| 1. |
- Caporale, N., et al.
(författare)
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From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6582
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Tidskriftsartikel (refereegranskat)abstract
- Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio, as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay. © 2022 American Association for the Advancement of Science. All rights reserved.
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| 2. |
- Agirre, J. A., et al.
(författare)
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The VALU3S ECSEL project : Verification and validation of automated systems safety and security
- 2021
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Ingår i: Microprocessors and microsystems. - : Elsevier BV. - 0141-9331 .- 1872-9436. ; 87, s. 104349-
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Tidskriftsartikel (refereegranskat)abstract
- Manufacturers of automated systems and their components have been allocating an enormous amount of time and effort in R&D activities, which led to the availability of prototypes demonstrating new capabilities as well as the introduction of such systems to the market within different domains. Manufacturers need to make sure that the systems function in the intended way and according to specifications. This is not a trivial task as system complexity rises dramatically the more integrated and interconnected these systems become with the addition of automated functionality and features to them. This effort translates into an overhead on the V&V (verification and validation) process making it time-consuming and costly. In this paper, we present VALU3S, an ECSEL JU (joint undertaking) project that aims to evaluate the state-of-the-art V&V methods and tools, and design a multi-domain framework to create a clear structure around the components and elements needed to conduct the V&V process. The main expected benefit of the framework is to reduce time and cost needed to verify and validate automated systems with respect to safety, cyber-security, and privacy requirements. This is done through identification and classification of evaluation methods, tools, environments and concepts for V&V of automated systems with respect to the mentioned requirements. VALU3S will provide guidelines to the V&V community including engineers and researchers on how the V&V of automated systems could be improved considering the cost, time and effort of conducting V&V processes. To this end, VALU3S brings together a consortium with partners from 10 different countries, amounting to a mix of 25 industrial partners, 6 leading research institutes, and 10 universities to reach the project goal.
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| 3. |
- Ambrosini, Valentina, et al.
(författare)
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Consensus on molecular imaging and theranostics in neuroendocrine neoplasms
- 2021
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 146, s. 56-73
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Forskningsöversikt (refereegranskat)abstract
- Nuclear medicine plays an increasingly important role in the management neuroendocrine neoplasms (NEN). Somatostatin analogue (SSA)-based positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT) have been used in clinical trials and approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). European Association of Nuclear Medicine (EANM) Focus 3 performed a multidisciplinary Delphi process to deliver a balanced perspective on molecular imaging and radionuclide therapy in well-differentiated neuroendocrine tumours (NETs). NETs form in cells that interact with the nervous system or in glands that produce hormones. These cells, called neuroendocrine cells, can be found throughout the body, but NETs are most often found in the abdomen, especially in the gastrointestinal tract. These tumours may also be found in the lungs, pancreas and adrenal glands. In addition to being rare, NETs are also complex and may be difficult to diagnose. Most NETs are non-functioning; however, a minority present with symptoms related to hypersecretion of bioactive compounds. NETs often do not cause symptoms early in the disease process. When diagnosed, substantial number of patients are already found to have metastatic disease. Several societies' guidelines address Neuroendocrine neoplasms (NENs) management; however, many issues are still debated, due to both the difficulty in acquiring strong clinical evidence in a rare and heterogeneous disease and the different availability of diagnostic and therapeutic options across countries. EANM Focus 3 reached consensus on employing 68gallium-labelled somatostatin analogue ([68Ga]Ga-DOTA-SSA)-based PET/CT with diagnostic CT or magnetic resonance imaging (MRI) for unknown primary NET detection, metastatic NET, NET staging/restaging, suspected extra-adrenal pheochromocytoma/paraganglioma and suspected paraganglioma. Consensus was reached on employing 18fluorine-fluoro-2-deoxyglucose ([18F]FDG) PET/CT in neuroendocrine carcinoma, G3 NET and in G1-2 NET with mismatched lesions (CT-positive/[68Ga]Ga-DOTA-SSA-negative). Peptide receptor radionuclide therapy (PRRT) was recommended for second line treatment for gastrointestinal NET with [68Ga]Ga-DOTA-SSA uptake in all lesions, in G1/G2 NET at disease progression, and in a subset of G3 NET provided all lesions are positive at [18F]FDG and [68Ga]Ga-DOTA-SSA. PRRT rechallenge may be used for in patients with stable disease for at least 1 year after therapy completion. An international consensus is not only a prelude to a more standardised management across countries but also serves as a guide for the direction to follow when designing new research studies.
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| 4. |
- Boström, Adrian Desai E., et al.
(författare)
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HPA-axis dysregulation is not associated with accelerated epigenetic aging in patients with hypersexual disorder
- 2022
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Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 141
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHypersexual disorder (HD) - a nonparaphilic sexual desire disorder with impulsivity component - was evaluated for inclusion as a diagnosis in the DSM-5 and the diagnosis compulsive sexual behavior disorder is included as an impulse control disorder in the ICD-11. Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity is believed to affect cellular senescence and has been implicated in HD. No previous study investigated HD or HPA-axis dysregulation in relation to measures of epigenetic age (EA) acceleration.MethodsThis study reports on a case-control study set-up from a well-characterized cohort, contrasting EA predictors in relation to 60 HD patients and 33 healthy volunteers (HV) and 19 mixed HD/HV exhibiting dexamethasone suppression test (DST) non-suppression to 73 mixed HD/HV DST controls. The genome-wide methylation pattern was measured in whole blood from 94 subjects using the Illumina Infinium Methylation EPIC BeadChip and preprocessed according to specialized protocols suitable for epigenetic age estimation. The online DNAm Age Calculator (https://dnamage.genetics.ucla.edu/) was implemented to retrieve various EA predictors, which were compared between the in-silico generated subgroups.ResultsQuality control analyses indicated strong correlations between the EA measure DNA methylation GrimAge (DNAm GrimAge – the EA clock most reliably associated with mortality risk) and chronological age in all sub-groups. The study was adequately powered to detect differences of 2.5 and 3.0 years in DNAm GrimAge minus age in relation to both HD and HPA-axis dysregulation, respectively. Baseline DNAm GrimAge exceeded chronological age by 2.8 years on average across all samples. No EA acceleration marker was associated with HD or DST suppression status (p > 0.05).ConclusionEA acceleration markers shown to be strongly predictive of physiological dysregulation and mortality-risk, are not related to HD or DST non-suppression status (measured after 0.5 mg dexamethasone). The independency of HPA-axis dysregulation to EA acceleration does not support the biological relevance of this dosage-regimen when applied to patients with HD. These findings do not support the notion of accelerated cellular senescence in HD. Studies stratifying DST non-suppressors according to established dosage-regimens in somatic settings are needed to fully elucidate the putative contribution of HPA-axis dysregulation to EA.
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| 5. |
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| 6. |
- Drakvik, E., et al.
(författare)
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Statement on advancing the assessment of chemical mixtures and their risks for human health and the environment
- 2020
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 134
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Tidskriftsartikel (refereegranskat)abstract
- The number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife are exposed to complex mixtures, never one chemical at a time and rarely with only one dominating effect. Hence there is an urgent need to develop strategies on how exposure to multiple hazardous chemicals and the combination of their effects can be assessed. A workshop, “Advancing the Assessment of Chemical Mixtures and their Risks for Human Health and the Environment” was organized in May 2018 together with Joint Research Center in Ispra, EU-funded research projects and Commission Services and relevant EU agencies. This forum for researchers and policy-makers was created to discuss and identify gaps in risk assessment and governance of chemical mixtures as well as to discuss state of the art science and future research needs. Based on the presentations and discussions at this workshop we want to bring forward the following Key Messages: • We are at a turning point: multiple exposures and their combined effects require better management to protect public health and the environment from hazardous chemical mixtures. • Regulatory initiatives should be launched to investigate the opportunities for all relevant regulatory frameworks to include prospective mixture risk assessment and consider combined exposures to (real-life) chemical mixtures to humans and wildlife, across sectors. • Precautionary approaches and intermediate measures (e.g. Mixture Assessment Factor) can already be applied, although, definitive mixture risk assessments cannot be routinely conducted due to significant knowledge and data gaps. • A European strategy needs to be set, through stakeholder engagement, for the governance of combined exposure to multiple chemicals and mixtures. The strategy would include research aimed at scientific advancement in mechanistic understanding and modelling techniques, as well as research to address regulatory and policy needs. Without such a clear strategy, specific objectives and common priorities, research, and policies to address mixtures will likely remain scattered and insufficient. © 2019 The Authors
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| 7. |
- Einig, Lucas, et al.
(författare)
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Deep learning denoising by dimension reduction: Application to the ORION-B line cubes
- 2023
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 677
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Tidskriftsartikel (refereegranskat)abstract
- Context. The availability of large bandwidth receivers for millimeter radio telescopes allows for the acquisition of position-position-frequency data cubes over a wide field of view and a broad frequency coverage. These cubes contain a lot of information on the physical, chemical, and kinematical properties of the emitting gas. However, their large size coupled with an inhomogenous signal-to-noise ratio (S/N) are major challenges for consistent analysis and interpretation. Aims. We searched for a denoising method of the low S/N regions of the studied data cubes that would allow the low S/N emission to be recovered without distorting the signals with a high S/N. Methods. We performed an in-depth data analysis of the 13CO and C17O (1-0) data cubes obtained as part of the ORION-B large program performed at the IRAM 30 m telescope. We analyzed the statistical properties of the noise and the evolution of the correlation of the signal in a given frequency channel with that of the adjacent channels. This has allowed us to propose significant improvements of typical autoassociative neural networks, often used to denoise hyperspectral Earth remote sensing data. Applying this method to the 13CO (1-0) cube, we were able to compare the denoised data with those derived with the multiple Gaussian fitting algorithm ROHSA, considered as the state-of-the-art procedure for data line cubes. Results. The nature of astronomical spectral data cubes is distinct from that of the hyperspectral data usually studied in the Earth remote sensing literature because the observed intensities become statistically independent beyond a short channel separation. This lack of redundancy in data has led us to adapt the method, notably by taking into account the sparsity of the signal along the spectral axis. The application of the proposed algorithm leads to an increase in the S/N in voxels with a weak signal, while preserving the spectral shape of the data in high S/N voxels. Conclusions. The proposed algorithm that combines a detailed analysis of the noise statistics with an innovative autoencoder architecture is a promising path to denoise radio-astronomy line data cubes. In the future, exploring whether a better use of the spatial correlations of the noise may further improve the denoising performances seems to be a promising avenue. In addition, dealing with the multiplicative noise associated with the calibration uncertainty at high S/N would also be beneficial for such large data cubes.
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| 8. |
- Ericson Öberg, Anna, et al.
(författare)
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Diagnostics of opportunities : A dialogue tool for addressing digital factory maturity
- 2024
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Ingår i: Advances in Transdisciplinary Engineering. - Amsterdam : IOS Press. - 9781643685106 - 9781643685113 ; , s. 395-406
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- For over 15 years, the concept of Industry 4.0, now transitioning into Industry 5.0, has been a focal point for the manufacturing sector. Yet, the success of companies in embracing digital transformation varies. There are numerous models and assessment tools for assessing digital readiness and maturity. Several models have been developed over the years, but firms also realize no “one-size-fits-all” exists when testing them. Previous studies show that firms must take charge of their own digital transformation (DT) journey to find a path that suits their specific needs.This qualitative paper is driven by a case study supported by a within-case analysis conducted with a heavy-machine industry with fourteen production plants worldwide – data collected from 2020 to 2023.Volvo Construction Equipment (Volvo CE), created Factory 4 Tomorrow (F4T) to address Industry 4.0. The central challenge for the F4T initiative was how to facilitate an inside-outside approach to identify an inclusive maturity model that emphasizes learning and collaboration. A diagnostic of opportunities model was created to aid the organisation’s transformation journey. It aimed to support all plants by evaluating their maturity in digital transformation, identifying gaps, and support in prioritising. Unlike traditional models that assess and compare plant levels, this model aimed to foster awareness and alignment, establishing a shared language. Thus, a unique model was explicitly crafted for the firm. The process of developing the model itself enhanced awareness and alignment. Therefore, this paper explores the development process - failures and successes - to compile a digital transformation maturity model tailor-made to a firm’s needs and goals. The objective is to offer comprehensive advice for firms to implement DT initiatives effectively in a way that suits them.
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| 9. |
- Ericson Öberg, A., et al.
(författare)
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Diagnostics of Opportunities : A Dialogue Tool for Addressing Digital Factory Maturity
- 2024
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Ingår i: Advances in Transdisciplinary Engineering. - Amsterdam : IOS Press BV. - 9781643685106 - 9781643685113 ; , s. 395-406
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Konferensbidrag (refereegranskat)abstract
- For over 15 years, the concept of Industry 4.0, now transitioning into Industry 5.0, has been a focal point for the manufacturing sector. Yet, the success of companies in embracing digital transformation varies. There are numerous models and assessment tools for assessing digital readiness and maturity. Several models have been developed over the years, but firms also realize no "one-size-fits-all" exists when testing them. Previous studies show that firms must take charge of their own digital transformation (DT) journey to find a path that suits their specific needs.This qualitative paper is driven by a case study supported by a within-case analysis conducted with a heavy-machine industry with fourteen production plants worldwide – data collected from 2020 to 2023. Volvo Construction Equipment (Volvo CE), created Factory 4 Tomorrow (F4T) to address Industry 4.0. The central challenge for the F4T initiative was how to facilitate an inside-outside approach to identify an inclusive maturity model that emphasizes learning and collaboration. A diagnostic of opportunities model was created to aid the organisation’s transformation journey. It aimed to support all plants by evaluating their maturity in digital transformation, identifying gaps, and support in prioritising. Unlike traditional models that assess and compare plant levels, this model aimed to foster awareness and alignment, establishing a shared language. Thus, a unique model was explicitly crafted for the firm. The process of developing the model itself enhanced awareness and alignment. Therefore, this paper explores the development process - failures and successes - to compile a digital transformation maturity model tailor-made to a firm's needs and goals. The objective is to offer comprehensive advice for firms to implement DT initiatives effectively in a way that suits them.
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| 10. |
- Ericson Öberg, Anna, et al.
(författare)
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Diagnostics of Opportunities – A Dialogue Tool for Addressing Digital Factory Maturity
- 2024
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Ingår i: Sustainable Production through Advanced Manufacturing, Intelligent Automation andWork Integrated Learning. - Amsterdam : IOS Press. - 9781643685106 - 9781643685113 ; , s. 395-406
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Konferensbidrag (refereegranskat)abstract
- For over 15 years, the concept of Industry 4.0, now transitioning into Industry 5.0, has been a focal point for the manufacturing sector. Yet, the success of companies in embracing digital transformation varies. There are numerous models and assessment tools for assessing digital readiness and maturity. Several models have been developed over the years, but firms also realize no "one-size-fits-all" exists when testing them. Previous studies show that firms must take charge of their own digital transformation (DT) journey to find a path that suits their specific needs.This qualitative paper is driven by a case study supported by a within-case analysis conducted with a heavy-machine industry with fourteen production plants worldwide – data collected from 2020 to 2023. Volvo Construction Equipment (Volvo CE), created Factory 4 Tomorrow (F4T) to address Industry 4.0. The central challenge for the F4T initiative was how to facilitate an inside-outside approach to identify an inclusive maturity model that emphasizes learning and collaboration. A diagnostic of opportunities model was created to aid the organisation’s transformation journey. It aimed to support all plants by evaluating their maturity in digital transformation, identifying gaps, and support in prioritising. Unlike traditional models that assess and compare plant levels, this model aimed to foster awareness and alignment, establishing a shared language. Thus, a unique model was explicitly crafted for the firm. The process of developing the model itself enhanced awareness and alignment. Therefore, this paper explores the development process - failures and successes - to compile a digital transformation maturity model tailor-made to a firm’s needs and goals. The objective is to offer comprehensive advice for firms to implement DT initiatives effectively in a way that suits them.
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