cssi/SciSciGPT-SciSciNet huggingface dataset:
The Effects of Sampling Location and Predictor Point Estimate Certainty on Posterior Support in Bayesian Phylogeographic Generalized Linear Models

The use of generalized linear models in Bayesian phylogeography has enabled researchers to simultaneously reconstruct the spatiotemporal history of a virus and quantify the contribution of predictor variables to that process. However, little is known about the sensitivity of this method to the choice of the discrete state partition. Here we investigate this question by analyzing a data set containing 299 sequences of the West Nile virus envelope gene sampled in the United States and fifteen predictors aggregated at four spatial levels. We demonstrate that although the topology of the viral phylogenies was consistent across analyses, support for the predictors depended on the level of aggregation. In particular, we found that the variance of the predictor support metrics was minimized at the most precise level for several predictors and maximized at more sparse levels of aggregation. These results suggest that caution should be taken when partitioning a region into discrete locations to ensure that interpretable, reproducible posterior estimates are obtained. These results also demonstrate why researchers should use the most precise discrete states possible to minimize the posterior variance in such estimates and reveal what truly drives the diffusion of viruses.
Ethics, standards, and TQM.

The most important ethical issue for our profession is the responsibility to assure the care delivered by our colleagues and ourselves meets a self-imposed standard of excellence. There is anecdotal and experimental evidence that we have not fulfilled this obligation. Peer review has proven, for a number of reasons, to be ineffective; however, improvements in the epidemiologic sciences should provide better standards and total quality management (TQM) might prove to be of value in monitoring, comparing and improving the decisions made by physicians. Its promise lies in its emphasis on statistical analysis, its focus on systematic rather than human error, and its use of outcomes as standards. These methods, however, should not diminish our other professional responsibilities: Altruism, peer review, and in Hippocrates' words "to prescribe regimens for the good of our patients-and never do harm to anyone."
Theorems about the Partition Function on Pages 189 and 182

Each of these two isolated pages has a connection with Ramanujan’s famous paper in which he gives the first proofs of the congruences p(5n+4)≡0 (mod 5) and p(7n+5)≡0 (mod 7). One of Ramanujan’s proofs hinges upon the beautiful identity $$\sum_{n=0}^{\infty}p(5n+4)q^n = 5 \frac{(q^5;q^5)_{\i}^5}{(q;q)_{\infty}^6}, \qquad |q|<1, $$ which is given on page 189. We provide a more detailed rendition of the proof given by Ramanujan, as well as a similarly beautiful identity yielding the congruence p(7n+5)≡0 (mod 7). On both pages, Ramanujan examines the more general partition function p r (n) defined by $$ \frac{1}{(q;q)_{\infty}^r}=\sum_{n=0}^{\infty}p_r(n)q^n, \qquad |q|<1. $$ In particular, he states new congruences for p r (n).
Cytomegaloviral adrenalitis and adrenal insufficiency in AIDS

In a review of 74 autopsy cases of acquired immune deficiency syndrome (AIDS), the incidence of cytomegalovirus (CMV) infection was found in 50% (37 cases). Of these 37 cases the adrenal glands were affected by CMV in 84%. The authors analyzed the histologic features of 30 of these 37 cases of CMV adrenalitis by grading the CMV inclusions, inflammation and necrosis (CMV score), focal versus diffuse involvement, and the degree of fibrosis (fibrosis score). The clinical data were not significant except for sodium to potassium ratio (Na:K), which was less than 30 in 11 cases. Focal CMV adrenalitis had low CMV and fibrosis scores and Na:K ratio higher than 30, whereas diffuse adrenalitis had high CMV and fibrosis scores and Na:K ratio less than 30. Adrenocorticotropic hormone (ACTH) stimulation tests performed in three patients revealed normal or elevated baseline cortisol levels with a blunted response after stimulation. The authors conclude that the adrenal gland is the most frequently affected organ in AIDS with CMV infection. ACTH tests on a larger number of selected cases of AIDS are needed for further evaluation of functional status of adrenal glands. Selection criteria for the test should include evidence of CMV infection from any site and a low Na:K ratio.
A Variational Procedure for Determining Spatially Dependent Thermal Spectra

Knowledge of the spatially dependent thermal spectrum near an interface between different media is important for many reactor calculations. The Kantorovich variational method is utilized to solve t...
An improved in-scene atmospheric retrieval and correction algorithm for long-wavelength infrared hyperspectral imagery

We describe a new algorithm, QUAC-IR (QUick Atmospheric Correction in the InfraRed), for automated, fast, atmospheric correction of LWIR (Long Wavelength InfraRed) hyperspectral imagery (HSI) and multi-spectral imagery (MSI) in the ~7-14 mm spectral region. QUAC-IR is an in-scene based algorithm, similar to the widely used ISAC (In- Scene Atmospheric Correction) algorithm. It improves upon the ISAC approach in several key ways, including providing absolute, versus relative, sensor-to-ground transmittances and radiances, as well as an estimate of the atmospheric downwelling sky radiance. The latter is important for retrieving emissivity from a reflective (i.e., non-blackbody) pixel. The key aspect of QUAC-IR is that it explicitly searches for blackbody pixels using an efficient approach involving a small number of spectral channels in which the atmospheric radiative transfer is dominated by the water continuum. This allows for fast and simplified Beer's Law (i.e., exponential) scaling of the path transmittance and radiance based on a compact library of pre-computed reference values. We apply QUAC-IR to well-calibrated data from the SEABASS1 and MAKO2 HSI sensors. The results are compared to those from a first-principles physics-based atmospheric code, FLAASH-IR.
Patient safety morning report: Innovation in teaching core patient safety principles to third-year medical students.

Introduction:Patient safety (PS) is one of the most important priorities in modern healthcare systems. Unfortunately, PS education is limited in many medical school curricula. Our objective was to ...
The Tax Cuts and Jobs Act and the Middle Class

This paper explores how the tax cuts and jobs act of 2017 impacts middle-class taxpayers by calculating the tax liability at different levels of income and deductions in 2017 versus 2018. The results confirm the statements supporting the positive effect of the tax change for the middle class. The tax cut and jobs act eliminates personal exemptions, changes the standard deductions at various incomes and family sizes, and lowers marginal tax rates. After providing details of the act, this research examines the definition of the U.S. middle class by using prior research from the Pew Research Center, the United States Census Bureau, and the federal reserve to determine which income levels are attributable to the middle class. Then the tax liability for these income classes is calculated for single and married filing jointly taxpayers in both 2017 and 2018 to determine if the tax cuts and jobs act reduces the tax liability for the middle class. The results show that in almost all scenarios the tax liability in 2018 will be lower than in 2017, regardless of whether standard or itemized deductions are taken. The marriage penalty is no longer applicable, and the new tax act provides a substantial benefit to large families
The Devastating Clinical Consequences of Child Abuse and Neglect: Increased Disease Vulnerability and Poor Treatment Response in Mood Disorders

A large body of evidence has demonstrated that exposure to childhood maltreatment at any stage of development can have long-lasting consequences. It is associated with a marked increase in risk for psychiatric and medical disorders. This review summarizes the literature investigating the effects of childhood maltreatment on disease vulnerability for mood disorders, specifically summarizing cross-sectional and more recent longitudinal studies demonstrating that childhood maltreatment is more prevalent and is associated with increased risk for first mood episode, episode recurrence, greater comorbidities, and increased risk for suicidal ideation and attempts in individuals with mood disorders. It summarizes the persistent alterations associated with childhood maltreatment, including alterations in the hypothalamic-pituitary-adrenal axis and inflammatory cytokines, which may contribute to disease vulnerability and a more pernicious disease course. The authors discuss several candidate genes and environmental factors (for example, substance use) that may alter disease vulnerability and illness course and neurobiological associations that may mediate these relationships following childhood maltreatment. Studies provide insight into modifiable mechanisms and provide direction to improve both treatment and prevention strategies.
A New Kind of Relevance for Archaeology

Traditional ways of doing archaeology impact the world in a variety of ways, but despite recent efforts the practical relevance of archaeology has remained limited. In this paper, I discuss why this is the case and suggest how archaeology can achieve greater practical relevance. I argue, first, that the traditional focus of archaeology on reconstructing the past is valuable but is unlikely to expand its practical relevance because the results are too context-specific. Second, I suggest traditional responses to the problem of historical contingency are also inadequate because the results are too general to connect to the specific issues and solutions society needs. Finally, I make a surprising and perhaps radical suggestion: that a productive way forward is to resuscitate and reformulate elements of the New Archaeology that were never realized by its proponents. I use the example of settlement scaling theory to illustrate that this is both possible and productive, and that additional work in this spirit would enhance the practical relevance of our field.
Folate Receptor Saturation, Recycling, and Release Kinetics in Activated Macrophages

Abstract Activated macrophages over-express a receptor for the vitamin, folic acid. Conjugation of folic acid to low molecular weight drugs, genes, liposomes, nanoparticles, and imaging agents does not significantly compromise the vitamin's affinity for its receptor, thus facilitating both therapeutic and imaging agents to be targeted as folate conjugates to activated macrophages. In these studies the in vivo kinetics and binding characteristics of the folate receptor on macrophages has been characterized with the objective of optimizing targeted drug delivery. Our results show that saturation of the receptor in inflamed tissues can be reached at a dose of 100 nmol/kg. Furthermore, the rapid recycling characteristics of the receptor (every 10–20 minutes) suggests that frequent dosing will allow for maximal uptake of folate conjugates by activated macrophages accumulated in inflamed tissues. Finally, the short circulation half-life (30 minutes) of the water-soluble folate conjugate used in this study minimizes the possibility of nonspecific uptake by receptor-negative tissues. The kinetic observations made in this study can be utilized to optimize the therapeutic efficacy and imaging agent delivery of folate conjugates to activated macrophages in vivo.
Framing the Anthropocene as Influence or Impact: The Importance of Interdisciplinary Contributions to Stratigraphic Classification

The designation of the Anthropocene formalizes the end of the 11,700-yearlong Holocene and the beginning of a new epoch. In the technical debates governing this transition, the stability of previou...
Association of adoption of transradial access for percutaneous coronary intervention in ST elevation myocardial infarction with door-to-balloon time.

OBJECTIVES We aimed to study adoption of transradial primary percutaneous coronary intervention (TR-PPCI) for ST elevation myocardial infarction (STEMI) ("radial first" approach) and its association with door-to-balloon time (D2BT). BACKGROUND TR-PPCI for STEMI is underutilized in the United States due to concerns about prolonging D2BT. Whether operators and hospitals adopting a radial first approach in STEMI incur prolonged D2BT is unknown. METHODS In 1,272 consecutive cases of STEMI with PPCI at our hospital from January 1, 2011, to December 31, 2016, we studied TR-PPCI adoption and its association with D2BT including a propensity matched analysis of similar risk TR-PPCI and trans-femoral primary PCI (TF-PPCI) patients. RESULTS With major increases in hospital-level TR-PPCI (hospital TR-PPCI rate: 2.6% in 2011 to 79.4% in 2016, p-trend<.001) and operator-level TR-PPCI (mean operator TR-PPCI rate: 2.9% in 2011 to 81.1% in 2016, p-trend = .005), median hospital level D2BT decreased from 102 min [81, 142] in 2011 to 84 min [60, 105] in 2016 (p-trend<.001). TF crossover (10.3%; n = 57) was not associated with unadjusted D2BT (TR-PPCI success 91 min [72, 112] vs. TF crossover 99 min [70, 115], p = .432) or D2BT adjusted for study year and presenting location (7.2% longer D2BT with TF crossover, 95% CI: -4.0% to +18.5%, p = .208). Among 273 propensity-matched pairs, unadjusted D2BT (TR-PPCI 98 [78, 117] min vs. TF-PPCI 101 [76, 132] min, p = .304), and D2BT adjusted for study year and presenting location (5.0% shorter D2BT with TR-PPCI, 95% CI: -12.4% to +2.4%, p = .188) were similar. CONCLUSIONS TR-PPCI can be successfully implemented without compromising D2BT performance.
Implications of deflation-inflation event models on Kīlauea Volcano, Hawaiʻi

Abstract Surface deformation of volcanic areas can reveal information about subsurface magma reservoirs and how magma is transported between them, which is an important part of volcano monitoring for hazard mitigation. One prominent style of deformation observed at Kīlauea volcano, Hawaiʻi, is episodic deflation-inflation (DI) events, which are recorded in surface deformation data and characterized by deflation of the summit region over hours to days followed by rapid re-inflation. The exact cause of DI events is unknown, however, a commonly proposed explanation is that a temporary blockage occurs in the conduit connecting the south caldera magma reservoir to the shallower Halemaʻumaʻu reservoir, thus interrupting the influx of magma. This model is investigated by testing the hypothesis that during the deflationary phase of a DI event, the volume of magma blocked from reaching the Halemaʻumaʻu reservoir is added to the south caldera reservoir. Using a mass balance approach and deformation modeling, the expected deformation (tilt) pattern was predicted for the reservoirs and compared to tilt observations from 16 large (>4 μrad magnitude) DI events between 2010 and 2012. While the predicted tilts due to inflation from the south caldera reservoir are strong enough to be detected, this signal is not seen in the tilt observations. We also explore the possibility that the blockage occurs below the south caldera reservoir, as well as alternative configurations that include a direct connection between the south caldera reservoir and the eruption site. None of the simple two-reservoir models we test are able to adequately satisfy the observations. Selected DI events show that tilt vectors change in both magnitude and azimuthal direction over the course of deflation. We conclude that the portion of the summit storage and plumbing system active during these DI events is more complicated than two connected chambers, and that it is more likely that these summit reservoirs have their own source conduits connecting in some complex way to the deep magma source.
Abstract Simulation Scenario Generation for Autonomous Vehicle Verification

Autonomous vehicle technology has the potential to have a significant impact on the transportation system and urban life. However, the autonomous vehicles must be proven to be at least as safe as human-driven vehicles before they are accepted as a new mode of transportation. Current methods of autonomous vehicle verification such as shadow driving or annotated images based testing are costly, slow and resource intensive. Hence, modeling and simulation is an indispensable asset to achieve verification goals for autonomous vehicles. In this paper, we propose an abstract simulation scenario generation framework for autonomous vehicle verification. The scenes and the related assertions are defined by a matrixbased semantic language and translated into test scenarios in simulation. The framework allows the design of all possible road topologies and the validation of generated scenarios. The scenarios generated in the framework form a ground truth for possible extended tests of rare conditions in other platforms.
Krabbe's Disease

Krabbe’s disease is a lysosomal storage disorder caused by deficient activity of galactosylceramidase, and characterized pathologically by the presence of globoid cells, destruction of white matter, and peripheral neuropathy. There is a marked accumulation of psychosine, which can reproduce the pathological phenotype when injected into experimental animals. The classic form of the disease presents in infancy, and rapidly progresses to death in early childhood. Later onset forms have been described, some of which may have a similarly acute course. More often, the phenotype mimics a slowly progressive spinocerebellar degeneration. Stem cell transplantation appears to prolong survival when initiated in the first few weeks of life for children with classic, early infantile disease, but the long-term outcome remains uncertain.
Women’s perceived contributions to diversity: The impact of target race and contextual gender salience:

Diversity is a desired attribute for many organizations. Yet, there is limited scientific understanding of what leads people to perceive diversity, and past studies focus on racial diversity to the...
The role of disaccharidases in the digestion - diagnosis and significance of their deficiency in children and adults

Disaccharidases are a group of enzymes of the small intestinal brush border, that are essential for degradation of disaccharides (sucrose, lactose, maltose, isomaltose, trehalose) into monosaccharides, which are then absorbed from the gastrointestinal tract. Their deficiency may occur at any stage of human life and have a genetic basis or be a secondary to ongoing gastrointestinal disease. Disaccharidase deficiencies cause disorders of digestion and absorption leading to occurrence of clinical symptoms such as abdominal pain, flatulence, diarrhea. For more than fifty years disaccharidase activity (DA) measurements in the small intestine biopsy samples are still considered the "gold standard" in the diagnostics for disaccharide deficiency. The aim of this review was to emphasize the role of disaccharidases in the digestion. Moreover, the significance of their deficiency in children and adults based on the current knowledge was described. It was showed that deficiency or inactivity of disaccharidases may lead to gastrointestinal intolerance symptoms. Early diagnostics allows the initiation of appropriate treatment, which contribute to reduction or complete resolution of clinical symptoms.
Preoperative Therapy Regimen Influences the Incidence and Implication of Nodal Downstaging in Patients with Gastric Cancer.

Purpose Nodal downstaging after preoperative therapy for gastric cancer has been shown to impart excellent prognosis, but this has not been validated in a national cohort. The role of neoadjuvant chemoradiation (NACR) in nodal downstaging remains unclear when compared with that of neoadjuvant chemotherapy alone (NAC). Furthermore, it is unknown whether the prognostic implications of nodal downstaging differ by preoperative regimen. Materials and methods Using the National Cancer Database, overall survival (OS) duration was compared among natural N0 (cN0/ypN0), downstaged N0 (cN+/ypN0), and node-positive (ypN+) gastric cancer patients treated with NACR or NAC. Factors associated with nodal downstaging were examined in a propensity score-matched cohort of cN+ patients, matched 1:1 by receipt of NACR or NAC. Results Of 7,426 patients (natural N0 [n=1,858, 25.4%], downstaged N0 [n=1,813, 24.4%], node-positive [n=3,755, 50.4%]), 58.2% received NACR, and 41.9% received NAC. The median OS durations of downstaged N0 (5.1 years) and natural N0 (5.6 years) patients were similar to one another and longer than that of node-positive patients (2.1 years) (P Conclusions Downstaged N0 patients have the same prognosis as natural N0 patients. Nodal downstaging occurred more frequently after NACR; however, the survival benefit of nodal downstaging after NACR may be less than that when such is achieved by NAC.
Marine animal tracking with classical and emerging localization algorithms

Localization algorithms applied to acoustic tags for tracking marine animals can also be used to localize marine robots.
Las Cumbres Observatory's end-to-end operations workflow

Las Cumbres Observatory is the only globally-distributed network of robotically-controlled telescopes. In 2018, we launched a program to overhaul the procedures by which network problems are detected, diagnosed and resolved. The program fostered numerous improvements, including new software tools to monitor active telescopes, documentation of recovery procedures, and daily reviews of operations problems. The benefit to users has been an increase in on-sky hours. We discuss the improvements we have made over the past two years. We emphasize the implementation of procedures ensuring problems are promptly addressed and completely resolved. We present our workflow as a model for how to manage a system of interconnected telescopes.
Proteolytic Processing of Big Endothelin-3 by the Kell Blood Group ProteinPresented in part in abstract form at the 40th annual meeting of the American Society of Hematology, December, 1998.

Kell blood group protein shares a consensus sequence (H.E.X.X.H) with a large family of zinc-dependent endopeptidases. Kell has closest homology with neutral endopeptidase 24.11, endothelin converting enzyme-1 (ECE-1), and the PEX gene product that, as a group, comprise the M13 subfamily of mammalian neutral endopeptidases. The proteolytic activity of the M13 members, but not of Kell, has been previously demonstrated. A secreted form of wild-type Kell protein (s-Kell), devoid of the intracellular and transmembrane domains, was expressed in sf9 cells. As a negative control, an inactive mutant Kell protein (E582G) was expressed. As determined by N-terminal amino acid sequencing and mass spectrometry of the cleaved products, wild-type s-Kell, but not the control mutant protein, specifically cleaved big endothelin-3 (ET-3) at Trp21-Ile22, yielding ET-3, and, to a much lesser extent, also cleaved big ET-1 and big ET-2 at Trp21-Val22, yielding ET-1 and ET-2. Enzymatic activity was partially inhibited by phosphoramidon. s-Kell has an acidic pH optimum (pH 6.0 to 6.5). Like the recombinant protein, red blood cells of common Kell phenotype also preferentially process big ET-3, in contrast to Ko (null) cells that do not. These data demonstrate that the Kell blood group protein is a proteolytic enzyme that processes big ET-3, generating ET-3, a potent bioactive peptide with multiple biological roles.
In vitro screening for chemical inhibition of the iodide recycling enzyme, iodotyrosine deiodinase

Abstract The iodide recycling enzyme, iodotyrosine deiodinase (IYD), is a largely unstudied molecular mechanism through which environmental chemicals can potentially cause thyroid disruption. This highly conserved enzyme plays an essential role in maintaining adequate levels of free iodide for thyroid hormone synthesis. Thyroid disruption following in vivo IYD inhibition has been documented in mammalian and amphibian models; however, few chemicals have been tested for IYD inhibition in either in vivo or in vitro assays. Presented here are the development and application of a screening assay to assess susceptibility of IYD to chemical inhibition. With recombinant human IYD enzyme, a 96-well plate in vitro assay was developed and then used to screen over 1800 unique substances from the U.S. EPA ToxCast screening library. Through a tiered screening approach, 194 IYD inhibitors were identified (inhibited IYD enzyme activity by 20% or greater at target concentration of 200 μM). 154 chemicals were further tested in concentration-response (0.032–200 μM) to determine IC50 and rank-order potency. This work broadens the coverage of thyroid-relevant molecular targets for chemical screening, provides the largest set of chemicals tested for IYD inhibition, and aids in prioritizing chemicals for targeted in vivo testing to evaluate thyroid-related adverse outcomes.
Ultrashort echo time adiabatic T1ρ (UTE-Adiab-T1ρ) is sensitive to human cadaveric knee joint deformation induced by mechanical loading and unloading.

Abstract Purpose The development of ultrashort echo time (UTE) MRI sequences has led to improved imaging of tissues with short T2 relaxation times, such as the deep layer cartilage and meniscus. UTE combined with adiabatic T1ρ preparation (UTE-Adiab-T1ρ) is an MRI measure with low sensitivity to the magic angle effect. This study aimed to investigate the sensitivity of UTE-Adiab-T1ρ to mechanical load-induced deformations in the tibiofemoral cartilage and meniscus of human cadaveric knee joints. Methods Eight knee joints from young (42 ± 12 years at death) donors were evaluated on a 3 T scanner using the UTE-Adiab-T1ρ sequence under four sequential loading conditions: load = 0 N (Load0), load = 300 N (Load1), load = 500 N (Load2), and load = 0 N (Unload). UTE-Adiab-T1ρ was measured in the meniscus (M), femoral articular cartilage (FAC), tibial articular cartilage (TAC), articular cartilage regions uncovered by meniscus (AC-UC), and articular cartilage regions covered by meniscus (AC-MC) within region of interests (ROIs) manually selected by an experienced MR scientist. The Kruskal–Wallis test, with corrected significance level for multiple comparisons, was used to examine the UTE-Adiab-T1ρ differences between different loading conditions. Results UTE-Adiab-T1ρ decreased in all grouped ROIs under both Load1 and Load2 conditions (−18.7% and − 16.9% for M, −18.8% and − 12.6% for FAC, −21.4% and − 10.7% for TAC, −26.2% and − 13.9% for AC-UC, and − 16.9% and − 10.7% for AC-MC). After unloading, average UTE-Adiab-T1ρ increased across all ROIs and within a lower range compared with the average UTE-Adiab-T1ρ decreases induced by the two previous loading conditions. The loading-induced differences were statistically non-significant. Conclusions While UTE-Adiab-T1ρ reduction by loading is likely an indication of tissue deformation, the increase of UTE-Adiab-T1ρ within a lower range by unloading implies partial tissue restoration. This study highlights the UTE-Adiab-T1ρ technique as an imaging marker of tissue function for detecting deformation patterns under loading.
Mechanisms of exTreg induction.

CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) play an important role in the maintenance of the immune system by regulating immune responses and resolving inflammation. Tregs exert their function by suppressing other immune cells and mediating peripheral self-tolerance. Under homeostatic conditions, Tregs are stable T cell populations. However, under inflammatory environments, Tregs are converted to CD4+ CD25low Foxp3low cells. These cells are termed "exTreg" or "exFoxp3" cells. The molecular mechanism of Treg transition to exTregs remains incompletely understood. Uncertainties might be explained by a lack of consensus of biological markers to define Treg subsets in general and exTregs in particular. In this review, we summarize known markers of Tregs and factors responsible for exTreg generation including cytokines, signaling pathways, transcription factors, and epigenetic mechanisms. We also identify studies demonstrating the presence of exTregs in various diseases and sources of exTregs. Understanding the biology of Treg transition to exTregs will help in designing Treg-based therapeutic approaches. This article is protected by copyright. All rights reserved.
Immunoglobulin GM and KM allotypes are associated with antibody responses to Pseudomonas aeruginosa antigens in chronically infected cystic fibrosis patients.

ABSTRACT Background Chronic infection with Pseudomonas aeruginosa (P. aeruginosa) is a leading cause of death in patients with cystic fibrosis (CF). Immunobiology of P. aeruginosa infection is complex and not well understood. Chronically infected CF patients generate high levels of antibodies to P. aeruginosa, but this response does not lead to clinical improvement. Therefore, additional studies aimed at identification and understanding of the host factors that influence naturally occurring immune responses to P. aeruginosa are needed. In this investigation, we evaluated the contribution of immunoglobulin GM (γ marker) and KM (κ marker) allotypes to the antibody responses to P. aeruginosa lipopolysaccharide (LPS) O1, O6, O11, and alginate antigens and the broadly-conserved surface polysaccharide expressed by many microbial pathogens, poly-N-acetyl-D-glucosamine (PNAG), in 58 chronically infected CF patients. Methods IgG1 markers GM 3 and 17 and IgG2 markers GM 23- and 23+ were determined by a pre-designed TaqMan® genotyping assay. The κ chain determinants KM 1 and 3 were characterized by PCR-RFLP. Antibodies to the LPS O antigens, alginate, and PNAG were measured by an ELISA. Results Several significant associations were noted with KM alleles. Particular KM 1/3 genotypes were individually and epistatically (with GM 3/17) associated with the level of IgG antibodies to O1, O11, alginate, and PNAG antigens. Conclusions Immunoglobulin GM and KM genotypes influence the magnitude of humoral immunity to LPS O, alginate, and PNAG antigens. These results, if confirmed in a larger study population, will be helpful in devising novel immunotherapeutic approaches against P. aeruginosa.
Understanding Resident Workflow and Educational Experience to Implement Advanced Practice Clinicians Into Neurology Residency Training Programs (P1.011)

Objective: 1. Assess workflow in a tertiary referral Neurology residency program 2. Incorporate advanced practice clinicians (APC) to address issues of patient safety and the resident education-service balance. Background: Neurology has one of the highest rates of burnout, and increased patient volume leads to feelings of depersonalization and job dissatisfaction. At our institution, stroke service discharges increased 71% from 2010–2015 and consult volume increased 24% from 2014–2015. Meanwhile, there was no increase in resident complement or hiring of additional staff. Design/Methods: We surveyed current and former residents on perceptions of patient volume, educational experience, adequacy of staffing, and patient safety. We tracked the timing of consults called to better assess patterns in workflow over one month. Based on survey results, we proposed hiring four APC to meet unmet workflow and educational needs. Results: Clinical volume was highest between 12 and 10 pm, which included a five-hour stretch with only one resident is in house. Although short call from 5–8pm is required for compliance with ACGME duty hour regulations, residents agreed that this yields inefficiencies, with simultaneous requirements for two rounds of handoff while fielding new consults and managing inpatient issues. Residents felt they needed assistance with tasks related to medication reconciliation, obtaining outside records, and preparing discharges before noon. They also felt patient safety was at risk for being compromised during handoff periods and after 8 pm on weekdays and 4 pm on weekends. Based on these results, we hired four APC to work staggered shifts from 7-4:30 pm and 12-8:30 pm seven days per week. Additionally, we designed APC roles around tasks deemed less educational for residents, including medication reconciliation and preparing discharges before noon. Conclusions: Understanding resident workflow and educational experience allows for implementation of an APC program that can optimize patient safety and resident education. Disclosure: Dr. Stein has nothing to disclose. Dr. Pace has nothing to disclose. Dr. Dhamoon has nothing to disclose. Dr. Krieger has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with acorda, bayer, biogen, emd serono, genentech, genzyme, mallinckrodt, medday, novartis, teva, and tg therapeutics .
Role of Immune Checkpoint Inhibitor Therapy in Advanced EGFR-Mutant Non-Small Cell Lung Cancer

Over the last decade, the treatment of advanced non-small cell lung cancer (NSCLC) has undergone rapid changes with innovations in oncogene-directed therapy and immune checkpoint inhibitors. In patients with NSCLC that harbors an epidermal growth factor receptor (EGFR) gene mutation (EGFRm), newer-generation tyrosine kinase inhibitors (TKIs) are providing unparalleled survival benefit and tolerability. Unfortunately, most of these patients will experience disease progression and thus an urgent need exists for improved subsequent lines of therapies. The concurrent revolution in immune checkpoint inhibitor (ICI) therapy is providing novel first and second line treatment options with improved clinical outcomes in wild-type EGFR (EGFRwt) NSCLC; however, the application of ICI therapy to advanced EGFRm NSCLC patients is controversial. Early studies demonstrated the inferiority of ICI monotherapy to EGFR TKI therapy in the first line setting and inferiority to chemotherapy in the second line setting. Additionally, combination ICI and EGFR TKI therapies have demonstrated increased toxicities, and EGFR TKI therapy given after first-line ICI therapy has been correlated with severe adverse events. Nonetheless, combination ICI therapies including dual-ICI blockade and ICI, chemotherapy, and angiogenesis inhibitors are areas of active study with some intriguing signals in preliminary studies. Here, we review previous and ongoing clinical studies of ICI therapy in advanced EGFRm NSCLC. We reviewed the data on ICI therapy in NSCLC with ALK, ROS1, BRAF, c-MET, RET, and NTRK mutations in a separate manuscript. We discuss advances in understanding the differences in the tumor biology and tumor microenvironment (TME) of EGFRm NSCLC tumors that may lead to novel approaches to enhance ICI efficacy. It is our goal to equip the reader with a knowledge of current therapies, past and current clinical trials, and exciting avenues of research that provide the promise of novel approaches and improved outcomes for patients with advanced EGFRm NSCLC.
Custom 3D Printed Titanium Reconstruction Plate with In-Situ Tissue Engineering for the Reconstruction and Dental Rehabilitation of a Severely Infected Atrophic Mandible. A Review of Technique

Abstract Purpose This article aims to introduce the novel technique of utilization of a custom 3D titanium printed reconstruction combined with in-situ tissue engineering for the reconstruction and dental rehabilitation of an infected severely atrophic mandible. Technique A 3-staged approach was used to remove the failing implants and debride the mandible, eradicating the infection, followed by reconstruction of the severely atrophic mandible using tissue engineering supported by a customized 3D-printed titanium undercarriage and reconstruction plate for vertical and horizontal augmentation. Finally, a CAD/CAM 3D-printed surgical guide was used for optimal placement of 4 dental implants. Conclusion A predictable and satisfactory reconstruct of a severely infected mandible with failing hardware to full dental rehabilitation and aesthetics was achieved by utilizing an amalgamation of state-of-the-art technology and tissue engineering.
Activated Sludge Process Modification Study

A laboratory study was conducted with a colloidal wastewater that was fed to model completely mixed and contact stabilization units. The units were operated at steady-state conditions at several mean cell residence time values. Using mean cell residence time as a basis for comparison it was determined that the cell yield coefficient and microorganism decay coefficient were similar for the two systems and that waste treatment efficiency was also similar. From these results it was determined there is no difference in the kinetics or operational performance between these two modifications to the activated sludge process.
Oxygenation of the human fetus and newborn infant during maternal metabolic acidosis.

Abstract The effects of maternal metabolic acidosis on fetal and newborn oxygenation were studied by comparing the oxygen content, oxygen saturation, and lactic and pyruvic acid contents in maternal, fetal, and newborn human blood. Observations were made without superimposed maternal acidosis, during and following the slow infusion of ammonium chloride, and during the following more rapid infusion. The results demonstrate that maternal metabolic acidosis is not accompanied by changes in concentrations of oxygen in maternal blood. The levels in fetal blood at birth and in newborn blood shortly after delivery, however, are significantly below control values.
Depolarization-Induced Mitochondrial Ca Accumulation in Sympathetic Neurons: Spatial and Temporal Characteristics

Several lines of evidence suggest that neuronal mitochondria accumulate calcium when the cytosolic free Ca(2+) concentration ([Ca(2+)](i)) is elevated to levels approaching approximately 500 nM, but the spatial, temporal, and quantitative characteristics of net mitochondrial Ca uptake during stimulus-evoked [Ca(2+)](i) elevations are not well understood. Here, we report direct measurements of depolarization-induced changes in intramitochondrial total Ca concentration ([Ca](mito)) obtained by x-ray microanalysis of rapidly frozen neurons from frog sympathetic ganglia. Unstimulated control cells exhibited undetectably low [Ca](mito), but high K(+) depolarization (50 mM, 45 sec), which elevates [Ca(2+)](i) to approximately 600 nM, increased [Ca](mito) to 13.0 +/- 1.5 mmol/kg dry weight; this increase was abolished by carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP). The elevation of [Ca](mito) was a function of both depolarization strength and duration. After repolarization, [Ca](mito) recovered to prestimulation levels with a time course that paralleled the decline in [Ca(2+)](i). Depolarization-induced increases in [Ca](mito) were spatially heterogeneous. At the level of single mitochondria, [Ca](mito) elevations depended on proximity to the plasma membrane, consistent with predictions of a diffusion model that considers radial [Ca(2+)](i) gradients that exist early during depolarization. Within individual mitochondria, Ca was concentrated in small, discrete sites, possibly reflecting a high-capacity intramitochondrial Ca storage mechanism. These findings demonstrate that in situ Ca accumulation by mitochondria, now directly identified as the structural correlate of the "FCCP-sensitive store, " is robust, reversible, graded with stimulus strength and duration, and dependent on spatial location.
Universalized Narratives: Patterns in How Faculty Members Define “Engineering”

Background U.S. engineering educators are discussing how we define engineering to ourselves and to others, such as in the recently released U.S. National Academy of Engineering (NAE) report, Changing the Conversation. In these conversations, leaders have proposed the skills, knowledge, processes, values, and attitudes that should define engineering. However, little attention has been paid to the daily work of engineering faculty, through their engineering research and teaching students to be new engineers, that puts these discipline-defining ideas into practice in academia. Purpose (Hypothesis) The different types of narratives engineering faculty explicitly or implicitly use to describe engineering are categorized. Categorizing these common narratives can help inform the nationwide conversation about whether these are the best narratives to tell in order to attract a diverse population of future engineers. Design/Method Interviews with ten engineering faculty at a research-extensive university were conducted. Interview transcripts were coded thematically through coarse then fine coding passes. The coarse codes were drawn from boundary theory; the fine codes emerged from the data. Results Faculty members' descriptions moved within and among the narratives of engineering as applied science and math, as problem-solving, and as making things. The narratives are termed “universalized” because of their broad-sweeping discursive application within and across participants' interviews. Conclusions These narratives drawn from academic engineers' practice put engineering at odds with recommendations from the NAE report. However, naming the narratives helps make them visible so we may then develop and practice telling contrasting narratives to future and current engineering students.
Photochemistry of bisphenol‐a based polycarbonate: The effect of the matrix and early detection of photo‐fries product formation

Abstract : The effect of polymer matrices on a photo-induced rearrangement process has been shown to be dependent upon whether the photoreactive group is attached to a polymer backbone, or free. If diphenylcarbonate is simply embedded in a polymer matrix, the rearrangement process is independent of whether the host film is above or below its glass transition. However, if the diphenylcarbonate group is incorporated as part of a polycarbonate backbone, the Fries rearrangement process is significantly reduced for photolyses conducted at temperatures well below the glass transition of polycarbonate. The utility of fluorescence spectroscopy in identification of the initial salicylate type photo-Fries type rearrangement product of polycarbonate is also demonstrated. The broad, structureless fluorescence spectrum with peak maximum at 470 nm produced by photolysis of polycarbonate films for short time periods is assigned to emission from phenyl salicylate type photoproducts.
Pyruvate kinase isozymes: a comparative study in tissues of various mammalian species.

Abstract 1. 1. Pyruvate kinase activity and electrophoretic patterns of pyruvate kinase isozymes of liver, kidney, heart and skeletal muscle were compared in male adult rats, hamsters, guinea pigs, rabbits, cats, dogs, monkeys and a human. Liver pyruvate kinase isozymes were separated and quantitated by DEAE-cellulose chromatography. 2. 2. Significant species differences in total pyruvate kinase activity occurred in all tissues but especially in the liver and skeletal muscle. 3. 3. Two electrophoretic distinct forms of pyruvate kinase were observed in the liver; one, four or five forms in the kidney; and one form in the heart and skeletal muscle of the species studied. 4. 4. DEAE-cellulose chromatography gave a quantitative recovery of two liver isozymes. Pyruvate kinase isozyme 1 predominated in most species. Only in the cat and human were liver isozymic activities about equally distributed between the two forms.
Physical limits in digital electronics

Miniaturization has steadily increased the economic usefulness of digital electronics through the past two decades. A variety of physical arguments are brought to bear on the question of how far miniaturization can be extended. The implications of the laws of quantum mechanics and thermodynamics for information storage are examined. The need for power dissipation in electrical information processing is demonstrated and the limits set on miniaturization by the problems of removing the heat thereby produced are estimated. limits with origins in properties of the materials used to make electronic devices are reviewed. The potential performance of various technologies based on nonsemiconductor phenomena is estimated and compared with the limits found for planar silicon technology. Attempts are made to guess at all of the many unknown parameters that enter into broadly applicable quantitative expressions of the properties of logic circuitry so that actual values of the limits can be estimated.
Nitrogen Removal by Orchardgrass and Smooth Bromegrass and Residual Soil Nitrate

Nitrogen removal by cool-season grasses may aid in capturing excess N from animal confinement operations or phytoremediation. Limited information exists on the N dynamics of these grasses near the asymptote of the N response curve. The objectives of this study were to evaluate N removal, residual soil NO 3 -N, and apparent N recovery in orchardgrass (Dactylis glomerata L.) and smooth bromegrass (Bromus iuermis Leyss.) at annual N rates of 224, 448, and 672 kg ha -1 . Species × harvest interactions were observed in both years, but no species x N rate interactions occurred. Orchardgrass removed 352 and 505 kg N ha -1 yr -1 at the 448 N rate compared with 207 and 371 in smooth bromegrass in 1999 and 2000, respectively. In a dry year, orchardgrass (r 2 = 0.41) and smooth bromegrass (r 2 = 0.31) exhibited linear N uptake. In a year with adequate rainfall, a quadratic relationship was observed for orchardgrass (R 2 = 0.92), while smooth bromegrass had linear uptake (r 2 = 0.66). Greater N removal was observed in orchardgrass partly because of superior fall growth, when 99 and 82 kg N ha -1 were removed in 1999 and 2000 at the 448 N rate compared with 23 and 15 kg N ha -1 in smooth bromegrass. These removal rates accounted for 28 and 16% of the seasonal total in 1999 and 2000 in orchardgrass and 11 and 4% in smooth bromegrass. Orchardgrass N removal exceeded smooth bromegrass in a three-cut system, and this difference was enhanced by utilizing the fall growth period to capture residual soil N.
Extent of stain penetration in sections prepared for electron microscopy.

Tissue embedded in Araldite 502 was sectioned for electron microscopy and stained in alcoholic uranyl acetate and lead citrate. Sections were then reembedded and resectioned perpendicularly. Such resulting preparations showed that these heavy metal salts completely penetrated through these thin sections for structures were stained throughout the section depth. Resectioning also showed the two surfaces of a thin section to have different textures. With sections cut by glass knives, the surface that touched the water of the knife trough was smooth, and the upper one was rougher. The upper surface was less rough when a diamond knife was used. The consequences of difference in texture of section surfaces and the extent of heavy metal staining are discussed in respect to the images produced by biological structures embedded in Araldite.
Efficacy of spider and ant predators on the cotton fleahopper (Hemiptera: Miridae).

The efficacy of predators of immature cotton fleahoppers,Pseudatomoscelis seriatus (Reuter), was calculated using field and laboratory cage confinement tests for consumption rate. The predators tested were the striped lynx spider,Oxyopes salticus Hentz; the black and white jumping spider,Phidippus audax (Hentz); the celer crab spider,Misumenops celer Hentz; and the red imported fire ant,Solenopsis invicta Buren. The spider predators were evaluated in a cotton field using predator-prey confinement cages on cotton plants. Average percent control (sensuAbbott 1925) of fleahoppers byO. salticus, P. audax, andM. celer were 42%, 66% and 32% respectively. The rate of fleahopper consumption by red imported fire ants was measured in the laboratory using various numbers of ants and fleahoppers. Daily percent control by ants ranged from 0.5% (single ant and fleahopper) to 100% (colony linked). The functional response of the 4 arthropod species to different prey numbers is illustrated and discussed as is the relative potential usefulness of natural enemies to suppress fleahoppers on cotton.