Observation of directly interacting coherent two-level systems in a solid

Parasitic two-level tunneling systems originating from structural material defects affect the functionality of various microfabricated devices by acting as a source of noise. In particular, superconducting quantum bits may be sensitive to even single defects when these reside in the tunnel barrier of the qubit's Josephson junctions, and this can be exploited to observe and manipulate the quantum states of individual tunneling systems. Here, we detect and fully characterize a system of two strongly interacting defects using a novel technique for high-resolution spectroscopy. Mutual defect coupling has been conjectured to explain various anomalies of glasses, and was recently suggested as the origin of low frequency noise in superconducting devices. Our study provides conclusive evidence of defect interactions with full access to the individual constituents, demonstrating the potential of superconducting qubits for studying material defects. All our observations are consistent with the assumption that defects are generated by atomic tunneling.Comment: 13 pages, 7 figures. Includes supplementary materia

Alaskan Natural Gas to Liquids (GTL) Using Microchannel Reactors

The proposed Alaskan natural gas to liquids (GTL) plant utilizes microchannel technology for both steam-methane reforming and Fischer-Tropsch synthesis. A natural gas feed of 21.8 million standard cubic feet per hour is sent to a microchannel steam reformer, where it reacts with steam to produce a mixture comprised mainly of carbon monoxide and hydrogen, or syngas. The syngas proceeds to another microchannel reactor, in which the Fischer-Tropsch reaction converts it to hydrocarbons. Approximately 117,600 bbl/day of C5+ liquid hydrocarbons (25.86% gasoline, 24.78% diesel, 21.40% naphtha, 21.72% C20+, 6.25% other) are recovered and fed to the Trans-Alaskan Pipeline System for delivery to the North American market. The product contains little wax and few impurities and has an above average quality. Using a 13% discount rate, the project yields a positive 25-year Net Present Value of $708 million in 2009 and a 14.96% Internal Rate of Return, suggesting that the project has the potential to be an attractive investment. The most promising alternative to the GTL project is the construction of a natural gas pipeline, which would commence operation no sooner than 2019. The project’s economic feasibility depends most strongly on the product’s selling price, which is tied to the price of oil. The project is also capital-intensive and therefore sensitive to the final capital investment. Sensitivity analysis has been done on both of these factors

Disaster Management: A State-of-the-Art Review

Disaster management involves the pillars of emergency management: planning and preparation, mitigation, response, and recovery. Emergencies are serious events that threaten health, life, and property and can be managed within the capabilities of the affected organization. Disasters, on the other hand, are hypercomplex emergencies, requiring resources not immediately available. Disaster management follows the principles of emergency management, and emphasizes flexibility, collaboration, and teamwork. Lack of resources will challenge people and organizations both in effects of disasters and the ability to manage them. Poverty, climate change, governance, and education are foundations to improve capacity. Hospitals play an important role in disaster response and can prepare accordingly. Plans, to be effective, must be implemented through appropriately-targeted exercises. Building on an all-hazards approach, to more hazard-specific considerations can improve disaster preparedness as well as day-to-day efficiency. Disaster management is complex and crucial. These principles are explored through the fictional tale of Tucci1, a coastal city in the worst flood anyone can remember. Well, almost anyone

The Use of Molecular Pathway Inhibitors in the Treatment of Osteosarcoma

Presently, the 5-year survival rate for metastatic osteosarcoma remains low despite advances in chemotherapeutics and neoadjuvant therapy. A majority of the morbidity and nearly all of the mortality in osteosarcoma rely not in the primary disease but in the metastatic disease. The pursuit of novel molecular therapies is attractive due to their targeted ability to combat metastasis. Unlike traditional chemotherapy agents, which work by targeting rapidly dividing cells, targeted therapies may spare normal cells and decrease the adverse effects of chemotherapy by targeting specific pathways. Here, we discuss key molecular pathways in osteosarcoma and their ability to be modulated for the goal of eradication of primary and metastatic disease. We focus specifically on the aldehyde dehydrogenase (ALDH), epidermal growth factor receptor (EGFR), and insulin-like growth factor-1 receptor (IGF-1R) pathways

Electroretinogram Analysis of the Visual Response in Zebrafish Larvae

The electroretinogram (ERG) is a noninvasive electrophysiological method for determining retinal function. Through the placement of an electrode on the surface of the cornea, electrical activity generated in response to light can be measured and used to assess the activity of retinal cells in vivo. This manuscript describes the use of the ERG to measure visual function in zebrafish. Zebrafish have long been utilized as a model for vertebrate development due to the ease of gene suppression by morpholino oligonucleotides and pharmacological manipulation. At 5-10 dpf, only cones are functional in the larval retina. Therefore, the zebrafish, unlike other animals, is a powerful model system for the study of cone visual function in vivo. This protocol uses standard anesthesia, micromanipulation and stereomicroscopy protocols that are common in laboratories that perform zebrafish research. The outlined methods make use of standard electrophysiology equipment and a low light camera to guide the placement of the recording microelectrode onto the larval cornea. Finally, we demonstrate how a commercially available ERG stimulator/recorder originally designed for use with mice can easily be adapted for use with zebrafish. ERG of larval zebrafish provides an excellent method of assaying cone visual function in animals that have been modified by morpholino oligonucleotide injection as well as newer genome engineering techniques such as Zinc Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9, all of which have greatly increased the efficiency and efficacy of gene targeting in zebrafish. In addition, we take advantage of the ability of pharmacological agents to penetrate zebrafish larvae to evaluate the molecular components that contribute to the photoresponse. This protocol outlines a setup that can be modified and used by researchers with various experimental goals

Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort.

Purpose Treatment with pembrolizumab, an anti-programmed death-1 antibody, at 10 mg/kg administered once every 2 weeks, displayed durable antitumor activity in programmed death-ligand 1 (PD-L1) -positive recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE-012 trial. Results from the expansion cohort, in which patients with HNSCC, irrespective of biomarker status, received a fixed dose of pembrolizumab at a less frequent dosing schedule, are reported. Patients and Methods Patients with R/M HNSCC, irrespective of PD-L1 or human papillomavirus status, received pembrolizumab 200 mg intravenously once every 3 weeks. Imaging was performed every 8 weeks. Primary end points were overall response rate (ORR) per central imaging vendor (Response Evaluation Criteria in Solid Tumors v1.1) and safety. Secondary end points included progression-free survival, overall survival, and association of response and PD-L1 expression. Patients who received one or more doses of pembrolizumab were included in analyses. Results Of 132 patients enrolled, median age was 60 years (range, 25 to 84 years), 83% were male, and 57% received two or more lines of therapy for R/M disease. ORR was 18% (95% CI, 12 to 26) by central imaging vendor and 20% (95% CI, 13 to 28) by investigator review. Median duration of response was not reached (range, ≥ 2 to ≥ 11 months). Six-month progression-free survival and overall survival rates were 23% and 59%, respectively. By using tumor and immune cells, a statistically significant increase in ORR was observed for PD-L1-positive versus -negative patients (22% v 4%; P = .021). Treatment-related adverse events of any grade and grade ≥ 3 events occurred in 62% and 9% of patients, respectively. Conclusion Fixed-dose pembrolizumab 200 mg administered once every 3 weeks was well tolerated and yielded a clinically meaningful ORR with evidence of durable responses, which supports further development of this regimen in patients with advanced HNSCC

nab-paclitaxel/xarboplatin in vulnerable populations with advanced non-small cell lung cancer: Pooled analysis

Introduction: Despite improvements in the treatment of advanced non-small cell lung cancer (NSCLC), certain patient populations remain underrepresented in clinical trials. Many patients have benefited from platinum doublets, including Methods: To better understand outcomes in these patient populations, we performed a pooled analysis using data from the ABOUND clinical trial program (ABOUND.SQM, ABOUND.PS2, ABOUND.70+) and the key phase III trial of Results: Median progression-free survival (PFS) ranged from 4.1 months in patients with ECOG PS 2 (95% CI, 2.04-5.09 months) to 7.7 months in patients with diabetes (95% CI, 5.88-10.12 months). PFS for elderly patients and patients with renal impairment was 6.9 months each (95% CI, 6.01-7.98 months and 4.47-9.79 months, respectively). Median overall survival (OS) was 18.2 months (95% CI, 10.94-28.22 months), 17.4 months (95% CI, 14.59-20.14 months), and 16.1 months (95% CI, 14.09-18.50 months) in patients with renal impairment, patients with diabetes, and elderly patients, respectively. Patients with ECOG PS 2 exhibited the shortest median OS: 5.6 months (95% CI, 3.98-11.37 months). Overall response rates were 56.9%, 54.6%, 45.9%, and 29.4% in patients with diabetes, elderly patients, patients with renal impairment, and patients with ECOG PS 2, respectively. Most treatment-related adverse events were hematologic. The most common grade 3/4 hematologic adverse events in patients with renal impairment, elderly patients, patients with diabetes, and patients with poor performance status included neutropenia, anemia, and thrombocytopenia. Conclusions: Although survival data in patients with ECOG PS 2 were notably inferior to the other cohorts, our findings are consistent with those previously reported in the population-specific studies of the ABOUND trials and lend additional support for the use o

Induction chemotherapy with cetuximab, carboplatin and paclitaxel for the treatment of locally advanced squamous cell carcinoma of the head and neck

Although controversy exists in the management of locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN), clinicians often use induction chemotherapy for treatment of the most advanced cases. One promising regimen combines weekly cetuximab (400 mg/m2 loading dose followed by 250 mg/m2) with carboplatin (AUC of 2) and paclitaxel (90 mg/m2). We retrospectively evaluated patients treated with this regimen prior to definitive chemoradiation or surgery between May 2008 and December 2011. The primary endpoint used for this retrospective analysis was feasibility. Thirty consecutive, unselected patients were included. Median follow-up was 13.7 months (range, 5.0–38.7 months). All but one patient had stage IV SCCHN. Dose intensity was high for carboplatin (92%), paclitaxel (93%) and cetuximab (85%). Grade 3–4 toxicities occurred in <7% of the study population and were limited to rash, neutropenia and infusion reactions. Response rate (RR) to induction chemotherapy was 97% (30% complete response, 67% partial response). All patients completed subsequent chemoradiotherapy or surgery. Nineteen patients (63%) demonstrated a complete response and 11 patients (37%) demonstrated a partial response. Median overall survival and progression-free survival data are not yet mature. The RR to therapy in our off-protocol experience is at least comparable to that observed in the two phase II studies of this regimen and appears superior to that observed with docetaxel, cisplatin and fluorouracil (TPF)