Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications, yet the benefits and risks of treatment beyond 1 year are uncertain.
Patients were enrolled after ...they had undergone a coronary stent procedure in which a drug-eluting stent was placed. After 12 months of treatment with a thienopyridine drug (clopidogrel or prasugrel) and aspirin, patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months; all patients continued receiving aspirin. The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death, myocardial infarction, or stroke) during the period from 12 to 30 months. The primary safety end point was moderate or severe bleeding.
A total of 9961 patients were randomly assigned to continue thienopyridine treatment or to receive placebo. Continued treatment with thienopyridine, as compared with placebo, reduced the rates of stent thrombosis (0.4% vs. 1.4%; hazard ratio, 0.29 95% confidence interval {CI}, 0.17 to 0.48; P<0.001) and major adverse cardiovascular and cerebrovascular events (4.3% vs. 5.9%; hazard ratio, 0.71 95% CI, 0.59 to 0.85; P<0.001). The rate of myocardial infarction was lower with thienopyridine treatment than with placebo (2.1% vs. 4.1%; hazard ratio, 0.47; P<0.001). The rate of death from any cause was 2.0% in the group that continued thienopyridine therapy and 1.5% in the placebo group (hazard ratio, 1.36 95% CI, 1.00 to 1.85; P=0.05). The rate of moderate or severe bleeding was increased with continued thienopyridine treatment (2.5% vs. 1.6%, P=0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment.
Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding. (Funded by a consortium of eight device and drug manufacturers and others; DAPT ClinicalTrials.gov number, NCT00977938.).
Metamaterial Apertures for Computational Imaging Hunt, John; Driscoll, Tom; Mrozack, Alex ...
Science (American Association for the Advancement of Science),
01/2013, Volume:
339, Issue:
6117
Journal Article
Peer reviewed
By leveraging metamaterials and compressive imaging, a low-profile aperture capable of microwave imaging without lenses, moving parts, or phase shifters is demonstrated. This designer aperture allows ...image compression to be performed on the physical hardware layer rather than in the postprocessing stage, thus averting the detector, storage, and transmission costs associated with full diffraction-limited sampling of a scene. A guided-wave metamaterial aperture is used to perform compressive image reconstruction at 10 frames per second of two-dimensional (range and angle) sparse still and video scenes at K-band (18 to 26 gigahertz) frequencies, using frequency diversity to avoid mechanical scanning. Image acquisition is accomplished with a 40:1 compression ratio.
Metamaterial microwave holographic imaging system Hunt, John; Gollub, Jonah; Driscoll, Tom ...
Journal of the Optical Society of America. A, Optics, image science, and vision,
10/2014, Volume:
31, Issue:
10
Journal Article
Peer reviewed
We demonstrate a microwave imaging system that combines advances in metamaterial aperture design with emerging computational imaging techniques. The flexibility inherent to guided-wave, complementary ...metamaterials enables the design of a planar antenna that illuminates a scene with dramatically varying radiation patterns as a function of frequency. As frequency is swept over the K-band (17.5-26.5 GHz), a sequence of pseudorandom radiation patterns interrogates a scene. Measurements of the return signal versus frequency are then acquired and the scene is reconstructed using computational imaging methods. The low-cost, frequency-diverse static aperture allows three-dimensional images to be formed without mechanical scanning or dynamic beam-forming elements. The metamaterial aperture is complementary to a variety of computational imaging schemes, and can be used in conjunction with other sensors to form a multifunctional imaging platform. We illustrate the potential of multisensor fusion by integrating an infrared structured-light and optical image sensor to accelerate the microwave scene reconstruction and to provide a simultaneous visualization of the scene.
► Provides a new evaluation framework for systemic problem structuring methods. ► Integrates case study and comparative evaluation approaches. ► Provides a questionnaire for practitioners to use in ...the context of the framework.
Operational researchers and social scientists often make significant claims for the value of systemic problem structuring and other participative methods. However, when they present evidence to support these claims, it is usually based on single case studies of intervention. There have been very few attempts at evaluating across methods and across interventions undertaken by different people. This is because, in any local intervention, contextual factors, the skills of the researcher and the purposes being pursued by stakeholders affect the perceived success or failure of a method. The use of standard criteria for comparing methods is therefore made problematic by the need to consider what is unique in each intervention. So, is it possible to develop a single evaluation approach that can support both locally meaningful evaluations and longer-term comparisons between methods? This paper outlines a methodological framework for the evaluation of systemic problem structuring methods that seeks to do just this.
The Pneumonia Etiology Research for Child Health (PERCH) project is a 7-country, standardized, comprehensive evaluation of the etiologic agents causing severe pneumonia in children from developing ...countries. During previous etiology studies, between one-quarter and one-third of patients failed to yield an obvious etiology; PERCH will employ and evaluate previously unavailable innovative, more sensitive diagnostic techniques. Innovative and rigorous epidemiologic and analytic methods will be used to establish the causal association between presence of potential pathogens and pneumonia. By strategic selection of study sites that are broadly representative of regions with the greatest burden of childhood pneumonia, PERCH aims to provide data that reflect the epidemiologic situation in developing countries in 2015, using pneumococcal and Haemophilus influenzae type b vaccines. PERCH will also address differences in host, environmental, and/or geographic factors that might determine pneumonia etiology and, by preserving specimens, will generate a resource for future research and pathogen discovery.
Non-small cell lung cancers (NSCLCs) with activating mutations in the kinase domain of the epidermal growth factor receptor (EGFR) demonstrate dramatic, but transient, responses to the reversible ...tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva). Some recurrent tumors have a common secondary mutation in the EGFR kinase domain, T790M, conferring drug resistance, but in other cases the mechanism underlying acquired resistance is unknown. In studying multiple sites of recurrent NSCLCs, we detected T790M in only a small percentage of tumor cells. To identify additional mechanisms of acquired resistance to gefitinib, we used NSCLC cells harboring an activating EGFR mutation to generate multiple resistant clones in vitro. These drug-resistant cells demonstrate continued dependence on EGFR and ERBB2 signaling for their viability and have not acquired secondary EGFR mutations. However, they display increased internalization of ligand-activated EGFR, consistent with altered receptor trafficking. Although gefitinib-resistant clones are cross-resistant to related anilinoquinazolines, they demonstrate sensitivity to a class of irreversible inhibitors of EGFR. These inhibitors also show effective inhibition of signaling by T790M-mutant EGFR and killing of NSCLC cells with the T790M mutation. Both mechanisms of gefitinib resistance are therefore circumvented by irreversible tyrosine kinase inhibitors. Our findings suggest that one of these, HKI-272, may prove highly effective in the treatment of EGFR-mutant NSCLCs, including tumors that have become resistant to gefitinib or erlotinib.
This “How I Do It” report describes modifications made to the OSIA bone conduction hearing implant surgery in order to reduce wound complications.
Laryngoscope, 132:1850–1854, 2022
Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive human malignancies, is thought to be initiated by KRAS activation. Here we find that transcriptional activation mediated by the Gli ...family of transcription factors, although dispensable for pancreatic development, is required for Kras-induced proliferation and survival in primary pancreatic epithelial cells in culture and for Kras-driven pancreatic intraepithelial neoplasia and PDAC formation in vivo. Further, ectopic Gli1 activation in the mouse pancreas accelerates Kras-driven tumor formation, underscoring the importance of Gli transcription factors in pancreatic tumorigenesis. Interestingly, we demonstrate Gli-regulated I-kappa-B kinase epsilon (IKBKE) and NF-κB activity in pancreatic cancer cells and show that this activity is a critical downstream mediator for Gli-dependent PDAC cell transformation and survival. Together, these studies demonstrate the requirement for Gli in Kras-dependent pancreatic epithelial transformation, suggest a mechanism of Gli-NF-κB oncogenic activation, and provide genetic evidence supporting the therapeutic targeting of Gli activity in pancreatic cancer.
Laboratory diagnostics are a core component of any pneumonia etiology study. Recent advances in diagnostic technology have introduced newer methods that have greatly improved the ability to identify ...respiratory pathogens. However, determining the microbial etiology of pneumonia remains a challenge, especially in children. This is largely because of the inconsistent use of assays between studies, difficulties in specimen collection, and problems in interpreting the presence of pathogens as being causally related to the pneumonia event. The laboratory testing strategy for the Pneumonia Etiology Research for Child Health (PERCH) study aims to incorporate a broad range of diagnostic testing that will be standardized across the 7 participating sites. We describe the current status of laboratory diagnostics for pneumonia and the PERCH approach for specimen testing. Pneumonia diagnostics are evolving, and it is also a priority of PERCH to collect and archive specimens for future testing by promising diagnostic methods that are currently under development.
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