| 1. |
- Montagnese, Sara, et al.
(författare)
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A pilot study of golexanolone, a new GABA-A receptor-modulating steroid antagonist, in patients with covert hepatic encephalopathy
- 2021
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 75:1, s. 98-107
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Golexanolone is a novel small molecule GABA-A receptor-modulating steroid antagonist under development for the treatment of cognitive and vigilance disorders caused by allosteric over-activation of GABA-A receptors by neurosteroids. It restored spatial learning and motor coordination in animal models of hepatic encephalopathy (HE) and mitigated the effects of intravenous allopregnanolone in healthy adults in a dose-dependent fashion. Herein, we report data on the safety, pharmacokinetics (PK) and efficacy of golexanolone in adult patients with cirrhosis.Methods: Following single/multiple ascending dose studies, adults with Child-Pugh A/B cirrhosis and abnormal continuous reaction time (CRT) on screening were randomized to 3 weeks’ dosing with golexanolone (10, 40 or 80 mg BID) or placebo. CRT, psychometric hepatic encephalopathy score (PHES), animal naming test (ANT), Epworth sleepiness scale (ESS) and electroencephalogram (mean dominant frequency [MDF]; delta+theta/alpha+beta ratio [DT/AB]) were obtained at baseline, 10, and 21 days.Results: Golexanolone exhibited satisfactory safety and PK. Baseline characteristics were similar between the 12 and 33 patients randomized to placebo or golexanolone, respectively. By prespecified analyses, golexanolone was associated with directionally favourable changes vs. placebo in ESS (p = 0.047), MDF (p = 0.142) and DT/AB (p = 0.021). All patients also showed directionally favourable changes in CRT, PHES and ANT, but with no statistical difference between golexanolone and placebo. Post hoc analyses taking into account the variability and improvement in CRT, PHES and ANT observed between screening and baseline suggested an efficacy signal by cognitive measures as well.Conclusion: Golexanolone was well tolerated and associated with improvement in cognitive performance. These results implicate GABA-A receptor-modulating neurosteroids in the pathogenesis of HE and support the therapeutic potential of golexanolone.Lay summary: Many patients with cirrhosis experience subtle but disabling cognitive problems, including sleepiness and poor attention span, that impair their ability to be gainfully employed or carry out activities of daily living. This pilot study tested the hypothesis that these problems with cognition, for which there is no approved treatment, might be improved by an experimental drug, golexanolone, designed to normalize the function of receptors which inhibit brain function. The results of this study suggest that golexanolone is well tolerated and may improve cognition, as reflected by measures of sleepiness, attention span and brain wave activity, paving the way for future larger studies of this promising experimental drug.Clinical trial registration number: EudraCT 2016-003651-30.
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| 2. |
- Botero, Carlos Alberto, et al.
(författare)
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Microstructural and mechanical evaluation of a cr-mo-v cold-work tool steel produced via electron beam melting (Ebm)
- 2021
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Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 14:11
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Tidskriftsartikel (refereegranskat)abstract
- In this work, a highly alloyed cold work tool steel, Uddeholm Vanadis 4 Extra, was manufactured via the electron beam melting (EBM) technique. The corresponding material microstructure and carbide precipitation behavior as well as the microstructural changes after heat treatment were characterized, and key mechanical properties were investigated. In the as-built condition, the mi-crostructure consists of a discontinuous network of very fine primary Mo-and V-rich carbides dispersed in an auto-tempered martensite matrix together with ≈15% of retained austenite. Adjusted heat treatment procedures allowed optimizing the microstructure by the elimination of Mo-rich carbides and the precipitation of fine and different sized V-rich carbides, along with a decrease in the retained austenite content below 2%. Hardness response, compressive strength, and abrasive wear properties of the EBM-manufactured material are similar or superior to its as-HIP forged counterparts manufactured using traditional powder metallurgy route. In the material as built by EBM, an impact toughness of 16–17 J was achieved. Hot isostatic pressing (HIP) was applied in order to further increase ductility and to investigate its impact upon the microstructure and properties of the material. After HIPing with optimized protocols, the ductility increased over 20 J.
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| 3. |
- Botero Vega, Carlos Alberto, et al.
(författare)
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Additive Manufacturing of a Cold-Work Tool Steel using Electron Beam Melting
- 2020
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Ingår i: Steel Research International. - : Wiley. - 1611-3683 .- 1869-344X. ; 19:5, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Metal additive manufacturing (AM) is on its way to industrialization. One of the most promising techniques within this field, electron beam melting (EBM), is nowadays used mostly for the fabrication of high‐performance Ti‐based alloy components for the aerospace and medical industry. Among the industrial applications envisioned for the future of EBM, the fabrication of high carbon steels for the tooling industry is of great interest. In this context, the process windows for dense and crack‐free specimens for a highly alloyed (Cr–Mo–V) cold‐work steel powder are presented in this article. High‐solidification rates during EBM processing lead to very fine and homogeneous microstructures. The influence of process parameters on the resulting microstructure and the chemical composition is investigated. In addition, preliminary results show very promising mechanical properties regarding the as‐built and heat‐treated microstructure of the obtained material.
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| 4. |
- Bäckström, Anna, et al.
(författare)
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Atypical motor planning in an interpersonal context in 9-year-old children with autism spectrum disorder (ASD)
- 2023
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Ingår i: 35th EACD Annual meeting European Academy of Childhood Disability. - : European Academy of Childhood Disability. ; , s. 254-254
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Konferensbidrag (refereegranskat)abstract
- Introduction: Motor planning deviances may negatively affect interpersonal motor interactions in ASD, although detailed studies are sparse. This study examined motor planning kinematics in an interpersonal and non-interpersonal context in 9-year-old children with ASD and neurotypical peers.Patients and methods: Twelve children with ASD and 17 controls performed two different sequential manual tasks (preferred hand): grasping and placing a peg on a wooden disc (non-interpersonal) or in the hand of an examiner (interpersonal). Three-dimensional kinematic recordings of arm/hand movements were performed. Group and task differences were explored for total movement duration (MD), and for peak velocity (PV) and placement of peak velocity (PPV) during reach-to-grasp and transport-to-place movements, respectively.Results: Task differences were found in terms of longer MD and higher transport-to-place-PV in the disc- compared to hand-task. An interaction effect was evident for reach-to-grasp-PPV, where the control-group, but not ASD, had earlier reach-to-grasp-PPV and longer relative deceleration in the hand-task compared to the disc-task.Conclusion: Results show that the interpersonal context influenced initial reach-to-grasp motor planning in the control-group, but not the ASD-group. Later in the sequential movement (transport-to-place), the interpersonal context seemed to influence motor planning independent of group. Taken together, this indicates support towards a more careful peg-placing in the interpersonal hand-task in the control-group but much less clearly so in the ASD-group.Relevance for users and families: Atypical motor planning may influence motor interaction with peers. Investigations of motor planning and movement organization in ASD could thus inform interventions also targeting interpersonal exchange.
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| 5. |
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| 6. |
- Bäckström, Anna, et al.
(författare)
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Motor imagery ability in 7-year-old children with autism spectrum disorder
- 2020
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Knowledge about motor imagery (MI) ability in autism spectrum disorder (ASD) is limited and inconclusive in young children with ASD. The aim of the current study was to investigate MI ability in 7-year-old children with ASD.Patients and methods: Thirteen children with ASD and 13 typically developing (TD) children performed a computerized hand laterality judgement task (HLJ) and a non-corporeal visual imagery (VI) control task. All participants passing a criterion test performed the tasks with images at 4 different rotational increments to vary the MI biomechanical demands (HLJ task) or VI angle rotational demands (VI task). Response times (RT) and accuracy were extracted.Results: Four children with ASD did not pass the HLJ criterion test and one failed the VI criterion test. The ASD-group had evidently more incorrect responses than TD on both tasks. Analyses of RT showed a biomechanical effect in the MI task and an angle increment effect in the VI task in both groups. Children with ASD had longer RT than TD children on VI but not MI tasks. Conclusion: Findings suggest that both the ASD and control children used MI to solve the HLJ task. However, failures to pass the HLJ criterion test and the increased error rate in the ASD group indicate that MI ability is weaker in young children with autism than TD controls. Notably, a large individual variability in employment of MI within the ASD group was found, ranging from functional, fractional but existing, to absent MI ability.
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| 7. |
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| 8. |
- Bäckström, Anna, et al.
(författare)
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Motor planning and movement execution during goal-directed sequential manual movements in 6-year-old children with autism spectrum disorder : A kinematic analysis
- 2021
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Ingår i: Research in Developmental Disabilities. - : Elsevier. - 0891-4222 .- 1873-3379. ; 115
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Tidskriftsartikel (refereegranskat)abstract
- Background: Atypical motor functioning is prevalent in children with autism spectrum disorder (ASD). Knowledge of the underlying kinematic properties of these problems is sparse.Aims: To investigate characteristics of manual motor planning and performance difficulties/diversity in children with ASD by detailed kinematic measurements. Further, associations between movement parameters and cognitive functions were explored.Methods and procedures: Six-year-old children with ASD (N = 12) and typically developing (TD) peers (N = 12) performed a sequential manual task comprising grasping and fitting a semi-circular peg into a goal-slot. The goal-slot orientation was manipulated to impose different motor planning constraints. Movements were recorded by an optoelectronic system.Outcomes and results: The ASD-group displayed less efficient motor planning than the TD-group, evident in the reach-to-grasp and transport kinematics and less proactive adjustments of the peg to the goal-slot orientations. The intra-individual variation of movement kinematics was higher in the ASD-group compared to the TD-group. Further, in the ASD-group, movement performance associated negatively with cognitive functions.Conclusions and implications: Planning and execution of sequential manual movements proved challenging for children with ASD, likely contributing to problems in everyday actions. Detailed kinematic investigations contribute to the generation of specific knowledge about the nature of atypical motor performance/diversity in ASD. This is of potential clinical relevance.
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| 9. |
- Bäckström, Anna, et al.
(författare)
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Visuomotor integration in action planning in 7-year-old children with autism spectrum disorder
- 2022
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Ingår i: Specia issue: Abstracts of the 34th annual meeting of the European Academy of Childhood Disability (EACD) Barcelona, Spain 18-21 May 2022. - : Mac Keith Press. ; , s. 65-65
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Konferensbidrag (refereegranskat)abstract
- Introduction: Difficulties with action planning and visuomotor integration may contribute to atypical motorfunctioning in children with autism spectrum disorder (ASD), although detailed studies of sensorimotorintegration in action planning are sparse. This ongoing study investigates visuomotor integration in actionplanning in 7-year-old children with and without ASD.Patients and methods: A sub-sample of 6 children with ASD and 6 typically developing (TD) controls wereincluded. Recordings of gaze synchronized with 3D kinematic registration were made during performance of amanual sequential peg rotation task with variations in goal insertion complexity. Group differences and relations between movement duration and number of gaze shifts over the sequential movement phases(latency, reach-to-grasp, grasp, and transport-to-fit) were explored.Results: No significant group differences were found for either movement duration or number of gaze shifts.When controlling for the between-participants variance, total number of gaze shifts and number of gaze shiftsin reach-to-grasp were related to movement duration in the initial phases of the movement in the TD-group but not in the ASD-group.Conclusion: The results indicate that, whilst performance measures were similar between groups, the overallpattern of visuomotor integration was related to feed-forward movement processes in the sequentialmovement in the TD-group but not in the ASD-group. This finding adds support to previous suggestions thatvisuomotor integration underpinning action planning may operate differently in ASD. Synchronizedexamination of gaze and detailed movement registration appears as a promising methodology for detailed investigation of visuomotor integration in action planning.
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| 10. |
- Domellöf, Erik, et al.
(författare)
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Kinematic characteristics of second‐order motor planning and performance in 6‐ and 10‐year‐old children and adults : Effects of age and task constraints
- 2020
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Ingår i: Developmental Psychobiology. - : John Wiley & Sons. - 0012-1630 .- 1098-2302 .- 0012-1649 .- 1939-0599. ; 62:2, s. 250-265
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Tidskriftsartikel (refereegranskat)abstract
- This study explored age‐related differences in motor planning as expressed in arm‐hand kinematics during a sequential peg moving task with varying demands on goal insertion complexity (second‐order planning). The peg was a vertical cylinder with either a circular or semicircular base. The task was to transport the peg between two positions and rotate it various amounts horizontally before fitting into its final position. The amount of rotation required was either 0°, 90°, 180°, or −90°. The reaching for the peg, the displacement of it, and the way the rotation was accomplished was analyzed. Assessments of end state comfort, goal interpretation errors, and type of grip used were also included. Participants were two groups of typically developing children, one younger (Mage = 6.7 years) and one older (Mage = 10.3 years), and one adult group (Mage = 34.9 years). The children, particularly 6‐year‐olds, displayed less efficient prehensile movement organization than adults. Related to less efficient motor planning, 6‐year‐olds, mainly, had shorter reach‐to‐grasp onset latencies, higher velocities, and shorter time to peak velocities, and longer grasp durations than adults. Importantly, the adults rotated the peg during transport. In contrast, the children made corrective rotations after the hand had arrived at the goal.
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