Knut Liestøl

• Julbø, Frida Marie Ihle; Henriksen, Audun Ljone; Pradhan, Manohar; Lindstrøm, Erika Kristina; Kostolomov, Ilyá & Oukrif, Dahmane [Vis alle 21 forfattere av denne artikkelen] (2026). Reliable classification of polyps based on artificial intelligence: a development and validation study. EClinicalMedicine. 93. doi: 10.1016/j.eclinm.2026.103826. Fulltekst i vitenarkiv Vis sammendrag

  Background The shortage of pathologists presents a significant bottleneck in delivering timely and accurate diagnoses. To address this challenge, we developed the POLyp Artificial Intelligence-based RISk classifier (POLARIS), a prescreening tool designed to assist pathologists in handling the increasing volume of colorectal biopsies. Methods Using 15,079 whole-slide images (WSIs) from 2993 patients in the UK bowel cancer screening program between 2014 and 2018 and the histological diagnoses as ground truth, POLARIS was developed applying the open-source foundation model H-optimus-0, multiple instance learning, and a training scheme designed to provide robust models. Each WSI was categorised into one of five classes based on the diagnosis, reflecting increasing risk of malignancy, and regrouped into two broader categories for clinical interpretation. One category includes only samples not requiring pathological review, specifically those classified as normal tissue or tubular adenomas with low-grade dysplasia (LGD). The second category includes all other types of polyps, which are polyps recommended for review by a pathologist. A prespecified validation protocol defined how a specific model should be evaluated on a geographically external dataset comprising 10,842 WSIs from Cheltenham General Hospital between 2008 and 2019 and acquired using two scanners, Leica Aperio AT2 and Hamamatsu NanoZoomer XR. After validation, three experienced pathologists independently assessed the cases in which model prediction differed most from clinical diagnosis and, blinded to model output, reached a consensus. Findings In the external validation, POLARIS correctly identified 98.94% (95% CI 96.92–99.78%) of polyps with high-grade dysplasia (HGD) and adenocarcinoma as POLARIS-positive, and correctly classified 83.04% (81.66–84.36%) of normal and tubular adenomas with LGD as POLARIS-negative. The overall balanced accuracy was 86.65% for this prespecified primary analysis. In the tuning set, balanced accuracy was 87.64%, the sensitivity for polyps with HGD and adenocarcinoma was 100% (95% CI 97.14–100), and the specificity for normal and tubular adenomas with LGD was 81.89% (79.94–83.70). POLARIS achieved an area under the receiver operating characteristic curve (AUROC) in external validation of 0.9449 (95% CI 0.9384–0.9507) for distinguishing normal and tubular adenomas with LGD from polyps recommended for review by a pathologist and 0.9788 (0.9718–0.9844) for polyps with HGD and adenocarcinoma cases specifically. The model predicted the same class for both scanners in 97.93% (97.49–98.32%) of the cases. In the review of selected cases, the pathologists agreed with the model and not the clinical diagnosis in 92.5% of the cases. Heatmaps highlighting regions where the model indicates high-risk features closely correlated with areas annotated by expert pathologists as high-risk. Interpretation POLARIS has the potential to enhance diagnostic workflows in colorectal pathology by reliably identifying high-risk lesions and highlighting high-risk regions while substantially reducing the number of slides requiring pathologist review.

• Skrede, Ole-Johan; Pradhan, Manohar; Isaksen, Maria; Hveem, Tarjei Sveinsgjerd; Vlatkovic, Ljiljana & Nesbakken, Arild [Vis alle 23 forfattere av denne artikkelen] (2026). Generalisation of automatic tumour segmentation in histopathological whole-slide images across multiple cancer types. NPJ precision oncology. 10. doi: 10.1038/s41698-026-01311-6. Fulltekst i vitenarkiv Vis sammendrag

  Deep learning is expected to aid pathologists in tasks such as tumour segmentation. We developed a general tumour segmentation model for histopathological images and examined its performance in different cancer types. The model was developed using over 20,000 whole-slide images from over 4000 patients with colorectal, endometrial, lung, or prostate carcinoma. Performance was validated in pre-planned analyses on external cohorts with over 3000 patients across six cancer types. Exploratory analyses included over 1500 additional patients from The Cancer Genome Atlas. Average Dice coefficient was over 80% in all validation cohorts with en bloc resection specimens and in The Cancer Genome Atlas cohorts. No performance loss was observed when comparing the general model with single-cancer models specialised in cancer types from the development set. In conclusion, extensive and rigorous evaluations demonstrate that generic tumour segmentation by a single model is possible across cancer types, patient populations, sample preparations and slide scanners.

• Kalsnes, Joakim; Isaksen, Maria; Julbø, Frida Marie Ihle; Pradhan, Manohar; Kleppe, Andreas & Raedt, Sepp de [Vis alle 33 forfattere av denne artikkelen] (2026). Applicability of mitotic figure counting by deep learning: a development and pan‐cancer validation study. FEBS Open Bio. 16(7), s. 1259–1270. doi: 10.1002/2211-5463.70210. Fulltekst i vitenarkiv Vis sammendrag

  Mitotic figure counting is an established measure of cell proliferation that is included in grading systems. We developed a deep learning method for mitotic figure counting and evaluated its prognostic impact in multiple external validation datasets. The deep learning method was trained in whole slide images of tissue sections stained with haematoxylin and eosin from a publicly available breast cancer dataset where mitotic figures have been annotated by expert pathologists. The final model was externally validated according to a protocol with predefined analyses of 14 571 patient samples from 13 patient cohorts from seven different cancer types. The predefined primary analysis was univariable Cox survival analysis of the number of mitotic figures detected per mm 2 . Automatic mitotic figure counting correlated well with known proliferation rates, and patients with more mitotic figures per mm 2 had significantly worse patient outcome in all the studied cancer types except colorectal cancer. This study demonstrates the practical potential of automated, deep learning‐based mitotic figure counting, both by automating pathology work and by suggesting expanded use in more cancer types, such as prostate cancer.

• Olsen, Eirik; Mariampillai, Julian Eek; Schmieder, Roland E.; Jamerson, Kenneth; Søraas, Camilla Lund & Mancia, Giuseppe [Vis alle 14 forfattere av denne artikkelen] (2025). On-treatment systolic blood pressure and preserved kidney function in hypertensive patients with proteinuria. The VALUE Trial. Blood Pressure. ISSN 0803-7051. 34(1). doi: 10.1080/08037051.2025.2544715. Fulltekst i vitenarkiv Vis sammendrag

  Aims We investigated on-treatment systolic BP (SBP) <130, 130–139 and ≥140 mmHg related to nephroprotection in 3065 patients with proteinuria and 10,738 patients without proteinuria in the VALUE Trial. Method and results Worsened kidney function (WKF) was ≥50% increase in serum creatinine, and end-stage kidney disease (ESKD) was dialysis/transplantation. Cox proportional hazards models were adjusted for covariates in the on-treatment SBP groups. Lower SBP was significantly related to less WKF (p < .001) in patients with proteinuria, both at <130 mmHg (n = 14/529, 2.6%) and 130–139 mmHg (n = 46/1176, 3.9%) compared to ≥140 mmHg (n = 145/1358, 10.7%). None of the 532 patients with proteinuria had ESKD at <130 mmHg, and only 11/1194 (0.9%) at 130–139 mmHg (p = .098) compared to 39/1339 (2.9%) at SBP ≥ 140 mmHg. In patients without proteinuria the relation between lower SBP and WKF was not significant (p = .23) at <130 mmHg (n = 24/1927, 1.2%) but significant (p = .04) at 130–139 mmHg (n = 74/4611, 1.6%) compared to SBP ≥ 140 mmHg (n = 117/4199, 2.8%). ESKD was 0.2%, 0.2% and 0.4% in the SBP groups, respectively. WKF fell from 12.1% in Q1 (highest SBP quartile) to 6.1% in Q2 (p = .023), 4.2% in Q3 (p = .006) and 2.8% in Q4 (p < .001) in patients with proteinuria and ESKD from 3.5% (Q1) to 1.6% (Q2) (p = .13), 0.7% (Q3) (p = .027) and 0.1% in Q4 (p = .009). In the patients without proteinuria, neither WKF nor ESKD showed statistically significant changes between SBP quartiles. Conclusions Our data suggest that, compared to SBP ≥ 140 mmHg, on-treatment SBP <130 and 130–139 mmHg were strongly related to nephroprotection in hypertensive patients with proteinuria.

• Olsen, Eirik; Søraas, Camilla Lund; Schmieder, Roland E; Jamerson, Kenneth; MacDonald, Thomas M & Mancia, Giuseppe [Vis alle 17 forfattere av denne artikkelen] (2025). Low Achieved Systolic Blood Pressure Related to Kidney Protection in Diabetic and Non-Diabetic High-Risk Hypertensive Patients. American Journal of Hypertension. ISSN 0895-7061. 38(12), s. 1106–1119. doi: 10.1093/ajh/hpaf093. Fulltekst i vitenarkiv Vis sammendrag

  BACKGROUND Protecting the kidneys by lowering systolic blood pressure (SBP) in hypertensive patients is not unequivocally settled. We tested the hypothesis that achieving lower average SBP in middle-aged and older high-risk hypertensive patients with and without type-2 diabetes mellitus through several years would clarify kidney protection. METHODS We analyzed patients 50–80 years with no cardiovascular events during the first 6 months of drug up-titration after randomization to valsartan or amlodipine, and with 3 or more visits onwards with standardized BP measurements. Adjusted Cox analyzes compared worsened kidney function defined as a 50% rise in se-creatinine on a minimum of two occasions at least 4 weeks apart or end-stage kidney disease (ESKD) in achieved SBP quartiles and in patients who achieved SBP < 130 and 130–139 mmHg with patients whose SBP remained ≥140 mmHg. RESULTS A total of 13,803 patients were investigated of whom 4,655 had DM. Patients with DM had less worsened kidney function at SBP 130–139 mmHg (HR = 0.524, 95% CIs 0.375–0.733, n = 1849, P < 0.001) and at SBP < 130 mmHg (HR = 0.538, CIs 0.316-0.915, n = 674, P = 0.022) compared with patients at ≥ 140 mmHg. They also had less ESKD at SBP 130-139 mmHg (HR = 0.442, CIs 0.196–1.000, P = 0.050) with a similar trend at SBP < 130 mmHg and in quartile analysis with only 1 ESKD in the lowest quartile. Findings in patients without DM (n = 9,148) were similar to DM. CONCLUSIONS In high-risk hypertensive patients aged 50–80 years, with and without DM, targeting SBP of 130–139 mmHg confers kidney protection with possible further benefit at the lower target of SBP < 130 mmHg. Clinical trials registration Trial Number NCT06395194, www.clinicaltrials.gov.

• Olsen, Eirik; Halvorsen, Lene Vernås; Rognstad, Stine; Aune, Arleen; Brobak, Karl Marius & Bergland, Ola Undrum [Vis alle 17 forfattere av denne artikkelen] (2025). Characteristics of adherent and non-adherent patients with hypertension in a Norwegian cross-sectional study. Exploration of Medicine. 6. doi: 10.37349/emed.2025.1001279. Fulltekst i vitenarkiv
• Olsen, Erik; Jamerson, Kenneth; Schmieder, Roland E.; Søraas, Camilla Lund; Mariampillai, Julian Eek & Mancia, Giuseppe [Vis alle 17 forfattere av denne artikkelen] (2024). Effects of valsartan vs amlodipine and achieved lower blood pressure on the incidence of end-stage kidney disease: The VALUE Trial. European journal of internal medicine. ISSN 0953-6205. doi: 10.1016/j.ejim.2024.12.021. Fulltekst i vitenarkiv Vis sammendrag

  Background There is a paucity of data investigating the impact of antihypertensive drug classes and blood pressure (BP) treatment targets on the incidence of end-stage kidney disease (ESKD). In patients with high-risk hypertension aged 50–80 years or above, we aimed to, 1) compare effects of valsartan, an angiotensin receptor blocker, with amlodipine, a calcium channel blocker and, 2) assess the effect of achieving systolic BP <135 vs ≥135 mmHg on the ESKD incidence. Methods The VALUE Trial was a multicenter prospective double-blinded randomized clinical trial in patients with essential hypertension and high cardiovascular risk including known coronary disease, left ventricular hypertrophy and previous stroke, in which ESKD was a secondary endpoint defined as progression to kidney transplant and/or dialysis. Patients were randomized to either valsartan or amlodipine, with other anti-hypertensive medications as add-on if needed to reach the systolic BP target of <140 mmHg. Cox proportional hazards ratio (HR) was used to compare different treatment groups and achieved systolic BP <135 with ≥135 mmHg, during 3–6 years of follow-up. Results 15,245 patients were randomized and followed until 63,631 patient-years with only 90 patients lost to follow-up. The primary outcome, a composite of cardiac morbidity and mortality, was neutral between valsartan and amlodipine. On valsartan 47 patients (0.61 %) and on amlodipine 50 patients (0.66 %) developed ESKD (HR=1.02, 95 % CI 0.68–1.52, p =0.94). Achieved SBP <135 mmHg was strongly related to less ESKD (n =9/5036 patients, 0.2 %) compared with achieved SBP ≥135 mmHg (n =73/8766 patients, 0.8 %) (HR=0.28, CI 0.14–0.58, p <0.001). Conclusions In hypertensive patients with a high cardiovascular risk, valsartan and amlodipine have a similar impact on the incidence of end-stage kidney disease. Achieving SBP <135 mmHg, averaging 128.8/77.3 mmHg, is highly efficacious in kidney protection.

• Halvorsen, Lene Vernås; Søraas, Camilla Lund; Larstorp, Anne Cecilie Kjeldsen; Hjørnholm, Ulla; Kjær, Vibeke Norheim & Liestøl, Knut [Vis alle 21 forfattere av denne artikkelen] (2024). Effect of Therapeutic Drug Monitoring on Adherence and Blood Pressure: A Multicenter Randomized Clinical Trial. American Journal of Hypertension. ISSN 0895-7061. 37(10), s. 826–836. doi: 10.1093/ajh/hpae059. Fulltekst i vitenarkiv Vis sammendrag

  BACKGROUND Drug concentration in blood or urine is an acknowledged method to detect nonadherence. Observational studies suggest that informing patients about low or absent serum drug levels improves blood pressure (BP). We performed a multicenter randomized clinical trial to test the hypothesis that therapeutic drug monitoring (TDM) could improve drug adherence and BP in patients with uncontrolled hypertension (HT). METHODS Patients were ≥18 years on stable treatment with at least 2 antihypertensive agents. We planned to randomize 80 nonadherent patients with a systolic daytime ambulatory BP ≥135 mm Hg to TDM intervention or not. The control group and the study personnel who measured BP remained uninformed about serum drug measurements throughout. All patients and physicians were blinded for BPs. Lifestyle advice and detailed information on the disease process and the importance of BP treatment were given to both groups. RESULTS From 2017 to 2022, we randomized 46 diagnosed nonadherent from a total of 606 patients with uncontrolled HT. The TDM group had a 6.7 (±14.5) mm Hg reduction from 147.9 (±10.3) to 141.1 (±14.1) mm Hg, and the control group experienced a 7.3 (±13.2) mm Hg reduction from 147.1 (±9.2) to 139.1 (±17.4) mm Hg, P = 0.9 between groups. Adherence improved in both groups, 73% in the TDM group and 59% in the control group became adherent at 3 months, P = 0.51. CONCLUSIONS In our prospective multicenter clinical trial of uncontrolled and nonadherent hypertensive patients, we found no additional effect of TDM on BP and drug adherence compared with standard care.

• Cyll, Karolina Urszula; Haug, Erik Skaaheim; Pradhan, Manohar; Vlatkovic, Ljiljana; Carlsen, Birgitte & Löffeler, Sven [Vis alle 14 forfattere av denne artikkelen] (2024). DNA ploidy and PTEN as biomarkers for predicting aggressive disease in prostate cancer patients under active surveillance. British Journal of Cancer. ISSN 0007-0920. doi: 10.1038/s41416-024-02780-x. Fulltekst i vitenarkiv Vis sammendrag

  Background: Current risk stratification tools for prostate cancer patients under active surveillance (AS) may inadequately identify those needing treatment. We investigated DNA ploidy and PTEN as potential biomarkers to predict aggressive disease in AS patients.<p><p> Methods: We assessed DNA ploidy by image cytometry and PTEN protein expression by immunohistochemistry in 3197 tumour-containing tissue blocks from 558 patients followed in AS at a Norwegian local hospital. The primary endpoint was treatment, with treatment failure (biochemical recurrence or initiation of salvage therapy) as the secondary endpoint. <p>Results: The combined DNA ploidy and PTEN (DPP) status at diagnosis was associated with treatment-free survival in univariable- and multivariable analysis, with a HR for DPP-aberrant vs. DPP-normal tumours of 2.12 (p < 0.0001) and 1.94 (p < 0.0001), respectively. Integration of DNA ploidy and PTEN status with the Cancer of the Prostate Risk Assessment (CAPRA) score improved risk stratification (c-index difference = 0.025; p = 0.0033). Among the treated patients, those with DPP-aberrant tumours exhibited a significantly higher likelihood of treatment failure (HR 2.01; p = 0.027). <p>Conclusions: DNA ploidy and PTEN could serve as additional biomarkers to identify AS patients at increased risk of developing aggressive disease, enabling earlier intervention for nearly 50% of the patients that will eventually receive treatment with current protocol.

• Erikssen, Gunnar; Liestøl, Knut; Aboulhosn, Jamil; Holmstrøm, Henrik; Wik, Gunnar & Døhlen, Gaute [Vis alle 14 forfattere av denne artikkelen] (2023). Preoperative versus postoperative survival in patients with univentricular heart: A nationwide, retrospective study of patients born in 1990-2015. BMJ Open. 13(7). doi: 10.1136/bmjopen-2022-069531. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Few data exist on mortality among patients with univentricular heart (UVH) before surgery. Our aim was to explore the results of intention to perform surgery by estimating preoperative vs postoperative survival in different UVH subgroups. Design Retrospective. Setting Tertiary centre for congenital cardiology and congenital heart surgery. Participants All 595 Norwegian children with UVH born alive from 1990 to 2015, followed until 31 December 2020. Results One quarter (151/595; 25.4%) were not operated. Among these, only two survived, and 125/149 (83.9%) died within 1 month. Reasons for not operating were that surgery was not feasible in 31.1%, preoperative complications in 25.2%, general health issues in 23.2% and parental decision in 20.5%. In total, 327/595 (55.0%) died; 283/327 (86.5%) already died during the first 2 years of life. Preoperative survival varied widely among the UVH subgroups, ranging from 40/65 (61.5%) among patients with unbalanced atrioventricular septal defect to 39/42 (92.9%) among patients with double inlet left ventricle. Postoperative survival followed a similar pattern. Postoperative survival among patients with hypoplastic left heart syndrome (HLHS) improved significantly (5-year survival, 42.5% vs 75.3% among patients born in 1990–2002 vs 2003–2015; p&lt;0.0001), but not among non-HLHS patients (65.7% vs 72.6%; p=0.22)—among whom several subgroups had a poor prognosis similar to HLHS. A total of 291/595 patients (48.9%) had Fontan surgery Conclusions Surgery was refrained in one quarter of the patients, among whom almost all died shortly after birth. Long-term prognosis was largely determined during the first 2 years. There was a strong concordance between preoperative and postoperative survival. HLHS survival was improved, but non-HLHS survival did not change significantly. This study demonstrates the complications and outcomes encountering newborns with UVH at all major stages of preoperative and operative treatment.

• Heimark, Sondre; Mehlum, Maria Hollund; Mancia, Giuseppe; Søraas, Camilla Lund; Liestøl, Knut & Wachtell, Kristian [Vis alle 12 forfattere av denne artikkelen] (2023). Middle-Aged and Older Patients With Left Ventricular Hypertrophy: Higher Mortality With Drug Treated Systolic Blood Pressure Below 130 mm Hg. Hypertension. ISSN 0194-911X. 80(8), s. 1739–1748. doi: 10.1161/HYPERTENSIONAHA.123.21454. Fulltekst i vitenarkiv
• Knutsen, Thomas M; Skretteberg, Torger; Vanberg, Paul; Kamal, Ziaullah; Halvorsen, Sigrun & Liestøl, Knut [Vis alle 8 forfattere av denne artikkelen] (2023). Transvenous lead extractions in a single high-volume center over a 24-year period: High success rate and low complication rate. Heart Rhythm O2. 4(4), s. 232–240. doi: 10.1016/j.hroo.2023.01.003. Fulltekst i vitenarkiv Vis sammendrag

  Background Transvenous lead extraction (TLE) procedures can be complicated and are associated with a small but significant risk of cardiovascular complications. However, methods and tools vary among centers. Objective The purpose of this study was to the present the methods and results of pacemaker and implantable cardioverter-defibrillator TLE procedures in our center over a 24-year period. Methods From April 1997 through 2020, we attempted to extract 2964 leads in 1780 procedures and 1642 patients. We mainly utilized single sheath technique using snaring or mechanical rotational sheaths and steel sheaths when necessary. Difficult procedures were performed by an experienced cardiologist, and close supervision was emphasized. Most of the extractions were performed using local anesthesia with sedation. Results Median age of patients was 65.0 [interquartile range 20.00] years, and median dwelling time of leads was 5.0 [7.0] years. Clinical success was achieved in 1739 procedures (97.7%) and complete technical success in 2841 leads (95.8%). Clinical success (leaving <4 cm of the lead in the body and achieving the clinical goal for the patient) was achieved for 79 leads (2.7%). TLE failed in 44 leads (1.1%) and 41 procedures (2.3%) among 36 patients (2.2%). There were 23 cases (1.3%) of major complications, with only 1 death directly related to the procedure (<0.1%). In addition, 2 patients with sepsis died within the first 24 hours after the procedure. No caval tears occurred. Conclusion Single sheath lead extractions utilizing snaring or mechanical rotational sheaths were effective and safe in our high-volume center as performed by experienced operators.

• Isaksen, Kathrine Thuestad; Galleberg, Renate Berget; Mastroianni, Maria Adele; Rinde, Marit; Rusten, Leiv Sindre & Barzenje, Dlawer Abdulla [Vis alle 15 forfattere av denne artikkelen] (2023). The Geriatric Prognostic Index: a clinical prediction model for survival of older diffuse large B-cell lymphoma patients treated with standard immunochemotherapy. Haematologica. ISSN 0390-6078. 108(9), s. 2454–2466. doi: 10.3324/haematol.2022.282289. Fulltekst i vitenarkiv Vis sammendrag

  The International prognostic Index (IPI) is the most widely used clinical prediction model for diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), but may be suboptimal in older patients. We aimed to develop and externally validate a clinical prediction model for older, RCHOP- treated DLBCL patients by examining geriatric assessment and lymphoma-related parameters in real-world cohorts. A population-based training set of 365 R-CHOP-treated DLBCL patients ≥70 years was identified through the Cancer Registry of Norway. The external test set consisted of a population-based cohort of 193 patients. Data on candidate predictors were retrieved from the Cancer Registry and through review of clinical records. Cox regression models for 2-year overall survival were used for model selection. Activities of daily living, the Charlson Comorbidity Index, age, sex, albumin, stage, Eastern Cooperative Oncology Group performance status and lactate dehydrogenase level were identified as independent predictors and combined into a Geriatric Prognostic Index (GPI). The GPI demonstrated good discrimination (optimismcorrected C-index 0.752), and identified low-, intermediate- and high-risk groups with significantly different survivals (2- year overall survival, 94%, 65%, and 25%, respectively). At external validation, the continuous and grouped GPI demonstrated good discrimination (C-index 0.727 and 0.710, respectively) and the GPI groups had significantly different survivals (2-year overall survival 95%, 65%, and 44%, respectively). Both the continuous and grouped GPI showed better discrimination than the IPI, revised-IPI and National Comprehensive Cancer Network (NCCN)-IPI (C-index 0.621, 0.583, and 0.670, respectively). In conclusion, we have developed and externally validated a GPI for older DLBCL patients treated with R-CHOP that outperformed the IPI, revised-IPI and NCCN-IPI. A web-based calculator is available at https://wide.shinyapps. io/GPIcalculator/.

• Holter, Øystein Gullvåg; Snickare, Lotta Karin & Liestøl, Knut (2022). Experiences in Academia: A New Survey Study. I Holter, Øystein Gullvåg & Snickare, Lotta Karin (Red.), Gender Equality in Academia – from Knowledge to Change. Cappelen Damm Akademisk. ISSN 9788202778026. s. 129–164. doi: 10.23865/noasp.179.ch5. Fulltekst i vitenarkiv
• Nikolaidis, Konstantinos; Kristiansen, Stein; Plagemann, Thomas Peter; Goebel, Vera Hermine; Liestøl, Knut & Kankanhalli, Mohan [Vis alle 11 forfattere av denne artikkelen] (2022). Learning Realistic Patterns from Visually Unrealistic Stimuli: Generalization and Data Anonymization (Extended Abstract). I Raed, Luc de (Red.), Proceedings of the Thirty-First International Joint Conference on Artificial Intelligence. AAAI Press. ISSN 9781956792003. s. 5762–5766. doi: 10.24963/ijcai.2022/806. Fulltekst i vitenarkiv Vis sammendrag

  Good training data is a prerequisite to develop useful Machine Learning applications. However, in many domains existing data sets cannot be shared due to privacy regulations (e.g., from medical studies). This work investigates a simple yet unconventional approach for anonymized data synthesis to enable third parties to benefit from such anonymized data. We explore the feasibility of learning implicitly from visually unrealistic, task-relevant stimuli, which are synthesized by exciting the neurons of a trained deep neural network. As such, neuronal excitation can be used to generate synthetic stimuli. The stimuli data is used to train new classification models. Furthermore, we extend this framework to inhibit representations that are associated with specific individuals. Extensive comparative empirical investigation shows that different algorithms trained on the stimuli are able to generalize successfully on the same task as the original model.

• Jørgensen, Magne; Halkjelsvik, Torleif & Liestøl, Knut (2022). When should we (not) use the mean magnitude of relative error (MMRE) as an error measure in software development effort estimation? Information and Software Technology. ISSN 0950-5849. 143. doi: 10.1016/j.infsof.2021.106784. Fulltekst i vitenarkiv
• Holter, Øystein Gullvåg; Snickare, Lotta Karin & Liestøl, Knut (2022). Men, Masculinities and Professional Hierarchies. I Holter, Øystein Gullvåg & Snickare, Lotta Karin (Red.), Gender Equality in Academia – from Knowledge to Change. Cappelen Damm Akademisk. ISSN 9788202778026. s. 53–79. doi: 10.23865/noasp.179.ch2. Fulltekst i vitenarkiv
• Holter, Øystein Gullvåg; Snickare, Lotta Karin & Liestøl, Knut (2022). The Bøygen Model: The Hypothesis of Accumulated Disadvantage. I Holter, Øystein Gullvåg & Snickare, Lotta Karin (Red.), Gender Equality in Academia – from Knowledge to Change. Cappelen Damm Akademisk. ISSN 9788202778026. s. 207–227. doi: 10.23865/noasp.179.ch7. Fulltekst i vitenarkiv
• Lobert, Viola; Skardal, Maren; Malerød, Lene; Simensen, Julie Elisabeth; Algra, Hermine Arida & Andersen, Aram Nikolai [Vis alle 12 forfattere av denne artikkelen] (2022). PHLPP1 regulates CFTR activity and lumen expansion through AMPK. Development. ISSN 0950-1991. 149(20), s. 1–10. doi: 10.1242/dev.200955. Fulltekst i vitenarkiv Vis sammendrag

  Complex organ development depends on single lumen formation and its expansion during tubulogenesis. This can be achieved by correct mitotic spindle orientation during cell division, combined with luminal fluid filling that generates hydrostatic pressure. Using a human 3D cell culture model, we have identified two regulators of these processes. We find that pleckstrin homology leucine-rich repeat protein phosphatase (PHLPP) 2 regulates mitotic spindle orientation, and thereby midbody positioning and maintenance of a single lumen. Silencing the sole PHLPP family phosphatase in Drosophila melanogaster, phlpp, resulted in defective spindle orientation in Drosophila neuroblasts. Importantly, cystic fibrosis transmembrane conductance regulator (CFTR) is the main channel regulating fluid transport in this system, stimulated by phosphorylation by protein kinase A and inhibited by the AMP-activated protein kinase AMPK. During lumen expansion, CFTR remains open through the action of PHLPP1, which stops activated AMPK from inhibiting ion transport through CFTR. In the absence of PHLPP1, the restraint on AMPK activity is lost and this tips the balance in the favour of channel closing, resulting in the lack of lumen expansion and accumulation of mucus.

• Nikolaidis, Konstantinos; Kristiansen, Stein; Plagemann, Thomas Peter; Goebel, Vera Hermine; Liestøl, Knut & Kankanhalli, Mohan [Vis alle 11 forfattere av denne artikkelen] (2022). My Health Sensor, My Classifier - Adapting a Trained Classifier to Unlabeled End-User Data. ACM Transactions on Computing for Healthcare (HEALTH). ISSN 2691-1957. 3(4), s. 1–24. doi: 10.1145/3559767. Fulltekst i vitenarkiv Vis sammendrag

  Sleep apnea is a common yet severely under-diagnosed sleep related disorder. Unattended sleep monitoring at home with low-cost sensors can be leveraged for condition detection, and Machine Learning offers a generalized solution for this task. However, patient characteristics, lack of sufficient training data, and other factors can imply a domain shift between training and end-user data; and reduced task performance. In this work, we address this issue with the aim to achieve personalization based on the patient’s needs. We present an unsupervised domain adaptation (UDA) solution with the constraint that labeled source data are not directly available. Instead, a classifier trained on the source data is provided. Our solution iteratively labels target data sub-regions based on classifier beliefs, and trains new classifiers from the expanding dataset. Experiments with sleep monitoring datasets and various sensors show that our solution outperforms the classifier trained on the source domain, with a kappa coefficient improvement from 0.012 to 0.242. Additionally, we apply our solution to digit classification DA between three well-established datasets, to investigate its generalizability, and allow for related work comparisons. Even without direct access to the source data, it outperforms several well-established UDA methods in these datasets.

• Kleppe, Andreas; Skrede, Ole-Johan; Raedt, Sepp De; Hveem, Tarjei Sveinsgjerd; Askautrud, Hanne Arenberg & Jacobsen, Jørn E. [Vis alle 14 forfattere av denne artikkelen] (2022). A clinical decision support system optimising adjuvant chemotherapy for colorectal cancers by integrating deep learning and pathological staging markers: a development and validation study. The Lancet Oncology. ISSN 1470-2045. 23(9), s. 1221–1232. doi: 10.1016/S1470-2045(22)00391-6. Fulltekst i vitenarkiv Vis sammendrag

  The DoMore-v1-CRC marker was recently developed using deep learning and conventional haematoxylin and eosin-stained tissue sections, and was observed to outperform established molecular and morphological markers of patient outcome after primary colorectal cancer resection. The aim of the present study was to develop a clinical decision support system based on DoMore-v1-CRC and pathological staging markers to facilitate individualised selection of adjuvant treatment. Methods We estimated cancer-specific survival in subgroups formed by pathological tumour stage (pT<4 or pT4), pathological nodal stage (pN0, pN1, or pN2), number of lymph nodes sampled (≤12 or >12) if not pN2, and DoMore-v1-CRC classification (good, uncertain, or poor prognosis) in 997 patients with stage II or III colorectal cancer considered to have no residual tumour (R0) from two community-based cohorts in Norway and the UK, and used these data to define three risk groups. An external cohort of 1075 patients with stage II or III R0 colorectal cancer from the QUASAR 2 trial was used for validation; these patients were treated with single-agent capecitabine. The proposed risk stratification system was evaluated using Cox regression analysis. We similarly evaluated a risk stratification system intended to reflect current guidelines and clinical practice. The primary outcome was cancer-specific survival. Findings The new risk stratification system provided a hazard ratio of 10·71 (95% CI 6·39–17·93; p<0·0001) for high-risk versus low-risk patients and 3·06 (1·73–5·42; p=0·0001) for intermediate versus low risk in the primary analysis of the validation cohort. Estimated 3-year cancer-specific survival was 97·2% (95% CI 95·1–98·4; n=445 [41%]) for the low-risk group, 94·8% (91·7–96·7; n=339 [32%]) for the intermediate-risk group, and 77·6% (72·1–82·1; n=291 [27%]) for the high-risk group. The guideline-based risk grouping was observed to be less prognostic and informative (the low-risk group comprised only 142 [13%] of the 1075 patients). Interpretation Integrating DoMore-v1-CRC and pathological staging markers provided a clinical decision support system that risk stratifies more accurately than its constituent elements, and identifies substantially more patients with stage II and III colorectal cancer with similarly good prognosis as the low-risk group in current guidelines. Avoiding adjuvant chemotherapy in these patients might be safe, and could reduce morbidity, mortality, and treatment costs.

• Isaksen, Kathrine Thuestad; Mastroianni, Maria Adele; Rinde, Marit; Rusten, Leiv Sindre; Barzenje, Dlawer Abdulla & Ramslien, Lloyd Frode [Vis alle 13 forfattere av denne artikkelen] (2021). A simplified frailty score predicts survival and can aid treatment-intensity decisions in older patients with DLBCL. Blood Advances. ISSN 2473-9529. 5(22), s. 4771–4782. doi: 10.1182/bloodadvances.2021004777. Fulltekst i vitenarkiv Vis sammendrag

  Diffuse large B-cell lymphoma (DLBCL) patients have a median age of 70 years. Yet, empirical knowledge on treatment for older patients is limited as they are frequently excluded from clinical trials. We aimed to construct a simplified frailty score and examine survival and treatment-related mortality (TRM) according to frailty status and treatment intensity in an older, real-world DLBCL population. All patients ≥70 years diagnosed with DLBCL 2006-2016 in south-eastern Norway (n=784) were included retrospectively, and divided into a training (n=522) and validation cohort (n=262). We constructed and validated a frailty score based on geriatric assessment variables, and examined survival and TRM according to frailty status and treatment. The frailty score identified three frailty groups with distinct survival and TRM, independent of established prognostic factors (2-year overall survival (OS) fit 82%, unfit 47%, frail 14%, P80%) was associated with better survival than attenuated R-CHOP (2-year OS 86% vs 70%, P=0.012), also in adjusted analysis. For unfit and frail patients, full-dose R-CHOP was not superior to attenuated R-CHOP, while an anthracycline-free regimen was associated with poorer survival in adjusted analyses. A simplified frailty score identified unfit and frail patients with higher risk of death and TRM, which can aid treatment intensity decisions in older DLBCL patients. In this study, fit patients benefit from full-dose R-CHOP, while unfit and frail patients have no benefit of full-dose R-CHOP over R-miniCHOP. An online calculator for assessment of the frailty score is available at https://wide.shinyapps.io/app-frailty/

• Bergland, Ola Undrum; Halvorsen, Lene Vernås; Søraas, Camilla Lund; Hjørnholm, Ulla; Kjær, Vibeke Norheim & Rognstad, Stine [Vis alle 22 forfattere av denne artikkelen] (2021). Detection of Nonadherence to Antihypertensive Treatment by Measurements of Serum Drug Concentrations. Hypertension. ISSN 0194-911X. 78(3), s. 617–628. doi: 10.1161/HYPERTENSIONAHA.121.17514. Fulltekst i vitenarkiv Vis sammendrag

  Nonadherence to drugs is a challenge in hypertension treatment. We aimed to assess the prevalence of nonadherence by serum drug concentrations compared with 2 indirect methods and relate to the prescribed drug regimens in a nationwide multicenter study. Five hundred fifty patients with hypertension using ≥2 antihypertensive agents participated. We measured concentrations of 23 antihypertensive drugs using ultra high performance liquid chromatography tandem mass-spectrometry and compared with patients’ self-reports and investigators’ assessment based on structured interview. We identified 40 nonadherent patients (7.3%) using serum drug concentrations. They had higher office diastolic blood pressure (90 versus 83 mm Hg, P<0.01) and daytime diastolic blood pressure (85 versus 80 mm Hg, P<0.01) though systolic blood pressures did not differ significantly. They had more prescribed daily antihypertensive pills (2.5 versus 2.1 pills, P<0.01) and total daily pills (5.5 versus 4.4 pills, P=0.03). Prescription of fixed-dose combination pills were lower among the nonadherent patients identified by serum concentrations (45.0 versus 67.1%, P<0.01). Fifty-three patients self-reported nonadherence, while the investigators suspected 69 nonadherent patients. These groups showed no or few differences in drug regimens, respectively. In summary, we detected 7.3% prevalence of nonadherence by serum drug measurements in patients using ≥2 antihypertensive agents in a nationwide study; they had higher office and ambulatory diastolic blood pressures, higher number of prescribed daily pills, more daily antihypertensive pills, and less frequent prescriptions of fixed-dose combination pills. Indirect methods showed poor overlap with serum drugs concentrations and no or minimal medication differences. Thus, serum measurements of drugs were useful in detection and characterization of nonadherence to antihypertensive treatment.

• Jørgensen, Magne; Bergersen, Gunnar R. & Liestøl, Knut (2021). Relations between Effort Estimates, Skill Indicators, and Measured Programming Skill. IEEE Transactions on Software Engineering. ISSN 0098-5589. 47(12), s. 2892–2906. doi: 10.1109/TSE.2020.2973638. Fulltekst i vitenarkiv
• Mariampillai, Julian Eek; Prestgaard, Erik Edvard; Kjeldsen, Sverre; Liestøl, Knut; Grundvold, Irene & Bodegard, Johan [Vis alle 9 forfattere av denne artikkelen] (2021). Novel insights into stroke risk beyond resting and maximal bicycle exercise systolic blood pressure. Journal of Hypertension. ISSN 0263-6352. 39(10), s. 2022–2029. doi: 10.1097/HJH.0000000000002894. Fulltekst i vitenarkiv
• Kleppe, Andreas; Skrede, Ole-Johan; Raedt, Sepp De; Liestøl, Knut; Kerr, David J. & Danielsen, Håvard Emil (2021). Designing deep learning studies in cancer diagnostics. Nature Reviews Cancer. ISSN 1474-175X. 21(3), s. 199–211. doi: 10.1038/s41568-020-00327-9. Fulltekst i vitenarkiv Vis sammendrag

  The number of publications on deep learning for cancer diagnostics is rapidly increasing, and systems are frequently claimed to perform comparable with or better than clinicians. However, few systems have yet demonstrated real-world medical utility. In this Perspective, we discuss reasons for the moderate progress and describe remedies designed to facilitate transition to the clinic. Recent, presumably influential, deep learning studies in cancer diagnostics, of which the vast majority used images as input to the system, are evaluated to reveal the status of the field. By manipulating real data, we then exemplify that much and varied training data facilitate the generalizability of neural networks and thus the ability to use them clinically. To reduce the risk of biased performance estimation of deep learning systems, we advocate evaluation in external cohorts and strongly advise that the planned analyses, including a predefined primary analysis, are described in a protocol preferentially stored in an online repository. Recommended protocol items should be established for the field, and we present our suggestions.

• Falk, Ragnhild Sørum; Mariampillai, Julian Eek; Prestgaard, Erik Edvard; Heir, Trond; Bodegard, Johan & Robsahm, Trude Eid [Vis alle 18 forfattere av denne artikkelen] (2021). The Oslo Ischaemia Study: cohort profile. BMJ Open. 11(10). doi: 10.1136/bmjopen-2021-049111. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Purpose The Oslo Ischaemia Study was designed to investigate the prevalence and predictors of silent coronary disease in Norwegian middle-aged men, specifically validating exercise electrocardiography (ECG) findings compared with angiography. The study has been important in investigating long-term predictors of cardiovascular morbidity and mortality, as well as investigating a broad spectrum of epidemiological and public health perspectives. Participants In 1972–1975, 2014 healthy men, 40–59 years old, were enrolled in the study. Comprehensive clinical examination included an ECG-monitored exercise test at baseline and follow-ups. The cohort has been re-examined four times during 20 years. Linkage to health records and national health registries has ensured complete endpoint registration of morbidity until the end of 2006, and cancer and mortality until the end of 2017. Findings to date The early study results provided new evidence, as many participants with a positive exercise ECG, but no chest pain (‘silent ischaemia’), did not have significant coronary artery stenosis after all. Still, they were over-represented with coronary disease after years of follow-up. Furthermore, participants with the highest physical fitness had lower risk of cardiovascular disease, and the magnitude of blood pressure responses to moderate exercise was shown to influence the risk of cardiovascular disease and mortality. With time, follow-up data allowed the scope of research to expand into other fields of medicine, with the aim of investigating predictors and the importance of lifestyle and risk factors. Future plans Recently, the Oslo Ischaemia Study has been found worthy, as the first scientific study, to be preserved by The National Archives of Norway. All the study material will be digitised, free to use and accessible for all. In 2030, the Oslo Ischaemia Study will be linked to the Norwegian Cause of Death Registry to obtain complete follow-up to death. Thus, a broad spectrum of additional opportunities opens.

• Holter, Øystein Gullvåg; Snickare, Lotta Karin & Liestøl, Knut (2021). Bøygen-modellen: Hypotesen om akkumulering av ulempe. I Holter, Øystein Gullvåg & Snickare, Lotta Karin (Red.), Likestilling i akademia - fra kunnskap til endring. Cappelen Damm Akademisk. ISSN 9788202669669. s. 193–212. doi: 10.23865/noasp.143.ch7. Fulltekst i vitenarkiv
• Holter, Øystein Gullvåg; Snickare, Lotta Karin & Liestøl, Knut (2021). Erfaringer i akademia – en ny kartlegging. I Holter, Øystein Gullvåg & Snickare, Lotta Karin (Red.), Likestilling i akademia - fra kunnskap til endring. Cappelen Damm Akademisk. ISSN 9788202669669. s. 119–152. doi: 10.23865/noasp.143.ch5. Fulltekst i vitenarkiv
• Snickare, Lotta Karin; Holter, Øystein Gullvåg & Liestøl, Knut (2021). Menn, maskuliniteter og faghierarkier. I Holter, Øystein Gullvåg & Snickare, Lotta Karin (Red.), Likestilling i akademia - fra kunnskap til endring. Cappelen Damm Akademisk. ISSN 9788202669669. s. 49–73. doi: 10.23865/noasp.143.ch2. Fulltekst i vitenarkiv
• Nikolaidis, Konstantinos; Kristiansen, Stein; Plagemann, Thomas Peter; Goebel, Vera Hermine; Liestøl, Knut & Kankanhalli, Mohan [Vis alle 11 forfattere av denne artikkelen] (2021). Learning realistic patterns from visually unrealistic stimuli: Generalization and data anonymization. The journal of artificial intelligence research. ISSN 1076-9757. 72, s. 1163–1214. doi: 10.1613/JAIR.1.13252. Fulltekst i vitenarkiv Vis sammendrag

  Good training data is a prerequisite to develop useful Machine Learning applications. However, in many domains existing data sets cannot be shared due to privacy regulations (e.g., from medical studies). This work investigates a simple yet unconventional approach for anonymized data synthesis to enable third parties to benefit from such anonymized data. We explore the feasibility of learning implicitly from visually unrealistic, task-relevant stimuli, which are synthesized by exciting the neurons of a trained deep neural network. As such, neuronal excitation can be used to generate synthetic stimuli. The stimuli data is used to train new classification models. Furthermore, we extend this framework to inhibit representations that are associated with specific individuals. We use sleep monitoring data from both an open and a large closed clinical study, and Electroencephalogram sleep stage classification data, to evaluate whether (1) end-users can create and successfully use customized classification models, and (2) the identity of participants in the study is protected. Extensive comparative empirical investigation shows that different algorithms trained on the stimuli are able to generalize successfully on the same task as the original model. Architectural and algorithmic similarity between new and original models play an important role in performance. For similar architectures, the performance is close to that of using the original data (e.g., Accuracy difference of 0.56%-3.82%, Kappa coefficient difference of 0.02-0.08). Further experiments show that the stimuli can provide state-ofthe-art resilience against adversarial association and membership inference attacks.

• Jørgensen, Magne; Bergersen, Gunnar & Liestøl, Knut (2020). Relations Between Effort Estimates, Skill Indicators, and Measured Programming Skill. IEEE Transactions on Software Engineering. ISSN 0098-5589. Fulltekst i vitenarkiv Vis sammendrag

  There are large skill differences among software developers, and clients and managers will benefit from being able to identify those with better skill. This study examines the relations between low effort estimates, and other commonly used skill indicators, and measured programming skill. One hundred and four professional software developers were recruited. After skill-related information was collected, they were asked to estimate the effort for four larger and five smaller programming tasks. Finally, they completed a programming skill test. The lowest and most over-optimistic effort estimates for the larger tasks were given by those with the lowest programming skill, which is in accordance with the well-known Dunning-Kruger effect. For the smaller tasks, however, those with the lowest programming skill had the highest and most over-pessimistic estimates. The other programming skill indicators, such as length of experience, company assessed skill and self-assessed skill, were only moderately correlated with measured skill and not particularly useful in guiding developer skill identification. A practical implication is that for larger and more complex tasks, the use of low effort estimates and commonly used skill indicators as selection criteria leads to a substantial risk of selecting among the least skilled developers.

• Mehlum, Maria Hollund; Liestøl, Knut; Kjeldsen, Sverre; Wyller, Torgeir Bruun; Julius, Stevo & Rothwell, Peter M. [Vis alle 10 forfattere av denne artikkelen] (2020). Blood pressure-lowering profiles and clinical effects of angiotensin receptor blockers versus calcium channel blockers. Hypertension. ISSN 0194-911X. 75(6), s. 1584–1592. doi: 10.1161/HYPERTENSIONAHA.119.14443. Fulltekst i vitenarkiv
• Mirza, Yusuf Ahmed; Prestgaard, Erik Edvard; Selmer, Randi Marie; Liestøl, Knut; Grundvold, Irene & Erikssen, Jan Emil [Vis alle 8 forfattere av denne artikkelen] (2020). Tiårsprediksjon av hjerte-og karsykdom hos friske norske menn basert på NORRISK-2. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 140(12), s. 1–10. doi: 10.4045/tidsskr.20.0089. Fulltekst i vitenarkiv Vis sammendrag

  BAKGRUNN Norske retningslinjer for primærforebygging av hjerte- og karsykdom anbefaler bruk av risikoskårmodellen NORRISK-2, med noen tillegg. Vi ønsket å undersøke om NORRISK-2 kunne predikere hjerte- og karsykdom hos friske norske menn som deltok i kohortstudien Oslo Ischemia Study. MATERIALE NORRISK-2-skår ble beregnet for 2 014 menn i aldersgruppen 40–60 år som i 1972–75 ble inkludert i Oslo Ischemia Study. Cox-regresjonsanalyser ble benyttet for å kalkulere hasardratio for død og hjerte- og karsykdom innen ti år etter førstegangsundersøkelsen. RESULTATER Ingen gikk tapt fra oppfølgingen. Av de 2 014 mennene døde 125 i første tiår etter inklusjon, hvorav 61 av kardiovaskulær sykdom. De som døde, var eldre enn de overlevende, med større andel dagligrøykere, og de hadde høyere systolisk blodtrykk og hvilepuls, økt totalkolesterol og lavere fysisk yteevne. Majoriteten av de som døde av akutt hjerteinfarkt og hjerneslag innen ti år, ble i NORRISK-2 klassifisert i høyrisikogruppen. FORTOLKNING NORRISK-2 identifiserte høyrisikopersonene godt i denne kohorten av friske, middelaldrende norske menn. Det støtter bruk av de norske retningslinjene i beslutningen om eventuell primærforebygging av hjerte- og karsykdom.

• Skrede, Ole-Johan; Raedt, Sepp De; Kleppe, Andreas; Hveem, Tarjei Sveinsgjerd; Liestøl, Knut & Maddison, John [Vis alle 20 forfattere av denne artikkelen] (2020). Deep learning for prediction of colorectal cancer outcome: a discovery and validation study. The Lancet. ISSN 0140-6736. 395:10221, s. 350–360. doi: 10.1016/S0140-6736(19)32998-8. Fulltekst i vitenarkiv Vis sammendrag

  Background Improved markers of prognosis are needed to stratify patients with early-stage colorectal cancer to refine selection of adjuvant therapy. The aim of the present study was to develop a biomarker of patient outcome after primary colorectal cancer resection by directly analysing scanned conventional haematoxylin and eosin stained sections using deep learning. Methods More than 12 000 000 image tiles from patients with a distinctly good or poor disease outcome from four cohorts were used to train a total of ten convolutional neural networks, purpose-built for classifying supersized heterogeneous images. A prognostic biomarker integrating the ten networks was determined using patients with a non-distinct outcome. The marker was tested on 920 patients with slides prepared in the UK, and then independently validated according to a predefined protocol in 1122 patients treated with single-agent capecitabine using slides prepared in Norway. All cohorts included only patients with resectable tumours, and a formalin-fixed, paraffin-embedded tumour tissue block available for analysis. The primary outcome was cancer-specific survival. Findings 828 patients from four cohorts had a distinct outcome and were used as a training cohort to obtain clear ground truth. 1645 patients had a non-distinct outcome and were used for tuning. The biomarker provided a hazard ratio for poor versus good prognosis of 3·84 (95% CI 2·72–5·43; p<0·0001) in the primary analysis of the validation cohort, and 3·04 (2·07–4·47; p<0·0001) after adjusting for established prognostic markers significant in univariable analyses of the same cohort, which were pN stage, pT stage, lymphatic invasion, and venous vascular invasion. Interpretation A clinically useful prognostic marker was developed using deep learning allied to digital scanning of conventional haematoxylin and eosin stained tumour tissue sections. The assay has been extensively evaluated in large, independent patient populations, correlates with and outperforms established molecular and morphological prognostic markers, and gives consistent results across tumour and nodal stage. The biomarker stratified stage II and III patients into sufficiently distinct prognostic groups that potentially could be used to guide selection of adjuvant treatment by avoiding therapy in very low risk groups and identifying patients who would benefit from more intensive treatment regimes.

• Nikolaidis, Konstantinos; Kristiansen, Stein; Goebel, Vera Hermine; Plagemann, Thomas Peter; Liestøl, Knut & Kankanhalli, Mohan (2020). Augmenting Physiological Time Series Data: A Case Study for Sleep Apnea Detection. I Koprinska, Irena (Red.), Workshops of the European Conference on Machine Learning and Knowledge Discovery in Databases (ECML PKDD 2020): SoGood 2020, PDFL 2020, MLCS 2020, NFMCP 2020, DINA 2020, EDML 2020, XKDD 2020 and INRA 2020). Springer. ISSN 9783030659646. doi: 10.1007/978-3-030-46133-1_23. Fulltekst i vitenarkiv
• Pladsen, Arne Valebjørg; Nilsen, Gro; Rueda, Oscar M.; Aure, Miriam Ragle; Borgan, Ørnulf & Liestøl, Knut [Vis alle 18 forfattere av denne artikkelen] (2020). DNA copy number motifs are strong and independent predictors of survival in breast cancer. Communications Biology. 3. doi: 10.1038/s42003-020-0884-6. Fulltekst i vitenarkiv Vis sammendrag

  Somatic copy number alterations are a frequent sign of genome instability in cancer. A precise characterization of the genome architecture would reveal underlying instability mechanisms and provide an instrument for outcome prediction and treatment guidance. Here we show that the local spatial behavior of copy number profiles conveys important information about this architecture. Six filters were defined to characterize regional traits in copy number profiles, and the resulting Copy Aberration Regional Mapping Analysis (CARMA) algorithm was applied to tumors in four breast cancer cohorts (n = 2919). The derived motifs represent a layer of information that complements established molecular classifications of breast cancer. A score reflecting presence or absence of motifs provided a highly significant independent prognostic predictor. Results were consistent between cohorts. The nonsite-specific occurrence of the detected patterns suggests that CARMA captures underlying replication and repair defects and could have a future potential in treatment stratification.

• Prestgaard, Erik Edvard; Mariampillai, Julian Eek; Engeseth, Kristian; Erikssen, Jan Emil; Bodegard, Johan & Liestøl, Knut [Vis alle 9 forfattere av denne artikkelen] (2020). Change in body weight and long-term risk of stroke and death in healthy men. Stroke. ISSN 0039-2499. 51(5), s. 1435–1441. doi: 10.1161/STROKEAHA.119.027233. Fulltekst i vitenarkiv
• Leppä, Sirpa; Jørgensen, Judit; Tierens, Anne; Meriranta, Leo; Østlie, Ingunn & Brown, Peter de Nully [Vis alle 23 forfattere av denne artikkelen] (2020). Patients with high-risk DLBCL benefit from dose-dense immunochemotherapy combined with early systemic CNS prophylaxis. Blood Advances. ISSN 2473-9529. 4(9), s. 1906–1915. doi: 10.1182/bloodadvances.2020001518. Fulltekst i vitenarkiv Vis sammendrag

  Survival of patients with high-risk diffuse large B-cell lymphoma (DLBCL) is suboptimal, and the risk of central nervous system (CNS) progression is relatively high. We conducted a phase 2 trial in 139 patients aged 18 to 64 years who had primary DLBCL with an age-adjusted International Prognostic Index (aaIPI) score of 2 to 3 or site-specific risk factors for CNS recurrence. The goal was to assess whether a dose-dense immunochemotherapy with early systemic CNS prophylaxis improves the outcome and reduces the incidence of CNS events. Treatment consisted of 2 courses of high-dose methotrexate in combination with biweekly rituximab (R), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP-14), followed by 4 courses of R-CHOP-14 with etoposide (R-CHOEP) and 1 course of high-dose cytarabine with R. In addition, liposomal cytarabine was administered intrathecally at courses 1, 3, and 5. Coprimary endpoints were failure-free survival and CNS progression rates. Thirty-six (26%) patients experienced treatment failure. Progression occurred in 23 (16%) patients, including three (2.2%) CNS events. At 5 years of median follow-up, failure-free survival, overall survival, and CNS progression rates were 74%, 83%, and 2.3%, respectively. Treatment reduced the risk of progression compared with our previous trial, in which systemic CNS prophylaxis was given after 6 courses of biweekly R-CHOEP (hazard ratio, 0.49; 95% CI, 0.31-0.77; P = .002) and overcame the adverse impact of an aaIPI score of 3 on survival. In addition, outcome of the patients with BCL2/MYC double-hit lymphomas was comparable to the patients without the rearrangements. The results are encouraging, with a low toxic death rate, low number of CNS events, and favorable survival rates. This trial was registered at www.clinicaltrials.gov as #NCT01325194.

• Steen, Chloe Beate; Leich, Ellen; Myklebust, June Helen; Lockmer, Sandra; Wise, Jillian & Wahlin, Björn Engelbrekt [Vis alle 14 forfattere av denne artikkelen] (2019). A clinico-molecular predictor identifies follicular lymphoma patients at risk of early transformation after first-line immunotherapy. Haematologica. ISSN 0390-6078. 104(10), s. 460–464. doi: 10.3324/haematol.2018.209080. Fulltekst i vitenarkiv
• Mehlum, Maria Hollund; Liestøl, Knut; Wyller, Torgeir Bruun; Hua, Tsushung A.; Rostrup, Morten & Berge, Eivind (2019). Blood pressure variability in hypertensive patients with atrial fibrillation in the VALUE trial. Blood Pressure. ISSN 0803-7051. 28(2), s. 77–83. doi: 10.1080/08037051.2018.1524707. Fulltekst i vitenarkiv
• Ersvær, Elin; Kildal, Wanja; Vlatkovic, Ljiljana; Cyll, Karolina Urszula; Pradhan, Manohar & Kleppe, Andreas [Vis alle 12 forfattere av denne artikkelen] (2019). Prognostic value of mitotic checkpoint protein BUB3, cyclin B1, and pituitary tumor-transforming 1 expression in prostate cancer. Modern Pathology. ISSN 0893-3952. s. 1–11. doi: 10.1038/s41379-019-0418-2. Fulltekst i vitenarkiv
• Mariampillai, Julian Eek; Liestøl, Knut; Kjeldsen, Sverre; Prestgaard, Erik Edvard; Engeseth, Kristian & Bodegard, Johan [Vis alle 11 forfattere av denne artikkelen] (2019). Exercise Systolic Blood Pressure at Moderate Workload Is Linearly Associated With Coronary Disease Risk in Healthy Men. Hypertension Research. ISSN 0916-9636. 75(1), s. 44–50. doi: 10.1161/HYPERTENSIONAHA.119.13528. Fulltekst i vitenarkiv Vis sammendrag

  There is no consensus on the definition of an exaggerated increase in systolic blood pressure (SBP) during exercise. The aim was to explore a potential threshold for exercise SBP associated with increased risk of coronary heart disease in healthy men using repeated exercise testing. Two thousand fourteen healthy white male employees were recruited into the Oslo Ischemia Study during early 1970s. At follow-up 7 years later, 1392 men were still considered healthy. A bicycle exercise test at 100 W workload was performed at both visits. Cox regression analyses were performed with increasing cutoff levels of peak exercise SBP at 100 W workload (SBP100W) from 160 mm Hg to 200 mm Hg, adjusted for cardiovascular risk factors and physical fitness. Participants with SBP100W below cutoff level at both baseline and first follow-up were compared with participants with SBP100W equal to or above cutoff level at both visits. Compared with participants with SBP100W below all cutoff levels between 165 and 195 mm Hg, coronary heart disease risk was increased among participants with SBP100W equal to or above cutoff at all levels. There was no evidence of a distinct threshold level for coronary heart disease risk, and the relation between SBP100W and coronary heart disease appears linear. When investigating exercise SBP at moderate workload measured at 2 exercise tests in healthy middle-aged white men, there is increasing risk of coronary heart disease with increasing exercise SBP independent of SBP at rest. The association is linear from the low range of exercise SBP, and there is no sign of a distinct threshold level for increased coronary disease risk.

• Mariampillai, Julian Eek; Prestgaard, Erik Edvard; Kjeldsen, Sverre; Liestøl, Knut; Engeseth, Kristian & Erikssen, Jan Emil [Vis alle 10 forfattere av denne artikkelen] (2019). SBP above 180 mmHg at moderate exercise workload increases coronary heart disease risk in healthy men during 28-year follow-up. Journal of Hypertension. ISSN 0263-6352. 37(5), s. 949–955. doi: 10.1097/HJH.0000000000001959. Fulltekst i vitenarkiv
• Lie-Jensen, Anette; Ivanauskiene, Kristina; Malerød, Lene; Jain, Ashish; Tan, Kia Wee & Lærdahl, Jon Kristen [Vis alle 9 forfattere av denne artikkelen] (2019). Centralspindlin Recruits ALIX to the Midbody during Cytokinetic Abscission in Drosophila via a Mechanism Analogous to Virus Budding. Current Biology. ISSN 0960-9822. 29(20), s. 3538–3548.e7. doi: 10.1016/j.cub.2019.09.025. Fulltekst i vitenarkiv
• Engeseth, Kristian; Prestgaard, Erik Edvard; Mariampillai, Julian Eek; Grundvold, Irene; Liestøl, Knut & Kjeldsen, Sverre [Vis alle 10 forfattere av denne artikkelen] (2018). Physical fitness is a modifiable predictor of early cardiovascular death: A 35-year follow-up study of 2014 healthy middle-aged men. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 25(15), s. 1655–1663. doi: 10.1177/2047487318793459. Fulltekst i vitenarkiv
• Mehlum, Maria Hollund; Liestøl, Knut; Kjeldsen, Sverre; Julius, Stevo; Hua, Tsushung A. & Rothwell, Peter M. [Vis alle 10 forfattere av denne artikkelen] (2018). Blood pressure variability and risk of cardiovascular events and death in patients with hypertension and different baseline risks. European Heart Journal. ISSN 0195-668X. 39(24), s. 2243–2251. doi: 10.1093/eurheartj/ehx760. Fulltekst i vitenarkiv
• Prestgaard, Erik Edvard; Mariampillai, Julian Eek; Engeseth, Kristian; Erikssen, Jan Emil; Bodegard, Johan & Liestøl, Knut [Vis alle 10 forfattere av denne artikkelen] (2018). Change in Cardiorespiratory Fitness and Risk of Stroke and Death. Stroke. ISSN 0039-2499. 50, s. 155–161. doi: 10.1161/STROKEAHA.118.021798. Fulltekst i vitenarkiv
• Westvik, Asbjørn; Weedon-Fekjær, Harald; Mæhlen, Jan & Liestøl, Knut (2018). Evaluating different breast tumor progression models using screening data. BMC Cancer. 18(1). doi: 10.1186/s12885-018-4130-2. Fulltekst i vitenarkiv Vis sammendrag

  Background Mammography screening is used to detect breast cancer at an early treatable stage, reducing breast cancer mortality. Traditionally, breast cancer has been seen as a disease with only progressive lesions, and here we examine the validity of this assumption by testing if incidence levels after introducing mammography screening can be reproduced assuming only progressive tumors. Methods Breast cancer incidence data 1990–2009 obtained from the initially screened Norwegian counties (Akershus, Oslo, Rogaland and Hordaland) was included, covering the time-period before, during and after the introduction of mammography screening. From 1996 women aged 50–69 were invited for biennial public screening. Using estimates of tumor growth and screening sensitivity based on pre-screening and prevalence screening data (1990–1998), we simulated incidence levels during the following period (1999–2009). Results The simulated incidence levels during the period with repeated screenings were markedly below the observed levels. The results were robust to changes in model parameters. Adjusting for hormone replacement therapy use, we obtained levels closer to the observed levels. However, there was still a marked gap, and only by assuming some tumors that undergo regressive changes or enter a markedly less detectable state, was our model able to reproduce the observed incidence levels. Conclusions Models with strictly progressive tumors are only able to partly explain the changes in incidence levels observed after screening introduction in the initially screened Norwegian counties. More complex explanations than a time shift in detection of future clinical cancers seem to be needed to reproduce the incidence trends, questioning the basis for many over-diagnosis calculations. As data are not randomized, similar studies in other populations are wanted to exclude effect of unknown confounders.

• Kristiansen, Stein; Hugaas, Mari Sønsteby; Goebel, Vera Hermine; Plagemann, Thomas Peter; Nikolaidis, Konstantinos & Liestøl, Knut (2018). Data Mining for Patient Friendly Apnea Detection. IEEE Access. 6, s. 74598–74615. doi: 10.1109/ACCESS.2018.2882270. Fulltekst i vitenarkiv Vis sammendrag

  Obstructive sleep apnea (OSA) is a common but severely under-diagnosed sleep disorder that affects the natural breathing cycle during sleep with the periods of reduced respiration or no airflow at all. It is our long-term goal to increase the percentage of diagnosed OSA cases and reduce the time to diagnosis with user friendly and cost-efficient tools for sleep analysis at home. As a first step towards this goal, we study in this paper whether a small subset of those physiological signals that are used in classical OSA diagnosis in combination with automatic classification allows to detect apnea events. We study the performance of five data mining techniques to classify the epochs of data from the Apnea-ECG and MIT-BIH databases from PhysioNet as either disrupted or normal breathing. The data are only slightly preprocessed (rate reduction and normalization). We focus in this paper on respiratory signals from the nose, abdomen, chest, and oxygen saturation. We measure for any combination of these signals the accuracy, sensitivity, specificity, and the Kappa statistics of classification with artificial neural network, support vector machine, decision tree, K-nearest neighbor (KNN), and random forest. For Apnea-ECG, we achieve an accuracy of 96.6% with a combination of respiration data from the chest and nose as input data and an accuracy of more than 90% for all signal combinations. Interestingly, these good results are also achieved with the simple KNN technique. The results for MIT-BIH are lower, because of noise, smaller size, and some class imbalance. The accuracy does not significantly improves with the number of signals included in the signal combinations. We conclude that one signal might be sufficient to detect disrupted breathing, if the data set is of sufficient quality and size, and that respiration from the abdomen is the preferable choice when considering both classification performance and patient comfort.

• Malerød, Lene; Borgne, Roland Le; Lie-Jensen, Anette Christensen; Eikenes, Åsmund Husabø; Brech, Andreas & Liestøl, Knut [Vis alle 8 forfattere av denne artikkelen] (2018). Centrosomal ALIX regulates mitotic spindle orientation by modulating astral microtubule dynamics. EMBO Journal. ISSN 0261-4189. 37(13), s. 1–21. doi: 10.15252/embj.201797741. Fulltekst i vitenarkiv
• Erikssen, Gunnar; Aboulhosn, Jamil; Lin, Jeannette; Liestøl, Knut; Estensen, Mette-Elise & Gjesdal, Ola [Vis alle 9 forfattere av denne artikkelen] (2018). Survival in patients with univentricular hearts: The impact of right versus left ventricular morphology. Open heart. 5:e000902(2), s. 1–9. doi: 10.1136/openhrt-2018-000902. Fulltekst i vitenarkiv Vis sammendrag

  Objective: Patients with univentricular hearts (UVH) have high mortality despite modern treatment, and better methods to identify patients at highest risk are needed. We wanted to improve risk stratification in patients with UVH by focusing on the prognostic significance of single right versus single left ventricular morphology (SRV vs SLV). Methods: All 395 patients with UVH operated at our centre were prospectively included from 1972 to 2016 (195 SRV, 166 SLV, 34 mixed or indeterminate ventricular morphology). Diagnoses, UVH morphology, types of all operations and time and causes of death or heart transplantation (HTX) were recorded. The primary endpoint was death or HTX. Results: Among the 111 non-Fontan patients, 88 died (SRV 62 vs SLV 20; p<0.0001), 32 due to heart failure (SRV 23 vs SLV 5; p=0.0012). Twenty-five  years of cumulative SRV versus SLV survival among the 284 Fontan patients (41 deaths/HTX) was 66.9% vs 87.9% (p=0.0027), partly explained by more deaths/HTX due to heart failure among patients with SRV (p=0.0006). Survival in patients with SRV with and without hypoplastic left heart syndrome (HLHS) was similar. SRV versus SLV was a strong predictor of death/HTX in multivariable proportional hazards analyses (RR 3.3, 95% CI 1.6 to 6.6). Conclusion: SRV versus SLV is a strong short-term and long-term predictor of survival among patients with UVH, mainly explained by higher rates of death/HTX due to heart failure in the SRV group. Our findings apply to patients with SRV both with and without HLHS.

• Mariampillai, Julian Eek; Engeseth, Kristian; Kjeldsen, Sverre Erik; Grundvold, Irene; Liestøl, Knut & Erikssen, Gunnar [Vis alle 9 forfattere av denne artikkelen] (2017). Exercise systolic blood pressure at moderate workload predicts cardiovascular disease and mortality through 35 years of follow-up in healthy, middle-aged men. Blood Pressure. ISSN 0803-7051. 26(4), s. 229–236. doi: 10.1080/08037051.2017.1291276. Fulltekst i vitenarkiv
• Prestgaard, Erik Edvard; Hodnesdal, Christian; Engeseth, Kristian; Erikssen, Jan Emil; Bodegard, Johan & Liestøl, Knut [Vis alle 10 forfattere av denne artikkelen] (2017). Long-term predictors of stroke in healthy middle-aged men. International Journal of Stroke. ISSN 1747-4930. 13(3), s. 292–300. doi: 10.1177/1747493017730760. Fulltekst i vitenarkiv
• Larssen, Marte Strømsnes; Steine, Kjetil; Hilde, Janne Mykland; Skjørten, Ingunn; Hodnesdal, Christian & Liestøl, Knut [Vis alle 7 forfattere av denne artikkelen] (2017). Mechanisms of ECG signs in chronic obstructive pulmonary disease. Open heart. 4(1). doi: 10.1136/openhrt-2016-000552. Fulltekst i vitenarkiv Vis sammendrag

  Objective: Patients with chronic obstructive pulmonary disease (COPD) often have abnormal ECGs. Our aim was to separate the effects on ECG by airway obstruction, emphysema and right ventricular (RV) afterload in patients with COPD. Methods: A cross-sectional study was performed on 101 patients with COPD without left heart disease and 32 healthy age-matched controls. Body mass index (BMI) was measured, and pulmonary function tests, ECG, echocardiography and right heart catheterisation (only patients) were performed. Variables were grouped into (1) airway obstruction by FEV% (percentage of forced expiratory volume)_predicted, (2) emphysema by residual volume/total lung capacity and residual volume (percent of predicted) and (3) RV afterload by mean pulmonary pressure, artery compliance, vascular resistance and RV wall thickness. Results: In multivariate regression analysis, emphysema correlated negatively to R+S amplitudes in horizontal and frontal leads, RV/left ventricle (LV) end-diastolic volume ratio to horizontal amplitudes and BMI negatively to frontal amplitudes. Increased airway obstruction, RV afterload and BMI correlated with horizontal QRS-axis clockwise rotation. Airway obstruction, RV afterload, RV/LV end-diastolic volume ratio and BMI correlated to the Sokolow-Lyon Index for RV, and RV afterload negatively to Sokolow-LyonIndex for LV. Several classical ECG changes could, however, not be ascribed to specific mechanisms. Conclusions: In COPD, the various pathophysiological mechanisms modify the ECG differently. Increased airway obstruction and RV afterload mainly increase the Sokolow-Lyon Index for RV mass and associate with clockwise rotation of the horizontal QRS-axis, whereas emphysema reduces the QRS amplitudes. BMI is an equally important determinant for the majority of the ECG changes.

• Myklebust, June; Brody, Joshua; Kohrt, Holbrook E.; Kolstad, Arne; Czerwinski, Debra K & Waelchli, Sebastien [Vis alle 15 forfattere av denne artikkelen] (2017). Distinct patterns of B-cell receptor signaling in non-Hodgkin lymphomas identified by single-cell profiling. Blood. ISSN 0006-4971. 129(6), s. 759–770. doi: 10.1182/blood-2016-05-718494. Fulltekst i vitenarkiv
• Jørgensen, Silje; Søraas, Arne Vasli; Sundsfjord, Arnfinn; Liestøl, Knut; Leegaard, Truls Michael & Jenum, Pål (2017). Fecal carriage of extended spectrum β-lactamase producing Escherichia coli and Klebsiella pneumoniae after urinary tract infection - A three year prospective cohort study. PLOS ONE. 12:e017w|(16), s. 13510–1. doi: 10.1371/journal.pone.0173510. Fulltekst i vitenarkiv Vis sammendrag

  We have performed a prospective cohort study to investigate the duration of and risk factors for prolonged fecal carriage of ESBL-producing Escherichia coli or Klebsiella pneumoniae in patients with community acquired urinary tract infection caused by these bacteria. From 2009 to 2011, 101 Norwegian patients were recruited. Stool swabs and questionnaires were collected every three months for one year and at the end of the study in 2012. Information on antibiotic prescriptions was collected from the Norwegian Prescription Database. Stool samples were cultured directly on ChromID ESBL agar as well as in an enrichment broth, and culture positive isolates were examined by blaCTX-M multiplex PCR. Isolates without blaCTX-M were investigated for alternative ESBL-determinants with a commercial microarray system. Time to fecal clearance of ESBL producing Enterobacteriaceae was also analysed using Kaplan-Meier estimates. Uni- and multivariate logistic regression was used to compare groups according to previously described risk factors. The ESBL point prevalence of fecal carriage were 61% at 4 months, 56% at 7 months, 48% at 10 months, 39% at 13 months, 19% after two years, and 15% after three years or more. We found no correlation between duration of carriage, comorbidity, antibiotic use or travel to ESBL high-prevalence countries. Prolonged carriage was associated with E. coli isolates of phylogroup B2 or D. Importantly, comparative MLST and MLVA analyses of individual paired urine and fecal E. coli isolates revealed that ESBL production commonly occurred in diverse strains within the same host. When investigating cross-transmission of ESBL producing bacteria in health care institutions, this notion should be taken into account.

• Barzenje, Dlawer Abdulla; Holte, Harald; Fosså, Alexander; Ghanima, Waleed Khalid; Liestøl, Knut & Delabie, Jan [Vis alle 7 forfattere av denne artikkelen] (2017). Long-term outcome for patients with early stage marginal zone lymphoma and mantle cell lymphoma. Leukemia and Lymphoma. ISSN 1042-8194. 58(3), s. 623–632. doi: 10.1080/10428194.2016.1204653. Fulltekst i vitenarkiv
• Christ, Liliane Florence; Wenzel, Eva; Liestøl, Knut; Raiborg, Camilla; Campsteijn, Coen & Stenmark, Harald Alfred (2016). ALIX and ESCRT-I/II function as parallel ESCRT-III recruiters in cytokinetic abscission. Journal of Cell Biology. ISSN 0021-9525. 212(5), s. 499–513. doi: 10.1083/jcb.201507009. Fulltekst i vitenarkiv
• Engeseth, Kristian; Hodnesdal, Christian; Grundvold, Irene; Liestøl, Knut; Gjesdal, Knut & Erikssen, Gunnar [Vis alle 10 forfattere av denne artikkelen] (2016). Heart rate reserve predicts cardiovascular death among physically unfit but otherwise healthy middle-aged men: a 35-year follow-up study. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 23(1), s. 59–66. doi: 10.1177/2047487314553202. Fulltekst i vitenarkiv
• Holland, Petter; Knævelsrud, Helene; Søreng, Kristiane; Mathai, Benan John; Lystad, Alf Håkon & Pankiv, Serhiy [Vis alle 16 forfattere av denne artikkelen] (2016). HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels. Nature Communications. 7. doi: 10.1038/ncomms13889. Fulltekst i vitenarkiv Vis sammendrag

  A fundamental question is how autophagosome formation is regulated. Here we show that the PX domain protein HS1BP3 is a negative regulator of autophagosome formation. HS1BP3 depletion increased the formation of LC3-positive autophagosomes and degradation of cargo both in human cell culture and in zebrafish. HS1BP3 is localized to ATG16L1- and ATG9-positive autophagosome precursors and we show that HS1BP3 binds phosphatidic acid (PA) through its PX domain. Furthermore, we find the total PA content of cells to be significantly upregulated in the absence of HS1BP3, as a result of increased activity of the PA-producing enzyme phospholipase D (PLD) and increased localization of PLD1 to ATG16L1-positive membranes. We propose that HS1BP3 regulates autophagy by modulating the PA content of the ATG16L1-positive autophagosome precursor membranes through PLD1 activity and localization. Our findings provide key insights into how autophagosome formation is regulated by a novel negative-feedback mechanism on membrane lipids.

• Hveem, Tarjei Sveinsgjerd; Njølstad, Tormund Salvesen; Nielsen, Birgitte; Syvertsen, Rolf Anders; Nesheim, John Arne & Kjæreng, Marna Lill [Vis alle 25 forfattere av denne artikkelen] (2016). Changes in Chromatin Structure in Curettage Specimens Identifies High-Risk Patients in Endometrial Cancer. Cancer Epidemiology, Biomarkers and Prevention. ISSN 1055-9965. 26(1), s. 61–67. doi: 10.1158/1055-9965.EPI-16-0215. Fulltekst i vitenarkiv
• Hveem, Tarjei Sveinsgjerd; Kleppe, Andreas; Vlatkovic, Ljiljana; Ersvær, Elin; Wæhre, Haakon & Nielsen, Birgitte [Vis alle 13 forfattere av denne artikkelen] (2016). Chromatin changes predict recurrence after radical prostatectomy. British Journal of Cancer. ISSN 0007-0920. 114(11), s. 1243–1250. doi: 10.1038/bjc.2016.96. Fulltekst i vitenarkiv
• Szymanska, Monika; Fosdahl, Anne-Marthe; Raiborg, Camilla; Dietrich, Markus; Liestøl, Knut & Stang, Espen [Vis alle 7 forfattere av denne artikkelen] (2016). Interaction with epsin 1 regulates the constitutive clathrin-dependent internalization of ErbB3. BBA - Molecular Cell Research. ISSN 0167-4889. 1863(6), s. 1179–1188. doi: 10.1016/j.bbamcr.2016.03.011. Fulltekst i vitenarkiv
• Jørgensen, Magne; Dybå, Tore; Liestøl, Knut & Sjøberg, Dag (2016). Incorrect results in software engineering experiments: How to improve research practices. Journal of Systems and Software. ISSN 0164-1212. 116, s. 133–145. doi: 10.1016/j.jss.2015.03.065. Fulltekst i vitenarkiv Vis sammendrag

  Context The trustworthiness of research results is a growing concern in many empirical disciplines. Aim The goals of this paper are to assess how much the trustworthiness of results reported in software engineering experiments is affected by researcher and publication bias, given typical statistical power and significance levels, and to suggest improved research practices. Method First, we conducted a small-scale survey to document the presence of researcher and publication biases in software engineering experiments. Then, we built a model that estimates the proportion of correct results for different levels of researcher and publication bias. A review of 150 randomly selected software engineering experiments published in the period 2002–2013 was conducted to provide input to the model. Results The survey indicates that researcher and publication bias is quite common. This finding is supported by the observation that the actual proportion of statistically significant results reported in the reviewed papers was about twice as high as the one expected assuming no researcher and publication bias. Our models suggest a high proportion of incorrect results even with quite conservative assumptions. Conclusion Research practices must improve to increase the trustworthiness of software engineering experiments. A key to this improvement is to avoid conducting studies with unsatisfactory low statistical power.

• Pharo, Heidi Dietrichson; Honne, Hilde; Vedeld, Hege Marie; Dahl, Christina; Andresen, Kim & Liestøl, Knut [Vis alle 9 forfattere av denne artikkelen] (2016). Experimental factors affecting the robustness of DNA methylation analysis. Scientific Reports. 6. doi: 10.1038/srep33936. Fulltekst i vitenarkiv
• Engeseth, Kristian; Hodnesdal, Christian; Grundvold, Irene; Liestøl, Knut; Gjesdal, Knut & Kjeldsen, Sverre Erik [Vis alle 9 forfattere av denne artikkelen] (2016). Temporal reduction in chronotropic index predicts risk of cardiovascular death among healthy middle-aged men: A 28-year follow-up study. Journal of the American Heart Association (JAHA). 5:e004555, s. 1–12. doi: 10.1161/JAHA.116.004555. Fulltekst i vitenarkiv Vis sammendrag

  Background Chronotropic index is a standardized measure of heart rate (HR) increment during exercise that reflects the combined effects of age, resting HR, and physical fitness. Low chronotropic index has been reported to predict disease and death. We tested whether temporal change in chronotropic index over 7 years influenced risk of cardiovascular death through up to 28 years. Methods and Results Chronotropic index was calculated ([achieved maximal HR−resting HR]/[age‐predicted maximal HR−resting HR]) after a symptom‐limited bicycle ECG exercise test in 1420 healthy men at 2 examinations 7 years apart, in 1972 and 1979. Events of cardiovascular death were registered by manual scrutiny of all participants’ hospital charts and the Norwegian Cause of Death Registry. The participants were divided into quartiles of temporal change in chronotropic index, with quartile one having the most negative value. Cox proportional hazard regression models were used to estimate risks and adjusted for classical cardiovascular risk factors. Incidence of cardiovascular death was 310 (22%) during median of 21 years of follow‐up. After multivariable adjustment, and comparison with quartile four (mean +0.11), quartiles one (−0.16), two (−0.04), and three (+0.02) were associated with hazard ratios 1.50 (95% CI 1.10–2.05), 1.10 (0.79–1.53), and 1.04 (0.74–1.45) for cardiovascular death. Results remained robust also after exclusion of 31 participants with exercise ECG‐induced signs of coronary ischemia. Conclusions Temporal reduction in chronotropic index was associated with increased long‐term risk of cardiovascular death and might be a clinically important predictor when assessing risk in healthy individuals over a longer time.

• Barzenje, Dlawer Abdulla; Småstuen, Milada C; Liestøl, Knut; Fosså, Alexander; Delabie, Jan & Kolstad, Arne [Vis alle 7 forfattere av denne artikkelen] (2015). Radiotherapy compared to other strategies in the treatment of stage I/II follicular lymphoma: A study of 404 patients with a median follow-up of 15 years. PLOS ONE. 10:e0131158(7). doi: 10.1371/journal.pone.0131158. Fulltekst i vitenarkiv
• Erikssen, Gunnar; Liestøl, Knut; Seem, Egil; Birkelance, Sigurce; Saatvedt, Kjell & Nilsen-Hoel, Tom [Vis alle 11 forfattere av denne artikkelen] (2015). Achievements in congenital heart defect surgery: A prospective, 40-year study of 7038 patients. Circulation. ISSN 0009-7322. 131, s. 337–346. doi: 10.1161/CIRCULATIONAHA.114.012033. Fulltekst i vitenarkiv
• Eikenes, Åsmund Husabø; Malerød, Lene; Christensen, Anette Lie; Steen, Chloe Beate; Mathieu, Juliette & Nezis, Ioannis P [Vis alle 10 forfattere av denne artikkelen] (2015). ALIX and ESCRT-III Coordinately Control Cytokinetic Abscission during Germline Stem Cell Division In Vivo. PLoS Genetics. ISSN 1553-7390. 11(1). doi: 10.1371/journal.pgen.1004904. Fulltekst i vitenarkiv
• Kumar, Neena Theresa; Liestøl, Knut; Løberg, Else Marit; Reims, Henrik Mikael & Mæhlen, Jan (2015). Apolipoprotein E allelotype is associated with neuropathological findings in Alzheimer's disease. Virchows Archiv. ISSN 0945-6317. 467(2), s. 225–235. doi: 10.1007/s00428-015-1772-1. Fulltekst i vitenarkiv
• Fiskvik, Idun Hege; Beiske, Klaus; Delabie, Jan; Yri, Olav Erich; Spetalen, Signe & Karjalainen-Lindsberg, Marja-Liisa [Vis alle 10 forfattere av denne artikkelen] (2015). Combining MYC, BCL2 and TP53 gene and protein expression alterations improves risk stratification in diffuse large B-cell lymphoma. Leukemia and Lymphoma. ISSN 1042-8194. 56(6), s. 1742–1749. doi: 10.3109/10428194.2014.970550. Fulltekst i vitenarkiv
• Eikenes, Åsmund Husabø; Malerød, Lene; Christensen, Anette Lie; Wegner, Catherine E Sem; Brech, Andreas & Liestøl, Knut [Vis alle 8 forfattere av denne artikkelen] (2015). Src64 controls a novel actin network required for proper ring canal formation in the drosophila male germline. Development. ISSN 0950-1991. 142(23), s. 4107–4118. doi: 10.1242/dev.124370. Fulltekst i vitenarkiv Vis sammendrag

  In many organisms, germ cells develop as cysts in which cells are interconnected via ring canals (RCs) as a result of incomplete cytokinesis. However, the molecular mechanisms of incomplete cytokinesis remain poorly understood. Here, we address the role of tyrosine phosphorylation of RCs in the Drosophila male germline. We uncover a hierarchy of tyrosine phosphorylation within germline cysts that positively correlates with RC age. The kinase Src64 is responsible for mediating RC tyrosine phosphorylation, and loss of Src64 causes a reduction in RC diameter within germline cysts. Mechanistically, we show that Src64 controls an actin network around the RCs that depends on Abl and the Rac/SCAR/Arp2/3 pathway. The actin network around RCs is required for correct RC diameter in cysts of developing germ cells. We also identify that Src64 is required for proper germ cell differentiation in the Drosophila male germline independent of its role in RC regulation. In summary, we report that Src64 controls actin dynamics to mediate proper RC formation during incomplete cytokinesis during germline cyst development in vivo.

• Thorvaldsen, Tor Espen; Pedersen, Nina Marie; Wenzel, Eva; Schultz, Sebastian; Brech, Andreas & Liestøl, Knut [Vis alle 9 forfattere av denne artikkelen] (2015). Structure, dynamics, and functionality of tankyrase inhibitor-induced degradasomes. Molecular Cancer Research. ISSN 1541-7786. 13(11), s. 1487–1501. doi: 10.1158/1541-7786.MCR-15-0125. Fulltekst i vitenarkiv
• Helmer, Caroline; Skranes, Janne Helen; Liestøl, Knut & Fugelseth, Drude (2015). Using adrenaline during neonatal resuscitation may have an impact on serum cardiac troponin-T levels. Acta Paediatrica. ISSN 0803-5253. 104(9), s. e378–e383. doi: 10.1111/apa.13055. Fulltekst i vitenarkiv
• Bruun, Jarle; Kolberg, Matthias; Ahlquist, Terje Cruickshank; Røyrvik, Ellen Christine; Nome, Torfinn & Leithe, Edward [Vis alle 18 forfattere av denne artikkelen] (2015). Regulator of chromosome condensation 2 identifies high-risk patients within both major phenotypes of colorectal cancer. Clinical Cancer Research. ISSN 1078-0432. 21(16), s. 3759–3770. doi: 10.1158/1078-0432.CCR-14-3294. Fulltekst i vitenarkiv
• Blaker, Yngvild Nuvin; Brodtkorb, Marianne; Maddison, John; Hveem, Tarjei Sveinsgjerd; Nesheim, John Arne & Mohn, Hans Martin [Vis alle 13 forfattere av denne artikkelen] (2015). Computerized image analysis of the Ki-67 proliferation index in mantle cell lymphoma. Histopathology. ISSN 0309-0167. 67(1), s. 62–69. doi: 10.1111/his.12624. Fulltekst i vitenarkiv
• Haugsten, Ellen Margrethe; Brech, Andreas; Liestøl, Knut; Norman, Jim C. & Wesche, Jørgen (2014). Photoactivation Approaches Reveal a Role for Rab11 in FGFR4 Recycling and Signalling. Traffic: The moving front of cell biology. ISSN 1398-9219. 15(6), s. 665–683. doi: 10.1111/tra.12168. Fulltekst i vitenarkiv
• Hveem, Tarjei Sveinsgjerd; Merok, Marianne Aarstad; Pretorius, Maria; Novelli, Marco; Silihagen, Mette & Sjo, Ole Helmer [Vis alle 12 forfattere av denne artikkelen] (2014). Prognostic impact of genomic instability in colorectal cancer. British Journal of Cancer. ISSN 0007-0920. 110(8), s. 2159–2164. doi: 10.1038/bjc.2014.133. Fulltekst i vitenarkiv
• Chen, Ying; Klingen, Tor Audun; Wik, Elisabeth; Aas, Hans; Vigeland, Einar & Liestøl, Knut [Vis alle 10 forfattere av denne artikkelen] (2014). Breast cancer stromal elastosis is associated with mammography screening detection, low Ki67 expression and favourable prognosis in a population-based study. Diagnostic Pathology. 9. doi: 10.1186/s13000-014-0230-8. Fulltekst i vitenarkiv Vis sammendrag

  Background: Mammography screen-detected breast cancers have a better prognosis than predicted from established prognostic markers. A search for additional features that are characteristic for these tumours and their prognosis is needed to reduce overtreatment, a recognized challenge in breast cancer patient management today. Here, we have investigated the occurrence and importance of tumour elastosis. Methods: We performed a population based retrospective study of breast cancers detected in the Norwegian Breast Cancer Screening Programme in Vestfold County during 2004–2009. In total, 197 invasive screen-detected cancers and 75 interval cancers in patients aged 50–69 years were compared with regard to standard clinico-pathological parameters and tumour shape, as well as ER, PR, HER2 and Ki67 expression. In particular, the presence of elastotic material in tumours was graded on a 4-tiered scale (score 0–3). Results: Screen-detected cancers had a significantly higher content of stromal elastosis than interval cancers (p < 0.001). High content of elastosis (score 3) correlated strongly with stellate tumour shape, low histological grade, and ER+/HER2- status. Further, high elastosis score was significantly associated with lower Ki67 expression. In survival analyses, cases with high elastosis demonstrated increased recurrence free (p = 0.03) and disease-specific survival (p = 0.11) compared to cases with low elastosis. Conclusion: There is a strong correlation between the presence of tumour elastosis, stellate tumour shape and mammography detection of breast cancers. To our knowledge, this is the first time elastosis has been studied in relation to breast cancer detection method. Presence of elastosis is associated with low tumour cell proliferation (Ki67) and a good prognosis.

• Bethge, Nicole; Honne, Hilde; Andresen, Kim; Hilden, Vera Irene; Trøen, Gunhild & Liestøl, Knut [Vis alle 10 forfattere av denne artikkelen] (2014). A gene panel, including LRP12, is frequently hypermethylated in major types of B-cell lymphoma. PLOS ONE. 9(9). doi: 10.1371/journal.pone.0104249. Fulltekst i vitenarkiv
• Blaker, Yngvild Nuvin; Eide, Marianne Brodtkorb; Liestøl, Knut; Lauritzsen, Grete Fossum; Kolstad, Arne & Fosså, Alexander [Vis alle 8 forfattere av denne artikkelen] (2014). High dose chemotherapy with autologous stem cell transplant for patients with transformed B-cell non-Hodgkin lymphoma in the rituximab era. Leukemia and Lymphoma. ISSN 1042-8194. 55(10), s. 2319–2327. doi: 10.3109/10428194.2013.871632. Fulltekst i vitenarkiv
• Bethge, Nicole; Lothe, Ragnhild A; Honne, Hilde; Andresen, Kim; Trøen, Gunhild & Eknæs, Mette [Vis alle 11 forfattere av denne artikkelen] (2014). Colorectal cancer DNA methylation marker panel validated with high performance in Non-Hodgkin lymphoma. Epigenetics. ISSN 1559-2294. 9(3), s. 428–436. doi: 10.4161/epi.27554. Fulltekst i vitenarkiv
• Søraas, Arne Vasli Lund; Sundsfjord, Arnfinn; Jørgensen, Silje Bakken; Liestøl, Knut & Jenum, Pål (2014). High rate of per oral mecillinam treatment failure in community-acquired urinary tract infections caused by ESBL-producing escherichia coli. PLOS ONE. 9(1:e85889). doi: 10.1371/journal.pone.0085889. Fulltekst i vitenarkiv Vis sammendrag

  A population-based study was performed to investigate the efficacy of mecillinam treatment of community-acquired urinary tract infections (CA-UTI) caused by extended-spectrum ß-lactamase (ESBL) producing Escherichia coli. The study was conducted in South-Eastern Norway. Data from patients with CA-UTI caused by ESBL-producing and non-producing (random controls) E. coli were collected through interviews, questionnaires, medical records and the Norwegian Prescription Database. Treatment failure was defined as a new antibiotic prescription appropriate for UTI prescribed within two weeks after the initial antimicrobial therapy. Multivariable logistic regression analysis was performed to identify treatment agents and patient- or bacterial traits associated with treatment failure. A total of 343 patients (mean age 59) were included, of which 158 (46%) were treated with mecillinam. Eighty-one patients (24%, mean age 54) had infections caused by ESBL producing E. coli, and 41 of these patients (51%) received mecillinam as the primary treatment. Mecillinam treatment failure was observed in 18 (44%) of patients infected by ESBL-producing strains and in 16 (14%) of patients with a CA-UTI caused by ESBL non-producing strains. Multivariable analysis showed that ESBL status (odds ratio (OR) 3.2, 95% confidence interval (CI) 1.3–7.8, p = 0.009) and increased MIC of mecillinam (OR 2.0 for each doubling value of MIC, CI 1.4–3.0, p<0.001) were independently associated with mecillinam treatment failure. This study showed a high rate of mecillinam treatment failure in CA-UTIs caused by ESBL producing E. coli. The high failure rate could not be explained by the increased MIC of mecillinam alone. Further studies addressing the use of mecillinam against ESBL-producing E. coli, with emphasis on optimal dosing and combination therapy with ß-lactamase inhibitors, are warranted.

• Lee, Anja; Nestaas, Eirik; Liestøl, Knut; Brunvand, Leif; Lindemann, Rolf & Fugelseth, Drude (2014). Tissue Doppler imaging in very preterm infants during the first 24 h of life: an observational study. Archives of Disease in Childhood: Fetal and Neonatal Edition. ISSN 1359-2998. 99(1), s. F64–F69. doi: 10.1136/archdischild-2013-304197. Fulltekst i vitenarkiv
• Thoresen, Sigrid Bratlie; Campsteijn, Coen; Vietri, Marina; Schink, Kay Oliver; Liestøl, Knut & Andersen, Jens S. [Vis alle 8 forfattere av denne artikkelen] (2014). ANCHR mediates Aurora-B-dependent abscission checkpoint control through retention of VPS4. Nature Cell Biology. ISSN 1465-7392. 16(6), s. 547–557. doi: 10.1038/ncb2959. Fulltekst i vitenarkiv
• Kumar, Neena Theresa; Liestøl, Knut; Løberg, Else Marit; Reims, Henrik Mikael & Mæhlen, Jan (2014). Postmortem heart weight: relation to body size and effects of cardiovascular disease and cancer. Cardiovascular pathology. ISSN 1054-8807. 23(1), s. 5–11. doi: 10.1016/j.carpath.2013.09.001. Fulltekst i vitenarkiv
• Eriksen, Beate Horsberg; Nestaas, Eirik; Hole, Torstein; Liestøl, Knut; Støylen, Asbjørn & Fugelseth, Drude (2014). Myocardial function in term and preterm infants. Influence of heart size, gestational age and postnatal maturation. Early Human Development. ISSN 0378-3782. 90(7), s. 359–364. doi: 10.1016/j.earlhumdev.2014.04.010. Fulltekst i vitenarkiv Vis sammendrag

  Background Sparse knowledge exists on the differences in cardiac function between term and preterm infants. This study examines the impact of heart size, gestational age and postnatal maturation on myocardial function. Aim To assess and compare serial echocardiographic indices of myocardial function in term and moderately preterm infants. Methods Longitudinal, prospective, observational echocardiographic cohort study of 45 healthy term infants examined at day three and at 12–20 weeks postnatal age and 53 moderately preterm infants (gestational age 31–35 weeks) examined at day three and at term equivalent (4–10 weeks postnatal age). Outcomes Primary: Systolic mitral and tricuspid annular plane excursions and annular peak systolic pulsed wave tissue Doppler (pwTDI) velocities. Secondary: Indices normalized for heart size. Results On day three, all indices were higher in the term than in the preterm infants whereas normalized systolic pwTDI velocities were lower in the term infants and normalized excursions showed no difference. All indices increased with advanced postnatal age. The indices in term infants on day three were lower than in preterm infants at term equivalent, with and without normalization. After postnatal maturation in both groups, all indices were higher in the term group (except left pwTDI), whereas normalized indices showed no consistent pattern. Conclusions Myocardial function indices increased with gestational age at birth and more profoundly with postnatal maturation. Serial examinations of non-normalized and normalized myocardial function indices showed no sustained differences between the preterm and the term infants. Normalization by heart size may be of value when assessing myocardial function in infants.

• Nilsen, Gro; Borgan, Ørnulf; Liestøl, Knut & Lingjærde, Ole Christian (2013). Identifying clusters in genomics data by recursive partitioning. Statistical Applications in Genetics and Molecular Biology. 12(5), s. 637–652. doi: 10.1515/sagmb-2013-0016. Fulltekst i vitenarkiv
• Skretteberg, Per Torger; Grundvold, Irene; Kjeldsen, Sverre Erik; Engeseth, Kristian; Liestøl, Knut & Erikssen, Gunnar [Vis alle 9 forfattere av denne artikkelen] (2013). Seven-Year Increase in Exercise Systolic Blood Pressure at Moderate Workload Predicts Long-Term Risk of Coronary Heart Disease and Mortality in Healthy Middle-Aged Men. Hypertension. ISSN 0194-911X. 61(5), s. 1134–1140. doi: 10.1161/HYPERTENSIONAHA.111.00793. Fulltekst i vitenarkiv
• Yri, Olav Erich; Ekstrøm, Per Olaf; Hilden, Vera Irene; Gaudernack, Gustav; Liestøl, Knut & Smeland, Erlend B [Vis alle 7 forfattere av denne artikkelen] (2013). Influence of polymorphisms in genes encoding immunoregulatory proteins and metabolizing enzymes on susceptibility and outcome in patients with diffuse large B-cell lymphoma treated with rituximab. Leukemia and Lymphoma. ISSN 1042-8194. 54(10), s. 2205–2214. doi: 10.3109/10428194.2013.774392. Fulltekst i vitenarkiv
• Vikne, Harald; Bakke, Eva; Liestøl, Knut; Engen, Stian Rugsveen & Vøllestad, Nina Køpke (2013). Muscle activity and head kinematics in unconstrained movements in subjects with chronic neck pain; cervical motor dysfunction or low exertion motor output? BMC Musculoskeletal Disorders. 14(1), s. 314–314. doi: 10.1186/1471-2474-14-314. Fulltekst i vitenarkiv Vis sammendrag

  Background: Chronic neck pain after whiplash associated disorders (WAD) may lead to reduced displacement and peak velocity of neck movements. Dynamic neck movements in people with chronic WAD are also reported to display altered movement patterns such as increased irregularity, which is suggested to signify impaired motor control. As movement irregularity is strongly related to the velocity and displacement of movement, we wanted to examine whether the increased irregularity in chronic WAD could be accounted for by these factors. Methods: Head movements were completed in four directions in the sagittal plane at three speeds; slow (S), preferred (P) and maximum (M) in 15 men and women with chronic WAD and 15 healthy, sex and age-matched control participants. Head kinematics and measures of movement smoothness and symmetry were calculated from position data. Surface electromyography (EMG) was recorded bilaterally from the sternocleidomastoid and splenius muscles and the root mean square (rms) EMG amplitude for the accelerative and decelerative phases of movement were analyzed. Results: The groups differed significantly with regard to movement velocity, acceleration, displacement, smoothness and rmsEMG amplitude in agonist and antagonist muscles for a series of comparisons across the test conditions (range 17 – 121%, all p-values < 0.05). The group differences in peak movement velocity and acceleration persisted after controlling for movement displacement. Controlling for differences between the groups in displacement and velocity abolished the difference in measures of movement smoothness and rmsEMG amplitude. Conclusions: Simple, unconstrained head movements in participants with chronic WAD are accomplished with reduced velocity and displacement, but with normal muscle activation levels and movement patterns for a given velocity and displacement. We suggest that while reductions in movement velocity and displacement are robust changes and may be of clinical importance in chronic WAD, movement smoothness of unconstrained head movements is not.

Se alle arbeider i NVA

• Kleppe, Andreas; Skrede, Ole-Johan; Liestøl, Knut; Kerr, David J. & Danielsen, Håvard Emil Greger (2024). Guidelines for study protocols describing predefined validations of prediction models in medical deep learning and beyond. Nature Machine Intelligence. 6(1), s. 2–3. doi: 10.1038/s42256-023-00774-7. Fulltekst i vitenarkiv
• Jørgensen, Magne; Bergersen, Gunnar; Liestøl, Knut & Apel, Sven (2021). Relations Between Effort Estimates, Skill Indicators, and Measured Programming Skill (A Journal first conference publication). Fulltekst i vitenarkiv Vis sammendrag

  There are large skill differences among software developers, and clients and managers will benefit from being able to identify those with better skill. This study examines the relations between low effort estimates, and other commonly used skill indicators, and measured programming skill. One hundred and four professional software developers were recruited. After skill-related information was collected, they were asked to estimate the effort for four larger and five smaller programming tasks. Finally, they completed a programming skill test. The lowest and most over-optimistic effort estimates for the larger tasks were given by those with the lowest programming skill, which is in accordance with the well-known Dunning-Kruger effect. For the smaller tasks, however, those with the lowest programming skill had the highest and most over-pessimistic estimates. The other programming skill indicators, such as length of experience, company assessed skill and self-assessed skill, were only moderately correlated with measured skill and not particularly useful in guiding developer skill identification. A practical implication is that for larger and more complex tasks, the use of low effort estimates and commonly used skill indicators as selection criteria leads to a substantial risk of selecting among the least skilled developers.

• Holter, Øystein Gullvåg; Snickare, Lotta Karin & Liestøl, Knut (2021). Metode. I Holter, Øystein Gullvåg & Snickare, Lotta Karin (Red.), Likestilling i akademia - fra kunnskap til endring. Cappelen Damm Akademisk. ISSN 9788202669669. s. 355–371. Fulltekst i vitenarkiv
• Liestøl, Knut; Kleppe, Andreas; Skrede, Ole-Johan; Raedt, Sepp De; Kerr, David J. & Danielsen, Håvard Emil Greger (2021). Deep learning and cancer biomarkers: recognising lead-time bias – Authors' reply. The Lancet. ISSN 0140-6736. 397(10270), s. 194–195. doi: 10.1016/S0140-6736(21)00035-0. Fulltekst i vitenarkiv
• Nikolaidis, Konstantinos; Kristiansen, Stein; Goebel, Vera Hermine; Plagemann, Thomas Peter & Liestøl, Knut (2019). Augmenting Physiological Time Series Data: A Case study for Sleep Apnea Detection. Fulltekst i vitenarkiv
• Frølich, Nicoline; Mangset, Marte; Teigen, Mari; Liestøl, Knut; Enli, Gunn & Christensen, Lina (2019). Endelig likestilling? Ikke ennå. [Journal]. Forskerforum.no. Fulltekst i vitenarkiv
• Mehlum, Maria Hollund; Liestøl, Knut; Kjeldsen, Sverre & Berge, Eivind (2018). Response to letters from Torp-Pedersen and colleagues and de Courson and colleagues. European Heart Journal. ISSN 0195-668X. 39(47), s. 4221–4221. doi: 10.1093/eurheartj/ehy605. Fulltekst i vitenarkiv
• Holter, Øystein Gullvåg; Liestøl, Knut; Tallaksen, Lena M. & Kristensen, Solveig (2016). Universitetene er sterkt konkurransedrevet. I dette løpet taper kvinnene. Kronikk Aftenposten 7.3.2016 http://www.aftenposten.no/meninger/kronikker/Kronikk-Universitetene-er-sterk t-konkurransedrevet-I-dette-lopet-taper-kvinnene-8380246.html. Fulltekst i vitenarkiv

Se alle arbeider i NVA