| 1. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 3. |
- Argyropoulos, Dimitris D. S., et al.
(författare)
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Kraft Lignin: A Valuable, Sustainable Resource, Opportunities and Challenges
- 2023
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Ingår i: ChemSusChem. - : John Wiley and Sons Inc. - 1864-5631 .- 1864-564X. ; 16:23
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Forskningsöversikt (refereegranskat)abstract
- Kraft lignin, a by-product from the production of pulp, is currently incinerated in the recovery boiler during the chemical recovery cycle, generating valuable bioenergy and recycling inorganic chemicals to the pulping process operation. Removing lignin from the black liquor or its gasification lowers the recovery boiler load enabling increased pulp production. During the past ten years, lignin separation technologies have emerged and the interest of the research community to valorize this underutilized resource has been invigorated. The aim of this Review is to give (1) a dedicated overview of the kraft process with a focus on the lignin, (2) an overview of applications that are being developed, and (3) a techno-economic and life cycle asseeements of value chains from black liquor to different products. Overall, it is anticipated that this effort will inspire further work for developing and using kraft lignin as a commodity raw material for new applications undeniably promoting pivotal global sustainability concerns.
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| 4. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 5. |
- Henriksson, Gunnar, et al.
(författare)
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Lignin-carbohydrate network in wood and pulps : A determinant for reactivity
- 2007
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Ingår i: Holzforschung. - 0018-3830 .- 1437-434X. ; 61:6, s. 668-674
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Tidskriftsartikel (refereegranskat)abstract
- Pretreatment of wood or kraft pulp with endoglucanase followed by swelling in urea leaves a non-crystalline residue that can be dissolved in strong aqueous sodium hydroxide-sodium borate solution. A stepwise precipitation process employing acid and barium ions can separate lignin-carbohydrate complexes enriched in individual polysaccharides. This procedure has been applied to eucalypt and birch wood and to the corresponding kraft pulps. Thioacidolysis of the various lignin-carbohydrate complexes was used as the major analytical technique to obtain information about the structure and structural changes in lignin. A combination of thioacidolysis and size exclusion chromatography was used to obtain knowledge on the degree of depolymerisation and repolymerisation of lignin when going from wood to chemical pulp. In contrast to spruce wood and kraft pulp, complete recovery of the lignin-carbohydrate complexes could not be obtained from hardwood samples.
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| 6. |
- Henriksson, Gunnar, 1965-, et al.
(författare)
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Monocomponent endoglucanases : an excellent tool in wood chemistry and pulp processing
- 2005
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Ingår i: 13th ISWFPC (International Symposium on Wood, Fibre and Pulping Chemistry), Auckland, New Zealand, 16-19 May 2005: Proceedings. ; , s. 503-508
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Konferensbidrag (refereegranskat)abstract
- Highly pure cellulases of endoglucanase type produced by genetically modified fungi are commercially available. They are useful tools both for analytical wood chemistry and potentially also as industrial chemicals for novel processes for the pulp and paper industry. Here the functionality of cellulases and some application of endoglucanases are reviewed. The mechanisms behind the effects of the enzyme are discussed.
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| 7. |
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| 8. |
- Henriksson, Martin, et al.
(författare)
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Assessing the cost effectiveness of using prognostic biomarkers with decision models: case study in prioritising patients waiting for coronary artery surgery
- 2010
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Ingår i: BRITISH MEDICAL JOURNAL. - : BMJ. - 0959-535X. ; 340
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Tidskriftsartikel (refereegranskat)abstract
- Objective To determine the effectiveness and cost effectiveness of using information from circulating biomarkers to inform the prioritisation process of patients with stable angina awaiting coronary artery bypass graft surgery. Design Decision analytical model comparing four prioritisation strategies without biomarkers (no formal prioritisation, two urgency scores, and a risk score) and three strategies based on a risk score using biomarkers: a routinely assessed biomarker (estimated glomerular filtration rate), a novel biomarker (C reactive protein), or both. The order in which to perform coronary artery bypass grafting in a cohort of patients was determined by each prioritisation strategy, and mean lifetime costs and quality adjusted life years (QALYs) were compared. Data sources Swedish Coronary Angiography and Angioplasty Registry (9935 patients with stable angina awaiting coronary artery bypass grafting and then followed up for cardiovascular events after the procedure for 3.8 years), and meta-analyses of prognostic effects (relative risks) of biomarkers. Results The observed risk of cardiovascular events while on the waiting list for coronary artery bypass grafting was 3 per 10 000 patients per day within the first 90 days (184 events in 9935 patients). Using a cost effectiveness threshold of 20 pound 000-30 pound 000 ((sic)22 000-(sic)33 000; $32 000-$48 000) per additional QALY, a prioritisation strategy using a risk score with estimated glomerular filtration rate was the most cost effective strategy (cost per additional QALY was andlt;410 pound compared with the Ontario urgency score). The impact on population health of implementing this strategy was 800 QALYs per 100 000 patients at an additional cost of 245 pound 000 to the National Health Service. The prioritisation strategy using a risk score with C reactive protein was associated with lower QALYs and higher costs compared with a risk score using estimated glomerular filtration rate. Conclusion Evaluating the cost effectiveness of prognostic biomarkers is important even when effects at an individual level are small. Formal prioritisation of patients awaiting coronary artery bypass grafting using a routinely assessed biomarker (estimated glomerular filtration rate) along with simple, routinely collected clinical information was cost effective. Prioritisation strategies based on the prognostic information conferred by C reactive protein, which is not currently measured in this context, or a combination of C reactive protein and estimated glomerular filtration rate, is unlikely to be cost effective. The widespread practice of using only implicit or informal means of clinically ordering the waiting list may be harmful and should be replaced with formal prioritisation approaches.
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| 9. |
- Henriksson, Martin, et al.
(författare)
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The cost-effectiveness of an early interventional strategy in non-ST-elevation acute coronary syndrome based on the RITA 3 trial
- 2008
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 94, s. 717-723
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence suggests that an early interventional strategy for patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) can improve health outcomes but also increase costs when compared with a conservative strategy. Objective: The aim of this study was to assess the cost-effectiveness of an early interventional strategy in different risk groups from a UK health-service perspective. Design: Decision-analytic model based on randomised clinical trial data. Main outcome measures: Costs in UK Sterling at 2003/2004 prices and quality-adjusted life years (QALYs) combined into an incremental cost-effectiveness ratio. Methods: Data from the third Randomised Intervention Trial of unstable Angina (RITA 3) was employed to estimate rates of cardiovascular death and myocardial infarction, costs and health-related quality of life. Cost-effectiveness was estimated over patients’ lifetimes within the decision-analytic model. Results: The mean incremental cost per QALY gained for an early interventional strategy was approximately £55 000, £22 000 and £12 000 for patients at low, intermediate and high risk, respectively. The early interventional strategy is approximately 1%, 35% and 95% likely to be cost-effective for patients at low, intermediate and high risk, respectively, at a threshold of £20 000 per QALY. The cost-effectiveness of early intervention in low-risk patients is sensitive to assumptions about the duration of the treatment effect. Conclusion: An early interventional strategy in patients presenting with NSTE-ACS is likely to be considered cost-effective for patients at high and intermediate risk, but this is less likely to be the case for patients at low risk.
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| 10. |
- Henriksson, Martin, et al.
(författare)
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The transfer of clinical prediction models for early trauma care had uncertain effects on mistriage
- 2020
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier BV. - 0895-4356 .- 1878-5921. ; 128, s. 66-73
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study aimed to assess how transfers of clinical prediction models for early trauma care between different care contexts within a single health system affected mistriage rates. Study Design and Setting: Patients aged 15 years or older, registered between 2011 and 2016 in the Swedish national trauma registry, SweTrau, were included. Three data set groups were created: high- and low-volume centers, metropolitan and nonmetropolitan centers, and multicenters and single centers. Clinical prediction models were developed using logistic regression in each data set group and transferred between data sets within groups. Model performance was evaluated using mistriage rate, undertriage rate, and overtriage rate. Multiple imputation using chained equations was used to handle missing data. Model performance was reported as medians with 95% confidence intervals (CIs). Results: A total of 26,965 patients were included. Changes in mistriage rates after transfer ranged from −0.25 (95% CI −0.21 to 0.04) to 0.29 (95% CI 0.13–0.39). Both overtriage and undertriage rates were affected. Conclusions: Transferring clinical prediction models for early trauma care is associated with substantial uncertainty in regards to the effect on model performance. Depending on the care context, model transfer led to either increased or decreased mistriage. Overtriage was more affected by model transfer than undertriage.
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| 11. |
- Holgersson, Georg, et al.
(författare)
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Swedish lung cancer radiation study group: the prognostic value of anaemia, thrombocytosis and leukocytosis at time of diagnosis in patients with non-small cell lung cancer
- 2012
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Ingår i: Medical Oncology. - : Humana Press (Springer Imprint). - 1357-0560 .- 1559-131X. ; 29:5, s. 3176-3182
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Tidskriftsartikel (refereegranskat)abstract
- There is a need to improve the prognostic and predictive indicators in non-small cell lung cancer (NSCLC). At present, the main focus is on genetic predictive markers while the prognostic value of the standard blood variables related to haematopoiesis has been subjected to relatively limited attention. To study the prognostic potential of haemoglobin (Hgb), platelet (Plt) and white blood cell (WBC) levels at time of diagnosis in NSCLC patients, 835 NSCLC patients, stage I-IV, who received radiotherapy with curative intention (andgt; 50 Gy), were included in the study. WBC, Plt, Hgb, gender, age at diagnosis, stage, surgery and first-line chemotherapy were studied in relation to overall survival. For patients with Hgb andlt; 110 g/L and Hgb a parts per thousand yen 110 g/L), the median survival was 11.2 and 14.5 months, respectively (p = 0.0032). For WBC andgt; 9.0 x 10(9)/L and andlt; 9.0 x 10(9)/L, the median survival was 11.6 and 15.4 months, respectively (p andlt; 0.0001). For Plt andgt; 350 x 10(9)/L and andlt; 350 x 10(9)/L, the median survival was 11.2 and 14.9 months, respectively (p andlt; 0.0001). The median survival in patients with pathological results in all three markers was half of that in patients with normal levels of all three markers (8.0 and 16.0 months, respectively (p andlt; 0.0001). The level of the three studied haematological biomarkers corresponds significantly to outcome in NSCLC. These results indicate that standard haematological variables may be used as guidance for the clinician in the decision-making regarding treatment intensity and patient information.
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| 12. |
- Holgersson, Georg, et al.
(författare)
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The value of induction chemotherapy for survival in patients with non-small cell lung cancer treated with radiotherapy.
- 2012
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Ingår i: Anticancer research. - : The International Institute of Anticancer Research. - 1791-7530 .- 0250-7005. ; 32:4, s. 1339-46
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The aim of the present study was to retrospectively investigate the impact of induction chemotherapy on treatment outcome in patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with a diagnosed NSCLC that have been subjected to curatively intended irradiation (≥50 Gy) and treated in an oncology department in Sweden during the years 1990-2000 were included in the study. Operated patients and patients having received concomitant chemotherapy were excluded. The included patients were localised by a manual search of all the oncology departments' medical records and radiation charts. RESULTS: Patients treated with induction chemotherapy (n=79) had a significantly better overall survival compared with patients treated with radiotherapy alone (p=0.0097) in a univariate Cox regression analysis. A platinum/taxane combination produced the greatest survival benefit; hazard ratio=0.49 (95% confidence interval=0.31 to 0.75). CONCLUSION: We found that patients treated with induction chemotherapy in addition to radiotherapy for NSCLC have a better overall survival than patients treated with radiotherapy alone and that the best results are achieved using a platinum/taxane combination.
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| 13. |
- Nasr, Patrik, et al.
(författare)
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A rapid, non-invasive, clinical surveillance for CachExia, sarcopenia, portal hypertension, and hepatocellular carcinoma in end-stage liver disease : the ACCESS-ESLD study protocol
- 2023
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Ingår i: BMC Gastroenterology. - : BioMed Central (BMC). - 1471-230X. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Liver cirrhosis, the advanced stage of many chronic liver diseases, is associated with escalated risks of liver-related complications like decompensation and hepatocellular carcinoma (HCC). Morbidity and mortality in cirrhosis patients are linked to portal hypertension, sarcopenia, and hepatocellular carcinoma. Although conventional cirrhosis management centered on treating complications, contemporary approaches prioritize preemptive measures. This study aims to formulate novel blood- and imaging-centric methodologies for monitoring liver cirrhosis patients.METHODS: In this prospective study, 150 liver cirrhosis patients will be enrolled from three Swedish liver clinics. Their conditions will be assessed through extensive blood-based markers and magnetic resonance imaging (MRI). The MRI protocol encompasses body composition profile with Muscle Assement Score, portal flow assessment, magnet resonance elastography, and a abbreviated MRI for HCC screening. Evaluation of lifestyle, muscular strength, physical performance, body composition, and quality of life will be conducted. Additionally, DNA, serum, and plasma biobanking will facilitate future investigations.DISCUSSION: The anticipated outcomes involve the identification and validation of non-invasive blood- and imaging-oriented biomarkers, enhancing the care paradigm for liver cirrhosis patients. Notably, the temporal evolution of these biomarkers will be crucial for understanding dynamic changes.TRIAL REGISTRATION: Clinicaltrials.gov, registration identifier NCT05502198. Registered on 16 August 2022. Link: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05502198 .
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| 14. |
- Pace, Andrea, et al.
(författare)
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Determining medical decision-making capacity in brain tumor patients : why and how?
- 2020
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Ingår i: Neuro-Oncology Practice. - : Oxford University Press. - 2054-2577 .- 2054-2585. ; 7:6, s. 599-612
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Tidskriftsartikel (refereegranskat)abstract
- Background: Brain tumor patients are at high risk of impaired medical decision-making capacity (MDC), which can be ethically challenging because it limits their ability to give informed consent to medical treatments or participation in research. The European Association of Neuro-Oncology Palliative Care Multidisciplinary Task Force performed a systematic review to identify relevant evidence with respect to MDC that could be used to give recommendations on how to cope with reduced MDC in brain tumor patients.Methods: A literature search in several electronic databases was conducted up to September 2019, including studies with brain tumor and other neurological patients. Information related to the following topics was extracted: tools to measure MDC, consent to treatment or research, predictive patient- and treatment-related factors, surrogate decision making, and interventions to improve MDC.Results: A total of 138 articles were deemed eligible. Several structured capacity-assessment instruments are available to aid clinical decision making. These instruments revealed a high incidence of impaired MDC both in brain tumors and other neurological diseases for treatment- and research-related decisions. Incapacity appeared to be mostly determined by the level of cognitive impairment. Surrogate decision making should be considered in case a patient lacks capacity, ensuring that the patient's "best interests" and wishes are guaranteed. Several methods are available that may help to enhance patients' consent capacity.Conclusions: Clinical recommendations on how to detect and manage reduced MDC in brain tumor patients were formulated, reflecting among others the timing of MDC assessments, methods to enhance patients' consent capacity, and alternative procedures, including surrogate consent.
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| 15. |
- Sanjiv, Kumar, et al.
(författare)
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MTH1 Inhibitor TH1579 Induces Oxidative DNA Damage and Mitotic Arrest in Acute Myeloid Leukemia
- 2021
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Ingår i: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 81:22, s. 5733-5744
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Tidskriftsartikel (refereegranskat)abstract
- Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, exhibiting high levels of reactive oxygen species (ROS). ROS levels have been suggested to drive leukemogenesis and is thus a potential novel target for treating AML. MTH1 prevents incorporation of oxidized nucleotides into the DNA to maintain genome integrity and is upregulated in many cancers. Here we demonstrate that hematologic cancers are highly sensitive to MTH1 inhibitor TH1579 (karonudib). A functional precision medicine ex vivo screen in primary AML bone marrow samples demonstrated a broad response profile of TH1579, independent of the genomic alteration of AML, resembling the response profile of the standard-of-care treatments cytarabine and doxorubicin. Furthermore, TH1579 killed primary human AML blast cells (CD45+) as well as chemotherapy resistance leukemic stem cells (CD45+Lin−CD34+CD38−), which are often responsible for AML progression. TH1579 killed AML cells by causing mitotic arrest, elevating intracellular ROS levels, and enhancing oxidative DNA damage. TH1579 showed a significant therapeutic window, was well tolerated in animals, and could be combined with standard-of-care treatments to further improve efficacy. TH1579 significantly improved survival in two different AML disease models in vivo. In conclusion, the preclinical data presented here support that TH1579 is a promising novel anticancer agent for AML, providing a rationale to investigate the clinical usefulness of TH1579 in AML in an ongoing clinical phase I trial.
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| 16. |
- Saudi, Aws, et al.
(författare)
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Immune-activated B cells are dominant in prostate cancer
- 2023
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- B cells are multifaceted immune cells responding robustly during immune surveillance against tumor antigens by presentation to T cells and switched immunoglobulin production. However, B cells are unstudied in prostate cancer (PCa). We used flow cytometry to analyze B-cell subpopulations in peripheral blood and lymph nodes from intermediate-high risk PCa patients. B-cell subpopulations were related to clinicopathological factors. B-cell-receptor single-cell sequencing and VDJ analysis identified clonal B-cell expansion in blood and lymph nodes. Pathological staging was pT2 in 16%, pT3a in 48%, and pT3b in 36%. Lymph node metastases occurred in 5/25 patients (20%). Compared to healthy donors, the peripheral blood CD19+ B-cell compartment was significantly decreased in PCa patients and dominated by naïve B cells. The nodal B-cell compartment had significantly increased fractions of CD19+ B cells and switched memory B cells. Plasmablasts were observed in tumor-draining sentinel lymph nodes (SNs). VDJ analysis revealed clonal expansion in lymph nodes. Thus, activated B cells are increased in SNs from PCa patients. The increased fraction of switched memory cells and plasmablasts together with the presence of clonally expanded B cells indicate tumor-specific T-cell-dependent responses from B cells, supporting an important role for B cells in the protection against tumors.
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| 17. |
- Aasa, Mikael, et al.
(författare)
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Cost and health outcome of primary percutaneous coronary intervention versus thrombolysis in acute ST-segment elevation myocardial infarction-Results of the Swedish Early Decision reperfusion Study (SWEDES) trial.
- 2010
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Ingår i: American heart journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 160:2, s. 322-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In ST-elevation myocardial infarction, primary percutaneous coronary intervention (PCI) has a superior clinical outcome, but it may increase costs in comparison to thrombolysis. The aim of the study was to compare costs, clinical outcome, and quality-adjusted survival between primary PCI and thrombolysis. METHODS: Patients with ST-elevation myocardial infarction were randomized to primary PCI with adjunctive enoxaparin and abciximab (n = 101), or to enoxaparin followed by reteplase (n = 104). Data on the use of health care resources, work loss, and health-related quality of life were collected during a 1-year period. Cost-effectiveness was determined by comparing costs and quality-adjusted survival. The joint distribution of incremental costs and quality-adjusted survival was analyzed using a nonparametric bootstrap approach. RESULTS: Clinical outcome did not differ significantly between the groups. Compared with the group treated with thrombolysis, the cost of interventions was higher in the PCI-treated group ($4,602 vs $3,807; P = .047), as well as the cost of drugs ($1,309 vs $1,202; P = .001), whereas the cost of hospitalization was lower ($7,344 vs $9,278; P = .025). The cost of investigations, outpatient care, and loss of production did not differ significantly between the 2 treatment arms. Total cost and quality-adjusted survival were $25,315 and 0.759 vs $27,819 and 0.728 (both not significant) for the primary PCI and thrombolysis groups, respectively. Based on the 1-year follow-up, bootstrap analysis revealed that in 80%, 88%, and 89% of the replications, the cost per health outcome gained for PCI will be <$0, $50,000, and $100,000 respectively. CONCLUSION: In a 1-year perspective, there was a tendency toward lower costs and better health outcome after primary PCI, resulting in costs for PCI in comparison to thrombolysis that will be below the conventional threshold for cost-effectiveness in 88% of bootstrap replications.
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| 18. |
- Amsteus, Martin, 1972-, et al.
(författare)
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The Sound of Choice
- 2016
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Ingår i: International Journal of Business and Social Science. - : Center for Promoting Ideas. - 2219-1933. ; 7:1, s. 42-49
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study is to testthe effect of suggestive music on consumer choice in cafés. It is proposed that suggestive music influences consumer choice in cafés. The hypotheses were tested through Chi-square on a totalof 283 measures. The results show that suggestive music has an effect on consumer choice in cafés. Managers who want to influence consumer choice in cafés through suggestive music may be able to do so. The results provide empirical support for the idea that suggestive music and the associations it carries represent information that consumers use for assessing choices and making selections.
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| 19. |
- Andaloussi, Mounir, et al.
(författare)
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Design, Synthesis, and X-ray Crystallographic Studies of alpha-Aryl Substituted Fosmidomycin Analogues as Inhibitors of Mycobacterium tuberculosis 1-Deoxy-D-xylulose 5-Phosphate Reductoisomerase
- 2011
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 54:14, s. 4964-4976
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Tidskriftsartikel (refereegranskat)abstract
- The natural antibiotic fosmidomycin acts via inhibition of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), an essential enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. Fosmidomycin is active on Mycobacterium tuberculosis DXR (MtDXR), but it lacks antibacterial activity probably because of poor uptake. alpha-Aryl substituted fosmidomycin analogues have more favorable physicochemical properties and are also more active in inhibiting malaria parasite growth. We have solved crystal structures of MtDXR in complex with 3,4-dichlorophenyl substituted fosmidomycin analogues; these show important differences compared to our previously described forsmidomycin-DXR complex. Our best inhibitor has an IC(50) = 0.15 mu M on MtDXR but still lacked activity in a mycobacterial growth assay (MIC > 32 mu g/mL). The combined results, however, provide insights into how DXR accommodates the new inhibitors and serve as an excellent starting point for the design of other novel and more potent inhibitors, particularly against pathogens where uptake is less of a problem, such as the malaria parasite.
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| 20. |
- Andersson, Martin, et al.
(författare)
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Co-simulation of Mobile Wireless Networked Embedded Systems in Physical Environments
- 2005
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Ingår i: RTiS 2005 – Proceedings of Real Time in Sweden 2005, the 8th Biennial SNART Conference on Real-Time Systems (Skövde University Studies in Informatics). - 1653-2325. - 9163173492 ; 2005:1
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Konferensbidrag (refereegranskat)abstract
- Embedded systems are becoming increasingly networked and aredeployed in application areas that require close interaction withtheir physical environment. Examples include distributed mobileagents and wireless sensor/actuator networks. The complexity ofthese applications make co-simulation a necessary tool during systemdevelopment. This paper presents a simulation environment thatfacilitates simulation of computer nodes and communication networksinteracting with the continuous-time dynamics of the real world.Features of the simulator include interrupthandling, task scheduling, wired and wireless communication, localclocks, dynamic voltage scaling, and battery-driven operation.Two simulation case studies are presented: a simple communicationscenario and a mobile robot soccer game.
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| 21. |
- Andersson, Martin, et al.
(författare)
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Simulation of Wireless Networked Control Systems
- 2005
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Ingår i: Proceedings of the 44th IEEE Conference on Decision and Control and the 2005 European Control Conference. - 0780395689 ; , s. 476-481
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Konferensbidrag (refereegranskat)abstract
- Embedded systems are becoming increasingly networked and are deployed in application areas that require close interaction with their physical environment. Examples include distributed mobile agents and wireless sensor/actuator networks. The complexity of these applications make co-simulation a necessary tool during system development. This paper presents a simulation environment that facilitates simulation of computer nodes and communication networks interacting with the continuous-time dynamics of the real world. Features of the simulator include interrupt handling, task scheduling, wired and wireless communication, local clocks, dynamic voltage scaling, and battery-driven operation. Two simulation case studies are presented: a simple communication scenario and a mobile robot soccer game.
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| 22. |
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| 23. |
- Andersson, Swen-Olof, et al.
(författare)
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Managing localized prostate cancer by radical prostatectomy or watchful waiting: Cost analysis of a randomized trial (SPCG-4)
- 2011
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Ingår i: SCANDINAVIAN JOURNAL OF UROLOGY AND NEPHROLOGY. - : Informa Healthcare. - 0036-5599 .- 1651-2065. ; 45:3, s. 177-183
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The cost of radical prostatectomy (RP) compared to watchful waiting (WW) has never been estimated in a randomized trial. The goal of this study was to estimate long-term total costs per patient associated with RP and WW arising from inpatient and outpatient hospital care. Material and methods. This investigation used the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) trial, comparing RP to WW, and included data from 212 participants living in two counties in Sweden from 1989 to 1999 (105 randomized to WW and 107 to RP). All costs were included from randomization date until death or end of follow-up in July 2007. Resource use arising from inpatient and outpatient hospital costs was measured in physical units and multiplied by a unit cost to come up with a total cost per patient. Results. During a median follow-up of 12 years, the overall cost in the RP group was 34% higher (p andlt; 0.01) than in the WW group, corresponding to euroa,not sign6123 in Sweden. The difference was driven almost exclusively by the cost of the surgical procedure. The cost difference between RP and WW was two times higher among men with low (2--6) than among those with high (7--10) Gleason score. Conclusion. In this economic evaluation of RP versus WW of localized prostate cancer in a randomized study, RP was associated with 34% higher costs. This difference, attributed exclusively to the cost of the RP procedure, was not overcome during extended follow-up.
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| 24. |
- Antov, Dago, et al.
(författare)
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European road users' risk perception and mobility : the SARTRE 4 survey
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The SARTRE (Social Attitudes to Road Traffic Risk in Europe) project started in 1991. It consists of a European wide survey about knowledge of road traffic laws and road traffic risks, attitudes regarding road safety issues, reported road traffic behaviours, transport habits and needs in several European countries. Various topics related to road safety are in the focus of the project such as alcohol, drugs, or phone use while driving, speeding, use of advanced driver assistance systems and the transport infrastructure and environment.
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| 25. |
- Appelberg, Kajsa, et al.
(författare)
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Cost-Effectiveness of Newborn Screening for Phenylketonuria and Congenital Hypothyroidism
- 2023
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Ingår i: The Journal of Pediatrics. - : MOSBY-ELSEVIER. - 0022-3476 .- 1097-6833. ; 256, s. 38-43.e3
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the long-term costs and health effects of the Swedish newborn screening program for classic phenylketonuria (PKU) alone and in combination with congenital hypothyroidism compared with no screening. Study design A decision-analytic model was developed to estimate and compare the long-term (80 years) costs and health effects of newborn screening for PKU and congenital hypothyroidism. Data were obtained from the liter-ature and translated to Swedish conditions. A societal perspective was taken, including costs falling on health care providers, municipal care and services, as well as production loss due to morbidity. Results Screening 100 000 newborns for PKU resulted in 73 gained quality-adjusted life-years (QALYs) compared with no screening. When adding congenital hypothyroidism, the number of gained QALYs was 232 compared with PKU alone, adding up to a total of 305 QALYs gained. Corresponding cost estimates were $80.8, $70.3, and $10.05 million USD for no screening, PKU screening, and PKU plus congenital hypothyroidism screening, respectively, indicating that screening for PKU plus congenital hypothyroidism was more effective and less costly compared with the other strategies. The majority of cost savings with PKU plus congenital hypothyroidism screening was due to reductions in productivity losses and municipal care and services costs. Conclusion The Swedish newborn screening program for PKU and congenital hypothyroidism saves substantial costs for society while generating additional QALYs, emphasizing the importance of public investments in early diagnosis and treatment. (J Pediatr 2023;256:38-43).
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| 26. |
- Askling, Helena, et al.
(författare)
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Allmän TBE-vaccination ger hälsovinst till rimlig kostnad [Subsidized TBE vaccination appears cost-effective in a life-time perspective]
- 2019
-
Ingår i: Läkartidningen. - Stockholm, Sweden : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 116
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Tidskriftsartikel (refereegranskat)abstract
- Given the setting of Stockholm County, a recently published health-economic analysis shows that the cost per Quality-adjusted life year (QALY) of a free TBE vaccinations program is below generally acceptable cost-effectiveness thresholds in Sweden. A report from the Public Health Agency (PHA), based on similar input data, shows that it is not cost effective to subsidize TBE vaccination in the Stockholm county. The main difference in the two analyses is the time horizon for the analyses; a life-time perspective versus 10-year perspective. Health economics of vaccination strategies should be based on a long time perspective and especially when the disease is more severe in older adults, i.e. TBE. Health-care decision-makers should be aware of the importance of the time horizon for the results when considering these evaluations in prioritization decisions. With a life-time perspective a TBE-vaccination program appears cost-effective.
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| 27. |
- Azhar, Shoaib, et al.
(författare)
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Chemoenzymatic separation of softwood polymers
- 2011
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Ingår i: Proceedings of the 16th international symposium of wood, fiber and pulp chemistry. - 9787501982066 ; , s. 932-936
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Konferensbidrag (refereegranskat)abstract
- Spruce wood chips were chemically pre-treated with sodium hydroxide to open up the compact structure of wood. The wood was then treated with enzymes (xylanase, gamanase and mannanase) and subjected to extraction with a mixture of methanol and alkali to efficiently isolate lignin and hemicelluloses. Chemical pre-treatment improved enzyme efficiency which consequently enhanced the extraction of lignocelluloses with higher average molar mass than the references.
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| 28. |
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| 29. |
- Azhar, Shoaib, et al.
(författare)
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Extraction of polymers from enzyme-treated softwood
- 2011
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Ingår i: BioResources. - 1930-2126. ; 6:4, s. 4606-4614
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Tidskriftsartikel (refereegranskat)abstract
- In a biorefinery context it is an advantage to fractionate and extract different wood components in a relatively pure form. However, one major obstacle for efficient extraction of wood polymers (lignin, polysaccharides etc.) is the covalent lignin-polysaccharide networks present in lignified cell walls. Enzymatic catalysis might be a useful tool for a controlled degradation of these networks, thereby enhancing the extraction of high molecular weight polymers. In this work, a methanol-alkali mixture was used to extract two different wood samples treated with endoxylanase and gammanase, respectively. Wood chips were pretreated with alkali prior to enzymatic treatment to enhance the cell-wall accessibility to enzymes. Extractions were also carried out on non-enzyme-treated samples to evaluate the enzymatic effects. Results showed that the enzymatic treatment increased the extraction yield, with gammanase as the more efficient of the two enzymes. Furthermore, polymers extracted from xylanase-treated wood had a higher degree of polymerization than the reference.
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| 30. |
- Ballin, Marcel, et al.
(författare)
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Adolescent Cardiorespiratory Fitness and Risk of Cancer in Late Adulthood : Nationwide Sibling-Controlled Cohort Study
- 2024
-
Ingår i: medRxiv : the preprint server for health sciences.
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- To investigate whether the higher risks of certain cancers associated with high cardiorespiratory fitness can be explained by increased detection and unobserved confounders.ObjectiveTo investigate whether the higher risks of certain cancers associated with high cardiorespiratory fitness can be explained by increased detection and unobserved confounders.Nationwide sibling-controlled cohort study of adolescents.DesignNationwide sibling-controlled cohort study of adolescents.Sweden.SettingSweden.1 124 049 men of which 477 453 were full siblings, who underwent mandatory military conscription examinations between 1972 and 1995 at a mean age of 18.3 years.Participants1 124 049 men of which 477 453 were full siblings, who underwent mandatory military conscription examinations between 1972 and 1995 at a mean age of 18.3 years.Hazard ratios (HR) and 95% confidence intervals (CI) of overall cancer diagnosis and cancer mortality, and 14 site-specific cancers (diagnosis or death), as recorded in the Swedish National Patient Register or Cause of Death Register until 31 December 2023, modelled using flexible parametric regressions.Main outcome measuresHazard ratios (HR) and 95% confidence intervals (CI) of overall cancer diagnosis and cancer mortality, and 14 site-specific cancers (diagnosis or death), as recorded in the Swedish National Patient Register or Cause of Death Register until 31 December 2023, modelled using flexible parametric regressions.Participants were followed until a median (maximum) age of 55.9 (73.5) years, during which 98 410 were diagnosed with cancer and 16 789 had a cancer-related death (41 293 and 6908 among full siblings respectively). The most common cancers were non-melanoma skin (27 105 diagnoses & 227 deaths) and prostate cancer (24 211 diagnoses & 869 deaths). In cohort analysis, those in the highest quartile of cardiorespiratory fitness had a higher risk of prostate (adjusted HR 1.10; 95% CI: 1.05 to 1.16) and skin cancer (e.g., non-melanoma HR 1.44; 1.37 to 1.50) compared to those in the lowest quartile, which led to a higher risk of any type of cancer diagnosis (HR 1.08; 1.06 to 1.11). However, those in the highest quartile had a lower risk of cancer mortality (HR 0.71; 0.67 to 0.76). When comparing full siblings, and thereby controlling for all behavioural, environmental, and genetic factors they share, the excess risk of prostate (HR 1.01; 0.90 to 1.13) and skin cancer (e.g., non-melanoma HR 1.09; 0.99 to 1.20) attenuated to the null. In contrast, the lower risk of overall cancer mortality was still statistically significant after control for such shared confounders (HR 0.78; 0.68 to 0.89). For other site-specific cancers, the influence of such confounding tended to vary, but none showed the same excess risk as prostate and non-melanoma skin cancer.ResultsParticipants were followed until a median (maximum) age of 55.9 (73.5) years, during which 98 410 were diagnosed with cancer and 16 789 had a cancer-related death (41 293 and 6908 among full siblings respectively). The most common cancers were non-melanoma skin (27 105 diagnoses & 227 deaths) and prostate cancer (24 211 diagnoses & 869 deaths). In cohort analysis, those in the highest quartile of cardiorespiratory fitness had a higher risk of prostate (adjusted HR 1.10; 95% CI: 1.05 to 1.16) and skin cancer (e.g., non-melanoma HR 1.44; 1.37 to 1.50) compared to those in the lowest quartile, which led to a higher risk of any type of cancer diagnosis (HR 1.08; 1.06 to 1.11). However, those in the highest quartile had a lower risk of cancer mortality (HR 0.71; 0.67 to 0.76). When comparing full siblings, and thereby controlling for all behavioural, environmental, and genetic factors they share, the excess risk of prostate (HR 1.01; 0.90 to 1.13) and skin cancer (e.g., non-melanoma HR 1.09; 0.99 to 1.20) attenuated to the null. In contrast, the lower risk of overall cancer mortality was still statistically significant after control for such shared confounders (HR 0.78; 0.68 to 0.89). For other site-specific cancers, the influence of such confounding tended to vary, but none showed the same excess risk as prostate and non-melanoma skin cancer.The association between high levels of adolescent cardiorespiratory fitness and excess risk of some cancers, such as prostate and non-melanoma skin cancer, appears to be fully explained by unobserved confounders shared between full siblings. However, the protective association with cancer mortality persists even after control for such confounding.ConclusionsThe association between high levels of adolescent cardiorespiratory fitness and excess risk of some cancers, such as prostate and non-melanoma skin cancer, appears to be fully explained by unobserved confounders shared between full siblings. However, the protective association with cancer mortality persists even after control for such confounding.
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| 31. |
- Ballin, Marcel, et al.
(författare)
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Genetic and Environmental Factors and Cardiovascular Disease Risk in Adolescents
- 2023
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Importance Cardiovascular risk factors in youth have been associated with future cardiovascular disease (CVD), but conventional observational studies are vulnerable to genetic and environmental confounding.Objective To examine the role of genetic and environmental factors shared by full siblings in the association of adolescent cardiovascular risk factors with future CVD.Design, Setting, and Participants This is a nationwide cohort study with full sibling comparisons. All men who underwent mandatory military conscription examinations in Sweden between 1972 and 1995 were followed up until December 31, 2016. Data analysis was performed from May 1 to November 10, 2022.Exposures Body mass index (BMI), cardiorespiratory fitness, blood pressure, handgrip strength, and a combined risk z score in late adolescence.Main Outcomes and Measures The primary outcome was fatal or nonfatal CVD, as recorded in the National Inpatient Register or the Cause of Death Register before 2017.Results A total of 1 138 833 men (mean [SD] age, 18.3 [0.8] years), of whom 463 995 were full brothers, were followed up for a median (IQR) of 32.1 (26.7-37.7) years, during which 48 606 experienced a CVD outcome (18 598 among full brothers). All risk factors were associated with CVD, but the effect of controlling for unobserved genetic and environmental factors shared by full siblings varied. In the sibling analysis, hazard ratios for CVD (top vs bottom decile) were 2.10 (95% CI, 1.90-2.32) for BMI, 0.77 (95% CI, 0.68-0.88) for cardiorespiratory fitness, 1.45 (95% CI, 1.32-1.60) for systolic blood pressure, 0.90 (95% CI, 0.82-0.99) for handgrip strength, and 2.19 (95% CI, 1.96-2.46) for the combined z score. The percentage attenuation in these hazard ratios in the sibling vs total cohort analysis ranged from 1.1% for handgrip strength to 40.0% for cardiorespiratory fitness. Consequently, in the sibling analysis, the difference in cumulative CVD incidence at age 60 years (top vs bottom decile) was 7.2% (95% CI, 5.9%-8.6%) for BMI and 1.8% (95% CI, 1.0%-2.5%) for cardiorespiratory fitness. Similarly, in the sibling analysis, hypothetically shifting everyone in the worst deciles of BMI to the middle decile would prevent 14.9% of CVD at age 60 years, whereas the corresponding number for cardiorespiratory fitness was 5.3%.Conclusions and Relevance In this Swedish national cohort study, cardiovascular risk factors in late adolescence, especially a high BMI, were important targets for CVD prevention, independently of unobserved genetic and environmental factors shared by full siblings. However, the role of adolescent cardiorespiratory fitness in CVD may have been overstated by conventional observational studies.
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| 32. |
- Barra, Mathias, et al.
(författare)
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Do not despair about severity—yet
- 2020
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Ingår i: Journal of Medical Ethics. - : BMJ Publishing Group Ltd. - 0306-6800 .- 1473-4257. ; 46:8, s. 557-558
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In a recent extended essay, philosopher Daniel Hausman goes a long way towards dismissing severity as a morally relevant attribute in the context of priority setting in healthcare. In this response, we argue that although Hausman certainly points to real problems with how severity is often interpreted and operationalised within the priority setting context, the conclusion that severity does not contain plausible ethical content is too hasty. Rather than abandonment, our proposal is to take severity seriously by carefully mapping the possibly multiple underlying accounts to well-established ethical theories, in a way that is both morally defensible and aligned with the term’s colloquial uses.
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| 33. |
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| 34. |
- Bengtsson, Kristofer, 1979, et al.
(författare)
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Emergency department overview - Improving the dynamic capabilities using an event-driven information architecture
- 2016
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Ingår i: IEEE International Conference on Emerging technologies and factory automation (ETFA) 2016.
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Konferensbidrag (refereegranskat)abstract
- It is challenging to get an overview and understand- ing of what is going on at an emergency department (ED). This is due to the sometimes turbulent work environment and a large variation in patient processes. To increase the dynamic capability and responsiveness of an ED, it is important that the staff and patients have an overview of what is going on and what will happen in the coming hours. This paper presents a smart online support software that shows the current state of the ED as well as a prediction of the coming hours. The software has been developed as a case study of using agile development ideas when developing new systems for hospitals. The result shows that the use of the event-driven information architecture for healthcare (EVAH) enabled a rapid development of a successful running application, helping the nurses getting an overview of current situation and the coming hours.
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| 35. |
- Berglund, Jennie, et al.
(författare)
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A molecular dynamics study of the effect of glycosidic linkage type in the hemicellulose backbone on the molecular chain flexibility
- 2016
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Ingår i: The Plant Journal. - : John Wiley & Sons Ltd.. - 0960-7412 .- 1365-313X. ; 88:1, s. 56-70
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Tidskriftsartikel (refereegranskat)abstract
- The macromolecular conformation of the constituent polysaccharides in lignocellulosic biomass influences their supramolecular interactions, and therefore their function in plants and their performance in technical products. The flexibility of glycosidic linkages from the backbone of hemicelluloses was studied by evaluating the conformational freedom of the φ and ψ dihedral angles using molecular dynamic simulations, additionally selected molecules were correlated with experimental data by NMR spectroscopy. Three types of β-(1→4) glycosidic linkages involving the monosaccharides (Glcp, Xylp and Manp) present in the backbone of hemicelluloses were defined. Different di- and tetrasaccharides with combinations of such sugar monomers from hemicelluloses were simulated and free energy maps of the φ - ψ space and hydrogen bonding patterns were obtained. The glycosidic linkage between Glc-Glc or Glc-Man (C-type) was the stiffest with mainly one probable conformation; the linkage from Man-Man or Man-Glc (M-type) was similar but with an increased probability for an alternative conformation making it more flexible, and the linkage between two Xyl-units (X-type) was the most flexible with two almost equally populated conformations. Glycosidic linkages of the same type showed essentially the same conformational space in both disaccharides and in the central region of tetrasaccharides. Different probabilities of glycosidic linkage conformations in the backbone of hemicelluloses can be directly estimated from the free energy maps, which to a large degree affect the overall macromolecular conformations of these polymers. The information gained contributes to an increased understanding of hemicelluloses’ function both in the cell wall and in technical products.
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| 36. |
- Berglund, Jennie, et al.
(författare)
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Acetylation and Sugar Composition Influence the (In)Solubility of Plant beta-Mannans and Their Interaction with Cellulose Surfaces
- 2020
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Ingår i: ACS Sustainable Chemistry and Engineering. - : AMER CHEMICAL SOC. - 2168-0485. ; 8:27, s. 10027-10040
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Tidskriftsartikel (refereegranskat)abstract
- Plant beta-mannans are complex heteropolysaccharides that represent an abundant resource from lignocellulosic biomass. The influence of the molecular motifs of plant mannans on the backbone flexibility, solubility, and the interaction with cellulose was investigated by computational and experimental approaches. The regioselectivity of the acetyl substitutions at C2 and C3 distinctively influenced backbone flexibility in aqueous media, as revealed by molecular dynamic simulations. The molecular weight and degree of acetylation were tailored for two model seed mannans (galactomannan and glucomannan) and compared to spruce acetylated galactoglucomannan. The thermal stability was enhanced with increasing acetyl substitutions, independently of the type of mannan. Dynamic light scattering and atomic force microscopy revealed that the occurrence of galactosylation and a low degree of acetylation (similar to that of native acetylated galactoglucomannans) enhanced solubility/dispersibility of mannans, whereas the solubility/dispersibility decreased for higher degrees of acetylation. Mannan solubility influenced their interactions with cellulose at water-cellulose interfaces in terms of adsorbed mass and viscoelastic properties of the adsorbed mannan layers. Our results reveal that modulating the molecular motifs of plant beta-mannans influences their macromolecular conformation and physicochemical properties, with fundamental implications for their role in the plant cell wall and the design of wood-based materials.
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- Berglund, Jennie, et al.
(författare)
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The structure of galactoglucomannan impacts the degradation under alkaline conditions
- 2018
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Ingår i: Cellulose. - : Springer. - 0969-0239 .- 1572-882X.
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Tidskriftsartikel (refereegranskat)abstract
- Galactoglucomannan (GGM) from sprucewas studied with respect to the degradation behavior inalkaline solution. Three reference systems includinggalactomannan from locust bean gum, glucomannanfrom konjac and the linear water-soluble carboxymethylcellulose were studied with focus onmolecular weight, sugar composition, degradationproducts, as well as formed oligomers, to identifyrelative structural changes in GGM. Initially allmannan polysaccharides showed a fast decrease inthe molecular weight, which became stable in the laterstage. The degradation of the mannan polysaccharidescould be described by a function corresponding to thesum of two first order reactions; one slow that wasascribed to peeling, and one fast that was connectedwith hydrolysis. The galactose side group wasstable under conditions used in this study (150 min,90 C, 0.5 M NaOH). This could suggest that, apartfrom the covalent connection to C6 in mannose, thegalactose substitutions also interact non-covalentlywith the backbone to stabilize the structure againstdegradation. Additionally, the combination of differentbackbone sugars seems to affect the stability of thepolysaccharides. For carboxymethyl cellulose thedegradation was linear over time which furthersuggests that the structure and sugar composition playan important role for the alkaline degradation. Moleculardynamics simulations gave details about theconformational behavior of GGM oligomers in watersolution, as well as interaction between the oligomersand hydroxide ions.
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| 41. |
- Berglund, Jennie
(författare)
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Wood Hemicelluloses - Fundamental Insights on Biological and Technical Properties
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hemicelluloses are a group of heterogeneous polysaccharides representing around 30 % of wood where the dominating types are xylans, glucomannans and xyloglucans. Hemicelluloses complex molecular structure makes it difficult to understand the relationship between structure and properties entirely, and their biological role is not yet fully verified. Additionally, hemicelluloses are sensitive to chemical processing and are not utilized to their full potentials for production of value-added products such as materials, additives to food and pharmaceutical products, etc. Increased knowledge regarding their functions is important for the development of both processes and products. The aim with this work has therefore been to increase the fundamental understanding about how the structure and properties of wood hemicelluloses are correlated, and properties such as flexibility, interaction with cellulose, solubility, resistance to chemical-, thermal-, and enzymatic degradation have been explored.Molecular dynamics (MD) simulations were used to, in detail, study the structures found in wood hemicelluloses. The flexibility was evaluated by comparing the impact of backbone sugars on the conformational space and also the impact of side groups was considered. Based on the conformational space of backbone glycosidic linkages the flexibility order of hemicelluloses in an aqueous environment was determined to be: xylan > glucomannan > xyloglucan. Additionally, the impact of xylan structure on cellulose interaction was evaluated by MD methods.Hemicelluloses were extracted from birch and spruce, and were used to fabricate different composite hydrogels with bacterial cellulose. These materials were studied with regards to mechanical properties, and it was shown that galactoglucomannans mainly contributed to an increased modulus in compression, whereas the most significant effect from xylan was increased strain under uniaxial tensile testing. Besides, other polysaccharides of similar structure as galactoglucomannans were modified and used as pure, well defined, models. Acetyl groups are naturally occurring decorations of wood hemicelluloses and can also be chemically introduced. Here, mannans with different degrees of acetylation were prepared and the influence of structure on solubility in water and the organic solvent DMSO were evaluated. Furthermore, the structure and water solubility influenced the interaction with cellulose. Acetylation also showed to increase the thermal and biological stability of mannans.With chemical pulping processes in mind, the degradability of spruce galactoglucomannans in alkaline solution were studied with regards to the structure, and the content of more or less stable structural regions were proposed.
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| 42. |
- Bi, Ran, et al.
(författare)
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Isolation and identification of microorganisms from soil able to live on lignin as a carbon source and to produce enzymes which cleave beta-O-4 bond in a lignin model compound
- 2012
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Ingår i: Cellulose Chemistry and Technology. - 0576-9787. ; 46:3-4, s. 227-242
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Tidskriftsartikel (refereegranskat)abstract
- Several strains of fungi were isolated and identified from Scandinavian soil using agar plates with lignin as a carbon source. The strains grew significantly faster on this medium than on control plates without lignin. Different types of technical lignins were used, some of which contained trace amounts of sugars, even if the increased growth rate seemed not related to the sugar content. Some strains were cultivated in shaking flask cultures with lignin as a carbon source, with lignin apparently consumed by microbes - while accumulation of the microorganism biomass occurred. The cell-free filtrates of these cultures could reduce the apparent molecular weights of lignosulphonates, while the culture filtrate of one strain could cleave the beta-O-4 bond in a lignin model compound.
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| 43. |
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| 44. |
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| 45. |
- Brodtkorb, Thor-Henrik, 1976-
(författare)
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Cost-effectiveness analysis of health technologies when evidence is scarce
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Given the increasing pressures on health care budgets, economic evaluation is used in many countries to assist decision-making regarding the optimal use of competing health care technologies. Although the standard methods of estimating cost-effectiveness underpinning these decisions have gained widespread acceptance, concerns have been raised that many technologies would not be considered for funding, due to scarcity of evidence. However, as long as the amount and quality of evidence used for the analysis are properly characterized, scarce evidence per se should not be seen as a hindrance to perform cost-effectiveness analyses. Characterizing uncertainty appropriately, though, may pose a challenge even when there is a large body of evidence available, and even more so when evidence is scarce. The aims of this thesis are to apply a methodological framework of cost-effectiveness analysis and explore methods for characterising uncertainty when evidence is scarce. Three case studies associated with limited evidence provide economic evaluations on current decision problems, investigate the feasibility of using the framework, and explore methods for characterizing uncertainty when evidence is scarce.The results of the case studies showed that, given current information, providing transfemoral amputees with C-Leg and Airsonett Airshower to patients with perennial allergic asthma could be considered cost-effective whereas screening for hyperthrophic cardiomyopathy among young athletes is unlikely to be cost-effective. In the cases of C-Leg and Airsonett Airshower conducting further research is likely to be cost-effective. The case studies indicate that it is feasible to apply methods of cost-effectiveness in health care for technologies not commonly evaluated due to lack of evidence. The analysis showed that failing to account for individual experts’ might have a substantial effect on the interpretation of the results of cost-effectiveness analysis. Formal expert elicitation is a promising method of characterizing uncertainty when evidence is missing, and thus enable cost-effectiveness and value of further research to be appropriately estimated in such situations.In conclusion, this thesis shows that scarcity of evidence should not preclude the use of cost-effectiveness analysis. On the contrary, in such cases it is probably more important than ever to use a framework that enable us to define key parameters for a decision problem and identify available evidence in order to determine cost-effectiveness given current information and provide guidance on further data collection.
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| 46. |
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| 47. |
- Brodtkorb, Thor-Henrik, et al.
(författare)
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Cost-effectiveness of C-Leg compared to non microprocessor controlled knees: a modeling approach
- 2008
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Ingår i: Archives of Physical Medicine and Rehabilitation. - : Institutionen för medicin och hälsa. - 0003-9993 .- 1532-821X. ; 89:1, s. 24-30
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To estimate the costs and health outcomes of C-Leg and non–microprocessor-controlled (NMC) knees using a decision-analytic model. Design: Data on costs, rates and duration of problems, knee survival, and health-related quality of life were obtained from interviews with patients and prosthetists with experience of both C-Leg and NMC knees. Interview data were assessed in a decision-analytic Markov model to estimate cost-effectiveness from a health care perspective. Setting: Outpatient. Participants: A population sample of 20 patients currently using the C-Leg and prior experience of nonmicroprocessor knees, and 5 prosthetists. Interventions: Not applicable. Main Outcome Measure: Incremental cost per quality-adjusted life year (QALY). Results: The mean incremental cost (in 2006 Euros) and QALYs for the C-Leg was €7657 and 2.38, respectively, yielding a cost per QALY gained of €3218. Conclusions: It is important to provide decision-makers with relevant information on costs and health outcomes of different treatment strategies on actual decision problems despite limited evidence. The results of the study, taking into account both costs and a broadly defined health outcome in terms of QALY, show that given existing albeit limited evidence the C-Leg appears to yield positive health outcomes at an acceptable cost.
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| 48. |
- Brodtkorb, Thor-Henrik, 1976-, et al.
(författare)
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Eliciting priors to characterize uncertainties in decision analytic models
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Expert opinions are often used in decision models when evidence is scarce. This study describes the details of a formal elicitation exercise to estimate parameter values and their associated uncertainty and compares the results in term of cost-effectiveness and value of information with results from only eliciting mean values from experts. Methods: Elicited distributions for 11 unknown parameters where incorporated into a previously developed cost-effectiveness model for prosthetic knees for amputees. The original model included elicited mean values for the missing values, thus ignoring any uncertainty across experts’ beliefs. Results: The incremental cost-effective ratio (ICER) for the analysis based on the current elicited distributions was substantially higher (€13 625) than the ICER in the original analysis (€3 258). Even decision uncertainty, at a €35 000 threshold, increased significantly, increasing the value of further research from €355 100 in the original analysis, to €5 987 444 for the current elicited values. Conclusions: Failing to account for the individual expert’s uncertainty might have a considerable impact on the result of cost-effectiveness analyses. Formal expert elicitation offers a plausible method to generate prior distributions representing the experts’ uncertainty and thereby more appropriately account for the true uncertainty of the decision.
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| 49. |
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| 50. |
- Brodtkorb, Thor-Henrik, 1976-, et al.
(författare)
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Screening for hypertrophic cardiomyopathy in young athletes : A cost-effectiveness analysis
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Screening to prevent sudden cardiac death among young athletes has been debated for some time and several countries have already introduced pre-participation cardiovascular screening to identify sports active individuals at risk. Although, hypertrophic cardiomyopathy (HCM) is the most common underlying disease that is documented to be detectable by screening the cost-effectiveness of such a screening strategy is still unclear. Methods: A screening program to detect HCM in young athletes was compared to a non screening strategy. Prevalence of HCM, mortality risks and test characteristics were estimated from published sources and formal expert elicitation. These estimates were incorporated in a decision analytic model to estimate costs and health outcomes, expressed in life years and quality adjusted life years (QALYs), over a lifetime perspective. Results: The screening strategy was associated with a mean incremental cost of €93 and a mean incremental gain of 0.0005 life years, yielding a cost per life year gained of €196 205. Taking quality of life into account, the screening strategy was associated with a loss of 0.034 QALY. Conclusions: The study shows that screening young athletes for hypertrophic cardiomyopathy is not likely to yield survival benefits at a cost normally considered to be cost-effective and if quality of life is considered in the analysis screening is associated with higher costs and a loss of QALYs. Thus, based on the present findings a strategy of screening young athletes for hypertrophic cardiomyopathy is unlikely to be cost effective.
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