| 1. |
- Canesin, Giacomo, et al.
(författare)
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STAT3 inhibition with galiellalactone effectively targets the prostate cancer stem-like cell population
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Cancer stem cells (CSCs) are a small subpopulation of quiescent cells with the potential to differentiate into tumor cells. CSCs are involved in tumor initiation and progression and contribute to treatment failure through their intrinsic resistance to chemo- or radiotherapy, thus representing a substantial concern for cancer treatment. Prostate CSCs’ activity has been shown to be regulated by the transcription factor Signal Transducer and Activator of Transcription 3 (STAT3). Here we investigated the effect of galiellalactone (GL), a direct STAT3 inhibitor, on CSCs derived from prostate cancer patients, on docetaxel-resistant spheres with stem cell characteristics, on CSCs obtained from the DU145 cell line in vitro and on DU145 tumors in vivo. We found that GL significantly reduced the viability of docetaxel-resistant and patient-derived spheres. Moreover, CSCs isolated from DU145 cells were sensitive to low concentrations of GL, and the treatment with GL suppressed their viability and their ability to form colonies and spheres. STAT3 inhibition down regulated transcriptional targets of STAT3 in these cells, indicating STAT3 activity in CSCs. Our results indicate that GL can target the prostate stem cell niche in patient-derived cells, in docetaxel-resistant spheres and in an in vitro model. We conclude that GL represents a promising therapeutic approach for prostate cancer patients, as it reduces the viability of prostate cancer-therapy-resistant cells in both CSCs and non-CSC populations.
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| 2. |
- Challis, Pontus, et al.
(författare)
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Factors associated with the increased incidence of necrotising enterocolitis in extremely preterm infants in Sweden between two population-based national cohorts (2004-2007 vs 2014-2016)
- 2024
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Ingår i: Archives of Disease in Childhood-Fetal and Neonatal Edition. - : BMJ Publishing Group Ltd. - 1359-2998 .- 1468-2052. ; 109, s. 87-93
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate potential risk factors behind the increased incidence of necrotising enterocolitis (NEC) in Swedish extremely preterm infants.Design Registry data from two population-based national cohorts were studied. NEC diagnoses (Bell stage >= II) were validated against hospital records.Patients All liveborn infants <27 weeks of gestation 2004-2007 (n=704) and 2014-2016 (n=895) in Sweden.Main outcome measures NEC incidence.Results The validation process resulted in a 28% reduction of NEC cases but still confirmed a higher NEC incidence in the later epoch compared with the earlier (73/895 (8.2%) vs 27/704 (3.8%), p=0.001), while the composite of NEC or death was lower (244/895 (27.3%) vs 229/704 (32.5%), p=0.022). In a multivariable Cox regression model, censored for mortality, there was no significant difference in early NEC (0-7 days of life) between epochs (HR=0.9 (95% CI 0.5 to 1.9), p=0.9), but being born in the later epoch remained an independent risk factor for late NEC (>7 days) (HR=2.7 (95% CI 1.5 to 5.0), p=0.001). In propensity score analysis, a significant epoch difference in NEC incidence (12% vs 2.8%, p<0.001) was observed only in the tertile of infants at highest risk of NEC, where the 28-day mortality was lower in the later epoch (35% vs 50%, p=0.001). More NEC cases were diagnosed with intramural gas in the later epoch (33/73 (45.2%) vs 6/26 (23.1%), p=0.047).Conclusions The increase in NEC incidence between epochs was limited to cases occurring after 7 days of life and was partly explained by increased survival in the most extremely preterm infants. Misclassification of NEC is common.
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| 3. |
- Farooqi, Aijaz, et al.
(författare)
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One-year survival and outcomes of infants born at 22 and 23 weeks of gestation in Sweden 2004-2007, 2014-2016 and 2017-2019
- 2024
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Ingår i: Archives of Disease in Childhood-Fetal and Neonatal Edition. - : BMJ Publishing Group Ltd. - 1359-2998 .- 1468-2052. ; 109:1, s. 10-17
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo explore associations between perinatal activity and survival in infants born at 22 and 23 weeks of gestation in Sweden. Design/SettingData on all births at 22 and 23 weeks' gestational age (GA) were prospectively collected in 2004-2007 (T1) or obtained from national registers in 2014-2016 (T2) and 2017-2019 (T3). Infants were assigned perinatal activity scores based on 3 key obstetric and 4 neonatal interventions. Main outcomeOne-year survival and survival without major neonatal morbidities (MNM): intraventricular haemorrhage grade 3-4, cystic periventricular leucomalacia, surgical necrotising enterocolitis, retinopathy of prematurity stage 3-5 or severe bronchopulmonary dysplasia. The association of GA-specific perinatal activity score and 1-year survival was also determined. Results977 infants (567 live births and 410 stillbirths) were included: 323 born in T1, 347 in T2 and 307 in T3. Among live-born infants, survival at 22 weeks was 5/49 (10%) in T1 and rose significantly to 29/74 (39%) in T2 and 31/80 (39%) in T3. Survival was not significantly different between epochs at 23 weeks (53%, 61% and 67%). Among survivors, the proportions without MNM in T1, T2 and T3 were 20%, 17% and 19% for 22 weeks and 17%, 25% and 25% for 23 weeks' infants (p>0.05 for all comparisons). Each 5-point increment in GA-specific perinatal activity score increased the odds for survival in first 12 hours of life (adjusted OR (aOR) 1.4; 95% CI 1.3 to 1.6) in addition to 1-year survival (aOR 1.2; 95% CI 1.1 to 1.3), and among live-born infants it was associated with increased survival without MNM (aOR 1.3; 95% CI 1.1 to 1.4). ConclusionIncreased perinatal activity was associated with reduced mortality and increased chances of survival without MNM in infants born at 22 and 23 weeks of GA.
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| 4. |
- Fransson, Per, et al.
(författare)
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Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC) : patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial
- 2021
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Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 22:2, s. 235-245
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The HYPO-RT-PC trial compared conventionally fractionated radiotherapy with ultra-hypofractionated radiotherapy in patients with localised prostate cancer. Ultra-hypofractionation was non-inferior to conventional fractionation regarding 5-year failure-free survival and toxicity. We aimed to assess whether patient-reported quality of life (QOL) differs between conventional fractionation and ultra-hypofractionation up to 6 years after treatment in the HYPO-RT-PC trial.METHODS: HYPO-RT-PC is a multicentre, open-label, randomised, controlled, non-inferiority, phase 3 trial done in 12 centres (seven university hospitals and five county hospitals) in Sweden and Denmark. Inclusion criteria were histologically verified intermediate-to-high-risk prostate cancer (defined as T1c-T3a with one or two of the following risk factors: stage T3a; Gleason score ≥7; and prostate-specific antigen 10-20 ng/mL with no evidence of lymph node involvement or distant metastases), age up to 75 years, and WHO performance status 0-2. Participants were randomly assigned (1:1) to conventional fractionation (78·0 Gy in 39 fractions, 5 days per week for 8 weeks) or ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) via a minimisation algorithm with stratification by trial centre, T-stage, Gleason score, and prostate-specific antigen. QOL was measured using the validated Prostate Cancer Symptom Scale (PCSS) and European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline, the end of radiotherapy, months 3, 6, 12, and 24 after radiotherapy, every other year thereafter up to 10 years, and at 15 years. The primary endpoint (failure-free survival) has been reported elsewhere. Here we report QOL, a secondary endpoint analysed in the per-protocol population, up to 6 years after radiotherapy. The HYPO-RT-PC trial is registered with the ISRCTN registry, ISRCTN45905321.FINDINGS: Between July 1, 2005, and Nov 4, 2015, 1200 patients were enrolled and 1180 were randomly assigned (conventional fractionation n=591, ultra-hypofractionation n=589); 1165 patients (conventional fractionation n=582, ultra-hypofractionation n=583) were included in this QOL analysis. 158 (71%) of 223 patients in the conventional fractionation group and 146 (66%) of 220 in the ultra-hypofractionation group completed questionnaires at 6 years. The median follow-up was 48 months (IQR 25-72). In seven of ten bowel symptoms or problems the proportion of patients with clinically relevant deteriorations at the end of radiotherapy was significantly higher in the ultra-hypofractionation group than in the conventional fractionation group (stool frequency [p<0·0001], rush to toilet [p=0·0013], flatulence [p=0·0013], bowel cramp [p<0·0001], mucus [p=0·0014], blood in stool [p<0·0001], and limitation in daily activity [p=0·0014]). There were no statistically significant differences in the proportions of patients with clinically relevant acute urinary symptoms or problems (total 14 items) and sexual functioning between the two treatment groups at end of radiotherapy. Thereafter, there were no clinically relevant differences in urinary, bowel, or sexual functioning between the groups. At the 6-year follow-up there was no difference in the incidence of clinically relevant deterioration between the groups for overall urinary bother (43 [33%] of 132 for conventional fractionation vs 33 [28%] of 120 for ultra-hypofractionation; mean difference 5·1% [95% CI -4·4 to 14·6]; p=0·38), overall bowel bother (43 [33%] of 129 vs 34 [28%] of 123; 5·7% [-3·8 to 15·2]; p=0·33), overall sexual bother (75 [60%] of 126 vs 59 [50%] of 117; 9·1% [-1·4 to 19·6]; p=0·15), or global health/QOL (56 [42%] of 134 vs 46 [37%] of 125; 5·0% [-5·0 to 15·0]; p=0·41).INTERPRETATION: Although acute toxicity was higher for ultra-hypofractionation than conventional fractionation, this long-term patient-reported QOL analysis shows that ultra-hypofractionation was as well tolerated as conventional fractionation up to 6 years after completion of treatment. These findings support the use of ultra-hypofractionation radiotherapy for intermediate-to-high-risk prostate cancer.
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| 5. |
- Gyllensvaerd, Johan, et al.
(författare)
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Antibiotic Use in Late Preterm and Full-Term Newborns
- 2024
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Ingår i: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Importance Antibiotic treatment saves lives in newborns with early-onset sepsis (EOS), but unwarranted antibiotic use is associated with resistant bacteria and adverse outcomes later in life. Surveillance is needed to optimize treatment strategies. Objective To describe antibiotic use in association with the incidence and mortality from EOS among late-preterm and full-term newborns. Design, Setting, and Participants The Sweden Neonatal Antibiotic Use study was a nationwide observational study that included all late-preterm and full-term neonates born from January 1, 2012, to December 31, 2020, in neonatal units of all levels. All hospital live births from 34 weeks' gestation during the study period were included in the study. Data were collected from the Swedish Neonatal Quality Register and the Swedish Medical Birth Register. Data were analyzed from August 2022 to May 2023. Exposure Admission for neonatal intensive care during the first week of life. Main Outcomes and Measures The main outcomes were the usage of intravenous antibiotics during the first week of life, the duration of antibiotic therapy, the rate of culture-proven EOS, and mortality associated with EOS. Results A total of 1 025 515 newborns were included in the study; 19 286 neonates (1.88%; 7686 girls [39.9%]; median [IQR] gestational age, 40 [38-41] weeks; median [IQR] birth weight, 3610 [3140-4030] g) received antibiotics during the first week of life, of whom 647 (3.4%) had EOS. The median (IQR) duration of antibiotic treatment in newborns without EOS was 5 (3-7) days, and there were 113 antibiotic-days per 1000 live births. During the study period there was no significant change in the exposure to neonatal antibiotics or antibiotic-days per 1000 live births. The incidence of EOS was 0.63 per 1000 live births, with a significant decrease from 0.74 in 2012 to 0.34 in 2020. Mortality associated with EOS was 1.39% (9 of 647 newborns) and did not change significantly over time. For each newborn with EOS, antibiotic treatment was initiated in 29 newborns and 173 antibiotic-days were dispensed. Conclusions and Relevance This large nationwide study found that a relatively low exposure to antibiotics is not associated with an increased risk of EOS or associated mortality. Still, future efforts to reduce unwarranted neonatal antibiotic use are needed.
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| 6. |
- Johnsson, Anders, et al.
(författare)
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Anal cancer in Sweden 2015-2019. Implementation of guidelines, structural changes, national registry and early results
- 2022
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Ingår i: Acta Oncologica. - : Taylor & Francis Group. - 0284-186X .- 1651-226X. ; 61:5, s. 575-582
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Tidskriftsartikel (refereegranskat)abstract
- Background Squamous cell cancer of the anus is an uncommon malignancy, usually caused by human papilloma virus (HPV). Chemoradiotherapy (CRT) is the recommended treatment in localized disease with cure rates of 60-80%. Local failures should be considered for salvage surgery. With the purpose of improving and equalizing the anal cancer care in Sweden, a number of actions were taken between 2015 and 2017. The aim of this study was to describe the implementation of guidelines and organizational changes and to present early results from the first 5 years of the Swedish anal cancer registry (SACR). Methods The following were implemented: (1) the first national care program with treatment guidelines, (2) standardized care process, (3) centralization of CRT to four centers and salvage surgery to two centers, (4) weekly national multidisciplinary team meetings where all new cases are discussed, (5) the Swedish anal cancer registry (SACR) was started in 2015. Results The SACR included 912 patients with a diagnosis of anal cancer from 2015 to 2019, reaching a national coverage of 95%. We could show that guidelines issued in 2017 regarding staging procedures and radiotherapy dose modifications were rapidly implemented. At baseline 52% of patients had lymph node metastases and 9% had distant metastases. Out of all patients in the SACR 89% were treated with curative intent, most of them with CRT, after which 92% achieved a local complete remission and the estimated overall 3-year survival was 85%. Conclusions This is the first report from the SACR, demonstrating rapid nation-wide implementation of guidelines and apparently good treatment outcome in patients with anal cancer in Sweden. The SACR will hopefully be a valuable source for future research.
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| 7. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 8. |
- Munshi, Bijit, et al.
(författare)
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Surgical Decision Making in Uncomplicated Type B Aortic Dissection : A Survey of Australian/New Zealand and European Surgeons
- 2020
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : W B SAUNDERS CO LTD. - 1078-5884 .- 1532-2165. ; 60:2, s. 194-200
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Tidskriftsartikel (refereegranskat)abstract
- Objective: There is controversy about the role of pre-emptive thoracic endovascular aortic repair (TEVAR) in uncomplicated type B aortic dissection (TBAD). The aim was to understand expert opinions and the factors influencing decision making. Methods: In 2018, surgeons from Australia/New Zealand (ANZ) and Europe (EUR) were contacted to participate in an online survey which comprised questions about preferences for pre-emptive TEVAR, followed by five case scenarios, and two ranking questions for anatomical and technical risk factors respectively. Case 1 was designed to favour TEVAR in a hypertensive patient with partial false lumen thrombosis and large diameter (aortic >= 40 mm, false lumen >= 22 mm). Case 2 had no risk factors mandating TEVAR, according to current evidence. Cases 3, 4, and 5 were designed to test one risk factor respectively, large entry tear on the inner aortic curvature (>= 10 mm), partial false lumen thrombosis, and large diameter alone. Results: There were 75 responses, 42 from EUR and 33 from ANZ. Almost half of surgeons (49.3%) endorsed preemptive TEVAR with 82.3% preferring to perform TEVAR in the subacute phase. In Case 1 and 5, 58.3% and 52.8% of surgeons respectively chose TEVAR, the highest rates obtained in the survey. Cases 1 and 5 included large diameters >= 40 mm, which were ranked the highest in importance when surgeons considered anatomical risk factors. Surgeons who recommend pre-emptive TEVAR were more likely to choose TEVAR in both Case 1 (83.3% vs. 33.3%, p < .001, 95% CI 27.6%-65.8%) and Case 5 (69.4% vs. 38.2%, p = .008, 95% CI 8.2%-50.0%). Conclusion: In this survey about uncomplicated TBAD, about half of surgeons recommended pre-emptive TEVAR in selected cases. The surgeon's predisposition towards intervention and large diameters appear to be the most influential factors in decision making. These findings underline the uncertainty in today's practice and emphasise the need for better predictive tools.
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| 9. |
- Patterson, Allison, et al.
(författare)
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Foraging range scales with colony size in high-latitude seabirds
- 2022
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 32:17, s. 3800-3807
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Tidskriftsartikel (refereegranskat)abstract
- Density-dependent prey depletion around breeding colonies has long been considered an important factor controlling the population dynamics of colonial animals.1, 2, 3, 4 Ashmole proposed that as seabird colony size increases, intraspecific competition leads to declines in reproductive success, as breeding adults must spend more time and energy to find prey farther from the colony.1 Seabird colony size often varies over several orders of magnitude within the same species and can include millions of individuals per colony.5,6 As such, colony size likely plays an important role in determining the individual behavior of its members and how the colony interacts with the surrounding environment.6 Using tracking data from murres (Uria spp.), the world’s most densely breeding seabirds, we show that the distribution of foraging-trip distances scales to colony size0.33 during the chick-rearing stage, consistent with Ashmole’s halo theory.1,2 This pattern occurred across colonies varying in size over three orders of magnitude and distributed throughout the North Atlantic region. The strong relationship between colony size and foraging range means that the foraging areas of some colonial species can be estimated from colony sizes, which is more practical to measure over a large geographic scale. Two-thirds of the North Atlantic murre population breed at the 16 largest colonies; by extrapolating the predicted foraging ranges to sites without tracking data, we show that only two of these large colonies have significant coverage as marine protected areas. Our results are an important example of how theoretical models, in this case, Ashmole’s version of central-place-foraging theory, can be applied to inform conservation and management in colonial breeding species.
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| 10. |
- Romanov, Pavel, et al.
(författare)
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Hardening of Cylindrical Bars with Water Impinging Jet Quenching Technique
- 2024
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Ingår i: Steel Research International. - : Wiley. - 1611-3683 .- 1869-344X. ; 95:6
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Tidskriftsartikel (refereegranskat)abstract
- Hardening of carbon steel products by austenitization and immersion in a quenching medium is a widely used heat treatment to obtain a hard and strong martensitic structure. To avoid the undesired consequences, such as residual stresses or insufficient hardening depth, the cooling rates must be accurately measured and controlled. This can be achieved using the impinging water jet quenching technique. The aim of this work is to perform hardening of four low-alloyed 70 mm cylindrical carbon steel bars, using impinging water jet quenching technique with different jet flow rates, and to analyze its effect on thermal evolution and residual stresses. The temperature evolution during quenching experiments is recorded and used as input to a comprehensive quenching model to predict phase transformations, final hardness, and residual stresses of cylindrical bars. All four quenching experiments result in a fully hardened martensitic state. Furthermore, a decrease in jets’ flow rate, within a certain interval, results in different thermal histories and in lower compressive residual stresses on the surface. The results from quenching simulations show promising hardness, microstructure, and residual stress predictions that are validated by hardness measurements, optical microscopy, and residual stress analysis using X-Ray diffraction method.
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