cssi/SciSciGPT-SciSciNet huggingface dataset:
Design and implementation of population-based specialty care programs.

Purpose The development, implementation, and scaling of 3 population-based specialty care programs in a large integrated healthcare system are reviewed, and the role of clinical pharmacy services in ensuring safe, effective, and affordable care is highlighted. Summary The Kaiser Permanente (KP) integrated healthcare delivery model allows for rapid development and expansion of innovative population management programs involving pharmacy services. Clinical pharmacists have assumed integral roles in improving the safety and effectiveness of high-complexity, high-cost care for specialty populations. These roles require an appropriate practice scope and are supported by an advanced electronic health record with disease registries and electronic surveillance tools for care-gap identification. The 3 specialty population programs described were implemented to address variation or unrecognized gaps in care for at-risk specialty populations. The Home Phototherapy Program has leveraged internal partnerships with clinical pharmacists to improve access to cost-effective nonpharmacologic interventions for psoriasis and other skin disorders. The Multiple Sclerosis Care Program has incorporated clinical pharmacists into neurology care in order to apply clinical guidelines in a systematic manner. The KP SureNet program has used clinical pharmacists and data analytics to identify opportunities to prevent drug-related adverse outcomes and ensure timely follow-up. Conclusion Specialty care programs improve quality, cost outcomes, and the patient experience by appropriating resources to provide systematic and targeted care to high-risk patients. KP leverages an integration of people, processes, and technology to develop and scale population-based specialty care.
MnSOD and Cyclin B1 Coordinate a Mito-Checkpoint during Cell Cycle Response to Oxidative Stress

Communication between the nucleus and mitochondrion could coordinate many cellular processes. While the mechanisms regulating this communication are not completely understood, we hypothesize that cell cycle checkpoint proteins coordinate the cross-talk between nuclear and mitochondrial functions following oxidative stress. Human normal skin fibroblasts, representative of the G₂-phase, were irradiated with 6 Gy of ionizing radiation and assayed for cyclin B1 translocation, mitochondrial function, reactive oxygen species (ROS) levels, and cytotoxicity. In un-irradiated controls, cyclin B1 was found primarily in the nucleus of G₂-cells. However, following irradiation, cyclin B1 was excluded from the nucleus and translocated to the cytoplasm and mitochondria. These observations were confirmed further by performing transmission electron microscopy and cell fractionation assays. Cyclin B1 was absent in mitochondria isolated from un-irradiated G₂-cells and present in irradiated G₂-cells. Radiation-induced translocation of cyclin B1 from the nucleus to the mitochondrion preceded changes in the activities of mitochondrial proteins, that included decreases in the activities of aconitase and the mitochondrial antioxidant enzyme, manganese superoxide dismutase (MnSOD), and increases in complex II activity. Changes in the activities of mito-proteins were followed by an increase in dihydroethidium (DHE) oxidation (indicative of increased superoxide levels) and loss of the mitochondrial membrane potential, events that preceded the restart of the stalled cell cycle and subsequently the loss in cell viability. Comparable results were also observed in un-irradiated control cells overexpressing mitochondria-targeted cyclin B1. These results indicate that MnSOD and cyclin B1 coordinate a cross-talk between nuclear and mitochondrial functions, to regulate a mito-checkpoint during the cell cycle response to oxidative stress.
Telotristat Ethyl for Patients With Carcinoid Syndrome Associated With Chest Pain and Hypertension

To the Editor:Telotristat ethyl, a tryptophan hydroxylase inhibitor, recently received Food and Drug Administration approval on February 28, 2017 for patients with carcinoid syndrome diarrhea that is refractory to somatostatin analog (SSA) therapy.1 The key article that was published earlier this ye
Torque Ripple Minimization for a Permanent Magnet Synchronous Motor Using a Modified Quasi-Z-Source Inverter

This paper presents a torque ripple minimization method for a permanent magnet synchronous motor (PMSM) drive system that utilizes a modified quasi-Z-source (qZS) inverter. The proposed modified qZS network is designed by adding an extra switching device to the conventional qZS topology and provides a wider range of capabilities for inverter input voltage control, e.g., both step-up and step-down operations. It also allows for modification of the traditional switching sequence selection scheme when using the space vector modulation (SVM) for switching. The provided flexibilities are leveraged to develop a control system that minimizes the torque ripples during PMSM operation while satisfying conventional control objectives such as shaft speed control. The control system is comprised of an input voltage optimization subsystem with the goal of torque ripple minimization, which provides the reference for a cascaded modulated model predictive control subsystem for the modified qZS network control, and a motor side predictive control subsystem. The control system employs a new switching sequence selection scheme for SVM modulation to further reduce PMSM torque ripples. Experimental results are provided to validate the theoretical outcomes.
Pursuit of the Gene(s) by Industrial-Academic Collaboration

Over a century ago, Kraepelin recognized that heredity played a major role in dementia praecox, yet little advance has occurred since to define the mechanism or any candidate genes responsible (Kraepelin 1899; reviewed in DeLisi 1997 a). The reasons for this are unclear, but could stem from a lack of both Mendelian familial segregation and biological and clinical uniformity among patients characterized with this illness. The latter has led to countless nosological debates and genetic speculation as to whether one or more genes contribute to illness independently in separate families or together by epistatic interaction. None of this has facilitated progress or contributed to any advancement in knowledge about schizophrenia. No one gene has yet to be implicated, much less more than one.
FURTHER STUDIES ON CENTRALLY MEDIATED HEMODYNAMIC EFFECTS OF ANGIOTENSIN II IN ANESTHETIZED CATS

Publisher Summary This chapter presents the hemodynamic alterations during the infusion on angiotensin II into the cerebrolateral ventricles of cats anesthetized with alpha-chloralose. The effects of intraventricular infusion of angiotensin II on heart rate, marked pressor responses to intravenous infusion of angiotensin II are accompanied by significant reflex bradycardia, which is consistent. Absence of bradycardia following central pressor effects of angiotensin II is because of the fact that any increase in reflex vagal activity is compromised by an increase in cardiac sympathetic neuronal activity to the heart. Angiotensin interferes with cardiovascular reflexes at the level of the central nervous system. Centrally mediated increase in peripheral resistance is specific in that while there was a significant increase in the resistance in the mesenteric and renal vasculature, no such changes occurred in skeletal muscle in an experiment described in the chapter. Thus, central angiotensin produces sustained alterations in renal vascular dynamics.
Ensheathing cells utilize dynamic tiling of neuronal somas in development and injury as early as neuronal differentiation

Glial cell ensheathment of specific components of neuronal circuits is essential for nervous system function. Although ensheathment of axonal segments of differentiated neurons has been investigated, ensheathment of neuronal cell somas, especially during early development when neurons are extending processes and progenitor populations are expanding, is still largely unknown. To address this, we used time-lapse imaging in zebrafish during the initial formation of the dorsal root ganglia (DRG). Our results show that DRG neurons are ensheathed throughout their entire lifespan by a progenitor population. These ensheathing cells dynamically remodel during development to ensure axons can extend away from the neuronal cell soma into the CNS and out to the skin. As a population, ensheathing cells tile each DRG neuron to ensure neurons are tightly encased. In development and in experimental cell ablation paradigms, the oval shape of DRG neurons dynamically changes during partial unensheathment. During longer extended unensheathment neuronal soma shifting is observed. We further show the intimate relationship of these ensheathing cells with the neurons leads to immediate and choreographed responses to distal axonal damage to the neuron. We propose that the ensheathing cells dynamically contribute to the shape and position of neurons in the DRG by their remodeling activity during development and are primed to dynamically respond to injury of the neuron.
Magnetic domain wall skyrmions

It is well established that the spin-orbit interaction in heavy metal/ferromagnet heterostructures leads to a significant interfacial Dzyaloshinskii-Moriya interaction (DMI), which modifies the internal structure of magnetic domain walls (DWs) to favor N\'eel- over Bloch-type configurations. However, the impact of such a transition on the structure and stability of internal DW defects (e.g., vertical Bloch lines) needs to be explored. We present a combination of analytical and micromagnetic calculations to describe a type of topological excitation called a DW skyrmion characterized by a ${360}^{\ensuremath{\circ}}$ rotation of the internal magnetization in a Dzyaloshinskii DW. We further propose a method to identify DW skyrmions experimentally using Fresnel-mode Lorentz transmission electron microscopy; simulated images of DW skyrmions using this technique are presented based on the micromagnetic results.
Articulatory-acoustic relations in the production of alveolar and palatal lateral sounds in Brazilian Portuguese

Lateral approximant speech sounds are notoriously difficult to measure and describe due to their complex articulation and acoustics. This has prevented researchers from reaching a unifying description of the articulatory and acoustic characteristics of laterals. This paper examines articulatory and acoustic properties of Brazilian Portuguese alveolar and palatal lateral approximants (/l/ and /ʎ/) produced by six native speakers. The methodology for obtaining vocal tract area functions was based on three-dimensional/four-dimensional (3D/4D) ultrasound recordings and 3D digitized palatal impressions with simultaneously recorded audio signals. Area functions were used to calculate transfer function spectra, and predicted formant and anti-resonance frequencies were compared with the acoustic recordings. Mean absolute error in formant frequency prediction was 4% with a Pearson correlation of r = 0.987. Findings suggest anti-resonances from the interdental channels are less important than a prominent anti-resonance from the supralingual cavity but can become important in asymmetrical articulations. The use of 3D/4D ultrasound to study articulatory-acoustic relations is promising, but significant limitations remain and future work is needed to make better use of 3D/4D ultrasound data, e.g., by combining it with magnetic resonance imaging.
Expression of genes that control core fucosylation in hepatocellular carcinoma: Systematic review

Background Changes in N-linked glycosylation have been observed in the circulation of individuals with hepatocellular carcinoma. In particular, an elevation in the level of core fucosylation has been observed. However, the mechanisms through which core fucose is increased are not well understood. We hypothesized that a review of the literature and related bioinformatic review regarding six genes known to be involved in the attachment of core fucosylation, the synthesis of the fucosylation substrate guanosine diphosphate (GDP)-fucose, or the transport of the substrate into the Golgi might offer mechanistic insight into the regulation of core fucose levels. Aim To survey the literature to capture the involvement of genes regulating core N-linked fucosylation in hepatocellular carcinoma. Methods The PubMed biomedical literature database was searched for the association of hepatocellular carcinoma and each of the core fucose-related genes and their protein products. We also queried The Cancer Genome Atlas Liver hepatocellular carcinoma (LIHC) dataset for genetic, epigenetic and gene expression changes for the set of six genes using the tools at cBioportal. Results A total of 27 citations involving one or more of the core fucosylation-related genes (FPGT, FUK, FUT8, GMDS, SLC35C1, TSTA3) and hepatocellular carcinoma were identified. The same set of gene symbols was used to query the 371 patients with liver cancer in the LIHC dataset to identify the frequency of mRNA over or under expression, as well as non-synonymous mutations, copy number variation and methylation level. Although all six genes trended to more samples displaying over expression relative to under-expression, it was noted that a number of tumor samples had undergone amplification of the genes of the de novo synthesis pathway, GMDS (27 samples) and TSTA3 (78 samples). In contrast, the other four genes had undergone amplification in 2 or fewer samples. Conclusion Amplification of genes involved in the de novo pathway for generation of GDP-fucose, GMDS and TSTA3, likely contributes to the elevated core fucose observed in hepatocellular carcinoma.
Applying theory to characterize impediments to dissemination of community-facing family health history tools: a review of the literature

Uptake of community-facing family health history (FHH) tools to identify those at highest risk of disease and target prevention efforts has been consistently low. This review uses the diffusion of innovations (DOI) as a framework to organize the FHH evidence base and identify potential strategies to improve uptake of community-facing FHH tools. Methods for this literature review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We completed systematic searches in PubMed, Embase, and Web of Science databases for studies from 2009 to 2017 and hand searched bibliographies of relevant literature to identify additional articles. We abstracted and synthesized results, which were then organized by the DOI including the innovation–decision making process and characteristics of the innovation likely to influence diffusion (e.g., compatibility, relative advantage, complexity, trialability, observa/bility). Of the 290 unique articles identified, 65 were eligible for full-text review after title and abstract screening; a total of 27 were included in the final abstraction. Eleven unique tools were identified. The most commonly used tool was the Surgeon General’s My Family Health Portrait (n =9/27). Only six studies directly evaluated participant perceptions shown to be associated with tool uptake. Studies tended to focus on improving compatibility by customizing tools to the target population’s needs and use of educational interventions. Results from this review suggest the need to evaluate strategies to increase the pace of uptake of community-facing FHH tools. These include pragmatic trials that compare different approaches to engage and evaluate participant perceptions of the relative advantage and complexity of tools. Ancillary support strategies may include collaborations with community networks to facilitate use and implementation study designs for rigorous evaluation.
Third-order optical nonlinearity of tungsten disulfide atomic layer with resonant excitation

Abstract The third-order optical nonlinearity of tungsten disulfide atomic layer was characterized with open and closed Z-scan techniques with a resonant excitation near an exciton absorption peak using a pulsed laser which has a temporal pulse width of ~6 ns and a Gaussian spatial beam profile. The normalized transmittance traces with open and closed Z-scan for the WS2 atomic layers displayed positive nonlinear absorption and negative nonlinear refraction. The nonlinear absorption and nonlinear refraction coefficients of WS2 with the resonant excitation were estimated to be ~6.0 × 10−8 m/W and ~-3.8 x 10−15 m2/W.
Device-Based Modulation of Neurocircuits as a Therapeutic for Psychiatric Disorders.

Device-based neuromodulation of brain circuits is emerging as a promising new approach in the study and treatment of psychiatric disorders. This work presents recent advances in the development of ...
Assessment in Mastery Learning

The purpose of assessment in mastery learning is to promote learner improvement. Assessment is a key and indispensable feature of the mastery learning bundle. Mastery learning approaches are linked to the ability to make accurate decisions. Accurate decisions depend on reliable data that have been collected using instruments and methods linked to curriculum learning objectives. This chapter has six sections that reveal the ways that instruction and assessment are inseparable in mastery learning: (a) curriculum and instruction, (b) validity argument, (c) assessment context, (d) assessment measures, (e) data, and (f) decisions. Health professions educators must collect validity evidence regularly to support the validity argument that they are making accurate decisions about learners at each step of assessment design and implementation.
Risk assessment in oil and gas industry using simulation and bow-tie analysis

Risks have been in the forefront of supply chain management because of the exponential rise of natural disasters and the noticeable increase of supply chain disruptions. In oil and gas industry, risk events can be associated with consequences that might lead to fatalities and loss of millions of dollars. Therefore, effective risk management is vital for oil and gas companies. In this research, a framework that combines simulation and Bow-Tie risk modeling is proposed to study the disruption risks in oil and gas supply chains. The simulation model captures the flow of material and information and accounts for the dynamic interactions among the system components. Bow-Tie analysis is used to quantify the risks and their impact. A case study is provided to demonstrate the application of the proposed framework and to show its effectiveness as a decision-support tool that can be used in disruption risk management.
Low-temperature performance grade characterisation of asphalt binder using the dynamic shear rheometer

Currently, the bending beam rheometer (BBR) test is the standard method for evaluating the low-temperature performance grade (PG) of asphalt binders. Despite its use, there are limitations with the...
Litigation Risk and the Financial Reporting Credibility of Big Four vs. Non-Big Four Audits: Evidence from Anglo-American Countries

Prior research suggests that Big Four auditors provide higher quality audits in the US in order to protect the firm's brand name reputation and to avoid costly litigation. In this study, we examine whether the perceived higher quality of a Big Four audit is related to auditor litigation exposure or to reputation concerns. Specifically, we utilize an estimable proxy for financial reporting credibility - the ex ante cost of equity capital - to examine whether Big Four auditors are perceived as providing higher quality audits (relative to non-Big Four auditors) in the US, and in the less litigious (but economically similar) environments in other Anglo-American countries during the 1990-99 period. We find that a Big Four audit is associated with a lower ex ante cost of equity capital for auditees in the US but not in Australia, Canada, or the UK. Our findings suggest that it is litigation exposure rather than brand name reputation protection that drives perceived audit quality.
Prevalence of cannabis use among individuals with a history of cancer in the United States.

Background Patients with cancer have played a key role in advocating for legal access to cannabis, but little is known about links between cancer and cannabis use or cannabis-related beliefs. The authors used data from a national survey to study these relationships. Methods Nationally representative data collected by the National Survey on Drug Use and Health from 2015 to 2019 were acquired. Patterns of cannabis use and cancer history were examined and tested within age group subpopulations via domain analysis using survey weights. Results Data for 214,505 adults, including 4741 individuals (3.8%) with past (>1 year ago) cancer diagnosis and 1518 individuals (1.2%) with recent (≤1 year ago) cancer diagnosis, were examined. Cannabis use was less common in those with past (8.9%; 95% CI, 8.0%-9.8%) or recent (9.9%; 95% CI, 6.9%-11.1%) cancer diagnosis than in those without a history of cancer (15.9%; 95% CI, 15.7%-16.1%). However, when analyses were stratified by age group, those 18 to 34 years of age were more likely to report past cannabis use, and those 35 to 49 years of age were more likely to report past or recent cannabis use if they had a history of cancer. Younger patients felt that cannabis was more accessible and less risky if they had a history of cancer. Conclusions Patients with cancer were less likely to report cannabis use, but there were different cannabis perceptions and use patterns by age. Age should be considered in studies of cannabis and cancer, and policy initiatives may be needed to aid provision of quality information on cannabis risk to those with cancer. Lay summary Cannabis (marijuana) use is increasing in the United States, but we do not have much information on the relationship between cannabis use and cancer. We studied information from a representative group of people and found that younger patients generally reported more past and/or recent cannabis use if they had been diagnosed with cancer whereas older individuals did not. Beliefs about cannabis risk and accessibility differed by age. Clinical trials to study cannabis should account for patient age, and accurate information about cannabis should be provided to help patients with cancer make decisions about cannabis use.
Grid Integration of Renewable Energy

This chapter presents the analysis of grid integration of renewable energy and discusses the equipment needed for successful grid integration of RE. The communication and control processes are also be discussed, along with a brief overview of grid modernization using renewables. The chapter ends with a case study.
Redundant Actuators without Direct Communication for Reactor Control Rod Positioning

In the design of nuclear reactor systems, reliability is always a top consideration. Their main control method is the movement of “control rods” which inhibit the rate of reaction. Various gravity-based fail-safe methods are available during the failure of an actuator, but even safe failures limit reactor capability. This is especially important for mobile platforms like submarines and aircraft carriers where it may be months before maintenance can be performed. By introducing a redundant system and adding features like hot-swapping, overall system reliability is improved. This paper proposes a design for supporting reactor control rods utilizing three independently powered and controlled linear motors. By utilizing a three motor design, the system becomes resilient to two points of motors failing off, or a single point of failure should a motor fail on or become corrupted in some way. In addition, there is no central computer, failure detection logic, or direct communication between these motors, which makes the system simpler and avoids single points of failure. Each motor acts independently and if one has a failure, the other two will overpower it.
Prevalence of Vector-Borne Pathogens in Reproductive and Non-Reproductive Tissue Samples from Free-Roaming Domestic Cats in the South Atlantic USA.

Reservoir to multiple species of zoonotic pathogens, free-roaming cats (FRCs) interact with domestic and wild animals, vectors, and humans. To assess the potential for feline vector-borne pathogens to be vertically transmitted, this study surveyed ear tip and reproductive tissues of FRCs from two locations in the South Atlantic United States for Anaplasma, Bartonella, Ehrlichia, hemotropic Mycoplasma, and Rickettsia species. We collected ovary (n = 72), uterus (n = 54), testicle (n = 74), and ear tip (n = 73) tissue from 73 cats, and fetal (n = 20) and placental (n = 19) tissue from 11 queens. Pathogen DNA was amplified utilizing qPCR, confirmed by sequencing. Cats were more frequently Bartonella henselae positive on reproductive tissues (19%, 14/73) than ear tip (5%, 4/73; p = 0.02). B. henselae was amplified from fetus (20%, 4/20) and placenta samples (11%, 2/19). Bartonella spp. infection was more common in cats from North Carolina (76%, 26/34) than Virginia (13%, 5/39; p < 0.0001). Fourteen percent (10/73) of both ear tip and reproductive tissues were positive for hemotropic Mycoplasma spp. Anaplasma, Ehrlichia, and Rickettsia spp. DNA was not amplified from any cat/tissue. These findings suggest that B. henselae preferentially infected cats’ reproductive tissue and reinforces the importance of investigating the potential for B. henselae vertical transmission or induction of reproductive failure.
150 Targeted delivery of a PD-L1-blocking scFv by CAR-NK cells shows potential as a new approach to immunotherapy for glioblastoma

Background Despite advances in treatment, glioblastoma (GBM) remains an incurable primary brain tumor with a median survival of only 15 months, highlighting the need for new therapeutic approaches. Natural killer (NK) cells, innate cytotoxic effectors, are showing potential for cancer immunotherapy including GBM. Even though GBM tumors are infiltrated by NK cells.1 However, their antitumor activities are impaired by the immunosuppressive tumor microenvironment (TME) via various mechanisms, including adenosine-mediated downregulation of NKG2D.2 Therefore, it is critical to understand more about how the TME in GBM modulates the NK cell-mediated immunity so that we can develop novel NK cell-based therapies specifically for GBM. Methods We isolated human peripheral blood NK cells from healthy volunteer donors. U87MG and GBM43 were used as GBM targets. We co-cultured NK cells with GBM cells and measured the PD-L1 expression on the NK cells. We built a transwell co-culture system to evaluate the crosstalk between NK and GBM cells on the PD-L1 expression on GBM target cells. We then generated gene-modified NK cells expressing an NKG2D.CAR which secretes anti-PD-L1 scFv locally in the TME. These NK cells are being evaluated for their efficacy against GBM both in vitro and in vivo. Results We have found that GBM target cells can upregulate PD-L1 expression on NK cells (figure 1A). And induced PD-L1+ NK cells present better in vitro anti-GBM activity, including higher killing, degranulation and IFN-γ release (figure 1B). We have revealed that the expression of PD-L1 on GBM cells gets further boosted after crosstalk with NK cells, which is dependent on the induced IFN-γ release (figure 1C). Accordingly, we have designed and synthesized a multifunctional CAR construct that enables NK cells to express a secretable PD-L1-blocking scFv and a CAR redirected against ligands for NKG2D (figure 1D). Conclusions After direct contact with GBM cells, the increased population of PD-L1+ NK cells with superior cytolytic functions have been found for the first time. Also, NK cells co-cultured with GBM cells can further trigger PD-L1 upregulation on GBM cells. Stimulated by these results, we have been generating NK cells that can, at once, secrete the PD-L1-blocking scFv to target PD-L1 both expressed on NK and GBM cells, and express the NKG2D.CAR to specifically target its ligands on GBM cells. We are currently testing the in vitro and in vivo therapeutic efficacy of these engineered NK cells, which we believe could be used as a promsing immunotherapy for GBM. References Wang J, Matosevic S. NT5E/CD73 as correlative factor of patient survival and natural killer cell infiltration in glioblastoma. J Clin Med 2019;8(10):1526. Wang J, Lupo KB, Chambers AM, Matosevic S. Purinergic targeting enhances immunotherapy of CD73+ solid tumors with piggyBac-engineered chimeric antigen receptor natural killer cells. J Immunother Cancer 2018;6(1):136.
A Qualitative Analysis of Provider Barriers and Solutions to HIV Testing for Substance Users in a Small, Largely Rural Southern State

Testing is an important strategy for reducing the spread of HIV for several reasons. First, the CDC estimates that about 20% of persons with HIV in the U.S. do not know they have it so may continue to unknowingly infect others.1-3 An estimated 50% of new HIV infections are transmitted by the 20% of persons who do not know they have HIV.2,3 Second, persons who are unaware of having the disease cannot benefit from antiretroviral treatment. Third, persons who are aware of being infected are less likely to engage in HIV risk behaviors than those who are not aware.2,3 Despite the many reasons testing can be beneficial, testing rates remain low; in fact, only 55% of adults in U.S. have ever been tested,4 and the reasons for non-testing remain unclear. Integrating HIV testing programs into substance use treatment is a promising avenue to help increase access to HIV testing services for rural drug users.5-7 Yet as recently as 2009, only 36% of urban and 11% of rural outpatient substance use treatment facilities in the U.S. provided HIV testing.8 Insufficient resources and reimbursement, complex funding requirements, and differences in program philosophy or treatment paradigm are some of the barriers to incorporating routine screening for HIV into substance abuse treatment programs that have been identified in other studies.9-19 However, we do not fully understand the barriers that rural substance use treatment providers and system administrators perceive to integrating HIV testing into their programs. Existing research sheds little light on the crucially important contextual and specific processes that may inhibit or facilitate integration of HIV testing with community substance abuse treatment, especially in the rural South, where HIV is spreading rapidly.20,21 The primary purpose of this qualitative study was to identify barriers to HIV testing for substance users as described by substance use treatment and HIV testing service administrators and providers in Arkansas.
Current problems in deaths of persons under 20 years of age as evidenced by a study of the situation in the past decade in New York City

In the past 10 years mortality rates for persons under 20 have declined less rapidly than in that of the previous decades. Nevertheless, the application of new and well recognized procedures in the prevention of deaths due to pneumonia, influenza, appendicitis, diarrhea and contagious diseases, and tuberculosis have led to striking reductions in deaths due to these causes. Because of these reductions, other causes of death have assumed new importance. Thus, in children over one year of age accidents are today the leading cause of death. Heart disease, tuberculosis and cancer claim a high percentage among those from 10 to 20, while contagious and respiratory diseases are still important in children under 10. In infants, the deaths occurring before, at or near birth are of chief importance, with those associated with premature birth assuming an importance that demands active and immediate attention. Despite the gains made, deaths associated with childbirth (i.e., fetal and neonatal deaths) stand second today in claiming lives of all ages in New York City. Only heart disease has a larger mortality. The time has come for physicians to take cognizance of these facts and to see that all mothers and babies get the kind of care which good pediatricians and obstetricians know can be given. In addition, there is a pressing need for an intensified research program to the end that deaths in infancy and those due to accidents and heart disease can more effectively be prevented.
DNase I Digestion of Isolated Nulcei for Genome-Wide Mapping of DNase Hypersensitivity Sites in Chromatin

DNase I hypersensitivity (DHS) analysis is a powerful method to analyze chromatin structure and identify genomic regulatory elements. Integration of a high throughput detection method into DHS analysis makes genome-wide mapping of DHS sites possible at a reasonable cost. Here we describe methods for DHS analysis carried out with mouse liver nuclei, involving DNase I digestion followed by isolation of DNase I-released DNA fragments suitable for high throughput, next generation DNA sequencing (DNase-seq). A real-time PCR-based assay used to optimize DNase I digestion conditions is also described.
Autosomal Dominant familial erythrocytosis due to autonomous erythropoietin production

A family is described in which four members spanning three consecutive generations have erythrocytosis associated with a normal hemoglobin oxygen affinity. When bone marrow from one affected family member was cultured in vitro, erythroid colonies formed only when erythropoietin was added to the culture. Serum erythropoietin, measured by radioimmunoassay, was significantly elevated above normal in each of the affected family members. Bioassayable erythropoietin was detected in the urine of two of the three affected family members. In two of the affected family members, erythropoietin was measured in serum by radioimmunoassay and in urine by bioassay before and for 4 days following an isovolemic phlebotomy, which reduced the red cell mass by 20%. Neither serum nor urinary erythropoietin levels changed following phlebotomy. The erythrocytosis in this family appears to be secondary to inappropriately increased erythropoietin production unassociated with a decrease in the blood oxygen-carrying capacity. This is the first instance in which autonomous erythropoietin production appears to be inherited on an autosomal dominant basis.
Digital Video Quality Assessment Algorithms

In this chapter we first describe some HVS-based approaches which try to model the visual processing stream described above, since these approaches were originally used to predict visual quality. We then describe recently proposed structural and information-theoretic approaches and feature-based approaches which are commonly used. Further, we describe recent motion-modeling based approaches, and detail performance evaluation and validation techniques for VQA algorithms. Finally, we touch upon some possible future directions for research on VQA and conclude the chapter.
Unenhanced Ramen Spectroscopy of CO Adsorbed on Nickel Particles

Our understanding of chemical bonding at surfaces has increased by using a variety of experimental techniques to study well-defined surfaces in high vacuum where surface impurities can be controlled. Studies of adsorption on these surfaces provide model systems that can be studied systematically to determine the evolution of molecular surface structure and bonding as environmental parameters are changed. A technique recently used to study chemical bonding on well-defined surfaces is normal unenhanced Raman spectroscopy (NURS). This technique was developed at the University of Kentucky, and it was used to obtain Raman spectra of molecules of low polarizability adsorbed on the non-enhancing metal surfaces Ni (111) and Ni(100). Raman signals from these adsorbates could be detected from one reflection off the metal surface. The technique is non-destructive of the surface species and low laser power (100–300 mW at the sample surface) is used.
A beta-blocker, propranolol, decreases the efficacy from enzyme replacement therapy in Pompe disease

Abstract Enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) fails to completely reverse muscle weakness in Pompe disease. β2-agonists enhanced ERT by increasing receptor-mediated uptake of rhGAA in skeletal muscles. Purpose To test the hypothesis that a β-blocker might reduce the efficacy of ERT, because the action of β-blockers opposes those of β2-agonists. Methods Mice with Pompe disease were treated with propranolol (a β-blocker) or clenbuterol in combination with ERT, or with ERT alone. Results Propranolol-treated mice had decreased weight gain (p Conclusion Propranolol, a commonly prescribed β-blocker, reduced weight, increased left ventricular mass and decreased glycogen clearance in skeletal muscle following ERT. β-Blockers might therefore decrease the efficacy from ERT in patients with Pompe disease.
PARP, Na+/H+-exchanger-1, and early diabetes-induced retinal changes

Purpose To evaluate the roles for PARP and Na+/H+-exchanger-1 (NHE-1) in early diabetes-induced changes in the retina and retinal capillary cells Methods Control (C) and STZ-diabetic (D) rats were treated with/without the PARP inhibitors, 1,5-isoquinolinediol (ISO, 3 mgkg-1d-1 i.p.) or 10-(4-Methyl-piperazin-1-ylmethyl)-2H-7-oxa-1,2-diaza-benzo[de]-anthracen-3-one (GPI 15427, 30 mgkg-1d-1), for 10 wks after 2 wks without treatment. Apoptosis was evaluated in flat-mounted retinas by TUNEL assay, and nitrotyrosine (NT), poly(ADP-ribose) (PAR), GFAP, BiP/GRP78 and GRP94 expressions by immunohistochemistry and Western blot analyses. Primary bovine retinal pericytes and endothelial cells were cultured with/without 0.6 mM palmitate, or in 5 mM or 30 mM glucose. Apoptosis was assessed by TUNEL and caspase-3 assays, superoxide production by ethidium fluorescence, and NT and PAR by immunocytochemistry. Results In the PARP study, the number of TUNEL-positive nuclei was increased ~4-fold in D, and this increase was prevented in D+ISO and D+GPI 15427. PARP inhibitors counteracted oxidative-nitrosative and endoplasmic reticulum stresses, and glial activation. Palmitate dose dependently increased superoxide production in cultured retinal cells. GPI 15427, 20 microM, prevented FFA-induced increase in the rate of apoptosis, and alleviated NT and PAR accumulation in both pericytes and endothelial cells. In the NHE-1 study, the specific NHE-1 inhibitor cariporide (10 microM) prevented high glucose-induced apoptosis, and alleviated oxidative-nitrosative stress and PAR accumulation in bovine retinal pericytes. In vivo studies in the STZ-diabetic rat model are in progress. Conclusion PARP and NHE-1 play an important role in early diabetes-induced changes in retina and retinal capillary cells.
Preferential Use of Central Metabolism In Vivo Reveals a Nutritional Basis for Polymicrobial Infection

The human genitourinary tract is a common anatomical niche for polymicrobial infection and a leading site for the development of bacteremia and sepsis. Most uncomplicated, community-acquired urinary tract infections (UTI) are caused by Escherichia coli, while another bacterium, Proteus mirabilis, is more often associated with complicated UTI. Here, we report that uropathogenic E. coli and P. mirabilis have divergent requirements for specific central pathways in vivo despite colonizing and occupying the same host environment. Using mutants of specific central metabolism enzymes, we determined glycolysis mutants lacking pgi, tpiA, pfkA, or pykA all have fitness defects in vivo for P. mirabilis but do not affect colonization of E. coli during UTI. Similarly, the oxidative pentose phosphate pathway is required only for P. mirabilis in vivo. In contrast, gluconeogenesis is required only for E. coli fitness in vivo. The remarkable difference in central pathway utilization between E. coli and P. mirabilis during experimental UTI was also observed for TCA cycle mutants in sdhB, fumC, and frdA. The distinct in vivo requirements between these pathogens suggest E. coli and P. mirabilis are not direct competitors within host urinary tract nutritional niche. In support of this, we found that co-infection with E. coli and P. mirabilis wild-type strains enhanced bacterial colonization and persistence of both pathogens during UTI. Our results reveal that complementary utilization of central carbon metabolism facilitates polymicrobial disease and suggests microbial activity in vivo alters the host urinary tract nutritional niche.
Effects of ethanol diets on cholesterol content and phospholipid acyl composition of rat hepatocytes

Chronic treatment of adult male rats with ethanol liquid diets resulted in alterations in phospholipid and cholesterol contents as well as the acyl composition of phosphatidylethanolamine (PE), phosphatidylinositol (PI)-phosphatidylserine (PS) mixture, and phosphatidylcholine (PC) of isolated hepatocytes. The influence of ethanol on these lipids was largely dependent on the proportion of dietary fat. Phospholipid and total cholesterol contents were elevated 23 and 27%, respectively, by ethanol when offered in a low-fat diet (5% corn oil). Only the percentage of arachidonic acid from PI-PS was significantly reduced in the low-fat ethanol group. Exposure to a high-fat (34% corn oil) diet in the presence of ethanol for 4–5 weeks resulted in a significant decrease in arachidonate/linoleate ratios of hepatic PE, PS-PI and PC, while total phospholipid content remained constant. In the high-fat, ethanol-treated group, hepatic cholesterol content was increased 2-fold. These results suggest that the level of dietary fat plays an important role in determining the effects of chronic ethanol consumption on hepatic cholesterol content and phospholipid acyl composition.
Fate in humans of the plasticizer, di 2 ethylhexyl phthalate, arising from transfusion of platelets stored in vinyl plastic bags

Platelet concentrates were shown to contain 18 to 38 mg/dl of a phthalate plasticizer (DEHP) which arose by migration from the vinyl plastic packs in which the platelets were prepared and stored. Transfusion of these platelets into six adult patients with leukemia resulted in peak blood plasma levels of DEHP ranging from 0.34 to 0.83 mg/dl (approximately 0.02 mg/dl plasma per mg DEHP administered per square meter of surface area). The blood levels fell monoexponentially with a mean rate of 2.83 per cent per minute and a half-life of 28.0 minutes. Urine was assayed by a method that would measure unchanged DEHP as well as all phthalic acid-containing metabolites. In two patients, at most 60 and 90 per cent of the infused dose, respectively, was excreted in the urine collected for 24 hours posttransfusion. These estimates, however, could be high due to the simultaneous excretion of DEHP remaining from previous transfusions or arising from uncontrolled environmental exposures.
Temporal summation related to the nature of the proximal stimulus for the warmth sense

Magnitude estimations of the warmth aroused by radiant stimulation of the forehead showed that warmth obeys the psychophysical power law when the’ duration of the stimulus is relatively long (3 or 6 sec). When duration is short (0.25, 0.5. or 1 sec), however, warmth grows as a more complex function of irradiation. The family of psychophysical functions measured for the various durations can be used to generate the rules by which radiant intensity and duration trade to preserve constant warmth. These rules vary systematically from complete temporal summation (i.e., complete reciprocity) near threshold to less and less complete summation as warmth level increases. When, however, the stimulus is expressed as an equivalent change of temperature in the skin, there is no summation, only adaptation. It can be shown that temporal summation observed psychophysically must result from the heat-transfer properties of skin tissue.
A systems analysis of the problem of road casualties in the United States

The problem of road casualties in the United States is analyzed from a systems viewpoint. Road accident data are reviewed, an accident causation model is proposed and accident causation factors are described in terms of human, vehicular and environmental contributions. A comprehensive program of safety-oriented research is outlined and difficulties in setting research priorities are discussed.
PRODUCTION OF NUCLEON ISOBARS BY 7.1 Gev/c PROTONS

We have measured the missing mass spectrum of nucleon isobars produced in the reaction p+p→ +p by 7.1 GeV/c protons incident on a liquid-hydrogen target. Scintillation counters detected the recoil protons after momentum analysis. Cross-sections were obtained for production of isobars of mass 1238, 1512 and 1688 MeV at momentum transfers of 0.09, 0.15, 0.24, 0.33, and about 5 (GeV)2. At low momentum transfers, the spectrum has additional structure at a mass of about 1430 MeV. TheT=1/2 isobar production cross-sections at |t|=5 (GeV)2 are comparable with the elastic scattering cross-section.
Evaluation of Potential Safety Modifications by Review of Accident Reports

Analysis of accident data for consumer products can be used to identify accident modes and to aid in decisions about the feasibility of safety interventions for reducing risk. Decisions based upon a large accident data set, rather than upon a single accident, are much more likely to address important problems and to avoid creating negative consequences (e.g., increases in other kinds of accidents, loss in product utility). This paper describes the application of accident report analysis to a proposed safety intervention for all-terrain vehicles (ATVs). In order to evaluate the suggested use of conspicuity flags as standard equipment on all ATVs to prevent collision-related accidents, we reviewed 287 operating-ATV-associated “In-Depth Investigations” (conducted by the Consumer Product Safety Commission for ATV-associated injuries reported by the National Electronic Injury Surveillance System during a 2.5 month period in 1985). It was found that flags could have influenced only a very small portion of ATV i...
Descartes' Theory of Ideas

David Clemenson: Descartes' Theory of Ideas, London and New York: Continuum International Publishing Group, 2007. xi + 162 pp. £60.00. ISBN 0-8264-87730-4 On an initial reading, Descartes' theory o...
In vivo uptake of wheat germ agglutinin-horseradish peroxidase conjugates into neuronal gerl and lysosomes

Abstract In published studies we have shown that lectins and cholera toxin bind at 4°C on surfaces in cultured neurons and neuroblastoma cells and, after incubations of labeled cells at 37°C, undergo endocytosis (adsorptive endocytosis) into GERL (Golgi-endoplasmic reticulum-lysosome). In this study conjugates of wheat germ agglutinin (WGA) with horseradish peroxidase (HRP), or free HRP, were injected in rat submandibular glands or over superior cervical ganglia, and their uptake was examined by electron microscopic cytochemistry for HRP. Lysosomes and vesicles and cisternae of GERL were involved in the uptake of WGA-HRP injected into the submandibular gland or into the superior cervical ganglion; HRP, administered in a similar fashion, but in amounts 10–15-fold higher than WGA-HRP, underwent endocytosis into lysosomes. The present in vivo studies, as well as previous in vitro studies, indicate that neuronal GERL is part of the endocytic pathway of various ligands which bind on corresponding surface (plasma membrane) ‘receptors’.
Far infrared spectrum and conformational potential function of n-butane

Abstract The far i.r. spectrum of gaseous n -butane obtained at 0.06 cm −1 resolution is reported between 80 and 230 cm −1 . Several transitions for the asymmetric torsion of the trans conformer have been identified. Utilizing these data along with the previously reported asymmetric torsional transitions of the gauche conformer from Raman spectroscopic data, the potential function for the conformational change has been obtained. The determined potential parameters were found to be: V 1 = 181, V 2 = 148, V 3 = 1154 and V 6 = −33 cm −1 . The s - trans to gauche , gauche to gauche , and gauche to s - trans barriers in cm −1 were found to be: 1315 (3.76 kcal/mol), 1090 (3.12 kcal/mol) and 1070 (3.06 kcal/mol), respectively. The potential functions obtained from these spectroscopic data are consistent with the trans to gauche energy difference, but not with the high trans / cis potential barrier suggested by recent ab initio calculations.