cssi/SciSciGPT-SciSciNet huggingface dataset:
Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia

Tyrosine-kinase inhibitor (TKI) therapy for human cancers is not curative, and relapse occurs owing to the continued presence of tumor cells, referred to as minimal residual disease (MRD). The survival of MRD stem or progenitor cells in the absence of oncogenic kinase signaling, a phenomenon referred to as intrinsic resistance, depends on diverse growth factors. Here we report that oncogenic kinase and growth-factor signaling converge to induce the expression of the signaling proteins FBJ osteosarcoma oncogene (c-FOS, encoded by Fos) and dual-specificity phosphatase 1 (DUSP1). Genetic deletion of Fos and Dusp1 suppressed tumor growth in a BCR-ABL fusion protein kinase-induced mouse model of chronic myeloid leukemia (CML). Pharmacological inhibition of c-FOS, DUSP1 and BCR-ABL eradicated MRD in multiple in vivo models, as well as in mice xenotransplanted with patient-derived primary CML cells. Growth-factor signaling also conferred TKI resistance and induced FOS and DUSP1 expression in tumor cells modeling other types of kinase-driven leukemias. Our data demonstrate that c-FOS and DUSP1 expression levels determine the threshold of TKI efficacy, such that growth-factor-induced expression of c-FOS and DUSP1 confers intrinsic resistance to TKI therapy in a wide-ranging set of leukemias, and might represent a unifying Achilles' heel of kinase-driven cancers.
Systematic Review of Veterans' Coping Strategies: How Can Rural Veterans Improve Their Quality of Life?

This systematic review examines the empirical literature on an emerging body of coping strategies (CS), both civilian readjustment and health-risk related, experienced by United States military veterans exposed to combat stress and other military lifestyle stressors. Studies that met inclusion criteria were selected among quantitative, qualitative, and mixed-methods studies published in peer-reviewed journals; the gray literature and white papers were considered as well. Population, Intervention, Comparison, and Outcome (PICO) criteria and Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) were applied to all studies. Seventeen reports meeting a priori inclusion criteria were extracted from 107 studies accessed through 9 electronic databases. Data were synthesized to investigate two research questions: What coping strategies do veterans use to deal with past military experience(s)? What are the health-risk coping strategies that veterans employ to adjust to past military life? There were five types of coping strategies (CS) that occurred most frequently: cognitive, religiosity/spirituality methods, drug and alcohol sedation, avoidance, and behavioral approaches. Veterans learn multiple coping strategies and techniques for overcoming and adapting to the demands of war during their military service. However, some behavioral coping strategies are associated with negative health-risks and some may not be as effective in the civilian world as they once were during active duty. Thus, these findings may assist social workers in collaborating with rurally located veterans in selecting optimal strategies to protect their health and advance their post-military service life goals.
Cell Lineage and Cell Interactions in the Determination of Developmental Cell Fates

A central problem of developmental biology is to understand the sequence of cellular and molecular events which transforms a fertilized egg into a mature organism composed of a precise spatial array of distinct cell types. A significant consideration in addressing this problem is the fact that each of the many cells in the mature organism is descended from the egg via a lengthy sequence of progenitor cell divisions. In order to reduce the number of variables associated with the problem, many embryologists have concentrated on invertebrates such as nematodes, annelids, molluscs and tunicates in which the sequence of embryonic cell divisions is highly stereotyped. Because of this regularity it is possible to portray the development of the entire organism by the genealogical relationship between the composite cells, and to identify individual cells on the basis of their lineage (Zur Strassen, 1896; Conklin, 1905; Schleip, 1936).
Truancy offenders in the juvenile justice system: A multicohort study

Truancy remains a persistent concern, with serious consequences for the individual, family, and society, as truancy is often linked to academic failure, disengagement with school, school dropout, a...
Vascular malformations: Part I

Cutaneous vascular malformations are rare disorders representing errors in vascular development. These lesions occur much less commonly but are often confused with the common infantile hemangioma. It is important to properly diagnose vascular malformations because of their distinct differences in morbidity, prognosis and treatment. Vascular malformations may be associated with underlying disease or systemic anomalies. Several of these syndromes are well defined and can often be distinguished on the basis of the flow characteristics of the associated vascular malformation. Learning objective At the completion of this learning activity, participants should have a better understanding of the different types of cutaneous vascular malformations. Because of the importance of proper diagnosis of these lesions, participants should also be better able to direct correct management and treatment.
Chemoreceptor Cells in Aquatic Invertebrates: Peripheral Mechanisms of Chemical Signal Processing in Decapod Crustaceans

The sensory capabilities of any animal are determined by a sequential set of physical and biological filters that regulate which environmental disturbances will stimulate the receptive surface of the animal. The environment itself is the first filter as it transmits physical or chemical disturbances from one or another source. The animal’s sense organs contain additional physical filters that select—each with its own degree of specificity—which part of the disturbances will have best access to the receptor membrane. Subsequent filtering occurs at the level of receptor cells and at each next level of the CNS. Environmental disturbances that alter the activity of receptor cells are called stimuli: they include disturbances that trigger molecular mechanisms, such as adaptation in the cell without necessarily causing it to fire nerve impulses or other means of information coding. Subsequent interneuronal steps of information processing are all based on neural signals that code certain aspects of the original stimuli.
Dual Regulation of Glutamatergic Transmission and Cognition by Stress in Prefrontal Cortex

Corticosterone, the major stress hormone, serves as a key controller for neuronal responses that underlie behavioral adaptation, as well as maladaptive changes that lead to cognitive and emotional disturbances in stress-related mental disorders. The molecular and cellular mechanisms underlying the complex actions of corticosteroid stress hormones are largely unknown. Here we demonstrate that acute versus chronic stress exerts opposite effects on glutamatergic transmission in prefrontal cortex (PFC), which leads to opposing effects on PFC-dependent cognitive functions. Acute stress induces synaptic potentiation by increasing surface delivery of N-methyl-D-aspartate (NMDA)-type and α-amino-3-hydroxy-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptor channels via glucocorticoid/serum- and glucocorticoid-inducible kinase (SGK)/Rab4 signaling, resulting in enhanced working memory performance. In contrast, repeated stress induces synaptic depression by increasing the ubiquitin/proteasome-mediated degradation of NMDA and AMPA receptor subunits, resulting in impaired recognition memory.
Evaluating the Harm Principle and the Best Interest of the Child: A Case Resolved Using Standard Microeconomics Principles

Johan Bester (2018) advocates for the best interest standard when making medical decisions for children. Bester’s defense of the best interest standard considers criticisms of, and insights from, h...
Intracranial Arteriovenous Malformations

Intracranial AVMs are complex lesions requiring multidisciplinary expertise for optimal patient outcomes. While the optimal treatment depends on AVM-specific factors such as rupture status, size, location within the brain, and the presence of deep venous drainage, the treating neurosurgeon must be able to synthesize the risks and benefits of multiple treatment options to best determine the safest treatment modality for each patient. In this chapter we present current review on best practices for the treatment of intracranial AVMs.
Supramolecular Gel as the Template for Catalysis, Inorganic Superstructure, and Pharmaceutical Crystallization

A supramolecular gel is a fascinating combination of flexibility and orderliness. While the supramolecular nature of crosslinking contributes towards the adaptivity and the reversibility of the system, orderliness at the molecular level amplifies the functional output and induces extraordinary selectivity into the system. Therefore, use of supramolecular gels as the soft template is an emerging area of research, which includes but not limited to catalysis of a chemical or a photochemical process, transcription of gel property to a substrate, or even controlling the nucleation of drug molecules. This review aims to highlight the template effect of supramolecular gels in the above-mentioned areas relevant to novel fundamental chemistry, technology, and healthcare.
Tools for enhancing resilience and addressing internalized heterosexism: bibliotherapy and cinematherapy in groupwork for individuals who come out as an adult

T his article shares the clinical application of bibliotherapy and cinematherapy as groupwork tools to build social support and to foster resilience among group members of LGBTQIA+ support groups for individuals coming out later in life. Coming out groups for LGBTQIA+ individuals, as well as specific tools and exercises to use within these groups remain under-researched. The importance of fostering resilience through groupwork for those leaving a heterocentric lifestyle is discussed, and suggested books, movies and discussion questions for groupwork are provided. Contra-indications for these exercises are also discussed
Effect of Shear on Modal Arrival Times

The sea bottom is generally modeled as a fluid for many of the shallow water acoustic propagation modeling applications. The inherent assumption is that the bottom does not support any shear wave propagation. This study explores the impact of this assumption on the dispersion behavior of acoustic normal modes. A sensitivity study is performed to investigate the effect of density, shear, and compressional wave speeds on modal dispersion. This study focuses on low-frequency (less than 100 Hz) and lower order modes (mode four and lower) in shallow water (70–90-m water depth). These modes and frequency bands are characterized by deeper penetration and larger depth averaging scales. This enabled the use of a simple half-space elastic model of the sea bottom for most of the analyses in this study. A depth-dependent bottom model was used to investigate the effect of a mud layer on modal dispersion. Sediment shear wave speeds were also estimated using broadband data from two shallow water experiments: Shelf Break Primer (1996) and Seabed Characterization Experiment (2017). The inversion results from these two experiments are compared and they are also compared with deep core data and prior inversions.
Controlling directional absorption with chiral exceptional surfaces

Significant efforts have been dedicated to engineering optical systems with predefined, excitation-dependent light absorption. An important concept along this line is that of exceptional points which allow for engineering directional light absorbing schemes. Current systems, however, do not lend themselves to easy design criterion or robust experimental realization. Here we demonstrate that an optical microring resonator coupled to a waveguide terminated with a mirror supports a chiral exceptional surface that can be used as a platform for tailoring directional light absorption in a straightforward fashion. We further demonstrate that this configuration can be used to implement a unidirectional coherent perfect absorber with controllable differential loss by tuning only a single parameter.
Sunitinib-associated hyperammonemic encephalopathy.

Abstract Sunitinib-associated hyperammonemic encephalopathy has not been previously reported in the emergency medicine literature. As newer treatments for cancer become more widespread and patients live longer, the emergence of previously unreported or rare adverse effects is expected to increase. Here we report the case of a 71-year-old woman with infiltrating ductal carcinoma of the breast with metastasis to the liver who developed hyperammonemic encephalopathy after taking sunitinib for 12 days. She presented to the emergency department (ED) with confusion and the initial workup revealed an elevated ammonia level (202 μmol/L; reference range, 11–51 μmol/L) without evidence of cirrhosis or portal hypertension. The patient was started on lactulose and admitted to the hospital, where her ammonia levels and mental status waxed and waned throughout her 12-day hospitalization. Further workup with magnetic resonance imaging and an electroencephalogram were negative. After 12 days, her ammonia level normalized and she was discharged without re-initiating Sunitinib. The patient was followed for three months post hospitalization without recurrence of symptoms. Patients on sunitinib should have their ammonia levels checked when presenting to the ED with altered mentation for early identification of hyperammonemic encephalopathy and its potential complications, such as seizures, brain edema, and death. Emergent management in the ED should include initiation of lactulose and consultation with the gastroenterology team.
Genomic Prediction of (Mal)Adaptation Across Current and Future Climatic Landscapes

Signals of local adaptation have been found in many plants and animals, highlighting the heterogeneity in the distribution of adaptive genetic variation throughout species ranges. In the coming dec...
A weighting system to build physical layer measurements maps by crowdsourcing data from smartphones

Mobile devices can sense different types of radio signals. For example, broadcast signals. These broadcasted signals allow the device to establish a connection to the access point broadcasting it. Moreover, mobile devices can record different physical layer measurements. These measurements are an indication of the service quality at the point they were collected. These measurements data can be aggregated to form physical layer measurement maps. These maps are useful for several applications such as location fixing, navigation, access control, and evaluating network coverage and performance. Crowdsourcing can be an efficient way to create such maps. However, users in a crowdsourcing application tend to have different devices with different capabilities, which might impact the overall accuracy of the generated maps. In this paper, we propose a method to build physical layer measurements maps by crowdsourcing physical layer measurements, GPS locations, from participating mobile devices. The proposed system gives different weights to each data point provided by the participating devices based on the data source’s trustworthiness. Our tests showed that the different models of mobile devices return GPS location with different location accuracies. Consequently, when building the physical layer measurements maps our algorithm assigns a higher weight to data points coming from devices with higher GPS location accuracy. This allows accommodating a wide range of mobile devices with different capabilities in crowdsourcing applications. An experiment and a simulation were performed to test the proposed method. The results showed improvement in crowdsourced map accuracy when the proposed method is implemented.
In memoriam: Marie Leonore ("Lennie") Farr, 6 September 1927-13 May 2014 First Woman President of MSA.

Dr. Marie L. Farr, known as Lennie, contributed to a systematic understanding of two major unrelated groups of organisms: slime molds and tropical fly speck and black mildew ascomycetes. Most of he...
Anesthetic Management for Thoracic Aortic Procedures

Surgical and anesthetic management for the repair of thoracic aorta pathology represents a significant clinical challenge and is associated with relatively high morbidity and mortality. Although open surgical correction of the thoracic aorta has traditionally been the gold standard for the management of a variety of thoracic aortic pathologies, newer hybrid or endovascular techniques have been developed in an effort to mitigate risk in patients with amenable anatomy. This chapter will focus on the anesthetic considerations for open surgical repair of aortic aneurysm and dissection. The anesthetic management of the endovascular and hybrid approach for repair of thoracic aortic pathology will be discussed elsewhere in this book.
HIV-1 Protease Inhibitors

Treatment of human immunodeficiency virus type 1 (HIV-1) infection with regimens that include protease inhibitors (PIs) has contributed to marked improvements in HIV-related disease progression and mortality. Five PIs are approved by the US Food and Drug Administration and have potent activity in vitro. PIs with 2 nucleoside analogue reverse transcriptase inhibitors have demonstrated prolonged suppression of HIV-1 replication in treated patients and improvements in disease progression and mortality. PIs combined with nonnucleoside reverse transcriptase inhibitors or other PIs produce marked antiretroviral effects. Although not all patients have prolonged responses to PIs, and salvage treatment has had mixed results for patients who have not responded to initial PI therapy or whose HIV RNA levels have relapsed during such therapy, newer PIs currently being developed hold promise. Most patients can successfully tolerate PI-including regimens; however, long-term side effects, such as body fat redistribution, insulin resistance, and increased serum lipids, are now being observed in some patients receiving PI-including therapy.
Teachers’ Knowledge of Fraction Magnitude

This article explores three attributes of teachers’ understanding of fraction magnitude: the accuracy and reasonableness of teachers’ estimations in response to fraction arithmetic tasks as well as the alignment of the estimation strategies they used with the concept of fraction magnitude. The data were collected from a national sample of mathematics teachers in grades 3–7 in which fraction concepts were taught (N = 603). The results indicated the teachers’ estimations were only partially accurate and reasonable, particularly when fraction division was involved. Furthermore, teachers’ credentials and the grade level at which they taught mathematics were significantly related to teachers’ understanding of fraction magnitude.
Increased Mortality Associated with Hypermagnesemia in Severe COVID-19 Illness

Abstract Background Although electrolyte abnormalities are common among patients with COVID-19, very little has been reported on magnesium homeostasis in these patients. Here we report the incidence of hypermagnesemia, and its association with outcomes among patients admitted with COVID-19. Methods We retrospectively identified all patients with a positive test result for SARS-CoV-2 who were admitted to a large quaternary care center in New York City in spring 2020. Details of the patients’ demographics and hospital course were obtained retrospectively from medical records. Patients were defined as having hypermagnesemia if their median magnesium over the course of their hospitalization was >2.4 mg/dl. Results A total of 1685 patients hospitalized with COVID-19 had their magnesium levels checked during their hospitalization, and were included in the final study cohort, among whom 355 (21%) had hypermagnesemia. Patients who were hypermagnesemic had a higher incidence of shock requiring pressors (35% vs 27%, P Conclusions In conclusion, we identified an association between hypermagnesemia among patients hospitalized with COVID-19 and increased mortality. Although the exact mechanism of this relationship remains unclear, hypermagnesemia potentially represents increased cell turnover and higher severity of illness, which is frequently associated with more severe forms of AKI.
DEMOCRACY, FREEDOM OF SPEECH, AND FEMINIST THEORY: A RESPONSE TO POST AND WEINSTEIN

1Their criticisms of these alternatives rest, however, on particular, flawed models of truth and autonomy. Feminist philosophers in both epistemology and moral/political theory have developed strong critiques of both the traditional, Cartesian model of truth and the traditional, liberal model of autonomy. These feminist critiques ground alternative approaches to truth and autonomy that are not subject to the criticisms raised by Post and Weinstein. Moreover, a feminist perspective reveals that Post and Weinstein’s democracy theories, while undoubtedly capturing a central concern of the First Amendment, also rest on a problematic model of autonomy. I will begin by responding to their criticisms of the truth and autonomy theories from the perspective of feminist epistemology and moral theory. I will then briefly outline the central difficulty with their democracy theory and the way in which it relies upon a flawed model of autonomy. Their theories require a division between realms of life in which autonomy must be assumed, which are defined as public discourse, and realms in which autonomy need not be recognized. But human experience does not divide in
Automation in an addiction treatment research clinic: Computerised contingency management, ecological momentary assessment and a protocol workflow system

Introduction and Aims. A challenge in treatment research is the necessity of adhering to protocol and regulatory strictures while maintaining flexibility to meet patients' treatment needs and to accommodate variations among protocols. Another challenge is the acquisition of large amounts of data in an occasionally hectic environment, along with the provision of seamless methods for exporting, mining and querying the data. Design and Methods. We have automated several major functions of our outpatient treatment research clinic for studies in drug abuse and dependence. Here we describe three such specialised applications: the Automated Contingency Management (ACM) system for the delivery of behavioural interventions, the transactional electronic diary (TED) system for the management of behavioural assessments and the Protocol Workflow System (PWS) for computerised workflow automation and guidance of each participant's daily clinic activities. These modules are integrated into our larger information system to enable data sharing in real time among authorised staff. Results. ACM and the TED have each permitted us to conduct research that was not previously possible. In addition, the time to data analysis at the end of each study is substantially shorter. With the implementation of the PWS, we have been able to manage a research clinic with an 80 patient capacity, having an annual average of 18 000 patient visits and 7300 urine collections with a research staff of five. Finally, automated data management has considerably enhanced our ability to monitor and summarise participant safety data for research oversight. Discussion and Conclusions. When developed in consultation with end users, automation in treatment research clinics can enable more efficient operations, better communication among staff and expansions in research methods. [Vahabzadeh M, Lin J-L, Mezghanni M, Epstein DH, Preston KL. Automation in an addiction treatment research clinic: Computerised contingency management, ecological momentary assessment and a protocol workflow system. Drug Alcohol Rev 2009;28:3–11]
The effect of smoking and oral contraceptives on the urinary excretion of epinephrine and norepinephrine.

Abstract Eight smokers and seven nonsmokers between the ages of 20 and 38 years were studied. None of these patients was pregnant. Three smokers and two nonsmokers were not taking oral contraceptives, as contrasted by three nonsmokers and four smokers taking oral contraceptives. Results approached statistical significance for urinary norepinephrine (p = 0.15) and epinephrine (p = 0.07) when the groups were compared. The values for nonsmoking/noncontraception tended to be low but, unexpectedly, the values for smoking/contraception also were low. When the smoking subjects (six of seven) stopped smoking there was a significant decline in norepinephrine (p = 0.02) and the epinephrine decline approached significance (p = 0.08). The study does not show any synergistic effect of oral contraceptives and smoking but demonstrates that the smoker can diminish stimulation of the adrenal gland (epinephrine) and sympathetic nervous system (norepinephrine) if she will stop smoking.
Laser-enhanced electron attachment and its possible application for optical switching

ABSTRACT Observation of enhanced electron attachment to electronically excited thiophenol (C6H5SH) and thioanisole (C6H5SCH3) molecules produced by excimer laser irradiation is reported. The potential significance of this finding for high-power diffuse discharge opening switches is indicated.
The Computer Operator and His Environment

To develop an increased understanding of the functioning of the computer operator and how he contributes to total computer system functioning, operator performance data were collected at a sample of six customer centers using the UNIVAC® 1108 and 494 computer systems. In addition, questionnaires were sent to all customer personnel using these systems. Data were collected on the proportion of time operators spend at various system activities, the frequency of usage of different equipment within the computer center, and the frequency of operator movement between system components. Reported operator information requirements are summarized, as are operator biographical data. A suggested computer center layout is presented based upon the collected data.
Growth and early neurodevelopmental outcomes in extremely low birth weight infants fed donor breast milk (247.1)

BACKGROUND: Breast milk (BM) is the recommended form of nutrition for premature infants; human donor breast milk (DBM) is an alternative when mother’s own milk (MOM) is unavailable or in low supply...
Analysis of wideband forward looking synthetic aperture radar for sensing land mines

[1] Signal processing algorithms are considered for the analysis of wideband, forward looking synthetic aperture radar data and for sensing metal and plastic land mines, with principal application to unpaved roads. Simple prescreening algorithms are considered for reduction of the search space required for a subsequent classifier. The classifier employs features based on viewing the target at multiple ranges, with classification implemented via a support vector machine and a relevance vector machine (RVM). Concerning classifier training, we consider cases for which training is performed on both mine and nonmine (clutter) data. In addition, motivated by the fact that the clutter statistics may vary significantly between the training and testing data, we also consider RVM implementation when we only train on mine data.
Pathdiag: automated TCP diagnosis

This paper describes a tool to diagnose network performance problems commonly affecting TCP-based applications. The tool, pathdiag, runs under a web server framework to provide non-expert network users with one-click diagnostic testing, tuning support and repair instructions. It diagnoses many causes of poor network performance using Web100 statistics and TCP performance models to overcome the lack of otherwise identifiable symptoms.
Silicon wafer-area network: intelligent communications fabric for parallel computing

The SWAN (silicon wafer-area network) project described explores the application of the high speed and high density of interconnections in WSI and MCM technologies to new communications schemes for general purpose, parallel arrays of computing nodes. The SWAN architecture seeks to provide on-demand, point-to-point communications through dynamically allocated routes for fine-grained communications. >
A general formulation for transition probabilities of Markov model and the application to fracture of composite materials

A generalized method for formulating unit-jump Markov chain model is presented. This method uses geometric series to determine the transition probabilities instead of using a moment generation function. Recursive equation for the transition probabilities has been derived in terms of the mean values. Present method is also compared by other method for robustness. Application of the unit-jump Markov chain model for characterizing fracture process of composites is described. By introducing a proper scaling factor, the entire probability history of the crack propagation at any loading states can be evaluated by the present model.
A plate tectonic origin for diamond-bearing kimberlites

Abstract It is proposed that diamond-bearing kimberlites are the result of activity at the deep end of a subducted oceanic plate. The source material consists of oceanic plate along with entrained hydrous and carbonaceous material that upon metamorphism or melting form diamond-bearing kimberlite. The emplacement should occur deep under continents and parallel to fold mountain ranges. The South African fields are cited as a specific example of the suggested process.
Differential development of progenitor activity for three B-cell lineages

Cell-transfer studies presented here distinguish three murine B cell lineages: conventional B cells, which develop late and are continually replenished from progenitors in adult bone marrow; Ly-1 B cells (B-1a), which develop early and maintain their numbers by self-replenishment; and Ly-1B "sister" (B-1b) cells, which share many of the properties of Ly-1 B cells, including self-replenishment and feedback regulation of development but can also readily develop from progenitors in adult bone marrow. The sequential emergence of these lineages, the time at which their progenitors function during ontogeny, and the distinctions among their repertoires and functions suggest that evolution has created a layered immune system in which the immune response potential of each successive lineage is adapted to its particular niche.
DEAE-silica gel and DEAE-controlled porous glass as ion exchangers for isolation of glycolipids

DEAE-silica gel and DEAE-controlled porous glass have been used for the quantitative isolation of gangliosides and neutral glycosphingolipids from animal tissues and cells. A direct comparative study between DEAE-silica gel, DEAE-controlled porous glass and DEAE-Sephadex was made; the results indicated that DEAE-silica gel is preferable to the other two ion exchangers. DEAE-silica gel has also been found to be suitable for the fractionation of ganglioside mixtures.
Goniometry of the proximal and distal interphalangeal joints, part I: A survey of instrumentation and placement preferences

A telephone survey of 231 occupational and physical therapists was conducted to determine goniometric instrumentation and placement preferences for measuring the proximal and distal interphalangeal joints of the upper extremity. The variables included were academic degree, hand therapy certification, years of therapy experience, years of specialty hand experience, and preferences for goniometric instrumentation and placement. Descriptive statistics revealed a highly experienced population (mean, 11 years) who predominantly preferred the 6" cut-off clear and metal goniometers. Eight additional instruments were also noted. Dorsal placement of the goniometer was preferred by 73% of the practitioners. Lateral placement was occasionally preferred (by 20%) in difficult clinical situations. Seven percent of the practitioners reported always preferring the lateral method. Chi-square analyses revealed no significant relationships between the variables.
Making your pharmacy practice department "in-dispense-able".

To the Editor. Pharmacy practice departments are responsible for the majority of experiential training within a doctor of pharmacy curriculum. Innovative practice is a critical component of this educational experience. Development of innovative practice opportunities can serve multiple purposes for a pharmacy practice department, in addition to promoting unique practice environments for pharmacists. At the same time, the economy is putting increased pressure on pharmacy school resources. Cohen described the need for innovation and entrepreneurship in pharmacy programs, illustrated by a number of opportunities which include identifying new revenue streams and developing joint ventures or partnerships.1 In the Pharmacy Practice department at Creighton University School of Pharmacy and Health Professions, we have developed unique relationships within our university and community that allow for innovative practice opportunities and a chance to demonstrate that the department is “indispensable.”
The methods of our madness: research on experimental documents

Research on Experimental Documents (RED) is the moniker for a small, interdisciplinary research group at Xerox PARC. We are eight researchers involved in the creation of new genres based on emerging media and technologies. We employ methods of speculative design and iterative prototyping while working in the mode of a design studio. Our current project, which we'll use as illustrative material, is the design and construction of twelve interactive exhibits for show in a hands-on technology museum.
Nuclear estrogen receptor in the avian liver: Correlation with biologic response

Abstract Diethylstilbestrol (DES) administration to cockerels resulted in an elevation (7-fold) in the number of high affinity binding sites measured in isolated liver nuclei by the [ 3 H]-estradiol exchange method. Increases were noted within 60 min, reached a maximum by 4 h and by 48 h had returned to control values. Elevation in the quantity of nuclear binding sites was estrogen-specific and 20% of the [ 3 H]-estradiol bound could be extracted by 0.4 M KC1. When isolated chromatin was used to evaluate estrogen-receptor interaction, the binding data were similar to those obtained with intact nuclei. To correlate estrogen binding with a specific hepatic response to this hormone, very low density lipoproteins (VLDL) synthesis was measured by immunochemical techniques in liver slices incubated in vitro in the presence of [ 3 H]-lysine following a single injection of DES. An increase in immunoprecipitable VLDL in the liver slices was first noted 2 h after estrogen administration, suggesting that nuclear receptor occupancy occurs prior to the earliest detectable stimulation of protein synthesis. To determine whether receptor binding and protein synthesis were temporally separated by estrogen-induced changes in transcription. RNA polymerase activities were measured in isolated nuclei and RNA synthesis initiation sites were quantified in chromatin preparations. Stimulation of RNA polymerase I and II activities as well as an 85% increase in chromatin initiation sites were demonstrable within 1 h following DES treatment. Thus. these effects were closely correlated in time with increases in nuclear estrogen receptor levels and again preceded enhanced VLDL synthesis. Finally, a dose-related correlation was noted between accumulation of nuclear estrogen-receptor complexes and elevation of plasma triglycerides and VLDL following DES treatment. Collectively, these data provide evidence that estrogen receptor interaction may underwrite the physiologically important regulation of plasma lipoproteins by a mechanism involving both transcription and translation.
The influence of dose and duration of estrogen treatment on corpus luteum regression in ewes

Abstract Estrogen-induced regression of corpora lutea (CL) was studied in two experiments using 190 cycling ewes. In an experiment with a 3 × 5 factorial design, the minimum amounts of estradiol-17β (E 2 ), estrone (E 1 ) and diethylstilbestrol (DES) required to induce CL regression by intramuscular injection were determined. Injections of either 0, 100, 250, 500 or 1,000 μg of each estrogen were administered on days 10 and 11 of the estrous cycle. Each dose level of estrogen significantly reduced CL weight by day 14, and the 250 μg and higher dosages significantly reduced CL progesterone content. The luteolytic potencies of the three estrogens did not differ significantly. In the second experiment, E 2 was infused into the jugular vein of ewes on day 10 of the estrous cycle at a rate of 1.3 to 41.6 μg/hr for either 12, 24, or 48 hours. Infusion of E 2 for 12 hr did not significantly reduce either the weight or progesterone content of CL, even when as much as 500 μg of E 2 (41.6 μg/hr) was administered. In contrast, a total of 62 μg of E 2 infused over a 24-hr period (2.6 μg/hr) significantly reduced CL weight and CL progesterone. Therefore, CL regression induced by infusion of E 2 on day 10 of the cycle was dependent on the duration of the E 2 treatment as well as on the amount of E 2 infused.
National variation in outcomes and costs for splenic injury and the impact of trauma systems: a population-based cohort study.

OBJECTIVE:: To measure national variation in splenectomy rates, mortality, and costs for hospitalized patients with splenic injury and the impact of state trauma systems on these outcomes. METHODS:: Using the HCUP State Inpatient Database for 2001, 2004, and 2007, all patients hospitalized with splenic injury were identified from 19 participating states. Multivariate regression was performed to compare splenectomy rates, inpatient mortality, and costs between states. Inclusiveness of statewide trauma systems was categorized based on the proportion of hospitals designated as a trauma center. RESULTS:: Of 33,131 patients, 26.2% underwent splenectomy, 6.1% died, and median hospital costs were $14,317. After adjusting for patient, injury, and hospital characteristics, there was a 1.7-fold variation (RR 1.67; 95% CI, 1.39-2.01) among the 19 states in rates of splenectomy. Adjusted inpatient mortality varied more than 2-fold between the highest and lowest states (RR 2.43; 95% CI, 1.76-3.37). Adjusted hospital costs varied over 60% between the highest and lowest states (cost ratio 1.61; 95% CI, 1.41-1.83). States with the most inclusive trauma systems had significantly lower splenectomy rate (RR 0.79; 95% CI, 0.68-0.92) and lower mortality (RR 0.71; 95% CI, 0.58-0.87), but similar hospital costs (CR 1.05; 95% CI, 0.95-1.16) compared to states with exclusive or no trauma systems. CONCLUSIONS:: Significant geographic variation in the management, outcome, and costs for splenic injury exists in the United States, and may reflect differences in quality of care. Inclusive trauma systems seem to improve outcomes without increasing hospital costs. Language: en
Fibrosis of extrahepatic biliary system after continuous hepatic artery infusion of floxuridine through an implantable pump (infusaid pump)

A case of severe fibrosis of the extrahepatic biliary system after hepatic artery infusion of floxuridine is described. The clinical and pathologic features are presented, and its pathogenesis discussed. The authors suggest investigation of an alternate drug schedule and/or dosage of floxuridine to eliminate or minimize this serious complication.
Germline p53 Mutations in a Cohort with Childhood Sarcoma: Sex Differences in Cancer Risk

To characterize cancer risk in heterozygous p53 mutation carriers, we analyzed cancer incidence in 56 germline p53 mutation carriers and 3,201 noncarriers from 107 kindreds ascertained through patients with childhood soft-tissue sarcoma who were treated at the University of Texas M. D. Anderson Cancer Center. We systematically followed members in these kindreds for cancer incidence for >20 years and evaluated their p53 gene status. We found seven kindreds with germline p53 mutations that include both missense and truncation mutation types. Kaplan-Meier analysis showed similar cancer risks between 21 missense and 35 truncation p53 mutation carriers (log-rank χ2=0.04; P=.84). We found a significantly higher cancer risk in female carriers than in male carriers (log-rank χ2=12.1; P 100-fold higher risk of sarcoma, female breast cancer, and hematologic malignancies for the p53 mutation carriers and agreed with the findings of an earlier segregation analysis based on the same cohort. These results quantitatively illustrated the spectrum of cancer risk in germline p53 mutation carriers and will provide valuable reference for the evaluation and treatment of patients with cancer.
Althusser and History: A Review Essay

Althusser and History: A Review Essay This review essay is available in Studies in 20th Century Literature: http://newprairiepress.org/sttcl/vol18/iss1/11
Protection by Bcl-2 against apoptotic but not autophagic cell death after photodynamic therapy

Photodynamic therapy (PDT) induces apoptosis in many cell types. Recent reports identified autophagy as an alternative cell-death process following PDT. Here we investigated the occurrence of autophagy after PDT with the photosensitizer Pc 4 in human cancer cells that are deficient in the pro-apoptotic factor Bax (human prostate cancer DU145) or the apoptosis mediator caspase-3 (human breast cancer MCF-7v) and in apoptosis-competent cells (MCF-7c3 stably overexpressing human pro-caspase-3 and Chinese hamster ovary CHO 5A100). Further, each cell line was also studied with and without stably overexpressed Bcl-2. By electron microscopy and immunoblot analysis, autophagy was observed in all cells studied, whether or not they were capable of typical apoptosis or overexpressed Bcl-2. Bcl-2 overexpression protected against PDT-induced apoptosis and loss of clonogenicity in apoptosis-competent cells (MCF-7c3 and CHO); however, it did not protect against the development of autophagy or against loss of clonogenicity in apoptosis-deficient cells (MCF-7v and DU145). The results show that autophagy may be the dominant cell death pathway following PDT in cells that are incapable of undergoing normal apoptosis. In such cells, Bcl-2 does not protect against autophagic death.
Carcinogenic heavy metals, As3+ and Cr6+, increase affinity of nuclear mono-ubiquitinated annexin A1 for DNA containing 8-oxo-guanosine, and promote translesion DNA synthesis.

To elucidate the biological roles of mono-ubiquitinated annexin A1 in nuclei, we investigated the interaction of purified nuclear mono-ubiquitinated annexin A1 with intact and oxidatively damaged DNA. We synthesized the 80mer 5'-GTCCACTATTAAAGAACGTGGACTCCAACGTCAAAGGGCGAAAAACCGTCTATCAGGGCGATGGCCCACTAC GTGAACCA-3' (P0G), and four additional 80mers, each with a selected single G in position 14, 30, 37 or 48 replaced by 8-oxo-guanosine (8-oxo-G) to model DNA damaged at a specific site by oxidation. Nuclear mono-ubiquitinated annexin A1 was able to bind oligonucleotides containing 8-oxo-G at specific positions, and able to anneal damaged oligonucleotide DNA to M13mp18 in the presence of Ca{sup 2+} or heavy metals such as As{sup 3+} and Cr{sup 6+}. M13mp18/8-oxo-G-oligonucleotide duplexes were unwound by nuclear annexin A1 in the presence of Mg{sup 2+} and ATP. The binding affinity of nuclear annexin A1 for ssDNA was higher for oxidatively damaged oligonucleotides than for the undamaged oligonucleotide P0G, whereas the maximal binding was not significantly changed. The carcinogenic heavy metals, As{sup 3+} and Cr{sup 6+}, increased the affinity of mono-ubiquitinated annexin A1 for oxidatively damaged oligonucleotides. Nuclear mono-ubiquitinated annexin A1 stimulated translesion DNA synthesis by Pol {beta}. Nuclear extracts of L5178Y tk(+/-) lymphoma cells also promoted translesion DNA synthesis in the presence of the heavy metals As{supmore » 3+} and Cr{sup 6+}. This DNA synthesis was inhibited by anti-annexin A1 antibody. These observations do not prove but provide strong evidence for the hypothesis that nuclear mono-ubiquitinated annexin A1 is involved in heavy metal promoted translesion DNA synthesis, thereby exhibiting the capacity to increase the introduction of mutations into DNA.« less
Medication characteristics beyond cost alone influence decisions to underuse pharmacotherapy in response to financial pressures.

Abstract Background and Objective Little is known about how patients facing medication cost pressures make choices about whether to underuse one or more of their prescription drugs. We calculated the probability that older adults would underuse prescription medications for common chronic illnesses because of cost concerns. We also identified differences in cost-related underuse between symptom-relief medications (e.g., analgesics) and primarily "preventive" medications (e.g., antihypertensives). Materials and Methods Older chronically ill patients using both symptom-relief and preventive medications ( N = 2,008) were identified as part of a nationwide survey in the United States and reported information about their cost-related underuse of 16 medication types. We used regression models to estimate the probability of underuse for each medication type, assuming average out-of-pocket costs, no prescription coverage, and the sociodemographic characteristics of a typical American aged 50+. Results 23% of respondents reported forgoing medication in the prior year due to cost. The likelihood of cost-related underuse was higher for symptom-relief medications (27%) than for primarily preventive medications (20%, P P Conclusions Medication characteristics beyond cost alone influence decisions to underuse treatment in response to financial pressures.
THE INFORMATIONAL ROLE OF BANK LOAN RATINGS

We analyze the relatively new phenomenon of credit ratings on syndicated loans, asking first whether they convey information to the capital markets. Our event studies show that initial loan ratings and upgrades are not informative, but downgrades are. The market anticipates downgrades to some extent, however. We also examine whether public information reflecting borrower default characteristics explains cross-sectional variation in loan ratings and find that ratings are only partially predictable. Our evidence suggests that loan and bond ratings are not determined by the same model. Finally, we estimate a credit spread model incorporating bank loan ratings and other factors reflecting default risk, information asymmetry, and agency problems. We find that ratings are related to loan rates, given the effect of other influences on yields, suggesting that ratings provide information not reflected in financial information. Ratings may capture idiosyncratic information about recovery rates, as each of the agencies claims, or information about default prospects not available to the market.
Father Residency and Symptoms of ADHD: Adult Male Involvement as a Mediator.

The purpose of the current study was to investigate the association between fathers' involvement and the presence of later symptoms of attention deficit hyperactivity disorder (ADHD) in children. A community‐based, nationally representative sample of children from the Early Childhood Longitudinal Study‐Kindergarten Cohort was utilised. Using a tripartite model, father involvement was investigated as a function of the time a father spent with the child and father's residency status. Structural equation modelling was employed to examine the association of father involvement during the spring semester of kindergarten with the presence of later symptoms of ADHD during the child's spring semester of first grade. Findings from the current study indicate that time children spent with an adult male may mediate the association between father residency and later symptoms of ADHD in children.