cssi/SciSciGPT-SciSciNet huggingface dataset:
Critical ethnography for communication studies: Dialogue and social justice in service learning

This essay presents a critical service‐learning that incorporates a perspective of hegemony and a pedagogy of praxis. It questions charity‐focused approaches and proposes dialogue as the transcendent means and method for student interaction with members of the community where service‐learning occurs. A course in critical ethnography for communication studies illustrates the connection between dialogue and social justice in service‐learning.
Diagnosis of Fanconi anemia in patients without congenital malformations: an international Fanconi Anemia Registry Study

Data were analyzed from 419 Fanconi anemia (FA) patients enrolled in the American Registry of the International Fanconi Anemia Registry (IFAR) to determine whether Fanconi anemia (FA) patients without major congenital malformations (CM) have distinguishing characteristics that can lead to an earlier diagnosis. These included 377 patients reported by physicians to the IFAR and 42 patients examined by us. The number of FA patients in each group without CM was 128 and 16, respectively; one third of all patients lacked CM. We found that height, weight, and head circumference were < or = 5th centile in 26.6%, 18.0%, and 8.6% of FA patients without CM referred to the IFAR, and in 43.8%, 25.0%, and 43.8% of FA patients without CM examined by us. Minor anomalies were reported in 9.4% of FA patients without CM referred to the IFAR and 100% of FA patients without CM examined by us. Most FA patients without CM have alterations in growth parameters, skin pigmentation abnormalities, or microphthalmia. Increased awareness of the complete spectrum of FA by clinicians will enable an earlier diagnosis to be made.
Distinctive features of pupil‐pupil classroom talk and their relationship to learning: How discursive exploration might be encouraged

Abstract In this paper classroom discourse is evaluated for the contribution it can make to pupils’ learning in groups. The emphasis, therefore, is on the interactional nature of the discourse insofar as it contributes to the maintenance of a dialogue and supports the extension of group understanding. The data recorded was of primary age children working at computers, and the analysis is qualitative. Three major categories are described; exploratory, cumulative and disputational talk, and their potential contribution to the children's learning is discussed. It is concluded that teachers play an important role in making explicit the strategies which optimise exploratory talk.
Applicability of red blood cell sorbitol measurements to monitor the clinical activity of sorbinil

Increased flux of glucose through the polyol pathway with resultant resultant accumulation of tissue sorbitol is implicated in the pathogenesis of the chronic complications of diabetes. Sorbinil is a potent inhibitor of aldose reductase (the first enzyme in the polyol pathway) and has been shown to normalize sorbitol levels in relevant tissues (eg, nerve, kidney, lens) of experimentally-induced diabetic animals. The purpose of this study was to identify a relatively noninvasive method of monitoring the intrinsic (or biochemical) efficacy of sorbinil in diabetic man. Specifically, the objective was to identify a readily accessible tissue that would be reflective of polyol pathway activity and the activity of sorbinil in clinically relevant but less accessible tissues. Based on several previous studies, which demonstrated that sorbitol accumulation in human red blood cells (RBCs) was a function of ambient glucose concentrations, either in vitro or in vivo, our investigations were conducted to determine if RBC sorbitol accumulation would correlate with sorbitol accumulation in lens and nerve tissue of diabetic rats; the effect of sorbinil in reducing sorbitol levels in lens and nerve tissue of diabetic rats would be reflected by changes in RBC sorbitol; and sorbinil would reduce RBC sorbitol in diabetic man.
A Randomized Comparison of Proximal and Distal Ultrasound‐Guided Adductor Canal Catheter Insertion Sites for Knee Arthroplasty

OBJECTIVES Proximal and distal (mid-thigh) ultrasound-guided continuous adductor canal block techniques have been described but not yet compared, and infusion benefits or side effects may be determined by catheter location. We hypothesized that proximal placement will result in faster onset of saphenous nerve anesthesia, without additional motor block, compared to a distal technique. METHODS Preoperatively, patients receiving an ultrasound-guided nonstimulating adductor canal catheter for knee arthroplasty were randomly assigned to either proximal or distal insertion. A local anesthetic bolus was administered via the catheter after successful placement. The primary outcome was the time to achieve complete sensory anesthesia in the saphenous nerve distribution. Secondary outcomes included procedural time, procedure-related pain and complications, postoperative pain, opioid consumption, and motor weakness. RESULTS Proximal insertion (n = 23) took a median (10th-90th percentiles) of 12.0 (3.0-21.0) minutes versus 6.0 (3.0-21.0) minutes for distal insertion (n = 21; P= .106) to anesthetize the medial calf. Only 10 of 25 (40%) and 10 of 24 (42%) patients in the proximal and distal groups, respectively, developed anesthesia at both the medial calf and top of the patella (P= .978). Bolus-induced motor weakness occurred in 19 of 25 (76%) and 16 of 24 (67%) patients in the proximal and distal groups (P = .529). Ten of 24 patients (42%) in the distal group required intravenous morphine postoperatively, compared to 2 of 24 (8%) in the proximal group (P = .008), but there were no differences in other secondary outcomes. CONCLUSIONS Continuous adductor canal blocks can be performed reliably at both proximal and distal locations. The proximal approach may offer minor analgesic and logistic advantages without an increase in motor block.
Topical photodynamic therapy in clinical dermatology

The growing incidence of cutaneous malignancies each year necessitates the development of new and more effective methods for both the diagnosis and the treatment of cancerous lesions, while assuring better cosmetic results and improving patient satisfaction. With that in mind, the use of topical photodynamic therapy (PDT) has been explored in the treatment as well as the diagnosis of various cutaneous malignancies. Using the intrinsic cellular haem biosynthetic pathway and principles of photoillumination, topical PDT carries the goal of selectively targeting abnormal cells, while preserving the normal surrounding structures. This paper will discuss the various applications and data on the use of topical PDT in dermatology.
The excretion of drugs across the gill of the dogfish, Squalus acanthias.

Abstract 1. 1. Eight drugs of widely different chemical and physical types were injected into Squalus acanthias , and their excretion by gill and kidney measured. 2. 2. The most lipid-soluble, non-polar substance, ethyl m -aminobenzoate (MS 222) was rapidly excreted by diffusion across the gill. 3. 3. The most lipid-insoluble, ionized substance, benzolamide (CL 11, 366) was excreted by active renal tubular secretion. 4. 4. In general, the rate of excretion across the gill was a function of lipid solubility. 5. 5. Study of the actual rates of excretion and half-lives of the drugs shows that gill excretion is relatively slow unless lipid solubility is very high 6. 6. Unless tubular secretion occurs the excretion by the kidney is also slow, since glomerular filtration rate is relatively low in this species. 7. 7. Many substances, therefore, are excreted more slowly in S. acanthias than in mammals; a typical example is sulfanilamide.
Infiltration and Surface Geometry Features of a Swelling Soil following Successive Simulated Rainstorms

The theory of water movement in high shrink/swell soils has experienced consistent revision since Haines first presented the topic in 1923. Several aspects of the infiltration process in cracking soils have proven to be difficult to measure; seal/crust formation and properties, crack network patterns, preferential flow zones and contributions, and soil moisture determinations within the profile (near crack and near center of prismatic column) to name a few. Here, we used simulated rainstorms, laser measurements of surface elevation, needle-penetrometer measurements, and mass measurements of infiltrating water over a 206- and 145-d period to examine water movement and cracking patterns in a large sample box filled with a swelling clay soil. Water movement was restricted to the neighborhood of the crack zone, since the formation of a surface seal/crust prohibited infiltration into the surface of the prismatic columns of soil between cracks. Also, the location of cracks was observed to alternate between rainstorms. The alternating crack pattern led to more uniform wetting with depth as time increased and the number of rainstorms increased, thereby reducing the extent of preferential flow.
Effects of in vitro adrenocorticotrophic hormone, cortisol and human recombinant interleukin-2 on porcine neutrophil migration and luminol-dependent chemiluminescence

Experiments were performed on isolated neutrophils tested in vitro to investigate the role of adrenocorticotrophic hormone (ACTH), cortisol and recombinant human interleukin-2 (rhIL-2) in modulating porcine polymorphonuclear (PMN) leukocyte function. Elevated levels of cortisol, similar to that observed during stressful experiences, caused a decrease in PMN chemokinesis (P < 0.02), chemotaxis (P < 0.001) and luminol-dependent chemiluminescence. ACTH at concentrations reflective of high stress conditions reduced PMN chemotaxis (P < 0.02) and chemokinesis (P < 0.01). In vitro rhIL-2 reversed (P < 0.05) the cortisol-induced and ACTH-induced suppression of PMN chemokinesis. These data indicate that specific neutrophil functions in pigs may be impaired by stress-related hormones of the pituitary-adrenal axis and that IL-2 may reverse some endocrine-induced suppression in chemokinesis.
The climate security divide: Bridging human and national security in Africa

National security is traditionally considered to have two dimensions : national defence against external aggressors and internal security against domestic enemies. States therefore pursue weapons and alliances to attain security with military procurement being an integral part of the pursuit of national security. Climate change has modified this state of affairs because it poses unique challenges to the regional security of Africa, and to general security on a global scale : it is a non-temporal threat, with no clearly defined parameters, and cannot be tackled by military means. In addition, it threatens not only the security of a state but the security of communities or entire portions of a state's population. It is therefore a risk to both national and human security. The advent of nuclear weapons has dramatically changed international relations in the 20th century and modified security relations amongst nations. Now climate change processes are redefining security in the 21st century. The security implications for Africa are the most dramatic and urgent. This paper explores the climate divide produced by climate change processes, particularly with regard to consequences of and effects on national and human security. To complement this analysis, two areas of security are examined, the first being the relationship between climate change and conflict and the second the security stressors in Africa that compound climate change and imperil security. In conclusion, the climate change scenario in Africa is linked to the pursuit of energy, conservation of forests and resolution of conflicts. The author also situates the African challenges in the multilateral processes of climate change.
Microflow Cytometer for optical analysis of phytoplankton

Analysis of the intrinsic fluorescence profiles of individual marine algae can be used in general classification of organisms based on cell size and fluorescence properties. We describe the design and fabrication of a Microflow Cytometer on a chip for characterization of phytoplankton. The Microflow Cytometer measured distinct side scatter and fluorescence properties of Synechococcus sp., Nitzschia d., and Thalassiosira p.; measurements were confirmed using the benchtop Accuri C6 flow cytometer. The Microflow Cytometer proved sensitive enough to detect and characterize picoplankton with diameter approximately 1 μm and larger phytoplankton of up to 80 μm in length. The wide range in size discrimination coupled with detection of intrinsic fluorescent pigments suggests that this Microflow Cytometer will be able to distinguish different populations of phytoplankton on unmanned underwater vehicles.
Osmoregulation of the lesser siren, Siren intermedia (Caudata: Amphibia)

Abstract 1. 1. Osmoregulation of Siren intermedia during saline stress and aestivation was studied. 2. 2. The LT-50 of sirens placed directly in 50% sea-water was 67.6 hr. 3. 3. Sirens acclimated to increasingly high concentrations of sea-water showed increases of plasma Na (99.9), K (120) and urea (320%). 4. 4. Sirens that had been aestivating for 36–63 days showed no significant increase in plasma Na and K, but plasma protein/amino acid concentrations increased by 120%.
Monocyte Chemoattractant Protein‐1 (CCL2) in Inflammatory Disease and Adaptive Immunity: Therapeutic Opportunities and Controversies

Monocyte chemoattractant protein (MCP)-1 (CCL2) specifically attracts monocytes and memory T cells. Its expression occurs in a variety of diseases characterized by mononuclear cell infiltration, and there is substantial biological and genetic evidence for its essential role in atherosclerosis and multiple sclerosis. Despite intensive screening, there are as yet no small-molecule antagonists of the receptor of MCP-1/CCL2, CCR2. However, biological agents, including antibodies and inhibitory peptides, have been developed and may be useful for these indications. Recent evidence from genetically modified mice indicates that MCP-1 and CCR2 have unanticipated effects on T helper (Th) cell development. However, unlike the identical phenotypes of MCP-1/CCL2(-/-) and CCR2(-/-) mice in inflammatory diseases, the phenotypes of these mice are disparate in adaptive immunity: MCP-1 stimulates Th2 polarization, whereas CCR2 activation stimulates Th1 polarization. This presents both a challenge and an opportunity for targeting the MCP-1/CCL2/CCR2 axis in disease.
SMARBot: a modular miniature mobile robot platform

Miniature robots have many advantages over their larger counterparts, such as low cost, low power, and easy to build a large scale team for complex tasks. Heterogeneous multi miniature robots could provide powerful situation awareness capability due to different locomotion capabilities and sensor information. However, it would be expensive and time consuming to develop specific embedded system for different type of robots. In this paper, we propose a generic modular embedded system architecture called SMARbot (Stevens Modular Autonomous Robot), which consists of a set of hardware and software modules that can be configured to construct various types of robot systems. These modules include a high performance microprocessor, a reconfigurable hardware component, wireless communication, and diverse sensor and actuator interfaces. The design of all the modules in electrical subsystem, the selection criteria for module components, and the real-time operating system are described. Some proofs of concept experimental results are also presented.
Optimization of continuous tube motion and step-and-shoot motion in digital breast tomosynthesis systems with patient motion

In digital breast tomosynthesis (DBT), a reconstruction of the breast is generated from projections acquired over a limited range of x-ray tube angles. There are two principal schemes for acquiring projections, continuous tube motion and step-and-shoot motion. Although continuous tube motion has the benefit of reducing patient motion by lowering scan time, it has the drawback of introducing blurring artifacts due to focal spot motion. The purpose of this work is to determine the optimal scan time which minimizes this trade-off. To this end, the filtered backprojection reconstruction of a sinusoidal input is calculated. At various frequencies, the optimal scan time is determined by the value which maximizes the modulation of the reconstruction. Although prior authors have studied the dependency of the modulation on focal spot motion, this work is unique in also modeling patient motion. It is shown that because continuous tube motion and patient motion have competing influences on whether scan time should be long or short, the modulation is maximized by an intermediate scan time. This optimal scan time decreases with object velocity and increases with exposure time. To optimize step-and-shoot motion, we calculate the scan time for which the modulation attains the maximum value achievable in a comparable system with continuous tube motion. This scan time provides a threshold below which the benefits of step-and-shoot motion are justified. In conclusion, this work optimizes scan time in DBT systems with patient motion and either continuous tube motion or step-and-shoot motion by maximizing the modulation of the reconstruction.
Motivations for parenthood among young adult college students

Two hundred and sixty three young adult college students responded to openended questions assessing their specific intentions, motives, and plans for having children. The most commonly stated motives for childbearing reflected a strong interest in establishing an identity and social network. Financial, marital, and emotional stability were identified as important factors influencing the timing of parenthood. Several significant sex differences were found for both motives and the timing of parenthood. These findings are discussed in terms of changing social norms regarding parenthood and changing sex role expectations.
Management Information Systems for Local Government: Discussion

Sjo and Biere have taken the initial steps in developing a conceptual framework relating management information systems (MIS), local government capacity building, and a general theory of local government behavior. To their credit, the authors avoid the common error of focusing on computer technology, technique, and case study examples rather than on the policy issue or problems MIS is designed to resolve. They have produced a thoughtful and stimulating paper. My major criticism of the paper is simply that the analysis of the governmental setting for MIS was not sufficiently developed. This criticism is not entirely appropriate, given the constraints on the length of the paper and the initial stage of development of the conceptual framework. I will briefly extract what I believe to be the key points of their argument, suggest some modifications and avenues for expansion, and identify some implications for research and extension. The authors note some critical differences
Divergent cellular phenotypes of human and mouse cells lacking the Werner syndrome RecQ helicase

Abstract Werner syndrome (WS) is a human autosomal recessive genetic instability and cancer predisposition syndrome with features of premature aging. Several genetically determined mouse models of WS have been generated, however, none develops features of premature aging or an elevated risk of neoplasia unless additional genetic perturbations are introduced. In order to determine whether differences in cellular phenotype could explain the discrepant phenotypes of Wrn−/− mice and WRN-deficient humans, we compared the cellular phenotype of newly derived Wrn−/− mouse primary fibroblasts with previous analyses of primary and transformed fibroblasts from WS patients and with newly derived, WRN-depleted human primary fibroblasts. These analyses confirmed previously reported cellular phenotypes of WRN-mutant and WRN-deficient human fibroblasts, and demonstrated that the human WRN-deficient cellular phenotype can be detected in cells grown in 5% or in 20% oxygen. In contrast, we did not identify prominent cellular phenotypes present in WRN-deficient human cells in Wrn−/− mouse fibroblasts. Our results indicate that human and mouse fibroblasts have different functional requirements for WRN protein, and that the absence of a strong cellular phenotype may in part explain the failure of Wrn−/− mice to develop an organismal phenotype resembling Werner syndrome.
Dispersal of Walleye Fingerlings after Stocking

Abstract Lake size and morphometry affected dispersal of fingerlings of walleyes Stizostedion vitreum following stocking in three Minnesota lakes. A portion of stocked fingerlings were marked with coded wire tags and released in September and October of 1986, 1987, and 1988. Walleyes were collected in subsequent years by spring electrofishing. Most tagged walleyes remained near the release site through their first spring, but this effect was inconsistent among lakes. Tagged fish dispersed by their first spring in Lake Mary (960 ha), which is the smallest of the three lakes and has little underwater structure. In Lake Miltona (2,363 ha), the largest lake in the study, fish were dispersed only marginally at age 3, likely due to the lake's size and its division into two basins. Walleyes in Lake Ida (1,736 ha), which is intermediate in size and habitat complexity, generally were dispersed by age 2. These results have important implications for release–recapture experiments. Failure to evaluate dispersal may b...
On the “Demystification” of Insight: A Critique of Neuroimaging Studies of Insight

Psychologists studying problem solving have, for over 100 years, been interested in the question of whether there are two different modes of solving problems. One mode—problem solving based on analysis—depends on application of past experience to the problem at hand and proceeds incrementally toward solution. The second mode—problem solving based on insight—involves breaking away from what one knows, typically after one has reached an impasse, and entails solution occurring suddenly, in a leap beyond what one knows. A number of recent studies have used neuroscientific methods (e.g., fMRI; EEG) to demystify insight, i.e., to dispel what is seen as the mystery of insight in problem solving. This research has been summarized by Lehrer (2008), in the context of examination of a real-life example of insightful problem solving: R. Wagner Dodge's creation of an escape fire to avoid near-certain death from a forest fire. This article presents a critical review of neuroscientific studies of insight, which indicate...
TDX: a high-performance table-driven XML parser

This paper presents TDX, a table-driven XML parser. TDX combines parsing and validation into one pass to increase the performance of XML-based applications, such as Web services. The TDX approach is based on the observation that context-free grammars can be automatically derived from XML schema. We developed a parser construction tool to automatically construct TDX grammar productions from a schema. Grammar tokens are defined by the specific schema element names, attribute names, and text. Because most of the structural constraints in XML schema are cast as grammar rules, parsing and validation of XML instances are efficiently implemented. The results show that TDX is several times faster than DOM or SAX parsing with validation enabled.
A hybrid model for diffusion through barrier films with multiple coatings

The amount of gas that penetrates the barrier of a vacuum insulation panels is directly linked to the service life of that panel. Therefore, to model and predict vacuum insulation panel service life, it is necessary to model the diffusion through its barriers. Best barriers on the market today are composites of multiple polymer layers with two or more inorganic coatings. It is accepted that the main part of diffusion, in such films, takes place through defects in the coating layers, but there are only a limited number of numerical models for this geometry with more than one coating. In this article, a hybrid model is presented that models gas permeation through film geometry with two coatings on a polymer substrate. Numerical calculations are combined with analytical ones to create a model that does take individual defect sizes as well as actual defect positions into account. Resulting oxygen transmission values calculated with this model have been compared to available manufacturer data with good agreement.
Laminar Pulsed Forced and Mixed Convection in a Vertical Isothermal Tube

Numerical fluid flow and heat transfer results were obtained for a pulsed laminar flow through a vertical, isothermal-walled tube for Gr/Re = 0 (no buoyancy) and 30 (buoyancy) at a cyclic-averaged Reynolds number of 5 x 10 2 . The pulsations resulted in cyclic-averaged Nusselt numbers Nu av that were greater than the steady, fully developed laminar Nusselt number, with Nu av increasing with increasing frequency. The Nusselt number also increased with increasing amplitude a for Gr/Re - 0, but it remained virtually constant beyond a - 0.1 for Gr/Re - 30. Although the NV av values at Gr/Re - 30 were greater than at Gr/Re = 0, they were offset by relatively large values of the cyclic-averaged dimensionless wall shear stress τ av , For Gr/Re = 30, Nu av /τ av was either the same or less than that for steady, fully developed laminar flow. Conversely, Nu av /τ av increased by as much as 39% for Gr/Re = 0.
A least-squares method for reduction of burnett data to compressibility factors and virial coefficients

Abstract A method is proposed for reducing Burnett compressibility data by a nonlinear least-squares analysis. This procedure produces apparatus constants and virial coefficients which are consistent with the data within least mean squares. The optimal number of virial coefficients and their error estimates are then obtained by using a technique presented earlier by the authors. Results for various reduction procedures are compared for helium at 0°C and nitrogen at -140°C. These data were chosen because they represent relatively easy reduction (He at 0°C) and very difficult reduction (N 2 at -140°C).
Detection of interspecific translocations in mouse-human hybrids by alkaline Giemsa staining

Abstract Alkaline Giemsa staining of chromosome preparations from mouse-human somatic cell hybrids has indicated the presence of interspecific translocations previously undetected by conventional banding procedures. The species specificity of the alkaline Giemsa stain has been substantiated by differential color staining of all mouse and human chromosomes and a mouse-human translocation in well characterized hybrid clones.
Statistical considerations in the design and analysis of environmental damage assessment studies

An environmental assessment of chemical and oil-spill effects presents unique statistical problems for both design and analysis. Because of the unplanned and accidental nature of a chemical spill, baseline data are usually absent and the quintessential elements of replication and randomization found in true experiments are absent. Alternative approaches to the design of damage assessment studies are presented that investigate spatial and/or temporal trends in biological responses centered about the spill event. Inferential and logistical limitations of alternative designs are discussed along with consideration of the spatial scale for pseudo-replication and the power of tests of impact. Meta-analysis is suggested to improve both the inferential capabilities and statistical power of damage assessments.
Human skin as an elastic membrane.

Abstract The equations governing the deformation of human skin are derived. First, the equations of an anisotropic, elastic membrane undergoing large deformations are recorded. Next, the kinematical condition is derived which restricts the skin to slide over the surface of a rigid foundation. Last, stress-strain relations are proposed which fit the known experimental data for skin. As a special case of this theory, the equations of a simple model for the flexure of a joint are solved. In another special case of the theory, the equations of a homogeneous, isotropic, elastic membrane lying in a plane and undergoing small deformations are solved by complex variable techniques for the case of a large sheet having a circular hole and subject to biaxial tension at infinity. Finally, some problems of interest to physicians and plastic surgeons are discussed.
A pipelined associated memory implemented in VLSI

A memory system which rapidly chooses the stored item most closely matching a given input is fundamental to a number of recognition tasks. A memory architecture which performs this function is discussed. In addition, a measure of the quality of the selected (best matching) memory is generated. The architecture is capable of significant data throughput rates and is amenable to implementation using conventional digital VLSI fabrication process. These characteristics are demonstrated by a prototype device fabricated using the MOSIS 3- mu m CMOS design rules, which can compare more than two million 9-bit input works per second. Behavioral simulations demonstrate the applicability of the architecture to some basic recognition tasks. >
Cervical Subarachnoid Hematoma of Unknown Origin: Case Report

Summary Objective and Importance. Spontaneous spinal subarachnoid hematoma is rare, having been reported in the English literature in only seven other cases. We describe the first case of spontaneous subarachnoid hematoma located in the cervical spinal cord of a 43-year-old man. The pathologic examination showed no apparent source of bleeding, but there was evidence of cervical spondylotic myelopathy. Clinical Presentation. The patient presented with a 10-day history of severe neck pain, followed by the onset of quadriparesis that was more evident on the left side, urinary retention, and sensory loss below C5. His medical history included hypertension. Magnetic resonance imaging showed a massive hemorrhage in the cervical spinal canal. Intervention. A C4-C5 subarachnoid hematoma was removed. The patient died due to respiratory distress and uncontrollable hypotension on day 6 after surgery. Surgical exploration, neuroradiologic examinations, and autopsy showed no evidence of vascular malformations, tumors, or other possible sources of bleeding. Conclusion. After excluding more common causes of spontaneous subarachnoid hematoma in this patient, we suggest that chronic spinal cord compression (spondylotic myelopathy) and arterial hypertension in this patient may have caused the pathogenesis of this rare clinical entity. Experimental data supporting this hypothesis are discussed.
Pharmacokinetic/Pharmacodynamic Modeling of Crizotinib for Anaplastic Lymphoma Kinase Inhibition and Antitumor Efficacy in Human Tumor Xenograft Mouse Models

Crizotinib [Xalkori; PF02341066; (R)-3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine] is an orally available dual inhibitor of anaplastic lymphoma kinase (ALK) and hepatocyte growth factor receptor. The objectives of the present studies were to characterize: 1) the pharmacokinetic/pharmacodynamic relationship of crizotinib plasma concentrations to the inhibition of ALK phosphorylation in tumors, and 2) the relationship of ALK inhibition to antitumor efficacy in human tumor xenograft models. Crizotinib was orally administered to athymic nu/nu mice implanted with H3122 non-small-cell lung carcinomas or severe combined immunodeficient/beige mice implanted with Karpas299 anaplastic large-cell lymphomas. Plasma concentration-time courses of crizotinib were adequately described by a one-compartment pharmacokinetic model. A pharmacodynamic link model reasonably fit the time courses of ALK inhibition in both H3122 and Karpas299 models with EC(50) values of 233 and 666 ng/ml, respectively. A tumor growth inhibition model also reasonably fit the time course of individual tumor growth curves with EC(50) values of 255 and 875 ng/ml, respectively. Thus, the EC(50) for ALK inhibition approximately corresponded to the EC(50) for tumor growth inhibition in both xenograft models, suggesting that >50% ALK inhibition would be required for significant antitumor efficacy (>50%). Furthermore, based on the observed clinical pharmacokinetic data coupled with the pharmacodynamic parameters obtained from the present nonclinical xenograft mouse model, >70% ALK inhibition was projected in patients with non-small-cell lung cancer who were administered the clinically recommended dosage of crizotinib, twice-daily doses of 250 mg (500 mg/day). The result suggests that crizotinib could sufficiently inhibit ALK phosphorylation for significant antitumor efficacy in patients.
The Role of Mentoring in Promoting Use of Research-Based Practices in Reading

This study explored two aspects of expanding the use of research-based practices in schools: (a) the extent to which mentor teachers could effectively teach a fellow teacher an instructional practice they had learned the previous year and (b) the extent to which the target practice would be implemented effectively by the partner after instruction from the mentor. Twelve teachers (11 third-grade, 1 second-grade) from two schools participated in this study. Six teachers who acquired the target strategy the previous year served as mentors. Mentors were asked to teach, coach, model, and provide feedback to their fellow teachers on the target practice. Results demonstrated that mentors and most of their partners implemented the target strategies effectively and that all teachers reported levels of satisfaction with the practice much higher than with traditional professional development.
Attitudes and Recycling: Does the Measurement of Affect Enhance Behavioral Prediction?

Recent attempts to improve the influence of social marketing have often focused on behavioral strategies, largely neglecting the concept of attitude. This is understandable given the weak performance of attitudinal variahles as a predictor in past studies of proenvironmental hehavior. However, we suggest that part of the reason for the poor association hetween attitudes and such hehavior is the possibility that many altruistic acts such as recycling are suhject to affective influences that may not he fully captured by commonly employed attitude measures. We also suggest that attitude strength might moderate the extent to which affective reactions account for additional variance in hehavior. Specifically, it is predicted that affect is more important for weak than for strong attitudes. Empirical results are presented to support these suggestions. © 1994 John Wiley & Sons, Inc.
Munchausen Syndrome by Proxy

Munchausen syndrome by proxy is the most difficult form of child abuse. It carries substantial morbidity and mortality. The diagnosis relies on appropriate suspicion and careful investigation. The psychological illness/need of the perpetrator is the main clinical feature. Early recognition and appropriate intervention prevent further abuse and criminal actions.
Echocardiographic predictors of poor outcome in infants with hypertrophic cardiomyopathy.

Although hypertrophic cardiomyopathy (HC) is readily diagnosed by echocardiography in infants with isolated ventricular hypertrophy, echocardiographic predictors of outcome have not been described in this age group. To identify echocardiographic predictors of poor outcome of infants with HC, we reviewed medical records and echocardiograms of all 19 patients with HC aged 12 months of age. At the initial postnatal examination, the Z value for LV posterior wall was larger (median, 5.2 vs 1.3, p <0.04) and, consequently, the ventricular septum/LV posterior wall ratio was lower (1.6 vs 2.3, p <0.04) in nonsurvivors than in survivors. In serial studies, the Z value for both the ventricular septum and the LV posterior wall thickness increased in nonsurvivors, but decreased in survivors. Nonsurvivors had intrinsic metabolic disease or Noonan syndrome. Survivors had classic HC or maternal diabetes. We conclude that, in infants with HC, early or progressive hypertrophy of the LV posterior wall is a predictor of poor outcome, regardless of associated disease.
Endoplasmic Reticulum Stress Responses in Plants

Endoplasmic reticulum (ER) stress is of considerable interest to plant biologists because it occurs in plants subjected to adverse environmental conditions. ER stress responses mitigate the damage caused by stress and confer levels of stress tolerance to plants. ER stress is activated by misfolded proteins that accumulate in the ER under adverse environmental conditions. Under these conditions, the demand for protein folding exceeds the capacity of the system, which sets off the unfolded protein response (UPR). Two arms of the UPR signaling pathway have been described in plants: one that involves two ER membrane-associated transcription factors (bZIP17 and bZIP28) and another that involves a dual protein kinase (RNA-splicing factor IRE1) and its target RNA (bZIP60). Under mild or short-term stress conditions, signaling from IRE1 activates autophagy, a cell survival response. But under severe or chronic stress conditions, ER stress can lead to cell death.
Computationally efficient resource allocation for multiuser OFDM systems

The optimal subcarrier, bit and power allocation problem for multiuser OFDM systems has been investigated. To achieve a numerically efficient solution the problem is divided into two separate optimization problems: one for subcarrier allocation and one for bit and power allocation. A novel and computationally efficient algorithm is presented for the bit and power allocation problem which results in a near-optimal solution. An efficient suboptimal solution is also presented for the subcarrier allocation problem. Numerical results are presented to show that the proposed methods achieve performance close to that of the optimal solution with considerably less computational complexity than those previously reported in the literature
Comparative temporal and dose-dependent morphological and transcriptional uterine effects elicited by tamoxifen and ethynylestradiol in immature, ovariectomized mice

Uterine temporal and dose-dependent histopathologic, morphometric and gene expression responses to the selective estrogen receptor modulator tamoxifen (TAM) were comprehensively examined to further elucidate its estrogen receptor-mediated effects. These results were systematically compared to the effects elicited by the potent estrogen receptor ligand 17α-ethynylestradiol (EE) to identify pathways similarly and uniquely modified by each compound. Three daily doses of 100 μg/kg TAM elicited a dose-dependent increase in uterine wet weight (UWW) in immature, ovariectomized C57BL/6 mice at 72 hrs with concurrent increases in luminal epithelial cell height (LECH), luminal circumference and glandular epithelial tubule number. Significant UWW and LECH increases were detected at 24 hrs after a single dose of 100 μg/kg TAM. cDNA microarray analysis identified 2235 differentially expressed genes following a single dose of 100 μg/kg TAM at 2, 4, 8, 12, 18 and 24 hrs, and at 72 hrs after three daily doses (3 × 24 hrs). Functional annotation of differentially expressed genes was associated with cell growth and proliferation, cytoskeletal organization, extracellular matrix modification, nucleotide synthesis, DNA replication, protein synthesis and turnover, lipid metabolism, glycolysis and immunological responses as is expected from the uterotrophic response. Comparative analysis of TAM and EE treatments identified 1209 common, differentially expressed genes, the majority of which exhibited similar profiles despite a temporal delay in TAM elicited responses. However, several conserved and treatment specific responses were identified that are consistent with proliferation (Fos, Cdkn1a, Anapc1), and water imbibition (Slc30a3, Slc30a5) responses elicited by EE. Overall, TAM and EE share similar gene expression profiles. However, TAM responses exhibit lower efficacy, while responses unique to EE are consistent with the physiological differences elicited between compounds.
Reform in the Making: The Implementation of Social Policy in Prison. By Ann Chih Lin. Princeton, NJ: Princeton University Press, 2000. 213p. $39.50.

During the last quarter of the twentieth century there was an explosion in the use of institutional corrections unparalleled in the annals of American penology. The numbers tell the story well: Just before the new millennium almost 1.3 million adults were confined in state and federal correctional facili- ties, which represents a tripling of the population in just under 20 years. One consequence of such a policy, and there are many, is that eventually a large proportion of these inmates will be released back into society. Their prospects do not look promising in terms of our current knowledge about recidivism rates, and we can expect a large and, most likely, increasing number of these individuals to rejoin the ranks of the incarcerated. The reasons for this policy failure are undoubtedly traceable to a number of forces, although one probably need not look beyond the prison walls as a place to start searching for answers.
Portal and Peripheral Vein Immunoreactive Insulin Concentrations Before and After Glucose Infusion

Catheterization of the portal vein via the umbilical vein was performed under local anesthesia in twelve nondiabetic subjects prior to exploratory laporatomy for a variety of conditions. Immunoreactive insulin (IRI) in simultaneously obtained portal and peripheral vein plasma was determined before, during, and after a two-minute glucose infusion (25 gm.). Two phases of insulin secretion were apparent from portal vein IRI concentrations. A rapid secretory phase beginning one minute after start of the infusion and lasting three to four minutes was followed by a slower secretory phase beginning approximately ten minutes after start of the glucose infusion. The absolute amount of “big” insulin (proinsulin-like material) in the portal vein was similar during the first phase and the early part of the second phase of insulin secretion. A significant positive correlation between portal vein and peripheral vein IRI responses to glucose was noted.
The effects of postpartum depression on child development: A meta-analysis

The adverse, short-term effects of postpartum depression on maternal-infant interaction have been repeatedly documented. Are there long-term sequelae for children whose mothers had experienced postpartum depression? The purpose of this meta-analysis was to determine the magnitude of the effect of postpartum depression on the cognitive and emotional development of children older than the age of 1 year. Nine studies which met the sample criteria were included in this meta-analysis. Results indicated that postpartum depression had a small but significant effect on children's cognitive and emotional development. The r indicator for effect size ranged from .18 to .22 whereas the d indicator ranged from .36 to .45. Implications for future research are addressed.
Effect of leucine supplementation on fat free mass with prolonged hypoxic exposure during a 13-day trek to Everest Base Camp: a double-blind randomized study.

Loss of body weight and fat-free mass (FFM) are commonly noted with prolonged exposure to hypobaric hypoxia. Recent evidence suggests protein supplementation, specifically leucine, may potentially ...
Was there a regulatory approval market for mortgages

Purpose – The purpose of this paper is to examine whether the underserved area requirements for Fannie Mae and Freddie Mac (the government-sponsored enterprises [GSEs]) and the community needs requirements of the Community Reinvestment Act (CRA) contributed to the house price run-up in the USA. Design/methodology/approach – This paper predicts the incidence of “Rebounds”, which indicate that a mortgage had been previously denied, to provide evidence on whether certain regulations caused excessively risky mortgage originations. As a different lender rejected the loan given the interest rate that they were willing to charge and information on the borrower, a higher incidence of Rebounds provides evidence that lenders were more frequently disagreeing about loans. This can indicate differences in regulatory pressure or oversight across lenders. Findings – This paper provides evidence that the GSEs were purchasing fewer Rebounds directly from lenders. However, evidence suggests that indirectly, the securitizat...
The Comorbidity of Physical, Mental, and Developmental Conditions Associated with Childhood Adversity: A Population Based Study

Objective Adverse childhood experiences (ACEs) are associated with myriad health conditions and risk behaviors in both adolescents and adults. In this study we examine the association between ACEs and specific physical, mental, and developmental conditions, as well as their comorbidity, in a nationally representative sample of children 0–17 years. Methods Data from the 2011–2012 National Survey for Child Health (NSCH) were used. A total of 95,677 random-digit-dial interviews with parents of children 0–17 years were conducted across all 50 states and the District of Columbia. Outcomes included singular condition domains (physical, mental, and developmental) as well as combinations of condition domains (e.g., physical plus mental, mental plus developmental, etc.). Results Twenty-three percent of parents reported that their child experienced 1 ACE; 9.2 % experienced 2 ACEs, and 10.3 % experienced three or more. Across all three condition domains and combinations of domains, children who experienced at least one ACE were more likely than children who experienced 0 ACEs to have at least one condition. Additionally, greater ACEs was associated with increased likelihood of at least one condition in each domain and in multiple domains. Conclusions for practice These findings support the extension of existing family environment screening tools in pediatric practices as well as the establishment of a system for monitoring ACEs in families with multiple or complex conditions.
Body Composition Relative to Motor Aptitude for Preadolescent Boys

Abstract The data for 40 variables were obtained from 81 Purdue University faculty sons between 10 and 12 years of age inclusive. Among the 40 variables, 680 correlation coefficients were obtained. Factor analysis was used to identify the factors which could explain the items measuring body composition and motor aptitude. As a result, eight factors were isolated and given names. The factors underlying the 40 variables seemed to permit the following names: growth and maturity factor, “body fitness” factor, body balance on object factor, coordination of the lower extremities factor, general kinesthetic sense factor, general static balance factor, directionality factor, and laterality factor. Observing the factor loadings in Factor I, it may be concluded that the measurement of lean body weight by liquid scintillation counting technique is significant in the assessment of growth and maturity in preadolescent boys. Furthermore, in the assessment of “body fitness” pertaining to preadolescent boys, it is reveal...
A dialogue monitoring scheme for a virtual doctor

In today's digital world the information exchange has reached very large volumes per minute, assisting people in doing their business from long distances, without their presence being necessary. At the same time, Human Machine Interaction (HMI) devices are used in many places of service and interaction by removing humans from the loop. Although these devices have advanced recently, they are still far away from replacing the human from the interaction loop. Their major problem is that they cannot reliably and efficiently respond to human requests; they mainly behave as "answer" machines. In response to this problem we propose a new HMI scheme, capable of offering a better communication and interaction to human users, based on SPN dialogue rather than answers to questions.