cssi/SciSciGPT-SciSciNet huggingface dataset:
Characteristics and Causes for Non-Accrued Clinical Research (NACR) at an Academic Medical Institution

Background: The impact of non-accrued clinical research (NACR) represents an important economic burden that is under consideration as the U.S. Department of Health and Human Services looks into reforming the regulations governing IRB review. NACR refers to clinical research projects that fail to enroll subjects. A delineation of the issues surrounding NACR is expected to enhance subject accrual and to minimize occurrence of NACR. The authors assessed demographics, characteristics, and reasons for NACR at an academic medical center, including time trends, funding source, research team (principal investigator, department), IRB resource utilization (IRB level of review, number of required IRB reviews, initial IRB turn-around time, and duration of NACR). Methods: The authors analyzed data from 848 clinical research study closures during 2010 and 2011 to determine proportion, incidence, and characteristics of NACR. S tudies with subject enrollment during the same time period were used as a comparative measure. Results: Data from 704 (83.0%) study closures reported enrollment of 1 or more subjects while 144 (17.0 %) reported NACR (zero enrollment). PI-reported reasons for NACR included: 32 (22.2%) contract or funding issues; 43 (30.0%) insufficient study-dedicated resources; 41 (28.4%) recruitment issues; 17 (11.8%) sponsor-initiated study closure and 11 (7.6%) were “other/reason unreported”. Conclusions : NACR is not uncommon, affecting about one in six clinical research projects in the study population and reported to be more common in some other institutions. The complex and fluid nature of research conduct, non-realistic enrollment goals, and delays in both the approval and/or accrual processes contribute to NACR. Results suggest some simple strategies that investigators and institutions may use to reduce NACR, including careful feasibility assessment, reduction of institutional delays, and prompt initiation of subject accrual for multi-center studies using competitive enrollment. Institutional action to support investigators in the conduct clinical research is also encouraged to reduce likelihood of NACR. doi: http://dx.doi.org/10.4021/jocmr1320w
Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East Asians than in Europeans.

Large data sets on human genetic variation have been collected recently, but their usefulness for learning about history and natural selection has been limited by biases in the ways polymorphisms were chosen. We report large subsets of SNPs from the International HapMap Project1,2 that allow us to overcome these biases and to provide accurate measurement of a quantity of crucial importance for understanding genetic variation: the allele frequency spectrum. Our analysis shows that East Asian and northern European ancestors shared the same population bottleneck expanding out of Africa but that both also experienced more recent genetic drift, which was greater in East Asians.
All-optical power-controlled switching in four-wave mixing

The use of four-wave mixing as an all-optical switching device is described. The switching process involves strong pump depletion and results from large-signal interactions. Interesting relationships among the input, the optical control, and the output signals and the parameters of the nonlinear medium are identified.
Prevalence and control of Babesiosis in the Americas

This review presents up-to-date information on the distribution and control measures of babesiosis in Latin America. Bovine babesiosis caused by Babesia bovis and B. bigemia will be emphasized. The disease is endemic in most countries and poses a serious economic burden on livestock production in the region (U.S. $1365 million/year, FAO, 1989). Of the estimated 250 million cattle in Central and South America, approximately 175 million (70%) are in tick-infested regions. Humid, tropical and subtropical areas favor development of the main vector, the one-host tick Boophilus microplus. In many regions bovine babesiosis is enzootically stable as a consequence of a balanced host-parasite relationship. However, Latin America offers a wide range of epidemiologic conditions that are influenced by variations from tropical to cool climates and by susceptible purebred cattle that are regularly imported to upgrade local stocks. The control measures employed in most countries for babesiosis essentially rely on chemotherapy, use of acaricides for B. microplus, and to a lesser degree, on immunization methods. In general, these measures are expensive, time consuming, and in many cases, provide limited success. Finally, the zoonotic potential of babesiosis will be addressed, with special emphasis on the situation in the United States. Even though bovine babesiosis has long been eradicated from the U.S.A., human babesiosis is endemic in the northeastern region of the country.
A Comparison of Multicast Feedback Control Mechanisms

In reliable multicast applications, packet loss needs to be reported by having group members send feedback messages. This results in the well-known feedback implosion problem. The available feedback control mechanisms can be classified as timer-based, hierarchy-based and router-assisted, among which the timer-based approach is more preferable due to its simplicity and flexibility. This paper compares the performance of a set of multicast protocols that use either the traditional timer-based feedback control or a combination of the traditional timers and some representatives in the feedback control. We investigate how the use of representatives and deterministic timers improves feedback control performance.
Labeling of drugs that interact with oral contraceptives

Background Labeling should clearly describe drug-drug interactions (DDI) between oral contraceptives (OCs) and other drugs. The purpose of this study was to survey the labels of drugs that interact with OCs. Methods Drugs known or suspected to interact with OCs were identified using DRUGDEX®. The following keywords were used: combination contraceptives, levonorgestrel, and norethindrone. Additional drugs were identified from a literature search. Labels were obtained from the Physicians' Desk Reference. Results Our search identified 61 drugs. Twenty-six labels (43%) contained general language about DDI of OCs and 35 (57%) specified interaction with estrogen/progestin components of OCs. Four labels described increased OC exposure but only 1 of these 4 labels recommended a dose reduction of OC. Two labels contained no recommendation about OC dose adjustment while 1 label recommended considering an increase in OC exposure when OCs are prescribed. Of 21 labels describing decrease in OC exposure, 16 recommended additional/different forms of contraception while 8 did not specify any dose adjustment. Four labels recommended a general precaution. Two labels reported unknown clinical significance of decreased OC exposure. Three labels reported a lack of DDI with OCs by evaluating the inhibition of ovulation. Conclusions Label recommendations for OCs regarding DDI vary considerably. DDI between a drug and a specific OC may not apply to all OCs because of different progestins in OCs. Clinical Pharmacology & Therapeutics (2005) 77, P13–P13; doi: 10.1016/j.clpt.2004.11.051
The Nonideal Coiled Coil of M Protein and Its Multifarious Functions in Pathogenesis

The M protein is a major virulence factor of Streptococcus pyogenes (group A Streptococcus, GAS). This gram-positive bacterial pathogen is responsible for mild infections, such as pharyngitis, and severe invasive disease, like streptococcal toxic shock syndrome. M protein contributes to GAS virulence in multifarious ways, including blocking deposition of antibodies and complement, helping formation of microcolonies, neutralizing antimicrobial peptides, and triggering a proinflammatory and procoagulatory state. These functions are specified by interactions between M protein and many host components, especially C4BP and fibrinogen. The former interaction is conserved among many antigenically variant M protein types but occurs in a strikingly sequence-independent manner, and the latter is associated in the M1 protein type with severe invasive disease. Remarkably for a protein of such diverse interactions, the M protein has a relatively simple but nonideal α-helical coiled coil sequence. This sequence nonideality is a crucial feature of M protein. Nonideal residues give rise to specific irregularities in its coiled-coil structure, which are essential for interactions with fibrinogen and establishment of a proinflammatory state. In addition, these structural irregularities are reminiscent of those in myosin and tropomyosin, which are targets for crossreactive antibodies in patients suffering from autoimmune sequelae of GAS infection.
Novel textured, small aperture, thin patch for L-band satellite communications

An L-band circularly polarized antenna is designed using genetic algorithms. The design has an impedance bandwidth of 12.5% at 1.6 GHz with a remarkably constant 4.2 dBi gain. Further, it is very thin (<lambda/40) and is less than lambda/3timeslambda/3 in aperture.
Cancer “photo-chemoprevention” with pulsed dye laser and celecoxib†

Background and Objectives Our previous study demonstrated the efficacy of pulsed dye laser (PDL) in inhibiting cancer growth. This study is to determine the synergic effect of PDL and Celecoxib, when they are combined for treatment of oral cancer. Study Design/Materials and Methods Fifteen mice were inoculated with oral cell carcinoma and divided into three groups of five each (30 seeding sites/group): (1) control (no treatment), (2) PDL only, and (3) treatment with combined PDL and Celecoxib (1,500 ppm). The number and volume of tumors were counted and measured for 21 days. Results The combined treatment developed tumor at the slowest rate. On day 21, the average tumor volumes were (1) 483.6 mm3 (control), (2) 312.1 mm3 (PDL only), and (3) 151.4 mm3 (combined treatment). Conclusions A synergic effect was found in the combined treatment group. This study provides the first evidence of the efficacy of a new strategy for the treatment of oral cancer, namely, cancer “photo-chemoprevention.” Lasers Surg. Med. 32:180–184, 2003. © 2003 Wiley-Liss, Inc.
A Percolation Model for Passivation in Stainless Steels

It is well-known that Fe-Cr, Ni-Cr, and Fe-ni-cr alloys require about 12 at.% chromium to become ''stainless.'' The transition around 12% Cr is quite abrupt, especially when expressed as the change in passivation potential (E/sub p/). The occurrence of this transitional behavior is insensitive to alloy composition (apart from Cr) and is probably almost independent of temperature. This suggests that the geometrical arrangement of Cr atoms in the lattice is important for passivation, independent of other factors. The most important geometrical consideration in this problem is the degree of connectivity of Cr atoms through the three-dimensional (3D) lattice, ;which is described by percolation theory. Percolation processes characteristically show a sharp threshold (p/sub c/) which represents the concentration of occupied sites (or bonds) at which a connected cluster of ''infinite'' extent suddenly appears.
Imaging-genetics in dyslexia: Connecting risk genetic variants to brain neuroimaging and ultimately to reading impairments

Dyslexia is a common pediatric disorder that affects 5-17% of schoolchildren in the United States. It is marked by unexpected difficulties in fluent reading despite adequate intelligence, opportunity, and instruction. Classically, neuropsychologists have studied dyslexia using a variety of neurocognitive batteries to gain insight into the specific deficits and impairments in affected children. Since dyslexia is a complex genetic trait with high heritability, analyses conditioned on performance on these neurocognitive batteries have been used to try to identify associated genes. This has led to some successes in identifying contributing genes, although much of the heritability remains unexplained. Additionally, the lack of relevant human brain tissue for analysis and the challenges of modeling a uniquely human trait in animals are barriers to advancing our knowledge of the underlying pathophysiology. In vivo imaging technologies, however, present new opportunities to examine dyslexia and reading skills in a clearly relevant context in human subjects. Recent investigations have started to integrate these imaging data with genetic data in attempts to gain a more complete and complex understanding of reading processes. In addition to bridging the gap from genetic risk variant to a discernible neuroimaging phenotype and ultimately to the clinical impairments in reading performance, the use of neuroimaging phenotypes will reveal novel risk genes and variants. In this article, we briefly discuss the genetic and imaging investigations and take an in-depth look at the recent imaging-genetics investigations of dyslexia.
Optimization of electron beam patterned hydrogen silsesquioxane mask edge roughness for low-loss silicon waveguides

We carried out a multiparameter fabrication study designed to reduce the line edge roughness (LER) of electron beam (e-beam) patterned hydrogen silsesquioxane resist for the purpose of producing low-loss silicon strip waveguides. Reduced mask roughness was achieved for 50°C pre-exposure baking, 5000 μC/cm 2 dose with a beam spot size more than twice as large as the electron beam step size, development in 25% tetramethylammonium hydroxide and postdevelopment baking with rapid thermal annealing in an O 2 ambient at 1000°C. The LER caused by pattern fracturing and stage stitches was reduced with multipass writing and per-pass linear and rotational offsets. Si strip waveguides patterned with the optimized mask have root-mean-square sidewall roughness of 2.1 nm with a correlation length of 94 nm, as measured by three-dimensional atomic force microscopy. Measured optical propagation losses of these waveguides across the telecommunications C-band were 2.5 and 2.8 dB/cm for the transverse magnetic and transverse electric modes, respectively. These reduced loss waveguides enable the fabrication of advanced planar lightwave circuit topologies.
New approaches to integer programming

Integer Programming (IP) is a powerful and widely-used formulation for combinatorial problems. The study of IP over the past several decades has led to fascinating theoretical developments, and has improved our ability to solve discrete optimization problems arising in practice. This thesis makes progress on algorithmic solutions for IP by building on combinatorial, geometric and Linear Programming (LP) approaches. We use a combinatorial approach to give an approximation algorithm for the feedback vertex set problem (FVS) in a recently developed Implicit Hitting Set framework [44, 45]. Our algorithm is a simple online algorithm which finds a nearly optimal FVS in random graphs. We also propose a planted model for FVS and show that an optimal hitting set for a polynomial number of subsets is sufficient to recover the planted subset. Next, we present an unexplored geometric connection between integer feasibility and the classical notion of discrepancy of matrices [66]. We exploit this connection to show a phase transition from infeasibility to feasibility in random IP instances. A recent algorithm for small discrepancy solutions [56] leads to an efficient algorithm to find an integer point for random IP instances that are feasible with high probability. Finally, we give a provably efficient implementation of a cutting-plane algorithm for perfect matchings. In our algorithm, cuts separating the current optimum are easy to derive while a small LP is solved to identify the cuts that are to be retained for later iterations. Our result gives a rigorous theoretical explanation for the practical efficiency of the cutting plane approach for perfect matching evident from implementations [38, 69]. In summary, this thesis contributes to new models and connections, new algorithms and rigorous analysis of well-known approaches for IP.
A MEMS-Based Evaluation of the Mechanical Properties of Metallic Thin Films

Characterizing the mechanical properties of metal thin films is critical for the design and fabrication of metal microelectromechanical systems and integrated circuit devices. This paper focuses on wafer-level determination of the mechanical behavior of sputtered aluminum and nickel thin films, using a variety of measurement techniques. Elastic moduli have been determined in devices fabricated with standard micromachining techniques using bulge testing of square diaphragms and lateral resonator structures. We find a Young's modulus of ~70 GPa for Al and ~200 GPa for Ni, in agreement with data for the bulk metals. Using pressurize/depressurize cycles, the load-deflection curves of the membranes have also been determined, and in conjunction with finite element simulations, were used to determine the yield strength and fracture strength of these films. Residual stresses in the films have also been investigated using wafer curvature, bulge testing, and X-ray diffraction. The merits of each measurement technique are discussed.
Verification validation and accreditation of simulation models

This paper presents guidelines for conducting verification, validation and accreditation (VV&A) of simulation models. Fifteen guiding principles are introduced to help the researchers, practitioners and managers better comprehend what VV&A is all about. The VV&A activities are described in the modeling and simulation life cycle. A taxonomy of more than 77 V&V techniques is provided to assist simulationists in selecting proper approaches for conventional simulation model V&V. Another taxonomy of 38 V&V techniques is presented for object-oriented simulation models. 1. INTRODUCTION Assuring total quality in a modeling and simulation (M&S) effort involves the measurement and assessment of a variety of quality characteristics such as accuracy, execution efficiency, maintainability, portability, reusability, and usability (human-computer interface). This paper is concerned only with the accuracy quality characteristic. Verification, validation, testing, accreditation, certification and credibility assessment activities primarily deal with the measurement and assessment of accuracy of models and simulations (M&S). Model VeriJication is substantiating that the model is transformed from one form into another, as intended, with sufficient accuracy. Model verification deals with building the model right. The accuracy of transforming a problem formulation into a model specification or the accuracy of converting a model representation from a micro flowchart form into an executable computer program is evaluated in model verification. Model Validation is substantiating that the model, within its domain of applicability, behaves with satisfactory accuracy consistent with the M&S objectives. Model validation deals with building the right model. An activity of accuracy assessment can be labeled as verification or validation based on an answer to the following question: In assessing the accuracy, is the model behavior compared with respect to the corresponding system behavior through mental or computer execution? If
Preschool instruction and children's emergent literacy growth

Preschoolers’ (N 156) classroom language and literacy experiences, defined across multiple dimensions, and their vocabulary and emergent literacy development were investigated. Videotaped classroom observations revealed substantial variability in amount and types of language and emergent literacy activities, across classrooms and for individual children within classrooms. Generally, more time in emergent code-focused activities was associated with preschoolers’ alphabet and letter–word recognition growth, whereas more time in meaning-focused activities (e.g., book reading) was related to vocabulary growth. Only teacher- and teacher– child-managed activities were associated with alphabet and letter– word growth, whereas child-managed experiences, including play, were also associated with vocabulary growth. Overall, the effect size for student-level, code-focused instruction (small group) was about 10 times greater than was its classroom-level (whole-class) counterpart. There were Child Instruction interactions, with the impact of different activities varying with preschoolers’ incoming vocabulary and emergent literacy.
Periodicity, the Canon and Sport

The topic according to this title is admittedly a broad one, embracing two very general concepts of time and of the cultural valuation of artistic products. Both phenomena are, in the present view, largely constructed by their contemporary cultures, and given authority to a great extent from the prestige of the past. The antiquity of tradition brings with it a certain cachet. Even though there may be peripheral debates in any given society which question the specifics of periodization or canonicity, individuals generally accept the consensus designation of a sequence of historical periods and they accept a list of highly valued artistic works as canonical or authoritative. We will first examine some of the processes of periodization and of canon-formation, after which we will discuss some specific examples of how these processes have worked in the sport of two ancient cultures, namely Greece and Mesoamerica.
COMBINED INTRA-ARTICULAR AND EXTRA-ARTICULAR ARTHRODESIS FOR TUBERCULOSIS OF THE HIP JOINT

Study of the end results in thirty-five cases discloses that bony fusion was secured in thirty-two (91.4 per cent.). The fact that there were no operative deaths indicates that among patients who are in good or fair general condition, a carefully conducted operation to produce arthrodesis in the hip should be advised without hesitation. From such a small series an opinion cannot be expressed as to its value for children, for there were only two patients in the first decade of life; union resulted in both cases, however. Although postoperative drainage due to dissemination of the tuberculosis to the contiguous soft parts is not a comfortable situation, and occurred in eleven of the cases, it was not as serious as might appear. Drainage followed in forty-four per cent. of cases in which there were "wet" joints and in twenty-two per cent. in which there were "dry" joints. It occurred in a higher percentage of cases when the operation was extra-articular than it did when the combined operation was employed. I interpret this to mean that the occurrence of drainage is less if the tuberculous tissue is cleanly removed, to the best of the surgeon's ability. A purely extra-articular operation is occasionally possible, but often tuberculous tissue is encountered. The percentage of "wet" joints in the combined intra-articular and extra-articular group and in the extra-articular group was the same. The great improvement in the general health in these patients following arthrodesis has been most striking. A stiff hip has not been an added handicap, for the hip was not only stiff before operation but was painful. More uniformly successful results have been obtained by the combined method of intra-articular and extra-articular operation together with bone graft than by any other method.
On the Asymptotic Behavior of Bessel Functions

(1963). On the Asymptotic Behavior of Bessel Functions. The American Mathematical Monthly: Vol. 70, No. 9, pp. 954-957.
Proteinases of the brown-rot fungus Postia placenta.

Proteinase formation by the brown-rot fungus Postia placenta was studied to determine whether differences in proteolytic enzyme production could be correlated with the ability to decay wood. Strain...
Survey and analysis on Chinese children abroad in Chinese language acquisition

Because of the work requirements of parents,many Chinese children accompany their parents to the U.S to live and study.Some of these students will return to China in the middle of their studies.Majority of these children are in the critical language development acquisition period,English could probably replace Chinese as the dominate language.This will create some problems when they return to their home country to continue their study.This article analyzes the advantages and disadvantages of these children's Chinese study in the United States.Based on the author's own experience,several Chinese teachers' teaching methods are presented.Also described in the article are the influence of the family environment on the children's study of Chinese language and some of the misunderstandings that can be avoided in the secondary education level.
Alterations in regional myocardial function after heterogeneous cardioplegia

Coronary stenoses lead to heterogeneous delivery of cardioplegic solution during cardiac operations. This situation was simulated by occlusion of the circumflex artery during cardioplegic infusion in canine right heart bypass preparations. Regional myocardial function (systolic shortening by sonomicrometer) was often diminished, despite preservation of global function. The correlation between recovery of circumflex regional function and recovery of stroke work or dP/dt (at constant aortic pressure, heart rate, and left atrial pressure) was poor (r = 0.17 and 0.07). The response of damaged regions to hemodynamic manipulations was studied. Increases in afterload after arrest did not lead to further deterioration of damaged regions. Volume loading (cardiac output 2 to 5 L/min) improved regional function even in severely damaged, bulging regions (p
Recent Advances in Modeling of the Atmospheric Boundary Layer and Land Surface in the Coupled WRF-CMAQ Model

Advances in the land surface model (LSM) and planetary boundary layer (PBL) components of the WRF-CMAQ coupled meteorology and air quality modeling system are described. The aim of these modifications was primarily to improve the modeling of ground level concentrations of trace chemical species such as nitrogen oxides (NOx), carbon monoxide (CO), particulate matter (PM), and ozone (O3) during the evening transition and overnight. However, evaluation of both meteorological and air quality quantities shows that the advanced algorithms added to the PX LSM and the ACM2 PBL schemes improved results both day and night. Modeling experiments at various grid spacings (1, 4, and 12 km) and for different years and seasons all show significant improvements. The revised versions of these components have already been released in WRFv3.7 and will be released in the fall of 2015 in CMAQv5.1.
Tolerance limits under normal mixtures

Upper tolerance limits are derived for (i) a normal mixture distribution, and (ii) for the distribution of the Euclidean norm of a bivariate normal mixture random variable, using asymptotic normality of the MLE and bootstrap calibration. Scenario (i) is used to model the peak cladding temperature (PCT) of nuclear power plants, to assess if the PCT distribution is below a safety threshold of 2200ź°F. Scenario (ii) is used to model impact location data on projectiles launched from different locations or systems, and the problem is inference concerning the circular error probable (CEP). Simulation studies show the accuracy of the proposed methodology.
A set of pictures facilitating the formulation of therapeutic objectives in patients with chronic low back pain

Background: It is crucial to establish objectives for patients with chronic back pain. The purpose of this qualitative study was to develop a set of pictures facilitating the determination of objectives. Methods: A clinical tool was developed, based on photographs of daily activities that patients identified as priorities along with graduated scales (0–10) appraising the importance of these activities, degree of difficulty and perceived apprehension for performing these. The tool was developed using semi-structured interviews (N = 15). The set of pictures was then tested (N = 20). The views of the multidisciplinary team concerning were also investigated (N = 14). A final set of photographs was developed taking into account all comments. Results: For >90% of patients, the clinical tool allowed for identifying priority activities better than a semi-structured interview alone. The graduated scales facilitated the formulation of objectives. The therapists’ responses showed that they valued the possibility of identifying personalized objectives. Discussion: This tool may help following the guidelines advice emphasizing the importance of evaluating limitations in daily activities to facilitate their pursuit. Conclusions: These pictures offered the possibility for developing personalized objectives; it allowed negotiating meaningful, measurable and achievable objectives in the care process.
The WGF and Moscow’s Relations with Germany

The changes in Eastern Europe were widely held to mark the end of the Cold War. The USSR accepted limited political pluralism in the other countries of the WTO and cooperated more with the United States and Western Europe. These acts were largely the result of the Soviet reforms and were, for the most part, intended consequences of new thinking. In the case of Eastern Europe, however, many of the new governments quickly began to move away from reform socialism and looked to develop closer ties with the West.
Nomenklatura Lite? The Cadres Reserve in Russian Public Administration

A return to organized personnel pools instead of a politically neutral civil service system may facilitate authoritarian rule in Russia.
Integrated ion sensor device applications based on printed hybrid material systems(Conference Presentation)

Comfortable, wearable sensors and computers will enhance every person’s awareness of his or her health condition, environment, chemical pollutants, potential hazards, and information of interest. In agriculture and in the food industry there is a need for a constant control of the condition and needs of plants, animals, and farm products. Yet many of these applications depend upon the development of novel, cheap devices and sensors that are easy to implement and to integrate. Organic semiconductors as well as several inorganic materials and hybrid material systems have proven to combine a number of intriguing optical and electronic properties with simple processing methods. As it will be reviewed in this contribution, these materials are believed to find their application in printed electronic devices allowing for the development of smart disposable devices in food-, health-, and environmental monitoring, diagnostics and control, possibly integrated into arrays of sensor elements for multi-parameter detection. In this contribution we review past and recent achievements in the field. Followed by a brief introduction, we will focus on two topics being on the agenda recently: a) the use of electrolyte-gated organic field-effect transistor (EGOFET) and ion-selective membrane based sensors for in-situ sensing of ions and biological substances and b) the development of hybrid material based resistive switches and their integration into fully functional, printed hybrid crossbar sensor array structures.
Pulmonary Metastases in Patients with Advanced Renal Cell Carcinoma: Role of Metastasectomy

The chest is the most common site of metastasis from renal cell carcinoma. Mastatectomy plays a central role in the management of these patients. Preoperative evaluation should focus on identifying patients who are likely to be completely resected. Improved long-term outcomes can be predicted in patients who do not exhibit regional lymph node involvement and who have adequate pulmonary reserve.
Rapamycin -- a Potential Mechanistically Targeted Therapeutic for Juvenile Myelomonocytic Leukemia.

Abstract Juvenile myelomonocytic leukemia (JMML) is a mixed myelodysplastic /myeloproliferative disorder (MDS/MPD) of infancy and early childhood. It is characterized by monocytosis, leukocytosis, elevated fetal hemoglobin, hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF), a low percentage of myeloblasts in the bone marrow, and absence of the Philadelphia chromosome or the BCR/ABL fusion gene. The pathogenesis of JMML has been clearly and definitively linked to dysregulated signal transduction through the RAS signaling pathway. A series of studies conducted over the last decade have shown that mutations or other abnormalities in RAS, NF1, and PTPN11, are potentially responsible for the pathogenesis of JMML in up to 75% of cases. Treatment has been very difficult. There is no effective therapy for JMML. Only allogeneic stem cell transplantation (SCT) can extend survival. However, the relapse rate from allogeneic SCT is inordinately high in JMML (28–55%), with 5-year disease-free survival rates of 25-40%. Rapamycin is a macrolide antibiotic with established clinical applications in organ transplantation. Recent studies have proved that the Mammalian Target of Rapamycin (mTOR) plays an important role in cytokine receptor signaling and induction of apoptosis. Numerous studies have suggested that mTOR functions as a nutritional checkpoint and is connected to energy sensing through AMP-dependent kinase (AMPK) which senses the AMP: ATP ratio in cells. Its function is regulated by the RAS/PI3-kinase pathway. In searching for novel mechanistically-targeted reagents to treat JMML, we conducted an in vitro pilot study with JMML cells. The CFU-GM formation assay was used to test the therapeutic sensitivity of rapamycin to JMML cells. Mononuclear cells (MNCs) from peripheral blood of 9 JMML patients were collected and plated on 0.3% agar medium with rapamycin at a concentration of 1-8nM(0.91-7.28μg/L) and carrier (DMSO). Greater than 50% inhibition of spontaneous CFU-GM growth was observed in all cultures in a dose-dependent fashion, with the exception of one patient sample which had colonies resistant to rapamycin. The effective concentrations in our cultures are equivalent to the safe and tolerable whole blood concentrations achieved in organ transplant patients in clinical settings (5-30μg/L). Our data suggests that rapamycin may be considered as a potentially safe and effective reagent to treat JMML, but that in vitro sensitivity testing might be recommended since one patient sample demonstrated complete resistance to rapamycin in vitro. Further studies are ongoing to explore the mechanism of rapamycin in inhibiting hypersensitivity of JMML cells to GM-CSF.
The Integral in One Variable

If f is a continuous real valued function on [a, b],show that one can approximate f uniformly by step functions whose values are less than or equal to those of f, and also by step functions whose values are greater than or equal to those of f. The integrals of these step functions are then the standard lower and upper Riemann sums.
From the Aegean to the Adriatic: Exploring the Earliest Neolithic Island Fauna

ABSTRACTFrameworks for understanding Neolithization have increasingly recognized the complex and multifaceted nature of the spread of domesticates from Southwest Asia into Europe. But how do these factors interplay in unique island settings as compared to the continental scale? This article takes a comparative approach using sites located on islands from the Aegean and the Adriatic to discuss subsistence in the earliest Neolithic, between approximately 7000 and 6000 cal BC. Based on zooarchaeological evidence, I explore differences between island and mainland use of terrestrial and marine fauna, and consider the role of island size, vegetation, and access to water resources. Located along a “crossroads” and presenting distinct environmental challenges, the islands of both the Aegean and the Adriatic are ideally situated for considering human ecodynamics at this pivotal transition from hunting and gathering to farming and herding.
Back Contact Engineering for Increased Performance in Kesterite Solar Cells

The thin-film photovoltaic absorber Cu2ZnSn(S,Se)4 (CZTSSe) holds considerable promise for large scale conversion of sunlight into electricity. CZTSSe is composed of Earth-abundant elements that exhibit low-toxicities, but improvements in device efficiency have been hampered by difficulties in increasing open circuit voltages (VOC) due, at least in part, to disorder induced band tailing. We present a method to increase VOC through direct modification of the back contact; our approach involves the separation of fully functioning devices from their Mo/glass substrate to reveal the back CZTSSe surface. Formation of a new back contact consisting of a thermally deposited high work function material (MoO3), together with a higly reflective (Au) capping layer, creates an electrostatic field that drives electrons to the front p-n junction and leads to a decrease in electron-hole recombination. Model simulations indicating an increase in VOC with decreasing absorber thickness are borne out by experiments with devices of varying thicknesses (0.7–2.0 μm). We report VOC increases of up to 49 mV for a 1 μm thick absorber, with even greater increases up to 61 mV when the back CZTSSe surface is etched with bromine-methanol.
The Narrow Road to the Deep Past: In Search of the Chemistry of the Origin of Life

The sequence of events that gave rise to the first life on our planet took place in the Earth's deep past, seemingly forever beyond our reach. Perhaps for that very reason the idea of reconstructing our ancient story is tantalizing, almost irresistible. Understanding the processes that led to synthesis of the chemical building blocks of biology and the ways in which these molecules self-assembled into cells that could grow, divide and evolve, nurtured by a rich and complex environment, seems at times insurmountably difficult. And yet, to my own surprise, simple experiments have revealed robust processes that could have driven the growth and division of primitive cell membranes. The nonenzymatic replication of RNA is more complicated and less well understood, but here too significant progress has come from surprising developments. Even our efforts to combine replicating compartments and genetic materials into a full protocell model have moved forward in unexpected ways. Fortunately, many challenges remain before we will be close to a full understanding of the origin of life, so the future of research in this field is brighter than ever!
From gallons to miles: A disaggregate analysis of automobile travel and externality taxes

Abstract Policymakers have prioritized increasing highway revenues as rising fuel economy and a fixed federal gasoline tax have led to highway funding deficits. We use a novel disaggregate sample of motorists to estimate the effect of the price of a vehicle mile traveled on VMT, and we provide the first national assessment of VMT and gasoline taxes that are designed to raise a given amount of revenue. We find that a VMT tax dominates a gasoline tax on efficiency, distributional, and political grounds when policymakers enact independent fuel economy policies and when the VMT tax is differentiated with externalities imposed per mile.
The role of moderating variables on music festival volunteer management

ABSTRACTThe growth and popularity of festivals and events has led to a need for examination of volunteer program management. An increase in music festivals in the United States in the last decade has resulted in managers recruiting and managing volunteers to operate music festivals. This research examines relationships between moderating variables and factors of self-image congruency, motivation, satisfaction, and intent to return as a volunteer at Austin City Limits, a large-scale music festival in the United States. This research demonstrates the benefit of incorporating self-concept theory in volunteer, event, and tourism research and provides practical implications for practitioners who manage volunteer programs.
The Business Education of Charismatic Leaders and Good Soldiers

This article describes how charismatic leaders inspire followers with a vision of a better future, but attaining that better future is not easy and requires hard work, extra effort, and sacrifice. In challenging organizational environments where crisis is present, one leadership style that emerges has been described as charismatic. Charismatic leaders have a tendency to create good soldiers, a loyal band of followers who engage in organizational citizenship behaviors. These good soldiers encourage others to join the effort to create a better world and achieve goals. The difficulty sets in when charismatic leaders and their good soldiers continually ask for more of their employees, take the spotlight, diminish the contributions of others, and create an environment where the performance of extra-role behaviors becomes the expected norm. When followers are pressured to perform citizenry behaviors, they no longer do so voluntarily, which places stress on employees and eventually dampens enthusiasm and motivation. Business educators preparing the next generation of leaders need to raise awareness of the strengths and possible weaknesses associated with charismatic leadership and organizational citizenship behaviors.
Cervical Spine Disorders (Pediatric)

Pediatric cervical spine disorders are varied in etiology, pathology, and treatment. Associations with congenital abnormalities are common. The pediatric cervical spine is unique from that of the adult and nuances in its care are important.
Approximate policy iteration using large-margin classifiers

We present an approximate policy iteration algorithm that uses rollouts to estimate the value of each action under a given policy in a subset of states and a classifier to generalize and learn the improved policy over the entire state space. Using a multiclass support vector machine as the classifier, we obtained successful results on the inverted pendulum and the bicycle balancing and riding domains.
Hypoxia-induced generation of nitric oxide free radicals in cerebral cortex of newborn guinea pigs.

Previous studies have shown that brain tissue hypoxia results in increased N-methyl-D-aspartate (NMDA) receptor activation and receptor-mediated increase in intracellular calcium which may activate Ca++-dependent nitric oxide synthase (NOS). The present study tested the hypothesis that tissue hypoxia will induce generation of nitric oxide (NO) free radicals in cerebral cortex of newborn guinea pigs. Nitric oxide free radical generation was assayed by electron spin resonance (ESR) spectroscopy. Ten newborn guinea pigs were assigned to either normoxic (FiO2 = 21%, n = 5) or hypoxic (FiO2 = 7%, n = 5) groups. Prior to exposure, animals were injected subcutaneously with the spin trapping agents diethyldithiocarbamate (DETC, 400 mg/kg), FeSO4.7H2O (40 mg/kg) and sodium citrate (200mg/kg). Pretreated animals were exposed to either 21% or 7% oxygen for 60 min. Cortical tissue was obtained, homogenized and the spin adducts extracted. The difference of spectra between 2.047 and 2.027 gauss represents production of NO free radical. In hypoxic animals, there was a difference (16.75 ± 1.70 mm/g dry brain tissue) between the spectra of NO spin adducts identifying a significant increase in NO free radical production. In the normoxic animals, however, there was no difference between the two spectra. We conclude that hypoxia results in Ca2+- dependent NOS mediated increase in NO free radical production in the cerebral cortex of newborn guinea pigs. Since NO free radicals produce peroxynitrite in presence of superoxide radicals that are abundant in the hypoxic tissue, we speculate that hypoxia-induced generation of NO free radical will lead to nitration of a number of cerebral proteins including the NMDA receptor, a potential mechanism of hypoxia-induced modification of the NMDA receptor resulting in neuronal injury.
Weight-related denial of insurance for an infant.

A breastfed infant in a high weight-for-length percentile is not necessarily at greater risk for future health problems than a leaner infant; a physician would be justified in advocating for such a child to receive insurance coverage. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.
Therapeutic Drug Monitoring of Atypical Antipsychotics

Despite its cost, therapeutic drug monitoring for the atypical antipsychotics is of clinical value as it affords the opportunity to reduce toxicity and increase compliance. Although data document the utility of routine monitoring of blood clozapine and olanzapine concentrations, there are no similar data available for either risperidone or quetiapine. Numerous studies have established an ideal lower therapeutic threshold plasma concentration for clozapine while fewer data are available for olanzapine.
Crisp Partitions Induced by a Fuzzy Set

Relationship between fuzzy sets and crisp partitions defined on the same finite set of objects X is studied. Granular structure of a fuzzy set is described by rough fuzzy sets and the quality of approximation of a fuzzy set by a crisp partition is evaluated. Measure of rough dissimilarity between clusters from a crisp partition of X with respect to a fuzzy set A defined on X is introduced. Properties of this measure are explored and some applications are provided. Classification of membership grades of A into linguistic categories is discussed.
Antibiotic and acid-suppression medications during early childhood are associated with obesity.

Objective Gut microbiota alterations are associated with obesity. Early exposure to medications, including acid suppressants and antibiotics, can alter gut biota and may increase the likelihood of developing obesity. We investigated the association of antibiotic, histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) prescriptions during early childhood with a diagnosis of obesity. Design We performed a cohort study of US Department of Defense TRICARE beneficiaries born from October 2006 to September 2013. Exposures were defined as having any dispensed prescription for antibiotic, H2RA or PPI medications in the first 2 years of life. A single event analysis of obesity was performed using Cox proportional hazards regression. Results 333 353 children met inclusion criteria, with 241 502 (72.4%) children prescribed an antibiotic, 39 488 (11.8%) an H2RA and 11 089 (3.3%) a PPI. Antibiotic prescriptions were associated with obesity (HR 1.26; 95% CI 1.23 to 1.28). This association persisted regardless of antibiotic class and strengthened with each additional class of antibiotic prescribed. H2RA and PPI prescriptions were also associated with obesity, with a stronger association for each 30-day supply prescribed. The HR increased commensurately with exposure to each additional medication group prescribed. Conclusions Antibiotics, acid suppressants and the combination of multiple medications in the first 2 years of life are associated with a diagnosis of childhood obesity. Microbiota-altering medications administered in early childhood may influence weight gain.
Simulating the Change in Young Adult Homeownership Through 2035: Effects of Growing Diversity and Rising Educational Attainment

In this article we highlight the scope of public policy and demographic change for the future path of homeownership. In so doing, we review the literature on the scope of impact of certain policy t...