| 31. |
- Kaaks, Rudolf, et al.
(author)
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Tumor-associated autoantibodies as early detection markers for ovarian cancer? : A prospective evaluation
- 2018
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In: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 143:3, s. 515-526
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Journal article (peer-reviewed)abstract
- Immuno-proteomic screening has identified several tumor-associated autoantibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer-testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs has been insufficiently explored in prospective studies. We performed ELISA measurements of AAbs to CTAG1A, CTAG2, P53 and NUDT11 proteins, for 194 patients with ovarian cancer and 705 matched controls from the European EPIC cohort, using serum samples collected up to 36 months prior to diagnosis under usual care. CA125 was measured using electrochemo-luminiscence. Diagnostic discrimination statistics were calculated by strata of lead-time between blood collection and diagnosis. With lead times 6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 [95% CI 0.08-0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10-0.44] for P53 (0.33 [0.11-0.68] for high-grade serous tumors). However, at longer lead-times, the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all invasive cases, range: 0.01-0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and CA125 did not improve detection sensitivity at equal level of specificity. The added value of these selected AAbs as markers for ovarian cancer beyond CA125 for early detection is therefore limited. What's new? Could autoantibodies against tumor antigens provide an early warning system for ovarian cancer? These authors tested how well certain antibodies detected ovarian cancer. They selected four candidate antibodies, to p53, CTAG1A, CTAG2 and NUDT11 proteins, which appear in elevated levels in cancer patients. None of them performed well as a herald of burgeoning cancer. They did not perform any better than the best currently available biomarker, CA125, and as lead times increased past 6 months prediagnosis, the effectiveness diminished. Surprisingly, elevated antibodies appeared in quite a few of the control samples, suggesting they might not be as cancer-specific as expected.
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| 32. |
- Larigauderie, Anne, et al.
(author)
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Biodiversity and ecosystem services science for a sustainable planet : the DIVERSITAS vision for 2012-20
- 2012
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In: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 4:1, s. 101-105
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Journal article (peer-reviewed)abstract
- DIVERSITAS, the international programme on biodiversity science, is releasing a strategic vision presenting scientific challenges for the next decade of research on biodiversity and ecosystem services: Biodiversity and Ecosystem Services Science for a Sustainable Planet. This new vision is a response of the biodiversity and ecosystem services scientific community to the accelerating loss of the components of biodiversity, as well as to changes in the biodiversity science-policy landscape (establishment of a Biodiversity Observing Network - GEO BON, of an Intergovernmental science-policy Platform on Biodiversity and Ecosystem Services - IPBES, of the new Future Earth initiative; and release of the Strategic Plan for Biodiversity 2011-2020). This article presents the vision and its core scientific challenges.
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| 33. |
- Manning, Alisa, et al.
(author)
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A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
- 2017
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In: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
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Journal article (peer-reviewed)abstract
- To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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| 34. |
- Mehta, Raghav, et al.
(author)
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QU-BraTS : MICCAI BraTS 2020 Challenge on QuantifyingUncertainty in Brain Tumor Segmentation - Analysis of Ranking Scores and Benchmarking Results
- 2022
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In: Journal of Machine Learning for Biomedical Imaging. - 2766-905X. ; , s. 1-54
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Journal article (peer-reviewed)abstract
- Deep learning (DL) models have provided the state-of-the-art performance in a wide variety of medical imaging benchmarking challenges, including the Brain Tumor Segmentation (BraTS) challenges. However, the task of focal pathology multi-compartment segmentation (e.g., tumor and lesion sub-regions) is particularly challenging, and potential errors hinder the translation of DL models into clinical workflows. Quantifying the reliability of DL model predictions in the form of uncertainties, could enable clinical review of the most uncertain regions, thereby building trust and paving the way towards clinical translation. Recently, a number of uncertainty estimation methods have been introduced for DL medical image segmentation tasks. Developing scores to evaluate and compare the performance of uncertainty measures will assist the end-user in making more informed decisions. In this study, we explore and evaluate a score developed during the BraTS 2019-2020 task on uncertainty quantification (QU-BraTS), and designed to assess and rank uncertainty estimates for brain tumor multi-compartment segmentation. This score (1) rewards uncertainty estimates that produce high confidence in correct assertions, and those that assign low confidence levels at incorrect assertions, and (2) penalizes uncertainty measures that lead to a higher percentages of under-confident correct assertions. We further benchmark the segmentation uncertainties generated by 14 independent participating teams of QU-BraTS 2020, all of which also participated in the main BraTS segmentation task. Overall, our findings confirm the importance and complementary value that uncertainty estimates provide to segmentation algorithms, and hence highlight the need for uncertainty quantification in medical image analyses. Our evaluation code is made publicly available at https://github.com/RagMeh11/QU-BraTS
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| 35. |
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| 36. |
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| 37. |
- Peters, Susan, et al.
(author)
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Narrative review of occupational exposures and noncommunicable diseases
- 2024
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In: ANNALS OF WORK EXPOSURES AND HEALTH. - 2398-7308 .- 2398-7316. ; 68:6, s. 562-580
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Research review (peer-reviewed)abstract
- Objective Within the scope of the Exposome Project for Health and Occupational Research on applying the exposome concept to working life health, we aimed to provide a broad overview of the status of knowledge on occupational exposures and associated health effects across multiple noncommunicable diseases (NCDs) to help inform research priorities.Methods We conducted a narrative review of occupational risk factors that can be considered to have "consistent evidence for an association," or where there is "limited/inadequate evidence for an association" for 6 NCD groups: nonmalignant respiratory diseases; neurodegenerative diseases; cardiovascular/metabolic diseases; mental disorders; musculoskeletal diseases; and cancer. The assessment was done in expert sessions, primarily based on systematic reviews, supplemented with narrative reviews, reports, and original studies. Subsequently, knowledge gaps were identified, e.g. based on missing information on exposure-response relationships, gender differences, critical time-windows, interactions, and inadequate study quality.Results We identified over 200 occupational exposures with consistent or limited/inadequate evidence for associations with one or more of 60+ NCDs. Various exposures were identified as possible risk factors for multiple outcomes. Examples are diesel engine exhaust and cadmium, with consistent evidence for lung cancer, but limited/inadequate evidence for other cancer sites, respiratory, neurodegenerative, and cardiovascular diseases. Other examples are physically heavy work, shift work, and decision latitude/job control. For associations with limited/inadequate evidence, new studies are needed to confirm the association. For risk factors with consistent evidence, improvements in study design, exposure assessment, and case definition could lead to a better understanding of the association and help inform health-based threshold levels.Conclusions By providing an overview of knowledge gaps in the associations between occupational exposures and their health effects, our narrative review will help setting priorities in occupational health research. Future epidemiological studies should prioritize to include large sample sizes, assess exposures prior to disease onset, and quantify exposures. Potential sources of biases and confounding need to be identified and accounted for in both original studies and systematic reviews.
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| 38. |
- Sandin, Ylva, et al.
(author)
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Design of Timber Buildings for Deconstruction and Reuse — Three methods and five case studies
- 2022
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Reports (other academic/artistic)abstract
- There is a need for a shift towards circular economy in the construction sector and design philosophies as Design for Deconstruction and Reuse (DfDR) and Design for Adaptability (DfA) are being developed as means to design out waste and enhance resource efficiency. However, applying these philosophies is not yet common practice. The amount of DfDR/A timber buildings described in literature is limited. This study aims at increasing and spreading knowledge on DfDR/A for timber buildings. It has four goals: 1) To suggest methods to apply DfDR/A. 2) To suggest new design solutions. 3) To collect experiences on connections in relation to DfDR. 4) To suggest how guidelines for deconstruction and reuse can be formulated. The study presents three methods that all proved valuable in applying DfDR/A: one discussion-based method to improve an already existing timber building design, one indicator system to assess the DfDR/A potential of building designs, and one matrix to guide design decisions. We used the first method to conduct five case studies in four European countries. The studied designs were judged to be well or relatively well adapted for deconstruction and reuse already today. The fact that the studied buildings are all offsite manufactured and of modular composition benefits the deconstruction process, partly because construction and deconstruction are similar processes so that the knowledge and infrastructure that companies have can be directly transferred to enable deconstruction and reuse. Where large modules can be recovered, the time and energy needed for deconstruction as well as the risk for damage will be reduced. Disadvantages to deconstruction and reuse identified were typically linked to the complexity of building modules and that individual components are not independent. This was reflected as irreversible or hidden connections, inaccessible services, interconnected layers of the structural modules and many different component sizes. One of the case study buildings, designed with mass timber panels, excelled in the simplicity and reduction of number of steps required for maximum material recovery. New designs suggested included making fasteners more accessible to deconstruction, avoiding letting sensitive materials as plastic foils and particle boards pass continuously over joints between elements, and (for cases where standard units are not already used) standardizing elements. One case suggested using solid wood components instead of engineered wood products to achieve durability. The study showed that simple changes in design can lead to an augmented reuse potential. Some of the new design solutions generated will be taken into production by the participating manufacturers. Insights on connections included recognizing the fact that the use of reversible screwed connections is not sufficient to ensure deconstructability and that although nailed or glued connections severely complicate reuse of components, they might be accepted within elements in case reuse on element level is the target. Guidelines for deconstruction and reuse were developed in all case studies. Taken as a group of studies, there are advantageous additions proposed to earlier guidance documents. Despite being based on the same source, the different plans suggested varied substantially. There was a noteworthy difference between manufacturers’ in-house plans to those proposed by architects, engineers, or researchers, which speaks to the uncertainty regarding the appropriate structure and format.
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| 39. |
- Sasamoto, Naoko, et al.
(author)
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Development and validation of circulating CA125 prediction models in postmenopausal women
- 2019
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In: Journal of Ovarian Research. - : BioMed Central (BMC). - 1757-2215. ; 12:1
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Journal article (peer-reviewed)abstract
- Background: Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker.Methods: We developed and validated linear and dichotomous (>= 35 U/mL) circulating CA125 prediction models in postmenopausal women without ovarian cancer who participated in one of five large population-based studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 26,981), European Prospective Investigation into Cancer and Nutrition (EPIC, n = 861), the Nurses' Health Studies (NHS/NHSII, n = 81), and the New England Case Control Study (NEC, n = 923). The prediction models were developed using stepwise regression in PLCO and validated in EPIC, NHS/NHSII and NEC. Result The linear CA125 prediction model, which included age, race, body mass index (BMI), smoking status and duration, parity, hysterectomy, age at menopause, and duration of hormone therapy (HT), explained 5% of the total variance of CA125. The correlation between measured and predicted CA125 was comparable in PLCO testing dataset (r = 0.18) and external validation datasets (r = 0.14). The dichotomous CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, time since menopause, and duration of HT with AUC of 0.64 in PLCO and 0.80 in validation dataset.Conclusions: The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening biomarker.
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| 40. |
- Sasamoto, Naoko, et al.
(author)
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Predicting Circulating CA125 Levels among Healthy Premenopausal Women
- 2019
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In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 28:6, s. 1076-1085
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Journal article (peer-reviewed)abstract
- Background: Cancer antigen 125 (CA125) is the most promising ovarian cancer screening biomarker to date. Multiple studies reported CA125 levels vary by personal characteristics, which could inform personalized CA125 thresholds. However, this has not been well described in premenopausal women. Methods: We evaluated predictors of CA125 levels among 815 premenopausal women from the New England Case Control Study (NEC). We developed linear and dichotomous (>= 35 U/mL) CA125 prediction models and externally validated an abridged model restricting to available predictors among 473 premenopausal women in the European Prospective Investigation into Cancer and Nutrition Study (EPIC). Results: The final linear CA125 prediction model included age, race, tubal ligation, endometriosis, menstrual phase at blood draw, and fibroids, which explained 7% of the total variance of CA125. The correlation between observed and predicted CA125 levels based on the abridged model (including age, race, and menstrual phase at blood draw) had similar correlation coefficients in NEC (r = 0.22) and in EPIC (r = 0.22). The dichotomous CA125 prediction model included age, tubal ligation, endometriosis, prior personal cancer diagnosis, family history of ovarian cancer, number of miscarriages, menstrual phase at blood draw, and smoking status with AUC of 0.83. The abridged dichotomous model (including age, number of miscarriages, menstrual phase at blood draw, and smoking status) showed similar AUCs in NEC (0.73) and in EPIC (0.78). Conclusions: We identified a combination of factors associated with CA125 levels in premenopausal women. Impact: Our model could be valuable in identifying healthy women likely to have elevated CA125 and consequently improve its specificity for ovarian cancer screening.
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