cssi/SciSciGPT-SciSciNet huggingface dataset:
A Hyperactive Signalosome Results in High Sensitivity to HSP90 Inhibitors in AML

Abstract HSP90 is well established in supporting tumorigenesis by stabilizing oncogenic client proteins. Given this crucial role, a number of HSP90 inhibitors have been tested in various types of cancer, including leukemia. However, clinical trials thus far revealed only a subset of AML patients benefited from the treatment. Therefore, precision medicine approaches to define parameters that predict the patients' response to HSP90 inhibitors are needed to select patients who are most likely to benefit. We have previously demonstrated that PU-H71, a novel purine scaffold HSP90 inhibitor with selectivity for a tumor-specific HSP90 and currently translating into Phase 2 clinical evaluation, is capable of ablating malignant blasts, progenitor and stem cells in AML patient samples using in vitro studies. We found that leukemia cell lines (n=18) and primary AML patient samples (n=26) with greater numbers of simultaneously activated signaling networks, including PI3K-AKT and JAK-STAT, were the most sensitive to HSP90 inhibition. Using different genetic models, our studies revealed that diverse oncogenic transformations that converge upon simultaneous hyperactivation of PI3K-AKT and JAK-STAT promote sensitivity to PU-H71. To validate the efficacy of PU-H71 in vivo, we generated AML-GFP-luciferase xenograft models using cell lines with hyperactive signalosome. Xenotransplanted mice were treated with PU-H71 one week post-engraftment. In vivo imaging indicated that MOLM-13 xenografted leukemia was rapidly and significantly reduced by PU-H71 treatment. Six doses of PU-H71 produced robust anti-leukemic activity as indicated by in vivo imaging and flow cytometric analysis of post-treatment bone marrow (no disease detected). In addition, we generated 7 AML patient-derived xenografts (PDX) cohorts with samples that displayed varied levels of activation of PI3K-AKT and JAK-STAT signaling pathways. After initial validation that status of the PI3K-AKT and JAK-STAT signaling pathways were preserved in the PDX, we initiated treatment with PU-H71 and found that, as predicted, the AML-PDX with the most hyperactive signalosome were the most sensitive to in vivo treatment to PU-H71. Importantly, samples with hyperactive PI3K-AKT and JAK-STAT signaling also demonstrated a significant reduction in LSC using secondary transplants. Taken together, we found that a hyperactive signalosome results in increased sensitivity to the HSP90 inhibitor PU-H71 in vitro and in vivo. Our study suggests that evaluation of PI3K-AKT and JAK-STAT signaling pathways may provide a means to select patients who are most likely to benefit from HSP90 inhibitory therapy. Disclosures No relevant conflicts of interest to declare.
Transformative Spaces: Dr. S. Paramasivan and Conservation Science in India in the Early Twentieth Century

ABSTRACTThe tenure of archaeological chemist Dr. S. Paramasivan (1903–1987) at the Chemical Conservation Laboratory of the Madras Government Museum, India, sheds light on the development of the fie...
Design of a ski lift inspection and maintenance system

Ski lifts transport 51.8 million passengers annually and have nearly doubled their operating days nationally from 117 to 204 days on average. However, the inspection frequency has remained constant due to the danger of climbing lift towers. A safer inspection system is needed to increase frequency without increasing cost. Based on a detailed requirements analysis, three design alternatives were identified: (1) the current manual inspection method in which inspectors climb the towers, (2) a stationary platform mounted on the lift towers with HD and thermal cameras, and (3) a mobile aerial platform with HD and thermal cameras. The images are processed to automatically identify component defects. A stochastic simulation was developed to compare the performance of the alternatives and evaluated based on 1,453 replications. Random variables were collected for human walking speed and mobile aerial platform velocity in stochastic wind conditions. Based on a Pairwise Analytical Hierarchy Process comparison of personnel safety, accuracy, availability, and the time to complete an inspection, the utility for each design alternative was calculated: Manual inspection (0.466), tower platform (0.670) and mobile aerial platform (0.691). Simulation results indicate an average time savings of 23 minutes per tower per inspection, a 20% reduction of workplace incidents annually, and a 50% accuracy improvement for the mobile aerial platform compared to manual inspections. The tower platform had an average time savings of 31 minutes per tower per inspection, a 5% reduction of workplace incidents annually, and a 45% accuracy improvement. Based on cost-benefit analysis, it is recommended that ski resorts implement the mobile aerial platform for safer, more frequent, more accurate, and less costly ski lift tower inspections.
Obesity and Anorexia Nervosa

Obesity and anorexia nervosa are two clinical disorders that result from a disturbance of normal energy regulation mechanisms. The regulation of energy is accomplished via a complex set of neurological and hormonal mechanisms (Ganong, 1975; Rodin, 1977). Technically, energy regulation can be affected by a large number of behavioral, biological, and environmental factors including energy intake and expenditure, body temperature, and climate. For humans, however, energy regulation is influenced primarily by the relative intake and expenditure of calories via eating and exercising (Ganong, 1975). Eating and exercising (or general activity level) are behaviors that to a great extent, are controlled by environmental and social factors. Clinical research studies of obesity and anorexia nervosa indicate that both of these disorders are directly caused by either excessive or inadequate eating and activity. In both cases the research suggests that these behaviors are strongly influenced by social situations and reinforcement contingencies. This chapter will discuss the nature of these two disorders and the types of interventions that have been used to modify them.
Novel D2-Like Dopamine Receptors in Schizophrenic Brain

For the past twenty-five years, the predominant neurochemical hypothesis associated with schizophrenia has involved a putative disturbance of dopamine neurotransmission. This model has undergone modification and refinement over the years, but the dopamine receptors have consistently been implicated in this disorder (Creese et al. 1976; Seeman et al. 1975; Snyder 1976). Classically, dopamine receptors were resolved into two subtypes, D1 and D2, based on pharmacological, behavioral, and neuro anatomical data (Attie et al. 1980; Stoof and Kebabian 1984; Memo et al. 1986; Onali et al. 1985). Most traditional antipsychotic drugs have a high affinity for the D2 subtype of dopamine receptor, and there is a well-established relationship between typical daily dose of these drugs and affinity for the D2 receptor (Creese et al. 1976; Seeman et al. 1975; Snyder 1976). These observations have been interpreted to suggest a primary alteration in the D2 receptor in schizophrenia or, at the very least, that the D2 receptor is a critical site of action for the antipsychotics.
Design of Reliability Test Plans: An Overview

Reliability prediction of new components, products, and systems is a difficult task due to the lack of well-designed test plans that yield “useful” information during the test and due to the stochastic nature of the normal operating conditions. The accuracy of the reliability prediction has a major effect on the warranty cost and repair and maintenance strategies. Therefore, it is important to design efficient test plans. In this chapter, we present an overview of reliability testing with emphasis on accelerated testing and address issues associated with the design of optimal test plans, stress application methods, and reliability prediction models. We further discuss the concept of equivalence of test plans and how it could be used for test time reduction. Finally, we present accelerated degradation modeling and the design of accelerated degradation test plans.
Device Identification via Analog Signal Fingerprinting: A Matched Filter Approach

As part of the Detecting Intrusions at Layer ONe (DILON) project, we show that Ethernet devices can be uniquely identified and tracked—using as few as 25 Ethernet frames—by analyzing variations in their analog signal caused by hardware and manufacturing inconsistencies. An optimal detector, the matched filter, is utilized to create signal profiles, which aid in identifying the device the signal originated from. Several non-traditional applications of the filter are presented in order to improve its ability to discriminate between signals from seemingly identical devices of the same manufacturing lot. The experimental results of applying these filters to three different models of Ethernet cards, totaling 16 devices, are presented and discussed. Important applications of this technology include intrusion detection (discovering node impersonation and network tampering), authentication (preventing unauthorized access to the physical network), forensic data collection (tying a physical device to a specific network incident), and assurance monitoring (determining whether a device will or is in the process of failing).
Evolution of Laparoscopic Hernia Repair

The concept of a posterior approach to the repair of abdominal wall hernias had its earliest beginnings in North America in 1878 in Utica, New York, when E. Hutchinson reported a case of inguinal hernia that was strangulated at the internal ring. Hutchinson made a midline incision between the umbilicus and the pubis. Entering the peritoneal cavity, he released the gangrenous bowel, but the patient died the following day.1
National carbon monoxide poisoning surveillance framework and recent estimates.

OBJECTIVES: Unintentional, non-fire-related (UNFR) carbon monoxide (CO) poisoning is a leading cause of poisoning in the United States. A comprehensive national CO poisoning surveillance framework is needed to obtain accurate estimates of CO poisoning burden and guide prevention efforts. This article describes the current national CO poisoning surveillance framework and reports the most recent national estimates. METHODS: We analyzed mortality data from the National Vital Statistics System multiple cause-of-death file, emergency department (ED) and hospitalization data from the Healthcare Cost and Utilization Project's Nationwide Emergency Department Sample and Nationwide Inpatient Sample, hyperbaric oxygen treatment (HBOT) data from HBOT facilities, exposure data from the National Poison Data System, and CO alarm prevalence data from the American Housing Survey and the National Health Interview Survey. RESULTS: In the United States, 2,631 UNFR CO deaths occurred from 1999 to 2004, an average of 439 deaths annually. In 2007, there were 21,304 (71 per one million population) ED visits and 2,302 (eight per one million population) hospitalizations for confirmed cases of CO poisoning. In 2009, 552 patients received HBOT, and from 2000 to 2009, 68,316 UNFR CO exposures were reported to poison centers. Most nonfatal poisonings were among children (65 years of age). More poisonings occurred during winter months and in the Midwest and Northeast. CONCLUSIONS: UNFR CO poisoning poses a significant public health burden. Systematic evaluation of data sources coupled with modification and expansion of the surveillance framework might assist in developing effective prevention strategies. Language: en
An Endoscopic Transluminal Approach, Compared With Minimally Invasive Surgery, Reduces Complications and Costs for Patients With Necrotizing Pancreatitis

Background & Aims Infected necrotizing pancreatitis is a highly morbid disease with poor outcomes. Intervention strategies have progressed from open necrosectomy to minimally invasive approaches. We compared outcomes of minimally invasive surgery vs endoscopic approaches for patients with infected necrotizing pancreatitis. Methods We performed a single-center, randomized trial of 66 patients with confirmed or suspected infected necrotizing pancreatitis who required intervention from May 12, 2014, through March 24, 2017. Patients were randomly assigned to groups that received minimally invasive surgery (laparoscopic or video-assisted retroperitoneal debridement, depending on location of collection, n = 32) or an endoscopic step-up approach (transluminal drainage with or without necrosectomy, n = 34). The primary endpoint was a composite of major complications (new-onset multiple organ failure, new-onset systemic dysfunction, enteral or pancreatic-cutaneous fistula, bleeding and perforation of a visceral organ) or death during 6 months of follow-up. Results The primary endpoint occurred in 11.8% of patients who received the endoscopic procedure and 40.6% of patients who received the minimally invasive surgery (risk ratio 0.29; 95% confidence interval 0.11–0.80; P = .007). Although there was no significant difference in mortality (endoscopy 8.8% vs surgery 6.3%; P = .999), none of the patients assigned to the endoscopic approach developed enteral or pancreatic-cutaneous fistulae compared with 28.1% of the patients who underwent surgery (P = .001). The mean number of major complications per patient was significantly higher in the surgery group (0.69 ± 1.03) compared with the endoscopy group (0.15 ± 0.44) (P = .007). The physical health scores for quality of life at 3 months was better with the endoscopic approach (P = .039) and mean total cost was lower ($75,830) compared with $117,492 for surgery (P = .039). Conclusions In a randomized trial of 66 patients, an endoscopic transluminal approach for infected necrotizing pancreatitis, compared with minimally invasive surgery, significantly reduced major complications, lowered costs, and increased quality of life. Clinicaltrials.gov no: NCT02084537
Exposure to ambient PM2.5 during pregnancy and preterm birth in metropolitan areas of the state of Georgia

A number of studies has pointed to air pollution as an additional factor that could be associated with preterm birth. We assessed in this study the association between exposure to PM2.5 in ambient air during pregnancy and preterm birth in metropolitan areas of the state of Georgia, where the rate of preterm birth has been among the highest in the nation over the years. Birth data were obtained from the National Center for Health Statistics natality dataset. The study population consisted of 53,094 singleton live births between January 1 and December 31, 2004 in nine metropolitan counties of Georgia. Preterm birth was defined as birth, which occurs before 37 weeks of gestation. County-level daily air quality index (AQI) data obtained from the US Environmental Protection Agency (EPA) was used to estimate individual exposure levels of PM2.5 for each study participant based on the county of residence for the duration of the pregnancy. A multivariate logistic regression analysis was conducted to assess the association, adjusting for potential confounders. Of the infants whose mothers resided in the nine metropolitan counties of Georgia, 4543 (8.6%) were born preterm. A higher rate of preterm birth (9.8%) was observed in infants whose mothers were exposed to ambient PM2.5 with AQI values > 50 than the ones with AQI ≤ 50 (EPA standard for good air quality conditions). Mothers with exposure to PM2.5 at average AQI values greater than 50 during the entire pregnancy were at increased risk of preterm birth (odds ratio 1.15; 95% CI 1.07, 1.25), after adjusting for sex of infant, mother’s age, race/ethnicity, education, marital status, prenatal care, cigarette smoking, alcohol consumption, and season of conception. The study provides more evidence on the role of PM2.5 in preterm birth. Reducing exposure to ambient particulate matter, especially in urban areas, for pregnant women would be necessary to improve the health of infants.
Is There a Role for the UN Security Council on Climate Change

iStock/TashkaAcross the United Nations, virtually all of the various programs, agencies, and affiliates have wrestled with how to address climate change as part of their work. The World Health Orga...
Streptococcus canis Bacteremia in a Renal Transplant Recipient

A middle-aged man presented with fever and shortness of breath. He had significant history of congestive heart disease and received deceased donor renal transplant 2 years prior to presentation. He was febrile and found to have sepsis. His initial blood cultures grew Streptococcus canis. Streptococcus canis causes rare infection in humans, and this is most likely the first case in the renal transplant population.
Loss of exercise- and stress-induced increases in circulating 2-arachidonoylglycerol concentrations in adults with chronic PTSD.

Abstract The endocannabinoid (eCB) system is a modulatory system that is both altered by stress and mediates the effects of acute stress, including contributing to restoration of homeostasis. Earlier studies suggest that circulating eCBs are dysregulated in adults with post-traumatic stress disorder (PTSD); however, it is not known whether circulating eCBs remain responsive to stress. The purpose of this study was to examine eCB and psychological responses to physical (exercise) and psychosocial (Trier Social Stress Test) stressors, using a randomized, counterbalanced procedure in adults with PTSD and healthy controls (N = 20, mean age = 24, SD = 7 yrs). Results from mixed-design, repeated measures ANOVAs revealed significant increases (p
Social patterning of acute respiratory illnesses in the Household Influenza Vaccine Evaluation (HIVE) Study 2014–2015

Social patterning of infectious diseases is increasingly recognised. Previous studies of social determinants of acute respiratory illness (ARI) have found that highly educated and lower income families experience more illnesses. Subjective social status (SSS) has also been linked to symptomatic ARI, but the association may be confounded by household composition. We examined SSS and ARI in the Household Influenza Vaccine Evaluation (HIVE) Study in 2014–2015. We used SSS as a marker of social disadvantage and created a workplace disadvantage score for working adults. We examined the association between these measures and ARI incidence using mixed-effects Poisson regression models with random intercepts to account for household clustering. In univariate analyses, mean ARI was higher among children <5 years old (P < 0.001), and females (P = 0.004) at the individual level. At the household level, mean ARI was higher for households with at least one child <5 years than for those without (P = 0.002). In adjusted models, individuals in the lowest tertile of SSS had borderline significantly higher rates of ARI than those in the highest tertile (incidence rate ratio (IRR) 1.34, 95% confidence interval (CI) 0.98–1.92). Households in the lowest tertile of SSS had significantly higher ARI incidence in household-level models (IRR 1.46, 95% CI 1.05–2.03). We observed no association between workplace disadvantage and ARI. We detected an increase in the incidence of ARI for households with low SSS compared with those with high SSS, suggesting that socio-economic position has a meaningful impact on ARI incidence.
The Secret History of RDX: The Super‐Explosive that Helped Win World War II. By Colin F. Baxter. (Lexington, KY: University Press of Kentucky, 2018. Pp. 214. $45.00.)

Colin F. Baxter has explored an under‐appreciated wartime achievement, the development of Research Department Explosive (RDX). He traces the conceptualization of RDX at the Woolrich Arsenal in Grea...
Measuring Selected Motor Skills in Fourth, Fifth, and Sixth Grades

Abstract This article presents seven tests which were devised for measuring selected motor skills in fourth, fifth, and sixth grade boys and girls. An analysis of the data indicated that the tests were reliable for the population measured, and that age, height, and weight factors were not statistically significant in determining performance as measured by these tests. Performance standards were computed for each sex within each grade level.
How Sensitive are Spatial Estimates of Wilderness Recreation Values to Information about Hiking Destinations

This study uses individual survey data to investigate the impact of information about hiking destinations on estimated wilderness values in a spatial context. The data is derived from a revealed preference survey of backcountry visitors who responded to questions about their recreation behavior in the San Jacinto Wilderness of southern California. Two GIS data layers are developed showing spatial representations of non-market values derived from a Kuhn- Tucker demand model, with and without destination information. Each pixel in each data layer contains an estimate of the recreation value at that location. The destination data provides more detailed information on recreation behavior that can be used to more accurately allocate the landscape values. Results show that including destination information produces significantly greater heterogeneity in parcel value estimates for large areas of the wilderness.
Experimental validation of complex non-minimum phase zeros in a flexure mechanism

Abstract In this paper, we present the design of an experimental setup that validates the existence of complex non-minimum phase (CNMP) zeros in a flexure mechanism under specific conditions. Using this setup, the dynamics of a lightly damped, nominally symmetric XY flexure mechanism comprising two double parallelogram flexure modules (DPFM) is experimentally studied while varying the operating point and parametric asymmetry. While CNMP zeros have been reported in analytical studies, a direct experimental validation of model-based prediction poses several challenges and is rare in the literature. The challenges addressed in the presented experimental setup design include isolating the specific dynamics of interest while minimizing extraneous dynamics, avoiding friction and backlash in the system to offer clean and repeatable measurements, and employing simple and practical sensing and actuation methods. This experimental setup is used to obtain X direction frequency response measurements and thereby record the presence or absence of CNMP zeros, while varying the Y direction operating point and the mass asymmetry between two DPFMs. This experimental evidence of the existence of CNMP zeros under specific conditions agrees well with the previous model-based predictions.
Solution Enumeration Abstraction: A Modeling Idiom to Enhance a Lightweight Formal Method

Formal methods are a key to engineering more reliable systems. In this paper, we focus on an important application of formal methods — enumerating solutions to logical formulas that encode properties of interest. Solution enumeration has many uses, e.g., in systematic software testing, model counting, or hardware analysis. We introduce solution enumeration abstraction, a novel idiom that allows users to define data abstractions to enhance solution enumeration by specifying how the solutions must differ, so enumeration creates a high quality set of solutions of a manageable size. We embody the idiom as a technique built on top of Alloy, a well-known lightweight formal method, which is comprised of a first-order relational logic with transitive closure, and a SAT-based analysis engine. Experimental results show that our technique supports a variety of data abstractions, and can substantially reduce the number of solutions enumerated and the time to enumerate them.
Sex Stereotyping in Vocational Counseling of Blind/Visually Impaired Persons: A National Study of Counselor Choices.

Examines whether vocational rehabilitation counselors’ vocational suggestions and salary predictions for hypothetical clients are influenced by the client's sex. Half the subjects were presented wi...
Peptidomimetic Vinyl Heterocyclic Inhibitors of Cruzain Effect Antitrypanosomal Activity

Cruzain, an essential cysteine protease of the parasitic protozoan, Trypanosoma cruzi, is an important drug target for Chagas disease. We describe here a new series of reversible but time-dependent inhibitors of cruzain, composed of a dipeptide scaffold appended to vinyl heterocycles meant to provide replacements for the irreversible reactive "warheads" of vinyl sulfone inactivators of cruzain. Peptidomimetic vinyl heterocyclic inhibitors (PVHIs) containing Cbz-Phe-Phe/homoPhe scaffolds with vinyl-2-pyrimidine, vinyl-2-pyridine, and vinyl-2-(N-methyl)-pyridine groups conferred reversible, time-dependent inhibition of cruzain (Ki* = 0.1-0.4 μM). These cruzain inhibitors exhibited moderate to excellent selectivity versus human cathepsins B, L, and S and showed no apparent toxicity to human cells but were effective in cell cultures of Trypanosoma brucei brucei (EC50 = 1-15 μM) and eliminated T. cruzi in infected murine cardiomyoblasts (EC50 = 5-8 μM). PVHIs represent a new class of cruzain inhibitors that could progress to viable candidate compounds to treat Chagas disease and human sleeping sickness.
Online Privacy Heuristics that Predict Information Disclosure

Online users' attitudes toward privacy are context-dependent. Studies show that contextual cues are quite influential in motivating users to disclose personal information. Increasingly, these cues are embedded in the interface, but the mechanisms of their effects (e.g., unprofessional design contributing to more disclosure) are not fully understood. We posit that each cue triggers a specific "cognitive heuristic" that provides a rationale for decision-making. Using a national survey (N = 786) that elicited participants' disclosure intentions in common online scenarios, we identify 12 distinct heuristics relevant to privacy, and demonstrate that they are systematically associated with information disclosure. Data show that those with a higher accessibility to a given heuristic are more likely to disclose information. Design implications for protection of online privacy and security are discussed.
Evaluating the Effects of Establishing Eye Contact on the Skill Acquisition of Individuals with Autism

Researchers widely assert that requiring eye contact from students with autism spectrum disorder (ASD) before instruction is highly important to the outcome of teaching (Greer and Ross in Verbal behavior analysis, Pearson Education, New York, 2008; Lovaas in J Consult Clin Psychol 55(1):3–9, 1977. https://doi.org/10.1037/0022-006x.55.1.3). However, to our knowledge, no research to date has evaluated the effects of this component of instruction on skill acquisition. In this current study, we evaluated the effect of requiring student eye contact from participants with ASD prior to giving an instruction on the rate of skill acquisition. Using an adapted alternating treatments design, this study compared the skill acquisition of three participants diagnosed with ASD during discrete-trial instruction (DTI) for expressive identification of novel items. Requiring eye contact was manipulated as a treatment integrity error during DTI in high-integrity, low-integrity, and control conditions. The experimenter established eye contact with the participants prior to giving an instruction during 100% of trials in the high-integrity condition, whereas eye contact was only established prior to the instruction in 67% of trials in the low-integrity condition. Results indicate that all three participants acquired expressive labels for items in fewer sessions in the high-integrity condition as compared to the low-integrity condition. Implications for the impact of eye contact on skill acquisition are discussed.
Development and implementation of a physician-pharmacist collaborative practice model for provision and management of buprenorphine/naloxone.

Introduction Physician-pharmacist collaborative practice models (PPCPM) decrease barriers and increase access to medications for opioid use disorder (MOUD) but are not routine in practice. The purpose of this quality improvement initiative is to develop and implement a PPCPM for management of patients on MOUD with buprenorphine/naloxone to minimize provider burden, expand access to treatment, and enhance overall patient care. Methods A PPCPM for management of patients on MOUD with buprenorphine/naloxone was piloted in an outpatient substance use disorder clinic. Approximately 4 hours per week were dedicated to physician-pharmacist collaborative medical appointments for a 5-month trial period. The pharmacist met with the patient first and then staffed the case with the collaborating psychiatrist. Descriptive data from PPCPM appointments was collected and compared to data from psychiatrist-only appointments. Results Twenty-five patients were seen over 44 appointments with an estimated 33 hours of psychiatrist time saved. Average initial and end buprenorphine doses, urine drug screen (UDS) results, and mental health (MH) medication interventions were similar between patients seen in PPCPM appointments compared with those seen in psychiatrist-only appointments. Collection of UDS, identification and management of MOUD adherence issues, other service referrals, and medication reconciliation intervention were more frequent in PPCPM appointments. Discussion Implementation of a PPCPM allowed for provision of a similar level of care regarding MOUD and MH-related medication management while saving psychiatrist time. Other enhancements to patient care provided through pharmacist intervention included more frequent identification and management of MOUD adherence issues, referral for other services, and medication reconciliation interventions.
Revisiting reactionary terrorism: definitions, causes, and consequences

Deriving a definition of terrorism has long been a focus of both academics and policymakers, but there have been few attempts to establish a clear definition of right-wing terrorism and its relatio...
Continuous-time deconvolutional regression for psycholinguistic modeling.

Abstract The influence of stimuli in psycholinguistic experiments diffuses across time because the human response to language is not instantaneous. The linear models typically used to analyze psycholinguistic data are unable to account for this phenomenon due to strong temporal independence assumptions, while existing deconvolutional methods for estimating diffuse temporal structure model time discretely and therefore cannot be directly applied to natural language stimuli where events (words) have variable duration. In light of evidence that continuous-time deconvolutional regression (CDR) can address these issues ( Shain & Schuler, 2018 ), this article motivates the use of CDR for many experimental settings, exposits some of its mathematical properties, and empirically evaluates the influence of various experimental confounds (noise, multicollinearity, and impulse response misspecification), hyperparameter settings, and response types (behavioral and fMRI). Results show that CDR (1) yields highly consistent estimates across a variety of hyperparameter configurations, (2) faithfully recovers the data-generating model on synthetic data, even under adverse training conditions, and (3) outperforms widely-used statistical approaches when applied to naturalistic reading and fMRI data. In addition, procedures for testing scientific hypotheses using CDR are defined and demonstrated, and empirically-motivated best-practices for CDR modeling are proposed. Results support the use of CDR for analyzing psycholinguistic time series, especially in a naturalistic experimental paradigm.
Timing of Transfer and Mortality in Neonates with Hypoplastic Left Heart Syndrome in California

Maternal race/ethnicity is associated with mortality in neonates with hypoplastic left heart syndrome (HLHS). We investigated whether maternal race/ethnicity and other sociodemographic factors affect timing of transfer after birth and whether timing of transfer impacts mortality in infants with HLHS. We linked two statewide databases, the California Perinatal Quality Care Collaborative and records from the Office of Statewide Health Planning and Development, to identify cases of HLHS born between 1/1/06 and 12/31/11. Cases were divided into three groups: birth at destination hospital, transfer on day of life 0–1 (“early transfer”), or transfer on day of life ≥ 2 (“late transfer”). We used log-binomial regression models to estimate relative risks (RR) for timing of transfer and Cox proportional hazard models to estimate hazard ratios (HR) for mortality. We excluded infants who died within 60 days of life without intervention from the main analyses of timing of transfer, since intervention may not have been planned in these infants. Of 556 cases, 107 died without intervention (19%) and another 52 (9%) died within 28 days. Of the 449 included in analyses of timing of transfer, 28% were born at the destination hospital, 49% were transferred early, and 23% were transferred late. Late transfer was more likely for infants of low birthweight (RR 1.74) and infants born to US-born Hispanic (RR 1.69) and black (RR 2.45) mothers. Low birthweight (HR 1.50), low 5-min Apgar score (HR 4.69), and the presence of other major congenital anomalies (HR 3.41), but not timing of transfer, predicted neonatal mortality. Late transfer was more likely in neonates born to US-born Hispanic and black mothers but was not associated with higher mortality.
Toddlers learn and flexibly apply multiple possibilities.

The ability to consider multiple possibilities forms the basis for a wide variety of human-unique cognitive capacities. When does this skill develop? Previous studies have narrowly focused on children's ability to prepare for incompatible future outcomes. Here, we investigate this capacity in a causal learning context. Adults (N = 109) and 18- to 30-month olds (N = 104) observed evidence that was consistent with two hypotheses, each occupying a different level of abstraction (individual vs. relational causation). Results suggest that adults and toddlers identified multiple candidate causes for an effect, held these possibilities in mind, and flexibly applied the appropriate hypothesis to inform subsequent inferences. These findings challenge previous suggestions that the ability to consider multiple alternatives does not emerge until much later in development.
A deep dive into CDK4/6 inhibitors: Evaluating real world toxicities and treatment paradigms in the elderly population.

Background Cyclin-dependent kinase 4/6 inhibitors have become part of the standard of care in the treatment of hormone receptor positive, Her2Neu negative metastatic breast cancer. There is concern regarding the efficacy and potential increased cyclin-dependent kinase 4/6 inhibitors toxicity in the geriatric population in the community compared to the clinical trial population. Methods We evaluated patients treated with cyclin-dependent kinase 4/6 inhibitors from 2015 to 2019 and stratified according to age ≥70 and Results A total of 202 patients were included, 73 were ≥70 years and 129 were Conclusions Our study showed similar progression-free survival and overall survival between age groups without significant differences in neutropenia or thrombocytopenia toxicity. Nevertheless, we found an association between starting dose and progression-free survival and overall survival that has not been previously reported. Given the good tolerability across age groups and the improvement in progression-free survival and overall survival, patients should be treated at the cyclin-dependent kinase 4/6 inhibitors recommended dose and monitored appropriately.
Effects of rheological properties on reactivity of energetic thin films

Abstract Magnesium (Mg) and manganese dioxide (MnO 2 ) powders were mixed with polyvinylidene fluoride (PVDF) binder and n-methyl pyrrolidone (NMP) solvent and blade cast onto stainless steel foil. The rheological properties of these mixtures were investigated to quantify the mixing condition. Parameters including wet film thickness, equivalence ratio and solids loading were varied. Flame speed and calorific output were investigated for each of these parameters. Results show energy propagation rates increased as a function of dry film thickness, although calorific output remained relatively constant. Stoichiometrically fuel rich compositions were self-quenching, demonstrating the necessity of available oxygen for reaction propagation. A 0.45 solids–liquid mixing ratio resulted in up to an order of magnitude higher energy propagation rate for both open and confined configurations. Rheometry measurements and physical characterizations of the films reveal that the solids loadings resulting in the most stable suspensions also produced the highest energy propagation. Changing solids loading affects the density of the film, which in turn affects energy propagation. Capillary drying forces at high liquid loadings result in higher porosity leading to reduced deposition density and thickness. Very high solids loading results in films with dilatant properties and poor mixing. These results show solids loading affects mixing and energy propagation and could impact slurry cast energetic materials as in additive manufacturing processes.
Perceptual Classification Images from Vernier Acuity Masked by Noise

Letting external noise rather than internal noise limit discrimination performance allows information to be extracted about the observer's stimulus classification rule. A perceptual classification image is the correlation over trials between the noise amplitude at a spatial location and the observer's responses. If, for example, the observer followed the rule of the ideal observer, the perceptual classification image would be an estimate of the ideal observer filter, the difference between the two unmasked images being discriminated. Perceptual classification images were estimated for a vernier discrimination task. The display screen had 48 pixels per degree horizontally and vertically. The no-offset image had a dark horizontal line of 4 pixels, a 1 pixel space, and 4 more dark pixels. Classification images were based on 1600 discrimination trials with the line contrast adjusted to keep the error rate near 25 percent. In the offset image, the second line was one pixel higher. Unlike the ideal observer filter (a horizontal dipole), the observer perceptual classification images are strongly oriented. Fourier transforms of the classification images had a peak amplitude near one cycle per degree and an orientation near 25 degrees. The spatial spread is much more than image blur predicts, and probably indicates the spatial position uncertainty in the task.
Higher order statistics of the discrete Wiener model for application in nonlinear process modeling and identification

The discrete Wiener model of nonlinear systems is used to represent discrete stochastic processes. The higher order statistics of the model output are analysed and shown to have properties that greatly reduce the complexity of their computation. An efficient and structured procedure of computing the cumulants of the output of this model is described. Finally, an example of applying these results in nonlinear system identification and random process modeling is presented. >
Modeling and Analysis of a Heat Transport Transient Test Facility for Space Nuclear Systems

The purpose of this study was to design a robust test facility for a small space nuclear power system and model its physical behavior under different scenarios. The test facility will be used to si...
Isometric immersions of constant mean curvature and triviality of the normal connection

In a recent paper [2] Nomizu and Smyth have determined the hypersurfaces Mn of non-negative sectional curvature iso-metrically immersed in the Euclidean space Rn+1 or the sphere Sn+1 with constant mean curvature under the additional assumption that the scalar curvature of Mn is constant. This additional assumption is automatically satisfied if Mn is compact. In this paper we extend these results to codimension p isometric immersions. We determine the n-dimensional submanifolds Mn of non-negative sectional curvature isometrically immersed in the Euclidean Space Rn+P or the sphere Sn+P with constant mean curvature under the additional assumptions that Mn has constant scalar curvature and the curvature tensor of the connection in the normal bundle is zero. By constant mean curvature we mean that the mean curvature normal is paral lel with respect to the connection in the normal bundle. The assumption that Mn has constant scalar curvature is automatically satisfied if Mn is compact. The assumption on the normal connection is automatically sa tisfied if p = 2 and the mean curvature normal is not zero.
The synthesis of metamaterial ferrites for RF applications using electromagnetic bandgap structures

It has been well known for many years that the desirable properties of conventional ferrite materials are seriously degraded for frequencies above 1 GHz. The paper demonstrates that electromagnetic bandgap (EBG) structures may be interpreted as an equivalent PEC-backed slab of magnetic material with a frequency dependent permeability. A design methodology is presented for realizing a metaferrite material using a GA optimization procedure. A standard HZ-FSS (high-impedance frequency selective surface) structure is shown to be equivalent to a thin PEC-backed slab of magnetic material with a frequency dependent permeability. By optimizing the surface impedance of the HZ-FSS, it is possible to synthesize a metaferrite with nearly any desired real and imaginary values of permeability. Finally, this design procedure allows for a low-loss negative permeability metaferrite to be realized, with potential application to the design of left-handed or double negative media.
Effect of Obesity on Complication Rate After Elbow Arthroscopy in a Medicare Population.

Purpose To use a national insurance database to explore the association of obesity with the incidence of complications after elbow arthroscopy in a Medicare population. Methods Using Current Procedural Terminology (CPT) and International Classification of Diseases , 9th Revision (ICD-9) procedure codes, we queried the PearlDiver database for patients undergoing elbow arthroscopy. Patients were divided into obese (body mass index [BMI] >30) and nonobese (BMI Results A total of 2,785 Medicare patients who underwent elbow arthroscopy were identified from 2005 to 2012; 628 patients (22.5%) were coded as obese or morbidly obese, and 628 matched nonobese patients formed the control group. There were no differences between the obese patients and matched control nonobese patients regarding type of elbow arthroscopy, previous elbow fracture or previous elbow arthroscopy. Obese patients had greater rates of all assessed complications, including infection (odds ratio [OR] 2.8, P = .037), nerve injury (OR 5.4, P = .001), stiffness (OR 1.9, P = .016) and medical complications (OR 6.9, P Conclusions Obesity is associated with significantly increased rates of all assessed complications after elbow arthroscopy in a Medicare population, including infection, nerve injury, stiffness, and medical complications. Level of Evidence Therapeutic Level III, case-control study.
On controller design for linear time-invariant dual-input single-output systems

Presents a method for the design of controllers for linear time-invariant dual-input/single-output (DISO) systems in continuous-time or discrete-time. The new method reduces the problem to two single input/single-output (SISO) design problems which are well suited to frequency response design techniques. The first part of the method is the design of a stabilizing compensator for an auxiliary feedback system. The auxiliary compensator parameterizes the two output blocks of the single-input/dual-output controller such that the zeros of the parallel system formed by cascade of the controller with the plant are stable. The auxiliary compensator also determines the relative contribution to the output of the two parallel subsystems of the DISO system. The second SISO compensator design is used to ensure that the feedback system is stable and that performance and robustness specifications are achieved. The paper includes a discrete time design example for a dual-stage actuator system for a disk drive. Straightforward extensions for multi input/single-output systems are discussed.
A Highly Stable Adamantyl-Substituted Pincer-Ligated Iridium Catalyst for Alkane Dehydrogenation

The adamantyl-substituted pincer-ligand precursor AdPCP-H [(AdPCP = κ3-C6H3-2,6-(CH2PAd2)2); Ad = 1-adamantyl] has been synthesized by the reaction of 1,3-dibromoxylene with di-1-adamantylphosphine in the presence of triethylamine. Treatment of AdPCP-H with [Ir(COD)Cl]2 (COD = 1,5-cyclooctadiene) affords the pincer-ligated complex (AdPCP)IrHCl, which was crystallographically characterized. Dehydrohalogenation of (AdPCP)IrHCl either with LiBEt3H or with KOtBu, under hydrogen atmosphere, yields the hydrides (AdPCP)IrH2 and (AdPCP)IrH4. (AdPCP)IrH2 catalyzes dehydrogenation of alkanes with a level of activity comparable to that of the previously reported (tBuPCP)IrH2, while it is thermally much more robust than the tBuPCP analogue, as well as iPrPCP or tBuPOCOP pincer complexes.
The effect of compatibilizer level on the mechanical properties of a nylon 6/ABS polymer blend

The influence of compatibilizer on the morphology and mechanical properties of a blend of nylon 6 and ABS has been studied. For this blend, the morphological domain size decreases significantly with increasing compatibilizer level. However, stiffness and tensile stress at yield are unaffected by these changes. Within the range of these experiments, lzod impact strength increases monotonically with increasing levels of compatibilizer, but the resistance to crack initiation (J c) and the resistance to steady state crack growth (R p) are both increased by the addition of a small amount of compatibilizer and are essentially independent of further increases.
Comparative stress responses to short transport and related events in Hereford and Brahman steers

Three summer experiments compared responses to transportation-related events in 2- to 4-yr-old Brahman (Bos indicus) and Hereford (B. taurus) steers. In Exp. 1, steers were hauled round-trip (4 h) or fasted in holding pens. Transport transiently increased (P < 0.01) plasma cortisol and glucose concentrations, decreased (P < 0.05) plasma triglyceride concentrations, and increased total leukocyte counts. Blood constituents were not altered for steers fasting in holding pens. Treatment-day BW shrink was greater (P < 0.01) in transported steers than penned steers. Blood constituent responses were unaffected (P < 0.05) by subspecies. Hereford experienced greater (P < 0.05) transport-day BW shrink than Brahman across treatments. Steers in Exp. 2 were hauled to a new farm for a 1-wk relocation period or hauled round-trip an equal time (0.67 h) and returned to the home station. Both treatments similarly experienced transport-day BW shrink and increased (P < 0.01) plasma cortisol and glucose. Subspecies did not affect (P < 0.05) blood constituent responses to transport. Hereford experienced greater (P < 0.05) transport-day shrink than Brahman. Relocation did not elicit (P < 0.05) changes in blood profiles beyond the day of transport. In Exp. 3, steers were loaded and unloaded without transport, transported round-trip (1 h), or fasted in a holding pen for 3 h. Cortisol increased (P < 0.01) after transport and after loading/unloading. Leukocytes and glucose increased (P < 0.01) after the 1 h transport. Steers transported experienced greater treatment-day BW shrink than those fasted or loaded and unloaded (P < 0.01; -3.13 vs. -1.36 and -0.35 ± 0.76%, respectively). The subspecies did not vary (P < 0.05) for blood constituent responses or shrink in Exp. 3. Animal responses were not evident 24 h after treatments in each experiment. In summary, transport caused stress, but Brahman steers were not more sensitive than Herefords. Hereford steers were susceptible to greater transport BW shrink than Brahman under the summer conditions.