cssi/SciSciGPT-SciSciNet huggingface dataset:
Intrathecal Administration of Tumor-Infiltrating Lymphocytes Is Well Tolerated in a Patient with Leptomeningeal Disease from Metastatic Melanoma: A Case Report

Patients with leptomeningeal disease (LMD) from melanoma have very poor outcomes and few treatment options. We present a case of intrathecal (i.t.) administration of autologous tumor-infiltrating lymphocytes (TIL) in a patient with LMD from metastatic melanoma. The patient developed LMD after previous treatments with surgery, high-dose bolus interleukin-2 (HD IL2), and systemic TIL infusion and experienced radiographic progression after intrathecal IL2 (i.t. IL2) therapy. The patient received weekly treatment with increasing numbers of i.t. TIL followed by twice-weekly i.t. IL2. The patient received three i.t. TIL infusions and did not experience any toxicities beyond those expected with i.t. IL2 therapy. Analysis of cerebrospinal fluid demonstrated increased inflammatory cytokines following the i.t. treatments. Subsequent imaging demonstrated disease stabilization, and neurological deficits also remained stable. The patient expired 5 months after the initiation of i.t. TIL therapy with disease progression in the brain, liver, lung, and peritoneal and retroperitoneal lymph nodes, but without LMD progression. These results demonstrate the safety of i.t. administration of TIL in melanoma patients with LMD and support the feasibility of conducting a prospective clinical trial to determine this therapy9s clinical benefit among these patients. Cancer Immunol Res; 3(11); 1201–6. ©2015 AACR.
Near‐surface in situ stress: 1. Strain relaxation measurements along the San Andreas Fault in southern California

Strain relaxation stress measurements were made in the Mojave Desert southeast of Palmdale, California, at two sites during the summers of 1979 and 1980, using the U.S. Bureau of Mines technique to depths of about 30 m. The field data and finite element modeling studies demonstrate that thermally induced stress dominates the results obtained in the upper 6 m. At depths greater than 6 m the average orientation for the horizontal maximum compressive stress at these sites is N22°W±9° at 2 km south of the San Andreas fault and N13°W±2° at 20 km north of the fault. These azimuths compare favorably with the average of N21°W determined with nearby hydrofracture stress measurements (Zoback et al, 1980). Savage et al. (1981) also found a NNW orientation for the maximum shortening from a geodetic network with a 15-km aperature in the Palmdale area. The fact that essentially the same orientation is recovered by three different techniques which sample to different depths and over different areal extents argues strongly for a contemporary tectonic origin for the stress. Finite element models of the San Andreas fault in southern California develop a stress field similar to that observed regionally (∼15°E for the maximum compressive stress) away from the fault when displacements corresponding to relative motion between lithospheric plates are applied on the boundaries of the models. Near the fault, however, the model principal stresses are rotated counterclockwise similar to those measured near Palmdale, demonstrating the influence of the faults on the principal stress orientations.
Evaluating taphonomic bias of paleoecological data in fossil benthic foraminiferal assemblages

Paleoecological analyses conducted over broad temporal and spatial scales can incorporate fossil assemblages of disparate taphonomic histories, resulting in samples where the record of the original communities is biased to different degrees. Testing for the effects of differential taphonomic biases is crucial to accurate interpretations of paleoecological patterns. To test for such effects in a shallow-marine benthic foraminiferal record from the early Miocene Astoria Formation, I developed a taphonomic grading system for benthic foraminifera and scored individuals for preservation state. Grading allows each sample to be subdivided into taphonomically similar subsamples. Subsamples are evaluated for similarity in species composition, species rank, and proportional abundances. Similarities are significantly higher in within-sample comparisons between taphonomic grades than they are among samples when taphonomic grade is held constant, indicating that ecological information is conserved despite variation in taphonomic grade within a single time-averaged assemblage. In addition, taphonomically homogenous subsamples (and nested sets of taphonomic grades) capture the same temporal patterns of species richness, community evenness, and the proportional abundances, although ordinations using subsamples with the poorest preservation do show some significant differences. Thus, although incorporating the most poorly preserved samples requires some caution, the quality of ecological information derived from these benthic foraminiferal samples is consistent across taphonomic grades. For this test case, I argue that paleoecological analyses will not be significantly affected by differences in preservation among samples. This method of taphonomic grading can be applied to other fossil groups and facilitates analyses of paleoecological results despite different degrees of taphonomic alteration.
A two-stage non-linear program for optimal electrical grid power balance under uncertainty

We propose a two-stage non-linear stochastic formulation for the economic dispatch problem under renewable-generation uncertainty. Each stage models dispatching and transmission decisions that are made on subsequent time periods. Certain generation decisions are made only in the first stage and the second stage realizes the actual renewable generation, where the uncertainty in renewable output is captured by a finite number of scenarios. Any resulting supply-demand mis-match must then be alleviated using extra, high marginal-cost power sources that can be tapped in short order. We propose two outer approximation algorithms to solve this nonconvex optimization problem to optimality. We show that under certain conditions the sequence of optimal solutions obtained under both alternatives has a limit point that is a globally-optimal solution to the original two-stage nonconvex program. Numerical experiments for a variety of parameter settings were carried out to indicate the efficiency and usability of this method of large practical instances.
Pulse Delay Via Tunable White Light Cavities Using Fiber-Optic Resonators

Previously, we proposed a data buffering system that makes use of a pair of white light cavities. For application to telecommunication systems, it would be convenient to realize such a device using fiber-optic resonators. In this paper, we present the design of such a system, where the white light cavity effect is produced by using stimulated Brillouin scattering. The system consists of a pair of fiber-optic white light cavities placed in series. As in the original proposal, the delay time can be controlled independently of the bandwidth of the data pulses. Furthermore, we show how the bandwidth of the system can be made as large as several times the Brillouin frequency shift. We also show that the net delay achievable in such a buffer can be significantly larger than what can be achieved using a conventional recirculating loop buffer.
Geologic history and stratigraphy of the Triassic-Jurassic Culpeper Basin, Virginia: Summary

The Culpeper Basin in northern Virginia extends from just south of the Albemarle-County—Orange County line northeastward to the Potomac River, a distance of more than 148 km (90 mi). The basin continues northward across the Potomac and terminates just southwest of Frederick, Maryland. It occupies the western part of the Piedmont province. On the west it is bounded by an east-dipping normal fault; the sedimentary and volcanic strata dip westward into the fault (Fig. 1). The rocks in this area traditionally have been considered part of the Newark Group and referred to as Triassic, but Cornet9s (1977) palynological study indicates that they range from Upper Triassic to Lower Jurassic. The Culpeper Basin is one of the many basins in North America in which sedimentation extended from Late Triassic to Early Jurassic time (Cornet, 1977). Other such basins include the Newark in New Jersey, the Gettysburg in Pennsylvania, the Hartford in Connecticut, the Deerfield in Massachusetts, and the Fundy in Nova Scotia. The southernmost basins contain only Upper Triassic rocks. They include the Durham, Sanford, Wadesboro, and Dan River Basins in North Carolina and the Danville and Richmond Basins in southern Virginia (Cornet, 1977).
Nonlinear Identification of Mechanical Parameters in a Squeeze Film Damper With Integral Mechanical Seal

End seals in squeeze film dampers (SFDs) aid to increase their damping capability while maintaining low lubricant flow rates and reducing the severity of air ingestion. This paper presents measurements of the forced response in a SFD integrating a contacting end seal and with closed flow ports, i.e. no lubricant thru flow. The system motion is non-linear due to dry friction interaction at the mechanical seal mating surfaces. Single parameter characterization of the test system would yield an equivalent viscous damping coefficient that is both frequency and motion amplitude dependent. Presently, an identification method suited for nonlinear systems allows determining simultaneously the squeeze film damping and inertia force coefficients and the seal dry friction force. The identification procedure shows similar (within 10%) force coefficients than those obtained with a more involved two-step procedure that first requires measurements without any lubricant in the test system. The identified SFD damping and inertia force coefficients agree well with model predictions that account for end flow effects at recirculation grooves. The overall test results demonstrate that the non-rotating end seal effectively eliminates side leakage and avoids air ingestion; thus maintaining a consistent damping performance throughout the test frequency range. The nonlinear identification procedure saves time and resources while producing reliable physical parameter estimations.Copyright © 2008 by ASME
Disease diagnostics of biological tissues using free-space technique in terahertz frequency range

The sensitivity of terahertz absorption to water, biological tissue structure content, and the degree of hydration of diseased tissues are exploited to distinguish between normal and malignant human skin tissues. This can be achieved using free-space technique in terahertz frequency range (110–170 GHz), with the reflection and transmission coefficients, which are converted into the dielectric constant.
Look ma, no templates! Problem-based learning of computational physics for novice programmers

We present a problem-based approach to teach computational physics to junior-level students with a variety of programming skill levels, many of whom have only 10 weeks of prior programming experience. The students solve tasks, relating to their current class topics, which are mathematically challenging but computationally tractable. The tasks are chosen to develop and reinforce student understanding of traditional physics content. We provide students with minimal code examples (47 lines of python code in a one-year lab sequence) and no textbook, and require students to search the internet for help to achieve the tasks assigned. This is effective through the use of a pair-programming pedagogy, when students are given tasks at a suitable level. This pedagogical approach should be transferable to any mathematical discipline for which computation is appropriate. Because student effort is focused towards accomplishing tasks within their discipline, they gain the practical skills needed to use computation effectively. Because we give students no templates or example code, they are forced to develop the skill of learning a programming language, and debugging code. This gives students confidence, and prepares them to learn other programming languages in their future career: a most important skill!
Option Valuation Based on Arithmetic Brownian Motion: Justification and Implementation Issues

We take another look at arithmetic Brownian motion as a framework for developing financial derivatives valuation and risk management tools. We compare and contrast option valuation based on geometric Brownian motion and arithmetic Brownian motion. An alternative way to handle negative stock prices within the arithmetic Brownian motion approach is identified that is more consistent with empirical observation than the traditional approach of assuming no possibility of zero prices within the geometric Brownian motion. After comparing a wide array of sensitivities with both models, we discuss numerous strengths and weakness of both approaches. Option valuation based on arithmetic Brownian motion appears to be a credible additional tool for financial quantitative analysis.
Abstract P603: Age and Angiotensin-(1-12) Expression in Human Atrial Tissue of Patients with Left Heart Disease

In the human heart formation of angiotensin (Ang) II results from the hydrolysis of an alternate angiotensin substrate, -Ang-(1-12)-, by chymase rather than angiotensin converting enzyme. In our recent study a higher Ang-(1-12) expression and upregulation of chymase mRNA and enzymatic activity was found in left (LAA) versus right atrial appendages (RAA) of subjects with left heart disease. Since aging is associated with prominent changes in cardiac structure and function, we assessed the relationships among age, Ang-(1-12), and chymase gene expression and activity in both LAA and RAA in 44 patients undergoing cardiac surgery for the correction of valvular heart disease, resistant atrial fibrillation or ischemic heart disease. Immunohistochemistry for Ang-(1-12) detection was performed using an affinity purified polyclonal antibody directed to the COOH terminus of the full length of the sequence of human Ang-(1-12). Quantitative real-time polymerase chain reaction was used to detect chymase mRNA levels whereas chymase activity was assessed by HPLC. We report that Ang-(1-12) immunostaining in atrial appendages (r=0.30; p
ierarchical Difference In Auditors Perceptions Of Lowballing: A Study Of Current Attitudes

Auditors are in the business of providing to their clients the value of their attestation services for financial reporting. Auditors (and other accountants) have a strict Code of Professional Conduct which is enforced by the American Institute of Certified Public Accountants (AICPA). According to this Code of Professional Conduct (AICPA 1988), the AICPA sets forth the requirement that all auditors comply with generally accepted auditing standards (GAAS) in all audit engagements. These rules are a necessary part of the audit process helping to ensure a quality result for the stakeholders of the organization. Lowballing, the practice of bidding under or at cost for an audit in order to attract new clients, may violate the independence in appearance clause of the Code of Professional Conduct. Researchers and regulatory authorities appear to differ on their treatment of this issue. Differences in option (AICPA 1978 compared to DeAngelo 1981) appear to center around the interpretation of independence in the Code of Professional Conduct. This study evaluates current attitudes towards lowballing for all levels of professional auditors within four public accounting firms and specifically addresses the question of whether lowballing is a violation of the impendence in appearance section of the Code. The study also questions auditors as to their beliefs about the Code of Professional Conducts potential for change to accommodate the practice of lowballing.
Regeneration of Appendages in the Tarantula Eurypelma Californica Ausserer.

The replacing of lost organs in spiders has received much attention, and several studies such as those by Dr. C. Heineken, Waldemar Wagner (discussed by McCook), and Henry C. McCook are very thorough as well as comprehensive. A curious feature that one observes in a brief survey of the literature is that although Dr. Heineken reached among other conclusions the one that spiders could reject a mutilated joint, neither McCook nor anyone else has been able to confirm this. Another feature of perhaps more significance is that all the investigators agree that when spiders have reached sexual maturity they undergo no more molts and consequently can no longer replace lost appendages.
Therapeutic Effect of Pidotimod on Recurrent Respiratory Infection in Children

Objective:To investigate the clinical effect of pidotimod in treating recurrent respiratory infection(RRI) of children.Methods:Two hundred and sixty children who suffered from recurrent respiratory infection were randomly divided into two groups,the treatment group(pidotimod group,n=140) and the control group(routine treatment group,n=120).The clinical effect was compared between the two groups after treatment.Results:The total effective rates of the treatment group and the contronl group were 95.0%(133/140) and 78.3%(94/120) respectively and there was significant difference between the two groups(P0.05).The time of pyretolysis,coughing relief,rale extinction decreased and there was significant difference between the two groups(P0.05).There were no significant adverse drug reactions during the treatment with pidotimod.Conclusions:Pidotimod is effective in treating and preventing RRI of children.
Alanine umbilical uptake, disposal rate, and decarboxylation rate in the fetal lamb

Fetal plasma alanine disposal rate (DR) and decarboxylation rate were measured at 132 +/- 1 days gestation in nine fetal lambs infused with L-[1-14C]alanine via a brachial vein. In five experiments...
CELL ANTIGENS AND CELL SPECIALIZATION. IV. ON THE H BLOOD GROUP ANTIGEN OF HUMAN PLATELETS AND NUCLEATED CELLS OF THE HUMAN BONE MARROW.

This article describes the specific agglutination of normoblasts, recitulocytes, megakaryocytes and platelets of human bone marrow with anti-H sera. It also describes the erythrocyte-platelet mixed agglutination reactions demonstrating H antigen receptors on all human platelets regardless of the ABO group of the donor with the exception of the Bombay blood.
Behavioral and Psychological Effects of Salvia divinorum: A Focus on Self-Reported Subjective Acute Behavioral Effects and Laboratory Studies

Abstract Salvia divinorum is a plant used as a recreational hallucinogen that is legally available in many states and countries. Salvia divinorum is not a popular substance of abuse, is rarely used frequently or regularly, and is used primarily out of curiosity, for interest in altered states of consciousness and for spiritual purposes. Smoking commercially available Salvia divinorum produces rapid onset and short duration of intense subjective effects (5–15 min), with few effects lasting more than 24 h after use. Preliminary evidence suggests that acute inhalation may lead to transient and reversible verbal learning memory deficits, but does not affect verbal working memory. Research subjects do not report euphoria or craving to use, and do not seek out Salvia divinorum, subsequent to experimental exposure. Large surveys have found little or no associations between Salvia divinorum use and adverse events, although Salvia divinorum use is correlated with use of other recreational substances, particularly hallucinogens and cannabis.
Discrete-time integral sliding model predictive control for unmatched disturbance attenuation

In this paper, a method of unmatched disturbance compensating integral sliding model predictive control for constrained linear discrete-time systems with bounded disturbances is presented. The basic idea is to shape a discrete-time integral sliding mode control into an optimal constrained control problem with model predictive control. By choosing another projection matrix in the integral sliding surface, the performance on the unmatched channel can be improved at the expense of the nominal MPC performance. For this reason, a final disturbance observer-based method is then introduced. The theoretical analysis and a numerical example illustrate the validity of the proposed method.
Von Willebrand Factor Levels Do Not Increase with Age in Patients with Type 1 Von Willebrand Disease.

Abstract A number of inherited and acquired factors modulate von Willebrand factor antigen (VWF:Ag) levels, including blood type, race, activity and stress level, thyroid hormone status, and, in women, time in menstrual cycle. In reported studies a positive correlation between VWF:Ag and/or factor VIII levels and age has been demonstrated, with an increase of 5 – 6 IU/dL per decade (Conlan MG et al, 1993; Kamphuisen PW et al, 1998). Those studies have primarily assessed VWF and factor VIII as risk factors for ischemic heart disease, cerebrovascular disease, and venous thromboembolism. None of the subjects had von Willebrand disease (VWD). Their VWF:Ag levels were in the higher normal or elevated range. The purpose of this study was to determine whether there is a relationship between age and VWF:Ag level in patients with Type 1 VWD. We collected the data from 36 patients who were diagnosed with type 1 VWD and followed at the Penn Comprehensive Hemophilia and Thrombosis Program up to a period of 13 years (See Table 1 below). For each patient, date of birth, VWF:Ag levels with corresponding test dates were collected by reviewing the medical histories and the lab results. Test results obtained during pregnancy, DDAVP testing, or during prophylaxis or therapy for bleeding control were excluded. One year was set as the observation period, so the adjacent VWF:Ag levels that were tested less than one year were excluded from the dataset. When two test results were available on a patient within a one-year period, the lower test result was used. To investigate whether there was a relationship between VWF:Ag levels and age, cross-sectional analyses (across each visit) and longitudinal analyses were performed using scatter plots, Spearman and Pearson correlations, and regression analysis. No significant increase in VWF:Ag levels with age was demonstrated. The fact that we did not find an increase in VWF:Ag levels over time in our patients could be due to the relatively small number of patients studied or could reflect a subtype of VWD, due to our selection criteria. Only patients with abnormal values were included. Some patients have a prior diagnosis of VWD and bleeding symptoms, but have normal values when tested. Since these patients are adults, this may be due, at least in part, to an age-related increase. Type 1 VWD may occur secondary to decreased VWF synthesis and/or clearance. It is possible that age-related effects on VWF levels will differ depending on the underlying factor(s) resulting in a lower VWF level. Further studies correlating a patient's values longitudinally with the underlying pathophysiology of their disease would aid in our understanding of their bleeding risks over time. Patient # Age at Last Visit, range (mean) Females (%) Race % (Cauc/AA/Other) VWF:Ag mean 36 17–70 (34) 89 78/19/3 49%
Overlearning hyperstabilizes a skill by rapidly making neurochemical processing inhibitory-dominant

Overlearning refers to the continued training of a skill after performance improvement has plateaued. Whether overlearning is beneficial is a question in our daily lives that has never been clearly answered. Here we report a new important role: overlearning in humans abruptly changes neurochemical processing, to hyperstabilize and protect trained perceptual learning from subsequent new learning. Usually, learning immediately after training is so unstable that it can be disrupted by subsequent new learning until after passive stabilization occurs hours later. However, overlearning so rapidly and strongly stabilizes the learning state that it not only becomes resilient against, but also disrupts, subsequent new learning. Such hyperstabilization is associated with an abrupt shift from glutamate-dominant excitatory to GABA-dominant inhibitory processing in early visual areas. Hyperstabilization contrasts with passive and slower stabilization, which is associated with a mere reduction of excitatory dominance to baseline levels. Using hyperstabilization may lead to efficient learning paradigms.
GI Bleeding/Hemorrhage

A pictorial algorithm to the approach of GI hemorrhage with an evidence-based decision rule included.
A Geographic Object-Based Approach for Land Classification Using LiDAR Elevation and Intensity

By providing detailed height and intensity land surface information, high-resolution LiDAR data have proved to be effective in supporting land classification when combined with other major geospatial data sources, such as hyperspectral images. However, rectifying and fusing multisource geospatial data involves what normally is a manual and time-consuming process. In this letter, we propose a geographic object-based image analysis approach to enable semiautomatic land classification and mapping using LiDAR elevation and intensity data. The methodological framework consists of a series of operations, including preprocessing, object-based segmentation, creation of statistical variables from elevation and intensity, and semisupervised classification. We have successfully applied this approach to the classification of multiple land features, including asphalt, grass, barren land, swimming pool, shrubland, pavement, and buildings. Results show that our proposed approach performs better than LiDAR analysis methods in classifying different land parcels.
Condition and Impacts of Climate Change

The State of Tennessee takes an all-hazards approach when responding to, preparing for, mitigating against, and recovering from disasters. This approach is articulated in the Tennessee Emergency Management Plan (TEMP) and its annexes, the Tennessee Catastrophic Annex (TNCAT) and the Tennessee Hazard Mitigation Plan (HZMIT). Because Tennessee uses an “all-hazards” approach, these plans are used to address the amplified impacts that result from climate change.
Antenna Arrays in the Time Domain: An introduction to timed arrays.

The term phased array comes from the time-harmonic/steady-state analysis of antenna arrays. These arrays use phase shifters to electronically steer the main beam. Phase shifters cause beam squint and pulse dispersion for wide-band signals, so time-delay units are needed to correct these errors. Adaptive and reconfigurable arrays also have time-dependent responses. In addition, time-dependent spurious signals arise due to nonlinearities in amplifiers. This article presents several time-varying issues related to antenna arrays that should not be modeled by the time-harmonic representation of an array. Future antenna arrays will be wideband and time varying, so antenna arrays will have to be designed in the time domain.
In situ monitoring of particle fracture in aluminium alloys

Material damage at the microscale involves both initiation and interaction effects that are typically activated long before the appearance of macroscopically observable failure events. These early appearances of damage have been broadly classified as microstructure-sensitive damage precursors or indicators. A particular class of such precursors which is of importance to aluminium and other precipitate-hardened alloys is the focus of this article. Specifically, the hard, intermetallic particles in aluminium alloys fracture before significant failure occur in the surrounding matrix. In this investigation, an effort to directly assess particle fracture activity at the time and scale that it occurs is made by coupling mechanical testing inside a scanning electron microscope with nondestructive evaluation techniques including digital image correlation as well as real-time acoustic emission monitoring. The use of a surface measurement technique along with a volumetric monitoring method at the microscope scale provides a way for coupling of fracture information at locations which are directly related to the particle activity. In this article, Al2024-T3 specimens in the as-received condition were subjected to tension as well as to tension-tension cyclic loading. The obtained in situ results demonstrate, for the first time to the best knowledge of the authors, that particle fracture occurs early in the damage process which justifies its characterization as a material damage precursor. The overall approach provides datasets capable to detect particle fracture initiation, which could become useful in future structural health monitoring applications.
Synthesis and hypolipidemic activity of 3-imino-1-oxoisoindolines in rodents.

A series of substituted 3-imino-l-oxoisoindolines derivatives demonstrated significant hypolipidemic activity, lowering both serum cholesterol and triglycerides levels after 16 days of dosing at 20 mg/kg/ day ip in CF1 mice. 2-Butyl-3-butylimino-l-oxoisoindoline lowered serum cholesterol levels 52% and serum triglyceride 42%. 2-Pentyl-3-imino-l-oxoisoindoline lowered serum cholesterol levels 42% and serum triglyceride 61%. These derivatives resulted in better activity than the parent compound, 3-imino-1-oxoisoindoline. These studies showed that compounds with N-alkyl substitution of nitrogen atoms in the ring and outside the ring possessed potent hypolipidemic activity at the low dose of 20 mg/kg/day ip in normolipidemic CF1 mice. Studies with 2-butyl-3-butylimino-l-oxoisoinodine in rats showed that serum cholesterol was reduced 60% and serum triglyceride 43% after 14 days of dosing at 20 mg/kg/day, orally. Treatment with this agent lowered lipid levels in the liver and aorta tissue, with increases in lipid levels in the small intestine tissue. Higher levels of cholesterol and phospholipids were excreted in the feces of treated animals compared to the control. Cholesterol levels of the very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) fractions were reduced, whereas the HDL cholesterol levels were elevated significantly. This ratio of low-density lipoprotein (LDL) cholesterol:HDL cholesterol levels suggests that the agent may be effective in treating hyperlipidemic states in humans.
Evaluation of the cost saving potential of introducing Benepali® and Flixabi® on the European and Italian markets

INTRODUCTION: Biosimilar products play an important role in improving the access to biological medicines for an increased number of patients and enhancing the financial sustainability of the health systems. AIM: To assess the cost saving potential associated with the introduction of two biosimilars (Benepali ® and Flixabi ® ) vs. their respective reference biological products on the European and Italian markets. METHODS: A budget impact model was developed to estimate the cost saving of the hypothetical introduction of Benepali ® and Flixabi ® vs. Enbrel ® and Remicade ® , respectively, in three European countries. The analysis was conducted from the payer perspective, over a 3-year period. In addition, the same model was used to assess the impact of Benepali ® vs. Enbrel ® in three Italian regions over a 2-year period. The model compares the costs associated with the current treatment patterns, used to manage patients with all the conditions which Benepali ® and Flixabi ® are authorized for, with that of a hypothetical treatment pattern in which biosimilar products have been introduced. Only direct costs associated with the drug acquisition were considered. The model was constructed using published country- or region-specific data, where available. Annual drug acquisition costs were calculated using the dosing information from SPCs and country-/region-specific price lists. RESULTS: The introduction of Benepali ® and Flixabi ® in the biologic therapeutic setting of three European countries resulted in substantial cost savings across the entire scenario, with different penetration over a 3-year period. Similarly, over a 2-year horizon, the introduction of Benepali ® in the biologic therapeutic setting of three Italian regions resulted in significant cost savings. In all cases, the greater savings were observed in the scenario where the biosimilars’ penetration was higher. CONCLUSIONS: The introduction of Benepali ® and Flixabi ® has a substantial cost saving potential for the Italian and European health systems, and the budget impact is sensitive to the uptake rates of the biosimilars market.
Mesenchymal Stem Cell Preparation and Transfection-free Ferumoxytol Labeling for MRI Cell Tracking.

Mesenchymal stem cells (MSCs) are multipotent cells and are the most widely studied cell type for stem cell therapies. In vivo cell tracking of MSCs labeled with an FDA-approved superparamagnetic iron-oxide (SPIO) particle by magnetic resonance imaging (MRI) provides essential information, e.g., MSC engraftment, survival, and fate, thus improving cell therapy accuracy. However, current methodology for labeling MSCs with Ferumoxytol (Feraheme®), the only FDA-approved SPIO particle, needs transfection agents. This unit describes a new “bio-mimicry” protocol to prepare more native MSCs by using more “in vivo environment” of MSCs, so that the phagocytic activity of cultured MSCs is restored and expanded MSCs can be labeled with Ferumoxytol, without the need for transfection agents and/or electroporation. Moreover, MSCs re-size to a more native size, reducing from 32.0 to 19.5 μm. The MSCs prepared from this protocol retain more native properties and would be useful for biomedical applications and MSC-tracking studies by MRI. © 2017 by John Wiley & Sons, Inc. Keywords: Ferumoxytol (Feraheme®); magnetic resonance imaging; stem cell culture and expansion; stem cell tracking; mesenchymal stem cells
Social Constructivism and Online Learning Environments: Toward a Theological Model for Christian Educators:

While many theories exist to explain the phenomenon of learning, one of the oldest and most supported models is Vygotsky's social constructivism. Although once a forgotten voice, many of the newer ...
English Writing Assessment and the Arabic Speaker: A Qualitative Longitudinal Retrospective on Arabic-Speaking Medical Students in Qatar

This chapter analyses successful English writing assessment in Arabic-speaking medical student populations at Weill Cornell Medicine-Qatar (WCM-Q) from 2006–16. Assessing L2 writers of English presents several unique challenges not only within the context of Science, Technology, Engineering, and Mathematics (STEM) academic writing but also within the American-style educational paradigm of Education City, Doha, Qatar. The Premedical Program at WCM-Q evolved from no writing instruction in 2002 to a full Writing Program curriculum and Writing Centre, distributed Peer Tutor Network, and the development of literacy culture initiatives ten years later. Writing gained increasing prominence within the institution and eventually led to discussions about creating a longitudinal writing component in a newly revised curriculum. At WCM-Q, L1 Arabic students writing in English have specifically struggled with: (1) the autonomous learning paradigm of American universities, (2) English language deficits (limited vocabulary, difficulties with nuance and connotation), (3) contextualised reading, (4) audience, (5) developing authorial voice, and (6) ethical sourcing of secondary materials (proper citation). The WCM-Q Writing Program developed a variety of innovative assessment strategies including rubric development workshops, site visits by the John S. Knight Institute for Writing in the Disciplines, and an in-house written diagnostic essay test. A Foundation Program was added in 2007 to specifically address English language deficits.
Mechanical Properties of a Primary Cilium from the Stochastic Motions of the Cilium Tip

The stochastic tip dynamics of a primary cilium held within an optical trap is quantified by combining experimental, analytical and computational tools. Primary cilia are cellular organelles, present on most vertebrate cells, hypothesized to function as a fluid flow sensor. The mechanical properties of a cilium remain incompletely characterized. We measured the fluctuating position of an optically trapped cilium tip under untreated, Taxol-treated, and HIF-stabilized conditions. We applied analytical modeling to derive the mean-squared displacement of the trapped tip of a cilium and compared the results with experimental measurements. We provide, for the first time, evidence that the effective flexural rigidity of a ciliary axoneme is length-dependent, and longer cilia are stiffer than shorter cilia. We then provide a rational explanation for both effects. We demonstrate that the apparent length-dependent flexural rigidity can be understood by a combination of modeling axonemal microtubules orthotropic elastic shells and including (actin-driven) active stochastic basal body motion. It is hoped that our improved characterization of cilia will result in deeper understanding of the biological function of cellular flow sensing by this organelle. Our model could be profitably applied to motile cilia and our results also demonstrate the possibility of using easily observable ciliary dynamics to probe interior cytoskeletal dynamics.
Polarography as a Tool for Investigations of Chemical Reactions Accompanying Electrode Processes

Polarographic investigation of three types of reactions connected with electrode processes is presented. Conjugated acids are in all instances reduced more easily (i.e. at more positive potentials) than conjugated bases. On the other hand, basic forms are more easily oxidized (at more positive potentials) than conjugated acids. From the current decrease in this pH range, the rate constant of protonation of the base (kr) can be determined, provided that protonation occurs in a homogeneous solution. Examples of studied systems of this type are given. Another type of chemical reactions preceding the electron transfer are conversions of covalently hydrated forms into reducible unhydrated species. Addition of OH- ions to aldehydes results in geminal diol anions (RCH(OH)-) which can be oxidized to carboxylic acids. Examples of chemical reactions interposed between two electron transfers are reactions of arylhydroxylamines formed in a four-electron reduction of nitro aromatic compounds. The roles of protonation, dehydration, condensation and some deactivation reactions of arylhydroxylamines are discussed.
What do youth tennis athletes say to themselves? Observed and self-reported self-talk on the court

Abstract Athlete self-talk is often measured by self-report, but seldom are self-reports compared to observed, audible self-talk. In this study, 28 tennis players attending a youth camp (Mage = 12 years) were observed in practice and match play for positive, negative, motivational, and instructional self-talk. They reported how often they used self-talk phrases (Automatic Self-Talk Questionnaire) and how much of their speech was aloud and inside their head (Self-Talk Use Questionnaire). We observed the same players on the court for overt self-talk use during practice and match play (Self-Talk and Gestures Rating Scale). In observation, players used more negative than positive self-talk, and they infrequently used instructional self-talk in matches and practice. Tennis athletes who reported more overt self-talk were observed to use more self-talk during tennis. In most cases, athlete self-report of positive and negative self-talk did not relate to observation of positive and negative self-talk. We argue that self-report for youth athletes needs to be confirmed by observation.
How to generate repeatable keys using physical unclonable functions: Correcting PUF errors with iteratively broadening and prioritized search

We present an algorithm for repeatably generating keys using entropy from a Physical Unclonable Function (PUF). PUFs are logically identical physical constructs with Challenge-Response Pairs (CRPs) unique to each device. Applications include initialization of server keys and encryption of FPGA configuration bitstreams. One problem with PUFs is response errors. Our algorithm corrects PUF errors that inhibit key repeatability. Our approach uses a PUF to generate an error-free PUF value in three steps. First, we repeatedly sample the PUF to determine the most likely value. Second, we apply an iteratively-broadening search to search up to some number of bit errors (in our experiments we use two). Third, we apply exhaustive search until the correct value is found or failure is declared. The searches are prioritized by the known bit error rates in decreasing magnitude. We assume the application includes a test for the correct value (e.g., some matching plaintextciphertext pairs). Previous algorithms often omit noisy PUF bits or use error-correcting codes and helper data. Our algorithm can use all PUF bits regardless of noise. Our approach is simple, and for appropriate parameter choices, fast. Unlike previous approaches using error-correcting codes, when used for public-key cryptography our method requires storing only the public key and no other helper N. Price E-mail: np1@umbc.edu A.T. Sherman E-mail: sherman@umbc.edu Cyber Defense Lab Department of Computer Science and Electrical Engineering University of Maryland, Baltimore County 1000 Hilltop Circle, Baltimore, MD 21784 data in non-volatile storage. We implemented a latch-based PUF on FPGAs and measured PUF characteristics to analyze the effectiveness of the algorithm. Tests for a 1024-bit PUF show 351 samples reduce the probability of errors to less than 10−6. The iterative broadening and exhaustive searches further reduce failure rates.
Evaluation of the Carcinogenic Effects of Estrogens, Progestins and Oral Contraceptives on Cervix, Uterus and Ovary of Animals and Man

Estrogens do not have the general biological effect of increasing the occurrence of cancer in various species of laboratory animals. The neoplastic effect of estrogens in animals is strain and species dependent. Estrogens may increase the incidence of uterine cervical cancer in some strains of mice, but not in other strains or other animal species. The progestins and oral contraceptives (OC) have not induced cervical cancer in animals and most studies demonstrate that the steroid anovulants do not increase the occurrence of abnormal cervical smears or cervical cancer in women.
Distributed project control management: using Fossil to get beyond source control

Effective source control practices are a requirement for most team software projects. For a great majority of these, web publishing, issue tracking, documentation maintenance, development news/blogs, and more are similarly critical. Engineers set out to choose from among several tools to support each of these project activities, find ways to integrate them, and, when possible, synchronize their histories, but this is not a trivial task. Typically, source control management is one of the first development support technologies selected, and with student teams and many open source projects it is often the last. Efforts to get a web site published and integrated with issue tracking and wiki systems quickly dissolve into good intentions as work toward them begins to be perceived as negatively impacting code inertia.
Pore–scale analysis of supercritical CO2–brine immiscible displacement under fractional–wettability conditions

Abstract The objective of this study was to investigate the effect of wettability heterogeneity on pore–scale characteristics of Supercritical (sc) CO2 displacement dynamics and its capillary trapping mechanism during a scCO2–brine drainage and imbibition cycle. A multiphase lattice Boltzmann (LB) model was employed to simulate scCO2–brine flow in rock samples of Tuscaloosa sandstone taken from the Cranfield CO2 injection site. Using a spectral method, we adopted various wettability fields to generate rock samples containing distributed CO2–wet regions. To gain a better insight into the effect of fractional wettability on scCO2 displacement patterns during drainage, we quantified the evolution of scCO2 interface with brine and rock surface for samples with various wettability heterogeneities. In addition, the effect of heterogeneous wettability on the drainage relative permeability and capillary pressure curves has been investigated in this study. According to our results, heterogeneous distribution of CO2–wet regions in the rock leads to more dispersed fluid distribution and, hence, more tortuous flow paths, resulting in higher interfacial area between fluid phases and rock surface at any given scCO2 saturation. Furthermore, the spatial distribution of wettability controls the scCO2 entrapment pattern and spatial distribution of residual scCO2 clusters during brine flooding. In fractional–wet samples, residence of scCO2 phase in CO2–wet regions creates more trapped scCO2 clusters, suppressing the connectivity of the CO2 phase, thus enhancing more residual trapping. Our results imply that the total number of scCO2 clusters and, as a result, their residual trapping, increases as the fraction of CO2–wet regions becomes larger, leading to a larger surface area of scCO2 with brine and rock surface, potentially, facilitating the likelihood of long-term dissolution and mineral trapping.
Suppression of human colorectal cancer cell proliferation by noncanonical Wnt 9A ligand induction.

e14621 Background: Malignant tissues are often characterized by dysfunctional Wnt signaling with the predominant feature involving the regulation of β-catenin. β-catenin is utilized by the canonica...
Correction to: Adverse Effects of Physostigmine

In "Adverse Effects of Physostigmine" by Arens et al in the July 2019 issue of JMT, reference #27 contains an error.
Perceptions of Rural SNAP-Authorized Food Store Owners and Managers About Healthy Product Availability

Abstract Objective Supplemental Nutrition Assistance Program (SNAP)–authorized retailers’ healthy perceptions and store availability of healthy products were explored to plan a healthy food retail program. Methods Cognitive anthropology (free list) and quantitative (food environment measure) methods were used to assess retailers’ healthy product perceptions and the availability of store products aligned with dietary guidance. Cultural domain analysis techniques and descriptive and inferential statistics were used to interpret data. Results SNAP–authorized retailers (n = 29) of rural grocery (17%), dollar (14%), convenience (66%), and specialty (3%) stores participated. There was low salience for what constituted healthy and misalignments with dietary guidance and inventory. Dried beans, nuts, and seeds were widely available products across all stores and were listed less frequently by retailers. Conclusions and Implications Engagement with SNAP–authorized retailers to develop retailer-focused nutrition education and/or training protocols is warranted to improve the capacity for retailers to market store products aligned with dietary guidance.
Integrating computer ethics components into the computer science curriculum

In addition to understanding the technical aspects of computer science, students today are expected to understand the role ethics plays in the computing field, how to conduct themselves in an ethical manner and how to apply ethical decision-making techniques. One method for including ethics in a computer science curriculum is to require a course on computing ethics. At Widener, we are developing such a course in conjunction with our philosophy faculty. The resulting course will be co-taught by a philosopher and a computer scientist. While this is a significant step, we can further emphasize the importance of ethics in computing by incorporating ethics components into our existing courses.