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| 2. |
- Bakker, M. K., et al.
(författare)
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Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:12, s. 1303-1313
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Tidskriftsartikel (refereegranskat)abstract
- Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits. Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability.
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| 3. |
- Kooij, J. J. S., et al.
(författare)
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Updated European Consensus Statement on diagnosis and treatment of adult ADHD
- 2019
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Ingår i: European psychiatry. - : Cambridge University Press (CUP). - 0924-9338 .- 1778-3585. ; 56, s. 14-34
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAttention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness.MethodsThe European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated.ResultsBesides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated?ConclusionsADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.
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| 5. |
- Wijns, W, et al.
(författare)
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Myocardial revascularization
- 2011
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Ingår i: REVISTA PORTUGUESA DE CARDIOLOGIA. - : Elsevier BV. - 0870-2551 .- 2174-2049. ; 30:12, s. 951-1005
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Kreins, AY, et al.
(författare)
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Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome
- 2015
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 212:10, s. 1641-1662
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Tidskriftsartikel (refereegranskat)abstract
- Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections and features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, and staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families and four different ethnic groups. These patients were homozygous for one of five null mutations, different from that seen in P1. They displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-α/β, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17+ T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease. Cellular responses to IL-21, IL-27, IFN-γ, IL-28/29 (IFN-λ), and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts of all seven newly identified TYK2-deficient patients, unlike those of P1, responded normally to IL-6, possibly accounting for the lack of HIES in these patients. The expression of exogenous wild-type TYK2 or the silencing of endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired responses to IL-12 and IFN-α/β. Moreover, impaired IL-6 responses and HIES do not appear to be intrinsic features of TYK2 deficiency in humans.
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| 9. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 12. |
- Niemela, Perttu S., et al.
(författare)
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Membrane Proteins Diffuse as Dynamic Complexes with Lipids
- 2010
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society. - 0002-7863 .- 1520-5126. ; 132:22, s. 7574-
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Tidskriftsartikel (refereegranskat)abstract
- We describe how membrane proteins diffuse laterally in the membrane plane together with the lipids surrounding them. We find a number of intriguing phenomena. The lateral displacements of the protein and the lipids are strongly correlated, as the protein and the neighboring lipids form a dynamical protein-lipid complex, consisting of similar to 50-100 lipids. The diffusion of the lipids in the complex is much slower compared to the rest of the lipids. We also find a strong directional correlation between the movements of the protein and the lipids in its vicinity. The results imply that in crowded membrane environments there are no ""free"" lipids, as they are all influenced by the protein structure and dynamics. Our results indicate that, in studies of cell membranes, protein and lipid dynamics have to be considered together.
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| 15. |
- Wood, David A., et al.
(författare)
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Timing of Staged Nonculprit Artery Revascularization in Patients With ST-Segment Elevation Myocardial Infarction COMPLETE Trial
- 2019
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 74:22, s. 2713-2723
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The COMPLETE (Complete vs Culprit-only Revascularization to Treat Multi-vessel Disease After Early PCI for STEMI) trial demonstrated that staged nonculprit lesion percutaneous coronary intervention (PCI) reduced major cardiovascular (CV) events in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (CAD). OBJECTIVES The purpose of this study was to determine the effect of nonculprit-lesion PCI timing on major CV outcomes and also the time course of the benefit of complete revascularization. METHODS Following culprit-lesion PCI, 4,041 patients with STEMI and multivessel CAD were randomized to staged nonculprit-lesion PCI or culprit-lesion only PCI. Randomization was stratified according to investigator-planned timing of nonculprit-lesion PCI: during or after the index hospitalization. The first coprimary outcome was the composite of CV death or myocardial infarction (MI). In pre-specified analyses, hazard ratios (HRs) were calculated for each time stratum. Landmark analyses of the entire population were performed within 45 days and after 45 days. RESULTS For nonculprit-lesion PCI planned during the index hospitalization (actual time: median 1 day), CV death or MI was reduced with complete revascularization compared with culprit-lesion only PCI (HR: 0.77; 95% confidence interval [CI]: 0.59 to 1.00). For nonculprit lesion PCI planned to occur after hospital discharge (actual time: median 23 days), CV death or MI was also reduced with complete revascularization (HR: 0.69; 95% CI: 0.49 to 0.97; interaction p = 0.62). Landmark analyses demonstrated an HR of 0.86 (95% CI: 0.59 to 1.24) during the first 45 days and 0.69 (95% CI: 0.54 to 0.89) from 45 days to the end of follow-up for intended nonculprit lesion PCI versus culprit lesion only PCI. CONCLUSIONS Among STEMI patients with multivessel disease, the benefit of complete revascularization over culprit-lesion only PCI was consistent irrespective of the investigator-determined timing of nonculprit-lesion intervention. The benefit of complete revascularization on hard clinical outcomes emerged mainly over the long term. (C) 2019 by the American College of Cardiology Foundation.
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| 18. |
- Hakola, T, et al.
(författare)
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Longer Work Shifts, Faster Forward Rotation-More Sleep and More Alert in Aircraft Inspection
- 2021
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 18:15
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this intervention study is to compare sleep, alertness, and work ability among aircraft inspectors working under two different shift schedules. The original schedule was forward rotating: MMM – – EEE – NNN – – – (M = morning, E = evening, N = night, – = day off). The new schedule was fast forward rotating: MEN – – with 10-h shifts. The baseline data were collected before the schedule changed, and the follow-up data 12 months (n = 10, Group A) or 5 months (n = 13, Group B) after the change. Three of subjects were women and average age was 46.6 years (range 31–58). The surveys included questions on sleep quantity, sleep quality, severe sleepiness, alertness, perceived stress, current work ability, and satisfaction with the shift schedule. The results indicated that in the new schedule, the sleeping times were longer and sleep loss was less. Moreover, shift specific severe sleepiness decreased, and alertness during shifts improved. Compared to baseline, perceived stress was lower and work ability was better. Satisfaction with the shift system had also improved. To conclude, the quickly forward rotating shift system might be beneficial in terms of increased sleep length and improved alertness and overall well-being especially among older aircraft inspectors.
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| 21. |
- Jolly, Sanjit S., et al.
(författare)
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Procedural Volume and Outcomes With Radial or Femoral Access for Coronary Angiography and Intervention
- 2014
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 63:10, s. 954-963
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The study sought to evaluate the relationship between procedural volume and outcomes with radial and femoral approach. Background RIVAL (RadIal Vs. femorAL) was a randomized trial of radial versus femoral access for coronary angiography/intervention (N = 7,021),which overall did not show a difference in primary outcome of death, myocardial infarction, stroke, or non-coronary artery bypass graft major bleeding. Methods In pre-specified subgroup analyses, the hazard ratios for the primary outcome were compared among centers divided by tertiles and among individual operators. A multivariable Cox proportional hazards model was used to determine the independent effect of center and operator volumes after adjusting for other variables. Results In high-volume radial centers, the primary outcome was reduced with radial versus femoral access (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.28 to 0.87) but not in intermediate-(HR: 1.23; 95% CI: 0.88 to 1.72) or low-volume centers (HR: 0.83; 95% CI: 0.52 to 1.31; interaction p 0.021). High-volume centers enrolled a higher proportion of ST-segment elevation myocardial infarction (STEMI). After adjustment for STEMI, the benefit of radial access persisted at high-volume radial centers. There was no difference in the primary outcome between radial and femoral access by operator volume: high-volume operators (HR: 0.79; 95% CI: 0.48 to 1.28), intermediate (HR: 0.87; 95% CI: 0.60 to 1.27), and low (HR: 1.10; 95% CI: 0.74 to 1.65; interaction p 0.536). However, in a multivariable model, overall center volume and radial center volume were independently associated with the primary outcome but not femoral center volume (overall percutaneous coronary intervention volume HR: 0.92, 95% CI: 0.88 to 0.96; radial volume HR: 0.88, 95% CI: 0.80 to 0.97; and femoral volume HR: 1.00, 95% CI: 0.94 to 1.07; p 0.98). Conclusions Procedural volume and expertise are important, particularly for radial percutaneous coronary intervention. (A Trial of Trans-radial Versus Trans-femoral Percutaneous Coronary Intervention [PCI] Access Site Approach in Patients With Unstable Angina or Myocardial Infarction Managed With an Invasive Strategy [RIVAL]; NCT01014273) (C) 2014 by the American College of Cardiology Foundation
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| 24. |
- Lehti, V, et al.
(författare)
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Use of benzodiazepine and related drugs in migrants and Finnish-born persons: a nationwide register-based study
- 2023
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Ingår i: Scandinavian journal of public health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 51:8, s. 1222-1230
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Tidskriftsartikel (refereegranskat)abstract
- Benzodiazepines and related drugs (BZDR) are often used longer than generally recommended. The aim is to study patterns of use among migrant and Finnish-born users of BZDR, and to identify factors that are associated with long-term use and BZDR polytherapy. Methods: This register-based study includes a nationwide sample of migrants ( n=8729) and their Finnish-born controls ( n=11 388) who had purchased BZDR in 2011–2014, but not in 2009–2010. Information on drug purchases was obtained from the National Prescription Register and the duration of drug use was estimated using PRE2DUP method. The main outcomes were long-term use of BZDR, polytherapy and time until discontinuation of BZDR use. Sociodemographic variables and information on preceding psychiatric diagnoses were included as covariates. Logistic and Cox regression analyses were the statistical methods used. Results: Only migrants from Sub-Saharan Africa were more likely to discontinue the medication once initiated than Finnish-born users. Migrants were significantly less likely to be long-term users (adjusted odds ratio 0.79, 95% CI 0.70–0.89) or polytherapy users (aOR 0.90, 95% CI 0.84–0.97) of BZDR compared with Finnish-born participants. Conclusions: Migrants had less long-term and concomitant use of several BZDR than Finnish-born participants. The pattern of use is more optimal among migrants, but it may also reflect poorer access to mental health treatment.
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| 28. |
- Merikukka, M, et al.
(författare)
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Association between parental hospital-treated somatic illnesses in childhood and later mental disorders among offspring up to early adulthood: An explorative study in the 1987 Finnish Birth Cohort
- 2020
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Ingår i: Scandinavian journal of public health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 48:2, s. 214-223
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Earlier studies on the associations between parental somatic illnesses and children’s psychological wellbeing have focused on the most common somatic illnesses or on specific groups of illnesses. In this study, we aimed to systematically examine whether parental somatic illnesses, diagnosed during an offspring’s childhood, are associated with later mental disorders of the offspring and, if so, identify which parental somatic illnesses in particular increase the likelihood for later mental disorders among the offspring. Methods: The 1987 Finnish Birth Cohort study yields longitudinal nationwide follow-up data that include a complete census of children born in a single year. Children have been followed over time through to the year 2012 using official registers maintained by the Finnish authorities. Parental diagnoses of specialised hospital inpatient care were identified from the Hospital Discharge Register after children’s birth and followed up until the end of 1995. Children’s psychiatric diagnoses from specialised hospital care were identified from the same register for the periods 1996/1998–2012. Logistic regression analyses were used to calculate sex-specific odds ratios for associations of mental disorders with maternal and paternal somatic illnesses using parental death, education, social assistance and psychiatric inpatient care as covariates. Results: Parental somatic illnesses during an offspring’s childhood seem to increase the risk for later mental disorders. Several previously unreported somatic parental illnesses were found to be significantly associated with offspring’s later mental health. Conclusions: Parental somatic illnesses should be considered as a significant adverse childhood life event, calling for preventive actions and child-centred support in adult healthcare.
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| 31. |
- Neelov, I.M., et al.
(författare)
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Computer simulations of stretching and collapse of polymer molecules in solution
- 2003
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Ingår i: Macromolecular Symposia. - : Wiley. - 1022-1360 .- 1521-3900. ; 191
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Konferensbidrag (refereegranskat)abstract
- Computer simulations are reported for system of linear polymer molecules, diblock copolymer and dendrimer in dilute solution without and with elongational flow. The effect of fluctuating hydrodynamics interactions (HI) on the coil-stretch transition of linear polymers and dendrimers in elongational flow is studied. The process of coiling of homo- and blockcopolymer from completely extended state is also simulated.
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| 35. |
- Olsson, Caroline, 1970, et al.
(författare)
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Autosegmentation based on different-sized training datasets of consistently-curated volumes and impact on rectal contours in prostate cancer radiation therapy
- 2022
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Ingår i: Physics and imaging in radiation oncology (PIRO). - : Elsevier BV. - 2405-6316. ; 22, s. 67-72
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Autosegmentation techniques are emerging as time-saving means for radiation therapy (RT) contouring, but the understanding of their performance on different datasets is limited. The aim of this study was to determine agreement between rectal volumes by an existing autosegmentation algorithm and manually-delineated rectal volumes in prostate cancer RT. We also investigated contour quality by differentsized training datasets and consistently-curated volumes for retrained versions of this same algorithm. Materials and methods: Single-institutional data from 624 prostate cancer patients treated to 50-70 Gy were used. Manually-delineated clinical rectal volumes (clinical) and consistently-curated volumes recontoured to one anatomical guideline (reference) were compared to autocontoured volumes by a commercial autosegmentation tool based on deep-learning (v1; n = 891, multiple-institutional data) and retrained versions using subsets of the curated volumes (v32/64/128/256; n = 32/64/128/256). Evaluations included dose-volume histogram metrics, Dice similarity coefficients, and Hausdorff distances; differences between groups were quantified using parametric or non-parametric hypothesis testing. Results: Volumes by v1-256 (76-78 cm(3)) were larger than reference (75 cm(3)) and clinical (76 cm(3)). Mean doses by v1-256 (24.2-25.2 Gy) were closer to reference (24.2 Gy) than to clinical (23.8 Gy). Maximum doses were similar for all volumes (65.7-66.0 Gy). Dice for v1-256 and reference (0.87-0.89) were higher than for v1-256 and clinical (0.86-0.87) with corresponding Hausdorff comparisons including reference smaller than comparisons including clinical (5-6 mm vs. 7-8 mm). Conclusion: Using small single-institutional RT datasets with consistently-defined rectal volumes when training autosegmentation algorithms created contours of similar quality as the same algorithm trained on large multiinstitutional datasets.
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