Theoretical investigation of transgastric and intraductal approaches for ultrasound-based thermal therapy of the pancreas.

BackgroundThe goal of this study was to theoretically investigate the feasibility of intraductal and transgastric approaches to ultrasound-based thermal therapy of pancreatic tumors, and to evaluate possible treatment strategies.MethodsThis study considered ultrasound applicators with 1.2 mm outer diameter tubular transducers, which are inserted into the tissue to be treated by an endoscopic approach, either via insertion through the gastric wall (transgastric) or within the pancreatic duct lumen (intraductal). 8 patient-specific, 3D, transient, biothermal and acoustic finite element models were generated to model hyperthermia (n = 2) and ablation (n = 6), using sectored (210°-270°, n = 4) and 360° (n = 4) transducers for treatment of 3.3-17.0 cm3 tumors in the head (n = 5), body (n = 2), and tail (n = 1) of the pancreas. A parametric study was performed to determine appropriate treatment parameters as a function of tissue attenuation, blood perfusion rates, and distance to sensitive anatomy.ResultsParametric studies indicated that pancreatic tumors up to 2.5 or 2.7 cm diameter can be ablated within 10 min with the transgastric and intraductal approaches, respectively. Patient-specific simulations demonstrated that 67.1-83.3% of the volumes of four sample 3.3-11.4 cm3 tumors could be ablated within 3-10 min using transgastric or intraductal approaches. 55.3-60.0% of the volume of a large 17.0 cm3 tumor could be ablated using multiple applicator positions within 20-30 min with either transgastric or intraductal approaches. 89.9-94.7% of the volume of two 4.4-11.4 cm3 tumors could be treated with intraductal hyperthermia. Sectored applicators are effective in directing acoustic output away from and preserving sensitive structures. When acoustic energy is directed towards sensitive structures, applicators should be placed at least 13.9-14.8 mm from major vessels like the aorta, 9.4-12.0 mm from other vessels, depending on the vessel size and flow rate, and 14 mm from the duodenum.ConclusionsThis study demonstrated the feasibility of generating shaped or conformal ablative or hyperthermic temperature distributions within pancreatic tumors using transgastric or intraductal ultrasound

Cellular localization and trafficking of vascular adhesion protein-1 as revealed by an N-terminal GFP fusion protein

Recent studies of vascular adhesion protein-1 (VAP-1) have greatly advanced our understanding of the important role this protein plays in the establishment and progression of inflammatory disease. To facilitate more detailed studies on the function of VAP-1, we developed a GFP-fusion protein that enabled us to monitor the trafficking of the protein in three selected cell types: hepatic sinusoidal endothelial cells, liver myofibroblasts and an hepatic stellate cell line (LX-2). The fusion protein was detected as punctate cytoplasmic GFP staining, but was present only at low levels at the cell surface in all cell types studied. The subcellular distribution of the protein was not altered in a catalytically inactive mutant form of the protein (Tyr471Phe) or in the presence of exogenous VAP-1 substrate (methylamine) or inhibitor (semicarbazide). The GFP-VAP-1 protein was localized to the Golgi apparatus (GM-130), endoplasmic reticulum (GRP94) and early endosomes (EEA-1). Additional staining for VAP-1 revealed that the overexpressed protein was also present in vesicles that were negative for GFP fluorescent signal and did not express EEA-1. We propose that these vesicles are responsible for recycling the fusion protein and that the fluorescence of the GFP moiety is quenched at the low pH within these vesicles. This feature of the protein makes it well suited for live cell imaging studies where we wish to track protein that is being actively trafficked within the cell in preference to that which is being recycled. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00702-013-1003-3) contains supplementary material, which is available to authorized users

Optimization of input parameters to a CN neuron model to simulate its activity during and between epileptic absence seizures

Peer reviewe

Recommendations to improve wildlife exposure estimation for development of soil screening and cleanup values

An integral component in the development of media-specific values for the ecological risk assessment of chemicals is the derivation of safe levels of exposure for wildlife. Although the derivation and subsequent application of these values can be used for screening purposes, there is a need to identify the threshold for effects when making remedial decisions during site-specific assessments. Methods for evaluation of wildlife exposure are included in the US Environmental Protection Agency (USEPA) ecological soil screening levels (Eco-SSLs), registration, evaluation, authorization, and restriction of chemicals (REACH), and other risk-based soil assessment approaches. The goal of these approaches is to ensure that soil-associated contaminants do not pose a risk to wildlife that directly ingest soil, or to species that may be exposed to contaminants that persist in the food chain. These approaches incorporate broad assumptions in the exposure and effects assessments and in the risk characterization process. Consequently, thresholds for concluding risk are frequently very low with conclusions of risk possible when soil metal concentrations fall in the range of natural background. A workshop held in September, 2012 evaluated existing methods and explored recent science about factors to consider when establishing appropriate remedial goals for concentrations of metals in soils. A Foodweb Exposure Workgroup was organized to evaluate methods for quantifying exposure of wildlife to soil-associated metals through soil and food consumption and to provide recommendations for the development of ecological soil cleanup values (Eco-SCVs) that are both practical and scientifically defensible. The specific goals of this article are to review the current practices for quantifying exposure of wildlife to soil-associated contaminants via bioaccumulation and trophic transfer, to identify potential opportunities for refining and improving these exposure estimates, and finally, to make recommendations for application of these improved models to the development of site-specific remedial goals protective of wildlife. Although the focus is on metals contamination, many of the methods and tools discussed are also applicable to organic contaminants. The conclusion of this workgroup was that existing exposure estimation models are generally appropriate when fully expanded and that methods are generally available to develop more robust site-specific exposure estimates. Improved realism in site-specific wildlife Eco-SCVs could be achieved by obtaining more realistic estimates for diet composition, bioaccumulation, bioavailability and/or bioaccessibility, soil ingestion, spatial aspects of exposure, and target organ exposure. These components of wildlife exposure estimation should be developed on a site-, species-, and analyte-specific basis to the extent that the expense for their derivation is justified by the value they add to Eco-SCV development

Modeling rain-fed maize vulnerability to droughts using the standardized precipitation index from satellite estimated rainfall-Southern Malawi case study

During 1990s, disaster risk reduction emerged as a novel, proactive approach to managing risks from natural hazards. The World Bank, USAlD, and other international donor agencies began making efforts to mainstream disaster risk reduction in countries whose population and economies were heavily dependent on rain-fed agriculture. This approach has more significance in light of the increasing climatic hazard patterns and the climate scenarios projected for different hazard prone countries in the world. The Famine Early Warning System Network (FEWS NET) has been monitoring the food security issues in the sub-Saharan Africa, Asia and in Haiti. FEWS NET monitors the rainfall and moisture availability conditions with the help of NOAA RFE2 data for deriving food security status in Africa. This paper highlights the efforts in using satellite estimated rainfall inputs to develop drought vulnerability models in the drought prone areas in Malawi. The satellite RFE2 based SPI corresponding to the critical tasseling and silking phases (in the months of January, February, and March) were statistically regressed with drought-induced yield losses at the district level. The analysis has shown that the drought conditions in February and early March lead to most damage to maize yields in this region. The district-wise vulnerabilities to drought were up scaled to obtain a regional maize vulnerability model for southern Malawi. The results would help in establishing an early monitoring mechanism for drought impact assessment, give the decision makers additional time to assess seasonal outcomes, and identify potential food-related hazards in Malawi

Temperature dependence of binary and ternary recombination of H3+ ions with electron

We study binary and the recently discovered process of ternary He-assisted recombination of H3+ ions with electrons in a low temperature afterglow plasma. The experiments are carried out over a broad range of pressures and temperatures of an afterglow plasma in a helium buffer gas. Binary and He-assisted ternary recombination are observed and the corresponding recombination rate coefficients are extracted for temperatures from 77 K to 330 K. We describe the observed ternary recombination as a two-step mechanism: First, a rotationally-excited long-lived neutral molecule H3* is formed in electron-H3+ collisions. Second, the H3* molecule collides with a helium atom that leads to the formation of a very long-lived Rydberg state with high orbital momentum. We present calculations of the lifetimes of H3* and of the ternary recombination rate coefficients for para and ortho-H3+. The calculations show a large difference between the ternary recombination rate coefficients of ortho- and para-H3+ at temperatures below 300 K. The measured binary and ternary rate coefficients are in reasonable agreement with the calculated values.Comment: 15 page

Combining machine learning and simulations of a morphologically realistic model to study modulation of neuronal activity in cerebellar nuclei

Abstract from 23rd Annual Computational Neuroscience Meeting: CNS 2014 © 2014 Alva et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Epileptic absence seizures are characterized by synchronized oscillatory activity in the cerebral cortex that can be recorded as so-called spike-and-wave discharges (SWDs) by electroencephalogram. Although the cerebral cortex and the directly connected thalamus are paramount to this particular form of epilepsy, several other parts of the mammalian brain are likely to influence this oscillatory activity. We have recently shown that some of the cerebellar nuclei (CN) neurons, which form the main output of the cerebellum, show synchronized oscillatory activity during episodes of cortical SWDs in two independent mouse models of absence epilepsy [1]. The CN neurons that show this significant correlation with the SWDs are deemed to “participate” in the seizure activity and are therefore used in our current study designed to unravel the potential causes of such oscillatory firing patternsPeer reviewe

Acceptability of Parental Financial Incentives and Quasi-Mandatory Interventions for Preschool Vaccinations: Triangulation of Findings from Three Linked Studies.

BACKGROUND: Childhood vaccinations are a core component of public health programmes globally. Recent measles outbreaks in the UK and USA have prompted debates about new ways to increase uptake of childhood vaccinations. Parental financial incentives and quasi-mandatory interventions (e.g. restricting entry to educational settings to fully vaccinated children) have been successfully used to increase uptake of childhood vaccinations in developing countries, but there is limited evidence of effectiveness in developed countries. Even if confirmed to be effective, widespread implementation of these interventions is dependent on acceptability to parents, professionals and other stakeholders. METHODS: We conducted a systematic review (n = 11 studies included), a qualitative study with parents (n = 91) and relevant professionals (n = 24), and an on-line survey with embedded discrete choice experiment with parents (n = 521) exploring acceptability of parental financial incentives and quasi-mandatory interventions for preschool vaccinations. Here we use Triangulation Protocol to synthesise findings from the three studies. RESULTS: There was a consistent recognition that incentives and quasi-mandatory interventions could be effective, particularly in more disadvantaged groups. Universal incentives were consistently preferred to targeted ones, but relative preferences for quasi-mandatory interventions and universal incentives varied between studies. The qualitative work revealed a consistent belief that financial incentives were not considered an appropriate motivation for vaccinating children. The costs of financial incentive interventions appeared particularly salient and there were consistent concerns in the qualitative work that incentives did not represent the best use of resources for promoting preschool vaccinations. Various suggestions for improving delivery of the current UK vaccination programme as an alternative to incentives and quasi-mandates were made. CONCLUSIONS: Parental financial incentives and quasi-mandatory interventions for increasing uptake of preschool vaccinations do not currently attract widespread enthusiastic support in the UK; but some potential benefits of these approaches are recognised.National Institute for Health Research (Grant ID: HTA 11/97/01)This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.015684