9 research outputs found

    VC-dimension of short Presburger formulas

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    We study VC-dimension of short formulas in Presburger Arithmetic, defined to have a bounded number of variables, quantifiers and atoms. We give both lower and upper bounds, which are tight up to a polynomial factor in the bit length of the formula

    Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

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    OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

    Republication of “How Will the Foot and Ankle Orthopedic Community Respond to the Growing Opioid Epidemic?”

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    In the midst of the current opioid crisis, it has become critically important to properly manage opioid-prescribing patterns for the treatment of postoperative pain. There is currently a scarcity of literature specifying prescription and consumption patterns following orthopedic surgery and specifically foot and ankle surgery. Clinical guidelines for postoperative pain management are deficient

    Supplemental Material, DS_10.1177_2473011418764463 - How Will the Foot and Ankle Orthopedic Community Respond to the Growing Opioid Epidemic?

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    <p>Supplemental Material, DS_10.1177_2473011418764463 for How Will the Foot and Ankle Orthopedic Community Respond to the Growing Opioid Epidemic? by Gabrielle S. Donahue, Noortje Catherine Hagemeijer, and Anne Holly Johnson in Foot & Ankle Orthopaedics</p

    Supplemental Material, FAO764463-ICMJE - How Will the Foot and Ankle Orthopedic Community Respond to the Growing Opioid Epidemic?

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    <p>Supplemental Material, FAO764463-ICMJE for How Will the Foot and Ankle Orthopedic Community Respond to the Growing Opioid Epidemic? by Gabrielle S. Donahue, Noortje Catherine Hagemeijer, and Anne Holly Johnson in Foot & Ankle Orthopaedics</p

    An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes

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    © 2015 Macmillan Publishers Limited. Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole-genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and 3 pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localize to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequencing data identified recessive mutations in PIBF1, also known as CEP90, and C21orf2, also known as LRRC76, as causes of the ciliopathies Joubert and Jeune syndromes. Biochemical approaches place C21orf2 within key ciliopathy-associated protein modules, offering an explanation for the skeletal and retinal involvement observed in individuals with C21orf2 variants. Our global, unbiased approaches provide insights into ciliogenesis complexity and identify roles for unanticipated pathways in human genetic disease

    The Americans with Disabilities Act and the Constitution of the United States (Dissertation)

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