19 research outputs found
3D Mapping, Localisation and Object Retrieval using Low Cost Robotic Platforms: A Robotic Search Engine for the Real-World
In this paper we present work in progress on
the development of a low-cost autonomous robotic platform
that integrates multiple state-of-the-art techniques in RGB-D
perception to form a system capable of completing a real-world
task in an entirely autonomous fashion. The task we set out to
complete is determining the location of a preselected object within
the physical world. This experiment requires a robotic framework
with a number of capabilities including autonomous exploration,
dense real-time localisation and mapping, object detection, path
planning and motion control
Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial
BACKGROUND AND OBJECTIVES: Primary mitochondrial myopathies (PMMs) encompass a group of genetic disorders that impair mitochondrial oxidative phosphorylation, adversely affecting physical function, exercise capacity, and quality of life (QoL). Current PMM standards of care address symptoms, with limited clinical impact, constituting a significant therapeutic unmet need. We present data from MMPOWER-3, a pivotal, phase-3, randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy and safety of elamipretide in participants with genetically confirmed PMM. METHODS: After screening, eligible participants were randomized 1:1 to receive either 24 weeks of elamipretide at a dose of 40 mg/d or placebo subcutaneously. Primary efficacy endpoints included change from baseline to week 24 on the distance walked on the 6-minute walk test (6MWT) and total fatigue on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA). Secondary endpoints included most bothersome symptom score on the PMMSA, NeuroQoL Fatigue Short-Form scores, and the patient global impression and clinician global impression of PMM symptoms. RESULTS: Participants (N = 218) were randomized (n = 109 elamipretide; n = 109 placebo). The m0ean age was 45.6 years (64% women; 94% White). Most of the participants (n = 162 [74%]) had mitochondrial DNA (mtDNA) alteration, with the remainder having nuclear DNA (nDNA) defects. At screening, the most frequent bothersome PMM symptom on the PMMSA was tiredness during activities (28.9%). At baseline, the mean distance walked on the 6MWT was 336.7 ± 81.2 meters, the mean score for total fatigue on the PMMSA was 10.6 ± 2.5, and the mean T score for the Neuro-QoL Fatigue Short-Form was 54.7 ± 7.5. The study did not meet its primary endpoints assessing changes in the 6MWT and PMMSA total fatigue score (TFS). Between the participants receiving elamipretide and those receiving placebo, the difference in the least squares mean (SE) from baseline to week 24 on distance walked on the 6MWT was -3.2 (95% CI -18.7 to 12.3; p = 0.69) meters, and on the PMMSA, the total fatigue score was -0.07 (95% CI -0.10 to 0.26; p = 0.37). Elamipretide treatment was well-tolerated with most adverse events being mild to moderate in severity. DISCUSSION: Subcutaneous elamipretide treatment did not improve outcomes in the 6MWT and PMMSA TFS in patients with PMM. However, this phase-3 study demonstrated that subcutaneous elamipretide is well-tolerated. TRIAL REGISTRATION INFORMATION: Trial registered with clinicaltrials.gov, Clinical Trials Identifier: NCT03323749; submitted on October 12, 2017; first patient enrolled October 9, 2017. CLINICALTRIALS: gov/ct2/show/NCT03323749?term = elamipretide&draw = 2&rank = 9. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that elamipretide does not improve the 6MWT or fatigue at 24 weeks compared with placebo in patients with primary mitochondrial myopathy
Fermi Gamma-ray Space Telescope: High-Energy Results from the First Year
The Fermi Gamma-ray Space Telescope (Fermi) was launched on June 11, 2008 and
began its first year sky survey on August 11, 2008. The Large Area Telescope
(LAT), a wide field-of-view pair-conversion telescope covering the energy range
from 20 MeV to more than 300 GeV, is the primary instrument on Fermi. While
this review focuses on results obtained with the LAT, the Gamma-ray Burst
Monitor (GBM) complements the LAT in its observations of transient sources and
is sensitive to X-rays and gamma-rays with energies between 8 keV and 40 MeV.
During the first year in orbit, the Fermi LAT has observed a large number of
sources that include active galaxies, pulsars, compact binaries, globular
clusters, supernova remnants, as well as the Sun, the Moon and the Earth. The
GBM and LAT together have uncovered surprising characteristics in the
high-energy emission of gamma-ray bursts (GRBs) that have been used to set
significant new limits on violations of Lorentz invariance. The Fermi LAT has
also made important new measurements of the Galactic diffuse radiation and has
made precise measurements of the spectrum of cosmic-ray electrons and positrons
from 20 GeV to 1 TeV.Comment: 39 pages, 16 figure
Gamma ray astrophysics: the EGRET results
Cosmic gamma rays provide insight into some of the most dynamic processes in
the Universe. At the dawn of a new generation of gamma-ray telescopes, this
review summarizes results from the Energetic Gamma Ray Experiment Telescope
(EGRET) on the Compton Gamma Ray Observatory, the principal predecessor mission
studying high-energy photons in the 100 MeV energy range. EGRET viewed a
gamma-ray sky dominated by prominent emission from the Milky Way, but featuring
an array of other sources, including quasars, pulsars, gamma-ray bursts, and
many sources that remain unidentified. A central feature of the EGRET results
was the high degree of variability seen in many gamma-ray sources, indicative
of the powerful forces at work in objects visible to gamma-ray telescopes.Comment: 23 pages, 24 figure
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Computed tomography using synchrotron radiation
X-ray computed tomography (CT) is a widely used method of obtaining cross-sectional views of objects. The high intensity, natural collimation, monochromaticity and energy tunability of synchrotron x-ray sources could potentially be used to provide CT images of improved quality. The advantages of these systems would be that images could be produced more rapidly with better spatial resolution and reduced beam artifacts. In addition, images, in some cases, could be acquired with elemental sensitivity. As a demonstration of the capability of such a system, CT images were obtained of four slices of an excised pig heart in which the arteries and the cardiac chambers were filled with an iodinated medium. Images were taken with incident x-rays tuned successively to energies just above and below the iodine K edge. Iodine specific images were obtained by logarithmically subtracting the low energy image data from the high energy data and then reconstructing the image. CT imaging using synchrotron radiation may become a convenient and non-destructive method of imaging samples difficult to study by other methods
Sublingual Dexmedetomidine for the Treatment of Acute Agitation in Adults With Schizophrenia or Schizoaffective Disorder: A Randomized Placebo-Controlled Trial
Determine if sublingual dexmedetomidine, a selective α adrenergic receptor agonist, reduces symptoms of acute agitation associated with schizophrenia or schizoaffective disorder. This phase 3, randomized, double-blind, placebo-controlled study was conducted in adults diagnosed with schizophrenia or schizoaffective disorder per the , Fifth Edition () criteria. The study was conducted at 15 US sites between January 23, 2020, and May 8, 2020. Participants were randomized to sublingual dexmedetomidine 180 ÎŒg, 120 ÎŒg, or matching placebo. The primary efficacy endpoint was mean change from baseline in the Positive and Negative Syndrome Scale-Excited Component (PEC) total score at 2 hours postdose. Altogether, 380 participants (mean age 45.6 years, 63.4% identifying as male, 77.9% identifying as Black or African American) were randomized; 380 (100%) self-administered study medication, and 372 (97.9%) completed the study. The mean PEC total score at baseline (17.6) indicated mild to moderate agitation. At 2 hours postdose, the least squares mean changes (SE) from baseline were -10.3 (0.4) for sublingual dexmedetomidine 180 ÎŒg, -8.5 (0.4) for 120 ÎŒg, and -4.8 (0.4) for placebo. Least squares mean differences (97.5% confidence intervals) in the sublingual dexmedetomidine groups were -5.5 (-6.7 to -4.3) for 180 ÎŒg and -3.7 (-4.9 to -2.5) for 120 ÎŒg (both â\u3câ.001 vs placebo). The most commonly encountered adverse events with dexmedetomidine (incidenceââ„â5% andââ„â2Ă rate observed with placebo) were somnolence, dry mouth, and hypotension for the 120 ÎŒg dose, and somnolence, dizziness, orthostatic hypotension, and oral hypoesthesia for the 180 ÎŒg dose. Treatment with sublingual dexmedetomidine 180 ÎŒg or 120 ÎŒg was more efficacious than placebo in reducing acute agitation associated with schizophrenia as measured by PEC scores at 2 hours postdose. ClinicalTrials.gov identifier: NCT04268303
Effect of Sublingual Dexmedetomidine vs Placebo on Acute Agitation Associated With Bipolar Disorder: A Randomized Clinical Trial
IMPORTANCE: Acute agitation is common in patients with bipolar disorder and requires urgent management to relieve distress and to prevent escalation to aggressive behavior. OBJECTIVE: To evaluate the effect of orally absorbed, sublingual dexmedetomidine, a selective α2A-adrenergic receptor agonist on symptoms of acute agitation in patients with bipolar disorder. DESIGN, SETTING, AND PARTICIPANTS: Phase 3, randomized, double-blind, placebo-controlled trial conducted in 15 sites in the US with enrollment between February 24, 2020, and April 27, 2020, and final follow-up on May 21, 2020. A total of 380 adults with bipolar I or II disorder were randomized and 362 completed the study. INTERVENTIONS: Participants were randomized to 3 groups: sublingual dexmedetomidine 180 ÎŒg (nâ=â127), sublingual dexmedetomidine 120 ÎŒg (nâ=â127), or placebo (nâ=â126). MAIN OUTCOMES AND MEASURES: The primary efficacy end point was the mean change from baseline at 2 hours for the Positive and Negative Syndrome Scale-Excited Component (PEC) total score. The range of possible total scores is 5 (absence of agitation) to 35 (extremely severe). The secondary end point was the earliest time of a statistically significant change in PEC total score from baseline for the drug vs placebo. On the primary efficacy end point, to account for multiplicity associated with comparing 2 sublingual dexmedetomidine doses with placebo, the 2-sided significance level for each dose vs placebo was set at .025. RESULTS: Of 380 patients randomized (mean age, 45.6 years; 54.8% women; and 56.1% Black individuals), 378 (99.5%) self-administered the study medication and completed the study. Baseline agitation was mild to moderate, with an overall mean PEC total score of 18.0. Two hours after taking the medication, the mean changes from baseline in PEC total score were -10.4 for sublingual dexmedetomidine 180 ÎŒg, -9.0 for sublingual dexmedetomidine 120 ÎŒg, and -4.9 for placebo. Least-square mean differences from placebo in the sublingual dexmedetomidine groups at 2 hours were -5.4 (97.5% CI, -6.6 to -4.2) for 180 ÎŒg and -4.1 (97.5% CI, -5.3 to -2.9) for 120 ÎŒg (both doses Pâ\u3câ.001 vs placebo). Treatment effects began 20 minutes after taking the medication among patients in the sublingual dexmedetomidine groups (least-square mean difference for 180 ÎŒg, -1.1 [97.5% CI, -2.0 to -0.2]; Pâ=â.007; for 120 ÎŒg, -1.0 [97.5% CI, -1.9 to -0.1]; Pâ=â.009). Adverse events occurred in 35.7% of patients taking 180 ÎŒg of dexmedetomidine, 34.9% taking 120 ÎŒg, and 17.5% taking placebo. The most common adverse events (â„5%) in the respective 180 ÎŒg, 120 ÎŒg, and placebo groups were somnolence (21.4% and 20.6% vs 4.8%); dry mouth (4.8% and 7.1% vs 0.8%); hypotension (6.3% and 4.8% vs 0%); and dizziness (5.6% and 5.6% vs 0.8%). CONCLUSIONS AND RELEVANCE: Among patients with mild to moderate agitation associated with bipolar disorder, treatment with a sublingual film formulation of dexmedetomidine 120 ÎŒg or 180 ÎŒg, compared with placebo, resulted in significantly greater reduction in the agitation score at 2 hours. Further research is needed to understand the spectrum of patients for whom this treatment would be effective and feasible and to better understand the clinical importance of the observed effect size. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04276883
Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial
Background and ObjectivesPrimary mitochondrial myopathies (PMMs) encompass a group of genetic disorders that impair mitochondrial oxidative phosphorylation, adversely affecting physical function, exercise capacity, and quality of life (QoL). Current PMM standards of care address symptoms, with limited clinical impact, constituting a significant therapeutic unmet need. We present data from MMPOWER-3, a pivotal, phase-3, randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy and safety of elamipretide in participants with genetically confirmed PMM.MethodsAfter screening, eligible participants were randomized 1:1 to receive either 24 weeks of elamipretide at a dose of 40 mg/d or placebo subcutaneously. Primary efficacy endpoints included change from baseline to week 24 on the distance walked on the 6-minute walk test (6MWT) and total fatigue on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA). Secondary endpoints included most bothersome symptom score on the PMMSA, NeuroQoL Fatigue Short-Form scores, and the patient global impression and clinician global impression of PMM symptoms.ResultsParticipants (N = 218) were randomized (n = 109 elamipretide; n = 109 placebo). The m0ean age was 45.6 years (64% women; 94% White). Most of the participants (n = 162 [74%]) had mitochondrial DNA (mtDNA) alteration, with the remainder having nuclear DNA (nDNA) defects. At screening, the most frequent bothersome PMM symptom on the PMMSA was tiredness during activities (28.9%). At baseline, the mean distance walked on the 6MWT was 336.7 & PLUSMN; 81.2 meters, the mean score for total fatigue on the PMMSA was 10.6 +/- 2.5, and the mean T score for the Neuro-QoL Fatigue Short-Form was 54.7 +/- 7.5. The study did not meet its primary endpoints assessing changes in the 6MWT and PMMSA total fatigue score (TFS). Between the participants receiving elamipretide and those receiving placebo, the difference in the least squares mean (SE) from baseline to week 24 on distance walked on the 6MWT was -3.2 (95% CI -18.7 to 12.3; p = 0.69) meters, and on the PMMSA, the total fatigue score was -0.07 (95% CI -0.10 to 0.26; p = 0.37). Elamipretide treatment was well-tolerated with most adverse events being mild to moderate in severity.DiscussionSubcutaneous elamipretide treatment did not improve outcomes in the 6MWT and PMMSA TFS in patients with PMM. However, this phase-3 study demonstrated that subcutaneous elamipretide is well-tolerated.Classification of EvidenceThis study provides Class I evidence that elamipretide does not improve the 6MWT or fatigue at 24 weeks compared with placebo in patients with primary mitochondrial myopathy