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Reliable preparation, manipulation and measurement protocols are necessary to exploit a physical system as a quantum bit (1). Spins in optically active quantum dots offer one potential realization (2,3) and recent demonstrations have shown high-fidelity preparation (4,5) and ultrafast coherent manipulation (6-8). The final challenge--that is, single-shot measurement of the electron spin--has proved to be the most difficult of the three and so far only time-averaged optical measurements have been reported (9-12). The main obstacle to optical spin readout in single quantum dots is that the same laser that probes the spin state also flips the spin being measured. Here, by using a gate-controlled quantum dot molecule (13-15), we present the ability to measure the spin state of a single electron in real time via the intermittency of quantum dot resonance fluorescence (12,16). The quantum dot molecule, unlike its single quantum dot counterpart, allows separate and independent optical transitions for state preparation, manipulation and measurement, avoiding the dilemma of relying on the same transition to address the spin state of an electron., The concept of using resonance fluorescence (RF) to probe internal atomic state dynamics dates from 1975 (ref. 17) with the first demonstrations from trapped ions in 1986 (refs 18-20) followed [...]

We present a new method for coherent control of trapped ion qubits in separate interaction regions of a multizone trap by simultaneously applying an electric field and a spin-dependent gradient. Both the phase and amplitude of the effective single-qubit rotation depend on the electric field, which can be localized to each zone. We demonstrate this interaction on a single ion using both laser-based and magnetic-field gradients in a surface-electrode ion trap, and measure the localization of the electric field.

We demonstrate coupling between the motions of two independently trapped ions with a separation distance of 620  μm. The ion-ion interaction is enhanced via a room-temperature electrically floating metallic wire which connects two surface traps. Tuning the motion of both ions into resonance, we show flow of energy with a coupling rate of 11 Hz. Quantum-coherent coupling is hindered by strong surface electric-field noise in our device. Our ion-wire-ion system demonstrates that room-temperature conductors can be used to mediate and tune interactions between independently trapped charges over distances beyond those achievable with free-space dipole-dipole coupling. This technology may be used to sympathetically cool or entangle remotely trapped charges and enable coupling between disparate physical systems.

Background: The coronavirus disease 2019 pandemic forced residency programs to adapt teaching to the virtual arena. Objective Structured Teaching Exercises (OSTEs) are a simulation-based session we previously implemented in our in-person pediatric curriculum. We aimed to assess feasibility of and resident satisfaction with the transition to virtual learning for simulation-based OSTEs., Methods: The pediatrics residency program at our hospital has a weekly academic half-day for residents where the OSTEs were held annually in person 2018 to 2019 and virtually in 2020. Surveys were collected from participating residents and faculty to compare teaching experience, feedback quality, and satisfaction with the session., Results: Over 3 academic years, there were 159 total teaching sessions, 3 of which were OSTEs. The OSTE session was highly rated each year and was the second highest rated virtual session. Residents felt the OSTEs improved their teaching regardless of the virtual versus in-person platform (P = .77), and the quality of feedback as rated by the resident teacher was higher for virtual sessions (P < .001)., Conclusions: Transitioning the OSTE to a virtual platform was both feasible and effective when compared to the in-person OSTE. In the transition to virtual learning, educators should consider opportunities for simulation-based teaching such as OSTEs., (Published by Elsevier Inc.)

Macrophages and related tissue macrophage populations use the classical NADPH oxidase (NOX2) for the regulated production of superoxide and derived oxidants for pathogen combat and redox signaling. With an emphasis on macrophages, we discuss how sorting into secretory storage vesicles, agonist-responsive membrane trafficking, and segregation into sphingolipid and cholesterol-enriched microdomains (lipid rafts) determine the subcellular distribution and spatial organization of NOX2 and superoxide dismutase-3 (SOD3). We discuss how inflammatory activation of macrophages, in part through small GTPase Rab27A/B regulation of the secretory compartments, mediates the coalescence of these two proteins on the cell surface to deliver a focalized hydrogen peroxide output. In interplay with membrane-embedded oxidant transporters and redox sensitive target proteins, this arrangement allows for the autocrine and paracrine signaling, which govern macrophage activation states and transcriptional programs. By discussing examples of autocrine and paracrine redox signaling, we highlight why formation of spatiotemporal microenvironments where produced superoxide is rapidly converted to hydrogen peroxide and conveyed immediately to reach redox targets in proximal vicinity is required for efficient redox signaling. Finally, we discuss the recent discovery of macrophage-derived exosomes as vehicles of NOX2 holoenzyme export to other cells.

Vitamins are the organic compounds that have long been known to play a significant role in our body by functioning as hormones and antioxidants. Vitamin D, a fat-soluble vitamin, is the main regulator of calcium hemostasis in our body. At the same time, it is also known to show its potential effects on the immune system by modulating the differentiation, activation, and proliferation of T and B lymphocytes. The immunomodulatory properties of vitamin D are also known to have a crucial role in the prevention and treatment of graft-versus-host disease. Patients undergoing hematopoietic stem cell transplantation are particularly at risk of vitamin D deficiency. This review article expands our understanding of vitamin D, its immunomodulatory effects, and its role in prevention and treatment of graft-versus-host disease., (Copyright © 2018 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

We describe the design, fabrication, and operation of a novel surface-electrode Paul trap that produces a radio-frequency-null along the axis perpendicular to the trap surface. This arrangement enables control of the vertical trapping potential and consequentially the ion-electrode distance via dc-electrodes only. We demonstrate the confinement of single 40 Ca + ions at heights between 50 μ m and 300 μ m above planar copper-coated aluminum electrodes. Laser-cooling and coherent operations are performed on both the planar and vertical motional modes. This architecture provides a platform for precision electric-field noise detection and trapping of vertical ion strings without excess micromotion and may have applications for scalable quantum computers with surface ion traps.

Importance: There is a significant need to find biomarkers of response to radiotherapy and cetuximab in locally advanced head and neck squamous cell carcinoma (HNSCC) and biomarkers that predict altered immunity, thereby enabling personalized treatment., Objectives: To examine whether the Kirsten rat sarcoma viral oncogene homolog (KRAS)-variant, a germline mutation in a microRNA-binding site in KRAS, is a predictive biomarker of cetuximab response and altered immunity in the setting of radiotherapy and cisplatin treatment and to evaluate the interaction of the KRAS-variant with p16 status and blood-based transforming growth factor β1 (TGF-β1)., Design, Setting, and Participants: A total of 891 patients with advanced HNSCC from a phase 3 trial of cisplatin plus radiotherapy with or without cetuximab (NRG Oncology RTOG 0522) were included in this study, and 413 patients with available samples were genotyped for the KRAS-variant. Genomic DNA was tested for the KRAS-variant in a CLIA-certified laboratory. Correlation of the KRAS-variant, p16 positivity, outcome, and TGF-β1 levels was evaluated. Hazard ratios (HRs) were estimated with the Cox proportional hazards model., Main Outcomes and Measures: The correlation of KRAS-variant status with cetuximab response and outcome, p16 status, and plasma TGF-β1 levels was tested., Results: Of 891 patients eligible for protocol analyses (786 male [88.2%], 105 [11.2%] female, 810 white [90.9%], 81 nonwhite [9.1%]), 413 had biological samples for KRAS-variant testing, and 376 had plasma samples for TGF-β1 measurement. Seventy patients (16.9%) had the KRAS-variant. Overall, for patients with the KRAS-variant, cetuximab improved both progression-free survival (PFS) for the first year (HR, 0.31; 95% CI, 0.10-0.94; P = .04) and overall survival (OS) in years 1 to 2 (HR, 0.19; 95% CI, 0.04-0.86; P = .03). There was a significant interaction of the KRAS-variant with p16 status for PFS in patients treated without cetuximab. The p16-positive patients with the KRAS-variant treated without cetuximab had worse PFS than patients without the KRAS-variant (HR, 2.59; 95% CI, 0.91-7.33; P = .07). There was a significant 3-way interaction among the KRAS-variant, p16 status, and treatment for OS (HR, for KRAS-variant, cetuximab and p16 positive, 0.22; 95% CI, 0.03-1.66; HR for KRAS-variant, cetuximab and p16 negative, 1.43; 95% CI, 0.48-4.26; HR for KRAS-variant, no cetuximab and p16 positive, 2.48; 95% CI, 0.64-9.65; and HR for KRAS-variant, no cetuximab and p16 negative, 0.61; 95% CI, 0.23-1.59; P = .02). Patients with the KRAS-variant had significantly elevated TGF-β1 plasma levels (median, 23 376.49 vs 18 476.52 pg/mL; P = .03) and worse treatment-related toxic effects., Conclusions and Relevance: Patients with the KRAS-variant with HNSCC significantly benefit from the addition of cetuximab to radiotherapy and cisplatin, and there is a significant interaction between the KRAS-variant and p16 status. Elevated TGF-β1 levels in patients with the KRAS-variant suggests that cetuximab may help these patients by overcoming TGF-β1-induced suppression of antitumor immunity., Trial Registration: clinicaltrials.gov Identifier: NCT00265941.

Purpose: To analyze the quality of life (QOL) and performance status (PS) (secondary outcome) in patients with stage III to IV head and neck cancer (HNC) enrolled on a prospective randomized phase 3 trial comparing radiation-cisplatin without cetuximab (CIS) or with cetuximab (CET/CIS). The QOL hypothesis proposed a between-arm difference in Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) total score of ≥10% of the instrument range from baseline to 1 year., Methods and Materials: Patients who gave consent to the QOL/PS study completed the FACT-HN, Performance Status Scale for HNC (PSS-HN), and EuroQol (EQ-5D) at baseline through to 5 years. The pretreatment QOL/PS scores were correlated with outcome and p16 status in patients with oropharyngeal cancer (OPC)., Results: Of 818 analyzable patients, the 1-year change from baseline score for FACT-HN total was -0.41 (CIS arm) and -5.11 (CET/CIS arm) (P=.016), representing a 3.2% between-arm change of the FACT-HN total score. The mean EQ-5D index and PSS-HN scores were not significantly different between arms. The p16-positive OPC patients had significantly higher baseline and 1-year scores for PSS-HN, FACT-HN total, physical and functional subscales, and 2-years for the EQ-5D index compared with p16-negative OPC patients. Higher pretreatment PSS-HN diet, PSS-HN eating, FACT-HN, and EQ-5D index scores were associated with better overall survival (OS) and progression-free (PFS) survival on multivariate analysis. Higher baseline FACT-HN total, functional, physical subscale, and EQ-5D index scores were associated with improved OS and PFS in p16-positive OPC patients but not in p16-negative and non-OPC patients., Conclusion: There was no clinically meaningful difference in QOL/PS between arms. The p16-positive OPC patients had significantly higher QOL/PS than did p16-negative patients. Pretreatment QOL/PS is a significant independent predictor of outcome in locally advanced HNC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The present study evaluated growing mink () as a model for dietary protein quality assessment of protein meals used in extruded dog foods. Three foods with similar CP content but of different protein quality were produced using different protein meals. The protein meals varied with respect to CP digestibility and AA composition and included lamb meal (LBM), poultry meal (PM), and fish meal (FM) with low, intermediate, and high protein quality, respectively. Nitrogen balance, BW gain, protein efficiency ratio (PER), and apparent total tract digestibility (ATTD) were used as measures of protein and AA bioavailability in growing mink. Standardized ileal digestibility (SID) was used to measure protein and AA bioavailability in adult dogs (). The mink study (3 × 3 Latin square design) included 12 kits aged 8 to 11 wk. The dog study included 12 dogs divided in 3 groups allocated to 1 of the experimental diets. The growing mink responded in accordance with the different AA supply between diets, as determined by the first limiting AA. The LBM diet deviated from the other diets with lower ( < 0.001) values for N retention, BW gain, and PER, and the diets differed ( < 0.001) in ATTD of CP and all AA, except for hydroxyproline. Retention of N was 0.66, 1.04, and 1.18 g·kg·d; BW gain was 8.2, 26.8, and 35.3 g/d; PER was 0.38, 1.39, and 1.71; and ATTD of CP was 66.8, 73.8, and 82.1% for the LBM, PM, and FM diets, respectively. In dogs, SID of CP and AA differed ( ≤ 0.017) between diets and was generally lowest for the LBM diet, intermediate for the PM diet, and greatest for the FM diet. For CP, SID was 71.5, 80.2, and 87.0% for the LBM, PM, and FM diets, respectively. The contents of digestible CP and AA (based on SID) covered the minimal requirement for adult dogs set by the NRC for all diets, except for the content of digestible Met + Cys in the LBM diet. Despite this, dietary content of Met + Cys in the LBM diet agreed with the recommended level set by the NRC and the Association of American Feed Control Officials for adult dogs but was below the level recommended by the European Pet Food Industry Federation. It was concluded that growth studies with mink kits can provide valuable information in protein quality assessment of extruded dog foods. Furthermore, the study showed that to ensure nutritional adequacy of dog food and to be able to compare protein quality of dog foods, information on AA composition and digestibility is crucial.

Resonance fluorescence arises from the interaction of an optical field with a two-level system, and has played a fundamental role in the development of quantum optics and its applications. Despite its conceptual simplicity, it entails a wide range of intriguing phenomena, such as the Mollow-triplet emission spectrum, photon antibunching and coherent photon emission. One fundamental aspect of resonance fluorescence--squeezing in the form of reduced quantum fluctuations in the single photon stream from an atom in free space--was predicted more than 30 years ago. However, the requirement to operate in the weak excitation regime, together with the combination of modest oscillator strength of atoms and low collection efficiencies, has continued to necessitate stringent experimental conditions for the observation of squeezing with atoms. Attempts to circumvent these issues had to sacrifice antibunching, owing to either stimulated forward scattering from atomic ensembles or multi-photon transitions inside optical cavities. Here, we use an artificial atom with a large optical dipole enabling 100-fold improvement of the photon detection rate over the natural atom counterpart and reach the necessary conditions for the observation of quadrature squeezing in single resonance-fluorescence photons. By implementing phase-dependent homodyne intensity-correlation detection, we demonstrate that the electric field quadrature variance of resonance fluorescence is three per cent below the fundamental limit set by vacuum fluctuations, while the photon statistics remain antibunched. The presence of squeezing and antibunching simultaneously is a fully non-classical outcome of the wave-particle duality of photons.

Objective: Stereotactic body radiation therapy (SBRT) facilitates highly conformal dose distributions to a targe tumor volume. Accurate tumor localization is extremely important, and lung tumors pose a unique challenge due to respiratory motion. Patients are required to fast before PET/CT but not before CT simulation and daily treatment, introducing potential variability from gastric distension., Methods: A case was reviewed involving a patient with early-stage NSCLC which was simulated and treated with SBRT. PET/CT performed while fasting showed an isolated left lower lobe lesion. Following CT simulation, CT and PET/CT images were superimposed for comparison and treatment planning., Results: Tumor location variation was apparent following image superimposition. Simulation CT showed significant gastric distension compared to PET/CT. The patient was resimulated while fasting, resulting in accurate and reproducible tumor localization for treatment planning., Conclusions: Gastric distension can alter tumor location and treatment volumes for radiotherapy planning, possibly resulting in inaccurate treatment administration.