cssi/SciSciGPT-SciSciNet huggingface dataset:
Stargazer: a software tool for calling star alleles from next-generation sequencing data using CYP2D6 as a model

Genotyping CYP2D6 is important for precision drug therapy because the enzyme it encodes metabolizes approximately 25% of drugs, and its activity varies considerably among individuals. Genotype analysis of CYP2D6 is challenging due to its highly polymorphic nature. Over 100 haplotypes (star alleles) have been defined for CYP2D6, some involving a gene conversion with its nearby nonfunctional but highly homologous paralog CYP2D7. We present Stargazer, a new bioinformatics tool that uses next-generation sequencing (NGS) data to call star alleles for CYP2D6 ( https://stargazer.gs.washington.edu/stargazerweb/ ). Stargazer is currently being extended for other pharmacogenes. Stargazer identifies star alleles from NGS data by detecting single nucleotide variants, insertion-deletion variants, and structural variants. Stargazer detects structural variation, including gene deletions, duplications, and conversions, by calculating paralog-specific copy numbers from read depths. We applied Stargazer to the NGS data of 32 ethnically diverse HapMap trios that were genotyped by TaqMan assays, long-range polymerase chain reaction, quantitative multiplex polymerase chain reaction, high-resolution melting analysis, and/or Sanger sequencing. CYP2D6 genotyping by Stargazer was 99.0% concordant with the data obtained by these methods, and showed that 28.1% of the samples had structural variation including CYP2D6/CYP2D7 hybrids. Accurate genotyping of pharmacogenes with NGS and subsequent allele calling with Stargazer will aid the implementation of precision drug therapy.
Scaling a framework for client-driven open source software projects: a report from three schools

While large ongoing humanitarian open source software (HFOSS) projects are often seen as a way to engage students in capstone courses, they can be difficult to incorporate into an academic setting. One way this problem can be mitigated is by growing student-oriented open source projects within academia while still involving real world clients. One such project, called Homebase, involved a team of students working with a local Ronald McDonald House to develop volunteer scheduling software. In true open source fashion, this project has since been extended over a number of course iterations, with different clients, and has been adopted at other schools. In this paper, we report on our experiences using this approach for similar projects at three quite different schools, and discuss ways to adapt and enhance this approach for differing student populations.
Generalized Airy Stress Functions

The classical Airy stress function in planar elastostatics cannot, in general, be a smooth function for multiply connected domains. Moreover, if a non-null body force field is active the classical Airy representation for the stress is not complete. Here, a generalized Airy representation for the stress is presented which preserves smoothness and which is complete. The generalized form identifies the explicit additional pieces that are needed for completeness in multiply connected domains and when a body force field is present.
Mechanism and effects of the binding of lupus anticoagulant IgG and prothrombin to surface phospholipid

We report here experiments on how lupus anticoagulant antibodies (LA IgG) that react with prothrombin bind to surface phospholipid and affect prothrombin's affinity for surface phospholipid and activation to thrombin. LA IgG was purified by protein A chromatography from the plasma of 16 patients of whom four had associated hypoprothrombinemia and 10 had experienced thrombosis. Many LA IgG bound, in the absence of phospholipid and calcium, not only to immobilized prothrombin but to both prothrombin 1 and fragment 1, which established at least an oligoclonal origin of LA IgG. No LA IgG bound to thrombin. Although prothrombin and Ca2+ were required to support binding of LA IgG to immobilized phosphatidylserine (PS), prothrombin at higher concentrations inhibited binding, presumably by competing with prothrombin/LA IgG complexes for PS binding sites. Prothrombin 1, which cannot bind to PS, also inhibited binding of many LA IgG to PS, presumably by forming competing soluble prothrombin 1/LA IgG complexes. Despite their ability to react with prothrombin independent of phospholipid, LA IgG enhanced binding of prothrombin to immobilized phospholipid and to cultured human umbilical vein endothelial cells. Prothrombin bound with LA IgG to the surface of endothelial cell monolayers could be activated to thrombin after supernatant prothrombin and LA IgG were washed away. The relation is discussed of these observations to a hypothesis that LA IgG mediated concentration of prothrombin on cell surface phospholipid represents a mechanism by which LA IgG could increase thrombotic risk.
EFFICIENCY AND SOLUTION APPROACHES TO BI-OBJECTIVE MATHEMATICAL PROGRAMS

The efficient frontier to the bi-objective problem is characterized via a perturbation function. This not only gives a new perspective to known results but it also yields new results, including interactive approaches which generalize methods given by Geoffrion.
The family in later years.

Throughout most of human history, the family has been both the primary context of social integration for aged individuals and the principal provider of economic support and physical assistance to the elderly in need. Within the lifetime of those Americans now approaching old age, however, a number of dramatic changes have occurred in social structure and culture∔changes that promise to alter traditional assumptions concerning aging, the family, and social supports in meeting the challenges of old age.
Iontophoretic Drug Delivery in the Oral Cavity

Iontophoresis is a noninvasive method to enhance systemic and local drug delivery by the application of an electric field. For systemic drug delivery in the oral cavity, iontophoresis was studied primarily for transbuccal delivery. Significant enhancement of drug delivery was observed in buccal iontophoresis compared to passive transport for different drugs. For local drug delivery in the oral cavity, iontophoresis could enhance drug penetration into the enamel, dentin, and other oral tissues for the treatment of oral diseases. Iontophoresis was evaluated in dentistry such as to produce local anesthesia and treat tooth decalcification and hypersensitivity, but this technology has not been fully utilized. The most common drugs in these evaluations were fluoride and lidocaine. In general, there is limited knowledge of the mechanisms of iontophoresis in the oral tissues. In vivo animal and human studies have suggested that iontophoresis is safe in the oral cavity under the conditions investigated. The present review covers the topics of iontophoretic drug delivery in the oral cavity for both systemic and local treatments. The anatomy and diseases in the oral cavity for iontophoretic drug delivery are also briefly reviewed, and the challenges for this drug delivery method are discussed.
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary utility in adult neuro-oncology

Background Neurocognitive assessments have become integral to comprehensive neuro-oncology care. Existing screening tools may be insensitive to cognitive changes caused by medical treatments. Research supports the clinical value and psychometric properties of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in various medical populations; however, there is minimal evidence for its use in neuro-oncology. The purpose of the current study was to further explore the cognitive profile of patients with primary brain tumor (PBT) using the RBANS and to assess rates of below-expectation performance compared to normative data and estimated intellectual functioning. Methods Data were collected on 82 PBT patients (54% male; age range, 19-81 years). All patients were administered the RBANS-Update and the Advanced Clinical Solutions-Test of Premorbid Functioning (TOPF) according to standardized instructions. Cognitive strengths and weaknesses were identified for PBT patients. Descriptive analyses, t tests, and chi-squared tests were utilized to identify and compare cognitive profiles. Results Overall, cognitive performance was low average for PBT patients. When compared to standardization data, PBT patients performed significantly worse across all 5 RBANS indexes, with Attention and Memory showing the largest discrepancies. Estimated intelligence analyses reflected greater deficits in cognitive functioning than when compared to a normal distribution. Conclusions Preliminary research demonstrates the RBANS is an efficient screening tool to assess cognitive deficits in PBT patients. Data also support the importance of comparison to self, rather than normative distribution in ensuring proper identification and classification of patients.
160) Development of the Analgesic Adverse Drug Response Measure

The purpose was to develop a measure of how people respond to an analgesic adverse drug event in an effort to increase safe analgesic use. A two-phase methodological design was used to develop and test the Analgesic Adverse Drug Response Measure. During phase I a panel of 6 experts rated 58 items developed from a pilot with adults who had experienced an analgesic adverse drug response (ADR). Items with a content validity index (CVI)=.83 or greater were retained. The final measure consisted of 17 items, CVI=.86. During phase II an online survey was conducted with a national Qualtrics panel of 292 adults who reported an ADR from a self-administered analgesic. Additional descriptive measures included demographics and description of the ADR and co-morbidities. The factor analysis is pending. Analgesics most frequently associated with an ADR included hydrocodone (23.6%), codeine (19.5%), and ibuprofen (14.0%). The majority reported that they were the first person to notice the ADR (93.8%) and identified the ADR within an hour of taking the analgesic (59.6%). The most frequent ADRs included nausea (31.2%), abdominal pain (15.4%), vomiting (14.0%), and dizziness (10.3%). Potentially life-threatening symptoms included gastrointestinal bleeding (3.1%) and anaphylaxis (2.1%). A total of 73.3% talked with their provider or pharmacist (28.0%) about the ADR. Twenty-four percent continued to take the analgesic despite the ADR. High risk groups who continue to take ADR associated analgesics and/or who do not consult with their provider about the ADR should be examined so that tailored risk reduction interventions can be developed. Our pending factor analysis will contribute to the construct validity of the Analgesic Adverse Drug Response Measure and use of the Analgesic Adverse Drug Response Measure to identify at risk groups and behaviors associated with analgesic ADRs.
Cell-Type-Specific Regulation of Nucleus Accumbens Synaptic Plasticity and Cocaine Reward Sensitivity by the Circadian Protein, NPAS2

The circadian transcription factor neuronal PAS domain 2 (NPAS2) is linked to psychiatric disorders associated with altered reward sensitivity. The expression of Npas2 is preferentially enriched in the mammalian forebrain, including the nucleus accumbens (NAc), a major neural substrate of motivated and reward behavior. Previously, we demonstrated that downregulation of NPAS2 in the NAc reduces the conditioned behavioral response to cocaine in mice. We also showed that Npas2 is preferentially enriched in dopamine receptor 1 containing medium spiny neurons (D1R-MSNs) of the striatum. To extend these studies, we investigated the impact of NPAS2 disruption on accumbal excitatory synaptic transmission and strength, along with the behavioral sensitivity to cocaine reward in a cell-type-specific manner. Viral-mediated knockdown of Npas2 in the NAc of male and female C57BL/6J mice increased the excitatory drive onto MSNs. Using Drd1a-tdTomato mice in combination with viral knockdown, we determined these synaptic adaptations were specific to D1R-MSNs relative to non-D1R-MSNs. Interestingly, NAc-specific knockdown of Npas2 blocked cocaine-induced enhancement of synaptic strength and glutamatergic transmission specifically onto D1R-MSNs. Last, we designed, validated, and used a novel Cre-inducible short-hairpin RNA virus for MSN-subtype-specific knockdown of Npas2 Cell-type-specific Npas2 knockdown in D1R-MSNs, but not D2R-MSNs, in the NAc reduced cocaine conditioned place preference. Together, our results demonstrate that NPAS2 regulates excitatory synapses of D1R-MSNs in the NAc and cocaine reward-related behavior.SIGNIFICANCE STATEMENT Drug addiction is a widespread public health concern often comorbid with other psychiatric disorders. Disruptions of the circadian clock can predispose or exacerbate substance abuse in vulnerable individuals. We demonstrate a role for the core circadian protein, NPAS2, in mediating glutamatergic neurotransmission at medium spiny neurons (MSNs) in the nucleus accumbens (NAc), a region critical for reward processing. We find that NPAS2 negatively regulates functional excitatory synaptic plasticity in the NAc and is necessary for cocaine-induced plastic changes in MSNs expressing the dopamine 1 receptor (D1R). We further demonstrate disruption of NPAS2 in D1R-MSNs produces augmented cocaine preference. These findings highlight the significance of cell-type-specificity in mechanisms underlying reward regulation by NPAS2 and extend our knowledge of its function.
Passive Beam Combining for the Development of High Power SOA-Based Tunable Fiber Compound-Ring Lasers Using Low Power Optical Components

A simple, stable, compact, and cost-effective dual-output port widely tunable SOA-based fiber compound-ring laser structure is demonstrated. Such a unique nested ring cavity enables the splitting of optical power into various branches where amplification and wavelength selection for each branch are achieved utilizing low-power SOAs and a tunable filter, respectively. Furthermore, splicing Sagnac Loop Mirrors at each end of the bidirectional fiber compound-ring cavity not only allows them to serve as variable reflectors but also enables them to channel the optical energy back to the same port thus omitting the need for high optical power combiners. Further discussed is how the said bidirectional fiber compound-ring laser structure can be extended to achieve a high-power fiber laser source by exclusively using low power optical components such as N × N couplers and (N > 1) number of SOAs. More than 98% coherent beam combining efficiency of two parallel nested fiber ring resonators is achieved over the C-band tuning range of 30 nm. Optical signal-to-noise ratio (OSNR) of +45 dB, and optical power fluctuation of less than ±0.02 dB are measured over 3 h at room temperature.
Pragmatist Media Ethics and the Challenges of Fake News

Increasing attention is being directed at the impact of fake news on democratic societies across the globe. Scholars in a range of fields are attempting to determine who is behind fake news propaga...
Adoption and Implementation of Evidence-Based Colorectal Cancer Screening Interventions Among Cancer Control Program Grantees, 2009-2015.

Author(s): Hannon, Peggy A; Maxwell, Annette E; Escoffery, Cam; Vu, Thuy; Kohn, Marlana J; Gressard, Lindsay; Dillon-Sumner, Laurel; Mason, Caitlin; DeGroff, Amy | Abstract: Purpose and objectivesColorectal cancer (CRC) is the second-leading cause of cancer death in the United States. Although effective CRC screening tests exist, CRC screening is underused. Use of evidence-based interventions (EBIs) to increase CRC screening could save many lives. The Colorectal Cancer Control Program (CRCCP) of the Centers for Disease Control and Prevention (CDC) provides a unique opportunity to study EBI adoption, implementation, and maintenance. We assessed 1) the number of grantees implementing 5 EBIs during 2011 through 2015, 2) grantees' perceived ease of implementing each EBI, and 3) grantees' reasons for stopping EBI implementation.Intervention approachCDC funded 25 states and 4 tribal entities to participate in the CRCCP. Grantees used CRCCP funds to 1) provide CRC screening to individuals who were uninsured and low-income, and 2) promote CRC screening at the population level. One component of the CRC screening promotion effort was implementing 1 or more of 5 EBIs to increase CRC screening rates.Evaluation methodsWe surveyed CRCCP grantees about EBI implementation with an online survey in 2011, 2012, 2013, and 2015. We conducted descriptive analyses of closed-ended items and coded open-text responses for themes related to barriers and facilitators to EBI implementation.ResultsMost grantees implemented small media (≥25) or client reminders (≥21) or both all program years. Although few grantees reported implementation of EBIs such as reducing structural barriers (n = 14) and provider reminders (n = 9) in 2011, implementation of these EBIs increased over time. Implementation of provider assessment and feedback increased over time, but was reported by the fewest grantees (n = 17) in 2015. Reasons for discontinuing EBIs included funding ending, competing priorities, or limited staff capacity.Implications for public healthCRCCP grantees implemented EBIs across all years studied, yet implementation varied by EBI and did not get easier with time. Our findings can inform long-term planning for EBIs with state and tribal public health institutions and their partners.
Translational Neurology of Slow Saccades

Extensive knowledge has been gained over recent decades about anatomic and pathophysiologic mechanisms governing saccades, rapid eye movements by which gaze is shifted between visual targets. In this focused review, we highlight the physiology and anatomy of normal saccades as they pertain to pathological saccade slowing of central brainstem origin, with emphasis on excitatory and inhibitory burst neurons and omnipause neuron function. We summarize insights into saccadic dysfunction from nonhuman basic science research and further utilize these insights to review advances from translational research in common and uncommon human central neurological disease states that lead to vertical and/or horizontal saccade slowing, such as progressive supranuclear palsy, Niemann-Pick type C, and post-cardiac surgery.
Infusing Humanities in STEM Education: Student Opinions of Disciplinary Connections in an Introductory Chemistry Course

The Next Generation Science Standards and other educational reforms support the formation of deep connections across the STEM disciplines. Integrated STEM is considered as a best practice by the educational communities of the disparate disciplines. However, the integration of non-STEM disciplines is understudied and generally limited to the integration of art (STEAM). Humanistic STEM blends the study of STEM with interest in and concern for human affairs, welfare, values, or culture. This study looks at an infusion of the humanities into an online chemistry course to see if there is an influence on student connection between course content and cross-disciplinary perspectives. Specifically, students were asked about the course making clear connection to STEM disciplines, between science and non-science, between science and the real world, and a widened perspective of science connection other courses in their degree programs. Items on a Likert scale were presented as part of the end of course evaluations and yielded 59 responses. Although no statistically significant difference in the pre- and post-infusion agreement, it is evident that the additional perspectives did no harm. The positive movement in this pilot study encourages further investigation with stronger infusions of both STEM and humanities content.
Calculation of α -Transition Probabilities

The decay rates for the ground-state transitions of all polonium isotopes and the odd-even astatine isotopes are discussed on the basis of the nuclear shell model. Good agreement with experimental data is obtained. In particular the behavior of the reduced width as a function of the neutron number around the magic number $N=126$ is well reproduced.
The Politics of White Racial Identity and Vote Choice in the 2018 Midterm Elections

Objectives This article examines the role of white racial identity or white racial group consciousness in the vote choice of whites for the U.S. House of Representatives in the 2018 midterm elections. Methods Data from the 2018 American National Election Study (ANES) Pilot Study are analyzed using a logistic regression model. Results White racial consciousness was a significant predictor of U.S. House vote choice in 2018, even after controlling for other relevant explanatory variables such as racial resentment, party identification, and ideology. The effects were especially evident for two quintessential swing groups: independents and moderates. Conclusion In the first national election of the Trump era, white racial group consciousness became a relevant electoral cleavage and determinant of white vote choice at the subpresidential level. Given the rhetoric and action of Trump as president, the Republican Party has morphed into a white identity political party, not dissimilar to populist right‐wing parties in Europe. While this might reap electoral benefits for the Republican Party in jurisdictions with smaller minority populations, it is likely to cost the party support where there is greater racial diversity. In the long term, the politics of white identity is likely to be an impediment to the Republican Party's ability to expand its electoral base.
Cleavage of the Perlecan-Semaphorin 3A-Plexin A1-Neuropilin-1 (PSPN) Complex by Matrix Metalloproteinase 7/Matrilysin Triggers Prostate Cancer Cell Dyscohesion and Migration.

The Perlecan-Semaphorin 3A-Plexin A1-Neuropilin-1 (PSPN) Complex at the cell surface of prostate cancer (PCa) cells influences cell–cell cohesion and dyscohesion. We investigated matrix metalloproteinase-7/matrilysin (MMP-7)’s ability to digest components of the PSPN Complex in bone metastatic PCa cells using in silico analyses and in vitro experiments. Results demonstrated that in addition to the heparan sulfate proteoglycan, perlecan, all components of the PSPN Complex were degraded by MMP-7. To investigate the functional consequences of PSPN Complex cleavage, we developed a preformed microtumor model to examine initiation of cell dispersion after MMP-7 digestion. We found that while perlecan fully decorated with glycosaminoglycan limited dispersion of PCa microtumors, MMP-7 initiated rapid dyscohesion and migration even with perlecan present. Additionally, we found that a bioactive peptide (PLN4) found in perlecan domain IV in a region subject to digestion by MMP-7 further enhanced cell dispersion along with MMP-7. We found that digestion of the PSPN Complex with MMP-7 destabilized cell–cell junctions in microtumors evidenced by loss of co-registration of E-cadherin and F-actin. We conclude that MMP-7 plays a key functional role in PCa cell transition from a cohesive, indolent phenotype to a dyscohesive, migratory phenotype favoring production of circulating tumor cells and metastasis to bone.
Sequential intraparticle Förster resonance energy transfer for multi-wavelength bioimaging

Core/shell nanoparticles composed of a silica core over which a propargyl methacrylate (PMA) shell was polymerized around were synthesized. To employ the shell coating, the surface of the silica nanoparticles (SiNPs) was modified with an alkene-terminated organometallic silane linker that allowed for the covalent attachment of a poly(propargyl methacrylate) (pPMA) shell. The alkyne groups resulting from the pPMA shell were utilized in copper(I)-catalyzed azide/alkyne cycloaddition (CuAAC) reactions to attach azide-modified Forster resonance energy transfer (FRET) pairs of naphthalimide (azNap), rhodamine B (azRhod), and silicon phthalocyanine (azSiPc) derivatives to the shell surface. The luminescence of the system was manipulated by the covalent attachment of one, two, or three of the fluorophores resulting in no energy transfer, one energy transfer, or two energy transfers, respectively. When all three fluorophores were attached to the core/shell particles, an excitation of azNap with a wavelength of 400 nm resulted in the sequential energy transfer between two FRET pairs and the sole emission of azSiPc at 670 nm. These particles may have applications as bioimaging probes as their luminescence is easily detected using fluorescence microscopy.
Data Needs for Economic Evaluations of Screening in Pediatric Primary Care: A Research Framework.

* Abbreviations: CEA — : cost-effectiveness analysis NTD — : neural tube defect QALY — : quality-adjusted life-year Although cost-effectiveness analyses could inform recommendations regarding preventive services in primary care, valid assessments are rarely conducted for policy makers in the United States, other than for immunizations. Assuming policy makers were interested, how could researchers provide them with useful information? Cost-effectiveness analyses compare the expected improvement in health outcomes, for example, quality-adjusted life-years, and the change in total costs relative to current practice. The cost-effectiveness of screening depends on factors related to the treatments that screening enables, the likelihood of uptake of screening, and the additional costs of screening itself that accrue to the whole targeted population, along with potential harms (eg, false positive screening results). Several data gaps exist that complicate the conduct of economic analyses for childhood screening in the primary care setting. Although clinical trials can provide strong evidence of efficacy, because of the time lag between when a preventive service is provided and when health outcomes occur, such trials often use proxy measures in place of health outcomes. Few trials of pediatric preventive services have been conducted, and even when available, clinical trials may have limited generalizability because of strict inclusion and exclusion criteria for study participants. Furthermore, the interventions delivered in trials may differ from what is practical to provide in primary care. Given these limitations, careful use of observational data and modeling techniques is generally required for the estimation of long-term effectiveness and associated costs. Particular attention needs to be paid in analyses of observational data to threats to validity, including sources of potential bias. How should considerations of cost and value … Address correspondence to Scott D. Grosse, PhD, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 4770 Buford Hwy, Mail Stop S106-4, Atlanta, GA 30341. E-mail: sgrosse{at}cdc.gov
Rat Calvarial Bone Regeneration by 3D-Printed Beta-Tricalcium Phosphate Incorporating MicroRNA-200c

Advanced fabrication methods of bone grafts designed to match defect sites that combine biodegradable, osteoconductive materials with potent, osteoinductive biologics would significantly impact the clinical treatment of large bone defects. In this study, we engineered synthetic bone grafts using a hybrid material approach that combined 3D-printed biodegradable, osteoconductive β-tricalcium phosphate (β-TCP) with osteoinductive microRNA(miR)-200c. 3D-printed β-TCP scaffolds were fabricated utilizing suspension-enclosing projection-stereolithography (SEPS) process to produce constructs with reproducible microarchitectures that enhanced the osteoconductive properties of β-TCP. 3D-printed β-TCP scaffolds coated with miR-200c incorporated collagen increased the transfection efficiency of miR-200c and osteogenic differentiation of hBMSCs in vitro. Furthermore, these hybrid material, miR-incorporated scaffolds significantly enhanced bone regeneration in critical-sized rat calvarial defects. These results strongly indicate that through use of SEPS 3D-printing technology, hybrid scaffolds combined by osteoconductive biomaterials and osteoinductive biologics can be used as superior bone substitutes for the clinical treatment of large bone defects.
Ethnic Disparities in the Care of Opioid-Exposed Newborns in Colorado Birthing Hospitals.

OBJECTIVES Investigate disparities by Hispanic ethnicity in the care of opioid exposed newborns (OENs) in Colorado birthing hospitals within a statewide quality improvement collaborative. METHODS This study is a secondary analysis of a quality improvement initiative aimed at standardizing hospital-based care of OENs through implementation of the Eat, Sleep, Console Model. We used statistical process control charts to compare time to special cause variation by Hispanic ethnicity for outcomes including infant length of stay, use of pharmacologic therapy, and breastfeeding eligibility and receipt. Only hospitals that delivered both Hispanic and non-Hispanic OENs during the study period were included, documented maternal ethnicity was required for inclusion. We investigated hospital variation in these outcomes among 4 hospitals that cared for Hispanic OENs for most of the study period. RESULTS We analyzed 799 mother–OEN dyads, 241 Hispanic and 558 non-Hispanic. Both Hispanic and non-Hispanic OENs experienced decreases in length of stay overall and among those who received postnatal opioids, although Hispanic OENs achieved these decreases 3 annual quarters after non-Hispanic OENs. Pharmacologic therapy use decreased by 55% for Hispanic OENs and 60% for non-Hispanic OENs. Hispanic OENs experienced a 1-quarter delay for this decrease. CONCLUSIONS Although this quality improvement initiative resulted in positive outcomes for Hispanic and non-Hispanic OENs, improvement was delayed among Hispanic infants, indicating a need to explore and address care practices of Hispanic mothers and infants affected by opioid use disorders.
Reciprocal impacts of telomerase activity and ADRN/MES differentiation state in neuroblastoma tumor biology.

Telomere maintenance and tumor cell differentiation have been separately implicated in neuroblastoma malignancy. Their mechanistic connection is unclear. We analyzed neuroblastoma cell lines and morphologic subclones representing the adrenergic (ADRN) and mesenchymal (MES) differentiation states and uncovered sharp differences in their telomere protein and telomerase activity levels. Pharmacologic conversion of ADRN into MES cells elicited consistent and robust changes in the expression of telomere-related proteins. Conversely, stringent down-regulation of telomerase activity triggers the differentiation of ADRN into MES cells, which was reversible upon telomerase up-regulation. Interestingly, the MES differentiation state is associated with elevated levels of innate immunity factors, including key components of the DNA-sensing pathway. Accordingly, MES but not ADRN cells can mount a robust response to viral infections in vitro. A gene expression signature based on telomere and cell lineage-related factors can cluster neuroblastoma tumor samples into predominantly ADRN or MES-like groups, with distinct clinical outcomes. Our findings establish a strong mechanistic connection between telomere and differentiation and suggest that manipulating telomeres may suppress malignancy not only by limiting the tumor growth potential but also by inducing tumor cell differentiation and altering its immunogenicity. Yu et al. identify marked differences in the telomere and immunologic profiles of neuroblastoma cell lines displaying MES and ADRN lineage characteristics. They show that pharmacologically converting ADRN into MES cells triggers associated switch in telomere/immunologic protein profiles whereas inhibiting telomerase activity in ADRN cells induces reversible conversion into MES cells.
Multiscale Analysis of Dynamic Deformation in Monocrystals

The dynamic deformation in FCC single crystals is investigated using a multiscale dislocation dynamic plasticity model. We examine the effect of strain rate, pulse duration, nonlinear elastic properties and crystal anisotropy on wave profiles and dislocation microstructures. The morphologies of the relaxed configurations of dislocations microstructures show formation deformation bands.
Lockouts under the LMRA: New Shadows on an Old Terrain

I N DEALING with bargaining lockouts under the LMRA, I will, with respect, be critical of what the NLRB has said and done and of what it has left unsaid. This contentious approach to a weapon of contention would at any time be a doubtful basis for an after-dinner talk. It may seem particularly ungracious right now; for there is increasing concern about the overt use of pressure in collective bargaining and increasing discussion of proposals for reducing such pressures. I am somewhat uncomfortable about examining rules of war in the face of this widespread preoccupation with the more amiable subject of promoting peace. I am also troubled because the apple of discord into which I am to bite has been well chewed in the law reviews.1 I am tempted to put all the blame on our Chairman for my troubles, but I am in the dock with him. He at least in mitigation can plead a benevolent purpose, that is, saving me from thinking. He tactfully hinted at that purpose when he invited me to present the substance of an article I wrote in 1956.2 But our plan for after-dinner featherbedding ran into a familiar obstacle. That area of journalism called labor law has not stood still, and I will compress my earlier observations in order to deal with more recent developments. These developments have not shaken my opinion that the Board's basic approach to lockouts is erroneous; they have, moreover, reenforced my conviction that that approach breeds unreal and unworkable distinctions, which impose unmanageable burdens on the Board and the courts. The Board has distinguished between three types of lockouts which arise in the bargaining context: the first I will call the bargaining lockout-that is, a shutdown initiated by an employer in order to break a bargaining impasse in circumstances where, apart from the lockout, the employer's conduct is blameless. The Board has in general condemned such lockouts.3 The Supreme Court has, however, not squarely ruled on this point, despite a generation of litiga-
Identification of a positive regulator of the Mu middle operon.

Abstract Transcription of bacteriophage Mu occurs in a regulatory cascade consisting of three phases: early, middle, and late. The 1.2-kb middle transcript is initiated at Pm and encodes the C protein, the activator of late transcription. A plasmid containing a Pm-lacZ operon fusion was constructed. beta-Galactosidase expression from the plasmid increased 23-fold after Mu prophage induction. Infection of plasmid-containing cells with lambda phages carrying different segment of the Mu early region localized the Pm-lacZ transactivation function to the region containing open reading frames E16 and E17. Deletion and linker insertion analyses of plasmids containing this region identified E17 as the transactivator; therefore we call this gene mor, for middle operon regulator. Expression of mor under the control of a T7 promoter and T7 RNA polymerase resulted in the production of a single polypeptide of 17 kDa as detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Insertion of a linker into mor substantially reduced the ability of Mu to form plaques. When growth of the mor mutant was assayed in liquid, lysis was delayed by about 50 min and the burst size was approximately one-fifth that of wild-type Mu. The mor requirement for plaque formation and normal growth kinetics was abolished when C protein was provided in trans, indicating that the primary function of Mor is to provide sufficient C for late gene expression. Comparison of the predicted amino acid sequence of Mor with other proteins revealed that Mor and C share substantial amino acid sequence homology.
Prelude to the Philosophy of Hollis Frampton

Not long before his death in 1984, Hollis Frampton left us with a collection of texts entitled _Circles of Confusion_, which, although tragically out of print, stands as one of the most important events in the study of cinema.
Abstract T P247: An Interdisciplinary Approach Using a Root Cause Analysis to Decrease Door to IV tPA Times

Background and Issues: The benchmark goal for stroke treatment is door to IV tPA in 60 minutes. In 2010, average door to IV tPA treatment time for acute stroke patients at our acute care, tertiary teaching hospital was 87 minutes. Purpose: As a TJC certified primary stroke center, our purpose was to improve door to IV tPA times. Methods: Causes for lengthy tPA treatment times were identified by the stroke interdisciplinary team using a root cause analysis approach. Identified delays included: lab turn-around times, order entry, clinical decision making time, and tPA preparation, delivery, and administration. Process improvement initiatives for order entry included revisions to electronic order sets to auto-populate and enhance efficiency and safety of order entry. Lab audits revealed that the BMP took the most time to process, resulting in initiation of point of care testing. For clinical decision making delays by neurology, immediate feedback was provided to the neurologist after each tPA administration. A year end summary was compiled showing door to tPA times for each attending neurologist. In addition, 3 APNs completed a neurovascular advanced practice fellowship program. Pharmacy instituted a tracking log to audit prep-to-delivery time which encouraged earlier notification and faster delivery times. Mixing of tPA was changed from (2) 50mg vials to reconstitution of (1) 100mg vial. Nurses who administer tPA were re-competencied using a simulation lab. Patients were triaged to a room in ED closer to the CT scanner. And, a count-down clock was initiated upon patient arrival to ED to enhance time awareness for all stroke team members. Results: Average door to tPA time has decreased from 87 minutes in 2010 to 50 minutes YTD 2013, a 37 minute improvement. In addition, volume increased by 25 more tPA administrations in 2012. Chi square comparisons of discharge dispositions showed no statistical differences for 2010 vs 2013 (p=.56) or 2012 vs 2013 (p= .18). Our hospital has received the American Stroke Association’s Target Stroke award for the past 2 years. Conclusions: An interdisciplinary approach using a root cause analysis is effective in identifying and implementing process improvements, ultimately leading to decreased door to IV tPA times.
Stevens–Johnson syndrome after Mycoplasma pneumonia infection in pediatric post‐liver transplant recipient: Case report and review of the literature

Tomaino J, Keegan T, Miloh T, Kerkar N, Mercer S, Birge M, Rocca J, Suchy F, Arnon R. Stevens–Johnson syndrome after Mycoplasma pneumonia infection in pediatric post-liver transplant recipient: case report and review of the literature. Abstract: Although Mycoplasma pneumonia infection is relatively common among school-aged children, it rarely leads to SJS. Herein, we report a seven-yr-old girl who presented with a Mycoplasma pneumonia infection that progressed to SJS five months after liver transplant. We suggest that children presenting with symptoms of Mycoplasma pneumonia infection in the immunosuppressed post-liver transplant setting be properly diagnosed and treated rapidly, as well as observed for symptoms of SJS and potentially serious extrapulmonary complications.
But who shall monitor the monitor

Three circumstances may (thinly) be argued to qualify the present writer as an "expert" commentator on the article by Kelly et al. in this issue of Pediatrics (p. 511): first (and nearly 20 years ago), that most humbling of all experiences for the pediatrician, the dismissal from one9s office of an apparently healthy 2-month-old infant with a minor upper respiratory tract infection who is brought dead on arrival to one9s own hospital not three hours later, the unavailability of any autopsy data (difficult to obtain from unsubsidized pathologists in small suburban hospitals ruled by the coroner system of forensic medicine) forcing the diagnosis of sudden infant death syndrome (SIDS) on bewildered parents and shaken physician; last, participation in a recent task force assembled by the American Academy of Pediatrics in an attempt to generate an omniscient statement to cover the optimal management of a dreaded condition ("near-miss SIDS") whose identification is by definition uncertain and concerning which a minimal base of factual knowledge is only now beginning to accrue.
The Similarity Eﬀect: A Consequence of Rational Choice

This paper highlights a logical contradiction in the currently accepted theory of choice. This contradiction occurs when a decision is reframed by adding a clone to the choice set. The current theory concludes that individuals have context-dependent preferences if they make consistent choices; it concludes that individuals have rational preferences if they systematically switch from one alternative to another.I argue that these are not the logical conclusions to draw from the data and that the currently accepted theory should be revised. Rational decision making assumes that individuals make consistent decisions and leads to the similarity effect. Luce’s IIA implies that adding a clone to the choice set makes an alternative more preferable, which is a framing effect.
Split products of fibrin in maternal serum in the perinatal period.

Abstract Serum levels of split products of fibrin as an assay for intravascular coagulation or primary fibrinolysis were measured in sera of 84 women in labor, in the immediate postpartum period, and for 3 days after delivery. Split products of fibrin (SPF) were present in 6 of 29 women (21 per cent) during labor, 27 of 84 women (32 per cent) in the immediate postpartum period, and 10 per cent of 33 women 24 to 72 hours after delivery. Serial coagulation studies on 12 normal primigravidas showed that a third had SPF and/or prolonged thrombin times during delivery. Other studies showed high fibrinogen levels, high plasminogen levels, and normal euglobulin clot lysis times, ruling out primary fibrinolysis in these patients. We conclude that local intravascular coagulation is a frequent occurrence during delivery and that acquired bleeding disorders with defibrination represent the extreme of this common event.
5-Hydroxytryptamine type 2A receptors regulate cyclic AMP accumulation in a neuronal cell line by protein kinase C-dependent and calcium/calmodulin-dependent mechanisms.

The effects of 5-hydroxytryptamine (5-HT)2A receptor activation on cAMP formation were studied in a cell line derived from embryonic rat cortex (A1A1). 5-HT (EC50 = 0.87 microM) amplified the amount of cAMP formed in response to 5'-N-ethylcarboxamidoadenosine (an adenosine A2 receptor agonist), cholera toxin, and forskolin after 15 min of coincubation in the presence of the phosphodiesterase inhibitor rolipram. This effect of 5-HT was blocked by 10 nM ketanserin as well as by 10 nM spiperone, indicating a response mediated by the 5-HT2A receptor subtype. Similarly, cAMP accumulation was enhanced by coincubation with the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore A23187. After exposure to PMA for 24 hr (PKC-depleted cells), 5-HT and A23187 still enhanced cAMP formed in response to forskolin and 5'-N-ethylcarboxamidoadenosine, whereas the amplifying effects of PMA were abolished. Analysis by Western blots and PKC activity measurements revealed that, of three PKC isoforms detected in A1A1 cells (alpha, delta, and epsilon), only the calcium-independent isoform PKC-epsilon remained in membrane fractions after long term PMA treatment. In PKC-depleted cells, 5-HT-mediated amplification was greatly reduced after treatment with the calcium chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (acetoxymethyl)-ester or the calmodulin antagonists calmidazolium and N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide hydrochloride. In addition, 5-HT-mediated amplification of cAMP accumulation was reduced by the PKC inhibitor staurosporine in normal cells but was unaffected in PKC-depleted cells. In conclusion, these data suggest that 5-HT2A receptor activation can amplify cAMP formation in A1A1 cells by two distinct pathways coupled to the hydrolysis of inositol phosphates, i.e., PKC and calcium/calmodulin.
Use of autopsy results in the emergency department quality assurance plan

Traditionally, the autopsy is viewed as the ultimate quality assurance indicator in clinical medicine, yet very few clinical departments actually incorporate autopsy results in their formal quality assurance plans. Consequently, to investigate how autopsy results can be included on our emergency department plan, the clinical and autopsy diagnoses of 244 patients were reviewed retrospectively and compared to identify conditions that were unapparent or misdiagnosed at the time of death. The study period was from January 1984 through June 1988. The average yearly ED census was 33,266. Differences between clinical and autopsy diagnoses were categorized as class 1, 2, 3, or 4 findings. Major unexpected findings (classes 1 and 2) were found in ten patients (4%); the most common missed diagnoses were aortic dissection 3 (1.2%) and pulmonary embolus 2 (0.8%). Minor unexpected findings (classes 3 and 4) were discovered in 14 patients (5.8%). The results clearly identify unexpected findings and point to the need for more aggressive evaluations of certain conditions. Systematic review of autopsy data as presented has led to meaningful changes and delivery of care to emergency patients. Autopsies are a vital source of outcome-based information that should be part of every ED's quality assurance and risk management plan.