| 1. |
- Abella, J., et al.
(author)
-
SAFEXPLAIN : Safe and Explainable Critical Embedded Systems Based on AI
- 2023
-
In: Proceedings -Design, Automation and Test in Europe, DATE. - : Institute of Electrical and Electronics Engineers Inc.. - 9783981926378
-
Conference paper (peer-reviewed)abstract
- Deep Learning (DL) techniques are at the heart of most future advanced software functions in Critical Autonomous AI-based Systems (CAIS), where they also represent a major competitive factor. Hence, the economic success of CAIS industries (e.g., automotive, space, railway) depends on their ability to design, implement, qualify, and certify DL-based software products under bounded effort/cost. However, there is a fundamental gap between Functional Safety (FUSA) requirements on CAIS and the nature of DL solutions. This gap stems from the development process of DL libraries and affects high-level safety concepts such as (1) explainability and traceability, (2) suitability for varying safety requirements, (3) FUSA-compliant implementations, and (4) real-time constraints. As a matter of fact, the data-dependent and stochastic nature of DL algorithms clashes with current FUSA practice, which instead builds on deterministic, verifiable, and pass/fail test-based software. The SAFEXPLAIN project tackles these challenges and targets by providing a flexible approach to allow the certification - hence adoption - of DL-based solutions in CAIS building on: (1) DL solutions that provide end-to-end traceability, with specific approaches to explain whether predictions can be trusted and strategies to reach (and prove) correct operation, in accordance to certification standards; (2) alternative and increasingly sophisticated design safety patterns for DL with varying criticality and fault tolerance requirements; (3) DL library implementations that adhere to safety requirements; and (4) computing platform configurations, to regain determinism, and probabilistic timing analyses, to handle the remaining non-determinism.
|
|
| 2. |
|
|
| 3. |
- Watt, F. E., et al.
(author)
-
Towards prevention of post-traumatic osteoarthritis : report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury
- 2019
-
In: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 27:1, s. 23-33
-
Journal article (peer-reviewed)abstract
- Objective: There are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury. Design: An evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors. Results: The evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventions. Considerations were grouped into three areas: justification of inclusion criteria including the classification of injury and participant age (as people over 35 may have pre-existing OA); careful consideration in the selection and timing of outcomes or biomarkers; definition of the intervention(s)/comparator(s) and the appropriate time-window for intervention (considerations may be particular to intervention type). Areas for further research included demonstrating the utility of patient-reported outcomes, biomarkers and imaging outcomes from ancillary/cohort studies in this area, and development of surrogate clinical trial endpoints that shorten the duration of clinical trials and are acceptable to regulatory agencies. Conclusions: These considerations represent the first international consensus on the conduct of interventional studies following acute knee joint trauma.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Longinetti, E, et al.
(author)
-
Risk of depression in multiple sclerosis across disease-modifying therapies
- 2022
-
In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 28:4, s. 632-641
-
Journal article (peer-reviewed)abstract
- Depression and use of antidepressants are more common among patients with multiple sclerosis (MS) compared to the general population, but the relation of psychiatric comorbidity to use of different disease-modifying therapies (DMTs) is less clear. Objective: To determine whether risk of incident depression or antidepressant use differed across DMTs, and to assess whether depression and antidepressants affected risk of DMT discontinuation and MS relapses. Methods: We prospectively followed for 8 years a register-based nationwide cohort of 3803 relapsing-remitting MS patients. Results: Patients on rituximab had a lower risk of being diagnosed with depression or initiating antidepressants compared with the reference group treated with interferons (hazard ratio (HR) = 0.72, 95% confidence interval (CI) = 0.54–0.96). Patients diagnosed with depression discontinued interferon treatment to a higher extent than patients without depression (HR = 1.51; 95% CI = 1.15–1.98), as did patients on fingolimod initiating an antidepressant compared to patients who did not initiate an antidepressant (HR = 1.47; 95% CI = 1.04–2.08). Conclusions: Our results indicate that the choice of DMT is associated with subsequent risk of depression in MS, but further studies are needed to establish whether there is a causal link. Overall, depression and use of antidepressants displayed limited associations with DMT discontinuation and MS relapse.
|
|
| 7. |
- Marcussen, A B, et al.
(author)
-
Increase in neurogenesis and behavioural benefit after chronic fluoxetine treatment in Wistar rats
- 2008
-
In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 117:2, s. 94-100
-
Journal article (peer-reviewed)abstract
- Objective - Disturbances in hippocampal neurogenesis may be involved in the pathophysiology of depression and it has been argued that an increase in the generation of new nerve cells in the hippocampus is involved in the mechanism of action of antidepressants. Materials and Methods - Adult Wistar rats were treated with fluoxetine (10 mg/kg) 1 h, daily for 5 (subchronic) or 28 days (chronic) before the Novelty Suppressed Feeding test was performed. Cell proliferation and neurogenesis were analysed using the markers 5-bromo-deoxy-2'-uridine, Ki-67, and doublecortin. Results - A significant behavioural effect was found after 28 days of fluoxetine administration. However, no behavioural improvement was demonstrated after acute and subchronic treatment with fluoxetine. We further demonstrate that chronic antidepressant treatment increases cell proliferation as well as neurogenesis in the dentate gyrus, here using Wistar rats. Conclusions - In further development of antidepressants, neurogenesis may serve as an important parameter to examine the efficacy and mechanism of action of novel drugs.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Svensson, F., et al.
(author)
-
Scrutinizing the cut-off for “pathological” meniscal body extrusion on knee MRI
- 2019
-
In: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 29:5, s. 2616-2623
-
Journal article (peer-reviewed)abstract
- Objectives: Medial meniscal body extrusion ≥ 3 mm on MRI is often considered “pathologic.” The aims of this study were to (1) assess the adequacy of 3 mm as cut-off for “pathological” extrusion and (2) find an optimal cut-off for meniscal extrusion cross-sectionally associated with radiographic knee osteoarthritis, bone marrow lesions (BMLs), and cartilage damage. Methods: Nine hundred fifty-eight persons, aged 50–90 years from Framingham, MA, USA, had readable 1.5 T MRI scans of the right knee for meniscal body extrusion (measured in mm). BMLs and cartilage damage were read using the whole organ magnetic resonance imaging score (WORMS). Knee X-rays were read according to the Kellgren and Lawrence (KL) scale. We evaluated the performance of the 3-mm cut-off with respect to the three outcomes and estimated a new cut-off maximizing the sum of sensitivity and specificity. Results: The study persons had mean age of 62.2 years, 57.0% were women and the mean body mass index was 28.5 kg/m2. Knees with radiographic osteoarthritis, BMLs, and cartilage damage had overall more meniscal extrusion than knees without. The 3-mm cut-off had moderate sensitivity and low specificity for all three outcomes (sensitivity between 0.68 [95% CI 0.63–0.73] and 0.81 [0.73–0.87], specificity between 0.49 [0.45–0.52] and 0.54 [0.49–0.58]). Using 4 mm maximized the sum of sensitivity and specificity and improved the percentage of correctly classified subjects (from between 54 and 61% to between 64 and 79%). Conclusions: The 4-mm cut-off may be used as an alternative cut-off for denoting pathological meniscal extrusion. Key Points: • Medial meniscal body extrusion is strongly associated with osteoarthritis. • The 3-mm cut-off for medial meniscal body extrusion has high sensitivity but low specificity with respect to bone marrow lesions, cartilage damage, and radiographic osteoarthritis. • The 4-mm cut-off maximizes the sensitivity and specificity with respect to all three osteoarthritis features.
|
|
