Measurement of Small Photon Numbers in Circuit QED Resonators.

Off-resonant interaction of fluctuating photons in a resonator with a qubit increases the qubit dephasing rate. We use this effect to measure a small average number of intracavity photons that are coherently or thermally driven. For spectral resolution, we do this by subjecting the qubit to a Carr-Purcell-Meiboom-Gill sequence and record the qubit dephasing rate for various periods between qubit π pulses. The recorded data is then analyzed with formulas for the photon-induced dephasing rate derived for the non-Gaussian noise regime with an arbitrary ratio of the resonator dispersive shift to decay rate. We show that the presented Carr-Purcell-Meiboom-Gill dephasing rate formulas agree well with experimental results and demonstrate measurement of thermal and coherent photon populations at the level of a few 10^{-4}.

Polymerization Induced Microphase Separation for the Fabrication of Nanostructured Materials.

Polymerization induced microphase separation (PIMS) is a strategy used to develop unique nanostructures with highly useful morphologies through the microphase separation of emergent block copolymers during polymerization. In this process, nanostructures are formed with at least two chemically independent domains, where at least one domain is composed of a robust crosslinked polymer. Crucially, this synthetically simple method is readily used to develop nanostructured materials with the highly coveted co-continuous morphology, which can also be converted into mesoporous materials by selective etching of one domain. As PIMS exploits a block copolymer microphase separation mechanism, the size of each domain can be tightly controlled by modifying the size of block copolymer precursors, thus providing unparalleled control over nanostructure and resultant mesopore sizes. Since its inception 11 years ago, PIMS has been used to develop a vast inventory of advanced materials for an extensive range of applications including biomedical devices, ion exchange membranes, lithium-ion batteries, catalysis, 3D printing, and fluorescence-based sensors, among many others. In this review, we provide a comprehensive overview of the PIMS process, summarize latest developments in PIMS chemistry, and discuss its utility in a wide variety of relevant applications.

Robot-assisted Laparoscopic Prostatectomy After SpaceOAR Placement.

BACKGROUND: Patients with prostate cancer are offered a wide range of treatments from radiation therapy to chemotherapy to surgery. When giving radiation therapy, SpaceOAR hydrogel has been part of the standard treatment for the last decade to reduce unnecessary radiation exposure to the rectum. In rare cases, SpaceOAR may be placed but the patient cannot go through with radiation. The hydrogel ideally persists in the body for 3months then gets absorbed at 6months. OBJECTIVES: In this video presentation, we discuss our unique surgical case involving robot-assisted laparoscopic prostatectomy in a patient with SpaceOAR placement for 2months. RESULTS: A 58-year-old Caucasian male presented with screening prostate-specific antigen 48.47 and a biopsy showed grade group (GG) 3 in three cores, GG2 in one core, and GG1 in five cores. Patient was seen by urology and radiation oncology and initially opted for radiation therapy. He underwent SpaceOAR placement and was given a 6months dose of androgen deprivation therapy. However, during CT planning, small bowel was seen in the radiation field, in proximity to the prostate. As a result, the radiation was thought to be unsafe and he was referred back to urology. We considered options of immediate prostatectomy or waiting 6months until the hydrogel had been fully absorbed. Due to concerns of the hydrogel causing scarring after absorption, we decided to proceed with surgery. The area of SpaceOAR placement created the plane between the prostate and the rectum, however, there was dense scarring around the lateral aspects where the gel had started to absorb. This made the case difficult, but feasible. There were no complications. Final pathology showed pT2N0 with negative margins. CONCLUSION: Robot-assisted Radical Prostatectomy after SpaceOAR placement can be safe with good oncologic and functional outcomes. Although it is unknown how the tissues will ultimately heal after full absorption of the gel, it may be prudent to perform the surgery before the hydrogel is absorbed in order to maintain the anatomic planes of dissection.

3D Printed Solid Polymer Electrolytes with Bicontinuous Nanoscopic Domains for Ionic Liquid Conduction and Energy Storage.

Solid polymer electrolytes (SPEs) offer several advantages compared to their liquid counterparts, and much research has focused on developing SPEs with enhanced mechanical properties while maintaining high ionic conductivities. The recently developed polymerization-induced microphase separation (PIMS) technique offers a straightforward pathway to fabricate bicontinuous nanostructured materials in which the mechanical properties and conductivity can be independently tuned. In this work SPEs with tunable mechanical properties and conductivities are prepared via digital light processing 3D printing, exploiting the PIMS process to achieve nanostructured ion-conducting materials for energy storage applications. A rigid crosslinked poly(isobornyl acrylate-stat-trimethylpropane triacrylate) scaffold provided materials with room temperature shear modulus above 400 MPa, while soft poly(oligoethylene glycol methyl ether acrylate) domains containing the ionic liquid 1-butyl-3-methylimidazolium bis-(trifluoromethyl sulfonyl)imide endowed the material with ionic conductivity up to 1.2 mS cm-1 at 30 °C. These features make the 3D-printed SPE very competitive for applications in all solid energy storage devices, including supercapacitors.

3D Printing Nanostructured Solid Polymer Electrolytes with High Modulus and Conductivity.

The development of advanced solid-state energy-storage devices is contingent upon finding new ways to produce and manufacture scalable, high-modulus solid-state electrolytes that can simultaneously provide high ionic conductivity and robust mechanical integrity. In this work, an efficient one-step process to manufacture solid polymer electrolytes composed of nanoscale ion-conducting channels embedded in a rigid crosslinked polymer matrix via Digital Light Processing 3D printing is reported. A visible-light-mediated polymerization-induced microphase-separation approach is utilized, which produces materials with two chemically independent nanoscale domains with highly tunable nanoarchitectures. By producing materials containing a poly(ethylene oxide) domain swelled with an ionic liquid, robust solid polymer electrolytes with outstanding room-temperature (22 °C) shear modulus (G' > 108 Pa) and ionic conductivities up to σ = 3 × 10-4 S cm-1 are achieved. The nanostructured 3D-printed electrolytes are fabricated into a custom geometry and employed in a symmetric carbon supercapacitor, demonstrating the scalability of the fabrication and the functionality of the electrolyte. Critically, these high-performance materials are manufactured on demand using inexpensive and commercially available 3D printers, which allows the facile modular design of solid polymer electrolytes with custom geometries.

Responding to COVID-19 Among U.S. Military Units in South Korea: The U.S. Forces Korea's Operation Kill the Virus.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) is a viral respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has led to one of the world's largest infectious disease outbreaks. COVID-19 first emerged in Wuhan, Hubei, China, in December 2019, and the emergence was especially concerning to the U.S. Forces Korea (USFK) stationed in the Republic of Korea (ROK, South Korea), which remains vital to peace and security of the East Asian region. The first wave of cases emerged in South Korea from China before a globally established response, which forced USFK into a challenging position to combat a novel virus with countless unknowns regarding effective control and portended impact. MATERIALS AND METHODS: As cases began to emerge in South Korea, USFK in early February began to proactively formulate peninsula-wide preventative health measures to protect the force. Eventually, USFK spearheaded a uniquely proactive Operation Kill the Virus that targeted COVID-19 as an enemy that must be rigorously defended against. Through the operation, USFK systematically employed eight key principles to successfully combat the pandemic, which are documented in this article. RESULTS: The operation's eight principles focused on (1) Treat it like a combat operation, (2) Protect the force to protect the mission, (3) Stay one step ahead of the curve by exercising an abundance of caution, (4) Use predictive analysis, (5) Maintain open and transparent dialog with the community every day, (6) Be empathetic but prepare the community for lifestyle and culture changes, (7) Follow and enforce rules, and finally (8) Keep your foot on the gas and fight complacency. By closely collaborating with the ROK government, especially the Korean Centers for Disease Control and Prevention, USFK effectively limited the number of locally acquired cases, including service members, families, and civilians, to 24 by April 2020. Vital to that success was ensuring a sufficient capability and capacity to test, trace, treat, and logistically support with personal protective equipment and sufficient infrastructure for quarantine and isolation. As the pandemic shifted to the USA and Europe, new cases in the ROK shifted from locally acquired to imported from international travelers. Fundamental to USFK's sustained preservation of readiness and training included aggressive quarantine and testing of all arrivals from the United States of America (USA), identification of hotspots in all installations, and perpetual fine-tuning of the operation's principles in collaboration with the ROK's aggressive approach to eradicate COVID-19 from the peninsula. CONCLUSIONS: In successfully executing the operation, USFK imparts three main lessons for future outbreaks. First, a military command should execute a health response similar to how it executes combat operations against a battlefield enemy. Second, the command should maintain flexibility to new changes or risks that alter courses of action. And finally, engagement with the local community, host nation, and international partners should not be compromised when formulating strategies. The USFK's immediate recognition of the public health threat by all levels of leadership and medical personnel enabled a unique and highly effective Operation Kill the Virus that engaged all members of the community, both local and international.

Nanostructure Control in 3D Printed Materials.

Currently, there are no straightforward methods to 3D print materials with nanoscale control over morphological and functional properties. Here, a novel approach for the fabrication of materials with controlled nanoscale morphologies using a rapid and commercially available Digital Light Processing 3D printing technique is demonstrated. This process exploits reversible deactivation radical polymerization to control the in-situ-polymerization-induced microphase separation of 3D printing resins, which provides materials with complex architectures controllable from the macro- to nanoscale, resulting in the preparation of materials with enhanced mechanical properties. This method does not require specialized equipment or process conditions and thus represents an important development in the production of advanced materials via additive manufacturing.

Rapid High-Resolution 3D Printing and Surface Functionalization via Type I Photoinitiated RAFT Polymerization.

RAFT facilitated digital light projection 3D printing of polymeric materials provides a convenient and facile route for inducing post-fabrication transformations via reactivation of dormant chain transfer agents. In this work, we report the use of a Norrish type I photoinitiator in conjunction with a RAFT agent to produce a variety of open-air 3D printable resins that rapidly cure under visible light irradiation. The photoinitiator-RAFT system polymerizes extremely quickly and provides high 3D printing build rates of up to 9.1 cm h-1 , representing a 7-fold increase compared to previous RAFT mediated 3D printing systems. 3D printed materials containing thiocarbonylthio groups can be also produced using low concentrations of divinyl comonomers in the initial resins, which has not been successfully achieved using other photocontrolled RAFT polymerization techniques. Interestingly, the inclusion of RAFT agents significantly improves 3D printing resolution compared to formulations without RAFT agent, allowing the fabrication of intricate and complex objects. Spatiotemporally controlled surface modifications of the 3D printed objects from the dormant RAFT agent groups on the material surfaces were also performed under one and two-pass configurations, inducing multiple successive post-printing transformations on the same object.

Community pharmacists' preparedness for substituting biologics and dispensing biosimilars - Lessons learned from a multinational survey.

Interchangeability between biological medicines and biosimilars, and subsequent substitution by pharmacists represent an important opportunity for costs savings for health care systems. Because biological medicines are complex products, the expert role of the pharmacist to inform patients and support physicians is indispensable. However, regulations on substitution of biosimilars differ around the globe, such that a substitution that is allowed in one country may be forbidden in another. Overall, pharmacists' knowledge of biosimilar medicines is incomplete and hesitancy to engage in substitutions is perceptible. As counter-balancing remedy, continued education about biosimilars is needed among practicing community pharmacists.

Quantitative determination of the surfactant-induced split ratio of influenza virus by fluorescence spectroscopy.

The majority of marketed seasonal influenza vaccines are prepared using viruses that are chemically inactivated and treated with a surfactant. Treating with surfactants has important consequences: it produces 'split viruses' by solubilizing viral membranes, stabilizes free membrane proteins and ensures a low level of reactogenicity while retaining high vaccine potency. The formulation stability and potency of split influenza vaccines are largely determined by the specifics of this 'splitting' process; namely, the consequent conformational changes of proteins and interactions of solubilized particles, which may form aggregates. Robust methods to quantitatively determine the split ratio need to be developed before optimal splitting conditions can be investigated to streamline production of superior influenza vaccines. Here, we present a quantitative method, based on both steady-state and time-resolved fluorescence spectroscopy, to calculate the split ratio of the virus after surfactant treatment. We use the lipophilic dye Nile Red (NR) as a probe to elucidate molecular interactions and track changes in molecular environments. Inactivated whole influenza viruses obtained from a sucrose gradient were incubated with NR and subsequently treated with increasing concentrations of the surfactant Triton X-100 (TX-100) to induce virus splitting. NR's emission spectra showed that the addition of TX-100 caused ˜27 nm red-shifts in the emission peak, indicative of increasingly hydrophilic environments surrounding NR. The emission spectra of NR at different surfactant concentrations were analyzed with multi-peak fitting to ascertain the number of different micro-environments surrounding NR and track its population change in these different environments. Results from both the emission spectra and fluorescence lifetime spectroscopy revealed that NR showed presence in 3 distinct molecular environments. The split ratio of the virus was then calculated from the percentages of NR in these environments using both fluorescence emission and lifetime data. This study can pave the way for the development of robust methods to rapidly quantify splitting extent during vaccine manufacturing.

Relative value of multiple plasma biomarkers as risk factors for coronary artery disease and death in an angiography cohort.

BACKGROUND: Although elevated levels of C-reactive protein (CRP), interleukin (IL)-6, serum amyloid A protein (SAA) and total homocysteine (tHcy) have been associated with the increased likelihood of cardiovascular events, the relative or combined utility of these biomarkers in predicting atherosclerosis and death in an angiography cohort is unknown. METHODS: A cohort of 1117 consecutive patients (797 men and 320 women), referred to 2 Vancouver teaching hospitals for selective coronary angiography, was recruited between 1993 and 1995. Angiography results were obtained for 1019 patients. In 2004 we determined that of 1050 patients who could be traced, 231 had died, 95 of CAD-related causes. We compared the relative utility of baseline measurements of CRP, IL-6, SAA and tHcy as well as of lipids for predicting angiographic CAD and all-cause and CAD-related death. RESULTS: The risk of death increased across quartiles for CRP, IL-6, SAA and tHcy. When comparing the highest and lowest quartiles, the greatest hazard ratios were associated with IL-6 (2.57, 95% confidence interval [CI] 1.62-4.09) and tHcy (2.36, 95% CI 1.53-3.65). A Cox regression model containing all plasma biomarkers and traditional risk factors indicated that age, angiographic CAD and baseline plasma levels of IL-6 and tHcy remained independent predictors of CAD-related death, whereas age, sex, smoking, diabetes and apolipoprotein B levels were independent predictors of angiographic CAD. Kaplan-Meier survival curves indicated a utility in combining measures of CRP, SAA, IL-6 and tHcy for predicting risk of all-cause and CAD-related death. INTERPRETATION: A comparison of elevated levels of CRP, IL-6, SAA and tHcy with traditional CAD risk factors indicated that IL-6 and tHcy were the strongest independent biomarkers for CAD-related death. Elevated levels of multiple biomarkers were associated with an increasing rate of all-cause and CAD-related death.

Long-term androgen deprivation therapy improves survival in prostate cancer patients presenting with prostate-specific antigen levels > 20 ng/mL.

PURPOSE: To assess the benefit of androgen deprivation (AD) and its optimal duration in patients with prostate cancer treated with external beam radiotherapy, who present with prostate-specific antigen levels > 20 ng/mL. METHODS AND MATERIALS: A total of 307 patients treated with external beam radiotherapy, AD, and presenting with a PSA level > 20 ng/mL were identified from the Prostate Cancer Outcomes Initiative database of the British Columbia Cancer Agency. Androgen deprivation was defined as short term (ST-AD, < 12 months) or long term (LT-AD, > or = 12 months). The endpoints analyzed were biochemical control (no evidence of disease) (bNED), overall survival, and cause-specific survival. Statistical analysis was conducted with Kaplan-Meier estimates, log-rank tests, and multivariate analyses with logistic and Cox regression models. RESULTS: There were 151 patients in the ST-AD group and 156 in the LT-AD group. The distributions of Gleason score and stage were comparable in the two cohorts. Median follow-up times were 48 months for patients treated with ST-AD and 45 months for patients treated with LT-AD. The median durations of AD were 6 and 25.6 months for the ST-AD and LT-AD groups, respectively. The bNED rate was 37% for the ST-AD group and 62.5% for the LT-AD group (p < 0.0001). The 5-year overall survival rate was 75% in the ST-AD group vs. 87.5% for the LT-AD group (p = 0.0091). The 5-year cause-specific survival rate was 82% for the ST-AD group vs. 94% for the LT-AD group (p = 0.0072). CONCLUSIONS: Several randomized trials have demonstrated the benefit of LT-AD in high-risk patients with prostate cancer. In some reports, the survival advantage seems to be restricted to patients with high Gleason score. The present analysis supports the hypothesis that LT-AD improves bNED and survival rates in patients presenting with a PSA level > 20, irrespective of Gleason score or T stage.

APOA5 gene polymorphism modulates levels of triglyceride, HDL cholesterol and FERHDL but is not a risk factor for coronary artery disease.

Variation in the APOA5 gene has been shown to be associated with triglyceride levels in several independent population studies. It was our objective to determine if a relationship existed between selected genotypes or haplotypes of the APOA5 gene and findings on selective coronary angiography (SCA) in an independent cohort. The Vancouver SCA Cohort consists of individuals referred for angiography between 1993 and 1995. DNA was extracted from 537 patients and analyzed for the -1131T>C and the c.56C>G polymorphisms which define three common haplotypes of the APOA5 gene. Plasma triglycerides and the fractional esterification rate in apoB-depleted lipoproteins (FER(HDL)), an index of high-density lipoprotein (HDL) composition, were significantly higher (P = 0.01 and P = 0.001, respectively), and HDL cholesterol (HDL-C) was significantly lower (P = 0.03) in Caucasians with genotypes containing the minor allele of the -1131T>C polymorphism compared to the homozygotes for the major allele. However, there was no relationship between the c.56C>G polymorphism of the APOA5 gene and any of the measured lipid and lipoprotein parameters. Subjects homozygous for the common haplotype APOA5*1 had decreased triglyceride levels and FER(HDL) (P = 0.04 and P < 0.001, respectively) and increased HDL-C levels (P = 0.01) compared to subjects with all other haplogenotypes. Multivariate linear regression analysis indicated that the -1131T>C polymorphism remained an independent predictor of triglyceride, HDL-C, and FER(HDL) following adjustment of several variables including age, gender, body mass index, diabetes, lipid lowering and beta-blocker medication. The APOA5*1/*1 haplogenotype remained an independent predictor of HDL-C and FER(HDL) following adjustment of the same variables. The relationship between APOA5 genotype or haplogenotype and FER(HDL) remained significant even after the addition of both HDL-C and triglyceride to the model. However, there was no association between APOA5 gene polymorphisms or haplotypes and coronary artery disease as determined by angiography.