391 research outputs found

    Mechanical properties of three-dimensional interconnected alumina/steel metal matrix composites

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    Three-dimensional interconnected alumina/steel metal matrix composites (MMCs) were produced by pressureless Ti-activated melt infiltration method using three types of Al2O3 powder with different sizes and shapes. By partial sintering during infiltration an interpenetrating ceramic network was realised. The effect of the ceramic particle size and shape on the resulting ceramic network, volume % fraction and the MMC properties is presented. The MMCs were characterised for mechanical properties at room temperature and elevated temperature. An increase in flexural strength and Young's modulus with decreasing particle size has been observed. In addition, the effect of the volume of ceramic content and the surface finish of the MMCs on the wear behaviour is show

    Attenuation of leukocyte sequestration by selective blockade of PECAM-1 or VCAM-1 in murine endotoxemia

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    Background: Molecular mechanisms regulating leukocyte sequestration into the tissue during endotoxemia and/or sepsis are still poorly understood. This in vivo study investigates the biological role of murine PECAM-1 and VCAM-1 for leukocyte sequestration into the lung, liver and striated skin muscle. Methods: Male BALB/c mice were injected intravenously with murine PECAM-1 IgG chimera or monoclonal antibody (mAb) to VCAM-1 ( 3 mg/kg body weight); controls received equivalent doses of IgG2a ( n = 6 per group). Fifteen minutes thereafter, 2 mg/kg body weight of Salmonella abortus equi endotoxin was injected intravenously. At 24 h after the endotoxin challenge, lungs, livers and striated muscle of skin were analyzed for their myeloperoxidase activity. To monitor intravital leukocyte-endothelial cell interactions, fluorescence videomicroscopy was performed in the skin fold chamber model of the BALB/c mouse at 3, 8 and 24 h after injection of endotoxin. Results: Myeloperoxidase activity at 24 h after the endotoxin challenge in lungs (12,171 +/- 2,357 mU/g tissue), livers ( 2,204 +/- 238 mU/g) and striated muscle of the skin ( 1,161 +/- 110 mU/g) was significantly reduced in both treatment groups as compared to controls, with strongest attenuation in the PECAM-1 IgG treatment group. Arteriolar leukocyte sticking at 3 h after endotoxin (230 +/- 46 cells x mm(-2)) was significantly reduced in both treatment groups. Leukocyte sticking in postcapillary venules at 8 h after endotoxin ( 343 +/- 69 cells/mm(2)) was found reduced only in the VCAM-1-mAb-treated animals ( 215 +/- 53 cells/mm(2)), while it was enhanced in animals treated with PECAM-1 IgG ( 572 +/- 126 cells/mm(2)). Conclusion: These data show that both PECAM-1 and VCAM-1 are involved in endotoxin-induced leukocyte sequestration in the lung, liver and muscle, presumably through interference with arteriolar and/or venular leukocyte sticking. Copyright (C) 2004 S. Karger AG, Basel

    Risk Factors and Outcome of Fontan‐Associated Plastic Bronchitis: A Case‐Control Study

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139068/1/jah3521.pd

    Proof-of-Principle of a Brain-Computer Interface approach to support post-stroke arm rehabilitation in hospitalized patients: design, acceptability and usability

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    Objective To evaluate the feasibility of brain-computer interface (BCI)-assisted motor imagery training to support hand/arm motor rehabilitation after stroke during hospitalization. Design Proof-of-principle study. Setting Neurorehabilitation hospital. Participants Convenience sample of patients (N=8) with new-onset arm plegia or paresis caused by unilateral stroke. Interventions The BCI-based intervention was administered as an "add-on" to usual care and lasted 4 weeks. Under the supervision of a therapist, patients were asked to practice motor imagery of their affected hand and received as a discrete feedback the movements of a "virtual" hand superimposed on their own. Such a BCI-based device was installed in a rehabilitation hospital ward. Main Outcome Measures Following a user-centered design, we assessed system usability in terms of motivation, satisfaction (by means of visual analog scales), and workload (National Aeronautics and Space Administration-Task Load Index). The usability of the BCI-based system was also evaluated by 15 therapists who participated in a focus group. Results All patients successfully accomplished the BCI training. Significant positive correlations were found between satisfaction and motivation (P=.001, r=.393). BCI performance correlated with interest (P=.027, r=.257) and motivation (P=.012, r=.289). During the focus group, professionals positively acknowledged the opportunity offered by BCI-assisted training to measure patients' adherence to rehabilitation. Conclusions An ecological BCI-based device to assist motor imagery practice was found to be feasible as an add-on intervention and tolerable by patients who were exposed to the system in the rehabilitation environment. © 2015 American Congress of Rehabilitation Medicine

    Comparison of joint mobilization and movement pattern training for patients with hip-related groin pain: A pilot randomized clinical trial

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    OBJECTIVE: The objective of this study was to assess the feasibility of completing a randomized clinical trial (RCT) and examine the preliminary effects of 2 interventions for hip-related groin pain (HRGP). METHODS: In this pilot RCT, patients with HRGP, who were 18 to 40 years old, were randomized (1:1 ratio) to a joint mobilization (JtMob) group or a movement pattern training (MoveTrain) group. Both treatments included 10 supervised sessions and a home exercise program. The goal of JtMob was to reduce pain and improve mobility through peripherally and centrally mediated pain mechanisms. The key element was physical therapist-provided JtMob. The goal of MoveTrain was to reduce hip joint stresses by optimizing the biomechanics of patient-specific tasks. The key element was task-specific instruction to correct abnormal movement patterns displayed during tasks. Primary outcomes were related to future trial feasibility. The primary effectiveness outcome was the Hip Disability and Osteoarthritis Outcome Score. Examiners were blinded to group; patients and treatment providers were not. Data collected at baseline and immediately after treatment were analyzed with analysis of covariance using a generalized linear model in which change was the dependent variable and baseline was the covariate. The study was modified due to the coronavirus disease 2019 (COVID-19) pandemic. RESULTS: The COVID-19 pandemic affected participation; 127 patients were screened, 33 were randomized (18 to the JtMob group and 15 to the MoveTrain group), and 29 (88%) provided posttreatment data. Treatment session adherence was 85%, and home exercise program component adherence ranged from 71 to 86%. Both groups demonstrated significant mean within-group improvements of ≄5 points on Hip Disability and Osteoarthritis Outcome Score scales. There were no between-group differences in effectiveness outcomes. CONCLUSIONS: A large RCT to assess the effects of JtMob and MoveTrain for patients with HRGP may be feasible. Preliminary findings suggested that JtMob or MoveTrain may result in improvements in patient-reported pain and activity limitations. IMPACT: The COVID-19 pandemic interfered with participation, but a randomized controlled trial may be feasible. Modification may be needed if the trial is completed during future pandemics

    <sup>11</sup> C radiolabeling of anle253b: A putative PET tracer for Parkinson's disease that binds to α-synuclein fibrils in vitro and crosses the blood-brain barrier.

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    There is an urgent clinical need for imaging of α-synuclein (αSyn) fibrils, the hallmark biomarker for Parkinson's disease, in neurodegenerative disorders. Despite immense efforts, promising tracer candidates for nuclear imaging of αSyn are rare. Diphenyl pyrazoles are known modulators of αSyn aggregation and thus bear potential for non-invasive detection of this biomarker in vivo. Here we demonstrate high-affinity binding of the family member anle253b to fibrillar αSyn and present a high-yielding site-selective radiosynthesis route for 11 C radiolabeling using in-situ generated [11 C]formaldehyde and reductive methylation. Radio-HPLC of the tracer after incubation with rat serum in vitro shows excellent stability of the molecule. Positron emission tomography in healthy animals is used to assess the pharmacokinetics and biodistribution of the tracer, showing good penetration of the blood-brain barrier and low background binding to the non-pathological brain

    Concerted changes in tropical forest structure and dynamics: evidence from 50 South American long-term plots

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    Several widespread changes in the ecology of old-growth tropical forests have recently been documented for the late twentieth century, in particular an increase in stem turnover (pan-tropical), and an increase in above-ground biomass (neotropical). Whether these changes are synchronous and whether changes in growth are also occurring is not known. We analysed stand-level changes within 50 long-term. monitoring plots from across South America spanning 1971-2002. We show that: (i) basal area (BA: sum of the cross-sectional areas of all trees in a plot) increased significantly over time (by 0.10 +/- 0.04 m(2) ha(-1) yr(-1), mean +/- 95% CI); as did both (ii) stand-level BA growth rates (sum of the increments of BA of surviving trees and BA of new trees that recruited into a plot); and (iii) stand-level BA mortality rates (sum of the cross-sectional areas of all trees that died in a plot). Similar patterns were observed on a per-stem basis: (i) stem density (number of stems per hectare; 1 hectare is 10(4) m(2)) increased significantly over time (0.94 +/- 0.63 stems ha(-1) yr(-1)); as did both (ii) stem recruitment rates; and (iii) stem mortality rates. In relative terms, the pools of BA and stem density increased by 0.38 +/- 0.15% and 0.18 +/- 0.12% yr(-1), respectively. The fluxes into and out of these pools-stand-level BA growth, stand-level BA mortality, stem recruitment and stem mortality rates-increased, in relative terms, by an order of magnitude more. The gain terms (BA growth, stem recruitment) consistently exceeded the loss terms (BA loss, stem mortality) throughout the period, suggesting that whatever process is driving these changes was already acting before the plot network was established. Large long-term increases in stand-level BA growth and simultaneous increases in stand BA and stem density imply a continent-wide increase in resource availability which is increasing net primary productivity and altering forest dynamics. Continent-wide changes in incoming solar radiation, and increases in atmospheric concentrations of CO2 and air temperatures may have increased resource supply over recent decades, thus causing accelerated growth and increased dynamism across the world's largest tract of tropical forest

    [11C]MODAG-001—towards a PET tracer targeting α-synuclein aggregates

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    Purpose Deposition of misfolded alpha-synuclein (αSYN) aggregates in the human brain is one of the major hallmarks of synucleinopathies. However, a target-specific tracer to detect pathological aggregates of αSYN remains lacking. Here, we report the development of a positron emission tomography (PET) tracer based on anle138b, a compound shown to have therapeutic activity in animal models of neurodegenerative diseases. Methods Specificity and selectivity of [3H]MODAG-001 were tested in in vitro binding assays using recombinant fibrils. After carbon-11 radiolabeling, the pharmacokinetic and metabolic profile was determined in mice. Specific binding was quantified in rats, inoculated with αSYN fibrils and using in vitro autoradiography in human brain sections of Lewy body dementia (LBD) cases provided by the Neurobiobank Munich (NBM). Results [3H]MODAG-001 revealed a very high affinity towards pure αSYN fibrils (Kd = 0.6 ± 0.1 nM) and only a moderate affinity to hTau46 fibrils (Kd = 19 ± 6.4 nM) as well as amyloid-ÎČ1–42 fibrils (Kd = 20 ± 10 nM). [11C]MODAG-001 showed an excellent ability to penetrate the mouse brain. Metabolic degradation was present, but the stability of the parent compound improved after selective deuteration of the precursor. (d3)-[11C]MODAG-001 binding was confirmed in fibril-inoculated rat striata using in vivo PET imaging. In vitro autoradiography showed no detectable binding to aggregated αSYN in human brain sections of LBD cases, most likely, because of the low abundance of aggregated αSYN against background protein. Conclusion MODAG-001 provides a promising lead structure for future compound development as it combines a high affinity and good selectivity in fibril-binding assays with suitable pharmacokinetics and biodistribution properties
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