cssi/SciSciGPT-SciSciNet huggingface dataset:
An individual double-blind crossover trial for assessing methylphenidate response in children with attention deficit disorder.

To obtain more objective data on response to therapy and to overcome parents', feachers', psychologists', and physicians' concerns about potential overuse, I instituted individual double-blind crossover trials of methylphenidate for children with attention deficit disorder (ADD). Each child is given 0.3 mg/kg/dose twice daily for 2 weeks and placebo for 2 weeks in random order and in double-blind fashion. Parents and teachers record observations of behavior and academic performance. Analysis of 70 trials and follow-up clinical data demonstrated that (1) 51 children showed improvement in one of the 2-week periods and that period corresponded with methylphenidate therapy in 48 (69%); (2) 6 of the 22 who did not respond to methylphenidate experienced worsening of function while taking the drug; (3) history and physical findings were not helpful in predicting methylphenidate response; (4) there were no serious side effects during the trial; and (5) all but three of the responders took methylphenidate for at least 1 year with sustained improvement in behavioral function, academic function, or both. Individual doubleblind crossover trials can be used in an office setting to identify objectively which children with ADD respond to treatment with methylphenidate. Because the trial demonstrates to parents, teachers, psychologists, and physicians that methylphenidate is or is not beneficial to a particular child, this clinical tool is associated with a high level of confidence that the drug is being appropriately prescribed.
Risk profile of hepatocellular carcinoma reveals dichotomy among US veterans.

Background Hepatocellular carcinoma (HCC) is traditionally associated with chronic liver injury resulting from hepatitis B virus (HBV) and hepatitis C virus (HCV) infection or excessive consumption of alcohol. In addition, recent evidence links HCC to diabetes.
Detection of antibodies against Turkey astrovirus in humans.

Astroviruses are a leading cause of gastroenteritis in mammals and birds worldwide. Although historically thought to be species-specific, increasing evidence suggests that astroviruses may cross species barriers. In this report, we used enzyme-linked immunosorbent assays to screen sera from three distinct human cohorts involved in influenza studies in Memphis, TN or Chapel Hill, NC, and Midwestern poultry abattoir workers for antibodies to turkey astrovirus type 2 (TAstV-2). Surprisingly, 26% of one cohort’s population was TAstV-2 positive as compared to 0 and 8.9% in the other cohorts. This cohort was composed of people with exposure to turkeys in the Midwestern United States including abattoir workers, turkey growers, and non-occupationally exposed participants. The odds of testing positive for antibodies against turkey astrovirus among abattoir workers were approximately 3 times higher than the other groups. These studies suggest that people with contact to turkeys can develop serological responses to turkey astrovirus. Further work is needed to determine if these exposures result in virus replication and/or clinical disease.
Direct fluorination of the anthraquinone nucleus: scope and application to the synthesis of novel rhein analogues

Abstract Direct fluorination of the functionalised anthraquinone dimethyl rhein methyl ester with Selectfluor TM proceeds regioselectively, providing a concise approach to fluorinated compounds of potential medicinal interest. This represents a new use for Selectfluor TM which hitherto has only been used for fluorinating relatively activated compounds.
Hybrid quick error detection (H-QED): accelerator validation and debug using high-level synthesis principles

Post-silicon validation and debug challenges of system-on-chips (SoCs) are getting increasingly difficult. As we reach the limits of Dennard scaling, efforts to improve system performance and energy efficiency have resulted in the integration of a wide variety of complex hardware accelerators in SoCs. Hence, it is essential to address post-silicon validation and debug of hardware accelerators. High-level synthesis (HLS) is a promising technique to rapidly create customized hardware accelerators. In this paper, we present the Hybrid Quick Error Detection (H-QED) approach that overcomes post-silicon validation and debug challenges for hardware accelerators by leveraging HLS techniques. H-QED improves error detection latencies (time elapsed from when a bug is activated to when it manifests as an observable failure) by 2 orders of magnitude and bug coverage 3-fold compared to traditional post-silicon validation techniques. H-QED also uncovered previously unknown bugs in the CHStone benchmark suite, which is widely used by the HLS community. H-QED incurs less than 2% chip-level area overhead with negligible performance impact, and we also introduce techniques to minimize any possible intrusiveness introduced by H-QED.
Factor-Input Demand Subject to Economic and Environmental Risk: Nitrogen Fertilizer in Kansas Dryland Corn Production

The purpose of this article is twofold: (1) to develop a model to estimate the external costs arising from excess factor inputs; and (2) to examine how factor-input demand is affected when economic and environmental risks are simultaneously accounted for in a producer's decisionmaking process. Firm-level demand for nitrogen fertilizer in the production of dryland corn in northeast Kansas is used as an example. Many studies have evaluated the economics of fertilizer management, the economics of crop rotations to reduce commercial fertilizer use, and/or the costs of nutrient pollution (Ayer et al.; Jacobs and Casler; Jordan et al.; Lambert; Papendick, Elliot, and Power; SriRamaratnam et al.; Stoecker and Onken; Taylor and Frohberg; Walker and Hoehn; Williams et al.). Similarly, several studies have evaluated the tools (input restrictions, standards, taxes, and charges) often considered for mediating nonpoint source pollution (Homer; Jacobs and Casler; Lambert; Sharp and Bromley; Shortle and Dunn). Although several of these studies addressed the economic risk associated
Genetic and Environmental Factors Affecting the Solids-Not-Fat Composition of Milk

Summary Evidence has been summarized from published studies which bear on the genetic and environmental influences on SNF composition of milk. Reports concerning the influence of season and climate, stage of lactation, and age of cow appear to be consistent enough to point out the general nature of the relationships. There is a pressing need for solid information on the nutritional influences on SNF, both from a fundamental and from a practical standpoint. The reasons for specific nutritional and physiological responses still are largely unexplained. Breed and sire differences for SNF constituents, broadly suggesting that part of the variation in milk composition is genetic, have been known for some time. Within the past 5 yr. preliminary estimates of genetic parameters, e.g., heritabilities and genetic correlations, have suggested that selection for SNF constituents should be effective. However, more precise information is sorely needed regarding the magnitude of both genetic and environmental parameters, so as to assist in developing breeding plans as soon as the long-range market requirements for individual SNF constituents are known.
Coherent modes coupling approach to partially coherent, partially polarized beams in atmospheric turbulence

A mode coupling approach was studied as a tool to describe the propagation of partially coherent, partially polarized beams in atmospheric turbulence. An approximate expression is derived for the mode power coupling coefficients and some specific cases are studied using numerical methods. Several general results derived from the properties of the coupling coefficients are also presented. Possible applications for sources with tunable polarization distribution characteristics will be discussed.
Optical Scanning System For Laser Velocimeter

An optical system was developed to provide fast incremental scanning of a backscattered laser velocimeter focus point over a 36-cm distance. The system is used to measure flow velocities at 16 positions along its optical axis and to scan these 16 positions up to 30 times a second. Dwell time at each location is approximately 2 milliseconds. Sample volumes typically are 0.2 mm in diameter by 1.4 cm in length. The optical scanning system consists of a wheel containing plane parallel quartz windows of various thicknesses. The laser velocimeter beams are imaged to a primary focus within the dead airspace of an optical cell. The beams emerging from the cell pass through the windows of the scanning wheel. The refraction of the beams passing through the windows causes an apparent shift of the focus within the optical cell and hence in the test zone. Light scattered from the secondary focus within the test zone is concurrently collected and reimaged through the same optical path which originally projected the primary focus. The reimaged backscattered light containing the velocity information is then collected and focused onto a photomultiplier detector system to complete the scanned laser velocimeter optical system.
The role of enhanced cutaneous IL-1β signaling in a rat tibia fracture model of complex regional pain syndrome

Tibia fracture in rats initiates a syndrome resembling the complex regional pain syndrome type I. Accumulating evidence indicates that IL-1beta is involved in the modulation of nociceptive information and it acts as an intermediate inflammatory mediator via up-regulation of NGF. We hypothesized that IL-1beta signaling might mediate the development of the CRPS-like changes after tibial fracture, either directly or by stimulating NGF expression. Rats underwent distal tibia fracture and casting for 4 weeks and were chronically treated with an IL-1 receptor antagonist (IL-1ra). Nociceptive testing and assessment of edema and hindpaw warmth were performed at baseline and after cast removal. Bone microarchitecture was evaluated by micro-computed tomography. Confocal immunofluorescence and in situ hybridization techniques were used to evaluate changes in the cutaneous expression of IL-1beta at 4 weeks post-fracture. The nociceptive and vascular effects of intraplantar IL-1beta injections were evaluated in intact rats at different time points after injection. We found that: (1) IL-1ra reduced fracture-induced nociceptive sensitization, but did not decrease hindpaw edema or warmth, (2) fracture chronically up-regulated IL-1beta mRNA and protein expression in hindpaw skin keratinocytes, (3) IL-1beta intraplantar injection induced mechanical allodynia in a dose-dependent manner and stimulated keratinocyte NGF expression in the hindpaw skin, and (4) intraplantar injection of NGF-induced nociceptive sensitization. Collectively, these results indicate that cutaneous IL-1beta signaling can contribute to chronic regional nociceptive sensitization after fracture, possibly by stimulating NGF over-expression in keratinocytes. Our data also highlight the importance of the keratinocyte as the primary source of post-traumatic IL-1beta over-expression.
Formal framework for a nonlocal generalization of Einstein’s theory of gravitation

The analogy between electrodynamics and the translational gauge theory of gravity is employed in this paper to develop an ansatz for a nonlocal generalization of Einstein's theory of gravitation. Working in the linear approximation, we show that the resulting nonlocal theory is equivalent to general relativity with ``dark matter.'' The nature of the predicted dark matter, which is the manifestation of the nonlocal character of gravity in our model, is briefly discussed. It is demonstrated that this approach can provide a basis for the Tohline-Kuhn treatment of the astrophysical evidence for dark matter.
Role of inflammatory mediators in colonic smooth muscle function in ulcerative colitis

Patients with ulcerative colitis have a decrease in colonic motility which may increase their diarrheal symptoms. Studies in patients with ulcerative colitis showed that the postprandial spike response was slightly decreased and the intraluminal pressure response was absent. In vitro studies showed that the circular smooth muscle, obtained from patients with ulcerative colitis or from a rabbit model of experimental colitis, generated decreased force compared to muscle not associated with mucosal inflammation. The decrease in muscle contraction was observed with bethanechol stimulation or electrical field stimulation. Since the response to an increased extracellular concentration of potassium ([K+]0) was also diminished, the decreased response appears to be caused by an abnormality in the intrinsic contractile mechanism of colonic smooth muscle. Further studies are necessary to determine if metabolic abnormalities are present in the colonic muscle in patients with colitis.
A TEST FOR THE DETECTION OF A POISSON PROCESS

A statistical test is presented to detect the presence of a Poisson input source into a queueing system. The fact that the arrival times of a Poisson input source are distributed independently and uniformly over time is used in conjunction with the central limit theorem to develop a test, based on the sum of the arrival times over a given interval of time, for the hypothesis that an input source into a queueing system is Poisson. Failure to reject this hypothesis gives one an extra degree of assurance that traditional queueing models assuming a Poisson input are applicable.
Primate censusing in northern Colombia: A comparison of two techniques

Five primate species were observed in an 83 hectare study site in northern Colombia. They wereAlouatta seniculus, Aotus trivirgatus, Ateles belzebuth hybridus, Cebus albifrons, andSaguinus leucopus. Average group size for the four diurnal species ranged from 5.3 individuals per sighting forCebus to 3.3 forAlouatta andAteles. BecauseCebus utilized regenerating forest, mature stands as well as cultivated sectors, they were able to use 30% more of the study site than the larger cebids. Monkey sightings along transects peaked at 0600–0800 and 1500–1800 and were lowest between 0900–1300 for the four diurnal cebids. The hourly rate of sighting the large cebids was 2–3 times greater for the point method than the transect method, but was less forCebus andSaguinus. However, consistently higher crude density estimates were obtained by the transect method than by the point method. As expected, there was less discrepancy between census methods for the large cebids which regularly utilized the upper canopy. The point method was barely 20% as effective as the transect method for estimating crude densities ofCebus andSaguinus. Factors influencing the effectiveness of the two census techniques as monkey detection and visibility, climatic conditions, and length of study are discussed. Recommendations for improving censusing effectiveness are listed.
Dramatic Form and Dramatic Imagination in Beaumont's The Knight of the Burning Pestle

Dans cette comedie burlesque, les spectateurs deviennent progressivement les habitants stupefaits d'un Pays de Cocagne ou le desir et sa realisation ne font qu'un. Cette metamorphose est en fait une manoeuvre formelle tres brillante, qui amene l'A. a s'interroger sur le rapport entre les procedes du comique conventionnel et la veritable substance du processus comique lui-meme.
Modulation of brain Na+ channels by a G-protein-coupled pathway.

Abstract Na+ channels in acutely dissociated rat hippocampal neurons and in Chinese hamster ovary (CHO) cells transfected with a cDNA encoding the alpha subunit of rat brain type IIA Na+ channel (CNaIIA-1 cells) are modulated by guanine nucleotide binding protein (G protein)-coupled pathways under conditions of whole-cell voltage clamp. Activation of G proteins by 0.2-0.5 mM guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]), a nonhydrolyzable GTP analog, increased Na+ currents recorded in both cell types. The increase in current amplitude was caused by an 8- to 10-mV negative shift in the voltage dependence of both activation and inactivation. The effects of G-protein activators were blocked by treatment with pertussis toxin or guanosine 5'-[beta-thio]diphosphate (GDP[beta S]), a nonhydrolyzable GDP analog, but not by cholera toxin. GDP[beta S] (2 mM) alone had effects opposite those of GTP[gamma S], shifting Na(+)-channel gating 8-10 mV toward more-positive membrane potentials and suggesting that basal activation of G proteins in the absence of stimulation is sufficient to modulate Na+ channels. In CNaIIA-1 cells, thrombin, which activates pertussis toxin-sensitive G proteins in CHO cells, caused a further negative shift in the voltage dependence of Na(+)-channel activation and inactivation beyond that observed with GTP alone. The results in CNaIIA-1 cells indicate that the alpha subunit of the Na+ channel alone is sufficient to mediate G protein effects on gating. The modulation of Na+ channels via a G-protein-coupled pathway acting on Na(+)-channel alpha subunits may regulate electrical excitability through integration of different G-protein-coupled synaptic inputs.
Cleaning-up data for sparse model synthesis: when symbolic-numeric computation meets error-correcting codes

The discipline of symbolic computation contributes to mathematical model synthesis in several ways. One is the pioneering creation of interpolation algorithms that can account for sparsity in the resulting multi-dimensional models, for example, by Zippel [12], Ben-Or and Tiwari [1], and in their recent numerical counterparts by Giesbrecht-Labahn-Lee [5] and Kaltofen-Yang-Zhi [9].
Comparison of Oxygen Saturation by Pulse Oximetry and Co-oximetry During Exercise Testing in Patients With COPD

Introduction Measurement of oxygen saturation by pulse oximetry (SpO 2 ) is frequently performed during exercise testing of patients with COPD to monitor for hypoxemia. The purpose of this study was to assess the accuracy and precision of pulse oximetry during exercise. We hypothesized that the SpO 2 would more closely reflect oxygen saturation as measured by co-oximetry (SaO 2 ) when it was corrected for carboxyhemoglobin (COHb). We also hypothesized that SpO 2 would more closely reflect SaO 2 when the pulse rate by oximeter was equivalent to the heart rate by ECG. Finally, we hypothesized that SpO 2 would be a better measure of SaO 2 at maximal workloads than at rest or submaximal workloads. Methods Eight white men with severe COPD (mean ± SD FEV 1 , 0.91±0.37) underwent progressive, symptom-limited exercise testing by cycle ergometry. SaO 2 was measured from arterial blood at each workload using a co-oximeter. SpO 2 and pulse rate were obtained by a pulse oximeter (Ohmeda 3700). Heart rate was continuously monitored by ECG. Results Reliable oximetric values as determined by a dicrotic notch in each waveform and adequate signal intensity were obtained in all eight patients. SpO 2 was a moderately accurate measure of SaO 2 (bias, 1.7%; precision, 2.9). The bias actually increased (4.1%) when SpO 2 was corrected for COHb. Accuracy of SpO 2 was not improved when pulse rate by oximetry and heart rate by ECG were equivalent, nor was the accuracy improved at maximal workloads relative to submaximal workloads during the exercise test. Conclusion Oxygen saturation as measured by pulse oximetry (SpO 2 ) in patients with COPD undergoing exercise testing is not sufficiently accurate to replace SaO 2 as the gold standard for oxygen saturation. ( CHEST 1996; 109:1151–55 )
Weakness of the will : Is a quick fix possible?

Weakness of the will may lead to ineffective goal striving in the sense that people lacking willpower fail to get started, to stay on track, to select instrumental means, and to act efficiently. However, using a simple self-regulation strategy (i.e., forming implementation intentions or making if-then plans) can get around this problem by drastically improving goal striving on the spot. After an overview of research investigating how implementation intentions work, I will discuss how people can use implementation intentions to overcome potential hindrances to successful goal attain- ment. Extensive empirical research shows that implemen- tation intentions help people to meet their goals no matter whether these hindrances originate from within (e.g., lack of cognitive capabilities) or outside the person (i.e., difficult social situations). Moreover, I will report recent research demonstrating that implementation intentions can even be used to control impulsive cognitive, affective, and behav- ioral responses that interfere with one's focal goal striving. In ending, I will present various new lines of implementation intention research, and raise a host of open questions that still deserve further empirical and theoretical analysis.
Online Estimation of Architectural Vulnerability Factor for Soft Errors

As CMOS technology scales and more transistors are packed on to the same chip, soft error reliability has become an increasingly important design issue for processors. Prior research has shown that there is significant architecture-level masking, and many soft error solutions take advantage of this effect. Prior work has also shown thatthe degree of such masking can vary significantly across workloads and between individual workload phases, motivating dynamic adaptation of reliability solutions for optimal cost and benefit. For such adaptation, it is important to be able to accurately estimate the amount ofmasking or the architecture vulnerability factor (AVF) online, while the program is running. Unfortunately, existing solutions for estimating AVF are often based on offline simulators and hard to implement in real processors. This paper proposes a novel way of estimating AVF online, using simple modifications to the processor. The estimation method applies to both logic and storage structures on the processor. Compared to previous methodsfor estimating AVF, our method does not require any offline simulation or calibration for different workloads. We tested our method with a widely used simulator from industry, for four processor structures and for 100 to 200 intervals of each of eleven SPEC benchmarks. The results show that our method provides acceptably accurate AVF estimates at runtime. The absoluteerror rarely exceeds 0.08 across all application intervals for all structures, and the mean absolute error for a given application and structure combination is always within 0.05.
Masting in ponderosa pine: comparisons of pollen and seed over space and time

Many plant species exhibit variable and synchronized reproduction, or masting, but less is known of the spatial scale of synchrony, effects of climate, or differences between patterns of pollen and seed production. We monitored pollen and seed cone production for seven Pinus ponderosa populations (607 trees) separated by up to 28 km and 1,350 m in elevation in Boulder County, Colorado, USA for periods of 4–31 years for a mean per site of 8.7 years for pollen and 12.1 for seed cone production. We also analyzed climate data and a published dataset on 21 years of seed production for an eighth population (Manitou) 100 km away. Individual trees showed high inter-annual variation in reproduction. Synchrony was high within populations, but quickly became asynchronous among populations with a combination of increasing distance and elevational difference. Inter-annual variation in temperature and precipitation had differing influences on seed production for Boulder County and Manitou. We speculate that geographically variable effects of climate on reproduction arise from environmental heterogeneity and population genetic differentiation, which in turn result in localized synchrony. Although individual pines produce pollen and seed, only one-third of the covariation within trees was shared. As compared to seed cones, pollen had lower inter-annual variation at the level of the individual tree and was more synchronous. However, pollen and seed production were similar with respect to inter-annual variation at the population level, spatial scales of synchrony and associations with climate. Our results show that strong masting can occur at a localized scale, and that reproductive patterns can differ between pollen and seed cone production in a hermaphroditic plant.
Obsessive‐compulsive disorder, trichotillomania, and anorexia nervosa: A case report

We report a case study of an 18-year-old female who presented with symptoms associated with several discrete diagnostic syndromes: obsessive-compulsive disorder, trichotillomania, major depression, and anorexia nervosa. Improvement in each occurred after treatment with the serotonin selective reuptake inhibitor, fluoxetine, suggesting that such syndromes share a common serotonin neurotransmitter disturbance. Furthermore, the combined effects of medication and psychotherapy resulted in improvement in assertiveness, sense of security, self-worth, flexibility, and self-regulation. We discuss the pharmacological and psychotherapeutic implications of possible psychophysiologic similarities among the previously mentioned syndromes.
Consumption Smoothing and Extended Families

In this paper we look at various issues pertaining the smoothing of consumption in village economies (small agricultural societies). We discuss how consumption smothing is possible despite the lack of enforceability of private contracts. We next discuss how outside institutions may aect the total provision of insurance both directly (via its own policies) and indirectly (via the changes that its policies induce in private behavior), and show how it is possible that well intentioned policies may reduce welfare because they destroy the social fabric of private insurance arrangements. Further we discuss how certain policies may improve welfare because they reinforce the social fabric. We also discuss the empirical implications of the models we consider. We show ample evidence that in traditional societies the allocations are far from the first best and at the same time there is ample, if incomplete, insurance provided not by the market, but by immediate members of society.
Factorial Design: Binocular and Monocular Depth Perception in Vertical and Horizontal Stimuli

This article describes a factorial experiment that is useful as a laboratory exercise in a research methods course. In the Howani-Dolman depth perception apparatus, two vertical rods are adjusted, using binocular or monocular vision, so they appear equidistant from the observer. The two rods can also be oriented horizontally, which allows a factorial design combining the factors of Viewing Condition (binocular and monocular) and Rod Orientation (vertical and horizontal). The exercise illustrates the nature of an interaction and the necessity of an additional analysis of simple main effects. It also provides a basis fir understanding a perceptual problem in the real world-the difficulty of localizing horizontally extended stimuli such as power lines.
Autonomous Lighting Audits: Part 2 — Light Identification and Analysis

Buildings are responsible for approximately 40% of all US energy use and carbon emissions. There exists large potential to improve building efficiency through retro-commissioning, but expense and required expertise of building auditors limit current implementation. Autonomous robotic assessments have the potential to provide consistent building energy audits with reduced cost and enhanced capabilities. As a first step in automating building audits, this paper presents work on automating the lighting analysis of a building.As an aerial vehicle navigates and explores a room, the prototype system captures images and collects spectrometer readings. These data are used to quantify and classify lighting in a room. Additionally, images acquired from the optical camera are merged to form a composite image of the area. This composite image is used for navigation to lights to record spectrometer readings. Lighting type is then classified from these spectrometer readings. The combined lighting quantification and classification is used to create a topology map of light levels. The combined data are used to perform a thorough analysis of lighting and make lighting recommendations.© 2014 ASME
Reduction of Escherichia coli O157:H7 shedding in cattle by addition of chitosan microparticles to feed.

ABSTRACT Enterohemorrhagic Escherichia coli O157:H7 (EHEC) is a significant human pathogen that resides in healthy cattle. It is thought that a reduction in the prevalence and numbers of EHEC in cattle will reduce the load of EHEC entering the food chain. To this end, an intervention strategy involving the addition of chitosan microparticles (CM) to feed in order to reduce the carriage of this pathogen in cattle was evaluated. Experiments with individual Holstein calves and a crossover study found that the addition of CM to feed decreased E. coli O157:H7 shedding. In the crossover study, CM resulted in statistically significant reductions in the numbers recovered from rectal swab samples (P
Predation inhibits the positive effect of dispersal on intraspecific and interspecific synchrony in pond metacommunities

Recent interest in the ecological drivers of compensatory and synchronous population dynamics has provided an improved yet incomplete understanding of local and regional population oscillations in response to variable environments. Here, we evaluate the effect of dispersal rate and spatiotemporal heterogeneity in predation by the selective planktivore, bluegill sunfish (Lepomis macrochirus), on local and regional dynamics of zooplankton in pond metacommunities. A metacommunity consisted of three pond mesocosm communities, one with constant presence of predators, one without predators, and one with alternating presence-absence of predators. The three communities were connected at either no, low (0.7% per day), or high (20% per day) planktonic dispersal. Results demonstrate that heterogeneous predation (1) prevents spatial synchrony among prey populations across local communities, (2) disrupts the synchronous population dynamics within communities produced by dispersal, and (3) induces local compensatory dynamics between species within communities regardless of dispersal rate. Taken together, the results emphasize that spatiotemporal heterogeneity in selective predation can inhibit both intraspecific and interspecific synchrony in metacommunities.
Alloimmunization to transfused platelets requires priming of CD4+ T cells in the splenic microenvironment in a murine model

BACKGROUND: Alloantibodies are a clinically significant sequelae of platelet (PLT) transfusion, potentially rendering patients refractory to ongoing PLT transfusion support. These antibodies are often IgG class switched, suggesting the involvement of CD4+ T-cell help; however, PLT-specific CD4+ T cells have not been visualized in vivo, and specifics of their stimulation are not completely understood. STUDY DESIGN AND METHODS: A murine model of alloimmunization to transfused PLTs was developed to allow in vivo assessment and characterization of CD4+ T cells specific for PLT major histocompatibility complex (MHC) alloantigen. PLTs were harvested from BALB/c mice, filter leukoreduced, and transfused into C57BL/6 recipients. PLT-specific CD4+ T-cell responses were visualized by using a T-cell receptor transgenic mouse that detects peptide from donor MHC I presented on recipient MHC II. Antibody responses were determined by indirect immunofluorescence using BALB/c donor targets. RESULTS: C57BL/6 recipients of BALB/c leukoreduced PLT transfusions produced BALB/c antibodies, with proliferation of antigen-specific CD4+ T cells seen in the spleen but not lymph nodes or liver. Depletion of recipient CD4+ cells or splenectomy independently abrogated the alloantibody response. CONCLUSION: We report a novel model to study antigen-specific CD4+ T cells during alloimmunization to PLT transfusion. The presented data support a critical role for CD4+ T-cell help in the humoral response to PLT transfusion and establish the spleen as a required microenvironment for effective CD4+ T-cell priming against donor PLT–derived MHC I.
Kcnd2 Mutation Associated with Autism and Epilepsy Impairs Inactivation Gating in Kv4.2 K+ Channels

Kv4 subunits underlie somatodendritic A-type K+ currents in neurons. A de novo Kv4.2 mutation, V404M, was identified by whole exome sequencing in a family with identical twins affected by autism and intractable seizures. V404 immediately follows the S6 PVP motif, which is involved in activation and inactivation gating. The effects of V404M on channel function were characterized in oocytes with or without KChIP3a and DPP10a, which associate with Kv4.2 in vivo. V404M currents reached peak amplitude more slowly and decayed more slowly and less completely than wild-type currents. Because the time to peak is determined by the rates of opening and inactivation, a longer time to peak likely reflects slower inactivation. The twins' genomes contain one wild-type and one mutant allele. To characterize channels containing both subunit types, wild type and V404M were co-expressed at a 1:1 ratio. Wild type/V404M currents resembled V404M alone indicating that the functional effects of V404M are dominant. When V404M was co-expressed with KChIP3a, little inactivation occurred during a 1 s pulse. Because KChIP3a prevents or inhibits open-state N-type inactivation, these results indicate that V404M significantly impairs closed-state inactivation. Co-expression with DPP10a confers fast open-state inactivation. However, slower closed-state inactivation was evident in V404M channels in the presence of DPP10a, indicating that V404M does not interfere with open-state inactivation conferred by DPP10a and that DPP10a does not mask the effect of V404M on closed-state inactivation. We conclude that the V404M mutation dramatically slows closed-state inactivation. In Kv4 channels, closed state inactivation likely results from uncoupling between the voltage sensor and the pore gate. We propose that replacing V404 with the larger methionine residue strengthens the physical interaction between the gate and voltage sensor so that opening is preferred over closed-state inactivation.
Myocardial Ischemic Injury After Heart Transplantation Is Associated With Upregulation of Vitronectin Receptor (αvβ3), Activation of the Matrix Metalloproteinase Induction System, and Subsequent Development of Coronary Vasculopathy

Background— Myocardial ischemic injury after heart transplantation is associated with subsequent development of graft vasculopathy. Both vitronectin receptor (integrin αvβ3) and tissue factor play key roles in vascular endothelial cell injury. Matrix metalloproteinases (MMPs) are activated in ischemic injury models. Methods and Results— Thirteen patients developed myocardial ischemic injury within 2 weeks of cardiac transplantation (ischemia group). These were compared with 10 transplantation patients who had no evidence of ischemia (control group). Endomyocardial biopsies were evaluated within 2 weeks of transplantation for αvβ3, tissue factor, and extracellular MMP inducer (EMMPRIN). At 1 year, MMPs were evaluated, and interstitial myocardial fibrosis was quantified. All patients underwent intravascular ultrasound at 1 month and 1 year after transplantation. Compared with control, the ischemia group demonstrated evidence of significant increased expression of αvβ3 (3.2-fold, P<0.001), tissue factor (2.5...
Drug-Related Suicide: A DAWN Profile*

Drug-related suicides and suicide attempts/gestures account for a relatively large percentage of the drug-involved cases seen by hospital emergency rooms and medical examiners. While tranquilizer involvement characterizes the largest subgroup of suicide cases in the emergency room, barbiturate involvement is most frequently true of suicide cases seen by medical examiners. However, in both settings the suicides tend to be older and to include relatively more females and fewer Blacks than the nonsuicides.
A novel, lower cost, thermally enhanced exposed silicon plastic package (ESPP)

The plastic Quad Flat Package has evolved into a large, high pin count package, however higher reliability and thermal dissipation requirements constitute the boundary conditions it must overcome to evolve as a viable high density package. The present mold compounds used as encapsulants have poor thermal conductivities and represent a large portion of the thermal resistance in the plastic package. Existing thermally enhanced plastic packages are prone to delamination, and higher costs. A new plastic package is proposed herein that achieves a new level of reliability and performance, all at a cost lower than the standard plastic package. The ESPP package integrity is analyzed and compared to other thermally enhanced packages. Thermal performance is measured and compared to other packages. >
X-ray absorption via Kα resonance complexes in oxygen ions

The Kα resonance complexes in oxygen ions O I‐O VI are theoretically computed, and resonance oscillator strengths and wavelengths are presented. The highly resolved photoionization cross-sections, with relativistic fine structure, are computed in the coupled channel approximation using the Breit‐Pauli R-matrix method. A number of strong Kα resonances are found to be appreciable, with resonance oscillator strengths f r > 0.1. The Kα resonance wavelengths of O I‐O VI lie in the relatively narrow wavelength range 22‐23.5 ˚ A, and the X-ray opacity in this region should therefore be significantly affected by K → L transitions in oxygen. The results should be useful in the interpretation of soft X-ray spectra observed from Chandra and
Analyzing dynamic performance of power systems over parameter space using normal forms of vector fields. II. Comparison of the system structure

Summary form only given. For pt. I see ibid., p. 1301 (2001). Part I proposed an approach to identify unfavorable operating regions by searching for resonance and near-resonance. The results show that near-resonance among critical inertial modes and control modes may contribute to the unsatisfactory behavior of the system. In this paper, the effect of strong nonlinear modal interactions on machine states is quantified. A new index is derived to measure the relative severity of the near-resonance. The linear and nonlinear characteristics of the system are separated and correlated to the transient stability of the system.
Low-grade mucinous neoplasm of the appendix managed with laparoscopic appendectomy

Mucocele of the appendix is uncommon and caused by a variety of pathologies. While the gold standard approach to these lesions has historically been exploratory laparotomy and right hemicolectomy, there is increasing experience with a minimally invasive approach and the resection limited to an appendectomy. A case is presented of an appendiceal mucocele diagnosed preoperatively and managed with a laparoscopic appendectomy. The pathology showed a low-grade mucinous neoplasm, with no evidence of recurrence on 30 month follow-up.
Pharmacology of 21-day oral etoposide given in combination with i.v. cisplatin in patients with extensive-stage small cell lung cancer: a cancer and leukemia group B study (CALGB 9062).

This was a pharmacological companion study to a randomized Phase III trial comparing 21-day oral versus 3-day i.v. etoposide in combination with i.v. cisplatin in patients with extensive-stage small cell lung cancer. Etoposide plasma concentrations were measured in patients randomized to the 21-day schedule and correlated with toxicity and tumor response. Patients were treated with etoposide (50 mg/m2/day) orally for 21 days and cisplatin (33 mg/m2/day) i.v. for 3 consecutive days every 28 days for 6 courses. Plasma samples before the daily etoposide dose (trough concentrations) and complete blood counts were obtained weekly during treatment. The average of three etoposide concentrations (EC) per course was calculated. Of 158 patients registered to this schedule of the study, 150 were eligible. In 106 patients, etoposide samples were obtained at least in the first course in which the mean EC was 0.39 microgram/ml (SD = 0.29). In 102 patients (missing albumin values in 4 of 106 patients), the concentration of etoposide not bound to protein (Efree) was estimated based on the following equation: percentage unbound = (1.4 x total bilirubin) - (6.8 x albumin) + 34.4. Regression analysis revealed that increasing age was correlated with higher EC (r = 0.27; two-tailed P < 0.01) and Efree (r = 0.31; two-tailed P < 0.01). Higher EC and Efree values were associated with lower WBC counts and absolute neutrophil counts after the first treatment course in 83 patients with nadir counts. Using multiple linear regression, a pharmacodynamic model was developed that included EC or Efree, age, and alkaline phosphatase. An interaction with bone marrow results at diagnosis was found, indicating a sharper decline in nadir counts with increasing EC or Efree when the marrow was involved with small cell lung cancer. This model explained 29% of the variation for WBC nadirs (P < 0.001) and 31% of the variation for absolute neutrophil count nadirs (P < 0. 001). Neither EC nor Efree showed a significant correlation with tumor response. A pharmacokinetic relationship between EC or Efree and age was found. A pharmacodynamic model could be developed for toxicity but not for tumor response.
VEGAN, a package of R functions for community ecology

Abstract VEGAN adds vegetation analysis functions to the general-purpose statistical program R. Both R and VEGAN can be downloaded for free. VEGAN implements several ordination methods, including Canonical Correspondence Analysis and Non-metric Multidimensional Scaling, vector fitting of environmental variables, randomization tests, and various other analyses of vegetation data. It can be used for large data. Graphical output can be customized using the R language's extensive graphics capabilities. VEGAN is appropriate for routine and research use, if you are willing to learn some R. Abbreviation: MDS = Multidimensional Scaling.
3D Shape Analysis of Intracranial Aneurysms Using the Writhe Number as a Discriminant for Rupture

Intracranial aneurysms are polymorphic focal arterial dilations, which harbor a variable risk of rupture leading to high morbidity and mortality. Increased detection of incidental aneurysms by non-invasive imaging has created a need for rupture risk stratification tools, in addition to simple aneurysm size, to guide optimal treatment strategy. To this end, shape analysis has emerged as a possible differentiator of rupture likelihood. A novel set of morphological parameters based on the writhe number are introduced here to describe aneurysms and discriminate rupture status. Classification in 117 saccular aneurysms (52 ruptured and 65 unruptured) is based on statistical analysis of writhe number distribution on the aneurysm surface. Aneurysms are analyzed both in isolation and including a portion of their parent vessel. Sidewall and bifurcation aneurysm subtypes were found to be best described by disjoint sets of shape parameters, yielding a morphological dichotomy between the two aneurysm classes. Writhe number analysis results in 86.7% accuracy on sidewall (SW) aneurysms and 71.2% accuracy on bifurcation (BF) aneurysms. This represents a 12% accuracy increase for both subtypes compared to the performance of seven established 2D and 3D indexes. The results support the utility of writhe number aneurysm shape analysis, with potential clinical value in rupture risk stratification.
Protein and Major Cations in California Cottage Cheese and Yogurt

Abstract To determine the concentrations of protein and major cations (calcium, potassium, magnesium, and sodium) in California cottage cheese and yogurt, 244 samples of cottage cheese and 52 samples of yogurt were collected from local retail stores. Mean concentrations of protein were 12.5% in cottage cheese and 4.50% in yogurt. Mean concentrations of calcium were 75.9 mg/100 g in cottage cheese and 152.1 mg/100 g in yogurt. Mean concentrations of potassium were 60 mg/100 g in cottage cheese and 219 mg/100 g in yogurt. Mean concentrations of magnesium were 10.8 mg/100 g in cottage cheese and 19.7 mg/100 g in yogurt. Mean concentrations of sodium were 393 mg/100 g in cottage cheese and 65.8 mg/100 g in yogurt. To measure the variation in concentrations of these constituents in cottage cheese due to time of year, samples of regular and lowfat cottage cheese were collected from a local plant each week for a year. Annual mean concentrations of protein, calcium, potassium, magnesium, and sodium were 12.37%, 92.9 mg/100 g, 63.7 mg/100 g, 13.4 mg/100 g, and 417 mg/100 g in regular cottage cheese and 12.58%, 106.9 mg/100 g, 85.6 mg/100 g, 15.3 mg/100 g, and 420 mg/100 g in lowfat cottage cheese. Differences between the means for regular and lowfat cottage cheese were statistically significant for all constituents except sodium. Time-of-year effects were significant for protein, calcium, potassium, and sodium.
Acceleration of hyperfractionated chemoradiation regimen for advanced head and neck cancer

Background. Our aim was to evaluate the acceler- ation of a hyperfractionated, concurrent chemoradiation regimen (HxCRT) for advanced head and neck squamous cell carcinoma (HNSCC). Methods. Patients with unresectable HNSCC were treated based on a previously published HxCRT regimen: 1.25 Gy twice daily to 70 Gy concurrent with cisplatin 12 mg/m 2 /day and 5-fluorouracil 600 mg/m 2 /day for 5 days, weeks 1, 5. This regimen was accelerated in this series by shortening the treatment from 7 to 6 weeks by omitting the planned mid-treatment 1-week break. Results. Forty-six patients with T3-4/N3 disease were treated. The main acute toxicity was pharyngeal. Median weight change during therapy in patients with and without enteral feeding tubes was � 3.8% and � 7.9%, respectively (p ¼ .08). Fifteen percent had late grade III pharyngeal toxicity. Local/regional and distant failure rates were 28% and 17%, respectively; 52% are alive without evidence of disease. Conclusions. In nonresectable HNSCC, acceleration of the HxCRT regimen is feasible, requiring enteral feeding tubes during
Positron emission tomography for initial staging of esophageal cancer among medicare beneficiaries

Background: The role of positron emission tomography (PET) in the initial staging of esophageal cancer is to detect occult metastases, but its ability to do so has not been evaluated at the population-level. In 2001, Medicare approved reimbursement of PET for esophageal cancer staging. We hypothesized rapid adoption of PET after 2001 and a coincident increase in the prevalence of stage IV disease. Methods: A retrospective cohort study [1997-2009] was conducted of 12,870 Medicare beneficiaries with esophageal cancer using the Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. Results: PET use increased from Conclusions: The increasing frequency of PET use and stage IV disease over time is more likely explained by improved documentation rather than PET’s ability to detect occult metastases. The absence of compelling population-level impact compliments previous studies, revealing an opportunity to increase value through selective use of PET.