cssi/SciSciGPT-SciSciNet huggingface dataset:
Race influences survival in glioblastoma patients with KPS ≥ 80 and associates with genetic markers of retinoic acid metabolism.

To study whether the clinical outcome and molecular biology of gliomas in African-American patients fundamentally differ from those occurring in Whites. The clinical information and molecular profiles (including gene expression array, non-silent somatic mutation, DNA methylation and protein expression) were downloaded from The Cancer genome atlas (TCGA). Electronic medical records were abstracted from Northwestern Medicine Enterprise Data Warehouse (NMEDW) for analysis as well. Grade II–IV Glioma patients were all included. 931 Whites and 64 African-American glioma patients from TCGA were analyzed. African-American with Karnofsky performance score (KPS) ≥ 80 have significantly lower risk of death than similar white Grade IV Glioblastoma (GBM) patients [HR (95% CI) = 0.47 (0.23, 0.98), P = 0.0444, C-index = 0.68]. Therefore, we further compared gene expression profiles between African-American GBM patients and Whites with KPS ≥ 80. Extrapolation of genes significantly associated with increased African-American patient survival revealed a set of 13 genes with a possible role in this association, including elevated expression of genes previously identified as increased in African-American breast and colon cancer patients (e.g. CRYBB2). Furthermore, gene set enrichment analysis revealed retinoic acid (RA) metabolism as a pathway significantly upregulated in African-American GBM patients who survive longer than Whites (Z-score = − 2.10, Adjusted P-value = 0.0449). African Americans have prolonged survival with glioma which is influenced only by initial KPS score. Genes previously associated with both racial disparities in cancer and pathways associated with RA metabolism may play an important role in glioma etiology. In the future exploration of these genes and pathways may inform novel therapies for this incurable disease.
Synaptic retinoic acid receptor signaling mediates mTOR-dependent metaplasticity that controls hippocampal learning

Homeostatic synaptic plasticity is a stabilizing mechanism engaged by neural circuits in response to prolonged perturbation of network activity. The non-Hebbian nature of homeostatic synaptic plasticity is thought to contribute to network stability by preventing "runaway" Hebbian plasticity at individual synapses. However, whether blocking homeostatic synaptic plasticity indeed induces runaway Hebbian plasticity in an intact neural circuit has not been explored. Furthermore, how compromised homeostatic synaptic plasticity impacts animal learning remains unclear. Here, we show in mice that the experience of an enriched environment (EE) engaged homeostatic synaptic plasticity in hippocampal circuits, thereby reducing excitatory synaptic transmission. This process required RARα, a nuclear retinoic acid receptor that doubles as a cytoplasmic retinoic acid-induced postsynaptic regulator of protein synthesis. Blocking RARα-dependent homeostatic synaptic plasticity during an EE experience by ablating RARα signaling induced runaway Hebbian plasticity, as evidenced by greatly enhanced long-term potentiation (LTP). As a consequence, RARα deletion in hippocampal circuits during an EE experience resulted in enhanced spatial learning but suppressed learning flexibility. In the absence of RARα, moreover, EE experience superactivated mammalian target of rapamycin (mTOR) signaling, causing a shift in protein translation that enhanced the expression levels of AMPA-type glutamate receptors. Treatment of mice with the mTOR inhibitor rapamycin during an EE experience not only restored normal AMPA-receptor expression levels but also reversed the increases in runaway Hebbian plasticity and learning after hippocampal RARα deletion. Thus, our findings reveal an RARα- and mTOR-dependent mechanism by which homeostatic plasticity controls Hebbian plasticity and learning.
The Role of Adenosine Monophosphate Activated Protein Kinase Alpha 1 (AMPK) in Gamma-Globin Regulation

Abstract Background: Fetal hemoglobin (HbF, α2g2) induction has long been an area of investigation, as it is known to reduce the clinical complications of sickle cell disease (SCD) and beta thalassemia. Progress in identifying novel HbF inducing strategies has been stymied by an incomplete understanding of gamma-globin regulation. We used natural genetic variation to identify novel genes and pathways associated with HbF levels in patients with SCD. Our whole exome sequencing analysis of 1290 samples from patients with SCD identified the insulin signaling pathway to be related to HbF regulation. Functional studies performed in hematopoietic stem and progenitor cells (HSPCs) from patients with SCD established that FOXO3 is a positive regulator of HbF, and that metformin, a FOXO3 and AMPK activator, can induce HbF (Zhang et al, Blood 2018). We hypothesized that other proteins in the insulin signaling pathway, particularly AMPK, a direct activator of FOXO3, may contribute to HbF regulation and be a potential target for pharmacologic induction of HbF. Objectives: We now seek to determine the role of AMPK and AMPK activators such as piceatannol in HbF regulation through functional studies in HSPCs from patients with SCD. Methods: HSPCs from 3 unique patients with SCD were transduced with AMPK shRNA on day 5 of two phase primary erythroid culture. AMPK, FOXO3, gamma and beta globin gene expression were measured by RT-qPCR and HbF by HPLC respectively on day 14 of culture. HSPCs from 3 unique patients with SCD were treated with AICAR, piceatannol at 12.5µM and metformin at 100 µM on day 7 of erythroid culture. Cell lysate was collected on day 14, and AMPK, FOXO3, gamma and beta globin gene expression and protein levels measured by RT-qPCR and western blot respectively. Levels of pAMPK, at Thr172, were quantified by western blot. 1 µM Compound C was added with piceatannol and with metformin in separate erythroid cultures on day 7, and the effect on gamma globin and phosphorylation of AMPK at Thr172 was measured on day 14 by RT-qPCR and western blot respectively. Results: 70% knockdown of AMPK resulted in a 50% decrease in HbF (p Conclusions: Knockdown of AMPK in HSPCs reduces gamma globin expression and %HbF, supporting the role of AMPK in gamma globin regulation. Drugs known to activate AMPK, metformin and piceatannol, increase gamma globin in SCD patient derived HSPCs. Pharmacologic blockage of AMPK activity with Compound C results in reduction of HbF induction, and reduces the gamma globin induction of metformin and piceatannol to untreated levels. We therefore conclude that AMPK is a positive regulator of HbF, and that pharmacologic induction of HbF with metformin and piceatannol requires AMPK activity. Further work is needed to establish if FOXO3 and AMPK alone are instrumental in HbF regulation, or if other proteins in the insulin signaling pathway may play a role in HbF regulation. Download : Download high-res image (141KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.
Demonstration of Ranking Issues for Students: A Case Study.

This article uses a case study of 2001 town and city data that we analyzed for Boston Magazine. We use this case study to demonstrate the challenges of creating a valid ranking structure. The data ...
Application of differential mobility-mass spectrometry for untargeted human plasma metabolomic analysis

Differential mobility spectrometry (DMS) has been gaining popularity in small molecule analysis over the last few years due to its selectivity towards a variety of isomeric compounds. While DMS has been utilized in targeted liquid chromatography-mass spectrometry (LC-MS), its use in untargeted discovery workflows has not been systematically explored. In this contribution, we propose a novel workflow for untargeted metabolomics based solely on DMS separation in a clinically relevant chronic kidney disease (CKD) patient population. We analyzed ten plasma samples from early- and late-stage CKD patients. Peak finding, alignment, and filtering steps performed on the DMS-MS data yielded a list of 881 metabolic features (unique mass-to-charge and migration time combinations). Differential analysis by CKD patient group revealed three main features of interest. One of them was putatively identified as bilirubin based on high-accuracy MS data and comparison of its optimum compensation voltage (COV) with that of an authentic standard. The DMS-MS analysis was four times faster than a typical HPLC-MS run, which suggests a potential for the utilization of this technique in screening studies. However, its lower separation efficiency and reduced signal intensity make it less suitable for low-abundant features. Fewer features were detected by the DMS-based platform compared with an HPLC-MS-based approach, but importantly, the two approaches resulted in different features. This indicates a high degree of orthogonality between HPLC- and DMS-based approaches and demonstrates the need for larger studies comparing the two techniques. The workflow described here can be adapted for other areas of metabolomics and has a value as a prescreening method to develop semi-targeted workflows and as a faster alternative to HPLC in large biomedical studies.
Measuring Nursing Workload in an Intensive Care Unit Using NGOMSL Model

The purpose of this study is to understand the impact on nursing workload due to patient severity and nurse experience by using Natural GOMS Language (NGOMSL) model. To develop the model, a time and motion study was conducted using a real-time location system. After that, the nurse’s location and time data were used to develop multiple hierarchical task analysis charts. These HTA charts were used to create the NGOMSL model and identified the ICU nurse’s workflow patterns. The analysis results from the NGOMSL model showed that the patient severity and the nurse’s experience had significant impacts on nurse’s workload for in-room patient care activities, out of room activities, peer support, and talking to other healthcare professionals. This research empirically demonstrates that patient severity and nurse’s experience significantly influenced the nursing workload in an intensive care unit, and the NGOMSL model could measure the workload.
Global List and Interactive Web Map of University-Based Hazards and Disaster Research Centers

AbstractThis paper describes a novel data set and an accompanying online listing and interactive web map that displays university-based hazards and disaster research centers globally. To date, this...
Effects of a naturalistic intervention on the speech outcomes of young children with cleft palate

Purpose: The purpose of this study was to investigate the extent to which a naturalistic communication intervention, Enhanced Milieu Teaching with Phonological Emphasis (EMT + PE) improved the spee...
Using helicity to investigate scalar transport in wall turbulence

Since flow regions of high helicity are associated with low dissipation of kinetic energy, helicity can be used to mark the flow structures that are major contributors to turbulent scalar dispersion. Employing a Lagrangian approach to compare the helicity between scalar tracers and fluid particles in the same flow field shows that flow structures that contribute to the transport of low Schmidt number markers are different than those for fluid particles. This is quite important in anisotropic wall turbulence, where the interplay between molecular and turbulent transport is critical.
Developmental data for several human mitochondrial DNA (mtDNA) long amplification targets.

Abstract Candidate long mtDNA targets ∼300 bp in length were identified on the revised Cambridge mtDNA reference sequence using Primer Express software (Applied Biosystems) with modified default analysis settings. The primer and hydrolysis probe sequences for the resultant three (3) targets were queried in the Mitomap database [1] to avoid common single nucleotide polymorphisms (SNPs) which, if present in a sample, could reduce binding to template and therefore result in inefficient amplification. Primers and probes identified by Primer Express, some synthesized degenerate to mitigate the presence of certain SNPs, were utilized in a Fast Advanced Master Mix (Applied Biosystems) reaction which was amplified on a 7500 Real Time PCR System using HID Real Time PCR Software v1.2 (Applied Biosystems) to collect and analyze the qPCR data. QPCR reaction conditions and software analysis settings were optimized and modified to yield efficient amplification and robust results. QPCR experiments were exported into Excel (Microsoft Corp.) for additional analyses and evaluation. The data was used to develop a triplex qPCR method, which includes amplification of one of the long targets, to quantify and assess degradation of human mtDNA, the results of which were previously published [2] . That triplex method also incorporated an internal positive control to test for the presence of amplification inhibitors in the sample [3] . The data presented herein may be used to develop alternative amplification methods for user-specific biomedical applications.
Investigating hierarchical effects of adaptive signal control system on crash severity using random-parameter ordered regression models incorporating observed heterogeneity.

Abstract By handling conflicting traffic movements and establishing dynamic coordination between intersections in real-time, the Adaptive Signal Control System (ASCS) can potentially improve the operation and safety of signalized intersections on a corridor. This study identifies the hierarchical effects of ASCS on the crash severity by exploring the heterogeneous effect of ASCS on the crash severity. Four different random-parameter ordered regression models (two ordered probit models, and two ordered logit models) are developed and compared. The analysis reveals that the random-parameter ordered probit and logit models (ROP and ROL) with observed heterogeneity perform better than the random-parameter ordered probit and logit models (RP and RL) without observed heterogeneity in terms of the Akaike information criteria and the goodness of fit of the model. The ROP model performs better than the ROL model in terms of classification model performance measures. The ROP model enables parameters (i.e., the coefficients of the explanatory variables) to vary as a function of explanatory variables as well as across observations, thus accounting for both observed (captured by available explanatory variables) and unobserved (not captured by available explanatory variables) heterogeneity. The analysis reveals that the presence of ASCS is associated with lower crash severity. In this study, observed heterogeneity of ASCS effects on the crash severity is captured by variables related to the intersection and corridor features. Other contributing factors besides ASCS, such as annual average daily traffic, speed limit, lighting, peak period, crash type (rear-end, angle), and pedestrian involvements, are also associated with the probability of crash severity. Unobserved heterogeneity of the effect of angle crash type on the crash severity is found to exist across the observations. The findings of this research have practical implications for establishing ASCS implementation guidelines in lowering the probability of higher crash severity.
Localized potential well vs binding site: Mapping solute dynamics in a membrane channel onto one-dimensional description

In the one-dimensional description, the interaction of a solute molecule with the channel wall is characterized by the potential of mean force U(x), where the x-coordinate is measured along the channel axis. When the molecule can reversibly bind to certain amino acid(s) of the protein forming the channel, this results in a localized well in the potential U(x). Alternatively, this binding can be modeled by introducing a discrete localized site, in addition to the continuum of states along x. Although both models may predict identical equilibrium distributions of the coordinate x, there is a fundamental difference between the two: in the first model, the molecule passing through the channel unavoidably visits the potential well, while in the latter, it may traverse the channel without being trapped at the discrete site. Here, we show that when the two models are parameterized to have the same thermodynamic properties, they automatically yield identical translocation probabilities and mean translocation times, yet they predict qualitatively different shapes of the translocation time distribution. Specifically, the potential well model yields a narrower distribution than the model with a discrete site, a difference that can be quantified by the distribution’s coefficient of variation. This coefficient turns out to be always smaller than unity in the potential well model, whereas it may exceed unity when a discrete trapping site is present. Analysis of the translocation time distribution beyond its mean thus offers a way to differentiate between distinct translocation mechanisms.
The costs of conflict

Abstract Violent conflict destroys resources. It generates “destruction costs.” These costs have an important effect on individuals’ decisions to cooperate or conflict. We develop two models of conflict: one in which conflict's destruction costs are independent of individuals’ investments in “arms”—the tools of conflict—and another in which conflict's destruction costs depend on those investments. Our models demonstrate that when conflict's destruction costs are arms-dependent, conflict is more costly, making cooperation more likely. We test this prediction with a laboratory experiment in which subjects first choose how heavily to invest in arms and then choose whether to cooperate or conflict in an environment where interaction is repeated. In one set of treatments conflict's destruction costs are arms-independent. In another they are arms-dependent. Our experimental results support our models’ predictions. Compared to when conflict's destruction costs are arms-independent, when those costs are arms-dependent, cooperation increases by nearly a third.
Fabrication of microcalcifications for insertion into phantoms used to evaluate x-ray breast imaging systems

Physical breast phantoms can be used to evaluate x-ray imaging systems such as mammography, digital breast tomosynthesis and dedicated breast computed tomography (bCT). These phantoms typically attempt to mimic x-ray attenuation properties of adipose and fibroglandular tissues within the breast. In order to use these phantoms for task-based objective assessment of image quality, relevant diagnostic features should be modeled within the phantom, such as mass lesions and/or microcalcifications. Evaluating imaging system performance in detecting microcalcifications is of particular interest due to its' clinical significance. Many previously-developed phantoms have used materials that model microcalcifications using unrealistic chemical composition, which do not accurately portray their desired x-ray attenuation and scatter properties. We report here on a new method for developing real microcalcification simulants that can be embedded in breast phantoms. This was achieved in several steps, including cross-linking hydroxyapatite and calcium oxalate powders with a binder called polyvinylpyrrolidone (PVP), and mechanical compression. The fabricated microcalcifications were evaluated by measuring their x-ray attenuation and scatter properties using x-ray spectroscopy and x-ray diffraction systems, respectively, and were demonstrated with x-ray mammography and bCT images. Results suggest that using these microcalcification models will make breast phantoms more realistic for use in evaluating task-based detection performance of the abovementioned breast imaging techniques, and bode well for extending their use to spectral imaging and x-ray coherent scatter computed tomography.
Fat3 Acts Through Independent Cytoskeletal Effectors to Coordinate Asymmetric Cell Behaviors During Polarized Circuit Assembly

The polarized flow of information through neural circuits depends on the orderly arrangement of neurons, their processes, and their synapses. This polarity emerges sequentially in development, starting with directed migration of neuronal precursors, which subsequently elaborate neurites that form synapses in specific locations. In other organs, Fat cadherins sense position and then polarize individual cells by inducing localized changes in the cytoskeleton that are coordinated across the tissue. Here, we show that the Fat-related protein Fat3 plays an analogous role during assembly of polarized circuits in the murine retina. We found that the Fat3 intracellular domain binds to cytoskeletal regulators and synaptic proteins, with discrete motifs required for amacrine cell migration and neurite retraction. Moreover, upon ICD deletion, extra neurites formed but did not make extra synapses, suggesting that Fat3 independently regulates synapse localization. Thus, Fat3 serves as a molecular node to coordinate asymmetric cell behaviors across development.
Anthocyanins in Leaves: Distribution, Phylogeny and Development

Abstract Red pigments, products of different metabolic pathways, occur in terrestrial plants. The flavonoid pathway contributes the greatest diversity, culminating in the prevalence of anthocyanins in the angiosperms. Anthocyanins are produced in flowers and fruits, and also in vegetative organs, but have been poorly researched in the latter. Anthocyanins are commonly produced in: 1. 1. rapidly expanding leaves of tropical plants; 2. 2. senescing leaves of temperate plants; 3. 3. undersurfaces of floating leaves of aquatic plants; 4. 4. abaxial surfaces of leaves of understory plants; and 5. 5. leaves subjected to various environmental stresses. The distribution of anthocyanins in leaves, both in presence and in tissue distribution, is influenced by both phylogeny and development. Few species produce anthocyanins in leaf tissues derived from both dermal and ground embryonic tissue. These influences will be important in resolving the ecological roles of anthocyanins in leaves.
Effect of exposure in steam or argon on the creep properties of Ni-based alloys: Creep properties of Ni-based alloys

Although expensive, Ni-based superalloys are of interest for the ultrasupercritical steam program because of their good creep and oxidation resistance at temperature above 700 C. However, the effect of steam oxidation on the alloy mechanical properties is unknown, and creep specimens of alloy CCA617, 740 and 230 were pre-oxidized for 2000 and 4000h in steam at 800 C before testing in air at the same temperature. Exposure in steam decreased the creep properties of alloy CCA617 compared with as fabricated material, had less of an effect on alloy 740, and did not affect alloy 230. Testing of a specimen repolished after steam exposure as well as microstructure observation indicate that the oxidation affected zone at the specimen surface is not responsible for the properties degradation. Surprisingly, a similar time anneal in an inert environment resulted in a drastic decrease of creep rupture life and an increase in the creep rate and elongation at rupture. TEM analysis revealed that the mechanical properties decrease for alloy CCA617 is related to the absence of precipitates in the grain.
Does aberrant membrane transport contribute to poor outcome in adult acute myeloid leukemia

Acute myeloid leukemia (AML) in adults is a highly heterogeneous disease. Gene expression profiling performed using unsupervised algorithms can be used to distinguish specific groups of patients within a large patient cohort. The identified gene expression signatures can offer insights into underlying physiological mechanisms of disease pathogenesis. Here, the analysis of several related gene expression clusters associated with poor outcome, worst overall survival and highest rates of resistant disease and obtained from the patients at the time of diagnosis or from previously untreated individuals is presented. Surprisingly, these gene clusters appear to be enriched for genes corresponding to proteins involved in transport across membranes (transporters, carriers and channels). Several ideas describing the possible relationship of membrane transport activity and leukemic cell biology, including the “Warburg effect”, the specific role of chloride ion transport, direct “import” of metabolic energy through uptake of creatine phosphate, and modification of the bone marrow niche microenvironment are discussed.
An Empirical Study of Remittances and Growth in the Developing World

At the microeconomic level, development is about analyzing the lives of the poor. How do citizens in the developing world live? How do they survive? While these important questions can be answered and studied in many ways, a common theme is surely about how they make a living. How much income do lower income countries have? Where do they get it from? Most importantly, how do they use it? This research paper concerns itself with the issue of how the less privileged parts of society procure the funds necessary to survive on a daily basis. Although wage labor, microfinancing, and government transfers undoubtedly play an important role, this paper will take up the issue of remittances and the role they play in developing countries. Remittances are the financial funds emigrants transfer back to their native countries. In other words, individuals who migrate to other countries often work abroad at higher wages and send a share of their wages back home to family members, friends, or business associates.
Interactive effects of social adversity and respiratory sinus arrhythmia activity on reactive and proactive aggression

Abnormal parasympathetic nervous system (PNS)-related cardiac activity has been linked to aggression. However, little is known about how it interacts with psychosocial adversity in predisposing to reactive-proactive aggression. In the current study, 84 male and female college students self-reported reactive and proactive aggression, and were assessed for respiratory sinus arrhythmia (RSA), a measure of PNS-related cardiac activity, during rest and when they contemplated an emotion-evoking decision-making task. Regression analyses showed that (a) resting RSA was positively linked to reactive aggression in conditions of high social adversity, and (b) RSA reactivity was positively associated with reactive but negatively associated with proactive aggression, in conditions of low social adversity. Main effects were not found for psychophysiological functioning or psychosocial adversity, suggesting the importance of their interaction. Findings support a biosocial basis for aggression and add additional support for the distinctions between reactive and proactive aggression.
GATEWAY TO KOREA: COLONIALISM, NATIONALISM, AND RECONSTRUCTING RUINS AS TOURIST LANDMARKS

This paper traces the evolution of the South Gate (Sungnye-mun) as a must-see destination representing the antiquity, beauty and patrimony of Seoul, the former capital of the 600 year-old Choson dynasty of Korea (1392-1910). Using the case study of the Republic of Korea's premier national treasure, this paper traces the preservation methods, educational, and commercial agendas of the producers, managers, and promoters of heritage remains. The earliest photographic records date back to the late nineteenth century when travel photo- graphs taken by stereo-view companies, photo-studios, and diplomats were recycled in newspapers, postcards, and guidebooks, giving foreigners the first glimpses into the “Hermit Kingdom.” The analysis relies on CRM archives such as photographs, guidebooks, architectural surveys, excavation reports, and material resources compiled by the Cultural Heritage Administration (CHA) during the five years of excavations and construction of a replica to replace the original destroyed in an arson fire in 2008. The paper concludes with the grand re-opening ceremony to celebrate not only the resurrection of South Gate but to showcase the successes of the government's centralized heritage management policies, and conservation methods dedicated to preserving the city's architectural heritage.
Building library collections: it's still about the user

Purpose – To address the need for dialogue between librarians, teachers and scholars in research institutions, as the information environment becomes increasingly complex.Design/methodology/approach – A discussion of the impact of technology, budgets and collection storage practices on library users and their research patterns; examination of the methodologies for assessing that impact and continuing to meet user needs in a changing environment.Findings – Despite trends toward shared collections and a library of access rather than ownership, it is still necessary to develop careful knowledge of one's patrons and to shape one's collections and services to meet local needs.Practical implications – Libraries must aggressively use focus groups, surveys and above all the personal relationship between faculty and library subject specialists to shape the development and management of their collections and the services they offer. These methods must shape not only one's title‐by‐title selection but one's larger, ...
Environmental effects on language development in normal and high-risk child populations.

This report describes language development from infancy through 8 years of life for a large sample of very low birth weight (VLBW) (high medical risk, n=94; low medical risk, n=132) and term (n=134) children. Children of high and low medical risk status showed lower levels and slower rates of development compared with term children. Although these children also showed nonverbal cognitive deficits, their language difficulties appeared to be independent of these general cognitive problems. Although lower socioeconomic status (SES) showed strong negative effects on rate of language development, this was comparable across the three risk groups. Within this generally lower SES sample of children, the type of interactive behaviors caregivers used in early childhood showed significant relations to skill growth. Children with faster rates of language growth had mothers who maintained their interests more often and were less likely to use highly directive behaviors.
Predicting workload requirements for scheduled health care services, with an application to radiology departments

Abstract A model is developed for predicting workload requirements for scheduled health care services. The model is then applied to an actual planning problem for a radiology department. The probability distribution of future workload is represented by the convolution of two families of random variables such that a compound Poisson process adequately describes workload requirements. The model developed herein can be applied to a wide assortment of capacity-expansion problems that are characterized by discrete demands (e.g. number of jobs) occurring in a given period of time, where the amount of time needed to complete each job is a continuous random variable.
What’s past is prologue: Organizational learning from a serious patient injury

This exploratory case study examines how one hospital learned from an adverse event (AE), a medication overdose that seriously injured a patient. Using qualitative data analysis, we examined how four professional groups reacted to the AE: physicians, nurses, pharmacists, and representatives from the combined quality assurance and risk management departments. Following the AE, each professional group classified the event differently, assessed a different segment of history, made decisions about different issues, and chose different courses of action. Despite these differences, the physician, nursing and pharmacy management teams all decided on which solutions to implement before the first root cause analysis meeting was convened. Indeed, to understand how the hospital implemented changes in the aftermath of the AE, it was necessary to examine the learning from near misses and other warnings that preceded it. This case highlights the importance of the politics of organizational learning and raises theoretical and practical questions about how hospitals learn from potential and actual adverse events.
Synthesis of luteinising hormone releasing factor and thyrotropin-releasing factor in glutamate-lesioned mice

THE arcuate nucleus (ARC) of the mammalian hypo-thalamus is thought to regulate tonic luteinising hormone (LH) secretion from the anterior pituitary1. But the immunohistochemical demonstration of luteinising hormone releasing factor (LHRF) in nerve fibres but not cell bodies of the ARC2,3 and the marked reduction in LHRF content after hypothalamic deafferentation4, suggest that the ARC is not a centre for LHRF synthesis. To clarify this issue we have used monosodium glutamate, a neurotoxin which when administered in a low dose to young animals selectively destroys ARC neurones While leaving intact axons passing through5–7. If the ARC perikarya synthesise LHRF, a marked reduction in the immunohistochemical staining and content of hypothalamic LHRF should be evident in glutamate-lesioned animals. Because thyroid function is unaffected by glutamate8, we examined brain tissue for thyrotropin releasing factor (TRF) content as a control for the LHRF studies.
Laparoscopic Fluorescent Visualization of the Ureter With Intravenous IRDye800CW

Abstract Objectives Ureter injury is a serious complication of laparoscopic surgery. Current strategies to identify the ureters, such as placement of a ureteral stent, carry additional risks for patients. We hypothesize that the systemically injected near-infrared (NIR) dye IRDye800CW-CA can be used to visualize ureters intraoperatively. Methods Adult female mixed-breed pigs weighing 24 to 41 kg (n = 2 per dose) were given a 30, 60, or 120 μg/kg systemic injection of IRDye800CW-CA. Using the Food and Drug Administration–cleared Pinpoint laparoscopic NIR system, images of the ureter and bladder were captured every 10 minutes for 60 minutes after injection. To determine the biodistribution of the dye, tissues were collected for ex vivo analysis with the Pearl Impulse system. ImageJ software was used to quantify fluorescence signal and signal-to-background ratio (SBR) for the intraoperative images. Results The ureter was identified in all pigs at each dose, with peak intensity reached by 30 minutes and remaining elevated throughout the duration of imaging (60 minutes). The 60 μg/kg dose was determined to be optimal for differentiating ureters according to absolute fluorescence (>60 counts/pixel) and SBR (3.1). Urine fluorescence was inversely related to plasma fluorescence ( R 2 = −0.82). Ex vivo imaging of kidney, ureter, bladder, and abdominal wall tissues revealed low fluorescence. Conclusion Systemic administration of IRDye800CW-CA shows promise in providing ureteral identification with high specificity during laparoscopic surgery. The low dose required, rapid time to visualization, and absence of invasive ureteral instrumentation inherent to this technique may reduce complications related to pelvic surgery.
Age Differences in Understandings of Disease Causality: AIDS, Colds, and Cancer

The development of concepts of disease causality was explored by asking 9-, 11-, and 13-year-olds and college students about risk factors for AIDS, colds, and cancer. Their knowledge became more accurate and differentiated with age. Although younger children knew a good deal about what causes each of the diseases, they lacked knowledge of what does not cause them, often inferring that risk factors for one disease, especially AIDS, cause other diseases as well. Knowledge of true risk factors for a disease was largely independent of knowledge of non-risk factors, and knowledge of one disease was largely independent of knowledge of another. These findings provide clues as to how disease understandings evolve with age and suggest that health educators must both understand students' current knowledge structures and explicitly teach students to make important differentiations between risk and non-risk factors for a given disease and between distinct diseases.
Saturn's rings - 3-mm observations and derived properties

Three-millimeter Saturn observations, obtained from 1965 through 1977 and with Jupiter as a reference, have been used to derive a ring brightness temperature of 18 + or - 8 K. The brightness temperature of the disk of Saturn is 156 + or - 9 K. Part of the ring brightness (approximately 6 K) may be accounted for as disk emission which is scattered from the rings; the remainder (12 + or - 8K) is attributed to ring particle thermal emission. Because this thermal component brightness temperature is so much less than the particle physical temperature, limits are placed on the mean size and composition of the ring particles. In particular, as found by others, the particles cannot be rocky, but must be either metallic or composed of extremely low-loss dielectric material such as water ice. If the particles are pure water ice, for example, then a simple slab model and a multiple-scattering model both give upper limits to the particle sizes of approximately 1 m, a value three times smaller than previously available. The multiple-scattering model gives a particle single-scattering albedo at 3 mm of 0.83 + or - 0.13.
Changes in the Frequency of Family Meals From 1999 to 2010 in the Homes of Adolescents: Trends by Sociodemographic Characteristics

Objective To examine secular trends from 1999 to 2010 in family meal frequency in a population-based sample of adolescents across sociodemographic characteristics.
Pharmacokinetic, biodistribution, and biophysical profiles of TNF nanobodies conjugated to linear or branched poly(ethylene glycol)

Covalent attachment of poly(ethylene glycol) (PEG) to therapeutic proteins has been used to prolong in vivo exposure of therapeutic proteins. We have examined pharmacokinetic, biodistribution, and biophysical profiles of three different tumor necrosis factor alpha (TNF) Nanobody-40 kDa PEG conjugates: linear 1 × 40 KDa, branched 2 × 20 kDa, and 4 × 10 kDa conjugates. In accord with earlier reports, the superior PK profile was observed for the branched versus linear PEG conjugates, while all three conjugates had similar potency in a cell-based assay. Our results also indicate that (i) a superior PK profile of branched versus linear PEGs is likely to hold across species, (ii) for a given PEG size, the extent of PEG branching affects the PK profile, and (iii) tissue penetration may differ between linear and branched PEG conjugates in a tissue-specific manner. Biophysical analysis (R(g)/R(h) ratio) demonstrated that among the three protein-PEG conjugates the linear PEG conjugate had the most extended time-average conformation and the most exposed surface charges. We hypothesized that these biophysical characteristics of the linear PEG conjugate accounts for relatively less optimal masking of sites involved in elimination of the PEGylated Nanobodies (e.g., intracellular uptake and proteolysis), leading to lower in vivo exposure compared to the branched PEG conjugates. However, additional studies are needed to test this hypothesis.
Technology Adoption and Technical Efficiency: Organic and Conventional Dairy Farms in the United States

We compare productivity and technical efficiency of organic and conventional dairy farms in the United States. We address self-selection into organic farming by using propensity score matching and explicitly test the hypothesis that organic and conventional farms employ a single, homogeneous technology. Utilizing the 2005 Agricultural Resource Management Survey on Dairy Costs and Returns Report (ARMS) data, we reject the homogeneous technology hypothesis and find that the organic dairy technology is approximately 13% less productive. However, we find little difference in technical efficiency between organic and conventional farms when technical efficiency is measured against the appropriate technology.
Open-label prospective trial of risperidone in combination with lithium or divalproex sodium in pediatric mania

Objective: This prospective 6-month open trial examined the safety and efficacy of two combination therapies for manic or mixed episodes of pediatric bipolar disorder: (1) divalproex sodium plus risperidone (DVPX+Risp), or (2) lithium plus risperidone (Li+Risp). Methods: Thirty-seven (37) subjects aged 5 and 18 (age=12.1±3.5 years) with DSM IV current mixed or manic episode and Young Mania Rating Scale (YMRS) score >20 were sequentially assigned to either DVPX+Risp or Li+Risp in a 6-month, prospective open-label trial. Outcome measures included the YMRS, Clinical Global Impression Scale for Bipolar Disorder (CGI-BP), Child Depression Rating Scale-Revised (CDRS-R) as well as measures of safety and tolerability. Results: Effect sizes (Cohen's d) based on change of YMRS scores from baseline were 4.36 for DVPX+Risp and 2.82 for Li+Risp. Response rates (≥50% change from baseline YMRS score at the end of study) were 80% for DVPX+Risp and 82.4% for Li+Risp. Both combination treatments were well tolerated. Significant improvements (p<0.001) from baseline were seen for mean scores on all efficacy measures, i.e., YMRS, CGI-BP, and CDRS-R. There were no significant group differences in safety or tolerability, and no serious adverse events during the 6-month trial. Conclusion: Both DVPX+Risp and Li+Risp show strong effects coupled with safety and tolerability in treating children and adolescents with manic or mixed episodes associated with type I bipolar disorder.
CTCF and ncRNA Regulate the Three-Dimensional Structure of Antigen Receptor Loci to Facilitate V(D)J Recombination

At both the immunoglobulin (Ig) heavy and kappa light chain loci, there are >100 functional variable (V) genes spread over >2 Mb that must move into close proximity in 3D space to the (D)J genes to create a diverse repertoire of antibodies. Similar events take place at the T cell receptor (TCR) loci to create a wide repertoire of TCRs. In this review, we will discuss the role of CTCF in forming rosette-like structures at the antigen receptor (AgR) loci, and the varied roles it plays in alternately facilitating and repressing V(D)J rearrangements. In addition, non-coding RNAs (ncRNA), also known as germline transcription, can shape the 3D configuration of the Igh locus, and presumably that of the other AgR loci. At the Igh locus, this could occur by gathering the regions being transcribed in the VH locus into the same transcription factory where Iμ is being transcribed. Since the Iμ promoter, Eμ, is adjacent to the DJH rearrangement to which one V gene will ultimately rearrange, the process of germline transcription itself, prominent in the distal half of the VH locus, may play an important and direct role in locus compaction. Finally, we will discuss the impact of the transcriptional and epigenetic landscape of the Igh locus on VH gene rearrangement frequencies.
SQUID measurement of metalloprotein magnetization. New methods applied to the nitrogenase proteins.

New techniques have been developed to exploit the sensitivity of a commercial SQUID susceptometer in the study of the magnetization of metalloproteins. Previous studies have ignored both the slow relaxation (hours) of spin I = 1/2 nuclei and residual ferromagnetic impurities in sample holders. These potential sources of noise were at or below the sensitivity of previous instruments. With these noise sources under control, one can now decrease the protein concentration by a factor of ten. In addition careful characterization of the frozen magnetization sample, including the use of a multi-instrument holder for combined study of the magnetization sample with Mossbauer spectroscopy, is required for reliable interpretation of the data in the face of paramagnetic impurities common to metalloprotein samples. Many previous magnetic studies of metalloproteins have been carried out in the Curie region. Saturation magnetization studies down to 1.8 K and up to 5 T can determine zero-field splitting parameters in addition to the spin and exchange coupling parameters measured in previous studies at lower fields and higher temperatures. Applications of these techniques to the study of the nitrogenase proteins of Azotobacter vinelandii are presented as examples.
A Multi-Sensor Robotics System For Object Recognition

An algorithm for object recognition based on the data from various contact and/or non-contact sensors is described. The sensors are primarily used for resolving the ambiguities which may be encountered in recognizing the object identity and its pose. The feature vector representing an object-state is partitioned into a finite number of feature subvectors each containing the features extracted from a different sensory source. To perform the recognition task through integration of data from different sensors, an a priori cost value is assigned to each feature. These feature costs and the object models are used for deriving a decision tree based on a sequential pattern, recognition approach. The decision tree guides the system during the recognition phase. General strategies for feature extraction from various sources are implemented as a finite state machine. A coordinator module supervises the coordination of manipulation and recognition processes and the execution of system state changes which are required to successfully implement the recognition algorithm.
Modified prostaglandins as internal standards for quantitative analysis of prostaglandins of the E series by combined gas chromatography-mass spectrometry.

Abstract ω-Homo-prostaglandin E1 and ω-nor-prostaglandin E2 are suitable standards for determination of prostaglandins of the E series by combined gas chromatography-mass spectrometry.
The immediate effects of silicon carbide whiskers upon ciliated tracheal epithelium

Considering the relationship between toxicity of dust and particle geometry, as exhibited by asbestos, we have examined short-term biological effects of SiC whiskers (SiCW) in vitro and in vivo. Cultured explants of tracheal epithelium were exposed to a range of SiCW concentrations. There were no dramatic effects on ciliary function as measured by an optical spectrum analysis system that provided discrete ciliary frequencies. Particles were swept by ciliary activity into nonciliated regions where foci of extensive cell damage and death were observed with whiskers penetrating epithelial layers into the underlying tissues. Similar necrotic foci were observed in tracheae from rats exposed by intratracheal instillation to SiC whiskers in vivo.
π-Acceptor induced thermal reactions: Bond cleavage reactions

Abstract TCNQ, TCNQF4, and DDQ have been found to initiate unusual bond breakage reactions. Benzylphenyl sulfide (BPS) and benzylphenyl ether (BPE) undergo cleavage of their interaryl bonds while bibenzyl (BB) does not cleave the interaryl bond and forms only trans-stilbene (TS) when reacted under the same conditions.
An optically active vinyl sulfoxide copolymer and the configuration of sulfoxide adjacent to radical or anionic sites

Optically active vinyl p-tolyl sulfoxide was synthesized and copolymerized with styrene to produce an optically active copolymer. The question of the configuration of sulfur in a sulfoxide when adjacent to a radical site is discussed. The configuration of sulfur in a sulfoxide is proven to be nonplanar when adjacent to an anionic site.