cssi/SciSciGPT-SciSciNet huggingface dataset:
Role of Ca2+-Independent Phospholipase A2 in the Regulation of Inducible Nitric Oxide Synthase in Cardiac Myocytes

Abstract —We have previously shown that the regulation by interleukin-1β (IL-1β) of inducible nitric oxide synthase (iNOS) involves phospholipase A2 (PLA2) metabolites in neonatal ventricular myocytes. Based on studies in which ONO-RS-082 is used to inhibit secretory PLA2 and methyl arachidonyl fluorophosphonate is used to inhibit cytosolic PLA2, our data suggest that a secretory PLA2 metabolite was involved in the regulation by IL-1β of iNOS. In addition, a third PLA2 isoform, which is Ca2+ independent (iPLA2), has also been detected in cardiac myocytes and shown to be regulated by cytokines. We tested whether iPLA2 metabolites are involved in the regulation by IL-1β of iNOS with the use of bromoenol lactone (BEL), a specific and irreversible inhibitor of iPLA2. For this, we measured IL-1β–stimulated nitrite (NOx) production with use of the Griess reagent, prostaglandin E2 (PGE2) production with use of an enzyme immunoassay, and arachidonic acid release in the presence and absence of BEL. We also detected iNOS and iPLA2 proteins by Western blotting. Treatment with IL-1β (5 ng/mL) for 24 hours stimulated NOx production by 8-fold and iNOS protein levels by at least 10-fold. In addition, arachidonic acid release was increased by 1.6-fold and PGE2 production was increased by 300-fold. When neonatal ventricular myocytes were treated with 10 μmol/L BEL, both IL-1β–stimulated PGE2 production and arachidonic acid release were inhibited. BEL inhibited IL-1β–stimulated NOx production and iNOS protein by 88% and 93%, respectively. Lysophosphatidic acid, but not arachidonic acid or lysophosphatidylcholine, stimulated iNOS expression. Our results indicate that an iPLA2 metabolite, perhaps lysophosphatidic acid, may be involved in the IL-1β–signaling pathway, regulating the synthesis of iNOS.
AvrB mutants lose both virulence and avirulence activities on soybean and Arabidopsis

The Pseudomonas syringae pv. glycinea effector protein AvrB induces resistance responses in soybean varieties that contain the resistance gene Rpg1-b and Arabidopsis varieties that carry RPM1. In addition to this avirulence activity, AvrB also enhances bacterial virulence on soybean plants that lack Rpg1-b and induces a chlorotic phenotype on Arabidopsis plants that lack RPM1. We screened a library of avrB mutants for loss of avirulence on soybean and Arabidopsis, and assayed selected avirulence mutants for loss of virulence on both plants. All mutants screened were recognized similarly on both plant species. Nine single-site avrB mutations that affected avirulence localized to a solvent-accessible pocket in the protein structure. Seven of these mutated residues are absolutely conserved between AvrB and its nine homologues. Avirulence mutants generally lost virulence enhancement on susceptible soybean varieties and lost the ability to induce a chlorotic response on the rpm1 null Arabidopsis variety Mt-0. Three of four avirulence mutants tested failed to interact with RIN4, an Arabidopsis protein previously shown to be required for RPM1 function. Our results suggest that soybean and Arabidopsis recognize AvrB in the same manner, and that AvrB enzymatic activity is required for its function as an avirulence and virulence effector on two different plant species.
Evaluation of Power Semiconductors Power Cycling Capabilities for Adjustable Speed Drive

This paper analyzes the power cycling capability of semiconductor under various conditions for adjustable speed drive (ASD). An analysis is made that calculates the mean time to failure (MTTF) of the semiconductor under various conditions, including low speed operation capability, high speed thermal capability and overload capability. After that, the MTTF estimations of the IGBT under different heatsink design and different drive ratings are studied. This paper will show that the MTTF of the inverter may be very short under some very common operating conditions. Thus, it is prudent to size the drive properly in order to avoid earlier failure.
Walter Reuther, the UAW, and the dilemmas of automation

Historians have slighted the importance of automation both as a cause of organized labor's decline in America and as a lively issue among labor leaders in the early post-WWII period. In part, this disregard stems from labor's own ambivalence about technological change. This essay considers that ambivalence by looking at Walter Reuther and the United Auto Workers. Reuther and his colleagues shared widespread hopes that the new production processes would relieve the burdens of assembly-line work and increase the working class's access to cultivated leisure. At the same time, however, they recognized that unchecked technological change would generate a wave of structural unemployment by displacing experienced workers while denying new, unskilled workers necessary jobs. Reuther and his colleagues feared that automation in this form would destroy the consumer capacity that the working class had so recently acquired, and in so doing would undermine the health of the entire economy. Reuther's strategy, therefore...
Blood glucose distribution in the domestic fowl.

Results and conclusionsThe results of these experiments are shown in Table I. Blood glucose was distributed almost entirely in the plasma at all ages studied. Erythrocytes of the newly-hatched chick do not have more glucose in them than do those of the adult bird. Quantity of glucose found in the red cells of the newly-hatched and young chicks is less than that reported for neonatal and young animals of other species. Replacement of fetal red cells by adult types which takes place in the first 3 weeks posthatching is not characterized by a glucose distribution shift. The partition at hatching is similar to that in the foal. Since the foal has adult erythrocytes in the blood at birth and the chick has a mixture of adult and fetal cells, it would appear that the differences in distribution of blood sugar as observed in other species may not be attributed simply to differences in carbohydrate metabolism of the 2 cell types.
Intercomparison of Imaging Sensors using Automated Ground Measurements

The reflectance-based method is a vicarious approach providing absolute radiometric calibration. A desire to increase the number of possible reflectance-based calibrations led the University of Arizona Remote Sensing Group (RSG) to deploy multispectral, downlooking radiometers at the RSG's Railroad Valley test site in Nevada. The radiometers are coupled with data from a sun photometer to provide the information needed for reflectance-based calibration without the need for on-site personnel. Results from these radiometers show similar uncertainties as on-site methods, and early results have led to their use with geostationary sensors, for derivation of surface bi-directional reflectance effects, and for comparisons of biases between sensors. The results show that radiometers with a single view angle are sufficient to characterize BRDF effects for Railroad Valley Playa. The results also give confidence in the automated approach as a means for cross-calibration relative to the vicarious results providing similar intercomparison results as with on-site personnel.
Discovery, synthesis and SAR of azinyl- and azolylbenzamides antagonists of the P2X7 receptor

Abstract The discovery, of a series of 2-Cl-5-heteroaryl-benzamide antagonists of the P2X7 receptor via parallel medicinal chemistry is described. Initial analogs suffered from poor metabolic stability and low Vdss. Multi parametric optimization led to identification of pyrazole 39 as a viable lead with excellent potency and oral bioavailability. Further attempts to improve the low Vdss of 39 via introduction of amines led to analogs 40 and 41 which maintained the favorable pharmacology profile of 39 and improved Vdss after iv dosing. But these analogs suffered from poor oral absorption, probably driven by poor permeability.
Perfect Recovery Conditions for Non-negative Sparse Modeling

Sparse modeling has been widely and successfully used in many applications, such as computer vision, machine learning, and pattern recognition. Accompanied with those applications, significant research has studied the theoretical limits and algorithm design for convex relaxations in sparse modeling. However, theoretical analyses on non-negative versions of sparse modeling are limited in the literature either to a noiseless setting or a scenario with a specific statistical noise model, such as Gaussian noise. This paper studies the performance of non-negative sparse modeling in a more general scenario where the observed signals have an unknown arbitrary distortion, especially focusing on non-negativity constrained and L1-penalized least squares, and gives an exact bound for which this problem can recover the correct signal elements. We pose two conditions to guarantee the correct signal recovery: minimum coefficient condition and nonlinearity versus subset coherence condition. The former defines the minimum weight for each of the correct atoms present in the signal and the latter defines the tolerable deviation from the linear model relative to the positive subset coherence, a novel type of “coherence” metric. We provide rigorous performance guarantees based on these conditions and experimentally verify their precise predictive power in a hyperspectral data unmixing application.
Membership has Its Privileges

Membership has its privileges. Professionals, including nurses, routinely talk about their work with non-profit organizations. What motivates a nurse to join a professional organization? What would drive you to join? What “privileges” are you looking for? What can you bring to an organization? Membership does have its privileges, but these exist only when leadership and membership collaborate and work to actualize common goals. Each person's level of involvement in the organization is a personal decision, but just like music, athletics or any extracurricular activity, effort determines reward. In general, full benefit from belonging to an organization takes time, participation and alliance with a mentor or motivator who has experienced the advantages of membership and advocates forth personal and professional value of belonging. For the pediatric nursing professional, joining an organization, such as the Society of Pediatric Nurses (SPN), can provide the nurse with a vast array of opportunities, some of which can be very individualized. Nurses may join an organization primarily for the benefit of keeping informed on current practice through publication of databased articles and reviews of current trends in healthcare. Nurses have commented that being informed of best practices through current research publications and presentations heightens the awareness of issues related to the state of pediatric nursing, thus creating the “bigger picture of nursing and health care overall.” Having the big picture in pediatric nursing can lead to new and exciting opportunities to advocate for the patient population that is served.
Clinical Issues in the Surgical Management of Screen-Identified Lung Cancers.

This review outlines the diagnostic and therapeutic challenges associated with the increased number of screen-identified indeterminate lung nodules, highlighting currently recommended follow-up and management algorithms, as well as the various methods of nodule localization, tissue diagnosis, and definitive local therapeutic modalities.
The challenge of an aged and shrinking population: Lessons to be drawn from Japan’s experience☆

Abstract Japan is the first industrial country to have an aged and shrinking population. Such a demographic situation poses numerous macroeconomic and microeconomic challenges, with the former further amplified by Japan’s high public debt level. This paper underscores the multiple criteria to consider in evaluating Japan’s policies as it has approached this demographic tipping point. In examining Japan’s macroeconomic policies as well as the specifics of its social insurance policy framework, it seeks to draw lessons relevant for countries confronting the prospect of an aged population, while recognizing the importance of viewing Japan’s policies in the context of its unusual culture and history. The paper notes Japan’s current initiatives to grapple with its recent years of anemic growth and with the fiscal and social challenges arising in an aged population.
World Marketing as a New Force for Peace

Something new is going on in the world today. Rather than world trade being dependent on world peace, as in times past, world peace may be influenced and brought nearer reality through burgeoning w...
Abstract 3473: Intra-person and inter-person biomarker variation for modeling longitudinal values of ovarian cancer early detection biomarkers.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC In 2012, an estimated 22,280 women will be diagnosed with ovarian cancer in the United States and 15,500 women will die from this disease. Though localized ovarian cancers have a survival rate of 92%, only 15-20% of ovarian cancers are detected at this stage. Developing an effective strategy for early detection could reduce mortality. While individual values of CA125 are neither sufficiently sensitive nor specific for early detection, monitoring CA125 over time shows greater specificity. The risk of ovarian cancer algorithm, ROCA, analyzes the trend of annual values for CA125, utilizing each woman's own baseline to refer a small fraction (<1-2%) of women to transvaginal sonography. Using this strategy, no more than three operations are required for each case of ovarian cancer detected. Use of multiple biomarkers might increase sensitivity for preclinical disease. Based on a multiplex assay of 96 biomarkers, a four biomarker panel was identified of CA125, HE4, MMP-7 and CA 72-4 with greater sensitivity than CA125 alone. To estimate the utility of these biomarkers for longitudinal screening, we assessed five annual longitudinal control serum samples from 200 women who did not develop ovarian cancer from the MDACC SPORE normal risk ovarian cancer screening study (NROSS). Utilizing WinBUGS, the inter-person and intra-person CVs were evaluated. Upon log transformation for CA125, HE4 and MMP-7 and log(log()+1) transformation for CA72-4, both the inter-person and intra-person CVs follow a log-normal distribution. The median inter-person CVs for CA125, HE4, MMP-7 and CA 72-4 were 49%, 20%, 35% and 84% respectively and the median intra-person CVs were 15%, 25%, 21% and 21% respectively. The ratios of intra-person CVs to inter-person CVs derived for CA125, HE4, MMP-7 and log(CA 72-4) were 0.31, 1.25, 0.6 and 0.31. We anticipate that the lower the ratio, the higher the contribution of each individual marker to early detection during longitudinal measurements. The intra-person CV's should permit development of a multi-marker algorithm. Assessment of longitudinal samples derived from 50 cases of preclinical ovarian cancer and 10 controls per case (UKCTOCS trial) are underway in order to establish such a longitudinal multi-marker algorithm for assessment of ovarian cancer risk. Citation Format: Archana Raamanathan, Zhen Lu, Robert C. Bast, Steven J. Skates. Intra-person and inter-person biomarker variation for modeling longitudinal values of ovarian cancer early detection biomarkers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3473. doi:10.1158/1538-7445.AM2013-3473
The Principal—Agent Problem and Transocean

Corporate responsibility lies in three realms — the economic, the ethical, and the legal. Much of the posturing between half a dozen entities, BP, Transocean, Halliburton, Cameron International, the regulatory agencies, and even first responders, are all based on fears of legal liability. However, there are greater principles invoked by the disaster and the responsibility of various interested parties who could have helped avoid it.
174 EFFECT OF PIOGLITAZONE ON INSULIN SIGNALING IN SKELETAL AND CARDIAC MUSCLES OF HIGH FAT-FED ZUCKER RATS.

Thiazolidinediones (TZDs) improve glycemic control in patients with diabetes partly by improving glucose utilization by peripheral tissues and enhancing glucose uptake and insulin signaling in skeletal muscle. However, the effects of TZDs on fat-induced derangements of insulin signaling are poorly understood. In this study, we investigated the effects of administration of pioglitazone (PIO) on phosphorylation and expression of key insulin signaling molecules in skeletal and cardiac muscles of high fat-fed fa/fa Zucker rats. Methods Zucker rats were fed a high-fat diet throughout the study. On study day 7, they were randomly assigned to a control group, 14-day PIO group, or a single-dose PIO group. Single-dose PIO received drug on the last study day via gavage (20 mg/kg). The 14-day PIO group received drug orally via admixture with chow. On study day 21, all animals were sacrificed within 6 hours after the last dose of PIO. Blood and tissues (heart, soleus, and plantaris muscle) were harvested and frozen for Western blot analysis of insulin receptor (InsR), ERK1,2, p38 MAPK, and Akt. Results Chronic exposure in the 14-day PIO group, but not in the acute group improved glycemia and reduced plasma insulin by 3-fold (p .05) and 60% (p Conclusion In insulin-resistant high fat-fed rats, administration of both single and 14-day PIO reduced InsR activation in cardiac and skeletal muscle. This was accompanied by activation of MAPKs in heart and plantaris, activation of Akt in plantaris, and no changes in MAPKs and Akt phosphorylation in soleus muscles. Therefore, the study suggests the presence of differential effects of PIO on insulin signaling among different types of striated muscles. The results also demonstrate the effects of acute PIO on muscle insulin signaling without drug effects on hyperglycemia and insulinemia.
Impact of nitric oxide on macrophage glucose metabolism and glyceraldehyde-3-phosphate dehydrogenase activity

Conflicting evidence has been presented regarding the role of nitric oxide (NO) in the regulation of cellular glucose metabolism. While it enhances glucose uptake and utilization through glycolysis and the hexose monophosphate shunt in macrophages and other cells, NO also inhibits glyceraldehyde-3-phosphate dehydrogenase, an enzyme catalyzing the metabolism of intermediates generated by both pathways. Indeed, it has been proposed that NO modulates glycolytic flux by suppressing glyceraldehyde-3-phosphate dehydrogenase activity. To establish the relative impact of these apparently incompatible actions, the effects of exogenous or endogenous NO on different aspects of glucose metabolism in macrophages were investigated. Cell activation increased NO production, maximal glyceraldehyde-3-phosphate dehydrogenase activity, and glucose metabolism through glycolysis and the hexose monophosphate shunt. NO generated endogenously or from S-nitroso-N-acetylpenicillamine (> 500 microM) reduced maximal glyceraldehyde-3-phosphate dehydrogenase activity in culture. The suppression of maximal glyceraldehyde-3-phosphate dehydrogenase coincided with decreased lactate accumulation only in concert with a marked loss of viable cells in the cultures. The maximal glyceraldehyde-3-phosphate dehydrogenase activity did not appear to be rate limiting for glucose metabolism when moderately inhibited by NO. A potential causal relationship between profound glyceraldehyde-3-phosphate dehydrogenase inhibition and cell death remains to be established.
Digital forensics in an eDiscovery world

Abstract The ever-changing landscape of digital evidence locations and hardware devices hosting electronic data, the Forensic Examiner and experts in the investigations field are looking for new ways to deal with vast amounts of unstructured data. eDiscovery workflows have the potential to enhance the digital forensic investigator’s ability to cull through vast amounts of electronic data collected from many devices that are now being brought into custody for examination. Recent leaps in software capabilities in the eDiscovery realm have given the digital examiner more options to apply EDRM workflows to successfully complete an investigation in a timely manner using techniques adopted in a Litigation or eDiscovery examination.
Characterization of cytidylyltransferase enzyme activity through high performance liquid chromatography.

The cytidylyltransferases are a family of enzymes that utilize cytidine 5'-triphosphate (CTP) to synthesize molecules that are typically precursors to membrane phospholipids. The most extensively studied cytidylyltransferase is CTP:phosphocholine cytidylyltransferase (CCT), which catalyzes conversion of phosphocholine and CTP to cytidine diphosphocholine (CDP-choline), a step critical for synthesis of the membrane phospholipid phosphatidylcholine (PC). The current method used to determine catalytic activity of CCT measures production of radiolabeled CDP-choline from (14)C-labeled phosphocholine. The goal of this research was to develop a CCT enzyme assay that employed separation of non-radioactive CDP-choline from CTP. A C18 reverse phase column with a mobile phase of 0.1 M ammonium bicarbonate (98%) and acetonitrile (2%) (pH 7.4) resulted in separation of solutions of the substrate CTP from the product CDP-choline. A previously characterized truncated version of rat CCTα (denoted CCTα236) was used to test the HPLC enzyme assay by measuring CDP-choline product formation. The Vmax for CCTα236 was 3850 nmol/min/mg and K0.5 values for CTP and phosphocholine were 4.07 mM and 2.49 mM, respectively. The HPLC method was applied to glycerol 3-phosphate cytidylyltransferase (GCT) and CTP:2-C-methyl-D-erythritol-4-phosphate cytidylyltransferase synthetase (CMS), members of the cytidylyltransferase family that produce CDP-glycerol and CDP-methylerythritol, respectively.
The effects of X-ray treatments on bioaccumulated murine norovirus-1 (MNV-1) and survivability, inherent microbiota, color, and firmness of Atlantic oysters (Crassostrea virginica) during storage at 5 °C for 20 days

Abstract In this study, we investigated the inactivation of human norovirus (HuNoV) surrogate Murine norovirus (MNV-1) by X-ray in whole-shell Atlantic oysters (Crassostrea virginica). We also investigated the effects of X-ray treatments on the survivability, inherent microbiota, color, and firmness of treated whole-shell Atlantic oysters during storage at 5 °C for 20 days. Plaque assays revealed that X-ray significantly reduced the population of internalized MNV-1 in live oysters from 4.3 ± 0.4 log PFU g−1 to 3.6 ± 0.5, 3.2 ± 0.2, 2.8 ± 0.2, and 2.5 ± 0.1 log PFU g−1, by 1.0, 2.0, 3.0, and 4.0 kGy X-ray, respectively. The population of MNV-1 was reduced to less than 2.0 log PFU g−1 at 5.0 kGy X-ray. The survivability of live oysters was not significantly affected by treatment with 1.0 and 5.0 kGy X-ray, in comparison with the control, for up to 15 and 10 days, respectively, during storage at 5 °C. Treatment of whole-shell oysters by 5.0 kGy X-ray significantly reduced the inherent microbiota and kept them lower than the control until day 20. No significant effect of X-ray treatment on oyster color or firmness was detected.
MOHANDAS KARAMCHAND GANDHI AND JAWAHARLAL NEHRU: A CONCISE COMPARATIVE STUDY

India was fortunate to have the charismatic and enlightened leadership of Mohandas Karamchand Gandhi and Jawaharlal Nehru. While these two legendary Indian leaders shared a few similarities, in most respects, they were very different. Mahatma Gandhi was one of the principal leaders of the Indian nationalist movement against British colonial rule, the father of the Indian nation, and one of the most successful and well-known practitioners of active, non-violent civil disobedience. His political strategy was emulated by Martin Luther King Jr. during the American Civil Rights Movement, feminists, environmentalists, and countless students and workers demonstrating for democratization all over the world. In contrast, Nehru was the architect of Indian democracy, rapid modernization, and one of the founding fathers of the Non-Aligned Movement. This paper compares these two famous figures from the developing world through a concise essay and unique table.
Scholarly Personal Narrative in the SoTL Tent

Scholarly personal narrative (SPN) extends the available methodologies by which researchers conduct the Scholarship of Teaching and Learning (SoTL). In this article, the authors define SPN, which interprets personal experience through scholarly frameworks, leveraging the power of reflective practice to understand the interpersonal dynamics of both the classroom and wider academic communities. SPN fosters disciplinary understandings of SoTL and bridges discourse barriers in order to illuminate the complex environments of teaching and learning. The article examines how widely-accepted definitions of scholarship apply to SPN and provides a scholarly approach for researchers to analyze personal experience as a pool of data, employ a range of analytical techniques, and identify significant results. Through an analysis of two articles, the authors discuss the usefulness of SPN both as a major and minor critical lens. The inclusion of SPN may enrich SoTL pluralism and contribute to the knowledge of the complex contexts and influences that shape instructors, learning environments, and student experiences.
Labyrinthotomy with streptomycin infusion: early results of a multicenter study. The LSI Multicenter Study Group.

Early results for hearing and vertigo are reported for 47 labyrinthotomies with streptomycin infusion (LSI) by 13 coinvestigator-surgeons. Sixty-eight percent of patients had worse hearing after surgery (10 dB or 15% word recognition). Patients with a preoperative pure-tone average better than or equal to 40 dB appeared to suffer less postoperative hearing loss than those with a greater preoperative deficit. Severe to profound postoperative hearing loss was experienced by 27 patients (57%), all of whom had preoperative pure-tone averages worse than 40 dB
Comment on "Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing".

Chen et al . (Reports, 28 October 2016, p. 468) proposed that an interaction between Xist RNA and Lamin B receptor (LBR) is necessary and sufficient for Xist spreading during X-chromosome inactivation. We reanalyzed their data and found that reported genotypes of mutants are not supported by the sequencing data. These inconsistencies preclude assessment of the role of LBR in Xist spreading.
Coffee consumption and risk of renal cell carcinoma.

Studies have suggested an inverse association between coffee consumption and risk of renal cell carcinoma (RCC); however, data regarding decaffeinated coffee are limited. We conducted a case–control study of 669 incident RCC cases and 1,001 frequency-matched controls. Participants completed identical risk factor questionnaires that solicited information about usual coffee consumption habits. The study participants were categorized as non-coffee, caffeinated coffee, decaffeinated coffee, or both caffeinated and decaffeinated coffee drinkers. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression, adjusting for multiple risk factors for RCC. Compared with no coffee consumption, we found an inverse association between caffeinated coffee consumption and RCC risk (OR 0.74; 95% CI 0.57–0.99), whereas we observed a trend toward increased risk of RCC for consumption of decaffeinated coffee (OR 1.47; 95% CI 0.98–2.19). Decaffeinated coffee consumption was associated also with increased risk of the clear cell RCC (ccRCC) subtype, particularly the aggressive form of ccRCC (OR 1.80; 95% CI 1.01–3.22). Consumption of caffeinated coffee is associated with reduced risk of RCC, while decaffeinated coffee consumption is associated with an increase in risk of aggressive ccRCC. Further inquiry is warranted in large prospective studies and should include assessment of dose–response associations.
In vitro characterization of high purity factor IX concentrates for the treatment of hemophilia B.

This study employed sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis and immunoblotting to assess the purity of seven high purity factor IX concentrates: Aimafix (Aima), AlphaNine-SD (Alpha Therapeutic), Factor IX VHP (Biotransfusion), Immunine (Immuno), Mononine (Armour Pharmaceutical), Nanotiv (Kabi Pharmacia), and 9MC (Blood Products Laboratory). The mean specific activity of these products ranged from 68 U factor IX/mg (Aimafix) to 246 U factor IX/mg (Mononine). SDS-PAGE analysis showed that the highest purity product, Mononine, had a single contaminating band under non-reducing conditions. Two additional bands were detected when this product was analyzed under reducing conditions. All other products had multiple contaminating bands that were more apparent under reducing than non-reducing conditions. The immunoblot for factor IX showed a dominant factor IX band for all products. In addition, visible light chain of factor IX was detected for AlphaNine-SD, Factor IX VHP, Immunine, Mononine, Nanotiv, and 9MC, suggesting that the factor IX in these products had undergone partial activation to factor IXa. Another contaminating band was visible at 49,500 for all of the products except 9MC. In addition to this band, high molecular weight contaminants were apparent for some products, most notably AlphaNine-SD. The identity of these bands is unknown. Immunoblotting failed to demonstrate factor VII as a contaminant of any of the high purity products, although factor Vila could be detected in some lots of Immunine, Nanotiv, and 9MC by a clot-based assay. Factor X contaminated Aimafix, AlphaNine-SD, Factor IX VHP, Immunine, Nanotiv, and 9MC, but activation products of factor X were not detected. Prothrombin contaminated all of the products except Mononine. Activation products of prothrombin were identified for three of four lots of Immunine and for one lot of Factor IX VHP. These results thus demonstrate that high purity factor IX concentrates differ substantially in the degree to which they are contaminated by potentially thrombogenic materials.
Wrapped to Adapt: Experience-Dependent Myelination

Activity of the nervous system has long been recognized as a critical modulator of brain structure and function. Influences of experience on the cytoarchitecture and functional connectivity of neurons have been appreciated since the classic work of Hubel and Wiesel (1963; Wiesel and Hubel, 1963a, 1963b). In recent years, a similar structural plasticity has come to light for the myelinated infrastructure of the nervous system. While an innate program of myelin development proceeds independently of nervous system activity, increasing evidence supports a role for activity-dependent, plastic changes in myelin-forming cells that influence myelin structure and neurological function. Accumulating evidence of complementary and likely temporally overlapping activity-independent and activity-dependent modes of myelination are beginning to crystallize in a model of myelin plasticity, with broad implications for neurological function in health and disease.
Evaluation of Medication Errors at the Transition of Care From an ICU to Non-ICU Location.

Objectives:To determine the point prevalence of medication errors at the time of transition of care from an ICU to non-ICU location and assess error types and risk factors for medication errors during transition of care.Design:This was a multicenter, retrospective, 7-day point prevalence study.Setti
Trigger bond analysis of nitroaromatic energetic materials using wiberg bond indices

The identification of trigger bonds, bonds that break to initiate explosive decomposition, using computational methods could help direct the development of novel, "green" and efficient high energy density materials (HEDMs). Comparing bond densities in energetic materials to reference molecules using Wiberg bond indices (WBIs) provides a relative scale for bond activation (%ΔWBIs) to assign trigger bonds in a set of 63 nitroaromatic conventional energetic molecules. Intramolecular hydrogen bonding interactions enhance contributions of resonance structures that strengthen, or deactivate, the CNO2 trigger bonds and reduce the sensitivity of nitroaniline-based HEDMs. In contrast, unidirectional hydrogen bonding in nitrophenols strengthens the bond to the hydrogen bond acceptor, but the phenol lone pairs repel and activate an adjacent nitro group. Steric effects, electron withdrawing groups and greater nitro dihedral angles also activate the CNO2 trigger bonds. %ΔWBIs indicate that nitro groups within an energetic molecule are not all necessarily equally activated to contribute to initiation. %ΔWBIs generally correlate well with impact sensitivity, especially for HEDMs with intramolecular hydrogen bonding, and are a better measure of trigger bond strength than bond dissociation energies (BDEs). However, the method is less effective for HEDMs with significant secondary effects in the solid state. Assignment of trigger bonds using %ΔWBIs could contribute to understanding the effect of intramolecular interactions on energetic properties. © 2018 Wiley Periodicals, Inc.
Predictor-Corrector Methods Using Updating

In iterative methods for numerically finding zero-points of a smooth map F : R N → R N it is often preferable to avoid the costly recalculation and decomposition of the Jacobian F′ at each iteration by using an approximation to F′. This results in sacrificing quadratic convergence in exchange for a superlinear convergence which is nearly as good, or a rather fast rate of linear convergence. When N is of at least moderate size, or F′ is otherwise cumbersome to calculate, this trade-off is usually to be preferred. It is reasonable to expect that the same situation should also hold in the corrector step of the predictor-corrector methods for numerically tracing H−1(0) where H : RN+1 → R N is a smooth map. Indeed, since the corrector process needs to be performed essentially at every predicted point, the possibility of saving computational effort in the corrector process becomes even more attractive for the predictor-corrector curve tracing methods.
Waves of simulation: Arguing authenticity in an era of surfing the hyperreal:

This article is an examination of the impact of new, technologically sophisticated wave pools upon the culture of surfers. Appropriating the concepts of simulation from the work of postmodern theor...
Racial Differences in Mechanisms Linking Childhood Socioeconomic Status With Growth in Adult Body Mass Index: The Role of Adolescent Risk and Educational Attainment.

Abstract Purpose The present study examined whether risk factors during adolescence, including substance use, depression, overweight status, and young adult educational attainment, mediated the association between low childhood socioeconomic status (SES) and higher body mass index (BMI) in adulthood. We also evaluated whether the hypothesized pathways differed based on racial group status. Methods Participants from the Seattle Social Development Project were followed from ages 10 to 39years. Thepresent study included white (n = 381), African American (n = 207), and Asian American (n = 171) participants. Structural equation models tested pathways linking low childhood SES to BMI from ages 24 to 39 years. Multiple-group modeling was used to test potential racial differences. Results Analyses indicated racial differences in the pathways linking low childhood SES with adult BMI. For whites, overweight status and educational attainment were significant mediators. For Asian Americans, there was an unmediated and significant pathway between low childhood SES and low adult BMI. For African Americans, there were no significant mediated or unmediated pathways. Conclusions Results stress that the pathways that link childhood SES with adult BMI may operate differently based on race. Research is particularly needed to identify mechanisms for African Americans in order to better inform obesity prevention efforts.
Wrist arthrodesis with the medial femoral condyle flap: Outcomes of vascularized bone grafting for osteomyelitis

Background Osteomyelitis of the wrist is rare but destructive. Subsequent bone defects often require vascularized bone for successful healing. Recent literature has pointed to the successful use of the medial femoral condylar (MFC) flap for difficult non-unions, yet it has not been specifically described for wrist fusion. We present our experience with this technique for limited and complete wrist arthrodesis. Patients and methods We reviewed 4 cases of radiocarpal bone loss from osteomyelitis. All cases utilized debridement of nonviable tissues, and at least 6 weeks of intravenous antibiotics, followed by vascularized bone grafting with a MFC flap. The flap was based on the horizontal periosteal branch of the descending geniculate artery, and utilized to directly bridge the bony defects following resection. Results Three patients healed primarily, and 1 patient required secondary cancellous bone grafting to reach union. One patient required revision of the donor site closure. None of the patients had a recurrence of infection or other complications. Average follow up was 8.5 months after reconstruction. Average time to union was 11.5 weeks. Three patients demonstrated full composite fist, and 1 patient had incomplete finger range of motion following several flexor and extensor tendon grafts. Conclusions These cases illustrate the use of the MFC in wrist arthrodesis after osteomyelitis defects. In all cases, there was complete union in a short time, no recurrence of infection, and low donor-site morbidity.
Uterine Corpus Malignancies in Appalachia Kentucky: Incidence, Survival, and Related Health Disparities.

OBJECTIVES Uterine cancer is the nation's most common gynecologic malignancy, but it is understudied in the geographically and socioeconomically diverse state of Kentucky (KY). Our aim was to assess the frequency, distribution, and survival of uterine corpus malignancies in KY, and specifically the differences between Appalachia (AP) and non-Appalachia (NAP) KY. METHODS This population-based cohort study used Surveillance, Epidemiology, and End Results data and the Kentucky Cancer Registry to study uterine corpus malignancy between January 1, 2000 and December 31, 2014. The analysis looked at the incidence between diagnoses in AP and NAP. The evaluation criteria included tumor histology (type I, type II, sarcoma, and mixed uterine malignancy), age, race, smoking status, stage at diagnosis, insurance status, and county of residence at diagnosis. RESULTS The overall age-adjusted incidence rate and survival are similar for US and KY populations; however, histologic types and distribution differ. Compared with the United States, the incidence of corpus cancers in KY is higher for type I (P = 0.03), but lower for type II (P = 0.003), sarcoma (P = 0.006), and mixed (P < 0.001). AP KY has a higher incidence of type I (P < 0.0001) and mixed malignancy (P = 0.04), younger age at diagnosis (P < 0.0001), larger non-Hispanic white population (P < 0.0001), fewer smokers (P = 0.002), and more uninsured and Medicaid recipients (P < 0.0001) compared with NAP KY. The hazard ratio for death is similar in AP and NAP KY (0.896; 95% confidence interval 0.795-1.009). CONCLUSIONS Type I and mixed uterine corpus cancers have a higher age-adjusted incidence and a younger age at diagnosis in AP compared with NAP KY.
“I see your True Colors”: Mitigating grouphate by exploring personality differences

Course: Small Group Communication.Objectives: Students will identify their personality traits; synthesize the relationship between personality, small-group interdependence, and grouphate; and apply...
Evaluating the Reliability Of MRI In Predicting The Degree Of ACL Tears In Pre-operative Planning For The Surgical Treatment Of ACL Tears: A Retrospective Study:

Objectives:Anterior cruciate ligament (ACL) repair has regained interest in recent years as it has been demonstrated to provide favorable outcomes in patients with proximal ACL tears or avulsions. ...
Dysphagia After Primary Transoral Robotic Surgery With Neck Dissection vs Nonsurgical Therapy in Patients With Low- to Intermediate-Risk Oropharyngeal Cancer.

Importance A major goal of primary transoral robotic surgery (TORS) for oropharyngeal cancer is to optimize swallowing outcomes by personalized treatment based on pathologic staging. However, swallowing outcomes after TORS are uncertain, as are the outcomes compared with nonsurgical options. Objectives To estimate rates of acute dysphagia and recovery after TORS and to compare swallowing outcomes by primary treatment modality (TORS or radiotherapy). Design, Setting, and Participants This case series study was a secondary analysis of prospective registry data from 257 patients enrolled from March 1, 2015, to February 28, 2018, at a single academic institution who, according to theAJCC Staging Manual, 7th edition TNM classification, had low- to intermediate-risk human papillomavirus–related oropharyngeal squamous cell carcinoma possibly resectable by TORS. Exposure Patients were stratified by primary treatment (75 underwent TORS and 182 received radiotherapy). Main Outcomes and Measures Modified barium swallow (MBS) studies graded per Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) and the MD Anderson Symptom Inventory–Head and Neck Module (MDASI-HN) questionnaires were administered at standard intervals. Prevalence and severity of dysphagia were estimated per DIGEST before and after TORS and 3 to 6 months after treatment. Moderate-severe dysphagia (DIGEST grade ≥2) was assessed using logistic regression and compared by primary treatment group. The MDASI swallowing symptom severity item scores during and after radiotherapy were compared using generalized estimating equations by treatment status at the start of radiotherapy, after induction, and after TORS. Results A total of 257 patients (mean [SD] age, 59.54 [9.07] years; 222 [86.4%] male) were included in the study. Dysphagia severity (per DIGEST) was significantly worse after TORS (r = −0.63; 95% CI, −0.78 to −0.44): 17 patients (22.7%; 95% CI, 13.8%-33.8%) had moderate-severe (DIGEST grade ≥2) acute post-TORS dysphagia significantly associated with primary tumor volume (odds ratio, 1.43; 95% CI, 1.11-1.84). DIGEST improved by 3 to 6 months but remained worse than that at baseline; at 3 to 6 months, the number of patients with DIGEST grade 2 or higher dysphagia was 5 (6.7%; 95% CI, 2.2%-14.9%) after primary TORS and 29 (15.9%; 95% CI, 10.9%-22.1%) after radiotherapy. At the start of radiotherapy, MDASI swallowing symptom severity item scores were significantly worse in the post-TORS group compared with postinduction (mean [SD] change, 2.6 [1.1]) and treatment-naive (mean [SD] change, 1.7 [0.3]) patients. This result inverted at radiotherapy end, and all groups converged at 3 to 6 months. Conclusions and Relevance Subacute swallowing outcomes were similar regardless of primary treatment modality among patients with low- to intermediate-risk oropharyngeal squamous cell carcinoma.
Utility of a Pigtail Cope Loop Catheter for Bladder Drainage in Treating a Large/Persistent Urethrovesical Anastomotic Leak Following Radical Prostatectomy.

Background: A large or persistent urethrovesical anastomotic leakage after a laparoscopic or robot-assisted laparoscopic radical prostatectomy (RALRP) although infrequent can be a difficult complication to treat. We describe a simple technique to facilitate resolution of a urethrovesical anastomotic leak by exchanging the in-place bladder Foley catheter for a pigtail drainage catheter. Case Presentation: Between 2014 and 2019, we had three patients who had a large/persistent urine leak after a radical prostatectomy (one laparoscopic and two robot assisted). All three patients had a wide bladder neck requiring bladder neck reconstruction with ureteral orifices close to the anastomosis. The bladder Foley catheter was exchanged to a pigtail Cope loop catheter™ (14F) or an Origin™ self-retaining drainage catheter (16F) under flexible cystoscopic guidance over a guidewire. Placement of a Cope loop bladder catheter stopped anastomotic leakage expeditiously with no need for further intervention. At minimum 3 months follow-up none had bladder neck stricture with 0-1 pad urinary incontinence. Conclusion: Drainage of the bladder through the use of a loop pigtail nephrostomy catheter can be useful in rapidly resolving a large persistent urethrovesical anastomotic leak.
Impact of admixture and ancestry on eQTL analysis and GWAS colocalization in GTEx

Abstract Background Population structure among study subjects may confound genetic association studies, and lack of proper correction can lead to spurious findings. The Genotype-Tissue Expression (GTEx) project largely contains individuals of European ancestry, but the final release (v8) also includes up to 15% of individuals of non-European ancestry. Assessing ancestry-based adjustments in GTEx provides an opportunity to improve portability of this research across populations and to further measure the impact of population structure on GWAS colocalization. Results Here, we identify a subset of 117 individuals in GTEx (v8) with a high degree of population admixture and estimate genome-wide local ancestry. We perform genome-wide cis-eQTL mapping using admixed samples in six tissues, adjusted by either global or local ancestry. Consistent with previous work, we observe improved power with local ancestry adjustment. At loci where the two adjustments produce different lead variants, we observe only 0.8% of tests with GWAS colocalization posterior probabilities that change by 10% or more. Notably, both adjustments produce similar numbers of significant colocalizations. Finally, we identify a small subset of GTEx v8 eQTL-associated variants highly correlated with local ancestry (R2 > 0.7), providing a resource to enhance functional follow-up. Conclusions We provide a local ancestry map for admixed individuals in the final GTEx release and describe the impact of ancestry and admixture on gene expression, eQTLs, and GWAS colocalization. While the majority of results are concordant between local and global ancestry-based adjustments, we identify distinct advantages and disadvantages to each approach.
Cognitive Behavioral Therapy for Anxiety Disorders

Several studies have shown that cognitive behavioral therapy (CBT) is efficacious for the treatment of anxiety disorders (Ellard and Chronopoulos, Cognitive behavioral therapy for anxiety disorders. In: The Massachusetts General Hospital handbook of cognitive behavioral therapy. Humana Press, New York, p 43–61, 2016; Hofmann et al., Cogn Ther Res, 36:427–440, 2012; Kessler et al., Arch Gen Psychiatry, 62:593–602, 2005). The core components of CBT for anxiety disorders include aspects derived from behavioral and cognitive therapies such as exposure exercises and cognitive restructuring, respectively (Sprich et al. In: Stern TA, Fava M, Rosenbaum JF, Wilens TE (eds) Massachusetts General Hospital comprehensive clinical psychiatry. Elsevier Health Sciences, p 152–64, 2016). This chapter discusses the history and development of CBT for anxiety disorders, giving an overview of both behavioral and cognitive therapies, and examines the core principles and practice of CBT for anxiety disorders in general as well as how CBT has been adjusted to target the symptoms of each anxiety disorder. Additionally, this chapter examines the efficacy and accessibility of CBT, discussing the potential for new delivery methods and cultural adaptations to increase accessibility and generalizability. Lastly, this chapter explores modifications of traditional CBT and future directions.