cssi/SciSciGPT-SciSciNet huggingface dataset:
Azorhizobium caulinodans respires with at least four terminal oxidases.

Abstract In culture, Azorhizobium caulinodans used at least four terminal oxidases, cytochrome aa3 (cytaa3), cytd, cyto, and a second a-type cytochrome, which together mediated general, respiratory electron (e-) transport to O2. To genetically dissect physiological roles for these various terminal oxidases, corresponding Azorhizobium apocytochrome genes were cloned, and three cytaa3 mutants, a cytd mutant, and a cytaa3, cytd double mutant were constructed by reverse genetics. These cytochrome oxidase mutants were tested for growth, oxidase activities, and N2 fixation properties both in culture and in symbiosis with the host plant Sesbania rostrata. The cytaa3 mutants grew normally, fixed N2 normally, and remained fully able to oxidize general respiratory e- donors (NADH, succinate) which utilize a cytc-dependent oxidase. By difference spectroscopy, a second, a-type cytochrome was detected in the cytaa3 mutants. This alternative a-type cytochrome (Amax = 610 nm) was also present in the wild type but was masked by bona fide cytaa3 (Amax = 605 nm). In late exponential-phase cultures, the cytaa3 mutants induced a new, membrane-bound, CO-binding cytc550, which also might serve as a cytc oxidase (a fifth terminal oxidase). The cloned Azorhizobium cytaa3 genes were strongly expressed during exponential growth but were deactivated prior to onset of stationary phase. Azorhizobium cytd mutants showed 40% lower N2 fixation rates in culture and in planta, but aerobic growth rates were wild type. The cytaa3, cytd double mutant showed 70% lower N2 fixation rates in planta. Pleiotropic cytc mutants were isolated by screening for strains unable to use N,N,N',N'-tetramethyl-p-phenylenediamine as a respiratory e- donor. These mutants synthesized no detectable cytc, excreted coproporphyrin, grew normally in aerobic minimal medium, grew poorly in rich medium, and fixed N2 poorly both in culture and in planta. Therefore, while aerobic growth was sustained by quinol oxidases alone, N2 fixation required cytc oxidase activities. Assuming that the terminal oxidases function as do their homologs in other bacteria, Azorhizobium respiration simultaneously employs both quinol and cytc oxidases. Because Azorhizobium terminal oxidase mutants were able to reformulate their terminal oxidase mix and grow more or less normally in aerobic culture, these terminal oxidases are somewhat degenerate. Its extensive terminal oxidase repertoire might allow Azorhizobium spp. to flourish in wide-ranging O2 environments.
Contact inhibition of division: involvement of the electrical transmembrane potential.

Measurements of simultaneous mitotic activity, electrical transmembrane potential (Em), and cell density levels in both 3T3 and Chinese hamster ovary (CHO) cell cultures reveal that a 5- to 6-fold increase in the Em level is associated with development of mitotic arrest at saturation densities. This rise occurs both in confluent monolayers and in interior areas of isolated colonies, and is independent of the rate at which confluence is attained. The Em rise is accompanied by a substantial decrease in intracellular Na. Electron microscopy of saturated CHO monolayer sections shows from 46 to 63% of the cell surfaces to be in close apposition (<300 A spacing). These results for contact inhibited cultures support the hypothesis that mitotic activity may be functionally coupled with the Em level and associated ionic concentration levels. It is suggested that contact inhibition of mitosis may result from a reduction in synthesis of mitogenically essential RNA following a decrease in intracellular Na produced by contact-induced alteration of surface ion-transport activity.
Current Role of Fetal Magnetic Resonance Imaging in Neurologic Anomalies

Magnetic resonance imaging (MRI) is used increasingly to image the fetus when important questions remain unanswered after ultrasonography, which might occur particularly with abnormal amniotic fluid volumes, difficult fetal lie or position, and maternal obesity. Ultrasonography also has limitations due to sound attenuation by bone, such as within the cranium and spine, and therefore MRI has a real advantage in delineating potentially complex neuroanatomical relationships. This article outlines current MRI protocols for evaluation of the fetal neural axis, describes indications for the use of MRI in the fetal brain and spine, and provides examples to illustrate the uses of available fetal sequences.
A time-dependent Lagrangian eyewall

The structure of a tropical cyclone eye and eyewall plays an important role in intensification. While the eyewall is usually defined in terms of instantaneous velocity and derived quantities such as vorticity, or thermodynamic variables such as equivalent potential temperature, or pressure, a Lagrangian eyewall definition is based on the transport of particles. In this paper, we analyse a Lagrangian eye–eyewall interface (LEEI), which is defined as a surface that acts as barrier to particle motion. The surface is identified with a maximal ridge of a hyperbolic Lagrangian field, and varies with the initial time at which particles are seeded. Our study extends a previous LEEI construction (Rutherford B, Dangelmayr G. 2010. Q. J. R. Meteorol. Soc. 136: 1931–1944) as follows. First, the ridge extraction algorithm used in our previous work is fully automated over time and z-levels, and smoothed by representing the ridge curves on z-slices in terms of Fourier descriptors. Secondly, the ridge curves for varying z-levels are matched to vertical basis functions leading to a 3D spatially continuous and low-dimensional representation of the LEEI, by truncating the combined azimuthal and vertical expansion. The surface is then analysed over varying initial time, and structural differences in time and height show that differences in Lagrangian structure and the degree of axisymmetry correspond to changes in intensity. Copyright © 2012 Royal Meteorological Society
Review of False-Positive Cultures for Mycobacterium tuberculosis and Recommendations for Avoiding Unnecessary Treatment

We reviewed reports of false-positive cultures for Mycobacterium tuberculosis and here propose guidelines for detecting and managing patients with possible false-positive cultures. Mechanisms of false-positive cultures included contamination of clinical devices, clerical errors, and laboratory cross-contamination. False-positive cultures were identified in 13 (93%) of the 14 studies that evaluated > or = 100 patients; the median false-positive rate was 3.1% (interquartile range, 2.2%-10.5%). Of the 236 patients with false-positive cultures reported in sufficient detail, 158 (67%) were treated, some of whom had toxicity from therapy, as well as unnecessary hospitalizations, tests, and contact investigations. Having a single positive culture was a sensitive but nonspecific criterion for detecting false-positive cultures. False-positive cultures for M. tuberculosis are not rare but are infrequently recognized by laboratory and clinical personnel. Laboratories and tuberculosis control programs should develop procedures to identify patients having only 1 positive culture. Such patients should be further evaluated for the possibility of a false-positive culture.
Chlortetracycline-Resistant Intestinal Bacteria in Organically Raised and Feral Swine

Organically raised swine had high fecal populations of chlortetracycline (CTC)-resistant (growing at 64 μg CTC/ml) Escherichia coli, Megasphaera elsdenii, and anaerobic bacteria. By comparison, CTC-resistant bacteria in feral swine feces were over 1,000-fold fewer and exhibited lower taxonomic diversity.
Adaptive Order Determination for Constructing Time Series Forecasting Models

In time series modeling consistent criteria like Bayesian Information Criterion (BIC) outperform in terms of predictability loss-efficient criteria like Akaike Information Criterion (AIC) when data are generated by a finite-order autoregressive process, and the reverse is true when data are generated by an infinite-order autoregressive process. Since in practice we don’t know the data-generating process, it is useful to have an adaptive criterion that behaves as either a consistent or just as a loss-efficient criterion, whichever performs better. Here we derive such a criterion. Moreover, our criterion is adaptive to effective sample sizes and not sensitive to maximum a priori determined order limits.
Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature characterized by endothelial cell apoptosis, smooth muscle proliferation and obliteration of pulmonary arterioles. This in turn results in right ventricular (RV) failure, with significant morbidity and mortality. Rodent models of PAH, in the mouse and the rat, are important for understanding the pathophysiology underlying this rare disease. Notably, different models of PAH may be associated with different degrees of pulmonary hypertension, RV hypertrophy and RV failure. Therefore, a complete hemodynamic characterization of mice and rats with PAH is critical in determining the effects of drugs or genetic modifications on the disease. Here we demonstrate standard procedures for assessment of right ventricular function and hemodynamics in both rat and mouse PAH models. Echocardiography is useful in determining RV function in rats, although obtaining standard views of the right ventricle is challenging in the awake mouse. Access for right heart catheterization is obtained by the internal jugular vein in closed-chest mice and rats. Pressures can be measured using polyethylene tubing with a fluid pressure transducer or a miniature micromanometer pressure catheter. Pressure-volume loop analysis can be performed in the open chest. After obtaining hemodynamics, the rodent is euthanized. The heart can be dissected to separate the RV free wall from the left ventricle (LV) and septum, allowing an assessment of RV hypertrophy using the Fulton index (RV/(LV+S)). Then samples can be harvested from the heart, lungs and other tissues as needed.
Diagnostic Techniques for Evaluation of the Paranasal Sinuses

Physical examination of the paranasal sinuses is often insufficient to confidently reach a conclusion concerning suspected pathology in these cavities. Often, other evaluation techniques are necessary. This article describes physical examination, rhinoscopy, sinus centesis, radiology, and sinus endoscopy of the equine paranasal sinuses. These techniques can be used to diagnosis and determine the cause of most sinus disorders.
Spectral Efficiency and Energy Efficiency Optimization via Mode Selection for Spatial Modulation in MIMO Systems

In this paper, we consider the multiple-input–multiple-output (MIMO) system employing spatial modulation (SM)-based transmission in Rayleigh fading channels with known slow-varying large-scale fading loss and channel correlations. Observing that the system performance is affected by transmission mechanisms and configurations, we propose a framework enabling the selection of the transmission mode for the optimal spectral efficiency (SE) or energy efficiency (EE) while conforming to transmission and error rate requirements with low complexity. In the framework, a closed-form error rate approximation is proposed. It renders the formulated SE- and EE-based selection problems solvable via naive exhaustive search method. Moreover, we propose to reduce the complexity via using lookup tables. Computer simulations are provided to evaluate the framework.
In and Out of the Commune: The Social Boundaries of Citizenship

Early one morning in January of 1609, an innkeeper in Frankfurt was awakened from his slumbers by an excited guest, who reported that his companions in the public room below were engaged in a violent fight. The group of men had already been well into their cups when the innkeeper decided to go to bed the night before, and now he hurried down the stairs in his night shirt to find one of the men wounded to the bone with a hunting knife (Weidner, also in widespread use as a side arm). The men had been gambling late at night and came to blows over an accusation of cheating, which ultimately escalated to a knife fight.1 A fight over cards and drinks in a public house was, of course, hardly unusual in early modern Germany. The only thing that differentiates this fight from thousands of other seventeenth-century tavern brawls is the fact that it took place in the Judengasse, Frankfurt’s Jewish quarter, and the men involved were not Christians but Jews. Even so, it does not seem to have been terribly out of the ordinary. What this fight and others like it illustrate is that despite even very recent assertions to the contrary, Jewish men lacked neither the weapons nor the propensity for violence that triggered a resort to arms.
CAT: high-precision acoustic motion tracking

Video games, Virtual Reality (VR), Augmented Reality (AR), and Smart appliances (e.g., smart TVs) all call for a new way for users to interact and control them. This paper develops high-preCision Acoustic Tracker (CAT), which aims to replace a traditional mouse and let a user play games, interact with VR/AR headsets, and control smart appliances by moving a smartphone in the air. Achieving high tracking accuracy is essential to provide enjoyable user experience. To this end, we develop a novel system that uses audio signals to achieve mm-level tracking accuracy. It lets multiple speakers transmit inaudible sounds at different frequencies. Based on the received sound, our system continuously estimates the distance and velocity of the mobile with respect to the speakers to continuously track it. At its heart lies a distributed Frequency Modulated Continuous Waveform (FMCW) that can accurately estimate the absolute distance between a transmitter and a receiver that are separate and unsynchronized. We further develop an optimization framework to combine FMCW estimation with Doppler shifts and Inertial Measurement Unit (IMU) measurements to enhance the accuracy, and efficiently solve the optimization problem. We implement two systems: one on a desktop and another on a mobile phone. Our evaluation and user study show that our system achieves high tracking accuracy and ease of use using existing hardware.
Politics, the ISS, and Private Enterprise

This chapter examines the next time period after the Space Shuttle—the ISS and Private Enterprise. During the Space Shuttle program, there was continuing interest in an Earth orbiting International Space Station (ISS) that is considered to be one of the greatest technological achievements. The ISS served as an orbiting research laboratory for experiments related to Earth’s atmosphere as well as exploring deep space. The ISS resulted in a number of important collaborations and research discoveries.
Promoting cervical cancer screening services through a breast cancer screening program

B67 Background: The Tennessee Breast and Cervical Cancer Screening Program (TBCSP), provides free breast and cervical cancer screening to women who are uninsured or underinsured. As a result, screening rates have significantly improved in all racial and ethnic groups over the past 10 years. However, there remains underutilization of the TBCSP, particularly by women who are never or rarely screened for cervical cancer. Mammograms in May (MIM) is a successful annual breast cancer screening program in Nashville, TN that offers no-cost screening mammograms at Nashville General Hospital. The Center for Women’s Health at Meharry is one of only two health clinics in Davidson County that provides cervical cancer screening and follow-up for the TBCSP. We hypothesized that inquiring about recent Pap test screening during the MIM visit would help identify women who had not undergone recent cervical cancer screening. Methods: When women arrived for mammography examinations they were asked if they had received a Pap test within the past 3 years. Women who had not were referred for services and eligible women were enrolled in the TBCSP. Results: Four hundred and twenty-nine screening mammograms were performed as a result of the MIM program in 2007. We identified one hundred and eighty-six (43%) women who had not had a Pap test in greater than 3 years. Ninety-three (22%) women were eligible for enrollment in the TBCSP and were scheduled to be seen at the Center for Women’s Health at Meharry. To date, 57/93 (61%) Pap tests have been completed. We have identified fewer than 5% abnormal Pap tests and have not diagnosed any cancers. Conclusion: All women who sought no cost mammography services through the MIM program were asked if they had undergone recent cervical cancer screening with Pap tests. Almost half of the women undergoing breast cancer screening examinations had not had a recent Pap test. Furthermore, one-fifth of the women were eligible for enrollment in the TBCSP, indicating their status as uninsured or underinsured. We made certain that Pap test services were readily available through close collaboration between the Center for Women’s Health at Meharry and the TBCSP. As a result, the appointment show rate was greater than 50%. These results are preliminary, but suggest further study is warranted to explore the approach of using breast cancer screening programs as a method of promoting utilization of cervical cancer screening services and engaging women in a health care system.
The medical therapy of osteoarthritis: thinking outside the box

A limited number of approved United States Federal Drug Administration (US-FDA) medical therapies are presently employed for the medical therapy of osteoarthritis (OA). Why is that? And why, despite the world-wide statistical evidence which has repeatedly shown that OA is the most common type of arthritis among adults with the incidence of OA especially high among elderly individuals has there been little in the way of progress in the development of drug therapies for OA? This question appears particularly relevant if one considers that the pharmaceutical revolution over the last 20 years or so gave rise to the FDA approving a slew of innovative medical interventions for the treatment of the much less common form of arthritis, namely, rheumatoid arthritis. Is the reason for the decision to essentially curtail drug development for OA that we know so little about what the relevant targets for potential drug therapy for OA might be? I don’t think so! Is it because there would be little financial reward for developing “disease-modifying-OA drugs” (DMOADs). No to that too!! So what’s the reason?
Human Cytomegalovirus Induces Cellular and Humoral Virus-specific Immune Responses in Humanized BLT Mice

The strict species specificity of Human Cytomegalovirus (HCMV) has impeded our understanding of antiviral adaptive immune responses in the context of a human immune system. We have previously shown that HCMV infection of human hematopoietic progenitor cells engrafted in immune deficient mice (huNSG) results in viral latency that can be reactivated following G-CSF treatment. In this study, we characterized the functional human adaptive immune responses in HCMV latently-infected huBLT (humanized Bone marrow-Liver-Thymus) mice. Following infection, huBLT mice generate human effector and central memory CD4+ and CD8+ T-cell responses reactive to peptides corresponding to both IE and pp65 proteins. Additionally, both HCMV specific IgM and IgG B-cell responses with the ability to neutralize virus were detected. These results indicate that the HCMV huBLT mouse model may provide a valuable tool to study viral latency and reactivation as well as evaluate HCMV vaccines and immune responses in the context of a functional human immune system.
Abstract DDT01-01: The discovery and preclinical characterization of AMG 176: A first-in-class Mcl-1 inhibitor in clinical development for multiple myeloma

Mcl-1 is a prosurvival member of the Bcl-2 family of proteins, which regulate programmed cell death via protein-protein interactions between prosurvival and proapoptotic members of the family. A variety of studies have demonstrated that Mcl-1 is a key prosurvival factor for many human cancers, making it a highly desirable target for therapeutic intervention. However, targeting Mcl-1 to induce tumor cell death has been an exceptional challenge for the development of drug-like small molecule inhibitors due to the high-affinity interaction of Mcl-1 with proapoptotic binding partners and the lack of an obvious small molecule binding pocket. In this presentation we will describe the application of structural analysis and molecular modeling to the optimization of an HTS screening hit that culminated in the identification of a clinical candidate, AMG 176. In addition, we will present data demonstrating that AMG 176 is a potent, highly selective, and reversible Mcl-1 inhibitor. Mechanism-of-action studies revealed that AMG 176 induces a rapid and irreversible commitment to apoptosis in tumor cells via the disruption of protein-protein interactions with proapoptotic members of the Bcl-2 family. Furthermore, the extensive profiling of a large and diverse tumor cell line panel revealed that lines derived from hematologic malignancies, such as multiple myeloma, acute myeloid leukemia, and non-Hodgkin lymphoma, are particularly sensitive to Mcl-1 inhibition with the expression of Bcl-xL inversely correlating with response. In addition, cell line profiling data revealed an activity profile distinct from a selective Bcl-2 inhibitor, further underscoring the unique therapeutic opportunity for an Mcl-1 inhibitor. Synergistic combinations were identified with therapies selectively targeting Bcl-2, the MAPK pathway, and proteasome inhibitors. In vivo, AMG 176 demonstrated robust inhibition of tumor xenograft growth with a clear PK/PD relationship, exhibiting on-mechanism activity as measured by Bak and caspase activation on a discontinuous dosing schedule of once or twice weekly. An ongoing phase 1 clinical trial is currently evaluating AMG 176 in multiple myeloma. Citation Format: Paul E. Hughes. The discovery and preclinical characterization of AMG 176: A first-in-class Mcl-1 inhibitor in clinical development for multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr DDT01-01. doi:10.1158/1538-7445.AM2017-DDT01-01
WEB BROWSERS: UNTANGLING THE WORLD WIDE WEB

Not only are Internet resources expanding exponentially, but they are becoming more sophisticated, incorporating a variety of multimedia and hypertext components. Internet documents on the World Wide Web may contain elaborately formatted text, color graphics, audio, and video as well as dynamic connections to other Internet resources via hypertext links. In addition to providing user-friendly access to hypermedia resources, most Web browsers (client software) provide a rich graphical environment for authoring and displaying electronic documents locally. This article describes the World Wide Web and a sampling of the available Web browsers. It then discusses a testproject developed at the University of Nebraska-Lincoln Libraries designed to explore the potential, demands, and pitfalls of Web access to the Internet, as well as to investigate hypermedia document creation in an academic libraryenvironment. The experiences with the project qonfirmed the importance of the World Wide Web and Web browsers to this environment, so much so that providing access to these Internet resources must be seen as mandatory to any academic or upper level educational library providing electronic information access.
Positive Urinary Cytology Following a Complete Response to Intravesical Bacillus Calmette-Guerin Therapy: Pattern of Recurrence

AbstractThe pattern of disease recurrence was examined in 75 patients with clinically undetectable positive urinary cytology results following a complete response to intravesical bacillus Calmette-Guerin (BCG) therapy for superficial bladder cancer. A complete response was defined as negative cystoscopy and biopsy findings, urine cytology and flow cytometry (when available) for at least 1 year following therapy. Urinary cytology was positive in the absence of clinical disease at a median of 25 months (range 12 to 96) after BCG administration. Clinically recognizable disease (defined by a positive biopsy or visible papillary tumor) developed at a median of 6 months (range 2 to 60) after positive cytology was detected in 62 patients (83%), while 13 (17%) had persistently positive cytology results without an obvious source at a median of 6 months (range 2 to 29).The bladder was the single most common site of recurrence, with 39 recurrences developing in 36 patients (58%, 3 of whom had recurrent cancer after ...
Adhesion of activated platelets to venous endothelial cells is mediated via GPIIb/IIIa.

Abstract Normal circulating platelets do not adhere to intact, undisturbed endothelium. Studies have shown, however, that platelets will adhere to virally infected or thrombin-stimulated human umbilical vein endothelial cells. Using a novel platelet/endothelial cell adhesion assay we studied the interaction of thrombin-activated platelets to human saphenous vein endothelial cells (HSVEC), and its mechanism(s). Biotinylated platelets were exposed to Hepes–Tyrode buffer, 10E5 or PAC-1 [monoclonal antibodies (Mabs) blocking GPIIb–IIIa], AK4 (Mab blocking P-selectin), 6D1 (Mab blocking vWf binding to GPIb), RGDS (small peptide blocking the fibrinogen binding site), or EDTA (dissociates GPIIb–IIIa complex) and then activated with thrombin. The platelets were subsequently exposed to thrombin-stimulated monolayer HSVEC. Phycoerythrin–streptavidin was added to the wells to fluorescently label the platelets, followed by formaldehyde fixation and washing to remove nonadherent platelets. Adhesion of platelets to HSVEC was assessed using a fluorescent multiwell plate reader. Antibodies which blocked the GPIIb–IIIa receptor and agents which competitively bound the receptor all significantly inhibited activated platelet adhesion to the activated HSVEC. We have found that thrombin significantly increases platelet/HSVEC adhesion, and this event is mediated via the integrin GPIIb–IIIa (fibrinogen receptor). These GPIIb–IIIa receptor blocking Mabs and RGDS may be useful adjuncts for improving patency following angiographic intervention and/or vein grafting in patients with high risk of thrombosis. The assay we have developed is a valuable and relatively simple method for assessing platelet/endothelial cell adhesion and activation.
Liquid Water—Acoustic Properties: Absorption and Relaxation

In general, liquids differ from solids primarily in their ability to flow. While in the process of flowing, however, a liquid is not in thermodynamic equilibrium. On a miscoscopic basis, for flow to occur, the molecules must rearrange relative to each other. In thermodynamic equilibrium, a liquid is completely characterized by a small number of state variables (e.g., the internal energy, volume, number of moles, total magnetic and electric moments, etc.). When a system initially in equilibrium is perturbed into a nonequilibrium state, the method by which equilibrium is restored is known as a relaxation process. Any such nonequilibrium state requires that parameters in addition to the state variables be specified for a complete characterization. In the present chapter, we will be concerned with structural relaxation. This is the process by which the molecules of a system “flow” from a nonequilibrium configuration to a new equilibrium configuration.
Perceptions of Liver Transplant Candidates with or Without an Alcohol Use History

Cirrhosis secondary to alcohol use is a primary cause of liver disease and a medical condition for which liver transplantation is a viable treatment option. However, there remains considerable debate within both the lay and the medical communities regarding the distribution of a scarce medical resource to adults with alcoholism. This study examined college students' perceptions toward an adult, presented in a written vignette, for whom liver transplantation was medically indicated. The influence of gender (female and male) and alcohol use history (no alcohol history, alcoholism history with long-term abstinence, alcoholism history with current use) on these ratings was examined. Subjects rated the adult presented with no alcohol history more positively than they did the adults presented with a history of alcoholism. Also, the adult with no alcohol history was more likely to be offered transplantation and was given higher priority ratings for transplantation by subjects. While subjects' own alcohol use history and organ donor registration status were not associated with ratings, having a family member with an alcohol problem and personally knowing a transplant recipient were related to more favorable ratings toward the adult presented in the vignette. Implications of these findings as well as limitations of the study are discussed.
Acquisition of sociophonetic variation: Intervocalic /d/ reduction in native and nonnative Spanish

This study investigates the acquisition of nativelike variation in the production of Spanish /d/ by English-speaking learners. Specifically, we examine the production of /d/ in word-internal intervocalic position in the speech of 13 highly advanced nonnative speakers (NNSs) and 13 native speakers (NSs) of Spanish in digitally-recorded sociolinguistic interviews. The analysis includes a discrete categorization of /d/ realization based on spectrographic examination (stop vs. spirant vs. deleted) and a continuous intensity difference measure. Tokens were coded for grammatical category, surrounding segments, stress, number of syllables, and lexical frequency. Results indicate that both NNSs and NSs exhibit /d/ spirantization and deletion, but these two processes are affected by different factors both between and across groups: NNS deletion patterns are predicted most significantly by lexical frequency, whereas degree of spirantization is influenced by articulatory/contextual factors of phonetic context and stress. NS patterns for both processes are influenced by most factors in a similar manner.
E-122 Preclinical evaluation of the daise, a novel thrombectomy system for acute ischemic stroke

Introduction/purpose The DAISe System (MIVI Neuroscience, Inc., Eden Prairie, MN) is a novel thrombectomy treatment system intended for acute ischemic stroke. It consists of an expandable, polymer, fiber-based element mounted onto a wire (figure 1) and a thromboaspiration catheter. When deployed, the fiber element acts as a mechanical backstop to usher the thrombus back to the mouth of the aspiration catheter for removal. This preclinical study examined the system’s ability to perform mock mechanical thrombectomy procedures in a porcine model and 3D anatomical flow models and bench experiments. Materials and methods Exogenous thrombi manufactured from autologous blood were introduced to porcine subjects to simulate ischemic stroke. Blood was centrifuged, allowed to clot, then aliquoted into clot sizes proportional to the target vessel dimensions. The thrombi were delivered into the neurovasculature one at a time, and subsequently retrieved aspiration via a 30 cc syringe and the DAISe System. This was repeated bilaterally in two subjects of 35 kg or greater. Contrast and angiography were used to visualize the vasculature before and after the procedure. Pathological assessment was performed on affected arteries. Additionally, a series of in vivo experiments were conducted including thrombectomy performed with both red and white clots, comparing the DAISe System, the DAISe System with aspiration, and two commercially available stent retrievers. Results All thrombectomy attempts in the porcine model with the DAISe System and aspiration were effective in removing clot and did not cause significant vascular damage as determined by pathological analysis. Each procedure was relatively rapid, taking no more than ten minutes per clot. In the in vitro thrombectomy test, the DAISe System plus aspiration resulted in the highest rate of success for both red (100%) and white clots (100%). The DAISe System without aspiration along with the Stent Retriever 1 both exhibited clot removal efficiencies of 80% and 60% for red and white clots respectively. Finally, Stent Retriever 2 had a red and white clot retrieval success rate of 60% and 40% respectively. Conclusion In this preclinical evaluation, the DAISe System successfully removed thrombi when used in junction with aspiration in an animal model. In addition, it demonstrated greater clot retrieval efficiency when used with aspiration in in vitro thrombectomy experimentation. Disclosures T. Long: None. J. Wolter: 5; C; MIVI Neuroscience, Inc. W. Bichard: None. M. Preul: None.
Educational needs in families of pediatric liver and kidney transplant recipients: A quality improvement project

Parents of pediatric liver and kidney transplant recipients were surveyed regarding their current education plans (eg, Individualized Education Program, 504), satisfaction with these plans, and interest in educational support from the psychosocial transplant team. Survey results indicate high rates of IEP and 504 plans, academic and related services, and accommodations among this population. The majority of parents/guardians reported satisfaction with their child's current school plan and did not report need for additional transplant team support specific to school services on the survey measure. However, other information highlights the importance for pediatric transplant teams to consider other ways to support this population's educational needs.
Utilization of therapeutic plasma exchange for hyperbilirubinemia in a premature newborn on extracorporeal membrane oxygenation

BACKGROUND We report a case of a premature newborn girl with a hospital course complicated by suspected respiratory syncytial virus pneumonitis for which she was placed on veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Despite phototherapy, her total bilirubin steadily increased to a peak of 50.4 mg/dL with concern for bilirubin-induced neurologic dysfunction, kernicterus. STUDY DESIGN AND METHODS Therapeutic plasma exchange (TPE) was achieved via connection with the VA-ECMO circuit. Our institution's standard apheresis procedural parameters were adjusted to account for the small body weight and thus the low blood volume of the neonate while on ECMO. These included calculating the total blood volume to include the patient as well as the ECMO circuit, priming of the apheresis instrument with packed red blood cells to limit the extracorporeal volume, using a lower inlet flow rate, the connection setup of the inlet and return line, and monitoring of ionized calcium and anticoagulation throughout the procedure. RESULTS A total of three TPE procedures were performed over three consecutive days. This resulted in improvement and stabilization of the patient's bilirubin. CONCLUSION This case emphasizes that TPE is feasible on a neonate with a suboptimal body weight and thus a low blood volume due to the increased blood volume provided while on ECMO. In the absence of ECMO, whole blood manual exchange transfusion is recommended as TPE would be unsafe due to significant extracorporeal volume that would occur during TPE in a pediatric patient with low body weight.
Beauregard: Cities in the Urban Age: A Dissent

Cities have been getting good press in recent years. Recent authors, most notably Edward Glaeser and Peter Hall, have celebrated cities as the sources of economic dynamism and social and artistic c...
Sexual dimorphism in hypothalamic inflammation in the offspring of dams exposed to a diet rich in high fat and branched-chain amino acids.

Branched-chain amino acid (BCAAs: leucine, isoleucine, and valine) contribute to the development of obesity-associated insulin resistance in the context of consumption of a high-fat diet (HFD) in h...
The impact of dissection and re-entry versus wire escalation techniques on long-term clinical outcomes in patients with chronic total occlusion lesions following percutaneous coronary intervention: An updated meta-analysis.

Background: The meta-analysis was performed to evaluate the effect of dissection and re-entry (DR) vs. wire escalation (WE) techniques on long-term clinical outcomes in patients with chronic total occlusion (CTO) lesions undergoing percutaneous coronary intervention. Methods: Studies were searched in electronic databases from inception to September, 2019. Results were pooled using random effects model and fixed effects model and are presented as risk ratios (RR) with 95% confidence intervals (CI). Results: Pooled analyses revealed that patients with DR techniques had overall higher complexity CTO lesions than patients with WE techniques and required a greater number of stents and a greater mean stent length. The “extensive” DR techniques may have a higher incidence of target vessel revascularization (TVR) (RR = 2.30, 95% CI: 1.77–2.98), in-stent restenosis (RR = 1.71, 95% CI: 1.30–2.23), in-stent reocclusion (RR = 1.86, 95% CI: 1.03–3.3) and death/myocardial infarction/TVR (RR = 2.10, 95% CI: 1.71–2.58), when compared with WE techniques, during the long-term follow-up. However, “limited” DR techniques result in more promising outcomes, and are comparable to conventional WE techniques. Conclusions: Dissection and re-entry techniques were associated with increased risk of long-term negative clinical events, especially “extensive” DR techniques. However, “limited” DR techniques resulted in good long-term outcomes, comparable to WE techniques.
Therapeutic Management of Immune-Mediated Necrotizing Myositis

The idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders characterized by skeletal muscle inflammation leading to chronic muscle weakness. Immune-mediated necrotizing myopathy (IMNM) is a distinct subgroup of inflammatory myopathy typically characterized by myofiber necrosis with minimal inflammatory infiltrates on muscle biopsy, highly elevated creatine kinase levels, and infrequent extra-muscular involvement. This review provides an overview of currently recommended treatment strategies for IMNM, including discussion of disease activity monitoring and recommended first-line immunomodulatory agents depending on clinical phenotype and autoantibody status. IMNM can be divided into three subtypes based on autoantibody positivity: anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) IMNM, anti-signal recognition particle (SRP) IMNM, and antibody-negative IMNM. Autoantibody status in IMNM has considerable correlation with clinical phenotype, prognosis, and recommended choice of immunosuppressive agent. Patients with anti-HMGCR IMNM tend to respond well to intravenous immunoglobulin (IVIG), and IVIG monotherapy may be a sufficient treatment for certain patients. In anti-SRP IMNM, early rituximab is commonly favored. More generally, prompt initiation of aggressive immunosuppression is often indicated, as both anti-SRP and anti-HMGCR IMNM can potentially cause debilitating weakness, muscle atrophy and irreversible fatty replacement happen early in the disease course. Patients with IMNM frequently require combination therapy to achieve disease control and have a high rate of relapse when tapering immunosuppression. Young age of onset is a poor prognostic factor. IMNM can be severely disabling and often requires aggressive immunosuppression. For any given patient, the treatment strategy should be informed by the severity of their presenting features and autoantibody status. While our ability to treat IMNM has certainly improved, there remains a need for more prospective trials to inform optimal treatment strategies.
Modeling Liver Organogenesis by Recreating Three-Dimensional Collective Cell Migration: A Role for TGFβ Pathway.

Three dimensional (3D) collective cell migration (CCM) is critical for improving liver cell therapies, eliciting mechanisms of liver disease, and modeling human liver development and organogenesis. Mechanisms of CCM differ in 2D vs 3D systems, and existing models are limited to 2D or transwell-based systems, suggesting there is a need for improved 3D models of CCM. To recreate liver 3D CCM, we engineered in vitro 3D models based upon a morphogenetic transition that occurs during liver organogenesis, which occurs rapidly between E8.5 and E9.5 (mouse). During this morphogenetic transition, 3D CCM is characterized by co-migration (multiple cell types), thick strand interactions with surrounding septum transversum mesenchyme (STM), branching morphogenesis, and 3D interstitial migration. Here we engineer several 3D in vitro culture systems, each of which mimics one of these processes in vitro. In mixed spheroids bearing both liver cells and uniquely MRC-5 (fetal lung) fibroblasts, we observed evidence of co-migration, and a significant increase in length and number of liver spheroid protrusions, which was highly sensitive to transforming growth factor beta 1 TGFs1 stimulation. In MRC-5 conditioned medium (M-CM) experiments, we observed dose-dependent branching morphogenesis associated with an upregulation of Twist1, which was inhibited by a broad TGFs inhibitor. In models of in which liver spheroids and MRC-5 spheroids were co-cultured, we observed complex strand morphogenesis, whereby thin, linear, 3D liver cell strands attach to the MRC-5 spheroid, anchor, and thicken to form permanent and thick anchoring contacts between the two spheroids. In these spheroid co-culture models, we also observed spheroid fusion and strong evidence for interstitial migration. In conclusion, we present several novel cultivation systems that re-create distinct features of liver 3D CCM. These methodologies will greatly improve our molecular, cellular, and tissue-scale understanding of liver organogenesis, liver diseases like cancer, and liver cell therapy, and will also serve as a tool to bridge conventional 2D studies and preclinical in vivo studies.
Prisoner's insomnia prevalence, insomnia associated factors and interventions with sleep as an outcome: a review and narrative analysis.

Purpose Insomnia is highly prevalent in prisoners. The purpose of this paper is a review of research evidence on interventions with sleep as an outcome (2000 to 2020) and rates of insomnia prevalence and associated factors in prisons (2015 to 2020). Design/methodology/approach An internet-based search used Medline, PubMed, PsycINFO (EBSCOhost), Embase, Web of Science and Scopus. Seven interventions and eight sleep prevalence or sleep-associated factor papers were identified. Findings Intervention research was very limited and the quality of the research design was generally poor. Interventions such as cognitive behavioural therapy for insomnia (CBT-I), yoga and mindfulness can be beneficial in a prison setting. This review identified a high prevalence of insomnia in prisons across the world, which was supported by recent evidence. Factors associated with insomnia include anxiety, depression, post-traumatic stress disorder, personality disorder and pain. Research limitations/implications There is a need for appropriately powered randomised control trials of CBT-I in prisons and a need to use objective measures of sleep quality. Originality/value Due to a lack of an up-to-date review, this paper fulfils the need for a review of the evidence on interventions in prison settings with sleep as an outcome, rates of insomnia prevalence and associated factors in prisons.
Management of premature ventricular complexes.

### Learning objectives Premature ventricular complexes (PVCs) are the most common arrhythmias in daily practice. At the cellular level, ventricular myocytes spontaneously depolarise to create an extrasystole ‘out of sync’ with the cardiac cycle.1 The prevalence depends on the characteristics and comorbidities of the population, the method by which the population is studied and the duration of observation. PVCs have been described in 1% of clinically normal people on standard electrocardiography (EKG) and 40%–75% of healthy people assessed by short-term ambulatory monitoring.2 Atherosclerosis Risk in Communities, a large population-based study of 15 792 Americans aged 45–65 years, demonstrated a higher prevalence of PVCs with age, structural heart disease (SHD), hypertension, African–American ethnicity, male sex and lower education.3 PVCs are generally benign in patients without SHD.4 5 However, PVCs can be a trigger for life-threating arrhythmias such as ventricular tachycardia (VT) and ventricular fibrillation (VF) causing sudden cardiac death (SCD), especially in patients post-myocardial infarction (MI). Risk stratification for PVCs varies in specific populations with underlying cardiac disease, family history, genetic variants and sometimes coupling interval. The differing implications with these variables is the basis of this review. The symptoms of PVCs are variable. Patients often have palpitations described as fluttering, pounding, skipping beats or often a strange sensation in the neck. Others may have fatigue, shortness of breath or change of stamina and endurance. The increased stroke volume of the post-PVC beat may cause chest discomfort. Non-sustained or sustained episodes of VT may be associated with presyncope or syncope. In contrast, many patients are …
Disparities in Eye Care Utilization During the COVID-19 Pandemic.

PURPOSE To assess the relationship between telemedicine utilization and sociodemographic factors among patients seeking eye care. DESIGN Comparative utilization analysis. METHODS We reviewed the eye care utilization patterns of a stratified random sample of 1720 patients who were seen at the University of Michigan Kellogg Eye Center during the height of the COVID-19 pandemic (April 30 to May 25, 2020) and their odds of having a video, phone, or in-person visit compared with having a deferred visit. Associations between independent variables and visit type were determined using a multinomial logistic regression model. RESULTS Older patients had lower odds of having a video visit (P = .007) and higher odds of having an in-person visit (P = .023) compared with being deferred, and in the nonretina clinic sample, older patients still had lower odds of a video visit (P = .02). Non-White patients had lower odds of having an in-person visit (P < .02) in the overall sample compared with being deferred, with a similar trend seen in the retina clinic. The mean neighborhood median household income was $76,200 (±$33,500) and varied significantly (P < .0001) by race with Blacks having the lowest estimated mean income. CONCLUSION Disparities exist in how patients accessed eye care during the COVID-19 pandemic with older patients-those for whom COVID-19 posed a higher risk of mortality-being more likely to be seen for in-person care. In our affluent participant sample, there was a trend toward non-White patients being less likely to access care. Reimbursing telemedicine solely through broadband internet connection may further exacerbate disparities in eye care.
Refugee Responsibility Sharing or Responsibility Dumping

A silver lining of recent migration crises is increased reliance on responsibility sharing arrangements in international actor responses. This new experience allows for evidence-based analysis of such arrangements. We distinguish between progressive arrangements—ones that shift responsibilities to more affluent, institutionally competent, and safer countries—and regressive arrangements that do the opposite and in fact constitute responsibility dumping. Focusing on examples from the United Nations, United States and the European Union, we classify different responsibility sharing arrangements as progressive or regressive based on four parameters: hosting commitments, monetary or equivalent contributions, multilateralism and legally binding instruments. The analysis suggests that first safe country arrangements are presumptively regressive, while arrangements that include hosting or material commitments are presumptively progressive. The EU model is a particularly progressive model that ought to spread. We also highlight the importance of assessing refugee policy solutions with a view to broader, systemic implications for host countries, and not just against an individual-focused legal threshold.