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Sökning: WFRF:(Holden J)

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  • Ederle, Joerg, et al. (författare)
  • Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
  • 2010
  • Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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  • Scott, G. D., et al. (författare)
  • Fluid and Tissue Biomarkers of Lewy Body Dementia: Report of an LBDA Symposium
  • 2022
  • Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • The Lewy Body Dementia Association (LBDA) held a virtual event, the LBDA Biofluid/Tissue Biomarker Symposium, on January 25, 2021, to present advances in biomarkers for Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLBs) and Parkinson's disease dementia (PDD). The meeting featured eight internationally known scientists from Europe and the United States and attracted over 200 scientists and physicians from academic centers, the National Institutes of Health, and the pharmaceutical industry. Methods for confirming and quantifying the presence of Lewy body and Alzheimer's pathology and novel biomarkers were discussed.
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  • Menkveld, Albert J., et al. (författare)
  • Nonstandard Errors
  • 2024
  • Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
  • Tidskriftsartikel (refereegranskat)abstract
    • In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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  • Laabei, M., et al. (författare)
  • Predicting the virulence of MRSA from its genome sequence
  • 2014
  • Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051. ; 24:5, s. 839-849
  • Tidskriftsartikel (refereegranskat)abstract
    • Microbial virulence is a complex and often multifactorial phenotype, intricately linked to a pathogen's evolutionary trajectory. Toxicity, the ability to destroy host cell membranes, and adhesion, the ability to adhere to human tissues, are the major virulence factors of many bacterial pathogens, including Staphylococcus aureus. Here, we assayed the toxicity and adhesiveness of 90 MRSA (methicillin resistant S. aureus) isolates and found that while there was remarkably little variation in adhesion, toxicity varied by over an order of magnitude between isolates, suggesting different evolutionary selection pressures acting on these two traits. We performed a genome-wide association study (GWAS) and identified a large number of loci, as well as a putative network of epistatically interacting loci, that significantly associated with toxicity. Despite this apparent complexity in toxicity regulation, a predictive model based on a set of significant single nucleotide polymorphisms (SNPs) and insertion and deletions events (indels) showed a high degree of accuracy in predicting an isolate's toxicity solely from the genetic signature at these sites. Our results thus highlight the potential of using sequence data to determine clinically relevant parameters and have further implications for understanding the microbial virulence of this opportunistic pathogen.
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  • Reed, Mark S., et al. (författare)
  • The future of the uplands
  • 2009
  • Ingår i: Land use policy. - : Elsevier Limited. - 0264-8377 .- 1873-5754. ; 26:Supplement 1
  • Tidskriftsartikel (refereegranskat)abstract
    • Upland areas provide UK society with many important functions, goods and services, but have experienced a number of disturbing trends and face an uncertain future. This paper outlines historic, current and future drivers of environmental, economic, socio-cultural and policy change in UK uplands, and assesses how these have affected or are likely to affect ways in which land is used and the provision of ecosystem services. Information is synthesised into scenarios summarising a range of possible futures anticipated for UK uplands to 2060 and beyond. Finally, innovations in science, technology, governance and policy are evaluated that could enable uplands to continue providing key ecosystem services under a range of scenarios. The paper concludes that many upland areas will need to be prepared for significant reductions in grazing and prescribed burning. Conversely, other areas could experience agricultural intensification, for example significant increases in grazing or an expansion of arable or bioenergy crops into upland valleys, due to anticipated increases in global demand for food and energy. These scenarios will take place in the context of climate change. Many may take place together and may interact with each other, with complex and unpredictable implications for the upland environment, economy and society. In this context, a number of advances are needed in science, technology and policy to maintain viable uplandcommunities and the future provision of ecosystem services. These may include funding for ecological and hydrological restoration via carbon offsetting or other means. It may also involve advances in ecosystem service modelling, mapping and valuation, which through stakeholder participation could facilitate more integrated rural planning. New forms of environmental governance need to be explored that can empower those interested in developing upland economies to maintain thriving upland communities, while managing the ecosystem services they provide as efficiently as possible.
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  • Colbourne, JK, et al. (författare)
  • The Precision Toxicology initiative
  • 2023
  • Ingår i: Toxicology letters. - 1879-3169. ; 383, s. 33-42
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Allen, K. D., et al. (författare)
  • Evaluating Osteoarthritis Management Programs: outcome domain recommendations from the OARSI Joint Effort Initiative
  • 2023
  • Ingår i: Osteoarthritis and Cartilage. - : ELSEVIER SCI LTD. - 1063-4584 .- 1522-9653. ; 31:7, s. 954-965
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To develop sets of core and optional recommended domains for describing and evaluating Osteoarthritis Management Programs (OAMPs), with a focus on hip and knee Osteoarthritis (OA). Design: We conducted a 3-round modified Delphi survey involving an international group of researchers, health professionals, health administrators and people with OA. In Round 1, participants ranked the importance of 75 outcome and descriptive domains in five categories: patient impacts, implementation outcomes, and characteristics of the OAMP and its participants and clinicians. Domains ranked as "important" or "essential" by & GE;80% of participants were retained, and participants could suggest addi-tional domains. In Round 2, participants rated their level of agreement that each domain was essential for evaluating OAMPs: 0 = strongly disagree to 10 = strongly agree. A domain was retained if & GE;80% rated it & GE;6. In Round 3, participants rated remaining domains using same scale as in Round 2; a domain was recommended as "core" if & GE;80% of participants rated it & GE;9 and as "optional" if & GE;80% rated it & GE;7. Results: A total of 178 individuals from 26 countries participated; 85 completed all survey rounds. Only one domain, "ability to participate in daily activities", met criteria for a core domain; 25 domains met criteria for an optional recommendation: 8 Patient Impacts, 5 Implementation Outcomes, 5 Participant Characteristics, 3 OAMP Characteristics and 4 Clinician Characteristics. Conclusion: The ability of patients with OA to participate in daily activities should be evaluated in all OAMPs. Teams evaluating OAMPs should consider including domains from the optional recommended set, with representation from all five categories and based on stakeholder priorities in their local context. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.
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  • Zou, J. Y., et al. (författare)
  • Rewetting global wetlands effectively reduces major greenhouse gas emissions
  • 2022
  • Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 15:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Carbon and nitrogen losses from degraded wetlands and methane emissions from flooded wetlands are both important sources of greenhouse gas emissions. However, the net-exchange dependence on hydrothermal conditions and wetland integrity remains unclear. Using a global-scale in situ database on net greenhouse gas exchanges, we show diverse hydrology-influenced emission patterns in CO2, CH4 and N2O. We find that total CO2-equivalent emissions from wetlands are kept to a minimum when the water table is near the surface. By contrast, greenhouse gas exchange rates peak in flooded and drained conditions. By extrapolating the current trajectory of degradation, we estimate that between 2021 and 2100, wetlands could result in greenhouse gas emissions equivalent to around 408 gigatons of CO2. However, rewetting wetlands could reduce these emissions such that the radiative forcing caused by CH4 and N2O is fully compensated by CO2 uptake. As wetland greenhouse gas budgets are highly sensitive to changes in wetland area, the resulting impact on climate from wetlands will depend on the balance between future degradation and restoration. Global in situ observations show greenhouse gas emissions from wetlands are lowest when the water table is near the surface, and therefore rewetting wetlands could substantially reduce future emissions.
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  • Eyles, J.P., et al. (författare)
  • Clinical Outcomes Of Osteoarthritis Management Programs: A Project Of The Oa Trial Bank And Oarsi Joint Effort Initiative Using Individual Participant Data
  • 2023
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier. - 1063-4584 .- 1522-9653. ; 31, s. S385-S386
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: People living with osteoarthritis (OA) often do not receive best evidence care. Coordinated OA management programs (OAMPs) have been implemented to address this global evidence-practice gap. An OAMP is defined as a package of care with the following: i) a personalized management plan; ii) with reassessment and progression; iii) using a minimum of 2 core treatments (education, exercise, weight control), and; iv) optional adjunctive therapies. Existing OAMP models differ in treatment mode, intensity, duration, the health professionals delivering care, and the healthcare systems and settings they operate within. Randomized trials (RCTs) and cohort studies assess the outcomes of different OAMPs, however, these models are unlikely to ever be compared in RCTs due to the huge expense and complicated logistics required. Prognosis research provides another method of comparing outcomes of different OAMP models. This study aimed to estimate the pain and self-reported function outcomes (at 12-, 26- and 52-weeks) of people with hip and/or knee OA who participated in international OAMPs. It also aimed to describe the characteristics of OAMP participants.Methods: This study was undertaken by members of the OARSI Joint Effort Initiative (JEI), in collaboration with the OA Trial Bank (Erasmus MC, Netherlands). RCTs and clinical cohorts assessing OAMPs were identified through the JEI membership and literature searches. Eligible studies included data from an ongoing OAMP, in any real-world setting, with participants who were diagnosed with hip or knee OA, and longitudinal measures of patient-reported pain and function. The investigators of eligible studies were invited to complete data delivery agreements with the OA Trial Bank, share individual participant data (IPD), contribute to study design and authorship. Investigators ensured they had local ethics review board approval to contribute IPD to the OA Trial bank. Each dataset was converted to a common format to enable merging into one dataset. The IPD were evaluated to convert pain and function variables to standardized scales as appropriate. Pain scores were converted to a 0-100 point scale (100 worst). Function scores were converted to a 0-100 point scale (100 best). A generalized estimating equations (GEE) model analysis was performed to assess the change in pain and function from baseline across weeks 12, 26, and 52. The model specification was based on an unstructured correlation structure and robust standard errors. Pain and function estimates were adjusted by age, sex and body mass index (BMI). Data analyses were carried out using Stata 15 (StataCorp 2015) and SPSS 17.Results: The investigators of 13 international OAMPs were invited to take part. IPD from 9 OAMPs were delivered: the OA Chronic Care Program, Ramsay Health OA Management Program, Joint Health Program, University of Wisconsin Health Knee and Hip Comprehensive Non-Surgical OA Management Clinic, Improved Management of Patients With Hip and Knee OA in Primary Health Care, Joint Academy, Amsterdam OA cohort, Management of OA In Consultations, and Collaborative model of care between Orthopaedics and allied healthcare professionals in knee OA. The characteristics of the OAMPs are summarised in table 1. The OAMPs were conducted in-person except for the Joint Academy that was implemented as an online OAMP. Individual participant data from 9819 participants were analyzed. The cohort studies were missing large amounts of data, as expected in clinical practice. The characteristics of OAMP participants are summarised in Table 2. The majority of OAMP participants reported the knee as their index joint, their mean age ranged between 62- 67 years, 58-74% were female, 25-48% were working and mean BMI indicated they were overweight at baseline. Pain was most commonly assessed using a Numeric Rating Scale or validated questionnaires e.g. the Knee Injury and OA Outcome Scale (KOOS). Function was mostly assessed using validated questionnaires such as the KOOS. The pain and fuction measured in the original datasets are reported in Table 1. The changes in pain and function of the OAMP participants from baseline across weeks 12, 26, and 52 are summarised in Table 3. There were reductions in pain scores and improvements in function scores seen across all programs at the majority of timepoints.Conclusions: We established the first data bank of IPD from different international OAMPs. Analysis of the IPD demonstrated modest improvements in pain and function across the programs at all timepoints. The most rapid improvements were made by week-12, however, these gains were maintained at week-52. In future work this project will use IPD meta-analysis to identify prognostic factors of people with OA who participate in OAMPs.
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  • Limpens, J., et al. (författare)
  • Peatlands and the carbon cycle : from local processes to global implications – a synthesis
  • 2008
  • Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 5:5, s. 1475-1491
  • Forskningsöversikt (refereegranskat)abstract
    • Peatlands cover only 3% of the Earth's land surface but boreal and subarctic peatlands store about 15-30% of the world's soil carbon ( C) as peat. Despite their potential for large positive feedbacks to the climate system through sequestration and emission of greenhouse gases, peatlands are not explicitly included in global climate models and therefore in predictions of future climate change. In April 2007 a symposium was held in Wageningen, the Netherlands, to advance our understanding of peatland C cycling. This paper synthesizes the main findings of the symposium, focusing on (i) small-scale processes, (ii) C fluxes at the landscape scale, and (iii) peatlands in the context of climate change. The main drivers controlling most are related to some aspects of hydrology. Despite high spatial and annual variability in Net Ecosystem Exchange ( NEE), the differences in cumulative annual NEE are more a function of broad scale geographic location and physical setting than internal factors, suggesting the existence of strong feedbacks. In contrast, trace gas emissions seem mainly controlled by local factors. Key uncertainties remain concerning the existence of perturbation thresholds, the relative strengths of the CO2 and CH4 feedback, the links among peatland surface climate, hydrology, ecosystem structure and function, and trace gas biogeochemistry as well as the similarity of process rates across peatland types and climatic zones. Progress on these research areas can only be realized by stronger co-operation between disciplines that address different spatial and temporal scales.
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  • Barocchi, M A, et al. (författare)
  • A pneumococcal pilus influences virulence and host inflammatory responses
  • 2006
  • Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 103:8, s. 2857-2862
  • Tidskriftsartikel (refereegranskat)abstract
    • Streptococcus pneumoniae (pneumococcus) is a major cause of morbidity and mortality world-wide. The initial event in invasive pneumococcal disease is the attachment of encapsulated pneumococci to epithelial cells in the upper respiratory tract. This work provides evidence that initial bacterial adhesion and subsequent ability to cause invasive disease is enhanced by pili, long organelles able to extend beyond the polysaccharide capsule, previously unknown to exist in pneumococci. These adhesive pili-like appendages are encoded by the pneumococcal rlrA islet, present in some, but not all, clinical isolates. Introduction of the rlrA islet into an encapsulated rlrA-negative isolate allowed pilus expression, enhanced adherence to lung epithelial cells, and provided a competitive advantage upon mixed intranasal challenge of mice. Furthermore, a pilus-expressing rlrA islet-positive clinical isolate was more virulent than a nonpiliated deletion mutant, and it out-competed the mutant in murine models of colonization, pneumonia, and bacteremia. Additionally, piliated pneumococci evoked a higher TNF response during systemic infection, compared with nonpiliated derivatives, suggesting that pneumococcal pili not only contribute to adherence and virulence but also stimulate the host inflammatory response.
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  • Helland, Ragnhild Holden, et al. (författare)
  • Segmentation of glioblastomas in early post-operative multi-modal MRI with deep neural networks.
  • 2023
  • Ingår i: Scientific reports. - 2045-2322. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Extent of resection after surgery is one of the main prognostic factors for patients diagnosed with glioblastoma. To achieve this, accurate segmentation and classification of residual tumor from post-operative MR images is essential. The current standard method for estimating it is subject to high inter- and intra-rater variability, and an automated method for segmentation of residual tumor in early post-operative MRI could lead to a more accurate estimation of extent of resection. In this study, two state-of-the-art neural network architectures for pre-operative segmentation were trained for the task. The models were extensively validated on a multicenter dataset with nearly 1000 patients, from 12 hospitals in Europe and the United States. The best performance achieved was a 61% Dice score, and the best classification performance was about 80% balanced accuracy, with a demonstrated ability to generalize across hospitals. In addition, the segmentation performance of the best models was on par with human expert raters. The predicted segmentations can be used to accurately classify the patients into those with residual tumor, and those with gross total resection.
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  • Hepburn, Lucy, et al. (författare)
  • A Spaetzle-like role for nerve growth factor beta in vertebrate immunity to Staphylococcus aureus
  • 2014
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6209, s. 641-646
  • Tidskriftsartikel (refereegranskat)abstract
    • Many key components of innate immunity to infection are shared between Drosophila and humans. However, the fly Toll ligand Spaetzle is not thought to have a vertebrate equivalent. We have found that the structurally related cystine-knot protein, nerve growth factor β (NGFβ), plays an unexpected Spaetzle-like role in immunity to Staphylococcus aureus infection in chordates. Deleterious mutations of either human NGFβ or its high-affinity receptor tropomyosin-related kinase receptor A (TRKA) were associated with severe S. aureus infections. NGFβ was released by macrophages in response to S. aureus exoproteins through activation of the NOD-like receptors NLRP3 and NLRP4 and enhanced phagocytosis and superoxide-dependent killing, stimulated proinflammatory cytokine production, and promoted calcium-dependent neutrophil recruitment. TrkA knockdown in zebrafish increased susceptibility to S. aureus infection, confirming an evolutionarily conserved role for NGFβ-TRKA signaling in pathogen-specific host immunity.
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  • Holden, Richard J., et al. (författare)
  • That's nice, but what does IT do? : Evaluating the impact of bar coded medication administration by measuring changes in the process of care
  • 2011
  • Ingår i: International Journal of Industrial Ergonomics. - : Elsevier BV. - 0169-8141 .- 1872-8219. ; 41:4, s. 370-379
  • Tidskriftsartikel (refereegranskat)abstract
    • Health information technology (IT) is widely endorsed as a way to improve key health care outcomes, particularly patient safety. Applying a human factors approach, this paper models more explicitly how health IT might improve or worsen outcomes. The human factors model specifies that health IT transforms the work system, which transforms the process of care, which in turn transforms the outcome of care. This study reports on transformations of the medication administration process that resulted from the implementation of one type of IT: bar coded medication administration (BCMA). Registered nurses at two large pediatric hospitals in the US participated in a survey administered before and after one of the hospitals implemented BCMA. Nurses' perceptions of the administration process changed at the hospital that implemented BCMA, whereas perceptions of nurses at the control hospital did not. BCMA appeared to improve the safety of the processes of matching medications to the medication administration record and checking patient identification. The accuracy, usefulness,, and consistency of checking patient identification improved as well. In contrast, nurses' perceptions of the usefulness, time efficiency, and ease of the documentation process decreased post-BCMA. Discussion of survey findings is supplemented by observations and interviews at the hospital that implemented BCMA. Relevance to industry: By considering the way that IT transforms the work system and the work process a practitioner can better predict the kind of outcomes that the IT might produce. More importantly, the practitioner can achieve or prevent outcomes of interest by using design and redesign aimed at controlling work system and process transformations.
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  • Qiu, Chunjing, et al. (författare)
  • A strong mitigation scenario maintains climate neutrality of northern peatlands
  • 2022
  • Ingår i: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 5:1, s. 86-97
  • Tidskriftsartikel (refereegranskat)abstract
    • Northern peatlands store 300–600 Pg C, of which approximately half are underlain by permafrost. Climate warming and, in some regions, soil drying from enhanced evaporation are progressively threatening this large carbon stock. Here, we assess future CO2 and CH4 fluxes from northern peatlands using five land surface models that explicitly include representation of peatland processes. Under Representative Concentration Pathways (RCP) 2.6, northern peatlands are projected to remain a net sink of CO2 and climate neutral for the next three centuries. A shift to a net CO2 source and a substantial increase in CH4 emissions are projected under RCP8.5, which could exacerbate global warming by 0.21°C (range, 0.09–0.49°C) by the year 2300. The true warming impact of peatlands might be higher owing to processes not simulated by the models and direct anthropogenic disturbance. Our study highlights the importance of understanding how future warming might trigger high carbon losses from northern peatlands.
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  • Tal, Tamara, et al. (författare)
  • New approach methods to assess developmental and adult neurotoxicity for regulatory use : a PARC work package 5 project
  • 2024
  • Ingår i: Frontiers in Toxicology. - : Frontiers Media S.A.. - 2673-3080. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • In the European regulatory context, rodent in vivo studies are the predominant source of neurotoxicity information. Although they form a cornerstone of neurotoxicological assessments, they are costly and the topic of ethical debate. While the public expects chemicals and products to be safe for the developing and mature nervous systems, considerable numbers of chemicals in commerce have not, or only to a limited extent, been assessed for their potential to cause neurotoxicity. As such, there is a societal push toward the replacement of animal models with in vitro or alternative methods. New approach methods (NAMs) can contribute to the regulatory knowledge base, increase chemical safety, and modernize chemical hazard and risk assessment. Provided they reach an acceptable level of regulatory relevance and reliability, NAMs may be considered as replacements for specific in vivo studies. The European Partnership for the Assessment of Risks from Chemicals (PARC) addresses challenges to the development and implementation of NAMs in chemical risk assessment. In collaboration with regulatory agencies, Project 5.2.1e (Neurotoxicity) aims to develop and evaluate NAMs for developmental neurotoxicity (DNT) and adult neurotoxicity (ANT) and to understand the applicability domain of specific NAMs for the detection of endocrine disruption and epigenetic perturbation. To speed up assay time and reduce costs, we identify early indicators of later-onset effects. Ultimately, we will assemble second-generation developmental neurotoxicity and first-generation adult neurotoxicity test batteries, both of which aim to provide regulatory hazard and risk assessors and industry stakeholders with robust, speedy, lower-cost, and informative next-generation hazard and risk assessment tools.
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  • Ardern, Clare L, et al. (författare)
  • Implementing the 27 PRISMA 2020 Statement items for systematic reviews in the sport and exercise medicine, musculoskeletal rehabilitation and sports science fields : The PERSiST (implementing Prisma in Exercise, Rehabilitation, Sport medicine and SporTs science) guidance
  • 2022
  • Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 56:4, s. 175-195
  • Tidskriftsartikel (refereegranskat)abstract
    • Poor reporting of medical and healthcare systematic reviews is a problem from which the sports and exercise medicine, musculoskeletal rehabilitation, and sports science fields are not immune. Transparent, accurate and comprehensive systematic review reporting helps researchers replicate methods, readers understand what was done and why, and clinicians and policy-makers implement results in practice. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement and its accompanying Explanation and Elaboration document provide general reporting examples for systematic reviews of healthcare interventions. However, implementation guidance for sport and exercise medicine, musculoskeletal rehabilitation, and sports science does not exist. The Prisma in Exercise, Rehabilitation, Sport medicine and SporTs science (PERSiST) guidance attempts to address this problem. Nineteen content experts collaborated with three methods experts to identify examples of exemplary reporting in systematic reviews in sport and exercise medicine (including physical activity), musculoskeletal rehabilitation (including physiotherapy), and sports science, for each of the PRISMA 2020 Statement items. PERSiST aims to help: (1) systematic reviewers improve the transparency and reporting of systematic reviews and (2) journal editors and peer reviewers make informed decisions about systematic review reporting quality.
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  • Brännmark, Mikael, et al. (författare)
  • Packages of participation : Swedish employees´experience of Lean depends on how they are involved
  • 2013
  • Ingår i: IIE Transactions on Occupational Ergonomics and Human Factors. - : Informa UK Limited. - 2157-7323 .- 2157-7331. ; 1:2, s. 93-108
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Lean production is a dominant approach in Swedish and global manufacturing and service industries. Studies of Lean’s employee effects are few and contradictory. Purpose: Employee effects from Lean are likely not uniform. This article investigates the effect of employees’ participation on their experiences of Lean. Method: This study investigated how different packages of employee participation in Lean affected manufacturing workers’ experiences of Lean. During 2008–2011, qualitative and quantitative data were collected from Swedish manufacturing companies participating in the national Swedish Lean production program Produktionslyftet. Data from 129 surveys (28 companies), 39 semi-structured interviews, and 30 reports were analyzed. In the main analysis, comparisons were made of the survey-reported Lean experiences of employees in three groups: temporary group employees (N = 36), who participated in Lean mostly through intermittent projects; continuous group employees (N = 69), who participated through standing improvement groups; and combined group employees (N = 24), who participated in both ways. Results: Continuous group employees had the most positive experience of Lean, followed by the combined group. Temporary group employees had the least positive experiences, being less likely than their counterparts to report that Lean improved teamwork; occupational safety; and change-related learning, decision making, and authority. Conclusions: These findings support the importance of continuous, structured opportunities for participation but raise the possibility that more participation may result in greater workload and role overload, mitigating some benefits of employee involvement. Consequently, companies should consider involving employees in change efforts but should attend to the specific design of participation activities.
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  • Clase, CM, et al. (författare)
  • Can Peer Review Be Kinder? Supportive Peer Review: A Re-Commitment to Kindness and a Call to Action
  • 2022
  • Ingår i: Canadian journal of kidney health and disease. - : SAGE Publications. - 2054-3581. ; 9, s. 20543581221080327-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Peer review aims to select articles for publication and to improve articles before publication. We believe that this process can be infused by kindness without losing rigor. In 2014, the founding editorial team of the Canadian Journal of Kidney Health and Disease (CJKHD) made an explicit commitment to treat authors as we would wish to be treated ourselves. This broader group of authors reaffirms this principle, for which we suggest the terminology “supportive review.”
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32.
  • Connolly, J., et al. (författare)
  • Detecting recent disturbance on montane blanket bogs in the Wicklow Mountains, Ireland, using the MODIS enhanced vegetation index
  • 2011
  • Ingår i: International Journal of Remote Sensing. - : Informa UK Limited. - 1366-5901 .- 0143-1161. ; 32:9, s. 2377-2393
  • Tidskriftsartikel (refereegranskat)abstract
    • Irish peat soils are extensive, covering approximately 14-20% of the national land area. They contain between 53% and 62% of the national soil organic carbon stock. Montane blanket bog covers approximately 25% or 242650ha of the total peatland area in Ireland and is the dominant peatland type covering the upland area of Wicklow. Blanket bogs are very sensitive systems and have experienced much disturbance in Ireland due to overgrazing, burning, drainage, forestry and turf cutting. It has been estimated that disturbance of blanket bog, on a national area basis, ranges from 74% to 82% and in Wicklow is 57%. Disturbance can be detrimental to stocks of soil organic carbon in peatlands. Monitoring disturbance in peatlands, which tend to cover large, remote areas, is difficult and expensive using conventional surveying methods. Satellite remote sensing offers a way to gather data for these areas. In this paper a method of determining the probability of disturbance is presented. This method uses the Moderate Resolution Imaging Spectroradiometer (MODIS) Enhanced Vegetation Index (EVI) in combination with univariate image differencing along with thresholding and binary logistic regression. A probability map was produced depicting the geospatial patterns and pressures on the peatland soil organic carbon stock in Wicklow. Peat soils in higher and steeper areas were more disturbed and the primary disturbance in between 2000 and 2005 was fire. Lower, flatter areas did not experience as much disturbance probably because they are wetter. The consumer's and producer's accuracy for the map was 76% and 42%, respectively.
  •  
33.
  • Dellve, Lotta, et al. (författare)
  • Health care clinicians' engagement in organizational redesign of care processes : Health care clinicians' engagement in organizational redesign of care processes
  • 2018
  • Ingår i: Applied Ergonomics. - : Elsevier. - 0003-6870 .- 1872-9126. ; 68, s. 249-257
  • Tidskriftsartikel (refereegranskat)abstract
    • The Swedish health care system is reorienting towards horizontal organization for care processes. A main challenge is to engage health care clinicians in the process. The aim of this study was to assess engagement (i.e. attitudes and beliefs, the cognitive state and clinical engagement behaviour) among health care clinicians, and to investigate how engagement was related to work resources and demands during organizational redesign. A cohort study was conducted, using a questionnaire distributed to clinicians at five hospitals working with care process improvement approaches, two of them having implemented Lean production. The results show that kinds of engagement are interlinked and contribute to clinical engagement behaviour in quality of care and patient safety. Increased work resources have importance for engagements in organizational improvements, especially in top-down implementations. An extended work engagement model during organizational improvements in health care was supported. The model contributes to knowledge about how and when clinicians are mobilized to engage in organizational changes.
  •  
34.
  • Dellve, Lotta, et al. (författare)
  • Health care clinicians’ engagement in organizational redesign of care processes : Health care clinicians’ engagement in organizational redesign of care processes
  • 2018
  • Ingår i: Applied Ergonomics. - : Elsevier BV. - 0003-6870. ; 68, s. 249-257
  • Tidskriftsartikel (refereegranskat)abstract
    • The Swedish health care system is reorienting towards horizontal organization for care processes. A main challenge is to engage health care clinicians in the process. The aim of this study was to assess engagement (i.e. attitudes and beliefs, the cognitive state and clinical engagement behaviour) among health care clinicians, and to investigate how engagement was related to work resources and demands during organizational redesign. A cohort study was conducted, using a questionnaire distributed to clinicians at five hospitals working with care process improvement approaches, two of them having implemented Lean production. The results show that kinds of engagement are interlinked and contribute to clinical engagement behaviour in quality of care and patient safety. Increased work resources have importance for engagements in organizational improvements, especially in top-down implementations. An extended work engagement model during organizational improvements in health care was supported. The model contributes to knowledge about how and when clinicians are mobilized to engage in organizational changes.
  •  
35.
  • Dellve, Lotta, 1965, et al. (författare)
  • Health care clinicians’ engagement in organizational redesign of care processes: The importance of work and organizational conditions
  • 2018
  • Ingår i: Applied Ergonomics. - : Elsevier BV. - 0003-6870 .- 1872-9126. ; 68, s. 249-257
  • Tidskriftsartikel (refereegranskat)abstract
    • The Swedish health care system is reorienting towards horizontal organization for care processes. A main challenge is to engage health care clinicians in the process. The aim of this study was to assess engagement (i.e. attitudes and beliefs, the cognitive state and clinical engagement behaviour) among health care clinicians, and to investigate how engagement was related to work resources and demands during organizational redesign. A cohort study was conducted, using a questionnaire distributed to clinicians at five hospitals working with care process improvement approaches, two of them having implemented Lean production. The results show that kinds of engagement are interlinked and contribute to clinical engagement behaviour in quality of care and patient safety. Increased work resources have importance for engagements in organizational improvements, especially in top-down implementations. An extended work engagement model during organizational improvements in health care was supported. The model contributes to knowledge about how and when clinicians are mobilized to engage in organizational changes.
  •  
36.
  • Downs, J., et al. (författare)
  • Detection of Suicidality in Adolescents with Autism Spectrum Disorders : Developing a Natural Language Processing Approach for Use in Electronic Health Records
  • 2017
  • Ingår i: AMIA Annual Symposium Proceedings. - : NLM (Medline). - 1942-597X. ; 2017, s. 641-649
  • Tidskriftsartikel (refereegranskat)abstract
    • Over 15% of young people with autism spectrum disorders (ASD) will contemplate or attempt suicide during adolescence. Yet, there is limited evidence concerning risk factors for suicidality in childhood ASD. Electronic health records (EHRs) can be used to create retrospective clinical cohort data for large samples of children with ASD. However systems to accurately extract suicidality-related concepts need to be developed so that putative models of suicide risk in ASD can be explored. We present a systematic approach to 1) adapt Natural Language Processing (NLP) solutions to screen with high sensitivity for reference to suicidal constructs in a large clinical ASD EHR corpus (230,465 documents), and 2) evaluate within a screened subset of 500 patients, the performance of an NLP classification tool for positive and negated suicidal mentions within clinical text. When evaluated, the NLP classification tool showed high system performance for positive suicidality with precision, recall, and F1 scores all > 0.85 at a document and patient level. The application therefore provides accurate output for epidemiological research into the factors contributing to the onset and recurrence of suicidality, and potential utility within clinical settings as an automated surveillance or risk prediction tool for specialist ASD services.
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37.
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38.
  • Eriksson, Andrea, et al. (författare)
  • A Case Study of Three Swedish Hospitals' Strategies for Implementing Lean Production
  • 2016
  • Ingår i: Nordic Journal of Working Life Studies. - : Roskilde Universitetsforlag. - 2245-0157. ; 6:1, s. 105-131
  • Tidskriftsartikel (refereegranskat)abstract
    • Many hospitals have recently implemented the management concept lean production. The aim of this study was to learn how and why three Swedish hospitals selected and developed their hospital-wide lean production strategies. Although previous research shows that the concept is implemented in various ways, there is limited research on how and why different hospitals choose different implementation strategies and if the chosen strategies contribute to sustainable participation in organizational development. A case study of three different Swedish hospitals implementing lean production was thus performed. We studied the content of the hospitals' selected implementation strategies, conditions and rationales behind their strategy selection, and how different organizational actors participated in the implementation. Qualitative interviews with 54 key actors at the studied hospitals were performed. In addition, a self-administered survey questionnaire to employees was answered at T1 (2012, n = 557), T2 (2013, n = 554), and T3 (2014, n = 366). The three studied hospitals chose different strategies for implementing lean production due to different contextual conditions and for different reasons. The hospital-wide implementation strategies were related to employees' interest and participation in lean production. The results show that many different actors at different organizational levels need to participate in lean production in order to sustain and diffuse change processes. Furthermore, broad motives including quality of care seem to be needed for engaging different professional groups.
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39.
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40.
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41.
  • Green, David C., 1987-, et al. (författare)
  • Dichroic Calcite Reveals the Pathway from Additive Binding to Occlusion
  • 2021
  • Ingår i: Crystal Growth & Design. - Washington, DC : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 21:7, s. 3746-3755
  • Tidskriftsartikel (refereegranskat)abstract
    • Organic additives play key roles in controlling the precipitation of calcium carbonate in the environment, industry, and biology, where they can direct polymorphism, alter crystal morphologies, and sometimes even become occluded, modifying bulk properties. However, significant questions remain regarding the pathway from adsorption on crystal surfaces to occlusion. Here, the optical properties of calcite crystals grown in the presence of the dye Congo red are used to characterize the organization of the additives within the crystal. Complemented by the analysis of surface adsorption through in situ atomic force microscopy (AFM), molecular simulations, and changes in crystal morphologies, we show that the occluded dye molecules are randomly oriented under fast growth conditions, but that slow growth engenders ordering of the dye within islands, whose orientation is determined by the dye/terrace interaction free energy. The islands are subsequently overgrown such that their internal structure is preserved. These results reveal that the occlusion of organic macromolecules into calcite can be understood by thermodynamics operating at the adsorption stage. This new insight will ultimately enable the design of additives to give specific material properties.
  •  
42.
  • Heap, Graham A., et al. (författare)
  • HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants
  • 2014
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:10, s. 1131-1134
  • Tidskriftsartikel (refereegranskat)abstract
    • Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 x 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the H LA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk.
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43.
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44.
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45.
  • Holden, Richard J. (författare)
  • Cognitive performance-altering effects of electronic medical records : an application of the human factors paradigm for patient safety
  • 2011
  • Ingår i: Cognition, Technology & Work. - : Springer Science and Business Media LLC. - 1435-5558 .- 1435-5566. ; 13:1, s. 11-29
  • Tidskriftsartikel (refereegranskat)abstract
    • According to the human factors paradigm for patient safety, health care work systems and innovations such as electronic medical records do not have direct effects on patient safety. Instead, their effects are contingent on how the clinical work system, whether computerized or not, shapes health care providers' performance of cognitive work processes. An application of the human factors paradigm to interview data from two hospitals in the Midwest United States yielded numerous examples of the performance-altering effects of electronic medical records, electronic clinical documentation, and computerized provider order entry. Findings describe both improvements and decrements in the ease and quality of cognitive performance, both for interviewed clinicians and for their colleagues and patients. Changes in cognitive performance appear to have desirable and undesirable implications for patient safety as well as for quality of care and other important outcomes. Cognitive performance can also be traced to interactions between work system elements, including new technology, allowing for the discovery of problems with "fit" to be addressed through design interventions.
  •  
46.
  • Holden, Richard J., et al. (författare)
  • Effects of mental demands during dispensing on perceived medication safety and employee well-being : A study of workload in pediatric hospital pharmacies
  • 2010
  • Ingår i: Research in Social and Administrative Pharmacy. - : Elsevier BV. - 1551-7411. ; 6:4, s. 293-306
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Pharmacy workload is a modifiable work system factor believed to affect both medication safety outcomes and employee outcomes, such as job satisfaction. Objectives: This study sought to measure the effect of workload on safety and employee outcomes in 2 pediatric hospitals and to do so using a novel approach to pharmacy workload measurement. Methods: Rather than measuring prescription volume or other similar indicators, this study measured the type and intensity of mental demands experienced during the medication dispensing tasks. The effects of external (interruptions, divided attention, and rushing) and internal (concentration and effort) task demands on perceived medication error likelihood, adverse drug event likelihood, job dissatisfaction, and burnout were statistically estimated using multiple linear and logistic regression. Results: Pharmacists and pharmacy technicians reported high levels of external and internal,mental demands during dispensing. The study supported the hypothesis that external demands (interruptions, divided attention, and rushing) negatively impacted medication safety and employee well-being outcomes. However, as hypothesized, increasing levels of internal demands (concentration and effort) were not associated with greater perceived likelihood of error, adverse drug events, or burnout and even had a positive effect on job satisfaction. Conclusions: Replicating a prior study in nursing, this study shows that new conceptualizations and measures of workload can generate important new findings about both detrimental and beneficial effects of workload on patient safety and employee well-being. This study discusses what those findings imply for policy, management, and design concerning automation, cognition, and staffing.
  •  
47.
  • Holden, Richard J. (författare)
  • Lean Thinking in Emergency Departments : A Critical Review
  • 2011
  • Ingår i: Annals of Emergency Medicine. - : Elsevier BV. - 0196-0644 .- 1097-6760. ; 57:3, s. 265-278
  • Forskningsöversikt (refereegranskat)abstract
    • Emergency departments (EDs) face problems with crowding, delays, cost containment, and patient safety. To address these and other problems, EDs increasingly implement an approach called Lean thinking. This study critically reviewed 18 articles describing the implementation of Lean in 15 EDs in the United States, Australia, and Canada. An analytic framework based on human factors engineering and occupational research generated 6 core questions about the effects of Lean on ED work structures and processes, patient care, and employees, as well as the factors on which Lean's success is contingent. The review revealed numerous ED process changes, often involving separate patient streams, accompanied by structural changes such as new technologies, communication systems, staffing changes, and the reorganization of physical space. Patient care usually improved after implementation of Lean, with many EDs reporting decreases in length of stay, waiting times, and proportion of patients leaving the ED without being seen. Few null or negative patient care effects were reported, and studies typically did not report patient quality or safety outcomes beyond patient satisfaction. The effects of Lean on employees were rarely discussed or measured systematically, but there were some indications of positive effects on employees and organizational culture. Success factors included employee involvement, management support, and preparedness for change. Despite some methodological, practical, and theoretic concerns, Lean appears to offer significant improvement opportunities. Many questions remain about Lean's effects on patient health and employees and how Lean can be best implemented in health care.
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48.
  • Holden, Richard J. (författare)
  • Physicians' beliefs about using EMR and CPOE : In pursuit of a contextualized understanding of health IT use behavior
  • 2010
  • Ingår i: International Journal of Medical Informatics. - : Elsevier BV. - 1386-5056 .- 1872-8243. ; 79:2, s. 71-80
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To identify and describe physicians' beliefs about use of electronic medical records (EMR) and computerized provider order entry (CPOE) for inpatient and outpatient care, to build an understanding of what factors shape information technology (IT) use behavior in the unique context of health care delivery. Methods: Semi-structured qualitative research interviews were carried out, following the beliefs elicitation approach. Twenty physicians from two large Midwest US hospitals participated. Physicians were asked questions to elicit beliefs and experiences pertaining to their use of EMR and CPOE. Questions were based on a broad set of behavior-shaping beliefs and the methods commonly used to elicit those beliefs. Results: Qualitative analysis revealed numerous themes related to the perceived emotional and instrumental outcomes of EMR and CPOE use; perceived external and personal normative pressure to use those systems; perceived volitional control over use behavior; perceived facilitators and barriers to system use; and perceptions about the systems and how they were implemented. EMR and CPOE were commonly believed to both improve and worsen the ease and quality of personal performance, productivity and efficiency, and patient outcomes. Physicians felt encouraged by employers and others to use the systems but also had personal role-related and moral concerns about doing so. Perceived facilitators and barriers were numerous and had their sources in all aspects of the work system. Conclusion: Given the breadth and detail of elicited beliefs, numerous design and policy implications can be identified. Additionally, the findings are a first step toward developing a theory of health IT acceptance and use contextualized to the unique setting of health care.
  •  
49.
  • Håkansson, Malin, et al. (författare)
  • Managerial practices that support lean and socially sustainable working conditions
  • 2017
  • Ingår i: Nordic Journal of Working Life Studies. - : Roskilde University. - 2245-0157. ; 7:3, s. 63-84
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite decades of using lean, there is little knowledge of how lean managerial practices affect working conditions. Thus, the aim of this study was to investigate in what ways managerial practices support socially sustainable working conditions (SSWCs) during a lean transformation. A mixed methods approach was used in this multiyear case study in a midsize Swedish manufacturing company. Assessment of work characteristics was combined with employee questionnaires and interviews with managers. Four practices were identified as instrumental for SSWCs: 1) a coherent lean approach with clear direction, 2) a value-creating leadership style comprising a participatorypromoting and caring leadership approach with joint focus on production and well-being, 3) conscious involvement of employees in a stepwise fashion, and 4) a focus on promoting meaningful jobs and health, aided by work environment management. Thus, managerial practices actively supporting important job resources as an integral part of the lean system seemed to support SSWCs.
  •  
50.
  • Håkansson, Malin, et al. (författare)
  • Sustained lean transformation of working conditions : A Swedish longitudinal case study
  • 2017
  • Ingår i: Human Factors and Ergonomics in Manufacturing. - : John Wiley & Sons. - 1090-8471 .- 1520-6564. ; 27:6, s. 268-279
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies of lean production’s effect on working conditions are mixed but point toward worsened conditions. The aim of this longitudinal study was to assess how lean contributes to transforming work characteristics in a medium-sized specialized industrial family business. A mixed methods approachwas used to combine an external assessment of work characteristics with selfreported employee questionnaires. Favorable psychosocial working conditions were indicated, with role conflicts decreasing over time. The assessment of work provided descriptions of how lean practices contributed to decreased task control due to standardized work and simplified work processes. At the same time, employees still had opportunities to influence their long-term work assignment. There was also a trend toward job enlargement through new, higher-skilled tasks, multiskilling, and extended opportunities to influence work through different continuous improvement activities. The participative lean approach and type of skilled jobs may have contributed to this transformation.
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