cssi/SciSciGPT-SciSciNet huggingface dataset:
Impact of cytoreductive nephrectomy on eligibility for systemic treatment and effects on survival: are surgical complications or disease related factors responsible?

Objective To understand the impact of cytoreductive nephrectomy on the ability to receive systemic therapy in patients with metastatic renal cell carcinoma. Causes of delayed eligibility and effect on overall survival (OS) were investigated. Methods Patients with metastatic renal cell carcinoma who underwent cytoreductive nephrectomy between 2002 and 2010 were identified. Those ineligible to receive systemic therapy >2 months after surgery were considered delayed. Reasons for delay and effect on OS were investigated, including a thorough analysis of surgical morbidity. Results Of 65 patients identified, 28% experienced delayed eligibility for systemic therapy. Reasons for delay were related to surgery in 33%, disease progression in 56%, and both in 11%. Of the entire cohort, pT4 and sarcomatoid disease predicted poor outcomes with median OS of 9.8 and 7.6 months, respectively. Comparison of the delay vs no delay groups revealed more intraoperative complications (P = .01), a trend toward more high-grade postoperative complications (17% vs 4%, P = .09), and a median OS of 4.8 vs 18.9 months. Controlling for grade and stage, delay and sarcomatoid features independently predicted poor OS (HR, 2.61; P = .01 and HR, 2.25; P = .02, respectively). Conclusion Delay in eligibility for systemic therapy after cytoreductive nephrectomy adversely affects OS and is most commonly caused by disease-related factors, although high-grade complications may contribute. Those with evidence of T4 or sarcomatoid disease features may best be served by systemic therapy followed by cytoreductive nephrectomy only in those exhibiting response.
The Lutonium: a sub-nanojoule asynchronous 8051 microcontroller

We describe the Lutonium, an asynchronous 8051 microcontroller designed for low Et/sup 2/. In 0.18 /spl mu/m CMOS, at nominal 1.8 V, we expect a performance of 0.5 nJ per instruction at 200 MIPS. At 0.5 V, we expect 4 MIPS and 40 pJ/instruction, corresponding to 25,000 MIPS/Watt. We describe the structure of a fine-grain pipeline optimized for Et/sup 2/ efficiency, some of the peripherals implementation, and the advantages of an asynchronous implementation of a deep-sleep mechanism.
The Production and Use of Concentrated Skim Milk Foam

Summary 1. Reconstituted dry skim milks and condensed skim milks of 25 per cent to 30 per cent solids content were mechanically whipped in a few minutes to a stiff white foam. An overrun of 150 to 450 per cent and a foam stability of 10 to 90 minutes were found for different milks. 2. Wide variations were observed in the whipping properties of skim milks. High heat treatment usually improved whipping properties. Commercial milks prepared for baking purposes generally exhibited excellent whipping ability. 3. Skim-milk-whips were set by rennet or acid, but subsequent disturbance caused wheying off. Fruit-whips similar to an egg white product were prepared by adding sugar to the skim milk foam and stabilizing the whip by stirring fruit pulp into it.
Nonparametric cross-covariance modeling as exemplified by soil heavy metal concentrations from the Swiss Jura

Geostatistics is used in soil science to map spatial distributions of soil properties from limited samples. Covariance models provide the basic measure of spatial continuity which is used to weight the information available at different sample locations, as in kriging. Traditionally, a closed-form analytical model is fitted to allow for interpolation of sample covariance values while ensuring the positive definiteness condition. For cokriging where several different properties are cross correlated with each other, the simultaneous modeling of several (cross) covariances is made more difficult because of the restrictions imposed by the linear coregionalization model. An algorithm for automatic joint modeling of multiple (cross) covariance tables is proposed, building on an extension of Bochner's positive definiteness theorem and eigenvalue correction. The objective of this paper is to present the new methodology and demonstrate its application to modeling large cross-covariance matrix. Such task is not easily done or, more bluntly, seldom done in the conventional way when the number of coregionalized variables becomes large. The data set used for the case study relates to heavy metal pollution in soil.
In one era and out the other.

A guided tour through much of photosynthesis research as I saw it, 1936–2001, is presented here. For earlier perspectives, see Myers 1974 (Plant Physiol 54: 420–426) and 1996 (Photosynth Res 50: 195–208).
Exploring population genetic models with recombination using efficient forward-time simulations.

We present an exact forward-in-time algorithm that can efficiently simulate the evolution of a finite population under the Wright–Fisher model. We used simulations based on this algorithm to verify the accuracy of the ancestral recombination graph approximation by comparing it to the exact Wright–Fisher scenario. We find that the recombination graph is generally a very good approximation for models with complete outcrossing, whereas, for models with self-fertilization, the approximation becomes slightly inexact for some combinations of selfing and recombination parameters.
Contingent Valuation of Sports

Past research measures the nonmarket benefits of sports stadiums and arenas but does not address the issues of temporal embedding or ordering effects. Temporal embedding exists if survey respondents do not differentiate between payment-period lengths and leads to unrealistic implicit discount rates. Multiple scenarios with alternative sports teams can lead to ordering effects that influence the nonmarket value of teams. This study elicits annual payments over different fixed time horizons (e.g., 5 or 10 years) for two teams in a city with a single professional sports team. We find that willingness to pay is sensitive to the length of the payment period. In one of two cases the ordering of the scenario weakly affects willingness to pay.
A Look into the Mind of the Negotiator: Mental Models in Negotiation

Negotiation can be conceptualized as a problem-solving enterprise in which mental models guide behavior. We examined the association between negotiation outcomes and mental models, as measured by negotiators’ associative networks. Four hypotheses were supported. First, negotiators who reached optimal settlements had mental models that reflected greater understanding of the negotiation’s payoff structure, and of the processes of trading and exchanging information, compared to negotiators who did not reach optimal settlements. Second, negotiators who reached optimal settlements exhibited greater within-dyad mental model similarity. Third, experience-based training was more likely than instruction-based training to produce mental models similar to the mental models of negotiators who actually reached optimal settlements. Finally, negotiators who received 10 weeks of experience-based training had mental models that were similar to novice negotiators who reached optimal settlements, except that the mental models of the experienced negotiators were more abstract.
Complete blood count risk score and its components, including RDW, are associated with mortality in the JUPITER trial.

BackgroundPreviously, we showed that sex-specific complete blood count (CBC) risk scores strongly predicted risk of all-cause mortality in multiple sets of general medical patients. This study evaluated the CBC risk score in an independent, well-studied international primary risk population of lower-risk individuals initially free from cardiovascular (CV) disease.DesignObservational secondary analysis of a randomized trial population.MethodsThe previously derived and validated CBC score was evaluated for association with all-cause mortality among CV disease-free females (n = 6568) and males (n = 10,629) enrolled for up to 5 years in the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. Associations of the CBC score with CV mortality and with major CV disease were also tested.ResultsThe CBC score predicted all-cause mortality, with univariable hazard ratio (HR) 4.83 (95% CI 3.70–6.31) for the third CBC score tertile vs. the first tertile, and...
The Effects of Depression on Impression Formation: The Role of Trait and Category Diagnosticity

Two studies examined the impact of trait and category diagnosticity on the social information processing of depressed and non-depressed participants. As suggested by the Weary, Marsh, Gleicher, and Edwards model of the effects of depression on social information processing, it was predicted that depressed participants would be especially sensitive to the diagnosticity of the available information when forming an impression of another person. In Study 1, depressed participants were more sensitive than nondepressed participants to trait diagnosticity when forming an impression. In Study 2, depressed participants were more sensitive than nondepressed participants to both trait and category diagnosticity when forming an impression.
Experimental and Computational Studies of the Neutral and Reduced States of Indeno[1,2-b]fluorene

This study examines the intrinsic structural and optoelectronic properties of the neutral indeno[1,2-b]fluorene skeleton as well as those of the corresponding anion radical and dianion. We report their characterization by analysis of solid-state structures and EPR, NMR, and absorbance spectra. Additionally, 20 popular density functional theory methods are used to evaluate their performance for predicting NMR chemical shifts, EPR hyperfine coupling constants, and low-energy transitions of the absorbance spectrum to act as a guide for future studies. This information can be used for a better understanding and tuning of the electron-transporting/accepting ability of the indenofluorene core for use in organic photovoltaics and organic field effect transistors.
Immunochemical detection of the occupational allergen, methylene diphenyl diisocyanate (MDI), in situ

Diisocyanate chemicals essential to polyurethane production are a well-recognized cause of occupational asthma. The pathogenesis of diisocyanate-induced asthma, including the pathways by which the chemical is taken up and its distribution in exposed tissue, especially the lung, remains unclear. We developed an antiserum with specificity for methylene diphenyl diisocyanate (MDI) the most abundantly produced and utilized diisocyanate world-wide, and established its ability to detect MDI in situ. Polyclonal MDI-specific IgG was induced by immunizing rabbits with MDI-conjugated to keyhole limpet hemocyanin (KLH) emulsified in complete Freund's adjuvant, followed by two booster injections with incomplete Freund's adjuvant. The antiserum contains IgG that recognize a variety of different MDI conjugated proteins, but not unconjugated or mock exposed proteins by dot blot analysis. The antiserum further demonstrates specificity for proteins conjugated with MDI, but not other commonly used diisocyanates. Immunochemical studies with cytospun airway cells and formalin-fixed paraffin embedded lung tissue sections from mice intranasally exposed to MDI (as reversibly reactive glutathione conjugates, e.g. GSH-MDI) demonstrated the antiserum's ability to detect MDI in tissue samples. The data demonstrate penetration of MDI into the lower airways, localized deposition in the epithelial region surrounding airways, and uptake by alveolar macrophages. The new immunochemical reagent should be useful for further studies delineating the uptake and tissue distribution of MDI, especially as it relates to adverse health effects from exposure.
Heterogeneous Risk Tolerance and Time Preference

This chapter extends the discussion to relative risk aversion, describing the associated survey evidence. This literature is characterized by wide differences in estimates. Meyer and Meyer point out that the coefficient of relative risk aversion is the percentage change in marginal utility divided by the percentage change in the argument of the utility function; in other words, relative risk aversion is the elasticity of marginal utility with respect to its underlying argument. They demonstrate that this elasticity is sensitive to how the underlying argument is defined. Specifically, it matters whether the argument of utility is wealth or consumption. After adjusting for the various functional arguments studied in the literature, they conclude that the various empirical estimates are mutually consistent. The models developed in this book involve utility functions whose arguments are consumption. It explores that BJKS surveyed investors' attitudes toward risk through the Health and Retirement Study (HRS) that was conducted in 1992. The survey yielded 11,707 responses to a series of questions about attitude to risk and risky activities. An interesting feature of the HRS survey methodology is that it is conducted in two waves, called Waves I and II. Notably, a subset of respondents answered the four risk tolerance questions in both waves.
Isolation of Pancreatic Cancer Cells from a Patient-Derived Xenograft Model Allows for Practical Expansion and Preserved Heterogeneity in Culture.

Commercially available, highly passaged pancreatic cancer (PC) cell lines are of limited translational value. Attempts to overcome this limitation have primarily consisted of cancer cell isolation and culture directly from human PC specimens. However, these techniques are associated with exceedingly low success rates. Here, we demonstrate a highly reproducible culture of primary PC cell lines (PPCLs) from patient-derived xenografts, which preserve, in part, the intratumoral heterogeneity known to exist in PC. PPCL expansion from patient-derived xenografts was successful in 100% of attempts (5 of 5). Phenotypic analysis was evaluated with flow cytometry, immunofluorescence microscopy, and short tandem repeat profiling. Importantly, tumorigenicity of PPCLs expanded from patient-derived xenografts was assessed by subcutaneous injection into nonobese diabeteic.Cg-Prkdc scid Il2rg tm1Wjl /SzJ mice. Morphologically, subcutaneous injection of all PPCLs into mice yielded tumors with similar characteristics to the parent xenograft. PPCLs uniformly expressed class I human leukocyte antigen, epithelial cell adhesion molecule, and cytokeratin-19. Heterogeneity within each PPCL persisted in culture for the frequency of cells expressing the cancer stem cell markers CD44, CD133, and c-Met and the immunologic markers human leukocyte antigen class II and programmed death ligand 1. This work therefore presents a reliable method for the rapid expansion of primary human PC cells and, thereby, provides a platform for translational investigation and, importantly, potential personalized therapeutic approaches.
The role of impulse oscillometry in determination of pulmonary function in asthmatic children

Objective To determine the value of impulse oscillometry in the diagnosis of asthma in children Methods The authors evaluated 217 healthy children, 121 children with paroxysmal asthma, and other 147 with paracmastic asthma using the impulse oscillometry and compared R 5, R 20 , X 5 and resonant frequency (Fres), respectively In addition, the authors tested 102 children with secular cough and for those with increased airway resistance the authors performed the bronchodialtion test as well Results In paroxysmal group R 5, R 20 , X 5 and Fres were 10 2 hPa/(L·s), 6 6 hPa/(L·s), -4 4 hPa/(L·s) and 23 7 Hz, respectively Compared with the control group the differences were significant ( P 0 01) In comparison with the paroxysmal group, the indices in the paracmastic cases were significantly improved ( P 0 01); those with airway resistance value 115% higher than expected accounted for 40 1% In secular cough group there were 38 cases with increased airway resistance and the bronchodilation test was performed for these cases, among whom 21 cases had positive results Conclusion Impulse oscillometry may be of great value in pediatric departments for determination of children′s pulmonary function and in evaluation of asthma
Regulatory T Cells: Central Concepts from Ontogeny to Therapy

The balanced differentiation of naive CD4+ T cells into either pro- or anti-inflammatory fates is a central regulator of immune homeostasis, dysregulation of which can lead to inflammatory disease or cancer. Accordingly, the development of diagnostics and therapeutics to measure and modulate this balance is of great interest. In this review, we focus on the predominant anti-inflammatory subset, regulatory T cells, discussing key concepts including development, function, antigen specificity, and lineage stability. In particular, we highlight how these notions are shaping the evolution of therapeutics, especially in the context of the transfusion medicine specialist, and identify several key areas that urgently need to be addressed.
Solving PDEs with Green’s Functions

This chapter solves the partial differential equations with Green's function. The chapter constructs the Green's function for the heat equation using the Dirac-δ function. The chapter helps in finding the Green's function for several forms of the heat equation. There are a few factors that can complicate a particular form of the heat equation, including boundary terms, initial conditions, and existence of a heat source or sink. When complicating factors are present, it is sometimes advantageous to separate the problem into pieces, each of which contains one of the complicating factors. The solutions to each of the pieces are added together to give the solution to the original problem. The method of images is a technique for solving heat equation-type problems on a bounded interval or semi-infinite interval. It uses imaginary heat sources or sinks at points outside the interval to obtain the desired boundary conditions.
Health Insurance Coverage in California in 2013 and 2014, After Implementation of the Affordable Care Act

This paper presents data on health insurance coverage in California in 2013 and 2014, based on the March 2014 and 2015 Supplements to the Current Population Survey (CPS). It reflects research done by the Employee Benefit Research Institute (EBRI) on health insurance coverage trends in California, recently published in the California Health Care Foundation’s California Health Care Almanac, and supported by the California Health Care Foundation, based in Oakland, CA. Because 2014 is the first year for which many of the key, coverage-expansion provisions of the Affordable Care Act of 2010 (ACA) were effective, the 2013-2014 data provide some initial findings on the ACA’s first-year impact. From 2013 to 2014, health insurance coverage expanded among individuals under age 65 in California, and the uninsured rate fell. In 2013, 5.5 million California individuals were uninsured, and this figure fell to 3.8 million individuals in 2014. In percentage terms, California’s uninsured rate fell from 16 percent in 2013 to 11 percent in 2014 (a 31 percent reduction). The 2013-2014 reductions in the uninsured rate were primarily due to expanded individual health insurance and Medicaid coverage, as there was very little increase in employment-based coverage. Younger adults and lower-income California residents had the highest uninsured rates in 2013, and experienced the greatest rate reductions, the lowest percentage-point reduction of any age group in 2014. With respect to firm size, workers in small firms had the highest uninsured rate in 2013, but workers in firms with more than 50 employees (particularly those in the 50-99 employee group) experienced the greatest reductions in uninsured rates. Among race/ethnic groups, Latinos had the highest uninsured rate for 2013 (22.8 percent) and saw that rate fall to 15.8 percent in 2014, a significant 31 percent year-over-year decline, but still the highest 2014 uninsured rate of the identified race/ethnic groups. Asians experienced the largest year-over-year uninsured rate reduction, moving from an uninsured rate of 12.1 percent to 7.7 percent (a 36 percent reduction).
Conduction, breakdown and electronic-ionic phenomena in liquids

The subject matter of this chapter covers the same areas of research as last year. The separation between topics covered under conduction phenomena and those covered under electronic and ionic phenomena is sometimes arbitrary, e.g. upon localization or scavenging, the mobility of a quasi-free electron changes, thus affecting the conductivity of the medium. I have taken the liberty to report such work in a given section according to the emphasis the authors themselves placed on their findings and interpretation. It was observed that the amount of effort spent in the conduction and breakdown field decreased substantially from that in the previous year, but it would appear that this is due to the historically observed cyclical nature of things rather than a definite trend of decreasing interest. On the other hand, a very large number of publications appeared in the areas covered by the electronic and ionic phenomena section. This is mainly due to the input from the proceedings of the 1976 International Conference on Electrons in Fluids which were published in the Canadian Journal of Chemistry in the spring of 1977.
Combining functional data with hierarchical Gaussian process models

Gaussian process models have been used in applications ranging from machine learning to fisheries management. In the Bayesian framework, the Gaussian process is used as a prior for unknown functions, allowing the data to drive the relationship between inputs and outputs. In our research, we consider a scenario in which response and input data are available from several similar, but not necessarily identical, sources. When little information is known about one or more of the populations it may be advantageous to model all populations together. We present a hierarchical Gaussian process model with a structure that allows distinct features for each source as well as shared underlying characteristics. Key features and properties of the model are discussed and demonstrated in a number of simulation examples. The model is then applied to a data set consisting of three populations of Rotifer Brachionus calyciflorus Pallas. Specifically, we model the log growth rate of the populations using a combination of lagged population sizes. The various lag combinations are formally compared to obtain the best model inputs. We then formally compare the leading hierarchical Gaussian process model with the inferential results obtained under the independent Gaussian process model.
Control of high-precision direct-drive mechatronic servos: Tracking control with adaptive friction estimation and compensation ☆

Abstract This paper examines nonlinear mechatronic systems with direct-drive limited-angle axial-topology actuators. The considered direct-drive servos are used in hard disk drives, manipulators, pointing systems, robots, rotating platforms, aerial vehicles, etc. High accuracy, precision and fast repositioning should be ensured despite friction and adverse phenomena which degrade overall performance and capabilities. Tracking control laws which compensate friction using the estimated parameters are designed. The adverse friction is compensated by a nonlinear feedback. Adaptive reconfiguration is ensured by estimating the unknown parameters in near real-time. Design and technological challenges are overcome by a consistent paradigm and hardware-centric concurrent design. The concept and solutions are experimentally verified.
Comparison of arterial occlusion and ischaemic exercise for the study of vasodilatation in the human calf.

1. Calf blood flow was measured by venous occlusion plethysmography to compare two stimuli for eliciting maximal calf vascular conductance: (i) 10 min of arterial occlusion and (ii) isolated exhaustive calf exercise with ischaemic occlusion. The subjects were semi-supine with the calf in position for immediate blood flow measurements after release of the occluding cuff. Three groups of subjects were studied: young [35 years (SD 9, n = 9)], old [57 years (SD 5, n = 10)] and patients with congestive heart failure [63 years (SD 7, n = 7)]. 2. Occlusion and ischaemic exercise were equally effective in producing maximal calf vascular conductance in each of the subject groups. Maximal calf vascular conductance (ml min −1 100 ml −1 mmHg −1 ) was equivalent in the young [ischaemic exercise 0.54 (SEM 0.03), occlusion 0.54 (SEM 0.05)] and old [ischaemic exercise 0.47 (SEM 0.05), occlusion 0.48 (SEM 0.04)] subjects. However, patients with congestive heart failure exhibited significantly reduced maximal calf vascular conductance [ischaemic exercise 0.20 (SEM 0.02), occlusion 0.20 (SEM 0.01)]. 3. Analysis of the curves, generated by plotting serial calf vascular conductance values obtained immediately and every 15 s after occlusion cuff release for 165 s, revealed differences in the pattern of vasodilatation after occlusion and ischaemic exercise. Maximal calf vascular conductance was more sustained after ischaemic exercise, and the shape of the calf vascular conductance curve was similar in all subject groups. After occlusion in the patients with congestive heart failure, maximal calf vascular conductance occurred at 6 s (SEM 3) after cuff release and declined rapidly, whereas, in the healthy subjects, calf vascular conductance increased after the first measurement, with maximal calf vascular conductance at 20 s (SEM 4) in the old and 27 s (SEM 6) in the young groups. The time delay for maximal calf vascular conductance in the healthy subjects is consistent with a velocity-mediated proximal arterial dilatation, and the rapid decline in the patients with congestive heart failure may reflect sympathetic vasoconstriction and endothelial dysfunction. 4. In conclusion, both occlusion and ischaemic exercise are equally useful for the determination of vasodilatory capacity of the human calf. The prolonged vasodilatation after ischaemic exercise allows more time for the measurement of maximal calf vascular conductance. However, analysis of the entire calf vascular conductance recovery curve after occlusion provides more information on the relative contributions of factors which sustain vasodilatation after a maximal stimulus.
Risk of bleeding after ultrasound-guided jugular central venous catheter insertion in severely thrombocytopenic oncologic patients.

Abstract Introduction We sought to assess the incidence and risk factors of bleeding after ultrasound-guided internal jugular (USGIJ) catheter insertion in severely thrombocytopenic cancer patients, as safe platelet (PLT) count threshold remains controversial. Methods Retrospective study of 52 patients with hematologic malignancies and severe thrombocytopenia who underwent USGIJ catheter insertion between 2014 and 2016. Group A included patients with prophylactic PLT transfusion and Group B without. Statistical analysis was performed. Results Group A included 28 patients and Group B 24. Baseline characteristics were equally distributed. Median catheter size was 12 Fr and tunneled in 20/52 patients. Median PLT count was not statistically different between the groups, before transfusion and after the procedure. Postoperative minor bleeding occurred in 10/52 patients, similar between groups. Lower PLT count, larger catheter caliber and trend for AML diagnosis were identified as risk factors for bleeding. Age, gender, BMI, renal dysfunction and tunneled insertion were not significant. Conclusion Incidence of minor bleeding is low in severely thrombocytopenic patients after USGIJ catheter insertion. Prophylactic platelet transfusion may be reserved for patients with identified risk factors.
The Concept of “Self”: An Operational Definition

Cultism is the curse of the thinking classes! There has been no shortage of studies of the self, of individual psychology, of human nature--call it what you will. Yet instead of progressing toward the common goal of an understanding of man as man, the proliferation of investigators has given rise to narrower and narrower viewpoints, each seeking to explain all of behavior through its particular expertise. As a result, the numerous schools of psychology form a veritable tower of Babel. Paradoxically, in psychology and its allied fields the quintessence of being human, the ability to communicate experience symbolically has been lost--and with it what Korzybski (1933) has termed “time binding”, the ability to use and profit from the work of previous generations. Significant discoveries by one group, in one or another area of character formation, are unknown, misunderstood, or disregarded by others. Unnecessary duplication of effort is common, and the need to fit findings on the Procrustean bed of a favored theoretical construct undermines otherwise useful experimental efforts.
Impact of Gender and Problem Severity upon Intervention Selection

The extent to which prejudicial views of both genders influence college students' clinical evaluations was investigated. Primarily White and working-class students listened to 1 of 4 audiotapes of either a male or a female actor with identical major or minor psychological problems. Participants selected 1 of 4 intervention levels (no intervention, workshops/seminars, counselor, or psychiatrist) for the actor and for themselves if they were to experience the actor's problems. The results indicated that both actor gender and participant gender influenced intervention choice. Participants, especially men, tended to select a higher intervention level for the actor than for themselves. These findings are congruent with the self-serving biases exhibited in therapeutic contexts and support the position that gender affects clinical decisions.
Developing and delivering a data warehousing and mining course

This paper describes the content and delivery of a Data Warehousing and Mining course that was developed for students in the Eberly College of Business at Indiana University of Pennsylvania. This elective course introduces students to the strategies, technologies, and techniques associated with this growing MIS specialty area. Students learn what is involved in planning, designing, building, using, and managing a data warehouse. Students also learn about how a data warehouse must fit into an over-all corporate data architecture that may include legacy systems, operational data stores, enterprise data warehouses, and data marts. In addition, students are exposed to the different data mining techniques used by organizations to derive information from the data warehouse for strategic and long-term business decision making.
Clinical Applications of Systems Biology Approaches

Completion of the Human Genome Project, rapid progress in The Cancer Genome Atlas (TCGA) and genome-wide association studies, and the ensuing development of high-throughput technologies for analysing patient samples at the DNA, RNA, protein, and metabolic levels, have resulted in a rapid accumulation of data capable of providing an atlas or ‘tool kit’ that describes the events that may occur during tumour initiation and progression. This body of data is challenging because of the incredible heterogeneity among types of tumours and the number of genetic aberrations found in epithelial cancer cells. The complexity of these aberrations makes identification of the emerging properties of tumours overwhelmingly difficult using current technologies. Thus, converting the abundant data into useful information about tumour initiation and progression, and, more importantly, obtaining the knowledge required to improve patient outcomes, will require new integrated approaches. Systems approaches that integrate data collected using multiple platforms and modalities with mathematical models of functional and phenotypic tumour outcomes will be necessary for the discovery of principles that can accelerate progress in translating preclinical studies into improved patient outcomes. This chapter focuses on the current and future clinical applications of systems biology approaches related to cancer, which include identification of diagnostic, prognostic, and therapeutic biomarkers, selection of suitable intervention strategies tailored to individual patients using combinatorial targeted therapy, and design of clinical trials.
Load Model Parameter Estimation by Transmission-Distribution Co-Simulation

In this paper, a novel approach for parameter estimation of static load models based on co-simulation of transmission and distribution dynamic simulators is presented. The advantage of a co-simulation based approach is that the aggregated response of the underlying three-phase unbalanced distribution system can be simulated. In this approach, the combined transmission and distribution dynamics is simulated with information exchanged at the distribution substation buses at each time step. The aggregated response (voltages, active and reactive powers) at the distribution substation bus is then fitted through a constrained linear least squares optimization to obtain the parameters of an equivalent load model. The validity of the proposed load modeling approach is demonstrated to estimate the parameters of a ZIP load model, with results being invariant to, perturbations with different magnitude and location, for multiple operating points, and under single and multiple instances of distribution feeder interfaced to transmission simulator. Furthermore, comparative studies between co-simulation approach and transmission only simulation with equivalenced loads modeled using parameters obtained through proposed approach is provided to illustrate the capability of the presented method in capturing load characteristics of distribution grid.
TCT-278 Incidence, Characteristics and Management of Residual Peri-Device Leak after Percutaneous Left Atrial Appendage Occlusion

Major residual peri-device flow was reported during follow-up in one-third of patients who underwent left atrial appendage occlusion (LAAO) in the PROTECT-AF trial. Although these leaks were not associated with major events in that trial, current recommendations are to continue oral anticoagulants (
Exercise training augments neuronal nitric oxide synthase dimerization in the paraventricular nucleus of rats with chronic heart failure.

Abstract Exercise training (ExT) is an established non-pharmacological therapy that improves the health and quality of life in patients with chronic heart failure (CHF). Exaggerated sympathetic drive characterizes CHF due to an imbalance of the autonomic nervous system. Neuronal nitric oxide synthase (nNOS) in the paraventricular nucleus (PVN) produce nitric oxide (NO•), which is known to regulate the sympathetic tone. Previously we have shown that during CHF, the catalytically active dimeric form of nNOS is significantly decreased with a concurrent increase in protein inhibitor of nNOS (PIN) expression, a protein that dissociates dimeric nNOS to monomers and facilitates its degradation. Dimerization of nNOS also requires (6R)-5,6,7,8-tetrahydrobiopterin (BH4) for stability and activity. Previously, we have shown that ExT improves NO-mediated sympathetic inhibition in the PVN; however, the molecular mechanism remains elusive. We hypothesized; ExT restores the sympathetic drive by increasing the levels and catalytically active form of nNOS by abrogating changes in the PIN in the PVN of CHF rats. CHF was induced in adult male Sprague-Dawley rats by coronary artery ligation, which reliably mimics CHF in patients with myocardial infarction. After 4 weeks of surgery, Sham and CHF rats were subjected to 3 weeks of progressive treadmill exercise. ExT significantly (p
In vitro comparison of frictional forces of a new polycrystalline ceramic bracket versus metal-insert ceramic bracket before and after aging

Summary Objective The purpose of this study was to compare the friction of two types of polycrystalline ceramic brackets before and after aging. Methods A total of 60 second-upper right premolar brackets were divided into two groups: Clarity™ Advanced (3M Unitek, Monrovia, CA) and Clarity™ (3M Unitek). All brackets had a nominal 0.022-in slot size and a McLaughlin Bennett Travesi (MBT) prescription. Each bracket was submitted to a friction test, using the YL01 UTM universal testing machine (YLE GMBH, Germany) before and after thermocycling. All tests were carried out in the presence of artificial saliva, using .019 × .025–in. rectangular stainless steel (SS) archwires (3M Unitek). Bracket slot surfaces were observed under an optical microscope (Olympus CX41, Tokyo, Japan) before and after aging. Results Before aging, the Clarity Advanced group showed significantly lower friction than the Clarity group (P = 0.011). After aging, the friction of the Clarity Advanced bracket decreased significantly (P Conclusions The new Clarity Advanced ceramic bracket shows good physical friction properties due to the various modifications added by the manufacturers.
Granular cold-water-soluble starch: preparation, characterization, and its use on controlled release of atrazine

Granular cold-water-soluble (GCWS) starches were prepared by an alcoholic-alkaline treatment. The method was carried out by treating starches with mixtures of ethanol and NaOH solution to swell starch granules. The treated starches were then neutralized with HCl, washed, and dried at 80°C for 3 h. The method was effective with wide varieties of starches, including normal, high-amylose, and waxy starches. The efficacy of the method depended mainly on starch varieties, concentrations of ethanol and NaOH, and reaction temperature. Different reaction conditions gave products different properties. Lower concentration of ethanol, higher concentration of NaOH, or higher reaction temperature gave the resulting starches better cold-water solubility. The resulting starches displayed about 70-90% cold water solubility. Trace amount of small molecule, mainly amylose, was leached out in the supernatant during the preparation. Total weight losses were about 0.01%, 0.4%, and 1.9% for waxy maize, normal maize, and high-amylose maize starches, respectively.
Structure-Activity Relationship of Pro- and Anticoagulant Effects of Fucus Vesiculosus Fucoidan

Abstract 3353 Fucoidans are sulfated polysaccharides extracted from brown algae. Fucoidans have a wide variety of biological activities including pro- and anticoagulant activities, which occur at different concentration ranges. Therefore, fucoidans have also been described as non-anticoagulant sulfated polysaccharides (NASPs, Liu et al. Thromb Haemost 2006; 95:68). Fucoidans have complex structures due to their large molecular weight (Mw), wide Mw distribution, variable degree and pattern of sulfation, diverse monosaccharide composition, branching of the sugar chain and different monomer linkages. This structural complexity challenges identification of the components responsible for fucoidan activities. The aim of the presented study was to fractionate Fucus vesiculosus (F.v.) fucoidan by size and to de- and oversulfate it to obtain compounds of varying Mw or degree of sulfation (DS), respectively. The fucoidans were then to be analyzed for their pro-and anticoagulant activities and structure, and the effect of modified fucoidan on the target protein Tissue Factor Pathway Inhibitor (TFPI) investigated. Two approaches were applied to generate F.v. fucoidan with different structural properties to the original. Firstly, fucoidan was fractionated by size using ultrafiltration. The Mw of the resulting fractions ranged from 8–180 kD. NMR, elemental analysis and HPAEC showed that other structural features, such as sulfate content and monosaccharide composition, were similar to those of the original fucoidan. Thrombin generation (CAT) assays showed an EC50 for procoagulant activity of 0.3–3 μg/mL; aPTT increased by 50% at 4–25 μg/mL. Generally, higher Mw increased procoagulant activity. Below 15 kD, this activity was markedly reduced. The minimum active length of F.v. fucoidan was 70 carbohydrate units. De- and oversulfated F.v. fucoidans were used to investigate the impact of charge on pro- and anticoagulant activities. In the CAT assay, oversulfated fucoidans showed improved procoagulant activity with an EC50 of 0.09–0.12 μg/mL, while desulfated fucoidans demonstrated reduced procoagulant activity compared to the original. A DS of 0.5 was estimated to be the limit for procoagulant activity. Inhibition of TFPI by fucoidan was assessed with a dilute prothrombin time assay (dPT) with added full-length TFPI. TFPI-blocking activity was mainly dependent on the DS and less on the fucoidans9 Mw. Interestingly, oversulfation also stimulated an undesired activation of the contact pathway. The presented study determined the minimal structural requirements for procoagulant activity of fucoidan molecules and identified features causing undesired biological effects. Disclosures: No relevant conflicts of interest to declare.
Exergy analysis of heating options for buildings in the Pacific Northwest

A framework for quantifying environmental impact in future energy codes is explored based on exergy analysis. An example exergy analysis is performed that quantifies the environmental impact of electric resistance heating with exergetic efficiency of only 13% compared to 30% and 40% for air source and ground source heat pumps. This provides motivation for removing electric resistance as a space heating option in future energy codes in the Northwest.
URIDINE MONOPHOSPHATE KINASE: A NEW GENETIC MARKER OF SUSCEPTIBILITY TO HAEMOPHILUS INFLUENZAE TYPE B DISEASE: 158

Alaskan Eskimos have the highest known incidence of invasive Haemophilus influenzae type b (Hib) disease, primarily meningitis, affecting 1-5% of all children in the first two years of life. We examined potential genetic explanations for this unique susceptibility by studying 93 Eskimo Hib cases and an equal number of healthy Eskimo controls matched for age and exposure (village). In this analysis, a polymorphic genetic variant of the pyrimidine pathway enzyme, uridine monophosphate kinase-3 (UMPK-3), was positively associated with invasive Hib disease, with a relative risk of 3.3 (McNemar matched pair, P<.01). All UMPK 3-3 homozygotes in this study were Hib cases. We also found that in cases and controls, there was no difference between UMPK phenotype and serum levels of total Hib antibody as measured by radioimmunoassay. This suggests that UMPK-3 may play a role in mediating the non-humoral immunity to Hib. However, unlike other enzyme variants in the nucleoside synthesis pathways which result in syndromes of severe immunodeficiency, this gene appears to confer a more subtle disease susceptibility. Thus, the UMPK-3 allele, although rare in many human populations, is associated with an increased risk of invasive Hib infection in Alaskan Eskimos.
Objective subtle cognitive difficulties predict future amyloid accumulation and neurodegeneration

Objective To determine the temporal sequence of objectively defined subtle cognitive difficulties (Obj-SCD) in relation to amyloidosis and neurodegeneration, the current study examined the trajectories of amyloid PET and medial temporal neurodegeneration in participants with Obj-SCD relative to cognitively normal (CN) and mild cognitive impairment (MCI) groups. Method A total of 747 Alzheimer9s Disease Neuroimaging Initiative participants (305 CN, 153 Obj-SCD, 289 MCI) underwent neuropsychological testing and serial amyloid PET and structural MRI examinations. Linear mixed effects models examined 4-year rate of change in cortical 18F-florbetapir PET, entorhinal cortex thickness, and hippocampal volume in those classified as Obj-SCD and MCI relative to CN. Result Amyloid accumulation was faster in the Obj-SCD group than in the CN group; the MCI and CN groups did not significantly differ from each other. The Obj-SCD and MCI groups both demonstrated faster entorhinal cortical thinning relative to the CN group; only the MCI group exhibited faster hippocampal atrophy than CN participants. Conclusion Relative to CN participants, Obj-SCD was associated with faster amyloid accumulation and selective vulnerability of entorhinal cortical thinning, whereas MCI was associated with faster entorhinal and hippocampal atrophy. Findings suggest that Obj-SCD, operationally defined using sensitive neuropsychological measures, can be identified prior to or during the preclinical stage of amyloid deposition. Further, consistent with the Braak neurofibrillary staging scheme, Obj-SCD status may track with early entorhinal pathologic changes, whereas MCI may track with more widespread medial temporal change. Thus, Obj-SCD may be a sensitive and noninvasive predictor of encroaching amyloidosis and neurodegeneration, prior to frank cognitive impairment associated with MCI.
Adjuvant therapy following resection of gastroenteropancreatic neuroendocrine tumors provides no recurrence or survival benefit

BACKGROUND AND OBJECTIVES Lack of high-level evidence supporting adjuvant therapy for patients with resected gastroenteropancreatic neuroendocrine tumors (GEP NETs) warrants an evaluation of its non-standard of care use. METHODS Patients with primary GEP NETs who underwent curative-intent resection at eight institutions between 2000 and 2016 were identified; 91 patients received adjuvant therapy. Recurrence-free survival (RFS) and overall survival (OS) were compared between adjuvant cytotoxic chemotherapy and somatostatin analog cohorts. RESULTS In resected patients, 33 received cytotoxic chemotherapy, and 58 received somatostatin analogs. Five-year RFS/OS was 49% and 83%, respectively. Cytotoxic chemotherapy RFS/OS was 36% and 61%, respectively, lower than the no therapy cohort (P < .01). RFS with somatostatin analog therapy (compared to none) was lower (P < .01), as was OS (P = .01). On multivariable analysis, adjuvant cytotoxic therapy was negatively associated with RFS but not OS controlling for patient/tumor-specific characteristics (RFS P < .01). CONCLUSIONS Our data, reflecting the largest reported experience to date, demonstrate that adjuvant therapy for resected GEP NETs is negatively associated with RFS and confers no OS benefit. Selection bias enriching our treatment cohort for individuals with unmeasured high-risk characteristics likely explains some of these results; future studies should focus on patient subsets who may benefit from adjuvant therapy.
The Changing Face of US Protestant Overseas Ministries: Trends from 1951 to 2016:

The release of the 22nd edition of the Mission Handbook (2017) has provided rich opportunities for scholars and practitioners to learn more about the current state of global missions from North Ame...