cssi/SciSciGPT-SciSciNet huggingface dataset:
Disease characteristics and clinical outcomes in patients aged less than 40 with chronic lymphocytic leukemia.

Abstract Outcomes in very young CLL patients (age ≤40) are not well characterized. We compared 71 consecutive patients aged ≤40 with 142 “older” matched patients >40 from our institution and used SEER database as an independent comparison group. Patients in the two age groups were diagnosed at similar Rai stage. At diagnosis, very young patients had a similar rate of adverse cytogenetics, IGHV mutation and ZAP70 expression and had lower beta-2-microglobulin and a lower incidence of second malignancies. There was no difference between the groups with respect to incidence of autoimmune manifestations, family history of lymphoma, time to initiation of CLL therapy, response to therapy, or Richter’s transformation. Variables including un-mutated IGHV and elevated LDH were associated with shorter times to treatment initiation in both groups. A trend to longer 5-year survival for very young patients in our institution (93% v 82%, p = 0.082) was validated by SEER data.
Associations Between Secondhand Tobacco Smoke Exposure and Nicotine Dependence and Smoking Cessation Attempts Among Adult Tobacco Users With a Psychiatric Disorder.

Introduction:Secondhand smoke exposure (SHSe) is predictive of greater nicotine dependence (ND) and poor smoking cessation (SC) outcomes. SHSe and its impact on ND and SC attempts in people with ps...
Abstract 3630: Deep and durable response with dual anti-CTLA-4 and PD-1 blockade in mismatch repair (MMR) proficient endometrial cancer

Immune checkpoint inhibitors have shown promising efficacy in multiple cancer types, but have yet to be extensively validated in endometrial cancer. However, the recent FDA approval of PD-1 inhibitors for mismatch repair (MMR) deficient tumors has extended use of these treatments to all cancer types. PD-L1 positivity in tumor tissue has also been shown to predict susceptibility to immunotherapy and has been used to guide use of these treatments. Despite these advances, the response to immunotherapy in endometrial cancer remains poorly understood. Here, we describe the case of a patient with MMR proficient, PD-L1-negative stage IV endometrial cancer with positive response to combination PD-1 and CTLA-4 inhibition. The patient initially presented with ascites and elevated tumor markers, and cytology from peritoneal fluid showed endometrial adenocarcinoma with squamous and mucinous differentiation and clear cell features. She underwent surgical debulking with both neoadjuvant and adjuvant cycles of docetaxel and carboplatin, but unfortunately had progressive metastatic disease within 4 months. The patient declined further chemotherapeutic agents, and thus was instead trialed on combination nivolumab and ipilimumab despite her cancer exhibiting MMR proficiency and negative PD-L1. She demonstrated deep and durable on-going partial response to this treatment that has persisted still after 10 months. Her course has notably been complicated by hypophysitis that manifested after 5 months of treatment as worsening fatigue, but she has been able to continue with her treatment regimen. This case indicates the potential existence of an endometrial cancer subtype that is sensitive to immune checkpoint blockade, but based on mechanisms other than those driven by MMR deficiency or PD-L1 positivity. Improved understanding of immunotherapy in advanced endometrial cancer is clearly needed and offers the potential to significantly enhance patient outcomes. Citation Format: Michael S. Oh, Young Chae. Deep and durable response with dual anti-CTLA-4 and PD-1 blockade in mismatch repair (MMR) proficient endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3630.
Variations of contrained domain functionals associated with boundary-value problems

We study variational formulas for maximizers for domain functionalsF(x0, u(x0)), x0∈Ώ, and ∫ΏF(x,u(x))dxover all Lipschitz domains Ώ satisfying the constraint∫Ώg(x) dx=1. Here, u is the solution ofa diffusion equation in Ώ. Functional variations arecomputed using domain variations which preserve the constraint exactly. Weshow that any maximizer solves a moving boundary problem for the diffusionequation. Further, we show that, for problems with symmetry, the optimaldomains Ώ are balls.
Targeting mitochondrial hexokinases increases efficacy of histone deacetylase inhibitors in solid tumor models

Abstract Hexokinase 1 and 2 have been shown to inhibit Bak- and Bax-mediated apoptosis, leading us to combine the histone deacetylase inhibitor romidepsin with clotrimazole or bifonazole, two compounds that reportedly decrease mitochondrial localization of hexokinases. Cancer cell lines derived from breast, kidney, lung, colon or ovarian cancers were treated with a short-term exposure to 25 ng/ml romidepsin combined with either clotrimazole or bifonazole. The combination of romidepsin with 25 µM clotrimazole or bifonazole resulted in increased annexin staining compared to cells treated with any of the drugs alone. Cell death was caspase-mediated, as the pan-caspase inhibitor Q-VD-OPh was found to inhibit apoptosis induced by the combination. A549 lung cancer cells or HCT-116 cells deficient in Bak and Bax were also resistant to apoptosis with the combination implicating the intrinsic apoptotic pathway. We found that a 24 h treatment with clotrimazole or bifonazole decreased total hexokinase 2 expression, resulting in a 76% or 60% decrease, respectively, of mitochondrial expression of hexokinase 2. Mitochondrial hexokinase 1 levels increased 2-fold or less. Our work suggests that the combination of a short-term romidepsin treatment with bifonazole or clotrimazole leads to increased apoptosis, most likely due to decreased mitochondrial expression of hexokinase 2.
Edroid: A Mutation Tool for Android Apps

Android applications have experienced an outstanding growth in recent years with a projected figure of 378 billion in the number of application downloads by 2020. As a result, verification and validation of Android apps and their graphical user interface through testing is crucial for quality assurance. One way to assess quality assurance is through the use of mutation testing. Mutation testing modifies the code of the System Under Test in small ways in order to produce faulty versions of the program called mutants and compare them to the original version. However, the cost of mutation testing can be expensive and time consuming. We propose a graphical user-friendly Android mutation tool called Edroid whose primary purpose is to mutate Android's main components such as activities, services, content providers and broadcast receivers using the source code of XML files. We introduce fourteen Android mutation operators, where ten of them are new, that are derived from operators used in different fields such as mutation testing for Graphical User Interface and XML schema. We evaluate Edroid on five real world Android applications using testing methodologies such as random testing and black box testing. Results from these experiments demonstrate that Edroid facilitates the generation of mutants. In addition and equally important, the set of proposed mutation operators are effective in revealing errors that improve the quality of a given test suite.
Semiconductor Nanocrystal Colloids

The study of nanometer size semiconductor crystals has been advancing at a rapid pace1,2. Much of the interest in these materials stems form the fact that their physical and chemical properties can be systematically tuned by variation of the size, according to increasingly well established scaling laws. This paper describes colloidal semiconductor nanocrystals belonging to the II-VI and III-V families, and outlines strategies for obtaining electrical access to such dots.
Modeling Approaches Toward Understanding Infectious Disease Transmission

Long-standing neglected diseases continue to challenge our global health infrastructure, and emerging pathogens pose new threats worldwide. To inform prevention and response efforts, mathematical models of infectious disease dynamics are being increasingly applied. Here we explain how models can be developed to enhance our understanding and predictive power over population-level disease trends, by capturing both fundamental aspects of transmission and also the effects of medical and behavioral interventions. We review advances in transdisciplinary approaches of disease modeling and illustrate these advances with applications including community-based initiatives undertaken during the Ebola epidemic in West Africa and age-targeting of influenza vaccination in the USA. We further discuss how modern statistical inference facilitates the incorporation of data from behavioral sciences and epidemiology into models, highlighting how data-driven models can constitute powerful tools to inform and improve public health strategies.
Andean rolling mosses gather on stone pavements: Geoecology of Grimmia longirostris Hook. in a high periglacial páramo

Abstract Rolling mosses of Grimmia longirostris Hook. were studied in Paramo Piedras Blancas, a high Andean area in Venezuela, using a geoecological research framework focused on interactions between geomorphic, ecological, and soil processes. Spatial patterns of mosses were analyzed downslope from granitic outcrops on three slopes at 4445–4480 m elevation. Fragments from epilithic mosses on the apex outcrops were the source of other mosses. Distance of moss transport below rocks was measured at all sites; mosses on the gentlest (≤4°), 34 m-long, slope were censused along a belt transect on 17 contiguous quadrats; density of moss growth forms, stone size, percent of bare-soil cover, and surface soil properties were determined. Surface clast morphology and profile characteristics of a periglacial stone pavement at the slope base were also examined. Mosses on this site included four growth forms: epilithic mosses on outcrops; mobile, rolling moss balls; epilithic mosses on loose clasts; and unattached elongated mosses. Moss balls (density: ≤0.87 mosses/m2) lay on upper-transect plots over bare soils (≤92% cover) disturbed by needle ice. Soils here contained ~43–51% fine grains (≤0.063 mm) and 2.9–5.9% organic matter; this made them exceptionally prone to ice segregation and needle-ice formation. Lower-transect plots showed 78–100% stone cover—cobbles and blocks—but little exposed soil; mosses attached to loose clasts were exceedingly abundant (≤31/m2) on this section. Unattached elongated mosses, often resting along boundaries between adjacent stones, were also common (≤5.5/m2). The basal stone pavement showed a shallow (≤7 cm) rock veneer over a 24 cm-thick profile with exceptionally fine soil—up to 83.2% fine grains, ≤8.6% organic matter. A conceptual developmental model emphasizing the close linkages among the spatial distribution of mosses, patterns of surface clasts, and characteristics of soils and stone pavements is proposed: (i) Stones and mosses are transported downhill by needle ice and other frost agents; moss fragments gradually assume a globular shape, forming rolling moss balls. (ii) When these reach the stones and pavements on the basal slope, they cannot be transported any further, and remain immobile. (iii) Some mosses come to rest along boundaries between stones and develop into unattached elongated mosses or, (iv) they may become gradually attached to cobbles on the stone pavement; clasts with epilithic mosses can continue moving toward the basin floor. (v) Some mosses become fragmented and provide a source of elongated mosses, or remain partially attached to clasts. Stone pavements develop by a combination of rock accumulation following needle-ice transport, rock upheaving and sorting by ground frost, slope runoff, and downward soil illuviation.
Humidity‐insensitive Tissue Oxygen Tension Sensing for Wearable Devices

Quantification of tissue oxygen partial pressure (pO2 ) at the skin surface is crucial for diagnostic applications in burns, reconstructive surgeries, diabetic ulcers, etc. Further, current advances in wearable and communications technologies have widened the use of transcutaneous oxygen monitors (TCOM) for home care or even enhance athletic performance. For TCOM technology to find widespread use, devices must function reliably yet independently of changes in environmental conditions, humidity in particular. To this end, we have explored the incorporation of an oxygen-sensing metalloporphyrin within different host matrix materials of different compositions with the goal of overcoming the humidity sensitivity of previously explored oxygen-sensing materials. We developed a tetraethyl orthosilicate (TEOS)-based, highly breathable, oxygen-sensing metalloporphyrin polymer film which responds to changes in oxygenation independent of humidity.
Teacher Dismissal on Grounds of Immorality: “The Times--They Are A Changin'"

AbstractFifty years ago, John G. Davis published an article on Teacher Dismissal on grounds of immorality and the “new morality” of the 1970s. While much has changed in terms of morality and moral ...
Nonlinear transmission of U.S. monetary policy shocks to international financial markets

Using local projection and event studies, this paper investigates the nonlinear effects of U.S. monetary policy shocks on financial‐asset prices in 10 advanced economies from 1990 to 2014. The international asset prices show evidence of the asymmetric or state‐dependent propagation of U.S. monetary shocks. Moreover, the results indicate that the nature of the nonlinearity in the propagation of the shocks differs across two asset classes, bond yields, and equity prices. Contractionary U.S. monetary policy shocks are quite influential in sovereign bond markets, while their impacts are largely insignificant in stock markets; the opposite is true for expansionary monetary policy shocks. These results are typical across open economies and suggest that U.S. monetary announcements and the subsequent reactions of international risk premiums may play a critical role in international shock propagation.
Diving into the Details: Constructing a Framework of Random Call Components

Random call is a randomized approach to select a student or group of students to share their thinking with the whole class. There are potential costs and benefits of random call in undergraduate courses, yet we lack insight about how this strategy is actually implemented and why instructors choose to use it. We interviewed 12 college biology instructors who use random call in courses with 50 or more students. Qualitative content analysis revealed why these instructors chose to use random call, the specific ways they implemented random call, and the reasoning behind their implementation. Instructors used random call to increase the diversity of voices heard in the classroom and to hold students accountable for working. Random call users showed concern about student anxiety and took specific steps to mitigate it. We break random call down into a series of components, identify the components that our participants considered most critical, and describe the reasoning underlying random call components. This work lays a foundation for future investigations of how specific random call components influence student outcomes, in what contexts, and for which students.
The Electoral Consequences of Roll Call Voting: Health Care and the 2018 Election

For years, Republicans in Congress promised to “repeal and replace” the Affordable Care Act. The results of the 2016 elections put them in position to take action on the seminal domestic policy achievement of outgoing President Barack Obama. Repeal efforts faced many obstacles, including angry constituents crowding town hall style meetings with Republican members. Many members faced a stark choice between voting with their constituents or voting with their party. We use data on the number of town halls held by members to analyze whether members who heard from upset constituents were more likely to oppose the repeal effort. Next, we utilize data on House primaries and the 2018 general election to test whether the member’s position on repeal had any effects on the member’s electoral success. We find clear evidence that member’s voting behavior on the health care repeal had electoral effects in the 2018 general election.
Melting points of alkali chlorides evaluated for a polarizable and non-polarizable model

Accurate molecular models of pure alkali halides are a prerequisite for developing transferable models of molten salts that can predict the properties of complex salt mixtures, such as those including dissolved actinide species and metal ions. Predicting the melting point of a substance represents a rigorous test of model quality. To this end, we compute the melting points of the alkali chlorides for a popular non-polarizable and polarizable model. Neither model yields more accurate predictions of the melting points across the entire family of alkali chlorides. Further calculations suggest that this may be because neither model simultaneously represents both the solid and liquid phases with sufficient accuracy across all four alkali chlorides. We find that the deviation from experiment in the model enthalpy of melting may be a good indicator of the deviation from experiment in the model melting temperature. Since the enthalpy of melting is easier to calculate in simulation than melting temperature, it may be a useful quantity to target when developing new force fields for molten salts.
Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial.

Author(s): Budoff, Matthew J; Bhatt, Deepak L; Kinninger, April; Lakshmanan, Suvasini; Muhlestein, Joseph B; Le, Viet T; May, Heidi T; Shaikh, Kashif; Shekar, Chandana; Roy, Sion K; Tayek, John; Nelson, John R | Abstract: AimsDespite the effects of statins in reducing cardiovascular events and slowing progression of coronary atherosclerosis, significant cardiovascular (CV) risk remains. Icosapent ethyl (IPE), a highly purified eicosapentaenoic acid ethyl ester, added to a statin was shown to reduce initial CV events by 25% and total CV events by 32% in the REDUCE-IT trial, with the mechanisms of benefit not yet fully explained. The EVAPORATE trial sought to determine whether IPE 4 g/day, as an adjunct to diet and statin therapy, would result in a greater change from baseline in plaque volume, measured by serial multidetector computed tomography (MDCT), than placebo in statin-treated patients.Methods and resultsA total of 80 patients were enrolled in this randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis as documented by MDCT (one or more angiographic stenoses with ≥20% narrowing), be on statin therapy, and have persistently elevated triglyceride (TG) levels. Patients underwent an interim scan at 9 months and a final scan at 18 months with coronary computed tomographic angiography. The pre-specified primary endpoint was change in low-attenuation plaque (LAP) volume at 18 months between IPE and placebo groups. Baseline demographics, vitals, and laboratory results were not significantly different between the IPE and placebo groups; the median TG level was 259.1 ± 78.1 mg/dL. There was a significant reduction in the primary endpoint as IPE reduced LAP plaque volume by 17%, while in the placebo group LAP plaque volume more than doubled (+109%) (P = 0.0061). There were significant differences in rates of progression between IPE and placebo at study end involving other plaque volumes including fibrous, and fibrofatty (FF) plaque volumes which regressed in the IPE group and progressed in the placebo group (P l 0.01 for all). When further adjusted for age, sex, diabetes status, hypertension, and baseline TG, plaque volume changes between groups remained significantly different, P l 0.01. Only dense calcium did not show a significant difference between groups in multivariable modelling (P = 0.053).ConclusionsIcosapent ethyl demonstrated significant regression of LAP volume on MDCT compared with placebo over 18 months. EVAPORATE provides important mechanistic data on plaque characteristics that may have relevance to the REDUCE-IT results and clinical use of IPE.
Microscopic Observation of Solid Electrolyte Interphase Bilayer Inversion on Silicon Oxide

Silicon has been investigated in recent years as an alloying anode material to enhance gravimetric energy density in lithium-ion batteries. While recent developments have suggested that silicon oxi...
The Effect of Training Status on Adaptations to 11 Weeks of Block Periodization Training

Some controversy exists as to the most efficacious method of training to achieve enhanced levels of sport performance. Controversy concerning the efficacy of periodization and especially block periodization (BP) likely stems from the use of poorly or untrained subjects versus trained who may differ in their responses to a stimulus. The purpose of this study was to investigate the effect of training status on performance outcomes resulting from 11 weeks of BP training. Fifteen males were recruited for this study and placed into strong (age = 24.3 ± 1.9 years., body mass (BM) = 87.7 ± 8.7 kg, squat: body mass = 1.96 ± 0.16), moderate (age = 25.3 ± 2.7 years., body mass = 100.2 ± 15.5 kg, squat: body mass = 1.46 ± 0.14), or weak (age = 23.2 ± 3.9 yrs., body mass = 83.5 ± 17.1 kg, squat: body mass = 1.17 ± 0.07) groups based on relative strength. Testing was completed at baseline, and after each block which consisted of 1 repetition maximum (1RM) squat, 0 kg static jump (SJ), 0 kg countermovement jump (CMJ), 20 kg SJ, and 20 kg CMJ. Absolute and relative strength were strongly correlated with rates of improvement for absolute strength, relative strength, 0 kg, and 20 kg vertical jumps. All subjects substantially improved back squat (p < 0.001), relative back squat (p < 0.001) with large–very large effect sizes between groups for percent change favoring the weak group over the moderate and strong group for all performance variables. All subjects showed statistically significant improvements in 0 kg SJ (p < 0.001), 0 kg CMJ (p < 0.001), 20 kg SJ (p = 0.002), and 20 kg CMJ (p < 0.001). Statistically significant between group differences were noted for both 20 kg SJ (p = 0.01) and 20 kg CMJ (p = 0.043) with the strong group statistically greater jump heights than the weak group. The results of this study indicate BP training is effective in improving strength and explosive ability. Additionally, training status may substantially alter the response to a resistance training program.
Isolated Facet Joint Arthritis in Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is a group of childhood inflammatory arthropathies which has variable clinical presentations and can affect multiple joints including the spine. Arthritis in facet joints is rare and very unusual to be the only presentation of JIA. We report a 16-year-old female who presented with back pain and stiffness, in which CT of the lumbar spine showed evidence of facet joint erosion and pelvis MRI showed facet joint arthritis consistent with juvenile idiopathic arthritis.
On the value relevance of SFAS No. 158

Abstract After considerable discussion and some controversy, Statement of Financial Accounting Standards No. 158 entitled, “Employers’ Accounting for Defined Benefit Pension and Other Postretirement Plans” was implemented in 2006. An important goal of these standards was to enhance financial reporting transparency for defined benefit pension plans ( FASB, 2006 ). This study evaluates how well SFAS No. 158 achieved its objective. In particular, we compare the respective pre and post-SFAS 158 incremental value relevance of the balance sheet and income statement for firms with defined benefit pension plans (DBPP). Results suggest that the value relevance of book value (net income) increased (decreased) for DBPP firms after the implementation of SFAS No. 158.
Graded Index Dielectric Superstrate for Phased Array Scan Compensation

This paper presents the use of additively manufactured graded index materials to improve the scan impedance variation of phased arrays. Solvent-based extrusion permits the programmatically controlled printing of chosen material properties with relative permittivity ranging from 2 to 24.5. This low-loss material shows promise for improvement of scan impedance variation for high scan angles in a smaller footprint than discrete layers.
The Power of Empathy: Cultivating Culturally Competent Lawyers

The ability to connect with diverse clients and audiences is not a soft skill, but a power skill. This connection is just as important as substantive knowledge and is essential for the competent practice of law. Fostering that connection must start with recognizing one’s own positionality, and thus one challenge in the classroom is cultivating the ability to recognize positionality. One way to cultivate this aspect of cultural competence is by building empathy. Being intentional about building empathy in the classroom as a pathway to cultivating culturally competent lawyers, in turn, can include (1) modeling awareness as the professor; and (2) integrating culturally meaningful facts into assignments.
General Education versus Vocational Training: Evidence from an Economy in Transition

Abstract This paper examines the relative benefits of general education and vocational training during Romania's transition to a market economy. We examine a 1973 educational reform that shifted a large proportion of students from vocational training to general education. Using census and household survey data, we analyze the effect of this policy with a regression discontinuity design. We find that men affected by the policy are significantly less likely to work in manual or craft-related occupations but have similar levels of labor market participation and earnings compared to their counterparts unaffected by the policy. We conclude that differences in labor market returns between graduates of vocational and general schools are largely driven by selection.
A metabolomic aging clock using human CSF.

Quantifying the physiology of aging is essential for improving our understanding of age-related disease and the heterogeneity of healthy aging. Recent studies have shown that in regression models using "-omic" platforms to predict chronological age, residual variation in predicted age is correlated with health outcomes, and suggest that these "omic clocks" provide measures of biological age. This paper presents predictive models for age using metabolomic profiles of cerebrospinal fluid from healthy human subjects, and finds that metabolite and lipid data are generally able to predict chronological age within 10 years. We use these models to predict the age of a cohort of subjects with Alzheimer's and Parkinson's disease and find an increase in prediction error, potentially indicating that the relationship between the metabolome and chronological age differs with these diseases. However, evidence is not found to support the hypothesis that our models will consistently over-predict the age of these subjects. In our analysis of control subjects, we find the carnitine shuttle, sucrose, biopterin, vitamin E metabolism, tryptophan, and tyrosine to be the most associated with age. We showcase the potential usefulness of age prediction models in a small dataset (n = 85), and discuss techniques for drift correction, missing data imputation, and regularized regression, which can be used to help mitigate the statistical challenges that commonly arise in this setting. To our knowledge, this work presents the first multivariate predictive metabolomic and lipidomic models for age using mass spectrometry analysis of cerebrospinal fluid.
Teacher-report of where preschool-aged children play and are physically active in indoor and outdoor learning centers:

The childcare environment impacts physical activity participation, but little descriptive information is available in different types of programs. Most studies focus on the schoolyard despite child...
A pragmatic assessment of proton pump inhibitors vs. histamine type 2 receptor antagonists on clinically important gastrointestinal bleeding and mortality when used for stress ulcer prophylaxis in the ICU.

OBJECTIVE Approximately 1%-5% of critically ill patients experience clinically important gastrointestinal bleeding (CIGB). This study assessed the effectiveness and safety of proton pump inhibitors (PPIs) compared to histamine type 2 receptor antagonists (H2RAs) for prevention of CIGB in mechanically ventilated patients. DESIGN This is a retrospective, single-center, pharmacoepidemiologic study. SETTING This study was carried out in six intensive care units (ICUs). PATIENTS Critically ill adults admitted between 9/1/14 and 9/1/19 who received PPIs or H2RAs within 24 h of intubation and for ≥48 h were included in this study. INTERVENTION PPIs or H2RAs for stress ulcer prophylaxis. MEASUREMENTS AND MAIN RESULTS Primary outcomes were CIGB occurring 48 h after ICU admission and hospital mortality. Secondary outcomes were pneumonia, Clostridioides difficile infection (CDI), acute kidney injury, myocardial infarction/ischemia, thrombocytopenia, and delirium. Outcomes were defined using International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10)-codes with manual cross-reference for a hemoglobin drop, transfusion, or hemodynamic compromise to further define CIGB. Of 3873 patients, 2061 (53.2%) received PPIs. CIGB was rare but higher in the PPI group (0.34% vs. 0%, RR = 1, 95% CI, 1-1; p = 0.013); however, substantial group differences existed possibly predisposing the PPI group to CIGB. Hospital mortality was higher in the PPI group (42.1% vs. 29.1%, RR = 1.23, 95% CI, 1.17-1.29; p < 0.0001). PPIs remained an independent risk factor for mortality after multivariate adjustment (RR = 1.61, 95% CI, 1.39-1.88; p < 0.0001). Rates of secondary outcomes were similar between groups except thrombocytopenia (4.3% vs. 2.2%, RR = 1.02, 95% CI, 1.01-1.03; p = 0.0003) and delirium (83.7% vs. 78.1%, RR = 1.34, 95% CI, 1.18-1.53; p < 0.0001) that were higher in the PPI group. CONCLUSION Proton pump inhibitors were associated with CIGB; however, the overall rate of CIGB was low. Compared to H2RAs, PPIs were associated with hospital mortality. Further identification of appropriate selection criteria for ulcer prophylaxis and comparisons of pharmacologic prevention strategies are warranted.
Seawater effects on transverse tensile strength of carbon/vinylester as determined from single-fiber and macroscopic specimens

The main objective of this work is to characterize the effect of seawater immersion on the transverse tensile strength of a carbon/vinylester composite. A recently developed single-fiber test was used to determine the tensile strength of the fiber/matrix interface at dry and seawater saturated conditions. Measured loads at onset of fiber/matrix debonding were combined with finite element stress analysis to determine the tensile strength of the fiber/matrix interface. It was found that seawater exposure had an insignificant influence on the interface strength. The transverse tensile modulus and strength of macroscopic composite test specimens were slightly reduced by exposure to seawater. The modulus only slightly exceeds the lower bound estimate for both the dry and seawater saturated composite. This may be a consequence of insufficient load transfer between fiber and matrix due to interface voids. The fiber/matrix interface strengths measured at dry and seawater saturated conditions were used as input in the Cooper–Kelly micromechanical model to predict the transverse tensile strength of the composite. Predictions of strength at dry and seawater saturated conditions, based on measured fiber/matrix interface strengths, were unconservative, which again may be the results of voids at the fiber/matrix interface.
The Preparation and Evaluation of a Tablet Dosage Form of Cyclosporine in Dogs

Cyclosporine (CsA) is commercially available for oral administration as a solution in olive oil with alcohol and an emulsifier. To improve its variable absorption and low patient acceptability, several oral formulations were prepared and tested in vitro and in vivo in dogs. A tablet formulation prepared by direct compression was then selected for comparison with the commercial oil solution placed into soft gelatin capsules. The study involved a randomized crossover design in six dogs. In order to determine absolute bioavailability and to compensate for any time-dependent changes in clearance, an intravenous tracer dose of 3H-CsA was administered along with each oral test product on each of two occasions. Absolute bioavailability (mean ± SD) was 46.0 ± 11.1 and 45.4 ± 9.9% for the capsules and tablets, respectively. Cmax, tmax, and mean absorption time were not significantly different between the two products. No differences were observed in the pharmacokinetics of the intravenously administered CsA in the two experiments, which were separated by 8–13 days. We conclude that the proposed tablet formulation for CsA is equivalent in dogs to the commercial dosage form placed into soft gelatin capsules.
Incident cataract surgery: the Beaver Dam eye study

Purpose: The authors describe the incidence of cataract surgery in participants of the Beaver Dam Eye Study. Methods: Objective evidence of cataract extraction as obtained at follow-up examinations of participants of a population-based cohort is given. Participants included all adults 43 to 84 years of age who lived in the city or township of Beaver Dam, Wisconsin. Results: Age-adjusted incidence is significantly greater for women, for those with lower diastolic blood pressure, for those with hypertension, widows/widowers, and for those who report that their vision is worse than it had been. Multivariate analyses disclose that the following characteristics (with their respective odds ratios) are significantly associated with incident cataract surgery: age (odds ratio [OR] for 10 years 1.40; 95% confidence interval [CI] 1.02, 1.91); cigarette smoking (≥ 35 pack years; OR 1.91; 95% CI 1.16, 3.17); nuclear cataract (OR 35.58; 95% CI 10. at age 50 years); cortical cataract (OR 3.75; 95% CI 2.40, 5.88); posterior subcapsular cataract (OR 15.51; 95% CI 8.27, 29.09); impaired vision (OR 3.76; 95% CI 2.33, 6.05); intraocular pressure (≥ 14 mmHg; OR 2.56; 95% Cl 1.50, 4.38); visual sensitivity to light (OR 1.94; 95% CI 1.19, 3.17); refractive error (myopic) (OR 1.99; 95% CI 1.22, 3.24); yellow color (OR 1.69; 95% CI 1.02, 2.81); and being examined by an ophthalmologist within 2 years (OR 1.54; 95% CI 1.03, 2.30). Conclusions: Many factors are associated with cataract surgery, but the prior presence of posterior subcapsular cataract is the most important lens opacity. In addition, visual function changes, which may be relatively mild, are associated with subsequent incident surgery.
Fast and High-Throughput Molecular Typing Methods

As our understanding of pathogens has expanded and the world’s food supply has become more interconnected, characterization and subtyping of foodborne pathogens have become critically important in monitoring specific foods, performing surveillance for foodborne pathogens, investigating foodborne outbreaks, and understanding the virulence properties of particular lineages or strains. This chapter provides an overview of the molecular subtyping methods most commonly employed, in particular focusing on those methods providing fast and high-throughput analysis of strains. The methods include pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), multilocus variable-number tandem repeat (VNTR) analysis, DNA microarrays, and mass spectrometry. The heterogeneity that is targeted in the methods falls into three general categories. First, single-nucleotide polymorphisms (SNPs) are single-base changes in one sequence in comparison to another, related sequence. SNPs typically arise through sporadic mutation, so they represent a means of measuring random genetic drift. A large number of SNPs between two sequences may indicate a more distant genetic relationship. Second, some regions of the genome are more likely to change than others; they provide a means of differentiating closely related strains. Examples include variable number tandem repeats and highly polymorphic genes such as some surface structure and virulence genes. Finally, the presence/absence of specific loci can be found in both distantly and closely related strains. The presence of additional sequences in a strain can result from the insertion of a bacteriophage in the chromosome, acquisition of a plasmid, or other horizontal transfer events.
54 Utilization of Sirolimus as Primary Immunosuppression Attenuates Cardiac Allograft Vasculopathy and Improves Late Survival in the Heart Transplant Population

Purpose We investigated the potential of SRL as primary immunosuppressant in the long term attenuation of CAV progression and its effects on cardiac related morbidity and longer term survival. Methods and Materials 37 cardiac transplant recipients were converted to SRL 3.1±3.2 years after transplantation with complete calcineurin inhibitor (CNI) withdrawal. Forty eight control subjects 4.1±4.0 years from transplantation were maintained on CNIs. Age (48.0±12.6 vs. 49.6±14.9 years), sex (54.1% vs. 45.8% female), ejection fraction (62.3±8% vs. 61.3±9%) and time from transplant to baseline intravascular ultrasound study (p>0.2 for all) were similar in both groups. Secondary immunosuppressants (azathioprine or mycophenolate) and steroids remained unchanged. Three-dimensional intravascular ultrasound studies were performed at baseline and 3.1±1.6 years later. Results The increase in mean plaque (media and intima) volume (PV) was significantly attenuated in the SRL group (1.6±3.0 vs 2.2±2.3 mm 3 /mm, P 0.2 for all comparisons). The patients were followed up for 5.3±1.5 years. Five-year survival was significantly improved in the SRL group (96.4±3.5percent, 78.5±6percent; p=0.03), as well as 5 year freedom from cardiac events (cardiac death, vasculopathy related heart failure, myocardial infarction, or need for coronary intervention 57.1±18.7percent vs. 50.2±13.2percent; p=0.02). Conclusions We report a single center experience showing that substituting CNI with SRL as primary immunosuppression attenuates long term CAV progression and improves clinical outcomes.
Mitogenic signaling pathways induced by G protein‐coupled receptors

G protein-coupled receptor (GPCR) agonists, including neurotransmitters, hormones, chemokines, and bioactive lipids, act as potent cellular growth factors and have been implicated in a variety of normal and abnormal processes, including development, inflammation, and malignant transformation. Typically, the binding of an agonistic ligand to its cognate GPCR triggers the activation of multiple signal transduction pathways that act in a synergistic and combinatorial fashion to relay the mitogenic signal to the nucleus and promote cell proliferation. A rapid increase in the activity of phospholipases C, D, and A2 leading to the synthesis of lipid-derived second messengers, Ca2+ fluxes and subsequent activation of protein phosphorylation cascades, including PKC/PKD, Raf/MEK/ERK, and Akt/mTOR/p70S6K is an important early response to mitogenic GPCR agonists. The EGF receptor (EGFR) tyrosine kinase has emerged as a transducer in the signaling by GPCRs, a process termed transactivation. GPCR signal transduction also induces striking morphological changes and rapid tyrosine phosphorylation of multiple cellular proteins, including the non-receptor tyrosine kinases Src, focal adhesion kinase (FAK), and the adaptor proteins CAS and paxillin. The pathways stimulated by GPCRs are extensively interconnected by synergistic and antagonistic crosstalks that play a critical role in signal transmission, integration, and dissemination. The purpose of this article is to review recent advances in defining the pathways that play a role in transducing mitogenic responses induced by GPCR agonists.
The art of impression management: self-presentation in local-level campaign literature

Abstract Campaign literature is a ubiquitous feature on the American electoral landscape. Candidates distribute written materials for the sole purpose of persuading voters to vote for them instead of for another candidate. The information a candidate includes in a piece of campaign literature, as well as how it is presented, can reveal his or her perception of the criteria citizens use when deciding for whom to vote. The findings from an examination of 288 pieces of campaign literature distributed by candidates for city council seats in 11 Ohio counties in November 1997, suggest that they perceive potential voters as being susceptible to both intellectual and emotional campaign messages.
Projectile Z dependence of Al K -shell vacancy production in 10-MeV/amu ion-solid collisions

Beams of 10-MeV/amu Ne, Ar, Cr, Kr, Xe, and Bi ions have been employed to examine the dependence on projectile atomic number ${(Z}_{1})$ of Al K-shell vacancy production in nearly symmetric ${(Z}_{1}{/Z}_{2}=0.8)$ to highly asymmetric ${(Z}_{1}{/Z}_{2}=6.4)$ collisions. Aluminum K x-ray yields were measured with a Si(Li) detector as a function of target thickness to establish cross sections for charge equilibrated projectiles. Average target atom L-shell vacancy distributions excited in K-shell vacancy-producing collisions and x-ray yield corrections for contributions from photoionization and secondary electron impact were deduced from high-resolution spectral measurements performed with a curved-crystal spectrometer. Knowledge of the average L-shell vacancy distributions provided the means for estimating the appropriate fluorescence yields needed to convert the x-ray yields to K-shell vacancy production cross sections. Theoretical cross sections greatly overestimate the experimental results for ${Z}_{1}g10.$ The ${Z}_{1}$ dependences of the K-shell vacancy production cross sections for both Al and Cu (from a previous study) are well characterized by a simple empirical scaling law.
Citation rates in mathematics: a study of variation by subdiscipline

Variation of citation counts by subdisciplines within a particular discipline is known but rarely systematically studied. This paper compares citation counts for award-winning mathematicians is different subdisciplines of mathematics. Mathematicians were selected for study in groups of rough equivalence with respect to peer evaluation, where this evaluation is given by the awarding of major prizes and grants: Guggenheim fellowships, Sloan fellowships, and National Science Foundation CAREER grants. We find a pattern in which mathematicians working in some subdisciplines have fewer citations than others who won the same award, and this pattern is consistent for all awards. So even after adjustment at the discipline level for different overall citation rates for disciplines, citation counts for different subdisciplines do not match peer evaluation. Demographic and hiring data for mathematics provides a context for a discussion of reasons and interpretations.
O9.5Novel multi-modal endpoints uncovered by radiogenomics integrating CT or MRI data

ABSTRACT Radiologic measurements of anti-tumor response in solid tumors is a central elements needed to demonstrate treatment efficacy. However, the current use of RECIST criteria, which is the most commonly applied guideline in non-CNS clinical trials, has inherent limitations. As a result, many therapies including molecular targeted treatments and immunotherapies have shown substantial survival benefits without significant tumor shrinkage based on RECIST criteria. Thus, there is a critical unmet need to develop, test and validate alternative radiologic based criteria that do not solely rely upon tumor size shrinkage for response. This presentation will highlight some of the more promising radiologic approaches for measuring anti-tumor activity in the age of molecular targeted agents and immunotherapies. These novel imaging assessments apply feature extraction analysis based upon tumor metabolic behavior, necrosis, volumetric change, textural and Radiogenomic linkages that may not only provide a better measurement for treatment response but may also deliver predictive and prognostic information that can help improve patient selection and clinical trial design.
Size matters: concurrency and the epidemic potential of HIV in small networks.

Background Generalized heterosexual epidemics are responsible for the largest share of the global burden of HIV. These occur in populations that do not have high rates of partner acquisition, and research suggests that a pattern of fewer, but concurrent, partnerships may be the mechanism that provides the connectivity necessary for sustained transmission. We examine how network size affects the impact of concurrency on network connectivity. Methodology/Principal Findings We use a stochastic network model to generate a sample of networks, varying the size of the network and the level of concurrency, and compare the largest components for each scenario to the asymptotic expected values. While the threshold for the growth of a giant component does not change, the transition is more gradual in the smaller networks. As a result, low levels of concurrency generate more connectivity in small networks. Conclusions/Significance Generalized HIV epidemics are by definition those that spread to a larger fraction of the population, but the mechanism may rely in part on the dynamics of transmission in a set of linked small networks. Examples include rural populations in sub-Saharan Africa and segregated minority populations in the US, where the effective size of the sexual network may well be in the hundreds, rather than thousands. Connectivity emerges at lower levels of concurrency in smaller networks, but these networks can still be disconnected with small changes in behavior. Concurrency remains a strategic target for HIV combination prevention programs in this context.
Intraocular camera for retinal prostheses: Design constraints based on visual psychophysics

Optical system design constraints for an intraocular camera are determined by visual psychophysics techniques, including pixellation limits adequate for navigation and object identification, optimal pre- and post-pixellation blurring, and the elimination of gridding artifacts.
Pursuing structure in microcrystalline solids with independent molecules in the unit cell using 1H-13C correlation data.

The 1H–13C solid-state NMR heteronuclear correlation (HETCOR) experiment is demonstrated to provide shift assignments in certain powders that have two or more structurally independent molecules in the unit cell (i.e. multiple molecules per asymmetric unit). Although this class of solids is often difficult to characterize using other methods, HETCOR provides both the conventional assignment of shifts to molecular positions and associates many resonances with specific molecules in the asymmetric unit. Such assignments facilitate conformational characterization of the individual molecules of the asymmetric unit and the first such characterization solely from solid-state NMR data is described. HETCOR offers advantages in sensitivity over prior methods that assign resonances in the asymmetric unit by 13C–13C correlations and therefore allows shorter average analysis times in natural abundance materials. The 1H–13C analysis is demonstrated first on materials with known shift assignments from INADEQUATE data (santonin and Ca(OAc)2 phase I) to verify the technique and subsequently is extended to a pair of unknown solids: (+)-catechin and Ca(OAc)2 phase II. Sufficient sensitivity and resolution is achieved in the spectra to provide assignments to one of the specific molecules of the asymmetric unit at over 54% of the sites.