cssi/SciSciGPT-SciSciNet huggingface dataset:
Inhibition of Platelet Function by Aspirin in Insulin Dependent Diabetics without Vascular Disease.

Abstract Abstract 4172 Diseases like diabetes that are associated with increased platelet production are reported to have decrease aspirin (ASA) induced platelet inhibition. ASA inhibition of platelet function is mediated via acetylation of platelet cylooxygenase, which is completed approximately 30 minutes after ingestion. Thereafter production of new non-acetylated platelets increases the proportion of normal platelets gradually reversing ASA platelet inhibition. We tested the hypothesis that insulin dependent diabetics (type 1) without clinical evidence of occlusive vascular disease have less aspirin platelet inhibition than normal controls. The amount of ASA (325mg) platelet inhibition was measured using the slope (S) of platelet prostaglandin agonist (PPA) stimulated light aggregation curve that decreases after ASA. Aggregation was measured at 3 time points: before ASA ingestion, time 0 (T0); 2 hours post ASA (T2); and 24 hours after ASA (T24). Percent recovery from aspirin inhibition was calculated using the formula (T24–T2)/ (T0-T2) x100. Eight adult insulin dependent diabetic patients without clinical evidence of vascular disease and who were not taking aspirin were compared with 11 nondiabetic controls. 24 hours after aspirin ingestion diabetic patients recovered 10% of their maximal ASA platelet inhibition compared to 13% in controls (p=0.69). We conclude that recovery of platelet function from ASA in insulin dependent diabetics without clinical vascular disease occurs at the same rate as normal controls, suggesting that the previously reported decrease in platelet inhibition in diabetic patients may be related to increased platelet production associated with clinically evident occlusive vascular disease. Disclosures: No relevant conflicts of interest to declare.
Hybrid integration of modified uni-traveling carrier photodiodes on a multi-layer silicon nitride platform using total reflection mirrors

We demonstrate hybrid integration of modified uni-traveling carrier photodiodes on a multi-layer silicon nitride platform using total reflection mirrors etched by focused ion beam. The hybrid photodetectors show external responsivity of 0.15 A/W and bandwidth of 3.5 GHz for devices with a diameter of 80 µm. The insertion loss of the waveguide is 3 dB and the coupling efficiency of the total reflection mirror is -3 dB. The highest RF output power is -0.5 dBm measured at 3 GHz with 9 mA photocurrent and -9 V bias.
A computational imaging target specific detectivity metric

Due to the large quantity of low-cost, high-speed computational processing available today, computational imaging (CI) systems are expected to have a major role for next generation multifunctional cameras. The purpose of this work is to quantify the performance of theses CI systems in a standardized manner. Due to the diversity of CI system designs that are available today or proposed in the near future, significant challenges in modeling and calculating a standardized detection signal-to-noise ratio (SNR) to measure the performance of these systems. In this paper, we developed a path forward for a standardized detectivity metric for CI systems. The detectivity metric is designed to evaluate the performance of a CI system searching for a specific known target or signal of interest, and is defined as the optimal linear matched filter SNR, similar to the Hotelling SNR, calculated in computational space with special considerations for standardization. Therefore, the detectivity metric is designed to be flexible, in order to handle various types of CI systems and specific targets, while keeping the complexity and assumptions of the systems to a minimum.
Rethinking scientific authority: Behavior genetics and race controversies

The controversy over the genetic explanation for racial differences in intelligence and behavior has been sustained by the platform the field of behavior genetics has offered race researchers. Explanations of this support have focused on political or scientific rationalities: behavior geneticists must support the claim that blacks are genetically less intelligent either for political reasons or they believe that conclusion is an unavoidable conclusion of objective science. These explanations do not withstand scrutiny given the field’s political diversity, self-image as a scientific endeavor, and skepticism about the scientificity of genetic racial explanations. Using qualitative data from interviews and the historical record, this article offers an alternate two-part explanation that focuses first, on the forces and struggles behavior geneticists faced as a field during the IQ and race controversy in the 1970s, and second, on the way sanctuary for race researchers has helped the field project images of strength to build scientific authority. The article offers a retheorization of scientific authority beyond the Weberian focus on legitimacy. It is shown to be first embedded in the relational structure of the field and second connected to the symbolic resources that provocative, though illegitimate, ideas can offer scientists.
Broadband Networks and Smart Grid: How Do We Build a Better Tomorrow?

The world is going digital, and broadband and Smart Grid deployment are leading the way. Along with these changes are others that are just as significant. For example, how culture and our way of life experience innovation is being transformed from reliance upon changes to the physical world as an indication of progress awareness arising from the marketing of new devices and services. Innovation over the last decade have been monumental, but in many ways subtle. Although changes are happening on the micro- and macro-level, often the most visible are the micro-changes in the form of new personal computing devices such as iPads, e-books, digital phones or faster and broadly available communication networks. The macro-changes are on the global scale but less visible, but they will influence how people experience work, leisure, and engage in civic affairs. The Digital Information Age is issuing in a macro-digital communication age where:
Artificial Moral Cognition: Moral Functionalism and Autonomous Moral Agency

This paper proposes a model of the Artificial Autonomous Moral Agent (AAMA), discusses a standard of moral cognition for AAMA, and compares it with other models of artificial normative agency. It is argued here that artificial morality is possible within the framework of a “moral dispositional functionalism.” This AAMA is able to read the behavior of human actors, available as collected data, and to categorize their moral behavior grounded in moral patterns herein. The present model is grounded in several analogies among artificial cognition, human cognition, and moral action. It is premised on the idea that moral agents should not be built on rule-following procedures, but on learning patterns from data. This idea is rarely implemented in AAMA models, albeit it has been suggested in the machine ethics literature (W. Wallach, C. Allen, J. Gips and especially M. Guarini). As an agent-based model, this AAMA constitutes an alternative to the mainstream action-centric models proposed by K. Abney, M. Anderson and S. Anderson, R. Arkin, T. Powers, W. Wallach, i.a. Moral learning and moral development of dispositional traits play here a fundamental role in cognition. By using a combination of neural networks and evolutionary computation, called “soft computing” (H. Adeli, N. Siddique, S. Mitra, L. Zadeh), the present model reaches a certain level of autonomy and complexity, which illustrates well “moral particularism” and a form of virtue ethics for machines, grounded in active learning. An example derived from the “lifeboat metaphor” (G. Hardin) and the extension of this model to the NEAT architecture (K. Stanley, R. Miikkulainen, i.a.) are briefly assessed.
Brown rat demography reveals pre-commensal structure in eastern Asia prior to expansion into Southeast Asia during the Song dynasty

Fossil evidence indicates that the globally-distributed brown rat (Rattus norvegicus) originated in northern China and Mongolia. Historical records report the human-mediated invasion of rats into Europe in the 1500s, followed by global spread due to European imperialist activity during the1600s-1800s. We analyzed 14 genomes representing seven previously identified evolutionary clusters and tested alternative demographic models to infer patterns of range expansion, divergence times, and changes in effective population (Ne) size for this globally important pest species. We observed three range expansions from the ancestral population that produced the Pacific (~4.8kya), eastern China (diverged ~0.55kya), and Southeast (SE) Asia (~0.53kya) lineages. Our model shows a rapid range expansion from SE Asia into the Middle East then continued expansion into central Europe 537 years ago (1478 AD). We observed declining Ne within all brown rat lineages from 150-1kya, reflecting population contractions during glacial cycles. Ne increased since 1kya in Asian and European, but not Pacific, evolutionary clusters. Our results support the hypothesis that northern Asia was the ancestral range for brown rats. We suggest that southward human migration across China between 800-1550s AD resulted in the introduction of rats to SE Asia, from which they rapidly expanded via existing maritime trade routes. Finally, we discovered that North America was colonized separately on both the Atlantic and Pacific seaboards, yet by evolutionary clusters of vastly different ages and genomic diversity levels. Our results should stimulate discussions among historians and zooarcheologists regarding the relationship between humans and rats.
RELATIONSHIP BETWEEN THE LOWER QUARTER Y-BALANCE TEST SCORES AND ISOKINETIC STRENGTH TESTING IN PATIENTS STATUS POST ACL RECONSTRUCTION.

Background ACL injuries are common among sports populations and achieving adequate lower extremity strength is important prior to return to play. Access to isokinetic testing equipment that measures lower extremity strength is limited. Screening tools that measure functional criteria are accessible to clinicians, however the tools' relationship to strength constructs have not been investigated in an ACL reconstructed (ACLR) population. Purpose The primary objective was to determine if relationships exist between isokinetic peak knee extension torque (PKET), peak knee flexion torque (PKFT), hamstring to quadriceps (HQ) ratios, and YBT-LQ performance following ACLR. The secondary objective was to observe differences in isokinetic strength ability between high and low performers on the YBT-LQ. Study Design Retrospective Chart Review. Methods Medical records of forty-five ACL-reconstructed subjects, between five-12 months post-surgery were queried for functional assessment data collected during the institution's standard outcome testing battery. Variables of interest included: demographic and anthropomorphic measures, YBT-LQ performance, and involved limb isokinetic PKET, PKFT, and HQ ratios. Performance on each measure, as well as asymmetry between sides, was analyzed using a correlation matrix. Results Statistically significant (p<0.01) relationships were identified between YBT-LQ anterior reach asymmetry and the PKET deficit (r=0.264). PKET and PKFT on the involved limb correlated to performance of anterior reach (r=0.591, p<0.01)(r=0.493, p<0.01), posteromedial reach (r=0.498, p<0.01)(r=0.577, p<0.01), and posterolateral reach (r=0.294, p<0.05)(r=0.445, p<0.01) respectively. Similar relationships existed on the uninvolved side, but to a lesser extent. High and low performers on the YBT-LQ demonstrated lower and higher extension torque deficits, respectively. Conclusion While each test measures unique constructs, there are associations between components of the tests. In the ACLR population, both the YBT-LQ and isokinetic strength testing can expose asymmetries and impact return to play decision making. Level of evidence 2b.
The Demography of Sexuality and the Labor Market

As of June 2012, 21 states, Washington, D.C., and many localities prohibit discrimination in employment on the basis of sexual orientation. In the majority of U.S. jurisdictions, however, employment decisions based on sexual orientation are not subject to state or local legal restrictions. And, although previously proposed, no federal law exists that prohibits discrimination on the basis of sexual orientation for hiring, promotion, compensation, or termination decisions. Sexual minorities are consequently legally vulnerable in most of the United States.
The Utility of Nomograms in Routine Clinical Practice

Despite significant advances in our understanding and treatment of prostate cancer, there remains much that is unknown about its tumor biology and natural history. Physicians and patients must therefore rely upon estimates of relevant clinical outcomes when making medical decisions. Historically, physician judgment has formed the foundation of outcomes prediction. However, this method of prediction is inherently biased and unable to account for the complexity of prostate cancer. In contemporary practice, prediction tools that are based on statistical models incorporating multiple prognostic variables offer far more accurate means of estimating outcomes. Nomograms in particular have gained favor among clinicians due to greater accuracy, ease of use, and their ability to generate outcomes tailored to the individual patient. In this chapter, we discuss the integral role of outcomes prediction in prostate cancer and how nomograms can facilitate decision-making at various clinical states of disease.
Amino acid uptake inAcetabularia

1. Acetabularia accumulated radiolabeled amino acids added to sterile Erd-Schreiber medium. This occured with a variety of amino acids: monoaminomonocarboxylic (glycine), diaminodicarboxylic (L-cystine), monoaminodicarboxylic (L-glutamic acid), diaminomonocarboxylic (L-arginine), and an imino acid (L-proline). 2. After correction for the protein-bound fraction, there was still a considerable quantity of “free” radiolabeled amino acid withinAcetabularia. Additional evidence for the active transport of glycine included a marked temperature dependence as well as sensitivity to-10−3 M cyanide. 3. For at least 21 days following enucleation ofAcetabularia, there was no diminution in glycine transport. Actinomycin D (50 μ/ml) had a minimal effect on transport (7% inhibition). These results suggest that amino acid transport byAcetabularia is either an extranuclear event, or that the nuclear information, once impressed on the organism, has a long persistence.
Flux Connections Between Gluconate Pathway, Glycolysis, and Pentose–Phosphate Pathway During Carbohydrate Metabolism in Bacillus megaterium QM B1551

Bacillus megaterium is a bacterium of great importance as a plant-beneficial bacterium in agricultural applications and in industrial bioproduction of proteins. Understanding intracellular processing of carbohydrates in this species is crucial to predicting natural carbon utilization as well as informing strategies in metabolic engineering. Here, we applied stable isotope-assisted metabolomics profiling and metabolic flux analysis to elucidate, at high resolution, the connections of the different catabolic routes for carbohydrate metabolism immediately following substrate uptake in B. megaterium QM B1551. We performed multiple 13C tracer experiments to obtain both kinetic and long-term 13C profiling of intracellular metabolites. In addition to the direct phosphorylation of glucose to glucose-6-phosphate (G6P) prior to oxidation to 6-phosphogluconate (6P-gluconate), the labeling data also captured glucose catabolism through the gluconate pathway involving glucose oxidation to gluconate followed by phosphorylation to 6P-gluconate. Our data further confirmed the absence of the Entner-Doudoroff pathway in B. megaterium and showed that subsequent catabolism of 6P-gluconate was instead through the oxidative pentose-phosphate (PP) pathway. Quantitative flux analysis of glucose-grown cells showed equal partition of consumed glucose from G6P to the Embden-Meyerhof-Parnas (EMP) pathway and from G6P to the PP pathway through 6P-gluconate. Growth on fructose alone or xylose alone was consistent with the ability of B. megaterium to use each substrate as a sole source of carbon. However, a detailed 13C mapping during simultaneous feeding of B. megaterium on glucose, fructose, and xylose indicated non-uniform intracellular investment of the different carbohydrate substrates. Flux of glucose-derived carbons dominated the gluconate pathway and the PP pathway, whereas carbon flux from both glucose and fructose populated the EMP pathway; there was no assimilatory flux of xylose-derived carbons. Collectively, our findings provide new quantitative insights on the contribution of the different catabolic routes involved in initiating carbohydrate catabolism in B. megaterium and related Bacillus species.
Improving the Charge/Discharge Efficiency and Dielectric Breakdown in High Temperature Polymer Dielectrics

Dielectric polymers which can operate at high temperature (> 150 °C) and high electric fields with high performance such as high charge/discharge efficiency and dielectric strength are required for many capacitor applications including energy storage and electric insulators. These dielectric performances are controlled directly by charge injection and conduction at high fields and high temperature. Nanoparticles, through interfacial effects, can markedly influence dielectric properties of the matrix. Here we report a research on a significantly enhanced charge/discharge efficiency in high glass transition temperature polymer, i. e. polymers in PEEK family by doping with very small amount of nanoparticles. The presence of nanoparticles reduces the leakage current of the polymer matrix in the conditions of high electric field and high temperature. Our results demonstrate a practicable way to enhance the performance of polymer-based capacitors working at high temperature and high electric field.
Interleukin-6 Therapy Improves Intestinal Recovery Following Ischemia.

Abstract Background Interleukin-6 (IL6) has both proinflammatory and anti-inflammatory pathways, but its effects on intestinal recovery following ischemia are unknown. We hypothesized that administration of IL6 following intestinal ischemia would improve mesenteric perfusion and mucosal injury. Methods Adult male C57Bl6J mice were anesthetized, and a laparotomy was performed. Baseline intestinal perfusion was assessed by laser Doppler imaging. Intestinal ischemia was induced for 60 min by temporarily occluding the superior mesenteric artery. After ischemia, treatments were administered intraperitoneally before closure (Vehicle: 250 μL phosphate-buffered-saline, IL6 low dose (20 ng), IL6 medium dose (200 ng), or IL6 high dose (2 μg)). Animals were allowed to recover for 24 h, were reanesthetized, and their mesenteric perfusion was reassessed. Perfusion was expressed as percentage of baseline. Animals were then sacrificed, and the intestines were explanted for histological analysis. Separate frozen samples were homogenized and analyzed by ELISA for vascular endothelial growth factor (VEGF) and interferon gamma-induced protein 10. Results IL6 increased mesenteric perfusion in low dose groups only, whereas it improved postischemic mucosal injury scores in both low and medium dose groups. No differences in perfusion or histology were seen when high dose IL6 was utilized. Intestinal VEGF was higher in the low dose IL6 group compared to vehicle, whereas IP-10 levels were lower in low and medium dose groups compared to vehicle. No differences were noted compared to vehicle in intestinal VEGF and IP-10 with high dose IL6 therapy. Conclusions Lower doses of IL6 may serve as effective therapy to decrease intestinal injury after ischemia. Further studies are needed to elucidate the downstream mechanisms before widespread clinical use.
“Sure, I Voted for the Winner!” Overreport of the Primary Vote for the Party Nominee in the National Election Studies

Misreport is a serious problem because inaccurate data may lead to erroneous substantive conclusions. This study examines the systematic misreport for the eventual presidential nominee in the American National Election Studies (ANES) presidential primary vote question. Using various data sources, this study demonstrates that misreport in presidential primaries is a serious problem leading to possible misinterpretation of the negative carryover hypothesis. Misreport also may be a product of time of interview. Earlier interviewing may help to solve part of the misreport problem.
Moiré-pattern fluctuations and electron-phason coupling in twisted bilayer graphene

In twisted bilayer graphene, long-wavelength lattice fluctuations on the scale of the moir\'e period are dominated by phason modes, i.e., acoustic branches of the incommensurate lattice resulting from coherent superpositions of optical phonons. In the limit of small twist angles, these modes describe the sliding motion of stacking domain walls separating regions of partial commensuration. The resulting soliton network is a soft elastic manifold, whose reduced rigidity arises from the competition between intralayer (elastic) and interlayer (adhesion) forces governing lattice relaxation. Shear deformations of the beating pattern dominate the electron-phason coupling to the leading order in ${t}_{\ensuremath{\perp}}/t$, the ratio between interlayer and intralayer hopping parameters. This coupling lifts the layer degeneracy of the Dirac cones at the corners of the moir\'e Brillouin zone, which could explain the observed fourfold (instead of eightfold) Landau level degeneracy. Electron-phason scattering gives rise to a linear-in-temperature contribution to the resistivity that increases with decreasing twist angle due to the reduction of the stiffness of the soliton network. This contribution alone, however, seems to be insufficient to explain the huge enhancement of the resistivity of the normal state close to the magic angle.
The Creation of a Low-cost Raspberry Pi Cluster for Teaching

Parallel programming is a computing model in which the computations are run on multiple processors simultaneously. In order to teach or learn parallel computing, there is a need for a computer system on which parallel programs can be executed. One such computing system is cluster computer in which a group of individual computers networked together to run multiple processes concurrently. Providing step-by-step instructions on building a cluster computer using 20 Raspberry Pi 3s, this experience report describes a low-cost cluster for teaching parallel computing in the undergraduate and high-school computing classrooms. The main contribution of this report is the detailed explanation on the software configuration including MPI (Message Passing Interface) when setting up the cluster. The MPI library described in this paper is Open-MPI.
Identification of Potential Barriers to Timely Access to Pediatric Hearing Aids

Importance Despite various barriers identified to early pediatric access to cochlear implantation, barriers to timely access to pediatric hearing aids are not well characterized. Objective To identify socioeconomic, demographic, and clinical factors that may be associated with pediatric access to hearing aids. Design, Setting, and Participants This retrospective cohort study included 90 patients aged 1 to 15 years who were referred for auditory brainstem response (ABR) testing and evaluation for hearing aids at a single tertiary care academic medical center from March 2004 to July 2018. Children who did not receive both ABR testing and hearing aids at the same center were excluded from analysis. Main Outcomes and Measures Associations of insurance type (private vs public), race/ethnicity (white vs other), primary language (English vs other), cause of hearing loss (complex vs not complex), zip code, hearing aid manufacturer, and severity of hearing loss (in decibels) with the duration of intervals from newborn hearing screening to ABR testing, from ABR testing to ordering of hearing aids, and from ABR testing to dispensing of hearing aids. Results Of the 90 patients, mean (SD) age was 5.6 (3.7) years, 56% were female, and 77 (86%) were non-Hispanic. Results of χ2tests indicated significant assocations existed between public insurance and race/ethnicity and between public insurance and primary language other than English. Variables associated with the interval from newborn hearing screening to ABR testing included insurance type (mean difference, 7.4 months; 95% CI, 2.6-12.2 months) and race/ethnicity (mean difference, 6.9 months; 95% CI, 2.7-11.1 months). Increased delays between birth and a child’s first ABR test were associated with public insurance (mean difference, 6.0 months; 95% CI, 1.8-10.2 months) and race/ethnicity other than white (mean difference, 6.0 months; 95% CI, 2.3-9.7 months). The mean time from birth to initial ABR testing was a mean of 6 months longer for patients from non–English-speaking families than for those from English-speaking families (mean [SD] interval, 14.9 [16.3] months vs 9.0 [8.5] months), although the difference was not statistically significant. Severity of hearing loss was associated with a decrease in the interval from ABR testing to ordering of hearing aids after accounting for other potential barriers (odds ratio, 0.6; 95% CI, 0.4-0.9). Zip code and complexity of the child’s medical condition did not appear to be associated with timely access to pediatric hearing aids. Conclusions and Relevance This study’s findings suggest that insurance type, race/ethnicity, and primary language may be barriers associated with pediatric access to hearing aids, with the greatest difference observed in time to initial ABR testing. Clinical severity of hearing loss appeared to be associated with a significant decrease in time from ABR testing to ordering of hearing aids. Greater efforts to assist parents with ABR testing and coordination of follow-up may help improve access for other at-risk children.
Constructing Cause Lawyering: Professionalism, Politics, & Social Change in 1960s America

Prior to 1969 a mere fifteen legal organizations devoted themselves to serving the causes of civil rights, civil liberties, and the needs of poor people. By 1975 that number had jumped to more than eighty.This "explosion" of explicitly activist lawyering marked a significant change in the composition of the American legal profession. More importantly, these lawyers shaped American social movements and politics in the era. Though it has long been understood that lawyers played a role in the upheavals in American society of the 1960s, no study has attempted to bring the many pieces together and set it within the historiography of the era. This dissertation thus sets the role of lawyers in a broad historical context, showing the ways in which the 1960s both shaped and were shaped by "cause" lawyering. In uncovering this history, the dissertation argues that one cannot simply understand "cause" lawyering as a single category of professional action. Rather, part of the struggle within the profession centered on the question of what type of cause lawyering was acceptable. Thanks to a variety of forces, both internal and external to the profession -- including social movements, philanthropic foundations, and changes in political alignment and philosophy -- lawyering that featured elite-led, court-based strategies thrived and survived while lawyering that deemphasized the importance of lawyers and litigation withered. Individual chapters explore the Supreme Court case of NAACP v. Button, lawyering during the direct action phase of the southern civil rights movement, the growth and collapse of the federally-funded Legal Services Program, radical lawyering and the anti-war movement, and the development of "public interest" lawyering for environmental, consumer, and government accountability causes.
Breast and cervical cancer screening disparities among transgender patients.

7024Background: Over a million Americans identify themselves as transgender and this population is growing. Transgender status was a pre-existing condition prior to the Affordable Care Act (ACA), a...
Appraising research on personalized learning: Definitions, theoretical alignment, advancements, and future directions

This article introduces a special issue comprising research on efforts to personalize learning in different academic subjects. We first consider the emergence of personalized learning (PL) and the ...
Comparison of three scoring methods using the FDA-approved 22C3 immunohistochemistry assay to evaluate PD-L1 expression in breast cancer and their association with clinicopathologic factors

In the evaluation of PD-L1 expression to select patients for anti-PD-1/PD-L1 treatment, uniform guidelines that account for different immunohistochemistry assays, different cell types and different cutoff values across tumor types are lacking. Data on how different scoring methods compare in breast cancer are scant. Using FDA-approved 22C3 diagnostic immunohistochemistry assay, we retrospectively evaluated PD-L1 expression in 496 primary invasive breast tumors that were not exposed to anti-PD-1/PD-L1 treatment and compared three scoring methods (TC: invasive tumor cells; IC: tumor-infiltrating immune cells; TCIC: a combination of tumor cells and immune cells) in expression frequency and association with clinicopathologic factors. In the entire cohort, positive PD-L1 expression was observed in 20% of patients by TCIC, 16% by IC, and 10% by TC, with a concordance of 87% between the three methods. In the triple-negative breast cancer patients, positive PD-L1 expression was observed in 35% by TCIC, 31% by IC, and 16% by TC, with a concordance of 76%. Associations between PD-L1 and clinicopathologic factors were investigated according to receptor groups and whether the patients had received neoadjuvant chemotherapy. The three scoring methods showed differences in their associations with clinicopathologic factors in all subgroups studied. Positive PD-L1 expression by IC was significantly associated with worse overall survival in patients with neoadjuvant chemotherapy and showed a trend for worse overall survival and distant metastasis-free survival in triple-negative patients with neoadjuvant chemotherapy. Positive PD-L1 expression by TCIC and TC also showed trends for worse survival in different subgroups. Our findings indicate that the three scoring methods with a 1% cutoff are different in their sensitivity for PD-L1 expression and their associations with clinicopathologic factors. Scoring by TCIC is the most sensitive way to identify PD-L1-positive breast cancer by immunohistochemistry. As a prognostic marker, our study suggests that PD-L1 is associated with worse clinical outcome, most often shown by the IC score; however, the other scores may also have clinical implications in some subgroups. Large clinical trials are needed to test the similarities and differences of these scoring methods for their predictive values in anti-PD-1/PD-L1 therapy.
Rural-Urban Differences in Nursing Home Risk-adjusted Rates of Emergency Department Visits: A Decomposition Analysis.

BACKGROUND Higher risk-adjusted rate of emergency department (ED) visits might reflect poor quality of nursing home (NH) care; however, existing evidence is limited regarding rural-urban differences in ED rates of NHs, especially for long-stay residents. OBJECTIVES To determine and quantify sources of rural-urban differences in NH risk-adjusted rates of any ED visit, ED without hospitalization or observation stay (outpatient ED), and potentially avoidable ED visits (PAED) of long-stay residents. RESEARCH DESIGN We calculated quarterly NH risk-adjusted rates using 2011-2013 national Medicare claims and Minimum Data Set 3.0, and then implemented Generalized Estimating Equation models to examine rural-urban differences in ED rates and Blinder-Oaxaca decomposition to quantify the contributions of NH and market factors. SUBJECTS Privately owned, free-standing NHs in the United States (N=13,260). RESULTS Over the study period, risk-adjusted rates averaged 9.8% for any ED, 3.3% for outpatient ED, and 3.2% for PAED. Compared with urban NHs, rural NHs were associated with significantly lower rates of any ED, outpatient ED, and PAED (β=-1.67%, -0.44%, and -0.28%; all P<0.01). Observable differences in market factors (nursing home bed concentration, hospital beds, and the existence of a critical access hospital) explained about half of the rural-urban differences in rates of any ED and PAED, but not outpatient ED. CONCLUSIONS Decomposition analyses suggested that lower ED rates in rural NHs appear to be related to market availability of hospital resources. Policymakers may focus on not only reducing unnecessary ED visits but also ensuring equitable hospital access in rural areas.
Consensus on simplicial complexes: Results on stability and synchronization

We consider a nonlinear flow on simplicial complexes related to the simplicial Laplacian and show that it is a generalization of various consensus and synchronization models commonly studied on networks. In particular, our model allows us to formulate flows on simplices of any dimension so that it includes edge flows, triangle flows, etc. We show that the system can be represented as the gradient flow of an energy functional and use this to deduce the stability of various steady states of the model. Finally, we demonstrate that our model contains higher-dimensional analogs of structures seen in related network models.
Effect of Postoperative Analgesic Exposure to the Cannabinoid Receptor Agonist WIN55 on Osteogenic Differentiation and Spinal Fusion in Rats.

Background After spinal surgery and other orthopaedic procedures, most patients receive opioids for pain, leading to potential complications such as pseudarthrosis and opioid abuse associated with long-term use. As an alternative, the endocannabinoid system has been shown to have antinociceptive activity, while contributing to bone homeostasis via the CB1 and CB2 cannabinoid receptors. This study evaluates the impact of the cannabinoid receptor agonist WIN55,212-2 (WIN55) on osteogenic differentiation in vitro as well as bone regeneration and spinal fusion in a preclinical rat model. Methods Primary rat bone marrow stromal cells were cultured in standard or osteogenic media and exposed to vehicle alone or WIN55. Runx2 and Alkaline phosphatase (Alpl) were quantified via qPCR (quantitative real-time polymerase chain reaction), followed by assessment of ALP activity and matrix mineralization. For in vivo evaluation, 45 female Sprague Dawley rats (n = 15 per group) underwent L4-L5 posterolateral spinal fusion with bilateral placement of collagen scaffolds preloaded with low-dose rhBMP-2 (recombinant human bone morphogenetic protein-2; 0.5 μg/implant). Postoperatively, rats received the vehicle alone or 0.5 or 2.5 mg/kg WIN55 via daily intraperitoneal injections for 5 days. Bone regeneration and spinal fusion were assessed using radiography, manual palpation-based fusion scoring, microcomputed tomography imaging, and histology. Results mRNA expression levels of Runx2 and Alp were similar among cells treated with vehicle alone and WIN55. Likewise, exposure to WIN55 did not inhibit ALP activity or bone matrix mineralization. In this animal model, no significant differences were found among groups with regard to mean fusion score, fusion rate, or new bone volume. Conclusions WIN55 showed no adverse impact on osteogenic differentiation, bone regeneration, and spinal fusion. This supports that cannabinoid receptor agonists should be further investigated as a potential alternative approach for postoperative analgesia following spinal fusion and other orthopaedic procedures requiring bone-healing. Clinical relevance The identification of alternative treatments for postoperative pain following orthopaedic surgical procedures is crucial in combating the ongoing opioid abuse crisis. The endocannabinoid system may represent a viable alternative target for addressing orthopaedic postoperative pain.
Flow-induced vibrations of a square prism free to oscillate in the cross-flow and inline directions

We study flow-induced vibrations of a square prism free to oscillate in two degrees of freedom (cross-flow (CF) and inline (IL)), and placed in flow at varying angles of attack, by measuring the prism's displacement and flow-induced forces in both degrees of freedom experimentally, and conducting hydrogen bubble visualizations, as well as bubble image velocimetry. At large angles of attack (where , the VIV response becomes negligible and elliptical trajectories are observed at higher reduced velocities. These elliptical trajectories then become four-lobe trajectories with amplitudes mainly in the CF direction at the lowest angles of attack (where a side of the square sees the flow first) and galloping-type response is observed, where the amplitude of oscillations is increased with increasing reduced velocity. Deviations from a typical galloping response are observed due to synchronizations between the shedding frequency and oscillation frequency at ranges of higher reduced velocities.
Denaturalizing the Lawyer-Statesman (Book Review)

Anthony Kronman's new book, The Lost Lawyer: Failing Ideals of the Legal Profession, is an eloquent and impassioned work of scholarship. It makes an important contribution to the growing body of literature devoted to the study of the legal profession. Indeed, at first sight, it presents claims that carry significant empirical and normative appeal. Yet, this appeal quickly wanes, leaving troubling Aristotelian claims of elite lawyer tradition-bound wisdom in judgment. This essay follows the structure of Kronman's main claims. Part I examines practical wisdom in the context of counseling, advocacy, and judging. Part II analyzes prudentialism in the setting of legal education and scholarship. Part Ill assesses craft and public service in the circumstances of large-firm corporate law practice.
Indium Phosphide (InP)

Publisher Summary It is observed that the index of refraction of Indium Phosphide (InP) is reported over a wide range of photon energies, 1.2 meV to 20 eV. Various techniques are employed in these measurements, and there is an overlap in the data obtained from different sources. Cardona measures the reflectivity of InP in the 1-20-eV range. The sample surfaces are prepared by mechanical polishing with Linde A-5175 compound. The reflection spectra are measured and the samples are etched in a 1:1 solution of HNO3 and HCl to remove any damage and to improve the reflectivity. The reflection spectra are Kramers-Kronig (KK) analyzed. The 6-eV cutoff of Cardona's values of refractive index n and extinction coefficient k results from the availability of better measurements from 1.5 to 6 eV. Aspnes and Studna have obtained the optical constants of InP and of other semiconductors, through the use of spectroscopic ellipsometry.
Mammalian cells that express Bacillus cereus phosphatidylinositol-specific phospholipase C have increased levels of inositol cyclic 1:2-phosphate, inositol 1-phosphate, and inositol 2-phosphate.

Abstract Phosphatidylinositol-specific phospholipase C (PtdIns-PLC) of Bacillus cereus catalyzes the conversion of PtdIns to inositol cyclic 1:2-phosphate and diacylglycerol. NIH 3T3, Swiss mouse 3T3, CV-1, and Cos-7 cells were transfected with a cDNA encoding this enzyme, and the metabolic and cellular consequences were investigated. Overexpression of PtdIns-PLC enzyme activity was associated with elevated levels of inositol cyclic 1:2-phosphate (2.5-70-fold), inositol 1-phosphate (2-20-fold), and inositol 2-phosphate (3-20-fold). The increases correlated with the levels of enzyme expression obtained in each cell type. The turnover of phosphatidylinositol (PtdIns) was also increased in transfected CV-1 cells by 13-fold 20 h after transfection. The levels of PtdIns, phosphatidic acid, diacylglycerol, or other inositol phosphates were not detectably altered. Expression of bacterial PtdIns-PLC decreased rapidly after 20 h implying that either the increased PtdIns turnover or the accumulation of inositol phosphates was detrimental to cells and that by some adaptive mechanism enzyme expression was suppressed.
Coenzyme Interactions VI. PROPERTIES OF THE PYRIMIDINE MOIETY OF THIAMINE

Abstract A discrete proton magnetic resonance signal is observed for the amino protons of the pyrimidine moiety of thiamine in water from pH 0 to pH 9; the integrated area of this signal is indicative of only two protons, confirming that the NH2 group is not the site of protonation of the aminopyrimidine moiety. The chemical shift of the (C-4') —NH2 signal is pH dependent, changing approximately 1.6 ppm over the range pH 0 to pH 7. A plot of chemical shift versus pH describes a "titration curve" with an inflection point at pH 5, corresponding to the pK1 for protonation of the pyrimidine moiety. The chemical shifts of all the other signals in the spectrum of thiamine are affected much less by pH changes, but all, like the (C-4')—NH2 signal, show a linear dependence on the fraction of thiamine in the protonated form. In addition, the line width of the amino signal is pH dependent, and a detailed study of changes in line width under various conditions suggest three mechanisms of exchange of the NH2 protons: (a) specific acidic catalysis, K30°h+ = 6.8 x 102 m-1 sec-1; (b) general acid-base catalysis, K30°thiamine = 1.8 x 102 m-1 sec-1; K30°acetate = 3.3 x 102 m-1 sec-1; (c) specific basic catalysis, K30°oh- = 1.6 x 108 m-1 sec -1. The energy of activation of the amino proton exchange was found to be similar for specific catalysis by H+ and OH-, and general acid-base catalysis by thiamine and by acetate; Ea = 12.5 to 12.9 Kcal per mole. The changes in width of the water signal were qualitatively similar to those of the thiamine (C-4')—NH2 signal. H-D exchange at the C-2 atom of the thiazolium ring proceeds approximately 10 times faster in the case of thiamine than in the case of oxythiamine, over the range of pH 3 to 6. The pK1 value for thiamine is lowered approximately 0.5 unit by complex formation with tryptophol in 50% methanol-water. Determination of apparent association constant for the 1:1 complex from potentiometric titration data (ΔpK) agreed with the value calculated from proton magnetic resonance data (Δδ), Kassoc = 1.5 m-1.
Evaluation of the deoxyuridine suppression test by using whole blood samples from folic acid-supplemented subjects

We performed the deoxyuridine suppression test (dUST) along with assessment of folate and vitamin B-12 status in blood specimens from 136 normal women and 109 women with cervical dysplasia. All tests were repeated at 2, 4, and 6 mo in subjects with dysplasia during a randomized, double-blind intervention trial in which 50 received a 10-mg daily oral folic acid supplement (F group) and 59 received a placebo (P group). Median folate concentration increased fivefold in plasma and threefold in erythrocytes of F group beginning at the second months and remained elevated whereas concentrations of the P group remained unchanged. Vitamin B-12 values did not vary significantly in either group. The dUST value decreased from 10.4 +/- 4.6% (means +/- SD) pretreatment to 4.5 +/- 4.7% in F group after 2 mo (p less than 0.001). The dUST values had significant negative correlation with plasma and erythrocyte folate concentrations. However, erythrocyte folate had the greatest power to distinguish P group from F group.
On anelliptic approximations for qP velocities in transversely isotropic and orthorhombic media

ABSTRACTAnelliptic approximations for phase and group velocities of qP waves in transversely isotropic (TI) media have been widely applied in various seismic data processing and imaging tasks. We have revisited previously proposed approximations and suggested two improvements. The first improvement involves finding an empirical connection between anelliptic parameters along different fitting axes based on laboratory measurements of anisotropy of rock samples of different types. The relationship between anelliptic parameters observed was strongly linear suggesting a novel set of anisotropic parameters suitable for the study of qP-wave signatures. The second improvement involves suggesting a new functional form for the anelliptic parameter term to achieve better fitting along the horizontal axis. These modifications led to improved three-parameter and four-parameter approximations for phase and group velocities of qP-waves in TI media. In several model comparisons, the new three-parameter approximations app...
Neonatal Magnetic Resonance Imaging Pattern of Brain Injury as a Biomarker of Childhood Outcomes following a Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy

Objective To examine the ability of magnetic resonance imaging (MRI) patterns of neonatal brain injury defined by the National Institute of Child Health and Human Development Neonatal Research Network to predict death or IQ at 6-7 years of age following hypothermia for neonatal encephalopathy. Study design Out of 208 participants, 124 had MRI and primary outcome (death or IQ Results Death or IQ P Conclusions The Neonatal Research Network MRI pattern of neonatal brain injury is a biomarker of neurodevelopmental outcome at 6-7 years of age. Trial registration ClinicalTrials.gov: NCT00005772.
The reaming of life: based on the 2010 Jim Gray eScience Award Lecture

SUMMARY We are well into the era of data intensive-digital scientific discovery, an era defined by Jim Gray as the Fourth Paradigm. From my own perspective of the life sciences, much has been accomplished, but there is much to do if we are to maximize our understanding of biological systems given the data we have today, let alone what is coming. In my 2010 Jim Gray eScience Award Lecture, I gave my own thoughts on what needs to be accomplished, and with an additional year of hindsight, I expand on that here. Copyright © 2012 John Wiley & Sons, Ltd.
Biomedical System Dynamics to Improve Anemia Control With Darbepoetin Alfa in Long-Term Hemodialysis Patients

Abstract Objective To determine the value of a biomedical system dynamics (BMSD) approach for optimization of anemia management in long-term hemodialysis patients because elevated hemoglobin levels and high doses of erythropoiesis-stimulating agents (ESAs) may negatively affect survival in this population. Patients and Methods A model of erythropoiesis and its response to ESAs on the basis of a BMSD method (Mayo Clinic Anemia Management System [MCAMS]) was developed. Thereafter, an open-label, prospective, nonrandomized practice quality improvement project was performed with retrospective analysis in 8 community-based outpatient hemodialysis facilities. All prevalent hemodialysis patients seen from January 1, 2007, through December 31, 2010 (300-342 patients per month), were included with darbepoetin as the ESA. The primary outcome was the percentage of patients who attained the desired hemoglobin level. Secondary outcome measures included the percentage of patients with hemoglobin values above the desired range and mean dose of darbepoetin used. Results The 3 treatment periods were (1) standard ESA protocol in 2007, (2) transition to the MCAMS (2008 to June 2009), and (3) stability period with the MCAMS used in all hemodialysis facilities (2009 to 2010). In the first 6 months of 2007, 69% of patients were in the desired range and 26% were above the range. In comparison, during the first 5 months of 2010, 83% were in and 6% were above the range ( P P Conclusion With the introduction of the MCAMS, more patients had hemoglobin levels in the desired range and fewer patients exceeded the target range, with a concomitant 40% reduction in darbepoetin use.