Visual scanning training dans la récupération fonctionnelle du patient héminégligent: travail de Bachelor

Introduction : La récupération fonctionnelle chez les patients hémiplégiques est retardée de façon importante par la présence d’héminégligence. Le Visual scanning training (VST) est une thérapie de l’héminégligence qui a vu le jour dans les années 70. Dès lors, l’effet de cette thérapie a souvent été étudié. Objectif : Evaluer l’effet du Visual scanning training seul ou combiné à un autre traitement comparé à un traitement standard sur l’amélioration de l’indépendance fonctionnelle chez les patients présentant une héminégligence. Méthodologie : Nous avons effectué nos recherches sur les bases de données Kinédoc, PEDro et Pubmed. Nous avons sélectionné des études randomisées contrôlées qui évaluaient l’effet du Visual scanning training seul ou combiné, comparé à un autre traitement standard chez des patients avec une lésion de l’hémisphère droit. Seules les études qui utilisaient le protocole de traitement selon Pizzamiglio et qui évaluaient l’indépendance fonctionnelle ont été inclues. Résultats : Cinq articles ont rempli nos critères d’inclusion et d’exclusion. Tous sont en défaveur de l’efficacité du Visual scanning training par rapport à un autre traitement standard. Une étude souligne que le Visual scanning training couplé à un autre traitement n’a pas d’effet statistiquement significatif. Conclusion : Il existe de nombreux traitements pour l’héminégligence. Avec de futures recherches, le Visual scanning training seul ou combiné à une autre thérapie pourrait être une piste dans l’amélioration fonctionnelle des patients héminégligent

Modelling Wind Turbine Wakes at Middelgrunden Wind Farm

This is the author accepted manuscript. The final version is available from the publisher via the URL in this record.As part of the development of an offshore wind farm layout optimisation tool, this paper explores the accuracy and computational time of wake models applied to Middelgrunden Wind Farm outside of Copenhagen, Denmark. In this study, four years of data from 2001 to 2004 are used to test the applicability, accuracy, and computational time of the Jensen, Larsen, Ishihara, and a simplified version of the Ainslie Eddy-Viscosity wake models. This study has shown that the size of the directional sector used in the comparison and if that directional sector is applied to all turbines’ incoming wind velocities or just the northernmost greatly affects the results. From this it is found that the Larsen wake model provides the best balance between accuracy and computational time. It also shows that even a simplified version of a field model takes significantly longer to compute than an analytic model. This study has also shown that using directional sectors of ±15◦ these models perform similarly to previous studies at Nysted and Horns Rev indicating that the close spacing (2.4D) at Middelgrunden is not too close for the use of these models

Offshore Wind Farm Electrical Cable Layout Optimization

This is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this record.This article explores an automated approach for the efficient placement of substations and the design of an inter-array electrical collection network for an offshore wind farm through the minimization of the cost. To accomplish this, the problem is represented as a number of sub-problems that are solved in series using a combination of heuristic algorithms. The overall problem is first solved by clustering the turbines to generate valid substation positions. From this, a navigational mesh pathfinding algorithm based on Delaunay triangulation is applied to identify valid cable paths, which are then used in a mixed-integer linear programming problem to solve for a constrained capacitated minimum spanning tree considering all realistic constraints. The final tree that is produced represents the solution to the inter-array cable problem. This method is applied to a planned wind farm to illustrate the suitability of the approach and the resulting layout that is generated

Role of cellular senescence and NOX4-mediated oxidative stress in systemic sclerosis pathogenesis.

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and numerous internal organs and a severe fibroproliferative vasculopathy resulting frequently in severe disability and high mortality. Although the etiology of SSc is unknown and the detailed mechanisms responsible for the fibrotic process have not been fully elucidated, one important observation from a large US population study was the demonstration of a late onset of SSc with a peak incidence between 45 and 54 years of age in African-American females and between 65 and 74 years of age in white females. Although it is not appropriate to consider SSc as a disease of aging, the possibility that senescence changes in the cellular elements involved in its pathogenesis may play a role has not been thoroughly examined. The process of cellular senescence is extremely complex, and the mechanisms, molecular events, and signaling pathways involved have not been fully elucidated; however, there is strong evidence to support the concept that oxidative stress caused by the excessive generation of reactive oxygen species may be one important mechanism involved. On the other hand, numerous studies have implicated oxidative stress in SSc pathogenesis, thus, suggesting a plausible mechanism in which excessive oxidative stress induces cellular senescence and that the molecular events associated with this complex process play an important role in the fibrotic and fibroproliferative vasculopathy characteristic of SSc. Here, recent studies examining the role of cellular senescence and of oxidative stress in SSc pathogenesis will be reviewed

Increased expression of NAPDH oxidase 4 in systemic sclerosis dermal fibroblasts: regulation by transforming growth factor β.

OBJECTIVE: Systemic sclerosis (SSc) is characterized by severe and often progressive fibrosis of the skin and multiple internal organs. The mechanisms responsible for these alterations remain obscure, although excessive reactive oxygen species (ROS)-mediated oxidative stress has been implicated. NOX-4 is 1 of 7 isoforms of NADPH oxidase responsible for the generation of ROS. The purpose of this study was to examine NOX-4 expression in skin and cultured dermal fibroblasts from SSc patients and to examine its regulation by transforming growth factor β1 (TGFβ1). METHODS: NOX-4 was assessed in normal and SSc skin by immunohistologic analysis and in normal and SSc cultured dermal fibroblasts by quantitative polymerase chain reaction analysis, fluorescence microscopy, and Western blotting. ROS levels were assessed by fluorescence measurement of H2 O2 production. Specific kinase inhibitors were used to study the TGFβ1 signaling involved in NOX-4 stimulation. NOX-4 inhibition/down-regulation was induced with a selective NOX-4 small-molecule inhibitor and NOX-4 small interfering RNA (siRNA). RESULTS: In contrast with normal skin fibroblasts, those from SSc skin showed intense NOX-4 staining. Cultured SSc fibroblasts displayed increased NOX-4 expression. TGFβ1 caused potent NOX-4 protein and messenger RNA stimulation in normal and SSc fibroblasts, which was mediated by the protein kinase Cδ (PKCδ) and Smad2/3 pathways. NOX-4 knockdown in SSc fibroblasts reduced the production of ROS and lowered the expression of type I collagen. CONCLUSION: NOX-4 expression and production were found to be constitutively elevated in SSc skin and cultured SSc dermal fibroblasts. TGFβ1 stimulated NOX-4 expression in normal and SSc fibroblasts through PKCδ and Smad2/3 signaling pathways. A small-molecule NOX-4 inhibitor decreased collagen and fibronectin production by normal and SSc fibroblasts, and NOX-4 siRNA knockdown reduced ROS and collagen production by SSc fibroblasts. These results demonstrate the involvement of NOX-4 in SSc-associated fibrosis and indicate NOX-4 inhibitors as novel therapeutic approaches for SSc

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Environmental interactions of tidal lagoons: A comparison of industry perspectives

Tidal lagoons are an attractive renewable energy option that could aid the UK in meeting its ambitious renewable energy targets. One of the main barriers to tidal range development in the UK to date has been regulatory environmental concern. In order for the nascent lagoon industry to move forward into development, the views of the developers and other influential stakeholders such as government bodies, regulators, conservationists and practitioners (herein referred to as 'influencing stakeholders' or 'influencers') need to be aligned. This study is the first of its kind using online questionnaires and semi-structured interviews to present and compare the views of both developers and influencing stakeholders on the environmental interactions of tidal lagoons. We find that, whilst both influencers and developers are working towards the common goal of a good environmental outcome for tidal lagoons, there are mismatches in their views in terms of the priorities given to the key environmental impacts, benefits and potential solution options. The work provides insight into what is at the forefront of developers' and influencers' minds, highlighting the key themes within their views and transforming this information into policy recommendations that will help the industry's development move forward

Novel Compound MMV1804559 from the Global Health Priority Box Exhibits In Vitro and In Vivo Activity against <i>Madurella mycetomatis</i>

Objectives: Eumycetoma is a neglected tropical disease (NTD) characterized by subcutaneous lesions and the formation of grains. Attempts to treat eumycetoma involve a combination of antifungal treatment and surgery, although the outcome is frequently disappointing. Therefore, there is a need to identify novel antifungal drugs to treat eumycetoma. In this respect, Medicines for Malaria Venture (MMV) has assembled libraries of compounds for researchers to use in drug discovery research against NTD. Therefore, we screened two MMVOpen compound libraries to identify novel leads for eumycetoma. Methods: A total of 400 compounds from the COVID Box and the Global Health Priority Box were screened in vitro at 100 µM and 25 µM against the most common causative agents of eumycetoma, namely Madurella mycetomatis and Falciformispora senegalensis, and the resulting IC50 and MIC50 values were obtained. Compounds with an IC50 &lt; 8 µM were identified for possible in vivo efficacy studies using an M. mycetomatis grain model in Galleria mellonella larvae. Results: Out of the 400 compounds, 22 were able to inhibit both M. mycetomatis and F. senegalensis growth at 100 µM and 25 µM, with compounds MMV1593278, MMV020335, and MMV1804559 being selected for in vivo testing. Of these three, only the pyrazolopyrimidine derivative MMV1804559 was able to prolong the survival of M. mycetomatis-infected G. mellonella larvae. Furthermore, the grains in MMV1804559-treated larvae were significantly smaller compared to the PBS-treated group. Conclusion: MMV1804559 shows promising in vitro and in vivo activity against M. mycetomatis

Identification of pan-flavivirus compounds from drug repurposing.

The incidence of orthoflavivirus infections is on the rise, yet effective antivirals are unavailable for all members of this family. Additionally, new orthoflaviviruses are emerging, highlighting the need for antiviral strategies with a pan-flavivirus activity. In response, the Global Health Priority Box was screened, leading to the identification of a compound with pan-flavivirus activity. This hit compound demonstrated inhibition of viral replication, consistent efficacy across various cell lines, and maintained activity even at high multiplicity of infection. Importantly it has a high barrier to resistance and possibly acts through a novel mechanism of action. Due to these attributes and its favorable in vitro ADMET profile, compound MMV1791425 emerges as a promising candidate for the future development of a pan-flavivirus antiviral

Novel Compound MMV1804559 from the Global Health Priority Box Exhibits In Vitro and In Vivo Activity against <i>Madurella mycetomatis</i>

Objectives: Eumycetoma is a neglected tropical disease (NTD) characterized by subcutaneous lesions and the formation of grains. Attempts to treat eumycetoma involve a combination of antifungal treatment and surgery, although the outcome is frequently disappointing. Therefore, there is a need to identify novel antifungal drugs to treat eumycetoma. In this respect, Medicines for Malaria Venture (MMV) has assembled libraries of compounds for researchers to use in drug discovery research against NTD. Therefore, we screened two MMVOpen compound libraries to identify novel leads for eumycetoma. Methods: A total of 400 compounds from the COVID Box and the Global Health Priority Box were screened in vitro at 100 µM and 25 µM against the most common causative agents of eumycetoma, namely Madurella mycetomatis and Falciformispora senegalensis, and the resulting IC50 and MIC50 values were obtained. Compounds with an IC50 &lt; 8 µM were identified for possible in vivo efficacy studies using an M. mycetomatis grain model in Galleria mellonella larvae. Results: Out of the 400 compounds, 22 were able to inhibit both M. mycetomatis and F. senegalensis growth at 100 µM and 25 µM, with compounds MMV1593278, MMV020335, and MMV1804559 being selected for in vivo testing. Of these three, only the pyrazolopyrimidine derivative MMV1804559 was able to prolong the survival of M. mycetomatis-infected G. mellonella larvae. Furthermore, the grains in MMV1804559-treated larvae were significantly smaller compared to the PBS-treated group. Conclusion: MMV1804559 shows promising in vitro and in vivo activity against M. mycetomatis