cssi/SciSciGPT-SciSciNet huggingface dataset:
Power analyses for longitudinal study designs with missing data

Existing methods for power analysis for longitudinal study designs are limited in that they do not adequately address random missing data patterns. Although the pattern of missing data can be assessed during data analysis, it is unknown during the design phase of a study. The random nature of the missing data pattern adds another layer of complexity in addressing missing data for power analysis. In this paper, we model the occurrence of missing data with a two-state, first-order Markov process and integrate the modelling information into the power function to account for random missing data patterns. The Markov model is easily specified to accommodate different anticipated missing data processes. We develop this approach for the two most popular longitudinal models: the generalized estimating equations (GEE) and the linear mixed-effects model under the missing completely at random (MCAR) assumption. For GEE, we also limit our consideration to the working independence correlation model. The proposed methodology is illustrated with numerous examples that are motivated by real study designs.
Measuring fire spread rates from repeat pass airborne thermal infrared imagery

The objective is to evaluate procedures for direct measurement of fire spread rates (FSRs) based on archived repeat pass airborne thermal infrared (ATIR) imagery and to identify requirements for more refined measurements of FSR and environmental factors that influence FSR. Flaming front positions are delineated on sequential FireMapper ATIR images captured at relatively short repeat intervals enabling fire spread vectors and units to also be delineated. This approach provides the only means for estimating FSR for wildfires at spatial scales in the order of 101–103 m and timescales from 102 to 105 s. Magnitudes of estimated FSR from the time sequential ATIR approach for the 2002 Williams fire in southern California tested here are reasonable, given the fire conditions are within the range of rates reported in the literature for wildland fires in Mediterranean shrublands.
Metabolic pathways and nitrogen metabolism inLegionella pneumophila

An examination of cellular extracts ofLegionella pneumophila (Philadelphia 1 and Knoxville 1) was undertaken and key enzymes of the Embden-Meyerhof-Parnas (EMP) and pentose phosphate (PP) pathways, and the Krebs cycle were found. No enzymatic evidence of the ED pathway was obtained. In regard to carbon flow in the EMP pathway, the activities of fructose-1,6-biphosphatase (6–7.3 nmol/min/mg protein) and of phosphofructokinase (0.67–0.8 nmol/min/mg protein) suggested a gluconeogenic role. In further support of this direction, good activities were detected for phosphoenolpyruvate carboxylase and phosphoenolpyruvate carboxykinase. While an energized membrane was required for glutamate uptake by whole cells, an energized mechanism for glucose uptake could not be demonstrated. The Krebs cycle was essentially complete and, despite high specific activities for isocitrate and malate dehydrogenases, whole cells failed to oxidize these substrates, suggesting a transport deficiency. The major carbon and energy sources serine and glutamate were catabolized vial-serine dehydratase and glutamate-aspartate transaminase, respectively. This study confirmed that amino acids are catabolized via the Krebs cycle and that sugars are synthesized by the gluconeogenic enzymes of the EMP pathway.
Metacomprehension During Rare Word Comprehension

To examine metacomprehension during comprehension, undergraduates (n = 133) were asked to provide descriptions of how they determined the meaning of four rare words presented in short passages. Content analysis of these written descriptions revealed task-specific metacomprehension reflecting lexical, textbase, and situation model processes. Cluster analysis yielded four metacomprehension groups with differing emphases on textbase and situation model processes. Participants also provided definitions, post-comprehension assessments, and completed the Metacomprehension Scale. Differences across the subgroups provide evidence that individual differences in task-specific metacomprehension influence interpretation accuracy and post-comprehension assessments. In contrast, global metacomprehension subscales were uncorrelated with interpretation accuracy.
Determination of high-precision GPS orbits using triple differencing technique

Precise orbits of the Global Positioning System (GPS) satellites are fundamental constituents of GPS-based space geodesy. Accurate baseline estimates with a precision of one to a few parts in 108 are essential to the study of Earth's dynamics problems. As a by-product of trajectory estimation, high resolution Earth Rotation Parameters (ERPs) can also be determined. A new application of triple differencing for efficient evaluation of GPS orbits in a PC environment is presented here. Initial tests show that this approach is capable of providing orbits that are highly compatible with the results obtained by the International GPS Service for Geodynamics (IGS). This approach allows for completely automated data processing without the overhead of working with very large normal matrices or cycle-slip fixing.
Induction of anchorage-independent growth in human diploid fibroblasts by the cyclopenta-polycyclic aromatic hydrocarbon, benz[l]aceanthrylene.

Abstract Cyclopenta-fused polycyclic aromatic hydrocarbons are a class of environmental PAH that have been recently identified. Many of these chemicals have been found to be more active than benzo[ a ]pyrene in tests for genetic toxicity using bacterial and rodent cells. Benz[ l ]aceanthrylene, a cyclopenta-polycyclic aromatic hydrocarbon related to benz[ a ]anthracene, and benzo[ a ]pyrene were compared for their activity to induce cytotoxicity and anchorage-independent growth with normal human diploid fibroblasts. Both benz[ l ]aceanthrylene and benzo[ a ]pyrene were relatively non-cytotoxic to normal human diploid fibbrolasts. However, benz[ l ]aceanthrylene was twice as active compared to benzo[ a ]pyrene over the concentration range examined as an inducer of anchorage-independent growth. The ability of benz[ l ]aceanthrylene to induce anchorage-independent colony growth in normal human cells, in combination with its demonstrated ability as a mouse-skin tumorigen, suggests this PAH to be a potential multi-species carcinogen.
Soviet Socialism: The Era of War Communism

The Soviet experiment on socialism provides several distinguishable politico‐economic models. Employing dialectical methodology, examines the political economy of War Communism (1917‐21) as an exemplar of the “Socialist Command Model”. Explores the economic, political and social forces that were responsible for the emergence of the model, its policies, programmes and consequences, and finally, the forces that made it obsolete for the subsequent stages of Soviet development.
Progressive spasticity in an infant

A 15-month-old girl with progressive spasticity presented for evaluation of cerebral palsy. Neurological examination revealed severe asymmetric spasticity with normal cranial nerves. Bayley developmental assessment showed a mental age of 12 months and a motor age of 9 months. Magnetic resonance imaging scan of the brain was normal, however a scan of the cervical spine showed an enhancing intramedullary lesion. Surgical exploration revealed an aneurysm which was successfully embolized. The differential diagnosis of cervical cord lesions in infants is discussed.
Compact modeling of collector base junction space charge region transit time effect on noise in SiGe HBTs

This paper investigates the impact of collector-base space charge region (CB SCR) transport on RF noise in bipolar transistor using compact modeling. A model applicable to any compact models is derived and implemented using Verilog-A. Comparison with noise measurement on a SiGe HBT technology shows that overall the noise modeling results are much improved. The imaginary part of optimum generator admittance is slightly worse than without this effect.
RADIATIVE CORRECTION TO EIKONAL FUNCTIONS IN ELECTRODYNAMICS.

We show that the second-order radiative correction changes the electron eikonal function into $[1+F({k}^{2})]\ifmmode\times\else\texttimes\fi{}[1+{F}^{\ensuremath{'}}({k}^{2})]E({k}^{2})$, where $E({k}^{2})$ is the bare eikonal, $k$ is the momentum transfer between the electrons ($e$ and ${e}^{\ensuremath{'}}$), and $F({k}^{2})$ is the second-order electric form factor. This suggests that in high-energy near-forward electrodynamic processes, the eikonals should be regarded as the basic carriers of the interaction.
Decoherence in nearly isolated quantum dots.

Decoherence in nearly isolated GaAs quantum dots is investigated using the change in the average Coulomb blockade peak height when time-reversal symmetry is broken. The normalized change in the average peak height approaches the predicted universal value of $1/4$ at temperatures well below the single-particle level spacing, $Tl\ensuremath{\Delta}$, but is greatly suppressed for $Tg\ensuremath{\Delta}$, suggesting that inelastic scattering or other dephasing mechanisms dominate in this regime.
Stress intensity factors of a radial crack in a rotating compound disk

Abstract A rotating compound disk or compound cylinder containing a radial crack is studied and the stress intensity factors of the crack are calculated. To approach the crack problem, the uncracked rotating compound disk solution is sought first and by superposition with the uncracked geometry, the crack problem may be reduced to a perturbation case. By integrating the corresponding dislocation solution, a singular integral equation may be generated. The stress intensity factor of the crack is related to the solution of the singular integral equation, and can be evaluated accurately by virtue of a collocation technique. Extensive numerical results for both plane strain and plane stress cases are presented in tabular and graphical forms.
A Trimming-Free CMOS Bandgap-Reference Circuit with Sub-1-V-Supply Voltage Operation

We propose a bandgap-reference circuit (BGR) that is very robust against voltage, temperature, and local device variations and features sub-l-V operation. The BGR achieves "3sigma = 2.5%" accuracy for local variation and operates at a 0.95-V-supply voltage.
Chronic lead exposure alters presynaptic calcium regulation and synaptic facilitation in Drosophila larvae.

Abstract Prolonged exposure to inorganic lead (Pb 2+ ) during development has been shown to influence activity-dependent synaptic plasticity in the mammalian brain, possibly by altering the regulation of intracellular Ca 2+ concentration ([Ca 2+ ] i ). To explore this possibility, we studied the effect of Pb 2+ exposure on [Ca 2+ ] i regulation and synaptic facilitation at the neuromuscular junction of larval Drosophila . Wild-type Drosophila (CS) were raised from egg stages through the third larval instar in media containing either 0 μM, 100 μM or 250 μM Pb 2+ and identified motor terminals were examined in late third-instar larvae. To compare resting [Ca 2+ ] i and the changes in [Ca 2+ ] i produced by impulse activity, the motor terminals were loaded with a Ca 2+ indicator, either Oregon Green 488 BAPTA-1 (OGB-1) or fura-2 conjugated to a dextran. We found that rearing in Pb 2+ did not significantly change the resting [Ca 2+ ] i nor the Ca 2+ transient produced in synaptic boutons by single action potentials (APs); however, the Ca 2+ transients produced by 10 Hz and 20 Hz AP trains were larger in Pb 2+ -exposed boutons and decayed more slowly. For larvae raised in 250 μM Pb 2+ , the increase in [Ca 2+ ] i during an AP train (20 Hz) was 29% greater than in control larvae and the [Ca 2+ ] i decay τ was 69% greater. These differences appear to result from reduced activity of the plasma membrane Ca 2+ ATPase (PMCA), which extrudes Ca 2+ from these synaptic terminals. These findings are consistent with studies in mammals showing a Pb 2+ -dependent reduction in PMCA activity. We also observed a Pb 2+ -dependent enhancement of synaptic facilitation at these larval neuromuscular synapses. Facilitation of EPSP amplitude during AP trains (20 Hz) was 55% greater in Pb 2+ -reared larvae than in controls. These results showed that Pb 2+ exposure produced changes in the regulation of [Ca 2+ ] i during impulse activity, which could affect various aspects of nervous system development. At the mature synapse, this altered [Ca 2+ ] i regulation produced changes in synaptic facilitation that are likely to influence the function of neural networks.
Co-expression of tissue inhibitor and matrix metalloproteinase in myocardium

Matrix metalloproteinases (MMP) are present in the latent form in normal myocardium. To examine the stringent balance between MMP and tissue inhibitor of metalloproteinase (TIMP) and to determine whether MMP are secreted simultaneously and in co-ordination with their inhibotors, we analyzed MMP and TIMP by immunological, isolation br gelpermeation and affinity chromatography, and enzymatic assays in tissues and extracts> Using antibodies to MMP-1 and TIMP-1, we found strong in situ staining of MMP-1 and TIMP-1 in tissues. The staining was uniform in the endo0 and subendomyocardium as well as in the interstitial space. TIMP-1 was present wherever MMP-1 was localized. From the tissue extract, proteins were separated on a gel-filtration column (Sephacryl S-200) and analysed for MMp and TIMP activity by zymography as well as by using succinyl-Gly-Pro-Leu-Gly-Pro-4-amido-7-methyl coumarin (Suc-GPLGP-AMC) as a selective fluorogenic substrate for collagenase. TIMP and MMP were further purified on collagen0Sepharose affinity column. The results indicated that MMP activity was co-eluted with TIMP activity. MMP-1, MMP-2 and TIMP-1 were further analysed by Northern blot for mRNA levels in the heart, skin, lung, liver and kidney. Results suggested co-expression of MMP-1 and TIMP-1 at the transcription level in all tissues. The level of MMP-2 mRNA was specifically higher in the biggest heart tissue, which suggest a role of MMP-2 in the integrity of cardiovascular structure. The study indicate that myocardium as well as other tissue have an endogenous inhibitory system, suggesting that the MMPs activity is co-ordinated by their inhibitors at both the gene and protein levels. Furthermore, MMP and TIMP were co-expressed and were tightly regulated in maintaining the architecture of the interstitial tissue.
Selective purification of the 20,000-Da light chains of smooth muscle myosin

Abstract The 20,000-Da light chains of gizzard smooth muscle myosin have been purified to homogeneity. Actomyosin, prepared by MgATP extraction of myofibrils, was denatured in 8 m urea, 1 m guanidine HCl, and 0.05% sodium dodecyl sulfate. Myosin heavy chains were precipitated with ethanol and the light chain enriched fraction was dialyzed and subjected to chromatography on DEAE-Sephacel. Fractions containing the 20,000-Da light chains were further purified by hydrophobic chromatography on phenyl-Sepharose. The 20,000-Da light chains eluted at low ionic strength from the phenyl-Sepharose column were judged to be >95% pure by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and contained only 0.04 mol of phosphate/mol of light chain. The yield of light chains was calculated to be 219 ± 17 mg/kg of starting gizzard smooth muscle. This method may be useful for preparation of homogenous 20,000-Da smooth muscle myosin light chains in the quantities necessary for study of contractile systems.
A note on the rogue failure of turbine blades

A residual amount of random non-uniformity in the properties of nominally identical products is inevitable, due to the stochastic nature of manufacturing processes. Such differences are usually ignored, since they are small and are within the tolerance limits. However, they are not always negligible in the case of turbine blades coupled together through the elasticity of the disc or shroud bands. It is shown that, under certain conditions, a small degree of imperfection can give rise to the localization of vibration around one or two blades, and that such a localization has the potential for inducing unexpected failure of rogue blades.
A Framework for Classifying Subsistence Production Types of Nepal

This paper defines a four-tiered, hierarchical system for classifying subsistence production types in Nepal and uses the system to describe the subsistence communities of central Nepal. The system first divides Nepal into a grid of homogenous parts or “cells,” second, it divides, the cells into “ridge-valley slope sequences,” third, defines “production types” for the ridge-valley slope sequences, and, finally, distinguishes local “variants” of the production types. After describing these tiers, I apply these categories to the northern portions of the central and western development regions where I have done research. I then define how representatives of Nepal as a whole are the production types defined for the central and western development regions. Finally, the paper locates some completed studies within its framework.
THE CLASSIFICATION OF NONLINEAR BEHAVIOR FOR CONTROL SYSTEMS WITH SINGULARITIES

Abstract Nonlinear dynamical systems exhibit complicated behavior around singular points. Because of the extra degrees of freedom introduced to the system and to the transformation group by the control input, some bifurcations of control systems have fundamentally different behavior from those in the classical theory of dynamical systems. There exists a wide variety of qualitatively different nonlinear behavior around singular points. Nevertheless, some elementary types of nonlinear behavior of control systems can be classified by using normal forms. This talk aims to introduce three related aspects of the classification of nonlinear behavior, namely the classification of singularities, the normal forms, and the qualitative properties of control systems. For the singularities, I will focus on those with low codimension. I will present the normal forms of control systems around singular points. These normal forms are useful as the representatives of general control systems for the purpose of analysis and design. In addition, I will discuss the classification of some critical qualitative properties and the closed-loop behavior of the normal forms. At the end of the talk, I will describe some topics and open problems for future research
Local Determination of a Moving Contrast Edge

This paper proposes an intensity-based method for determining the spatial orientation and observed velocity of a continuously moving edge. Space-time relations arise from the translation of a straight edge across a fixed detector array; a tesselation unit comprised of three equidistant detectors is used to exploit these relationships. The time ordering of cells within this unit can estimate edge direction and velocity. More precise edge determination is possible when intercell times are available and constant edge velocity is assumed; a sensitivity analysis examines the effect of relaxing the velocity constraint. The simulation of a translating synthetic image over an array of detectors is presented in order to demonstrate the method.
An unwindowed RLS adaptive lattice algorithm

A covariance-RLS lattice adaptive-filtering algorithm is presented. The algorithm permits nonzero initial conditions and need not 'warn' N-1 iterations in advance of the first iteration to preserve its low computational requirements. These are both improvements over previous lattice algorithms. The algorithm also has a slight computational advantage over previous solutions, rendering it more applicable to adaptive-filtering applications such as fast-starting adaptive equalizers and echo cancellers, where the initial data in the adaptive filter are not, and cannot be assumed to be, zero. >
Finite region density increase effects in the Lee-Wick model

We investigate the effect of nuclear density increase in a finite space-time region. Field theoretical treatment of the nucleon field but classical treatment of the mesonic field leads to a solvable interaction of pair theory type in the nuclear field. A mesonic soliton solution is discussed. Energy transfer into the nucleon field is calculated.
Exchange effects in the 7Li(3He, α)6Li reaction

Abstract Angular distributions of α-particles from the 7Li(3He, α)6Li reaction at 3He bombarding energies of 16 and 18 MeV are analyzed with an exact finite-range two-mode DWBA formalism using the computer code FANLU2. It is demonstrated that within the formalism used it is essential to include the exchange mode of the reaction. The overall features of the angular distributions are described remarkably well, but a strong dependence on optical model parameter sets makes it essential to adhere to a characteristic class of such sets. Spectroscopic factors for direct and exchange modes are extracted and discussed.
A working memory “theory of relativity”: elasticity in temporal, spatial, and modality dimensions conserves item capacity in radial maze, verbal tasks, and other cognition

Abstract It is remarkable that working memory (WM) capacity for numbers of items remains modest, at approximately 7 ± 2 (the so-called “magical number”), across a wide variety of kinds of material. Indeed, consideration of radial maze studies together with more traditional memory research shows that WM capacity remains fairly constant whether the items are verbal or visuospatial, and that this same capacity is true of other species as of humans. In contrast to their limited numerousness, WM items are extremely flexible in ways that are here brought under the heading of “dimensionality.” Therefore, the physical items represented in WM, can vary widely in any quantitative characteristic and in the temporal pace at which they are encountered. Combinatorial considerations suggest that WM numerousness results from evolution of a middle ground between a sterile parsimony and an overwhelming excess, for organizing neurocognitive associations. Such natural selection seems likely to have worked opportunistically to yield diverse characteristics of neuronal tissue, from subcellular components to properties of ensembles, which converge on the required cognitive properties of WM. Priming and implicit memory may play supporting roles with WM. These intermediate-term memory phenomena allow certain kinds of background information to be accumulated at higher volume than seems possible from the textbook, “modal model” of memory. By expediting attentional focus on subsets of information already in long-term memory, priming may help WM chunks to emerge in limited number as appropriately scaled “figures” from the primed “ground.” The larger neuronal dynamic patterns that embody these cognitive phenomena must regulate their microscopic component systems, automatically selecting those having parameters of temporal persistence, rhythm, and connectivity patterns that are pertinent to the current task. Relevant neural phenomena may include “Hebbian” associativity and persistence of firing patterns in prefrontal or hippocampal neurons. A conceivable basis for scaling and normalizing WM representations, along arbitrarily long or short ranges of any cognitive dimension, involves harmonic multiplier relationships among brain electrical rhythms and/or among topographical spatial periodic representations.
A three-stage model of integrated marketing communications at the marketing-sales interface

Abstract The marketing and sales functions in many firms are often at odds despite their common goal of increasing revenue and profit. The finger pointing goes both ways: Marketing complains of poor lead follow-up by sales, and in turn, sales grumbles about the quality of leads generated by marketing. This disconnect can be damaging; high lead volumes generated through effective marketing campaigns could actually hurt downstream sales because of wasted effort on poorly qualified leads and/or delays in sales follow-up resulting from limited sales force capacity. To examine the revenue and profit implications of coordinated communications efforts at the marketing–sales interface, the authors develop a three-stage model that captures the effects of sequential marketing/sales communications on lead generation, appointment conversion, and sales closure. The results, which are based on a collaborative effort with a large home improvement retailer, suggest a complex interplay among marketing efforts (multiple me...
Heaven in the American Imagination, by Gary Scott Smith, Oxford University Press: New York, 2011, xii + 339 pp. ISBN 978 0 19 973895 3, US$29.95 (cloth)

Heaven in the American Imagination, by Gary Scott Smith, Oxford University Press: New York, 2011, xii + 339 pp. ISBN 978 0 19 973895 3, US$29.95 (cloth) In the preface to Heaven in the American Ima...
Thermostable llama single domain antibodies for detection of botulinum A neurotoxin complex.

Immunoglobulins from animals of the Camelidae family boast unique forms that do not incorporate light chains. Antigen binding in these unconventional heavy-chain homodimers is mediated through a single variable domain. When expressed recombinantly these variable domains are termed single domain antibodies (sdAb) and are among the smallest naturally IgG-derived antigen binding units. SdAb possess good solubility, thermostability, and can refold after heat and chemical denaturation making them promising alternative recognition elements. We have constructed a library of phage-displayed sdAb from a llama immunized with a cocktail of botulinum neurotoxin (BoNT) complex toxoids and panned the library for binders for BoNT A complex toxoid. Six unique binders were isolated and found to specifically bind BoNT A complex in toxoid and untoxoided forms and when used in optimal combinations in buffer and milk could detect 100 pg/mL untoxoided complex. All sdAb retained their ability to specifically bind target after h...
Fertility Impairment in Mice on a Low Fluoride Intake

Female mice maintained on a low fluoride diet over two generations showed a progressive decline in litter production. Mice receiving the same diet supplemented with fluoride reproduced normally and at consistent intervals. Addition of fluoride to the intake of females with demonstrated impaired fertility restored their reproductive capacity.
Niemann–Pick type C pathogenesis and treatment: from statins to sugars

The isolation of the causative genes for Niemann–Pick type C disease, a panethnic lysosomal lipid storage disorder, has provided models of how sterols and other lipids such as glycosphingolipids traverse the membranes of eukaryotic cells. Unfortunately, these molecular advances have yet to reciprocate with a cure for this devastating neurodegenerative disorder where neuronal replenishment will most likely yield the greatest benefit. In the meantime, stabilizing treatment strategies based on the removal of presumably toxic metabolites are in place. For example, the small molecule inhibition of glucosylceramide synthase by miglustat limits ganglioside accumulation and is now the only approved treatment of Niemann-Pick type C. In addition, 2-hydroxypropyl-B-cyclodextrin, a lipid chelator, relieves the lysosomal to endoplasmic reticulum blockage and markedly increases the life expectancy of the murine model. Ultimately, these strategies, targeting the primary biochemical lesion in these cells, and others will likely be combined to provide a synergistic cocktail approach to treating this disease.
In Vivo Needle-Based Electromechanical Reshaping of Pinnae: New Zealand White Rabbit Model

ImportanceElectromechanical reshaping (EMR) is a low-cost, needle-based, and simple means to shape cartilage tissue without the use of scalpels, sutures, or heat that can potentially be used in an ...
Landscape variation in phosphorus concentration and effects on detritus‐based tropical streams

Landscape-scale variation in streamwater phosphorus (P) concentration can affect aquatic food webs. Such variation occurs naturally in streams at La Selva Biological Station in Costa Rica due to spatially variable inputs of geothermally modified groundwater. We examined effects of this gradient on detrital food web components at 16 stream sites. The Michaelis-Menten model provided a good fit of the relationship between soluble reactive phosphorus (SRP) and leaf decay rate, fungal biomass, and invertebrate biomass, indicating that these variables were controlled by P concentration and that half-saturation constants were relatively low (7‐13 m gL 21 SRP). In a subsequent short-term (3 week) whole-stream P enrichment study, we found no effect of P addition on leaf decay rate or on biomass or density of invertebrates. However, laboratory tests of P, N, and Ca concentrations on mass loss of leaves showed detectable stimulation by both N and P after 3 weeks. A fourth study assessed the relative contribution of invertebrate consumption versus P concentration in determining decay rates among streams. The majority of variation was due to P concentration (71%), compared to effects of invertebrates (3%) or invertebrate 3 P interactions (14%). Overall, we found that a landscape-scale natural gradient in P concentration influenced decay rates of organic matter and biomass of consumers, providing evidence that benthic detrital food webs can be limited from the bottom up by nutrients. Microbial processes appeared to be most important in driving differences in organic matter decay among sites, but invertebrates also contributed to elevated decay rates at high-P sites.
Recovery, Dependence or Death After Discharge

Authors’ Reply—Thank you for your comments1 related to our article on prediction of recovery, dependence or death in elders who become disabled during hospitalization.2 We agree that validation of prognostic models such as the one we developed is critical. There are two key reasons for validation.3 The first is to account for the ‘optimism’ that occurs when a model is initially developed, since it is ‘optimized’ to the data. This can be thought of as ‘internal’ validation, and strategies such as dividing the sample into development and validation cohorts or bootstrapping techniques are utilized to estimate the extent to which c statistics may be inflated due to optimism.4 We utilized bootstrapping techniques, and the optimism-adjusted c statistics are reported at the end of the third paragraph of the results section (recovery: 0.76; dependence: 0.66; death: 0.73). The second reason for validation is to determine whether the model developed is predictive in other study populations and can be thought of as ‘external’ validation.3 We acknowledged lack of external validation of our tool as a limitation. Since our article was published, we have been contacted by several other investigators with data that may allow us to take this important next step.
Is there a case for regulating executive pay in the financial services industry

Since at least as early as the 1950s, the press, general public, politicians, and academic researchers have remarked on the high levels of US CEO pay and questioned whether these levels are fair and appropriate, as well as whether executive compensation provides proper incentives. Undoubtedly, executive compensation and incentives will continue to be a hotly debated issue for years to come and we do not contend to settle these disputes in this article. Rather, we begin by highlighting some basic descriptive analysis of CEO pay levels and incentives, in general, as well as a comparative analysis of CEO pay and incentives in the financial services industry. We then describe recent proposals to regulate executive pay in the financial services industry (and more generally), and discuss the merits of such regulation. In summary, although we agree broadly with regulators 鈂 views on the principles that should guide executive compensation practices, we believe that many of these principles are already engrained in the typical executive compensation plan. We also have serious reservations about whether several of the regulatory proposals would achieve their stated objectives.
S-Adenosylmethionine metabolism and DNA methylation in hydrazine-treated rats

The treatment of rats with hepatotoxic doses of hydrazine (NH2-NH2) induces the rapid formation of 7-methylguanine and O6-methylguanine in liver DNA. The methyl moiety in these reactions might be derived from the cellular S-adenosylmethionine pool because radioactivity administered to these rats as methionine rapidly appears in the DNA as methylated guanine. An increased incorporation of radioactivity into 5-methylcytosine was previously reported followed by subsequent suppression. This increased radiolabeling of 5-methylcytosine coincided with time of maximal DNA guanine methylation. To determine the nature of S-adenosylmethionine metabolism during the period of DNA methylation induced by hydrazine treatment, and to determine if the increased radiolabeling of 5-methylcytosine at this time reflected an actual increase in 5-methylcytosine synthesis, liver DNA synthesis and S-adenosylmethionine levels and turnover were assayed. Liver S-adenosylmethionine concentrations varied slightly between control rats and hydrazinetreated rats during the first five hours after hydrazine administration, and no difference was detectable in the incorporation of administered [3H]methionine into S-adenosylmethionine. Because S-adenosylmethionine specific radioactivity in hydrazine-treated rats was not different from control rats, the previously observed increased radiolabeling of 5-methylcytosine appeared to represent an actual increase in synthesis. This conclusion was supported by finding that incorporation of radioactive thymidine into DNA was also accelerated immediately following hydrazine administration, again followed by a decrease. 5-Methylcytosine sythesis, therefore, appears to follow DNA synthesis during hydrazine toxicity, and formation of 7-methylguanine and O6-methylguanine in liver DNA of hydrazine-treated rats occurs during a short period of increased DNA sythesis and 5-methylcytosine formation very early in hydrazine toxicity.
Velocity analysis for plane-wave source migration using the finite-frequency sensitivity kernel

Summary We derive the finite-frequency sensitivity kernel which relating the errors in migration velocity model to residual moveout in common image gathers obtained from planewave source prestack depth migration. The broadband sensitivity kernel is validated by the directly measured sensitivity map. Based on this kernel, we propose a new wave-equation migration velocity analysis approach particularly for plane-wave source migration. This method avoids the expensive local angle or offset decomposition. Numerical method based on the one-way propagator is designed to calculate the sensitivity kernel. Using a simple 2D synthetic data set, we demonstrate the potential application of this new method in migration velocity analysis.
Gene therapy for arthritis

Arthritis is among the leading causes of disability in the developed world. There remains no cure for this disease and the current treatments are only modestly effective at slowing the disease's progression and providing symptomatic relief. The clinical effectiveness of current treatment regimens has been limited by short half-lives of the drugs and the requirement for repeated systemic administration. Utilizing gene transfer approaches for the treatment of arthritis may overcome some of the obstacles associated with current treatment strategies. The present review examines recent developments in gene therapy for arthritis. Delivery strategies, gene transfer vectors, candidate genes, and safety are also discussed.
Reducing the harm of opioid overdose with the safe use of naloxone : a pharmacologic review

Introduction: Opioid overdose fatality has increased threefold since 1999. As a result, prescription drug overdose surpassed motor vehicle collision as the leading cause of unintentional injury-related death in the USA. Naloxone, an opioid antagonist that has been available for decades, can safely reverse opioid overdose if used promptly and correctly. However, clinicians often overestimate the dose of naloxone needed to achieve the desired clinical outcome, precipitating acute opioid withdrawal syndrome (OWS).Areas covered: This article provides a comprehensive review of naloxone’s pharmacologic properties and its clinical application to promote the safe use of naloxone in acute management of opioid intoxication and to mitigate the risk of precipitated OWS. Available clinical data on opioid-receptor kinetics that influence the reversal of opioid agonism by naloxone are discussed. Additionally, the legal and social barriers to take home naloxone programs are addressed.Expert opinion: Naloxone is an intrin...
Polyphenols and Cholesterol Efflux: Is Coffee the Next Red Wine?

Despite strong evidence for an inverse association between high-density lipoprotein cholesterol (HDL-C) levels and cardiovascular risk,1 successful therapeutic strategies to target HDL have remained elusive. A recent Phase III clinical trial failed to show clinical benefit with the cholesteryl ester transfer protein inhibitor torcetrapib despite markedly increased HDL-C levels.2,3 This outcome reinforced a growing consensus that measurement of HDL-C alone may be an incomplete surrogate for the in vivo functionality of HDL and the clinical efficacy of targeting HDL. The careful mechanistic assessment of HDL function has thus emerged as a potential way forward.4 Macrophage reverse cholesterol transport (RCT), the process by which cholesterol is transported from macrophage “foam” cells to the liver for ultimate fecal excretion, has been postulated to play a major role in HDL-mediated atheroprotection.5 Indeed, quantitative measures of macrophage RCT are more strongly associated with atherosclerosis than plasma HDL-C concentrations in mice.6 The first critical step of macrophage RCT involves efflux of cellular cholesterol to circulating HDL particles. Research in recent years has documented a specific role for the macrophage transporters ATP-binding cassette subfamilies A1 and G1 (ABCA1 and ABCG1) in cholesterol efflux (see the Figure). These findings have stimulated efforts to target the macrophage at the cellular level as a means of enhancing overall RCT. For example, pharmacological agonism of the liver X receptor (LXR) upregulates both ABCA1 and ABCG1 expression,7,8 promotes macrophage cholesterol efflux ex vivo and RCT in vivo, …
Transient corticotropin deficiency in critical illness

We describe three critically ill patients who displayed indirect evidence of transient corticotropin deficiency. All these patients were elderly, were poorly nourished, and had unexplained hypotension intraoperatively or immediately postoperatively. During the hypotensive episodes, they had inappropriately low plasma cortisol levels (10, 12, and 6 μg/dl) and responded dramatically to the administration of glucocorticoids. A normal response to infusion of synthetic corticotropin excluded primary adrenal insufficiency. Two patients tested had low thyroxine levels without increased thyrotropin concentrations and depressed levels of gonadotropins. In all three patients, the dose of glucocorticoids was successfully tapered and then discontinued. After recovery, serum thyroxine levels increased, gonadotropins reverted to normal concentrations, and the administration of metyrapone to two patients demonstrated normal hypothalamic-pituitary-adrenal function. Cortisol levels of less than 15 μg/dl in critically ill patients suggest the presence of adrenal insufficiency. The infusion of synthetic corticotropin may not exclude adrenal insufficiency attributable to corticotropin deficiency. If direct tests of corticotropin reserve are impractical, treatment with glucocorticoids is warranted.
Modulation of cocaine-induced place preferences by alcohol.

Abstract Behavioral and physiological evidence suggests that alcohol modulates the effects produced by cocaine. To assess whether such modulation is evident with cocaine's affective properties, the present studies examined the effects of alcohol on cocaine-induced conditioned place preferences (CPP). In Experiment 1, male Sprague–Dawley rats were assigned to one of three groups based on whether they were conditioned with 20 mg/kg cocaine (Group C), 0.5 g/kg alcohol (Group A), or the combination (Group C/A). On the first conditioning trial, animals were injected with the drug(s) or vehicle and placed on one side of a place preference apparatus. On the next day, animals initially injected with drug received vehicle (and vice versa) and placed on the other side of the chamber. This cycle was repeated four times. Animals were then tested for their compartment preference. In Experiment 2, subjects were treated identically except that 1.5 g/kg alcohol was administered. In both experiments, Group C displayed a significant preference for the drug-paired compartment. Group A (in both experiments) showed no conditioned effect. In Experiment 1, Group C/A failed to display a significant preference, spending an amount of time in each compartment that was the numerical average of Groups C and A. In Experiment 2, the cocaine-induced preference was completely abated by 1.5 g/kg alcohol. These results indicate that alcohol produces a dose-dependent modulation of the affective properties of cocaine.
The critical role of phosphate in vanadium phosphate oxide for the catalytic activation and functionalization of n-butane to maleic anhydride.

We used density functional theory to study the mechanism of n-butane oxidation to maleic anhydride on the vanadium phosphorus oxide (VPO) surface. We found that O(1)═P on the VVOPO4 surface is the active center for initiating the VPO chemistry through extraction of H from alkane C–H bonds. This contrasts sharply with previous suggestions that the active center is either the V–O bonds or else a chemisorbed O2 on the (VIVO)2P2O7 surface. The ability of O(1)═P to cleave alkane C–H bonds is due to its strong basicity coupled with large reduction potentials of nearby VV ions. We examined several pathways for the subsequent functionalization of n-butane to maleic anhydride and found that the overall barrier does not exceed 21.7 kcal/mol.
Maternal, fetal and neonatal mortality: lessons learned from historical changes in high income countries and their potential application to low-income countries

There are large differences in pregnancy outcome between high income countries and many middle and low income countries. In fact, maternal, fetal and neonatal mortality rates in many low-income countries approximate those that were seen in high-income countries nearly a century ago. This paper documents the very substantial reductions in maternal, fetal and neonatal mortality rates in high income countries over the last century and explores the likely reasons for those reductions. The conditions responsible for the current high mortality rates in low and middle income countries are discussed as are the interventions likely to result in substantial reductions in maternal, fetal and neonatal mortality from those conditions. The conditions that result in maternal mortality are often responsible for fetal and neonatal mortality and the interventions that save maternal lives often reduce fetal and neonatal mortality as well. Single interventions rarely achieve substantial reductions in mortality. Instead, upgrading the system of care so that appropriate interventions could be applied at appropriate times is most likely to achieve the desired reductions in maternal, fetal and neonatal mortality.
A model of fads, fashions, and group formation

I develop a model of consumer behavior where agents purchase goods in order to signify personal characteristics. Agents purchase goods in order to imitate agents similar to them and agents they want to emulate. Depending on parameter values of consumer preferences the model generates stable groups, fads, and fashion cycles, or a mixture of both. The model is unique to the economic literature on fads in that the extinction of fads occurs endogenously in the model.
Teacher Unions and No Child Left Behind Reconstitution: The Calm before the Storm.

This article examines the intersection of teacher unions, school reform and the No Child Left Behind Act. Specifically, this article highlights the legal challenges that school leaders are likely t...
Outstanding Questions In First Amendment Law Related To Food Labeling Disclosure Requirements For Health

The federal and state governments are increasingly focusing on food labeling as a method to support good health. Many such laws are opposed by the food industry and may be challenged in court, raising the question of what is legally feasible. This article analyzes outstanding questions in First Amendment law related to commercial disclosure requirements and conducts legal analysis and policy evaluation for three current policies. These include the Food and Drug Administration’s draft regulation requiring an added sugar disclosure on the Nutrition Facts panel, California’s proposed sugar-sweetened beverage safety warning label bill, and Vermont’s law requiring labels of genetically engineered food to disclose this information. I recommend several methods for policy makers to enact food labeling laws within First Amendment parameters, including imposing factual commercial disclosure requirements, disclosing the government entity issuing a warning, collecting evidence, and identifying legitimate governmental...
The Progressive City

In the last decade or so, cities have become sites for a flowering of progressive policy developments. Local recognition of same-sex marriage, municipal minimum wage campaigns, local health care mandates, and labor-friendly municipal ordinances are examples. This brief Essay reviews the relationship between progressivism and decentralization and argues that progressives should embrace a form of decentralization that has its roots in the urban reforms of the early twentieth century. This Essay argues that cities are both appropriate sites for a resurgent progressive politics and particularly reliable sites for such a politics.
Textbook Buddhism: introductory books on the Buddhist religion

Textbooks on Buddhism comprise a large, varied genre and have long been used to introduce the religion to students in academic settings. This review essay examines ten textbooks on the subject, noting their distinctive features, strengths, and weaknesses, as well as the types of courses that are well suited to each work. Additional information from a survey on Buddhism textbooks conducted by the author is used to supplement our understanding of which sources are regularly used in Buddhism courses and why. Unresolved tensions over whether to stress the coherence or diversity of Buddhism, and how comprehensive a textbook should be, are noted. Arguing that ‘Textbook Buddhism,' as a product of scholarly imagination, is a distinctive form of the tradition, it behooves specialists to be more reflective about their use of textbooks and to be more intentional in helping students to read them critically.