On 17 August 2017, Swope Supernova Survey 2017a (SSS17a) was discovered as the optical counterpart of the binary neutron star gravitational wave event GW170817. We report time-series spectroscopy of ...SSS17a from 11.75 hours until 8.5 days after the merger. Over the first hour of observations, the ejecta rapidly expanded and cooled. Applying blackbody fits to the spectra, we measured the photosphere cooling from
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kelvin, and determined a photospheric velocity of roughly 30% of the speed of light. The spectra of SSS17a began displaying broad features after 1.46 days and evolved qualitatively over each subsequent day, with distinct blue (early-time) and red (late-time) components. The late-time component is consistent with theoretical models of r-process–enriched neutron star ejecta, whereas the blue component requires high-velocity, lanthanide-free material.
On 17 August 2017, gravitational waves (GWs) were detected from a binary neutron star merger, GW170817, along with a coincident short gamma-ray burst, GRB 170817A. An optical transient source, Swope ...Supernova Survey 17a (SSS17a),was subsequently identified as the counterpart of this event. We present ultraviolet, optical, and infrared light curves of SSS17a extending from 10.9 hours to 18 days postmerger. We constrain the radioactively powered transient resulting from the ejection of neutron-rich material. The fast rise of the light curves, subsequent decay, and rapid color evolution are consistent with multiple ejecta components of differing lanthanide abundance. The late-time light curve indicates that SSS17a produced at least ~0.05 solar masses of heavy elements, demonstrating that neutron star mergers play a role in rapid neutron capture (r-process) nucleosynthesis in the universe.
Margetuximab is an anti-HER2 antibody that binds with elevated affinity to both the lower and higher affinity forms of CD16A, an Fc-receptor important for antibody dependent cell-mediated ...cytotoxicity (ADCC) against tumor cells. A Phase 1 study was initiated to evaluate the toxicity profile, maximum tolerated dose (MTD), pharmacokinetics, and antitumor activity of margetuximab in patients with HER2-overexpressing carcinomas.
Patients with HER2-positive breast or gastric cancer, or other carcinomas that overexpress HER2, for whom no standard therapy was available, were treated with margetuximab by intravenous infusion at doses of 0.1–6.0 mg/kg for 3 of every 4 weeks (Regimen A) or once every 3 weeks (10–18 mg/kg) (Regimen B).
Sixty-six patients received margetuximab (34 patients for Regimen A and 32 patients for Regimen B). The MTD was not reached for either regimen. Treatment was well-tolerated, with mostly Grade 1 and 2 toxicities consisting of constitutional symptoms such as pyrexia, nausea, anemia, diarrhea, and fatigue. Among 60 response-evaluable patients, confirmed partial responses and stable disease were observed in 7 (12%) and 30 (50%) patients, respectively; 26 (70%) of these patients had received prior HER2-targeted therapy. Tumor reductions were observed in over half (18/23, 78%) of response-evaluable patients with breast cancer including durable (>30 weeks) responders.Ex vivo analyses of patient peripheral blood mononuclear cell samples confirmed the ability of margetuximab to support enhanced ADCC compared with trastuzumab.
Margetuximab was well-tolerated and has promising single-agent activity. Further development efforts of margetuximab as single agent and in combination with other therapeutic agents are ongoing.
NCT01148849.
Bone development and homeostasis require the interplay between several cell types, including mesenchymal osteoblasts and osteocytes, as well as hematopoietic osteoclasts. Recent evidence suggests ...that cell proliferation, differentiation and apoptosis of both mesenchymal and hematopoietic stem cells, which are fundamental for tissue regeneration and treatment of degenerative diseases, are controlled by P2 receptors (i.e., P2X and P2Y receptors). Both types of P2 receptors are versatile transducers of diverse signals activated by extracellular nucleotides like ATP that are released in response to tissue injury, infection or shear stress. The P2X family of receptors has been shown to mediate multiple signaling events including the influx of calcium, activation of mitogen activated protein kinases (MAPKs) and induction of AP-1 family members known to regulate bone development. Support for the significance of P2X7 in regulating bone development and homeostasis has been provided by several studies focusing on animal models and single nucleotide polymorphisms. P2 receptors are functionally expressed in both bone forming osteoblasts and bone resorbing osteoclasts, while recent findings also suggest that these receptors translate mechanical stimuli in osteocytes. Their ability to respond to external nucleotide analogs renders these cell surface proteins excellent targets for skeletal regenerative therapies. This overview summarizes mechanisms by which nucleotide receptors control skeletal cells and contribute to bone tissue development remodeling and repair.
•Function of nucleotide receptors in mesenchymal and hematopoietic stem cells•Transcriptional targets of nucleotide receptors in mesenchymal stem cells•Downstream molecular targets of nucleotide receptors in hematopoietic stem cells•Calcium oscillations, mesenchymal and hematopoietic stem cells•P2 receptors and bone
Although oxylipins can be synthesized from free fatty acids, recent evidence suggests that oxylipins are components of plastid-localized polar complex lipids in Arabidopsis (Arabidopsis thaliana). ...Using a combination of electrospray ionization (ESI) collisionally induced dissociation time-of-flight mass spectrometry (MS) to identify acyl chains, ESI triple-quadrupole (Q) MS in the precursor mode to identify the nominal masses of complex polar lipids containing each acyl chain, and ESI Q-time-of-flight MS to confirm the identifications of the complex polar lipid species, 17 species of oxylipin-containing phosphatidylglycerols, monogalactosyldiacylglycerols (MGDG), and digalactosyldiacylglycerols (DGDG) were identified. The oxylipins of these polar complex lipid species include oxophytodienoic acid (OPDA), dinor-OPDA (dnOPDA), 18-carbon ketol acids, and 16-carbon ketol acids. Using ESI triple-Q MS in the precursor mode, the accumulation of five OPDA- and/or dnOPDA-containing MGDG and two OPDA-containing DGDG species were monitored as a function of time in mechanically wounded leaves. In unwounded leaves, the levels of these oxylipin-containing complex lipid species were low, between 0.001 and 0.023 nmol/mg dry weight. However, within the first 15 min after wounding, the levels of OPDA-dnOPDA MGDG, OPDA-OPDA MGDG, and OPDA-OPDA DGDG, each containing two oxylipin chains, increased 200- to 1,000-fold. In contrast, levels of OPDA-hexadecatrienoic acid MGDG, linolenic acid (18:3)-dnOPDA MGDG, OPDA-18:3 MGDG, and OPDA-18:3 DGDG, each containing a single oxylipin chain, rose 2- to 9-fold. The rapid accumulation of high levels of galactolipid species containing OPDA-OPDA and OPDA-dnOPDA in wounded leaves is consistent with these lipids being the primary products of plastidic oxylipin biosynthesis.
Electronic health record (EHR) systems have transformed the medical industry. Despite their known benefits, their implementation has resulted in new digital administrative tasks and responsibilities ...for physicians. This increase in administrative burden has been shown to contribute to physician burnout. Most sources of EHR-related burnout can be categorized into three groups: poor usability, excessive time spent in the EHR, and inefficient workflows. Evidence-based interventions for EHR-related burnout focus on training and education, which improve efficiency in EHR use and may reduce burnout. Optimization of the EHR interface, including personalization and use of targeted workflows, can help address physician frustrations and improve productivity. In the United States, the federal government regulates EHR system development and sets usability requirements. These requirements are critical because visualization and operational design of the user interface have been shown to directly affect patient care and safety. Negative effects of EHR implementation generally are related to increased administrative burden. Positive effects include greater clinician productivity and administrative cost savings. EHR adoption has consistently been associated with positive financial and clinical outcomes. Federal laws continue to be implemented to improve EHR usability, interoperability, and standards for data access and security.
Purpose - Three layer-additive manufacturing methods were evaluated to producing nickel-titanium graded composition material. One potential application is fabrication of attachment clips that join ...thermal protection systems to launch vehicle structure. Thermal gradients during flight generate excessive bending and shear loads that limit the service lifetime of the Inconel clips currently used. It is envisioned that a graded composition component could be tailored to reduce the stress concentrations.Design methodology approach - Deposits with nearly continuous composition grade were built from Ti-6-4 and Inconel 718 powder using laser direct metal deposition. Layered deposits were produced by flat wire welding from Ti-6-4 and Inconel 718 wire. Ultrasonic consolidation was used to produce layered deposits from pure nickel and commercially pure titanium foils. Microstructure, bond line morphology, chemical composition, and reaction phases were characterized.Findings - All three manufacturing methods require further development before graded composition material can be reliably produced. Laser direct metal deposition samples exhibited coarse dendritic microstructures and significant elemental segregation. Chemistries varied from calculated targets by up to 20 percent and macroscopic cracking occurred for chemistries greater than 60 percent Inconel 718. Flat wire welded deposits exhibited good mixing between the wire layers, however brittle cracking occurred adjacent to a 5 μm thick reaction layer. Ultrasonically-consolidated samples demonstrated metallurgical bonding between pure Ni and commercially pure (CP) Ti foils, with material reaction limited to a 1 μm layer.Originality value - Producing nickel-titanium graded composition materials had not been attempted by the selected manufacturing methods. A refined experimental program is needed to resolve the remaining technical issues.
BACKGROUND:Increasing evidence suggests that open reduction and internal fixation of condylar base fractures in adults results in improved outcomes in regard to interincisal opening, jaw movement, ...pain, and malocclusion. However, most of the condylar fractures are managed by maxillomandibular fixation alone due to the need for specialized training and equipment. Our aim was to present an algorithm for condylar base fractures to simplify surgical management.
METHODS:A retrospective review was performed of patients (n = 22) with condylar base fractures treated from 2016 to 2020. Patients who presented with operative fractures that require open treatment underwent 1 of 2 different techniques depending on the fracture typea preauricular approach with a transoral approach if the condyle was dislocated (n = 2) or a transoral only approach (n = 20) in nondislocated cases. Operative time, occlusion, range of motion, and postoperative complications were assessed.
RESULTS:Condylar base fractures were combined with other mandibular fractures in 16 of 22 patients. Patients with condylar dislocation were managed with a preauricular approach with a secondary transoral incision (n = 2, median 147 minutes). Those without dislocation were treated with a transoral approach (n = 20, median 159 minutes). Most patients were restored to their preoperative occlusion without long-term complications.
CONCLUSIONS:We present a simplified algorithm for treating condylar base fractures. Our case series suggests that reduction in operative time and clinical success can be achieved with open reduction and internal fixation using a transoral approach alone or in combination with a preauricular approach for dislocated fractures.
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