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- Couch, Fergus J., et al.
(author)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Journal article (peer-reviewed)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 7. |
- Charette, M, et al.
(author)
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The Transpolar Drift as a Source of Riverine and Shelf‐Derived Trace Elements to the Central Arctic Ocean
- 2020
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In: Journal of Geophysical Research - Oceans. - 2169-9275 .- 2169-9291. ; 125, s. 1-34
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Journal article (peer-reviewed)abstract
- A major surface circulation feature of the Arctic Ocean is the Transpolar Drift (TPD), a current that transports river‐influenced shelf water from the Laptev and East Siberian Seas toward the center of the basin and Fram Strait. In 2015, the international GEOTRACES program included a high‐resolution pan‐Arctic survey of carbon, nutrients, and a suite of trace elements and isotopes (TEIs). The cruises bisected the TPD at two locations in the central basin, which were defined by maxima in meteoric water and dissolved organic carbon concentrations that spanned 600 km horizontally and ~25–50 m vertically. Dissolved TEIs such as Fe, Co, Ni, Cu, Hg, Nd, and Th, which are generally particle‐reactive but can be complexed by organic matter, were observed at concentrations much higher than expected for the openocean setting. Other trace element concentrations such as Al, V, Ga, and Pb were lower than expected due to scavenging over the productive East Siberian and Laptev shelf seas. Using a combination of radionuclide tracers and ice drift modeling, the transport rate for the core of the TPD was estimated at 0.9 ± 0.4 Sv(106m3 s−1). This rate was used to derive the mass flux for TEIs that were enriched in the TPD, revealing the importance of lateral transport in supplying materials beneath the ice to the central Arctic Ocean and potentially to the North Atlantic Ocean via Fram Strait. Continued intensification of the Arctic hydrologicc ycle and permafrost degradation will likely lead to an increase in the flux of TEIs into the Arctic Ocean.
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- Mavaddat, Nasim, et al.
(author)
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Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants
- 2015
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 107:5, s. 036-036
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Journal article (peer-reviewed)abstract
- Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.
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- Curigliano, G, et al.
(author)
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De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.
- 2017
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In: Annals of oncology : official journal of the European Society for Medical Oncology. - : Elsevier BV. - 1569-8041. ; 28:8, s. 1700-1712
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Journal article (peer-reviewed)abstract
- The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.
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- Phillips, Helen R. P., et al.
(author)
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Global distribution of earthworm diversity
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 366:6464, s. 480-
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Journal article (peer-reviewed)abstract
- Soil organisms, including earthworms, are a key component of terrestrial ecosystems. However, little is known about their diversity, their distribution, and the threats affecting them. We compiled a global dataset of sampled earthworm communities from 6928 sites in 57 countries as a basis for predicting patterns in earthworm diversity, abundance, and biomass. We found that local species richness and abundance typically peaked at higher latitudes, displaying patterns opposite to those observed in aboveground organisms. However, high species dissimilarity across tropical locations may cause diversity across the entirety of the tropics to be higher than elsewhere. Climate variables were found to be more important in shaping earthworm communities than soil properties or habitat cover. These findings suggest that climate change may have serious implications for earthworm communities and for the functions they provide.
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| 19. |
- Stone, D., et al.
(author)
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A method of establishing a transect for biodiversity and ecosystem function monitoring across Europe
- 2016
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In: Applied Soil Ecology. - : Elsevier BV. - 0929-1393 .- 1873-0272. ; 97, s. 3-11
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Journal article (peer-reviewed)abstract
- The establishment of the range of soil biodiversity found within European soils is needed to guide EU policy development regarding the protection of soil. Such a base-line should be collated from a wide-ranging sampling campaign to ensure that soil biodiversity from the majority of soil types, land-use or management systems, and European climatic (bio-geographical zones) were included. This paper reports the design and testing of a method to achieve the large scale sampling associated with the establishment of such a baseline, carried out within the remit of the EcoFINDERS project, and outlines points to consider when such a task is undertaken. Applying a GIS spatial selection process, a sampling campaign was undertaken by 13 EcoFINDERS partners across 11 countries providing data on the range of indicators of biodiversity and ecosystem functions including; micro and meso fauna biodiversity, extracellular enzyme activity, PLEA and community level physiological profiling (MicroResp (TM) and Biolog (TM)). Physical, chemical and bio-geographical parameters of the 81 sites sampled were used to determine whether the model predicted a wide enough range of sites to allow assessment of the biodiversity indicators tested. Discrimination between the major bio-geographical zones of Atlantic and Continental was possible for all land-use types. Boreal and Alpine zones only allowed discrimination in the most common land-use type for that area e.g. forestry and grassland sites, respectively, while the Mediterranean zone did not have enough sites sampled to draw conclusions across all land-use types. The method used allowed the inclusion of a range of land-uses in both the model prediction stage and the final sites sampled. The establishment of the range of soil biodiversity across Europe is possible, though a larger targeted campaign is recommended. The techniques applied within the EcoFINDERS sampling would be applicable to a larger campaign. (C) 2015 Elsevier B.V. All rights reserved.
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- Marto, João Pedro, et al.
(author)
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Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.
- 2023
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In: Neurology. - 1526-632X. ; 100:7
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Journal article (peer-reviewed)abstract
- COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
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| 28. |
- Valk, O., et al.
(author)
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Importance of Hydrothermal Vents in Scavenging Removal of Th-230 in the Nansen Basin
- 2018
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In: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 45:19, s. 10539-10548
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Journal article (peer-reviewed)abstract
- In this study we present dissolved and particulate Th-230 and Th-232 results, as well as particulate Th-234 data, obtained as part of the GEOTRACES central Arctic Ocean sections GN04 (2015) and IPY11 (2007). Samples were analyzed following GEOTRACES methods and compared to previous results from 1991. We observe significant decreases in Th-230 concentrations in the deep waters of the Nansen Basin. We ascribe this nonsteady state removal process to a variable release and scavenging of trace metals near an ultraslow spreading ridge. This finding demonstrates that hydrothermal scavenging in the deep-sea may vary on annual time scales and highlights the importance of repeated GEOTRACES sections. Plain Language Summary This study presents new results of thorium isotopes from the central Arctic Ocean. Thorium-230 is produced continuously in seawater by radioactive decay of U-234 and subsequently removed by particle scavenging. We show that observed changes in Th-230 concentrations compared to earlier times are related to submarine volcanic eruptions. We use Th-230 data from three different expeditions conducted in 1991, 2007, and 2015. The Nansen Basin is part of the Eurasian Basin of the Arctic Ocean. It is divided from the Amundsen Basin by the Gakkel Ridge. The Gakkel Ridge is a region where the Eurasian and the North American plates spread apart, triggering volcanism. Submarine volcanos and hydrothermal vents release trace elements such as iron. Iron is known to be oxidized to particles that react with Th-230. Thus, when iron particles sink they remove Th-230 from the water column. In the Nansen Basin this process took place between 2007 and 2015, triggered by earthquake-induced volcanic eruptions in 2001. In this study, we present a conceptual hydrothermal scavenging process and plume dispersal by deep water circulation.
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- Lopes Cardozo, Josephine M N, et al.
(author)
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Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival
- 2023
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In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 41:10, s. 1849-1863
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Journal article (peer-reviewed)abstract
- PURPOSE: A polygenic risk score (PRS) consisting of 313 common genetic variants (PRS313) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS313 with clinicopathologic characteristics of, and survival following, breast cancer.METHODS: Women with invasive breast cancer were included, 98,397 of European ancestry and 12,920 of Asian ancestry, from the Breast Cancer Association Consortium (BCAC), and 683 women from the European MINDACT trial. Associations between PRS313 and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analyses. Associations of PRS313 (continuous, per standard deviation) with overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated with Cox regression, adjusted for clinicopathologic characteristics and treatment.RESULTS: The PRS313 was associated with more favorable tumor characteristics. In BCAC, increasing PRS313 was associated with lower grade, hormone receptor-positive status, and smaller tumor size. In MINDACT, PRS313 was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS313 was associated with better OS and BCSS: hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.97) and 0.96 (95% CI, 0.94 to 0.98), but the association disappeared after adjustment for clinicopathologic characteristics (and treatment): OS HR, 1.01 (95% CI, 0.98 to 1.05) and BCSS HR, 1.02 (95% CI, 0.98 to 1.07). The results in MINDACT and Asian women from BCAC were consistent.CONCLUSION: An increased PRS313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS313 as increasing PRS313 is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.
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| 31. |
- Valk, Ole, et al.
(author)
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Decrease in Th-230 in the Amundsen Basin since 2007 : far-field effect of increased scavenging on the shelf?
- 2020
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In: Ocean Science. - : Copernicus GmbH. - 1812-0784 .- 1812-0792. ; 16:1, s. 221-234
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Journal article (peer-reviewed)abstract
- This study provides dissolved and particulate Th-230 and Th-232 results as well as particulate( )(234)Th data collected during expeditions to the central Arctic Ocean (GEO-TRACES, an international project to identify processes and quantify fluxes that control the distributions of trace elements; sections GN04 and GIPY11). Constructing a time series of dissolved Th-230 from 1991 to 2015 enables the identification of processes that control the temporal development of Th-230 distributions in the Amundsen Basin. After 2007, Th-230 concentrations decreased significantly over the entire water column, particularly between 300 and 1500 m. This decrease is accompanied by a circulation change, evidenced by a concomitant increase in salinity. A potentially increased inflow of water of Atlantic origin with low dissolved Th-230 concentrations leads to the observed depletion in dissolved Th-230 in the central Arctic. Because atmospherically derived tracers (chlorofluorocarbon (CFC), sulfur hexafluoride (SF6)) do not reveal an increase in ventilation rate, it is suggested that these interior waters have undergone enhanced scavenging of Th during transit from Fram Strait and the Barents Sea to the central Amundsen Basin. The Th-230 depletion propagates downward in the water column by settling particles and reversible scavenging.
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| 32. |
- van der Kamp, Ananda, et al.
(author)
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Automated Deep Learning-Based Classification of Wilms Tumor Histopathology
- 2023
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In: Cancers. - : MDPI. - 2072-6694. ; 15:9
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Journal article (peer-reviewed)abstract
- Wilms tumor (WT) is the most frequent pediatric tumor in children and shows highly variable histology, leading to variation in classification. Artificial intelligence-based automatic recognition holds the promise that this may be done in a more consistent way than human observers can. We have therefore studied digital microscopic slides, stained with standard hematoxylin and eosin, of 72 WT patients and used a deep learning (DL) system for the recognition of 15 different normal and tumor components. We show that such DL system can do this task with high accuracy, as exemplified by a Dice score of 0.85 for the 15 components. This approach may allow future automated WT classification.(1) Background: Histopathological assessment of Wilms tumors (WT) is crucial for risk group classification to guide postoperative stratification in chemotherapy pre-treated WT cases. However, due to the heterogeneous nature of the tumor, significant interobserver variation between pathologists in WT diagnosis has been observed, potentially leading to misclassification and suboptimal treatment. We investigated whether artificial intelligence (AI) can contribute to accurate and reproducible histopathological assessment of WT through recognition of individual histopathological tumor components. (2) Methods: We assessed the performance of a deep learning-based AI system in quantifying WT components in hematoxylin and eosin-stained slides by calculating the Sorensen-Dice coefficient for fifteen predefined renal tissue components, including six tumor-related components. We trained the AI system using multiclass annotations from 72 whole-slide images of patients diagnosed with WT. (3) Results: The overall Dice coefficient for all fifteen tissue components was 0.85 and for the six tumor-related components was 0.79. Tumor segmentation worked best to reliably identify necrosis (Dice coefficient 0.98) and blastema (Dice coefficient 0.82). (4) Conclusions: Accurate histopathological classification of WT may be feasible using a digital pathology-based AI system in a national cohort of WT patients.
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| 33. |
- Wilson, A. R. M., et al.
(author)
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The requirements of a specialist Breast Centre
- 2013
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 49:17, s. 3579-3587
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Journal article (peer-reviewed)abstract
- Introduction: In recognition of the advances and evidence based changes in clinical practice that have occurred in recent years and taking into account the knowledge and experience accumulated through the voluntary breast unit certification programme, Eusoma has produced this up-dated and revised guidelines on the requirements of a Specialist Breast Centre (BC). Methods: The content of these guidelines is based on evidence from the recent relevant peer reviewed literature and the consensus of a multidisciplinary team of European experts. The guidelines define the requirements for each breast service and for the specialists who work in specialist Breast Centres. Results: The guidelines identify the minimum requirements needed to set up a BC, these being an integrated Breast Centre, dealing with a sufficient number of cases to allow effective working and continuing expertise, dedicated specialists working with a multidisciplinary approach, providing all services throughout the patients pathway and data collection and audit. It is essential that the BC also guarantees the continuity of care for patients with advanced (metastatic) disease offering treatments according to multidisciplinary competencies and a high quality palliative care service. The BC must ensure that comprehensive support and expertise may be needed, not only through the core BC team, but also ensure that all other medical and paramedical expertise that may be necessary depending on the individual case are freely available, referring the patient to the specific care provider depending on the problem. Conclusions: Applying minimum requirements and quality indicators is essential to improve organisation, performance and outcome in breast care. Efficacy and compliance have to be constantly monitored to evaluate the quality of patient care and to allow appropriate corrective actions leading to improvements in patient care. (C) 2013 Elsevier Ltd. All rights reserved.
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| 38. |
- Kok, Ellen M., et al.
(author)
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The effects of gaze-display feedback on medical students’ self-monitoring and learning in radiology
- 2024
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In: Advances in Health Sciences Education. - 1382-4996.
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Journal article (peer-reviewed)abstract
- Self-monitoring is essential for effectively regulating learning, but difficult in visual diagnostic tasks such as radiograph interpretation. Eye-tracking technology can visualize viewing behavior in gaze displays, thereby providing information about visual search and decision-making. We hypothesized that individually adaptive gaze-display feedback improves posttest performance and self-monitoring of medical students who learn to detect nodules in radiographs. We investigated the effects of: (1) Search displays, showing which part of the image was searched by the participant; and (2) Decision displays, showing which parts of the image received prolonged attention in 78 medical students. After a pretest and instruction, participants practiced identifying nodules in 16 cases under search-display, decision-display, or no feedback conditions (n = 26 per condition). A 10-case posttest, without feedback, was administered to assess learning outcomes. After each case, participants provided self-monitoring and confidence judgments. Afterward, participants reported on self-efficacy, perceived competence, feedback use, and perceived usefulness of the feedback. Bayesian analyses showed no benefits of gaze displays for post-test performance, monitoring accuracy (absolute difference between participants’ estimated and their actual test performance), completeness of viewing behavior, self-efficacy, and perceived competence. Participants receiving search-displays reported greater feedback utilization than participants receiving decision-displays, and also found the feedback more useful when the gaze data displayed was precise and accurate. As the completeness of search was not related to posttest performance, search displays might not have been sufficiently informative to improve self-monitoring. Information from decision displays was rarely used to inform self-monitoring. Further research should address if and when gaze displays can support learning.
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