cssi/SciSciGPT-SciSciNet huggingface dataset:
Debaters as Storytellers: The Narrative Perspective in Academic Debate.

This paper argues that academic debate has become elitist. Our students make arguments which can be understood by highly trained expert judges, but not by public audiences. The paper argues that we...
Pediatric aortoiliac injury following blunt abdominal trauma: A case report

Abstract Introduction The most common mechanism of aortic injury involves motor vehicle collisions resulting in aortic disruptions, occurring almost exclusively in the chest. Injury to the abdominal aorta following blunt trauma is nearly twenty times less likely to occur than the thoracic aorta. Because of the low incidence, there are few reports regarding the presentation and repair of these particular injuries, especially in the pediatric population. Presentation of case We present a case of a 7-year-old boy involved in a high speed motor vehicle accident with an abdominal aorta transection at the aortic bifurcation extending into the left iliac artery. The injury was repaired using bovine pericardium with the adventitia and intima of the vessel approximated over the bovine bridge. Discussion Primary repair of thoracic aortic injury has been thoroughly described in the literature with good outcomes yet, abdominal aortic repair remains ambiguous. Few techniques and materials have been described with even less data surrounding the long-term outcomes. Conclusion Bovine pericardium is a strong and stable acellular collagenous material with the potential to accelerate endothelialization and tissue regeneration. This remains an interesting field of research as stenosis and pseudo-coarction data have yet to be determined.
Clubfoot relapse: does presentation differ based on age at initial relapse?

AbstractPurposeTreatment of idiopathic clubfoot with the Ponseti method is now standard, but predicting relapse can be difficult. Most experts recommend bracing to the age of four years, but this can be challenging for families, and may not be necessary in all patients. The purpose of this study is to compare patterns of bracing and age of relapse to help determine if predictable patterns exist.MethodsThe 70 patients with idiopathic clubfoot treated initially with the Ponseti technique who had relapse of their clubfoot were identified. Relapse was defined as a return to casting or surgery due to recurrent deformity. Data collected included demographics, treatment and brace adherence. Patients who sustained initial relapse before the age of two years were compared with those who sustained initial relapse after the age of two years.ResultsIn total 56% (39/70) had their initial relapse prior to age two years while 44% (31/70) were after age two years. Of the patients who relapsed prior to the age of two year...
Climate change and the transition to neoliberal environmental governance

Abstract What are the guiding principles of contemporary international governance of climate change and to what extent do they represent neoliberal forms? We document five main political and institutional shifts within the UN Framework Convention on Climate Change (UNFCCC) and outline core governance practices for each phase. In discussing the current phase since the Paris Agreement, we offer to the emerging literature on international neoliberal environmental governance an analytical framework by which the extent of international neoliberal governance can be assessed. We conceptualize international neoliberal environmentalism as characterized by four main processes: the prominence of libertarian ideals of justice, in which justice is defined as the rational pursuit of sovereign self-interest between unequal parties; marketization, in which market mechanisms, private sector engagement and purportedly ‘objective’ considerations are viewed as the most effective and efficient forms of governance; governance by disclosure, in which the primary obstacles to sustainability are understood as ‘imperfect information’ and onerous regulatory structures that inhibit innovation; and exclusivity, in which multilateral decision-making is shifted from consensus to minilateralism. Against this framework, we argue that the contemporary UNFCCC regime has institutionalized neoliberal reforms in climate governance, although not without resistance, in a configuration which is starkly different than that of earlier eras. We conclude by describing four crucial gaps left by this transition, which include the ability of the regime to drive adequate ambition, and gaps in transparency, equity and representation.
Link Prediction and Hybrid Strategies for Updating a Social Graph Snapshot via a Limited API

We study the problem of updating a social network snapshot when the social system provides a limited public API to access the graph. We propose novel link prediction and hybrid strategies that beat a state-of-the-art competing graph strategy [1]. Our strategies make educated guesses for edge removals and creations based on graph “fingerprints”. We also propose an improved baseline strategy and more accurate cost analysis. Our experimental results are based on 12 large weekly snapshots, allowing us to study staleness and refresh frequency issues. Our new strategies are robust to staleness, and the runtime grows linearly as a snapshot becomes staler. Our strategies can reduce API calls by an order of magnitude with minimal error.
A bioreducible N-oxide-based probe for photoacoustic imaging of hypoxia

Hypoxia occurs when limited oxygen supply impairs physiological functions and is a pathological hallmark of many diseases including cancer and ischemia. Thus, detection of hypoxia can guide treatment planning and serve as a predictor of patient prognosis. Unfortunately, current methods suffer from invasiveness, poor resolution and low specificity. To address these limitations, we present Hypoxia Probe 1 (HyP-1), a hypoxia-responsive agent for photoacoustic imaging. This emerging modality converts safe, non-ionizing light to ultrasound waves, enabling acquisition of high-resolution 3D images in deep tissue. HyP-1 features an N-oxide trigger that is reduced in the absence of oxygen by heme proteins such as CYP450 enzymes. Reduction of HyP-1 produces a spectrally distinct product, facilitating identification via photoacoustic imaging. HyP-1 exhibits selectivity for hypoxic activation in vitro, in living cells, and in multiple disease models in vivo. HyP-1 is also compatible with NIR fluorescence imaging, establishing its versatility as a multimodal imaging agent.
Optical Coatings for Displays

Electronic displays are one of the fastest growing industries in the world. Displays provide a critical interface between human and electronic information. They are widely used in computer monitors, computer aided design, engineering and manufacturing, multimedia, presentations, electronic games, mapping, medical and military applications, television, digital cinemas, virtual reality, etc [Machover 1997]. Many different display technologies co-exist today [Tannas 1985; Karim 1999; Goede 1999; Stupp and Brennesholtz 1999; MacDonald and Lowe 1997]. Each has its advantages and disadvantages and hence targets different applications.
How mechanical forces shape the developing eye

In the vertebrate embryo, the eyes develop from optic vesicles that grow laterally outward from the brain tube and contact the overlying surface ectoderm. Within the region of contact, each optic vesicle and the surface ectoderm thicken to form placodes, which then invaginate to create the optic cup and lens pit, respectively. Eventually, the optic cup becomes the retina, while the lens pit closes to form the lens vesicle. Here, we review current hypotheses for the physical mechanisms that create these structures and present novel three-dimensional computer (finite-element) models to illustrate the plausibility and limitations of these hypotheses. Taken together, experimental and numerical results suggest that the driving forces for early eye morphogenesis are generated mainly by differential growth, actomyosin contraction, and regional apoptosis, with morphology mediated by physical constraints provided by adjacent tissues and extracellular matrix. While these studies offer new insight into the mechanics of eye development, future work is needed to better understand how these mechanisms are regulated to precisely control the shape of the eye.
The importance of meaning in the relationship between religion and death

The mystery of human existence lies not in just staying alive, but in finding something to live for. —Fyodor Dostoyevsky, The Brothers KaramazovJong and Halberstadt (2016) provide a compelling and ...
Examining phase contrast sensitivity to signal location and tissue thickness in breast imaging

X-Ray phase contrast imaging (PCI) is being developed as an alternative to overcome the poor contrast sensitivity of existing attenuation imaging techniques. The “phase sensitivity” can be achieved using a number of phase-enhancing geometries such as free space propagation, grating interferometry and edge illumination (also known as coded aperture) technique. The enhanced contrast in the projected intensities (that combine absorption and phase effect) can vary by object shape, size and its material properties as well as the particular PCI method used. We show a comparison of this signal enhancement for both FSP and coded aperture (CA) PCI. Our data shows that the phase enhancement is significantly higher for CA in comparison to FSP. Our preliminary results indicate that the enhanced phase effect decreases in all PCI techniques with increasing background thickness. Investigations involving signal location and background tissue thickness dependent signal enhancement (and/or loss of this signal) are very important in determining the true benefit of PCI methods in a practical application involving thick organs like breast imaging.
Pathways, timing, and evolution of Pacific Winter Water through Barrow Canyon

Abstract Observations from a ship-based campaign in July-August 2009, combined with idealized numerical simulations, are used to investigate the seasonal delivery of Pacific Winter Water to Barrow Canyon and the subsequent adjustment of the flow down the canyon. As the current advects dense water, it transitions from a nearly barotropic structure near the canyon head to a strongly baroclinic flow with a subsurface maximum near the canyon mouth. Both the data and model indicate that the transit times along the three Chukchi Shelf pathways feeding Barrow Canyon – a coastal pathway, a southern Hanna Shoal pathway, and a northern Hanna Shoal pathway – modulate the mode of winter water that occupies the canyon at a given time. In particular, remnant Pacific Winter Water carried along the rapid coastal pathway can precede the arrival of newly ventilated Pacific Winter Water carried along the two interior pathways. The observations and model indicate that the transition between water types draining from the canyon can occur rapidly over time scales of days to weeks. We also demonstrate that mixing along the path of the current is unlikely to result in the observed down-canyon transition from newly ventilated Pacific Winter Water to remnant winter water, further supporting the dominant role of advection. While the focus here is on the transition of winter water modes, the implication that seasonality within Barrow Canyon is tied to seasonality of the Bering Strait inflow, together with the relative transit times along advective pathways, should hold for other water types as well.
Modeling Dissolution of High Explosive Formulations

A water dissolution model for solid-phase compounds in soil has been developed that is a variation of previous such models. The formulation for this model is presented along with comparison to prev...
Puberty and Its Disorders in Girls

Current concepts of normal and pathologic puberty have been reviewed. The key event in normal puberty is the commencement of pulsatile secretion of GnRH during sleep, which leads to augmentation of LH levels with the onset of sleep. Schemata are presented for the initial evaluation of patients with primary amenorrhea and secondary amenorrhea based on whether they are hypoestrogenic or estrogenized. Menstrual abnormalities are also discussed from a diagnosis-based perspective. The role of the bone age in differential diagnosis of pubertal disorders is emphasized. The variable presentations of Turner syndrome, hyperprolactinemia, and PCOS are reviewed. Current understanding of the role of undernutrition and stress in anorexia nervosa, psychogenic amenorrhea, and athletic amenorrhea is presented, and management guidelines are reviewed. The evidence that premature pubarche is usually due to premature adrenarche is discussed. The concept that premature thelarche lies on a spectrum between normal and early puberty is discussed. The reader is also reminded that many girls with idiopathic true sexual precocity do not require treatment to preserve height potential.
Metabolism of Lyso(bis)Phosphatidic Acid in Rabbit Alveolar Macrophages

Lyso (bis)phosphatidic acid [L(bis)PA] is a phosphatidyl glycerol isomer with one fatty acid esterified to each glycerol moiety. This novel phospholipid was first identified by Body and Gray (1), and has since been found in a variety of mammalian tissues (2–5), normally comprising less than 1% of the total cellular lipid phosphorus. It appears that the stereochemistry of the lipid is unique, having the phosphoester bonds attached to the sn-1 carbons of each glycerol (6,7). The possible functional role of this lipid is only beginning to be understood.
Deterministic-Stochastic Oceanographic Descriptions for Ocean-Acoustic Experiments

The SACLANT Research Centre led the way twenty years ago in the design and performance of oceanographic-acoustic experiments that took into account the inevitable variability of the ocean, and hence of the acoustic propagation through it. One of these early experiments will be described from the perspective of modern knowledge of the ocean. The principal conclusion is that ocean acoustic experiments should assume ocean variability and be designed accordingly. The corollary conclusion is that knowledge of the oceanic processes causing the variability can greatly simplify the measurement and description problem. The blending of statistical and deterministic ocean descriptions, and the effect of sparse knowledge, will briefly be discussed.
Integrating Children into Families Separated by Migration: A Caribbean-American Case Study

Caribbean peoples have been migrating to the United States for over one hundred years. Since the liberation of immigration policy in 1965, migration from the Caribbean has increased considerably and has presented with an interesting permutation. Many single mothers have migrated leaving young children behind until the mother's situation is stable in the United States. Upon reunification of child and parent, there are reports of marked adjustment difficulties. This paper examines one such case, which was presented for mandated treatment. Issues around intention strategy and implementation are explored in detail with references to case history and clinical theory.
Role of the p53 Family in Stabilizing the Genome and Preventing Polyploidization

Cellular defects resulting in chromosomal instability and aneuploidy are the most common features of human cancers. As a major tumor suppressor and intrinsic part of several cellular checkpoints, p53 contributes to maintenance of the stability of the genetic material, both in quality (ensures faithful replication) and quantity (preservation of diploidy). Although the exact trigger of p53 in case of numerical chromosomal aberrations is unknown, the absence of p53 allows polyploid cells to proliferate and generate unstable aneuploid progeny. A more recent addition to the p53 family, p73, emerged as an important contributor to genomic integrity when p53 is inactivated. p73 loss in p53-null background leads to a rapid increase in polyploidy and aneuploidy, markedly exceeding that caused by p53 loss alone. Constitutive deregulation of Cyclin-Cdk and p27/Kip1 activities and excess failure of the G2/M DNA damage checkpoint are important deficiencies associated with p73 loss.
Research impacting the practice of congestion control

Many algorithms proposed in networking research papers are widely used in many areas, including Congestion Control, Routing, Traffic Engineering, and Load Balancing. In this paper, we present algorithmic advancements that have impacted the practice of Congestion Control (CC) in datacenters and the Internet. Where possible, we also describe negative examples, ideas that looked promising on paper or in simulations but that performed poorly in practice. We conclude the paper with observations on the characteristics shared by these ideas in taking them from research to impacting practice.
The experience of low-income men with prostate cancer transitioning from disease-specific coverage to comprehensive insurance under the affordable care act

Abstract Purpose To describe the insurance enrollment process under the Affordable Care Act (ACA) for a vulnerable population of previously uninsured men with prostate cancer. To understand tradeoffs between high-touch (patient navigation, education, and counseling services) disease-specific coverage and comprehensive insurance for low-income men with prostate cancer. Apply beneficial concepts from each to inform higher quality coverage for patients with cancer. Methods Analysis of 27 semi-structured interviews with men transitioning from California’s IMPACT (Improving Access, Counseling and Treatment for Californians with Prostate Cancer) program to insurance under the ACA. Results We identified six themes: 1) Concerns about gaps in care and confusion about ongoing IMPACT eligibility, 2) Applying for insurance was aided by participants’ families and enrollment resources, 3) Men missed IMPACT’s social support, 4) Men sought new sources for patient education, 5) New challenges arose accessing and navigating care with insurance, and 6) The transition to insurance financially benefitted men with chronic conditions most. Conclusions Taken together, the results support the integration of disease-specific coverage transition plans, social support, navigation, and educational services into insurance benefits. In the face of resource constraints, disease-specific coverage models may provide critical access to medical services for select populations.
Exploring CSR through the Lens of Corporate Social Action (CSA) and its Dimensions

We propose that research on corporate social responsibility (CSR) would be greatly enriched by a more explicit focus on corporate social action (CSA) and its multidimensionality. It is common to us...
Pheromone Robotics

We describe techniques for coordinating the actions of large numbers of small-scale robots to achieve useful large-scale results in surveillance, reconnaissance, hazard detection, and path finding. We exploit the biologically inspired notion of a “virtual pheromone,” implemented using simple transceivers mounted atop each robot. Unlike the chemical markers used by insect colonies for communication and coordination, our virtual pheromones are symbolic messages tied to the robots themselves rather than to fixed locations in the environment. This enables our robot collective to become a distributed computing mesh embedded within the environment, while simultaneously acting as a physical embodiment of the user interface. This leads to notions of world-embedded computation and world-embedded displays that provide different ways to think about robot colonies and the types of distributed computations that such colonies might perform.
Touchscreen Haptic Augmentation Effects on Tapping, Drag and Drop, and Path Following

We study the effects of haptic augmentation on tapping, path following, and drag & drop tasks based on a recent flagship smartphone with refined touch sensing and haptic actuator technologies. Results show actuated haptic confirmation on tapping targets was subjectively appreciated by some users but did not improve tapping speed or accuracy. For drag & drop, a clear performance improvement was measured when haptic feedback is applied to target boundary crossing, particularly when the targets are small. For path following tasks, virtual haptic feedback improved accuracy at a reduced speed in a sitting condition. Stronger results were achieved in a physical haptic mock-up. Overall, we found actuated touchscreen haptic feedback particularly effective when the touched object was visually interfered by the finger. Participants subjective experience of haptic feedback in all tasks tended to be more positive than their time or accuracy performance suggests. We compare and discuss these findings with previous results on early generations of devices. The work provides an empirical foundation to product design and future research of touch input and haptic systems.
Spectral redshift of the thermal near field scattered by a probe

The physics underlying spectral redshift of thermally generated surface phonon polaritons (SPhPs) observed in near-field thermal spectroscopy is investigated. Numerically exact fluctuational electrodynamics simulations of the thermal near field emitted by a silicon carbide surface scattered in the far zone by an intrinsic silicon probe show that SPhP resonance redshift is a physical phenomenon. A maximum SPhP redshift of $19\phantom{\rule{0.16em}{0ex}}\mathrm{c}{\mathrm{m}}^{\ensuremath{-}1}$ is predicted for a 200-nm-diameter hemispherical probing tip and a vacuum gap of 10 nm. Resonance redshift is mediated by electromagnetic gap modes excited in the vacuum gap separating the probe and the surface when the probing tip is much larger than the gap size. The impact of gap modes on the scattered field can be mitigated with a probing tip size approximately equal to or smaller than the vacuum gap. However, sharp probing tips induce important spectral broadening of the scattered field. It is also demonstrated that a dipole approximation with multiple reflections cannot be used for explaining the physics and predicting the amount of redshift in near-field thermal spectroscopy. This work shows that the scattered field in the far zone is a combination of the thermal near field emitted by the surface, and electromagnetic interactions between the probe and the surface. Spectroscopic analysis of near-field thermal emission thus requires a numerically exact fluctuational electrodynamics framework for modeling probe-surface interactions.
Current Challenges and Approaches in Securing Communications for Sensors and Actuators

Recent advances in MEMS hardware have enabled small-footprint and inexpensive sensors to be deployed in hard-to-access locations and to form wireless sensor networks (WSNs). WSNs are typically mission-oriented networks and offer appealing solutions to a range of practical problems. However, due to the characteristics of WSN, their design principles differ from other types of networks. For instance, the severe limitations of computational and energy resources in the network nodes restrict their ability to process and communicate information. These characteristics, particular to WSNs, dictate new security challenges and require new approaches to implementation of security protocols. In this chapter, we present some of the WSNs security challenges and discuss a number of selected solutions presented in the technical literature. The structure of the chapter is as follows. In Sect. 1, we provide background material on WSN security; in particular, we present the security goals, implementation constraints, potential attacks and defenses, and evaluation benchmarks. In Sect. 2, we discuss basic security challenges and approaches, including cryptography schemes, key management schemes, and attack detection and prevention mechanisms. Then, in Sects. 3, 4, and 5, we discuss secure routing, secure localization, and secure data aggregation, respectively. Finally, we conclude the survey in Sect. 6.
Relativistic DFT Calculations of 1JWH and 1JWC Provide Detailed Structural Insight of Cyclopentadienyl Binding in Cp2WH2.

Experimental measurements of the one-bond scalar coupling of Cp2WH2 in tetrahydrofuran (1JWH = 73.4 Hz and 1JWC = 4.8 Hz) are compared to density functional theory calculations of the same based up...
Dynamin regulates the dynamics and mechanical strength of the actin cytoskeleton as a multifilament actin-bundling protein

The dynamin GTPase is known to bundle actin filaments, but the underlying molecular mechanism and physiological relevance remain unclear. Our genetic analyses revealed a function of dynamin in propelling invasive membrane protrusions during myoblast fusion in vivo. Using biochemistry, total internal reflection fluorescence microscopy, electron microscopy and cryo-electron tomography, we show that dynamin bundles actin while forming a helical structure. At its full capacity, each dynamin helix captures 12–16 actin filaments on the outer rim of the helix. GTP hydrolysis by dynamin triggers disassembly of fully assembled dynamin helices, releasing free dynamin dimers/tetramers and facilitating Arp2/3-mediated branched actin polymerization. The assembly/disassembly cycles of dynamin promote continuous actin bundling to generate mechanically stiff actin super-bundles. Super-resolution and immunogold platinum replica electron microscopy revealed dynamin along actin bundles at the fusogenic synapse. These findings implicate dynamin as a unique multifilament actin-bundling protein that regulates the dynamics and mechanical strength of the actin cytoskeletal network. Zhang et al. show that dynamin forms a helical structure with actin and, upon disruption, enhances branched actin polymerization, constituting a dynamic cycle to regulate actin cytoskeleton mechanical strength.
Association of Changes in Primary Care Spending and Use With Participation in the US Affordable Care Act Health Insurance Marketplaces.

This cross-sectional study examined whether the US Affordable Care Act (ACA) Marketplace was associated with changes in primary care spending and use.
The Architecture of Scientific Software: The Conference

In this chapter we provide some background information on the conference that broght together the researchers whose work is described in this volume.
Optimal Assignments in Mobility-on-Demand Systems Using Event-Driven Receding Horizon Control

We develop an event-driven Receding Horizon Control (RHC) scheme for a Mobility-on-Demand System (MoDS) in a transportation network where vehicles may be shared to pick up and drop off passengers so as to minimize a weighted sum of passenger waiting and traveling times. Viewed as a discrete event system, the event-driven nature of the controller significantly reduces the complexity of the vehicle assignment problem, thus enabling its real-time implementation. Simulation results using actual city maps and real taxi traffic data illustrate the effectiveness of the RH controller in terms of real-time implementation and performance relative to known greedy heuristics.
Unveiling unexpected complexity and multipotentiality of early heart fields

Complex organs are composed of a multitude of specialized cell types which assemble to form functional biological structures. How these cell types are created and organized remains to be elucidated for many organs including the heart, the first organ to form during embryogenesis. Here, we show the ontogeny of mammalian mesoderm at high-resolution single cell and genetic lineage/clonal analyses, which revealed an unexpected complexity of the contribution and multi-potentiality of mesodermal progenitors to cardiac lineages creating distinct cell types forming specific regions of the heart. Single-cell transcriptomics of Mesp1 lineage-traced cells during embryogenesis and corresponding trajectory analyses uncovered unanticipated developmental relationships between these progenitors and lineages including two mesodermal progenitor sources contributing to the first heart field (FHF), an intraembryonic and a previously uncharacterized extraembryonic-related source, that produce distinct cardiac lineages creating the left ventricle. Lineage-tracing studies revealed that these extraembryonic-related FHF progenitors reside at the extraembryonic-intraembryonic interface in gastrulating embryos and generate cardiac cell types that form the epicardium and the dorsolateral regions of the left ventricle and atrioventricular canal myocardium. Clonal analyses further showed that these progenitors are multi-potent, creating not only cardiomyocytes and epicardial cell types but also extraembryonic mesoderm. Overall, these results reveal unsuspected multiregional origins of the heart fields, and provide new insights into the relationship between intraembryonic cardiac lineages and extraembryonic tissues and the associations between congenital heart disease and placental insufficiency anomalies.
Fundamentals of Neurological Emergencies

This chapter discusses the physiology of the central and peripheral nervous system as well as the pathophysiology of common emergent neurological illnesses.
Challenges to detection: humidity as a spur to chemical agent change

Detecting chemical agents in outdoor environments such as a battlefield is made challenging by not only the spurious signatures from background chemicals and surfaces (e.g. asphalt, dirt, concrete), but also by the chemical transformation of the actual agents. The change of CW agents to other species can be catalyzed by other chemicals present in the scene, by different substrates, as well as by local weather conditions. Some of the final environmental transformation products are known (e.g. for the G agents methylphosphonic acid), but many of the intermediate chemical states are not, nor are the rates of transformation to the other intermediates or the end products. In this study we have made preliminary optical investigations into the degradation products of a G-agent intermediate, namely methylphosphonic anhydride and its rate of conversion to the more stable methylphosphonic acid. Using infrared and Raman spectroscopies, we have found that the relative humidity greatly affects the rate of change and we report first results from these studies.
Utilization and Cost of Radium-223 Dichloride (Xofigo®) for Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPR) in the U.S. Medicare Population

1309 Objectives: Ra-223 dichloride (Xofigo) is a radiotherapeutic infusion approved for treatment of metastatic, castration-resistant prostate cancer (mCRPC). The aim of this retrospective study is to estimate direct Medicare payments associated with Ra-223 therapy and utilization patterns from 2015-2017. Such information is helpful to clinicians as cost considerations can inform clinical decision making, particularly for medical adjuncts such as Ra-223. Additionally, analysis of actual medication costs, drug price inflation and accompanying billing practices are also useful to inform future Medicare policy reform. Methods: Utilizing the 2015-2017 Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File (POSPUF) and corresponding HCPCS code aggregate tables, the HCPCS code for Xofigo administration (code A9606) was extracted from each file. The number of providers administering Xofigo, number of unique Medicare beneficiaries served, units billed, and average payment amounts were tabulated by year and by provider specialty. Results: A total of 3,717 unique Medicare beneficiaries were treated with Ra-223 from 2015 to 2017. Number of treated patients increased by 43.4% in 2017 as compared to 2015. During this three-year interval the CMS spent over $133 million for Ra-223 therapy. The top-four treating specialties were radiation oncologists (57.1%), nuclear medicine (32.9%), urologists (5%) and diagnostic radiologists (3.2%). Conclusions: In the first three years after its approval, both the utilization of Ra-223 and the direct drug costs of Ra-223 increased significantly. The majority of Ra-223 infusions are managed by radiation oncologists.
Capsule Commentary on Chodos et al., Hospitalization-Associated Disability in Adults Admitted to a Safety Net Hospital

The study by Chodos et al.1 investigated hospitalization-associated disability, which is new or additional disability in activities of daily living at hospital discharge compared to pre-admission baseline,2 and its association with age in adults aged 55 and older hospitalized at a safety net hospital. Adults treated at safety net hospitals also tend to be more prone to hospitalization-associated disability due to a concentration of risk factors, including minority race, functional impairment, low socioeconomic status, substance abuse, and homelessness.3,4 The authors found that hospitalization-associated disability was common, occurring in one-fourth of adults aged 55–59, only very slightly higher among those aged 70–79 (30.3 %), and highest in adults aged 80 and above (61.7 %). They concluded that interventions to reduce hospitalization-associated disability should be considered in hospitalized adults as young as 55, but particularly among those 70 years and older at safety net hospitals.
Balanced Bayesian LASSO for Heavy Tails

Regression procedures are not only hindered by large p and small n, but can also suffer in cases when outliers are present or the data generating mechanisms are heavy tailed. Since the penalized estimates like the least absolute shrinkage and selection operator (LASSO) are equipped to deal with the large p small n by encouraging sparsity, we combine a LASSO type penalty with the absolute deviation loss function, instead of the standard least squares loss, to handle the presence of outliers and heavy tails. The model is cast in a Bayesian setting and a Gibbs sampler is derived to efficiently sample from the posterior distribution. We compare our method to existing methods in a simulation study as well as on a prostate cancer data set and a base deficit data set from trauma patients.
The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux.

Cytochrome P450 3A4 is an important mediator of drug catabolism that can be regulated by the steroid and xenobiotic receptor (SXR). We show here that SXR also regulates drug efflux by activating expression of the gene MDR1, which encodes the protein P-glycoprotein (ABCB1). Paclitaxel (Taxol), a commonly used chemotherapeutic agent, activated SXR and enhanced P-glycoprotein–mediated drug clearance. In contrast, docetaxel (Taxotere), a closely related antineoplastic agent, did not activate SXR and displayed superior pharmacokinetic properties. Docetaxel's silent properties reflect its inability to displace transcriptional corepressors from SXR. We also found that ET-743, a potent antineoplastic agent, suppressed MDR1 transcription by acting as an inhibitor of SXR. These findings demonstrate how the molecular activities of SXR can be manipulated to control drug clearance.
Nicotine and cotinine increases the brain penetration of saquinavir in rat

J. Neurochem. (2010) 115, 1495–1507. Abstract Endothelial tight junctions and efflux transporters of the blood–brain barrier (BBB) significantly limit brain accumulation of many drugs, including protease inhibitors such as saquinavir. The cholinergic agonist nicotine is one of the most commonly used drugs in the world and the incidence is even higher in the human immune deficiency virus population (∼70%). We examined the ability of nicotine and its primary metabolite cotinine to modify brain uptake of saquinavir in rats. Both nicotine and cotinine at pharmacological concentrations matching those in smokers, increased brain saquinavir uptake by two fold. Co-perfusion with nicotinic receptor antagonists and passive permeability markers showed that the effect was not caused by receptor activation or BBB permeability disruption. Transport inhibition studies demonstrated that brain saquinavir uptake is limited by multiple efflux transporters, P-glycoprotein (P-gp), breast cancer resistance protein and multidrug resistance-associated protein. In situ perfusion and in vitro experiments using a classical P-gp substrate rhodamine 123 linked the effect of nicotine to inhibition of BBB P-gp transport. The effect was confirmed in vivo in chronic 14 day nicotine administration animals. These data suggest nicotine increases antiretroviral drug exposure to brain and may represent a significant in vivo drug–drug interaction at the BBB. Although this may slightly benefit CNS antiretroviral efficacy, it may also expose the brain to potential serious neurotoxicity.
An analysis of ABSTRIPS

ABSTRIPS [Sacerdoti, 1974] was the first system to automate the construction of abstraction hierarchies for planning. Despite the seminal nature of this work, the method ABSTRIPS uses to construct abstraction hierarchies is only described in vague terms, and there is no analysis of how the method works or when it will be effective. This paper fills this gap and presents a reconstruction and analysis of the algorithm used in ABSTRIPS. The analysis shows that the method for constructing abstractions implicitly assumes that the preconditions that are determined to be details will be independent. In those cases where the independence assumption fails to hold, ABSTRIPS can degrade the performance of the planner. The paper also compares the ABSTRIPS approach to generating abstractions to the one used in ALPINE [Knoblock, 1990] and describes how ALPINE avoids the problem that arises in ABSTRIPS.
Using independence assumption to improve multimodal biometric fusion

There is an increased interest in the combination of biometric matchers for person verification. Matchers of different modalities can be considered as independent 2-class classifiers. This work tries to answer the question of whether assumption of the classifier independence could be used to improve the combination method. The combination added error was introduced and used to evaluate performance of various combination methods. The results show that using independence assumption for score density estimation indeed improves combination performance. At the same time it is likely that a generic classifier like SVM will still perform better. The magnitudes of experimentally evaluated combination added errors are relatively small, which means that choice of the combination method is not really important.
Monopoly Linear and Nonlinear Pricing

This pedagogical note explains how the same basic principle can be applied to explain the profit-maximizing behavior of a monopolist under both linear and nonlinear pricing by introducing an average price function. It is shown that optimal conditions under nonlinear pricing are similar to that of linear pricing. These conditions can be explained through a simple graphical exposition. The optimal conditions under monopolistic linear and nonlinear price discriminations are also similar.
Isoenzyme-specific Translocation of Protein Kinase C (PKC)βII and not PKCβI to a Juxtanuclear Subset of Recycling Endosomes INVOLVEMENT OF PHOSPHOLIPASE D

Elucidation of isoenzyme-specific functions of individual protein kinase C (PKC) isoenzymes has emerged as an important goal in the study of this family of kinases, but this task has been complicated by modest substrate specificity and high homology among the individual members of each PKC subfamily. The classical PKCβI and PKCβII isoenzymes provide a unique opportunity because they are the alternatively spliced products of the β gene and are 100% identical except for the last 50 of 52 amino acids. In this study, it is shown that green fluorescent protein-tagged PKCβII and not PKCβI translocates to a recently described juxtanuclear site of localization for PKCα and PKCβII isoenzymes that arises with sustained stimulation of PKC. Mechanistically, translocation of PKCβII to the juxtanuclear region required kinase activity. PKCβII, but not PKCβI, was found to activate phospholipase D within this time frame. Inhibitors of phospholipase D (1-butanol and a dominant negative construct) prevented the translocation of PKCβII to the juxtanuclear region but not to the plasma membrane, thus demonstrating a role for phospholipase D in the juxtanuclear translocation of PKCβII. Taken together, these results define specific biochemical and cellular actions of PKCβII when compared with PKCβI.
Enhanced hypervelocity launcher - capabilities to 16 km/s

Abstract A systematic study is described which has led to the successful launch of thin flier plates to velocities of 16 km/s. The energy required to launch a flier plate to 16 km/s is approximately 10 to 15 times the energy required to melt and vaporize the plate. The energy must, therefore, be deposited in a well-controlled manner to prevent melt or vaporization. This is achieved by using a graded-density assembly to impact a stationary flier-plate. Upon impact, time-dependent, structured, high pressure pulses are generated and used to propel the plates to hypervelocities without melt or fracture. In previous studies, a graded-density impact of 7.3 km/s was used to launch a 0.5 mm thick plate to a velocity of over 12 km/s. If impact techniques alone were to be used to achieve flier-plate velocities approaching 16 km/s, this would require that the graded-density impact occur at - 10 km/s. In this paper, we describe a new technique that has been implemented to enhance the performance of the Sandia hypervelocity launcher. This technique of creating an impact-generated acceleration reservoir, has allowed the launch of 0.5 mm to 1.0 mm thick plates to record velocities up to 15.8 km/s. In these experiments, both titanium (Ti-6A1-4V) and aluminum (6061-T6) alloy were used for the flier-plate material. These are the highest metallic projectile plate velocities ever achieved for masses in the range of 0.1 g to 1 g.
SU‐E‐T‐458: Adjoint Sensitivity Based Greedy Heuristic Treatment Planning Algorithm: Application To Multicatheter Interstitial High Dose Rate Brachytherapy For Accelerated Partial Breast Irradiation

Purpose: Development of an automated, 3‐D greedy heuristic optimization algorithm utilizing the adjoint sensitivity fields for treatment planning in multi‐catheter interstitial high dose rate breast implants is presented. The optimization is based on maximizing the dose homogeneity in a breast implant. Methods: Patient CT‐scans were taken from the UW‐hospitals and clinics and the ROI volumes were redrawn and catheters marked. CTV was defined as 1.5cm margin around the seroma. The CTV contour is limited 5mm inside the skin surface and near the pectoralis muscle. For ROI‐adjiont maps skin and muscle are contoured. The contoured volumes were — Seroma: 5.7cc, CTV: 75.0cc, Skin: 79.5cc, Muscle: 55.9, Body: 1736.6cc. Prescribed dose was 3.4Gy to the CTV. Isodoses, dose volume histograms and a list of evaluation parameters were quantified to assess the quality of treatment plan generated. Results: On all CT slices, the 150% isodoses were well separated from each other, the 100% isodose always stayed inside the skin surface with separation from the skin between 7mm−3mm, the 80% isodose covered the PTV entirely and stayed inside the outer skin surface. The V100, V150 and V200 for the PTV were 96%, 17.6% and 7.2%, respectively with DHI of 0.82 and CN of 0.68. The V100 and D100 for the seroma were 100% and 3.58Gy, respectively. The V100, V85 and D90 for the contoured skin were 0.85%, 4.46% and 0.15Gy, respectively. The V100 and D90 for the contoured muscle were 15.8% and 0.92Gy. Conclusions: Our work demostrates development and use of new treatment planning engine based on adjoint sensitivity data, for breast brachytherapy. The treatment planning tool maximizes dose homogeneity in a breast implant and offers the capability of dose quantification and modulation in any number of contoured structures like the PTV, skin and pectoralis muscle doses.
Performance testing of color‐difference metrics using a color tolerance dataset

A color-difference dataset was developed for testing the performance of color metrics. The dataset comprises 45 color-difference vectors varying in five directions at nine color centers under conditions typical of commercial color decisions. Probit analysis was used to estimate the parameters of the population distribution of tolerances for each vector. In addition to estimating the median tolerance, the anlysis allows one to estimate the uncertainty of a tolerance and to test the adequacy of the underlying model tolerance distribution. The median tolerances were used to specify 45 color-difference pairs with equal visual color-difference magnitudes. The performance of eight color-difference metrics was compared using the normalized standard deviation of the color differences of the visually equal difference pairs as a measure of uniformity. A bootstrap statistical technique was used to quantify the variation in performance with varying samples of color centers and color-difference directions and to determine the significance of observed differences in uniformity performance. Some metrics based on weighted CIELAB dl*, dC*, dH* color-difference components had significantly superior performance compared to the CIE recommended color-difference metrics.
CD25 Blockade Depletes and Selectively Reprograms Regulatory T Cells in Concert with Immunotherapy in Cancer Patients

Regulatory T cells (Tregs) are key mediators of immune tolerance and feature prominently in cancer. Depletion of CD25+ FoxP3+ Tregs in vivo may promote T cell cancer immunosurveillance, but no strategy to do so in humans while preserving immunity and preventing autoimmunity has been validated. We evaluated the Food and Drug Administration–approved CD25-blocking monoclonal antibody daclizumab with regard to human Treg survival and function. In vitro, daclizumab did not mediate antibody-dependent or complement-mediated cytotoxicity but rather resulted in the down-regulation of FoxP3 selectively among CD25high CD45RAneg Tregs. Moreover, daclizumab-treated CD45RAneg Tregs lost suppressive function and regained the ability to produce interferon-γ, consistent with reprogramming. To understand the impact of daclizumab on Tregs in vivo, we performed a clinical trial of daclizumab in combination with an experimental cancer vaccine in patients with metastatic breast cancer. Daclizumab administration led to a marked and prolonged decrease in Tregs in patients. Robust CD8 and CD4 T cell priming and boosting to all vaccine antigens were observed in the absence of autoimmunity. We conclude that CD25 blockade depletes and selectively reprograms Tregs in concert with active immune therapy in cancer patients. These results suggest a mechanism to target cancer-associated Tregs while avoiding autoimmunity.
Reentrant ν=1 quantum Hall state in a two-dimensional hole system.

We report the observation of a reentrant quantum Hall state at the Landau level filling factor {nu} = 1 in a two-dimensional hole system confined to a 35-nm-wide (001) GaAs quantum well. The reentrant behavior is characterized by a weakening and eventual collapse of the {nu} = 1 quantum Hall state in the presence of a parallel magnetic field component B{parallel}, followed by a strengthening and reemergence as B{parallel} is further increased. The robustness of the {nu} = 1 quantum Hall state during the transition depends strongly on the charge distribution symmetry of the quantum well, while the magnitude of B{parallel} needed to invoke the transition increases with the total density of the system.