cssi/SciSciGPT-SciSciNet huggingface dataset:
Anaplastic thyroid carcinoma: Current diagnosis and treatment

Summary Background Anaplastic thyroid carcinoma (ATC), accounting for 5% to 15% of primary malignant thyroid neoplasms, is one of the most aggressive solid tumors in humans. Generally, it is rapidly fatal, with a mean survival of six months after diagnosis. Multimodality treatment with surgery and/or external beam radiotherapy and chemotherapy are of fundamental importance for local control of disease and to enhance survival. Design We evaluated consecutive patients with ATC observed at the Mayo Clinic from 1971 to 1993 and reviewed relevant articles published in major English-language medical journals. We used the MEDLINE database, selected bibliographies, and articles available in our personal files. Results ATC usually does not concentrate radioiodine or express thyroglobulin. It is essential to verify the diagnosis histologically because insular thyroid cancer, lymphomas, and medullary thyroid cancer are occasionally confused with undifferentiated neoplasms. Immunohistochemical study is helpful in establishing the diagnosis. Multimodal therapy and the development of effective systemic chemotherapeutic agents should result in improvements in survival, although no single agent has yet been identified. Conclusions Aggressive multimodality treatment regimens show promis in improving local control in patients with ATC. However, survival rates remain low. Despite intense application of such therapy, no standardized successful treatment protocol has been established.
Prevention of Chronic Rejection in Murine Cardiac Allografts: A Comparison of Chimerism- and Nonchimerism-Inducing Costimulation Blockade-Based Tolerance Induction Regimens

We have previously described a nonirradiation-based regimen combining costimulation blockade, busulfan, and donor bone marrow cells that promotes stable, high level chimerism, deletion of donor-reactive T cells, and indefinite survival of skin allografts in mice. The purpose of the current study is to determine the efficacy of this tolerance regimen in preventing acute and chronic rejection in a vascularized heart graft model and to compare this regimen with other putative tolerance protocols. Mice receiving costimulation blockade (CTLA4-Ig and anti-CD40 ligand) alone or in combination with donor cells enjoyed markedly prolonged heart graft survival and initially preserved histological structure. However, tolerance was not achieved, as evidenced by the eventual onset of chronic rejection characterized by obliterative vasculopathy and the rejection of secondary skin grafts. In contrast, following treatment with costimulation blockade, busulfan, and bone marrow, heart grafts survived indefinitely without detectable signs of chronic rejection or structural damage, even 100 days after placement of a secondary donor skin graft. We detected multilineage chimerism in peripheral blood, spleen, lymph nodes, and thymus, and peripheral deletion of donor-reactive cells was complete by day 90. These findings indicate that only the CD40/CD28 blockade chimerism induction regimen prevents both acute and chronic rejection of vascularized organ transplants. Further testing of these strategies in a preclinical large animal model is warranted.
Common Lower Extremity Injuries in the Skeletally Immature Athlete

Lower extremity musculoskeletal pain is a common complaint in the adolescent athlete. During rapid growth, several common biomechanical changes occur that may predispose to overuse injury. Unlike fractures, most of these office-based sports medicine complaints are initially evaluated by the primary care provider. This review discusses several of the most common complaints and briefly discusses some clinically significant conditions that masquerade as common injuries. The article discusses only the injuries unique to the growing athlete. The article's goal is to help develop a framework for the pediatric clinician to evaluate common complaints and formulate a plan that includes simple stretches and physical therapy recommendations.
Group Vocal Patterns and Leadership in India Effects of Task, Language, and Sex of Subjects

This study was concerned with the effects of language and sex of subjection social and task conversations among university students in India. Each of 20 same-sex 5-person groups, 10 male and 10 female, participated in three 10-minute discussions. The social conversation was in English or Telugu and the two task discussions were in English and Telugu, in counterbalanced order. Results showed more talking and simultaneous speech in Telugu than in English discussions. Although leaders talked more than nonleaders, the correlation was lower than that found in the United States. Analyses suggest that, cross-culturally, leadership is more highly correlated with turns, which consist of both talking and silence, rather than with talking alone.
Ecosystem cross‐sector collaboration: conceptualizing an adaptive approach to sustainability governance

This paper explores the theoretical underpinnings of collaboration and ecosystem management in order to identify the relationships and processes involved in implementing ecosystem management programs through cross-sector collaboration. Ecosystem management requires a highly adaptive and resilient social–ecological governance approach, which addresses spatiality and temporality issues. In order to explore possible implementation issues with ecosystem management, propositions are developed dealing with adaptive governance, institutional isomorphism and collective action. The paper concludes with a discussion of the theoretic underpinnings involved in implementing ecosystem management through cross-sector collaborations. Copyright © 2010 John Wiley & Sons, Ltd and ERP Environment.
Evidence That Mutant PfCRT Facilitates the Transmission to Mosquitoes of Chloroquine-Treated Plasmodium Gametocytes

Resistance of the human malarial parasite Plasmodium falciparum to the antimalarial drug chloroquine has rapidly spread from several independent origins and is now widely prevalent throughout the majority of malaria-endemic areas. Field studies have suggested that chloroquine-resistant strains might be more infective to mosquito vectors. To test the hypothesis that the primary chloroquine resistance determinant, mutations in PfCRT, facilitates parasite transmission under drug pressure, we have introduced a mutant or wild-type pfcrt allele into the rodent model malarial parasite Plasmodium berghei. Our results show that mutant PfCRT from the chloroquine-resistant 7G8 strain has no effect on asexual blood stage chloroquine susceptibility in vivo or ex vivo but confers a significant selective advantage in competitive mosquito infections in the presence of this drug, by protecting immature gametocytes from its lethal action. Enhanced infectivity to mosquitoes may have been a key factor driving the worldwide spread of mutant pfcrt.
Shear Stress Regulates Endothelial Nitric-oxide Synthase Promoter Activity through Nuclear Factor κB Binding

We have previously demonstrated that shear stress increases transcription of the endothelial nitric-oxide synthase (eNOS) by a pathway involving activation of the tyrosine kinase c-Src and extracellular signal-related kinase 1/2 (ERK1/2). In the present study sought to determine the events downstream of this pathway. Shear stress activated a human eNOS promoter chloramphenicol acetyl-CoA transferase chimeric construct in a time-dependent fashion, and this could be prevented by inhibition of the c-Src and MEK1/2. Studies using electromobility shift assays, promoter deletions, and promoter mutations revealed that shear activation of the eNOS promoter was due to binding of nuclear factor κB subunits p50 and p65 to a GAGACC sequence –990 to –984 base pairs upstream of the eNOS transcription start site. Shear induced nuclear translocation of p50 and p65, and activation of the eNOS promoter by shear could be prevented by co-transfection with a dominant negative I kappa Bα. Exposure of endothelial cells to shear resulted in Iκ kinase phosphorylation, and this was blocked by the MEK1/2 inhibitor PD98059 and the cSrc inhibitor PP1, suggesting these signaling molecules are upstream of NFκB activation. These experiments indicate that shear stress increases eNOS transcription by NFκB activation and p50/p65 binding to a GAGACC sequence present of the human eNOS promoter. While NFκB activation is generally viewed as a proinflammatory stimulus, the current data indicate that its transient activation by shear may increase expression of eNOS, which via production of nitric oxide could convey anti-inflammatory and anti-atherosclerotic properties.
Management of the difficult airway.

Abstract Airway management skills are critical to patient care in many settings. Patients with a difficult airway present unique challenges and considerations, and clinicians should assess for this condition by obtaining a thorough history and physical examination. Familiarity with difficult airway management guidelines, algorithms, tools, and techniques is essential to formulating a safe and effective plan for intubation as well as extubation. This article focuses on airway evaluation, identification, planning, extubation, and care of the patient with a difficult airway.
Stochastic Analysis of Flow in Heterogeneous Porous Media

It is becoming widely recognized that natural earth materials are rather heterogeneous in terms of their hydrologic properties. Figure 1 shows observations of permeability and porosity in a sandstone aquifer in Illinois. These data are based on laboratory analysis of cores collected from deep boreholes in the Mt. Simon aquifer in central Illinois. The variation of permeability is seen to be rather large; the values range over four orders of magnitude. Porosity on the other hand shows a somewhat smaller degree of variability but still a significant percentagewise change. Figure 2 is the second example of the variability of permeability in earth materials. These data show observed infiltration rates of surface soils along a transect some 700 m long in an irrigated area near Socorro, New Mexico. Here the saturated hydraulic conductivity is seen to vary over two orders of magnitude. The observations in Figure 1 and 2 also illustrate that the variation of hydraulic conductivity or permeability is not completely disordered in space. There is some spatial structure which should be taken into account when considering the effects of such heterogeneity. Many other observations from different geologic environments show similar kinds of natural variability of permeability and other properties.
SB 1070: Testing the “Frustration” Hypothesis

Arizona’s Support Our Law Enforcement and Safe Neighborhoods Act, popularly known as SB 1070, is the first state law to directly challenge the federal government’s claim of plenary power over enforcement of its immigration law. Arizona’s law is justifiably famous (or notorious) for that accomplishment. But every milestone has its history. This chapter is about that history, specifically the history of Arizona’s efforts to inform the federal government of its concerns as a border state coping with unauthorized immigration.
Seasonal and static Gravity Field of Mars from MGS, Mars Odyssey and MRO Radio Science

Abstract We present a spherical harmonic solution of the static gravity field of Mars to degree and order 120, GMM-3, that has been calculated using the Deep Space Network tracking data of the NASA Mars missions, Mars Global Surveyor (MGS), Mars Odyssey (ODY), and the Mars Reconnaissance Orbiter (MRO). We have also jointly determined spherical harmonic solutions for the static and time-variable gravity field of Mars, and the Mars k 2 Love numbers, exclusive of the gravity contribution of the atmosphere. Consequently, the retrieved time-varying gravity coefficients and the Love number k 2 solely yield seasonal variations in the mass of the polar caps and the solid tides of Mars, respectively. We obtain a Mars Love number k 2 of 0.1697 ± 0.0027 (3- σ ). The inclusion of MRO tracking data results in improved seasonal gravity field coefficients C 30 and, for the first time, C 50 . Refinements of the atmospheric model in our orbit determination program have allowed us to monitor the odd zonal harmonic C 30 for ∼1.5 solar cycles (16 years). This gravity model shows improved correlations with MOLA topography up to 15% larger at higher harmonics ( l = 60–80) than previous solutions.
A Dynamic Network Measure of Technological Change

This article outlines a network approach to the study of technological change. We propose that new inventions reshape networks of interlinked technologies by shifting inventors’ attention to or away from the knowledge on which those inventions build. Using this approach, we develop novel indexes of the extent to which a new invention consolidates or destabilizes existing technology streams. We apply these indexes in analyses of university research commercialization and find that, although federal research funding pushes campuses to create inventions that are more destabilizing, deeper commercial ties lead them to produce technologies that consolidate the status quo. By quantifying the effects that new technologies have on their predecessors, the indexes we propose allow patent-based studies of innovation to capture conceptually important phenomena that are not detectable with established measures. The measurement approach presented here offers empirical insights that support theoretical development in stu...
Integration by Parts for Stieltjes Integrals

(1960). Integration by Parts for Stieltjes Integrals. The American Mathematical Monthly: Vol. 67, No. 5, pp. 419-423.
Complete Right Bundle-Branch Block

Complete right bundle-branch block is characterized electrocardiographically by three identifying patterns. The typical vectorcardiographic and electrocardiographic features and some of the possible variations in right bundle-branch block are discussed.
Distribution Characteristics and Models of Vehicle Specific Power on Urban Expressways

The development of new fuel consumption and emission models creates the need to characterize traffic conditions by using the Vehicle Specific Power(VSP) distribution.However,in the existing transportation engineering,there has been the lack of knowledge of relationships between the VSP distribution and the commonly used traffic parameters,and the lack of models to develop the VSP distribution from traffic parameters.In order to examine how traffic conditions impact the VSP distributions,this study uses large samples of floating car data collected from the expressways in Beijing to associate the VSP distributions with various average travel speeds.After a comprehensive analysis,regular patterns are found between the VSP distribution and the average travel speed.Specifically,when the average travel speed is higher than 20 km/h,the VSP distribution comes close to a normal distribution.The mean of the VSP distribution is the VSP value when cruising at the average travel speed,and the standard deviation could be expressed as a power function of the average travel speed.Based on these findings,a mathematical model for developing the VSP distributions is then derived by using the average travel speed.Finally,a comparative analysis between the estimated and actual fuel consumption demonstrates that the VSP distributions developed by the proposed model are applicable for fuel consumptions estimations.This study indicates a possibility of developing VSP distributions mathematically for different traffic conditions,which can be integrated efficiently with traffic models or data for the real-time estimation of fuel consumption and emissions.
Roman life expectancy: Ulpian's evidence.

DEMOGRAPHY studies human populations through statistical methods; it primarily measures size and the increase or reduction in numbers of people.' Historical demography provides one method for studying societies of the past. A human population, at any given period in its history, possesses in theory a characteristic demographic structure which can be approximately described through statistics, provided only that a historian has sufficient reliable data to construct such a model. The required data fall into three classes: first, the functions of mortality indicating how many males and females of varying ages will pass out of the population through death; second, the functions of fertility indicating how many new members will be born into the population; and third, the functions of migration indicating the transfer of members into and out of the population. Birth, death, and the movement of peoples across the globe these are universal and profoundly affecting themes, but demographers since the time of Thomas Malthus have stared piteously at such statistics for what they tell about some of the harsh realities societies must confront if they are to endure and even to prosper.
Interactions between individual and perceived environmental factors on Latinas' physical activity.

Background Latinas have disproportionately low levels of physical activity (PA) and the ecological correlates of their PA remain unclear. This study aims to test interactions between individual and environmental factors on Latinas' PA. Methods We analyzed baseline data from 436 Latinas participating in a PA randomized controlled trial in San Diego, CA [Fe en Accion/Faith in Action]. Measures included demographics, perceived environment, PA and anthropometrics. Mixed effects models examined interactions between individual and environmental factors on self-reported leisure-time and transportation, and accelerometer-assessed PA. Results Significant positive associations were found between neighborhood aesthetics and leisure-time moderate-to-vigorous PA (MVPA) and between having destinations within walking distance from home and transportation PA (P < 0.05). We found significant interactions of income with aesthetics and sidewalk maintenance as well as between weight status and safety from crime. Favorable aesthetics was related to more leisure-time MVPA only among lower income women (odds ratio (OR) = 1.57; 95% confidence interval (CI): 1.18, 2.08); however, higher income women reporting better sidewalk maintenance reported more leisure-time MVPA (OR = 1.51; 95% CI: 1.06, 2.15). Higher perceived safety from crime was positively related to transportation PA only among overweight/obese women. Conclusions Subgroup differences should be considered when developing interventions targeting the neighborhood environment to promote Latinas' PA.
The unquiet homefront

Catholic women and children experienced both positive and negative changes in their traditional roles during the war. Massive historiographical shifts in social and cultural histories of the First World War have demonstrated women's fundamental importance during the conflict. The process of total war was already dramatically reordering pre-war conceptions of gender roles, creating a fundamental tension between traditional images and new expectations for both men and women in Central Europe. The war saw attempts both to challenge gender roles and to restore order. Even in progressive nations like Weimar Germany and the United States where women gained the right to vote comparatively early as a direct result of the war, there was often a wide gap between the rhetoric and the practical reality of women's roles in the new social orders. As Erika Kuhlman has argued in a path-breaking transnational study, new public focus on human rights and equality did not correct unequal imbalances in gender relations. Through discourses on motherhood and female virtue, women were active agents in a process whereby “nations reinforced traditional, patriarchal relationships among men and women (in which masculinity remained privileged and femininity continued to be valued) by shunting women back to traditional female employment and honoring women as mothers (and fallen soldiers as heroes).” While new generations of scholarship have blurred boundaries between home front and battlefront, women's religious experience of the war, especially in defeated Central Europe, remains a comparatively unexplored aspect of the cultural history of the war. The historiography of gender in the Habsburg monarchy during the war, long neglected in comparison to other combatant states, has seen recent advances. As Christa Hoammerle has recently argued, multifaceted conceptions of gender reflect the all-encompassing social relations of the drive toward total war, thus illuminating changing identities during periods of immense upheaval and reform.
Authority and Discretion

Discretion is a phenomenon of paramount importance to constitutional government, especially the democratic one, as it is indeed to all law. John Locke discussed the problem of discretion when considering the ‘prerogative’. ‘This power to act according to discretion for the public good, without the prescription of the law and sometimes even against it, is that which is called the prerogative,’ he stated in the Second Essay.1 He also asserted that ‘the good of society requires that several things should be left to the discretion of him that has the executive power’.2 Much later, Dicey defined authoritatively the prerogative in Britain as ‘the residue of discretionary or arbitrary authority which at any time is legally left in the hands of the crown’.3 While it proved difficult for the king to maintain such a prerogative against a prime minister backed by a compact parliamentary majority, it remains in the background to be used in an emergency. It will be recalled that it provided one of the main bones of contention between James i and the parliament, and more particularly in his quarrels with Sir Edward Coke representing the judiciary. It was an ancient institution in Britain, anticipating in some ways the concept of sovereignty as developed in continental Europe.
Predicting Molecular Crystal Properties from First Principles: Finite-Temperature Thermochemistry to NMR Crystallography

ConspectusMolecular crystals occur widely in pharmaceuticals, foods, explosives, organic semiconductors, and many other applications. Thanks to substantial progress in electronic structure modeling of molecular crystals, attention is now shifting from basic crystal structure prediction and lattice energy modeling toward the accurate prediction of experimentally observable properties at finite temperatures and pressures. This Account discusses how fragment-based electronic structure methods can be used to model a variety of experimentally relevant molecular crystal properties. First, it describes the coupling of fragment electronic structure models with quasi-harmonic techniques for modeling the thermal expansion of molecular crystals, and what effects this expansion has on thermochemical and mechanical properties.Excellent agreement with experiment is demonstrated for the molar volume, sublimation enthalpy, entropy, and free energy, and the bulk modulus of phase I carbon dioxide when large basis second-or...
Primary spectrum and composition with IceCube/IceTop

Abstract IceCube, with its surface array IceTop, detects three different components of extensive air showers: the total signal at the surface, GeV muons in the periphery of the showers and TeV muons in the deep array of IceCube. The spectrum is measured with high resolution from the knee to the ankle with IceTop. Composition and spectrum are extracted from events seen in coincidence by the surface array and the deep array of IceCube. The muon lateral distribution at the surface is obtained from the data and used to provide a measurement of the muon density at 600 meters from the shower core up to 30 PeV. Results are compared to measurements from other experiments to obtain an overview of the spectrum and composition over an extended range of energy. Consistency of the surface muon measurements with hadronic interaction models and with measurements at higher energy is discussed.
Hemibonding between Water Cation and Water.

The hemibonding interaction in the water dimer cation is studied using coupled cluster electronic structure methods. The hemibonded dimer cation geometry is a local minimum structure characterized by the two participating monomers having both a very short separation and a near parallel relative orientation. It is shown that the vertically ionized dimer at its optimum neutral geometry can convert to the hemibonded dimer cation structure with essentially no energetic hindrance. Direct conversion to the hemibonded structure is therefore an energetically facile alternative to the minimum energy path that connects the vertically ionized neutral water dimer to the global minimum proton-transferred structure. A substantial barrier must be surmounted to convert the hemibonded dimer cation to the proton-transferred structure. The optical absorption spectrum of the hemibonded dimer cation is characterized by three excited near-UV states, two of which have very large oscillator strengths. Relative resonance Raman in...
Photic reinforcement as a function of optimal level of stimulation

The concept of an optimal level of stimulation as an explanation for the reinforcing effects of weak light onset was explored in four experiments. Experiment I employed 4 groups of 8 rats each and demonstrated that the Ss would respond at higher levels to obtain weak illumination than to terminate weak illumination. Experiment II involved a group of 8 rats subject to the same level of illumination. By choosing between appropriate levers the animals could either put the test cubicle in darkness for 2 sec. or increase the illumination level for 2 sec. All Ss showed a preference for increasing the illumination. Experiment III introduced a “novelty effect” in that the position of the illumination source changed in response to lever pressing. The Ss’ behavior indicated that this effect was not reinforcing. Experiment IV was designed to study the influence of increased drive on the reinforcing effect of weak light. Results were inconclusive although the trend was in the predicted direction. The ad lib group tended to make more responses to the lever activating the light source than did the deprivation (high drive) group. Results of the four experiments were sufficiently supportive of the hypothesis to suggest that further investigation would be fruitful.
Flow cytometry crossmatching for solid organ transplantation.

Publisher Summary This chapter discusses the flow cytometric crossmatching (FCXM) for solid organ transplantation. The FCXM uses indirect immunofluorescence to detect human alloantibody that has bound to target lymphocytes. Although immunoglobulin G (IgG) class antibodies appear to be most associated with early rejection and accelerated graft loss, the detection of other immunoglobulin isotypes may also be informative. In contrast to the complement-dependent lymphocytotoxicity (CDC), the FCXM can easily discriminate between the isotypes and subclasses of immunoglobulins. Additionally, due to the differential expression and distribution of human leukocyte antigen (HLA) molecules, it is beneficial to discriminate between T cell and B cell reactivities. Interpretation of the FCXM is done by directly comparing the fluorescence intensity of the test cell population treated with the patient's serum to the fluorescence intensity of the same cell population treated with a known negative control serum. This interpretation is in direct contrast to the subjective visual assessment used in the CDC technique. Hence, the FCXM is more objective and has the additional potential to quantitatively assess bound alloantibody.
The Conspicuity Benefits of Dynamic and Static Bicycle Taillights at Night

A total of 729 bicyclist fatalities and approximately 50,000 bicyclist injuries were reported in the United States in 2014. Of the bicyclist fatalities, roughly 50% involved crashes that occurred at civil twilight or after dark (National Center for Statistics and Analysis, 2016). Also regarding bicyclist fatalities, Hutchinson and Lindsay (2009) found that the majority of bicyclists’ deaths resulted from collisions where the cyclists were hit from behind, especially at night, after investigating Australian bicycle/motor vehicle crashes. In addition, Bil, Bilovaa, & Muller, (2010) found that the highest percentages of cyclists’ fatalities occurred on straight road segments (23%) and curved road segments (16%) after analyzing patterns found in 5428 cyclists/motor vehicle collisions in the Czech Republic.Bicycle taillights have been found to enhance nighttime conspicuity (for a review, see Kwan & Mapstone, 2004). However, there are several gaps in the relevant literature, such as whether there is an optimal ...
Characteristics of psychiatric emergency department use among privately insured adolescents with autism spectrum disorder

This study examined differences in the rates of psychiatric-related emergency department visits among adolescents with autism spectrum disorder, adolescents with attention deficit hyperactivity dis...
Implementation of an abdominal closure bundle to reduce surgical site infection in patients on a gynecologic oncology service undergoing exploratory laparotomy.

Abstract Objective Surgical site infections (SSI) are associated with increased morbidity, mortality, and healthcare costs. This study investigated whether implementation of an abdominal closure bundle reduces surgical site infection rates. We aimed to identify sub-populations that would benefit the most from this intervention. Methods We conducted a retrospective cohort study of all patients that underwent exploratory laparotomy by a Gynecologic Oncologist from January 1, 2011 to April 1, 2017. The abdominal closure bundle was implemented on May 6, 2014. SSI rates were assessed overall and within subgroups. Results 875 patients were included in the analysis. Overall, SSI rate was reduced, albeit not significantly, from 48/471 (10.2%) to 32/404 (7.9%) (p = 0.148) with implementation of the closing bundle. In patients that underwent a tumor debulking procedure, SSI was noted in 36/277 (13.0%) in the pre-bundle group and 14/208 (6.7%) in the post-bundle cohort (p = 0.017). In patients with malignant pathology, the pre-bundle cohort had an SSI rate of 38/282 (13.5%), which reduced to 18/215 (8.4%) in the post-bundle group (p = 0.049). In patients with FIGO stage III or IV disease, the SSI rate was reduced from 21/114 (18.4%) to 8/87 (8.4%) with implantation of the closure bundle (p = 0.028). In patients with intra-operative ascites, SSI rate decreased from 19/119 (15.9%) pre-bundle to 4/104 (3.8%) in the post-bundle group (p = 0.002). Conclusions Implementation of an abdominal closure bundle was not associated with a significant reduction in overall SSI rate. However, multiple subpopulations associated with advanced gynecologic cancer benefited from this intervention.
Targeted Therapy for Patients With Metastatic Non–Small Cell Lung Cancer

Molecular testing is recommended for initial diagnosis in patients with non-small cell lung cancer (NSCLC), according to the updated NCCN Guidelines, because targeted therapies are available that can improve patient outcomes. Targeted therapies are currently approved for EGFR mutations, ALK and ROS1 gene rearrangements, and BRAF mutations, with the list of emerging "actionable" targets growing. The 2018 NCCN Guidelines for NSCLC incorporate new therapies, including the EGFR tyrosine kinase inhibitor osimertinib and the ALK inhibitor alectinib, as first-line preferences.
The Scrapie Agent In Vitro

Precise biochemical characterization of the scrapie agent has not been attained. This is thought by many investigators to be due to the agent’s tenacious association with membranes (Hunter et al. 1968; Hunter 1979) as well as other characteristics considered unusual for conventional viruses (Alper 1985; Bellinger-Kawahara et al. 1987; Dees et al. 1985; Gibbons and Hunter 1967; Kasper et al. 1982; Rohwer 1984; Brown et al. 1982). As a result, scientists have sought tissue cultures supporting scrapie replication as an alternate source of scrapie agent. It has been reasoned that such cultures would be free of at least some of the tissue-derived by-products encountered in animal tissue sources and might provide the agent in a substrate that would allow determination of its structure. In addition, infected cultures could provide a system whereby the biology of agent-cell interactions could be studied in vitro. Such cultures could also conceivably lead to the development of an in vitro system for rapid agent titration.
Unusual Presentations of Schizophrenia

Through the years, the diagnostic criteria for schizophrenia have undergone many revisions, with the syndrome being classified in myriad ways. A listing of some proposed subtypes of schizophrenia illustrates this diversity: hebephrenic, catatonic, simple, paranoid, chronic undifferentiated, latent, process, reactive, schizoaffective, atypical, affect-laden paraphrenia, cataphasia, schizophasia, good prognosis, poor prognosis, systematic, nonsystematic, and oneirophrenia. At the other extreme, one is also confronted with a group of psychiatrists who deny the very existence of the entity called “schizophrenia” (Szasz, 1974).
Effects of Aggressive Versus Conventional Lipid-Lowering Therapy by Simvastatin on Human Atherosclerotic Lesions: A Prospective, Randomized, Double-Blind Trial With High-Resolution Magnetic Resonance Imaging

Objectives This study sought to compare the effects of aggressive and conventional lipid lowering by two different dosages of the same statin on early human atherosclerotic lesions using serial noninvasive magnetic resonance imaging (MRI). Background Regression of atherosclerotic lesions by lipid-lowering therapy has been reported. Methods Using a double-blind design, newly diagnosed hypercholesterolemic patients (n = 51) with asymptomatic aortic and/or carotid atherosclerotic plaques were randomized to 20 mg/day (n = 29) or 80 mg/day (n = 22) simvastatin. Mean follow-up was 18.1 months. A total of 93 aortic and 57 carotid plaques were detected and sequentially followed up by MRI every six months after lipid-lowering initiation. The primary MRI end point was change in vessel wall area (VWA) as a surrogate for atherosclerotic burden. Results Both statin doses reduced significantly total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) versus baseline (p Conclusions Effective and protracted lipid-lowering therapy with simvastatin is associated with a significant regression of atherosclerotic lesions. No difference in vessel wall changes was seen between high and conventional doses of simvastatin. Changes in vessel wall parameters are more related to LDL-C reduction rather than to the dose of statin.
Disordered eating behaviors and cardiometabolic risk among young adults with overweight or obesity

Objective To determine if unhealthy weight control behaviors or binge-eating behaviors among young adults with overweight/obesity are associated with body mass index (BMI) change and cardiometabolic risk at 7-year follow-up. Methods We used longitudinal cohort data from 5,552 young adults with overweight/obesity at baseline (18-24 years) with 7-year follow-up (24-32 years) from the National Longitudinal Study of Adolescent to Adult Health. Baseline predictors were: (a) unhealthy weight control behaviors such as vomiting, fasting, skipping meals, or laxative/diuretic use to lose weight; or (b) binge-eating behaviors. Participants reporting either unhealthy weight control behaviors or binge-eating behaviors were considered to engage in any disordered eating behavior (DEB). Outcomes at 7-year follow-up were BMI change, incident diabetes, incident hypertension, and incident hyperlipidemia. Results Young adults with overweight/obesity reporting unhealthy weight control behaviors at baseline had higher BMI and weight at 7-year follow-up than those without unhealthy weight control behaviors. In regression models adjusting for baseline BMI, race/ethnicity, age, and education, unhealthy weight control behaviors were associated with greater change in BMI in both sexes and binge-eating behavior at baseline was associated with greater odds of incident hyperlipidemia (odds ratio 1.90, 95% CI 1.29-2.79) at 7-year follow-up in males. Conclusions The higher risk for increased BMI (in both males and females) and incident hyperlipidemia (in males) over time in young adults with overweight/obesity who engage in DEBs underscores the need to screen for DEBs in this population and provide referrals and tailored interventions as appropriate.
Efectos del contexto de inmersión en la competencia sociolingüística de EL2: La adquisición del laísmo madrileño

Although abundant research has been conducted on the impact of immersion in Spanish second language learners over the past two decades, questions pertaining to the degree of their exposure to the local community and the acquisition of patterns of language variation common to a particular speech community remain unanswered. This article presents the quantitative results of a study of the acquisition of variable structures of language, specifically the phenomenon of laismo, by forty (N=40) Spanish learners (experimental groups) participating in two types of immersion programs (traditional academic and service-learning programs) for four months in Madrid (Spain). The oral production of these participants is compared to the performance of thirty (N=30) native speakers (control group). The statistical analysis reveal that a greater contact with the target speech community considerably promotes the incorporation of non-conventional forms into the sociolinguistic competence. This work contributes to better understand the acquisition of dialectal variation and to provide new knowledge about the linguistic impact of a service-learning program during an international academic experience.
Residual native left ventricular function optimization using quantitative 3D echocardiographic assessment of rotational mechanics in patients with left ventricular assist devices.

Preservation of native left ventricular (LV) function in patients supported with LV assist device (LVAD) may be beneficial to attain optimal hemodynamics and enhance potential recovery. Currently, LVAD speed optimization is based on hemodynamic parameters, without considering residual native LV function. We hypothesized that alternatively, LV rotational mechanics can be quantified by 3D echocardiography (3DE), and may help preserve native LV function while optimizing LVAD speed. The goal of this study was to test the feasibility of quantifying the effects of LVAD implantation on LV rotational mechanics and to determine whether conventional speed optimization maximally preserves native LV function. We studied 55 patients with LVADs, who underwent 3DE imaging and quantitative analysis of LV twist. Thirty patients were studied before and after LVAD implantation. The remaining 25 patients were studied during hemodynamic ramp studies. The pump speed at which LV twist was maximal was compared with the hemodynamics-based optimal speed. LV twist decreased following LVAD implantation from 4.2 ± 2.7 to 2.3 ± 1.9° (P < 0.01), reflecting the constricting effects on native function. With lower pump speeds, no significant changes were noted in LV twist, which peaked at a higher speed. In 11/25 (44%) patients, the conventional hemodynamic/2DE methodology and 3DE assessment of maximal residual function did not indicate the same optimal conditions, suggesting that a higher pump speed would have better preserved native function. In conclusion, quantitative 3DE analysis of LV rotational mechanics provides information, which together with hemodynamics may help select optimal pump speed, while maximally preserving native LV function.
Terraced and Smooth Gradient Polymer Brushes via a Polymer Single‐Crystal Assisted Grafting‐To Method

Gradient polymer brushes provide a spatial gradient change in molecular characteristics of the brush, and such a change can be utilized to study structure-property relationships in a combinatorial fashion. In this study, a bottom-up method was used to synthesize gradient polymer brushes with a predesigned and precisely controlled grafting density gradient and brush pattern. A polymer single-crystal assisted grafting-to (PSCAGT) method was employed where end-functionalized polymers were grown into two-dimensional polymer single crystals. The latter were chemically coupled to a solid substrate to form well-defined polymer brushes. To tune the grafting density, end-dissimilar polymers were used to co-crystallize into one single crystal. Programmed single-crystal growth was introduced to synthesize brushes with two different gradient architectures, that is, terraced and smooth gradient with pyramid patterns. This work demonstrates that the PSCAGT method offers a unique means to tune polymer brush nanostructure.
The Tasks and Contexts of Understanding in Dilthey and Seebohm

One of the main tasks of Thomas Seebohm’s History as a Science and the System of the Sciences is to properly characterize the human sciences and relate them to the natural sciences. Since one of his points of reference is the way Wilhelm Dilthey distinguishes those two kinds of sciences, I will show that Seebohm goes too far when he claims that Dilthey excludes explanative laws from the human sciences. That Dilthey merely delimits the scope of explanations to special contexts delineated by understanding will become clear when I expand on the interesting ways that Seebohm modifies Dilthey’s distinction between elementary and higher understanding. Seebohm claims that if we define history as a fact-based science rooted in the natural attitude of the lifeworld then elementary understanding can already provide causal explanations. Because Dilthey has a more encompassing conception of history he doubts that elementary understanding can already explain its complexities. Only delimited socio-cultural historical contexts defined by higher understanding can set the stage for explanations.
11.10 – Neuroimmunology☆

The nervous and immune systems are known to communicate with each other to influence each other’s function. A role for such a bidirectional communication in helping to maintain homeostasis is becoming well established. However, any type of miscommunication between the two systems and its relevance in mediating the development and/or progression of a disease state remains inconclusive and understudied. The latter limitation is complicated further when one considers that the nervous and immune systems are often studied as separate disciplines, which contributes much to an understanding of how each system functions autonomously, but not to an understanding of how a communication between the two systems might be relevant clinically. This article will review the evidence supporting the existence of a functional line of communication between the sympathetic nervous system and the immune system, with a particular emphasis on the role of the neurotransmitter norepinephrine and immune cell-derived cytokines in modulating immune and nervous system function, respectively. This article will also discuss some possibilities as to how a toxicant might target this neuroimmune communication to potentially affect immune responsiveness, contribute to a disruption in homeostasis, and subsequently contribute to the possible development of clinical disease, without ever directly affecting any cells of the immune system itself.
The maintenance of adult peripheral adult nerve and microvascular networks in the rat mesentery culture model

Abstract Background Neurovascular patterning is an emerging area of microvascular research. While overlapping molecular signals highlight links between angiogenesis and neurogenesis, advancing our understanding is limited by a lack of in vitro models containing both systems. One potential model is the rat mesentery culture model, which our laboratory has recently introduced as an ex vivo tool to investigate cellular dynamics during angiogenesis in a microvascular network scenario. The objective of this study was to demonstrate the use of the rat mesentery culture model as an ex vivo platform for maintaining the spatiotemporal relationship between blood vessels and peripheral nerves during angiogenesis in adult microvascular networks. Methods Adult male Wistar rat mesenteric tissue windows were harvested, rinsed in sterile DPBS and medium and then cultured per group: 1) MEM alone and 2) NBM with NGF and 20 % FBS (nerve culture medium). On day 3 post culture tissues were labeled for endothelial (PECAM) and neural (class III β-tubulin, NG2, tyrosine hydroxylase, CGRP) markers. Results In MEM alone tissues nerve segment degeneration was supported by discontinuous nerve or absence of nerve marker labeling. Nerve presence at the arteriole level and capillary level was maintained for the nerve culture medium group compared to day 0, non-cultured control group (unstimulated). Comparison with existing methods and conclusions The results support the use of specific medium types to maintain nerve presence across cultured microvascular networks and implicates the rat mesentery culture model as a novel ex vivo tool for investigating neurovascular patterning in adult tissues.
Sclerostin depletion induces inflammation in the bone marrow of mice

ABSTRACT Romosozumab, a humanized monoclonal antibody specific for sclerostin, has been approved for treatment of post-menopausal women with osteoporosis at high risk for fracture. In several Phase III clinical trials, romosozumab decreased the risk of vertebral fractures up to 73% and increased total hip area bone mineral density by 3.2%. Previous work in 12 to 15-week-old sclerostin-knockout (Sost-/-) mice indicated that changes in immune cell development occur in the bone marrow (BM), which could be a possible side effect to follow in human patients. Our overall goal was to define the mechanisms that guide behavior of long-term hematopoietic stem cells (LT-HSCs) after exposure to an irregular BM microenvironment. SOST plays an important role in maintaining bone homeostasis, as demonstrated by the increased ratio of bone volume to total volume observed in Sost-/- mice. Here, we examined the effects of short-term sclerostin depletion in the BM on hematopoiesis in young (8 week-old) mice receiving sclerostin-antibody (Scl-Ab) treatment for 6 weeks, and the effects of long-term Sost-deficiency on wild-type (WT) LT-HSCs transplanted into older (16-22 week-old) cohorts of Sost-/- mice. Our analyses revealed an increased frequency of granulocytes and decreased frequency of lymphocytes in the BM of Scl-Ab treated mice and WT→Sost-/- hematopoietic chimeras, indicating myeloid-biased differentiation in Sost-deficient BM microenvironments. This myeloid bias extended to extramedullary hematopoiesis in the spleen and was correlated with an increase in inflammatory cytokines TNFα, IL-1α and MCP-1 in the serum of the Sost-/- BM. Additionally, we observed alterations in erythrocyte differentiation in the BM and spleen of Sost-/- mice. Taken together, our current study indicates novel roles for Sost in the regulation of myelopoiesis and control of inflammation in the BM. Our animal studies strongly recommend tracking of hematopoietic function in patients treated with romosozumab.
Developmental trajectory of subtle motor signs in attention-deficit/hyperactivity disorder: A longitudinal study from childhood to adolescence.

This study examined the developmental trajectory of neurodevelopmental motor signs among boys and girls with attention-deficit/hyperactivity disorder (ADHD) and typically-developing (TD) children. ...