cssi/SciSciGPT-SciSciNet huggingface dataset:
Prevalence of Metabolic Syndrome and Obesity in Adolescents Aged 12 to 19 Years: Comparison between the United States and Korea

This study compared the prevalence of metabolic syndrome (MetS), its risk factors, and obesity in adolescents in the United States (US) and Korea. Data were obtained from 2003-2004 US National Health and Nutrition Examination Survey (NHANES) and 2005 Korea NHANES for adolescents aged 12-19 yr in the US (n=734) and in Korea (n=664). The 2007 International Diabetes Federation (IDF) pediatric definition for diagnosis of MetS and the 2000 US Growth Charts and 2007 Korea Growth Charts for assessment of obesity were utilized. The prevalence of metabolic syndrome in US and Koreans was 5.5% and 2.5%, respectively. The prevalence of obesity was 18.1% in US compared to 9.0% in Koreans. The prevalence of abdominal obesity, hyperglycemia, and hypertriglyceridemia were higher in the US, whereas that of low HDL-C levels was higher in Korea. Despite the doubled prevalence for the single entities of MetS and obesity in the US, the prevalence of MetS in obese US and Koreans did not differ (20.8% and 24.3%, respectively). In conclusion, there are differences in the prevalence of MetS, obesity, and the individual MetS risk factors between the US and Korean adolescents; however, the risk of MetS among obese adolescents is similar in both countries.
Case Report: Compartment Syndrome After a Suspected Black Widow Spider Bite

Widow spider envenomations generally produce systemic neurologic syndromes without significant local injury. We report a patient who sustained a black widow spider bite to the left forearm and presented to the emergency department with rhabdomyolysis and compartment syndrome. We documented a decrease in symptoms and compartment pressure after administration of antivenom. No surgical intervention was performed. We believe this report to be the first documenting compartment syndrome associated with black widow spider bite.
A dynamic model of ventricular interaction and pericardial influence

A mathematical model describing the dynamic interaction between the left and the right ventricle over the complete cardiac cycle is presented. The pericardium-bound left and right ventricles are represented as two coupled chambers consisting of the left and right free walls and the interventricular septum. Time-varying pressure-volume relationships characterize the component compliances, and the interaction of these components produces the globally observed ventricular pump properties (total chamber pressure and volume). The model 1) permits the simulation of passive (diastolic) and active (systolic) ventricular interaction, 2) provides temporal profiles of hemodynamic variables (e.g., ventricular pressures, volumes, and flow) that agree well with reported observations, and 3) can be used to examine the effect of the pericardium on ventricular interaction and ventricular mechanics. It can be reduced to equivalency with models previously reported by invoking simplifying assumptions. Furthermore, model-generated "dynamic interaction gains" are employed to quantify the mode and degree of ventricular interaction. The model also yields qualitative predictions of septal and free wall displacements similar to those detected experimentally via M-mode echocardiography. Such analogies may be extended easily to the study of pathophysiological states via appropriate modifications to 1) the pressure-volume characteristics of the component walls (and/or pericardium) and/or 2) the specific time course of activation of the ventricular free wall or the septum. A limited number of examples are included to demonstrate the utility of the model, which may be used as an adjunct to new experimental investigations into ventricular interaction.
Investigation of Finite Element Thermal Models for Workpiece Temperature in Cylinder Boring

The accuracy and computational efficiency of four finite element thermal models for workpiece temperature in cylinder boring are studied. High temperature in precision cylinder boring of automotive engine block can distort the workpiece, leading to thermally-induced dimensional and geometrical errors. In cylinder boring, the depth of cut is small compared to the bore diameter, so a fine mesh is usually needed to analyze the workpiece temperature distribution; however fine mesh on a relatively large workpiece also takes extensive computational resources. To understand the trade-off between accuracy and computational efficiency, the advection, surface heat, heat carrier, and ring heat finite element thermal models are introduced and compared quantitatively in a boring process. It is found comparable global temperature estimation from all four models. For the temperature near the cutting zone, the advection and surface heat models are more accurate to predict local temperatures but consume more computational resources. The heat carrier model predicts the surface temperature with reasonable accuracy and computational time. The ring heat model is the most computationally efficient but fails to accurately estimate local peak temperatures.Copyright © 2015 by ASME
Brand value co-creation in a digitalized world: An integrative framework and research implications

Abstract We present an integrative framework of brand value co-creation with theoretical underpinnings in joint agencial experiencial creation of brand value. Central to this framework are brand engagement platforms entailing both relational activities and offerings, at the intersection of joint agency of experiencial co-creators (whether in their role as customers, employees, partners, or any other stakeholder) and co-creational enterprises as organizing the practice of brand value co-creation (whether in their role as innovating or marketing offerings, or managing network relations). Using two illustrative examples of Starbucks and Apple, we discuss how brand value co-creation is enacted through brand engagement platforms, embodied in brand experience domains, and emergent from brand capability ecosystems, valorizing outcomes with stakeholding individuals. Subsequently, using another illustrative example of Nike, we discuss the concept of co-creational enterprises as a nexus of co-creational platforms of engagements, and elaborate upon the organizational practice of brand value co-creation in a digitalized world. We conclude with several implications for future brand research.
SINGLE BOOK REVIEWS

Warring Souls: Youth, Media, and Martyrdom in Post-Revolution Iran. Roxanne Varzi. Durham, NC: Duke University Press, 2006. 290 pp.
Bias in Analysts' Earnings Forecasts as an Explanation for the Long-Run Underperformance of Stocks Following Equity Offerings

For firms conducting initial or seasoned equity offerings, recent studies document that their stock returns are lower than those of non-issuers for about five years following the issue, and this underperformance is greater for small issuers. This study shows that analysts' earnings forecasts have greater optimistic bias for issuers than for non-issuers during the five year period. Moreover, the incremental optimistic bias is greater for small issuers. This result is consistent with the Loughran and Ritter (1995) conjecture that one of the reasons for the long-run underperformance of issuers' stocks is optimistic bias in the market's expectations of these firms' earnings.
Examining Ohio's Commercial Activity Tax

The author looks at the arguments for an against the adoption of Ohio's commercial activity tax. The tax could have an adverse impact on businesses that don't make a profit, the author says.
β-Arrestin drives MAP kinase signalling from clathrin-coated structures after GPCR dissociation

β-Arrestins critically regulate G-protein-coupled receptor (GPCR) signalling, not only 'arresting' the G protein signal but also modulating endocytosis and initiating a discrete G-protein-independent signal through MAP kinase. Despite enormous recent progress towards understanding biophysical aspects of arrestin function, arrestin cell biology remains relatively poorly understood. Two key tenets underlie the prevailing current view: β-arrestin accumulates in clathrin-coated structures (CCSs) exclusively in physical complex with its activating GPCR, and MAP kinase activation requires endocytosis of formed GPCR-β-arrestin complexes. We show here, using β1-adrenergic receptors, that β-arrestin-2 (arrestin 3) accumulates robustly in CCSs after dissociating from its activating GPCR and transduces the MAP kinase signal from CCSs. Moreover, inhibiting subsequent endocytosis of CCSs enhances the clathrin- and β-arrestin-dependent MAP kinase signal. These results demonstrate β-arrestin 'activation at a distance', after dissociating from its activating GPCR, and signalling from CCSs. We propose a β-arrestin signalling cycle that is catalytically activated by the GPCR and energetically coupled to the endocytic machinery.
A case report of bilateral mirror clubfeet and bilateral hand polydactyly

We report a rare case of a patient with bilateral mirror clubfeet and bilateral hand polydactyly. The patient presented to our orthopaedic clinic with bilateral mirror clubfeet, each with eight toes, and bilateral hands with six fingers and a hypoplastic thumb. The pattern does not fit any described syndrome such as Martin or Laurin-Sandrow syndrome. Treatments by an orthopaedic pediatric surgeon and an orthopaedic pediatric hand surgeon are described. The patient achieved excellent functional and cosmetic outcomes at four year follow-up.
Abstract CN06-02: Epigenetic Deregulation of MicroRNAs During Tobacco Carcinogen-Induced Transformation of Bronchial Epithelial Cells

Epigenetic silencing of genes and microRNAs (miRs) via chromatin remodeling and cytosine methylation has emerged as a major mechanism in lung cancer etiology. The reversal of gene and miR silencing using pharmacological agents by affecting cytosine-DNA methyltransferases (DNMTs), histone methyltransferases (HMTs), or histone deacetylases (HDACs) offers new strategies for prevention and intervention for lung cancer. We have developed an in vitro model using hTERT/cdk4 immortalized human bronchial epithelial cell lines (HBECs) that identifies molecular changes driving transformation of preneoplastic lung epithelial cells during exposure to carcinogens found in mainstream and environmental tobacco smoke. Our studies provided a mechanistic link between increased DNMT1 protein, de novo methylation of genes, and reduced DNA repair capacity that together seemed causal for transformation. Our recent studies show that the exposure of HBECs to carcinogens for 4 wk induces a persistent and irreversible, multifaceted dedifferentiation program characterized by the epithelial-to-mesenchymal transition (EMT). EMT induction was epigenetically driven, initially by chromatin remodeling involving H3K27me3 enrichment, with ensuing DNA methylation sustaining the silencing of miR-200b, -200c, and -205 implicated in this developmental program and persisting in malignant tumors. Over expression of these miRs reversed transformation. Next generation sequencing of transformed HBEC lines has identified 25 miRs whose silencing may be regulated through chromatin remodeling and promoter methylation. The impact of specific miRs identified by sequencing on transformation, regulation by chromatin, and their prevalence in lung cancer will be described. (Supported by R01 ES008801 and P50 CA58184). Citation Format: Steven A. Belinsky, Avrum Spira, Carmen Tellez. Epigenetic deregulation of microRNAs during tobacco carcinogen-induced transformation of bronchial epithelial cells. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr CN06-02.
Experience of pharmaceutical care by clinical pharmacists in obstetrical department

A wide range of physiological changes occur during perinatal period, these changes can significantly affect pharmacokinetics of drugs. The development and function of the tissue and organ in fetus can be infl uenced after use of medicines in perinatal period patients because of placental transport and milk transport. Neonates are particularly sensitive to the toxic and side effect of most kinds of medicines. So the clinical use of drugs should be paid more attention to during perinatal period. In this article, the cases of pharmaceutical care by clinical pharmacists were discussed, such as assisting doctors to optimize the drug therapy regime for pregnant and lactational women, offering pharmaceutical care for patient with intravenous use of magnesium sulfate injection, providing medication education for patients, collecting the adverse drug reactions and so on. These measures ensure the safety of drug utilization in patients and promote the rational drug use in clinic.
Economic Globalization and Relative Advantage

The exertion of relative advantage is the basic approach to gain from economic globalization, which optimizes resource collocation in terms of market mechanism within the scope of the seven seas. Innovations are the key of transform from relative advantage based on resource to the one based on technology. Therefore, we should bring relative advantage into full play, reinforce our competitive power and all- around national power, and on basis of that, realize optimization and upgrade of relative advantage.
Epigenetically maintained SW13+ and SW13- subtypes have different oncogenic potential and convert with HDAC1 inhibition

The BRM and BRG1 tumor suppressor genes are mutually exclusive ATPase subunits of the SWI/SNF chromatin remodeling complex. The human adrenal carcinoma SW13 cell line can switch between a subtype which expresses these subunits, SW13+, and one that expresses neither subunit, SW13-. Loss of BRM expression occurs post-transcriptionally and can be restored via histone deacetylase (HDAC) inhibition. However, most previously used HDAC inhibitors are toxic and broad-spectrum, providing little insight into the mechanism of the switch between subtypes. In this work, we explore the mechanisms of HDAC inhibition in promoting subtype switching and further characterize the oncogenic potential of the two epigenetically distinct SW13 subtypes. SW13 subtype morphology, chemotaxis, growth rates, and gene expression were assessed by standard immunofluorescence, transwell, growth, and qPCR assays. Metastatic potential was measured by anchorage-independent growth and MMP activity. The efficacy of HDAC inhibitors in inducing subtype switching was determined by immunofluorescence and qPCR. Histone modifications were assessed by western blot. Treatment of SW13- cells with HDAC1 inhibitors most effectively promotes re-expression of BRM and VIM, characteristic of the SW13+ phenotype. During treatment, hyperacetylation of histone residues and hypertrimethylation of H3K4 is pronounced. Furthermore, histone modification enzymes, including HDACs and KDM5C, are differentially expressed during treatment but several features of this differential expression pattern differs from that seen in the SW13- and SW13+ subtypes. As the SW13- subtype is more proliferative while the SW13+ subtype is more metastatic, treatment with HDACi increases the metastatic potential of SW13 cells while restoring expression of the BRM tumor suppressor. When compared to the SW13- subtype, SW13+ cells have restored BRM expression, increased metastatic capacity, and significantly different expression of a variety of chromatin remodeling factors including those involved with histone acetylation and methylation. These data are consistent with a multistep mechanism of SW13- to SW13+ conversion and subtype stabilization: histone hypermodification results in the altered expression of chromatin remodeling factors and chromatin epigenetic enzymes and the re-expression of BRM which results in restoration of SWI/SNF complex function and leads to changes in chromatin structure and gene expression that stabilize the SW13+ phenotype.
Modulation of Tropical Instability Wave Intensity by Equatorial Kelvin Waves

AbstractTropical instability waves (TIWs) and equatorial Kelvin waves are dominant sources of intraseasonal variability in the equatorial Pacific Ocean, and both play important roles in the heat and momentum budgets of the large-scale flow. While individually they have been well studied, little is known about how these two features interact, although satellite observations suggest that TIW propagation speed and amplitude are modulated by Kelvin waves. Here, the influence of Kelvin waves on TIW kinetic energy (TIWKE) is examined using an ensemble set of 1/4° ocean model simulations of the equatorial Pacific Ocean. The results suggest that TIWKE can be significantly modified by 60-day Kelvin waves. To leading order, TIWs derive kinetic energy from the meridional shear and available potential energy of the background zonal currents, while losing TIWKE to friction and the radiation of waves. The passage of Kelvin waves disrupts this balance. Downwelling (upwelling) Kelvin waves induce decay (growth) in TIWKE ...
Assessing the Airway Microbiota in Cystic Fibrosis

Abstract Cystic fibrosis (CF) lung disease is characterized by chronic airway bacterial infections and airway inflammation. Microbiologic cultures of CF airway samples identify a narrow spectrum of pathogenic bacteria. More recently, culture-independent techniques have identified much more diverse microbial communities within the CF airways. The role of these bacterial communities in CF disease progression and pulmonary exacerbations is under investigation. This review discusses advances in molecular approaches for microbiota analysis; challenges in airway sampling; recent findings in airway microbiota in CF, including longitudinal changes with disease progression and pulmonary exacerbations; and areas for future study.
Mechanistic insights into mammalian stress granule dynamics

The accumulation of stalled translation preinitiation complexes (PICs) mediates the condensation of stress granules (SGs). Interactions between prion-related domains and intrinsically disordered protein regions found in SG-nucleating proteins promote the condensation of ribonucleoproteins into SGs. We propose that PIC components, especially 40S ribosomes and mRNA, recruit nucleators that trigger SG condensation. With resolution of stress, translation reinitiation reverses this process and SGs disassemble. By cooperatively modulating the assembly and disassembly of SGs, ribonucleoprotein condensation can influence the survival and recovery of cells exposed to unfavorable environmental conditions.
Flow cytometry analysis of DNA ploidy levels and protein profiles distinguish between populations of Lumbriculus (Annelida: Clitellata)

Variations in DNA ploidy have been observed in Lumbriculus, a freshwater annelid, as well as in other clitellates. Interpretation and application of experimental results using these animals may be impacted as ploidy levels affect the protein expression, reproductive behavior, and response to stressors. Ploidy is typically determined by chromosome spreads, a time-consuming and inefficient method. We adapted flow cytometry protocols used on vertebrates and plants to determine the ploidy levels in different populations of Lumbriculus, including a laboratory strain (Environmental Protection Agency), a commercial strain (Aquatic Foods), and worms collected from natural habitats. To isolate nuclei, worms were homogenized, filtered to remove cell debris, and centrifuged through Optiprep™ density gradients. Nuclei were recovered, treated with RNAse, and stained with propidium iodide. Flow cytometry of the labeled nuclei showed that Lumbriculus from natural habitats in Minnesota and Iowa were diploid, with an estimated genome size of 2.7 pg. Populations from natural habitats in California and Oregon were highly polyploid, as were the laboratory and commercial strains. Chromosome spreads verified the high ploidy levels indicated by flow cytometry results, but also suggested that flow cytometry may be underestimating the DNA content levels. Staining of nuclei with diamidino-2-phenylindole indicated that this may be due to high levels of heterochromatin in nuclei from polyploid forms of Lumbriculus. To further compare the populations, proteins in worm homogenates were subjected to isoelectrofocusing gel electrophoresis. Distinct protein profiles were seen; one was shared in common by the diploid worms, the other was characteristic of polyploid populations. Diploid worms could also be distinguished from polyploid worms based on differences in hemoglobin linker proteins. The results further support taxonomic classification of the diploid and polyploid forms of Lumbriculus as distinct species.
Stream depletion rate for a radial collector well in an unconfined aquifer near a fully penetrating river

The stream depletion rate (SDR) is computed for a radial collector well installed in a semi-infinite, anisotropic, homogeneous, unconfined aquifer near a fully penetrating stream with a streambed with reduced conductivity. For small pumping rates dimensional analysis and other arguments allow the SDR to be expressed as a function of eight parameters that describe the effect of properties of the aquifer and streambed as well as the configuration and placement of the well. The calculations employ some results from Huang et al. (2012, J. Hydrol.), who expressed the SDR as a quintuple integral, but by computing four of the integrals analytically, the present solution requires less computational effort. Analytical calculation shows that the SDR in steady state does not depend on the streambed properties (or any other parameters): Given enough time, the flow through the streambed will equal the pumping rate of the well. Values of SDR are supported by comparing to previous solutions for special cases corresponding to appropriate limiting values of the parameters. Effects of the eight dimensionless parameters are studied systematically: The properties of the streambed, anisotropy of the aquifer, and the position of the well affect the SDR more strongly than the orientation, length, and depth of the laterals.
Creative Potential of Humanism

The article analyzes the gist and certain specific features of contemporary humanism, reveals its creative and unifying potentials, and sheds light on the role it plays in solving the global problems the humanity faces in the current complicated and critical period of the development of civilization.
Online Reasoning for Semantic Error Detection in Text

Identifying incorrect content (i.e., semantic error) in text is a difficult task because of the ambiguous nature of written natural language and the many factors that can make a statement semantically erroneous. Current methods identify semantic errors in a sentence by determining whether it contradicts the domain to which the sentence belongs. However, because these methods are constructed on expected logic contradictions, they cannot handle new or unexpected semantic errors. In this paper, we propose a new method for detecting semantic errors that is based on logic reasoning. Our proposed method converts text into logic clauses, which are later analyzed against a domain ontology by an automatic reasoner to determine its consistency. This approach can provide a complete analysis of the text, since it can analyze a single sentence or sets of multiple sentences. When there are multiple sentences to analyze, in order to avoid the high complexity of reasoning over a large set of logic clauses, we propose rules that reduce the set of sentences to analyze, based on the logic relationships between sentences. In our evaluation, we have found that our proposed method can identify a significant percentage of semantic errors and, in the case of multiple sentences, it does so without significant computational cost. We have also found that both the quality of the information extraction output and modeling elements of the ontology (i.e., property domain and range) affect the capability of detecting errors.
High Involvement Ergonomics and Total Quality Management: A Comparison and Evaluation

Two different approaches to work systems and organizational design are presented: high involvement ergonomics and total quality management. Both espouse worker involvement and organizational change. Similarities and differences between these programs are discussed, an evaluation is made of both approaches, and the conclusion is reached that both may lead to improved organizational performance when work systems and organizations are designed which integrate appropriate features from both approaches.
Effect of FDA Investigation on Opioid Prescribing to Children After Tonsillectomy/Adenoidectomy.

BACKGROUND: In August 2012, the Food and Drug Administration investigated the safety of codeine use by children after tonsillectomy and/or adenoidectomy, culminating in a black box warning in February 2013. The objective of this study was to evaluate the association between the investigation and opioid prescribing to children undergoing these surgeries. METHODS: We identified 362 992 privately insured children in the 2010–2015 Truven MarketScan Commercial Claims and Encounters database who underwent tonsillectomy and/or adenoidectomy. Using an interrupted time series design, we estimated level and slope changes in the proportion of children with ≥1 prescription fills for codeine and ≥1 fills for an alternative opioid, such as hydrocodone, within 7 days of surgery. RESULTS: The investigation was associated with a significant −13.3 (95% confidence interval: −14.5 to −12.1) percentage point level change in the proportion of children with ≥1 prescription fills for codeine after tonsillectomy and/or adenoidectomy. Despite this drop, 5.1% of children had ≥1 prescription fills for codeine in December 2015. The investigation was not associated with significant level changes in alternative opioid prescribing, although the proportion of children receiving alternative opioids increased during the study period because of other factors. CONCLUSIONS: The Food and Drug Administration investigation substantially decreased codeine prescribing to children after tonsillectomy and/or adenoidectomy. However, 1 in 20 children undergoing these surgeries were still prescribed codeine in December 2015 despite its well-documented safety and efficacy issues.
Gender and Parentage: Family Law's Equality Project in Our Empirical Age

This essay joins the debate about the place of gender in the law of parentage, an issue that looms large in today’s “culture war,” including the continuing battle over same-sex marriage. As part of the conversation about contrasting conceptions first presented at a conference on What is Parenthood? and later revised for a forthcoming book with the same title (edited by Daniel Cere and Linda McClain), this essay makes the case for a legal regime based on the “diversity approach.” This approach supports recognition of a diverse range of parent-child relationships, without regard to sex or gender, in contrast to the “integrated model,” which calls for an understanding of parentage that integrates biological and other functions and aspects of parentage. In advocating that parentage laws reflect the diversity approach, this essay makes two primary contributions. First, it challenges the constitutional validity of parentage laws that would impose an integrated model. Most proponents of this model, by one route or another, conclude that children need exactly one mother and one father - a gendered combination missing or disrupted when a child has two legal parents who are both women or both men, when a child has only one legal parent, or in the occasional case in which courts have recognized three legal parents for a given child. This essay shows how this model and its underlying normative premises rest on gender stereotypes that equality jurisprudence and family law have thoroughly repudiated. Second, this essay questions recent arguments, both for and against laws based on the integrated model, that rely on empirical investigations of the purported effect of various familial arrangements on children. Whatever the contemporary attraction of multidisciplinary analyses, empirical data cannot resolve disputes about competing laws of parentage. In particular, empirical findings purporting to show that the normative one-mother-one-father configuration serves most children well would not justify enshrining it in parentage rules applicable to all children. Several reasons support this position. For one, across-the-board rules based on empirical evidence of an optimal parental arrangement for children in general would sacrifice the best interests of some individual children, while also contravening family law’s frequent preference for fact-specific assessments. In addition, conclusions based on such evidence not only rest on value judgments and questionable assumptions about causality but also change over time. Finally, reliance on such empirical evidence fails appropriately to take into account the power of family laws to shape the experiences of the very children and other family members in question. The essay concludes by using some ingredients from the integrated model to begin to sketch an alternative framework based on the diversity approach. These preliminary steps in turn show why the analysis outlined in this essay makes sense as a matter of family law and promises to address children’s interests at least as well as the alternatives.
Inter-Rater Agreement of Intensivists Evaluating the Goal Concordance of Preference-Sensitive ICU Interventions.

Abstract Context Goal-concordant care has been identified as an important outcome of advance care planning and shared decision-making initiatives. However, validated methods for measuring goal concordance are needed. Objectives To estimate the inter-rater reliability of senior critical care fellows rating the goal concordance of preference-sensitive interventions performed in intensive care units (ICUs) while considering patient-specific circumstances as described in a previously proposed methodology. Methods We identified ICU patients receiving preference-sensitive interventions in three adult ICUs at Johns Hopkins Hospital. A simulated cohort was created by randomly assigning each patient one of 10 sets of goals and preferences about limiting life support. Critical care fellows then independently reviewed patient charts and answered two questions: 1) Is this patient's goal achievable? and 2) Will performing this intervention help achieve the patient's goal? When the answer to both questions was yes, the intervention was rated as goal concordant. Inter-rater agreement was summarized by estimating intraclass correlation coefficient using mixed-effects models. Results Six raters reviewed the charts of 201 patients. Interventions were rated as goal concordant 22%–92% of the time depending on the patient's goal-limitation combination. Percent agreement between pairs of raters ranged from 59% to 86%. The intraclass correlation coefficient for ratings of goal concordance was 0.50 (95% CI 0.31–0.69) and was robust to patient age, gender, ICU, severity of illness, and lengths of stay. Conclusion Inter-rater agreement between intensivists using a standardized methodology to evaluate the goal concordance of preference-sensitive ICU interventions was moderate. Further testing is needed before this methodology can be recommended as a clinical research outcome.
Utility Decomposition for Planning under Uncertainty for Autonomous Driving

The objective of this research is to provide scalable decision making algorithms for autonomously navigating urban environments. The vehicle must plan in a stochastic environment with many entities to avoid, rapid changes in driver behavior, and partial observability. Partially observable Markov decision processes (POMDP) offer a theoretically grounded framework to model such problems. We aim at developing a scalable POMDP formulation that takes into account dynamic occlusions, interaction between entities, and can generalize to a variety of different scenarios. This work demonstrates utility fusion and deep reinforcement learning methods to efficiently find optimal policies to navigate occluded urban environments.
Regulation of Ethylene Biosynthesis in Higher Plants: Induction and Identification of l-Aminocyclopropane-l-Carboxylate Synthase

Of all the known plant growth regulators, ethylene is one of the most immediate hormonal signals involved in promoting processes that cause cell separation (abscission, fruit softening) and plant tissue senescence (see Lieberman, 1979; Mattoo and Aharoni, 1988). Cell separation occurs as a result of cell wall hydrolysis in target cells within the separation layer (Osborne, 1979). Enzymes that specifically hydrolyze cell walls, viz. cellulase and polygalacturonase, are known to be regulated positively by ethylene and negatively by auxin (Abeles, 1973; Greenberg et al., 1975; Jeffrey et al., 1984; Tucker et al., 1988).
Competing Displacive Interactions, Phonon Anomalies, and Structural Transitions Which Do Not “Soften”

Displacive structural phase transitions (i.e. diffusionless) comprise a significant fraction of all phase transformations. Interest among materials scientists was greatly stimulated by the idea put forth by Cochran and by Anderson that some phonons “softened” to ω s 2 → 0 at a transition temperature, and thereby the transformed material adopted the displacement patterns of that soft mode. This simple, but powerful, idea has stimulated many experiments over the past 30 years. However, after a few early successes (A-15, perovskites, K2Se04) in which a special mode did soften, more careful and extensive study has shown that hardly any materials transform in this manner. Although they have phonon anomalies, and product structures are related to those, it is clear that a different explanation is needed. This paper suggests an alternative mechanism, taking into account nonlinear effects leading to perhaps weak but definitely first order transition.
Sneddon's syndrome: a cause of cognitive decline in young adults.

Objective To review the clinical, psychometric, laboratory, and radiologic findings of 6 patients with Sneddon's syndrome (SS) who presented with cognitive dysfunction rather than stroke. Design and methods Case series. All patients fulfilled were diagnosed as SS based on the co-occurrence of livedo racemosa and neurologic disease. Patients presenting with clinical stroke were excluded. Results Patients presented with cognitive complaints at an early age and all noted skin lesions from 6 months to 10 years before onset of cognitive symptoms. Associated systemic disorders included hypertension and seizures. Laboratory evidence of a hypercoagulable condition was identified in 4 of 6 cases. Brain MRI scans demonstrated atrophy, especially in parieto-occipital regions and cerebral blood flow on brain SPECT scan was reduced in a similar distribution. Conclusion Patients with SS can develop dementia without antecedent clinical stroke. While the specific pathogenic mechanism of dementia in SS remains speculative, the disease predominantly injures brain tissue in vascular "watershed" territories.
Testacy and Intestacy: The Dynamics of Wills and Demographic Status

In this Article, I seek to investigate several questions relating to testacy and intestacy. First, who is intestate? Are there demographic characteristics that predict intestacy and is there a class divide among whom the law serves? (Statistical analyses of original empirical data are used to shed light on these issues.) Next, does intestacy matter - what are the consequences of intestacy? Finally, what does intestacy mean or signify? On a theoretical and abstract level, how can we characterize intestacy - how do we define it, and how does it define us? These questions, when carefully considered, lead to a theory: that there is a connection between hierarchical socio-demographic roles and the legal status of testacy or intestacy that parallels these roles. Specifically, I compare the dynamics created by testacy/intestacy and analogize to the roles created by men/women and whites/non-whites, and argue that the overlap between the individuals who fill each status role is not coincidental. Finally, I develop the theory that when hierarchical status is created by law, there may be a connection to social status in filling those roles. More explicitly, when we identify areas of the law that create the dominant/non-dominant dynamic we tend to see in race and sex relationships, we should scrutinize the law to determine whether it is a reflection of - or possibly a contributor to - the dynamics of race and sex.
Ion Channels of Unicellular Microbes

Before the first “nervous system,” there must have been “nervous molecules”. The quintessential nervous molecules are the ion channels. These integral membrane proteins enclose the hydrophilic pathways across the hydrophobic membrane that would be otherwise impenetrable for charged or polar molecules. Since a room without a door is but a tomb, one could argue on first principles that channels probably evolved soon after cell membranes. Arguments and speculations aside, we have now shown that protozoa, yeast, and even bacteria all have ion channels. It appears that all cellular forms of life have ion channels. We are also forced to conclude that they must have evolved very early.
Walking through a maze: a groovy graphics assignment

This assignment supports the key concepts in a first course in Computer Graphics for students in Computer Science and Engineering: modeling, geometry, transformations and interaction. The core of the assignment is to create a maze that can be walked through via the mouse or other interactive tools. The maze should have only one entrance and one exit. The walls are planes extruded from the floor.
A Hotspot for Disease-Associated Variants of Human PGM1 Is Associated with Impaired Ligand Binding and Loop Dynamics.

Summary Human phosphoglucomutase 1 (PGM1) plays a central role in cellular glucose homeostasis, catalyzing the conversion of glucose 1-phosphate and glucose 6-phosphate. Recently, missense variants of this enzyme were identified as causing an inborn error of metabolism, PGM1 deficiency, with features of a glycogen storage disease and a congenital disorder of glycosylation. Previous studies of selected PGM1 variants have revealed various mechanisms for enzyme dysfunction, including regions of structural disorder and side-chain rearrangements within the active site. Here, we examine variants within a substrate-binding loop in domain 4 (D4) of PGM1 that cause extreme impairment of activity. Biochemical, structural, and computational studies demonstrate multiple detrimental impacts resulting from these variants, including loss of conserved ligand-binding interactions and reduced mobility of the D4 loop, due to perturbation of its conformational ensemble. These potentially synergistic effects make this conserved ligand-binding loop a hotspot for disease-related variants in PGM1 and related enzymes.
Organization of Normal and Abnormal Human Globin Genes by Restriction Enzyme Analysis

ABSTRACT Restriction endonuclease mapping of cellular DNA has provided a detailed map of the γ, δ, and β globin genes in man. This technique already provides the basis for the prenatal diagnosis of sickle cell anemia and some of the thalassemias by analysis of amniocentesis fluid cell DNA. In δβ thalassemia, certain cases of β° thalassemia and the α thalassemias, deletion of specific globin gene-containing DNA fragments can be used to establish a diagnosis using fetal DNA. In sickle cell anemia, a polymorphism associated with the sickle cell βs gene can be used to diagnose SS disease in 25 to 50% of fetuses at risk. Extension of this technology can be expected to result in the precise diagnosis of β+ and β° thalassemia and other cases of sickle cell anemia as well as in the near future.
Peer-Mediated Interventions to Address Social Competence Needs of Young Children With ASD: Systematic Review of Single-Case Research Design Studies:

We conducted a systematic review and summarized the outcomes of single-case research design studies conducted in the last decade that have implemented peer-mediated interventions (PMI) to address t...
An age-based, RNA expression paradigm for survival biomarker identification for pediatric neuroblastoma and acute lymphoblastic leukemia

Pediatric cancer survival rates overall have been improving, but neuroblastoma (NBL) and acute lymphoblastic leukemia (ALL), two of the more prevalent pediatric cancers, remain particularly challenging. One issue not yet fully addressed is distinctions attributable to age of diagnosis. In this report, we verified a survival difference based on diagnostic age for both pediatric NBL and pediatric ALL datasets, with younger patients surviving longer for both diseases. We identified several gene expression markers that correlated with age, along a continuum, and then used a series of age-independent survival metrics to filter these initial correlations. For pediatric NBL, we identified 2 genes that are expressed at a higher level in lower surviving patients with an older diagnostic age; and 4 genes that are expressed at a higher level in longer surviving patients with a younger diagnostic age. For pediatric ALL, we identified 3 genes expressed at a higher level in lower surviving patients with an older diagnostic age; and 17 genes expressed at a higher level in longer surviving patients with a younger diagnostic age. This process implicated pan-chromosome effects for chromosomes 11 and 17 in NBL; and for the X chromosome in ALL.
A Control Region Near the Fibroblast Growth Factor 23 Gene Mediates Response to Phosphate, 1,25(OH)2D3, and LPS In Vivo

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone involved in the control of phosphate (P) homeostasis and vitamin D metabolism. Despite advances, however, molecular details of this gene's regulation remain uncertain. In this report, we created mouse strains in which four epigenetically marked FGF23 regulatory regions were individually deleted from the mouse genome using CRISPR/Cas9 gene-editing technology, and the consequences of these mutations were then assessed on Fgf23 expression and regulation in vivo. An initial analysis confirmed that bone expression of Fgf23 and circulating intact FGF23 (iFGF23) were strongly influenced by both chronic dietary P treatment and acute injection of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. However, further analysis revealed that bone Fgf23 expression and iFGF23 could be rapidly upregulated by dietary P within 3 and 6 hours, respectively; this acute upregulation was lost in the FGF23-PKO mouse containing an Fgf23 proximal enhancer deletion but not in the additional enhancer-deleted mice. Of note, prolonged dietary P treatment over several days led to normalization of FGF23 levels in the FGF23-PKO mouse, suggesting added complexity associated with P regulation of FGF23. Treatment with 1,25(OH)2D3 also revealed a similar loss of Fgf23 induction and blood iFGF23 levels in this mouse. Finally, normal lipopolysaccharide (LPS) induction of Fgf23 expression was also compromised in the FGF23-PKO mouse, a result that, together with our previous report, indicates that the action of LPS on Fgf23 expression is mediated by both proximal and distal Fgf23 enhancers. These in vivo data provide key functional insight into the genomic enhancers through which Fgf23 expression is mediated.
Transferrable Market Exclusivity Extensions to Promote Antibiotic Development: An Economic Analysis.

Background To address the growing threat of multidrug-resistant organisms, policymakers are seeking ideas to promote development of novel antibiotics. In 2018, the REVAMP Act was proposed in Congress to reward manufacturers of certain novel antibiotics with transferrable market exclusivity vouchers. Methods We estimated the economic impact of this proposal by identifying antimicrobial drugs approved by the FDA from 2007-2016 that would likely have qualified for an exclusivity voucher and matching each drug to the highest-revenue fast-track drug facing generic entry within 4 years after the antibiotic was approved. Assuming a spending decrease of 75% after generic entry, we calculated the per-drug and total societal costs of these transferrable market exclusivity extensions over a decade. Results We identified 10 antimicrobials that would have qualified for an exclusivity voucher, each of which was matched with 1 of 17 fast-track drugs facing generic entry through July 2019. These 10 drugs had a median annual revenue before generic entry of $249 million (range, $26 million-$2.7 billion). Accounting for a 75% spending reduction after generic entry, the median excess spending associated with 12 months of extended exclusivity was $187 million, for a total of $4.5 billion over 10 years. Conclusions While market exclusivity extensions are a politically appealing mechanism to encourage novel antibiotic development, this approach would cost public and private payers billions of dollars over the next decade.
Childhood adversity and cardiovascular disease risk: An appraisal of recall methods with a focus on stress-buffering processes in childhood and adulthood.

Abstract Introduction Associations between childhood/adolescent adversity and poor adult physical health have been reported in past work. Much of this work has relied on either retrospective or prospective measures of childhood experiences. However, the effect of different assessment methods on potential stress buffering processes remains largely unknown. Objective We first examined the extent to which long-term cardiovascular disease risk (CVD) was predicted by reports obtained from 10-year old youth regarding adversity experienced in the prior year and those obtained from the same individuals as adults (age 29) regarding their experience of childhood adversity from ages 0–10, focusing in each case on similar types of adversity. To test stress buffering perspectives, we examined the effects of parental emotional support on the association between each measure of childhood adversities and cardiovascular health. Methods We used data from a longitudinal sample of 454 African Americans enrolled in the Family and Community Health Study. The outcome variable was a 30-year CVD risk score computed from the Framingham algorithm. The hypotheses were tested with beta regression models. Results The findings revealed a link between childhood adversity and adult CVD risk at age 29, for both measures of adversity. Consistent with the stress-buffering hypothesis, prospectively assessed parental emotional support in adolescence, but not adulthood, buffered effects on cardiovascular risk for each type of assessment of childhood adversity. Conclusions Prospective and retrospective measures correlated in a manner similar to prior reports (i.e. significantly, but poorly). Further, in line with stress-buffering hypothesis, parental emotional support received at age 10 yielded different buffering effects than parental emotional support received at age 29. The study's findings suggest that theoretically consistent patterns of stress-buffering are detectable using either type of assessment of childhood adversity and provide useful information in the prediction of adult CVD risk.