cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 3470: Obesity and metformin alter progression of triple negative breast cancer

Background: Epidemiological studies from us and others have reported an association of obesity with more aggressive breast tumors and >30% higher risk of recurrence and mortality compared to normal weight patients. This includes poorer outcomes for triple negative breast cancer (TNBC), an aggressive subtype with early recurrence and shorter survival. Metformin is a leading frontline therapy for type 2 diabetes and its safety profile is well documented. Laboratory and clinical studies including ours suggest that metformin may have anti-tumor effects in breast cancer. However, the nature and molecular mechanisms of these correlations are poorly understood. Experimental design and methods: We used a PDX (patient-derived xenograft) breast cancer model in diet-induced obese mice to study how obesity promotes breast cancer growth and how metformin antagonizes these effects. After feeding the mice with a high-fat diet (HFD) vs. a control diet (CD), we transplanted a TNBC PDX into the mammary fat pads. When tumors reached about 50 mm3, mice in HFD and CD groups were randomly assigned to metformin treatment or no treatment. Tumor volumes were measured bi-weekly, and blood, tumors, and organs were collected after 4 weeks of treatment. Histological and immunohistochemical staining, serum adipokines array and metabolomics and lipidomics analyses were performed to examine potential mechanisms. Results: HFD (obese) group compared to CD (lean) group was associated with larger tumors, whereas metformin compared to no treatment was associated with smaller tumors. A panel of adipokines and metabolites was identified to be differentially expressed between the groups. Conclusion: Our results suggest a growth promoting effect of obesity in TNBC, while metformin appears to have the opposite effect. The identification of adipokines and metabolites involved in these effects will help us understand the mechanisms by which obesity and metformin alter the progression of TNBC. Citation Format: Laura Camacho, Lei Xue, Lacey Dobrolecki, Susan G. Hilsenbeck, Chandandeep Nagi, Nagireddy Putluri, Michael T. Lewis, Arun Sreekumar, Sao Jiralerspong. Obesity and metformin alter progression of triple negative breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3470.
Conc-iSE: incremental symbolic execution of concurrent software

Software updates often introduce new bugs to existing code bases. Prior regression testing tools focus mainly on test case selection and prioritization whereas symbolic execution tools only handle code changes in sequential software. In this paper, we propose the first incremental symbolic execution method for concurrent software to generate new tests by exploring only the executions affected by code changes between two program versions. Specifically, we develop an inter-thread and inter-procedural change-impact analysis to check if a statement is affected by the changes and then leverage the information to choose executions that need to be re-explored. We also check if execution summaries computed in the previous program can be used to avoid redundant explorations in the new program. We have implemented our method in an incremental symbolic execution tool called Conc-iSE and evaluated it on a large set of multithreaded C programs. Our experiments show that the new method can significantly reduce the overall symbolic execution time when compared with state-of-the-art symbolic execution tools such as KLEE.
A Methodical Approach to Accelerated Screening of Card Assemblies, Static Burn-In Case

The methodical approach presented for screening cards establishes values of critical parameters, such as apparent activation energy and maximum temperature hence shortest time for screening, and statistical life distributions of assemblies. We conducted one step-stress and two life tests at 120°C (248°F) and 135°C (275°F) using relatively small samples of 40 and 50 cards per test, which, nonetheless, gave us the desired information. The approximate screening parameters that resulted have been successfully used to tailor the stress screening of card assemblies. In our experiments, a trimodal, log-normal life distribution has been revealed, which seems to suggest that the traditional bathtub curve of a life distribution is not applicable to card assemblies.
T-Box Genes and Developmental Gene Regulatory Networks in Ascidians

Ascidians are invertebrate chordates with a biphasic life cycle characterized by a dual body plan that displays simplified versions of chordate structures, such as a premetamorphic 40-cell notochord topped by a dorsal nerve cord and postmetamorphic pharyngeal slits. These relatively simple chordates are characterized by rapid development, compact genomes and ease of transgenesis, and thus provide the opportunity to rapidly characterize the genomic organization, developmental function, and transcriptional regulation of evolutionarily conserved gene families. This review summarizes the current knowledge on members of the T-box family of transcription factors in Ciona and other ascidians. In both chordate and nonchordate animals, these genes control a variety of morphogenetic processes, and their mutations are responsible for malformations and developmental defects in organisms ranging from flies to humans. In ascidians, T-box transcription factors are required for the formation and specialization of essential structures, including notochord, muscle, heart, and differentiated neurons. In recent years, the experimental advantages offered by ascidian embryos have allowed the rapid accumulation of a wealth of information on the molecular mechanisms that regulate the expression of T-box genes. These studies have also elucidated the strategies employed by these transcription factors to orchestrate the appropriate spatial and temporal deployment of the numerous target genes that they control.
Money and Capital or Financial Deepening in Economic Developments

Publisher Summary This chapter discusses the effect of financial conditions on influence saving and growth. It presents an empirical test of models of finance in economic development developed by McKinnon and Shaw. The pooled time series analysis was done using annual observations for seven Asian less developed countries (LDCs)—Burma (1962–69), India (1962–1972), Korea (1962–1972), Malaysia (1963–1972), Philippines (1962–1972), Singapore (1965–1972), and Taiwan (1962–1972). The empirical results show that the real rate of interest has a positive effect on domestic saving and economic growth in the Asian LDCs analyzed. The demand-for-money estimates, however, do not support McKinnon's complementarity hypothesis, which is based on the assumptions that investment is, in the main, self-financed, and money is the predominant financial repository of domestic savings in these countries. The Asian LDCs used in this analysis have achieved stages of financial development well beyond the phase in which the complementarity assumptions might hold.
Short-circuit analysis in large-scale distribution systems with high penetration of distributed generators

In this paper a short-circuit computation U+0028 SCC U+0029 procedure for large-scale distribution systems with high penetration of distributed generators based on contemporary technologies is proposed. The procedure is suitable for real-time calculations. Modeling of modern distributed generators differs from the modeling of traditional synchronous and induction generators. Hence, SCC procedures found on the presumption of distribution systems with only traditional generators are not suitable in nowadays systems. In the work presented in this paper, for computation of the state of the system with short-circuit, the improved backward U+002F forward sweep U+0028 IBFS U+0029 procedure is used. Computation results show that the IBFS procedure is much more robust than previous SCC procedures, as it takes into account all distribution system elements, including modern distributed generators.
Sandra Bem: Revolutionary and Generative Feminist Psychologist

This introduction to The Past, Present, and Future of Masculinity, Femininity and Gender: Honoring Feminist Scholar Sandra L. Bem (1944–2014), Part 1 briefly highlights Sandra Bem’s career and provides an overview of each paper included in the first of two special issues. In doing so, we highlight how Sandra Bem’s works changed the way scholars understood gender and how much of Bem’s work continues to influence current day scholarship on gender.
Data Sharing and Data Registries in Physical Medicine and Rehabilitation

Abstract The field of physical medicine & rehabilitation (PMR (2) focused on recovery or maintenance of any function; and (3) used data repositories or research databases. We identified 398 articles that cited 244 data sources. The data sources included 66 data repositories and 179 research databases. We categorized the data sources based on their purposes and uses, geographic distribution, and other characteristics. This study collates the range of databases, data repositories, and data-sharing mechanisms that have been used in PM&R internationally. In recent years, these data sources have provided significant information for the field, especially at the population-health level. Implications and future directions for data sources also are discussed.
Adding Value to Trade Space Exploration When Designing Complex Engineered Systems

Design decision-making involves tradeoffs between many design variables and attributes, which can be difficult to model and capture in complex engineered systems. To choose the best design, the decision maker is often required to analyze many different combinations of these variables and attributes and process the information internally. Trade Space Exploration (TSE) tools, including interactive and multidimensional data visualization, can be used to aid in this process and provide designers with a means to make better decisions, particularly during the design of complex engineered systems that have multiple, competing objectives. In this paper, we investigate the use of TSE tools to support decision makers using a Value-Driven Design (VDD) approach for complex engineered systems. A VDD approach necessitates a rethinking of TSE, and we outline and illustrate four different uses of a VDD approach to TSE. The research leverages existing TSE paradigms and multidimensional data visualization tools to identify optimal designs when using a value function for a system. A satellite design example is used to demonstrate the differences between a VDD approach to design complex engineered systems and a multiobjective approach to capture the Pareto frontier. Ongoing and future work is also discussed.
Biogeography of Root-Associated Fungal Endophytes

Healthy plant roots usually host heterogeneous communities of root endophytes that are abundant in all plants and ecosystems. Despite their abundance, current understanding of the distribution of these endophytes is superficial at the best. A comprehensive treatise of the distribution of variety of fungi described as root endophytes would most likely prove an exhausting exercise in futility, given the large gaps in current data. As a result, we broadly target the helotialean endophytes that are commonly observed in temperate and boreal, forested ecosystems and the pleosporalean endophytes commonly observed in grassland ecosystems. To explore the sparse data available for the distribution of these root-associated fungal endophytes, we combine references from current literature and a case study to evaluate whether or not the endophyte communities (1) shift over environmental gradients, (2) respond to some specific drivers, or (3) seem limited by dispersal by showing distance-decay responses. The data indicate that communities of endophytic fungi indeed change over large geographical scales. The available data suggest a Helotiales-dominated endophyte guild in forested ecosystems and a Pleosporales-dominated assemblage in grassland ecosystems. Further, large-scale studies and our preliminary analyses of communities across North American grassland ecosystems suggest some shifts corresponding to geographical/environmental gradients. However, specific drivers are difficult to distinguish because abiotic gradients are often correlated, resulting in complex model selection problems. Finally, we observed that our own and published data reach no agreement on distance decay, even though both agree that the distance decay may be of rather minor importance.
Colt: concept lineage tool for data flow metadata capture and analysis

Most organizations are becoming increasingly data-driven, often processing data from many different sources to enable critical business operations. Beyond the well-addressed challenge of storing and processing large volumes of data, financial institutions in particular are increasingly subject to federal regulations requiring high levels of accountability for the accuracy and lineage of this data. For companies like GE Capital, which maintain data across a globally interconnected network of thousands of systems, it is becoming increasingly challenging to capture an accurate understanding of the data flowing between those systems. To address this problem, we designed and developed a concept lineage tool allowing organizational data flows to be modeled, visualized and interactively explored. This tool has novel features that allow a data flow network to be contextualized in terms of business-specific metadata such as the concept, business, and product for which it applies. Key analysis features have been implemented, including the ability to trace the origination of particular datasets, and to discover all systems where data is found that meets some user-defined criteria. This tool has been readily adopted by users at GE Capital and in a short time has already become a business-critical application, with over 2,200 data systems and over 1,000 data flows captured.
Leaky mode coupling in asymmetric subwavelength dielectric gratings

Asymmetric subwavelength dielectric gratings can couple to symmetry-protected leaky modes, enabling normal incidence filtering. Finite element simulations calculate the transmittance profile and dispersion relation of a two-step high contrast grating. Further, linewidth broadening due to leaky mode coupling and angular dependence are established.
Luminescent Solar Concentrator Paintings: Connecting Art and Energy

The increased awareness of greenhouse gas emissions on long-term climate trends has put the spotlight back on the development of renewable energy technologies to mitigate these processes. Solar based electricity generation has gained widespread recognition as a viable source of renewable energy but has been slowed by a number of factors including cost and available application areas. Luminescent solar concentrators (LSC) are being investigated as a low-cost route to expand solar energy harvesting into new spaces. With this demonstration, we develop kits for educating students about renewable and solar energy while promoting a sense of creativity often lacking in STEM demonstrations. Students design LSC devices by painting newly developed luminescent dyes on plastic waveguides. Thin solar cell strips are mounted around the edges of the LSC paintings to generate power. Creativity in design, a central part of scientific discovery and advancement, is promoted throughout the painting and testing of LSC materials.
Indications and outcomes in adult lung transplantation

Lung transplantation (LTx) is a treatment option for end-stage lung disease that would be otherwise fatal for specific patient populations. The most common indications for LTx in adults remain to be chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis, alpha-1 antitrypsin deficiency, and idiopathic pulmonary arterial hypertension. Recent trends include performing retransplantation while more patients over the age of 65 years are undergoing LTx. Even with these tendencies, slight improvements in survival have occurred. This article briefly reviews recent developments in adults undergoing LTx.
Differential Association, Differential Social Organization, and the Epidemiology of Crime

Any theory purporting to explain a specific kind of social behaviour such as criminality and delinquency should have two distinct but consistent aspects. First, there should be a statement that explains the statistical distribution of the behaviour in time and space (epidemiology), and from which predictive statements about unknown statistical distributions can be derived. Second, there should be a statement that identifies, at least by implication, the process by which individuals come to exhibit the behaviour in question, and from which can be derived predictive statements about the behaviour of individuals. Concentration on either the epidemiological segment or the individual conduct segment of a theoretical problem is sometimes necessary, but it is erroneous and inefficient to ignore the second segment, to turn it over to another academic discipline, or to leave its solution to a specialized set of workers within a single discipline.
Accounting for environmental change in continuous-time stochastic population models

The demographic rates (e.g., birth, death, migration) of many organisms have been shown to respond strongly to short- and long-term environmental change, including variation in temperature and precipitation. While ecologists have long accounted for such nonhomogeneous demography in deterministic population models, nonhomogeneous stochastic population models are largely absent from the literature. This is especially the case for models that use exact stochastic methods, such as Gillespie’s stochastic simulation algorithm (SSA), which commonly assumes that demographic rates do not respond to external environmental change (i.e., assumes homogeneous demography). In other words, ecologists are currently accounting for the effects of demographic stochasticity or environmental variability, but not both. In this paper, we describe an extension of Gillespie’s SSA (SSA + ) that allows for nonhomogeneous demography and examine how its predictions differ from a method that is partly naive to environmental change (SSAn) for two fundamental ecological models (exponential and logistic growth). We find important differences in the predicted population sizes of SSA + versus SSAn simulations, particularly when demography responds to fluctuating and irregularly changing environments. Further, we outline a computationally inexpensive approach for estimating when and under what circumstances it can be important to fully account for nonhomogeneous demography for any class of model.
How to Prove that the Transition from Pre Planckian to Planckian Space Time Physics May Allow Octonionic Gravity Conditions to Form. and How to Measure that Transition from Pre Octionic to Octionic Gravity, and Check Into Conditions Permitting Possible Multiple Universes

We ask if Octonionic quantum gravity [1] is a relevant consideration near the Planck scale. Furthermore, we examine whether gravitational waves would be generated during the initial phase, and look into multiple universe generation. And an Ergodic mapping which may allow multiple universe embedding of Octonionic gravity as a starting point to inflation
Reparations as Redistribution

Most proponents of slavery reparations seem to have in mind a program that includes substantial redistribution of resources from whites to blacks within the U.S. This Article takes seriously the idea of slavery reparations as a program of redistribution. The Article, therefore, has a normative component in that it offers a new justification for some degree of racial redistribution, a justification that takes into account distributive justice concerns as well as efficiency concerns. The argument, in brief, is that, since race strongly correlates with differences in well-being, is relatively immutable (or at least not a function of work/leisure choices), and is relatively observable, a program of racial redistribution can have the properties of a distributively just lump-sum transfer. There are, of course, reasonably strong arguments to be made against doing any redistribution by race. Those arguments are also discussed in the Article. As to the questions of precisely how much racial redistribution their ought to be, what forms such redistribution should take, and whether the types of racial redistribution that we already have (via targeted spending programs and prohibitions against statistical discrimination as well as through race-based affirmative-action programs) are sufficient, the Article provides no answers. It does, however, suggest some of the general types of programs that should be considered and the criteria for evaluating them. Moreover, what is most relevant for the current debate over slavery reparations, I suggest that the slavery reparations debate would be improved if more attention were given to these distributive justice, efficiency, and policy-design issues.
Identification of State-space Linear Time-varying Systems with Sum-of-norms Regularization

In this paper, we propose a method for the estimation of state-space models for linear time-varying systems using sum-of-norms regularization. Specifically, the system parameters are assumed to follow a probability distribution with a Markovian dependency across time samples. This prior information is incorporated in a Bayesian framework, which leads to a maximum-a-posteriori criterion involving a sum-of-norms penalty term. The resulting estimation problem is addressed with a generalized expectation maximization algorithm, whose maximization step consists of a ‘difference of convex’ optimization problem, for which a monotone procedure is established. Controlled computational experiments using synthetic data are performed to show the effectiveness of the approach. The proposed algorithm is expected to find practical application in modeling dynamical processes arising in different domains, particularly in the fields of economics and neuroscience.
Local Stochastic Vortex Structure Method for Synthetic Turbulence Computation in Flight Simulators

Rapid turbulence approximation on and around a vehicle is necessary for development of improved flight simulators for helicopters and aircraft, used both for pilot training and for video-gaming app...
Sponsored Search and Market Efficiency

Sponsored search is the mechanism whereby where advertisers pay a fee to Internet search engines to be displayed alongside organic (non-sponsored) web search results. Based on prior literature, we draw an analogy between these markets and financial markets. We use the analogy as well as the key differences to present a theoretical framework consisting of a set of research questions about the pricing of keywords and design choices available to firms in sponsored search markets. These questions define an agenda for future research in sponsored search markets. They also have practical implications for advertisers and online marketplaces such as search engines and social media sites that support advertising.
Arousal-State Dependent Alterations in VTA-GABAergic Neural Activity

Abstract Decades of research have implicated the ventral tegmental area (VTA) in motivation, reinforcement learning and reward processing. We and others recently demonstrated that it also serves as an important node in sleep/wake circuitry. Specifically, VTA-dopaminergic neuron activation is sufficient to drive wakefulness and necessary for the maintenance of wakefulness. However, the role of VTA gamma-aminobutyric acid (GABA)-expressing neurons in arousal regulation is not fully understood. It is still unclear whether VTA-GABAergic neurons predictably alter their firing properties across arousal states, what is the nature of interactions between VTA-GABAergic activity and cortical neural oscillations, and how activity in VTA-GABAergic neurons relates to VTA-dopaminergic neurons in the context of sleep/wake regulation. To address these questions, we simultaneously recorded population activity from VTA-GABAergic or VTA-dopaminergic neurons and EEG/EMG signals during spontaneous sleep/wake states and in the presence of salient stimuli in freely-behaving male mice. We observed that VTA-GABAergic neurons exhibit robust arousal-state-dependent alterations in population activity, with high activity and calcium transients during wakefulness and rapid-eye-movement (REM) sleep compared to non-REM (NREM) sleep. During wakefulness, population activity of VTA-GABAergic neurons, but not VTA-dopaminergic neurons, was positively correlated with EEG gamma power and negatively correlated with EEG theta power. During NREM sleep, population activity in both VTA-GABAergic and VTA-dopaminergic neurons negatively correlated with delta, theta, and sigma EEG power bands. Salient stimuli, with both positive and negative valence, activated VTA-GABAergic neurons. The strongest activation was observed for social stimuli irrespective of valence. Together, our data indicate that VTA-GABAergic neurons, like their dopaminergic counterparts, drastically alter their activity across sleep-wake states. Changes in their activity predicts cortical oscillatory patterns reflected in the EEG, which are distinct from EEG spectra associated with dopaminergic neural activity. Statement of Significance Little is known about how ventral tegmental area (VTA) neural ensembles couple arousal to motivated behaviors. Using cell-type specific genetic tools, we investigated the population activity of GABAergic and dopaminergic neurons within the VTA across sleep/wake states and in the presence of salient stimuli. We demonstrate that coordinated neural activity within VTA-GABAergic neurons peaks during wakefulness and REM sleep. Furthermore, neuronal activity in VTA-GABAergic neurons is correlated with high frequency, low amplitude cortical oscillations during waking, but negatively correlated with high amplitude slower frequency oscillations during NREM sleep. Our results demonstrate that VTA-GABAergic neuronal activity is tightly linked to cortical arousal and highlight this population as a potential important node in sleep/wake regulation.
Malignancy risk for solitary and multiple nodules in Hürthle cell-predominant thyroid fine-needle aspirations: A multi-institutional study.

BACKGROUND Hurthle cell metaplasia is common in hyperplastic nodules, particularly within the setting of lymphocytic thyroiditis (LT). The Bethesda System for Reporting Thyroid Cytopathology indicates that it is acceptable to classify Hurthle cell-predominant fine-needle aspiration (HC FNA) specimens as atypia of undetermined significance (AUS) rather than suspicious for a Hurthle cell neoplasm (HUR) within the setting of multiple nodules or known LT. The goal of the current study was to address whether this approach is justified. METHODS HC FNA specimens were identified and correlated with ultrasound and surgical pathology reports if available. Multinodularity was determined based on findings on macroscopic examination if imaging results were unavailable. RESULTS A total of 698 HC FNA specimens were identified, including 576 resected nodules, 455 of which (79%) were benign. The overall risk of malignancy for HUR was 27%, whereas the risk of malignancy for AUS was 10%. The mean size of the benign nodules was 2.1 cm on surgical resection specimens, with multiple nodules noted in 293 cases (64%) and histologic LT noted in 116 cases (25%). The mean size of the malignant nodules was 2.8 cm, with multiple nodules and histologic LT noted in 74 cases (61%) and 22 cases (18%), respectively. The malignancy rate did not differ between solitary or multiple nodules (P = .52) or in the presence or absence of LT (P = .12). However, size did significantly differ between malignant and benign nodules (P < 0.01). CONCLUSIONS The malignancy rate did not differ significantly in the presence of multiple nodules or LT, although the latter demonstrated a statistical trend. A diagnosis of AUS over HUR based solely on the presence of multinodularity is not warranted.
The Impact of Tax Refund Delays on the Experience of Hardship and Unsecured Debt

The Earned Income Tax Credit (EITC) provides substantial financial support to low-income workers, yet around a quarter of EITC payments are estimated to be erroneous or fraudulent. Beginning in 2017, the Protecting Americans from Tax Hikes Act of 2015 requires the Internal Revenue Service to spend additional time processing early EITC claims, delaying the issuance of tax refunds. Leveraging unique data, we investigate how delayed tax refunds affected the experience of hardship and unsecured debt among EITC recipients. We find that early filers experienced increased food insecurity relative to later filers after the implementation of the refund delay.
Clonal hematopoiesis in the inherited bone marrow failure syndromes

Inherited bone marrow failure syndromes (IBMFSs) are characterized by ineffective hematopoiesis and increased risk for developing myeloid malignancy. The pathophysiologies of different IBMFSs are variable and can relate to defects in diverse biological processes, including DNA damage repair (Fanconi anemia), telomere maintenance (dyskeratosis congenita), and ribosome biogenesis (Diamond-Blackfan anemia, Shwachman-Diamond syndrome). Somatic mutations leading to clonal hematopoiesis have been described in IBMFSs, but the distinct mechanisms by which mutations drive clonal advantage in each disease and their associations with leukemia risk are not well understood. Clinical observations and laboratory models of IBMFSs suggest that the germline deficiencies establish a qualitatively impaired functional state at baseline. In this context, somatic alterations can promote clonal hematopoiesis by improving the competitive fitness of specific hematopoietic stem cell clones. Some somatic alterations relieve baseline fitness constraints by normalizing the underlying germline deficit through direct reversion or indirect compensation, whereas others do so by subverting senescence or tumor-suppressor pathways. Clones with normalizing somatic mutations may have limited transformation potential that is due to retention of functionally intact fitness-sensing and tumor-suppressor pathways, whereas those with mutations that impair cellular elimination may have increased risk for malignant transformation that is due to subversion of tumor-suppressor pathways. Because clonal hematopoiesis is not deterministic of malignant transformation, rational surveillance strategies will depend on the ability to prospectively identify specific clones with increased leukemic potential. We describe a framework by which an understanding of the processes that promote clonal hematopoiesis in IBMFSs may inform clinical surveillance strategies.
Who cycles to work and where? A comparative multilevel analysis of urban commuters in the US and Mexico

Abstract In this paper, we develop comparable multilevel logistic models predicting whether a sample of 5.7 million workers commute by bicycle in the hundred largest urban areas in the US and Mexico. In both contexts, men in relatively poor households without motor vehicles are likeliest to cycle. The similarities in cycling commuters generally stop with these commonalities, however. The archetypal US bike commuter is a recent college graduate, lives by himself in a centrally located apartment in a moderate-to- high density city, like Portland, OR, and works in a relatively low-paying service sector job, perhaps at a restaurant or a not-for-profit. The archetypal Mexican bike commuter, by contrast, is in his mid-forties, has only a few years of formal education, lives with a large family in a house in the suburbs of either a small city or a dense metropolitan area, and commutes to a relatively low-paying agriculture, construction, or manufacturing job. Local context matters and the most effective public policies to promote urban cycling will almost certainly vary across national borders. For example, our analysis suggests that suburban cycling investments will likely do a lot more to support Mexican cyclists than US ones. Last, we conclude that there is a need for studies that include comparable measures of cycling infrastructure, local built environments, and non-work trips across national contexts.
Performance of Three Inherited Risk Measures for Predicting Prostate Cancer Incidence and Mortality: A Population-based Prospective Analysis.

Abstract Background Single nucleotide polymorphism–based genetic risk score (GRS) has been developed and validated for prostate cancer (PCa) risk assessment. As GRS is population standardized, its value can be interpreted as a relative risk to the general population. Objective To compare the performance of GRS with two guideline-recommended inherited risk measures, family history (FH) and rare pathogenic mutations (RPMs), for predicting PCa incidence and mortality. Design, setting, and participants A prospective cohort was derived from the UK Biobank where 208 685 PCa diagnosis-free participants at recruitment were followed via the UK cancer and death registries. Outcome measurements and statistical analysis Rate ratios (RRs) of PCa incidence and mortality for FH (positive vs negative), RPMs (carriers vs noncarriers), and GRS (top vs bottom quartile) were measured. Results and limitations After a median follow-up of 9.67 yr, 6890 incident PCa cases (419 died of PCa) were identified. Each of the three measures was significantly associated with PCa incidence in univariate analyses; RR (95 % confidence interval [CI]) values were 1.88 (1.75–2.01) for FH, 2.89 (1.89–4.25) for RPMs, and 1.97(1.87–2.07) for GRS (all p Conclusions This population-based prospective study suggests that GRS complements two guideline-recommended inherited risk measures (FH and RPMs) for stratifying the risk of PCa incidence and mortality. Patient summary In a large population-based prostate cancer (PCa) prospective study derived from UK Biobank, genetic risk score (GRS) complements two guideline-recommended inherited risk measures (family history and rare pathogenic mutations) in predicting PCa incidence and mortality. These results provide critical data for including GRS in PCa risk assessment.
A Brownian Motion Foundation for Informational Diversity and Proximity, with Application to Rational Expectations Equilibrium.

We propose a tractable new informational framework for large economies with informationally heterogeneous individuals, and then apply it to analyze rational expectations equilibria. Our framework subsumes both public and conditionally independent private signals as special cases, but most importantly captures informational geography and social network effects. Our approach is to identify agents in a formally static world with moments in time: Agent t's signal is then a time-t realization of a Gaussian stochastic process with a known covariance function and uncertain mean. Individuals differ by their social weighting function used in this stochastic process. As an application, we explore rational expectations equilibria with conditionally correlated information. We find that the behaviour of prices and investors substantially differs from the world with conditionally independent signals. For instance, an agent's price impact is no longer solely determined by her signal's precision. Furthermore, investors may trade against their information and, in particular, rationally trade on different sides of the market at a public announcement. In a focal example of a circular world, we explore how correlation affects market efficiency and expected prices. We find, for instance, that for a fixed precision of individual signals, prices convey less information as the quality of aggregate information improves, provided the signal correlation is high enough.
Collaborative response and social capital theory in the context of disaster management

Disaster management in developing countries is an ongoing challenge. This paper investigates government-non-profit partnership for disaster management in a western state of India. Applying the interview method, the study focuses on the challenges facing government and non-profit organisations in their cross-sector collaboration initiatives, using social capital theory as a framework. The findings indicate that elements of social capital, such as trust and collaboration, are important for establishing a network of relationships to respond to the aftermath of disasters. This will generate norms, shared meaning, and common values among the network of organisations from both sectors. Such common understanding of vision and goals will help collaborations at the time of emergency events and reduce the challenges of networked relationships.
Tissue-specific differences in HIV DNA levels and mechanisms that govern HIV transcription in blood, gut, genital tract and liver in ART-treated women.

Author(s): Moron-Lopez, Sara; Xie, Guorui; Kim, Peggy; Siegel, David A; Lee, Sulggi; Wong, Joseph K; Price, Jennifer C; Elnachef, Najwa; Greenblatt, Ruth M; Tien, Phyllis C; Roan, Nadia R; Yukl, Steven A | Abstract: IntroductionSex-specific differences affect multiple aspects of HIV infection, yet few studies have quantified HIV levels in tissues from women. Since an HIV functional cure will likely require a major reduction of infected cells from most tissues, we measured total and intact HIV DNA and the HIV transcription profile in blood, gut, genital tract and liver from HIV-positive antiretroviral therapy (ART) -treated women.MethodsPeripheral blood mononuclear cells (PBMC) and biopsies from the gastrointestinal (ileum, colon, rectosigmoid +/- liver) and genital (ectocervix, endocervix and endometrium) tracts were collected from 6 ART-treated (HIV RNAnln200ncopies/mL) women. HIV DNA (total and intact) and levels of read-through, initiated (total), 5'elongated, polyadenylated and multiply spliced HIV transcripts were measured by droplet digital PCR. Immunophenotyping of cells was performed using Cytometry by time of flight (CyTOF).ResultsWe detected total HIV DNA in all tissues and intact HIV DNA in blood, ileum, colon, rectosigmoid and ectocervix. Initiated HIV transcripts per provirus were higher in PBMC and endometrium than in ileum, colon, rectosigmoid, ectocervix or endocervix, and higher in the rectum than either ileum or colon. 5'Elongated HIV transcripts per provirus were comparable in PBMC and endometrium, but higher than in gut or cervical samples. Polyadenylated and multiply spliced HIV transcripts were detected in PBMC (6/6 and 3/6 individuals respectively), but rarely in the tissues.ConclusionsThese results suggest tissue-specific differences in the mechanisms that govern HIV expression, with lower HIV transcription in most tissues than blood. Therapies aimed at disrupting latency, such as latency-reversing or latency-silencing agents, will be required to penetrate into multiple tissues and target different blocks to HIV transcription.
The Impact of Air Pollution on Human Capital Wealth

Abstract Human capital, measured as the discounted sum of expected lifetime earnings, is the largest component of global wealth (64% in 2014, the latest year currently available from the World Bank ’s program on comprehensive wealth). Building human capital is a key driver of economic development. Although human capital accounts for only 41% of national wealth in low-income countries, it constitutes 70% of national wealth in high-income OECD countries and it is growing faster than any other asset. However, air pollution can cause premature mortality, reducing the accumulation of human capital. This chapter measures the impact of from both indoor and outdoor air pollution as the gap between human capital estimated under actual pollution conditions and the hypothetical value of human capital if there were no premature deaths from air pollution. Losses of human capital from air pollution have declined globally from 1995 to 2014 but vary greatly across countries.
Imagination and the Experience of Moral Objectivity

Different notions of objectivity support different notions of what is required for a moral value or obligation to be experienced as objective. If the objectivity of a property (moral or otherwise) requires that it can exist even when we fail to notice its existence, then experiencing a property (moral or otherwise) as objective will require that we imagine it appearing in some way that is not presently available to us. Explaining what that imagining involves is the central task of this paper. Defending the epistemic value of such imagining is a secondary aim.
HSP90 function is required for T2R bitter taste receptor nitric oxide production and innate immune responses in human airway epithelial cells and macrophages

Bitter taste receptors (T2Rs) are G protein-coupled receptors (GPCRs) expressed in various cell types including ciliated airway epithelial cells and macrophages. T2Rs in these two airway innate immune cell types are activated by bitter products, including those secreted by common airway pathogens like Pseudomonas aeruginosa, leading to Ca2+-dependent activation of endothelial nitric oxide (NO) synthase (eNOS). NO production leads to enhanced mucociliary clearance and direct antibacterial effects by ciliated epithelial cells as well as increased phagocytosis by macrophages. Using biochemistry and live cell imaging, we explored the role of heat shock protein 90 (HSP90) in regulating T2R-dependent NO pathways in primary sinonasal epithelial cells, primary monocyte-derived macrophages, and a human bronchiolar cell line (H441). We used immunofluorescence to show that H441 cells express eNOS and certain T2Rs and that the bitterant denatonium benzoate activates NO production in an HSP90-dependent manner in cells grown either as submerged cultures and at air liquid interface. In primary sinonasal epithelial cells, we determined that HSP-90 inhibition reduces T2R-stimulated NO production and ciliary beating which are crucial for pathogen clearance. In primary monocyte-derived macrophages, we found that HSP-90 is integral to T2R-stimulated NO production and phagocytosis of FITC-labeled Escherichia coli and pHrodo-Staphylococcus aureus. Our study demonstrates that HSP90 serves an innate immune role by regulating NO production downstream of T2R signaling by augmenting eNOS activation without impairing upstream calcium signaling. These findings suggest that HSP90 plays an important role in airway antibacterial innate immunity and may be an important target in airway diseases like chronic rhinosinusitis, asthma, or cystic fibrosis.
Letter to the editor to update the article "Remote monitoring for heart failure using implantable devices: a systematic review, meta-analysis, and meta-regression of randomized controlled trials".

Our recently published systematic review and meta-analysis of heart failure (HF) remote monitoring using implantable devices (Hajduczok et al. in HF Reviews 1-20, 1) has been updated to reflected new data from the GUIDE-HF trial (Lindenfeld et al. in Lancet 398(10304):991-1001, 2). Data from randomized controlled trials (RCTs) was assessed to determine the effectiveness of implantable remote monitoring on the improvement of outcomes in HF patients. With the inclusion of the data from 1000 patients followed for 12 months in GUIDE-HF, our conclusions remain unchanged: Compared to standard of care, remote monitoring using implantable devices did not reduce mortality, CV, or HF hospitalizations. However, right ventricular/pulmonary pressure monitoring may reduce HF hospitalizations.
Optimal Management of Proliferative Verrucous Leukoplakia: A Systematic Review of the Literature.

ObjectiveProliferative verrucous leukoplakia (PVL) is a rare and recalcitrant form of leukoplakia. The purpose of this review is to further characterize the risk factors, clinical course, and optimal treatment for this highly aggressive, premalignant lesion.Data SourcesTwenty-six articles on PVL with a total of 329 PVL cases.Review MethodsA systematic review of the literature using Ovid, PubMed, Cochrane Database, and gray literature was conducted of all PVL cases reported between 1985 and 2014. Inclusion criteria required reporting of patient follow-up and recurrence rates. Data were analyzed using descriptive statistics. Student t test and Fisher exact test were used to identify factors associated with malignant transformation.ResultsThe mean patient age was 63.9 years. Most patients were female (66.9%) and nontobacco users (65.22%). Mean follow-up was 7.4 years, with an average of 9.0 biopsies per patient during this period. Proliferative verrucous leukoplakia exhibited histopathologic features along a...
The Hyperbolic Map and Applications to the Linear Quadratic Regulator

Qualitative dynamics of the hyperbolic iteration map.- General solution derivation for the hyperbolic iteration map.- Appendix A extension to the multidimensional case.- Appendix B some interesting applications of the hyperbolic map.- The linear quadratic regulator - Background.- The linear quadratic regulator under negative Q.- Conclusion.
The limits of bodily integrity : abortion, adultery, and rape legislation in comparative perspective

Contents: Introduction Reproduction and race suicide Sexuality and citizenship formation Defining Europe Women and the political norm Conclusion Bibliography Index.
Working for Well-Being: Uncovering the Protective Benefits of Work Through Mixed Methods Analysis

Previous research mostly defines the benefits of work as the absence of unemployment’s negative outcomes or as benefits to employers, such as increased productivity. This study uses mixed methods to investigate the ways that work can enhance the well-being of the worker. Two hundred and two participants from a rural area participated in semi-structured qualitative interviews and quantitative surveys. Participants’ qualitative discussions of work in the interviews were coded with grounded theory. The majority (74.8 %) of participants mentioned work at least once during the interview, which focused on prominent moments in their life stories, and 53.3 % of work mentions were positive. Two main themes encompassing the protective benefits of work arose: self-oriented benefits and other-oriented benefits. Each main theme was further divided into three subthemes. Self-oriented subthemes were autonomy, personal development, and empowerment; other-oriented subthemes were providing for dependents, generativity, and helping others. Participants spoke about how each of these benefits enhances their well-being and happiness. The empowerment subtheme was positively correlated with workplace integration and negatively correlated with financial strain. This study uncovered protective benefits of work that have not been addressed by previous scholarship. Qualitative data provided the flexibility to explore work-related domains for which quantitative scales do not currently exist. Work is one of the main activities of most adults, and the study of the psychological benefits of work can improve our understanding of adult well-being and happiness.