cssi/SciSciGPT-SciSciNet huggingface dataset:
SAT0227 The Effect of Deuteration of VX-509 (Decernotinib) on Drug-Drug Interactions (DDI) with Midazolam

Background VX-509 is an oral selective Janus Kinase 3 inhibitor that has been studied in patients with rheumatoid arthritis (RA). In vitro and in vivo studies suggest that a major metabolite of VX-509, VRT-1123001 (M3) is a potent inhibitor of Cytochrome P450 3A4 (CYP3A4). It was hypothesized that deuteration of VX-509 could decrease the formation of M3 in vivo and consequently reduce the inhibition of CYP3A4. Midazolam (MDZ), a sensitive CYP3A4 substrate, is commonly used as a probe to study the potential DDI of CYP3A4 inhibitors. Objectives To evaluate the effect of deuteration on the extent of DDI between VX-509 and MDZ in healthy subjects. Methods Fourteen healthy subjects (ages 23-52 years, 12 female and 2 male) were randomized into two cohorts and received 4 treatments in a partial crossover design - (A) single oral dose of MDZ 2 mg; (B) [ 2 H]-VX-509 100 mg once daily (qd) on Days 1-8; (C) VX-509 100 mg qd on Days 1-8; (D) [ 2 H]-VX-509 200 mg qd on Days 1-8. Treatments B, C and D all received an oral dose of MDZ 2 mg on Day 7. Full PK profiles of MDZ and its metabolite, [ 2 H]-VX-509, VX-509 and M3 were obtained. Geometric least-squares mean (GLSM) ratios (and associated 90% confidence intervals) of AUC 0–∞ ) and C max of MDZ with and without coadministration of [ 2 H]-VX-509 or VX-509 were calculated to evaluate the extent of DDI. Results [ 2 H]-VX-509 100 mg qd increased MDZ exposure by 4.2-fold, significantly less than that of VX-509 100 mg (6.9-fold, p 2 H]-VX-509 is a moderate CYP3A4 inhibitor at 100 mg qd and that deuteration reduced the extent of DDI with CYP3A4 substrates [Table 1]. Deuteration of VX-509 reduced the systemic exposure to M3 without affecting the exposure to VX-509 following doses of 100 mg qd [Table 2]. The effect of [ 2 H]-VX-509 on MDZ exposure was approximately 2-fold higher following 200 mg qd dose than that following 100 mg qd dose. The most common treatment emergent AE was nervous system disorders (N=2). Both VX-509 and [ 2 H]-VX-509 were generally safe and well tolerated. Conclusions Deuteration of VX-509 significantly reduced the extent of DDI between VX-509 and MDZ without affecting the exposure to VX-509 in healthy subjects. These results suggest deuteration could be a useful method to improve the clinical DDI profile of a compound. Disclosure of Interest J. Huang Shareholder of: Vertex, Employee of: Vertex, F. Yang Shareholder of: Vertex, Employee of: Vertex, J. Yogaratnam Shareholder of: Vertex, Employee of: Vertex, J. Shen Shareholder of: Vertex, Employee of: Vertex
Tasini Re Dux

This brief work discusses the Supreme Court's decision in the case of Tasini suing the New York Times for copyright infringement, as well as a few subsequent cases dealing with almost the same issues. The most substantive case discussed which followed the Tasini case is the case of Greenberg suing National Geographic over photos reprinted in a CD version of its paper issues, and the various nuances of the court's ruling.
Eschewing silence coerced by law: the political core and protected periphery of freedom of expression

(1994). Eschewing Silence Coerced by Law: The Political Core and Protected Periphery of Freedom of Expression. South African Journal on Human Rights: Vol. 10, No. 3, pp. 301-335.
Can liquid metal flow in microchannels made of its own oxide skin

Rapid surface oxidation of gallium-based liquid metals complicates their manipulation but can also be used to stabilize them into 3D shapes. We show that GaInSn can readily flow within such structures. The oxide skin microchannel walls are flexible and, if ruptured, are restored through oxidation of exposed liquid metal. These flexible-wall microchannels can be repeatedly deflated and refilled with the liquid metal.
First and Second Collision Source for Mitigating Ray Effects in Discrete Ordinates Calculations

This work revisits the problem of ray effects in discrete ordinates calculations that frequently occurs in two- and three-dimensional systems which contain isolated sources within a highly absorbin...
Mobilization of GLUT-4 from intracellular vesicles by insulin and K(+) depolarization in cultured H9c2 myotubes.

The insulin-responsive glucose transporter, GLUT-4, moves from an intracellular compartment to the cell surface in response to insulin and/or muscle contraction. Treatment of H9c2 myotubes with ins...
Black Lives Matter: Reviewing Jill Leovy, Ghettoside: A True Story of Murder in America (Spiegel & Grau 2015)

This essay reviewing a work of journalism about the investigation and prosecution of criminal homicide in South Los Angeles considers the author's argument that serious shortcomings in the police investigation of homicides with black victims contributes significantly to high rates of violence in the black community. The essay touches on the emotional toll of homicide, tensions between detectives and patrol officers in homicide investigations, qualities of the most effective detectives, differential resources given to homicide cases according to location of offense and data on homicide clearance rates in the United States.
Hemingway’s Hills like White Elephants

(1994). Hemingway’s Hills like White Elephants. The Explicator: Vol. 52, No. 2, pp. 107-109.
Hydrogeological response to climate change in alpine hillslopes

Climate change threatens water resources in snowmelt-dependent regions by altering the fraction of snow and rain and spurring an earlier snowmelt season. The bulk of hydrological research has focused on forecasting response in streamflow volumes and timing to a shrinking snowpack; however, the degree to which subsurface storage offsets the loss of snow storage in various alpine geologic settings, i.e. the hydrogeologic buffering capacity, is still largely unknown. We address this research need by assessing the affects of climate change on storage and runoff generation for two distinct hydrogeologic settings present in alpine systems: a low storage granitic and a greater storage volcanic hillslope. We use a physically based integrated hydrologic model fully coupled to a land surface model to run a base scenario and then three progressive warming scenarios, and account for the shifts in each component of the water budget. For hillslopes with greater water retention, the larger storage volcanic hillslope buffered streamflow volumes and timing, but at the cost of greater reductions in groundwater storage relative to the low storage granite hillslope. We found that the results were highly sensitive to the unsaturated zone retention parameters, which in the case of alpine systems can be a mix of matrix or fracture flow. The presence of fractures and thus less retention in the unsaturated zone significantly decreased the reduction in recharge and runoff for the volcanic hillslope in climate warming scenarios. This approach highlights the importance of incorporating physically based subsurface flow in to alpine hydrology models, and our findings provide ways forward to arrive at a conceptual model that is both consistent with geology and hydrologic principles. Copyright © 2016 John Wiley & Sons, Ltd.
NEW STATISTICAL METHODS FOR ALLOMETRY WITH APPLICATION TO FLORIDA RED-WINGED BLACKBIRDS.

Allometry, the association of size and shape in populations of organisms, is the subject of an extensive literature (Reeve and Huxley, 1945; Gould, 1966, 1975; Spielman, 1973; Sprent, 1972; Thorpe, 1976). In this paper we present new statistical methods for the study of size and shape, and use these methods to study the morphology of red-winged blackbirds, Agelaius phoeniceus, breeding in Florida. We use definitions of size and shape variables that permit the study of the entire statistical distribution of a given variable. We offer these methods as an alternative to classical methods based on the allometric equation in which relations are summarized in single coefficients reflecting at best the mean trend of shape with some size variables. Our alternative goal is to determine visually and geometrically meaningful size and shape variables which permit the direct study of the association of size and shape. This paper is in two parts. In the first part we discuss definitions of size and shape variables and summarize statistical results which include exact tests for sizeshape associations (Mosimann, 1970, 1975a, 1975b). In the second part we use these methods to study geographic variation in red-winged blackbirds in Florida. Throughout we consider the following situation: N individuals are independently sampled from some population. For each individual there are k positive measurements, all in the same units, say millimeters. For the i-th individual we then
A Study of the Influence of Dehydrated Alfalfa Meal on the Production of Blood Spots in Eggs

Abstract BLOOD spots in eggs represent a serious loss to the poultry industry and the loss may become greater with more general use of electronic blood spot detection in the future. Numerous workers have investigated the effects of nutrients on the incidence of blood spots. Nalbandov and Card (1944) observed that blood spots were due to hemorrhaging within the follicular membrane and reported that vitamins A, C, D, E, K, and P had no effect on the incidence of blood spots, but that there was a definite seasonal increase from December through the following July. However, these same workers (1947) reported the feeding of cerograss reduced the incidence of blood spots materially in one of 2 years’ studied. Bearse et al. (1960) found that vitamin A was essential in reducing blood spots and that low levels of vitamin A increased blood spot incidence. The level of vitamin A recommended by the…
T-shape Knowledge structure and Horizontal Movement

Today's writers are supposed to fill up their stores of knowledge as well as improve their minds and behaviours.They have to construct "T"-shape knowledge stucture,especially to widen their visions,namely to absorb knowledge in a dynamic way.
Under the Pressure of Two Response——Analysis of Different Poetry Steering between Mainland and Taiwan

Cold war is a very special time,due to special reasons and the segmentation of Chinese poetry on both belong to the two camps,so common confronted with hitherto unknown external pressure.In the same weight,the poets take a completely different coping styles,developed their unique poetic landscape.
Is Subdural Peritoneal Shunt Placement an Effective Tool for the Management of Recurrent/Chronic Subdural Hematoma?

UNLABELLED OBJECTIVE : To describe a surgical technique and to report using a retrospective study the efficacy of peritoneal shunts for the treatment of recurrent/chronic subdural hematoma (CSDH). We describe the considerations, complications, and outcomes related to this technique. METHODS : In a retrospective cohort study, 125 charts with a diagnosis of subacute/chronic subdural hematoma were assigned for evaluation. Of the charts reviewed, 18 charts were found from subjects with a diagnosis of recurrent sub-acute or chronic subdural hematoma. All patients had undergone initial surgical treatment of their condition followed by peritoneal shunt placement to help alleviate intracranial pressure. Factors including the age, size of subdural hematoma, number of previous events, BMI, complications, survival, and clinical course were analyzed. RESULTS : After subdural peritoneal shunt placement all patients had full neurological recovery with no complaints of headaches, lethargy, weakness, confusion or seizures. None of the cases had new subdural hematoma episodes after placement for a minimum of a two-year period (mean 26.1 months) (range 24.3-48.6 months). No postoperative complications were reported. The rates of postoperative hemorrhage, infection, distal catheter revision, and perioperative seizures was found to be zero percent. Shunt drainage was successful in all cases, draining 85% of the blood in the first 48 hours. There was no significant relationship between complications and the use of anticoagulants four weeks after surgery. CONCLUSIONS Peritoneal shunts, though rarely used, are a viable option in the treatment of sub-acute/chronic subdural hematomas. When pursuing this treatment, this technique is recommended to mitigate the risks of repeat surgical intervention and lessen perioperative time in high-risk patients.
The pseudoirreversible inhibition of monoamine oxidase by allylamine.

Allylamine was shown to inhibit flavin-linked monoamine oxidase in a pseudoirreversible manner. The enzyme was irreversibly inhibited with incorporation of radioactivity from [14C]allylamine. Inhibition and incorporation of radioactivity were time-dependent, and the radioactivity and inhibition persisted during dialysis and gel filtration. Enzymatic turnover of allylamine preceded the inactivation step. Reaction of the allylamine-inactivated enzyme with benzylamine resulted in the formation of 3-benzylaminopropionaldehyde. Simultaneously with inactivation, the ultraviolet spectrum of the holoenzyme changed to one indicative of the reduced form of the coenzyme. In the presence of a substrate, benzylamine, the ultraviolet spectrum of the enzyme reverted to normal, the radioactivity was removed, and activity was restored. A mechanism for the inactivation and reactivation by benzylamine is presented.
An Empirical Analysis of the Psychic Distance Argument for Export Development

Considerable theoretical and empirical knowledge has been developed to explain the process by which firms export their products. The intent of this stream of research has been to better understand the internationalization of the firm in order to provide managers and policymakers with information about stimulation possibilities for this process. One issue that has been explored is the process by which firms determine the countries on which they focus their exporting efforts. While many isolated factors such as management education, foreign travel experience, language training and foreign heritage have been mentioned as possible facilitators for the focus on specific countries, one major theory which has emerged to explain this focus is the concept of "psychic distance." The purpose of this research is to attempt an empirical verification of this theory.
Neoliberal narratives and the logic of abstinence only education: why are we Still having this conversation?

ABSTRACTGiven the lack of citizen or medical support for abstinence-only education, we ask how abstinence-education maintains such a stronghold in America and other Western democracies’ public policy and consciousness. Our response has three parts. In the first, we outline the disproportionately negative health outcomes of sex education experienced by female, impoverished, ethnic and racial minorities, and LGBT youth. Next we address prominent narratives in sex education. We use the work of Pierre Bourdieu as a frame to understand neoliberal narratives and the accrual of cultural capital. Next we address two specific narratives in sex education, both of which align with broad tenets of neoliberal thought: the first of these is a focus on individual responsibility at the expense of understanding broader social structures. The second questions the role of education in a democratic nation that privileges the private over the overall health of the citizenry. In closing, we highlight comprehensive alternatives...
Percutaneous transluminal angioplasty of extra- and intracranial cerebral vascular disease

Cerebral percutaneous transluminal angioplasty (PTA) is being performed with increasing frequency in patients with angiographically documented stenosis of greater than 70%, who are symptomatic and are not good candidates for surgical endarterectomy. The initial reports of cerebral PTA were described in the early 1980s. Over the past decade, with the development of microballoons and guidewires which have allowed the interventional neuroradiologists safer access to the head and neck vessels, more centers have been performing angioplasty for both extra- and intracranial lesions including atherosclerosis, fibromuscular dysplasia, ateritis, vessel dissection, and postsurgical intimai hyperplasia. We report our experience in treating 274 patients with stenosis of the brachiocephalic vessels treated by balloon angioplasty techniques.
Recommend, but also Discuss: Different Patterns of Physician-Perceived Barriers to Discussing HPV Vaccination and Their Association with Vaccine Administration in 11–12 Year-Old Girls

Objectives We examined variation in primary care physicians' (PCPs') perceptions of barriers to physician-initiated discussion of HPV vaccination, and how this is associated with the rates at which they discuss, initiate and continue to administer vaccination with 11-12 year-old girls. Methods We surveyed 301 PCPs using systematic random sampling. PCP variation in perceived barriers to discussing HPV vaccination was modeled using latent class analysis (LCA). The distinct PCP groups identified were compared with each other using three iterative logistic regression models to predict the likelihood of initiating vaccine discussion and the reported percentages of 11-12 year-old patients who initiated HPV vaccination and received follow-up shots. Results LCA revealed three groups of PCPs who perceived major, moderately significant and relatively minor barriers (17.9, 41.9 and 40.2 % of respondents, respectively). Pediatricians, PCPs who were female, had minority racial/ethnic status and who perceived only minor barriers had significantly higher odds of initiating discussion. PCPs were more likely to initiate HPV vaccination if they had initiated discussion and perceived minor or moderate communication barriers. Increased likelihood to administer follow-up HPV vaccine was associated with having initiated discussion, perceiving only minor barriers and working outside Deep South states, but not with having initiated vaccination. Conclusions for Practice PCPs who discuss HPV vaccination with girls aged 11-12 and their mothers are more likely to start and sustain vaccine administration. However, different PCPs perceive barriers to discussion in different ways. Interventions tailored to different groups of PCPs should assist them in overcoming barriers to discussing their recommendations when necessary.
Fast charge battery electric transit bus in-use fleet evaluation

The focus of this interim fleet evaluation is to characterize and evaluate the operating behavior of Foothill Transit's fast charge battery electric buses (BEBs). Future research will compare the BEBs' performance to conventional vehicles. In an effort to better understand the impacts of drive cycle characteristics on advanced vehicle technologies, researchers at the National Renewable Energy Laboratory analyzed over 148,000 km of in-use operational data, including driving and charging events. This analysis provides an unbiased evaluation of advanced vehicle technologies in real-world operation demonstrating the importance of understanding the effects of road grade and heating, ventilating and air conditioning requirements when deploying electric vehicles. The results of this analysis show that the Proterra BE35 demonstrated an operating energy efficiency of 1.34 kWh/km over the data reporting period.
Television Advertising: uses of Information in the U.S. and Latin America

Critics of current marketing practices complain that consumers do not have adequate information on which to base decisions. These information deficiencies, it is argued, result in higher prices, “artificial" brand differences and a stress on product attributes that represent no real value to consumers. Further, there appears to be widespread controversy between marketers and critics as to the usefulness of information communicated through advertising, especially television advertising.
Is hepatectomy justified for patients with RAS mutant colorectal liver metastases? An analysis of 524 patients undergoing curative liver resection

Background RAS mutations are associated with limited overall survival after resection of colorectal liver metastases. Our aim was to determine criteria for considering hepatectomy for patients with RAS mutant colorectal liver metastases. Methods Of 1,163 patients who underwent liver resection for colorectal liver metastases during 2005–2014, all patients operated on with curative intent who had known RAS mutation status were included. Factors associated with overall survival were determined using multivariate analysis. Results A total of 524 patients met the inclusion criteria; 212 (40%) had mutated RAS. Mutations were located on codon 12 in 128 patients (60%) and codon 13 in 29 (14%). At median follow-up of 38 months, median overall survival was 72.6 months for wild-type RAS and 50.9 months for mutated RAS ( P P = .839), significantly worse than for patients with wild-type RAS ( P = .005, and P = .038 for codon 12 and 13, respectively). For patients with RAS mutation, factors associated independently with worse overall survival were node-positive primary tumor, tumor >3 cm, and >7 cycles of preoperative chemotherapy. Major and 2-stage hepatectomy were not associated independently with overall survival. Median overall survival was 57, 41, and 21.5 months for patients with 1, 2, and 3 risk factors, respectively. There were no 4-year survivors in the highest-risk group. Conclusion Patients with multiple risk factors had poor overall survival after curative resection of RAS mutant colorectal liver metastases. For such patients, hepatectomy may be ill advised, and alternative therapies or further systemic therapy should be considered.
Enabling real-time execution: Runtime-efficiency improvements for the next-generation airborne collision avoidance algorithms

The Federal Aviation Administration is currently developing the Airborne Collision Avoidance System X (ACAS X), a critical safety system intended to be installed on all large aircraft to prevent mid-air collisions. We identify methods of speeding up the ACAS X algorithms in order to address concerns about ACAS X's ability to meet real-time constraints on practical avionics hardware. The approaches involve state- and grid-point combination, pre- and hierarchical interpolation, memory-locality maximization, and selected use of fixed-point computation. These modifications, which are mathematically equivalent to the original ACAS X design, improved the speed of ACAS X's primary runtime-contributing component by a factor of approximately 7.3 on a 32-bit x86 platform. Along with improved hardware, they enabled the system to meet execution-time objectives in flight testing. The techniques developed are general and potentially applicable to systems that approximate a continuous value function using multilinear interpolation over the values for discrete states and to systems that compute weighted sums of these values across multiple points.
Strategies to Promote Bone Health in Female Athletes

The current definition of the Female Athlete Triad is defined as a spectrum disorder including an energy imbalance, amenorrhea, and reduced bone mineral density (BMD). Not all three components must be present for the athlete to suffer from long-term negative consequences. The true incidence of reduced BMD among athletes compared with age-matched controls is unknown. While both sexes will lose BMD over time, females undergo menopause that results in an accelerated bone loss. There is a strong need to educate physicians about the Triad spectrum because the best approach to identifying patients who have or who are at risk for developing the Female Athlete Triad centers on obtaining a comprehensive history. Previous studies have shown that overall awareness of the Triad is low. Increasing awareness of the Female Athlete Triad also ought to be done at the patient- and community-based level. A team-centered approach will maximize the patient’s recovery through the development of a comprehensive treatment plan with a strong emphasis on patient education.
Long-term Follow-up of a Matched Cohort Study Evaluating the Role of Adjuvant Radiotherapy for Organ-confined Prostate Cancer With a Positive Surgical Margin

Objective To evaluate if adjuvant radiation therapy (ART) is associated with improved long-term oncologic outcomes for pT2N0R1 prostate cancer (PCa). Methods Men with pT2N0 PCa and a single positive surgical margin following radical prostatectomy and pelvic lymphadenectomy were identified (1987-1996). Men who received ART were matched 1:1 to men who did not receive ART based on age, year of surgery, Gleason score, preoperative prostate-specific antigen, site of positive surgical margin, and DNA ploidy. Biochemical recurrence (BCR), local recurrence, distant metastasis, and overall survival (OS) were compared between groups in time-to-event analyses. Results The cohort included 152 men (76 per group) with a median follow-up of 20 years (interquartile range 19,22). ART was associated with a lower cumulative incidence of BCR (25% vs 52%; P P = .03), but no significant differences in cumulative incidence of distant metastasis (10% vs 7%; P = .44) or in probability of OS (56% vs 68%; P = .08) at 20 years. In competing risks models, receipt of ART was associated with reduced risks of BCR (hazard ratio [HR] = 0.40; 95% confidence interval [CI] 0.23-0.70; P P = .05), but not distant metastasis (HR = 1.56; 95% CI 0.51-4.75; P = .43). In the Cox model, ART was not associated with improved OS (HR = 1.56; 95% CI 0.94-2.57; P = .08). Conclusion ART was associated with reduced risks of BCR and local recurrence for men with pT2N0R1 PCa. However, ART was not significantly associated with metastasis-free or OS benefits, as recurrences in these patients generally followed an indolent trajectory with 20 years of median follow-up.
When Your App is Under the Spotlight

Due to the nature of apps as experience goods and the vast product space, new product discovery in the mobile app market has become a very salient problem for developers and consumers. Our paper investigates developers’ best response to the platform’s recommendation, where the featured apps enjoy a reduction in search cost and an endorsement of quality for a limited period of time. Specifically, we consider three response options available to the developers: releasing a version update, increasing price, and decreasing price. We find that only the price decrease strategy has a positive effect on sales during the featuring window, while the effect of the price increase and version update strategy is not significant.
A temporal analysis of the association between breast cancer and socioeconomic and environmental factors

Although some biological factors have been confirmed to increase the risk of breast cancer, they only account for a small portion of the overall incidence in females. Women’s socioeconomic status and hazardous exposures to potential breast cancer carcinogens could modify their risks of breast cancer. From a public health perspective, it is important to understand what socioeconomic and environmental factors are associated with an elevated risk of breast cancer and how they vary geographically, temporally, and among different populations. Using an integrated approach, this study examines the associations between the incidence rate of invasive breast cancer and socioeconomic characteristics and environmental risks over time in Illinois for two periods: 1999–2003 and 2009–2013. Based on data from the US Census, ACS, and EPA, this study builds two sets of regression models to investigate the associations. The findings reveal that compared to environmental risks, socioeconomic factors are much more significant factors associated with the risk of breast cancer. The significant explanatory variables differ somehow between the two periods, yet with some agreement. Among the environmental risk variables examined, two toxic carcinogens, ethylene oxide and benzene were associated with an elevated risk of breast cancer for each time period respectively.
Nutrient interactions of detritus and decomposers

In nearly all ecosystems, the majority of primary production is not consumed by herbivores, but passes directly to dead organic matter, or detritus. A smaller fraction of primary production is incorporated into herbivores and carnivores, which becomes detritus when these organisms die. The decomposition of dead organic matter is carried out by a diverse collection of organisms, ranging from microorganisms (fungi and bacteria) to relatively large animals (earthworms and millipedes). These, in turn, support an array of predators that obtain their sustenance wholly or largely from energy and nutrients stored in detritus.
Biochemical application of a new ion exchange/sorbent, polybenzimidazole (PBI)

PBI is a unique polymer for ion exchange/sorption or affinity chromatography. The excellent flow and ion exchange properties of PBI resins have been demonstrated by their applications for determination of urinary VMA and PBG. Furthermore, PBI was also applied successfully as an affinity chromatography medium for several enzymes with polymeric molecules as their substrates. These studies concluded that PBI polymer has versatile biochemical applications.
Spinal Cord Ependymoma

Ependymomas of the spinal cord are glial tumors arising from ependymal cells along the central canal of the spinal cord. They are rare, typically have a long natural history, and behave differently than their intracranial counterparts. They are grouped based on the World Health Organization (WHO) classification from grade I to III, with grade II spinal cord ependymomas appearing to be the most indolent despite their intermediate grade. Myxopapillary ependymoma (MPE) is a distinct subset that occurs almost exclusively in the conus medullaris, cauda equina, or filum terminale. Spinal cord ependymomas often present insidiously with back pain or neurologic deficits that are dependent on their location within the cord. Management consists of surgical resection, with gross total resection (GTR) offering the best chance for long-term control and possible cure. The role of postoperative radiation is controversial, but in general, radiation is employed locally for subtotal resection (STR), grade III (anaplastic) ependymomas, or after re-resection for recurrent disease. Long-term survival is excellent with rates over 85% at 10 years. However, 17 to 30% will recur, often years following initial treatment. As such, continued follow-up with surveillance imaging is essential.
Communication of prognostic information between oncologists and patients with advanced lung cancer.

29Background: A critical domain of patient-provider communication is helping cancer patients understand their prognosis, as well as the efficacy of treatment options. In this qualitative study, we explored the ways oncology providers approached prognostic discussions during initial office visits with patients with metastatic lung cancer. Methods: Transcripts of initial visits between unannounced standardized patients portraying metastatic non-small cell lung cancer and their oncologists were recorded at multiple practice sites in community and academic settings, as part of a large NIH-funded study. Thematic analysis was conducted on a subset of these recorded visits from one study site. In this secondary analysis, three coders (one medical oncologist, one palliative care physician and one research assistant) reviewed transcripts independently to extract quotes related to prognosis, meeting regularly to review selected quotes and to decide on codes. This process repeated until saturation of themes was achi...
Principles of Conflict Economics: The Political Economy of War, Terrorism, Genocide, and Peace

Conflict economics contributes to an understanding of violent conflict and peace in two important ways. First, it applies economic concepts and models to help one understand diverse conflict activities such as war, terrorism, genocide, and peace. Second, it treats coercive appropriation as a fundamental economic activity, joining production and exchange as a means of wealth acquisition. In the second edition of their book Principles of Conflict Economics, Anderton and Carter provide comprehensive, up-to-date coverage of the key themes and principles of conflict economics. Along with new scholarship on well-established areas such as war, terrorism and alliances and under-researched areas including genocides, individual and family aspects of war, and conflict prevention, they apply new economic tools to the study of war and peace such as behavioral economics and economics of identity and offer deeper research and policy insights into how to reconstitute societies after large-scale violence.
Clinical significance of zero coronary artery calcium in individuals with LDL cholesterol ≥190 mg/dL: The Multi-Ethnic Study of Atherosclerosis.

Abstract Background and aims Individuals with low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL are considered high-risk and current guidelines recommend initiating high-intensity statin therapy in this group. We sought to examine the predictive ability of zero CAC in this high-risk group. Methods Multi-Ethnic Study of Atherosclerosis participants without clinical cardiovascular disease and baseline LDL-C ≥190 mg/dL were identified. Cardiovascular risk factors were compared between those with CAC = 0 and CAC >0. Multivariable Poisson regression was used to identify predictors of CAC = 0. Association of CAC = 0 with incident cardiovascular events over a median follow-up of 13.2 years was examined using multivariable-adjusted Cox regression. Results 246 individuals (mean age = 63 ± 9.4 years; 42% male; 31% white; 37% CAC = 0) with LDL-C ≥190 mg/dL were identified (mean LDL-C = 215 ± 27 mg/dL). Age 0 (incidence rate per 1000 person-years = 26.4; 10-year risk = 20%; risk/year = 2.0%), adjusted HR 0.25 (95%CI = 0.10–0.66). Conclusions Among persons with LDL-C ≥190 mg/dL, younger age, female sex, and the absence of diabetes were associated with CAC = 0. CAC = 0 was associated with a low risk of cardiovascular events, suggesting the utility of CAC assessment for stratifying risk in this high-risk group.
Challenges and treatments in estimating crash frequency

Abstract The conditions that support claiming a traffic conflict include an unacceptably short separation. Fitting curves to a series of crash frequency estimates under various threshold separations supports selecting a proper separation threshold that provides the most efficient estimation of the expected number of crashes. A binomial test is helpful to confirm the linearity of a log-log. The effect of the separation measurement error on the expected crash estimation is limited when the separation error does not produce incorrectly claimed conflicts. The estimation efficiency of the proposed single-parameter and benchmark methods is comparable for a small number of conflicts. The single-parameter method considerably over-performs the benchmark method for larger samples. The response delay is not observed when a crash occurs. A method to account for this censoring is proposed.
The effect of exogenous product familiarity on endogenous consumer search

When a consumer is familiar with one product but not its competitor, she is faced with a decision: either buy what she knows, or engage in search to learn more. When search is costly, competing firms may attempt to encourage or discourage search by adjusting prices. In this paper we consider how competitive dynamics between two quality differentiated firms are affected if one product enjoys a familiarity advantage. Familiarity is defined as a consumer’s ex-ante knowledge of fit for a particular product. An increase in the level of familiarity for one product allows a firm to charge higher prices since there are more consumers with information on that product relative to the competition. We call this the direct effect of familiarity. However, an increase in familiarity also has an indirect effect, since it gives the rival firm a stronger incentive to decrease price in order to encourage searching, in turn increasing overall competition. The effect of familiarity on profits depends on the magnitudes of these effects, and it is moderated by the level of quality differentiation between products. For very high or very low levels of differentiation, the results are relatively straightforward. However, when the level of differentiation is moderate, the results are more nuanced, with the higher-quality firm realizing higher profits from more familiarity, even if it must lower prices due to the indirect effect. We also find that, contrary to conventional wisdom, overall competition may be higher when firms are more quality differentiated. This is driven by the fact that higher quality differences bolster the indirect effect, with a lower quality firm providing deeper price cuts to counter increased familiarity of a high quality rival. We conclude by examining how changes in the cost of searching impact equilibrium outcomes.
Checkpoint kinase inhibition in prostate cancer cells resistant to poly ADP-ribose polymerase inhibitors.

150Background: Poly ADP-ribose polymerase inhibitors (PARPi) have shown promise in the treatment of metastatic castration-resistant prostate cancer patients with DNA damage response defects. The ph...
Effects of Surveying for the Federally Endangered Spruce-Fir Moss Spider (Microhexura montivaga Crosby & Bishop) on its Bryophyte Habitat

Microhexura montivaga (Spruce-fir Moss Spider) is a federally endangered arachnid endemic to high-elevation montane conifer forests of the southern Appalachian Mountains. The spider is cryptic and difficult to monitor because this species lives in the interface between the bryophyte mat and the rock surface. Since temporary removal of the bryophyte mat is necessary to monitor the spider, surveyors may negatively impact the spider's habitat during monitoring. To help inform survey protocol for this endangered species, we studied reattachment rates of bryophyte mats to rock surfaces after their removal. In 2017, we surveyed sixty 10 cm × 10 cm plots, assigning a plot to either control or treatment (i.e., application of water post-reattachment). We monitored plots for 1 year post-survey to determine reattachment rates. The majority of plots (70%) reestablished after 1 year, whereas 15% did not reattach or showed substantial prolonged (e.g., ∼1 year) desiccation and 15% completely fell off or had 100% prolonged desiccation and were chlorotic. We found that mat depth and overstory canopy cover had no effect on mat reestablishment, although bryophyte type did. We found no difference between treatment and control plots, suggesting that no treatment is needed for mats to reestablish under the conditions described. Rock slope significantly influenced reestablishment rates, highlighting that surveying bryophyte mats on slopes >80% may diminish or destroy habitat. Further research is needed to determine long-term monitoring effects on the spider and its habitat, especially in relation to disturbance regimes and ecological restoration of Picea rubens (Red Spruce).
Abstract MP48: Intracranial Dolichoectasia in Patients With Symptomatic Intracranial Atherosclerotic Disease: The Myriad Study

Background: It is unknown whether intracranial atherosclerotic disease (IAD), in addition to vessel narrowing, also contributes to the abnormal dilation and increased tortuosity of intracranial ves...
The Nup2 meiotic-autonomous region relieves autoinhibition of Nup60 to promote progression of meiosis and sporulation in Saccharomyces cerevisiae

During meiosis, chromosomes undergo dramatic changes in structural organization, nuclear positioning, and motion. Although the nuclear pore complex has been shown to affect genome organization and function in vegetative cells, its role in meiotic chromosome dynamics has remained largely unexplored. Recent work in the budding yeast Saccharomyces cerevisiae demonstrated that the mobile nucleoporin Nup2 is required for normal progression through meiosis I prophase and sporulation in strains where telomere-led chromosome movement has been compromised. The meiotic autonomous region (MAR), a short fragment of Nup2 responsible for its role in meiosis, was shown to localize to the nuclear envelope via Nup60 and to bind to meiotic chromosomes. To understand the relative contribution these two activities have on MAR function, we first carried out a screen for MAR mutants defective in sporulation and found that all the mutations disrupt interaction with both Nup60 and meiotic chromosomes. Moreover, nup60 mutants phenocopy nup2 mutants, exhibiting similar nuclear division kinetics, sporulation efficiencies, and genetic interactions with mutations that affect the telomere bouquet. Although full-length Nup60 requires Nup2 for function, removal of Nup60s C-terminus allows Nup60 to bind meiotic chromosomes and promote sporulation without Nup2. In contrast, binding of the MAR to meiotic chromosomes is completely dependent on Nup60. Our findings uncover an inhibitory function for the Nup60 C-terminus and suggest that Nup60 mediates recruitment of meiotic chromosomes to the nuclear envelope, while Nup2 plays a secondary role counteracting Nup60s autoinhibition.
Culture Change and the American Cowboy

The modern American cowboy is an anachronism, or, in the words to a song by Kris Kristofferson, "a walking contradiction, partly truth and partly fiction." On the rodeo circuit, you can find bull—riders from Brooklyn; on the range are ranchers riding herd on Honda motorcycles or surveying their spread from the cockpit of a Cessna. The striking thing about this blend of past and present is that it does not seem unusual at all, particularly to those who are doing it.
Reduction of the fertilizing capacity of sea urchin sperm by cannabinoids derived from marihuana. III: Activation of phospholipase A2 in sperm homogenate by Δ9-tetrahydrocannabinol

Inhibition of the egg jelly induced acrosome reaction by delta 9-tetrahydrocannabinol (THC) is associated with the localized disruption of the nuclear envelope and the formation of lipid deposits in sea urchin sperm. This suggests that THC may activate phospholipase(s) within the sperm. We now report effects of THC on phospholipase A2 activity in homogenates of sea urchin sperm using 1-stearoyl-2-[1-14C]arachidonyl phosphatidylcholine as substrate. The release of radioactive arachidonic acid was measured after a 30-min incubation with the enzyme. In the absence of exogenous Ca2+, 100 microM THC produced a significant (P less than 0.001) increase in phospholipase A2 activity. THC activated phospholipase A2 in a concentration (1-100 microM) and time-dependent (0-30 min) manner. Exogenous calcium (10 mM) significantly augmented basal (P less than 0.001) and THC-stimulated (P less than 0.005) phospholipase A2 activity. Calcium chelators [ethylene glycol bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid (EGTA) and 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)] inhibited the basal level of phospholipase A2 activity in the sperm homogenate, and prevented the activation of phospholipase A2 by THC. Submicromolar levels of free calcium ions were required for THC stimulation of phospholipase A2. Cannabinol which mimics the effects of THC on the acrosome reaction also activated phospholipase A2 in sperm homogenate. These results suggest that THC may alter lipid metabolism in sperm by activating calcium-dependent phospholipase A2. Putative metabolites derived from this process may inhibit the acrosome reaction and thereby reduce the fertilizing capacity of sea urchin sperm.
Spectral image processing and analysis of the Archimedes Palimpsest

The Archimedes Palimpsest is a 10th-century parchment manuscript that was erased in the 13th century and overwritten with a Christian prayer book. The Walters Art Museum in Baltimore, MD, USA has supervised a ten-year collaboration by conservators, imaging scientists, and scholars to image and transcribe the original writings. This paper reports on the variety of optical imaging and image processing techniques used in the project. Image analysis tools to clarify texts included supervised segmentation via a spectral pseudoinverse calculation, deterministic renderings in pseudocolor, and statistical analysis with dynamical pseudocolor rendering.
Reversal of Growth Arrest in Adolescents with Crohn's Disease After Parenteral Alimentation

Growth arrest and delayed onset of puberty often complicate childhood onset Crohn's disease of the small bowel (granulomatous enteritis). Nutritional deficits arising from inadequate dietary intake, malabsorption, and increased caloric needs may contribute to growth retardation. To assess whether a sustained high caloric and nitrogen intake could reestablish growth, 4 children with extensive Crohn's disease of the small bowel were studied before and after parenteral alimentation which was instituted for symtomatic disease control. Weight gain, positive nitrogen balance, and improved nutritional status were achieved during parenteral alimentation in each patient. In 2 patients weight gain was sustained using oral nutritional supplements, and a substantial increase in linear skeletal growth continued in the ensuing months. One patient entered puberty within 4 months of parenteral alimentation and another had the onset of menarche and the development of secondary sex characteristics 4 months after parenteral alimentation and resection of diseased bowel. Growth may be reestablished in some growth-arrested children if intake is sufficient to establish a sustained positive caloric and nitrogen balance. Nutritional requirements imposed by the demands of growth and active disease and often compounded by the catabolic effects of corticosteroids may be excessive; growth may occur only if these needs are met orally and/or parenterally.
Polycyclic aromatic hydrocarbons and cytochrome P450 in HIV pathogenesis

High prevalence of cigarette smoking in HIV patients is associated with increased HIV pathogenesis and disease progression. While the effect of smoking on the occurrence of lung cancer has been studied extensively, the association between smoking and HIV pathogenesis is poorly studied. We have recently shown the possible role of cytochrome P450 (CYP) in smoking/nicotine-mediated viral replication. In this review, we focus on the potential role of CYP pathway in polycyclic aromatic hydrocarbons (PAH), important constituents of cigarette smoke, mediated HIV pathogenesis. More specifically, we will discuss the role of CYP1A1 and CYP1B1, which are the major PAH-activating CYP enzymes. Our results have shown that treatment with cigarette smoke condensate (CSC) increases viral replication in HIV-infected macrophages. CSC contains PAH, which are known to be activated by CYP1A1 and CYP1B1 into procarcinogens/toxic metabolites. The expression of these CYPs is regulated by aryl hydrocarbon receptors (AHR), the cellular target of PAH, and an important player in various diseases including cancer. We propose that PAH/AHR-mediated CYP pathway is a novel target to develop new interventions for HIV positive smokers.
Similarity of Cardinal Directions

Like people who casually assess similarity between spatial scenes in their routine activities, users of pictorial databases are often interested in retrieving scenes that are similar to a given scene, and ranking them according to degrees of their match. For example, a town architect would like to query a database for the towns that have a landscape similar to the landscape of the site of a planned town. In this paper, we develop a computational model to determine the directional similarity between extended spatial objects, which forms a foundation for meaningful spatial similarity operators. The model is based on the direction-relation matrix. We derive how the similarity assessment of two direction-relation matrices corresponds to determining the least cost for transforming one direction-relation matrix into another. Using the transportation algorithm, the cost can be determined efficiently for pairs of arbitrary direction-relation matrices. The similarity values are evaluated empirically with several types of movements that create increasingly less similar direction relations. The tests confirm the cognitive plausibility of the similarity model.