cssi/SciSciGPT-SciSciNet huggingface dataset:
Gene and cell therapy for cystic fibrosis

Since the discovery of the CF gene over a decade ago, several groups worldwide have explored the potential of gene therapy, the insertion of a normal copy of the gene into the respiratory epithelium. Both viral and synthetic gene transfer agents have been designed to this end, although problems with repeat application have occurred with the former have occurred. Here, we will briefly review success in clinical trials to date. Cell therapy, replacement of the CF cell with a healthy, normal cell, is at a much earlier stage of development, studies mainly being preclinical or observational. Some evidence of plasticity of, for example, bone marrow cells, has been demonstrated, although for the airway, levels of correction appear to be extremely low and a degree of damage seems to be a prerequisite. Whether this approach will be able to achieve clinical success remains to be seen.
Value of imperfect input information in agricultural production

Abstract The paper develops a general analytical framework for evaluating imperfect information concerning a stochastic input when choosing the level of a purchased input. Second order approximations of utility yield intuitive results summarized in three propositions. Perfect information is more valuable the more it increases the efficiency of purchased input use and the more variable the stochastic input. Imperfect information is more valuable the more it increases the efficiency of purchased input use, the more the imperfect signal is correlated with the stochastic input, and the less variable the signal. A Monte Carlo evaluation of soil nitrogen testing finds that risk aversion increases the value of perfect information, while risk aversion and signal noise reduce the value of imperfect information. The propositions substantially underestimate the value of information—predicting less than half the actual value.
Development of 13 microsatellites for Gunnison Sage-grouse (Centrocercus minimus) using next-generation shotgun sequencing and their utility in Greater Sage-grouse (Centrocercus urophasianus)

Gunnison Sage-grouse are an obligate sagebrush species that has experienced significant population declines and has been proposed for listing under the U.S. Endangered Species Act. In order to examine levels of connectivity among Gunnison Sage-grouse leks, we identified 13 novel microsatellite loci though next-generation shotgun sequencing, and tested them on the closely related Greater Sage-grouse. The number of alleles per locus ranged from 2 to 12. No loci were found to be linked, although 2 loci revealed significant departures from Hardy–Weinberg equilibrium or evidence of null alleles. While these microsatellites were designed for Gunnison Sage-grouse, they also work well for Greater Sage-grouse and could be used for numerous genetic questions including landscape and population genetics.
The damping of flexural and acoustic waves by a bias-flow perforated elastic plate

An analysis is made of the damping of sound and structural vibrations by vorticity production in the apertures of a bias flow, perforated elastic plate. Unsteady motion causes vorticity to be generated at the aperture edges; the vorticity and its energy are swept away by the bias flow and result in a net loss of acoustic and vibrational energy. In this paper we investigate the interaction of an arbitrary fluid-structure disturbance with a small circular aperture in the presence of a high Reynolds number, low Mach number bias flow. By considering the limit in which the aperture is small compared to the length scale of the impinging disturbance, it is shown that the effect of the interaction can be represented by a concentrated source in the plate bending wave equation consisting of a delta function and two of its axisymmetric derivatives. A generalized bending wave equation is then formulated for a plate perforated with an homogeneous distribution of small, bias flow circular apertures. This equation is used to predict the attenuation of sound and resonant bending waves by vorticity production. Acoustic damping is found to be significant provided the fluid loading is sufficiently small for the plate to be regarded as rigid (e.g. for an aluminium plate in air when the frequency is not too small). On the other hand, a bending wave is effectively damped only when the fluid loading is large enough for the wave to produce a substantial pressure drop across the plate; when this occurs the predicted attenuations are comparable with those usually achieved by the application of elastomeric damping materials. Numerical predictions are presented for steel and aluminium plates in air and water.
Cocaine and lidocaine have similar psychological effects after intranasal application.

Abstract Drug experienced subjects were administered three matched doses of intranasal cocaine and lidocaine. For each dose psychological ratings were similar for both drugs. The subjects were unable to discriminate between the drugs.
Relative performance of impedance-matched lumped-element and traveling-wave integrated-optical phase modulators

The performance of impedance-matched lumped-element and traveling-wave integrated-optical phase modulators is compared. This analysis shows that the performance of lumped-element modulators in LiNbO/sub 3/ exceeds that of traveling-wave devices when the product of the modulation frequency and electrode length is less than approximately 20 GHz-mm. Impedance-matched lumped-element modulators are particularly applicable to narrow band systems operating up to several gigahertz. >
Behavior of Hybrid Optical/RF Channels over Varying Link Distances

This paper investigates the behavior of optical and hybrid optical/RF links over varying link distances. We first describe inclusion of various factors affecting the optical link, such as the atmospheric absorption, beam divergence and atmospheric turbulence. A technique to analyze outage probability of the hybrid link for low density parity check (LDPC) codes is presented. Our results show that the hybrid link can improve outage probability by orders of magnitude over an optical only link. In haze conditions, the hybrid link can extend the coverage distance of an optical only link by hundreds of meters by diverting a small fraction of the data through the RF link.
Parametric resonance voltage response of electrostatically actuated Micro-Electro-Mechanical Systems cantilever resonators

Abstract This paper investigates the parametric resonance voltage response of nonlinear parametrically actuated Micro-Electro-Mechanical Systems (MEMS) cantilever resonators. A soft AC voltage of frequency near natural frequency is applied between the resonator and a parallel ground plate. This produces an electrostatic force that leads the structure into parametric resonance. The model consists of an Euler–Bernoulli thin cantilever under the actuation of electrostatic force to include fringe effect, and damping force. Two methods of investigation are used, namely the Method of Multiple Scales (MMS) and Reduced Order Model (ROM) method. ROM convergence of the voltage response and the limitation of MMS to small to moderate amplitudes with respect to the gap (gap-amplitudes) are reported. MMS predicts accurately both Hopf supercritical and supercritical bifurcation voltages. However, MMS overestimates the large gap-amplitudes of the resonator, and. misses completely or overestimates the saddle-node bifurcation occurring at large gap-amplitudes. ROM produces valid results for small and/or large gap-amplitudes for a sufficient number of terms (vibration modes). As the voltage is swept up at constant frequency, the resonator maintains zero amplitude until reaches the subcritical Hopf bifurcation voltage where it loses stability and jumps up to large gap-amplitudes, next the gap-amplitude decreases until it reaches the supercritical Hopf bifurcation point, and after that the gap-amplitude remains zero, for the voltage range considered in this work. As the voltage is swept down at constant frequency, the zero gap-amplitude of the resonator starts increasing continuously after reaching the supercritical Hopf bifurcation voltage until it reaches the saddle-node bifurcation voltage when a sudden jump to zero gap-amplitude occurs. Effects of frequency, damping and fringe parameters on the voltage response show that (1) the supercritical Hopf bifurcation is shifted to lower voltage values with the increase of any of the mentioned parameters, (2) the subcritical Hopf bifurcation is shifted to larger voltage values with the increase of damping, shifted to lower voltage values with the increase of the fringe parameter, and not significantly altered by the change in frequency, (3) the saddle-node bifurcation voltage decreases with the increase of frequency and damping, and decrease of fringe parameter, and (4) the saddle-node bifurcation gap-amplitude decreases with the increase of frequency and damping, and it is not significantly altered by the change of the fringe parameter.
When Goal Violation Prompts Justification: Conflicting Goals and Reason Based Choices

Consumers often have multiple goals that are active simultaneously, and make choices to satisfy those goals. However, no work to date has studied how people choose when all available options serve a goal (e.g., a choice-set goal) that conflicts with another goal they hold (e.g., an incidental goal). We demonstrate that in such contexts, consumers are more likely to choose the option that is most instrumental for attaining the choice-set goal, even when that option poses the greatest violation of the incidental goal. This occurs because the experience of goal conflict increases consumers’ need to justify their choices. Since the consumer will violate their incidental goal by choosing any of the available alternatives, we propose that the most justifiable reason for violating the incidental goal would be to maximize on the choice-set goal. Six experiments provide evidence for these effects and the underlying theoretical mechanism.
“Uh Oh. Cue the [New] Mommy Wars”: The Ideology of Combative Mothering in Popular U.S. Newspaper Articles About Attachment Parenting

Through critique of concordance, we argue that popular U.S. newspaper articles about attachment parenting perpetuate the ideology of combative mothering, where mothers are in continuous competition with one another over parenting choices. Specifically, article writers construct a new, singular metaphorical mommy war between proattachment parenting and antiattachment parenting proponents by prepackaging attachment parenting and its debate, advocating for attachment parenting through instinct and science, and rejecting attachment parenting because of harm to children, relationships, and mothers. A minority of articles, however, avoided reifying this pro-/antiattachment parenting mommy war by exploring the complexities of parenting beyond prepackaged philosophies. We explore the implications of this new mommy war on ideologies of motherhood and the politics of choice.
Applicable or non-applicable: investigations of clinical heterogeneity in systematic reviews

Clinical heterogeneity can be defined as differences in participant characteristics, types or timing of outcome measurements and intervention characteristics. Clinical heterogeneity in systematic reviews has the possibility to significantly affect statistical heterogeneity leading to inaccurate conclusions and misled decision making. The aim of this study is to identify to what extent investigators are assessing clinical heterogeneity in both Cochrane and non-Cochrane systematic reviews. The most recent 100 systematic reviews from the top five journals in medicine—JAMA, Archives of Internal Medicine, British Medical Journal, The Lancet, and PLOS Medicine—and the 100 most recently published and/or updated systematic reviews from Cochrane were collected. Various defined items of clinical heterogeneity were extracted from the included reviews. Investigators used chi-squared tests, logarithmic modeling and linear regressions to determine if the presence of such items served as a predictor for clinical heterogeneity when comparing Cochrane to non-Cochrane reviews. Extracted variables include number of studies, number of participants, presence of quantitative synthesis, exploration of clinical heterogeneity, heterogeneous characteristics explored, basis and methods used for investigating clinical heterogeneity, plotting/visual aids, author contact, inferences from clinical heterogeneity investigation, reporting assessment, and the presence of a priori or post-hoc analysis. A total of 317 systematic reviews were considered, of which 199 were in the final analysis. A total of 81 % of Cochrane reviews and 90 % of non-Cochrane reviews explored characteristics that are considered aspects of clinical heterogeneity and also described the methods they planned to use to investigate the influence of those characteristics. Only 1 % of non-Cochrane reviews and 8 % of Cochrane reviews explored the clinical characteristics they initially chose as potential for clinical heterogeneity. Very few studies mentioned clinician training, compliance, brand, co-interventions, dose route, ethnicity, prognostic markers and psychosocial variables as covariates to investigate as potentially clinically heterogeneous. Addressing aspects of clinical heterogeneity was not different between Cochrane and non-Cochrane reviews. The ability to quantify and compare the clinical differences of trials within a meta-analysis is crucial to determining its applicability and use in clinical practice. Despite Cochrane Collaboration emphasis on methodology, the proportion of reviews that assess clinical heterogeneity is less than those of non-Cochrane reviews. Our assessment reveals that there is room for improvement in assessing clinical heterogeneity in both Cochrane and non-Cochrane reviews.
Structural and Biochemical Characterization of CASK PDZ Interaction with Protein and Lipid Binding Partners

PSD-95/Dlg/ZO-1 (PDZ) domains are protein-protein interaction modules that generally interact with the C-terminus of partner scaffold proteins to participate in signal transduction processes. A subset of PDZ domains also interact with phophoinositides (PtdIns) and/or cholesterol. Our study focuses on the calcium/calmodulin-dependent serine protein kinase (CASK) PDZ domain that has been shown to synergistically interact with both protein binding partners and PtdIns. First, we quantitate the interaction between the CASK PDZ domain and known interaction partners. We show that the CASK PDZ domain binds to neurexin1 (NRXN1) and phosphorylated syndecan1 (pSDC1) with micromolar affinity, and only weakly (>100 μM) with unphosphorylated syndecan isoforms (SDC1-4). Second, we determined the crystal structure of the CASK PDZ domain alone and complexed with several peptides. A comparison of the CASK PDZ/NRXN1 structure with the CASK PDZ/SDC structures indicates that peptide-binding shifts the α2-helix adjacent to the binding pocket resulting in a more expanded binding groove. Moreover, the CASK/pSDC1 crystal structure shows an interaction between residue R517 and the phosphoryl group of pSDC1, suggesting that his new feature provides specificity and affinity. Consistent with previous literature, protein-lipid blot analysis data showed that the CASK PDZ binds to various PtdIns molecules. However, NMR-based titration data indicated that this interaction is weak. Future experiments will explore the cooperativity of peptides and PtdIns in binding the CASK PDZ in the context of cell membranes.
ER Protein Processing Under Oxidative Stress: Implications and Prevention

Elevated levels of mitochondrial nitrosative stress have been associated with the pathogenesis of both Parkinson's and Alzheimer's diseases. The mechanism involves catalytic poisoning of the endoplasmic reticulum (ER)-resident oxidoreductase chaperone, protein disulfide isomerase (PDI), and the subsequent accumulation of ER-processed substrate proteins. Using a model system to mimic mitochondrial oxidative and nitrosative stress, we demonstrate a PDI-independent mechanism whereby reactive oxygen species (ROS) compromise regeneration rates of disulfide bond-containing ER-processed proteins. Under ROS-duress, the secretion-destined traffic adopts disulfide-exposed structures making the protein flux retrotranslocation biased. We also demonstrate that ROS-compromised protein maturation rates can be rescued by the polyphenol ellagic acid (EA). Our results are significant in that they reveal an additional mechanism which could promote neurodegenerative disorders. Furthermore, our data reveal that EA possesses therapeutic potential as a lead prophylactic agent against oxidative/nitrosative stress-related neurodegenerative diseases.
Correlation effects in La, Ce, and lanthanide ions

We carry out a comprehensive study of higher-order correlation effects to the excitation energies of La, ${\mathrm{La}}^{+}$, Ce, ${\mathrm{Ce}}^{+}$, ${\mathrm{Ce}}^{2+}$, and ${\mathrm{Ce}}^{3+}$. The calculations are carried out using two hybrid approaches that combine configuration interaction with second-order perturbation theory and the linearized coupled-cluster all-order method. Use of two approaches allows us to isolate the effects of third- and higher-order corrections for various configurations. We also study the contribution of higher partial waves and investigate methods to extrapolate the effect of omitted partial waves. The effects of the higher partial waves for the monovalent configuration of ${\mathrm{La}}^{2+}$ and ${\mathrm{Ce}}^{3+}$ are compared with analogous effects in multivalent configurations of La, ${\mathrm{La}}^{+}$, Ce, ${\mathrm{Ce}}^{+}$, and ${\mathrm{Ce}}^{2+}$. Tests of our extrapolation techniques are carried out for several Cd-like lanthanide ions. The results of the present studies are of particular interest to the development of high-precision methods for treatment of systems with partially filled $nf$ shells that are of current experimental interest for a diverse set of applications.
The DQβ Chain Dictates DQ Type for DQw2 and DQw3

The association of a number of diseases with the HLA-DR5 haplotype led us to sequence the expressed class II molecules of this haplotype to establish structure-function relationships, and to possibly elucidate a structural basis for predisposition to disease. We have made a cDNA library from the DR5 cell line, Swei (DR5, DRw52, Dw25, DQw7(w3), DPw4) and report here the sequence of the cDNA’s corresponding to the DQw7α and DQw7β chains from this cell line (1). From our analysis and that of Saiki et al. (2), DQα appears to have one region of major variability. In contrast, DQβ appears to have four regions of variability. A comparison of DQα and DQβ chain sequences from DQw7 with those from other DQ types indicates that DQw7α derived from DR5 (denoted DQw7α (DR5)) is distinct from DQw7α (DR4), and DQw2α (DR3) is different from DQw2α (DR7) (3). Moreover, DQw7α (DR5) is identical to DQw2α (DR3). In contrast, DQw7β (DR5) is almost identical to DQw7β (DR4), and DQw2β (DR3) is identical to DQw2β (DR7). Thus, at least for DQw2 and w7, the DQβ chain dictates the DQ specificity. In addition, these data indicate that recombination occurs between DQA1 and DQB1. In contrast to data from DQw2 and DQw7, sequence data has indicated that DQwlα from DR1, 2, and w6 differ by only one amino acid and that the first domains of DQw1β derived from DR1 and DRw6 are identical. Thus, it is possible that both DQα and β chains contribute to the formation of the DQw1 epitope.
The London Monetary and Economic Conference of 1933 and the End of the Great Depression

In this paper I analyze the London Monetary and Economic Conference of 1933, an almost forgotten episode in U.S. monetary history. I study how the Conference shaped dollar policy during the second half of 1933 and early 1934. I use daily data to investigate the way in which the Conference and related policies associated to the gold standard affected commodity prices, bond prices, and the stock market. My results show that the Conference itself did not impact commodity prices or the stock market. However, it had a small effect on bond prices. I do find that the events associated with the abandonment of the gold standard impacted prices in a significant way, even before the actual monetary and currency channels were at work. These results are consistent with the “change in regime” hypothesis of Sargent (1983).
Classical Fractals and Quantum Chaos in Ultracold Dipolar Collisions.

We examine a dipolar-gas model to address fundamental issues regarding the correspondence between classical chaos and quantum observations in ultracold dipolar collisions. The theoretical model consists of a short-range Lennard-Jones potential well with an anisotropic, long-range dipole-dipole interaction between two atoms. Both the classical and quantum dynamics are explored for the same Hamiltonian of the system. The classical chaotic scattering is revealed by the fractals developed in the scattering function (defined as the final atom separation as a function of initial conditions), while the quantum chaotic features lead to the repulsion of the eigenphases from the corresponding quantum $S$ matrix. The nearest-eigenphase-spacing statistics have an intermediate behavior between the Poisson and the Wigner-Dyson distributions. The character of the distribution can be controlled by changing an effective Planck constant or the dipole moment. The degree of quantum chaos shows a good correspondence with the overall average of the classical scattering function. The results presented here also provide helpful insights for understanding the role of the inherent dipole-dipole interaction in the currently ongoing experiments on ultracold collisions of highly magnetic atoms.
New Typographic Experience in the Post-digital Age with 3D Printing and Ceramics

This research explores unconventional methods of creating three-dimensional type with materials and techniques unique to type design, such as ceramics and 3D printing. Today, technological convergence and new manufacturing processes using computer numerical controls have broadened creative possibilities and the perception of the three-dimensional experience for artists and designers. With the development of digital technologies, letters can be printed in three-dimensional space, and this will cause a paradigm shift in the typographic experience regarding the development of material and manufacturing technologies.
Delayed and Unreported Drug-Susceptibility Testing Results in the US National Tuberculosis Surveillance System, 1993-2014.

Objectives:Drug-susceptibility testing (DST) of Mycobacterium tuberculosis is necessary for identifying drug-resistant tuberculosis, administering effective treatment regimens, and preventing the s...
An analysis of retinal receptor orientation. I. Angular relationship of neighboring photoreceptors.

The orientation of retinal receptors is important in the understanding of retinal physiology. The photoreceptors of spider monkey eyes tend to be oriented toward an anterior point in the eye rather than to the center of the retinal sphere. In this paper some of the implications of this finding are considered. Differences in cell orientation have been computed for both a center- and an anterior-pointing hypothesis. The meaning of the derived values is considered in some detail.
Obligatory role of hypothalamic neuroestradiol during the estrogen-induced LH surge in female ovariectomized rhesus monkeys.

Negative and positive feedback effects of ovarian 17β-estradiol (E2) regulating release of gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) are pivotal events in female reproductive function. While ovarian feedback on hypothalamo–pituitary function is a well-established concept, the present study shows that neuroestradiol, locally synthesized in the hypothalamus, is a part of estrogen’s positive feedback loop. In experiment 1, E2 benzoate-induced LH surges in ovariectomized female monkeys were severely attenuated by systemic administration of the aromatase inhibitor, letrozole. Aromatase is the enzyme responsible for synthesis of E2 from androgens. In experiment 2, using microdialysis, GnRH and kisspeptin surges induced by E2 benzoate were similarly attenuated by infusion of letrozole into the median eminence of the hypothalamus. Therefore, neuroestradiol is an integral part of the hypothalamic engagement in response to elevated circulating E2. Collectively, we will need to modify the concept of estrogen’s positive feedback mechanism.
Do Bilingual and Monolingual Preschoolers Acquire False Belief Understanding Similarly? The Role of Executive Functioning and Language.

Bilingual children often show advanced executive functioning (EF) and false belief (FB) understanding compared to monolinguals. The latter has been attributed to their enhanced inhibitory control E...
Polyacetylene: Myth and reality

Polyacetylene, the simplest and oldest of potentially conducting polymers, has never been made in a form that permits rigorous determination of its structure. Trans polyacetylene in its fully extended form will have a potential energy surface with two equivalent minima. It has been assumed that this results in bond length alternation. It is, rather, very likely that the zero-point energy is above the Peierls barrier. The experimental studies that purport to show bond alternation are reviewed and shown to be compromised by serious experimental inconsistencies or by the presence, for which there is considerable evidence, of finite chain polyenes. In this view, addition of dopants results in conductivity by facilitation of charge transport between finite polyenes. The double minimum potential that necessarily occurs for polyacetylene, if viewed as the result of elongation of finite chains, originates from admixture of the 1¹Ag ground electronic state with the 2¹Ag excited electronic singlet state. This excitation is diradical (two electron) in character. The polyacetylene limit is an equal admixture of these two ¹Ag states making theory intractable for long chains. A method is outlined for preparation of high molecular weight polyacetylene with fully extended chains that are prevented from reacting with neighboring chains.
Subgroups and Product Groups

In this chapter, we learn how to find small groups inside of large groups, and then how to build large groups out of small groups. The point is to help you better understand symmetry groups. If you can recognize an object’s symmetry group as having been built out of smaller groups, then this realization might help you to much more clearly understand its underlying algebraic structure.
Human Parasitic Protozoa

The clear dependence of many protozoa on exogenous sources of nutrition and their small size have led some to invade and inhabit the cells, tissues, or cavities of animals, where a rather constant environment and rich source of nutriments occur. Some of these parasitic species, during the long course of their evolution within animal systems, have developed an obligate relationship with the host and acquired specialized cellular structures and functions to efficiently utilize the unique environment they inhabit. But, this high level of specialization also has a cost. Many of the parasitic species have become so closely adapted to their parasitic existence that they are incapable of existing outside the host except as resistant stages. Digenetic species with alternating generations in two different hosts (inhabiting two different genera, hence digenetic) often exhibit complex structural and functional changes accompanying the different phases of existence. An example is the malarial parasite that has one form during invasion of the mammalian host and different forms during part of its growth in the insect host. Some have become adapted to invading specialized cells of animals such as erythrocytes (eg, malarial parasites), and the wandering cells of the immune system (eg, leishmanial parasites), where the restricted volume and accommodation to intracytoplasmic physiology have favored the evolution of a very small size. Some of these species also exhibit very simplified intracellular organelles. Those inhabiting host spaces with little oxygen (anaerobic environments) often lack mitochondria.
Muscarinic Acetylcholine Receptor Knockout Mice

Muscarinic acetylcholine receptors (mAChRs) play critical roles in regulating the activity of many important functions of the central and peripheral nervous system. However, identification of the physiological and pathophysiological roles of the individual mAChR subtypes (M1-M5) has proven a difficult task, primarily due to the lack of ligands endowed with a high degree of receptor subtype selectivity and the fact that most tissues and organs express multiple mAChRs. To circumvent these difficulties, we and others have used gene targeting strategies to generate mutant mouse lines containing inactivating mutations of the M1-M5 mAChR genes. The different mAChR mutant mice and the corresponding wild-type control animals were subjected to a battery of physiological, pharmacological, behavioral, biochemical, and neurochemical tests. The M1-M5 mAChR mutant mice (MXR-/- mice) were all viable and reproduced normally. However, each mutant mouse line displayed distinct phenotypical changes. For example, M1R-/- mice showed a pronounced increase in locomotor activity, probably due to the increase in dopamine release in the striatum. In addition, pilocarpine-induced epileptic seizures were absent in M1R-/- mice. Pharmacological analysis of M2R-/- mice indicated that the M2 subtype plays a key role in mediating three of the most striking central muscarinic effects: tremor, hypothermia, and analgesia. As expected, muscarinic agonist-mediated bradycardia was abolished in M2R-/- mice. M3R-/- mice displayed a significant decrease in food intake, reduced body weight and peripheral fat deposits, and very low serum leptin and insulin levels. Additional studies showed that the M3 receptor subtype also plays a key role in mediating smooth muscle contraction and glandular secretion. Behavioral analysis of M4R-/- mice suggested that M4 receptors mediate inhibition of D1 dopamine receptor-mediated locomotor stimulation, probably at the level of striatal projection neurons. Studies with M5R-/- mice indicated that vascular M5 receptors mediate cholinergic relaxation of cerebral arteries and arterioles. Behavioral and neurochemical studies showed that M5 receptor activity modulates both morphine reward and withdrawal processes, probably through activation of M5 receptors located on midbrain dopaminergic neurons. These results offer promising new perspectives for the rational development of novel muscarinic drugs.
The Paradox of Education in the 21st Century

In the 21st century an educational paradox confronts us. Knowledge is abundant, nearly free, and can be accessed without memorization. Nonetheless, the value of an education across many quality of life dimensions is increasing. Educated people are becoming increasingly better off, while at the same time, much of the valuable work traditionally performed by educated people is being off-loaded to computers. To understand these trends, we must move beyond the argument that education is simply the acquisition of certain attributes in order to succeed in the modern economy. These arguments fall short because they view education solely in terms of knowledge and skills that can be tested and ignore many dimensions that cannot be easily quantified. For example, the Common Core—the latest incarnation of the deficit model of education—is a backward facing approach to education reform that treats children as robots to be programmed. Children are autonomous human beings capable of meaningful relationships with others. Education should focus on changing our relationships. In fact, “change-focused” education is happening all around us. The power of education to radically change our relatedness to each other and to our environments is why the authentically educated enjoy such an enhanced quality of life.
Comparison of Antibiotic Prescribing for Pediatric Community-Acquired Pneumonia in Children’s and Non-Children’s Hospitals

This analysis uses hospital billing databases of inpatient discharges to compare antibiotic prescribing for community-acquired pneumonia by hospital type.
Clinical Presentation, Management, and Prognosis of Pseudogout in Joint Arthroplasty: A Retrospective Cohort Study

Introduction: Calcium pyrophosphate deposition disease (CPPD), or pseudogout, is rare in prosthetic joints, but can mimic prosthetic joint infection (PJI) according to case reports. The purpose of this case series is to describe the demographics, presentation, management, and outcomes of a cohort of these patients seen at our academic medical center. Methods: Patients with post-implant pseudogout, who were evaluated at our medical center between January 1, 2000 and June 30, 2016, were identified from our EHR. Data pertaining to demographics, presentation, management, and outcomes were abstracted, and patients were categorized into two groups based on presence of concomitant infection along with positive CPDD findings in synovial fluid. Results: 22 patients were included. 90.9% of cases involved a TKA. The most common indication for arthroplasty was degenerative joint disease. Only four patients had a history of previous gout or pseudogout, three of which belonged to the group with no evidence of concomitant joint infection. Clinical features for patients without concomitant infection included pain (100%), swelling at the joint (88.9%), redness (33.3%), fever (22.2%), and decreased range of motion (100%). 45.5% of patients received antibiotics prior to joint aspiration (44.4% of patients with negative synovial fluid cultures, 46.2% of patients with concomitant infection). Conclusion: Our study suggests similar clinical presentation between post-implant pseudogout and PJI. Among patients with pseudogout as well as in those with PJI, the first dose of antibiotics should not be given before sampling for synovial culture. Unfortunately, many patients receive antibiotics prior to culture ascertainment, which raises concern for antibiotic overuse.
Fate of engineered nanomaterials in natural environments and impacts on ecosystems

Abstract In this chapter, the focus is on engineered nanomaterials (ENMs) that enter natural environments with potential impacts to ecosystems. This chapter provides an overview of the major types of ENMs in use, and how they enter the environment based on manufacture, application, and disposal. This sets the stage for reviewing the evidence for ENM exposure in the environment on the basis of sample recovery and quantitative analysis. Issues of discerning ENMs from natural nanomaterials are discussed, with attention to method development. Modeling the entry and fates of ENMs in the environment is reviewed, reinforcing the importance of material flow analysis plus mechanistic fate models to improve estimations of environmental exposures. Still, ENMs have multiple fates in the environment, which can alter their integrity and bioavailability to biological receptors. The major fate interactions are discussed, including agglomeration, dissolution, degradation, and organismal uptake. Under these conditions of exposure, we discuss the potential for ENMs to affect organisms and ecosystems, plus evidence therein. We conclude with summarizing key concepts and points, including an overview of uncertainties and opportunities to advance understanding in the future.
The role of school race/ethnic composition in mental health outcomes: A systematic literature review

Abstract Introduction This systematic literature review provides evidence concerning the association of school race/ethnic composition in mental health outcomes among adolescents (ages 11–17 years). A range of mental health outcomes were assessed (e.g., internalizing behaviors, psychotic symptoms) in order to broadly capture the relationship between school context on mental health and psychological wellbeing. Methods: A search across six databases from 1990 to 2018 resulted in 13 articles from three countries (United States, United Kingdom, and the Netherlands) that met inclusion criteria following a two step review of titles/abstracts and full-text. Results: The existing research on school race/ethnic composition and mental health point to two distinct measures of school composition: density—the proportion of one race/ethnic group enrolled in a school, and diversity—an index capturing the range and size of all race/ethnic groups enrolled in a school. Overall, higher same race/ethnic peer density was associated with better mental health for all adolescents. In contrast, there was no overall strong evidence of mental health advantage in schools with increased diversity. Conclusions: Theoretical and methodological considerations for future research towards strengthening causal inference, and implications for policies and practices concerning the mental health of adolescent-aged students are discussed.
Helping Babies Breathe: Improving Neonatal Resuscitation and Global Neonatal Mortality

Abstract Significant progress has been made in reducing global child mortality rates over the past 2 decades, with the improvements in survival primarily occurring among children between 1 month and 5 years of age. As a result, neonatal mortality now accounts for almost half of all deaths in children less than 5 years of age. Helping Babies Breathe is a neonatal resuscitation program developed by the American Academy of Pediatrics for use in low-resource settings and aims to teach basic resuscitation skills to providers who are present at deliveries. Using a train-the-trainer curricular model and low-cost simulator and equipment, Helping Babies Breathe has been implemented in more than 80 countries to train 500 000 providers and has resulted in a marked decline in early neonatal deaths and fresh stillbirths. Ongoing research is being done to optimize strategies to maintain resuscitation skills and knowledge over time, as well as to develop additional methods to improve neonatal resuscitation in low-resource settings, with hopes of achieving the United Nations Sustainable Development Goals for neonatal mortality rates by 2030 worldwide.
Identifying targets for preventing epilepsy using systems biology of the human brain

Approximately one third of all epilepsy patients are resistant to current therapeutic treatments. Some patients with focal forms of epilepsy benefit from invasive surgical approaches that can lead to large surgical resections of human epileptic neocortex. We have developed a systems biology approach to take full advantage of these resections and the brain tissues they generate as a means to understand underlying mechanisms of neocortical epilepsy and to identify novel biomarkers and therapeutic targets. In this review, we will describe our unique approach that has led to the development of a 'NeuroRepository' of electrically-mapped epileptic tissues and associated data. This 'Big Data' approach links quantitative measures of ictal and interictal activities corresponding to a specific intracranial electrode to clinical, imaging, histological, genomic, proteomic, and metabolomic measures. This highly characterized data and tissue bank has given us an extraordinary opportunity to explore the underlying electrical, cellular, and molecular mechanisms of the human epileptic brain. We describe specific examples of how an experimental design that compares multiple cortical regions with different electrical activities has led to discoveries of layer-specific pathways and how these can be 'reverse translated' from animal models back to humans in the form of new biomarkers and therapeutic targets. This article is part of the special issue entitled 'New Epilepsy Therapies for the 21st Century - From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy'.
Computational Analysis of Structural Defects in Silica Aerogels

Technological advances in synthesis and preparation of aerogels have resulted in formulations that have the mechanical integrity (while retaining flexibility) to be utilized in a broad range of applications and have overcome the initial brittleness that this class of materials was once known for. Both structural and functional aerogels show a drop in performance when subjected to certain cyclic thermal or impact loading due to the wear and formation of cracks, which reduces their lifespan. Here we present the proof-of-concept of a computational toolset that connects the change in thermal profile to structural failure and degradation. In combination with an appropriate finite element (FEM) solver, we have developed a genetic algorithm that can reconstruct the size and shape of the defective region in silica aerogels given the temperatures from a sensor grid. Results show that a heatmap can be used as the foundation for reconstructing faults and defects in thermally insulating materials. Furthermore, the model developed in this study can be expanded to accommodate other material types. Experimental setup can used to benchmark and refine the computational toolset.
Intraspinal Plasticity Associated With the Development of Autonomic Dysreflexia After Complete Spinal Cord Injury

Traumatic spinal cord injury (SCI) leads to disruption of sensory, motor and autonomic function, and triggers structural, physiological and biochemical changes that cause reorganization of existing circuits that affect functional recovery. Propriospinal neurons (PN) appear to be very plastic within the inhibitory microenvironment of the injured spinal cord by forming compensatory circuits that aid in relaying information across the lesion site and, thus, are being investigated for their potential to promote locomotor recovery after experimental SCI. Yet the role of PN plasticity in autonomic dysfunction is not well characterized, notably, the disruption of supraspinal modulatory signals to spinal sympathetic neurons after SCI at the sixth thoracic spinal segment or above resulting in autonomic dysreflexia (AD). This condition is characterized by unmodulated sympathetic reflexes triggering sporadic hypertension associated with baroreflex mediated bradycardia in response to noxious yet unperceived stimuli below the injury to reduce blood pressure. AD is frequently triggered by pelvic visceral distension (bowel and bladder), and there are documented structural relationships between injury-induced sprouting of pelvic visceral afferent C-fibers. Their excitation of lumbosacral PN, in turn, sprout and relay noxious visceral sensory stimuli to rostral disinhibited thoracic sympathetic preganglionic neurons (SPN) that manifest hypertension. Herein, we review evidence for maladaptive plasticity of PN in neural circuits mediating heightened sympathetic reflexes after complete high thoracic SCI that manifest cardiovascular dysfunction, as well as contemporary research methodologies being employed to unveil the precise contribution of PN plasticity to the pathophysiology underlying AD development.
Strategic Implications of Current Small Business Waste Reduction Programs

The strategic importance of environmental awareness has received a great deal of recognition recently, but attention has centered primarily on residential or municipal recycling and waste reduction efforts. The small amount of research done on commercial waste reduction policies has focused on the altitudes and programs of large corporations. As governmental agencies impose waste reduction mandates on communities and corporations, many small businesses will be forced 10 adopt waste reduction programs in the future. In addition, a growing body of evidence suggests that environmental programs are associated with profitability, indicating the need for a more strategic approach 10 the management of environmental issues in order to effectively administer required programs. This study presents results of survey research indicating that small businesses are willing 10 commit 10 strategic waste reduction programs, but are concerned primarily with the convenience of such programs. Although convenience is frequently related 10 operating cost in small businesses, issues regarding the expense of waste reduction programs are of secondary concern 10 small business executives. The implications of these results are discussed, along with recommendations for small business executives, consult­ ants, and policy makers.
Assessing performance validity with the TOMM and automatized sequences task in a pediatric psychiatric inpatient setting.

This study examined the performance of children consecutively admitted to an inpatient psychiatric unit on the Test of Memory Malingering (TOMM) (aged 5–12; n = 96) and Automatized Sequences Task (...
Midodrine As A Bridge To Enable Use of Life Enhancing Therapies In Chronic Heart Failure

Introduction The pathophysiology of heart failure (HF) is characterized by hemodynamic, neurohormonal and autonomic perturbations. Alterations in receptor activation from this autonomic imbalance may have profound effects on cardiac function and structure. The optimal counteraction of the excessive sympathetic activity is still unclear. An excessive blockade of the sympathetic nervous system may result in adverse outcomes. Evidence from preclinical and human studies reveals that α1-adrenergic receptors mediate adaptive and protective effects in the heart. Midodrine is an α1 receptor agonist exerting its actions via activation of the alpha-adrenergic receptors of the arteriolar and venous vasculature, producing an increase in vascular tone and elevation of blood pressure without stimulating cardiac beta-adrenergic receptors. Hypothesis Use of midodrine to improve autonomic dysfunction and SBP, thus enabling optimization of life saving medications, has not been evaluated adequately. Methods The goal of the Cardiorenal center is to reduce 30-day hHF, 90-day hHF, optimize GDMT, improve QOL, prevent CKD progression, and enhance survival. A comprehensive, multidisciplinary, nurse-directed, physician guided heart failure management program including those with CKD was started in 2017. The program of intensive face to face weekly or bimonthly encounters demonstrated fewer rehospitalizations and improved QOL. The multicomponent program consists of the INSPIRE HF framework: 1) Identify individualized priorities and nature of multimorbidity, 2) Nutrition intervention, 3) Stabilize fluid status 4) Psychosocial motivational empowerment, 5) Initiate GDMT 6) Revisit comorbidities with biomarker assessments and 7) Education and exercise programs.. A total of 162 patients discharged from the hospital enrolled within a week at the clinic were followed for 30 months on a weekly basis. Sixty patients were identified as having autonomic dysfunction with low SBP Results A total of 60 patients (Men 67 %, F 33 %) were started on midodrine. Mean midodrine dose was 20.7 mg a day .Over a period of 6 weeks, 75% of patients were able to be initiated on beta blockers (p=0.04); 50 % on ARNI (p=0.08) and 33 % on MRA (p Conclusion Cardio-selective α1-AR activation with low doses of agonists such as midodrine appears to be feasible, safe and enables GDMT utilization in patients with autonomic dysfunction and hypotension. Further randomized clinical trial may be beneficial in understanding the role of alpha agonists in patients with heart failure.
A Coherence- Based Technique to Separate and Quantify Sources of Image Degradation in vivo with Application to Transcranial Imaging

Thermal noise and acoustic clutter both impede robust transcranial ultrasound imaging, leading to difficulties in clinical translation. Currently it is not known which one is a more significant contributor to image degradation because there is no good way to separately measure their contributions in vivo. In this work we derive and validate a coherence-based approach for quantifying the individual contributions of thermal noise and acoustic clutter to image degradation and apply it to in vivo transcranial imaging of five subjects.