Distributions of Human Exposure to Ozone During Commuting Hours in Connecticut using the Cellular Device Network

Epidemiologic studies have established associations between various air pollutants and adverse health outcomes for adults and children. Due to high costs of monitoring air pollutant concentrations for subjects enrolled in a study, statisticians predict exposure concentrations from spatial models that are developed using concentrations monitored at a few sites. In the absence of detailed information on when and where subjects move during the study window, researchers typically assume that the subjects spend their entire day at home, school or work. This assumption can potentially lead to large exposure assignment bias. In this study, we aim to determine the distribution of the exposure assignment bias for an air pollutant (ozone) when subjects are assumed to be static as compared to accounting for individual mobility. To achieve this goal, we use cell-phone mobility data on approximately 400,000 users in the state of Connecticut during a week in July, 2016, in conjunction with an ozone pollution model, and compare individual ozone exposure assuming static versus mobile scenarios. Our results show that exposure models not taking mobility into account often provide poor estimates of individuals commuting into and out of urban areas: the average 8-hour maximum difference between these estimates can exceed 80 parts per billion (ppb). However, for most of the population, the difference in exposure assignment between the two models is small, thereby validating many current epidemiologic studies focusing on exposure to ozone

Radical Prostatectomy: Hospital volumes and surgical volumes – does practice make perfect?

<p>Abstract</p> <p>Background</p> <p>Between the years 1993 and 2003, more than 140,000 men underwent radical prostatectomy (RP), thus making RP one of the most common treatment options for localized prostate cancer in the United States.</p> <p>Discussion</p> <p>Localized prostate cancer treated by RP is one of the more challenging procedures performed by urologic surgeons. Studies suggest a definite learning curve in performing this procedure with optimal results noted after performing >500 RPs. But is surgical volume everything? How do hospital volumes of RP weigh in? Could fellowship training in RP reduce the critical volume needed to reach an 'experienced' level?</p> <p>Summary</p> <p>As we continue to glean data as to how to optimize outcomes after RP, we must not only consider surgeon and hospital volumes of RP, but also consider training of the individual surgeon.</p

Distribution of human exposure to ozone during commuting hours in Connecticut using the cellular device network

Epidemiologic studies have established associations between various air pollutants and adverse health outcomes for adults and children. Due to high costs of monitoring air pollutant concentrations for subjects enrolled in a study, statisticians predict exposure concentrations from spatial models that are developed using concentrations monitored at a few sites. In the absence of detailed information on when and where subjects move during the study window, researchers typically assume that the subjects spend their entire day at home, school, or work. This assumption can potentially lead to large exposure assignment bias. In this study, we aim to determine the distribution of the exposure assignment bias for an air pollutant (ozone) when subjects are assumed to be static as compared to accounting for individual mobility. To achieve this goal, we use cell-phone mobility data on approximately 400,000 users in the state of Connecticut, USA during a week in July 2016, in conjunction with an ozone pollution model, and compare individual ozone exposure assuming static versus mobile scenarios. Our results show that exposure models not taking mobility into account often provide poor estimates of individuals commuting into and out of urban areas: the average 8-h maximum difference between these estimates can exceed 80 parts per billion (ppb). However, for most of the population, the difference in exposure assignment between the two models is small, thereby validating many current epidemiologic studies focusing on exposure to ozone

Expression of Ifnlr1 on intestinal epithelial cells is critical to the antiviral effects of IFN-lambda against norovirus and reovirus

Lambda interferon (IFN-λ) has potent antiviral effects against multiple enteric viral pathogens, including norovirus and rotavirus, in both preventing and curing infection. Because the intestine includes a diverse array of cell types, however, the cell(s) upon which IFN-λ acts to exert its antiviral effects is unclear. Here, we sought to identify IFN-λ-responsive cells by generation of mice with lineage-specific deletion of the receptor for IFN-λ, Ifnlr1. We found that expression of IFNLR1 on intestinal epithelial cells (IECs) in the small intestine and colon is required for enteric IFN-λ antiviral activity. IEC Ifnlr1 expression also determines the efficacy of IFN-λ in resolving persistent murine norovirus (MNoV) infection and regulates fecal shedding and viral titers in tissue. Thus, the expression of Ifnlr1 by IECs is necessary for the response to both endogenous and exogenous IFN-λ. We further demonstrate that IEC Ifnlr1 expression is required for the sterilizing innate immune effects of IFN-λ by extending these findings in Rag1-deficient mice. Finally, we assessed whether our findings pertained to multiple viral pathogens by infecting mice specifically lacking IEC Ifnlr1 expression with reovirus. These mice phenocopied Ifnlr1-null animals, exhibiting increased intestinal tissue titers and enhanced reovirus fecal shedding. Thus, IECs are the critical cell type responding to IFN-λ to control multiple enteric viruses. This is the first genetic evidence that supports an essential role for IECs in IFN-λ-mediated control of enteric viral infection, and these findings provide insight into the mechanism of IFN-λ-mediated antiviral activity. IMPORTANCE Human noroviruses (HNoVs) are the leading cause of epidemic gastroenteritis worldwide. Type III interferons (IFN-λ) control enteric viral infections in the gut and have been shown to cure mouse norovirus, a small-animal model for HNoVs. Using a genetic approach with conditional knockout mice, we identified IECs as the dominant IFN-λ-responsive cells in control of enteric virus infection in vivo. Upon murine norovirus or reovirus infection, Ifnlr1 depletion in IECs largely recapitulated the phenotype seen in Ifnlr1(−/−) mice of higher intestinal tissue viral titers and increased viral shedding in the stool. Moreover, IFN-λ-mediated sterilizing immunity against murine norovirus requires the capacity of IECs to respond to IFN-λ. These findings clarify the mechanism of action of this cytokine and emphasize the therapeutic potential of IFN-λ for treating mucosal viral infections

Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy

It is generally believed that increase in adult contractile cardiac mass can be accomplished only by hypertrophy of existing myocytes. Documentation of myocardial regeneration in acute stress has challenged this dogma and led to the proposition that myocyte renewal is fundamental to cardiac homeostasis. Here we report that in human aortic stenosis, increased cardiac mass results from a combination of myocyte hypertrophy and hyperplasia. Intense new myocyte formation results from the differentiation of stem-like cells committed to the myocyte lineage. These cells express stem cell markers and telomerase. Their number increased >13-fold in aortic stenosis. The finding of cell clusters with stem cells making the transition to cardiogenic and myocyte precursors, as well as very primitive myocytes that turn into terminally differentiated myocytes, provides a link between cardiac stem cells and myocyte differentiation. Growth and differentiation of these primitive cells was markedly enhanced in hypertrophy, consistent with activation of a restricted number of stem cells that, through symmetrical cell division, generate asynchronously differentiating progeny. These clusters strongly support the existence of cardiac stem cells that amplify and commit to the myocyte lineage in response to increased workload. Their presence is consistent with the notion that myocyte hyperplasia significantly contributes to cardiac hypertrophy and accounts for the subpopulation of cycling myocytes

How to Motivate Your Dragon: Teaching Goal-Driven Agents to Speak and Act in Fantasy Worlds.

We seek to create agents that both act and communicate with other agents in pursuit of a goal. Towards this end, we extend LIGHT (Urbanek et al. 2019)—a large-scale crowd-sourced fantasy text-game—with a dataset of quests. These contain natural language motivations paired with in-game goals and human demonstrations; completing a quest might require dialogue or actions (or both). We introduce a reinforcement learning system that (1) incorporates large-scale language modeling-based and commonsense reasoning-based pre-training to imbue the agent with relevant priors; and (2) leverages a factorized action space of action commands and dialogue, balancing between the two. We conduct zero-shot evaluations using held-out human expert demonstrations, showing that our agents are able to act consistently and talk naturally with respect to their motivations

Syntactic or semantic gender agreement in Dutch, German, and German learner Dutch. A speeded grammaticality judgement task

Dutch is currently undergoing a ‘resemanticisation’ of its pronominal gender, in which syntactic agreement is replaced with a system in which pronouns are chosen in accordance with the degree of individuation of the antecedent. Current accounts of resemanticisation link the process to the extent to which the three-way nominal gender distinctions are still entrenched. Using experimental data gathered with speeded grammaticality judgements from speakers of both Netherlandic and Belgian varieties of Dutch, of German, and of German learners of Dutch, we unambiguously relate the rise of semantic agreement in Dutch to an increased uncertainty with respect to grammatical gender. In addition, reaction time measurements suggest that an agreement system with a strong propensity towards grammatical agreement allows for faster processing of agreement relations than systems in which semantic agreement plays a larger role.Im Niederländischen findet zurzeit eine ‘Resemantisierung’ des pronominalen Genus statt, durch die syntaktische Kongruenz zunehmend durch ein System ersetzt wird, in dem die Wahl pronominaler Formen vom Grad der Individuierung des Antezedenten abhängt. Es wurde vermutet, dass der Prozess mit dem Grad der Verankerung (entrenchment) des Drei-Genera-Systems zusammenhängt. Anhand von Grammatikalitätsurteilen unter Zeitdruck (speeded grammaticality judgements) mit Sprechern niederländischer und belgischer Varietäten und mit Sprechern des Deutschen durchgeführt, sowie auch mit deutschen Niederländischlernern, demonstrieren wir eindeutig den Zusammenhang zwischen der Zunahme semantischer Kongruenz und einer Unsicherheit in Bezug auf das grammatische Genus. Darüber hinaus sprechen die Analysen der Reaktionszeiten dafür, dass sein stark grammatisch basiertes Genussystem eine schnellere Verarbeitung von Kongruenzbeziehungen erlaubt als ein System, in dem semantische Kongruenz eine größere Rolle spielt

Childhood and adult social conditions and risk of stroke

Background: Socioeconomic conditions may strongly influence the risk of stroke. We tested the hypotheses that indexes of social status in different life periods including childhood are inversely associated with stroke risk and that there is a cumulative effect of social conditions during lifetime on the risk of stroke. Furthermore, we investigated whether social advancement compared to the parental generation is associated with reduced stroke risk. Methods: In a case-control study, we assessed parental professional status, highest school degree, professional education and the last professional activity in 370 consecutive patients with ischemic or hemorrhagic stroke or transient ischemic attack [TIA; age 60.7 +/- 12.8 years (mean +/- standard deviation); 31.1% women] and 370 age-and sex-matched control subjects randomly selected from the general population of the same area. Results: Higher level of school exams [odds ratio (OR) 0.58, 95% confidence interval (CI) 0.39-0.86], university or polytechnic high school degrees (OR 0.39, 95% CI 0.24-0.63), nonmanual (last or current) professional activity (OR 0.51, 95% CI 0.37-0.71) and father’s nonmanual professional activity (OR 0.64, 95% 0.43-0.97) were associated with a lower risk of stroke/TIA. Adjustment for vascular risk factors including current smoking and alcohol consumption reduced the strength of these associations and rendered them nonsignificant except for university or polytechnic high school degrees (OR 0.49, 95% CI 0.27-0.87). Additional adjustment for regular sports activity further attenuated the association between academic degrees and risk of stroke/TIA (OR 0.56, 95% CI 0.31-1.02). A score summarizing 4 lifetime social indexes was not independently associated with stroke risk (OR 0.67, 95% CI 0.39-1.16). Social advancement as assessed by changes from paternal manual work to nonmanual work in the index generation was more common among control subjects (23.5%) than patients (15.3%; p = 0.0097), but such advancement was not independently associated with stroke/TIA after adjustment for all covariables (OR 0.82, 95% CI 0.50–1.33). Conclusions: Socioeconomic conditions were inversely linked to the risk of stroke/TIA. These associations were strongly influenced by lifestyle factors such as smoking, alcohol consumption and mainly sports activity. Stroke preventive strategies may have a particularly large potential if they focus on such lifestyle habits in socially disadvantaged groups. Copyright © 2012 S. Karger AG, Base

Geophysics

Contains reports on three research projects