| 1. |
- Bach, Dominik R., et al.
(author)
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Human Hippocampus Arbitrates Approach-Avoidance Conflict
- 2014
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In: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 24:5, s. 541-547
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Journal article (peer-reviewed)abstract
- Animal models of human anxiety often invoke a conflict between approach and avoidance [1, 2]. In these, a key behavioral assay comprises passive avoidance of potential threat and inhibition, both thought to be controlled by ventral hippocampus [2-6]. Efforts to translate these approaches to clinical contexts [7, 8] are hampered by the fact that it is not known whether humans manifest analogous approach-avoidance dispositions and, if so, whether they share a homologous neurobiological substrate [9]. Here, we developed a paradigm to investigate the role of human hippocampus in arbitrating an approach-avoidance conflict under varying levels of potential threat. Across four experiments, subjects showed analogous behavior by adapting both passive avoidance behavior and behavioral inhibition to threat level. Using functional magnetic resonance imaging (fMRI), we observe that threat level engages the anterior hippocampus, the human homolog of rodent ventral hippocampus [10]. Testing patients with selective hippocampal lesions, we demonstrate a causal role for the hippocampus with patients showing reduced passive avoidance behavior and inhibition across all threat levels. Our data provide the first human assay for approach-avoidance conflict akin to that of animal anxiety models. The findings bridge rodent and human research on passive avoidance and behavioral inhibition and furnish a framework for addressing the neuronal underpinnings of human anxiety disorders, where our data indicate a major role for the hippocampus.
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| 2. |
- Jussila, Miro-Pekka, et al.
(author)
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Late vertebral side effects in long-term survivors of irradiated childhood brain tumor
- 2018
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:12
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Journal article (peer-reviewed)abstract
- Purpose: Long-term side effects of the treatments are common in survivors of irradiated pediatric brain tumors. Ionizing radiation in combination with surgery and chemotherapy during childhood may reduce vertebral height and bone mineral density (BMD), and cause growth failure. The aim of this study was to evaluate the late consequences of tumor treatments on vertebrae in survivors of childhood brain tumors.Methods: 72 adult survivors (mean age 27.8 years, standard deviation 6.7) of irradiated childhood brain tumor were studied by spinal magnetic resonance imaging (MRI) for vertebral abnormalities from the national cohort of Finland. Patients were treated in five university hospitals in Finland between the years 1970 and 2008. Subject height and weight were measured and body mass index (BMI) was calculated. The morphology and height/ depth ratio of the vertebrae in the middle of the kyphotic thoracic curvature (Th8) and lumbar lordosis (L3) were examined. Vertebrae were analyzed by Genant's semiquantative (SQ) method and spinal deformity index (SDI) was calculated. BMD was measured by using dual X-ray absorptiometry.Results: 4.2% (3/72) of the patients had undiagnosed asymptomatic vertebral fracture and 5.6% (4/72) of patients had radiation- induced decreased vertebral body height. Male patients had flatter vertebrae compared with females. Patient age at the time of irradiation, BMI and irradiation area correlated to vertebral morphology differentially in males and females. BMD had no association with the vertebral shape. Patients who had received craniospinal irradiation were shorter than the general population.Conclusion: Childhood brain tumor survivors had a high number of vertebral abnormalities in young adulthood. Irradiation was associated with abnormal vertebral morphology and compromised final height. Male gender may predispose vertebrae to the side effects of irradiation.
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| 3. |
- Proenza, Julian, et al.
(author)
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Managing Redundancy in CAN-based Networks Supporting N-Version Programming
- 2009
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In: Computer Standards & Interfaces. - : Elsevier BV. - 0920-5489 .- 1872-7018. ; 31:1, s. 120-127
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Journal article (peer-reviewed)abstract
- Software is a major source of reliability degradation in dependable systems. One of the classical remedies is to provide software fault tolerance by using N-Version Programming (NVP). However, due to requirements on non-standard hardware and the need for changes and additions at all levels of the system, NVP solutions are costly, and have only been used in special cases. In a previous work, a low-cost architecture for NVP execution was developed. The key features of this architecture are the use of off-the-shelf components including communication standards and that the fault tolerance functionality, including voting, error detection, fault-masking, consistency management, and recovery, is moved into a separate redundancy management circuitry (one for each redundant computing node). In this article we present an improved design of that architecture, specifically resolving some potential inconsistencies that were not treated in detail in the original design. In particular, we present novel techniques for enforcing replica determinism. Our improved architecture is based on using the Controller Area Network (CAN). This choice goes beyond the obvious interest of using standards in order to reduce the cost, since all the rest of the architecture is designed to take full advantage of the CAN standard features, such as data consistency, in order to significantly reduce the complexity, the efficiency and the cost of the resultant system. Although initially developed for NVP, our redundancy management circuitry also supports other software replication techniques, such as active replication.
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| 4. |
- Proenza, Julian, et al.
(author)
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Redundancy Management in a Low-Cost Distributed Hardware and Firmware Support for Software-Fault Tolerance
- 2007
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Reports (other academic/artistic)abstract
- Software is a major source of reliability degradation in dependable systems.One of the classical remedies is to provide software fault-tolerance by using NVersionProgramming (NVP). However, due to requirements on special hardwareand the need for changes and additions at all levels of the system, NVP solutionsare costly, and have only been used in special cases.In a previous work, a low-cost architecture for NVP execution was developed.The key features of this architecture are the use of off-the-shelf componentsand that the fault-tolerance functionality, including voting, error detection,fault-masking, consistency management, and recovery, is moved into a separateredundancy management circuitry (one for each redundant computing node).In this article we present an improved design of that architecture, specificallyresolving some potential inconsistencies that were not treated in detail in the originaldesign. In particular, we present novel techniques for enforcing replica determinismand a method for reintegration of the redundancy management circuitryafter a transient failure.Our improved architecture is based on using the Controller Area Network(CAN). This has several benefits, including low-cost, and that the CAN data consistencyallows us to simplify the mechanisms for replica determinism and reintegration.Although initially developed for NVP, our redundancy management circuitryalso supports other software replication techniques, such as active replication.
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| 5. |
- Spierings, Julia, et al.
(author)
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A randomised, open-label trial to assess the optimal treatment strategy in early diffuse cutaneous systemic sclerosis : The UPSIDE study protocol
- 2021
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In: BMJ Open. - : BMJ. - 2044-6055. ; 11:3
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Journal article (peer-reviewed)abstract
- Introduction Systemic sclerosis (SSc) is a chronic, autoimmune connective tissue disease associated with high morbidity and mortality, especially in diffuse cutaneous SSc (dcSSc). Currently, there are several treatments available in early dcSSc that aim to change the disease course, including immunosuppressive agents and autologous haematopoietic stem cell transplantation (HSCT). HSCT has been adopted in international guidelines and is offered in current clinical care. However, optimal timing and patient selection for HSCT are still unclear. In particular, it is unclear whether HSCT should be positioned as upfront therapy or rescue treatment for patients refractory to immunosuppressive therapy. We hypothesise that upfront HSCT is superior and results in lower toxicity and lower long-term medical costs. Therefore, we propose this randomised trial aiming to determine the optimal treatment strategy for early dcSSc by comparing two strategies used in standard care: (1) upfront autologous HSCT versus (2) immunosuppressive therapy (intravenous cyclophosphamide pulse therapy followed by mycophenolate mofetil) with rescue HSCT in case of treatment failure. Methods and analysis The UPSIDE (UPfront autologous hematopoietic Stem cell transplantation vs Immunosuppressive medication in early DiffusE cutaneous systemic sclerosis) study is a multicentre, randomised, open-label, controlled trial. In total, 120 patients with early dcSSc will be randomised. The primary outcome is event-free survival at 2 years after randomisation. Secondary outcomes include serious adverse events, functional status and health-related quality of life. We will also evaluate changes in nailfold capillaroscopy pattern, pulmonary function, cardiac MR and high-resolution CT of the chest. Follow-up visits will be scheduled 3-monthly for 2 years and annually in the following 3 years. Ethics and dissemination The study was approved by the Dutch Central Committee on Research Concerning Human Subjects (NL72607.041.20). The results will be disseminated through patient associations and conventional scientific channels. Trial registration numbers NCT04464434; NL 8720.
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