cssi/SciSciGPT-SciSciNet huggingface dataset:
Proximal row carpectomy

Abstract Excision of the proximal carpal row has proven over the past 60 years to be an effective technique for certain disorders of the wrist, including degenerative sequelae of scapholunate ligament dissociation and scaphoid nonunions, Kienbock disease, Preisser disease, and other fracture-dislocations of the wrist. The durability of this procedure may be due to remodeling of the capitate head to the lunate fossa. Poor results have been noted in patients with rheumatoid arthritis and arthrogrypotic wrist deformities. Preservation of relatively normal cartilage of the capitate head as well as the lunate fossa is critical for success of this procedure. Average outcomes of this procedure include a wrist extension-flexion arc of 75° and grip strength of 60% of the uninvolved wrist. Revision to total wrist arthrodesis is required in 10% of patients. Approximately 90% have pain relief and can return to moderate use activity. Copyright © 2001 by the American Society for Surgery of the Hand
Externally Linear Time Invariant Digital Signal Processors

We present a technique whereby internal signals in a DSP can be externally controlled without causing any output disturbances. While the resulting system is in general internally time-varying or internally nonlinear, the external input-output behavior is time-invariant and identical to that of the prototype linear time invariant (LTI) system. Our technique can be used to dynamically scale the input, output, and all internal states of a fixed-point DSP such that they always stay close to full scale, thus spanning most of the available bits and making possible a large signal-to-noise-plus-distortion ratio (SNDR) over a large (external) input range. We show that this application of our technique is an extension of companding (compressing/expanding) to DSPs. A hardware implementation of a companding DSP is presented. At low and medium signal levels, the output SNDR of our companding DSP is significantly larger than that of the corresponding classical DSP using the same number of bits.
Applying the interpersonal circumplex to the behavioral styles of dogs and cats

The present study examined the viability of the interpersonal circumplex, which was designed to examine human social behavior, as a model for considering the behavioral styles of dogs and cats. This was accomplished by recruiting 555 pet owners to report on the behavioral styles of their pets as well as their own interpersonal styles. The instrument used to assess the behavioral styles of household pets conformed to the expected circular structure for both dogs (CI = 0.93, P < 0.001) and cats (CI = 0.93, P < 0.001) which suggests that the instrument is suitable for use with at least these non-human species. The results of hierarchical multiple regression analyses found that owners reported more positive attitudes toward their pets when the behavioral styles of their pets complemented their own interpersonal styles. The owners of both dogs and cats were more satisfied when they perceived their pets as exhibiting a level of warmth that was similar to their own but this tendency was especially strong for cat owners. For dominance, however, cat owners reported more positive attitudes toward their pets when there was reciprocity between their own interpersonal styles and the perceived behavioral styles of their pets (e.g., dominant cat owners reported more positive attitudes toward their pets when they perceived their pets as submissive). Complementarity on the dominance dimension did not emerge as a significant predictor of positive attitudes toward dogs.
Anterior haptic flexing and in-the-bag subluxation of an accommodating intraocular lens due to excessive capsular bag contraction

We describe the case of a patient who had cataract surgery with implantation of the hydrophilic acrylic Tetraflex accommodating intraocular lens (IOL), with subsequent development of capsulorhexis phimosis and in-the-bag IOL subluxation. Contraction of the capsular bag secondary to fibrosis resulted in significant anterior flexing of the lens haptic component. Explantation of the IOL–capsular bag complex was required 7 years after implantation. Histopathologic analysis demonstrated multiple areas of thick anterior subcapsular fibrosis. Pseudoexfoliative material was present throughout the surface of the lens capsule. Intraocular lenses manufactured from hydrophilic acrylic material are highly flexible and may be more susceptible to capsule contraction, even in the absence of predisposing ocular and systemic conditions. This case highlights the importance of developing guidelines regarding patient screening and selection for the appropriate use of accommodating and other highly flexible IOLs. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.
An FDTD model for low and high altitude lightning-generated EM fields

To explore lightning-generated electromagnetic wave behavior and lightning-related ionospheric phenomena, a full-wave two-dimensional cylindrical finite-difference time-domain (FDTD) model was developed to simulate lightning-generated electromagnetic wave propagation in the ionosphere with high altitude and long distance capabilities. This FDTD model removes the approximations made in other similar models to extend its applicability, and incorporates a variety of existing methods and new techniques. A dispersive and anisotropic realization of the nearly perfectly matched layer (NPML) absorbing boundary condition is adopted in this numerical model for ease of implementation. Earth curvature is included in the model through the modified refractive index method. The surface impedance boundary condition is adopted to treat arbitrary but homogeneous ground parameters. We quantify the errors through dispersion relations, and the solution convergence is analyzed. Comparisons between our simulation, numerical waveguide mode theory, and experimental data validate this model and show its capabilities compared to other methods. Although this FDTD model was developed for the lightning-generated electromagnetic field simulation, it is also applicable for other very low frequency (VLF, 3-30 kHz) and extremely low frequency (ELF, 3-3000 Hz) wave propagation problems
An Information Economic Approach for Model Selection In Engineering Design

An important element of successful engineering design is the effective management of resources to support design decisions. Design decisions can be thought of as having two phases—a formulation phase and a solution phase. As part of the formulation phase, engineers must decide which models to use in support of design decisions. Although more accurate models typically lead to better decisions, they also cost more. The question therefore is: Which model provides the best cost-benefit trade-off? In this paper, we focus in particular on the situation in which the systematic error in the models can be bounded by an interval. Based on principles of information economics, the interval-based model error results in bounds on the expected economic value of using a particular model in support of a certain design decision. The decision maker can then select the model that provides the best overall value, considering both the expected benefits resulting from the decision and the cost of the decision-making process. The approach is illustrated with the design of an I-beam structure.Copyright © 2006 by ASME
A writer's collaborative assistant

In traditional human-computer interfaces, a human master directs a computer system as a servant, telling it not only what to do, but also how to do it. Collaborative interfaces attempt to realign the roles, making the participants collaborators in solving the person's problem. This paper describes Writer's Aid, a system that deploys AI planning techniques to enable it to serve as an author's collaborative assistant. Writer's Aid differs from previous collaborative interfaces in both the kinds of actions the system partner takes and the underlying technology it uses to do so. While an author writes a document, Writer's Aid helps in identifying and inserting citation keys and by autonomously finding and caching potentially relevant papers and their associated bibliographic information from various on-line sources. This autonomy, enabled by the use of a planning system at the core of Writer's Aid, distinguishes this system from other collaborative interfaces. The collaborative design and its division of labor result in more efficient operation: faster and easier writing on the user's part and more effective information gathering on the part of the system. Subjects in our laboratory user study found the system effective and the interface intuitive and easy to use.
Establishing the Steric Bulk of Main Group Hydrides in Reduction Reactions

The steric bulk of reducing agents has been widely employed in the generation of chiral centers and selective reductions of organic compounds, but reports addressing the quantification of the steric bulk surrounding the main group hydride have been virtually non-existent. To address the limited amount of steric bulk information of main group reducing agents, the cone angles of 84 main group hydrides related to the chemistry of frustrated Lewis pairs are reported. Of the 84 main group hydrides, the steric bulk of two carbon-based hydrides, four aluminum hydrides, 11 borane-Lewis base adducts derived from borenium cations, nine organosilanes, two organostannanes, one organogermane, and 55 borohydrides are investigated. In addition to the main group hydride complexes reported, the cone angle of four highly active metal-hydride complexes, used in the asymmetric reduction of ketones, are determined and compared with chiral main group hydrides. Steric bulk analysis suggests that chiral hydride complexes exhibiting cone angles >165° achieve highly enantioselective reductions (>90 % ee).
Programmable bacteria detect and record an environmental signal in the mammalian gut.

The mammalian gut is a dynamic community of symbiotic microbes that interact with the host to impact health, disease, and metabolism. We constructed engineered bacteria that survive in the mammalian gut and sense, remember, and report on their experiences. Based on previous genetic memory systems, we constructed a two-part system with a “trigger element” in which the lambda Cro gene is transcribed from a tetracycline-inducible promoter, and a “memory element” derived from the cI/Cro region of phage lambda. The memory element has an extremely stable cI state and a Cro state that is stable for many cell divisions. When Escherichia coli bearing the memory system are administered to mice treated with anhydrotetracycline, the recovered bacteria all have switched to the Cro state, whereas those administered to untreated mice remain in the cI state. The trigger and memory elements were transferred from E. coli K12 to a newly isolated murine E. coli strain; the stability and switching properties of the memory element were essentially identical in vitro and during passage through mice, but the engineered murine E. coli was more stably established in the mouse gut. This work lays a foundation for the use of synthetic genetic circuits as monitoring systems in complex, ill-defined environments, and may lead to the development of living diagnostics and therapeutics.
Determination of Critical Microstructural Features in an Austenitic Stainless Steel Using Image-Based Finite Element Modeling

Two-dimensional (2-D) and three-dimensional (3-D) image-based finite element (FE) modeling and scientific visualization techniques were employed to determine the critical microstructural features that control mechanical behavior in a commercial austenitic stainless steel, AL-6XN. Two-dimensional FE meshes were generated using microstructural images obtained from electron backscatter diffraction (EBSD), and three-dimensional meshes were generated from microstructural reconstructions created using serial-sectioning techniques and EBSD. Image-based FE simulations were run using anisotropic elasticity. The 2-D simulations revealed that higher local elastic stresses are produced near grain boundaries than at grain interiors for various loading conditions. Under normal uniaxial loading conditions, higher stresses were observed at faceted grain boundaries, particularly those with a Σ = 3 coincident site lattice misorientation. Under simple shear loading conditions, however, the highest stresses were observed at general high-angle grain boundaries. In the 3-D simulations, similar relationships held, with the highest elastic stresses observed at the junction between two Σ3 boundaries under normal uniaxial loading and slightly lower elastic stresses at these junctions under simple shear loading. In the 3-D models, high elastic stresses were associated only with grain boundaries and triple junctions and showed little to no correlation with grain size or morphology.
Is there a connection between carbon monoxide exposure and hypertension

Exposure to carbon monoxide in our society is a frequent occurrence, from auto exhaust, industrial effluents, and cigarette smoke, and takes place over a wide range of concentrations. It has been suggested that chronic CO inhalation may alter blood pressure, even possibly provoking hypertension by acting alone or in combination with other environmental stressors. Some studies examining the response to CO exposure have reported decreases in blood pressure, whereas others have found increases or no change. Blood pressure in long-term cigarette smokers is generally decreased relative to nonsmokers, albeit a slight decrease. The strength of this finding is somewhat clouded by the effect of the lower body weight in smokers. The increases in blood pressure observed acutely with smoking are mainly due to nicotine. Chronically, the hypertensive action of nicotine is largely offset by the hypotensive action of CO. Several studies support the notion that environmental CO exposure or smoking accelerates or exacerbates hypertension in some people. It has been asserted that chronic CO exposure increases the development of atherosclerotic disease; however, convincing evidence from animal experiments is lacking. Nevertheless, CO may elevate plasma cholesterol and does appear to enhance atherosclerosis when serum cholesterol is greatly elevated by diet. Using the borderline hypertensive rat, an animal model reputed to have increased sensitivity to environmental stimuli, we found no evidence to suggest a provocatory role for CO in the development of hypertension; instead, CO exposure produced hypotension. On the whole, the human and animal literature, as well as our studies, fail to support the hypothesis that long-term CO exposure is capable of provoking an increase in blood pressure, even in borderline hypertensive or sensitive individuals.
Mitigating Attacks Against Measurement-Based Adaptation Mechanisms in Unstructured Multicast Overlay Networks

Many multicast overlay networks maintain application-specific performance goals such as bandwidth, latency, jitter and loss rate by dynamically changing the overlay structure using measurement-based adaptation mechanisms. This results in an unstructured overlay where no neighbor selection constraints are imposed. Although such networks provide resilience to benign failures, they are susceptible to attacks conducted by adversaries that compromise overlay nodes. Previous defense solutions proposed to address attacks against overlay networks rely on strong organizational constraints and are not effective for unstructured overlays. In this work, we identify, demonstrate and mitigate insider attacks against measurement-based adaptation mechanisms in unstructured multicast overlay networks. The attacks target the overlay network construction, maintenance, and availability and allow malicious nodes to control significant traffic in the network, facilitating selective forwarding, traffic analysis, and overlay partitioning. We propose techniques to decrease the number of incorrect or unnecessary adaptations by using outlier detection. We demonstrate the attacks and mitigation techniques in the context of a mature, operationally deployed overlay multicast system, ESM, through real-life deployments and emulations conducted on the PlanetLab and DETER testbeds, respectively.
Microwave Synthesis of Metal Oxide Nanoparticles

This chapter summarizes microwave irradiation methods for the preparation of metal oxide nanoparticles and their catalytic and sensing properties and applications. Microwave irradiation provides rapid decomposition of metal precursors and can be extended for synthesis of a wide range of metal oxide nanoparticles with various compositions, sizes and shapes. This chapter introduces the microwave method and describes the nucleation and growth process for the formation nanocrystals. We offer a broad overview of metal oxide nanostructures synthesized by microwave irradiation including: ZnO, TiO2, CeO2, other rare earth metal oxides, transitional metal oxides and metal ferrite nanostructures. Finally, we describe the application of metal oxides in the photocatalytic degradation of organic dyes and gas sensing devices.
Oakridge Research and Education Prairie

Reconstructed tallgrass prairies (prairies that have been replanted) in Iowa and elsewhere in the Great Plains often lose many of the planted species over time, leading to lower diversity compared with prairie remnants. Establishment and maintenance of diversity in these reconstructions may be heavily influenced by herbivores. Herbivores such as white-tailed deer (Odocoileus virginianus), rabbits, and voles (Microtus spp.) may increase prairie diversity by eating competitively dominant plants, or decrease diversity by eating rare species. In addition to consuming adult plants, herbivores may further affect plant diversity by consuming seeds and seedlings and/or dispersing seeds to new locations.
Microscopic Relativistic Description of Proton - Nucleus Scattering

Microscopic relativistic optical potentials have been calculated for closed shell nuclei at energies near 200 MeV. These calculations go beyond the simple RIA by resolving ambiguities in the relativistic NN amplitudes and including Pauli blocking corrections.
Pencil-beam and simple fanned-beam antennas

The term “pencil beam” is applied to a highly directive antenna pattern consisting of a single major lobe contained within a cone of small solid angle and almost circularly symmetrical about the direction of peak intensity. As used here, it will apply to beams with half-power width less than 15°. These beams are analogous to searchlight beams, and, as with an optical search light, the elevation and azimuth coordinates of a target in space can be simply correlated with the similar coordinates that define the orientations of the antenna. In connection with the technique of using radar echoes for obtaining range information, the pencil-beam antenna serves to define the position of a target completely.
3-D HYDRAULIC MODEL OF WAVES GENERATED BY DISPLACEMENTS

Measurements were made of the water waves generated by the horizontal motion of submerged plungers. The results obtained in a three-dimensional hydraulic model experiment, using a plunger 0.5 ft. wide and 0.25 ft. high, were compared with both the experimental results and theory for the two dimensional case. It was found that at a given location the ratio of the elevation above the still water level (SWL) of the first wave (the largest wave of the group for the range of variables tested) to the displacement of the plunger (HgA) was found to be dependent upon the Froude Number Npa (based upon the average plunger speed and the water depth) and upon the ratio of the height of the plunger to the water depth (D/d). For a constant value of 9, H3/A increased with increasing Npav„ and D/d. A few additional tests were made using a plunger 2.0 ft. wide and 0.25 ft. high. The results show that Ho/A depends also upon the ratio of water depth to the width of the plunger (d/W).
NEGATIVE STIMULUS DURATION AS A FACTOR IN FREQUENCY DISCRIMINATION BY CATS LACKING AUDITORY CORTEX.

The learning of frequency discrimination by the cat after removal of auditory cortex depends on the duration of the negative conditioned stimulus. Generally, this stimulus must be presented for at least 1 min., if learning is to occur.
INTERNAL HERNIA THROUGH A DEFECT IN THE BROAD LIGAMENT OF THE UTERUS -A CASE REPORT-

今回われわれは腸閉塞で緊急手術を施行した子宮広間膜裂孔ヘルニアの1例を経験したので,若干の文献的考察を加えて報告する.症例は53歳,女性,既往歴は妊娠3回,分娩3回.腹痛,嘔吐を認め当院内科受診.受診時,下腹部に圧痛,筋性防御を認めた.腹部造影CTにて拡張腸管と腹水の貯留が認められた.内ヘルニアによる絞扼性イレウスと診断し緊急手術を施行した.開腹すると回腸末端より150cmの部位から30cmにわたる回腸が,左側子宮広間膜に生じた異常裂孔に陥入し絞扼されていた.陥入した腸管を整復し,腸切除を行った.子宮広間膜の裂孔を閉鎖し手術を終了した.子宮広間膜裂孔ヘルニアは稀な疾患であり,診断にはCTが有用とされているが,本疾患を念頭に置かない限り術前診断は困難であると考えられる.
"Rule out ectopic": Asking the right questions, getting the right answers.

Abstract Sonographic evaluation of the pregnant patient suspected of harboring an ectopic pregnancy (EP) helps determine patient management. Although clinicians typically ask sonologists to "rule out" EP in these patients, the sonologist actually must answer 3 questions: (1) Is there an intrauterine pregnancy (IUP)? (2) Is the possibility of normally developing IUP reliably excluded? (3) Are there sonographic findings that identify or increase the likelihood of an EP? Understanding the rationale behind these questions and the sonographic findings that help to answer these questions enables the sonologist to contribute meaningfully to the care of patients with possible EP. Beginning the sonographic examination with a limited transabdominal approach has value. An IUP can be confidently diagnosed by identification of an intradecidual sac exhibiting the double decidual sac sign, yolk sac, or embryo. When the serum β human chorionic gonadothropin exceeds 2000 mIU/mL, a technically excellent sonographic examination should identify an intradecidual sac potentially representing an IUP. Even without directly visualizing a yolk sac or embryo in the adnexa, the presence of an extraovarian mass or hemoperitoneum strongly predicts the possibility of EP. An intraovarian mass with peripheral hypervascularity is more likely to represent the corpus luteum rather than an intraovarian EP. Cervical EP can be distinguished from the cervical phase of a spontaneous abortion in progress by either demonstrating fetal heart motion or persistence or enlargement of findings on short-interval follow-up. Absence of a myometrial mantle surrounding one edge of an IUP positioned at the fundus is suspicious for an interstitial EP.
The context of health care policy: a social exchange approach to cost-effectiveness.

This article reviews four cost-effectiveness problems in the United State health care system and seven solutions to them proposed by former Secretary of Health, Education and Welfare, Joseph A. Califano Jr. (1988). It considers contextual issues of how these problems developed and builds on the proposed recommendations form a social exchange view. Suggested expansions and revisions to Secretary Califano's recommendations are discussed.
Multiple inhibitory effects of genistein on stimulus-secretion coupling in rat pancreatic acini

Genistein, a tyrosine kinase inhibitor, inhibited cholecystokinin (CCK)-induced maximal amylase release from rat pancreatic acini by 18, 31, and 46% at concentrations of 100, 300, and 750 microM, respectively, after 30 min preincubation. Genistein similarly decreased amylase release stimulated by bombesin but not that stimulated by secretin or vasoactive intestinal peptide. The steps of stimulus-secretion coupling affected by genistein were further evaluated. We found genistein dose dependently suppressed CCK-as well as NaF-induced polyphosphoinositide hydrolysis with a 50% inhibitory concentration of 380 and 400 microM, respectively, but only slightly suppressed the increase of intracellular Ca2+ concentration in response to either low or high concentrations of CCK. Genistein at 300 microM also decreased incorporation of [3H]inositol into phosphatidylinositol 4,5-bisphosphate. Most strikingly, 300 microM genistein inhibited Ca(2+)-stimulated amylase release by 85% in streptolysin O-permeabilized acini and thapsigargin-stimulated amylase release by 69% in intact acini. Daidzein, the inactive analogue of genistein, had no effect on any of the above parameters. Genistein, up to 750 microM, did not affect amylase release in response to phorbol ester. To relate these inhibitory effects of genistein to its inhibition of tyrosine phosphorylation, Western blotting was performed with an anti-phosphotyrosine monoclonal antibody. Genistein at 100 microM partly and at 300 microM completely inhibited CCK-induced tyrosine phosphorylation. In conclusion, genistein inhibits amylase release at multiple stages of stimulus-secretion coupling. These effects most likely involve both tyrosine kinase-dependent and -independent mechanisms.
Application of CBERS-02 CCD data in flood monitoring——a case study of Xincai,Henan province

In order to statistic water flood information,the spectral reflectance characteristics of different depth water was analyzed in flood period、Reflection characteristic of different objects on CBERS-02 CCD data was given a comparative analysis.By model building on ERDAS software,the water area was extracted of 2,3,4 bands in CCD data.The extracted result was given a contrast with history remote image to analyse the water change,and maps of basic informational layers were superposed by using GIS technology for analysis and operations.The monitor result was credible and accorded with the truth.
Convergent Evolution, Adaptive Radiation, and Species Diversification in Plants

Similar ecological conditions often favor phenotypic convergence, which can arise through convergent evolution or through species sorting along environmental gradients based on their biological equipment. Convergence may be tempered by competition among functionally similar species, leading to divergence; such divergence in ecology and phenotype within lineages is termed adaptive radiation, which in many ways is the converse of convergent evolution. Adaptive radiation and the evolution of particular phenotypes can accelerate speciation. Patterns of convergence, divergence, and diversification in plants of two extreme environments – alpine habitats and deserts – are reviewed.
Abstract IA04: Neuroblastoma as a paradigm of MYC(N) driven cancers

Neuroblastoma is an enigmatic childhood cancer with phenotypes ranging from spontaneous regression of seemingly advanced disease to relentless metastatic progression. MYCN amplification was defined as a powerful predictor of metastatic potential and acquisition of therapy resistance in the 19809s, and arguably was the first genomic biomarker utilized in routine clinical practice to stratify therapeutic intensity. While there have been incremental improvements in cure rates over the last three decades, these have come at the cost of a highly complex and intensive chemoradiotherapeutic regimen that leaves survivors with significant long-term morbidity. Here we will discuss our ongoing efforts to define the genetic basis of neuroblastoma, and recent insight into how heritable DNA variation influences neuroblastoma susceptibility and clinical phenotypes, including MYCN amplification. We will also discuss the major oncogenic drivers of high-risk neuroblastoma beyond MYCN, including recent insights into the role of MYC in the MYCN-non-amplified high-risk cases, as well as the major role of the ALK oncogene, often in cooperation with MYCN. Finally, we will discuss recent efforts to leverage this information therapeutically, with a focus on how therapeutically targetable oncogenic pathways evolve under the selective pressure of chemoradiotherapy. Finally, we will discuss nascent efforts to deliver on the holy grail of neuroblastoma translational research—targeting the MYCN oncoprotein itself, discussing opportunities and challenges. Citation Format: John M. Maris. Neuroblastoma as a paradigm of MYC(N) driven cancers. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr IA04.
Plant Genetic Engineering, Ecological Issues

In recent years, ecologists have come to realize the influence that plant genetic factors can have on associated communities of insects, microbes, or herbivores, and that these interactions can lead to altered ecosystem functions. With the advent of genetic engineering, novel transgenic modifications have the potential to further influence communities and ecosystems. An extensive review of the literature reveals that transgenic modifications often have no significant influence on nontarget communities and ecosystem processes, but when significant influences are demonstrated, they are much more likely to be negative influences than positive influences. Given the diversity of scientific results to date, it is clear that genetically modified (GM) plants sometimes have negative influences on associated, nontarget communities and ecosystem functions, but often their influence is no different from non-GM plants. The precautionary principle would have us wait until all GM products are deemed safe in all circumstances. Clearly with over 95% of the three most common crops in US production coming from GM seed in 2014, industry and agribusiness are not waiting for a biosafety blessing. Whether personal ethics argue for prudence may be irrelevant given the current scale of GM production in the United States.
[18F](2S,4R)4-Fluoroglutamine PET Detects Changes in Glutamine Pool in Triple Negative Breast Cancer in Response to Glutaminase Inhibition

1363 Objectives - Methods Mice bearing human TNBC (HCC1806) or receptor positive breast cancer (MCF-7) xenografts undergo [18F]Fluoroglutamine PET imaging before and after treatment with glutaminase inhibitors or vehicle solution. Metabolic conversion of [18F]Fluoroglutamine to [18F]Fluoroglutamate in the tumor and blood was analyzed. Tumor glutamine pool (µmole/gram) was estimated by high resolution proton magnetic resonance spectroscopy (1H MRS) of aqueous metabolites extracted from tumor homogenates. Tumor-to-blood-activity-ratios (T/B) derived from [18F]Fluoroglutamine PET images were compared between GLS inhibitor vs. vehicle treated mice and were correlated with tumor glutamine pool size quantified by independent 1H MRS. Results HCC1806 cells and tumors, due to high GLS activity, exhibit low cellular glutamine concentration, which was markedly increased after GLS inhibition. In contrast, glutamine concentration was much higher and exhibited little change upon GLS inhibition in MCF-7 tumor, whose GLS activity is inherently low. Minimal metabolic conversion of [18F]Fluoroglutamine to [18F]Fluoroglutamate was identified in the blood and tumor regardless treatment by GLS inhibitor or vehicle, suggesting [18F]Fluoroglutamine (parent tracer) is the major species in blood and tumor within the time frame of PET imaging. In mice bearing TNBC tumors, T/B values increased significantly in response to GLS inhibition, whereas no change was induced by vehicle treatment. In receptor-positive tumors, however, GLS inhibitor was not able to induce changes in T/B ratio. Furthermore, in HCC1806 and MCF-7 tumors after glutaminase inhibitor or vehicle treatment, a positive correlation between T/B values (obtained from PET) versus glutamine concentrations (by MRS) was identified (R2=0.8). Finally, glutamine distribution volume (DV), which provides an estimate of the glutamine pool size, has been obtained via compartment modeling of dynamic PET data and preliminary results are reported in a separate abstract. Conclusions breast cancers with high glutaminase activity, changes of cellular glutamine pool size in response to GLS inhibitor treatment can be detected by [18F]Fluoroglutamine PET. This biomarker may facilitate the development of this new category of cancer therapeutics.
Analysis of Factors Affecting Successful Clinical Trial Enrollment in the Context of Three Prospective, Randomized, Controlled Trials.

Purpose Challenges can arise when attempting to maximize patient enrollment in clinical trials. There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to clinical trial enrollment, particularly the influence of timing, in context of three prospective, randomized oncology trials where one arm was considered more aggressive than the other. Methods and Materials From June 2011 to March 2015, patients who were enrolled on 3 prospective institutional protocols (an oligometastatic non-small cell lung cancer [NSCLC] trial and 2 proton vs intensity modulated radiation therapy trials in NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher's exact test, Student's t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients. Results A total of 309 eligible patients were approached about trial enrollment. The enrollment success rate during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligometastatic protocol: 5 vs 3 appointments [ P P =.0018]; esophageal protocol: 3 vs 2 appointments [ P =.0086]). No other factors or patient characteristics significantly affected enrollment success rate. Conclusion Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success and may help overcome accrual barriers without compromising trial design.
The Prevalence of Lipoprotein(a) Measurement and Degree of Elevation Among 2710 Patients With Calcific Aortic Valve Stenosis in an Academic Echocardiography Laboratory Setting

Lipoprotein(a; Lp[a]) and its associated oxidized phospholipids are causal, genetic risk factors for calcific aortic valve stenosis (CAVS). We determined the prevalence of Lp(a) measurement among 2710 patients with CAVS and 1369 control patients (∼50% of study group) without CAVS with an echocardiogram between January 2010 and February 2016 in an academic echocardiography laboratory. Lipoprotein(a) measurements were performed at a referral laboratory using an isoform-independent assay. The prevalence of any Lp(a) measurement was 4.6% (124 of the 2710) in patients with CAVS and 3.1% (42 of the 1369) in the control group ( P = .021). In patients with CAVS, mean (standard deviation) Lp(a) levels were 38 (54) mg/dL and median (interquartile range) Lp(a) levels were 14 (6-48) mg/dL. Of the 124 patients with CAVS having Lp(a) measurements, 83 (66.9%) had Lp(a) <30 mg/dL and 41 (33.1%) had Lp(a) ≥30 mg/dL. This study reflects low physician testing of Lp(a) levels in CAVS. Given the role of Lp(a) as a causal risk factor for CAVS, and the ongoing development of therapies to normalize Lp(a) levels, our results suggest that Lp(a) measurements in CAVS should be more widely obtained in clinical practice.
Differential effects of cannabinoid CB1 inverse agonists and antagonists on impulsivity in male Sprague Dawley rats: identification of a possibly clinically relevant vulnerability involving the serotonin 5HT 1A receptor

Cannabinoid CB1 inverse agonists hold therapeutic promise as appetite suppressants but have produced suicidal behaviors among a small subpopulation in clinical trials. Anatomical and pharmacological evidence implicate the 5HT1A serotonin receptor in suicide in humans and impulsivity in humans and animals. The objective of the study is to assess whether 5HT1A blockade is necessary for CB1 ligands to produce impulsivity. Sprague Dawley rats were administered the CB1 inverse agonist AM 251, the CB1 antagonist AM 6527, or the peripherally restricted antagonist AM 6545, with or without pretreatment with the 5HT1A antagonist WAY 100,635 (WAY) on the paced fixed consecutive number (FCN) task, which measures choice to terminate a chain of responses prematurely. As FCN is sensitive to changes in time perception, which have been demonstrated with CB1 blockade, a novel variable consecutive number task with discriminative stimulus (VCN-S D ) was also performed and proposed to be less sensitive to changes in timing. Pretreatment with WAY enabled mild but significant reductions in FCN accuracy for AM 251 and AM 6527. No effects were found for AM 6545. On the VCN-S D task, substantial impairments were found for the combination of WAY and AM 251. AM 251, but not the antagonists AM 6527 or AM 6545, produced impulsivity only following systemic 5HT1A blockade. Although preliminary, the results may indicate that disrupted serotonin signaling produces a vulnerability to undesirable effects of CB1 inverse agonists, which is not evident in the general population. Furthermore, neutral CB1 antagonists do not produce this effect and therefore may have greater safety.
The De Beers Group: Exploring the Diamond Reselling Opportunity

In September 2014, Tom Montgomery (SVP of Strategic Initiatives at the De Beers Group) and his team launched a pilot program in the United States to explore the $1 billion market for pre-owned (recycled) diamonds. According to Montgomery, the motivation for the pilot program was to improve the consumer reselling experience and to enhance “diamond equity.” Somewhat paradoxically, consumers often received very low prices when they tried to resell diamonds leaving them reluctant to purchase diamonds in the future and making them into ambassadors of ill will. At a meeting scheduled for November 2015, the De Beers Executive Committee would have to decide whether to end the pilot program, extend it for another year to gather more information, or convert it into a new standalone business unit. Because De Beers had historically focused on producing rough diamonds (the “upstream” business), yet the new business unit offered an opportunity to enter and enhance the market for polished diamonds (the “downstream” business), the decision was particularly noteworthy. This case illustrates the process of strategy implementation as it analyzes the decision to vertically integrate at one of the world’s most iconic companies and brands (De Beers: A Diamond is Forever). De Beers created a pilot program designed to enhance customer value (common value) by creating a more viable secondary market for pre-owned diamonds. The case challenges students to understand whether and how the secondary market will impact the primary market for diamonds. The answer to this question lies on the balance between the benefits and the risks of changing scope. Through this analysis, students must resolve two apparent paradoxes present in the diamond industry: first, why diamonds, a product with little intrinsic value, sell for such high prices; and second, why “recycled” or pre-owned diamonds, an infinitely durable good, sell for such low prices (often 10-20% or retail price)? In answering these two questions, students learn about the role of advertising in creating a strategic asset, the difference between creating common value and creating competitive advantage, and the challenge of selling durable goods.
Impact of sleep apnea on in-hospital outcomes after transcatheter aortic valve replacement: insight from National Inpatient Sample database 2011–2014

Background: Sleep apnea is associated with worse outcomes following various kinds of surgeries. There is a paucity of data on the association of sleep apnea with clinical outcomes after transcatheter aortic valve replacement (TAVR). Methods: We used National Inpatient Sample (NIS) data 2011–2014 to identify patients undergoing TAVR. Association between sleep apnea and in-hospital postoperative outcomes were assessed by multivariate logistic regression and 1:1 propensity score matching analyses. Results: Of 42,189 patients who received TAVR, 4,605 patients (10.9%) had sleep apnea. Patients with sleep apnea were more likely to be younger and male with higher prevalences of hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, pulmonary hypertension and obesity who less frequently received transapical access than those without sleep apnea. The group with sleep apnea had less bleeding requiring transfusion (8.6% vs . 11.9%, P=0.01) than the counterpart. After adjusting for confounders, the presence of sleep apnea was no longer independently associated with any of the studied outcomes including all-cause mortality (OR 0.95; 95% CI: 0.64–1.42), stroke (OR 1.08; 95% CI: 0.65–1.81), myocardial infarction (OR 0.66; 95% CI: 0.36–1.22), acute respiratory failure (OR 0.94; 95% CI: 0.72–1.23), pneumothorax (OR 0.64; 95% CI: 0.26–1.59), vascular complication (OR 0.91; 95% CI: 0.69–1.22), bleeding requiring transfusion (OR 0.85; 95% CI: 0.65-1.11), acute kidney injury requiring hemodialysis (OR 0.94; 95% CI: 0.53–1.66) and permanent pacemaker implantation (OR 1.12; 95% CI: 0.87–1.43). The length and cost of hospital stay were not affected by sleep apnea, either. Conclusions: With a prevalence of 10.9%, the presence of sleep apnea was not independently associated with postoperative in-hospital outcomes in patients undergoing TAVR in NIS data 2011 to 2014.
Properly Funding the Copyright Office: The Case for Significantly Differentiated Fees

The United States Copyright Office performs a variety of functions crucial to the copyright system. Through its core registration and recordation functions, it provides critical information about the authorship, ownership, and copyright status of millions of works of authorship created over the last century; it also advises Congress, other federal agencies, and the courts on copyright law; conducts studies on various aspects of copyright law; participates in international meetings; produces educational programs and publications; and engages in many other activities relating to the administration of copyright law. However, the Copyright Office is seriously underfunded, compromising all of its functions. The essentially flat, front-end fees that the Office charges for registration and recordation fail to generate nearly enough revenue for the Office to survive, let alone thrive. Because the Office depends on Congress to appropriate taxpayer dollars to fund over a third of a tight budget, and depends on its parent agency, the Library of Congress, to request those appropriations, it is chronically short of funds. In this article, I argue that the Copyright Office should follow the example of the Patent and Trademark Office, and charge significantly differentiated fees for registration and recordation. Just as patent and trademark fees are, those fees should be differentiated across time – over the life of a copyright – by splitting payment up into “front-end” fees imposed at the time of application, and “back-end” fees charged for renewal. They should also be differentiated across different works and applicants at the same time. In addition, I argue that the Copyright Office should be able to set fees based, not just on current costs of services rendered, but also on anticipated capital improvement costs, and on the cost of non-service activities that support the copyright system, such as the preparation of reports on copyright issues and the provision of public information about copyright law. Whether differentiated copyright fees can provide ample funds for an entirely self-supporting Copyright Office is an open question, and it will need to remain open for some time. “Back-end” renewal fees would and should probably only be imposed on new registrations, with the result that back-end revenue would not start flowing until those fees came due on new registrations. Although it would thus take years to fully implement differentiated fees, such fees would eventually produce a wide variety of benefits. They would enable the Copyright Office to better fulfill all of its missions; they would make registration and recordation more affordable for modest applicants and works, thus enlarging the stock of copyright information provided by the Copyright Office; and they would decrease or eliminate reliance on taxpayer support of the Office.
Psychosocial challenges for patients with advanced lung cancer: interventions to improve well-being

As compared to other cancers, lung malignancies are associated with high symptom burden, poorer prognosis, and stigmatization. Such factors increase psychological distress and negatively impact quality of life. Research has documented the efficacy of psychosocial interventions to alleviate psychological distress and promote well-being among patients with cancer. This article summarizes the current literature on psychosocial interventions in lung cancer. Major types of psychosocial interventions in lung cancer include cognitive-behavioral therapies, psycho-education, mind-body, exercise, and supportive or palliative care strategies. Discussion relative to the purpose, sample, research design, outcomes, and quality of the studies is presented. Findings may be useful in clinical environments as a resource to help health providers better understand mental health treatment options and care for patients facing lung cancer. The need to direct future research toward the advancement of science and improve well-being and quality of life outcomes for patients with advanced lung cancer and their family members is discussed.
Abstract B043: Mithramycin-SA analogues with reduced toxicity for the treatment of ETS transcription factor-driven tumors

Introduction: Chromosomal translocations involving the ETS family of transcription factors are common in Ewing sarcoma, prostate cancer, and leukemia. These translocations lead in overexpression of aberrant ETS transcription factors, which drive tumorigenesis. Mithramycin (MTM) inhibits EWS-FLI1, the most common ETS-related transcription factor in Ewing sarcoma, presumably through interference at its DNA binding sites on promoter regions. However, MTM has a narrow therapeutic window marked by severe liver and hematologic toxicities. These are likely the result of interference with the ubiquitously expressed SP1 transcription factor. Here, we sought to develop analogues with specificity toward ETS transcription factors and reduced interaction with SP1. Methods: Using MTM-SA and semisynthetic approaches a series of analogues were obtained. To determine specificity toward cells expressing ETS-related chromosomal translocations, MTM-SA analogues were screened for growth inhibition in a panel of Ewing sarcoma cell lines (n=8), all expressing EWS-ETS translocations, and compared to a panel of non-Ewing cell lines (n=9) that do not express these translocations. Luciferase reporter constructs were developed to evaluate interference with EWS-FLI1 and SP1 regulated genes following MTM-SA analogue treatment. Select analogues were tested in vivo to identify the maximum tolerated dose and determine pharmacokinetics (PK). Results: In growth inhibition assays, several MTM-SA analogues resulted in > 10-fold specificity toward Ewing sarcoma cell lines vs. MTM. Luciferase reporter assays identified two analogues, MTM-SA-Tryptophan-A2 and MTM-SA-Tryptophan-A10, with 10-fold reduced inhibition of SP1 but similar inhibition of EWS-FLI1, as compared to MTM. Additionally, MTM-SA-Phe analogue has lower toxicity, despite longer plasma half-life. Conclusion: These data show that MTM-SA analogues are cytotoxic against tumor cell lines expressing aberrant ETS transcription factors. Further, their reduced interference with the ubiquitously expressed SP1 transcription factor, as well as their improved PK, may result in a wider therapeutic window. Citation Format: Markos Leggas, Joseph Eckenrode, Prithiba Mitra, Amit Jha, Shaimaa Salem, Abhisek Mandal, Jon Thorson, Jurgen Rohr. Mithramycin-SA analogues with reduced toxicity for the treatment of ETS transcription factor-driven tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B043.