cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 16554: Rapid Identification of Familial Hypercholesterolemia From Electronic Health Records

Background: Familial hypercholesterolemia (FH) is an important public health burden as it is a relatively common Mendelian genetic disorder which is associated with dramatically increased lifetime risk for premature atherosclerotic cardiovascular disease (ASCVD) due to elevated plasma low-density lipoprotein cholesterol (LDL-C) levels. Little is known about prevalence and control of FH in the US. Objective: To develop an electronic phenotyping algorithm for rapid identification of FH in electronic health records (EHRs) and thereby address knowledge gaps in prevalence and control of FH. Methods: We identified patients in the Mayo Employee and Community Health (ECH) system who met the following inclusion criteria: 1) gave research authorization, 2) any LDL-C in EHR ≥190 mg/dL; 2) triglycerides <400 mg/dL; 3) absence of secondary causes of hyperlipidemia (hypothyroidism, cholestatic liver diseases, nephrotic syndrome, renal failure, and pregnancy). Next we applied the Dutch Lipid Clinic Network (DLCN) criteria to ascertain FH cases. ASCVD-related diagnosis codes, laboratory data, and medications were obtained from structured EHR datasets. We used the Mayo natural language processing (NLP) system to ascertain presence of family and personal history of premature ASCVD, xanthomas and corneal arcus from clinical text notes. Results: Of a total of 131,000 patients seen in ECH clinics between July 1993 and December 2014, 6018 met the inclusion criteria. Implementing the electronic phenotyping algorithm for FH in these patients identified 178 definite and 369 probable cases (DLCN score >8 and 6-8 points, respectively) with an overall FH prevalence of 0.4% (1:240). Blinded expert review of 160 randomly chosen patients showed positive and negative predictive values for electronic phenotyping algorithm at 85% and 90%, respectively. Only 40% of these patients achieved LDL-C ≤100 mg/dL on treatment. Conclusions: 1) An EHR-based phenotyping algorithm that included NLP had reasonable accuracy in ascertaining FH cases. 2) Implementing this algorithm revealed the prevalence of FH in the study cohort to be nearly twice the current estimate of 1:500 in the general population. 3) Less than half of the FH patients had optimal LDL-C levels on treatment.
Measurement of quality of care for adjuvant chemotherapy of colorectal cancer

6071 Background: Although adjuvant chemotherapy (CT) is a crucial component of the therapy for stage III colon cancer and stage II and III rectal cancer patients, little is known about how best to ...
Closing Reflection: Militiamen Get Paid; Women Borrowers Get Beaten

A rural poor woman wants to withdraw from the microcredit scheme, but her husband slaps her when she even suggests not renewing her loan.
Power in Bayesian Mediation Analysis for Small Sample Research

It was suggested that Bayesian methods have potential for increasing power in mediation analysis (Koopman, Howe, Hollenbeck, & Sin, 2015; Yuan & MacKinnon, 2009). This paper compares the power of Bayesian credibility intervals for the mediated effect to the power of normal theory, distribution of the product, percentile, and bias-corrected bootstrap confidence intervals at N≤ 200. Bayesian methods with diffuse priors have power comparable to the distribution of the product and bootstrap methods, and Bayesian methods with informative priors had the most power. Varying degrees of precision of prior distributions were also examined. Increased precision led to greater power only when N≥ 100 and the effects were small, N < 60 and the effects were large, and N < 200 and the effects were medium. An empirical example from psychology illustrated a Bayesian analysis of the single mediator model from prior selection to interpreting results.
Evolved pesticide tolerance influences susceptibility to parasites in amphibians

Because ecosystems throughout the globe are contaminated with pesticides, there is a need to understand how natural populations cope with pesticides and the implications for ecological interactions. From an evolutionary perspective, there is evidence that pesticide tolerance can be achieved via two mechanisms: selection for constitutive tolerance over multiple generations or by inducing tolerance within a single generation via phenotypic plasticity. While both mechanisms can allow organisms to persist in contaminated environments, they might result in different performance trade-offs including population susceptibility to parasites. We have identified 15 wood frog populations that exist along a gradient from close to agriculture and high, constitutive pesticide tolerance to far from agriculture and inducible pesticide tolerance. Using these populations, we investigated the relationship between evolutionary responses to the common insecticide carbaryl and host susceptibility to the trematode Echinoparyphium lineage 3 and ranavirus using laboratory exposure assays. For Echinoparyphium, we discovered that wood frog populations living closer to agriculture with high, constitutive tolerance experienced lower loads than populations living far from agriculture with inducible pesticide tolerance. For ranavirus, we found no relationship between the mechanism of evolved pesticide tolerance and survival, but populations living closer to agriculture with high, constitutive tolerance experienced higher viral loads than populations far from agriculture with inducible tolerance. Land use and mechanisms of evolved pesticide tolerance were associated with susceptibility to parasites, but the direction of the relationship is dependent on the type of parasite, underscoring the complexity between land use and disease outcomes. Collectively, our results demonstrate that evolved pesticide tolerance can indirectly influence host-parasite interactions and underscores the importance of including evolutionary processes in ecotoxicological studies.
Vom Electronic zum Mobile Commerce

Folgt man dem Global Mobile Commerce Forum, so ist Mobile Commerce „the delivery of electronic commerce capabilities directly into the consumer’s device, anywhere, anytime via wireless networks“. Ist dies auch noch keine prazise Definition, wird doch die Richtung sehr deutlich.
Tututepec: A Postclassic-period Mixtec conquest state

Around a.d. 1000 a political empire centered at Tututepec on Oaxaca's Pacific Coast formed and rose to prominence under the leadership of the great Mixtec lord 8 Deer. The extensive (25,000 km2) and ethnically diverse Tututepec empire was integrated by a system of conquest and alliance, tribute and service, military conscription, trade, a three- to four-level political hierarchy, and a simple administrative network. It was further linked by a system of royal marital alliance and trade to the Mixtec states in the Mixteca Aha and Mixteca Baja in the mountains to the north. The empire, smaller but more tightly integrated than the Chulhua-Mexica empire and smaller but more loosely integrated than the Purepecha (Tarascan) empire, dominated the Oaxaca Coast until the arrival of the Spaniards in the early 1520s.
Automation-Induced Complacency Potential: Development and Validation of a New Scale

Complacency, or sub-optimal monitoring of automation performance, has been cited as a contributing factor in numerous major transportation and medical incidents. Researchers are working to identify individual differences that correlate with complacency as one strategy for preventing complacency-related accidents. Automation-induced complacency potential is an individual difference reflecting a general tendency to be complacent across a wide variety of situations which is similar to, but distinct from trust. Accurately assessing complacency potential may improve our ability to predict and prevent complacency in safety-critical occupations. Much past research has employed an existing measure of complacency potential. However, in the 25 years since that scale was published, our conceptual understanding of complacency itself has evolved, and we propose that an updated scale of complacency potential is needed. The goal of the present study was to develop, and provide initial validation evidence for, a new measure of automation-induced complacency potential that parallels the current conceptualization of complacency. In a sample of 475 online respondents, we tested 10 new items and found that they clustered into two separate scales: Alleviating Workload (which focuses on attitudes about the use of automation to ease workloads) and Monitoring (which focuses on attitudes toward monitoring of automation). Alleviating workload correlated moderately with the existing complacency potential rating scale, while monitoring did not. Further, both the alleviating workload and monitoring scales showed discriminant validity from the previous complacency potential scale and from similar constructs, such as propensity to trust. In an initial examination of criterion-related validity, only the monitoring-focused scale had a significant relationship with hypothetical complacency (r = -0.42, p < 0.01), and it had significant incremental validity over and above all other individual difference measures in the study. These results suggest that our new monitoring-related items have potential for use as a measure of automation-induced complacency potential and, compared with similar scales, this new measure may have unique value.
Nonpituitary Sellar Masses and Infiltrative Disorders

Supra- and intrasellar tumors constitute 10% of all pediatric CNS tumors and may cause endocrine dysfunction due to their close proximity to the hypothalamic-pituitary axis. Endocrine dysfunction may exist at presentation or can occur after surgical intervention or evolve subsequently during or after completion of chemotherapy or radiotherapy. Apart from pituitary adenomas, which comprise approximately 90% of all sellar tumors, there are tumors or tumor-mimicking lesions of non-pituitary origin occurring in the suprasellar region. These non-pituitary sellar masses can be developmental in origin, inflammatory, immunologic or vascular in nature and are further categorized as benign or malignant. In this chapter, we discuss the clinical and neuroradiologic presentation of non-pituitary supra- and intrasellar tumors that occur in the pediatric population, along with the histologic and molecular characterization of these tumors.
The Impact of Interdisciplinary Education on Skills and Attitudes of Surgery and Emergency Medicine Residents.

Background Interdisciplinary education (IDE) has been proposed as a means to improve patient safety by enhancing the performance of diverse health care teams. The improved camaraderie between members of different specialties may enhance communication and can foster a more supportive and positive work environment. Objective This study was aimed to assess the effect of IDE on the procedural skills of general surgery (GS) and emergency medicine (EM), as well as the perceptions that GS and EM residents have of one another. Methods EM and GS residents participated in two separate IDE sessions (4 months apart) designed to teach extended focused assessment with sonography in trauma (e-FAST), tube thoracostomy, and complex wound closure. Surveys were administered to determine the effects that IDE had on confidence in performing bedside procedures, perceptions of IDE, and perceptions of one another's specialty. Survey responses were recorded using a 5-point Likert's scale. Results Nine GS residents and 10 EM residents participated in the entire study. Significant improvements in the confidence levels of performing bedside procedures were noted among both groups of residents. We also report a significant improvement in the perceived respect and communication between EM and GS residents. Conclusions Although further studies with a larger sample size are required, we have shown that IDE can improve the confidence levels of EM and GS residents in performing tube thoracostomy, e-FAST, and complex wound closure. These IDE sessions also improve the perceptions that the residents have of one another. IDE is a useful tool and may translate into improved consultation, collaboration, and patient care.
Acoustical emphasis not possible: The case of emphatic morphemes in Lakota

In languages like English, emphasis can be expressed acoustically by an increase in pitch or amplitude. These types of pitch excursions and increase in amplitude are often how metrical stress is marked in languages. This type of representation of metrical stress is true for Lakota. While this type of acoustic representation of stress is not uncommon, it does present a unique problem for Lakota speakers when it comes to encoding emphasis acoustically in their speech. Lakota (a member of the Dakota family of languages with less than 9000 speakers), has a very rigid set of rules for where stress can be applied in languages, often having several minimal pairs that differ only in which syllable receives primary stress. As such, they are unable to utilize these common acoustic markers for emphasis in their speech. Field research conducted on the Pine Ridge Reservation (2018, 2016) has resulted in the discovery that Lakota possesses two emphatic morphemes: [kʃto] for female speakers and [jelo] for males, which s...
Limb-girdle muscular dystrophy: A perspective from adult patients on what matters most.

Introduction Limb-girdle muscular dystrophy (LGMD) consists of over 30 genetic conditions with varying clinical phenotypes primarily affecting pelvic girdle, shoulder girdle, and other proximal limb muscles. Studies focusing on the physical, mental, and social effects of this disease from the patient's perspective are limited. Methods Adults with LGMD were interviewed and asked to identify issues that have the greatest impact on their quality of life. Each interview was recorded, transcribed, coded, and analyzed. Results Participants provided 1385 direct quotes. One hundred sixty-five potential symptoms of importance were identified and grouped into 15 larger themes. The most frequently reported themes included limitations with mobility, difficulty performing activities, social role limitations, and emotional distress. Discussion There are multiple symptoms that alter the lives of adults with LGMD. These affect their physical, emotional, and social health, and may be amenable to medical intervention.
Essential roles of interstitial cells in testicular development and function.

Background Testicular architecture and sperm production are supported by a complex network of communication between various cell types. These signals ensure fertility by: regulating spermatogonial stem/progenitor cells; promoting steroidogenesis; and driving male-specific differentiation of the gonad. Sertoli cells have long been assumed to be the major cellular player in testis organogenesis and spermatogenesis. However, cells in the interstitial compartment, such as Leydig, vascular, immune, and peritubular cells, also play prominent roles in the testis but are less well understood. Objectives Here, we aim to outline our current knowledge of the cellular and molecular mechanisms by which interstitial cell types contribute to spermatogenesis and testicular development, and how these diverse constituents of the testis play essential roles in ensuring male sexual differentiation and fertility. Methods We surveyed scientific literature and summarized findings in the field that address how interstitial cells interact with other interstitial cell populations and seminiferous tubules (i.e., Sertoli and germ cells) to support spermatogenesis, male-specific differentiation, and testicular function. These studies focused on 4 major cell types: Leydig cells, vascular cells, immune cells, and peritubular cells. Results and discussion A growing number of studies have demonstrated that interstitial cells play a wide range of functions in the fetal and adult testis. Leydig cells, through secretion of hormones and growth factors, are responsible for steroidogenesis and progression of spermatogenesis. Vascular, immune, and peritubular cells, apart from their traditionally acknowledged physiological roles, have a broader importance than previously appreciated and are emerging as essential players in stem/progenitor cell biology. Conclusion Interstitial cells take part in complex signaling interactions with both interstitial and tubular cell populations, which are required for several biological processes, such as steroidogenesis, Sertoli cell function, spermatogenesis, and immune regulation. These various processes are essential for testicular function and demonstrate how interstitial cells are indispensable for male fertility.
Safe Expectations: Current State and Future Directions for Medication Safety in Pregnancy Research.

Abstract Medication use in pregnancy is common, but information about the safety of most medications in pregnant women or their infants is limited. In the absence of data from randomized clinical trials to guide decisions made by regulators, clinicians, and patients, we often have to rely on well-designed observational studies to generate valid evidence about the benefits and risks of medications in pregnancy. Spontaneous reporting, primary case–control and cohort studies, pregnancy exposure registries, and electronic health data have been used extensively for studying medication safety in pregnancy. This article discusses these data sources, their strengths and limitations, and possible strategies and approaches to mitigating limitations when planning studies or interpreting findings from the literature. Strategies discussed include combining data sources across institutional or national borders, developing and using more sophisticated study designs, and taking advantage of existing analytic methods for more complex data structures, such as time-varying exposure or unmeasured confounding. Finally, we make recommendations for study designs that aid in better risk-related communication.
Robotic vs. open surgical management of ureteroenteric anastomotic strictures: technical modifications to enhance success

Development of ureteroanastamotic strictures (UAS) after urinary diversion is not uncommon, but is challenging to treat. Poor outcomes are likely with endoscopic and radiologic management, and definitive surgical treatment can cause significant morbidity. The comparative advantages of an operative approach have not yet been fully described in the literature. We retrospectively reviewed the prospectively maintained Tulane University Department of Urology quality assurance database of 12 patients who underwent operative UAS repair between 2012 and 2018. Data were reviewed for operative approach, demographics, baseline disease characteristics, operative variables, and perioperative and pathological outcomes. Of the 12 patients analyzed, 5 underwent open repair (OR) (2 bilateral, 2 right, 1 left) and 7 underwent robotic repair (RR) (3 right, 4 left). One robotic case required conversion to open due to significant intestinal and peri-ureteral adhesions. The median ages were 59 years in OR and 60 years in RR. Two patients in each group had failed previous endoscopic repair. Median time from cystectomy to treatment of enteroanastamotic stricture was 13 months for OR and 10 months for RR (p = 0.25). Median estimated blood loss was 80 mL in both OR and RR (p = 1.0), median operative time was 260 min in OR and 255 min in RR (p = 0.13), and median hospital stay was 8 and 4 days, respectively (p = 0.06). There were two intra-operative and one post-operative complication in the OR group, one of whom required further surgical intervention, and no complications in the robotic cohort. A minimally invasive, robotic approach offers a non-inferior alternative to OR with similar outcomes for appropriately selected patients with UAS. High success rates combined with minimal morbidity may provide definitive therapy at an earlier stage of the stricture state.
Excited-state electronic coherence in vinyl bromide ions

We have performed time-dependent density functional theory calculations on the molecule vinyl bromide under ionization by a laser and have found long-lived coherent oscillations in the electron density created by a superposition of orbitals. The superposition of the molecular orbitals is quite pronounced for some intensities and is compared to varied alignments and strengths of the exciting laser. The coherence between the orbitals is also shown to be strongly dependent upon atomic motion.
Social media governance: can social media companies motivate voluntary rule following behavior among their users?

The purpose of these studies is to examine whether the procedural justice of a social media platform enforcement system for content moderation shapes offenders' post-message takedown recidivism rates. Users whose posts have been removed from the platform (taken down) for rule violations evaluate the justice of the platform enforcement procedure. The impact of those evaluations upon subsequent rule violations is measured. In addition, in study 2, users are randomly assigned to receive a message emphasizing the procedural justice of platform procedures and the impact of that message upon subsequent rule violations is assessed. In both studies, users who indicate that the procedures involved in the removal of their post have been fair are less likely to post new violating content in the future. In addition, those users who receive a message emphasizing the procedural justice of the platform’s mechanisms of enforcement are less likely to post new violating content in the future in comparison to those users randomly chosen to be no-message controls. Social media platforms are under government and public pressure to regulate the content of the posts that appear on their sites. One enforcement strategy that has been found to be effective in legal settings is to encourage self-regulation through procedural-justice-based approaches to rule enforcement. This paper tests the viability of extending these approaches to social media platforms. Results of both studies suggest that a strategy of encouraging self-regulation by the use of procedures that users rate as being just can successfully lower recidivism rates in a social media setting.
A sandwich smoother for spatio-temporal functional data

Abstract Statistical analysis of spatio-temporal data has been evolving to handle increasingly large data sets. For example, the North American CORDEX program is producing daily values of climate-related variables on spatial grids with approximately 100,000 locations over 150 years. Smoothing of such massive and noisy data is essential to understanding their spatio-temporal features. It also reduces the size of the data by representing them in terms of suitable basis functions, which facilitates further computations and statistical analysis. Traditional tensor-based methods break down under the size of such massive data. We develop a penalized spline method for representing such data using a generalization of the sandwich smoother proposed by Xiao et al. (2013). Unlike the original method, our generalization treats the spatial and temporal dimensions distinctly and allows the methodology to be directly applied to non-gridded data. We demonstrate the practicality of the methodology using both simulated and real data. The new smoother, as well as the original sandwich smoother, is implemented in the hero R package.
Case 3: Unexpected Respiratory Failure and Hypotonia in a Term Neonate.

A female infant is born at 36 weeks and 5 days of gestation to a 28-year-old gravida 3, para 2-0-0-2 woman. The infant is born via spontaneous vaginal delivery at an outside hospital with a level 1 mother-infant unit. The pregnancy had been complicated by preeclampsia with severe features for which the mother received intrapartum magnesium sulfate. Membranes rupture approximately 1 hour before delivery with blood-tinged fluid. The resuscitation requires positive pressure ventilation for 4 breaths and DeLee suctioning. The infant’s Apgar scores are 6, 5, and 8 at 1, 5, and 10 minutes, respectively. Her arterial cord gas values are as follows: pH 7.26, Pco2 61 mm Hg (8.1 kPa), Po2 27 mm Hg (3.6 kPa), bicarbonate 27 mEq/L (27 mmol/L), and base excess −1.7. The prenatal laboratory findings were all within normal limits, including a negative group B Streptococcus status. She has a birthweight of 2.87 kg and the head circumference is 33 cm, which are appropriate for gestational age. Her examination findings at birth are unremarkable, and she notably has a strong grasp, suck, and symmetric movements of her extremities and appears morphologically normal. Three hours after birth, she develops increased work of breathing with grunting and retractions, at which point our team is contacted for potential transfer. She is moved to the nursery and continuous positive airway pressure (CPAP) is initiated without improvement to her respiratory status. A …
Data Protection in Disarray

Businesses routinely lose or misuse individuals’ private information, with results that can be devastating. Federal courts often leave those individuals without legal recourse by dismissing their lawsuits for lack of standing, even though plaintiffs in these cases provide stronger showings of harm than courts usually require. Using an original data set, this Article shows how standing analysis in these cases has gone awry and argues that the standing inquiry in today’s data-protection cases harms both public policy and standing doctrine. This Article makes three contributions to literatures in federal courts and privacy. First, it shows that current federal court practice too often allows data collectors to cause harm without penalty. Data collectors — from theme parks and grocery stores to Equifax and Google — routinely collect private information improperly and inadequately protect the data they collect. This Article unpacks the various ways federal courts get standing wrong in the lawsuits that follow, such as by focusing on the particular scraps of information collected or lost via data breach to find plaintiffs have not suffered an “injury in fact.” Second, this Article draws on an original data set of 217 federal data-protection decisions to demonstrate systemic pressures that lead federal courts to misapply standing doctrine in data-protection litigation. Existing scholarship focuses on analyzing a handful of leading appellate cases and therefore misses the full scope of federal courts’ seeming hostility toward data-protection lawsuits. Third, by bringing to light systemic issues that have not been considered in this context, this Article proposes changes to federal courts’ approach to standing in these cases that will help align the incentives and costs of data collection and help to develop a robust body of federal law on issues of data protection.
EccDNA formation is dependent on MMEJ, repressed by c-NHEJ pathway, and stimulated by DNA double-strand break

ABSTRACT Extrachromosomal circular DNAs (eccDNA) are widespread in normal and cancer cells and are known to amplify oncogenic genes. However, the mechanisms that form eccDNA have never been fully elucidated due to the complex interactions of DNA repair pathways and lack of a method to quantify eccDNA abundance. Through the development of a sensitive and quantitative assay for eccDNA we show that the formation of eccDNA is through resection dependent repair of double-strand DNA breaks, especially micro-homology mediated end joining, and through mismatch repair. The most significant decreases in eccDNA levels occurred in cells lacking PARP1, POLQ, NBS1, RAD54, and FAN1. Further, a significant increase in eccDNA occurred in cells lacking c-NHEJ proteins DNA-PKcs, XRCC4, XLF, LIG4 and 53BP1. This suggests that when alt-NHEJ pathways are utilized to repair DNA breaks by necessity, the formation of eccDNA is increased. Induced and site-directed double-strand DNA breaks increase eccDNA formation, even from a single break. Additionally, we find that eccDNA levels accumulate as cells undergo replication in S-phase and that levels of eccDNA are decreased if DNA synthesis is prevented. Together, these results show that the bulk of eccDNA form by resection based alt-NHEJ pathways, especially during DNA replication and the repair of double-strand breaks.
Accelerated Molecular Dynamics Methods for Long-Time Simulations in Materials

Many important processes in materials and chemical systems are intrinsically atomistic in nature but involve timescales that span many orders of magnitude, thus exceeding what can be directly simulated using molecular dynamics. In this paper, dedicated to William A. Goddard III, we give a brief introduction to the accelerated molecular dynamics (AMD) methodology, which is aimed at this problem. AMD methods exploit the infrequent-event nature of the activated processes that typically comprise this long-time evolution. In favorable cases, these methods can predict state-to-state evolution that approximates what would result from an extremely long molecular dynamics simulation, and the most accurate of the methods can do this to arbitrary accuracy. We present some examples of applications of these methods and discuss the greatest ongoing challenge for the methods.
Molecular and Functional Characteristics of Cloned Human Organic Cation Transporters

Within the last 5 years the organic cation transport field has moved from tissue and cellular levels to a molecular level of investigation. As we gain a better understanding of the genes and proteins responsible for the multiple mechanisms of organic cation transport, we can begin to apply this knowledge to pharmaceutical and drug discovery research. For example, in the future, we will know all of the transporters that are expressed in each tissue and have a substrate/inhibitor profile for each transporter. With this information, we could begin to predict, for example, organ-specific clearances or organ-specific distributions of drugs. Perhaps we will discover a brain-specific organic cation transporter which could serve as a drug target. It will be years and perhaps several more decades before all of these transporters are cloned and characterized. We have made a good start and there will be years of exciting work and discovery in the organic cation transport field in the future.
Structure/effect studies of fatty acid isomers as skin penetration enhancers and skin irritants

Comparisons were made of branched vs unbranched saturated fatty acids and cis vs trans unsaturated fatty acids as skin penetration enhancers and primary skin irritants. Skin penetration studies used naloxone base as the diffusant, propylene glycol as the vehicle, and human skin. Maximum naloxone flux was with C9–12-branched and unbranched fatty acids. For C5–14 fatty acids, branched and unbranched isomers had similar effects. One branched C18 fatty acid isomer (C16-branched isostearic acid) was more effective in enhancing skin penetration than a differently branched (C2-branched isostearic acid) or unbranched C18 isomer (stearic acid). There was no significant difference between cis and trans unsaturated C16–18 fatty acid isomers in their effects on naloxone flux, and all unsaturated fatty acids were more effective enhancers than the corresponding saturated isomers. Several of these fatty acid/propylene glycol vehicles were evaluated in a rabbit primary skin irritation test. Irritation indices were poorly correlated with the effectiveness of the vehicles in enhancing naloxone flux. It was possible to enhance naloxone skin penetration greatly with a vehicle with only minimal skin irritation potential.
Analysis of precipitation extremes with the assessment of regional climate models over the Willamette River Basin, USA

An appropriate, rapid and effective response to extreme precipitation and any potential flood disaster is essential. Providing an accurate estimate of future changes to such extreme events due to climate change are crucial for responsible decision making in flood risk management given the predictive uncertainties. The objective of this article is to provide a comparison of dynamically downscaled climate models simulations from multiple model including 12 different combinations of General Circulation Model (GCM)–regional climate model (RCM), which offers an abundance of additional data sets. The three major aspects of this study include the bias correction of RCM scenarios, the application of a newly developed performance metric and the extreme value analysis of future precipitation. The dynamically downscaled data sets reveal a positive overall bias that is removed through quantile mapping bias correction method. The added value index was calculated to evaluate the models' simulations. Results from this metric reveal that not all of the RCMs outperform their host GCMs in terms of correlation skill. Extreme value theory was applied to both historic, 1980–1998, and future, 2038–2069, daily data sets to provide estimates of changes to 2- and 25-year return level precipitation events. The generalized Pareto distribution was used for this purpose. The Willamette River basin was selected as the study region for analysis because of its topographical variability and tendency for significant precipitation. The extreme value analysis results showed significant differences between model runs for both historical and future periods with considerable spatial variability in precipitation extremes. Copyright © 2012 John Wiley & Sons, Ltd.
A 0.5/spl mu/m CMOS programmable discrete-time /spl Delta/-/spl Sigma/ modulator with floating gate elements

This paper describes a tunable /spl Delta/-/spl Sigma/ modulator using floating gate elements. In a previous work, the feasibility of using these structures in a conventional switch capacitor modulator was shown. Floating gate electronic potentiometers (e-pots) in the modulator loop were used to provide convenient and accurate programmable on-chip reference voltages. These voltages determined the feedback coefficients of the modulator. In this work time-domain modelling of the modulator in SIMULINK as well as SPICE simulations is used to predict optimal coefficients, which are programmed into the modulator at runtime. Simulation and experimental results for a 2nd order modulator are presented. The modulator achieves 57 dB peak SNR and 55 dB SINAD giving ENOB=9 bits.
Depletion of calcium stores regulates calcium influx and signal transmission in rod photoreceptors

Tonic synapses are specialized for sustained calcium entry and transmitter release, allowing them to operate in a graded fashion over a wide dynamic range. We identified a novel plasma membrane calcium entry mechanism that extends the range of rod photoreceptor signalling into light-adapted conditions. The mechanism, which shares molecular and physiological characteristics with store-operated calcium entry (SOCE), is required to maintain baseline [Ca(2+)](i) in rod inner segments and synaptic terminals. Sustained Ca(2+) entry into rod cytosol is augmented by store depletion, blocked by La(3+) and Gd(3+) and suppressed by organic antagonists MRS-1845 and SKF-96365. Store depletion and the subsequent Ca(2+) influx directly stimulated exocytosis in terminals of light-adapted rods loaded with the activity-dependent dye FM1-43. Moreover, SOCE blockers suppressed rod-mediated synaptic inputs to horizontal cells without affecting presynaptic voltage-operated Ca(2+) entry. Silencing of TRPC1 expression with small interference RNA disrupted SOCE in rods, but had no effect on cone Ca(2+) signalling. Rods were immunopositive for TRPC1 whereas cone inner segments immunostained with TRPC6 channel antibodies. Thus, SOCE modulates Ca(2+) homeostasis and light-evoked neurotransmission at the rod photoreceptor synapse mediated by TRPC1.
TOBACCO DISPLAY BANS: A GLOBAL FAILURE

This paper examines the effects of tobacco display bans in four countries: Canada, Iceland, Thailand and Ireland. The empirical evidence suggests that the bans have not been effective at reducing the incidence of smoking. They have, however, succeeded in severely damaging the revenues of the independent retail sector and bolstering the illicit market in tobacco.
Two-Dimensional Simulation of Single Event Indujced Bipolar Current in CMOS Structures

Single particle effects are analyzed using an advanced two-dimensional transient numerical simulator. Layered structures representative of an n-channel MOSFET drain in a p-well are modeled. TWo major results have been obtained. First, the well structure inherently provides better charge collection at the well-substrate compared to the drain-well junction. Ihis provides single event protection for the drain node. Second, large charge density tracks generated by very high energy particles can forward bias the drain-well junction resulting in bipolar action from the inherent parasitic n-p-n transistor of the well structure. This bipolar current is opposite to the photocurrent, suggesting a different SEU protection mechanism. However, it opens the possibility of upset of the "on" n-channel and, most critically, provides a mechanism for triggering latch-up in CMOS circuits.
A molecular based model for polymer viscoelasticity: Intra- and inter-molecular variability

We develop dynamic equations for rubber viscoelasticity based on a stick-slip continuum molecular-based model. The model developed is a continuum tube reptation model in which a chemically cross-linked (CC) system of molecules act as constraint box per unit volume for a physically constrained (PC) system of molecules. The CC-system carries along the PC-system during instantaneous step deformations. The subsequent relaxation of the PC-system is determined by the configuration of the CC-system, its own configuration and confirmation, and external force fields. Conversely, the deformation of the PC-system acts as an internal variable affecting the deformations of the constraining CC-system. We model the relationship between these processes to derive a model of viscoelasticity in rubber deformation. In developing a relaxation process for the PC-system, we start from the fact that the PC-system is composed of long molecular chains. The dynamics of these molecular chains are developed by modelling them as chains of beads connected by springs, which represent inter-molecular potentials. Various segments of the molecular chains relax at different rates. In addition, variability in relaxation times across molecular chains is permitted.
Cell Wall of Melampyrum lineare Seed: Carbohydrate Components

Extraction with alkali of cell wall material from the seed of Melampyrum lineare leaves a residue (62.7 percent) which on hydrolysis yields over 70 percent mannose. Hydrolysis of the alkali-soluble hemicellulose fraction of the cell wall also yields largely mannose. In contrast, cell wall isolated from Melampyrum stem contains over 95 percent of glucose residues in the alkaliinsoluble fraction, and mostly xylose residues in the hemicellulose.
Relation between monthly variations of global ozone and solar activity

Monthly averaged variations of global ozone determined from infrared interferometer spectrometer measurements aboard Nimbus 4 are shown to be consistently in agreement with monthly averaged variations of solar activity. The relationship between monthly changes of ozone and solar activity are found to be generally consistent with the longer-term variations of ozone over the last solar cycle and can be accounted for by assuming monthly solar flux variations near 0.2 micron of about 2%.
Reliability of a stool consistency classification system

Purpose Reliability and validity are important measures of the quality of a research or clinical instrument. This research determined the inter-rater and test-retest reliability of a stool consistency classification system and the agreement between the subjects' and expert investigators' classifications. Methods Two studies were conducted with adult volunteers. Stool consistency was described by words only and words + diagrams. To determine inter-rater reliability, subjects in each of 3 groups (20 nurses, 20 nursing students, and 20 lay persons) classified the consistency of 12 stool specimens. To determine test-retest reliability, 43 additional subjects classified the consistency of 9 stool specimens in 2 sessions. Outcome measures Outcome measures were reported per individual stool specimen and for all stool specimens. The outcome measures were the consistency classifications by the 3 groups of raters when the 2 types of descriptors (word only and word + diagram) were used. Other outcomes were the consistency classifications of the subjects on the 2 days of stool evaluation and the classifications of the subjects compared with those of the investigators. Results No significant difference was found among the stool consistency classifications among nurses, nursing students, or lay persons. Classifications were similar for 11 of 12 stool specimens when either word-only or word + diagram descriptions were used. No significant difference was found among the classifications between days 1 and 2. At least 75% of the subjects' classifications of stool consistency in both studies agreed highly with those of the investigators. Conclusions The reliability and validity of the stool consistency classification system are good. The word-only descriptions of the consistency classifications appeared to be equally as effective as the word + diagram descriptions.
State Supreme Courts and the Effects of Statutory Constraint: A Test of the Model of Contingent Discretion

Do state supreme court judges render decisions according to their ideological preferences, or are they constrained by the language of state statutes? Using data from the Judge-Level State Supreme C...
Amine derivatives of cyanuric chloride.

A number of new substituted amino, chloroamino, and hydroxyamino derivatives of cyanuric chloride have been prepared. Various methods of achieving the condensations were attempted.
Phospholipase D signaling is essential for meiosis

Abstract Phospholipid metabolism plays an important role in cellular regulation by generating second messengers for signal transduction. Many stimuli activate a phospholipase D, which catalyzes the hydrolysis of phosphatidylcholine, producing phosphatidic acid and choline. Here we report that the yeast SP014 gene, which is essential for meiosis [Honigberg, S. M., Conicella, C. & Esposito, R. E. (1992) Genetics 130, 703-716], encodes a phospholipase D. SP014 RNA and protein activity are induced during late meiotic prophase, and the enzyme has properties similar to mammalian phosphatidylinositol 4,5-bisphosphate-regulated phospholipase D. Characterization of an unusual allele of SP014 defines regions of the protein important for enzyme catalysis and regulation. These results implicate phospholipase D signaling in regulating cellular differentiation.
Effect of Pulse Pressure and Mean Arterial Pressure Modification on Renal Hemodynamics and Electrolyte and Water Excretion

Studies were conducted to evaluate the influence of pulsatile versus nonpulsatile arterial perfusion pressure on plasma flow, filtration rate, sodium excretion, and urine volume. Through a wide range of mean renal arterial pressures, reduction of pulse pressure was without effect on renal function. The level of the mean arterial pressure, however, had a very dominant role in the electrolyte and water handling, decreases and increases in excretion paralleling the direction of change of the mean pressure. These alterations were observed even though filtration rate and plasma flow exhibited a marked degree of autonomy in the face of these pressure variations. Mechanisms by which these modifications in salt and water excretion could result from alteration in the mean arterial pressure are discussed.
Relation of adult size to movements and distribution of smallmouth bass in a central Maine Lake

Abstract Forty-four smallmouth bass Micropterus dolomieu of three size-classes were radio-tracked in Green Lake, Maine, during summer 1993 (10 June–1 September) to determine whether adult size influenced distribution and movement. Large smallmouth bass (>406 mm) used deep water (>8 m) more often than did small (248–279 mm) or medium-sized (305–356 mm) smallmouth bass during the late summer (15 July–1 September). Large smallmouth bass also were found at middepths (4–8 m) significantly more often than were small individuals during late summer. Small fish used cover more frequently than large ones during early summer (10 June–13 July). Both small and medium-sized individuals were associated with cover more frequently than large smallmouth bass were during the late summer. Small smallmouth bass exhibited significantly smaller summer total ranges than did large individuals, and mean active displacement differed among all three size-classes.
Epicuticular terpenoids and an aurone from flowers of Helianthus annuus

Abstract Inspection of the epicuticular floral chemistry of the cultivated sunflower afforded the new germacranolides 3- O -methylniveusin A and 1,10- O -dimethyl-3-dehydroargophyllin B diol, the eudesmanoic acid eudesma-1,3,11(13)-trien-12-oic acid, the diterpene 7-oxo-trachyloban-15α, 19-diol and the new 5-hydroxy-4,6,4′-trimethoxyaurone. The sesquiterpenes were strongly antifeedant to adult western corn rootworm, Diabrotica virgifera virgifera , in a squash disk consumption bioassay.
Becoming a Fan: On the Seductions of Opera

The following is a sociological report on a particular segment of an opera audience. Its purpose is to explicate the processes of initiation in an activity typically considered “high culture.” It differs from other accounts of cultural consumption in that it is concerned not with the correspondence between social background and taste, but with the processes whereby taste is assembled. Drawing upon an 18-month-long ethnography on opera fans in Buenos Aires, this paper has two aims. First, it shows that passionate opera fans enjoy opera based on their belief that opera is something that needs to be learned in order to be properly enjoyed. Second, it describes three diverse instances in which people learn about opera. Furthermore, this paper also has a theoretical objective: to extend and refine the classic model of affiliation and initiation into cultural practices established by Howard Becker with his case study of marijuana use.
Non-targeted metabolomics of Brg1/Brm double-mutant cardiomyocytes reveals a novel role for SWI/SNF complexes in metabolic homeostasis

Mammalian SWI/SNF chromatin-remodeling complexes utilize either BRG1 or Brm as alternative catalytic subunits to alter the position of nucleosomes and regulate gene expression. Genetic studies have demonstrated that SWI/SNF complexes are required during cardiac development and also protect against cardiovascular disease and cancer. However, Brm constitutive null mutants do not exhibit a cardiomyocyte phenotype and inducible Brg1 conditional mutations in cardiomyocyte do not demonstrate differences until stressed with transverse aortic constriction, where they exhibit a reduction in cardiac hypertrophy. We recently demonstrated the overlapping functions of Brm and Brg1 in vascular endothelial cells and sought here to test if this overlapping function occurred in cardiomyocytes. Brg1/Brm double mutants died within 21 days of severe cardiac dysfunction associated with glycogen accumulation and mitochondrial defects based on histological and ultrastructural analyses. To determine the underlying defects, we performed nontargeted metabolomics analysis of cardiac tissue by GC/MS from a line of Brg1/Brm double-mutant mice, which lack both Brg1 and Brm in cardiomyocytes in an inducible manner, and two groups of controls. Metabolites contributing most significantly to the differences between Brg1/Brm double-mutant and control-group hearts were then determined using the variable importance in projection analysis. Increased cardiac linoleic acid and oleic acid suggest alterations in fatty acid utilization or intake are perturbed in Brg1/Brm double mutants. Conversely, decreased glucose-6-phosphate, fructose-6-phosphate, and myoinositol suggest that glycolysis and glycogen formation are impaired. These novel metabolomics findings provide insight into SWI/SNF-regulated metabolic pathways and will guide mechanistic studies evaluating the role of SWI/SNF complexes in homeostasis and cardiovascular disease prevention.