cssi/SciSciGPT-SciSciNet huggingface dataset:
Prophylactic Dual Catheter Technique to Prevent Side Branch Snowplowing Complications during Angioplasty and Stenting.

Objective Angioplasty and Stenting of intracranial atherosclerotic lesions have a higher complication rate and a large proportion of this is attributable to side branch arterial occlusion from forceful displacement of the atheroma into the ostia or snowplowing effect. This can result in severe disabilities when it result in small infarcts involving eloquent areas in the posterior circulation or the motor tracts. Materials and methods We present a series of 6 cases utilizing a new dual catheter technique for maintaining the patency of at-risk vessels during angioplasty and stenting. There are several methods previously described to help reduce the incidence of stroke but because they do not have a physical presence in the ostia to protect it, they are unable to guarantee the patency of the vessel. Results All 6 patients underwent angioplasty and stenting with the technique. The patients were assessed for complications with post-procedure magnetic resonance imaging and no complications were found. Conclusion In this preliminary series, the dual catheter technique appears to safe and effective in preventing occlusion of the adjacent branch arteries. This technique may facilitate the use of the Wingspan stent in the treatment of intracranial atherosclerotic stenotic segments by reducing the risk of peri-procedural stroke.
Predicting requirement change propagation through investigation of physical and functional domains

Requirements play a critical role in the design process and are important to the project’s success. The design process is iterative, and requirements are constantly changed and updated to reflect stakeholders’ expectations, design changes, regulations, and resource limitations. Since requirements drive product development from initial development of concepts to final production of the finished product, mismanaged requirement changes can lead to monetary and time losses. The ability to assess a requirement change, predict its propagation, and evaluate the impact early in the design process will enable engineers to make informed decisions regarding change implementation. Prior research performed by Morkos culminated in the Automated Requirement Change Propagation Prediction (ARCPP) tool to mitigate issues due to requirement change propagation. The ARCPP tool utilized syntactic natural language data, part of speech (POS) elements in requirement statements, as relators to form relationships between requirements. The resulting requirement network serves to predict change propagation as a result of an initiating requirement change using the performance metric of the tool, requirement review depth. Whereas the prior research proved that change propagation can be predicted using requirements, the purpose of this research is to understand why requirements can be used. Specifically, what parts of a requirement affect its ability to predict change propagation? This is performed by addressing three key research questions (RQs): (1) Is the requirement review depth affected by the number of relators selected to relate requirements, (2) Is the requirement review depth affected by the frequency of relators selected to relate requirements, and (3) Which element of a requirement, the physical or functional domain, is responsible for instigating change propagation? The results indicate that the review depth, an indicator of the performance of the ARCPP tool, is not affected by the number and frequency of relators, but rather by the ability of relators in capturing the propagating relationships. Further, the physical domain is found to contribute more towards predicting change propagation than the functional domain. Finally, a recommendation on selecting the number of requirement relators is presented.
Barriers and Facilitators to Oral PrEP Use Among Transgender Women in New York City.

Transgender women may face a disparate risk for HIV/AIDS compared to other groups. In 2012, Truvada was approved for daily use as HIV pre-exposure prophylaxis (PrEP). However, there is a dearth of research about barriers and facilitators to PrEP in transgender women. This paper will shed light on transgender women living in New York City’s perceived and actual challenges to using PrEP and potential strategies to overcome them. After completing an initial screening process, four 90-min focus groups were completed with n = 18 transgender women. Participants were asked what they like and dislike about PrEP. Participants identified the following barriers: uncomfortable side effects, difficulty taking pills, stigma, exclusion of transgender women in advertising, and lack of research on transgender women and PrEP. Facilitators included: reducing pill size, increasing the types of available HIV prevention products, and conducting scientific studies to evaluate PrEP in transgender women.
Revisiting of ‘Revisiting the Stop-and-Stare Algorithms for Influence Maximization’

SSA/DSSA were introduced in SIGMOD’16 as the first algorithms that can provide rigorous \(1-1/e-\epsilon \) guarantee with fewer samples than the worst-case sample complexity \(O(nk \frac{\log n}{\epsilon ^2 OPT_k})\). They are order of magnitude faster than the existing methods. The original SIGMOD’16 paper, however, contains errors, and the new fixes for SSA/DSSA, referred to as SSA-fix and D-SSA-fix, have been published in the extended version of the paper [11]. In this paper, we affirm the correctness on accuracy and efficiency of SSA-fix/D-SSA-fix algorithms. Specifically, we refuse the misclaims on ‘important gaps’ in the proof of D-SSA-fix’s efficiency raised by Huang et al. [5] published in VLDB in May 2017. We also replicate the experiments to dispute the experimental discrepancies shown in [5]. Our experiment results indicate that implementation/modification details and data pre-processing attribute for most discrepancies in running-time. (We requested the modified code from VLDB’17 [5] last year but have not received the code from the authors. We also sent them the explanation for the gaps they misclaimed for the D-SSA-fix’s efficiency proof but have not received their concrete feedback.)
Surveillance after curative-intent ovarian cancer treatment: The impact of HMOs.

e16530 Background: Over 21,000 women are diagnosed with ovarian cancer in the US annually. Most patients receive curative-intent treatment. Post-treatment surveillance is commonly done. We have pre...
Role of Vasoactive Agents and Hypertension in Accelerated Atherogenesis

“The casual reader of recent literature might wonder whether some authors conceive of an atherosclerosis so independent of the substrate of the vessel wall that it might occur in the absence of the blood vessels themselves” (Duff and McMillan, 1951).
SARILUMAB FOR RECALCITRANT CYSTOID MACULAR EDEMA IN NON-PARANEOPLASTIC AUTOIMMUNE RETINOPATHY.

Purpose To demonstrate a rapid improvement of recalcitrant cystoid macular edema (CME) and perivascular leakage, in a patient with non-paraneoplastic autoimmune retinopathy and autoimmune optic neuropathy after treatment with sarilumab, a human anti-interleukin-6 (IL-6) receptor antibody. Methods Observational case report. Results A 29-year-old woman was diagnosed with non-paraneoplastic autoimmune retinopathy and autoimmune optic neuropathy and followed over 1.5 years. She had recalcitrant CME despite local corticosteroid and immunosuppressive therapy that included azathioprine and adalimumab. Subcutaneous sarilumab was initiated at a dose of 200 mg every 2 weeks. Cystoid macular edema significantly decreased after two injections and resolved after four injections with associated improvement in visual acuity and significant improvement in perivascular leakage on fluorescein angiography. There was a sustained visual and anatomical improvement at 6 months along with mild improvement in electroretinogram responses. The patient tolerated the medication with no side effects. Conclusion Management of CME in non-paraneoplastic autoimmune retinopathy is challenging, and long-term immunosuppression is often employed with varying degrees of success. The improvement in refractory CME and perivascular leakage in this case supports the potential role of an IL-6 inhibitor to treat CME associated with non-paraneoplastic autoimmune retinopathy suggesting the role.
Associations between timing and quality of solid food introduction with infant weight-for-length z-scores at 12 months: Findings from the Nurture cohort.

Abstract This study assesses associations of the timing and quality of solid foods introduced during infancy with weight-for-length (WFL) z-scores at 12 months within the Nurture cohort. Women from North Carolina self-reported sociodemographics, the timing and type of solid food introduction, and reasons for introducing solids; infant anthropometrics were measured every 3 months through 1 year (n = 666). Frequency (0–5x/day) infants consumed fruits and vegetables was used to compute a mean (4–12 months) healthy food score (HFS), and sweets, french fries, snacks, and ice cream was used to compute a mean unhealthy food score (UnHFS). Multivariable-adjusted generalized linear models were used to examine the relationship of early solid food introduction, HFS quartiles (Q), UnHFS quartiles, and interactions between these variables with WFL z-scores at 12 months (n = 449). Exploratory analyses evaluated WFL z-scores among 4 groups of infants with high/low HFS and high/low UnHFS. On average, mothers were 28 years with a pre-pregnancy BMI of 30.5 kg/m2; 65% were Non-Hispanic Black, and 59% had incomes
Transformative Leadership Approaches to Inclusion, Equity, and Social Justice:

The purpose of this article is to examine the leadership beliefs and practices of three school leaders in a large urban school district in the Rocky Mountain West to determine whether any are consi...
MULTIPLE FACTORS INFLUENCING SUCCESSFUL AGING

Empirically-based theories on successful aging have emphasized the multidimensional nature of aging well, including physical health and functioning, cognitive and emotional well-being, and social connectedness and engagement (e.g., Rowe & Kahn, 1987, Depp & Jeste, 2006). Yet, the field is still continuing to discover, deeply characterize, and better understand the biopsychosocial mechanisms through which varying social, physical, or cognitive activities may influence unique domains of successful aging. The current symposium builds on this growing body of research by addressing factors supporting successful aging across multiple dimensions of well-being and among a diversity of samples ranging from urban to rural, West Coast to Midwest, and community populations to professional athletes. Webster and Antonucci examine the links between social engagement and successful aging among affordable senior housing residents. They found that more frequent participation in social activities was associated with increases in life satisfaction over time. Toyama and Fuller examine how social engagement and health affect aging well, finding that older adults’ subjective health plays a more important role than objective health in maintaining social integration over time. Similarly, Turner describes the role of social networks and religiosity for health outcomes among aging NFL athletes. Finally, Casaletto and colleagues examined mechanisms underlying cognitive wellness as an aspect of successful aging. They found that engagement in both physical and cognitive activities independently support brain health and cognitive reserve in late-life. Taken together, these presentations provide a diverse and broad perspective on how varying factors influence the multiple dimensions of successful aging.
Redundancy Scheduling in Systems with Bi-Modal Job Service Time Distributions

Queuing systems with redundant requests have drawn great attention because of their promise to reduce the job completion time and variability. Despite a large body of work on the topic, we are still far from fully understanding the benefits of redundancy in practice. We here take one step towards practical systems by studying queuing systems with bi-modal job service time distribution. Such distributions have been observed in practice, as can be seen in, e.g., Google cluster traces. We develop an analogy to a classical urns and balls problem, and use it to study the queuing time performance of two non-adaptive classical scheduling policies: random and round-robin. We introduce new performance indicators in the analogous model, and argue that they are good predictors of the queuing time in non-adaptive scheduling policies. We then propose a non-adaptive scheduling policy that is based on combinatorial designs, and show that it has better performance indicators. Simulations confirm that the proposed scheduling policy, as the performance indicators suggest, reduces the queuing times compared to random and round-robin scheduling.
Cranial Ultrasound and Minor Motor Abnormalities at 2 Years in Extremely Low Gestational Age Infants.

OBJECTIVES The objectives of this study are to determine whether abnormalities on neonatal cranial ultrasound (CUS) are associated with minor motor abnormalities at 2 years' corrected age (CA) and to assess functional outcomes and resource utilization among children with minor motor abnormalities. METHODS Infants born at <27 weeks in the National Institute of Child Health and Human Development Neonatal Research Network between January 1, 2010, and December 31, 2014, who underwent neuroimaging with CUS at both <28 days and ≥28 days and were evaluated at 18 to 26 months' CA, were included. Follow-up included Bayley-3, neuromotor examination, Gross Motor Function Classification System (GMFCS) level, and parent questionnaires about special services and resource needs. Children were classified by the most severe motor abnormality at 18 to 26 months' CA as follows: none, minor, or major motor function abnormality. Minor motor abnormalities were defined as any of the following: (1) Bayley-3 motor composite, fine motor score, or gross motor score 1 to 2 SDs below the test normative means; (2) mild abnormalities of axial or extremity motor skills on standardized neuromotor examination; or (3) GMFCS level 1. RESULTS A total of 809 (35%) of 2306 children had minor motor function abnormalities alone. This did not increase substantially with CUS findings (no intraventricular hemorrhage [IVH]: 37%, grade I IVH: 32%, grade II IVH: 38%, grade III/IV IVH: 30%, isolated ventriculomegaly: 33%, and cystic periventricular leukomalacia: 24%). The adjusted odds of minor axial and upper extremity function abnormalities and GMFCS level 1 were significantly higher in children with more severe CUS findings. Children with minor motor abnormalities had increased resource utilization and evidence of functional impairment compared with those without motor function abnormalities. CONCLUSION Minor motor abnormalities at 2 years' CA are common and cannot be predicted by neonatal CUS abnormalities alone. Minor motor abnormalities are associated with higher resource utilization and evidence of functional impairment. These findings have important implications for early counseling and follow-up planning for extremely preterm infants.
Collective Trauma and Mental Health Hospitalization Rates Among Children in New York State, 1999–2013: Age, Period, and Cohort Effects

Mental health hospitalization rates among U.S. children have been increasing locally and nationally in recent decades. Children in New York State (NYS) have also witnessed several collective traumatic events during the last two decades including the September 11, 2001, terrorist attacks (9/11), the Great Recession, and Hurricane Sandy (2012) and its aftermath. Decomposition of these rates into age, period, and cohort effects may help elucidate how large-scale collective traumatic events may be driving time trends. This study examined age-period-cohort effects in children and youth mental health hospitalizations in NYS from 1999-2013. Age effects followed a linear trend from age 5 years, B = -2.76, 95% CI [-3.48, -2.03)] up to age 15 years, B = 1.62, 95% CI [1.52, 1.73]. The largest period effects were noted in 2004, B = 0.36, 95% CI [0.28, 0.45], and in 2013, B = 0.31, 95% CI [0.15, 0.47], approximately 3 years after 9/11 and the Great Recession, respectively. The largest birth cohort effect was noted for children born in 1992-1995 (range: 0.29 for children born in 1992-0.27 for children born in 1995), suggesting that the birth cohorts who experienced the 9/11 attacks during middle childhood and the Great Recession during puberty are at increased risk of mental health hospitalizations compared to other birth cohorts.
Is Periconceptional Substance Use Associated with Unintended Pregnancy

Background: To evaluate the relationship between periconceptional (period before and/or after conception) substance use and unfavorable pregnancy contexts, including unintended pregnancy. Materials...
Effects of ethanol, naltrexone, nicotine and varenicline in an ethanol and nicotine co-use model in Sprague-Dawley rats.

Abstract Background As alcohol and nicotine use disorders are entwined, it may be possible to develop a single medication to treat both. We previously developed a model for ethanol (EtOH) and nicotine co-use in female selectively bred alcohol-preferring (P) rats. To model co-use in a genetically diverse population, we adapted the model to outbred Sprague-Dawley rats of both sexes and assessed the effect of drug pretreatments. Methods In phase 1, rats were trained in a 2-bottle choice between water and a sweetened or unsweetened EtOH solution in operant chambers. In phase 2, rats were trained in nicotine self-administration under an increasing fixed ratio (FR) schedule with 2 bottles containing water or saccharin-sweetened EtOH also available. In phase 3, rats were pretreated with EtOH (0.5, 1.5 g/kg), naltrexone (0.3 mg/kg), nicotine (0.2, 0.6 mg/kg), varenicline (3.0 mg/kg) or vehicle before the session. Results Sweetening the EtOH solution was required to obtain pharmacologically relevant levels of consumption in Phase 1, with males showing increased sweetened EtOH preference compared to females. In Phase 2, increasing the FR requirement for nicotine decreased nicotine infusions, but increased EtOH consumption. In Phase 3, EtOH, naltrexone, and nicotine failed to alter EtOH consumption; however, varenicline decreased both EtOH and nicotine intake. Conclusions The co-use model was successfully adapted to Sprague-Dawley rats by adding saccharin to the EtOH solution. In contrast to previous results in P rats, varenicline reduced both EtOH and nicotine intake, indicating it may be a useful monotherapy for co-use in a genetically diverse population.
Synchronous reference frame sliding mode observers for the inverse of the rotor time constant of the induction motor

The paper discusses the problem of inverse rotor time constant estimation for the induction motor (IM) and presents two sensorless sliding-mode observers (SMOs) that are constructed using synchronous reference frame models. Estimation is done assuming that the magnitude of the flux is available. A voltage model observer is used to estimate the αβ fluxes: these are used to compute the field-orientation angle and the flux magnitude. The paper develops an observer based on the first-order model; however, this does not perform well under parameter variations. A second observer is developed using an augmented model (which now involves the speed of the motor) - this is transformed into a sensorless design by feeding it with a speed estimate (assumed inaccurate). It is shown how to design the feedback gains in order to reduce the sensitivity of the estimate to the input speed error. The theoretical developments are supported with simulations and experiments.
Geometric sensitivity of electrochemical fin shape on three dimensional microstructure network conductivity analysis

Abstract A rapid microstructural assessment tool has previously been developed to support electrode design efforts by modeling charge transport and surface electrochemistry through networks of transport channels represented by ideal axisymmetric electrochemical fins. Analytical solutions have allowed these fins to take the form of a positive curvature sphere, a neutral curvature conical frustum, and a negative curvature smooth exponential profile. The present paper aims to enhance the geometric sensitivity of the network modeling tool by fitting ideal fin shapes to individual channels within the microstructure via dimensionless parameters describing channel morphology. The tool is used to directly compute effective transport properties of a range of microstructures, including artificial packed sphere structures and real solid oxide fuel cell electrode and gas membrane material microstructures imaged by X-ray nanotomography. Results obtained are compared with detailed finite element analyses and predictions from percolation theory. It is shown that the model can capture transport losses associated with microstructure on the particle scale, highlighting its potential as a less computationally demanding complement to detailed numerical models such as finite element or lattice Boltzmann methods for preliminary electrode design screening. Results also emphasize the importance of capturing local microstructural effects of specific transport networks, as electrochemical fin results provide more accurate performance predictions than percolation theory for structures near their percolation threshold.
Analysis of fuel rod behavior during loss-of-coolant accidents using the BISON code: Cladding modeling developments and simulation of separate-effects experiments

Abstract BISON is a finite-element based, multidimensional fuel performance code developed at Idaho National Laboratory. In this paper, we present BISON modeling developments for Zircaloy nuclear fuel cladding behavior under loss-of-coolant accident (LOCA) conditions and code validation to separate-effects experiments. Code developments include models for cladding high-temperature creep, crystallographic phase transition, high-temperature steam oxidation and failure due to burst. Code validation is performed against a substantial number of experimental tests for ballooning and burst behavior of Zircaloy claddings under LOCA conditions. Validation calculations are completed using 2D axisymmetric models. Additionally, we present a 3D calculation that demonstrates simulation of the cladding response in presence of azimuthal temperature variations. Calculated results are systematically compared to experimental data of cladding temperature, inner pressure and time at burst failure. Several of the presented BISON validation cases were developed in the framework of the IAEA Coordinated Research Project FUMAC. BISON modeling developments for UO2 fuel behavior under LOCA conditions and code validation to integral fuel rod experiments are presented in a complementary paper.
Safe Implementation of a Respiratory Therapist-Driven NICU Ventilator Weaning Protocol

Background: Utilization of invasive ventilation can lead to adverse events or hospital-acquired conditions for the neonatal patient such as long-term damage to the lungs, increased risk of infection, ventilator-associated events, and unplanned extubations. Implementation of a respiratory therapist (RT) driven protocol can safely standardize ventilator weaning strategies in post-operative neonatal patients, thereby reducing associated risks to patients. Methods: An RT driven protocol was developed, allowing the RT to manage the weaning of post-operative patients within the Neonatal Intensive Care Unit (NICU). Post-op patients greater than 2 kg were included if they did not receive blood products in surgery. Patients with pulmonary or airway comorbidities potentially impacting extubation success were excluded. The implementation of the protocol required a provider order. The Institutional Review Board approved this protocol. Real-time data was collected on patients admitted post-operatively to the NICU from November 1, 2016 to April 2, 2017. The NICU Post-op Ventilator Weaning Protocol was initiated on April 3, 2017. On December 3, 2019 the protocol was updated to be more inclusive; expanded to all invasively ventilated patients with postmenstrual age of greater than 29 weeks, and eliminated post-operative and weight requirements. Results: During the 6-month pre-data collection period, 5 patients were identified as fitting the protocol requirements. Mean weight was 2.69 kg, ranging from 2.44 to 2.84 kg. Average time to extubation was 17.8 hours, ranging from 7 hours to 23.75 hours. During the first two years, 33 patients were ordered for the NICU Ventilator Post-op Weaning Protocol. Of these, 5 patients were removed due to provider preference and 1 patient was removed due to multiple failed weaning attempts. There were 27 patients who successfully completed the protocol to extubation. Mean weight was 2.78 kg, ranging from 1.75 to 4.04 kg. The average time to extubation decreased slightly from the pre-data sample to 17.5 hours, ranging from 1.08 hours to 54.5 hours. Only one patient was reintubated within 24 hours of extubation due to stridor. No adverse events were reported. Conclusions: Implementation of a RT driven ventilator weaning protocol allows the RT to expand their scope of care and safely standardize the ventilator weaning process. Additionally, increasing the autonomy of the RT at the bedside, improved both RT staff and provider satisfaction
A hidden threshold in motor neuron gene networks revealed by modulation of miR-218 dose.

Summary Disruption of homeostatic microRNA (miRNA) expression levels is known to cause human neuropathology. However, the gene regulatory and phenotypic effects of altering a miRNA’s in vivo abundance (rather than its binary gain or loss) are not well understood. By genetic combination, we generated an allelic series of mice expressing varying levels of miR-218, a motor neuron-selective gene regulator associated with motor neuron disease. Titration of miR-218 cellular dose unexpectedly revealed complex, non-ratiometric target mRNA dose responses and distinct gene network outputs. A non-linearly responsive regulon exhibited a steep miR-218 dose-dependent threshold in repression that, when crossed, resulted in severe motor neuron synaptic failure and death. This work demonstrates that a miRNA can govern distinct gene network outputs at different expression levels and that miRNA-dependent phenotypes emerge at particular dose ranges because of hidden regulatory inflection points of their underlying gene networks.
WormCat 2.0 defines characteristics and conservation of poorly annotated genes in Caenorhabditis elegans

Genome-wide measurement of mRNA or protein levels provides broad data sets for biological discovery. However, subsequent computational methods are essential for uncovering the functional implications of the data as well as intuitively visualizing the findings. Current computational tools are biased toward well-described pathways, limiting their utility for novel discovery. Recently, we developed an annotation and category enrichment tool for Caenorhabditis elegans genomic data, WormCat, that provides an intuitive visualization output. Unlike GO, which excludes genes with no annotation information, WormCat 2.0 retains these genes as a special UNASSIGNED category. Here, we show that the UNASSIGNED gene category enrichment exhibits tissue-specific expression patterns and include genes with biological functions. Poorly annotated genes have previously been considered to lack homologs in closely related species. Instead, we find that around 3% of the UNASSIGNED genes have poorly characterized human orthologs. These human orthologs are themselves have little annotation information. A recently developed method that incorporates lineage relationships (abSENSE) indicates that failure of BLAST to detect homology explains the apparent lineage specificity for many UNASSIGNED genes, suggesting that a larger subset could be related to human genes. WormCat provides an annotation strategy that allows association of UNASSIGNED genes with specific phenotypes and known pathways. Our analysis indicates that the UNASSIGNED gene category contains candidates that merit further functional study which could yield insight into understudied areas of biology.
Pharmacological Inhibition of Protein Lipidation

Lipid modifications of mammalian proteins are widespread, modifying thousands of targets involved in all aspects of cellular physiology cellular physiology. Broadly, lipidations serve to increase protein hydrophobicity and association with cellular membranes. Often, these modifications are absolutely essential for protein stability and localization, and serve critical roles in dynamic regulation of protein function. A number of lipidated proteins are associated with diseases, including parasite infections, neurological diseases, diabetes, and cancer, suggesting that lipid modifications represent potentially attractive targets for pharmacological intervention. This review briefly describes the various types of posttranslational protein lipid modifications, proteins modified by them, and the enzymatic machinery associated with these. We then discuss several case studies demonstrating successful development of lipidation inhibitors of potential (and more rarely, realized) clinical value. Although this field remains in its infancy, we believe these examples demonstrate the potential utility of targeting protein lipidation as a viable strategy for inhibiting the function of pathogenic proteins.
Vesicovaginal and Ureterovaginal Fistulas: A Summary of 25 Years of Experience

The difficult problem of a vesicovaginal fistula originally was cured surgically by Sims in 1849. During the last 25 years at UCLA and affiliated hospitals 68 patients have been treated by urologic surgeons for fistulas between the vagina and the urinary tract: 21 ureterovaginal and 47 vesicovaginal and urethrovaginal fistulas. The ureterovaginal fistulas often were complex and patients presented the most challenging diagnostic problem. However, they usually were repaired successfully by simple ureteroneocystostomy. Vesicovaginal and urethrovaginal fistulas were repaired transvaginally in 24 cases, with 70% success at the first attempt and 92% success with 2 attempts. Transabdominal or combined approaches were less successful. Only 58% of the cases were closed at first attempt. The transvaginal approach required less operating time, and resulted in less blood loss and shorter hospital stays than the transabdominal approach and will be described in detail.
Theory and Instrumentation of Mass Spectrometry and its Application to Drug Metabolism

Adsorption, distribution, metabolism, and excretion (ADME) studies demand that analytical methodologies used for analyses be sensitive, selective, accurate, precise, robust, and reproducible. Because of these requirements, liquid chromatography–mass spectrometry (LC-MS) has emerged as the preferred bioanalytical technique in ADME and drug metabolism and pharmacokinetic (DMPK) research. This article reviews the latest LC-MS instrumentation and techniques used in drug metabolism studies. For LC, the use and appropriateness of various chromatographic stationary phases as well as the use of ultraperformance (UP) LC and chip separations are discussed. The development of atmospheric pressure ionization (API) techniques, such as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), have made LC separation amenable to MS analysis. Typical mass analyzers used in drug discovery include the triple-stage quadrupole (TSQ), ion trap, and hybrid mass analyzers. In addition, the authors include information on the use of stable isotope dilution (SID) methodology, high-throughput techniques, and multivariate data analysis (MDA) as they pertain to drug metabolism studies. Keywords: LC-MS; drug metabolism; atmospheric pressure ionization; triple-stage quadrupole; ion-trap; stable isotope dilution; high-throughput analysis; multivariate data analysis
Origin Narratives and the Making of Dynastic History in al‐Dīnawarī's Akhbār

This article takes the reader on a journey into the historical writing of the ninth century Muslim historian al-Dīnawarī (d. 895) and examines the motives behind composing his al-Akhbār al-ṭiwāl. The themes and narrative arrangements of this work give insight into al-Dīnawarī's historical agenda that demonstrates his interest in royal histories that exemplify the rise and fall of nations, dynasties, and powerful rulers. Al-Dīnawarī's emphasis on specific episodes and events demonstrates that only certain ethnic groups whose political legitimacy derives from a respectable and prominent origin can bring about political and social stability. By dealing with these sociopolitical concerns, this article also sheds new light on the intellectual discourses and political crises that dominated Islamic society during the eighth and ninth centuries and the way al-Dīnawarī reacted to these challenges.
Pioneer Venus Overview

A Pioneer Venus Overview is discussed. Pioneer Venus consists of two basic spacecraft: Orbiter and Multiprobe. The latter was separated into five separate vehicles near Venus. These were the probe transporter (called the Bus), a large atmospheric entry probe (dubbed Sounder) and three identical smaller probes (called North , Day, and Night in accordance with their entry locations). At Venus all six spacecraft communicated directly back to the Earth-based Deep Space Network (DSN) and, in the case of the Multiprobe mission, to two special receiving sites near Guam and Santiago (Chile). At the time this Special Issue was submitted for publication the nominal mission was complete and the Orbiter was continuing into an extended mission phase. It appears so that sufficient fuel remains to permit full operation through calendar year 1980, at least. The scientific payload, Principle Investigator, and his affiliation are listed for each Pioneer Venus spacecraft. This special issue is primarily devoted to short descriptions of the instruments listed with the exception of the Orbitor Cloud Photopolarimeter. Detailed instrument descriptions for this experiment have been published. Before proceeding with descriptions of the individual instruments, four special archival-type reports are included. The first deals with spacecraft design and operation. The Pioneer Venus spacecraft were unique and very special design features and operational modes needed to be incorporated. These are summarized therein. It should be noted that neither the scientific objectives nor the scientific results of the Pioneer Venus program are described or discussed in detail. The objectives have been published elsewhere.
Cell proliferation during morphogenetic change; analysis of frontonasal morphogenesis in the chick embryo employing DNA labeling indices

SUMMARY The role of cell proliferation was analyzed in the chick embryo system employing DNA labeling indices during the invagination of the olfactory placode and the development of the lateral and medial nasal processes. Chick embryos were labeled for 1 h with [ 3 H]thymidine and processed histologically and autoradiographically. The percentage of labeled mesenchymal cells in delineated areas within and adjacent to the nasal processes was determined. From analysis of labeling indices of each area at successive developmental stages, it was concluded that cell proliferation of mesenchyme, as measured by DNA labeling indices, did not appear to increase during the formation of the nasal processes, and that cell proliferation actually declined during the later stages of nasal process formation. Differences were also found between the labeling indices of the mesenchyme of the nasal processes as compared to that of adjacent areas. These differences tended to become greater as development progressed. In all of the areas studied, cell proliferation declined during the Jater stages of development but the magnitude of the decline was greater in the areas adjacent to the nasal processes. Differential rates of decline, rather than acceleration of cell proliferation, therefore, appears to be operative as a morphogenetic mechanism during early primary palate formation.
Multipolar interactions in metallic rare-earth compounds

Abstract The existence of multipolar pair interactions in rare-earth compounds is well established but it has been difficult to determine the origins of these couplings in specific systems. Here we review some of the evidence and origins of these interactions.
Collision complex formation in the low-energy dynamics of the C+ + O2 reaction

Abstract A crossed beam study of CO + production from the C + + O 2 reaction at a collision energy of 0.57 eV is presented. Very clear collision complex dynamics are observed which are shown to be consistent with the decay of a transient complex having a lifetime of approximately 0.5 ps. An analysis of the reactive scattering using an adiabatic state correlation diagram indicates that the formation of X-state CO 2 + by insertion of C + into the O 2 bond is accessible from the reagents and correlates adiabatically with ground-state products. The average kinetic energy release is approximately 23% of the available energy. A comparison of the present data with the chemiluminescent studies of A-state production of CO + indicates that the dominant channels at low energies are production of ground-state CO + through the X 2 Π g and a 4 Π u state of CO 2 + .
Hyperplane method for reachable state estimation for linear time-invariant systems

A numerical algorithm is presented for generating inner and outer approximations for the set of reachable states for linear time-invariant systems. The algorithm is based on analytical results characterizing the solutions to a class of optimization problems which determine supporting hyperplanes for the reachable set. Explicit bounds on the truncation error for the finite-time case yield a set of so-called e-supporting hyperplanes which can be generated to approximate the infinite-time reachable set within an arbitrary degree of accuracy. At the same time, an inner approximation is generated as the convex hull of points on the boundary of the finite-time reachable set. Numerical results are presented to illustrate the hyperplane method. The concluding section discusses directions for future work and applications of the method to problems in trajectory planning in servo systems.
Hepatic adenoma. Biochemical and electron microscopic study

Five cases of benign tumors of the liver designated as hepatic adenomas were examined. In addition to light microscopy, tissues were available from 2 cases for electron and biochemical analyses. The gross appearance of these tumors was characterized by the central fibrous tissue core, with peripheral extensions producing nodulation. Light and electron microscopy revealed that these tumors were composed of normal-appearing hepatic cells and bile ducts, lacking only the organization into hepatic lobules. Another characteristic feature was the proliferation of bile ducts in the centers of the tumor nodules. The most striking finding was the excessive accumulation of cytoplasmic glycogen in some of these tumors. However, biochemical analysis demonstrated normal values of the enzymes which are deficient in glycogen storage diseases. In addition, the activity of those enzymes decreased in experimental hepatomas was within normal limits in our material, thus indicating the benign nature of these lesions. Differentiation of regenerative hyperplasia, hamartoma, and adenoma of the liver is discussed.
Work and Rest Cycles in Anesthesia Practice

A questionnaire inquiring about existing and desirable work and rest patterns appeared in a newsletter mailed to about 22,000 anesthesiologists and anesthesiology residents and 24,000 nurse anesthetists (CRNA). Almost 3,000 anonymous replies were received and analyzed. Respondents reported mean work weeks of 47.5 h (CRNA) to 69.8 h (residents), longest continuous period of administering anesthesia without a break of 6.6 h (CRNA) to 7.7 h (residents), and longest period of administering anesthesia with or without breaks of 14.1 h (CRNA) to 20 h (resident). However, the respondents considered it safe to administer anesthesia without a break for 4.2 (CRNA) to 5.2 h (anesthesiologists) and with break for 12.8 h (CRNA) to 15 h (residents). A substantial number of respondents believed that they work at least occasionally beyond their perceived self-limitations. The majority of respondents recalled having made errors in the administration of anesthesia that they attributed to fatigue. These results may not be representative of work patterns or attitudes among American anesthesia providers because of the small sample size and the resultant potential for bias. Yet, the subject deserves attention and further study because fatigue can affect professional performance, ability to learn, and family life.
Adaptive Remediation in Complex Skill Training

Research has demonstrated that complex skill acquisition can be improved for some learners by implementing a Multiple Emphasis on Components (MEC) protocol during training. However, as learners vary in ability and experience, multiple emphasis may not be appropriate for all, and adaptive or individualized instructional paradigms may prove useful for training on some tasks. In addition, verbal elaboration has sometimes proven useful for improving training. In the present study, 118 participants were randomly assigned to one of six conditions representing the factorial combination of three emphasis conditions (total score, MEC, or MEC-adative remediation) and two verbal elaboration elaboration conditions (elaboration or no elaboration condition) and were trained on the complex task Space Fortress. Results support the use of adaptive multiple emphasis training on some task components. Results for verbal elaboration were mixed. Implications for training and computer-based adaptive training protocols are discu...
The solar neutrino problem: Mixing of neutrinos and mixing in the sun☆

I review the current status of the solar neutrino problem, including the exciting possibility of matter enhanced neutrino oscillations. Neutrino flux measurements, independent of questions of solar dynamics, appear to leave only one competing candidate astrophysical solution, at least in the case of steady-state solar models. That possibility — mixing of the solar core on time scales of 3He equilibration — appears to have some attractive features. A “score card” is presented in which the two alternatives — mixed neutrinos or a mixed sun — are handicapped.
Spheres tangent to all the faces of a simplex

Abstract There are at most 2n spheres tangent to all n + 1 faces of an n-simplex. It has been shown that the minimum number of such spheres is 2 n − c(n, 1 2 (n + 1)) if n is odd and 2 n − c(n, 1 2 (n + 1)) if n is even. The object of this note is to show that this result is a consequence of a theorem in graph theory.
Literacy and “Empowerment”? A Case Study of Literacy behind Bars

A Chicano prison inmate's progress in a year-long literacy tutorial course demonstrates ways in which writing can negotiate and reorganize race, class, gender, and power identities for both tutor and student, and legitimize the student's voice, native language, and discourse stance. Through dialogue, the student progresses from the passive-learner role to a presentation of self as knowledgeable expert; from denial of his prison group-membership, he progresses to a critical analysis of the power structure it represents.
Conditioning the eyeblink response to sound in infants

Eyeblink conditioning to a complex sound was investigated in eight experimental and 12 control infants, with a median age of 69.5 days. All eight experimental Ss reached criterion of nine blinks on 10 successive trials. In control groups for spontaneous blinking, for effects of presentations of CS alone, and for effects of unpaired presentations of CS and UCS, no S approached the criterion of conditioning.
Accurate Inversion of High-Resolution Snow Penetrometer Signals for Microstructural and Micromechanical Properties

[1] Measurements of snow using a high-resolution micropenetrometer can be used to discriminate between different snow types; in lower-density snow the signal is sensitive to microstructure, and micromechanical properties can be estimated. Although a physics-based snow penetration theory was first developed almost a decade ago, since that time the majority of studies using snow micropenetrometers have focused on using direct hardness measurements in statistical relationships. We use Monte-Carlo simulations to rigorously test the existing physics-based snow micropenetration theories over a wide range of parameters. These tests revealed four major sources of error in the inversion, which are corrected in this analysis. It is shown that this improved inversion algorithm can recover micromechanical parameters in synthetic data with much greater accuracy over the entire range of micromechanical properties observed in natural snow. Detailed examples of the inversion results are shown for eight different snow types, collected in both Alaskan and alpine snowpacks. The resulting micromechanical properties are distinctly different, indicating that a snow characterization from snow micropenetrometer estimates of micromechanical properties is likely possible. Estimates of the microscale elastic modulus, microscale strength, and structural element length make sense physically when compared to the qualitative descriptions of the different snow types. Microscale strength estimates are used to estimate macroscale strength values, and results from 33 different snow samples, covering a wide range of densities and snow types, are consistent with previously reported values from macroscale tests.
A case for 77-bromine labelled radiopharmaceuticals

Abstract The use of radiobromine as a label for radiopharmaceuticals was demonstrated by the synthesis of 82 Br-2,4-dibromoesterone, using the procedure of Slaunwhite and Neely . Structure determination of the brominated steroid was accomplished by the use of melting point data, paper chromatoraphy and mass spectra analysis. Tissue distribution studies in animals demonstrated rapid blood clearance and excretion in the bile. Calculated radiation exposure dose for 77 Br-2,4-dibromoestrone is less than 131 I-Rose Bengal. A significant difference in tissue distribution was found when the data for 82 Br-2,4-dibromoesterone was compared to literature values for 82 Br-7,8-dibromoesterone. Comparison with 131 I-Rose Bengal and 99 m Tc-pyrodoxylideneglutamate suggest 77 Br-2,4-dibromoestrone would be a tracer of potential value for liver and gallbladder function studies.
DHIS: discriminating hierarchical storage

A typical storage hierarchy comprises of components with varying performance and cost characteristics, providing multiple options for data placement. We propose and evaluate a hierarchical storage system, DHIS, that uses application-level hints to discriminate between data with different access characteristics, and then customizes its placement and caching policies to each type. The data placement decisions in DHIS are made in an online fashion, during data creation. Most existing solutions that attempt to customize data layout require moving data around, based on access characteristics. DHIS uses two kinds of information to make its decisions. First, it uses knowledge about higher-level pointers between blocks (for example, file system pointers) to understand the relationship between blocks and consequently, their importance. Second, DHIS defines a set of generic attributes that the higher layers can use to annotate data, conveying various properties such as importance, access pattern, etc. Based on these attributes, DHIS dynamically decides to place the data in the hierarchy best suited for its requirements. By doing so, DHIS solves a critical problem faced by storage vendors and developers of higher level storage software, in terms of choosing the most efficient policy among many alternatives. Through several benchmarks, we show that DHIS's data placement decisions improve performance significantly.
Telephone conferencing in administrative hearings

Abstract A research summary of the Fair Hearing Project underway at the University of New Mexico aimed at evaluation the use of telephone conferencing in administrative hearings.