independent predictor of OS, NRM, and probability of needing dialysis after alloHCT. An eGFR-based HCT-CI is a validated index for predicting outcomes in adults with hematologic malignancies undergoing alloHCT. The outcomes of alloHCT recipients on dialysis are dismal; therefore, one should strongly weigh the significant risks of being on hemodialysis as a factor in determining alloHCT candidacy.
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28.
  • Farhadfar, Nosha, et al. (författare)
  • Weighty choices : selecting optimal G-CSF doses for stem cell mobilization to optimize yield
  • 2020
  • Ingår i: Blood Advances. - : AMER SOC HEMATOLOGY. - 2473-9529 .- 2473-9537. ; 4:4, s. 706-716
  • Tidskriftsartikel (refereegranskat)abstract
    • There are limited data on the effect of donor body mass index (BMI) on peripheral blood stem cell (PBSC) mobilization response to granulocyte colony-stimulating factor (G-CSF), especially in unrelated donors. Obesity has been associated with persistent leukocytosis, elevated circulating progenitor cells, and enhanced stem cell mobilization. Therefore, we hypothesized that adequate collection of CD34(+) cells may be achieved with lower doses (per kilogram of body weight) of G-CSF in donors with higher BMI compared with donors with lower BMI. Using the Center for International Blood and Marrow Transplant Research database, we evaluated the impact of donor BMI on G-CSF-mobilized PBSC yield in healthy unrelated donors. We examined 20 884 PBSC donations collected at National Marrow Donor Program centers between 2006 and 2016. We found significantly higher collection yields in obese and severely obese donors compared with normal and overweight donors. An increase in average daily G-CSF dose was associated with an increase in stem cell yield in donors with normal or overweight BMI. In contrast, an increase in average daily G-CSF dose beyond 780 mu g per day in obese and 900 mg per day in severely obese donors did not increase cell yield. Pain and toxicities were assessed at baseline, during G-CSF administration, and postcollection. Obesity was associated with higher levels of self-reported donation-related pain and toxicities in the pericollection and early postdonation recovery periods. This study suggests a maximum effective G-CSF dose for PBSC mobilization in obese and severely obese donors, beyond which higher doses of G-CSF add no increased yield.
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29.
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30.
  • Gerkin, Richard C., et al. (författare)
  • Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms
  • 2021
  • Ingår i: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 46
  • Tidskriftsartikel (refereegranskat)abstract
    • In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0–100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19−; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19− groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: −82.5 ± 27.2 points; C19−: −59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0–10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.
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31.
  • Gordon, Amy R., et al. (författare)
  • Human scent as a first-line defense against disease
  • 2023
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Individuals may have a different body odor, when they are sick compared to healthy. In the non-human animal literature, olfactory cues have been shown to predict avoidance of sick individuals. We tested whether the mere experimental activation of the innate immune system in healthy human individuals can make an individuals' body odor be perceived as more aversive (intense, unpleasant, and disgusting). Following an endotoxin injection (lipopolysaccharide; 0.6 ng/kg) that creates a transient systemic inflammation, individuals smelled more unpleasant compared to a placebo group (saline injection). Behavioral and chemical analyses of the body odor samples suggest that the volatile components of samples from sick individuals changed qualitatively rather than quantitatively. Our findings support the hypothesis that odor cues of inflammation in axillary sweat are detectable just a few hours after experimental activation of the innate immune system. As such, they may trigger behavioral avoidance, hence constituting a first line of defense against pathogens of infected conspecifics.
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32.
  • Hansson, Lina S., 1986-, et al. (författare)
  • Pointing out sickness : Detection of sickness from gait patterns
  • 2021
  • Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 98, s. 21-21
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: The ability to detect sick individuals is crucial for survival, by allowing avoidance of contagion. We have shown that humans can detect sick individuals from facial cues and body odors, but perception of these cues requires close proximity to the infectious person. Given that gait patterns can be detected from a distance and are altered during sickness, it would be beneficial to detect sickness from biological motion. Methods: We collected videos and point-light displays of walking individuals who were either made sick experimentally with an injection of lipopolysaccharide, or who were healthy (placebo). In study 1, 106 naive subjects watched these displays and rated them as coming from someone sick or healthy. In study 2, 106 other subjects rated health, sadness and tiredness of the displays on a VAS scale. Results: In Study 1, the sensitivity was 59% for videos and 57% for point-light displays, while the specificity was 74% for videos and 61% for point-light displays. Additional results will be presented at the conference. Conclusion: This study will indicate if sickness can be detected from gait patterns, possibly adding to immune defensive behaviors by facilitating avoidance of contagious peers.
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33.
  • Hansson, Lina S., et al. (författare)
  • Regulation of emotions during experimental endotoxemia : A pilot study
  • 2021
  • Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 93, s. 420-424
  • Tidskriftsartikel (refereegranskat)abstract
    • Even though dysfunctional emotion regulation is prominent in depression and a link between depression and inflammation is well established, there is little knowledge about how inflammation affects the regulation of emotions. The aim of this pilot study was to explore the effect of experimentally induced inflammation on the cognitive reappraisal of emotions, and to assess domain specificity by comparing success in regulation of emotions towards two unpleasant stimuli classes (general negative stimuli and disgust stimuli). In a between-subject design, ten healthy participants were injected with an intravenous injection of lipopolysaccharide (2 ng/kg body weight) and eleven were injected with saline. Participants performed a cognitive reappraisal task, in which they had to down-regulate or up-regulate their emotions towards general negative stimuli and disgust stimuli, 5–6 h post-injection. Contrary to our hypotheses, participants injected with lipopolysaccharide reported greater success in down-regulating emotional responses towards unpleasant stimuli as compared to the saline group. In addition, both groups were poorer at down-regulating emotions towards disgust stimuli as compared to general negative stimuli. The current pilot study indicates that cognitive reappraisal of emotions is affected during experimental endotoxemia, and suggests that disgust stimuli might be difficult to reappraise.
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34.
  • Hansson, Lina S., et al. (författare)
  • The walking sick : Perception of experimental sickness from biological motion
  • 2023
  • Ingår i: Brain, behavior, and immunity. - : Elsevier. - 0889-1591 .- 1090-2139. ; 113, s. 319-327
  • Tidskriftsartikel (refereegranskat)abstract
    • Identification of sick conspecifics allows for avoidance of infectious threats, and is therefore an important behavioral defense against diseases. Here, we investigated if humans can identify sick individuals solely from biological motion and posture (using point-light displays). Additionally, we sought to determine which movements and sickness parameters would predict such detection. We collected video clips and derived point-light displays (one stride presented in a loop) of sick walkers (injected with lipopolysaccharide at 2.0 ng/kg body weight) and the same walkers when healthy (injected with saline). We then presented these displays to two groups, one group classified each walker as sick or healthy (study 1, n = 106), and the other group scored the walkers’ health on a visual analogue scale (study 2, n = 106). The raters were able to identify sick individuals above chance, and rated sick walkers as having worse health, both from observing video clips and point-light displays. Furthermore, both sickness detection and worse apparent health were predicted by inflammation-induced increase in rigidity and slower walking, but not other cues. Altogether, these findings indicate that biological motion can serve as a sickness cue, possibly allowing humans to identify sick conspecifics from a distance, and thereby allowing for disease avoidance.
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35.
  • Hansson, Lina S., 1986-, et al. (författare)
  • The walking sick : what predicts the detection of walking sick individuals?
  • 2022
  • Ingår i: Brain, behavior, and immunity. - : Elsevier. - 0889-1591 .- 1090-2139. ; 106, s. 36-36
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Methods: In two studies, raters watched video recordings and point-light displays (i.e. dots depicting the body joints) of walking individuals who were either experimentally sick (after injection with lipopolysaccharide at 2.0 ng/kg bw) or healthy (after a placebo injection). In study 1, 106 raters classified each walking individual as either sick or healthy. In study 2, 106 other raters graded health of the stimuli on a visual analogue scale. We assessed the predicting effect on sickness detection (study 1) and apparent health (study 2) of walking parameters (objective measures of stride length, width, time, as well as knee angle, arm angle, and head angle) and well-known sickness responses (Sickness Questionnaire score, pain intensity, body temperature, and interleukin-6 concentration).Results: In study 1, shorter steps was the only predictor of the detection of sick individuals from video recordings (β=0.712(0.257), p=0.02). In the point-light displays, slower, wider, stiffer and shorter steps, all predicted a better sickness detection (β=0.0003(0.0001)-0.415(0.126), p<0.05).In study 2, lipopolysaccharide-induced slower, shorter and stiffer steps (B=5.214(1.888)-6.385(2.083), p<0.01), as well as higher interleukin-6 concentrations (B=0.051(0.020), p=0.01), predicted worse health ratings of sick individuals in the video recordings. In the point-light displays, lipopolysaccharide-induced slower, shorter and stiffer steps, and more head tilting, predicted worse health ratings of sick individuals (B=4.185(1.892)-6.701(2.092), p<0.05).Conclusions: The results imply that specific changes in walking parameters may aid in sickness detection, possibly regulating approach-avoidance behaviors towards sick peers.
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36.
  • Hellström, Daniel, et al. (författare)
  • Let's go thrift shopping : exploring circular business model innovation in fashion retail
  • 2024
  • Ingår i: Technological Forecasting and Social Change. - 0040-1625. ; 198, s. 1-13
  • Tidskriftsartikel (refereegranskat)abstract
    • The circular economy offers promising opportunities for the fashion industry to decouple revenue streams from resource use. To take advantage of these opportunities, this research study investigates circular business model innovation and advances knowledge on what drives such innovation and how this process can be accelerated. In a collaborative setting, we developed and validated a circular business model that supports clothing reuse. Inspired by design science and supported by business model theory, the research reveals that consumer centricity drives circular business model innovation, and logistics services act as a catalyst accelerating this process. These findings provide foresight to support retail transformation toward the circular economy. Thirteen business model-oriented propositions are put forward to elaborate theory.
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37.
  • Hellström, Daniel, et al. (författare)
  • Let’s go thrift shopping : exploring circular business model innovation in fashion retail
  • 2023
  • Konferensbidrag (refereegranskat)abstract
    • The circular economy offers promising opportunities for the fashion industry to decouple revenue streams from resource use. To take advantage of these opportunities, this research investigates circular business model innovation and advances knowledge of what drives such innovation and how this process can be accelerated. In a collaborative setting, we developed and validated a circular business model that supports clothing reuse. Inspired by design-science and supported by business model theory, the model reveals patterns of circular business model innovation that revolve around consumer centricity as an innovation driver, the role of logistics as an innovation catalyst, and how these affect business model transition toward a circular economy. Thirteen business model-oriented propositions that elaborate theory are put forward based on these findings.
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38.
  • Hellström, Daniel, et al. (författare)
  • Systemförändring för omställning till hållbar e-handel : Kraftsamling som accelererar innovation
  • 2021
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • E-handeln ökar snabbare än någonsin vilket medför en mängd hållbarhetsutmaningar för hela samhället. För att nå de globala målen råder inget tvivel om att vi behöver transformera e-handel till ett hållbart system. Likaså vet vi att kunskap och innovation är avgörande för att ge sig på denna komplexa samhällsutmaning. Men vilka områden behövs förändras för att åstadkomma stor effekt på hela systemet och på så sätt bidrar till den omställning som framtiden kräver? Vilka knäckfrågor måste adresseras? Detta undersöktes i en workshopserie, baserat på Design Thinking metodik, för att få en tydlig behovsbild över vilka frågor och centrala områden som kräver en genomgripande förändring.Med hjälp av aktörer från olika privata och offentliga sektorer, branscher och discipliner identifierades åtta sammanhängande problemområden. Dessa områden är starkt sammanhängande och kretsar kring ”den hållbara leveransen”. Genom att skapa förändringar på något av dessa områden skapas stor effekt på hela systemet vilket kan bidrar till den omställning som eftersträvas. De är följande:1. Konsumtion och livsstil2. Leveransplatser3. Dynamisk och flexibel leverans4. Retur5. Förpackningssystem6. Försörjning och logistik7. Samordnad distribution8. StadsplaneringFör att effektivt åstadkomma genomgripande systemförändring finns det ett tydligt behov att kraftsamla kring de identifierade områdena. De viktigaste orsakerna till behovet av en central kraftsamling är:• Det saknas ett helhetsgrepp och sammanhållen nod för strategisk koordinering av initiativ• Det råder stor kunskapsbrist hos likväl företag och offentlig sektor som hos konsumenterna – det behövs en drivande part för att fylla kunskapsgapet• Marknaden kan inte lösa problematiken på egen hand utan behöver stöd och guidning för hur vi tillsammans tar oss hållbart framåt• Få igång och intensifiera samordning och strategisk koordinering mellan det offentliga och privataFörlag till kraftsamling är en integrerad samverkansarena och kompetenscenter för hållbar e-handel där CLOSER och ReLog ingår ett strategiskt samarbete för att binda samman kompetenser och gemensamt driva forskning- och innovationsprojekt. Förslaget innebär en ny och helt unik samverkansmiljö där vi integrerar två nationellt starka kunskapsnoder, skapar en sammanhållande nod med vetenskapligt- och behovsbaserad projektverkstad som tar ett helhetsgrepp på e-handelns möjligheter och utmaningar. CLOSER och ReLog har gemensamt ett upparbetat strukturkapital och ett nationellt renommé för att driva komplexa samverkansprojekt i gränssnitt mellan offentliga och privata aktörer. Sammanvävningen innebär en konsolidering av två starka nätverk inom olika sektorer, branscher, och mellan offentliga och privata aktörer – en förutsättning för att få förändring på plats eftersom ingen har förmågan att åstadkomma systemförändring ensamt, men tillsammans har de unika möjligheter.
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39.
  • Hellström, Daniel, et al. (författare)
  • Så ställer vi om till hållbar e-handel
  • 2021
  • Ingår i: Supply Chain Effect. - 2000-8457. ; 2021:2, s. 38-41
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • E-commerce is a complex societal challenge with an enormous potential to contribute to sustainable development. In order to capture this potential and transform e-commerce into a sustainable system requires radical change. But which areas are in need of change in order to achieve a grand effect and what key issues must addressed?
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40.
  • Hellström, Daniel, et al. (författare)
  • Transition Towards Sustainable E-Commerce: A Design Thinking Approach
  • 2022
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • AimTo achieve the sustainable development goals there is no doubt that we need to transform e-commerce into a sustainable system. Individual efforts are not enough. We need changes at the system level. We also know that research and innovation are crucial for tackling this global and complex societal challenge. How do we transform e-commerce into a sustainable system? What key areas and issues need to be addressed?MethodologyGrounded in Design Thinking, we approach this complex challenge from a user perspective. In total four workshops were conducted with about 20 participants in each session. A wide range of actors, e.g. authorities, municipalities, industries, and business, participated in each workshop, which lasted approximately three hours. Multiple investigators collected and analysed the data.Key results/conclusionsThis study identifies eight multidisciplinary and interconnected areas in need of radical change in order to transform e-commerce into a sustainable system. These are: dynamic and flexible delivery, delivery location, packaging, horizontal distribution collaboration, returns, consumption lifestyles, logistics predictions, and urban planning and design. Strategic change in the form of new knowledge and innovation in these areas have the potential to effect the entire e-commerce system. Based on these insights and to effectively bring about radical system change, we formed an Alliance for SusTainable E-commeRce (ASTER) acting as the national competence hub to strategically coordinate initiatives and accelerate demonstration and collaboration projects. ASTER use Vinnova's mission-oriented approach, which means getting different actors to work together in the same direction towards common goals.
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41.
  • Hsu, Jack W., et al. (författare)
  • Collection of Peripheral Blood Progenitor Cells in 1 Day Is Associated with Decreased Donor Toxicity Compared to 2 Days in Unrelated Donors
  • 2020
  • Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 26:6, s. 1210-1217
  • Tidskriftsartikel (refereegranskat)abstract
    • Peripheral blood stem cells (PBSCs) have been increasingly used for allogeneic hematopoietic cell transplantation instead of bone marrow stem cells. Current National Marrow Donor Program policy recommends 5 days of daily filgrastim, followed by either 1 or 2 days of apheresis for unrelated donors, depending on collection center choice. To date, there are no published studies comparing the differences in donor experience between 1 day and 2 days of apheresis. We examined 22,348 adult unrelated donor collections in 184 centers between 2006 and 2016. Of these 22,348 donors, 20,004 (89.5%) had collection on 1 day, and the other 2344 (9.5%) had collection over 2 days. Information on why donors underwent apheresis in 1 day or 2 days was not available. Donors who underwent apheresis in 1 day were more likely to be male (67% versus 46%; P < .001), younger (age <30 years, 48% versus 36%; P < .001), and have a higher body weight (83.0 kg versus 75.9 kg; P< .001) and body mass index (BMI; >30, 30% versus 22%; P < .001). Successful collection of the requested CD34(+) cell count was achieved on the first day in 82% of 1-day collections and in 16% of 2-day collections. Despite not administering filgrastim the evening after the first day of collection in patients who underwent 2 days of apheresis, the median concentration of CD34' cells/I, in the product was higher on the second day of apheresis compared with the first day (23.8 x 10(6) CD34(+)/L. on day 1 versus 28.7 x 10(6) CD34(+)/L. on day 2; P< .001). Donors who underwent collection in 1 day were less likely to experience citrate toxicity (36% versus 52%; P< .001), hospitalization (1% versus 6%; P< .001), and other side effects related to apheresis (Modified Toxicity Criteria incidence: 20% versus 26%; P < .001). Female sex, older age, collection via central lines, and higher BMI were factors associated with greater likelihood for the development of toxicity, whereas less toxicity was noted in those with higher CD34(+) counts and more blood processed on the first day of collection. We conclude that although unrelated donors can be successfully collected in 1 day or 2 days, 1-day apheresis procedures were associated with less overall toxicity, and thus we recommend single-day collections, especially if the requested number of cells have been collected in 1 day.
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42.
  • Humphries, Sophia, et al. (författare)
  • Association between β-blocker dose and quality of life after myocardial infarction : a real-world Swedish register-linked study
  • 2022
  • Ingår i: European Heart Journal. - : Oxford University Press. - 2048-8726 .- 2048-8734. ; 11:6, s. 491-500
  • Tidskriftsartikel (refereegranskat)abstract
    • Background β-blockers are routinely administered to patients following myocardial infarction (MI), yet their potential effect on health-related quality of life (HRQoL) is not entirely understood. We investigated the relationship between two different doses of β-blockers with HRQoL following MI.Methods and results This nationwide observational study used Swedish national registries to collate sociodemographic, clinical, medication, and HRQoL {the latter operationalized using EuroQol [European Quality of Life Five Dimensions Questionnaire (EQ-5D)]}. Estimates at 6–10 weeks and 12–14 months post-MI follow-up from pooled linear and logistic models were calculated after multiple imputation. We identified 35 612 patients with first-time MI, discharged with β-blockers, and enrolled in cardiac rehabilitation between 2006 and 2015. Upon discharge, patients were either dispensed <50% [24 082 (67.6%)] or ≥50% [11 530 (32.4%)] of the target dosage, as defined in previous trials. After adjusting for pre-defined covariates, neither the EQ-5D Index nor the Emotional Distress items were statistically different between groups. The EQ-VAS score was significantly lower in patients treated with ≥50% target β-blocker dose than those treated with <50% of the target dose [−0.87 [−1.23, −0.46], P < .001]. Results were similar at the 12-month follow-up and across sub-groups separated by sex and age.Conclusion No difference in HRQoL was found among patients taking <50% vs. ≥50% of the target β-blocker dose, except for the EQ-VAS in which higher scores were reported in those taking a lower dose. The clinical meaningfulness of this statistical significance is likely low.
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43.
  • Humphries, Sophia, et al. (författare)
  • Internet-Based Cognitive Behavioral Therapy for Patients Reporting Symptoms of Anxiety and Depression After Myocardial Infarction : U-CARE Heart Randomized Controlled Trial Twelve-Month Follow-up
  • 2021
  • Ingår i: Journal of Medical Internet Research. - : JMIR Publications. - 1438-8871. ; 23:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The U-CARE Heart trial was one of the first randomized controlled trials to evaluate the effect of internet-based cognitive behavioral therapy on self-reported symptoms of anxiety or depression for patients with a recent myocardial infarction. While the effects of internet-based cognitive behavioral therapy on Hospital Anxiety and Depression Scale (HADS) scores at 14 weeks postbaseline were not significant, in this study, we investigated possible long-term effects of treatment.Objective: The aim of this study was to evaluate the long-term effectiveness of internet-based cognitive behavioral therapy on self-reported symptoms of anxiety and depression in patients 12 months after a myocardial infarction and to explore subsequent occurrences of cardiovascular disease events.Methods: Shortly after acute myocardial infarction, 239 patients (33% female, mean age 59.6 years) reporting mild-to-moderate symptoms of anxiety or depression were randomized to 14 weeks of therapist-guided internet-based cognitive behavioral therapy (n=117) or treatment as usual (n=122). Data from national registries were used to explore group differences in clinical outcomes such as cardiovascular disease and cardiovascular-related mortality for a follow-up period of up to 5 years: group differences in HADS total score 1 year post-myocardial infarction, the primary outcome, was analyzed using multiple linear regression. Secondary outcomes, such as HADS anxiety and depression subscales and the Cardiac Anxiety Questionnaire total score (CAQ), which measures heart-focused anxiety, were analyzed in the same way. Multiple imputation was used to account for missing data, and a pooled treatment effect was estimated. Adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) for data pertaining to registry outcomes.Results: Both groups reported lower HADS total scores 1 year after myocardial infarction than those at baseline. HADS total scores were not significantly different between the treatment and control groups 1 year after myocardial infarction (beta=-1.14, 95% CI -2.73 to 0.45, P=.16). CAQ was the only measure improved significantly by internet-based cognitive behavioral therapy when compared with treatment as usual ( beta=-2.58, 95% CI -4.75 to -0.42, P=.02) before adjusting for multiple comparisons. The composite outcome of nonfatal cardiovascular events and cardiovascular-related mortality did not differ between groups but was numerically higher in the internet-based cognitive behavioral therapy group, who were at slightly greater risk (HR 1.8, 95% CI 0.96 to 3.4, P=.07). Adjusting for previous myocardial infarction and diabetes attenuated this estimate (HR 1.5, 95% CI 0.8 to 2.8, P=.25).Conclusions: Internet-based cognitive behavioral therapy was not superior in reducing self-reported symptoms of depression or anxiety compared to treatment as usual at the 1-year follow-up after myocardial infarction. A reduction in cardiac-related anxiety was observed but was not significant after adjusting for multiple comparisons. There was no difference in risk of cardiovascular events between the treatment groups. Low treatment adherence, which might have affected treatment engagement and outcomes, should be considered when interpreting these results.
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44.
  • Ideböhn, Veronica, 1992, et al. (författare)
  • Symmetry breaking in core-valence double ionisation of allene
  • 2023
  • Ingår i: Communications Chemistry. - : Springer Nature. - 2399-3669. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Allene serves as a model to study multiple ionization of organic molecules. Here, the authors use synchrotron radiation-based multi-particle coincidence techniques and high-level ab initio calculations to propose a simple physical model to elucidate the symmetry breaking in core-valence double ionization of allene. Conventional electron spectroscopy is an established one-electron-at-the-time method for revealing the electronic structure and dynamics of either valence or inner shell ionized systems. By combining an electron-electron coincidence technique with the use of soft X-radiation we have measured a double ionisation spectrum of the allene molecule in which one electron is removed from a C1s core orbital and one from a valence orbital, well beyond Siegbahns Electron-Spectroscopy-for-Chemical-Analysis method. This core-valence double ionisation spectrum shows the effect of symmetry breaking in an extraordinary way, when the core electron is ejected from one of the two outer carbon atoms. To explain the spectrum we present a new theoretical approach combining the benefits of a full self-consistent field approach with those of perturbation methods and multi-configurational techniques, thus establishing a powerful tool to reveal molecular orbital symmetry breaking on such an organic molecule, going beyond Lowdins standard definition of electron correlation.
  •  
45.
  • Im, Annie, et al. (författare)
  • Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide
  • 2020
  • Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 26:8, s. 1459-1468
  • Tidskriftsartikel (refereegranskat)abstract
    • Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.
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46.
  • John, Meenu Mary, et al. (författare)
  • Advancing MLOps from Ad hoc to Kaizen
  • 2023
  • Ingår i: 2023 49th Euromicro Conference on Software Engineering and Advanced Applications (SEAA). - : Institute of Electrical and Electronics Engineers (IEEE). - 9798350342352 - 9798350342369
  • Konferensbidrag (refereegranskat)abstract
    • Companies across various domains increasingly adopt Machine Learning Operations (MLOps) as they recognise the significance of operationalising ML models. Despite growing interest from practitioners and ongoing research, MLOps adoption in practice is still in its initial stages. To explore the adoption of MLOps, we employ a multi-case study in seven companies. Based on empirical findings, we propose a maturity model outlining the typical stages companies undergo when adopting MLOps, ranging from Ad hoc to Kaizen. We identify five dimensions associated with each stage of the maturity model as part of our MLOps framework. We also map these seven companies to the identified stages in the maturity model. Our study serves as a roadmap for companies to assess their current state of MLOps, identify gaps and overcome obstacles to successfully adopting MLOps.
  •  
47.
  • John, Meenu Mary, et al. (författare)
  • Advancing MLOps from Ad hoc to Kaizen
  • 2023
  • Ingår i: Proceedings - 2023 49th Euromicro Conference on Software Engineering and Advanced Applications, SEAA 2023. ; , s. 94-101
  • Konferensbidrag (refereegranskat)abstract
    • Companies across various domains increasingly adopt Machine Learning Operations (MLOps) as they recognise the significance of operationalising ML models. Despite growing interest from practitioners and ongoing research, MLOps adoption in practice is still in its initial stages. To explore the adoption of MLOps, we employ a multi-case study in seven companies. Based on empirical findings, we propose a maturity model outlining the typical stages companies undergo when adopting MLOps, ranging from Ad hoc to Kaizen. We identify five dimensions associated with each stage of the maturity model as part of our MLOps framework. We also map these seven companies to the identified stages in the maturity model. Our study serves as a roadmap for companies to assess their current state of MLOps, identify gaps and overcome obstacles to successfully adopting MLOps.
  •  
48.
  • John, Meenu Mary, et al. (författare)
  • AI deployment architecture: Multi-case study for key factor identification
  • 2020
  • Ingår i: Proceedings - Asia-Pacific Software Engineering Conference, APSEC. - : IEEE. - 1530-1362. ; 2020-December, s. 395-404
  • Konferensbidrag (refereegranskat)abstract
    • Machine learning and deep learning techniques are becoming increasingly popular and critical for companies as part of their systems. However, although the development and prototyping of ML/DL systems are common across companies, the transition from prototype to production-quality deployment models are challenging. One of the key challenges is how to determine the selection of an optimal architecture for AI deployment. Based on our previous research, and to offer support and guidance to practitioners, we developed a framework in which we present five architectural alternatives for AI deployment ranging from centralized to fully decentralized edge architectures. As part of our research, we validated the framework in software-intensive embedded system companies and identified key challenges they face when deploying ML/DL models. In this paper, and to further advance our research on this topic, we identify factors that help practitioners determine what architecture to select for the ML/D L model deployment. For this, we conducted a follow-up study involving interviews and workshops in seven case companies in the embedded systems domain. Based on our findings, we identify three key factors and develop a framework in which we outline how prioritization and trade-offs between these results in certain architecture. The contribution of the paper is threefold. First, we identify key factors critical for AI system deployment. Second, we present the architecture selection framework that explains how prioritization and trade-offs between key factors result in the selection of a certain architecture. Third, we discuss additional factors that mayor may not influence the selection of an optimal architecture.
  •  
49.
  • John, Meenu Mary, et al. (författare)
  • AI on the Edge: Architectural Alternatives
  • 2020
  • Ingår i: Proceedings - 46th Euromicro Conference on Software Engineering and Advanced Applications, SEAA 2020. - : IEEE. ; , s. 21-28
  • Konferensbidrag (refereegranskat)abstract
    • Since the advent of mobile computing and IoT, a large amount of data is distributed around the world. Companies are increasingly experimenting with innovative ways of implementing edge/cloud (re)training of AI systems to exploit large quantities of data to optimize their business value. Despite the obvious benefits, companies face challenges as the decision on how to implement edge/cloud (re)training depends on factors such as the task intent, the amount of data needed for (re)training, edge-to-cloud data transfer, the available computing and memory resources. Based on action research in a software-intensive embedded systems company where we study multiple use cases as well as insights from our previous collaborations with industry, we develop a generic framework consisting of five architectural alternatives to deploy AI on the edge utilizing transfer learning. We validate the framework in four additional case companies and present the challenges they face in selecting the optimal architecture. The contribution of the paper is threefold. First, we develop a generic framework consisting of five architectural alternatives ranging from a centralized architecture where cloud (re)training is given priority to a decentralized architecture where edge (re)training is instead given priority. Second, we validate the framework in a qualitative interview study with four additional case companies. As an outcome of validation study, we present two variants to the architectural alternatives identified as part of the framework. Finally, we identify the key challenges that experts face in selecting an ideal architectural alternative.
  •  
50.
  • John, Meenu Mary, et al. (författare)
  • Architecting AI Deployment: A Systematic Review of State-of-the-Art and State-of-Practice Literature
  • 2021
  • Ingår i: Lecture Notes in Business Information Processing. - Cham : Springer International Publishing. - 1865-1356 .- 1865-1348. ; 407, s. 14-29, s. 14-29
  • Konferensbidrag (refereegranskat)abstract
    • Companies across domains are rapidly engaged in shifting computational power and intelligence from centralized cloud to fully decentralized edges to maximize value delivery, strengthen security and reduce latency. However, most companies have only recently started pursuing this opportunity and are therefore at the early stage of the cloud-to-edge transition. To provide an overview of AI deployment in the context of edge/cloud/hybrid architectures, we conduct a systematic literature review and a grey literature review. To advance understanding of how to integrate, deploy, operationalize and evolve AI models, we derive a framework from existing literature to accelerate the end-to-end deployment process. The framework is organized into five phases: Design, Integration, Deployment, Operation and Evolution. We make an attempt to analyze the extracted results by comparing and contrasting them to derive insights. The contribution of the paper is threefold. First, we conduct a systematic literature review in which we review the contemporary scientific literature and provide a detailed overview of the state-of-the-art of AI deployment. Second, we review the grey literature and present the state-of-practice and experience of practitioners while deploying AI models. Third, we present a framework derived from existing literature for the end-to-end deployment process and attempt to compare and contrast SLR and GLR results.
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