cssi/SciSciGPT-SciSciNet huggingface dataset:
Surgical Approaches to Tumors of the Occipito-Cervical, Subaxial Cervical, and Cervicothoracic Spine: An Algorithm for Standard versus Extended Anterior Cervical Access.

Objective To propose a surgical approach algorithm for the tumors of the cervicothoracic spine. Methods All patients operated for vertebral column tumors involving the occipito-cervicothoracic spine were reviewed. Oncologic characteristics and surgical approach were gathered. Approach was classified by the use of staging and trajectory (posterior, transnasal, transoral, transmandibular, transcervical, transsternal). Angle of attack was defined for the occipitocervical junction tumor as the angle inscribed by the inferior mandibular plane and line connecting the superior tumor pole and mandibular angle. For lesions extending below the thoracic inlet, angle of attack was that inscribed by the plane of the thoracic inlet and the line connecting the jugular notch and inferior tumor pole. Results In total, 115 patients were included (mean age 56.7 years, 64 [56%] male, average size 26.5 cm3, 39 [34%] primary tumors). Sixty-nine (60%) of patients had single-stage procedures (57 [49.6%] posterior-only, 12 [10.4%] anterior-only), 35 (30.4%) had 2-stage procedures, and 11 (9.6%) had 3- or 4-stage approaches. Lesions requiring a combined transmandibular-transcervical approach all involved the C2 and C3 levels and had a significantly steeper angle of attack (42.5 ± 9.5 vs. 6.1 ± 13.3°; P = 0.01) and greater superior tumor extent above the inferior plane of the mandible (3.69 ± 2.18 vs. 0.33 ± 0.78; P = 0.002). Lateral tumor extent, tumor size, nor inferior angle of attack differed significantly between approach groups. Conclusions Here, we present a preliminary decision-making algorithm for the management of vertebral column tumors of the cervicothoracic spine. Based on this single-center experience, we suggest which patients, assessed via a combination of tumor histology and regional anatomy, may benefit from extended anterior surgical access.
Remote TPC Internships: Infrastructures for Success

Though the remote internship is certainly not a new phenomenon, the COVID-19 pandemic has accelerated the growth of this model for undergraduate experiential learning. As we consider this shift, we...
Have Students Used Techniques to Stop the Bleed

INTRODUCTION The Stop the Bleed course was initiated in response to the Hartford Consensus and over 1 million people have been taught basic bleeding control techniques. Our study sought to determine the extent to which this training has been utilized. METHODS Surveys were sent by email to students that had taken the Stop the Bleed course through our institution in 2017 or 2018. Data were collected utilizing the REDCap system and statistical calculations were performed. RESULTS 2505 surveys were sent with 445 (18%) responses. The mean age of respondents was 48 years of age, 343 (77%) were female, and 230 (52%) were in the medical field. There were 17 respondents (3.8%) that stated they had utilized the techniques taught in the course; 16 out of 17 put pressure on a wound, 7 packed a wound, and 6 used a tourniquet. Patients had been injured by a variety of mechanisms including gunshot wound, stabbing, accidental laceration, and motor vehicle collision. Patients had good outcomes with 3 out of 17 surviving to emergency medical services arrival without known final outcome and the remaining 14 were known to do well. CONCLUSION The Stop the Bleed course is important to enable bystanders to provide hemorrhage control. Our study shows that the techniques have been utilized with 17 treated patients having a good outcome and while a utilization rate of 3.8% may appear low, it is similar to the utilization rate of cardiopulmonary resuscitation instruction of 2%.
Chromosomes and chromosomal progression of malignant human gliomas: theoretical and practical implications

We karyotyped 27 malignant human gliomas including 3 anaplastic astrocytomas (AA), 23 glioblastoma multiformes (GBM), and 1 gliosarcoma (GS) in direct preparation, short term culture, or both, and found that they could be grouped according to their karyotypic patterns. Six of these tumors (3 GBM) had normal stemlines or only lacked one sex chromosome (Group la). Two tumors (Group lb) lacked one sex chromosome but showed, in addition, numerical and structural deviations. Three tumors were near-tetraploid (Group II) and contained double minutes (DMs). The remaining 16 tumors (I AA, 14 GBM, 1 GS) had near-diploid stemlines (Group III), often with gains of No. 7, loss of No. 10, structural abnormalities of No. 9 and DMs. These different patterns could be reflecting activation and/or amplification of different oncogenes. Alternatively they could be reflecting induction by different agents. But quite apart from their theoretical significance these karyotypic patterns could prove useful as prognostic indicators. The observa-tion that near-diploid human gliomas double their chromosome complements as they establish in culture and as transplantable lines in nude mice suggests that the near-tetraploid tumors in Group II are at a later stage of karyotypic progression than the near-diploid tumors in Groups I and III. There is also a spectrum of stage of karyotypic progression within Groups I and III ranging from tumors with only simple numerical deviations to those with complex numerical and structural abberations. The present series is too small and therapeutic regimens of individual patients are too diverse to determine if stage of karyotypic progression is a useful prognostic indicator. Long term studies of a large group of patients will be necessary to define these relationships.
The Pebble Game and Logics of Programs

Publisher Summary The chapter is a computer scientist's commentary on a small part of Friedman's article titled “Algorithmic procedures, generalized Turing algorithms, and elementary recursion theory.” The focus of the chapter is on the pebble game and logics of programs. The pebble game is a basic technique in theoretical computer science and has been particularly successful in studies that compare time and space requirements of computations. Thus, by far the most numerous applications of the pebble game are in the area of time–space tradeoffs. There are important applications of the pebble game in the areas of comparative schematology, logics of programs, and code generation and optimization, among others. Friedman's original formulation is somewhat different from Paterson's and Hewitt's original formulation, and neither is expressed in terms of pebbles and pebbling. The logic of programs is a formal language for reasoning about program properties, and it combines “assertion formalism” and “programming formalism” in a single language.
We Were Our Age

DUKE'S BROTHER DIED under the ice in spring, the season I met Duke. The other kid survived?shivering, fat-lipped, the instigator, littler. A miracle, the search team said. Just a hurt front tooth, a gash, a stitch. A boy's likely story. This is what I heard, but not from Duke. Duke said, "Go." Duke said, "Ladies first, please." Rock, rock, gap, stone-cold to the lighthouse?Duke and I were spiny in the dark. Weeds swam up. Weak sunk stars, a lap, suck and bubble. The usual. Lake and pier. Us and us. Month after month. Duke was always finding things to skip across to who knew where. August. Pinkness hovered.
The Interstate School Leaders Licensure Consortium: A Standards-Based Approach to Strengthening Educational Leadership

In this article, we describe the Interstate School Leaders Licensure Consortium (ISLLC), as well as its intellectual ground and reform efforts. We begin by examining the foundations that provide shape to the ISLLC standards. We review new visions of learning and teaching, changing conceptions of organizations, and reconfigured relationships between schools and their communities. We also analyze the evolving context of schooling, focusing on movements underway in the economic, social, and political domains of the education industry. The middle part of the article reviews the picture of educational leadership that informs the work of the consortium. In the final section, we describe the principles and core tenets that provide the architecture for the standards and outline the standards themselves. We also chronicle how the ISLLC standards are being used to strengthen educational leadership throughout the United States.
Effects of Mosquitofish, Gambusia affinis, on Channel Catfish, Ictalurus puncatatus, Production Ponds

Mosquitofish, Gambusia sp., have been spread throughout the world to biologically control mosquitoes. However, the fish has gained a reputation as an invasive species and has been implicated in displacing native aquatic species. Gambusia affinis are native to the southeastern United States and commonly occur in commercial channel catfish, Ictalurus punctatus, production ponds. We investigated effects of mosquitofish presence on zooplankton populations, water quality, disease occurrence, and fish production in experimental ponds. There were no differences between ponds with or without mosquitofish in numbers of calanoid copepods, cyclopoid copepods, total copepods, Bosmina sp., Ceriodaphnia sp., Moina sp., Daphnia sp., or total cladocerans. There were also no differences in copepod and cladoceran sizes. Copepod nauplii were more numerous during the summer months in ponds with mosquitofish. There were no differences in water quality variables (soluble reactive phosphorus, nitrate, nitrite, ammonia, total nitrogen, total phosphorus, pH) or phytoplankton density between ponds stocked with and without mosquitofish. Catfish production and disease occurrence were also similar between ponds with and without mosquitofish. Although mosquitofish may cause problems when stocked outside their native range, there does not appear to be any adverse effects of mosquitofish presence in catfish production ponds.
Is it Gender, Religion or Both? A Survey Experiment on Voter Preferences in Transitional Tunisia

Scholars, policymakers, and citizens express concern about the impact of gender and Islam on political participation. Despite the attention, many questions remain: do male or female, religious or secular candidates, compete on an equal playing field? How do gender and Islam interact to affect electability? If biases exist, what explains them? We explore these questions through an experiment embedded in the Tunisian Post-Election Survey (TPES). We find little support for expectations drawn from modernization theory; secular, well-educated Tunisians are not more likely to support female candidates than religious, less-educated citizens. However, role congruity theory receives support. Religious voters of both genders support religious, female candidates, while those of both genders and religious orientations who value female participation support secular, female candidates. Explicating the mechanisms underlying biases extends our theoretical understanding of the relationship between gender, religion, and politics, and provides theoretical and policy insights into how biases can be diminished.
Chromatin and histones in hen erythrocyte nuclei: Morphologic change induced by selective binding of histones with a synthetic polyanion

Abstract Polystyrene sulfonate (PSS), has been shown in the mealy bug to decondense chromatin and to activate RNA synthesis [1]. Previous work [2] suggests that this decondensation and activation results from interaction of PSS with histone. This paper examines the mechanism of decondensation in hen erythrocyte nuclei prepared by saponin lysis and treated with increasing doses of PSS. Histones were extracted with 0.5 N H2SO4 and analysed by polyacrylamide gel electrophoresis. The decreased amount of histone recoverable from PSS treated nuclei indicates that PSS binds to the histone of chromatin in the ratio of 1.0:1.7 on a dry weight basis. The F2c serine-rich fraction is removed first. The remaining fractions are bound to PSS in the sequence F3, F2a1, F2b, F1. Since the F3 histone has been shown to be the most tightly bound to the DNA, it appears that the unique order of extraction with PSS may result from steric interactions rather than from relative binding strengths of DNA and histones. Electron microscopy shows that a loosening of the highly condensed chromatin structure occurs at the concentration of PSS required for binding of the F2c fraction. Electron microscopic cytochemistry with ammoniacal silver confirms that histones are removed from the chromatin with PSS.
Origins of lean management in America: The role of Connecticut businesses

Purpose – The purpose of this paper is to provide a historical account of the significant role that Connecticut businesses and business leaders had in the spread of Lean management throughout the USA. The paper aims to describe what happens when managers do not understand and apply an important principle of Lean management.Design/methodology/approach – Survey of published and unpublished records, as well as personal communications with key figures.Findings – Establishes the role and importance of Connecticut businesses and business leaders in the discovery and dissemination of Lean management in America since 1979, external to Toyota and its affiliated suppliers.Research limitations/implications – The accuracy of some past events necessarily relies on the recollection of key figures that were obtained by personal communications.Practical implications – Describes how an important principle, “respect for people,” was not understood by most management practitioners, thus hindering efforts to correctly practi...
A Robust Regression Model for a First-Order Autoregressive Time Series with Unequal Spacing: Technical Report

Time series arise often in environmental monitoring settings, which typically involve measuring processes repeatedly over time. In many such applications, observations are irregularly spaced and, additionally, are not distributed normally. We describe the technical details justfying a simple, robust approach for estimating regression parameters and a rst-order autocorrelation parameter in a time series where the observations are irregularly spaced. Estimates are obtained from an estimating equation constructed as a linear combination of estimated innovation errors, suitably robustied by symmetric and possibly bounded functions. Under MCAR assumption and mild regularity conditions, the proposed estimating equation yields consistent and asymptotically normal estimates. Technical details are developed using the theory of mixingales described by Davidson (1994) and standard Z-estimation theory as described by van der Vaart (1998). In particular, the sequence of estimating function components can be shown to be an ergodic L1 mixingale to which a weak law of large numbers and a central limit theorem apply. Lipschitz conditions ensure the functional convergence required to complete the proof.
Tails, Fears, and Equilibrium Option Prices

Recent empirical evidence suggests that the compensation for rare events accounts for a large fraction of the average equity and variance premia. I replicate this fact in a parsimonious consumption-based asset pricing model based on a (generalized) disappointment averse investor and conditionally Gaussian fundamentals. In the model, regime-switches in endowment volatility interact with the investor’s tail aversion to produce large endogenous return jumps and a realistic implied volatility smirk. The presence of multiple shock frequencies in volatility gives the variance premium the ability to predict returns over short horizons and the price-dividend ratio the ability to predict returns over long horizons.
A looming joblessness crisis for new pharmacy graduates and the implications it holds for the academy.

The new millennium ushered in a period of hope and change for the profession of pharmacy. The doctor of pharmacy (PharmD) degree became the exclusive first professional degree as of 2000, bringing with it expectations for a dramatic expansion of direct patient care roles for pharmacists. Just 1 year later the pharmacy academy began a period of unprecedented growth, fueled by a long-standing shortage of pharmacists and an outstanding job market for new pharmacy graduates, making jobs for PharmD graduates easy to find and causing salaries to spiral upward. As a result, the PharmD degree became a hot commodity, generating a seemingly inexhaustible supply of applicants to colleges and schools of pharmacy. Inevitably, higher education came to see pharmacy as a “golden goose.” But no goose harbors an infinite supply of golden eggs, and the inordinate rate of academic growth that ensued has put the academy at risk, along with its students. Calls for measured academic growth, brought forth in published commentaries in 2005 and 2010, went largely unnoticed.1,2 The house of student delegates of the American Pharmacists Association-Academy of Student Pharmacists even weighed in on the subject in 2012 by approving resolution 2012:2 — Creation, Expansion, or Reductions of Schools and Colleges of Pharmacy Relative to Pharmacist Demand, which called upon current and future schools to evaluate the demand for pharmacists before taking action.3 Remarkably, most leaders of pharmacy organizations and academic institutions remained relatively silent on the matter. This commentary examines the massive increase in the number of pharmacy graduates since 2001 and the vast overestimations, in the author’s opinion, made back in 2001 about the number of pharmacists that would be needed by 2020. It also identifies potential implications of the changing pharmacist job market for the pharmacy academy.
Psychiatric drugs as agents of trauma

Drawing on the work of numerous psychiatrists and psychopharmacologists and my own observations, I describe how most common psychiatric drugs are not only toxic but can be chronically traumatic, which I define in some detail throughout this paper. In addition to observing this occurrence among numerous of my patients over the past 20 years, I surveyed 9 mental health clinicians who had taken antidepressant drugs long-term. Of these 9, 7 (77%) experienced bothersome toxic drug effects and 2 (22%) had become clearly worse than they were before they had started the drugs. Based on others' and my observations I describe the genesis of this worsened condition which I call the Drug Stress Trauma Syndrome. These drug effects can be and are often so detrimental to the quality of life among a distinct but significant minority of patients that they can no longer be considered trivial or unimportant. Instead, they are so disruptive to many patients' quality of life that their effect becomes traumatic, and are thereby agents of trauma. These observations and preliminary data may encourage others to look into this matter in more depth.
The Big (Data) Bang: Policy, Prospects, and Challenges

Big data is increasingly the cornerstone on which policy making is based. However, with potential benefits and applications come challenges and dilemmas. In this set of symposium articles, authors examine the promise and problems of big data, exploring associated prospects, risks, parameters, and payoffs from a variety of perspectives. The articles address myriad challenges in the handling of big data sets, such as collection, validation, integrity, and security; ontological issues attending data analytics and conceptual transformations; the foundations of big data collection for social science research; the gap between the acquisition of data and its use to advance discovery and innovation; the costs and benefits of using big data in decision making and analysis; and, finally, related problems of privacy, security, and ethics. Issues such as these will continue to arise with increased use of big data as fundamental to policy making and governance in today's growing information society.
Some comparative aspects of the organ distribution of superoxide dismutase activity in the freshwater turtle, Pseudemys scripta elegans.

Abstract 1. 1. Superoxide dismutase activities in five tissues of the relatively anaerobic freshwater turtle were compared with SOD activities in the same tissues of two mammalian species (mouse and rabbit) with a more usual pattern of dependence on O 2 availability. 2. 2. SOD activities in brain, lung and skeletal muscle, but not liver or cardiac muscle, are significantly lower in the turtle. The turtle also shows differences in the pattern of relative SOD activities in various tissues as compared to the two mammalian species. 3. 3. The data indicate that a relationship does exist between SOD activities and O 2 exposure in intact vertebrate systems, and is consistent with a physiological role for SOD in tissue O 2 metabolism.
Torque algorithms: The permanent multipole and induced dipole vector contributions in a set of charge distributions

Two algorithms for the permanent multipole contribution to the mutual torques in a set of charge distributions are presented. The first is in the conventional Newtonian formulation; the second is in terms of generalized forces. Both noncooperative and cooperative algorithms for the induced dipole vector contribution are given. The algorithms are based on earlier algorithms for the permanent multipole and induced dipole vector contributions to the energy in the Maxwell Invariant Form.
A COMPARISON BETWEEN GEOSTROPHIC AND NONGEOSTROPHIC NUMERICAL FORECASTS OF HURRICANE MOVEMENT WITH THE BAROTROPIC STEERING MODEL

Abstract The steering flow of a hurricane is obtained by eliminating the vortex pattern from the total flow field. The evolution of the steering flow is predicted by solving the barotropic nondivergent vorticity equation. Based upon the steering-flow prediction, a forecast of the hurricane movement is obtained with the use of an equation which provides for interaction between the hurricane and the steering flow. In the geostrophic model, the geostrophic-wind assumption is used in solving the vorticity equation. In the nongeostrophic model, the stream function governed by the ‘balance equation’ is adopted. With the above two prediction models, 45 pairs of predictions of the 24-hr and 48-hr movement of hurricanes Diane and Connie (August 1955) and Betsy (August 1956) at the 500- and 700-mb levels were prepared by the use of an electronic computer. A detailed comparison between performances of the two prediction models is presented. Generally speaking, there is a remarkable similarity between the nongeostrop...
Monads in Semantics

Abstract In this extended abstract we provide a very brief overview of the notion of a monad along with some examples of applications to programming language semantics. The treatment is by no means exhaustive but rather chooses examples and results that either illustrate the wide variety of uses of this abstract tool or which bear some connection to other work presented at the workshop. The abstract begins with some preliminary definitions and examples, proceeds to categories of algebras and ends with some results and examples of the author using monadic lifting.
Effects of low dose cocaine on REM sleep in the freely moving rat.

Cocaine administration can be disruptive to sleep. In compulsive cocaine users, sleep disruption may be a factor contributing to relapse. The effects of cocaine on sleep, particularly those produced by low doses, have not been extensively studied. Low dose cocaine may stimulate brain reward systems that are linked to the liability of abusing of this drug. This study was designed to assess the effects of the acute administration of low to moderate cocaine doses on sleep in the rat. Polygraphic recordings were obtained from freely moving, chronically instrumented rats over a 6-h period after the administration of either cocaine (as a 2.5–10 mg/kg intraperitoneal dose) or saline. Following cocaine administration, time spent by the rats in wakefulness increased and slow wave sleep decreased in a dose-dependent manner, compared to controls. These changes lasted between 1 to 3 h following the cocaine administration. Rapid eye movement (REM) sleep was decreased during a 2- to 3-h period following the injection of 5 and 10 mg/kg doses of cocaine. In contrast, REM sleep increased during the periods 2–4 h after the administration of 2.5 and 5 mg/kg doses of cocaine. These results indicate that sleep can be significantly altered by low doses of cocaine when administered subacutely.
Molecular mechanisms of adrenergic stimulation in the heart

Increased cardiac output in response to beta-adrenergic receptor stimulation is achieved by rapid alteration of the activity of cardiac ion channels, pumps, and exchangers. Over the past decade, the discovery of macromolecular complexes, which include the ion channels and pumps and the kinases that control their level of phosphorylation, has led to an increased understanding of the molecular mechanisms behind the cardiac adrenergic response. The increased understanding has led to the discovery of a new long QT gene encoding an accessory protein in one of these macromolecular complexes. This article briefly reviews the major components of the beta-adrenergic pathway in the heart and discusses the direction of current and future research.
Basic elements in a fluid mechanics laboratory experience: an engineering science approach

Experiments for a first fluid mechanics course are described. The basic concepts of pressure and velocity as the primitive variables, the control volume equations and the field equations with Reynolds number dependent properties are reinforced in these experiments. The use of such experiments, as the experimental background for future lecture instruction, is emphasized.
Hormonal contraceptive discontinuation patterns according to formulation: investigation of associations in an administrative claims database

Abstract Background Hormonal contraceptive use is generally characterized by poor adherence and relatively high discontinuation. This study investigated whether specific hormonal contraceptive formulations and/or delivery systems might be correlated with discontinuation of contraception. Study Design This was a retrospective descriptive analysis within a large administrative claims database. The sample included women aged 15–40 years with a pharmacy benefit and at least one new hormonal contraception prescription during the study period and no prescription in the previous 6 months. Filled contraceptive prescriptions were grouped into several categories of delivery system, dosage, progestin type and monophasic vs. triphasic formulations. In each, a baseline number of women was established who filled a first prescription for a contraceptive formulation in the specified category. Then, the percentage of these women who filled a prescription for a contraceptive in the same category within 3 months' time was determined. Continuation or change rates were compared within each group. Results Oral contraceptives (OCs) were the least likely to be discontinued at 3 months; injectables were the most likely. OC formulations associated with increased risk of discontinuation (odds ratios above 1.3 representing a 5% or higher increased discontinuation) included very-low-dose (20–25 mcg ethinyl estradiol) pills containing norethindrone acetate or norgestimate, as compared to a preparation with the same progestin type but with a higher dose of estrogen. Desogestrel and norethindrone-containing triphasics were more likely to be discontinued than other triphasic progestins. OC formulations with desogestrel and norethindrone/norethindrone acetate were more likely than formulations with other progestins to be discontinued overall. Conclusions This investigation in a sample of nearly 250,000 women suggests possible associations between discontinuation of hormonal contraception and factors such as estrogen dosing, progestin type and changes in dosage during the cycle. Identification of factors correlated with contraceptive discontinuation may inform management and improve adherence.
OCT detects collagen fiber alignment in human cadaveric lumbar facet capsular ligament during mechanical loading

The lumbar facet capsular ligament (FCL) is a highly collagenous structure that functions to constrain lumbar spinal motion. Two FCLs are found at each level of the spine, flanking the spinous process. The ligament spans from the inferior articular process (IAP) of the superior vertebra to the superior articular process (SAP) of the inferior vertebra forming the posterior portion of the facet capsule (Figure 1). Along with the anteriorly located ligamentum flavum, the FCL contains the synovial fluid that lubricates the facet joint. The facet capsule is highly innervated [1] and may be involved in low back pain or proprioception. Thus, changes in collagen fiber alignment from mechanical loading may activate mechanoreceptors leading to proprioception or nociceptors leading to pain.Copyright © 2012 by ASME
Web-based forms for ILL using HTML

ABSTRACT In order to facilitate more effective communication between interlibrary loan users and office staff, a collaborative effort was initiated to develop a new and enhanced electronic ILL request form. Development of the Web-based form is described along with a description of HTML, the infrastructure of the Web and how Web forms collect and organize ILL requests.
Changes in the probability of bankruptcy and equity value

Abstract Work in finance suggests that changes in the probability of bankruptcy likely affect firm value by affecting perceptions of the cost of transacting with the firm. In this paper, accounting information from the balance sheet as well as the income statement is used in conjunction with Ohlson's (1980) bankruptcy prediction model to calculate unexpected changes in the probability of bankruptcy. For a sample of firms with a large estimated probability of bankruptcy sometime during the ten-year study period, unexpected changes in the probability of bankruptcy are useful in explaining security returns even after controlling for unexpected earnings.
Distribution of Nitrate and Orthophosphate in Selected Streams in Central Nebraska

: The Central Nebraska Basins is one of 60 study units in the National Water-Quality Assessment Program of the U.S. Geological Survey. The study unit includes the Platte River and two major tributaries, the Loup and Elkhorn Rivers. Agriculture is the predominant land use in the study unit, with only eight urbanized communities exceeding a population of 10,000. Water samples were collected from selected streams in the study unit during 1993–1995. The data were used to assess the distribution of nitrogen compounds and phosphorus in the streams and to relate the concentrations of these constituents to environmental settings. This article focuses on dissolved nitrate and orthophosphate. Dissolved nitrate concentrations were highest (90th percentiles were less than 7.0 milligrams per liter as nitrogen) in areas with extensive cropland and pasture, where chemical fertilizers are intensively applied. Synoptic measurements conducted in March and August 1994 indicate that relatively little residual fertilizer, as nitrate, applied during a single crop-growing season enters streams. Dissolved nitrate concentrations showed a seasonal pattern, being highest during winter months and lowest during the late spring and summer. Dissolved orthophosphate concentrations tended to be low across the study unit, 90 percent of all analyses did not exceed 1.7 milligrams per liter as phosphorus.
Autophagy induced by deficiency of sphingosine-1-phosphate phosphohydrolase 1 is switched to apoptosis by calpain-mediated autophagy-related gene 5 (Atg5) cleavage.

Sphingosine 1-phosphate (S1P) and ceramide have been implicated in both autophagy and apoptosis. However, the roles of these sphingolipid metabolites in the links between these two processes are not completely understood. Depletion of S1P phosphohydrolase-1 (SPP1), which degrades intracellular S1P, induces the unfolded protein response and endoplasmic reticulum stress-induced autophagy (Lepine, S., Allegood, J. C., Park, M., Dent, P., Milstien, S., and Spiegel, S. (2011) Cell Death Differ. 18, 350–361). Surprisingly, however, treatment with doxorubicin, which by itself also induced autophagy, markedly reduced the extent of autophagy mediated by depletion of SPP1. Concomitantly, doxorubicin-induced apoptosis was greatly enhanced by down-regulation of SPP1. Autophagy and apoptosis seemed to be sequentially linked because inhibiting autophagy with 3-methyladenine also markedly attenuated apoptosis. Moreover, silencing Atg5 or the three sensors of the unfolded protein response, IRE1α, ATF6, and PKR-like eIF2α kinase (PERK), significantly decreased both autophagy and apoptosis. Doxorubicin stimulated calpain activity and Atg5 cleavage, which were significantly enhanced in SPP1-depleted cells. Inhibition or depletion of calpain not only suppressed Atg5 cleavage, it also markedly decreased the robust apoptosis induced by doxorubicin in SPP1-deficient cells. Importantly, doxorubicin also increased de novo synthesis of the pro-apoptotic sphingolipid metabolite ceramide. Elevation of ceramide in turn stimulated calpain; conversely, inhibiting ceramide formation suppressed Atg5 cleavage and apoptosis. Hence, doxorubicin switches protective autophagy in SPP1-depleted cells to apoptosis by calpain-mediated Atg5 cleavage.
Novel cyclic peptide inhibits intercellular adhesion molecule-1-mediated cell aggregation

Leukocyte adherence mediated by intercellular adhesion molecule-1 (ICAM-1) binding to leukocyte function-associated antigen (LFA-1) is required for proper inflammatory and immune function. Inhibition of ICAM-1\LFA-1 binding using monoclonal antibodies (mAb) has been shown to be efficacious at inhibiting lymphoma metastasis as well as leukocyte emigration into tissue in a number of inflammatory diseases such as ischemia-reperfusion injury, septic shock and rheumatoid arthritis. In this report, we describe the development and characterization of a small peptide antagonist of ICAM-1-dependent cell aggregation. By using repeated selection of a cyclic nonapeptide phage display library on purified ICAM-1, we identified phage that were competitively eluted with anti-ICAM-1 mAb. The peptide sequences were determined by nucleotide sequencing, and the peptide sequence (C*LLRMRSIC*) (IP01) that occurred most frequently was chosen for further study. Phage expressing this peptide sequence specifically bound ICAM-1 over a range of 5 x 10(6) to 1 x 10(8) phage/microL. A cyclic IP01 peptide, linear IP01 peptide, a cyclic nonapeptide with a scrambled IP01 sequence, and a random, cyclic nonapeptide were synthesized. The cyclic and linear IP01 peptides were able to inhibit ICAM-1-mediated cell aggregation at a concentration of 1 mM, whereas the random and scrambled peptide sequences did not alter aggregation. Cyclic IP01 had a half-maximal inhibitory concentration of approximately 970 microM. Cyclic IP01 did not inhibit cellular aggregation that was dependent on ICAM-2 or ICAM-3. Alanine substitutions in the cyclic IP01 identified at least four amino acids necessary for inhibition of ICAM-1 dependent cell aggregation; leucine 2, leucine 3, methionine 5, and arginine 6. Finally, we showed that cyclic IP01 can inhibit firm adhesion of neutrophils to endothelium, a critical event in inflammatory diseases, in an assay that recapitulates physiologic flow conditions. Homology of IP01 with the primary amino acid sequences of the alpha or beta subunit of LFA-1 was not identified. Thus, we identified a unique molecule that inhibits ICAM-1 dependent cell adhesion, but is not related to the primary sequence of the ICAM-1 ligand LFA-1. Due to the small size and ability to block cell-cell adhesion, IP01 may serve as a useful tool for study of ICAM-1 and LFA-1 biology as well as for the development of small molecule therapeutics.
gamma-Butyrobetaine as a specific antagonist for carnitine in the development of the early chick embryo.

The effect of γ-butyrobetaine alone and with the addition of carnitine on the development of the early excised chick embryo has been studied. γ-Butyrobetaine in appropriate amounts exerts an inhibitory effect which can be relieved or annulled by the inclusion of appropriate amounts of carnitine. This has been interpreted as a metabolite-antimetabolite relationship, in which the normal metabolite, carnitine, is antagonized by the structurally closely related γ-butyrobetaine, and is regarded as evidence of an important role of carnitine in the metabolism of the developing chick embryo.
Kinetic mechanism of the Cu(II) enzyme galactose oxidase.

The steady-state kinetics of four redox reactions catalyzed by galactose oxidase have been determined. The alcohol substrate used in each case was galactose; the four oxidant substrates used were O2, IrCl62−, porphyrexide, and Fe(CN)63−. With the exception of the last reagent, saturation behavior is exhibited by all substrates. Double reciprocal plots of rate data obtained varying one substrate at various concentrations of the other are intersecting for all pairs that exhibited saturation behavior. Thus, these reactions are kinetically sequential processes involving single central complexes. These complexes involve enzyme, galactose, and one molecule of oxidant, whether or not the oxidant is a one- or two-electron acceptor. This result indicates that for one-electron oxidants, an enzyme-alcohol-derived radical species may exist as a transient prior to the reaction of the second electron equivalent of oxidant. A similar substrate transient is postulated in the reaction involving O2. The inhibition by H2O2 has also been studied in detail. H2O2 apparently binds to the enzyme at two sites. The nature of alcohol and O2 binding to the enzyme Cu(II) is discussed in light of these kinetic results.
DNA-dependent PK inhibits adeno-associated virus DNA integration

Recent studies have shown that recombinant adeno-associated virus (rAAV) can persist in episomal form; however, factors affecting rAAV persistence are poorly understood. DNA-dependent PK (DNA-PK) is a DNA repair enzyme, which we previously found played an important role in determining the molecular fate of the rAAV genome in mouse skeletal muscle. In the present study, we tested the effect of DNA-PK on AAV serotype 2 integration in vitro and in vivo in mouse liver. In an in vitro integration system, addition of DNA-PK decreased AAV integration, whereas antibody against DNA-PKcs increased integration. In vivo, matched doses of a recombinant AAV serotype 2 vector were injected into the portal vein of either C57BL/6 (DNA-PKcs+/+) or severe combined immunodeficient (DNA-PKcs-/-) mice. After partial hepatectomy to stimulate hepatocyte proliferation, retention of vector genomes and of transgene expression was substantially higher in severe combined immunodeficient mice, indicating that in the absence of DNA-PKcs, a greater proportion of genomes integrated into the cellular genome. In summary, we have provided evidence that DNA-PK inhibits AAV integration both in vitro and in vivo.
Model of Eddy Current Damping Mechanism for the Suppression of Beam Vibrations

The movement of a conductor through a stationary magnetic field or a time varying magnetic field through a stationary conductor generates electromagnetic forces that can be used to suppress the vibrations of a flexible structure. In the present study, a new electromagnetic damping mechanism is introduced. This mechanism differs from previously developed electromagnetic braking systems and eddy current dampers because the system investigated in the following manuscript uses the radial magnetic flux of a permanent magnet to generate the electromagnetic damping force rather than the flux perpendicular to the magnet’s face as done in other studies. One important advantage of the proposed mechanism is that it is simple and easy to be applied. Additionally, a single magnet can be used to damp the transverse vibrations that are present in many structures. Furthermore, it doesn’t require any electronic devices or external power supplies, therefore functioning as a non-contacting passive damper. A theoretical model of the system is derived using electromagnetic theory, enabling us to estimate the electromagnetic damping force induced on the structure. The proposed eddy current damper was constructed and experiments were performed to verify the precision of the theoretical model. It is found that the proposed eddy current damping mechanism increases the damping ratio by up to 150 times and provides sufficient damping force to quickly suppress the beam’s vibration.Copyright © 2004 by ASME
Prospective detection of large prediction errors: a hypothesis testing approach

Real-time motion management is important in radiotherapy. In addition to effective monitoring schemes, prediction is required to compensate for system latency, so that treatment can be synchronized with tumor motion. However, it is difficult to predict tumor motion at all times, and it is critical to determine when large prediction errors may occur. Such information can be used to pause the treatment beam or adjust monitoring/prediction schemes. In this study, we propose a hypothesis testing approach for detecting instants corresponding to potentially large prediction errors in real time. We treat the future tumor location as a random variable, and obtain its empirical probability distribution with the kernel density estimation-based method. Under the null hypothesis, the model probability is assumed to be a concentrated Gaussian centered at the prediction output. Under the alternative hypothesis, the model distribution is assumed to be non-informative uniform, which reflects the situation that the future position cannot be inferred reliably. We derive the likelihood ratio test (LRT) for this hypothesis testing problem and show that with the method of moments for estimating the null hypothesis Gaussian parameters, the LRT reduces to a simple test on the empirical variance of the predictive random variable. This conforms to the intuition to expect a (potentially) large prediction error when the estimate is associated with high uncertainty, and to expect an accurate prediction when the uncertainty level is low. We tested the proposed method on patient-derived respiratory traces. The 'ground-truth' prediction error was evaluated by comparing the prediction values with retrospective observations, and the large prediction regions were subsequently delineated by thresholding the prediction errors. The receiver operating characteristic curve was used to describe the performance of the proposed hypothesis testing method. Clinical implication was represented by miss detection rate and delivery efficiency. Both characterizations demonstrated the promising results and provided insight into the tradeoffs in the detection task. This study opens the discussion on real-time analysis of prediction accuracy and promises important information in automatically adjusting treatment and/or target monitoring schemes.
The Search for Simplicity: A.K. Romney and Building Models From Systematic Data

For more than 50 years, A.K. Romney and his many collaborators have published a steady stream of methods, ideas, critiques, and findings. This influential body of work has been characterized by a strong interest in quantification, extensive use of graphics and visual presentations of data, a focus on empirical issues, a search for cultural universals, intensive collaboration with other researchers, and a striving for conciseness and clarity. Of these, the search for simplicity is perhaps the most notable and pervasive characteristic of his work. This article reviews some of Romney’s early work on kinship, tracing the way in which Romney’s treatment of kinship data was influenced by his basic notion of humans as accurate and principled categorizers.
Misdiagnosis of Appendicitis and the Use of Diagnostic Imaging

Background CT and ultrasound (US) are increasingly recommended to establish the diagnosis of appendicitis, but population-based rates of misdiagnosis (negative appendectomy [NA]) have not improved over time. The objective of this study was to determine the relationship between CT/US and NA in common practice. Study design Using data from the Group Health Cooperative on all patients undergoing appendectomy between 1980 and 1999, a longitudinal study was conducted to determine the frequency of NA over time and a case-control, medical record–based study of a subset of patients from the 1990s was conducted to determine the accuracy of CT/US. Results Of 4,058 patients undergoing appendectomy (mean age 31 ± 18.6 [SD] years, 49.6% women), 631 (15.5%) had an NA. The overall incidence of NA remained stable over time at 1.5/10,000 patient-years, as did the age and gender adjusted rate (incident rate ratio 0.95, 95% CI 0.97, 1.01). In 1999, nearly 40% of patients had either CT or US. The aggregate sensitivity of these tests was only 74.2% (95% CI 65.7, 83.7), with a positive predictive value of 95.1% (95% CI 91.5, 96.8). CT scans were 88.3% sensitive, with 97.2% positive predictive value (95% CI 92.9, 100). Ultrasounds were 69.5% sensitive, with a positive predictive value of 94.1% (95% CI 89.6, 96.4). More than one in five tests obtained in patients with NA were positive for appendicitis (21.7% for CT and 20.8% for US). Conclusions The rate of NA was unchanged over time despite the introduction and use of CT/US, and this appeared to be related to the inconsistent performance characteristics of the tests. This study cautions against overreliance on CT/US in diagnosing appendicitis and emphasizes the need for test benchmarking in routine practice before establishing protocols for presumed appendicitis.
Continuous Peripheral Nerve Block for Postoperative Pain Control at Home: A Prospective Feasibility Study in Children

Background and Objectives: We assessed the feasibility and efficacy of postoperative pain control by continuous peripheral nerve blockade (CPNB) in children after early home discharge under parental surveillance. Methods: All children scheduled for primary elective ankle or foot surgery under sciatic popliteal CPNB and general anesthesia were evaluated. After obtaining the surgeon9s consent, the children were discharged on either the day (D) of surgery (D0), or on postoperative D1 or D2 (depending on whether they needed a plaster cast or a suction drainage). The CPNB was continuously infused, using an elastomeric pump. Before the procedure, the parents were taught how to assess their children9s pain, to use rescue analgesia, and to manage an infusion elastomeric pump device, and when to call the hospital in case of emergency. The children returned to the hospital for catheter removal and the recording of any postoperative event. Results: Forty-seven children were entered into this observational study. Two were discharged home on the same day, 30 were discharged home 1 day after surgery, and 15 were discharged home 2 days after surgery. The mean duration of infusion elastomeric pump at home was 3 days (range, 2 to 4 days). Analgesia was rated as excellent or good in 89% of the cases, and the quality of sleep was always good, except for three patients. Some minor untoward effects were recorded. Two children returned to the hospital because of accidental disconnection of the infusion elastomeric pump from the catheter. Four patients presented skin redness at the puncture site, but no infection was observed, and all catheters remained sterile. No parents called the hospital. The children9s quality of life was rated as excellent or as satisfactory overall, by both the children and their parents. Conclusions: Shortening hospital stays with the use of at-home CPNB under sole parental supervision is feasible, after selecting children with a suitable family environment.