cssi/SciSciGPT-SciSciNet huggingface dataset:
Sympatric Apes in Sacred Forests: Shared Space and Habitat Use by Humans and Endangered Javan Gibbons (Hylobates moloch)

In this research, we use a combination of ethnographic observation and GIS analysis to explore the use of space by humans and gibbons (Hylobates moloch) to determine areas of potential space competition in the sacred forest and nature reserve Cagar Alam Leuweung Sancang in West Java, Indonesia. More specifically, we test whether gibbons respond to the presence of humans in a manner consistent with predator-avoidance and predicted that the gibbon study subjects would avoid areas visited by humans (Risk-Disturbance Hypothesis). Data were collected August 2010-June 2011. We collected GPS locations and behavioral data on both the humans (6,652 hours) and the gibbons (1,253 hours) in the forest using 10 minute instantaneous sampling. Results indicate that humans preferentially assemble at the most sacred spot in the forest (Cikajayaan waterfall). Two gibbon groups’ home ranges encompassed most of the sacred areas. Group B avoided areas of high human use, as high human use areas and high gibbon use areas did not overlap. Group C, though, continued to use areas that were heavily visited by humans. We thus found partial support for the Risk-Disturbance Hypothesis, although the variation in gibbon response to human disturbance indicates behavioral flexibility. We suggest that understanding the effects of shared space on wildlife is necessary for informing conservation policy in human-visited forests.
Sustainability of a Practice-based Interprofessional Introductory Pharmacy Practice Experience Course

Objective. To describe a successfully sustained interprofessional introductory pharmacy practice experience (IPPE) in which third-year pharmacy students were paired with nonpharmacist practitioners. Methods. Course data were retrospectively reviewed and analyzed to reveal details about the program. Provider participant numbers and student perception data were reviewed and reported on. Results. The number of students and providers participating increased during the 13 years of the program. On average, preceptors participated for 3 years and hosted 4 pharmacy students. Students consistently agreed the course helped increase student communication competencies and integration into interdisciplinary practice (mean agreement of 88.4% and 91.6%, respectively). Conclusion. A required interprofessional IPPE course designed to develop students’ self-confidence working and communicating with nonpharmacist practitioners has been successfully sustained for more than a decade. Students report improvements in self-confidence and achievement of the course’s primary outcomes.
Transition Economies: Who Lost Russia?

Consider several of the differences between a command economy and a market economy: • In a command economy the means of production — the factories and airlines, the banks and retail stores, the houses and apartments, are owned by the state; in the market economy the factories et al. are owned by companies and individuals. • In a command economy prices are set by the planners in the central government and are only tangentially related to the costs of production; in the market economy the price of each good and service is closely related to its costs of production. • In the command economy the funds necessary to finance the costs of government are collected in the prices of goods (which is essentially a form of indirect taxation); in the market economy the taxes necessary to finance the costs of government are added to the prices of goods and a significant part of taxes are direct individual incomes and corporate incomes. • In the command economy the major task of the factory manager is to produce the volume of goods necessary to satisfy the targets set by the central planners; in the market economy the major task of the factory manager is to design the goods that the consumers are eager to buy. • In the command economy everyone had a job and there was full employment; in the market economy there have been high levels of unemployment because some individuals wanted to take more out of the pot in the form of wages than they were contributing to the pot in the form of productivity. In effect they weren’t earning their keep — which meant that they had discovered a free lunch or a partial free lunch. • In the market economy each worker receives the value of his or her marginal product — at least, that is what the textbooks say. • In the command economy engineers are at the top of the decisionmaking hierarchies; in the market economy the marketing specialists or the finance MBAS are at the top of the hierarchies. • In the command economy of what had been the Soviet Union and its allies in Eastern Europe, there was a strong belief that the most efficient pattern of production involved extremely large factories, so that each major good would be produced in only one or several plants. The factories that produced certain inputs would at times be at a considerable distance, and even in different countries, from the factories that used these inputs. • In the command economy there are no commercial disputes because there is no private property; in the market economy there is a need for a system of courts — and of lawyers and independent judges — to resolve disputes between producers and consumers and among different producers. • In the command economy those who get to the top have sharp elbows; in the market economy those who get to the top have sharp elbows.
Protective role of Indoleamine 2,3 dioxygenase in Respiratory Syncytial Virus associated immune response in airway epithelial cells

RSV is a major cause of severe lower respiratory infection in infants and young children. With no vaccine yet available, it is important to clarify mechanisms of disease pathogenesis. Since indoleamine-2,3-dioxygenase (IDO) is an immunomodulatory enzyme and is upregulated with RSV infection, we studied it in vivo during infection of BALB/c mice and in vitro in A549 cells. RSV infection upregulated IDO transcripts in vivo and in vitro. IDO siRNA decreased IDO transcripts ~2 fold compared to control siRNA after RSV infection but this decrease did not affect RSV replication. In the presence of IFN-γ, siRNA-induced a decrease in IDO expression that was associated with an increase in virus replication and increased levels of IL-6, IL-8, CXCL10 and CCL4. Thus, our results show IDO is upregulated with RSV infection and this upregulation likely participates with IFN-γ in inhibition of virus replication and suppression of some host cell responses to infection.
Representative Bureaucracy: Examining the Effects of Female Teachers on Girls’ Education in Ghana

ABSTRACTScholars have examined representative bureaucracy as a viable means to make the bureaucracy more responsive to citizens in a democratic society. The theory argues that a diverse public service that mirrors the social demographics of its population in terms of gender, race, and ethnicity (passive representation) is more likely to be responsive to the needs of all citizens (active representation). Although a substantial body of empirical research exists, a comparative understanding of the theory is lacking in Africa. This study expands the empirical research on the theory to Ghana. It investigates whether passive representation of female teachers makes the education bureaucracy more responsive to girls. The analysis of a nationally representative data set on senior high schools (SHS) within the 216 districts of Ghana revealed that increasing the presence of female teachers is positively associated with the performance of girls on math and science exit exams.
Using Maple Cloud Computing in Financial Education of Pre-service Teachers

The paper deals with an original collection of educational materials developed by the authors at the Faculty of Education at the University of South Bohemia. Main goal of these materials is to support the financial education of future teachers with interactive environment in addition to the usual computer means of financial computation such as spreadsheet and online calculators. Maple enables to create interactive documents whose interactivity consists in implementation of a simple user interface beyond the framework of usual document. This fact enables the user to influence the computation result by a change in input parameters and thus de facto to simulate an inexhaustible number of situations.
Fractional Calculus in Bioengineering

Fractional calculus (integral and differential operations of noninteger order) is not often used to model biological systems. Although the basic mathematical ideas were developed long ago by the mathematicians Leibniz (1695), Liouville (1834), Riemann (1892), and others and brought to the attention of the engineering world by Oliver Heaviside in the 1890s, it was not until 1974 that the first book on the topic was published by Oldham and Spanier. Recent monographs and symposia proceedings have highlighted the application of fractional calculus in physics, continuum mechanics, signal processing, and electromagnetics, but with few examples of applications in bioengineering. This is surprising because the methods of fractional calculus, when defined as a Laplace or Fourier convolution product, are suitable for solving many problems in biomedical research. For example, early studies by Cole (1933) and Hodgkin (1946) of the electrical properties of nerve cell membranes and the propagation of electrical signals are well characterized by differential equations of fractional order. The solution involves a generalization of the exponential function to the Mittag-Leffler function, which provides a better fit to the observed cell membrane data. A parallel application of fractional derivatives to viscoelastic materials establishes, in a natural way, hereditary integrals and the power law (Nutting/Scott Blair) stress-strain relationship for modeling biomaterials. In this review, I will introduce the idea of fractional operations by following the original approach of Heaviside, demonstrate the basic operations of fractional calculus on well-behaved functions (step, ramp, pulse, sinusoid) of engineering interest, and give specific examples from electrochemistry, physics, bioengineering, and biophysics. The fractional derivative accurately describes natural phenomena that occur in such common engineering problems as heat transfer, electrode/electrolyte behavior, and sub-threshold nerve propagation. By expanding the range of mathematical operations to include fractional calculus, we can develop new and potentially useful functional relationships for modeling complex biological systems in a direct and rigorous manner.
Ferroelectric Thin Films and Device Applications

Ferroelectrics are one of the few classes of materials which have been extensively investigated in their crystal and ceramic form. In the recent past 5–7 years, the activity has been extended to develop their thin film counterparts which is also further paved with the recent advances in thin film growth technology. Growth techniques that have received major attention include both of physical and chemical nature. Almost every technique appeared to offer ferroelectric thin films with properties qualifying for an extensive investigation. Besides, mere understanding the fundamental differences in phenomenology between thin films and bulk crystals, most of the thin film growth activity has been prompted by their potential applications, closely linked with semiconductor technology. Various applications are possible, however, non-volatile memories have assumed a leading place, while it is hoped that other possible applications such as piezoelectric based micro-mechanical devices, electro-optic based signal processors, and pyroelectric based IR imaging systems, would also follow the trend in the future efforts. Present review deals with the preliminary introduction to ferroelectric phenomena and some popular materials and also enlists the device applications based on individual phenomena.
Conservative fourth-order finite-volume Vlasov–Poisson solver for axisymmetric plasmas in cylindrical (r,vr,vθ) phase space coordinates

Abstract A fourth-order finite-volume Vlasov–Poisson algorithm is developed for simulating axisymmetric plasma configurations in ( r , v r , v θ ) phase space coordinates. The Vlasov equation for cylindrical phase space coordinates is cast into conservation-law form and is discretized on a structured grid. The conservative finite-volume discretization is based on fifth-order upwind reconstructions of the distribution function and a fourth-order quadrature rule that accounts for transverse variations of fluxes along control volume surfaces. High-order specular reflection boundary conditions enable high-fidelity treatment of plasma distribution functions at the axis and at wall boundaries. The numerical method is applied to simulate a confined uniform neutral gas to assess convergence properties for an equilibrium system in which effects of finite-temperature and acceleration due to centrifugal and Coriolis forces are present. The discretization is also applied to a Z-pinch configuration to study electrostatic ion confinement and the dynamics of the associated breathing mode. Simulations show that the ion distribution function exhibits non-Maxwellian features and that a temperature anisotropy develops and is sustained. The finite-volume implementation is demonstrated to converge at fourth-order for both applications.
A Common Representation of Serial Position in Language and Memory

Abstract Speaking, spelling, and serial recall require a sequence of items to be produced one at a time in the correct order. The representations that underlie this ability, at a minimum, contain information about the identities and positions of the items in the sequence. This chapter summarizes a series of studies that investigate whether similar principles underlie how position is represented in different cognitive domains. In each domain, a variety of hypotheses have been proposed for how the position of an item is represented. An analysis framework has been developed that allows for controlled cross-domain experimentation that considers a common set of hypotheses to investigate whether there are commonalities in how position is represented. Careful analysis of the patterns of errors produced by neuropsychological case studies and unimpaired adults in a range of tasks support a both-edges representation of position, a scheme in which each item's position is represented both by its distance from the beginning of the sequence and its distance from the end of the sequence. The fact that a similar scheme is used to represent position across a range of cognitive domains suggests that serial order processing may rely on some domain-general representational principles. I discuss implications of this pattern of results for situating language processing in domain-general mechanisms and propose some tentative hypotheses as to why this edge-based representation of position is so prevalent.
Domain-Focused CRISPR-Cas9 Screen Identifies the E3 Ubiquitin Ligase Substrate Adaptor Protein Spop As a Novel Repressor of Fetal Hemoglobin

Abstract Elevated levels of fetal hemoglobin (HbF) are beneficial to patients with sickle cell disease (SCD) and b-thalassemia. The identification of pharmacologically controllable pathways that regulate HbF levels remains an important goal in the treatment of these disorders. BCL11A and LRF (ZBTB7A) are the two major transcriptional repressors of g-globin (fetal beta-type globin). However, since transcription factors are challenging to inhibit with small molecules, we aimed to identify novel HbF regulators that might be amenable to control by pharmacologic means. Using an improved protein-domain based CRISPR-Cas9 screen recently developed in our laboratory (Grevet et al., Science 361:6399, 285-290), we screened for new HbF regulators using a gRNAs library targeting chromatin associated proteins including BTB domain containing factors. We identified SPOP, a substrate adaptor of the CUL3 ubiquitin ligase complex, as a novel inhibitor of g-globin expression. Depletion of SPOP strongly elevated the mRNA and protein levels of g-globin in both HUDEP-2 and primary human CD34+ derived erythroid cells. The effects of SPOP loss were remarkably selective as evidenced by RNA-seq and whole cell mass spectrometry. Importantly, SPOP depletion did not appear to impair cell growth or differentiation. Mechanistically, we demonstrated that the repressive role of SPOP on g-globin levels is dependent on the CUL3 ubiquitin ligase complex. Additionally, forced expression of a dominant negative form of SPOP (Y87N) unable to bind to its substrates strongly induced HbF production. We also found that SPOP depletion did not measurably alter LRF levels and modestly reduced BCL11A levels. Overexpression of BCL11A did not restore g-globin silencing in SPOP depleted cells, indicating that SPOP works largely independently of these two factors. Finally, we tested whether the effects of SPOP depletion can be augmented through the use of experimental pharmacologic HbF inducers, such as pomalidomide. In proof of principle experiments we found that SPOP depletion and pomalidomide treatment induced HbF production to levels higher than either treatment alone. In sum, our work uncovered SPOP as a new regulator of HbF and suggests targeting SPOP alone or in combination with other HbF inducers may provide a novel therapeutic strategy for the treatment of hemoglobinopathies such as sickle cell disease and b-thalassemia. Disclosures No relevant conflicts of interest to declare.
Restoration of wall shear stress in the cephalic vein during extreme hemodynamics

The surgical creation of an artery-vein connection via a Brachicephalic fistula (BCF) in patients with end stage renal disease (ESRD) provides a unique opportunity to study blood vessel response mechanisms to extreme hemodynamic conditions in relatively short timeframes. After BCF creation, the flow rate in the vein increases by an order of magnitude leading to separated flows and corresponding abnormally low, or negative, wall shear stress (WSS) in the curved arch segment of the cephalic vein. Locations of abnormally low WSS are shown to correlate with development of neointimal hyperplasia (NH) and subsequent stenosis. It is found that the stenosis, prior to a surgical intervention, restores the normal physiological WSS in the vein. As a result, this investigation provides evidence that the adaptation principle, known to apply in the arterial system, is also valid in the venous system. A novel graphical method is developed that combines clinical and computational data to assist in interpreting these physiological mechanisms including adaptation that lead to changes in vein geometry over time.
Investigation of Cathodo-Luminescence with the Petrographic Microscope

An attachment can be constructed for any electron microscope which allows bombardment of a solid sample surface by the electron beam and simultaneous observation with a petrographie microscope, Cathodoluminescence is found to be sufficiently specific in multiphase systems to permit identification of major phases, recognition and determination of the distribution of fine-grained and interstitial phases, and investigation of textural feamres, such as zoning, exsolution, and grain boundary relations. In combination with a photomultiplier tube, the technique could be used to determine the relative amounts of phases in a sample.
Coolies of the Empire: Indentured Indians in the Sugar Colonies, 1830–1920: by Ashutosh Kumar, Cambridge, Cambridge University Press, 2017, xvi + 320 pp. US$105.00 (hard cover), ISBN: 9781107147959

Following the abolition of slavery in the nineteenth century, the British Government allowed its overseas as well as the French, Dutch, and Danish colonies to import Indian indentured laborers to m...
Dual number-based variational data assimilation: Constructing exact tangent linear and adjoint code from nonlinear model evaluations

Dual numbers allow for automatic, exact evaluation of the numerical derivative of high-dimensional functions at an arbitrary point with minimal coding effort. We use dual numbers to construct tangent linear and adjoint model code for a biogeochemical ocean model and apply it to a variational (4D-Var) data assimilation system when coupled to a realistic physical ocean circulation model with existing data assimilation capabilities. The resulting data assimilation system takes modestly longer to run than its hand-coded equivalent but is considerably easier to implement and updates automatically when modifications are made to the biogeochemical model, thus making its maintenance with code changes trivial.
The Role of Bile Acids in Chronic Diarrhea

Bile acids (BAs) are the central signals in enterohepatic communication, and they also integrate microbiota-derived signals into enterohepatic signaling. The tissue distribution and signaling pathways activated by BAs through natural receptors, farsenoid X receptor and G protein-coupled BA receptor 1 (GPBAR1, also known as Takeda G-coupled receptor 5), have led to a greater understanding of the mechanisms and potential therapeutic agents. BA diarrhea is most commonly encountered in ileal resection or disease, in idiopathic disorders (with presentation similar to functional diarrhea or irritable bowel syndrome with diarrhea), and in association with malabsorption such as chronic pancreatitis or celiac disease. Diagnosis of BA diarrhea is based on Se-homocholic acid taurine retention, 48-hour fecal BA excretion, or serum 7αC4; the latter being a marker of hepatic BA synthesis. BA diarrhea tends to be associated with higher body mass index, increased stool weight and stool fat, and acceleration of colonic transit. Biochemical markers of increased BA synthesis or excretion are available through reference laboratories. Current treatment of BA diarrhea is based on BA sequestrants, and, in the future, it is anticipated that farsenoid X receptor agonists may also be effective. The optimal conditions for an empiric trial with BA sequestrants as a diagnostic test are still unclear. However, such therapeutic trials are widely used in clinical practice. Some national guidelines recommend definitive diagnosis of BA diarrhea over empirical trial.
Opioid-free anesthesia-caution for a one-size-fits-all approach.

Post-operative pain management should ideally be optimized to ensure patient’s mobilization and ability to partake in effective pulmonary exercises for patient’s early recovery. Opioids have traditionally been the main mode for analgesia strategy in the perioperative period. However, the recent focus on opioid crisis in the USA has generated a robust discussion on rational use of opioids in the perioperative period and also raised the concept of “opioid-free anesthesia” in certain circles. Opioid-related adverse drug events (ORADE) and questionable role of opioids in cancer progression have further deterred some anesthesiologists from the routine perioperative use of opioids including their use for breakthrough pain. However, judicious use of opioid in conjunction with the use of non-opioid analgesics and regional anesthetic techniques may allow for optimal analgesia while reducing the risks associated with the use of opioids. Importantly, the opioid epidemic and opioid-related deaths seem more related to the prescription practices of physicians and post-discharge misuse of opioids. Focus on patient and clinician education, identification of high-risk patients, and instituting effective drug disposal and take-back policies may prove useful in reducing opioid misuse.
Vocabulary accessibility and acquisition: do you get more from a financestor or a sociophite?

Background The purpose of the current study was to examine how the morphological structure of a real word or novel word affected the incidental vocabulary learning of participants and to examine how these target items are processed as they are read. In addition, we examined the roles of vocabulary depth and breadth in the process of incidental vocabulary learning. Methods We had participants read short passages that contained real words or novel words that differed on their morphological accessibility as we collected eye movement data. Participants also completed several vocabulary depth and breadth measures. Results Accessible real words and novel words were learned better than inaccessible and less accessible items, but there was a processing cost associated with accessible real words compared with inaccessible real words. In contrast, participants spent more time on the less accessible novel words compared with accessible novel words, but that extra processing time did not translate into better acquisition scores. Finally, both vocabulary breadth and depth explained variance in incidental vocabulary acquisition, while breadth explained variance in gaze duration and depth explained variance in regressive eye movements. Conclusions Accessibility of the targets affected both acquisition and reading time, and depth and breadth are both individual differences that explain variance in incidental acquisition and the processing of those words.
Becoming an Individual: Promoting Twins’ Identity Development through Counseling Techniques

Adolescent twins develop differently than singled birthed individuals. In order for counselors to serve this unique population effectively, counselors need to be aware of common issues encountered ...
Skin testing and oral amoxicillin challenge in the outpatient allergy and clinical immunology clinic in pregnant women with penicillin allergy.

Abstract Background Penicillin allergy is frequently reported. In pregnant women, reported penicillin allergy is associated with negative health outcomes and suboptimal group B streptococcal prophylaxis. For individuals having penicillin allergy, skin testing followed by an observed oral challenge is recommended. Previous data indicate a low risk of adverse reaction with skin testing in pregnant women, but the subsequent oral challenge was not routinely pursued. Objective To determine whether skin testing followed by the outpatient oral challenge is tolerated by pregnant women. Methods We conducted a retrospective review of all pregnant women who underwent penicillin allergy evaluation at an outpatient allergy and clinical immunology clinic. The patients underwent oral amoxicillin challenges based on the discretion of the allergy provider. We evaluated the index reaction history, skin test results, oral challenge results, and subsequent antibiotic exposure. Results A total of 46 pregnant women underwent skin testing without adverse reactions, of whom 44 patients (95.6%) received negative results. A total of 18 women (39%) completed an oral challenge without adverse reactions. Patients challenged vs not challenged did not differ in patient age, gestational age, latency since index reaction, or reaction history risk level. Notably, 28 women received intrapartum antibiotics. There was no difference in intrapartum antibiotic administration between those who did or who did not complete an in-office oral challenge (P = .90). Conclusion Penicillin skin testing and oral challenge in pregnant women can safely be performed in the outpatient setting. There was no difference in the intrapartum antibiotic use between women who were and those who were not challenged. Further research is needed to determine the utility of oral challenge in pregnant patients.
Readmissions for Depression and Suicide Attempt following Stroke and Myocardial Infarction.

Background and purpose Rates of depression after ischemic stroke (IS) and myocardial infarction (MI) are significantly higher than in the general population and associated with morbidity and mortality. There is a lack of nationally representative data comparing depression and suicide attempt (SA) after these distinct ischemic vascular events. Methods The 2013 Nationwide Readmissions Database contains >14 million US admissions for all payers and the uninsured. Using International Classification of Disease, 9th Revision, Clinical Modification Codes, we identified index admission with IS (n = 434,495) or MI (n = 539,550) and readmission for depression or SA. We calculated weighted frequencies of readmission. We performed adjusted Cox regression to calculate hazard ratio (HR) for readmission for depression and SA up to 1 year following IS versus MI. Analyses were stratified by discharge home versus elsewhere. Results Weighted depression readmission rates were higher at 30, 60, and 90 days in patients with IS versus MI (0.04%, 0.09%, 0.12% vs. 0.03%, 0.05%, 0.07%, respectively). There was no significant difference in SA readmissions between groups. The adjusted HR for readmission due to depression was 1.49 for IS versus MI (95% CI 1.25-1.79, p 70 years (0.46 [0.37-0.56]) and discharge home (0.69 [0.57-0.83]) were associated with reduced hazards of readmission due to depression. Conclusions IS was associated with greater hazard of readmission due to depression compared to MI. Patients with a history of depression, smoking, and alcoholism were more likely to be readmitted with depression, while advanced age and discharge home were protective. It is unclear to what extent differences in type of ischemic tissue damage and disability contribute, and further investigation is warranted.
Undervaluation of Employee Satisfaction

The prior literature has shown that firms in the list of 100 Best Companies to Work for in America (hereafter BC) earn positive abnormal returns in the period after the list is published in Fortune magazine. In this paper, we assess to what extent the prior performance of stocks is related to this anomaly. We find that these abnormal returns are indeed confined to a subset of BC that have performed poorly over the previous two years. Specifically, over the sample period 1998-2017, a value-weighted portfolio of loser BC earns an annualized three-factor alpha of 12.65% in the subsequent year, while the same figure for other BC is an insignificant 1.11%. Our findings are consistent with the view that mispricing forms over time and support the hypothesis that undervaluing human capital plays a vital role in the BC anomaly.
Vemurafenib Drives Epithelial-to-Mesenchymal Transition Gene Expression in BRAF Inhibitor‒Resistant BRAFV600E/NRASQ61K Melanoma Enhancing Tumor Growth and Metastasis in a Bioluminescent Murine Model.

BRAF inhibitor (BRAFi) resistance compromises long-term survivorship of patients with malignant melanoma, and mutant NRAS is a major mediator of BRAFi resistance. In this study, employing phenotypic and transcriptomic analysis of isogenic melanoma cells that differ only by NRAS mutational status (BRAFi-sensitive A375-BRAFV600E/NRASQ61 vs. BRAFi-resistant A375-BRAFV600E/NRASQ61K), we show that BRAFi (vemurafenib) treatment selectively targets BRAFV600E/NRASQ61K cells upregulating epithelial-to-mesenchymal transition (EMT) gene expression, paradoxically promoting invasiveness and metastasis in vitro and in vivo. First, NanoString nCounter transcriptomic analysis identified the upregulation of specific gene expression networks (EMT and EMT to metastasis) as a function of NRASQ61K status. Strikingly, BRAFi treatment further exacerbated the upregulation of genes promoting EMT in BRAFV600E/NRASQ61K cells (with opposing downregulation of EMT-driver genes in the BRAFV600E/NRASQ61 genotype) as detected by EMT-focused RT2 Profiler qPCR array analysis. In BRAFV600E/NRASQ61K cells, BRAFi treatment enhanced proliferation and invasiveness, together with activation of phosphorylated protein kinase B (Ser473), with opposing phenotypic effects observable in BRAFV600E/NRASQ61 cells displaying downregulation of phosphorylated protein kinase B and phosphorylated extracellular signal–regulated kinase 1/2. In a SCID mouse bioluminescent melanoma metastasis model, BRAFi treatment enhanced lung tumor burden imposed by BRAFV600E/NRASQ61K cells while blocking BRAFV600E/NRASQ61 metastasis. These preclinical data document the BRAFi-driven enhancement of tumorigenesis and metastasis in BRAFi-resistant human BRAFV600E/NRASQ61K melanoma, a finding with potential clinical implications for patients with NRAS-driven BRAFi-resistant tumors receiving BRAFi treatment.
Urinary metabolites of the antitumor agent cyclophosphamide.

2-Carboxyethyl N, N -bis(2-chloroethyl)phosphorodiamidate and 4-ketocyclophosphamide (2-[bis(2-chloroethyl)amino]tetrahydro-2 H -1,3,2-oxazaphosphorin-4-one 2-oxide) have been isolated and identified as urinary metabolites of dogs treated with the anticancer agent cyclophosphamide (2-[bis(2-chloroethyl)amino]tetrahydro-2 H -1,3,2-oxazaphosphorine 2-oxide). 2-Carboxyethyl N, N -bis(2-chloroethyl)phosphorodiamidate is the major urinary metabolite, whereas 4-ketocyclophosphamide is a minor metabolite and represents the first known product of cyclophosphamide which retains the ring structure. Another urinary metabolite yields β-hydroxypropionamide on hydrolysis, a further indication that the primary oxidative step in the metabolism of cyclophosphamide occurs on carbon 4 of the ring. Neither of the two isolated metabolites is highly cytotoxic to human epidermoid cancer cells in vitro or to Leukemia L1210 cells in vivo . Neither compound is on a pathway leading to an active form of the drug. ACKNOWLEDGMENTS We are very grateful to Miss D. Adamson and Mrs. M. H. Vail for performing the cytotoxicity studies with cloned cells. Dr. L. Wilkoff and Dr. F. Schabel of the Chemotherapy Department of Southern Research Institute determined the cytotoxicity tests in swirl cultures, with monolayers of cells, and with mice implanted with tumor cells. Human urine was obtained from patients at M. D. Anderson Hospital, Houston, through the courtesy of Dr. James Luce. Mr. T. C. Herren and Mr. H. E. Finch assayed samples for radioactivity. The microanalytical and spectral determinations were performed by Dr. W. C. Coburn, Jr., and associates. Some of the analyses were performed by Galbraith Laboratories, Knoxville, Tenn. We are indebted to Dr. N. Brock for a recent gift of a sample of synthetic 4-ketocyclophosphamide, and to Dr. A. Takamizawa for a sample of synthetic 2-carboxyethyl N,N -bis(2-chloroethyl)phosphorodiamidate.
Why Do Neurologists and Psychiatrists Not Talk to Each Other

The close and complex relationships between psychiatric and neurologic disorders have been identified for a long time. This chapter briefly discusses this disorder, which comprises the explanation why neurologists and psychiatrists should talk to one another, their consequences, the cause of lack in communication, the neurologists' perspective, and the psychiatrists' perspective. The difficulty that arises between psychiatrists and neurologists may stem from fear and discomfort, as psychiatrists are not familiar enough with medicine in general, and specifically neurology. The same holds true for neurologists dealing with psychiatric problems in their patients. As a result, instead of admitting difficulty, which has its own set of problems, the practitioner may deny the existence of the problem or avoid asking questions that would put him or her in an unfamiliar situation; thus, it leads in lack of communication.
Adult cardiovascular physician resources and needs assessment: Report of the 1992 and 1993 American College of Cardiology surveys on physician training and resource requirements

Summary Training for procedures will remain an important issue. At the present time, primary care physicians principally perform exercise tests and interpret ECGs among cardiovascular procedures, and their training is supplemental to their routine program. If more cardiovascular procedures are to be performed by primary care physicians, some additional formal training will be necessary to provide skills equivalent to those attained by cardiovascular specialists in the course of their training. However, risk factors are frequently managed by the primary care physician without cardiovascular support. The surveys indicate a sufficiency in the perceived number of cardiologists and a perceived oversupply of invasive cardiologists. Cardiologists provide a significant proportion of primary care for their patients with cardiologic diagnoses, and primary care physicians provide a considerable proportion of routine cardiovascular care, particularly involving risk modification. As care models change in the future, it will be important to continue to examine the referral patterns and relative provision of cardiovascular care by both primary care physicians and cardiologists. Future cardiovascular physician requirements will reflect changing needs relating to geography, technical expertise and the use of advanced practice nursing and physician assistants. Adequate procedure experience remains a concern for cardiologists because the procedure volumes frequently fall below recommended minimal standards. All these issues will continue to have an impact on the need for additional cardiovascular practitioners.
Primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (MALT): single institution experience in a large cohort of patients

Extranodal marginal zone B-cell lymphoma is the most common orbital tumour. We conducted a retrospective analysis to examine: (i) the impact of initial presentation and staging on outcome and (ii) response to various treatment modalities and the effect of the latter on recurrence. Ninety patients with primary ocular adnexal marginal zone lymphoma (POAML) diagnosed at our institution between 1984 and 2009 were studied. POAML was associated with monoclonal gammopathy (13%) at presentation. Most POAML patients (86%) presented with Ann-Arbor stage I disease. Radiotherapy led to excellent local control, but relapses occurred in 18% of Ann-Arbor stage I patients during a median follow-up of 5 years. Local relapses, including secondary central nervous system (CNS) involvement, were observed in patients receiving radiation doses <30·6 Gy. No differences in relapse rate and survival were observed between patients who did or did not undergo staging bone marrow biopsy. Ann-Arbor stage II-IV disease and high lactate dehydrogenase levels were associated with shorter freedom from progression. In conclusion, POAML is an indolent lymphoma with continuous risk for relapse. Radiation doses of at least 30·6 Gy should be given in Ann-Arbor stage I disease, since lower doses may be more frequently associated with relapses, including CNS relapses.
Tariff Incidence in AmericaAS Gilded Age

In the late nineteenth century, the United States imposed high tariffs to protect domestic manufacturers from foreign competition. This paper examines the magnitude of protection given to import-competing producers and the costs imposed on export-oriented producers by focusing on changes in the domestic prices of traded goods relative to non-traded goods. Because the tariffs tended to increase the prices of non-traded goods, the degree of protection was much less than indicated by nominal rates of protection; the results here suggest that the 30 percent average tariff on imports yielded a 15 percent implicit subsidy to import-competing producers while effectively taxing exporters at a rate of 11 percent. The paper also finds that tariff policy redistributed large amounts of income (about 9 percent of GDP) across groups, although the impact on consumers was only slightly negative because they devoted a sizeable share of their expenditures to exportable goods. These findings may explain why import-competing producers pressed for even greater protection in the face of already high tariffs and why consumers (as voters) did not strongly oppose the policy.
Progress on Model Atmospheres and Line Data

I discuss errors in theory and in interpreting observations that are produced by the failure to consider resolution in space, time, and energy. I discuss convection in stellar model atmospheres and in stars. One dimensional convective models can never work well, but the errors in predicted diagnostics for temperature, gravity, and abundances can be calibrated. I discuss the variation of microturbulent velocity with depth, effective temperature, and gravity. These variations must be dealt with in computing models and grids and in any type of photometric calibration. I describe the state of the art in computing a model atmosphere and complete spectrum for stars with arbitrary abundances. I have made no significant progress on atomic or molecular line data for the last two years, but I will soon begin large scale production. I will continue to distribute the results on CD-ROMs, and I will make them available on the World Wide Web.
The effect of epidural analgesia upon fetal and neonatal status

Abstract The effect of epidural analgesia on the fetal and neonatal status was studied in 72 patients who received a standard epidural block during labor. Recordings were made of maternal blood pressure, fetal heart rate, and uterine contractions. Observations on the neonates continued to the day of discharge from the hospital. A control group of 100 patients who received either no analgesia during labor or a form of pain relief other than epidural block was also studied. The control patients were monitored for obstetric indications and therefore are not strictly comparable to the study group. The study group of patients was subdivided into 4 groups (SG1 to SG4). Twenty-four patients in SG2 received oxytocin and did not develop hypotension; 7 patients in SG3 did not receive oxytocin and developed hypotension; 20 patients in SG4 neither received oxytocin nor developed hypotension. Significant fetal heart rate (FHR) decelerations were seen in 55 per cent of the study patients; these occurred most frequently in those patients who developed hypotension (71 per cent) but also developed in 40 per cent of those patients whose blood pressure remained stable. The most common significant FHR pattern was that of late deceleration, occurring in 33.3 per cent of the study group of patients. Of the neonates from the study group of mothers, 9.7 per cent had low Apgar scores compared to 17 per cent of the control neonates. The majority recovered shortly after the 5 minute Apgar observation and continued normally until the day of discharge.
Visual self-motion perception during head turns

Extra-retinal information is critical in the interpretation of visual input during self-motion. Turning our eyes and head to track objects displaces the retinal image but does not affect our ability to navigate because we use extra-retinal information to compensate for these displacements. We showed observers animated displays depicting their forward motion through a scene. They perceived the simulated self-motion accurately while smoothly shifting the gaze by turning the head, but not when the same gaze shift was simulated in the display; this indicates that the visual system also uses extra-retinal information during head turns. Additional experiments compared self-motion judgments during active and passive head turns, passive rotations of the body and rotations of the body with head fixed in space. We found that accurate perception during active head turns is mediated by contributions from three extra-retinal cues: vestibular canal stimulation, neck proprioception and an efference copy of the motor command to turn the head.
ML optimality of PDE-based segmentation algorithms

Summary form only given, as follows. Building on our image restoration and segmentation algorithms developed in Pollak et al. (2000), we present a very simple nonlinear diffusion equation and show its utility both for image segmentation and for the detection of abrupt changes in 1-D. We show that it may be interpreted as a variant of the Perona-Malik (1990) equation, as the steepest descent equation for the total variation (Bouman and Sauer 1991, Rudin et al. 1992), and-in 1-D-as a solver of a simple version of the Mumford-Shah (1985) problem. The analysis of our equation in 1-D reveals it to be an exact solver of certain maximum likelihood detection/estimation problems. The major advantage over other methods to solve these problems is O(N log N) computational complexity in one spatial dimension. Finally, we show our method to be a robust estimator (in the spirit of H-infinity estimation (Nagpal and Khargonekar 1991)) for a restricted class of 1-D problems. Experiments suggest that the 2-D version of our algorithm retains robustness properties of the 1-D version. Moreover, if only a binary segmentation is required, the computational complexity of our 2-D algorithm is still O(N log N). A remaining challenge is to extend our probabilistic analysis of the 1-D algorithm to 2-D, designing fast and optimal image segmentation algorithms.
Optimal Consumption-Investment Decisions Allowing for Bankruptcy: A Brief Survey

This paper surveys the research on the optimal consumption and investment problem of an agent who is subject to bankruptcy that has a specified utility (reward or penalty). The bankruptcy utility, modelled by a parameter, may be the result of welfare subsidies, the agent’s innate ability to recover from bankruptcy, psychic costs associated with bankruptcy, etc. Models with nonnegative consumption, positive subsistence consumption, risky assets modelled by geometric Brownian motion or semi-martingales are discussed. The paper concludes with suggestions for open research problems.
Gene Synthesis: Assembly of Target Sequences Using Mutually Priming Long Oligonucleotides

This protocol uses pairs of oligonucleotides annealed at a short duplex segment at their 3' ends as both templates and primers (mutually primed synthesis) to generate desired sequences up to 400 bp in a single step. The procedure is divided into three sections: design of the oligonucleotides, extension by mutually primed synthesis, and cloning of the extension products. The strategy for design of oligonucleotides is discussed in the commentary.
Increased risk for substance use and health-related problems among homeless veterans.

Background and Objectives The first aim of this study was to compare self-reported causes of homelessness between veterans and nonveterans. A second aim examined whether homeless male veterans were more likely than homeless male nonveterans to experience current problems with addictions, mental health, and physical health. Additionally, a third aim was to compare frequency of emergency room visits and treatment needs between the two groups. Methods Secondary data analyses compared male homeless veterans and nonveterans (N = 353) enrolled in the Alachua County Point in Time study in central Florida. Participants completed a questionnaire on demographics and health variables. Additional questions included recent emergency room visits and medical or other needs not being met. Results Veterans reported higher rates of substance use and mental health problems as a primary cause of homelessness when compared to nonveterans. Homeless veterans were more likely than nonveterans to report current problems with addictions (OR = 6.29, 95% CI: 3.43–11.53, p < .001), mental health problems (OR = 4.12, 95% CI: 2.28–7.42, p < .001), and physical problems (OR = 1.83, 95% CI: 1.08–3.67, p < .01). Finally, over half of homeless veterans (53.1%) reported an ER visit in the past year compared to only 40.9% of nonveterans (OR = 1.73, 95% CI: 1.07–2.80, p < .05). Conclusion and Scientific Significance Veterans may be more likely to become homeless due to addiction and mental health and over half of homeless veterans are presenting to hospital emergency rooms. Given the greater utilization among homeless veterans, emergency rooms may serve as a prime opportunity to provide brief treatment and referrals for needed services. (Am J Addict 2015;XX:1–5)