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Due to the curative potential and improvement in progression-free survival (PFS), high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is considered the standard of care for several hematologic malignancies, such as multiple myeloma, and lymphomas. ASCT typically involves support with blood product transfusion. Thus, difficulties arise when Jehovah’s Witness patients refuse blood transfusions. In order to demonstrate the safety of performing “bloodless” ASCT (BL-ASCT), we performed a retrospective analysis of 66 Jehovah's Witnesses patients who underwent BL-ASCT and 1114 non-Jehovah’s Witness patients who underwent transfusion-supported ASCT (TF-ASCT) at Cedars-Sinai Medical Center between January 2000 and September 2018. Survival was compared between the two groups. Transplant-related complications, mortality, engraftment time, length of hospital stay, and number of ICU transfers were characterized for the BL-ASCT group. One year survival was found to be 87.9% for both groups (P = 0.92). In the BL-ASCT group, there was one death prior to the 30 days post transplant due to CNS hemorrhage, and one death prior to 100 days due to sepsis. Based on our data, BL-ASCT can be safely performed with appropriate supportive measures, and we encourage community oncologists to promptly refer JW patients for transplant evaluation when ASCT is indicated.

A novel digital PCR (dPCR) platform combining off-the-shelf reagents, a micro-molded plastic microfluidic consumable with a fully integrated single dPCR instrument was developed to address the needs for routine clinical diagnostics. This new platform offers a simplified workflow that enables: rapid time-to-answer; low potential for cross contamination; minimal sample waste; all within a single integrated instrument. Here we showcase the capability of this fully integrated platform to detect and quantify non-small cell lung carcinoma (NSCLC) rare genetic mutants (EGFR T790M) with precision cell-free DNA (cfDNA) standards. Next, we validated the platform with an established chronic myeloid leukemia (CML) fusion gene (BCR-ABL1) assay down to 0.01% mutant allele frequency to highlight the platform’s utility for precision cancer monitoring. Thirdly, using a juvenile myelomonocytic leukemia (JMML) patient-specific assay we demonstrate the ability to precisely track an individual cancer patient’s response to therapy and show the patient’s achievement of complete molecular remission. These three applications highlight the flexibility and utility of this novel fully integrated dPCR platform that has the potential to transform personalized medicine for cancer recurrence monitoring.

Background: Patients with mild asthma represent a substantial proportion of the population with asthma, yet there are limited data on their true burden of disease. We aimed to describe the clinical and healthcare resource utilisation (HCRU) burden of physician-assessed mild asthma. Methods: Patients with mild asthma were included from the NOVEL observational longiTudinal studY (NOVELTY; NCT02760329), a global, 3-year, real-world prospective study of patients with asthma and/or chronic obstructive pulmonary disease from community practice (specialised and primary care). Diagnosis and severity were based on physician discretion. Clinical burden included physician-reported exacerbations and patient-reported measures. HCRU included inpatient and outpatient visits. Results: Overall, 2004 patients with mild asthma were included; 22.8% experienced >= 1 exacerbation in the previous 12 months, of whom 72.3% experienced >= 1 severe exacerbation. Of 625 exacerbations reported, 48.0% lasted >1 week, 27.7% were preceded by symptomatic worsening lasting >3 days, and 50.1% required oral corticosteroid treatment. Health status was moderately impacted (St George's Respiratory Questionnaire score: 23.5 [standard deviation +/- 17.9]). At baseline, 29.7% of patients had asthma symptoms that were not well controlled or very poorly controlled (Asthma Control Test score = 2 exacerbations in the previous year. In terms of HCRU, at least one unscheduled ambulatory visit for exacerbations was required by 9.5% of patients, including 9.2% requiring >= 1 emergency department visit and 1.1% requiring >= 1 hospital admission. Conclusions: In this global sample representing community practice, a significant proportion of patients with physician-assessed mild asthma had considerable clinical burden and HCRU.

We have been developing gallium nitride (GaN) monolithic microwave integrated circuits (MMICs) towards the goal of implementing a single chip transceiver frontend for cloud radar arrays at Ka-band. We present our first effort design, fabrication and test cycle implementation of GaN power amplifiers (PAs), low noise amplifiers (LNAs), driver amplifier, single-pole-double and triple throw switches, and voltage controlled attenuator. These components are necessary for implementing a transceiver unit cell concept with digital calibration capabilities to enable scalable array sizes for radar and radiometry.

Background: ANDHI was done to assess the efficacy of benralizumab, including onset of effect and impact on health-related quality of life (HRQOL), exacerbation rate, lung function, and nasal polyposis symptoms. Methods: This phase 3b, randomised, double-blind, parallel-group, placebo-controlled ANDHI study was completed in adults (aged 18–75 years) with severe eosinophilic asthma with at least 2 exacerbations in the previous year, despite high-dose inhaled corticosteroid plus additional controllers, screening blood eosinophil counts of at least 150 cells per μL, and an Asthma Control Questionnaire 6 (ACQ-6) score of 1·5 or more. Patients who met eligibility criteria were randomly assigned (2:1; stratified by previous exacerbation count [two, or three or more], maintenance oral corticosteroid use, and region), using an integrated web-based response system, to receive benralizumab at 30 mg every 8 weeks (first three doses given 4 weeks apart) or matched placebo for 24 weeks. Primary efficacy measure was annualised asthma exacerbation rate, with rate ratio (RR) calculated over the approximate 24-week follow-up. Secondary efficacy measures included change from baseline to end of treatment (week 24) in St George's Respiratory Questionnaire (SGRQ) total score (key secondary endpoint), FEV1, peak expiratory flow (PEF), ACQ-6, Predominant Symptom and Impairment Assessment (PSIA), Clinician Global Impression of Change (CGI-C), Patient Global Impression of Change (PGI-C), and Sino-Nasal Outcome Test-22 (SNOT-22). All efficacy analyses, except for SNOT-22, were summarised and analysed using the full analysis set on an intention-to-treat population (all randomly assigned patients receiving investigational product, regardless of protocol adherence or continued participation in the study). SNOT-22 was summarised for the subgroup of patients with physician-diagnosed nasal polyposis with informed consent. This study is registered with ClinicalTrials.gov, NCT03170271. Findings: Between July 7, 2017, and Sept 25, 2019, 656 patients received benralizumab (n=427) or placebo (n=229). Baseline characteristics were consistent with severe eosinophilic asthma. Benralizumab significantly reduced exacerbation risk by 49% compared with placebo (RR estimate 0·51, 95% CI 0·39–0·65; p5%) were nasopharyngitis (30 [7%]), headache (37 [9%]), sinusitis (28 [7%]), bronchitis (22 [5%]), and pyrexia (26 [6%]). Fewer serious adverse events were reported for benralizumab (23 [5%]) versus placebo (25 [11%]), and the only common serious adverse event (experienced by >1% of patients) was worsening of asthma, which was reported for nine (2%) patients in the benralizumab group and nine (4%) patients in the placebo group. Interpretation: Our results extend the efficacy profile of benralizumab for patients with severe eosinophilic asthma, showing early clinical benefits in patient-reported outcomes, HRQOL, lung function, and nasal polyposis symptoms. Funding: AstraZeneca.

We are developing Ka-band gallium nitride (GaN) monolithic microwave integrated circuits (MMICs) for a compact transceiver frontend. We present the design, fabrication and test results of a GaN power amplifier (PA), low noise amplifier (LNA), and single-pole-double-throw (SPDT) switch. These components are necessary for implementing a radar transceiver unit cell concept with digital calibration capabilities for future cloud radar arrays.

Digital PCR (dPCR) technology has been proven to be highly sensitive and accurate in detecting copy number variations (CNV). However, a higher-order multiplexing dPCR assay for measuring SMN1 and SMN2 copy numbers in spinal muscular atrophy (SMA) samples has not been reported. Described here is a rapid multiplex SMA dPCR genotyping assay run on a fully integrated dPCR instrument with five optical channels. The hydrolysis probe-based multiplex dPCR assay quantifies SMN1, SMN2, and the total SMN (SMN1 + SMN2) while using RPPH1 gene as an internal reference control. The quadruplex assay was evaluated with characterized control DNA samples and validated with 15 blinded clinical samples from a previously published study. SMN1 and SMN2 copy numbers were completely concordant with previous results for both the control and blinded samples. The dPCR-based SMA copy number determination was accomplished in 90 min with a walk-away workflow identical to real-time quantitative PCR (qPCR). In summary, presented here is a simple higher-order multiplexing solution on a novel digital PCR platform to meet the growing demand for SMA genotyping and prognostics.

A hybrid multiplier chain with a Si micromachined stack housing the 2.06-THz sub-harmonic Schottky-diode based mixer is developed for the purpose of THz sensing for NASA in space. Low-noise temperature measurements are performed using this hybrid local-oscillator (LO) chain.

We report on the design, fabrication, and testing of a new generation of all-solid-state frequency-multiplied terahertz sources providing up to ten times more output power at room temperature than the previous state of the art. These new sources benefit from both a novel “on-chip” power combined topology recently introduced and new devices and circuits thoroughly optimized for high-power operation. Prototypes centered at 180 GHz, 240 GHz, 340 GHz, 530 GHz, 1 THz, and 1.6 THz have been designed, fabricated, and tested. All sources exhibit record performances with conversion efficiencies reaching the theoretical limit predicted by physics-based numerical models. Measured nominal room-temperature output power levels are 500 mW at 180 GHz, 110 mW at 220 GHz, 35 mW at 330 GHz, 30 mW at 550 GHz, 2 mW at 1.03 THz, and 0.7 mW at 1.64 THz.

Human bioavailability data on chlorophyll (Chl) is very limited. The distribution of Chl-related compounds (CRCs) derived from dietary spinach was investigated in human blood. Eight healthy adults, aged from 21 to 61 year-old, consumed 1.2 kg of just-boiled fresh spinach after an 8-h overnight fast. Before and then 3 h after consuming the spinach, blood samples were taken from each participant. Freeze-dried blood samples were prepared, and 80% acetone was added for grinding. Eight peaks were found in the blood using high-performance liquid chromatography (HPLC), and the main CRCs in the samples were pheophytin (Phe) and pheophorbide (Pho) derivates. Compared to a fasted state, markedly higher levels of blood CRCs were detected in all subjects, except that Pho metabolites were not found in two subjects. No significant differences were seen in most of the peaks between males and females; however, relatively higher CRCs levels were observed in females, particular of Pho derivates. In addition, the blood contained significantly higher levels of Phe in the 36~61-year-old group than in the 21~35-year-old group. These results suggest that the conversion of Chls to CRCs is a rapid process, and Chls obtained by ingestion can be absorbed by the human body.

Video telephone systems are convenient media for people to communicate remotely in life. If the video can be analyzed in the process of video chat to extract the relevant physiological indicators of the communicators such as emotions or stress, it can help the communicators to make proper conversations. In this paper, we propose (1) Similar Brightness Area Selection Method (2) and Difference-driven Weight-Setting Method to measure the heart rate in the non-contact image mode that can be adapted to the video signal in the videophone. After the image is compressed, it is transmitted through the network. After being transmitted to the video receiver for image decompression, we also propose that the luminance (Y) instead of Green channel (G) of the image should be utilized based on Photoplethysmography (PPG) to infer the heart rate. In our experiment, we have adjusted the weight range of our Difference-driven Weight-Setting Method for four commonly used video compression codecs including H.264, H.265, VP8, and VP9 together with five different compression bit rates and the results have shown to be effective in improving the accuracy of the heart rate measurement. The root mean square error (RMSE) of the heart rate measurement has also been calculated as evaluation metrics in the experiment. The mean and standard deviation of the overall RMSE is 2.14±0.52 bpm (beats per minute) that have shown the feasibility of our proposed methods to effectively and accurately measure the heart rate in the video telephony system.

Heart rate variability (HRV) is an objective measure of emotional regulation. This study aimed to estimate the accuracy with which an artificial neural network (ANN) algorithm could classify emotions using HRV data that were obtained using wristband heart rate monitors. Four emotions were evoked during gameplay: pleasure, happiness, fear, and anger. Seven normalized HRV features (i.e., 3 time-domain features, 3 frequency-domain features, and heart rate), which yielded 29,727 segments during gameplay, were collected and analyzed first by statistics and then classified by the trained ANN model. General linear model adjusted for individual differences in HRV showed that all HRV features significantly differed across emotions, despite disparities in their magnitudes and associations. When compared to neutral status (i.e., no emotion evoked), the mean of R-R interval was significantly higher for pleasure and fear but lower for happiness and anger. In addition, pleasure evidenced the HRV features that suggested a superior parasympathetic to sympathetic activation. Happiness was associated with a prominent sympathetic activation. These statistical findings suggest that HRV features significantly differ across emotions evoked by gameplay. When further utilizing ANN-based emotion classification, the accuracy rates for prediction were above 75.0% across the 4 emotions with accuracy rates for classification of paired emotions ranging from 82.0% to 93.4%. For classifying emotion in an individual person, the trained ANN model utilizing HRV features yielded a high accuracy rate in our study. ANN is a time-efficient and accurate means to classify emotions using HRV data obtained from wristband heart rate monitors. Thus, this integrated platform can help monitor and quantify human emotions and physiological biometrics.

In this paper, we report on a new 6-way MMIC power combiner amplifier utilizing cavity modes. The combiner is designed around a square cavity operating in the TM320 electromagnetic mode. Such a configuration produces a total of 6 lobes of maximum field intensity inside the cavity. By placing probes (attached to MMIC amplifier chips) in alignment with the points of maximum field strength, a highly compact power combiner can be achieved. We illustrate this concept using a set of 1 Watt W-band GaN MMIC chips, placed in layered copper sheets and oriented so the MMICs line up with the regions of maximum field strength. A 6-way power combiner was built and was able to deliver 5.5 Watts of output power and 13.4% PAE using a miniature package.

Dexras1 is a novel GTPase that acts at a confluence of signaling mechanisms associated with psychiatric and neurological disease including NMDA receptors, NOS1AP and nNOS. Recent work has shown that Dexras1 mediates iron trafficking and NMDA-dependent neurodegeneration but a role for Dexras1 in normal brain function or psychiatric disease has not been studied. To test for such a role, mice with germline knockout (KO) of Dexras1 were assayed for behavioral abnormalities as well as changes in NMDA receptor subunit protein expression. Because Dexras1 is up-regulated during stress or by dexamethasone treatment, we included measures associated with emotion including anxiety and depression. Baseline anxiety-like measures (open field and zero maze) were not altered, nor were depression-like behavior (tail suspension). Measures of memory function yielded mixed results, with no changes in episodic memory (novel object recognition) but a significant decrement on working memory (T-maze). Alternatively, there was an increase in pre-pulse inhibition (PPI), without concomitant changes in either startle amplitude or locomotor activity. PPI data are consistent with the direction of change seen following exposure to dopamine D2 antagonists. An examination of NMDA subunit expression levels revealed an increased expression of the NR2A subunit, contrary to previous studies demonstrating down-regulation of the receptor following antipsychotic exposure (Schmitt et al., 2003) and up-regulation after exposure to isolation rearing (Turnock-Jones et al., 2009). These findings suggest a potential role for Dexras1 in modulating a selective subset of psychiatric symptoms, possibly via its interaction with NMDARs and/or other disease-related binding-partners. Furthermore, data suggest that modulating Dexras1 activity has contrasting effects on emotional, sensory and cognitive domains.

Many have argued that measuring financial instruments at fair value might not reflect firms’ financial condition. Prior study finds that managers manipulate the “disclosure” of fair value measurement (Song et al. 2010). In this study, we attempt to provide evidence regarding manager’s incentive to manipulate the disclosure of fair value measurements by examining whether the disclosure of less relevant fair value measurement is related to the odds of earnings management. We find that firms with more Level 3 assets and liabilities (i.e., less value relevant fair value measurement) are more likely to recognize positive unrealized gains to meet or beat analyst forecast target. In addition, we find that only firms with weak corporate governance disclose more Level 3 fair value liabilities and recognize unrealized gains into reported earnings to meet or beat analyst forecast target. This evidence suggests that managers manipulate the disclosure of fair value measurement in order to manage reported earnings via the adoption of fair value option.

This paper presents thermal characterization results for three high-power THz Schottky frequency multipliers in the temperature range of 20–380 K. All measured multipliers have different substrates: a 5- $\mu\hbox{m}$ -thick GaAs membrane, a 40- $\mu\hbox{m}$ -thick GaAs substrate, and a 5- $\mu\hbox{m}$ -thick GaAs membrane glued to a 20- $\mu\hbox{m}$ -thick CVD diamond substrate with polymer bonding agent. The thermal characterization results include such parameters as the maximum average junction temperature of the anodes, device total thermal resistance, and device cooling (or heating) times. The results enable designers to better optimize their devices for the maximum power level and temperature range and system engineers to better predict the overall performance of the system in an environment, where the ambient conditions might change. For example, from the thermal resistance point of view the GaAs membrane on diamond substrate clearly outperforms the device on GaAs membrane alone at room temperature or above. However, perhaps surprisingly, at temperatures below 125 K, the GaAs membrane is on par, or even has lower thermal resistance than the membrane on diamond.

In a large fraction of ER+/HER2- metastatic breast cancer (MBC) patients, treatment with aromatase inhibitors fails due to emerging resistance. A key mechanism of this resistance is associated with a limited set of missense mutations in the gene encoding for the estrogen receptor (ESR1). These mutations are primarily found in the ligand binding domain of the protein. They result in a constitutively active estrogen receptor, are infrequently found in primary tumors ( Citation Format: Jennifer N. Bernier, Johanna E. Takach, Tiffany Wang, Steve Gallagher, Robert Lin, Andrew Zayac, Paul Hung, Matthew Lesho, Douglas Whitman. Discriminatory 11-plex assay designed to monitor estrogen receptor mutations using a novel, melt-analysis capable digital PCR platform [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4113.

Digital PCR (dPCR) has gained popularity in recent years for cancer research such as rare mutation detection, minimal residual disease, treatment selection, and recurrence monitoring. However, currently available technologies suffer from several limitations such as tedious workflow, long time-to-result, poor multiplexity, and inconsistent reagent digitization that severely hindered its broad adoption. We have designed and manufactured a dPCR platform that is capable of consistent sample digitization, thermal cycling and simultaneous interrogation of 20,000 partitions with walk-away workflow. The instrument integrates a loading and digitization manifold, a thermal cycler and an imaging engine with 5 optical channels into a single benchtop box. The Microfluidic Array Partitioning (MAP) consumable is a micro-injection molded, automation-ready plate that contains 16 individual units that can be loaded simultaneously. Each unit partitions an individual sample into 20,000 fluidically isolated partitions while utilizing >90% of inputted sample. We utilized an oncology standard assay, confocal microscopy, and real-time imaging to validate the dynamic range, sample utilization, and digitization consistency of the platform, respectively. Using the European Breast Cancer Standards ERM-AD623 we quantified replicates that were serially diluted from 1 × 105cp/μL down to 10cp/μL. We demonstrated that the dPCR platform can consistently quantify targets over 5-orders-of-magnitude of concentration with high consistency in both quantification and partition numbers. With confocal microscopy, the reagent inside the partitions are visualized to characterize sample utilization. Using conventional qPCR calibration dye ROX and real-time imaging, we show that over 99% of the partitions can be consistently analyzed for high quantification confidence. With the combination of ease-of-use, fast time-to-result and consistent performance, we believe this novel dPCR platform provides unparalleled usability and capability and will allow dPCR to fulfill its promise to impact cancer patient care. Citation Format: Robert Lin, Andrew Zayac, Steve Gallagher, Lingxia Jiang, Felicia Linn, Paul Hung. Fully integrated single instrument imaging-based digital PCR platform [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 43.

Introduction Due to the curative potential and improvement in progression-free survival (PFS), high dose chemotherapy followed by autologous stem cell transplantation (ASCT) is considered the standard of care for several hematologic malignancies such as multiple myeloma, and lymphomas in different treatment stages. However, the process of ASCT typically involves support with blood product transfusion until neutrophil and platelet engraftment occurs. Thus, difficulties arise when ASCT is indicated for Jehovah's witness patients - a religious group known for refusing blood products. Objectives 1. Assess for differences in overall survival between BL-ASCT and TS-ASCT. 2. Outline the key complications associated with BL-ASCT. Methods Retrospective analysis of 66 Jehovah's Witnesses who underwent BL-ASCT, and 1114 non-Jehovah's Witness patients who underwent transfusion-supported ASCT (TS-ASCT) at Cedars-Sinai Medical Center between January 2000 and September 2018 was performed. Patients included in the study had one of the following diagnoses: multiple myeloma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, or germ cell tumor. The BL-ASCT group received supportive measures to minimize bleeding risk and blood loss (detailed in table 1). Overall survival was estimated using the Kaplan-Meier method. Transplant-related complications were characterized for the BL-ASCT group. Results One year overall survival (OS) was found to be 87.9% for both groups (P = 0.92). Survival at five years for the BL-ASCT group was 72.7%, and 69.0% for the TS-ASCT (P = 0.79). In the BL-ASCT group, there was one death prior to the 30 days post-transplant due to CNS hemorrhage, and one death prior to 100 days due to sepsis. Conclusion Given that overall survival is not significantly different between BL-ASCT and TS-ASCT at the 1-year and 5-year marks, we encourage transplant centers to consider performing bloodless transplants in select patients with appropriate supportive measures. Future directions include analysis of overall differences in the financial burden between BL-ASCT and TS-ASCT, and further refinement of supportive care measures.

This paper proposes to infer emotion of game users with a platform that integrates heart rate wristbands, smartphones and emotion inference mechanisms on backend computers. The inferred user emotions can subsequently be utilized by game developers to promptly understand the user reaction to the game content in order to improve the game quality. In this paper, the subjects play four kinds of games that can stimulate emotions such as Pleasure, Happy, Fear and Angry. The subjects' heart rate signals and facial expressions are recorded when they play the games. The facial expressions are then used to determine the emotions of the subjects as the ground truths. The heart rate signals with determined emotions are subsequently extracted and used to calculate the normalized features. Seven normalized features and determined emotions are then used as inputs and outputs to Artificial Neural Network (ANN) for machine learning. The trained ANN model can subsequently be used to classify the emotions of the subjects when they play games. Experimental results show that the average recognition accuracy of the players' emotions of Pleasure, Happy, Fear, Angry and Neutral are 84.41%, 79.08%, 86.81%, 88.64% and 75.30% respectively. We have also selected two, three and four out of the five emotions for recognition as comparison, and the results show that inclusion of more emotions will lead to less recognition accuracy. In the end, data of all the subjects have been merged into a big data set for training and testing. The overall recognition rate falls maybe because of the uniqueness of each subject. It is thus recommended that personal data of a subject should be used as training data for better recognition results.