| 1. |
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| 2. |
- Reid, Sarah, et al.
(författare)
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High genetic risk score is associated with early disease onset, damage accrual and decreased survival in systemic lupus erythematosus
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 79:3, s. 363-369
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate associations between a high genetic disease risk and disease severity in patients with systemic lupus erythematosus (SLE).METHODS: Patients with SLE (n=1001, discovery cohort and n=5524, replication cohort) and healthy controls (n=2802 and n=9859) were genotyped using a 200K Immunochip single nucleotide polymorphism array. A genetic risk score (GRS) was assigned to each individual based on 57 SLE risk loci.RESULTS: SLE was more prevalent in the high, compared with the low, GRS-quartile (OR 12.32 (9.53 to 15.71), p=7.9×10-86 and OR 7.48 (6.73 to 8.32), p=2.2×10-304 for the discovery and the replication cohorts, respectively). In the discovery cohort, patients in the high GRS-quartile had a 6-year earlier mean disease onset (HR 1.47 (1.22 to 1.75), p=4.3×10-5), displayed higher prevalence of damage accrual (OR 1.47 (1.06 to 2.04), p=2.0×10-2), renal disorder (OR 2.22 (1.50 to 3.27), p=5.9×10-5), anti-dsDNA (OR 1.83 (1.19 to 2.81), p=6.1×10-3), end-stage renal disease (ESRD) (OR 5.58 (1.50 to 20.79), p=1.0×10-2), proliferative nephritis (OR 2.42 (1.30 to 4.49), p=5.1×10-3), anti-cardiolipin-IgG (OR 1.89 (1.13 to 3.18), p=1.6×10-2), anti-β2-glycoprotein-I-IgG (OR 2.29 (1.29 to 4.06), p=4.8×10-3) and positive lupus anticoagulant test (OR 2.12 (1.16 to 3.89), p=1.5×10-2) compared with patients in the low GRS-quartile. Survival analysis showed earlier onset of the first organ damage (HR 1.51 (1.04 to 2.25), p=3.7×10-2), first cardiovascular event (HR 1.65 (1.03 to 2.64), p=2.6×10-2), nephritis (HR 2.53 (1.72 to 3.71), p=9.6×10-7), ESRD (HR 6.78 (1.78 to 26.86), p=6.5×10-3) and decreased overall survival (HR 1.83 (1.02 to 3.30), p=4.3×10-2) in high to low quartile comparison.CONCLUSIONS: A high GRS is associated with increased risk of organ damage, renal dysfunction and all-cause mortality. Our results indicate that genetic profiling may be useful for predicting outcomes in patients with SLE.
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| 3. |
- Sandling, Johanna K., et al.
(författare)
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Molecular pathways in patients with systemic lupus erythematosus revealed by gene-centred DNA sequencing
- 2021
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 80:1, s. 109-117
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease with extensive heterogeneity in disease presentation between patients, which is likely due to an underlying molecular diversity. Here, we aimed at elucidating the genetic aetiology of SLE from the immunity pathway level to the single variant level, and stratify patients with SLE into distinguishable molecular subgroups, which could inform treatment choices in SLE. Methods: We undertook a pathway-centred approach, using sequencing of immunological pathway genes. Altogether 1832 candidate genes were analysed in 958 Swedish patients with SLE and 1026 healthy individuals. Aggregate and single variant association testing was performed, and we generated pathway polygenic risk scores (PRS). Results: We identified two main independent pathways involved in SLE susceptibility: T lymphocyte differentiation and innate immunity, characterised by HLA and interferon, respectively. Pathway PRS defined pathways in individual patients, who on average were positive for seven pathways. We found that SLE organ damage was more pronounced in patients positive for the T or B cell receptor signalling pathways. Further, pathway PRS-based clustering allowed stratification of patients into four groups with different risk score profiles. Studying sets of genes with priors for involvement in SLE, we observed an aggregate common variant contribution to SLE at genes previously reported for monogenic SLE as well as at interferonopathy genes. Conclusions: Our results show that pathway risk scores have the potential to stratify patients with SLE beyond clinical manifestations into molecular subsets, which may have implications for clinical follow-up and therapy selection.
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| 4. |
- Aasa, Ulrika, et al.
(författare)
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Variability of lumbar spinal alignment among power- and weightlifters during the deadlift and barbell back squat
- 2022
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Ingår i: Sports Biomechanics. - : Routledge. - 1476-3141 .- 1752-6116. ; 21:6, s. 707-717
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Tidskriftsartikel (refereegranskat)abstract
- The aims of the study were to evaluate the relative and absolute variability of upper (T11-L2) and lower (L2-S2) lumbar spinal alignment in power- and weightlifters during the deadlift and back squat exercises, and to compare this alignment between the two lifting groups. Twenty-four competitive powerlifters (n = 14) and weightlifters (n = 10) performed three repetitions of the deadlift and the back squat exercises using a load equivalent to 70% of their respective one-repetition maximum. The main outcome measures were the three-dimensional lumbar spinal alignment for start position, minimum and maximum angle of their spinal alignment, and range of motion measured using inertial measurement units. Relative intra-trial reliability was calculated using the two-way random model intraclass correlation coefficient (ICC) and absolute reliability with minimal detectable change (MDC). The ICC ranged between 0.69 and 0.99 and the MDC between 1 degrees-8 degrees for the deadlift. Corresponding figures for the squat were 0.78-0.99 and 1 degrees-6 degrees. In all participants during both exercises, spinal adjustments were made in both thoracolumbar and lumbopelvic areas in all three dimensions. In conclusion, when performing three repetitions of the deadlift and the squat, lumbar spinal alignment of the lifters did not change much between repetitions and did not differ significantly between power- and weightlifters.
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| 5. |
- Adamson, Carly, et al.
(författare)
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Efficacy of Dapagliflozin in Heart Failure with Reduced Ejection Fraction According to Body Mass Index.
- 2021
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Ingår i: European journal of heart failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 23:10, s. 1662-1672
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: In heart failure with reduced ejection fraction (HFrEF), there is an ’obesity paradox’, where survival is better in patients with a higher body mass index (BMI) and weight loss is associated with worse outcomes. We examined the effect of a sodium-glucose co-transporter 2 inhibitor according to baseline BMI in the Dapagliflozin And Prevention of Adverse- outcomes in Heart Failure trial (DAPA-HF). METHODS AND RESULTS: Body mass index was examined using standard categories, i.e. underweight ($<$18.5 kg/m(2) ); normal weight (18.5-24.9 kg/m(2) ); overweight (25.0-29.9 kg/m(2) ); obesity class I (30.0-34.9 kg/m(2) ); obesity class II (35.0-39.9 kg/m(2) ); and obesity class III ($>$/=40 kg/m(2) ). The primary outcome in DAPA-HF was the composite of worsening heart failure or cardiovascular death. Overall, 1348 patients (28.4%) were under/normal- weight, 1722 (36.3%) overweight, 1013 (21.4%) obesity class I and 659 (13.9%) obesity class II/III. The unadjusted hazard ratio (95% confidence interval) for the primary outcome with obesity class 1, the lowest risk group, as reference was: under/normal-weight 1.41 (1.16-1.71), overweight 1.18 (0.97-1.42), obesity class II/III 1.37 (1.10-1.72). Patients with class I obesity were also at lowest risk of death. The effect of dapagliflozin on the primary outcome and other outcomes did not vary by baseline BMI, e.g. hazard ratio for primary outcome: under/normal-weight 0.74 (0.58-0.94), overweight 0.81 (0.65-1.02), obesity class I 0.68 (0.50-0.92), obesity class II/III 0.71 (0.51-1.00) (P-value for interaction = 0.79). The mean decrease in weight at 8 months with dapagliflozin was 0.9 (0.7-1.1) kg (P $<$ 0.001). CONCLUSION: We confirmed an ’obesity survival paradox’ in HFrEF. We showed that dapagliflozin was beneficial across the wide range of BMI studied. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03036124.
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| 6. |
- Adamson, Carly, et al.
(författare)
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Liver Tests and Outcomes in Heart Failure with Reduced Ejection Fraction : Findings from DAPA-HF.
- 2022
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Ingår i: European journal of heart failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 24:10, s. 1856-1868
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Reflecting both increased venous pressure and reduced cardiac output, abnormal liver tests are common in patients with severe heart failure and are associated with adverse clinical outcomes. We aimed to investigate the prognostic significance of abnormal liver tests in ambulatory patients with heart failure with reduced ejection fraction (HFrEF), explore any treatment interaction between bilirubin and sodium- glucose cotransporter 2 (SGLT2) inhibitors and examine change in liver tests with SGLT2 inhibitor treatment. METHODS AND RESULTS: We explored these objectives in the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF) trial, with focus on bilirubin. We calculated the incidence of cardiovascular death or worsening heart failure by bilirubin tertile. Secondary cardiovascular outcomes were examined, along with the change in liver tests at the end-of-study visit. Baseline bilirubin was available in 4720 patients (99.5%). Participants in the highest bilirubin tertile (T3) have more severe HFrEF (lower left ventricular ejection fraction, higher N-terminal pro-B-type natriuretic peptide [NT-proBNP] and worse New York Heart Association class), had a greater burden of atrial fibrillation but less diabetes. Higher bilirubin (T3 vs. T1) was associated with worse outcomes even after adjustment for other predictive variables, including NT-proBNP and troponin T (adjusted hazard ratio for the primary outcome 1.73 [95% confidence interval 1.37-2.17], p $<$ 0.001; and 1.52 [1.12-2.07], p = 0.01 for cardiovascular death). Baseline bilirubin did not modify the benefits of dapagliflozin. During follow-up, dapagliflozin had no effect on liver tests. CONCLUSION: Bilirubin concentration was an independent predictor of worse outcomes but did not modify the benefits of dapagliflozin in HFrEF. Dapagliflozin was not associated with change in liver tests. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03036124.
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| 7. |
- Alieva, Jamila, 1987-
(författare)
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Digital Waste – misjudged element of value stream in lean manufacturing
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The increasing prevalence of digital technologies in manufacturing is aimed at enhancing and streamlining traditional lean processes. However, the rapid automation of manufacturing brings about challenges due to a limited understanding of production waste mechanisms by practitioners. There is growing concern about the potential emergence of digital waste as a result of the influence of digital technologies on lean manufacturing. This thesis aims to examine the role of digital waste within the overall waste in digitalized lean manufacturing, as well as the impact of technologies on lean waste and practices.The thesis is driven by three research questions and comprises five papers that stem from five individual studies. The initial study explores the potential classification of uncollected and unprocessed data as a novel manifestation of Muda, or digital waste. The subsequent study seeks to assess the capability of implementing ERP at a supply chain level to amplify latent lean efficiencies within entities. Lastly, the third study delves into the perceived impacts of soft management practices, employee behaviors, the integration of digital technologies in manufacturing facilities, and their connection to the emergence of digital waste. The fourth study delves into the digital waste generated by companies with automated lean practices, while the fifth study explores the factors contributing to digital waste within the European manufacturing sector.The findings uncover the existence of a novel type of waste, known as digital waste, which may originate from either the product itself or the production process. The findings reveal that the use of ERP technology has a significant impact on identifying hidden lean potential across three categories: unlocked hidden lean potential in an unconnected ERP system, unlocked hidden lean potential in a connected ERP system, and hidden lean potential in a shared ERP system. Furthermore, the study indicates that various aspects such as top management leadership, middle management involvement, employee education, corporate social responsibility focus, innovation, knowledge sharing, work-family balance, psychological capital, job satisfaction, and career commitment, which fall under soft lean management practices, are positively influenced by the digital transformation process. Conversely, soft lean management practices, such as employee training, creativity, discretionary effort, turnover intention, and proactivity, appear to be negatively impacted by digital transformation. Additionally, the final results suggest the existence of digital waste in supplier-related lean practices (specifically, automated JIT delivery) within product-oriented and service-oriented technologies, as well as in internally related lean practices (specifically, automated set-up) within process-oriented technologies. Furthermore, evidence of digital waste is observed in customer-related lean practices, particularly those involving digitally engaged customers, across product-, service-, and process-oriented technologies. Finally, the study reveals that a majority of European manufacturers collect and process data for multiple purposes.The research presented in this thesis adds significant value to the ongoing discourse surrounding lean waste by engaging in a theoretical discussion of both physical and digital waste in the context of technological advancements. This thesis contributes to the discourse surrounding the automation of lean methodologies across product, process, and system domains, while also examining the influence of digital transformation on lean management practices. Furthermore, it investigates the role and consequences of Enterprise Resource Planning (ERP) systems in lean production. In practical terms, the thesis validates the presence of a novel type of waste that can impact the cost management of manufactured products, fosters transparency for digital collaboration, and advocates for increased investment in technologies and specialized personnel to offer analytical services in conjunction with manufacturing products.
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| 8. |
- Arandia Arzabe, Franco, et al.
(författare)
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Business model innovation factors of small and medium-sized enterprises in Bolivia
- 2024
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Ingår i: Journal of Risk and Financial Management. - 1911-8066. ; 17:8
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Tidskriftsartikel (refereegranskat)abstract
- This paper aims to explore how four Bolivian small and medium-sized enterprises’ business has overcome the gaps in reliance on traditional small and medium-sized enterprises’ business models, i.e., to extract and sell raw unrefined natural resources in a local area, and instead make productive use of innovation inputs (technology, higher-educated people) by innovating their business models. We were particularly interested in how the small and medium-sized enterprises could manage to develop their business models in relation to the socio-cultural, economic, and technological contexts in a lower middle-income country such as Bolivia. We employ an exploratory multiple case study. The study’s results show that the four selected small and medium-sized enterprises’ business model innovation processes followed two different business model innovation patterns, a technology-driven pattern and market-driven pattern shaped by the macro-level factors of availability of natural resources, the informally organized economy, regulations, and access to higher education resources. The paper ends with presenting the managerial, policy, and theoretical implications of the study.
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| 9. |
- Arena, Maurizio, et al.
(författare)
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Novel Aluminum Alloy Tailored for Additive Manufacturing : Structural Characterization and Qualification Perspectives
- 2024
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Ingår i: Applied Sciences. - : MDPI AG. - 2076-3417. ; 14:11
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Tidskriftsartikel (refereegranskat)abstract
- Featured Application The paper demonstrates key structural characteristics of a novel aluminum alloy conceived for AM-based components in the aviation frame.Abstract The recent advances achieved in additive manufacturing (AM) technology demonstrate the potential to realize customized metal components, ensuring weight reduction opportunities. These benefits make AM attractive for high-cost aerospace applications, especially where high geometric complexity is required. In the context of an EU research scenario, the H2020 MANUELA (Additive Manufacturing Using Metal Pilot Line) project promotes the development of new technologies for design optimization by enabling the application of novel materials in AM. This paper illustrates recent advances in a new aluminum alloy (Al-HS1) with high strength emphasizing all of the characterization steps at the coupon level. This material has been employed in the re-engineering of a conventional hydraulic manifold using a powder bed fusion-laser beam (PBF-LB) process. Both the simulations and structural tests allowed for proving its compliance and technological maturity with industrial standards and applicable airworthiness requirements.
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| 10. |
- Asplund, Carl Johan, et al.
(författare)
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Knowledge spillover from Master of Science Theses in Engineering Education in Sweden
- 2020
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Ingår i: European Journal of Engineering Education. - : Informa UK Limited. - 0304-3797 .- 1469-5898. ; 45:3, s. 443-456
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Tidskriftsartikel (refereegranskat)abstract
- Educational collaboration activities are generally under-researched part of the interactive learning between universities and industry. The study based on 529 Master of Science (MSc) theses from a major Swedish engineering school, the faculty of engineering LTH at Lund University, shows that MSc theses are a frequently used collaboration mechanism between university and industry in engineering education. Collaborating firms benefit mainly by recruiting students and the transfer of technological knowledge. Moreover, mainly regional large firms benefit from the educational collaboration and firms collaborate mostly on knowledge related to product innovations and in the early stages of the product innovation process. Small and medium-sized enterprises (SMEs) tend to relate to newer engineering disciplines, have relatively more MSc thesis projects related to product innovations and later process stages, specifically in prototype development and testing, than large firms have. The paper suggests a number of university actions to increase knowledge spillover to SMEs.
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