Ligation of protease-activated receptor 1 enhances alpha(v)beta(6) integrin-dependent TGF-beta activation and promotes acute lung injury

Activation of latent TGF-beta by the alpha(v)beta(6) integrin is a critical step in the development of acute lung injury. However, the mechanism by which a alpha(v)beta(6)-mediated TGF-beta activation is regulated has not been identified. We show that thrombin, and other agonists of protease-activated receptor 1(PAR1), activate TGF-beta in an alpha(v)beta(6) integrin-specific manner. This effect is PART specific and is mediated by RhoA and Rho kinase. Intratracheal instillation of the PART-specific peptide TFLLRN increases lung edema during high-tidal-volume ventilation, and this effect is completely inhibited by a blocking antibody against the alpha(v)beta(6) integrin. Instillation of TFLLRN during high-tidal-volume ventilation is associated with increased pulmonary TGF-beta activation; however, this is not observed in Itgb6(-/-) mice. Furthermore, Itgb6(-/-) mice are also protected from ventilator-induced lung edema. We also demonstrate that pulmonary edema and TGF-beta activity are similarly reduced in Par1(-/-) mice following bleomycin-induced lung injury. These results suggest that PART-mediated enhancement of a alpha(v)beta(6)-dependent TGF-beta activation could be one mechanism by which activation of the coagulation cascade contributes to the development of acute lung injury, and they identify PART and the alpha(v)beta(6) integrin as potential therapeutic targets in this condition

A Centrality Measure for Urban Networks Based on the Eigenvector Centrality Concept.

A massive amount of information as geo-referenced data is now emerging from the digitization of contemporary cities. Urban streets networks are characterized by a fairly uniform degree distribution and a low degree range. Therefore, the analysis of the graph constructed from the topology of the urban layout does not provide significant information when studying topology–based centrality. On the other hand, we have collected geo-located data about the use of various buildings and facilities within the city. This does provide a rich source of information about the importance of various areas. Despite this, we still need to consider the influence of topology, as this determines the interaction between different areas. In this paper, we propose a new model of centrality for urban networks based on the concept of Eigenvector Centrality for urban street networks which incorporates information from both topology and data residing on the nodes. So, the centrality proposed is able to measure the influence of two factors, the topology of the network and the geo-referenced data extracted from the network and associated to the nodes. We detail how to compute the centrality measure and provide the rational behind it. Some numerical examples with small networks are performed to analyse the characteristics of the model. Finally, a detailed example of a real urban street network is discussed, taking a real set of data obtained from a fieldwork, regarding the commercial activity developed in the city

The role of superficial geology in controlling groundwater recharge in the weathered crystalline basement of semi-arid Tanzania

Study region: Little Kinyasungwe River Catchment, central semi-arid Tanzania. Study focus: The structure and hydraulic properties of superficial geology can play a crucial role in controlling groundwater recharge in drylands. However, the pathways by which groundwater recharge occurs and their sensitivity to environmental change remain poorly resolved. Geophysical surveys using Electrical Resistivity Tomography (ERT) were conducted in the study region and used to delineate shallow subsurface stratigraphy in conjunction with borehole logs. Based on these results, a series of local-scale conceptual hydrogeological models was produced and collated to generate a 3D conceptual model of groundwater recharge to the wellfield. New hydrological insights for the region: We propose that configurations of superficial geology control groundwater recharge in dryland settings as follows: 1) superficial sand deposits act as collectors and stores that slowly feed recharge into zones of active faulting; 2) these fault zones provide permeable pathways enabling greater recharge to occur; 3) ‘windows’ within layers of smectitic clay that underlie ephemeral streams may provide pathways for focused recharge via transmission losses; and 4) overbank flooding during high intensity precipitation events increases the probability of activating such permeable pathways. These conceptual models provide a physical basis to improve numerical models of groundwater recharge in drylands, and a conceptual framework to evaluate strategies (e.g., Managed Aquifer Recharge) to artificially enhance the availability of groundwater resources in these regions

Disentangling the Effects of Vapor Pressure Deficit and Soil Water Availability on Canopy Conductance in a Seasonal Tropical Forest During the 2015 El Niño Drought

Water deficit in the atmosphere and soil are two key interactive factors that constrain transpiration and vegetation productivity. It is not clear which of these two factors is more important for the water and carbon flux response to drought stress in ecosystems. In this study, field data and numerical modeling were used to isolate their impact on evapotranspiration (ET) and gross primary productivity (GPP) at a tropical forest site in Barro Colorado Island (BCI), Panama, focusing on their response to the drought induced by the El Niño event of 2015–2016. Numerical simulations were performed using a plant hydrodynamic scheme (HYDRO) and a heuristic approach that ignores stomatal sensitivity to leaf water potential in the Energy Exascale Earth System Model (E3SM) Land Model (ELM). The sensitivity of canopy conductance (Gs) to vapor pressure deficit (VPD) obtained from eddy-covariance fluxes and measured sap flux shows that, at both ecosystem and plant scale, soil water stress is more important in limiting Gs than VPD at BCI during the El Niño event. The model simulations confirmed the importance of water stress limitation on Gs, but overestimated the VPD impact on Gs compared to that estimated from the observations. We also found that the predicted soil moisture is less sensitive to the diversity of plant hydraulic traits than ET and GPP. During the dry season at BCI, seasonal ET, especially soil evaporation at VPD \u3e 0.42 kPa, simulated using HYDRO and ELM, were too strong and will require alternative parameterizations

Drift Velocities and Momentum Distributions of Hot Carriers in MOSFETs at Low Supply Voltages

Abstract: In this paper we determine the momentum distribution and drift velocity of hot carriers in silicon under the condition of finite supply energy. We show that the momentum distribution varies between the nearly isotropic in high field to strongly anisotropic when the carrier's energy is comparable to the supply energy. 1

Identification of key parameters controlling demographically structured vegetation dynamics in a land surface model: CLM4.5(FATES)

Vegetation plays an important role in regulating global carbon cycles and is a key component of the Earth system models (ESMs) that aim to project Earth's future climate. In the last decade, the vegetation component within ESMs has witnessed great progress from simple "big-leaf" approaches to demographically structured approaches, which have a better representation of plant size, canopy structure, and disturbances. These demographically structured vegetation models typically have a large number of input parameters, and sensitivity analysis is needed to quantify the impact of each parameter on the model outputs for a better understanding of model behavior. In this study, we conducted a comprehensive sensitivity analysis to diagnose the Community Land Model coupled to the Functionally Assembled Terrestrial Simulator, or CLM4.5(FATES). Specifically, we quantified the first- and second-order sensitivities of the model parameters to outputs that represent simulated growth and mortality as well as carbon fluxes and stocks for a tropical site with an extent of 1×1°. While the photosynthetic capacity parameter (Vc;max25) is found to be important for simulated carbon stocks and fluxes, we also show the importance of carbon storage and allometry parameters, which determine survival and growth strategies within the model. The parameter sensitivity changes with different sizes of trees and climate conditions. The results of this study highlight the importance of understanding the dynamics of the next generation of demographically enabled vegetation models within ESMs to improve model parameterization and structure for better model fidelity

A randomized trial of mail vs. telephone invitation to a community-based cardiovascular health awareness program for older family practice patients [ISRCTN61739603]

BACKGROUND: Family physicians can play an important role in encouraging patients to participate in community-based health promotion initiatives designed to supplement and enhance their in-office care. Our objectives were to determine effective approaches to invite older family practice patients to attend cardiovascular health awareness sessions in community pharmacies, and to assess the feasibility and acceptability of a program incorporating invitation by physicians and feedback to physicians. METHODS: We conducted a prospective randomized trial with 1 family physician practice and 5 community pharmacies in Dundas, Ontario. Regular patients 65 years or older (n = 235) were randomly allocated to invitation by mail or telephone to attend pharmacy cardiovascular health awareness sessions led by volunteer peer health educators. A health record review captured blood pressure status, monitoring and control. At the sessions, volunteers helped patients to measure blood pressure using in-store machines and a validated portable device (BPM-100), and recorded blood pressure readings and self-reported cardiovascular risk factors. We compared attendance rates in the mail and telephone invitation groups and explored factors potentially associated with attendance. RESULTS: The 119 patients invited by mail and 116 patients contacted by telephone had a mean age of 75.7 (SD, 6.4) years and 46.8% were male. Overall, 58.3% (137/235) of invitees attended a pharmacy cardiovascular health awareness session. Patients invited by telephone were more likely to attend than those invited by mail (72.3% vs. 44.0%, OR 3.3; 95%CI 1.9–5.7; p < 0.001). CONCLUSION: While the attendance in response to a telephone invitation was higher, response to a single letter was substantial. Attendance rates indicated considerable interest in community-based cardiovascular health promotion activities. A large-scale trial of a pharmacy cardiovascular health awareness program for older primary care patients is feasible

Abatement costs of alternative tax systems to regulate agricultural nitrogen loss

Nitrogen emissions from agriculture are considered an important environmental problem in Denmark motivating consideration of different tax schemes as regulatory instruments. In this paper, input/output behaviour of Danish pig farmers is estimated with farm level panel data using the dual profit function approach, and emission functions for nitrogen loss are derived. With the estimated model we are able to compare cost-effectiveness of a comprehensive Pigouvian tax on nitrogen loss with simpler tax schemes that focus on nitrogen use. We find that both a fertilizer tax and a feed tax generate substantially higher abatement costs than Pigouvian incentives. A tax on nitrogen in all inputs will, on the other hand, only generate a marginal increase in abatement costs. These results are of interest because a tax on all nitrogen inputs is easier to implement than a comprehensive nitrogen loss tax. Our result implies that even a limited administrative cost advantage may make the input tax preferable to implementing Pigouvian incentives through an nitrogen loss tax

Homo- and Heterosubtypic Low Pathogenic Avian Influenza Exposure on H5N1 Highly Pathogenic Avian Influenza Virus Infection in Wood Ducks (Aix sponsa)

Wild birds in the Orders Anseriformes and Charadriiformes are the natural reservoirs for avian influenza (AI) viruses. Although they are often infected with multiple AI viruses, the significance and extent of acquired immunity in these populations is not understood. Pre-existing immunity to AI virus has been shown to modulate the outcome of a highly pathogenic avian influenza (HPAI) virus infection in multiple domestic avian species, but few studies have addressed this effect in wild birds. In this study, the effect of pre-exposure to homosubtypic (homologous hemagglutinin) and heterosubtypic (heterologous hemagglutinin) low pathogenic avian influenza (LPAI) viruses on the outcome of a H5N1 HPAI virus infection in wood ducks (Aix sponsa) was evaluated. Pre-exposure of wood ducks to different LPAI viruses did not prevent infection with H5N1 HPAI virus, but did increase survival associated with H5N1 HPAI virus infection. The magnitude of this effect on the outcome of the H5N1 HPAI virus infection varied between different LPAI viruses, and was associated both with efficiency of LPAI viral replication in wood ducks and the development of a detectable humoral immune response. These observations suggest that in naturally occurring outbreaks of H5N1 HPAI, birds with pre-existing immunity to homologous hemagglutinin or neuraminidase subtypes of AI virus may either survive H5N1 HPAI virus infection or live longer than naïve birds and, consequently, could pose a greater risk for contributing to viral transmission and dissemination. The mechanisms responsible for this protection and/or the duration of this immunity remain unknown. The results of this study are important for surveillance efforts and help clarify epidemiological data from outbreaks of H5N1 HPAI virus in wild bird populations

The U.S. training institute for dissemination and implementation research in health

Abstract Background The science of dissemination and implementation (D&amp;I) is advancing the knowledge base for how best to integrate evidence-based interventions within clinical and community settings and how to recast the nature or conduct of the research itself to make it more relevant and actionable in those settings. While the field is growing, there are only a few training programs for D&amp;I research; this is an important avenue to help build the field’s capacity. To improve the United States’ capacity for D&amp;I research, the National Institutes of Health and Veterans Health Administration collaborated to develop a five-day training institute for postdoctoral level applicants aspiring to advance this science. Methods We describe the background, goals, structure, curriculum, application process, trainee evaluation, and future plans for the Training in Dissemination and Implementation Research in Health (TIDIRH). Results The TIDIRH used a five-day residential immersion to maximize opportunities for trainees and faculty to interact. The train-the-trainer-like approach was intended to equip participants with materials that they could readily take back to their home institutions to increase interest and further investment in D&amp;I. The TIDIRH curriculum included a balance of structured large group discussions and interactive small group sessions. Thirty-five of 266 applicants for the first annual training institute were accepted from a variety of disciplines, including psychology (12 trainees); medicine (6 trainees); epidemiology (5 trainees); health behavior/health education (4 trainees); and 1 trainee each from education &amp; human development, health policy and management, health services research, public health studies, public policy and social work, with a maximum of two individuals from any one institution. The institute was rated as very helpful by attendees, and by six months after the institute, a follow-up survey (97% return rate) revealed that 72% had initiated a new grant proposal in D&amp;I research; 28% had received funding, and 77% had used skills from TIDIRH to influence their peers from different disciplines about D&amp;I research through building local research networks, organizing formal presentations and symposia, teaching and by leading interdisciplinary teams to conduct D&amp;I research. Conclusions The initial TIDIRH training was judged successful by trainee evaluation at the conclusion of the week’s training and six-month follow-up, and plans are to continue and possibly expand the TIDIRH in coming years. Strengths are seen as the residential format, quality of the faculty and their flexibility in adjusting content to meet trainee needs, and the highlighting of concrete D&amp;I examples by the local host institution, which rotates annually. Lessons learned and plans for future TIDIRH trainings are summarized