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  • Eeg-Olofsson, Måns, 1967, et al. (author)
  • TTCOV19: timing of tracheotomy in SARS-CoV-2-infected patients: a multicentre, single-blinded, randomized, controlled trial
  • 2022
  • In: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 26:1
  • Journal article (peer-reviewed)abstract
    • Background: Critically ill COVID-19 patients may develop acute respiratory distress syndrome and the need for respiratory support, including mechanical ventilation in the intensive care unit. Previous observational studies have suggested early tracheotomy to be advantageous. The aim of this parallel, multicentre, single-blinded, randomized controlled trial was to evaluate the optimal timing of tracheotomy. Methods: SARS-CoV-2-infected patients within the Region Vastra Gotaland of Sweden who needed intubation and mechanical respiratory support were included and randomly assigned to early tracheotomy (<= 7 days after intubation) or late tracheotomy (>= 10 days after intubation). The primary objective was to compare the total number of mechanical ventilation days between the groups. Results: One hundred fifty patients (mean age 65 years, 79% males) were included. Seventy-two patients were assigned to early tracheotomy, and 78 were assigned to late tracheotomy. One hundred two patients (68%) underwent tracheotomy of whom sixty-one underwent tracheotomy according to the protocol. The overall median number of days in mechanical ventilation was 18 (IQR 9; 28), but no significant difference was found between the two treatment regimens in the intention-to-treat analysis (between-group difference:- 1.5 days (95% CI -5.7 to 2.8); p= 0.5). A significantly reduced number of mechanical ventilation days was found in the early tracheotomy group during the per-protocol analysis (between-group difference: - 8.0 days (95% CI - 13.8 to - 2.27); p= 0.0064). The overall correlation between the timing of tracheotomy and days of mechanical ventilation was significant (Spearman's correlation: 0.39, p < 0.0001). The total death rate during intensive care was 32.7%, but no significant differences were found between the groups regarding survival, complications or adverse events. Conclusions: The potential superiority of early tracheotomy when compared to late tracheotomy in critically ill patients with COVID-19 was not confirmed by the present randomized controlled trial but is a strategy that should be considered in selected cases where the need for MV for more than 14 days cannot be ruled out.
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  • Larsson, Johanna, et al. (author)
  • Säkerhetskultur och självkörande fordon och maskiner
  • 2024
  • Reports (other academic/artistic)abstract
    • Självkörande fordon inom transportsektorn befinner sig ännu i utvecklingsstadiet. Att införa självkörande fordon och maskiner i befintliga verksamheter innebär ofta förändringar både i organisationen och den fysiska miljön och kan även innebära nya risker. I detta sammanhang kan säkerhetskulturen, både hos utvecklare och hos användare, spela viktig roll för att självkörande fordon och maskiner ska fungera säkert och effektivt i olika verksamheter. Projektets mål har varit att utveckla metoder för att förbättra säkerhetskultur där människor och automatiserad teknik samverkar som agenter i ett gemensamt system, samt att utveckla mätverktyg där hållbarhet, jämställdhet och säkerhet utvärderas för införande av självkörande fordon och maskiner. Projektet har utgått ifrån fallstudier från två olika domäner – självkörande bussar och självkörande industritruckar. Intervjuer har genomförts med utvecklare, kunder och slutanvändare. En enkät har tagits fram att mäta säkerhetskultur, jämställdhetskultur och hållbarhetskultur i organisationer som utvecklar självkörande fordon. Utöver detta har data från incidentrapporter analyserats. Lärdomarna från resultaten och projektdeltagarnas tidigare erfarenheter har resulterat i ett första utkast av en processmodell där säkerhetskultur integreras i utvecklingen av självkörande fordon och maskiner. Intervjuerna med utvecklare och kunder av självkörande fordon visade att säkerhetskultur inte var ett etablerat begrepp vare sig hos utvecklarna eller hos kunderna och att det därför inte var en faktor som man medvetet beaktade. Lärdomar från enkäten var att det finns skillnader mellan produktföretag och som markant påverkar formuleringar av frågeställningar. Det gick inte att fastställa om det föreligger kopplingar mellan hållbarhets-, jämställdhets- och säkerhetskultur. Fallstudien med bussarna visade bland annat att kund och leverantör pratar om olika typer av säkerhet samt att säkerheten ofta, men inte alltid, är prioriterad över effektiviteten. Utifrån analyserna av incidentdata från självkörande bussar samt förarlösa industritruckar har en lista med förslag på nyckeltal för att kunna analysera incidenter med självkörande fordon tagits fram inom projektet.
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  • Blind, Per-Jonas, et al. (author)
  • Fast-Track Program for Liver Resection - Factors Prolonging Length of Stay
  • 2014
  • In: Hepato-Gastroenterology. - 0172-6390. ; 61:136, s. 2340-2344
  • Journal article (peer-reviewed)abstract
    • Background/Aims: Fast-track programs involving multi-modal measures to enhance recovery after surgery, reduce morbidity and decrease hospital length of stay (LOS) are used for different major surgical procedures. For liver resections, factors influencing LOS within a fast-track program have been studied only to a limited extent, which was the aim of the present study. Methodology: The present study comprises the first 64 patients included in a fast-track program for liver resections introduced in March 2012. Patient outcomes were compared to a historical cohort of patients (n=62) operated in 2009. Factors prolonging LOS was analyzed by uni- and multivariate analysis. Results: Median LOS was 6 days (range 3-42 days) within the fast-track program as compared with 8 days (range 5-47 days) in the historical cohort (P=0.004). On multivariate analysis, factors increasing LOS in the fast-track group were found to be the presence of complication (P=0.018), extent of resection (major as compared to minor) (P=0.001) and inability to drink > 1250 ml on the day after surgery (P=0.002). Conclusion: Patients who can only drink limited amounts of fluid the day after-liver resection represent a subset of patients that should be given special attention within a fast-track program.
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  • Gilg, Stefan, et al. (author)
  • The impact of post-hepatectomy liver failure on mortality : a population-based study
  • 2018
  • In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 53:10-11, s. 1335-1339
  • Journal article (peer-reviewed)abstract
    • Background: Post-hepatectomy liver failure (PHLF) is considered a main reason for death after major hepatectomy. The reported PHLF-related mortality differs largely and the data mainly originate from single centers.Aim: A retrospective, population-based register study was designed to evaluate the impact of PHLF on 90-day mortality after hepatectomy.Method: All patients who underwent liver resection in Sweden between 2005 and 2009 were retrospectively identified using the Swedish Hospital Discharge Registry. 30- and 90-day mortality were identified by linkage to the Registry of Causes of Death. Additional clinical data were obtained from the medical charts in all seven university hospitals in Sweden. PHLF was defined according to Balzan criteria (Bilirubin >50 µg/L and international normalized ratio >1.5) on postoperative day 5.Results: A total of 2461 liver resections were performed (2194 in university hospitals). 30- and 90-day mortality were 1.3% and 2.5%, respectively. 90-day mortality at university hospitals was 2.1% (n = 46). In 41% (n = 19) of these patients, PHLF alone or in combination with multi-organ failure was identified as cause of death. Between the PHLF and non-PHLF group, there was no significant difference regarding age, sex, American Society of Anesthesiologists-classification, or preoperative chemotherapy. Cholangiocarcinoma as indication for surgery, need for vascular reconstruction and an extended resection were significantly overrepresented in the PHLF-group. Between groups, the incidence of 50:50 criteria differed significantly already on postoperative day 3.Conclusion: Overall mortality is very low after hepatectomy in Sweden. PHLF represents the single most important cause of death even in a population-based setting.
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  • Hasselgren, K., et al. (author)
  • ALPPS Improves Survival Compared With TSH in Patients Affected of CRLM Survival Analysis From the Randomized Controlled Trial LIGRO
  • 2021
  • In: Annals of Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 0003-4932 .- 1528-1140. ; 273:3, s. 442-448
  • Journal article (peer-reviewed)abstract
    • Objective: To evaluate the oncological outcome for patients with colorectal liver metastases (CRLM) randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or 2-stage hepatectomy (TSH). Background: TSH with portal vein occlusion is an established method for patients with CRLM and a low volume of the future liver remnant (FLR). ALPPS is a less established method. The oncological outcome of these methods has not been previously compared in a randomized controlled trial. Methods: One hundred patients with CRLM and standardized FLR (sFLR) <30% were included and randomized to resection by ALPPS or TSH, with the option of rescue ALPPS in the TSH group, if the criteria for volume increase was not met. The first radiological follow-up was performed approximately 4 weeks postoperatively and then after 4, 8, 12, 18, and 24 months. At all the follow-ups, the remaining/recurrent tumor was noted. After the first follow-up, chemotherapy was administered, if indicated. Results: The resection rate, according to the intention-to-treat principle, was 92% (44 patients) for patients randomized to ALPPS compared with 80% (39 patients) for patients randomized to TSH (P = 0.091), including rescue ALPPS. At the first postoperative follow-up, 37 patients randomized to ALPPS were assessed as tumor free in the liver, and also 28 patients randomized to TSH (P = 0.028). The estimated median survival for patients randomized to ALPPS was 46 months compared with 26 months for patients randomized to TSH (P = 0.028). Conclusions: ALPPS seems to improve survival in patients with CRLM and sFLR <30% compared with TSH.
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  • Hasselgren, Kristina, et al. (author)
  • ALPPS Improves Survival Compared With TSH in Patients Affected of CRLM Survival Analysis From the Randomized Controlled Trial LIGRO
  • 2021
  • In: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 273:3, s. 442-448
  • Journal article (peer-reviewed)abstract
    • Objective: To evaluate the oncological outcome for patients with colorectal liver metastases (CRLM) randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or 2-stage hepatectomy (TSH). Background: TSH with portal vein occlusion is an established method for patients with CRLM and a low volume of the future liver remnant (FLR). ALPPS is a less established method. The oncological outcome of these methods has not been previously compared in a randomized controlled trial. Methods: One hundred patients with CRLM and standardized FLR (sFLR) <30% were included and randomized to resection by ALPPS or TSH, with the option of rescue ALPPS in the TSH group, if the criteria for volume increase was not met. The first radiological follow-up was performed approximately 4 weeks postoperatively and then after 4, 8, 12, 18, and 24 months. At all the follow-ups, the remaining/recurrent tumor was noted. After the first follow-up, chemotherapy was administered, if indicated. Results: The resection rate, according to the intention-to-treat principle, was 92% (44 patients) for patients randomized to ALPPS compared with 80% (39 patients) for patients randomized to TSH (P = 0.091), including rescue ALPPS. At the first postoperative follow-up, 37 patients randomized to ALPPS were assessed as tumor free in the liver, and also 28 patients randomized to TSH (P = 0.028). The estimated median survival for patients randomized to ALPPS was 46 months compared with 26 months for patients randomized to TSH (P = 0.028). Conclusions: ALPPS seems to improve survival in patients with CRLM and sFLR <30% compared with TSH.
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  • Hasselgren, Kristina, 1976-, et al. (author)
  • Future Liver Remnant (FLR) Increase in Patients with Colorectal Liver Metastases Is Highest the First Week After Portal Vein Occlusion: FLR Increase in Patients with CRLM Is Highest the First Week After PVO
  • 2019
  • In: Journal of Gastrointestinal Surgery. - : Springer Science and Business Media LLC. - 1091-255X .- 1873-4626. ; 23:3, s. 556-562
  • Journal article (peer-reviewed)abstract
    • BackgroundPortal vein occlusion (PVO) is an established method to increase the volume of the future liver remnant (FLR). The main reasons for not proceeding to radical hepatectomy are lack of volume increase and tumor progression due to a wait-time interval of up to 8weeks. The hypothesis was that the increase in FLR volume is not linear and is largest during the first weeks.MethodsPatients with colorectal liver metastases (CRLM) and standardized future liver remnant (sFLR) <30% treated with PVO were prospectively included. All patients had at least one CT evaluation before radical hepatectomy.ResultsForty-eight patients were included. During the first week after PVO, the kinetic growth rate (KGR) was 5.4 (4), compared to 1.5 (+/- 2) between the first and second CT (p<0.05). For patients reaching adequate FLR and therefore treated with radical hepatectomy, the KGR was 7 (+/- 4) the first week, compared to 4.3 (+/- 2) for patients who failed to reach a sufficient volume (p=0.4). During the interval between the first and second CT, the KGR was 2.2 (+/- 2), respectively (+/- 0.1) (p=0.017).Discussion p id=Par4 The increase in liver volume after PVO is largest during the first week. As KGR decreases over time, it is important to shorten the interval between PVO and the first volume evaluation; this may aid in decision-making and reduce unnecessary waiting time.
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  • Hasselgren, Kristina, et al. (author)
  • Liver resection is beneficial for patients with colorectal liver metastases and extrahepatic disease
  • 2020
  • In: Annals of Translational Medicine. - : AME Publishing Company. - 2305-5839 .- 2305-5847. ; 8:4
  • Journal article (peer-reviewed)abstract
    • Background: Liver metastases are the most common cause of death for patients with colorectal cancer and affect up to half of the patients. Liver resection is an established method that can potentially be curative. For patients with extrahepatic disease (EHD), the role of liver surgery is less established. Methods: This is a retrospective study based on data from the national quality registry SweLiv. Data were obtained between 2009 and 2015. SweLiv is a validated registry and has been in use since 2009, with coverage above 95%. Patients with liver metastases and EHD were analyzed and cross-checked against the national death cause registry for survival analysis. Results: During the study period, 2,174 patients underwent surgery for colorectal liver metastases (CRLM), and 277 patients with EHD were treated with resection or ablation. The estimated median survival time for the entire cohort from liver resection/ablation was 40 months (95% CI, 32-47). The survival time for patients treated with liver resection was 45 months compared to 26 months for patients treated with ablation (95% CI 38-53, 18-33, P=0.001). A subgroup analysis of resected patients revealed that the group with pulmonary metastases had a significantly longer estimated median survival (50 months; 95 % CI, 39-60) than the group with lymph node metastases (32 months; 95% CI, 7-58) or peritoneal carcinomatosis (28 months; 95% CI, 14-41) (P=0.022 and 0.012, respectively). Other negative prognostic factors were major liver resection and nonradical liver resection. Conclusions: For patients with liver metastases and limited EHD, liver resection results in prolonged survival compared to what can be expected from chemotherapy alone.
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  • Henriksson, Martin, et al. (author)
  • Treatment patterns and survival in patients with hepatocellular carcinoma in the Swedish national registry SweLiv
  • 2020
  • In: BJS Open. - : JOHN WILEY & SONS LTD. - 2474-9842. ; 4:1, s. 109-117
  • Journal article (peer-reviewed)abstract
    • Background Consistent data on clinical features, treatment modalities and long-term survival in patients with hepatocellular carcinoma (HCC) using nationwide quality registers are lacking. This study aimed to describe treatment patterns and survival outcomes in patients diagnosed with HCC using a national maintained database. Methods Characteristics and treatment patterns in patients diagnosed with HCC and registered in the national register of liver and bile duct tumours (SweLiv) between 2009 and 2016 were reviewed. Overall survival (OS) was estimated using Kaplan-Meier analysis and the log rank test to compare subgroups for clinical features, treatment modalities and outcomes according to the year of treatment. Results A total of 3376 patients with HCC were registered over 8 years, 246 (7 center dot 3 per cent) of whom underwent transplantation. Some 501 (14 center dot 8 per cent) and 390 patients (11 center dot 6 per cent) had resection and ablation as primary treatment. Transarterial chemoembolization and systemic sorafenib treatment were intended in 476 (14 center dot 1 per cent) and 426 patients (12 center dot 6 per cent) respectively; the remaining 1337 (39 center dot 6 per cent) were registered but referred for best supportive care (BSC). The 5-year survival rate was approximately 75 per cent in the transplantation group. Median OS was 4 center dot 6 (i.q.r. 2 center dot 0 to not reached) years after resection and 3 center dot 1 (2 center dot 3-6 center dot 7) years following ablation. In patients referred for palliative treatment, median survival was 1 center dot 4 (0 center dot 8-2 center dot 9), 0 center dot 5 (0 center dot 3-1 center dot 2) and 0 center dot 3 (0 center dot 1-1 center dot 0) years for the TACE, sorafenib and BSC groups respectively (P amp;lt; 0 center dot 001). Median survival was 0 center dot 9 years for the total HCC cohort in 2009-2012, before publication of the Swedish national treatment programme, increasing to 1 center dot 4 years in 2013-2016 (P amp;lt; 0 center dot 001). Conclusion The survival outcomes reported were in line with previous results from smaller cohorts. The introduction of national guidelines may have contributed to improved survival among patients with HCC in Sweden.
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  • Ivanova, Natalia, et al. (author)
  • Structure probing of tmRNA in distinct stages of trans-translation
  • 2007
  • In: RNA. - : Cold Spring Harbor Laboratory. - 1355-8382 .- 1469-9001. ; 13:5, s. 713-722
  • Journal article (peer-reviewed)abstract
    • Ribosomes stalled on problematic mRNAs in bacterial cells can be rescued by transfer-messenger RNA (tmRNA), its helperprotein (small protein B, SmpB), and elongation factor Tu (EF-Tu) through a mechanism called trans-translation. In this work weused lead(II) footprinting to probe the interactions of tmRNA with SmpB and other components of the translation machinery atdifferent steps of the trans-translation cycle. Ribosomes with a short nascent peptide stalled on a truncated mRNA were reactedwith Ala-tmRNA EF-Tu GTP, SmpB, and other translation components to initiate and execute trans-translation. Free tmRNA was                  d      dprobed with lead(II) acetate with and without SmpB, and ribosome bound tmRNA was probed in one of four different trans-translation states stabilized by antibiotic addition or selective exclusion of translation components. For comparison, we alsoanalyzed lead(II) cleavage patterns of tmRNA in vivo in a wild-type as well as in an SmpB-deficient Escherichia coli strain. Weobserved some specific cleavages/protections in tmRNA for the individual steps of trans-translation, but the overall tmRNAconformation appeared to be similar in the stages analyzed. Our findings suggest that, in vivo, a dominant fraction of tmRNA isin complex with SmpB and that, in vitro, SmpB remains tmRNA bound at the initial steps of trans-translation.
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  • Jacobs, Susan S., et al. (author)
  • Home oxygen therapy for adults with chronic lung disease an official american thoracic society clinical practice guideline
  • 2020
  • In: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 202:10, s. 121-141
  • Journal article (peer-reviewed)abstract
    • Background: Evidence-based guidelines are needed for effective delivery of home oxygen therapy to appropriate patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). Methods: The multidisciplinary panel created six research questions using a modified Delphi approach. A systematic review of the literature was completed, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to formulate clinical recommendations. Recommendations: The panel found varying quality and availability of evidence and made the following judgments: 1) strong recommendations for long-term oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe chronic resting hypoxemia, 2) a conditional recommendation against long-term oxygen use in patients with COPD with moderate chronic resting hypoxemia, 3) conditional recommendations for ambulatory oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe exertional hypoxemia, 4) a conditional recommendation for ambulatory liquidoxygen use in patients who are mobile outside the home and require .3 L/min of continuous-flow oxygen during exertion (very-lowquality evidence), and 5) a recommendation that patients and their caregivers receive education on oxygen equipment and safety (bestpractice statement). Conclusions: These guidelines provide the basis for evidence-based use of home oxygen therapy in adults with COPD or ILD but also highlight the need for additional research to guide clinical practice.
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  • Jakobsson, Fredrik L. E., 1974-, et al. (author)
  • Towards all-plastic flexible light emitting diodes
  • 2006
  • In: Chemical Physics Letters. - : Elsevier BV. - 0009-2614 .- 1873-4448. ; 433:1-3, s. 110-114
  • Journal article (peer-reviewed)abstract
    • All-plastic light emitting diodes require the design and fabrication of low work function plastic electrodes. Here, we show that the work function of poly(3,4-ethylenedioxythiophene)-polystyrenesulfonic acid (PEDOT-PSS) can be decreased from 4.8 eV to 3.9 eV by surface reaction with the strong electron-donor tetrakis(dimethylamino)ethylene (TDAE). The surface modification was characterized by photoelectron spectroscopy and optical spectroscopy. The low work function plastic electrode was used in a first prototype for all-plastic light emitting diodes.
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  • Lindell, Linda, 1976-, et al. (author)
  • Characterization of the interface dipole at the paraphenylenediamine-nickel interface : A joint theoretical and experimental study
  • 2005
  • In: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 122:8, s. 84712-
  • Journal article (peer-reviewed)abstract
    • In organic-based (opto)electronic devices, charge injection into conjugated materials is governed to a large extent by the metal-organic interface dipole. Controlling the injection of charges requires a better understanding of the fundamental origin of the interface dipole. In this context, photoelectron spectroscopies and density functional theory calculations are used to investigate the interaction between para-phenylenediamine (PPDA), an electron donor, and a polycrystalline nickel surface. The interface dipole formed upon chemisorption of one PPDA monolayer strongly modifies the work function of the nickel surface from 5.10 to 3.55 eV. The work function decrease of 1.55 eV is explained by the electron-donor character of PPDA and the modification of the electronic density at the metal surface. PPDA monolayers are composed of tilted molecules interacting via the nitrogen lone-pair and PPDA molecules chemisorbed parallel to the surface via their π-electron density. Annealing the monolayer leads to dehydrogenation of PPDA activated by the nickel surface, as found for other amines.
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  • Lindell, Linda, et al. (author)
  • Transparent, plastic, low-work-function poly(3,4-ethylenedioxythiophene) electrodes
  • 2006
  • In: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 18:18, s. 4246-4252
  • Journal article (peer-reviewed)abstract
    • Novel applications for flexible electronics, e.g., displays and solar cells, require fully flexible, transparent, stable, and low-work-function electrodes that can be manufactured via a low-cost process. Here, we demonstrate that surface chemistry constitutes a route to producing transparent low-work-function plastic electrodes. The work function of the conducting polymer poly(3,4-ethylenedioxythiophene)-tosylate, or PEDOT-Tos, is decreased by submonolayer surface redox reaction with a strong electron donor, tetrakis-(dimethylamino)ethylene (TDAE), allowing it to reach a work function of 3.8 eV. The interface formed between TDAE and PEDOT is investigated in a joint experimental and theoretical study using photoelectron spectroscopy and quantum chemical calculations. © 2006 American Chemical Society.
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  • Lindell, Mats, et al. (author)
  • Among demons and angels: Attitudes towards system evaluation for quality improvement in advanced vocational education
  • 2002
  • In: Quality in Higher Education. - : Informa UK Limited. - 1353-8322 .- 1470-1081. ; 8:2, s. 127-136
  • Journal article (peer-reviewed)abstract
    • This paper investigates attitudes among educational organisations towards the use of system evaluation for quality improvement in Swedish higher education. The subject of this investigation is the evaluation of the pilot project on advanced vocational education (AVE), which was conducted between 1997 and 1999 by a research team at the Luleå Technological University. The investigation was carried out in the form of a telephone inquiry with a strategic selection of the education organisers. The investigation shows that 65% of the respondents regard the work of the research team, built on the system-evaluation model, as an instrument to inspire confidence and contribute to renewal.
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  • Lindell, Magnus, 1969- (author)
  • Lead(II) as a Tool for Probing RNA Structure in vivo
  • 2005
  • Doctoral thesis (other academic/artistic)abstract
    • Chemical modification and limited enzymatic hydrolysis are powerful methods to obtain detailed information on the structure and dynamics of RNAs in solution. In the work presented here I have taken advantage of the properties of the divalent metal ion lead(II) to establish it as a new probe for investigating the structure of RNA in vivo. Besides highly specific lead(II)-induced cleavage due to the presence of tight metal ion binding sites, lead(II) is known to cleave RNA within single-stranded regions, loops and bulges. The detailed structural data obtained with three different RNAs: tmRNA, CopT, and the leader region of the ompF mRNA, show that lead(II) has great potential for in vivo studies of RNA structure. In P. fluorescens, the activity and stability of RsmY, a small regulatory RNA, was shown to be strongly dependent on repeated GGA motifs in single-stranded regions. In vivo lead(II) probing essentially confirmed predicted secondary structures and also indicated binding to a protein, RsmA. The potential in using lead(II) for mapping protein binding sites on RNAs was shown for the interaction between E. coli tmRNA and the SmpB protein. In vivo and in vitro data show protections in the tRNA-like domain of tmRNA due to binding to the SmpB protein, indicating that the SmpB protein is associated with the majority of tmRNA in the cell. Furthermore, the overall conformation/ structure of E. coli RNase P was analyzed by probing the native structure of M1 RNA in vivo with lead(II). The observed cleavages suggests that M1 RNA is present in two main conformations in the cell, one being characteristic of free RNase P, and one of an RNase P-tRNA complex. The results also indicate that the C5 protein subunit has only minor effects on the overall structure of the RNA subunit.
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  • Lindell, Magnus, et al. (author)
  • Lead(II) cleavage analysis of RNase P RNA in vivo.
  • 2005
  • In: RNA. - 1355-8382. ; 11:9, s. 1348-54
  • Journal article (peer-reviewed)abstract
    • The overall conformation of M1 RNA, the catalytic RNA subunit of RNase P in Escherichia coli, was analyzed in vivo and, in the presence of the C5 protein subunit, in vitro by lead(II) acetate probing. The partial cleavage patterns obtained are congruent with previous structure mapping performed in vitro. Most of the known major and minor cleavages in M1 RNA were supported and could be mapped onto a secondary structure model. The data obtained indicate that C5 has only minor effects on the overall structure of the RNA subunit. The similar cleavage patterns obtained in vitro and in vivo furthermore suggest that the intracellular environment does not greatly alter the overall conformation of M1 RNA within the holoenzyme complex. Moreover, our data indicate that M1 RNA in vivo is present in at least two states-the major fraction is bound to tRNA substrates and a minor fraction is substrate free. Finally, both in this and previous work we found that lead(II) probing data from in vivo experiments conducted on longer RNAs (tmRNA and M1 RNA) generally gives superior resolution compared to parallel in vitro experiments. This may reflect the absence of alternative conformers present in vitro and the more natural state of these RNAs in the cell due to proper, co-transcriptional folding pathways and possibly the presence of RNA chaperones.
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  • Mao, Guanzhong, 1985-, et al. (author)
  • Critical domain interactions for type A RNase P RNA catalysis with and without the specificity domain
  • 2018
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:3
  • Journal article (peer-reviewed)abstract
    • The natural trans-acting ribozyme RNase P RNA (RPR) is composed of two domains in which the catalytic (C-) domain mediates cleavage of various substrates. The C-domain alone, after removal of the second specificity (S-) domain, catalyzes this reaction as well, albeit with reduced efficiency. Here we provide experimental evidence indicating that efficient cleavage mediated by the Escherichia coli C-domain (Eco CP RPR) with and without the C5 protein likely depends on an interaction referred to as the "P6-mimic". Moreover, the P18 helix connects the C-and S-domains between its loop and the P8 helix in the S-domain (the P8/P18-interaction). In contrast to the "P6-mimic", the presence of P18 does not contribute to the catalytic performance by the C-domain lacking the S-domain in cleavage of an all ribo model hairpin loop substrate while deletion or disruption of the P8/P18-interaction in full-size RPR lowers the catalytic efficiency in cleavage of the same model hairpin loop substrate in keeping with previously reported data using precursor tRNAs. Consistent with that P18 is not required for cleavage mediated by the C-domain we show that the archaeal Pyrococcus furiosus RPR C-domain, which lacks the P18 helix, is catalytically active in trans without the S-domain and any protein. Our data also suggest that the S-domain has a larger impact on catalysis for E. coli RPR compared to P. furiosus RPR. Finally, we provide data indicating that the absence of the S-domain and P18, or the P8/P18-interaction in full-length RPR influences the charge distribution near the cleavage site in the RPR-substrate complex to a small but reproducible extent.
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34.
  • Persson Lindell, Olof, et al. (author)
  • Clinical decision support for familial hypercholesterolemia (CDS-FH) : Rationale and design of a cluster randomized trial in primary care
  • 2022
  • In: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 247, s. 132-148
  • Journal article (peer-reviewed)abstract
    • Background: Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder with high risk of premature atherosclerotic cardiovascular disease and death. Clinical decision support (CDS) systems have the potential to aid in the identification and management of patients with FH. Prior studies using computer-based systems to screen patients for FH have shown promising results, but there has been no randomized controlled trial conducted. The aim of the current cluster randomized study is to evaluate if a CDS can increase the identification of FH.Methods: We have developed a CDS integrated in the electronic health records that will be activated in patients with elevated cholesterol levels (total cholesterol > 8 mmol/L or low-density lipoprotein-cholesterol > 5.5 mmol/L, adjusted for age, ongoing lipid lowering therapy and presence of premature coronar y arter y disease) at increased risk for FH. When activated, the CDS will urge the physician to send an automatically generated referral to the local lipid clinic for further evaluation. To evaluate the effects of the CDS, all primary care clinics will be cluster randomized 1:1 to either CDS intervention or standard care in a Swedish region with almost 500,000 inhabitants. The primary endpoint will be the number of patients diagnosed with FH at 30 months. Resource use and long-term health consequences will be estimated to assess the cost-effectiveness of the intervention.Conclusion : Despite increasing awareness of FH, the condition remains underdiagnosed and undertreated. The present study will investigate whether a CDS can increase the number of patients being diagnosed with FH.
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35.
  • Quttineh, Nils-Hassan, et al. (author)
  • An optimization approach to the design of outdoor thermal fire detection systems
  • 2022
  • In: Fire safety journal. - : Elsevier Science Ltd. - 0379-7112 .- 1873-7226. ; 129
  • Journal article (peer-reviewed)abstract
    • With the recent growing usage of bio-fuels the need for fire detection in outdoor bio-fuel depots has increased, and several fire detection technologies for this purpose have been proposed. We consider the use of thermal cameras and present the problem of designing the placement of such cameras. Bio-fuel depots are often large and it might be prohibitively expensive to surveil the complete areas of interest, and it is therefore required to generate compromise solutions between area coverage and cost, to be presented to a customer. We give a bi-objective mathematical optimization formulation of the problem and fast heuristics that find compromise solutions, and present results from calculating camera placements for several real-world bio-fuel depots. Our approach has been implemented in a decision support software, which is currently in use.
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36.
  • Sandstrom, P., et al. (author)
  • ALPPS Improves Resectability Compared With Conventional Two-stage Hepatectomy in Patients With Advanced Colorectal Liver Metastasis Results From a Scandinavian Multicenter Randomized Controlled Trial (LIGRO Trial)
  • 2018
  • In: Annals of Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 0003-4932 .- 1528-1140. ; 267:5, s. 833-840
  • Journal article (peer-reviewed)abstract
    • Objective: The aim of the study was to evaluate if associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) could increase resection rates (RRs) compared with two-stage hepatectomy (TSH) in a randomized controlled trial (RCT). Background: Radical liver metastasis resection offers the only chance of a cure for patients with metastatic colorectal cancer. Patients with colorectal liver metastasis (CRLM) and an insufficient future liver remnant (FLR) volume are traditionally treated with chemotherapy with portal vein embolization or ligation followed by hepatectomy (TSH). This treatment sometimes fails due to insufficient liver growth or tumor progression. Methods: A prospective, multicenter RCTwas conducted between June 2014 and August 2016. It included 97 patients with CRLM and a standardized FLR (sFLR) of less than 30%. Primary outcome-RRs were measured as the percentages of patients completing both stages of the treatment. Secondary outcomes were complications, radicality, and 90-day mortality measured from the final intervention. Results: Baseline characteristics, besides body mass index, did not differ between the groups. The RR was 92% [ 95% confidence interval (CI) 84%-100%] (44/48) in the ALPPS arm compared with 57% (95% CI 43%-72%) (28/49) in the TSH arm [rate ratio 8.25 (95% CI 2.6-26.6); P < 0.0001]. No differences in complications (Clavien- Dindo >= 3a) [ 43% (19/44) vs 43% (12/28)] [1.01 (95% CI 0.4-2.6); P = 0.99], 90-day mortality [8.3% (4/48) vs 6.1% (3/49)] [ 1.39 [95% CI 0.3-6.6]; P = 0.68] or R0 RRs [77% (34/44) vs 57% (16/28)] [2.55 [95% CI 0.9-7.1]; P = 0.11)] were observed. Of the patients in the TSH arm that failed to reach an sFLR of 30%, 12 were successfully treated with ALPPS. Conclusion: ALPPS is superior to TSH in terms of RR, with comparable surgical margins, complications, and short- term mortality.
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37.
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38.
  • Sandström, Per, et al. (author)
  • ALPPS Improves Resectability Compared with Conventional Two-stage Hepatectomy in Patients with Advanced Colorectal Liver Metastasis : Results from a Scandinavian Multicenter Randomized Controlled Trial (LIGRO Trial)
  • 2018
  • In: Annals of Surgery. - : LIPPINCOTT WILLIAMS & WILKINS. - 0003-4932 .- 1528-1140. ; 267:5, s. 833-840
  • Journal article (peer-reviewed)abstract
    • Objective: The aim of the study was to evaluate if associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) could increase resection rates (RRs) compared with two-stage hepatectomy (TSH) in a randomized controlled trial (RCT). Background: Radical liver metastasis resection offers the only chance of a cure for patients with metastatic colorectal cancer. Patients with colorectal liver metastasis (CRLM) and an insufficient future liver remnant (FLR) volume are traditionally treated with chemotherapy with portal vein embolization or ligation followed by hepatectomy (TSH). This treatment sometimes fails due to insufficient liver growth or tumor progression. Methods: A prospective, multicenter RCT was conducted between June 2014 and August 2016. It included 97 patients with CRLM and a standardized FLR (sFLR) of less than 30%. Primary outcome - RRs were measured as the percentages of patients completing both stages of the treatment. Secondary outcomes were complications, radicality, and 90-day mortality measured from the final intervention. Results: Baseline characteristics, besides body mass index, did not differ between the groups. The RR was 92% [95% confidence interval (CI) 84%-100%] (44/48) in the ALPPS arm compared with 57% (95% CI 43%-72%) (28/49) in the TSH arm [rate ratio 8.25 (95% CI 2.6-26.6); P < 0.0001]. No differences in complications (Clavien-Dindo ≥3a) [43% (19/44) vs 43% (12/28)] [1.01 (95% CI 0.4-2.6); P = 0.99], 90-day mortality [8.3% (4/48) vs 6.1% (3/49)] [1.39 [95% CI 0.3-6.6]; P = 0.68] or R0 RRs [77% (34/44) vs 57% (16/28)] [2.55 [95% CI 0.9-7.1]; P = 0.11)] were observed. Of the patients in the TSH arm that failed to reach an sFLR of 30%, 12 were successfully treated with ALPPS. Conclusion: ALPPS is superior to TSH in terms of RR, with comparable surgical margins, complications, and short-term mortality.
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39.
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41.
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42.
  • Sinno, Hiam, 1983-, et al. (author)
  • Amphiphilic semiconducting copolymer as compatibility layer for printing polyelectrolyte-gated OFETs
  • 2013
  • In: Organic electronics. - : Elsevier. - 1566-1199 .- 1878-5530. ; 14:3, s. 790-796
  • Journal article (peer-reviewed)abstract
    • We report a method for inkjet-printing an organic semiconductor layer on top of the electrolyte insulator layer in polyelectrolyte-gated OFETs by using a surface modification treatment to overcome the underlying wettability problem at this interface. The method includes depositing an amphiphilic diblock copolymer (P3HT-b-PDMAEMA). This material is designed to have one set of blocks that mimics the hydrophobic properties of the semiconductor (poly(3-hexylthiophene) or P3HT), while the other set of blocks include polar components that improve adhesion to the polyelectrolyte insulator. Contact angle measurements, atomic force microscopy, and X-ray photoelectron spectroscopy confirm formation of the desired surface modification film. Successful inkjet printing of a smooth semiconductor layer allows us to manufacture complete transistor structures that exhibit low-voltage operation in the range of 1 V.
  •  
43.
  • Sternby Eilard, Malin, 1974, et al. (author)
  • Survival and prognostic factors after transplantation, resection and ablation in a national cohort of early hepatocellular carcinoma
  • 2021
  • In: HPB. - : Elsevier BV. - 1365-182X .- 1477-2574. ; 23:3, s. 394-403
  • Journal article (peer-reviewed)abstract
    • © 2020 International Hepato-Pancreato-Biliary Association Inc. Background: In patients with early hepatocellular cancer (HCC) and preserved liver function, the choice between transplantation, resection and ablation and which factors to consider is not obvious and guidelines differ. In this national cohort study, we aimed to compare posttreatment survival in patients fulfilling predefined criteria, and to analyse preoperative risk factors that could influence decision. Methods: We used data from HCC-patients registered with primary transplantation, resection or ablation 2008–2016 in the SweLiv-registry. In Child A-subgroups, 18–75 years, we compared survival after transplantation or resection, with different tumour criteria; either corresponding to our transplantation criteria (N = 257) or stricter with single tumours ≤50 mm (N = 159). A subgroup with single tumours ≤30 mm, compared all three treatments (N = 193). Results: We included 1022 HCC-patients; transplantation n = 223, resection n = 438, ablation n = 361. In the transplant criteria subgroup, differences in five-year survival, adjusted for age and gender, were not significant, with 71.2% (CI 62.3–81.3) after transplantation (n = 109) and 63.5% (CI 54.9–73.5) after resection (n = 148). Good liver function (Child 5 vs. 6, Albumin ≥36), increased the risk after transplantation, but decreased the risk after resection and ablation. Conclusion: Even within Child A, detailed liver function assessment is important before treatment decision, and for stratifying survival comparisons.
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44.
  • Strandberg Holka, Peter, et al. (author)
  • Significance of poor performance status after resection of colorectal liver metastases
  • 2018
  • In: World Journal of Surgical Oncology. - : Springer Science and Business Media LLC. - 1477-7819. ; 16:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Performance status (PS) is known as one of the strongest prognostic factors for survival in metastatic colorectal cancer patients. The aim of the present study was to analyze factors associated with poor PS assessed after resection for colorectal liver metastases and the impact on survival.METHODS: All patients undergoing curative resection for colorectal liver metastases between 2010 and 2015 in a single center were reviewed retrospectively.RESULTS: A total of 284 patients were included, out of whom 74 patients (26%) presented with a postoperative PS WHO > 2 precluding administration of adjuvant chemotherapy. These patients had a shorter recurrence-free survival (P = 0.002) and shorter overall survival (P < 0.001). Multivariable analysis showed that patients with PS > 2 after surgery had higher preoperative ASA score, had a higher frequency of major complications after surgery, and had more frequently synchronous liver and lung metastases. PS was found to be the strongest independent factor predicting survival (hazard ratio 0.45). When patients with postoperative PS > 2 developed recurrent disease (54 of 74), 43 (80%) received tumor specific treatment.CONCLUSIONS: Patients with postoperative PS > 2 who did not receive adjuvant chemotherapy had decreased recurrence-free and overall survival after liver resection for colorectal liver metastases. After recurrence, a large majority of these patients had had improvement in PS allowing for administration of tumor specific treatment.
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45.
  • Strandh, Magnus, et al. (author)
  • On robustness of turbo coded OFDM systems over frequency selective channels
  • 2003
  • In: 8th International OFDM-Workshop.
  • Conference paper (peer-reviewed)abstract
    • The robustness of fixed Turbo coded communication systems over frequency selective channels are investigated. The simulated amplitude functions are based on an idealised two level function and a decaying function. The results indicate that the system can cope with severe disturbances without to much loss.
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46.
  • Sundström, Magnus, et al. (author)
  • KRAS analysis in colorectal carcinoma : analytical aspects of Pyrosequencing and allele-specific PCR in clinical practice
  • 2010
  • In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 10, s. 660-
  • Journal article (peer-reviewed)abstract
    • Background: Epidermal growth factor receptor inhibitor therapy is now approved for treatment of metastatic colorectal carcinomas (CRC) in patients with tumors lacking KRAS mutations. Several procedures to detect KRAS mutations have been developed. However, the analytical sensitivity and specificity of these assays on routine clinical samples are not yet fully characterised.Methods: The practical aspects and clinical applicability of a KRAS-assay based on Pyrosequencing were evaluated in a series of 314 consecutive CRC cases submitted for diagnostic KRAS analysis. The performance of Pyrosequencing compared to allele-specific, real-time PCR was then explored by a direct comparison of CE-IVD-marked versions of Pyrosequencing and TheraScreen (DxS) KRAS assays for a consecutive subset (n = 100) of the 314 clinical CRC samples.Results: Using Pyrosequencing, 39% of the 314 CRC samples were found KRAS-mutated and several of the mutations (8%) were located in codon 61. To explore the analytical sensitivity of the Pyrosequencing assay, mutated patient DNA was serially diluted with wild-type patient DNA. Dilutions corresponding to 1.25-2.5% tumor cells still revealed detectable mutation signals. In clinical practice, our algorithm for KRAS analysis includes a reanalysis of samples with low tumor cell content (< 10%, n = 56) using an independent assay (allele-specific PCR, DxS). All mutations identified by Pyrosequencing were then confirmed and, in addition, one more mutated sample was identified in this subset of 56 samples. Finally, a direct comparison of the two technologies was done by re-analysis of a subset (n = 100) of the clinical samples using CE-IVD-marked versions of Pyrosequencing and TheraScreen KRAS assays in a single blinded fashion. The number of samples for which the KRAS codon 12/13 mutation status could be defined using the Pyrosequencing or the TheraScreen assay was 94 and 91, respectively, and both assays detected the same number of codon 12 and 13 mutations.Conclusions: KRAS mutation detection using Pyrosequencing was evaluated on a consecutive set of clinical CRC samples. Pyrosequencing provided sufficient analytical sensitivity and specificity to assess the mutation status in routine formalin-fixed CRC samples, even in tissues with a low tumor cell content.
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47.
  • Valdimarsson, Valentinus T., et al. (author)
  • Outcomes of liver-first strategy and classical strategy for synchronous colorectal liver metastases in Sweden
  • 2018
  • In: HPB. - : Elsevier BV. - 1365-182X .- 1477-2574. ; 20:5, s. 441-447
  • Journal article (peer-reviewed)abstract
    • Background: Patients with synchronous colorectal liver metastases (sCRLM) are increasingly operated with liver resection before resection of the primary cancer. The aim of this study was to compare outcomes in patients following the liver-first strategy and the classical strategy (resection of the bowel first) using prospectively registered data from two nationwide registries. Methods: Clinical, pathological and survival outcomes were compared between the liver-first strategy and the classical strategy (2008-2015). Overall survival was calculated. Results: A total of 623 patients were identified, of which 246 were treated with the liver-first strategy and 377 with the classical strategy. The median follow-up was 40 months. Patients chosen for the classical strategy more often had T4 primary tumours (23% vs 14%, P = 0.012) and node-positive primaries (70 vs 61%, P = 0.015). The liver-first patients had a higher liver tumour burden score (4.1 (2.5-6.3) vs 3.6 (2.2-5.1), P = 0.003). No difference was seen in five-year overall survival between the groups (54% vs 49%, P = 0.344). A majority (59%) of patients with rectal cancer were treated with the liver-first strategy. Conclusion: The liver-first strategy is currently the dominant strategy for sCRLM in patients with rectal cancer in Sweden. No difference in overall survival was noted between strategies.
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48.
  • Valdimarsson, Valentinus T., et al. (author)
  • Outcomes of Simultaneous Resections and Classical Strategy for Synchronous Colorectal Liver Metastases in Sweden: A Nationwide Study with Special Reference to Major Liver Resections
  • 2020
  • In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 44, s. 2409-2417
  • Journal article (peer-reviewed)abstract
    • Background About 20% of patients with colorectal cancer have liver metastases at the time of diagnosis, and surgical resection offers a chance for cure. The aim of the present study was to compare outcomes for patients that underwent simultaneous resection to those that underwent a staged procedure with the bowel-first (classical) strategy by using information from two national registries in Sweden. Methods In this prospectively registered cohort study, we analyzed clinical, pathological, and survival outcomes for patients operated in the period 2008-2015 and compared the two strategies. Results In total, 537 patients constituted the study cohort, where 160 were treated with the simultaneous strategy and 377 with the classical strategy. Patients managed with the simultaneous strategy had less often rectal primary tumors (22% vs. 31%, p = 0.046) and underwent to a lesser extent a major liver resection (16% vs. 41%, p < 0.001), but had a shorter total length of stay (11 vs. 15 days, p < 0.001) and more complications (52% vs. 36%, p < 0.001). No significant 5-year overall survival (p = 0.110) difference was detected. Twenty-five patients had a major liver resection in the simultaneous strategy group and 155 in the classical strategy group without difference in 5-year overall survival (p = 0.198). Conclusion Simultaneous resection of the colorectal primary cancer and liver metastases can possibly have more complications, with no difference in overall survival compared to the classical strategy.
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