"Life after Prison." Successful Community Reintegration Programs Reduce Recidivism in Illinois.

ERIC Educational Resources Information Center

Black, Hartzel L.; And Others

The Southeastern Illinois College Correctional Educational Division (SIC-CED) begins its involvement at the offender's entry into the correctional institution and continues through the community networking system upon his or her release from the Illinois Department of Corrections. Funding has been awarded for development and implementation of the…

Radiation exposure from diagnostic imaging in young patients with testicular cancer.

PubMed

Sullivan, C J; Murphy, K P; McLaughlin, P D; Twomey, M; O'Regan, K N; Power, D G; Maher, M M; O'Connor, O J

2015-04-01

Risks associated with high cumulative effective dose (CED) from radiation are greater when imaging is performed on younger patients. Testicular cancer affects young patients and has a good prognosis. Regular imaging is standard for follow-up. This study quantifies CED from diagnostic imaging in these patients. Radiological imaging of patients aged 18-39 years, diagnosed with testicular cancer between 2001 and 2011 in two tertiary care centres was examined. Age at diagnosis, cancer type, dose-length product (DLP), imaging type, and frequency were recorded. CED was calculated from DLP using conversion factors. Statistical analysis was performed with SPSS. In total, 120 patients with a mean age of 30.7 ± 5.2 years at diagnosis had 1,410 radiological investigations. Median (IQR) surveillance was 4.37 years (2.0-5.5). Median (IQR) CED was 125.1 mSv (81.3-177.5). Computed tomography accounted for 65.3 % of imaging studies and 98.3 % of CED. We found that 77.5 % (93/120) of patients received high CED (>75 mSv). Surveillance time was associated with high CED (OR 2.1, CI 1.5-2.8). Survivors of testicular cancer frequently receive high CED from diagnostic imaging, mainly CT. Dose management software for accurate real-time monitoring of CED and low-dose CT protocols with maintained image quality should be used by specialist centres for surveillance imaging. • CT accounted for 98.3 % of CED in patients with testicular cancer. • Median CED in patients with testicular cancer was 125.1 mSv • High CED (>75 mSv) was observed in 77.5 % (93/120) of patients. • Dose tracking and development of low-dose CT protocols are recommended.

Programmed Cell Death During Caenorhabditis elegans Development

PubMed Central

Conradt, Barbara; Wu, Yi-Chun; Xue, Ding

2016-01-01

Programmed cell death is an integral component of Caenorhabditis elegans development. Genetic and reverse genetic studies in C. elegans have led to the identification of many genes and conserved cell death pathways that are important for the specification of which cells should live or die, the activation of the suicide program, and the dismantling and removal of dying cells. Molecular, cell biological, and biochemical studies have revealed the underlying mechanisms that control these three phases of programmed cell death. In particular, the interplay of transcriptional regulatory cascades and networks involving multiple transcriptional regulators is crucial in activating the expression of the key death-inducing gene egl-1 and, in some cases, the ced-3 gene in cells destined to die. A protein interaction cascade involving EGL-1, CED-9, CED-4, and CED-3 results in the activation of the key cell death protease CED-3, which is tightly controlled by multiple positive and negative regulators. The activation of the CED-3 caspase then initiates the cell disassembly process by cleaving and activating or inactivating crucial CED-3 substrates; leading to activation of multiple cell death execution events, including nuclear DNA fragmentation, mitochondrial elimination, phosphatidylserine externalization, inactivation of survival signals, and clearance of apoptotic cells. Further studies of programmed cell death in C. elegans will continue to advance our understanding of how programmed cell death is regulated, activated, and executed in general. PMID:27516615

Putting Learning First: Governing and Managing the Schools for High Achievement.

ERIC Educational Resources Information Center

Committee for Economic Development, New York, NY.

This statement by the Research and Policy Committe of the Committee for Economic Development (CED), a nonprofit organization of 250 business leaders and educators, calls for major behavioral changes in those who govern and manage schools in the United States. It articulates an effective incentive structure for students, teachers, and…

Model of Collaboration between Two Universities: Meeting the Challenge.

ERIC Educational Resources Information Center

Easterbrooks, Susan R.; Laughton, Joan M.

This paper describes a collaborative program of Georgia State University and the University of Georgia to train prospective teachers of the deaf in accordance with recent standards developed by the Council on Education of the Deaf (CED). The program involves: (1) a shared advisory committee; (2) foundation coursework taken separately at the two…

Are we there yet? A Practitioner's View of DO-178C/ED-12C

NASA Astrophysics Data System (ADS)

Daniels, Dewi

RTCA DO-178B/EUROCAE ED-12B is the industry-accepted guidance for determining that the software aspects of airborne systems and equipment comply with airworthiness requirements. DO-178B/ED-12B, published in 1992, is being updated to DO-178C/ED-12C. Nearly six years in the making, DO- 178C/ED-12C is expected to be completed in December 2010. It will be accompanied by a new set of supplements providing additional and much-needed guidance on tool qualification, model based development and verification, objectoriented technologies, and formal methods. Written by a member of the DO-178C/ED-12C editorial team who is also a practising software developer and verifier, this paper provides a practitioner's view of the new standard and its supplements. It explains how they will affect your organisation, focusing on the practical implications of the many changes between DO-178B/ED-12B and DO-178C/ED-12C.

Concentration rather than dose defines the local brain toxicity of agents that are effectively distributed by convection-enhanced delivery.

PubMed

Zhang, Rong; Saito, Ryuta; Mano, Yui; Kanamori, Masayuki; Sonoda, Yukihiko; Kumabe, Toshihiro; Tominaga, Teiji

2014-01-30

Convection-enhanced delivery (CED) has been developed as a potentially effective drug-delivery strategy into the central nervous system. In contrast to systemic intravenous administration, local delivery achieves high concentration and prolonged retention in the local tissue, with increased chance of local toxicity, especially with toxic agents such as chemotherapeutic agents. Therefore, the factors that affect local toxicity should be extensively studied. With the assumption that concentration-oriented evaluation of toxicity is important for local CED, we evaluated the appearance of local toxicity among different agents after delivery with CED and studied if it is dose dependent or concentration dependent. Local toxicity profile of chemotherapeutic agents delivered via CED indicates BCNU was dose-dependent, whereas that of ACNU was concentration-dependent. On the other hand, local toxicity for doxorubicin, which is not distributed effectively by CED, was dose-dependent. Local toxicity for PLD, which is extensively distributed by CED, was concentration-dependent. Traditional evaluation of drug induced toxicity was dose-oriented. This is true for systemic intravascular delivery. However, with local CED, toxicity of several drugs exacerbated in concentration-dependent manner. From our study, local toxicity of drugs that are likely to distribute effectively tended to be concentration-dependent. Concentration rather than dose may be more important for the toxicity of agents that are effectively distributed by CED. Concentration-oriented evaluation of toxicity is more important for CED. Copyright © 2013 Elsevier B.V. All rights reserved.

75 FR 52007 - Proposed Information Collection Activity; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-24

...) Community Economic Development (CED) and Job Opportunities for Low-Income Individuals (JOLI) Standard... key information about projects funded through the Community Economic Development (CED) and Job... previously approved questionnaire, Office of Management and Budget (OMB) Control Number: 0970-0317. Questions...

An integrated evaluation for the performance of clinical engineering department.

PubMed

Yousry, Ahmed M; Ouda, Bassem K; Eldeib, Ayman M

2014-01-01

Performance benchmarking have become a very important component in all successful organizations nowadays that must be used by Clinical Engineering Department (CED) in hospitals. Many researchers identified essential mainstream performance indicators needed to improve the CED's performance. These studies revealed mainstream performance indicators that use the database of a CED to evaluate its performance. In this work, we believe that those indicators are insufficient for hospitals. Additional important indicators should be included to improve the evaluation accuracy. Therefore, we added new indicators: technical/maintenance indicators, economic indicators, intrinsic criticality indicators, basic hospital indicators, equipment acquisition, and safety indicators. Data is collected from 10 hospitals that cover different types of healthcare organizations. We developed a software tool that analyses collected data to provide a score for each CED under evaluation. Our results indicate that there is an average gap of 67% between the CEDs' performance and the ideal target. The reasons for the noncompliance are discussed in order to improve performance of CEDs under evaluation.

The Conservation Efforts Database: Improving our knowledge of landscape conservation actions

USGS Publications Warehouse

Heller, Matthew M.; Welty, Justin; Wiechman , Lief A.

2017-01-01

The Conservation Efforts Database (CED) is a secure, cloud-based tool that can be used to document and track conservation actions across landscapes. A recently released factsheet describes this tool ahead of the rollout of CED version 2.0. The CED was developed by the U.S. Fish and Wildlife Service, the USGS, and the Great Northern Landscape Conservation Cooperative to support the 2015 Endangered Species Act status review for greater sage-grouse. Currently, the CED accepts policy-level data, such as Land Use Plans, and treatment level data, such as conifer removals and post-fire recovery efforts, as custom spatial and non-spatial records. In addition to a species assessment tool, the CED can also be used to summarize the extent of restoration efforts within a specific area or to strategically site conservation actions based on the location of other implemented actions. The CED can be an important tool, along with post-conservation monitoring, for implementing landscape-scale adaptive management.

Complications associated with cervical endoscopic discectomy with the holmium laser.

PubMed

Haufe, Scott M W; Mork, Anthony R

2004-02-01

Our aim was to determine the rate of surgical complications associated with cervical endoscopic discectomy (CED). There are no studies that state the degree of complications after CED. Forty-one patients underwent CED with holmium laser. Two out of 41 patients incurred vascular compromise during the procedure. One patient developed recurrent laryngeal nerve damage. One patient developed discitis, and two patients complained of a "clicking" sensation postoperatively. Although CED has a relatively high success rate, there is a 15% rate of complications associated with the procedure. Most of the complications were minor (such as vascular compromise, recurrent laryngeal nerve injury, and postoperative "clicking" sensations), but there was one case of severe discitis, and there is the potential of serious complication from both vascular compromise and neural injury.

77 FR 38580 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-28

... CEDS planning process and resulting CEDS is designed to guide the economic growth of an area and...: Economic Development Administration (EDA). Title: Comprehensive Economic Development Strategies. OMB... and Economic Adjustment programs, applicants must undertake a planning process that results in a...

Politics and its intersection with coverage with evidence development: a qualitative analysis from expert interviews.

PubMed

Bishop, Danielle; Lexchin, Joel

2013-03-09

Pressures on health care budgets have led policy makers to discuss how to balance the provision of costly technologies to populations in need and making coverage decisions under uncertainty. Coverage with evidence development (CED) is being employed to meet these challenges. Twenty-four interviews were carried out between June 2009 and December 2010 with researchers, decision makers and policy makers from Australia, Canada, United Kingdom and United States. Three phases of coding occurred, the first being manual coding where the interviews were read and notes were taken and nodes were extracted and imputed. NVIVO coding was applied to the interview transcripts, with both broad general searches for word usages and imputed nodes. Four overarching thematic areas emerged out of contextual analysis of the interviews - (1) what constitutes CED; (2) the lack of a systematic approach/governance structure; (3) the role of the pharmaceutical industry and overt political considerations in CED; and (4) alternatives and barriers to CED. We explore these themes and then use concrete examples of CED projects in each of the four countries to illustrate the political issues that our interviewees raised. Until the underlying political nature of CED is recognized then fundamental questions about its usefulness and operation will remain unresolved.

Politics and its intersection with coverage with evidence development: a qualitative analysis from expert interviews

PubMed Central

2013-01-01

Background Pressures on health care budgets have led policy makers to discuss how to balance the provision of costly technologies to populations in need and making coverage decisions under uncertainty. Coverage with evidence development (CED) is being employed to meet these challenges. Methods Twenty-four interviews were carried out between June 2009 and December 2010 with researchers, decision makers and policy makers from Australia, Canada, United Kingdom and United States. Three phases of coding occurred, the first being manual coding where the interviews were read and notes were taken and nodes were extracted and imputed. NVIVO coding was applied to the interview transcripts, with both broad general searches for word usages and imputed nodes. Results Four overarching thematic areas emerged out of contextual analysis of the interviews – (1) what constitutes CED; (2) the lack of a systematic approach/governance structure; (3) the role of the pharmaceutical industry and overt political considerations in CED; and (4) alternatives and barriers to CED. We explore these themes and then use concrete examples of CED projects in each of the four countries to illustrate the political issues that our interviewees raised. Conclusion Until the underlying political nature of CED is recognized then fundamental questions about its usefulness and operation will remain unresolved. PMID:23497271

Convection enhanced delivery of carmustine to the murine brainstem: a feasibility study.

PubMed

Sewing, A Charlotte P; Caretti, Viola; Lagerweij, Tonny; Schellen, Pepijn; Jansen, Marc H A; van Vuurden, Dannis G; Idema, Sander; Molthoff, Carla F M; Vandertop, W Peter; Kaspers, Gertjan J L; Noske, David P; Hulleman, Esther

2014-12-30

Systemic delivery of therapeutic agents remains ineffective against diffuse intrinsic pontine glioma (DIPG), possibly due to an intact blood-brain-barrier (BBB) and to dose-limiting toxicity of systemic chemotherapeutic agents. Convection-enhanced delivery (CED) into the brainstem may provide an effective local delivery alternative for DIPG patients. The aim of this study is to develop a method to perform CED into the murine brainstem and to test this method using the chemotherapeutic agent carmustine (BiCNU). To this end, a newly designed murine CED catheter was tested in vitro and in vivo. After determination of safety and distribution, mice bearing VUMC-DIPG-3 and E98FM-DIPG brainstem tumors were treated with carmustine dissolved in DW 5% or carmustine dissolved in 10% ethanol. Our results show that CED into the murine brainstem is feasible and well tolerated by mice with and without brainstem tumors. CED of carmustine dissolved in 5% DW increased median survival of mice with VUMC-DIPG-3 and E98FM-DIPG tumors with 35% and 25% respectively. Dissolving carmustine in 10% ethanol further improved survival to 45% in mice with E98FM-DIPG tumors. Since genetically engineered and primary DIPG models are currently only available in mice, murine CED studies have clear advantages over CED studies in other animals. CED in the murine brainstem can be performed safely, is well tolerated and can be used to study efficacy of chemotherapeutic agents orthotopically. These results set the foundation for more CED studies in murine DIPG models. Copyright © 2014 Elsevier B.V. All rights reserved.

CED-10/Rac1 Regulates Endocytic Recycling through the RAB-5 GAP TBC-2

PubMed Central

Sun, Lin; Liu, Ou; Desai, Jigar; Karbassi, Farhad; Sylvain, Marc-André; Shi, Anbing; Zhou, Zheng; Rocheleau, Christian E.; Grant, Barth D.

2012-01-01

Rac1 is a founding member of the Rho-GTPase family and a key regulator of membrane remodeling. In the context of apoptotic cell corpse engulfment, CED-10/Rac1 acts with its bipartite guanine nucleotide exchange factor, CED-5/Dock180-CED-12/ELMO, in an evolutionarily conserved pathway to promote phagocytosis. Here we show that in the context of the Caenorhabditis elegans intestinal epithelium CED-10/Rac1, CED-5/Dock180, and CED-12/ELMO promote basolateral recycling. Furthermore, we show that CED-10 binds to the RAB-5 GTPase activating protein TBC-2, that CED-10 contributes to recruitment of TBC-2 to endosomes, and that recycling cargo is trapped in recycling endosomes in ced-12, ced-10, and tbc-2 mutants. Expression of GTPase defective RAB-5(Q78L) also traps recycling cargo. Our results indicate that down-regulation of early endosome regulator RAB-5/Rab5 by a CED-5, CED-12, CED-10, TBC-2 cascade is an important step in the transport of cargo through the basolateral recycling endosome for delivery to the plasma membrane. PMID:22807685

Convection-Enhanced Delivery for Diffuse Intrinsic Pontine Glioma Treatment.

PubMed

Zhou, Zhiping; Singh, Ranjodh; Souweidane, Mark M

2017-01-01

Convection-enhanced delivery (CED) is a technique designed to deliver drugs directly into the brain or tumors. Its ability to bypass the blood-brain barrier (BBB), one of the major hurdles in delivering drugs to the brain, has made it a promising drug delivery method for the treatment of primary brain tumors. A number of clinical trials utilizing CED of various therapeutic agents have been conducted to treat patients with supratentorial high-grade gliomas. Significant responses have been observed in certain patients in all of these trials. However, the insufficient ability to monitor drug distribution and pharmacokinetics hampers CED from achieving its potentials on a larger scale. Brainstem CED for diffuse intrinsic pontine glioma (DIPG) treatment is appealing because this tumor is compact and has no definitive treatment. The safety of brainstem CED has been established in small and large animals, and recently in early stage clinical trials. There are a few current clinical trials of brainstem CED in treating DIPG patients using targeted macromolecules such as antibodies and immunotoxins. Future advances for CED in DIPG treatment will come from several directions including: choosing the right agents for infusion; developing better agents and regimen for DIPG infusion; improving instruments and technique for easier and accurate surgical targeting and for allowing multisession or prolonged infusion to implement optimal time sequence; and better understanding and control of drug distribution, clearance and time sequence. CED-based therapies for DIPG will continue to evolve with new understanding of the technique and the disease.

Convection-Enhanced Delivery for Diffuse Intrinsic Pontine Glioma Treatment

PubMed Central

Zhou, Zhiping; Singh, Ranjodh; Souweidane, Mark M.

2017-01-01

Convection-enhanced delivery (CED) is a technique designed to deliver drugs directly into the brain or tumors. Its ability to bypass the blood-brain barrier (BBB), one of the major hurdles in delivering drugs to the brain, has made it a promising drug delivery method for the treatment of primary brain tumors. A number of clinical trials utilizing CED of various therapeutic agents have been conducted to treat patients with supratentorial high-grade gliomas. Significant responses have been observed in certain patients in all of these trials. However, the insufficient ability to monitor drug distribution and pharmacokinetics hampers CED from achieving its potentials on a larger scale. Brainstem CED for diffuse intrinsic pontine glioma (DIPG) treatment is appealing because this tumor is compact and has no definitive treatment. The safety of brainstem CED has been established in small and large animals, and recently in early stage clinical trials. There are a few current clinical trials of brainstem CED in treating DIPG patients using targeted macromolecules such as antibodies and immunotoxins. Future advances for CED in DIPG treatment will come from several directions including: choosing the right agents for infusion; developing better agents and regimen for DIPG infusion; improving instruments and technique for easier and accurate surgical targeting and for allowing multisession or prolonged infusion to implement optimal time sequence; and better understanding and control of drug distribution, clearance and time sequence. CED-based therapies for DIPG will continue to evolve with new understanding of the technique and the disease. PMID:27306036

The Use of Surrogate and Patient-Relevant Endpoints in Outcomes-Based Market Access Agreements : Current Debate.

PubMed

Toumi, Mondher; Jarosławski, Szymon; Sawada, Toyohiro; Kornfeld, Åsa

2017-02-01

The high cost of novel treatments is the major driver of negative or restricted reimbursement decisions by healthcare payers in many countries. Costly drugs can be subject to Market Access Agreements (MAAs), which are financial (Commercial Agreements [CAs]) or outcomes-based (Payment for Performance Agreements [P4Ps] or Coverage with Evidence Development agreements [CEDs]). Outcomes in outcomes-based MAAs are assessed through changes in surrogate endpoints (SEPs) or patient-relevant endpoints (PEPs). In May 2015, we reviewed published and grey literature on MAAs between manufacturers and large, institutionalised payers from all geographical areas, and classified the schemes into CAs, P4Ps and CEDs, as well as by therapeutic area and country. Outcomes-based MAAs were further categorized by the endpoint used. Overall, we identified 143 MAAs, 56 (39.2 %) of which were pure CAs, 53 (37.1 %) were CEDs, and 34 (23.8 %) were P4Ps. Among the CEDs, 49 were PEP CEDs and four were SEP CEDs; of the 34 P4Ps, 29 were SEP P4Ps for 30 drugs, and five were PEP P4Ps for at least six drugs; and among 87 outcomes-based MAAs (CEDs + P4Ps), PEP CEDs were the most common (56.3 %), followed by SEP P4Ps (34.1 %). The high proportion of SEPs used in P4Ps contrasts with the high proportion of PEPs used in CEDs. CEDs employ PEPs and it appears that they are used to reduce uncertainty about a drug's clinical outcomes and/or real-life use, and thus allow payers to align a product's value with price. We argue that P4Ps do not reduce uncertainty about real-life effectiveness and can only constitute an outcome guarantee for payers if they are based on PEPs or validated SEPs.

New French Coverage with Evidence Development for Innovative Medical Devices: Improvements and Unresolved Issues.

PubMed

Martelli, Nicolas; van den Brink, Hélène; Borget, Isabelle

2016-01-01

We describe here recent modifications to the French Coverage with Evidence Development (CED) scheme for innovative medical devices. CED can be defined as temporary coverage for a novel health product during collection of the additional evidence required to determine whether definitive coverage is possible. The principle refinements to the scheme include a more precise definition of what may be considered an innovative product, the possibility for device manufacturers to request CED either independently or in partnership with hospitals, and the establishment of processing deadlines for health authorities. In the long term, these modifications may increase the number of applications to the CED scheme, which could lead to unsustainable funding for future projects. It will also be necessary to ensure that the study conditions required by national health authorities are suitable for medical devices and that processing deadlines are met for the scheme to be fully operational. Overall, the modifications recently applied to the French CED scheme for innovative medical devices should increase the transparency of the process, and therefore be more appealing to medical device manufacturers. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Development and application of air quality models at the US ...

EPA Pesticide Factsheets

Overview of the development and application of air quality models at the U.S. EPA, particularly focused on the development and application of the Community Multiscale Air Quality (CMAQ) model developed within the Computation Exposure Division (CED) of the National Exposure Research Laboratory (NERL). This presentation will provide a simple overview of air quality model development and application geared toward a non-technical student audience. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-support tools, and models to be applied to media-specific or receptor-specific problem areas. CED uses modeling-based approaches to characterize exposures, evaluate fate and transport, and support environmental diagnostics/forensics with input from multiple data sources. It also develops media- and receptor-specific models, process models, and decision support tools for use both within and outside of EPA.

Convection-Enhanced Delivery.

PubMed

Mehta, A M; Sonabend, A M; Bruce, J N

2017-04-01

Convection-enhanced delivery (CED) is a promising technique that generates a pressure gradient at the tip of an infusion catheter to deliver therapeutics directly through the interstitial spaces of the central nervous system. It addresses and offers solutions to many limitations of conventional techniques, allowing for delivery past the blood-brain barrier in a targeted and safe manner that can achieve therapeutic drug concentrations. CED is a broadly applicable technique that can be used to deliver a variety of therapeutic compounds for a diversity of diseases, including malignant gliomas, Parkinson's disease, and Alzheimer's disease. While a number of technological advances have been made since its development in the early 1990s, clinical trials with CED have been largely unsuccessful, and have illuminated a number of parameters that still need to be addressed for successful clinical application. This review addresses the physical principles behind CED, limitations in the technique, as well as means to overcome these limitations, clinical trials that have been performed, and future developments.

Undernutrition in the Kora Mudi tribal population, West Bengal, India: a comparison of body mass index and mid-upper-arm circumference.

PubMed

Bisai, Samiran; Bose, Kaushik

2009-03-01

Undernutrition among adult tribal women is a major health problem in India. To compare the utility of two different anthropometric indicators of chronic energy deficiency (CED) among tribal Kora Mudi women and to determine which of these two is a better indicator of undernutrition. A cross-sectional study of 123 individuals was conducted. The body mass index (BMI) and mid-upper-arm circumference (MUAC) were used to evaluate CED. The prevalence of CED based on BMI less than 18.5 was 55.3%, and the prevalence of CED based on MUAC less than 22.0 cm was 51.2%. Both of these prevalence rates are classified in the very high-prevalence category (> or = 40%) and indicate a critical situation according to World Health Organization recommendations. Mean BMI increased significantly with higher quartile of MUAC. There was a significant difference in the prevalence of CED between the MUAC quartiles. The risk ratio for CED for women in the lowest quartile of MUAC was 9.33 compared with those in the highest quartile. There was a significant positive association between MUAC and BMI. Regression analysis demonstrated that MUAC had a significant positive impact on BMI; the percentage of the variation in BMI explained by MUAC was 52%. Logistic regression analysis demonstrated that overall, 82.11% of cases of CED were correctly classified with the use of MUAC. The use of MUAC correctly diagnosed 82.35% of cases of CED and 81.82% of women with normal nutritional status. This population was facing severe nutritional stress. With limited resources and in the absence of skilled manpower, it may be more appropriate to use MUAC for human population surveys, particularly among tribal populations of developing countries.

Special funding schemes for innovative medical devices in French hospitals: the pros and cons of two different approaches.

PubMed

Martelli, Nicolas; van den Brink, Hélène

2014-07-01

Financing innovative medical devices is an important challenge for national health policy makers, and a crucial issue for hospitals. However, when innovative medical devices are launched on the European market there is generally little clinical evidence regarding both efficacy and safety, both because of the flaws in the European system for regulating such devices, and because they are at an early stage of development. To manage the uncertainty surrounding the reimbursement of innovation, several European countries have set up temporary funding schemes to generate evidence about the effectiveness of devices. This article explores two different French approaches to funding innovative in-hospital devices and collecting supplementary data: the coverage with evidence development (CED) scheme introduced under Article L. 165-1-1 of the French Social Security Code; and national programs for hospital-based research. We discuss pros and cons of both approaches in the light of CED policies in Germany and the UK. The CED policies for devices share common limitations. Thus, transparency of CED processes should be enhanced and decisions need to be made in a timely way. Finally, we think that closer collaboration between manufacturers, health authorities and hospitals is essential to make CED policies more operational. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

75 FR 81614 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-28

... (CED) and Job Opportunities for Low-Income Individuals (JOLI) Standard Reporting Format. OMB No.: New... funded through the Community Economic Development (CED) and Job Opportunities for Low-Income Individuals... Report (PPR) is a new proposed reporting format that will collect information concerning the outcomes and...

Planning for Life: Career Planning Excellence in America, A National Policy Forum (Washington, D.C., August 4, 1993). Recognition Program: Summer 1994.

ERIC Educational Resources Information Center

1994

The Career Planning for Life Forum was a national policy forum sponsored by the Committee for Economic Development (CED) and hosted by the U.S. Army. More than 250 representatives of business, education, government, and labor attended the forum and spent the day discussing the preparation of the country's young work force for the global economy.…

Convection-enhanced delivery in glioblastoma: a review of preclinical and clinical studies

PubMed Central

Jahangiri, Arman; Chin, Aaron T.; Flanigan, Patrick M.; Chen, Rebecca; Bankiewicz, Krystof; Aghi, Manish K.

2017-01-01

Glioblastoma is the most common malignant brain tumor, and it carries an extremely poor prognosis. Attempts to develop targeted therapies have been hindered because the blood-brain barrier prevents many drugs from reaching tumors cells. Furthermore, systemic toxicity of drugs often limits their therapeutic potential. A number of alternative methods of delivery have been developed, one of which is convection-enhanced delivery (CED), the focus of this review. The authors describe CED as a therapeutic measure and review preclinical studies and the most prominent clinical trials of CED in the treatment of glioblastoma. The utilization of this technique for the delivery of a variety of agents is covered, and its shortcomings and challenges are discussed in detail. PMID:27035164

Quantifying intermolecular interactions of ionic liquids using cohesive energy densities.

PubMed

Lovelock, Kevin R J

2017-12-01

For ionic liquids (ILs), both the large number of possible cation + anion combinations and their ionic nature provide a unique challenge for understanding intermolecular interactions. Cohesive energy density, ced , is used to quantify the strength of intermolecular interactions for molecular liquids, and is determined using the enthalpy of vaporization. A critical analysis of the experimental challenges and data to obtain ced for ILs is provided. For ILs there are two methods to judge the strength of intermolecular interactions, due to the presence of multiple constituents in the vapour phase of ILs. Firstly, ced IP , where the ionic vapour constituent is neutral ion pairs, the major constituent of the IL vapour. Secondly, ced C+A , where the ionic vapour constituents are isolated ions. A ced IP dataset is presented for 64 ILs. For the first time an experimental ced C+A , a measure of the strength of the total intermolecular interaction for an IL, is presented. ced C+A is significantly larger for ILs than ced for most molecular liquids, reflecting the need to break all of the relatively strong electrostatic interactions present in ILs. However, the van der Waals interactions contribute significantly to IL volatility due to the very strong electrostatic interaction in the neutral ion pair ionic vapour. An excellent linear correlation is found between ced IP and the inverse of the molecular volume. A good linear correlation is found between IL ced IP and IL Gordon parameter (which are dependent primarily on surface tension). ced values obtained through indirect methods gave similar magnitude values to ced IP . These findings show that ced IP is very important for understanding IL intermolecular interactions, in spite of ced IP not being a measure of the total intermolecular interactions of an IL. In the outlook section, remaining challenges for understanding IL intermolecular interactions are outlined.

Quantifying intermolecular interactions of ionic liquids using cohesive energy densities

PubMed Central

2017-01-01

For ionic liquids (ILs), both the large number of possible cation + anion combinations and their ionic nature provide a unique challenge for understanding intermolecular interactions. Cohesive energy density, ced, is used to quantify the strength of intermolecular interactions for molecular liquids, and is determined using the enthalpy of vaporization. A critical analysis of the experimental challenges and data to obtain ced for ILs is provided. For ILs there are two methods to judge the strength of intermolecular interactions, due to the presence of multiple constituents in the vapour phase of ILs. Firstly, cedIP, where the ionic vapour constituent is neutral ion pairs, the major constituent of the IL vapour. Secondly, cedC+A, where the ionic vapour constituents are isolated ions. A cedIP dataset is presented for 64 ILs. For the first time an experimental cedC+A, a measure of the strength of the total intermolecular interaction for an IL, is presented. cedC+A is significantly larger for ILs than ced for most molecular liquids, reflecting the need to break all of the relatively strong electrostatic interactions present in ILs. However, the van der Waals interactions contribute significantly to IL volatility due to the very strong electrostatic interaction in the neutral ion pair ionic vapour. An excellent linear correlation is found between cedIP and the inverse of the molecular volume. A good linear correlation is found between IL cedIP and IL Gordon parameter (which are dependent primarily on surface tension). ced values obtained through indirect methods gave similar magnitude values to cedIP. These findings show that cedIP is very important for understanding IL intermolecular interactions, in spite of cedIP not being a measure of the total intermolecular interactions of an IL. In the outlook section, remaining challenges for understanding IL intermolecular interactions are outlined. PMID:29308254

CED-9 and mitochondrial homeostasis in C. elegans muscle

PubMed Central

Tan, Frederick J.; Husain, Michelle; Manlandro, Cara Marie; Koppenol, Marijke; Fire, Andrew Z.; Hill, R. Blake

2009-01-01

Summary Mitochondrial homeostasis reflects a dynamic balance between membrane fission and fusion events thought essential for mitochondrial function. We report here that altered expression of the C. elegans BCL2 homolog CED-9 affects both mitochondrial fission and fusion. Although striated muscle cells lacking CED-9 have no alteration in mitochondrial size or ultrastructure, these cells appear more sensitive to mitochondrial fragmentation. By contrast, increased CED-9 expression in these cells produces highly interconnected mitochondria. This mitochondrial phenotype is partially suppressed by increased expression of the dynamin-related GTPase DRP-1, with suppression dependent on the BH3 binding pocket of CED-9. This suppression suggests that CED-9 directly regulates DRP-1, a model supported by our finding that CED-9 activates the GTPase activity of human DRP1. Thus, CED-9 is capable of regulating the mitochondrial fission-fusion cycle but is not essential for either fission or fusion. PMID:18827010

Convection-enhanced Delivery of Therapeutics for Malignant Gliomas.

PubMed

Saito, Ryuta; Tominaga, Teiji

2017-01-15

Convection-enhanced delivery (CED) circumvents the blood-brain barrier by delivering agents directly into the tumor and surrounding parenchyma. CED can achieve large volumes of distribution by continuous positive-pressure infusion. Although promising as an effective drug delivery method in concept, the administration of therapeutic agents via CED is not without challenges. Limitations of distribution remain a problem in large brains, such as those of humans. Accurate and consistent delivery of an agent is another challenge associated with CED. Similar to the difficulties caused by immunosuppressive environments associated with gliomas, there are several mechanisms that make effective local drug distribution difficult in malignant gliomas. In this review, methods for local drug application targeting gliomas are discussed with special emphasis on CED. Although early clinical trials have failed to demonstrate the efficacy of CED against gliomas, CED potentially can be a platform for translating the molecular understanding of glioblastomas achieved in the laboratory into effective clinical treatments. Several clinical studies using CED of chemotherapeutic agents are ongoing. Successful delivery of effective agents should prove the efficacy of CED in the near future.

Convection-enhanced Delivery of Therapeutics for Malignant Gliomas

PubMed Central

SAITO, Ryuta; TOMINAGA, Teiji

2017-01-01

Convection-enhanced delivery (CED) circumvents the blood–brain barrier by delivering agents directly into the tumor and surrounding parenchyma. CED can achieve large volumes of distribution by continuous positive-pressure infusion. Although promising as an effective drug delivery method in concept, the administration of therapeutic agents via CED is not without challenges. Limitations of distribution remain a problem in large brains, such as those of humans. Accurate and consistent delivery of an agent is another challenge associated with CED. Similar to the difficulties caused by immunosuppressive environments associated with gliomas, there are several mechanisms that make effective local drug distribution difficult in malignant gliomas. In this review, methods for local drug application targeting gliomas are discussed with special emphasis on CED. Although early clinical trials have failed to demonstrate the efficacy of CED against gliomas, CED potentially can be a platform for translating the molecular understanding of glioblastomas achieved in the laboratory into effective clinical treatments. Several clinical studies using CED of chemotherapeutic agents are ongoing. Successful delivery of effective agents should prove the efficacy of CED in the near future. PMID:27980285

The Core Molecular Machinery Used for Engulfment of Apoptotic Cells Regulates the JNK Pathway Mediating Axon Regeneration in Caenorhabditis elegans.

PubMed

Pastuhov, Strahil Iv; Fujiki, Kota; Tsuge, Anna; Asai, Kazuma; Ishikawa, Sho; Hirose, Kazuya; Matsumoto, Kunihiro; Hisamoto, Naoki

2016-09-14

The mechanisms that govern the ability of specific neurons to regenerate their axons after injury are not well understood. In Caenorhabditis elegans, the initiation of axon regeneration is positively regulated by the JNK-MAPK pathway. In this study, we identify two components functioning upstream of the JNK pathway: the Ste20-related protein kinase MAX-2 and the Rac-type GTPase CED-10. CED-10, when bound by GTP, interacts with MAX-2 and functions as its upstream regulator in axon regeneration. CED-10, in turn, is activated by axon injury via signals initiated from the integrin α-subunit INA-1 and the nonreceptor tyrosine kinase SRC-1 and transmitted via the signaling module CED-2/CrkII-CED-5/Dock180-CED-12/ELMO. This module is also known to regulate the engulfment of apoptotic cells during development. Our findings thus reveal that the molecular machinery used for engulfment of apoptotic cells also promotes axon regeneration through activation of the JNK pathway. The molecular mechanisms of axon regeneration after injury remain poorly understood. In Caenorhabditis elegans, the initiation of axon regeneration is positively regulated by the JNK-MAPK pathway. In this study, we show that integrin, Rac-GTPase, and several other molecules, all of which are known to regulate engulfment of apoptotic cells during development, also regulate axon regeneration. This signaling module activates the JNK-MAPK cascade via MAX-2, a PAK-like protein kinase that binds Rac. Our findings thus reveal that the molecular machinery used for engulfment of apoptotic cells also promotes axon regeneration through activation of the JNK pathway. Copyright © 2016 the authors 0270-6474/16/369710-12$15.00/0.

Evaluation of a novel sodium borocaptate-containing unnatural amino acid as a boron delivery agent for neutron capture therapy of the F98 rat glioma.

PubMed

Futamura, Gen; Kawabata, Shinji; Nonoguchi, Naosuke; Hiramatsu, Ryo; Toho, Taichiro; Tanaka, Hiroki; Masunaga, Shin-Ichiro; Hattori, Yoshihide; Kirihata, Mitsunori; Ono, Koji; Kuroiwa, Toshihiko; Miyatake, Shin-Ichi

2017-01-23

Boron neutron capture therapy (BNCT) is a unique particle radiation therapy based on the nuclear capture reactions in boron-10. We developed a novel boron-10 containing sodium borocaptate (BSH) derivative, 1-amino-3-fluorocyclobutane-1-carboxylic acid (ACBC)-BSH. ACBC is a tumor selective synthetic amino acid. The purpose of this study was to assess the biodistribution of ACBC-BSH and its therapeutic efficacy following Boron Neutron Capture Therapy (BNCT) of the F98 rat glioma. We evaluated the biodistribution of three boron-10 compounds, ACBC-BSH, BSH and boronophenylalanine (BPA), in vitro and in vivo, following intravenous (i.v.) administration and intratumoral (i.t.) convection-enhanced delivery (CED) in F98 rat glioma bearing rats. For BNCT studies, rats were stratified into five groups: untreated controls, neutron-irradiation controls, BNCT with BPA/i.v., BNCT with ACBC-BSH/CED, and BNCT concomitantly using BPA/i.v. and ACBC-BSH/CED. In vitro, ACBC-BSH attained higher cellular uptake F98 rat glioma cells compared with BSH. In vivo biodistribution studies following i.v. administration and i.t. CED of ACBC-BSH attained significantly higher boron concentrations than that of BSH, but much lower than that of BPA. However, following convection enhanced delivery (CED), ACBC-BSH attained significantly higher tumor concentrations than BPA. The i.t. boron-10 concentrations were almost equal between the ACBC-BSH/CED group and BPA/i.v. group of rats. The tumor/brain boron-10 concentration ratio was higher with ACBC-BSH/CED than that of BPA/i.v. group. Based on these data, BNCT studies were carried out in F98 glioma bearing rats using BPA/i.v. and ACBC-BSH/CED as the delivery agents. The corresponding mean survival times were 37.4 ± 2.6d and 44.3 ± 8.0d, respectively, and although modest, these differences were statistically significant. Our findings suggest that further studies are warranted to evaluate ACBC-BSH/CED as a boron delivery agent.

Memory and Coping with Stress: The Relationship Between Cognitive-Emotional Distinctiveness, Memory Valence, and Distress

PubMed Central

Boals, Adriel; Rubin, David C.; Klein, Kitty

2011-01-01

Cognitive-emotional distinctiveness (CED), the extent to which an individual separates emotions from an event in the cognitive representation of the event, was explored in four studies. CED was measured using a modified multidimensional scaling procedure. The first study found that lower levels of CED in memories of the September 11 terrorist attacks predicted greater frequency of intrusive thoughts about the attacks. The second study revealed CED levels are higher in negative events, in comparison to positive events and that low CED levels in emotionally intense negative events are associated with a pattern of greater event-related distress. The third study replicated the findings from the previous study when examining CED levels in participants’ memories of the 2004 Presidential election. The fourth study revealed that low CED in emotionally intense negative events is associated with worse mental health. We argue that CED is an adaptive and healthy coping feature of stressful memories. PMID:18569690

Convection-enhanced delivery for the treatment of glioblastoma

PubMed Central

Vogelbaum, Michael A.; Aghi, Manish K.

2015-01-01

Effective treatment of glioblastoma (GBM) remains a formidable challenge. Survival rates remain poor despite decades of clinical trials of conventional and novel, biologically targeted therapeutics. There is considerable evidence that most of these therapeutics do not reach their targets in the brain when administered via conventional routes (intravenous or oral). Hence, direct delivery of therapeutics to the brain and to brain tumors is an active area of investigation. One of these techniques, convection-enhanced delivery (CED), involves the implantation of catheters through which conventional and novel therapeutic formulations can be delivered using continuous, low–positive-pressure bulk flow. Investigation in preclinical and clinical settings has demonstrated that CED can produce effective delivery of therapeutics to substantial volumes of brain and brain tumor. However, limitations in catheter technology and imaging of delivery have prevented this technique from being reliable and reproducible, and the only completed phase III study in GBM did not show a survival benefit for patients treated with an investigational therapeutic delivered via CED. Further development of CED is ongoing, with novel catheter designs and imaging approaches that may allow CED to become a more effective therapeutic delivery technique. PMID:25746090

Small GTPase CDC-42 promotes apoptotic cell corpse clearance in response to PAT-2 and CED-1 in C. elegans

PubMed Central

Neukomm, L J; Zeng, S; Frei, A P; Huegli, P A; Hengartner, M O

2014-01-01

The rapid clearance of dying cells is important for the well-being of multicellular organisms. In C. elegans, cell corpse removal is mainly mediated by three parallel engulfment signaling cascades. These pathways include two small GTPases, MIG-2/RhoG and CED-10/Rac1. Here we present the identification and characterization of CDC-42 as a third GTPase involved in the regulation of cell corpse clearance. Genetic analyses performed by both loss of cdc-42 function and cdc-42 overexpression place cdc-42 in parallel to the ced-2/5/12 signaling module, in parallel to or upstream of the ced-10 module, and downstream of the ced-1/6/7 module. CDC-42 accumulates in engulfing cells at membranes surrounding apoptotic corpses. The formation of such halos depends on the integrins PAT-2/PAT-3, UNC-112 and the GEF protein UIG-1, but not on the canonical ced-1/6/7 or ced-2/5/12 signaling modules. Together, our results suggest that the small GTPase CDC-42 regulates apoptotic cell engulfment possibly upstream of the canonical Rac GTPase CED-10, by polarizing the engulfing cell toward the apoptotic corpse in response to integrin signaling and ced-1/6/7 signaling in C. elegans. PMID:24632947

Small GTPase CDC-42 promotes apoptotic cell corpse clearance in response to PAT-2 and CED-1 in C. elegans.

PubMed

Neukomm, L J; Zeng, S; Frei, A P; Huegli, P A; Hengartner, M O

2014-06-01

The rapid clearance of dying cells is important for the well-being of multicellular organisms. In C. elegans, cell corpse removal is mainly mediated by three parallel engulfment signaling cascades. These pathways include two small GTPases, MIG-2/RhoG and CED-10/Rac1. Here we present the identification and characterization of CDC-42 as a third GTPase involved in the regulation of cell corpse clearance. Genetic analyses performed by both loss of cdc-42 function and cdc-42 overexpression place cdc-42 in parallel to the ced-2/5/12 signaling module, in parallel to or upstream of the ced-10 module, and downstream of the ced-1/6/7 module. CDC-42 accumulates in engulfing cells at membranes surrounding apoptotic corpses. The formation of such halos depends on the integrins PAT-2/PAT-3, UNC-112 and the GEF protein UIG-1, but not on the canonical ced-1/6/7 or ced-2/5/12 signaling modules. Together, our results suggest that the small GTPase CDC-42 regulates apoptotic cell engulfment possibly upstream of the canonical Rac GTPase CED-10, by polarizing the engulfing cell toward the apoptotic corpse in response to integrin signaling and ced-1/6/7 signaling in C. elegans.

Analysis of environmental and general science efficacy among instructors with contrasting class ethnicity distributions: A four-dimensional assessment

NASA Astrophysics Data System (ADS)

Taylor, Bryan Keith

Scope and method of study. The context and nature of self-efficacy beliefs provides a vector upon which to explore science instructors' perceptions of their own competence, self beliefs, and beliefs concerning their students as a function of ethnicity (Pajares, 1996). Currently, available cross-sectional data that concomitantly compares efficacy for environmental and general science curricula among instructors with contrasting class ethnicity distributions (CED) (minority vs. non-minority) is diminutive. Here, a modified research instrument that incorporates the Environmental Education Efficacy Belief Instrument (Sia, 1992), the Science Teaching Efficacy Beliefs Instrument (Riggs & Enochs, 1990), and factors 2 & 3 from the Ohio State Teacher Efficacy Scale (Tschannen-Moran & Hoy, 2001) is employed to create a bi-disciplinary four dimensional assessment that measures personal teacher efficacy (PTE), outcome expectancy (OE), classroom management (CM), and student engagement (SE). Instructors' willingness to, and utilization of, practical instruction to reinforce science learning is also assessed. Findings and conclusions. Overall, efficacy levels for environmental and general science curriculum among instructors with high minority CED (n=22) were consistently lower than that of instructors with high non-minority CED (n = 18); consistently diminished efficacy levels were evidenced upon analysis of CED and all independent variables analyzed. While all four dimensions of efficacy were consistently low for instructors with high minority CED, markedly low mean CM and SE responses were evidenced. A link exists between teacher self-efficacy and the conditions present that impinge on the successful completion of work goals (Metz, 1978). Many studies have examined the lowered-level of minority involvement in environmental careers, issues, and concerns (Taylor, 1989). While all science instructors were willing to utilize outdoor classrooms, markedly lower outdoor classroom utilization was evidenced among instructors with high minority CED. The consistently low efficacy scores referenced herein for science instructors with high minority CED can be utilized to highlight science teacher efficacy as a critical point of concern as well as a crucial factor in tracing the genesis of the minority achievement gap in science. This research provides for the determination of efficacy as a contributive factor within the pathway for substantive rationale underlying the lack of minority representation and achievement within the many disciplines of science.

Interplay between CedA, rpoB and double stranded DNA: A step towards understanding CedA mediated cell division in E. coli.

PubMed

Sharma, Pankaj; Tomar, Anil Kumar; Kundu, Bishwajit

2018-02-01

Cell division is compromised in DnaAcos mutant E. coli cells due to chromosome over-replication. In these cells, CedA acts as a regulatory protein and initiates cell division by a hitherto unknown mechanism. CedA, a double stranded DNA binding protein, interacts with various subunits of RNA polymerase complex, including rpoB. To reveal how this concert between CedA, rpoB and DNA brings about cell division in E. coli, we performed biophysical and in silico analysis and obtained mechanistic insights. Interaction between CedA and rpoB was shown by circular dichroism spectrometry and in silico docking experiments. Further, CedA and rpoB were allowed to interact individually to a selected DNA and their binding was monitored by fluorescence spectroscopy. The binding constants of these interactions as determined by BioLayer Interferometry clearly show that rpoB binds to DNA with higher affinity (K D2 =<1.0E-12M) as compared to CedA (K D2 =9.58E-09M). These findings were supported by docking analysis where 12 intermolecular H-bonds were formed in rpoB-DNA complex as compared to 4 in CedA-DNA complex. Based on our data we propose that in E. coli cells chromosome over-replication signals CedA to recruit rpoB to specific DNA site(s), which initiates transcription of cell division regulatory elements. Copyright © 2017 Elsevier B.V. All rights reserved.

Next-generation concurrent engineering: developing models to complement point designs

NASA Technical Reports Server (NTRS)

Morse, Elizabeth; Leavens, Tracy; Cohanim, Babak; Harmon, Corey; Mahr, Eric; Lewis, Brian

2006-01-01

Concurrent Engineering Design (CED) teams have made routine the rapid development of point designs for space missions. The Jet Propulsion Laboratory's Team X is now evolving into a 'next-generation CED; in addition to a point design, the Team develops a model of the local trade space. The process is a balance between the power of a model developing tools and the creativity of humal experts, enabling the development of a variety of trade models for any space mission. This paper reviews the modeling method and its practical implementation in the ED environment. Example results illustrate the benefit of this approach.

Convection-enhanced delivery for the treatment of glioblastoma.

PubMed

Vogelbaum, Michael A; Aghi, Manish K

2015-03-01

Effective treatment of glioblastoma (GBM) remains a formidable challenge. Survival rates remain poor despite decades of clinical trials of conventional and novel, biologically targeted therapeutics. There is considerable evidence that most of these therapeutics do not reach their targets in the brain when administered via conventional routes (intravenous or oral). Hence, direct delivery of therapeutics to the brain and to brain tumors is an active area of investigation. One of these techniques, convection-enhanced delivery (CED), involves the implantation of catheters through which conventional and novel therapeutic formulations can be delivered using continuous, low-positive-pressure bulk flow. Investigation in preclinical and clinical settings has demonstrated that CED can produce effective delivery of therapeutics to substantial volumes of brain and brain tumor. However, limitations in catheter technology and imaging of delivery have prevented this technique from being reliable and reproducible, and the only completed phase III study in GBM did not show a survival benefit for patients treated with an investigational therapeutic delivered via CED. Further development of CED is ongoing, with novel catheter designs and imaging approaches that may allow CED to become a more effective therapeutic delivery technique. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Identification of functional interactome of a key cell division regulatory protein CedA of E.coli.

PubMed

Sharma, Pankaj; Tomar, Anil Kumar; Kundu, Bishwajit

2018-01-01

Cell division is compromised in DnaAcos mutant Escherichia coli cells that results in filamentous cell morphology. This is countered by over-expression of CedA protein that induces cytokinesis and thus, regular cell morphology is regained; however via an unknown mechanism. To understand the process systematically, exact role of CedA should be deciphered. Protein interactions are crucial for functional organization of a cell and their identification helps in revealing exact function(s) of a protein and its binding partners. Thus, this study was intended to identify CedA binding proteins (CBPs) to gain more clues of CedA function. We isolated CBPs by pull down assay using purified recombinant CedA and identified nine CBPs by mass spectrometric analysis (MALDI-TOF MS and LC-MS/MS), viz. PDHA1, RL2, DNAK, LPP, RPOB, G6PD, GLMS, RL3 and YBCJ. Based on CBPs identified, we hypothesize that CedA plays a crucial and multifaceted role in cell cycle regulation and specific pathways in which CedA participates may include transcription and energy metabolism. However, further validation through in-vitro and in-vivo experiments is necessary. In conclusion, identification of CBPs may help us in deciphering mechanism of CedA mediated cell division during chromosomal DNA over-replication. Copyright © 2017 Elsevier B.V. All rights reserved.

New configuration for efficient and durable copper coating on the outer surface of a tube

DOE PAGES

Ahmad, Irfan; Chapman, Steven F.; Velas, Katherine M.; ...

2017-03-27

A well-adhered copper coating on stainless steel power coupler parts is required in superconducting radio frequency (SRF) accelerators. Radio frequency power coupler parts are complex, tubelike stainless steel structures, which require copper coating on their outer and inner surfaces. Conventional copper electroplating sometimes produces films with inadequate adhesion strength for SRF applications. Electroplating also requires a thin nickel strike layer under the copper coating, whose magnetic properties can be detrimental to SRF applications. Coaxial energetic deposition (CED) and sputtering methods have demonstrated efficient conformal coating on the inner surfaces of tubes but coating the outer surface of a tube ismore » challenging because these coating methods are line of sight. When the substrate is off axis and the plasma source is on axis, only a small section of the substrate’s outer surface is exposed to the source cathode. The conventional approach is to rotate the tube to achieve uniformity across the outer surface. This method results in poor film thickness uniformity and wastes most of the source plasma. Alameda Applied Sciences Corporation (AASC) has developed a novel configuration called hollow external cathode CED (HEC-CED) to overcome these issues. HEC-CED produces a film with uniform thickness and efficiently uses all eroded source material. Furthermore, the Cu film deposited on the outside of a stainless steel tube using the new HEC-CED configuration survived a high pressure water rinse adhesion test. HEC-CED can be used to coat the outside of any cylindrical structure.« less

New configuration for efficient and durable copper coating on the outer surface of a tube

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmad, Irfan; Chapman, Steven F.; Velas, Katherine M.

A well-adhered copper coating on stainless steel power coupler parts is required in superconducting radio frequency (SRF) accelerators. Radio frequency power coupler parts are complex, tubelike stainless steel structures, which require copper coating on their outer and inner surfaces. Conventional copper electroplating sometimes produces films with inadequate adhesion strength for SRF applications. Electroplating also requires a thin nickel strike layer under the copper coating, whose magnetic properties can be detrimental to SRF applications. Coaxial energetic deposition (CED) and sputtering methods have demonstrated efficient conformal coating on the inner surfaces of tubes but coating the outer surface of a tube ismore » challenging because these coating methods are line of sight. When the substrate is off axis and the plasma source is on axis, only a small section of the substrate’s outer surface is exposed to the source cathode. The conventional approach is to rotate the tube to achieve uniformity across the outer surface. This method results in poor film thickness uniformity and wastes most of the source plasma. Alameda Applied Sciences Corporation (AASC) has developed a novel configuration called hollow external cathode CED (HEC-CED) to overcome these issues. HEC-CED produces a film with uniform thickness and efficiently uses all eroded source material. Furthermore, the Cu film deposited on the outside of a stainless steel tube using the new HEC-CED configuration survived a high pressure water rinse adhesion test. HEC-CED can be used to coat the outside of any cylindrical structure.« less

Conducted energy devices: pilot analysis of (non-)attributability of death using a modified Naranjo algorithm.

PubMed

Fox, Anthony W; Payne-James, J Jason

2012-11-30

Alleged fatalities associated with conductive-energy devices (CEDs) are similar to alleged serious adverse events (SAEs) after the use of pharmaceutical products: both types of case arise rarely, in complex (if not unique) combinations of circumstances, frequently when there are multiple concomitant putative aetiologies for the injury, and after the suspected product has been previously well-designed and tested. Attribution (or otherwise) of SAEs to pharmaceutical products is often assessed by use of the Naranjo algorithm. The purpose of this study was to investigate whether an adapted Naranjo algorithm could be used to assess alleged CED-associated fatalities. Unique cases had four independent identifiers. Prospectively, 7 (of the 10) Naranjo algorithm questions were chosen as being potentially applicable to CED use. These had maximum score 9, and the associated ordinal probability scale (doubtful, possible, probable, and definite) was retained by linear proportion to the integral scores. An arbitrary requirement was for database sufficiency≥50%=([n unique cases×7 questions answerable]×0.5); a pilot sample (n=29 unique cases) suggested feasibility (see below). One hundred and seventy-five unique cases were found, with a data sufficiency of 56.8%. Modified Naranjo algorithm scores had an unequally bimodal distribution. CED-attributability was suggested in 21 (12% of 175) cases. Substantial numbers of concomitant conditions existed among cases with low algorithm scores, all being potentially lethal under field conditions without CED exposure. The number of CED-administered shocks sustained was unrelated to CED-attributability of fatality. Two of the Naranjo questions (regarding dechallenge and the effects of challenge with a non-identical but similar agent) proved to be non-contributory. An algorithmic approach to assessment of CED-associated fatality seems feasible. By these pharmacovigilance standards, some published case fatality rates attributable to CED exposure seem exaggerated. CED-attributable deaths have close similarity to Type-B SAEs. The latter are rare, unpredictable, and usually due to a patient idiosyncrasy. In the person being restrained, such idiosyncratic factors may be unavoidable by law enforcement officers (LEO) in the field. These are unlike predictable (Type-A) SAEs, which have their corollary amongst secondary CED-associated deaths, e.g., head injury among cyclists or ignition of an inflammable atmosphere by the CED, and are identifiable risk factors for which LEO can train. Regardless, absolute CED tolerability is obviously greater than that for firearms. A prospective registry of CED deployments would measure this more precisely. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Convection-Enhanced Delivery (CED) in an Animal Model of Malignant Peripheral Nerve Sheath Tumors and Plexiform Neurofibromas

DTIC Science & Technology

2011-09-01

with an accelerated schedule Convection-Enhanced Delivery ( CED ), Malignant Peripheral Nerve Sheath ( MPNST ), Plexiform Neurofibromas (PN...the distribution of macromolecules delivered to intraneural PNs and MPNST via CED . Design: Orthotopic xenograft models of sciatic intraneural NF1...determine the efficacy CED of the epidermal growth factor receptor (EGFR) inhibitor erlotinib in animal models of intraneural PNs and MPNST

A Comparison of Three Sequences of Moves for Teaching Conjunctive and Relational Mathematical Concepts to Students in Elementary Education.

ERIC Educational Resources Information Center

Catanzano, Robert

Thirty-six prospective elementary education teachers were randomly assigned to three instructional moves: a characterization-exemplification with declarative statements (CED), a characterization-exemplification with interrogative statements (CEI), and an exemplification (E). The purposes of the study were to: (1) examine the efforts of the three…

Development of a portable quality control application using a tablet-type electronic device.

PubMed

Ono, Tomohiro; Miyabe, Yuki; Akimoto, Mami; Mukumoto, Nobutaka; Ishihara, Yoshitomo; Nakamura, Mitsuhiro; Mizowaki, Takashi

2018-03-01

Our aim was to develop a portable quality control (QC) application using a thermometer, a barometer, an angle gauge, and a range finder implemented in a tablet-type consumer electronic device (CED) and to assess the accuracies of the measurements made. The QC application was programmed using Java and OpenCV libraries. First, temperature and atmospheric pressure were measured over 30 days using the temperature and pressure sensors of the CED and compared with those measured by a double-tube thermometer and a digital barometer. Second, the angle gauge was developed using the accelerometer of the CED. The roll and pitch angles of the CED were measured from 0 to 90° at intervals of 10° in the clockwise (CW) and counterclockwise (CCW) directions. The values were compared with those measured by a digital angle gauge. Third, a range finder was developed using the tablet's built-in camera and image-processing capacities. Surrogate markers were detected by the camera and their positions converted to actual positions using a homographic transformation method. Fiducial markers were placed on a treatment couch and moved 100 mm in 10-mm steps in both the lateral and longitudinal directions. The values were compared with those measured by the digital output of the treatment couch. The differences between CED values and those of other devices were compared by calculating means ± standard deviations (SDs). The means ± SDs of differences in temperature and atmospheric pressure were -0.07 ± 0.25°C and 0.05 ± 0.10 hPa, respectively. The means ± SDs of the difference in angle was -0.17 ± 0.87° (0.15 ± 0.23° degrees excluding the 90° angle). The means ± SDs of distances were 0.01 ± 0.07 mm in both the lateral and longitudinal directions. Our portable QC application was accurate and may be used instead of standard measuring devices. Our portable CED is efficient and simple when used in the field of medical physics. © 2018 American Association of Physicists in Medicine.

Convection-Enhanced Delivery (CED) in an Animal Model of Malignant Peripheral Nerve Sheath (MPNST) Tumors and Plexiform Neurofibromas (PN)

DTIC Science & Technology

2012-09-01

TITLE: Convection-Enhanced Delivery ( CED ) in an Animal Model of Malignant Peripheral Nerve Sheath ( MPNST ) Tumors and Plexiform Neurofibromas (PN...within the sciatic nerve. 15. SUBJECT TERMS Convection-Enhanced Delivery ( CED ), Malignant Peripheral Nerve Sheath ( MPNST ), Plexiform Neurofibromas...determine the distribution of macromolecules delivered to intraneural PNs and MPNST via CED . Design: Orthotopic xenograft models of sciatic intraneural

Voxelized Computational Model for Convection-Enhanced Delivery in the Rat Ventral Hippocampus: Comparison with In Vivo MR Experimental Studies

PubMed Central

Kim, Jung Hwan; Astary, Garrett W.; Kantorovich, Svetlana; Mareci, Thomas H.; Carney, Paul R.; Sarntinoranont, Malisa

2012-01-01

Convection-enhanced delivery (CED) is a promising local delivery technique for overcoming the blood–brain barrier (BBB) and treating diseases of the central nervous system (CNS). For CED, therapeutics are infused directly into brain tissue and the drug agent is spread through the extracellular space, considered to be highly tortuous porous media. In this study, 3D computational models developed using magnetic resonance (MR) diffusion tensor imaging data sets were used to predict CED transport in the rat ventral hippocampus using a voxelized modeling previously developed by our group. Predicted albumin tracer distributions were compared with MR-measured distributions from in vivo CED in the ventral hippocampus up to 10 μL of Gd-DTPA albumin tracer infusion. Predicted and measured tissue distribution volumes and distribution patterns after 5 and 10 μL infusions were found to be comparable. Tracers were found to occupy the underlying landmark structures with preferential transport found in regions with less fluid resistance such as the molecular layer of the dentate gyrus. Also, tracer spread was bounded by high fluid resistance layers such as the granular cell layer and pyramidal cell layer of dentate gyrus. Leakage of tracers into adjacent CSF spaces was observed towards the end of infusions. PMID:22532321

Convection-Enhanced Delivery (CED) in an Animal Model of Malignant Peripheral Nerve Sheath Tumors and Plexiform Neurofibromas

DTIC Science & Technology

2013-02-01

successfully establish the xenograft within the sciatic nerve. Convection-Enhanced Delivery ( CED ), Malignant Peripheral Nerve Sheath ( MPNST ), Plexiform...intraneural PNs and MPNST via CED . Design: Orthotopic xenograft models of sciatic intraneural NF1 MPNST and PNs in scid mice as described by Perrin et...using convection-enhanced delivery ( CED ). Relative Growth of MPNST cells in vivo treated with rapamycin, imatinib or erlotinib: Elotinib

Excess male chronic energy deficiency among adolescents: a cross-sectional study in the context of patrilineal and matrilineal societies in Northeast India.

PubMed

Khongsdier, R; Varte, R; Mukherjee, N

2005-09-01

To determine the sex differences in chronic energy deficiency (CED) among adolescents in the context of patrilineal and matrilineal societies in Northeast India. Cross-sectional, community-based study of the Hmar patrilineal society and the Khasi (War and Khynriam) matrilineal society. Mizoram and Meghalaya in Northeast India. In total, 1733 adolescent boys and girls aged 9-16 y: Khynriam Khasis (n = 1005), War Khasis (n = 305) and Hmars (n = 423). Weight, height, and socio-economic characteristics. Body mass index (weight in kg/height in m2) was used for assessing CED relative to the international reference values. The overall prevalence of CED was significantly greater in boys than in girls. The sex differences in the prevalence of CED were 5, 10 and 6% points in the Khynriam Khasis, War Khasis and Hmars, respectively. Allowing for age and socio-economic variables, the risks of CED were about 1.82 (95% CI 1.14-2.90), 1.83 (95% CI 1.19-3.33) and 1.78 (95% CI 1.10-3.25) times greater in boys than in girls among the Khynriam Khasis, War Khasis and Hmars, respectively. Using logistic regression analysis, the prevalence of CED was negatively associated with family income across study populations. No significant association was found between CED and religion. Patrilineal and matrilineal forms of society were not reflected in the prevalence of CED among adolescents. Subject to further studies of the research problems concerning the nutritional status of adolescents, girls fare better than boys with respect to the prevalence of CED.

Health technology assessment in Switzerland: a descriptive analysis of “Coverage with Evidence Development” decisions from 1996 to 2013

PubMed Central

Brügger, Urs; Horisberger, Bruno; Ruckstuhl, Alexander; Plessow, Rafael; Eichler, Klaus; Gratwohl, Alois

2015-01-01

Objectives To identify factors associated with the decisions of the Federal Department of Home Affairs concerning coverage with evidence development (CED) for contested novel medical technologies in Switzerland. Design Quantitative, retrospective, descriptive analysis of publicly available material and prospective, structured, qualitative interviews with key stakeholders. Setting All 152 controversial medical services decided on by the Federal Commission on Health Insurance Benefits within the framework of the new federal law on health insurance in Switzerland from 1997 to 2013, with focus on 33 technologies assigned initially to CED and 33 to evidence development without coverage. Main outcome measures Factors associated with numbers and type of contested services assigned to CED per year, the duration and final outcome of the evaluations and perceptions of key stakeholders. Results The rate of CED decisions (82 total; median 1.5/year; range 0–9/year), the time to final decision (4.5 years median; 0.75 to +11 years) and the probability of a final ‘yes’ varied over time. In logistic regression models, the change of office of the commission provided the best explanation for the observed outcomes. Good intentions but absence of scientific criteria for decisions were reported as major comments by the stakeholders. Conclusions The introduction of CED enabled access to some promising technologies early in their life cycle, and might have triggered establishment of registries and research. Impact on patients’ outcome and costs remain unknown. The primary association of institutional changes with measured end points illustrates the need for evaluation of the current health technology assessment (HTA) system. PMID:25818273

Meet Karen Dilka, Executive Director of the Council on Education of the Deaf

ERIC Educational Resources Information Center

Montgomery, Judy K.

2008-01-01

In April 2007, at the annual Council for Exceptional Children (CEC) Convention in Louisville, the author had the pleasure of meeting and then dining with Dr. Karen Dilka, executive director of the Council on Education of the Deaf (CED). Dilka also contributed as the on-site liaison and local arrangements chairperson for the Division for…

Exploration of resistive targets within shallow marine environments using the circular electrical dipole and the differential electrical dipole methods: a time-domain modelling study

NASA Astrophysics Data System (ADS)

Haroon, Amir; Mogilatov, Vladimir; Goldman, Mark; Bergers, Rainer; Tezkan, Bülent

2016-05-01

Two novel transient controlled source electromagnetic methods called circular electrical dipole (CED) and differential electrical dipole (DED) are theoretically analysed for applications in shallow marine environments. 1-D and 3-D time-domain modelling studies are used to investigate the detectability and applicability of the methods when investigating resistive layers/targets representing hydrocarbon-saturated formations. The results are compared to the conventional time-domain horizontal electrical dipole (HED) and vertical electrical dipole (VED) sources. The applied theoretical modelling studies demonstrate that CED and DED have higher signal detectability towards resistive targets compared to TD-CSEM, but demonstrate significantly poorer signal amplitudes. Future CED/DED applications will have to solve this issue prior to measuring. Furthermore, the two novel methods have very similar detectability characteristics towards 3-D resistive targets embedded in marine sediments as VED while being less susceptible towards non-verticality. Due to the complex transmitter design of CED/DED the systems are prone to geometrical errors. Modelling studies show that even small transmitter inaccuracies have strong effects on the signal characteristics of CED making an actual marine application difficult at the present time. In contrast, the DED signal is less affected by geometrical errors in comparison to CED and may therefore be more adequate for marine applications.

Functional analysis of CedA based on its structure: residues important in binding of DNA and RNA polymerase and in the cell division regulation

PubMed Central

Abe, Yoshito; Fujisaki, Naoki; Miyoshi, Takanori; Watanabe, Noriko; Katayama, Tsutomu; Ueda, Tadashi

2016-01-01

DnaAcos, a mutant of the initiator DnaA, causes overinitiation of chromosome replication in Escherichia coli, resulting in inhibition of cell division. CedA was found to be a multi-copy suppressor which represses the dnaAcos inhibition of cell division. However, functional mechanism of CedA remains elusive except for previously indicated possibilities in binding to DNA and RNA polymerase. In this study, we searched for the specific sites of CedA in binding of DNA and RNA polymerase and in repression of cell division inhibition. First, DNA sequence to which CedA preferentially binds was determined. Next, the several residues and β4 region in CedA C-terminal domain was suggested to specifically interact with the DNA. Moreover, we found that the flexible N-terminal region was required for tight binding to longer DNA as well as interaction with RNA polymerase. Based on these results, several cedA mutants were examined in ability for repressing dnaAcos cell division inhibition. We found that the N-terminal region was dispensable and that Glu32 in the C-terminal domain was required for the repression. These results suggest that CedA has multiple roles and residues with different functions are positioned in the two regions. PMID:26400504

The distribution and mortality impact of chronic energy deficiency among adult Nigerian men and women.

PubMed

Rotimi, C; Okosun, I; Johnson, L; Owoaje, E; Lawoyin, T; Asuzu, M; Kaufman, J; Adeyemo, A; Cooper, R

1999-09-01

To determine the prevalence of chronic energy deficiency (CED) and associated mortality risk in a cohort of adult Nigerians followed from 1992 to 1997. The data for this investigation were derived from an international collaborative study on chronic diseases in populations of the African diaspora. Body mass index (BMI) was used to define three grades of CED in 4061 men and women aged 25 years and older: Grade I (mild CED) as BMI 17.5-18.4, Grade II (moderate CED) as BMI 16.0-17.4, and Grade III (severe CED) as BMI < 16.0 and BMI > or = 18.5 was considered normal. The odds of mortality associated with differing grades of CED was estimated with logistic regression analysis. The prevalence of CED (BMI < 18.5) increased from 14.3% in 1992 to 19.6% in 1997, both genders combined. The prevalence of CED was similar for both sexes in 1992 (14%) but increased to 22.4% in men and 17.4% in women by 1997. The prevalence of CED was 8.5%, 7.6 and 3.4 for Grades I, II and III, respectively. Two hundred and seven deaths occurred during the follow-up period. The mortality rate for the 5.5 y of follow-up was 5.1% (207/4061). The odds ratios (95% CIs) for all cause mortality were 1.4 (0.5, 3.8), 2.4 (1.2, 4.9) and 2.5 (1.0, 6.2), respectively, for CED grades I, II and III adjusting for age and sex. Under nutrition is an increasing problem in Nigerian men and women. The economic reforms (structural adjustment program (SAP)) introduced in 1986 in combination with the continued economic woes brought on by political instability, corruption and nepotism have been advanced by several investigators as the main factors in the growing problem of inadequate calorie intake. Intervention strategies both at the government and private sectors are urgently needed to increase food availability.

Convection-enhanced delivery of a hydrophilic nitrosourea ameliorates deficits and suppresses tumor growth in experimental spinal cord glioma models.

PubMed

Ogita, Shogo; Endo, Toshiki; Sugiyama, Shinichiro; Saito, Ryuta; Inoue, Tomoo; Sumiyoshi, Akira; Nonaka, Hiroi; Kawashima, Ryuta; Sonoda, Yukihiko; Tominaga, Teiji

2017-05-01

Convection-enhanced delivery (CED) is a technique allowing local infusion of therapeutic agents into the central nervous system, circumventing the blood-brain or spinal cord barrier. To evaluate the utility of nimustine hydrochloride (ACNU) CED in controlling tumor progression in an experimental spinal cord glioma model. Toxicity studies were performed in 42 rats following the administration of 4 μl of ACNU CED into the mid-thoracic spinal cord at concentrations ranging from 0.1 to 10 mg/ml. Behavioral analyses and histological evaluations were performed to assess ACNU toxicity in the spinal cord. A survival study was performed in 32 rats following the implantation of 9 L cells into the T8 spinal cord. Seven days after the implantation, rats were assigned to four groups: ACNU CED (0.25 mg/ml; n = 8); ACNU intravenous (i.v.) (0.4 mg; n = 8); saline CED (n = 8); saline i.v. (n = 8). Hind limb movements were evaluated daily in all rats for 21 days. Tumor sizes were measured histologically. The maximum tolerated ACNU concentration was 0.25 mg/ml. Preservation of hind limb motor function and tumor growth suppression was observed in the ACNU CED (0.25 mg/ml) and ACNU i.v. groups. Antitumor effects were more prominent in the ACNU CED group especially in behavioral analyses (P < 0.05; log-rank test). ACNU CED had efficacy in controlling tumor growth and preserving neurological function in an experimental spinal cord tumor model. ACNU CED can be a viable treatment option for spinal cord high-grade glioma.

Convection-enhanced delivery of SN-38-loaded polymeric micelles (NK012) enables consistent distribution of SN-38 and is effective against rodent intracranial brain tumor models.

PubMed

Zhang, Rong; Saito, Ryuta; Mano, Yui; Sumiyoshi, Akira; Kanamori, Masayuki; Sonoda, Yukihiko; Kawashima, Ryuta; Tominaga, Teiji

2016-10-01

Convection-enhanced delivery (CED) of therapeutic agents is a promising local delivery technique that has been extensively studied as a treatment for CNS diseases over the last two decades. One continuing challenge of CED is accurate and consistent delivery of the agents to the target. The present study focused on a new type of therapeutic agent, NK012, a novel SN-38-loaded polymeric micelle. Local delivery profiles of NK012 and SN-38 were studied using rodent brain and intracranial rodent brain tumor models. First, the cytotoxicity of NK012 against glioma cell lines was determined in vitro. Proliferations of glioma cells were significantly reduced after exposure to NK012. Then, the distribution and local toxicity after CED delivery of NK012 and SN-38 were evaluated in vivo. Volume of distribution of NK012 after CED was much larger than that of SN-38. Histological examination revealed minimum brain tissue damage in rat brains after delivery of 40 µg NK012 but severe damage with SN-38 at the same dose. Subsequently, the efficacy of NK012 delivered via CED was tested in 9L and U87MG rodent orthotopic brain tumor models. CED of NK012 displayed excellent efficacy in the 9L and U87MG orthotopic brain tumor models. Furthermore, NK012 and gadolinium diamide were co-delivered via CED to monitor the NK012 distribution using MRI. Volume of NK012 distribution evaluated by histology and MRI showed excellent agreement. CED of NK012 represents an effective treatment option for malignant gliomas. MRI-guided CED of NK012 has potential for clinical application.

The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: Synergism with the benzodiazepine diazepam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultz, M.K.; Wright, L.K.M.; Stone, M.F.

2012-03-15

Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of γ-aminobutyric acid A (GABA{sub A}) receptors. However, seizure activity itself causes the endocytosis of GABA{sub A} receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-D-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20 mg/kg, im) and DZP (10 mg/kg, sc), administered both separately and in combination, at 10, 20 or 30 min followingmore » seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD{sub 50}; 132 μg/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2 mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20–30 min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity. -- Highlights: ► Soman (GD) produced seizure activity resulting in neuropathology in rats. ► Tx: caramiphen (CED) and/or diazepam (DZP) @ 10, 20 or 30 min after seizure onset. ► CED/DZP showed superior anticonvulsant and neuroprotective capacity. ► Physostigmine (PHY) was examined as an adjunct post-exposure therapy. ► PHY attenuated GD-induced seizure development, but not seizure duration.« less

Functional analysis of CedA based on its structure: residues important in binding of DNA and RNA polymerase and in the cell division regulation.

PubMed

Abe, Yoshito; Fujisaki, Naoki; Miyoshi, Takanori; Watanabe, Noriko; Katayama, Tsutomu; Ueda, Tadashi

2016-02-01

DnaAcos, a mutant of the initiator DnaA, causes overinitiation of chromosome replication in Escherichia coli, resulting in inhibition of cell division. CedA was found to be a multi-copy suppressor which represses the dnaAcos inhibition of cell division. However, functional mechanism of CedA remains elusive except for previously indicated possibilities in binding to DNA and RNA polymerase. In this study, we searched for the specific sites of CedA in binding of DNA and RNA polymerase and in repression of cell division inhibition. First, DNA sequence to which CedA preferentially binds was determined. Next, the several residues and β4 region in CedA C-terminal domain was suggested to specifically interact with the DNA. Moreover, we found that the flexible N-terminal region was required for tight binding to longer DNA as well as interaction with RNA polymerase. Based on these results, several cedA mutants were examined in ability for repressing dnaAcos cell division inhibition. We found that the N-terminal region was dispensable and that Glu32 in the C-terminal domain was required for the repression. These results suggest that CedA has multiple roles and residues with different functions are positioned in the two regions. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Liposomal temozolomide drug delivery using convection enhanced delivery.

PubMed

Nordling-David, Mirjam M; Yaffe, Roni; Guez, David; Meirow, Hadar; Last, David; Grad, Etty; Salomon, Sharona; Sharabi, Shirley; Levi-Kalisman, Yael; Golomb, Gershon; Mardor, Yael

2017-09-10

Even though some progress in diagnosis and treatment has been made over the years, there is still no definitive treatment available for Glioblastoma multiforme (GBM). Convection-enhanced delivery (CED), a continuous infusion-mediated pressure gradient via intracranial catheters, studied in clinical trials, enables in situ drug concentrations several orders of magnitude greater than those achieved by systemic administration. We hypothesized that the currently limited efficacy of CED could be enhanced by a liposomal formulation, thus achieving enhanced drug localization to the tumor site with minimal toxicity. We hereby describe a novel approach for treating GBM by CED of liposomes containing the known chemotherapeutic agent, temozolomide (TMZ). A new technique for encapsulating TMZ in hydrophilic (PEGylated) liposomes, characterized by nano-size (121nm), low polydispersity index (<0.13) and with near-neutral charge (-ʒ,0.2mV), has been developed. Co-infusion of PEGylated Gd-DTPA liposomes and TMZ-liposomes by CED in GBM bearing rats, resulted in enhanced tumor detection with longer residence time than free Gd-DTPA. Treatment of GBM-bearing rats with either TMZ solution or TMZ-liposomes resulted in greater tumor inhibition and significantly higher survival. However, the longer survival and smaller tumor volumes exhibited by TMZ liposomal treatment in comparison to TMZ in solution were insignificant (p<0.053); and only significantly lower edema volumes were observed. Thus, there are no clear-cut advantages to use a liposomal delivery system of TMZ via CED over a drug solution. Copyright © 2017 Elsevier B.V. All rights reserved.

A simulation study to quantify the impacts of exposure ...

EPA Pesticide Factsheets

A simulation study to quantify the impacts of exposure measurement error on air pollution health risk estimates in copollutant time-series models The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-support tools, and models to be applied to media-specific or receptor-specific problem areas. CED uses modeling-based approaches to characterize exposures, evaluate fate and transport, and support environmental diagnostics/forensics with input from multiple data sources. It also develops media- and receptor-specific models, process models, and decision support tools for use both within and outside of EPA.

12 CFR 28.15 - Capital equivalency deposits.

Code of Federal Regulations, 2011 CFR

2011-01-01

... provided by the OCC, a foreign bank's capital equivalency deposits (CED) must consist of: (i) Investment... increase its CED above the minimum amount. For example, the OCC may require an increase if a Federal branch... arrangements. A foreign bank should require its depository bank to segregate its CED on the depository bank's...

12 CFR 28.15 - Capital equivalency deposits.

Code of Federal Regulations, 2012 CFR

2012-01-01

... provided by the OCC, a foreign bank's capital equivalency deposits (CED) must consist of: (i) Investment... increase its CED above the minimum amount. For example, the OCC may require an increase if a Federal branch... arrangements. A foreign bank should require its depository bank to segregate its CED on the depository bank's...

12 CFR 28.15 - Capital equivalency deposits.

Code of Federal Regulations, 2014 CFR

2014-01-01

... provided by the OCC, a foreign bank's capital equivalency deposits (CED) must consist of: (i) Investment... or agency in a state, it shall determine the CED and the amount of liabilities requiring capital... cases or otherwise, that a foreign bank increase its CED above the minimum amount. For example, the OCC...

12 CFR 28.15 - Capital equivalency deposits.

Code of Federal Regulations, 2013 CFR

2013-01-01

... provided by the OCC, a foreign bank's capital equivalency deposits (CED) must consist of: (i) Investment... or agency in a state, it shall determine the CED and the amount of liabilities requiring capital... cases or otherwise, that a foreign bank increase its CED above the minimum amount. For example, the OCC...

12 CFR 28.15 - Capital equivalency deposits.

Code of Federal Regulations, 2010 CFR

2010-01-01

... provided by the OCC, a foreign bank's capital equivalency deposits (CED) must consist of: (i) Investment... increase its CED above the minimum amount. For example, the OCC may require an increase if a Federal branch... arrangements. A foreign bank should require its depository bank to segregate its CED on the depository bank's...

Convection-enhanced delivery of nanoliposomal CPT-11 (irinotecan) and PEGylated liposomal doxorubicin (Doxil) in rodent intracranial brain tumor xenografts

PubMed Central

Krauze, Michal T.; Noble, Charles O.; Kawaguchi, Tomohiro; Drummond, Daryl; Kirpotin, Dmitri B.; Yamashita, Yoji; Kullberg, Erika; Forsayeth, John; Park, John W.; Bankiewicz, Krystof S.

2007-01-01

We have previously shown that convection-enhanced delivery (CED) of highly stable nanoparticle/liposome agents encapsulating chemotherapeutic drugs is effective against intracranial rodent brain tumor xenografts. In this study, we have evaluated the combination of a newly developed nanoparticle/liposome containing the topoisomerase I inhibitor CPT-11 (nanoliposomal CPT-11 [nLs-CPT-11]), and PEGylated liposomal doxorubicin (Doxil) containing the topoisomerase II inhibitor doxorubicin. Both drugs were detectable in the CNS for more than 36 days after a single CED application. Tissue half-life was 16.7 days for nLs-CPT-11 and 10.9 days for Doxil. The combination of the two agents produced synergistic cytotoxicity in vitro. In vivo in U251MG and U87MG intracranial rodent xenograft models, CED of the combination was also more efficacious than either agent used singly. Analysis of the parameters involved in this approach indicated that tissue pharmacokinetics, tumor microanatomy, and biochemical interactions of the drugs all contributed to the therapeutic efficacy observed. These findings have implications for further clinical applications of CED-based treatment of brain tumors. PMID:17652269

Convection-enhanced delivery of maghemite nanoparticles: Increased efficacy and MRI monitoring

PubMed Central

Perlstein, Benny; Ram, Zvi; Daniels, Dianne; Ocherashvilli, Aharon; Roth, Yiftach; Margel, Shlomo; Mardor, Yael

2008-01-01

Convection-enhanced drug delivery (CED) is a novel approach to delivering drugs into brain tissue. Drugs are delivered continuously via a catheter, enabling large volume distributions of high drug concentrations with minimum systemic toxicity. Previously we demonstrated that CED formation/extent of small molecules may be significantly improved by increasing infusate viscosities. In this study we show that the same methodology can be applied to monodispersed maghemite nanoparticles (MNPs). For this purpose we used a normal rat brain model and performed CED of MNPs over short infusion times. By adding 3% sucrose or 3%–6% polyethylene glycol (PEG; molecular weight 400) to saline containing pristine MNPs, we increased infusate viscosity and obtained increased CED efficacy. Further, we show that CED of dextran-coated MNPs (dextran-MNPs) resulted in increased efficacy over pristine MNPs (p < 0.007). To establish the use of MRI for reliable depiction of MNP distribution, CED of fluorescent dextran-MNPs was performed, demonstrating a significant correlation between the distributions as depicted by MRI and spectroscopic images (r2 = 0.74, p < 0.0002). MRI follow-up showed that approximately 80%–90% of the dextran-MNPs were cleared from the rat brain within 40 days of CED; the rest remained in the brain for more than 4 months. MNPs have been tested for applications such as targeted drug delivery and controlled drug release and are clinically used as a contrast agent for MRI. Thus, combining the CED method with the advantages of MNPs may provide a powerful tool to treat and monitor brain tumors. PMID:18316474

7 CFR 1221.232 - Disposition of records.

Code of Federal Regulations, 2012 CFR

2012-01-01

... summaries. Such records will be placed in a secure location under the custody of FSA CED for a period of not... FSA CED will place in sealed containers marked with the identification of the “Sorghum Checkoff... the Administrator, FSA, by the end of the 12 month period as described above, the CED or designee...

7 CFR 1221.232 - Disposition of records.

Code of Federal Regulations, 2013 CFR

2013-01-01

... summaries. Such records will be placed in a secure location under the custody of FSA CED for a period of not... FSA CED will place in sealed containers marked with the identification of the “Sorghum Checkoff... the Administrator, FSA, by the end of the 12 month period as described above, the CED or designee...

7 CFR 1221.232 - Disposition of records.

Code of Federal Regulations, 2011 CFR

2011-01-01

... summaries. Such records will be placed in a secure location under the custody of FSA CED for a period of not... FSA CED will place in sealed containers marked with the identification of the “Sorghum Checkoff... the Administrator, FSA, by the end of the 12 month period as described above, the CED or designee...

7 CFR 1221.232 - Disposition of records.

Code of Federal Regulations, 2014 CFR

2014-01-01

... summaries. Such records will be placed in a secure location under the custody of FSA CED for a period of not... FSA CED will place in sealed containers marked with the identification of the “Sorghum Checkoff... the Administrator, FSA, by the end of the 12 month period as described above, the CED or designee...

Application of corona electrical discharge plasma on modifying the physicochemical properties of banana starch indigenous to Taiwan.

PubMed

Wu, Tsung-Yen; Sun, Nan-Nong; Chau, Chi-Fai

2018-01-01

Corona electrical discharge (CED) belongs to an atmospheric pressure cold plasma. In this study, raw banana starch (indigenous to Taiwan), which contained resistant starch and amylose at a level of 58.4 g/100 g and 14.5 g/100 g, respectively, was treated by CED at 30 kV/cm, 40 kV/cm, and 50 kV/cm for 3 minutes. After the CED treatment, starch analyses showed that there were no apparent changes in the resistant starch and amylose contents. Only surface and nonpenetrative damage caused by plasma etching at different voltage strengths were observed on the starch granules. The CED treatments reduced the total area of diffraction peak, gelatinization enthalpy (by -21% to -38%), and different pasting behaviors including peak viscosity, breakdown, final viscosity, and setback. The CED treatments were capable of increasing relative crystallinity and gelatinization temperature. This study revealed the potential of CED plasma technology as a tool to modify the characteristics of banana starch. Copyright © 2017. Published by Elsevier B.V.

Convection-enhanced drug delivery to the brain: therapeutic potential and neuropathological considerations.

PubMed

Barua, Neil U; Gill, Steven S; Love, Seth

2014-03-01

Convection-enhanced delivery (CED) describes a direct method of drug delivery to the brain through intraparenchymal microcatheters. By establishing a pressure gradient at the tip of the infusion catheter in order to exploit bulk flow through the interstitial spaces of the brain, CED offers a number of advantages over conventional drug delivery methods-bypass of the blood-brain barrier, targeted distribution through large brain volumes and minimization of systemic side effects. Despite showing early promise, CED is yet to fulfill its potential as a mainstream strategy for the treatment of neurological disease. Substantial research effort has been dedicated to optimize the technology for CED and identify the parameters, which govern successful drug distribution. It seems likely that successful clinical translation of CED will depend on suitable catheter technology being used in combination with drugs with optimal physicochemical characteristics, and on neuropathological analysis in appropriate preclinical models. In this review, we consider the factors most likely to influence the success or failure of CED, and review its application to the treatment of high-grade glioma, Parkinson's disease (PD) and Alzheimer's disease (AD). © 2013 International Society of Neuropathology.

Determination of glycated nucleobases in human urine by a new monoclonal antibody specific for N2-carboxyethyl-2'-deoxyguanosine.

PubMed

Schneider, Marc; Thoss, Gerlinde; Hübner-Parajsz, Christa; Kientsch-Engel, Rose; Stahl, Peter; Pischetsrieder, Monika

2004-10-01

Sugars and sugar degradation products react in vivo readily with proteins (glycation) resulting in the formation of a heterogeneous group of reaction products, which are called advanced glycation end products (AGEs). AGEs notably change the structure and function of proteins so that extended protein-AGE formation is linked to complications such as nephropathy, atherosclerosis, and cataract. DNA can be glycated in vitro in a similar way as proteins, and the two diastereomers of N(2)-carboxyethyl-2'-deoxyguanosine (CEdG(A,B)) were identified as major DNA AGEs. It was postulated that DNA AGEs play an important role in aging, diabetes, and uremia. However, at the moment, sensitive methods to measure the extent and impact of DNA AGEs in vivo do not exist. In this study, we developed a monoclonal antibody, which recognized CEdG(A,B) with high affinity and specificity (MAb M-5.1.6). The I(50) value for CEdG(A,B) was 2.1 ng/mL, whereas other modified nuclueobases and AGE proteins showed negligible cross-reactivity. Unmodified 2'-deoxyguanosine was only weakly recognized with an I(50) value > 600,000 ng/mL, which is the limit of solubility. MAb M-5.1.6 was then used to measure the urinary excretion of AGE-modified nucleobases in a competitive enzyme-linked immunosorbent assay. The recovery of CEdG(A,B) from human urine was between 87.4 and 99.7% with coefficients of variations between 8.0 and 22.2%. The detection limit was 0.06 ng/mL, and the determination limit was 0.15 ng/mL with a linear range between 0.3 and 100 ng/mL. CEdG equivalents were analyzed in urine samples from 121 healthy volunteers, and concentrations between 1.2 and 117 ng CEdG equiv/mg creatinine were detected.

Repeat Intracranial Expansion After Skull Regrowth in Hyperostotic Disease: Technical Note.

PubMed

Wong, Timothy; Herschman, Yehuda; Patel, Nitesh V; Patel, Tushar; Hanft, Simon

2017-06-01

Camurati-Engelmann disease (CED) is a rare, autosomal-dominant genetic disorder resulting in hyperostosis of the long bones and skull. Patients often develop cranial nerve dysfunction and increased intracranial pressure secondary to stenosis of nerve foramina and hyperostosis. Surgical decompression may provide symptomatic relief in select patients; however, a small number of reports document the recurrence of symptoms due to bony regrowth. We present a patient who had been treated previously with bilateral frontal and parietal craniotomy who experienced recurrence of symptoms due to reossification of her cranial bones. This report underscores the progressive nature of CED and its influence on surgical management. Furthermore, we propose a novel surgical approach with multiple craniectomies and titanium mesh cranioplasties that could potentially offer long-term symptomatic relief. A 46-year-old female patient with CED who was treated with ventriculoperitoneal shunting, posterior fossa decompression, and multiple craniotomies 2 decades prior presented with signs and symptoms of increased intracranial pressure. Studies of the skull at presentation demonstrated rethickening of cranial bones that resulted in severely decreased intracranial volume. A radical craniectomy, requiring 4 separate bone flaps made up of bilateral frontal and parietal bones, was performed. The remaining coronal and sagittal bony struts were drilled to approximately 1 cm thick. Cranioplasties with 4 separate titanium meshes were performed to preserve the natural contour of the patient's skull. Although surgical decompression could provide some patients with CED symptomatic relief, clinicians should consider managing CED as a chronic condition. To the authors' knowledge, this is one of few case reports documenting the recurrence of symptoms in a patient with CED treated by surgical intervention. Furthermore, we propose that multiple craniectomies with titanium mesh cranioplasties confer more permanent symptomatic control, and, more importantly, lower the risk of recurrence secondary to cranial hyperostosis. Copyright © 2017 Elsevier Inc. All rights reserved.

77 FR 45599 - CED Rock Springs, Inc.; Supplemental Notice That Revised Market-Based Rate Tariff Filing Includes...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-01

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket Nos. ER02-2546-000; ER02-2546-001] CED Rock Springs, Inc.; Supplemental Notice That Revised Market- Based Rate Tariff Filing...-referenced proceeding of CED Rock Springs, Inc.'s tariff revision filing, noting that such filing includes a...

Convection-enhanced delivery of a synthetic retinoid Am80, loaded into polymeric micelles, prolongs the survival of rats bearing intracranial glioblastoma xenografts.

PubMed

Yokosawa, Michiko; Sonoda, Yukihiko; Sugiyama, Shin-ichiro; Saito, Ryuta; Yamashita, Yoji; Nishihara, Masamichi; Satoh, Taku; Kumabe, Toshihiro; Yokoyama, Masayuki; Tominaga, Teiji

2010-08-01

Prognosis for the patients with glioblastoma, the most common malignant brain tumor, remains dismal. A major barrier to progress in treatment of glioblastoma is the relative inaccessibility of tumors to chemotherapeutic agents. Convection-enhanced delivery (CED) is a direct intracranial drug infusion technique to deliver chemotherapeutic agents to the central nervous system, circumventing the blood-brain barrier and reducing systemic side effects. CED can provide wider distribution of infused agents compared to simple diffusion. We have reported that CED of a polymeric micelle carrier system could yield a clinically relevant distribution of encapsulated agents in the rat brain. Our aim was to evaluate the efficacy of CED of polymeric micellar Am80, a synthetic agonist with high affinity to nuclear retinoic acid receptor, in a rat model of glioblastoma xenografts. We also used systemic administration of temozolomide, a DNA-alkylating agent, which has been established as the standard of care for newly diagnosed malignant glioma. U87MG human glioma cells were injected into the cerebral hemisphere of nude rats. Rats bearing U87MG xenografts were treated with CED of micellar Am80 (2.4 mg/m(2)) on day 7 after tumor implantation. Temozolomide (200 mg/m(2)/day) was intraperitoneally administered daily for 5 days, starting on day 7 after tumor implantation. CED of micellar Am80 provided significantly longer survival than the control. The combination of CED of micellar Am80 and systemic administration of temozolomide provided significantly longer survival than single treatment. In conclusion, temozolomide combined with CED of micellar Am80 may be a promising method for the treatment of malignant gliomas.

Time-reversal Techniques in Ultrasound-assisted Convection-enhanced Drug Delivery to the Brain: Technology Development and In Vivo Evaluation

PubMed Central

Lewis, George K.; Guarino, Sabrina; Gandhi, Gaurav; Filinger, Laurent; Lewis, George K.; Olbricht, Willam L.; Sarvazyan, Armen

2011-01-01

We describe a drug delivery method that combines Time-Reversal Acoustics (TRA) with Convection-Enhanced Delivery (CED) to improve the delivery of therapeutics to the interstitium of the brain. The Ultrasound-assisted CED approach (UCED) circumvents the blood-brain barrier by infusing compounds through a cannula that is inserted into the brain while simultaneously delivering ultrasound to improve the penetration of pharmaceuticals. CED without ultrasound-assistance has been used to treat a variety of neural disorders, including glioblastoma multiforme, a malignancy that presents a very poor prognosis for patients. We describe a novel system that is used to infuse fluids into the brain parenchyma while simultaneously exposing the tissue to safe levels of 1-MHz, low intensity, ultrasound energy. The system includes a combined infusion needle-hydrophone, a 10-channel ultralow-output impedance amplifier, a broad-band ultrasound resonator, and MatLab®-based TRA control and user-interface. TRA allows easy coupling of ultrasound therapy through the skull without complex phase-correction and array design. The smart targeting UCED system has been tested in vivo and results show it provides 1.5-mm spatial resolution for UCED and improves tracer distribution in the brain over CED alone. PMID:21881622

Development of coverage with evidence development for medical technologies in Switzerland from 1996 to 2012.

PubMed

Brügger, Urs; Ruckstuhl, Andreas; Horisberger, Bruno; Gratwohl, Alois

2014-07-01

The aim of this study was to assess incidence, time frame, and outcome of "Coverage with Evidence Development" (CED) decisions in the Swiss Basic Health Insurance scheme. Analysis of all controversial medical technologies submitted to review by the Swiss Federal Office of Public Health (FOPH) from 1996 to 2012 with focus on decisions with constraints. Description of types of technology, type of initial decision, duration of evaluation period, final decision, and search for potential factors associated with changes over time. Forty-five (37.5 percent) of 120 controversial health technologies were classified as "yes, in evaluation, reimbursed" for a certain period of time and thirty-five (29.2 percent) as "no, in evaluation, not reimbursed" by the Federal Department of Home Affairs from 1996 to 2012. The rate of CED decisions ranged between zero and nine per year and was influenced by type of technology and calendar year. Forty-four of forty-five decisions were subject to further restrictions, to a "center or a specialist" (76 percent), "indications" (49 percent), "registry" (31 percent), or "other" (49 percent). The time to a final decision ranged from 1.5 to 11 years (median, 6 years). No factors associated with initial decision and final outcome could be identified. CED as a reality in Switzerland might have enabled patients to obtain access to promising technologies early in their life cycle. CED might have acted as a trigger to a successful implementation of a comprehensive national registry. The lack of qualitative data stresses the urgent need for evaluation of the HTA decisions and their impact on patient outcome and costs.

A locus at 7p14.3 predisposes to refractory celiac disease progression from celiac disease.

PubMed

Hrdlickova, Barbara; Mulder, Chris J; Malamut, Georgia; Meresse, Bertrand; Platteel, Mathieu; Kamatani, Yoichiro; Ricaño-Ponce, Isis; van Wanrooij, Roy L J; Zorro, Maria M; Jan Bonder, Marc; Gutierrez-Achury, Javier; Cellier, Christophe; Zhernakova, Alexandra; Nijeboer, Petula; Galan, Pilar; Withoff, Sebo; Lathrop, Mark; Bouma, Gerd; Xavier, Ramnik J; Jabri, Bana; Bensussan, Nadine C; Wijmenga, Cisca; Kumar, Vinod

2018-05-21

Approximately 5% of patients with celiac disease (CeD) do not respond to a gluten-free diet and progress to refractory celiac disease (RCD), a severe progression that is characterized by infiltration of intraepithelial T lymphocytes. Patients with RCD type II (RCDII) show clonal expansions of intraepithelial T lymphocytes that result in a poor prognosis and a high mortality rate through development of aggressive enteropathy-associated T-cell lymphoma. It is not known whether genetic variations play a role in severe progression of CeD to RCDII. We performed the first genome-wide association study to identify the causal genes for RCDII and the molecular pathways perturbed in RCDII. The genome-wide association study was performed in 38 Dutch patients with RCDII, and the 15 independent top-associated single nucleotide polymorphism (SNP) variants (P<5×10) were replicated in 56 independent French and Dutch patients with RCDII. After replication, SNP rs2041570 on chromosome 7 was significantly associated with progression to RCDII (P=2.37×10, odds ratio=2.36) but not with CeD susceptibility. SNP rs2041570 risk allele A was associated with lower levels of FAM188B expression in blood and small intestinal biopsies. Stratification of RCDII biopsies based on rs2041570 genotype showed differential expression of innate immune and antibacterial genes that are expressed in Paneth cells. We have identified a novel SNP associated with the severe progression of CeD to RCDII. Our data suggest that genetic susceptibility to CeD might be distinct from the progression to RCDII and suggest a role for Paneth cells in RCDII progression.

Solution structure and interactions of the Escherichia coli cell division activator protein CedA.

PubMed

Chen, Ho An; Simpson, Peter; Huyton, Trevor; Roper, David; Matthews, Stephen

2005-05-10

CedA is a protein that is postulated to be involved in the regulation of cell division in Escherichia coli and related organisms; however, little biological data about its possible mode of action are available. Here we present a three-dimensional structure of this protein as determined by NMR spectroscopy. The protein is made up of four antiparallel beta-strands, an alpha-helix, and a large unstructured stretch of residues at the N-terminus. It shows structural similarity to a family of DNA-binding proteins which interact with dsDNA via a three-stranded beta-sheet, suggesting that CedA may be a DNA-binding protein. The putative binding surface of CedA is predominantly positively charged with a number of basic residues surrounding a groove largely dominated by aromatic residues. NMR chemical shift perturbations and gel-shift experiments performed with CedA confirm that the protein binds dsDNA, and its interaction is mediated primarily via the beta-sheet.

Hypothalamic amenorrhea in a Camurati-Engelmann disease--a case report.

PubMed

Meczekalski, Blazej; Czyzyk, Adam; Podfigurna-Stopa, Agnieszka; Rydzewski, Bogdan; Sroczynski, Jakub; Lipinska, Małgorzata; Sokalski, Jerzy; Krawczynski, Maciej; Jamsheer, Aleksander; Katulski, Krzysztof; Genazzani, Alessandro

2013-05-01

A case report of a patient diagnosed with Camurati-Engelmann Disease (CED) in association with the functional hypothalamic amenorrhea disturbances. CED is a very rare genetically determined disorder classified as a type of bone dysplasia. Case report. Department of Gynecological Endocrinology, 3rd grade Medical University Hospital. Twenty-one years old female patient with CED admitted to the hospital because of primary amenorrhea. Her history revealed skeletal deformities and hearing impairment. Clinical examination, ultrasound, laboratory evaluations (including serum gonadotropins (FSH, LH) at basal state and after stimulation with gonadotropin-releasing hormone, serum basal estradiol) radiological studies (X-ray of the head, the lumbar spine and lower extremities; a computed tomography of the head), G-banding karyotype, polymerase chain reaction and DNA sequencing. Hormonal serum evaluations were made using an enzyme-linked immunosorbent assay. The exon 4 of the transforming growth factor beta 1 gene was amplified by a polymerase chain reaction and the product was directly sequenced. The hormonal analysis was characteristic for the hypogonadotropic hypogonadism. Radiological and molecular analyses confirmed CED diagnosis. The hypothalamic amenorrhea in a patient with CED may be explained as a consequence of fat hypotrophy and very low body mass index. Therefore, impairment within hypothalamic-pituitary axis in patients with CED should be treated with special attention.

Association between Farming and Chronic Energy Deficiency in Rural South India

PubMed Central

Subasinghe, Asvini K.; Walker, Karen Z.; Evans, Roger G.; Srikanth, Velandai; Arabshahi, Simin; Kartik, Kamakshi; Kalyanram, Kartik; Thrift, Amanda G.

2014-01-01

Objective To examine factors associated with chronic energy deficiency (CED) and anaemia in disadvantaged Indian adults who are mostly involved in subsistence farming. Design A cross-sectional study in which we collected information on socio-demographic factors, physical activity, anthropometry, blood haemoglobin concentration, and daily household food intake. These data were used to calculate body mass index (BMI), basal metabolic rate (BMR), daily energy expenditure, and energy and nutrient intake. Multivariable backward stepwise logistic regression was used to assess socioeconomic and lifestyle factors associated with CED (defined as BMI<18 kg/m2) and anaemia. Setting The study was conducted in 12 villages, in the Rishi Valley, Andhra Pradesh, India. Subjects Individuals aged 18 years and above, residing in the 12 villages, were eligible to participate. Results Data were available for 1178 individuals (45% male, median age 36 years (inter quartile range (IQR 27–50)). The prevalence of CED (38%) and anaemia (25%) was high. Farming was associated with CED in women (2.20, 95% CI: 1.39–3.49) and men (1.71, 95% CI: (1.06–2.74). Low income was also significantly associated with CED, while not completing high school was positively associated with anaemia. Median iron intake was high: 35.7 mg/day (IQR 26–46) in women and 43.4 mg/day (IQR 34–55) in men. Conclusions Farming is an important risk factor associated with CED in this rural Indian population and low dietary iron is not the main cause of anaemia. Better farming practice may help to reduce CED in this population. PMID:24475286

Uric acid is associated with inflammation, coronary microvascular dysfunction, and adverse outcomes in postmenopausal women

PubMed Central

Prasad, Megha; Matteson, Eric L.; Herrmann, Joerg; Gulati, Rajiv; Rihal, Charanjit S.; Lerman, Lilach O.; Lerman, Amir

2016-01-01

Uric acid is a risk factor for coronary artery disease (CAD) in postmenopausal women but the association with inflammation and coronary microvascular endothelial dysfunction (CED) is not well-defined. The aim of this study was to determine the relationship of serum uric acid (SUA), inflammatory markers and CED. In this prospective cohort study, serum uric acid, hsCRP levels, and neutrophil count were measured in 229 postmenopausal women who underwent diagnostic catheterization, were found to have no obstructive CAD and underwent coronary microvascular function testing, to measure coronary blood flow (CBF) response to intracoronary acetylcholine. The average age was 58 years (IQR 52, 66) years. Hypertension was present in 48%, type 2 diabetes mellitus in 5.6%, and hyperlipidemia in 61.8%. CED was diagnosed in 59% of postmenopausal women. Mean uric acid level was 4.7 ± 1.3 mg/dL. Postmenopausal women with CED had significantly higher SUA compared to patients without CED (4.9 ± 1.3 vs. 4.4 ± 1.3 mg/dL; p=0.02). There was a significant correlation between SUA and % change in CBF to acetylcholine (p=0.009), and this correlation persisted in multivariable analysis. SUA levels were significantly associated with increased neutrophil count (p=0.02) and hsCRP levels (p=0.006) among patients with CED, but not those without CED. Serum uric acid is associated with coronary microvascular endothelial dysfunction in postmenopausal women and may be related to inflammation. These findings link serum uric acid levels to early coronary atherosclerosis in postmenopausal women. PMID:27993955

Effects of Colored Enrichment Devices on Circadian Metabolism and Physiology in Male Sprague-Dawley Rats.

PubMed

Wren-Dail, Melissa A; Dauchy, Robert T; Ooms, Tara G; Baker, Kate C; Blask, David E; Hill, Steven M; Dupepe, Lynell M; Bohm, Rudolf P

2016-01-01

Environmental enrichment (EE) gives laboratory animals opportunities to engage in species-specific behaviors. However, the effects of EE devices on normal physiology and scientific outcomes must be evaluated. We hypothesized that the spectral transmittance (color) of light to which rats are exposed when inside colored enrichment devices (CED) affects the circadian rhythms of various plasma markers. Pair-housed male Crl:SD rats were maintained in ventilated racks under a 12:12-h light:dark environment (265.0 lx; lights on, 0600); room lighting intensity and schedule remained constant throughout the study. Treatment groups of 6 subjects were exposed for 25 d to a colored enrichment tunnel: amber, red, clear, or opaque. We measured the proportion of time rats spent inside their CED. Blood was collected at 0400, 0800, 1200, 1600, 2000, and 2400 and analyzed for plasma melatonin, total fatty acids, and corticosterone. Rats spent more time in amber, red, and opaque CED than in clear tunnels. All tubes were used significantly less after blood draws had started, except for the clear tunnel, which showed no change in use from before blood sampling began. Normal peak nighttime melatonin concentrations showed significant disruption in the opaque CED group. Food and water intakes and body weight change in rats with red-tinted CED and total fatty acid concentrations in the opaque CED group differed from those in other groups. These results demonstrate that the color of CED altered normal circadian rhythms of plasma measures of metabolism and physiology in rats and therefore might influence the outcomes of scientific investigations.

Mapping Urban Risk: Flood Hazards, Race, & Environmental Justice In New York”

PubMed Central

Maantay, Juliana; Maroko, Andrew

2009-01-01

This paper demonstrates the importance of disaggregating population data aggregated by census tracts or other units, for more realistic population distribution/location. A newly-developed mapping method, the Cadastral-based Expert Dasymetric System (CEDS), calculates population in hyper-heterogeneous urban areas better than traditional mapping techniques. A case study estimating population potentially impacted by flood hazard in New York City compares the impacted population determined by CEDS with that derived by centroid-containment method and filtered areal weighting interpolation. Compared to CEDS, 37 percent and 72 percent fewer people are estimated to be at risk from floods city-wide, using conventional areal weighting of census data, and centroid-containment selection, respectively. Undercounting of impacted population could have serious implications for emergency management and disaster planning. Ethnic/racial populations are also spatially disaggregated to determine any environmental justice impacts with flood risk. Minorities are disproportionately undercounted using traditional methods. Underestimating more vulnerable sub-populations impairs preparedness and relief efforts. PMID:20047020

Politics in an Adult Education Program or Don't Laugh, This Could Happen to YOU!

ERIC Educational Resources Information Center

Vitzthum, Edward F.; Schulze, Larry D.

The Cooperative Extension Division (CED) of the University of Nebraska's Institute of Agriculture and Natural Resources has presented pesticide applicator training (PAT) for nearly 2 decades. Because Nebraska did not pass the complementary state legislation, the U.S. Environmental Protection Agency (EPA), as provided in the Federal Insecticide,…

The Use of Convection-Enhanced Delivery with Liposomal Toxins in Neurooncology

PubMed Central

Fiandaca, Massimo S.; Berger, Mitchel S.; Bankiewicz, Krystof S.

2011-01-01

Liposomes have long been effective delivery vehicles for transport of toxins to peripheral cancers. The combination of convection-enhanced delivery (CED) with liposomal toxins was originally proposed to circumvent the limited delivery of intravascular liposomes to the central nervous system (CNS) due to the blood-brain-barrier (BBB). CED offers markedly improved distribution of infused therapeutics within the CNS compared to direct injection or via drug eluting polymers, both of which depend on diffusion for parenchymal distribution. This review examines the basis for improved delivery of liposomal toxins via CED within the CNS, and discusses preclinical and clinical experience with these therapeutic techniques. How CED and liposomal technologies may influence future neurooncologic treatments are also considered. PMID:22069714

Market Access Agreements for pharmaceuticals in Europe: diversity of approaches and underlying concepts.

PubMed

Jarosławski, Szymon; Toumi, Mondher

2011-10-08

Market Access Agreements (MAA) between pharmaceutical industry and health care payers have been proliferating in Europe in the last years. MAA can be simple discounts from the list price or very sophisticated schemes with inarguably high administrative burden. We distinguished and defined from the health care payer perspective three kinds of MAA: Commercial Agreements (CA), Payment for Performance Agreements (P4P) and Coverage with Evidence Development (CED). Apart from CA, the agreements assumed collection and analysis of real-life health outcomes data, either from a cohort of patients (CED) or on per patient basis (P4P). We argue that while P4P aim at reducing drug cost to payers without a systematic approach to addressing uncertainty about drugs' value, CED were implemented provisionally to reduce payer's uncertainty about value of a medicine within a defined time period. We are of opinion that while CA and P4P have a potential to reduce payers' expenditure on costly drugs while maintaining a high list price, CED address initial uncertainty related to assessing the real-life value of new drugs and enable a final HTA recommendation or reimbursement and pricing decisions. Further, we suggest that real cost to health care payers of drugs in CA and P4P should be made publicly available in a systematic manner, to avoid a perverse impact of these MAA types on the international reference pricing system.

13 CFR 303.7 - Requirements for Comprehensive Economic Development Strategies.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Economic Development Strategies. 303.7 Section 303.7 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE PLANNING INVESTMENTS AND COMPREHENSIVE ECONOMIC DEVELOPMENT STRATEGIES § 303.7 Requirements for Comprehensive Economic Development Strategies. (a) General. CEDS are designed...

13 CFR 303.7 - Requirements for Comprehensive Economic Development Strategies.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Economic Development Strategies. 303.7 Section 303.7 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE PLANNING INVESTMENTS AND COMPREHENSIVE ECONOMIC DEVELOPMENT STRATEGIES § 303.7 Requirements for Comprehensive Economic Development Strategies. (a) General. CEDS are designed...

13 CFR 303.7 - Requirements for Comprehensive Economic Development Strategies.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Economic Development Strategies. 303.7 Section 303.7 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE PLANNING INVESTMENTS AND COMPREHENSIVE ECONOMIC DEVELOPMENT STRATEGIES § 303.7 Requirements for Comprehensive Economic Development Strategies. (a) General. CEDS are designed...

13 CFR 303.7 - Requirements for Comprehensive Economic Development Strategies.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Economic Development Strategies. 303.7 Section 303.7 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE PLANNING INVESTMENTS AND COMPREHENSIVE ECONOMIC DEVELOPMENT STRATEGIES § 303.7 Requirements for Comprehensive Economic Development Strategies. (a) General. CEDS are designed...

13 CFR 303.7 - Requirements for Comprehensive Economic Development Strategies.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Economic Development Strategies. 303.7 Section 303.7 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE PLANNING INVESTMENTS AND COMPREHENSIVE ECONOMIC DEVELOPMENT STRATEGIES § 303.7 Requirements for Comprehensive Economic Development Strategies. (a) General. CEDS are designed...

Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study.

PubMed

Green, Daniel M; Liu, Wei; Kutteh, William H; Ke, Raymond W; Shelton, Kyla C; Sklar, Charles A; Chemaitilly, Wassim; Pui, Ching-Hon; Klosky, James L; Spunt, Sheri L; Metzger, Monika L; Srivastava, DeoKumar; Ness, Kirsten K; Robison, Leslie L; Hudson, Melissa M

2014-10-01

Few data define the dose-specific relation between alkylating agent exposure and semen variables in adult survivors of childhood cancer. We undertook this study to test the hypothesis that increased exposure to alkylating agents would be associated with decreased sperm concentration in a cohort of adult male survivors of childhood cancer who were not exposed to radiation therapy for their childhood cancer. We did semen analysis on 214 adult male survivors of childhood cancer (median age 7·7 years [range 0·01-20·3] at diagnosis, 29·0 years [18·4-56·1] at assessment, and a median of 21·0 years [10·5-41·6] since diagnosis) who had received alkylating agent chemotherapy but no radiation therapy. Alkylating agent exposure was estimated using the cyclophosphamide equivalent dose (CED). Odds ratios (ORs) and 95% CIs for oligospermia (sperm concentration >0 and <15 million per mL) and azoospermia were calculated with logistic regression modelling. Azoospermia was noted in 53 (25%) of 214 participants, oligospermia in 59 (28%), and normospermia (sperm concentration ≥15 million per mL) in 102 (48%) participants. 31 (89%) of 35 participants who received CED less than 4000 mg/m(2) were normospermic. CED was negatively correlated with sperm concentration (correlation coefficient=-0·37, p<0·0001). Mean CED was 10 830 mg/m(2) (SD 7274) in patients with azoospermia, 8480 mg/m(2) (4264) in patients with oligospermia, and 6626 mg/m(2) (3576) in patients with normospermia. In multivariable analysis, CED was significantly associated with an increased risk per 1000 mg/m(2) CED for azoospermia (OR 1·22, 95% CI 1·11-1·34), and for oligospermia (1·14, 1·04-1·25), but age at diagnosis and age at assessment were not. Impaired spermatogenesis was unlikely when the CED was less than 4000 mg/m(2). Although sperm concentration decreases with increasing CED, there was substantial overlap of CED associated with normospermia, oligospermia, and azoospermia. These data can inform pretreatment patient counselling and use of fertility preservation services. US National Cancer Institute, American Lebanese Syrian Associated Charities. Copyright © 2014 Elsevier Ltd. All rights reserved.

Safety of intraparenchymal convection-enhanced delivery of cintredekin besudotox in early-phase studies.

PubMed

Kunwar, Sandeep; Chang, Susan M; Prados, Michael D; Berger, Mitchel S; Sampson, John H; Croteau, David; Sherman, Jeffrey W; Grahn, Amy Y; Shu, Vince S; Dul, Jeanne L; Husain, Syed R; Joshi, Bharat H; Pedain, Christoph; Puri, Raj K

2006-04-15

Convection-enhanced delivery (CED) is an increasingly used novel local/regional delivery method targeted directly to tissue. It relies on a continuous pressure gradient for distribution of therapeutic agents into the interstitial space, with administration of the infusate over a few days. Cintredekin besudotox (also known as IL13- PE38QQR) is a recombinant chimeric cytotoxin consisting of interleukin-13 and a truncated exotoxin produced by the Pseudomonas aeruginosa bacterium, which targets malignant glioma cells. Cintredekin besudotox was administered via intraparenchymal CED after resection of supratentorial recurrent malignant glioma. The safety and toxicity profile was reviewed for 53 patients in whom infusion catheters had been placed; 51 of them received CED of the study drug. Adverse events were categorized based on time of onset in relation to CED, and the causal relationship with catheter placement or delivery of cintredekin besudotox. Catheters were placed in 53 patients, although only 51 of them received cintredekin besudotox. Most adverse events related to catheter placement or the study drug originated from the central nervous system. Three symptomatic windows were defined: the first one was between surgical procedure and CED; the second was during CED and up to 1 week after its completion; and the third window was 2 to 10 weeks after treatment. Those windows generally reflected adverse events related to surgical procedures, mass effect from infusate, and drug effect on tumor-infiltrated and normal brain parenchyma, respectively. The symptomatic windows identified in this study apply to any CED clinical trials, particularly those in which chimeric cytotoxins are used, and will help to determine the most likely underlying pathophysiological process causing symptoms. This information, in turn, will help to prevent adverse events or minimize their severity. Those events also have implications for dose escalation and outcome measures.

Celiac disease and other autoimmune diseases in patients with collagenous colitis.

PubMed

Vigren, Lina; Tysk, Curt; Ström, Magnus; Kilander, Anders F; Hjortswang, Henrik; Bohr, Johan; Benoni, Cecilia; Larson, Lasse; Sjöberg, Klas

2013-08-01

Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. Patients with CC answered questionnaires about demographic data and disease activity. The patient's files were scrutinized for information about autoimmune diseases. A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55-73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjögren's syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.

Safety of real-time convection-enhanced delivery of liposomes to primate brain: a long-term retrospective.

PubMed

Krauze, Michal T; Vandenberg, Scott R; Yamashita, Yoji; Saito, Ryuta; Forsayeth, John; Noble, Charles; Park, John; Bankiewicz, Krystof S

2008-04-01

Convection-enhanced delivery (CED) is gaining popularity in direct brain infusions. Our group has pioneered the use of liposomes loaded with the MRI contrast reagent as a means to track and quantitate CED in the primate brain through real-time MRI. When co-infused with therapeutic nanoparticles, these tracking liposomes provide us with unprecedented precision in the management of infusions into discrete brain regions. In order to translate real-time CED into clinical application, several important parameters must be defined. In this study, we have analyzed all our cumulative animal data to answer a number of questions as to whether real-time CED in primates depends on concentration of infusate, is reproducible, allows prediction of distribution in a given anatomic structure, and whether it has long term pathological consequences. Our retrospective analysis indicates that real-time CED is highly predictable; repeated procedures yielded identical results, and no long-term brain pathologies were found. We conclude that introduction of our technique to clinical application would enhance accuracy and patient safety when compared to current non-monitored delivery trials.

Pieces of the Puzzle: Tracking the Chemical Component of the ...

EPA Pesticide Factsheets

This presentation provides an overview of the risk assessment conducted at the U.S. EPA, as well as some research examples related to the exposome concept. This presentation also provides the recommendation of using two organizational and predictive frameworks for tracking chemical components in the exposome. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-support tools, and models to be applied to media-specific or receptor-specific problem areas. CED uses modeling-based approaches to characterize exposures, evaluate fate and transport, and support environmental diagnostics/forensics with input from multiple data sources. It also develops media- and receptor-specific models, process models, and decision support tools for use both within and outside of EPA.

The Air Quality Model Evaluation International Initiative ...

EPA Pesticide Factsheets

This presentation provides an overview of the Air Quality Model Evaluation International Initiative (AQMEII). It contains a synopsis of the three phases of AQMEII, including objectives, logistics, and timelines. It also provides a number of examples of analyses conducted through AQMEII with a particular focus on past and future analyses of deposition. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-support tools, and models to be applied to media-specific or receptor-specific problem areas. CED uses modeling-based approaches to characterize exposures, evaluate fate and transport, and support environmental diagnostics/forensics with input from multiple data sources. It also develops media- and receptor-specific models, process models, and decision support tools for use both within and outside of EPA.

13 CFR 300.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL... meanings: Assistant Secretary means the Assistant Secretary for Economic Development within the Department. Comprehensive Economic Development Strategy or CEDS means a strategy that meets the requirements of § 303.7 of...

13 CFR 307.5 - Application requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... ECONOMIC ADJUSTMENT ASSISTANCE INVESTMENTS General § 307.5 Application requirements. (a) Each application... EDA) a CEDS, except that a CEDS is not required when applying for a Strategy Grant; and (2) Explain...

CedA is a novel Escherichia coli protein that activates the cell division inhibited by chromosomal DNA over-replication.

PubMed

Katayama, T; Takata, M; Sekimizu, K

1997-11-01

We isolated and characterized a new gene related to the control of cell division regulation in Escherichia coli. At 30 degrees C, the dnaAcos mutant causes over-replication of the chromosome, and colony formation is inhibited. We found that, at this temperature, the dnaAcos cells form filaments; therefore, septum formation is inhibited. This inhibition was independent of SfiA, an inhibitor of the septum-forming protein, FtsZ. To identify factors involved in this pathway of inhibition, we isolated seven multicopy suppressors for the cold-sensitive phenotype of the dnaAcos mutant. One of these proved to be a previously unknown gene, which we named cedA. This gene encoded a 12 kDa protein and resided at 38.9min on the E. coli genome map. A multicopy supply of the cedA gene to the dnaAcos cells did not repress over-replication of the chromosome but did stimulate cell division of the host, the result being growth of cells with an abnormally elevated chromosomal copy number. Therefore, the expression level of the cedA gene seems to be important for inhibiting cell division of the dnaAcos mutant at 30 degrees C. We propose that over-replication of the chromosome activates a pathway for inhibiting cell division and that the cedA gene modulates this division control. In the dnaA+ background, cedA also seems to affect cell division.

Evaluation of the Community Multi-scale Air Quality (CMAQ) ...

EPA Pesticide Factsheets

The Community Multiscale Air Quality (CMAQ) model is a state-of-the-science air quality model that simulates the emission, transport and fate of numerous air pollutants, including ozone and particulate matter. The Computational Exposure Division (CED) of the U.S. Environmental Protection Agency develops the CMAQ model and periodically releases new versions of the model that include bug fixes and various other improvements to the modeling system. In the fall of 2015, CMAQ version 5.1 was released. This new version of CMAQ will contain important bug fixes to several issues that were identified in CMAQv5.0.2 and additionally include updates to other portions of the code. Several annual, and numerous episodic, CMAQv5.1 simulations were performed to assess the impact of these improvements on the model results. These results will be presented, along with a base evaluation of the performance of the CMAQv5.1 modeling system against available surface and upper-air measurements available during the time period simulated. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-support tools, and models to be applied to media-specific or receptor-specific problem areas. CED uses modeling-based approaches to characterize exposures, evaluate fate and transport, and support environmental diagnostics/forensics with input from multiple data sources. It also develops media- and receptor-specific models, proces

Convection-enhanced delivery of etoposide is effective against murine proneural glioblastoma.

PubMed

Sonabend, Adam M; Carminucci, Arthur S; Amendolara, Benjamin; Bansal, Mukesh; Leung, Richard; Lei, Liang; Realubit, Ronald; Li, Hai; Karan, Charles; Yun, Jonathan; Showers, Christopher; Rothcock, Robert; O, Jane; Califano, Andrea; Canoll, Peter; Bruce, Jeffrey N

2014-09-01

Glioblastoma subtypes have been defined based on transcriptional profiling, yet personalized care based on molecular classification remains unexploited. Topoisomerase II (TOP2) contributes to the transcriptional signature of the proneural glioma subtype. Thus, we targeted TOP2 pharmacologically with etoposide in proneural glioma models. TOP2 gene expression was evaluated in mouse platelet derived growth factor (PDGF)(+)phosphatase and tensin homolog (PTEN)(-/-)p53(-/-) and PDGF(+)PTEN(-/-) proneural gliomas and cell lines, as well as human glioblastoma from The Cancer Genome Atlas. Correlation between TOP2 transcript levels and etoposide susceptibility was investigated in 139 human cancer cell lines from the Cancer Cell Line Encyclopedia public dataset and in mouse proneural glioma cell lines. Convection-enhanced delivery (CED) of etoposide was tested on cell-based PDGF(+)PTEN(-/-)p53(-/-) and retroviral-based PDGF(+)PTEN(-/-) mouse proneural glioma models. TOP2 expression was significantly higher in human proneural glioblastoma and in mouse proneural tumors at early as well as late stages of development compared with normal brain. TOP2B transcript correlated with susceptibility to etoposide in mouse proneural cell lines and in 139 human cancer cell lines from the Cancer Cell Line Encyclopedia. Intracranial etoposide CED treatment (680 μM) was well tolerated by mice and led to a significant survival benefit in the PDGF(+)PTEN(-/-)p53(-/-) glioma model. Moreover, etoposide CED treatment at 80 μM but not 4 μM led to a significant survival advantage in the PDGF(+)PTEN(-/-) glioma model. TOP2 is highly expressed in proneural gliomas, rendering its pharmacological targeting by intratumoral administration of etoposide by CED effective on murine proneural gliomas. We provide evidence supporting clinical testing of CED of etoposide with a molecular-based patient selection approach. Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Antenatal and Postnatal Psychopathology Among Women with Current and Past Eating Disorders: Longitudinal Patterns

PubMed Central

Easter, Abigail; Solmi, Francessca; Bye, Amanda; Taborelli, Emma; Corfield, Freya; Schmidt, Ulrike; Treasure, Janet; Micali, Nadia

2015-01-01

This study aims to investigate longitudinal patterns of psychopathology during the antenatal and postnatal periods among women with current (C-ED) and past (P-ED) eating disorders. Women were recruited to a prospective longitudinal study: C-ED (n = 31), P-ED (n = 29) and healthy control (HC; n = 57). Anxiety, depression and ED symptoms were measured at four time points: first/second trimester, third trimester, 8 weeks and 6 months postpartum. Linear mixed effects models were used to test for group differences. Women with C-ED and P-ED, in all diagnostic categories, had significantly higher levels of psychopathology at all time points. ED symptoms decreased in the C-ED group, compared with an overall increase in the other two groups but subsequently increased after pregnancy. Overall, depression and state and trait anxiety scores decreased in the C-ED group compared with the HC group throughout the antenatal and postnatal periods. High levels of psychopathology are common throughout the antenatal and postnatal periods among women with current and past ED, and despite some overall reductions, symptoms remain clinically significant. © 2014 The Authors. European Eating Disorders Review published by John Wiley & Sons, Ltd. PMID:25345371

Convection-enhanced delivery of cetuximab conjugated iron-oxide nanoparticles for treatment of spontaneous canine intracranial gliomas.

PubMed

Freeman, A Courtenay; Platt, Simon R; Holmes, Shannon; Kent, M; Robinson, Kelsey; Howerth, Elizabeth; Eagleson, Joe; Bouras, Alexandros; Kaluzova, Milota; Hadjipanayis, Constantinos G

2018-05-01

Cetuximab conjugated iron-oxide nanoparticles (cetuximab-IONPs) have shown both in-vitro and in-vivo anti-tumor efficacy against gliomas. The purpose of this pilot study was to evaluate the safety and potential efficacy of cetuximab-IONPs for treatment of spontaneously occurring intracranial gliomas in canines after convection-enhanced delivery (CED). The use of CED allowed for direct infusion of the cetuximab-IONPs both intratumorally and peritumorally avoiding the blood brain barrier (BBB) and limiting systemic effects. A total of eight dogs participated in the study and only two developed mild post-operative complications, which resolved with medical therapy. All canines underwent a single CED treatment of the cetuximab-IONPs over 3 days and did not receive any further adjuvant treatments. Volumetric analysis showed a median reduction in tumor size of 54.9% by MRI at 1-month (4-6 weeks) follow-up. Five dogs were euthanized due to recurrence of neurological signs other than seizures, two due to recurrent seizures, and one dog died in his sleep. Median survival time after surgery was 248 days (mean 367 days).

Interventional MRI-guided catheter placement and real time drug delivery to the central nervous system.

PubMed

Han, Seunggu J; Bankiewicz, Krystof; Butowski, Nicholas A; Larson, Paul S; Aghi, Manish K

2016-06-01

Local delivery of therapeutic agents into the brain has many advantages; however, the inability to predict, visualize and confirm the infusion into the intended target has been a major hurdle in its clinical development. Here, we describe the current workflow and application of the interventional MRI (iMRI) system for catheter placement and real time visualization of infusion. We have applied real time convection-enhanced delivery (CED) of therapeutic agents with iMRI across a number of different clinical trials settings in neuro-oncology and movement disorders. Ongoing developments and accumulating experience with the technique and technology of drug formulations, CED platforms, and iMRI systems will continue to make local therapeutic delivery into the brain more accurate, efficient, effective and safer.

Impacts of Lateral Boundary Conditions on US Ozone ...

EPA Pesticide Factsheets

Chemical boundary conditions are a key input to regional-scale photochemical models. In this study, we perform annual simulations over North America with chemical boundary conditions prepared from two global models (GEOS-CHEM and Hemispheric CMAQ). Results indicate that the impacts of different boundary conditions on ozone can be significant throughout the year. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-support tools, and models to be applied to media-specific or receptor-specific problem areas. CED uses modeling-based approaches to characterize exposures, evaluate fate and transport, and support environmental diagnostics/forensics with input from multiple data sources. It also develops media- and receptor-specific models, process models, and decision support tools for use both within and outside of EPA.

Sequential testing with different tissue transglutaminase antibodies, a new approach for diagnosis of celiac disease.

PubMed

Venugopal, Giriprasad; Mechenro, John; Makharia, Govind; Singh, Alka; Pugazhendhi, Srinivasan; Balamurugan, Ramadass; Ramakrishna, Balakrishnan S

2017-11-01

The diagnosis of celiac disease (CeD) in clinical practice relies on serological testing for IgA antibodies to human tissue transglutaminase (anti-tTG) which diagnose CeD autoimmunity. We compared three kits for their performance in diagnosis of the disease and evaluated the point prevalence of CeD autoimmunity in a South Indian urban population. In the first part of the study, sera from 90 patients with documented CeD and 92 healthy controls were tested for anti-tTG using three different kits. One thousand nine hundred and seventeen healthy adults residing in urban areas of Vellore and Kancheepuram districts were tested for CeD autoimmunity using a sequential two-test strategy. The sensitivity, specificity, false positivity, false negativity, positive predictive value, and negative predictive value for the three assays respectively were as follows: 95.5%, 82.6%, 17.3%, 4.4%, 84.3%, and 95% for the Aeskulisa New Generation Assay; 85.5%, 100%, 0%, 14.4%, 100%, and 87.6% for Quanta Lite; and 71.1%, 100%, 0%, 28.8%, 100%, and 71% for Celiac Microlisa. The ROC curves showed good discrimination for all three ELISAs with an AUC of 0.947, 0.950, and 0.886 for the Aeskulisa, Quanta Lite, and Celiac Microlisa, respectively. Of 1917 (males 908, females 1009) healthy adults, 113 (5.89%) were seropositive for IgA anti-htTG in the Aeskulisa test. Two of the latter tested positive in the Quanta Lite assay and/or the Celiac Microlisa assay. The CeD autoimmunity prevalence in this urban population was 1.0 per thousand (95% confidence interval 0.3 to 3.7 per thousand). Sequential testing for anti-tTG using first a highly sensitive assay followed by a very specific assay is a new strategy for screening for CeD in clinical practice.

Corneal endothelial cell loss and corneal biomechanical characteristics after two-step sequential or combined phaco-vitrectomy surgery for idiopathic epiretinal membrane.

PubMed

Hamoudi, Hassan; Christensen, Ulrik Correll; La Cour, Morten

2017-08-01

To assess the impact of sequential and combined surgery [cataract surgery and 23-gauge pars plana vitrectomy (PPV) with peeling] on corneal endothelium cell density (CED) and corneal biomechanical characteristics. Phakic eyes with epiretinal membrane (ERM) were prospectively allocated to (i) cataract surgery and subsequent PPV (CAT group), (ii) PPV and subsequent cataract surgery (VIT group) or (iii) phacovitrectomy (COMBI group). Eyes were examined at baseline, 1 month after each surgery, and at 3 and 12 months follow-up. Corneal endothelium cell density (CED) was assessed with non-contact specular microscopy. Pachymetry [central cornea thickness (CCT)], keratometry and cornea volume (CV) were measured with Pentacam Scheimpflug camera. Primary outcome was change in CED after 12 months; secondary outcomes were changes in CCT and CV after 12 months. Sixty-two eyes were enrolled and allocated to the three groups. The mean preoperative CED was 2776, 2794 and 2653 cells/mm 2, which decreased significantly at 12 months by 15.3, 20.0 and 19.3% in the CAT, VIT and COMBI group. There was no significant difference in percentage cell loss between the groups at final follow-up. The CED decreased significantly after cataract surgery, but was unaffected by PPV. Central cornea thickness (CCT) increased by 10 μm (p = 0.005) and CV by 1.38 mm 3 (2.3%, p < 0.001) in the COMBI group. There were no significant differences in CCT or CV between the groups at final follow-up. Combined and sequential surgery in ERM leads to a small decrease in CED. Performing cataract surgery before, after or in combination with vitrectomy did not make any significant difference with respect to final CED, CCT or CV. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Synthesis and structural characterization of CdS nanoparticles using nitrogen adducts of mixed diisopropylthiourea and dithiolate derivatives of Cd(II) complexes

NASA Astrophysics Data System (ADS)

Osuntokun, Jejenija; Ajibade, Peter A.

2015-07-01

[Cd(diptu)2(ced)], [Cd(diptu)2(ced)(bpy)], [Cd(diptu)2(ced)(phen)], (where diptu = diisopropyl thiourea; ced = 1-cyano-1-carboethoxylethylene-2,2‧-dithiolate; bpy = 2,2‧-bipyridine and phen = 1,10-phenanthroline) have been prepared and used as single source precursors for the preparation of hexadecylamine capped CdS nanoparticles. The precursor complexes were characterized by elemental analysis, FTIR and TGA. The structural properties of the nanoparticles were investigated using powder X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy techniques (SEM). The optical properties of the nanoparticles were studied using UV-Visible and photoluminescence spectroscopy. The XRD analysis showed that the nanoparticles were indexed to the hexagonal phase of CdS and the TEM results showed CdS nanoparticles with average crystallite sizes of 4.00-8.80 nm.

Convection Enhanced Delivery of Recombinant Adeno-associated Virus into the Mouse Brain.

PubMed

Nash, Kevin R; Gordon, Marcia N

2016-01-01

Recombinant adeno-associated virus (rAAV) has become an extremely useful tool for the study of gene over expression or knockdown in the central nervous system of experimental animals. One disadvantage of intracranial injections of rAAV vectors into the brain parenchyma has been restricted distribution to relatively small volumes of the brain. Convection enhanced delivery (CED) is a method for delivery of clinically relevant amounts of therapeutic agents to large areas of the brain in a direct intracranial injection procedure. CED uses bulk flow to increase the hydrostatic pressure and thus improve volume distribution. The CED method has shown robust gene transfer and increased distribution within the CNS and can be successfully used for different serotypes of rAAV for increased transduction of the mouse CNS. This chapter details the surgical injection of rAAV by CED into a mouse brain.

Removal and recovery of inhibitory volatile fatty acids from mixed acid fermentations by conventional electrodialysis.

PubMed

Jones, Rhys Jon; Massanet-Nicolau, Jaime; Guwy, Alan; Premier, Giuliano C; Dinsdale, Richard M; Reilly, Matthew

2015-08-01

Hydrogen production during dark fermentation is inhibited by the co-production of volatile fatty acids (VFAs) such as acetic and n-butyric acid. In this study, the effectiveness of conventional electrodialysis (CED) in reducing VFA concentrations in model solutions and hydrogen fermentation broths is evaluated. This is the first time CED has been reported to remove VFAs from hydrogen fermentation broths. During 60 min of operation CED removed up to 99% of VFAs from model solutions, sucrose-fed and grass-fed hydrogen fermentation broths, containing up to 1200 mg l(-1) each of acetic acid, propionic acid, i-butyric acid, n-butyric acid, i-valeric acid, and n-valeric acid. CED's ability to remove VFAs from hydrogen fermentation broths suggests that this technology is capable of improving hydrogen yields from dark fermentation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Community Economic Development: Perspectives on Research and Policy.

ERIC Educational Resources Information Center

Galaway, Burt, Ed.; Hudson, Joe, Ed.

This book contains 27 papers that were originally developed for a research and policy symposium at which Canadian community economic development (CED) was examined in terms of research and policy requirements. The book contains the following papers: "Community Economic Development Practice in Canada" (Brodhead); "Community Economic…

Development and application of air quality models at the U.S. EPA

EPA Science Inventory

Overview of the development and application of air quality models at the U.S. EPA, particularly focused on the development and application of the Community Multiscale Air Quality (CMAQ) model developed within the Computation Exposure Division (CED) of the National Exposure Resear...

Detection of infusate leakage in the brain using real-time imaging of convection-enhanced delivery.

PubMed

Varenika, Vanja; Dickinson, Peter; Bringas, John; LeCouteur, Richard; Higgins, Robert; Park, John; Fiandaca, Massimo; Berger, Mitchel; Sampson, John; Bankiewicz, Krystof

2008-11-01

The authors have shown that convection-enhanced delivery (CED) of gadoteridol-loaded liposomes (GDLs) into different regions of normal monkey brain results in predictable, widespread distribution of this tracking agent as detected by real-time MR imaging. They also have found that this tracking technique allows monitoring of the distribution of similar nanosized agents such as therapeutic liposomes and viral vectors. A limitation of this procedure is the unexpected leakage of liposomes out of targeted parenchyma or malignancies into sulci and ventricles. The aim of the present study was to evaluate the efficacy of CED after the onset of these types of leakage. The authors documented this phenomenon in a study of 5 nonhuman primates and 7 canines, comprising 54 CED infusion sessions. Approximately 20% of these infusions resulted in leakage into cerebral ventricles or sulci. All of the infusions and leakage events were monitored with real-time MR imaging. The authors created volume-distributed versus volume-infused graphs for each infusion session. These graphs revealed the rate of distribution of GDL over the course of each infusion and allowed the authors to evaluate the progress of CED before and after leakage. The distribution of therapeutics within the target structure ceased to increase or resulted in significant attenuation after the onset of leakage. An analysis of the cases in this study revealed that leakage undermines the efficacy of CED. These findings reiterate the importance of real-time MR imaging visualization during CED to ensure an accurate, robust distribution of therapeutic agents.

Convection-enhancement delivery of platinum-based drugs and Lipoplatin™ to optimize the concomitant effect with radiotherapy in F98 glioma rat model

PubMed Central

Shi, Minghan; Fortin, David; Sanche, Léon; Paquette, Benoit

2015-01-01

The prognosis for patients with glioblastoma remains poor with current treatments. Although platinum based drugs are sometimes offered at relapse, their efficacy in this setting is still disputed. In this study, we use convection-enhanced delivery (CED) to deliver the platinum-based drugs (cisplatin, carboplatin, and Lipoplatin™-liposomal formulation of cisplatin) directly into the tumor of F98 glioma-bearing rats that were subsequently treated with γ radiation (15 Gy). CED increased by factors varying between 17 and 111, the concentration of these platinum-based drugs in the brain tumor compared to intra-venous (i.v.) administration, and by 9- to 34-fold, when compared to intra-arterial (i.a.) administration. Furthermore, CED resulted in a better systemic tolerance to platinum drugs compared to their i.a. injection. Among the drugs tested, carboplatin showed the highest maximum tolerated dose (MTD). Treatment with carboplatin resulted in the best median survival time (MeST) (38.5 days), which was further increased by the addition of radiotherapy (54.0 days). Although the DNA-bound platinum adduct were higher at 4 h after CED than 24 h for carboplatin group, combination with radiotherapy led to similar improvement of median survival time. However, less toxicity was observed in animals irradiated 24 h after CED-based chemotherapy. In conclusion, CED increased the accumulation of platinum drugs in tumor, reduced the toxicity, and resulted in a higher median survival time. The best treatment was obtained in animals treated with carboplatin and irradiated 24 h later. PMID:25784204

Convection-enhancement delivery of platinum-based drugs and Lipoplatin(TM) to optimize the concomitant effect with radiotherapy in F98 glioma rat model.

PubMed

Shi, Minghan; Fortin, David; Sanche, Léon; Paquette, Benoit

2015-06-01

The prognosis for patients with glioblastoma remains poor with current treatments. Although platinum-based drugs are sometimes offered at relapse, their efficacy in this setting is still disputed. In this study, we use convection-enhanced delivery (CED) to deliver the platinum-based drugs (cisplatin, carboplatin, and Lipoplatin(TM) - liposomal formulation of cisplatin) directly into the tumor of F98 glioma-bearing rats that were subsequently treated with γ radiation (15 Gy). CED increased by factors varying between 17 and 111, the concentration of these platinum-based drugs in the brain tumor compared to intra-venous (i.v.) administration, and by 9- to 34-fold, when compared to intra-arterial (i.a.) administration. Furthermore, CED resulted in a better systemic tolerance to platinum drugs compared to their i.a. injection. Among the drugs tested, carboplatin showed the highest maximum tolerated dose (MTD). Treatment with carboplatin resulted in the best median survival time (MeST) (38.5 days), which was further increased by the addition of radiotherapy (54.0 days). Although the DNA-bound platinum adduct were higher at 4 h after CED than 24 h for carboplatin group, combination with radiotherapy led to similar improvement of median survival time. However, less toxicity was observed in animals irradiated 24 h after CED-based chemotherapy. In conclusion, CED increased the accumulation of platinum drugs in tumor, reduced the toxicity, and resulted in a higher median survival time. The best treatment was obtained in animals treated with carboplatin and irradiated 24 h later.

Convection-enhanced delivery to the central nervous system.

PubMed

Lonser, Russell R; Sarntinoranont, Malisa; Morrison, Paul F; Oldfield, Edward H

2015-03-01

Convection-enhanced delivery (CED) is a bulk flow-driven process. Its properties permit direct, homogeneous, targeted perfusion of CNS regions with putative therapeutics while bypassing the blood-brain barrier. Development of surrogate imaging tracers that are co-infused during drug delivery now permit accurate, noninvasive real-time tracking of convective infusate flow in nervous system tissues. The potential advantages of CED in the CNS over other currently available drug delivery techniques, including systemic delivery, intrathecal and/or intraventricular distribution, and polymer implantation, have led to its application in research studies and clinical trials. The authors review the biophysical principles of convective flow and the technology, properties, and clinical applications of convective delivery in the CNS.

13 CFR 303.3 - Application requirements and evaluation criteria.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., DEPARTMENT OF COMMERCE PLANNING INVESTMENTS AND COMPREHENSIVE ECONOMIC DEVELOPMENT STRATEGIES § 303.3... involvement of the Region's business leadership at each stage of the preparation of the CEDS, short-term...

Antenatal and postnatal psychopathology among women with current and past eating disorders: longitudinal patterns.

PubMed

Easter, Abigail; Solmi, Francessca; Bye, Amanda; Taborelli, Emma; Corfield, Freya; Schmidt, Ulrike; Treasure, Janet; Micali, Nadia

2015-01-01

This study aims to investigate longitudinal patterns of psychopathology during the antenatal and postnatal periods among women with current (C-ED) and past (P-ED) eating disorders. Women were recruited to a prospective longitudinal study: C-ED (n = 31), P-ED (n = 29) and healthy control (HC; n = 57). Anxiety, depression and ED symptoms were measured at four time points: first/second trimester, third trimester, 8 weeks and 6 months postpartum. Linear mixed effects models were used to test for group differences. Women with C-ED and P-ED, in all diagnostic categories, had significantly higher levels of psychopathology at all time points. ED symptoms decreased in the C-ED group, compared with an overall increase in the other two groups but subsequently increased after pregnancy. Overall, depression and state and trait anxiety scores decreased in the C-ED group compared with the HC group throughout the antenatal and postnatal periods. High levels of psychopathology are common throughout the antenatal and postnatal periods among women with current and past ED, and despite some overall reductions, symptoms remain clinically significant. © 2014 The Authors. European Eating Disorders Review published by John Wiley & Sons, Ltd. © 2014 The Authors. European Eating Disorders Review published by John Wiley & Sons, Ltd.

Effective Drug Delivery in Diffuse Intrinsic Pontine Glioma: A Theoretical Model to Identify Potential Candidates

PubMed Central

El-Khouly, Fatma E.; van Vuurden, Dannis G.; Stroink, Thom; Hulleman, Esther; Kaspers, Gertjan J. L.; Hendrikse, N. Harry; Veldhuijzen van Zanten, Sophie E. M.

2017-01-01

Despite decades of clinical trials for diffuse intrinsic pontine glioma (DIPG), patient survival does not exceed 10% at two years post-diagnosis. Lack of benefit from systemic chemotherapy may be attributed to an intact bloodbrain barrier (BBB). We aim to develop a theoretical model including relevant physicochemical properties in order to review whether applied chemotherapeutics are suitable for passive diffusion through an intact BBB or whether local administration via convection-enhanced delivery (CED) may increase their therapeutic potential. Physicochemical properties (lipophilicity, molecular weight, and charge in physiological environment) of anticancer drugs historically and currently administered to DIPG patients, that affect passive diffusion over the BBB, were included in the model. Subsequently, the likelihood of BBB passage of these drugs was ascertained, as well as their potential for intratumoral administration via CED. As only non-molecularly charged, lipophilic, and relatively small sized drugs are likely to passively diffuse through the BBB, out of 51 drugs modeled, only 8 (15%)—carmustine, lomustine, erlotinib, vismodegib, lenalomide, thalidomide, vorinostat, and mebendazole—are theoretically qualified for systemic administration in DIPG. Local administration via CED might create more therapeutic options, excluding only positively charged drugs and drugs that are either prodrugs and/or only available as oral formulation. A wide variety of drugs have been administered systemically to DIPG patients. Our model shows that only few are likely to penetrate the BBB via passive diffusion, which may partly explain the lack of efficacy. Drug distribution via CED is less dependent on physicochemical properties and may increase the therapeutic options for DIPG. PMID:29164054

Backflow-free catheters for efficient and safe convection-enhanced delivery of therapeutics.

PubMed

Lueshen, Eric; Tangen, Kevin; Mehta, Ankit I; Linninger, Andreas

2017-07-01

Convection-enhanced delivery (CED) is an invasive drug delivery technique used to target specific regions of the brain for the treatment of cancer and neurodegenerative diseases while bypassing the blood-brain barrier. In order to prevent the possibility of backflow, low volumetric flow rates are applied which limit the achievable drug distribution volumes from CED. This can render CED treatment ineffective since a small convective flow produces narrow drug distribution inside the treatment region. Novel catheter designs and CED protocols are needed to improve the drug distribution inside the treatment region. This is especially important when administering toxic chemotherapeutics which could adversely affect other organs if backflow occurred and these drugs entered the circulating blood stream. In order to help elucidate the causes of backflow and to design backflow-free catheters, we have studied the impact that microfluid flow has on deformable brain phantom gels experimentally as well as numerically. We found that fluid injections into porous media have considerable effects on local transport properties such as porosity and hydraulic conductivity. These phenomena not only alter the bulk flow velocity distribution of the microfluid flow due to the changing porosity, but significantly modify flow direction and even volumetric flow distribution due to induced local hydraulic conductivity anisotropy. These studies led us to the development of novel backflow-free catheters with safe volumetric flow rates up to 10 µL/min. The catheter designs, numerical simulations and experimental results are described throughout this article. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

13 CFR 303.9 - Requirements for short-term Planning Investments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Planning Investments. 303.9 Section 303.9 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE PLANNING INVESTMENTS AND COMPREHENSIVE ECONOMIC DEVELOPMENT STRATEGIES § 303.9 Requirements for short-term Planning Investments. (a) In addition to providing support for CEDS...

75 FR 70008 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... OMB Review; Comment Request Title: Office of Community Services (OCS) Community Economic Development... funded through the Community Economic Development (CED) and Job Opportunities for Low-Income Individuals... questions in this tool were adapted from a previously approved questionnaire, Office of Management and...

Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model.

PubMed

Singleton, W G; Collins, A M; Bienemann, A S; Killick-Cole, C L; Haynes, H R; Asby, D J; Butts, C P; Wyatt, M J; Barua, N U; Gill, S S

2017-01-01

The pan-histone deacetylase inhibitor panobinostat is a potential therapy for malignant glioma, but it is water insoluble and does not cross the blood-brain barrier when administered systemically. In this article, we describe the in vitro and in vivo efficacy of a novel water-soluble nano-micellar formulation of panobinostat designed for administration by convection enhanced delivery (CED). The in vitro efficacy of panobinostat-loaded nano-micelles against rat F98, human U87-MG and M059K glioma cells and against patient-derived glioma stem cells was measured using a cell viability assay. Nano-micelle distribution in rat brain was analyzed following acute CED using rhodamine-labeled nano-micelles, and toxicity was assayed using immunofluorescent microscopy and synaptophysin enzyme-linked immunosorbent assay. We compared the survival of the bioluminescent syngenic F98/Fischer344 rat glioblastoma model treated by acute CED of panobinostat-loaded nano-micelles with that of untreated and vehicle-only-treated controls. Nano-micellar panobinostat is cytotoxic to rat and human glioma cells in vitro in a dose-dependent manner following short-time exposure to drug. Fluorescent rhodamine-labelled nano-micelles distribute with a volume of infusion/volume of distribution (Vi/Vd) ratio of four and five respectively after administration by CED. Administration was not associated with any toxicity when compared to controls. CED of panobinostat-loaded nano-micelles was associated with significantly improved survival when compared to controls (n=8 per group; log-rank test, P <0.001). One hundred percent of treated animals survived the 60-day experimental period and had tumour response on post-mortem histological examination. CED of nano-micellar panobinostat represents a potential novel therapeutic option for malignant glioma and warrants translation into the clinic.

A novel implantable catheter system with transcutaneous port for intermittent convection-enhanced delivery of carboplatin for recurrent glioblastoma.

PubMed

Barua, Neil U; Hopkins, Kirsten; Woolley, Max; O'Sullivan, Stephen; Harrison, Rob; Edwards, Richard J; Bienemann, Alison S; Wyatt, Marcella J; Arshad, Azeem; Gill, Steven S

2016-01-01

Inadequate penetration of the blood-brain barrier (BBB) by systemically administered chemotherapies including carboplatin is implicated in their failure to improve prognosis for patients with glioblastoma. Convection-enhanced delivery (CED) of carboplatin has the potential to improve outcomes by facilitating bypass of the BBB. We report the first use of an implantable CED system incorporating a novel transcutaneous bone-anchored port (TBAP) for intermittent CED of carboplatin in a patient with recurrent glioblastoma. The CED catheter system was implanted using a robot-assisted surgical method. Catheter targeting accuracy was verified by performing intra-operative O-arm imaging. The TBAP was implanted using a skin-flap dermatome technique modeled on bone-anchored hearing aid surgery. Repeated infusions were performed by attaching a needle administration set to the TBAP. Drug distribution was monitored with serial real-time T2-weighted magnetic resonance imaging (MRI). All catheters were implanted to within 1.5 mm of their planned target. Intermittent infusions of carboplatin were performed on three consecutive days and repeated after one month without the need for further surgical intervention. Infused volumes of 27.9 ml per day were well tolerated, with the exception of a single seizure episode. Follow-up MRI at eight weeks demonstrated a significant reduction in the volume of tumor enhancement from 42.6 ml to 24.6 ml, and was associated with stability of the patient's clinical condition. Reduction in the volume of tumor enhancement indicates that intermittent CED of carboplatin has the potential to improve outcomes in glioblastoma. The novel technology described in this report make intermittent CED infusion regimes an achievable treatment strategy.

Application of Factor Analysis to Identify Dietary Patterns and Use of Factor Scores to Study Their Relationship with Nutritional Status of Adult Rural Populations

PubMed Central

Brahmam, G.N.V.; Vijayaraghavan, K.

2011-01-01

The prevalence of chronic energy deficiency (CED) among one-third of the Indian population is attributed to inadequacy of consumption of nutrients. However, considering the complexity of diets among Indians, the relationship between a particular dietary pattern and the nutritional status of the population has not been established so far. A community-based cross-sectional study was undertaken to assess estimates, at district level, of diet and nutritional status in Orissa State, India. Factor analysis was used for exploring the existence of consumption pattern of food and nutrients and their relationship with the nutritional status of rural adult population. Data on 2,864 adult men and 3,525 adult women in Orissa state revealed that there exists six patterns among food-groups explaining 59% of the total variation and three patterns among nutrients that explain 73% of the total variation among both adult men and women. The discriminant function analysis revealed that, overall, 53% of the men were correctly classified as either with chronic energy deficiency (CED) or without CED. Similarly, overall, 54% of the women were correctly classified as either with CED or without CED. The sensitivity of the model was 65% for both men and women, and the specificity was 46% and 41% respectively for men and women. In the case of classification of overweight/obesity, the prediction of the model was about 75% among both men and women, along with high sensitivity. Using factor analysis, the dietary patterns were identified from the food and nutrient intake data. There exists a strong relationship between the dietary patterns and the nutritional status of rural adults. These results will help identify the community people with CED and help planners formulate nutritional interventions accordingly. PMID:21957671

Knowledge Collisions: Perspectives from CED Practitioners Working with Women. NALL Working Paper.

ERIC Educational Resources Information Center

Stratton, Mary; Jackson, Ted

A study explored the ways that front-line community development workers across Canada gained information needed to work with women participants in community economic development initiatives. Data were gathered through focus groups, a preliminary study with 15 key informants employed in community development organizations, and structured telephone…

Isatis indigotica induces hepatocellular cancer cell death via caspase-independent apoptosis-inducing factor translocation apoptotic pathway in vitro and in vivo.

PubMed

Chung, Ying-Cheng; Tang, Feng-Yao; Liao, Jiunn-Wang; Chung, Chia-Hua; Jong, Ting-Ting; Chen, Shih-Shiung; Tsai, Ching-Hsiu; Chiang, En-Pei

2011-06-01

Isatis indigotica is a biennial herbaceous cruciferous medical herb with antipyretic, antiviral, anti-inflammatory, and anti-endotoxin activity. This study explored the chemotherapeutic potential of I indigotica on human hepatoma cells and investigated the mechanism by which metabolites from I indigotica inhibit hepatoma cell growth. Antitumor activity was discovered in dried I indigotica leaf chloroform extracts (CEDLI). In nude mice xenotransplanted with human hepatoma cells, CEDLI supplementation inhibited tumor growth by ~40% compared with nonsupplemented animals without affecting body weight/food intake. CEDLI induced sub-G1 cell cycle arrest and apoptosis in hepatoma cells. Furthermore, CEDLI activates p53 and Bax, reduces Bcl-2 expression, and causes mitochondrial stress and the release of apoptosis-inducing factor into the cytosol followed by its translocation into the nucleus, resulting in hepatoma cell apoptosis. This study provides novel in vivo evidence of I indigotica's antitumor activity. The chemotherapeutic activity against human hepatoma tumorigenesis was because of a distinguished caspase-independent apoptotic pathway.

The effect of less-lethal weapons on injuries in police use-of-force events.

PubMed

MacDonald, John M; Kaminski, Robert J; Smith, Michael R

2009-12-01

We investigated the effect of the use of less-lethal weapons, conductive energy devices (CEDs), and oleoresin capsicum (OC) spray on the prevalence and incidence of injuries to police officers and civilians in encounters involving the use of force. We analyzed data from 12 police departments that documented injuries to officers and civilians in 24,380 cases. We examined monthly injury rates for 2 police departments before and after their adoption of CEDs. Odds of injury to civilians and officers were significantly lower when police used CED weapons, after control for differences in case attributes and departmental policies restricting use of these weapons. Monthly incidence of injury in 2 police departments declined significantly, by 25% to 62%, after adoption of CED devices. Injuries sustained during police use-of-force events affect thousands of police officers and civilians in the United States each year. Incidence of these injuries can be reduced dramatically when law enforcement agencies responsibly employ less-lethal weapons in lieu of physical force.

The Integration of Emotions in Memories: Cognitive-Emotional Distinctiveness and Posttraumatic Stress Disorder

PubMed Central

Boals, Adriel; Rubin, David C.

2013-01-01

The current study examined cognitive-emotional distinctiveness (CED), the extent to which emotions are linked with event information, in memories associated with PTSD. Participants either with PTSD (n=68) or without PTSD (n=40) completed a modified multidimensional scaling technique to measure CED for their most negative and most positive events. The results revealed that participants in the PTSD group evidenced significantly lower levels of CED. This group difference remained significant when we limited the analysis to traumatic events that led to a PTSD diagnosis (n=33) in comparison to control participants who nominated a traumatic event that did not result in PTSD (n=32). Replicating previous findings, CED levels were higher in memories of negative events, in comparison to positive events. These results provide empirical evidence that memories associated with PTSD do contain special organizational features with respect to the links between emotions and memory. Implications for understanding and treating PTSD are discussed. PMID:23436960

Convection enhanced delivery of carboplatin in combination with radiotherapy for the treatment of brain tumors.

PubMed

Yang, Weilian; Huo, Tianyao; Barth, Rolf F; Gupta, Nilendu; Weldon, Michael; Grecula, John C; Ross, Brian D; Hoff, Benjamin A; Chou, Ting-Chao; Rousseau, Julia; Elleaume, Hélène

2011-02-01

The purpose of this study was to further evaluate the therapeutic efficacy of convection enhanced delivery (CED) of carboplatin in combination with radiotherapy for treatment of the F98 rat glioma. Tumor cells were implanted stereotactically into the brains of syngeneic Fischer rats, and 13 or 17 d. later carboplatin (20 μg/10 μl) was administered by either CED over 30 min or by Alzet osmotic pumps (0.5 μg/μl/h for 168 h.) beginning at 7 d after tumor implantation. Rats were irradiated with a 15 Gy fractionated dose (5 Gy × 3) of 6 MV photons to the whole brain beginning on the day after drug administration. Other groups of rats received either carboplatin or X-irradiation alone. The tumor carboplatin concentration following CED of 20 μg in 10 μl was 10.4 μg/g, which was equal to that observed following i.v. administration of 100 mg/kg b.w. Rats bearing small tumors, treated with carboplatin and X-irradiation, had a mean survival time (MST) of 83.4 d following CED and 111.8 d following pump delivery with 40% of the latter surviving >180 d (i.e. cured) compared to 55.2 d for CED and 77.2 d. for pump delivery of carboplatin alone and 31.8 d and 24.2 d, respectively, for X-irradiated and untreated controls. There was no microscopic evidence of residual tumor in the brains of all long-term survivors. Not surprisingly, rats with large tumors had much shorter MSTs. Only modest increases in MSTs were observed in animals that received either oral administration or CED of temozolomide plus X-irradiation (23.2 d and 29.3 d) compared to X-irradiation alone. The present survival data, and those previously reported by us, are among the best ever obtained with the F98 glioma model. Initially, they could provide a platform for a Phase I clinical trial to evaluate the safety and potential therapeutic efficacy of CED of carboplatin in patients with recurrent glioblastomas, and ultimately a Phase II trial of carboplatin in combination with radiation therapy.

The Importance of Being a Complement: CED Effects Revisited

ERIC Educational Resources Information Center

Jurka, Johannes

2010-01-01

This dissertation revisits subject island effects (Ross 1967, Chomsky 1973) cross-linguistically. Controlled acceptability judgment studies in German, English, Japanese and Serbian show that extraction out of specifiers is consistently degraded compared to extraction out of complements, indicating that the Condition on Extraction domains (CED,…

7 CFR 1220.623 - Canvassing requests.

Code of Federal Regulations, 2010 CFR

2010-01-01

... designate the County Executive Director (CED) and a county or State FSA office employee to canvass the... CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.623 Canvassing requests. (a... for this function is impractical, and designate the CED and/or another county or State FSA office...

7 CFR 1220.623 - Canvassing requests.

Code of Federal Regulations, 2013 CFR

2013-01-01

... designate the County Executive Director (CED) and a county or State FSA office employee to canvass the... CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.623 Canvassing requests. (a... for this function is impractical, and designate the CED and/or another county or State FSA office...

7 CFR 1220.623 - Canvassing requests.

Code of Federal Regulations, 2012 CFR

2012-01-01

... designate the County Executive Director (CED) and a county or State FSA office employee to canvass the... CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.623 Canvassing requests. (a... for this function is impractical, and designate the CED and/or another county or State FSA office...

7 CFR 1220.623 - Canvassing requests.

Code of Federal Regulations, 2014 CFR

2014-01-01

... designate the County Executive Director (CED) and a county or State FSA office employee to canvass the... CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.623 Canvassing requests. (a... for this function is impractical, and designate the CED and/or another county or State FSA office...

7 CFR 1220.623 - Canvassing requests.

Code of Federal Regulations, 2011 CFR

2011-01-01

... designate the County Executive Director (CED) and a county or State FSA office employee to canvass the... CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.623 Canvassing requests. (a... for this function is impractical, and designate the CED and/or another county or State FSA office...

Clinical and molecular characterization of 40 patients with classic Ehlers–Danlos syndrome: identification of 18 COL5A1 and 2 COL5A2 novel mutations

PubMed Central

2013-01-01

Background Classic Ehlers–Danlos syndrome (cEDS) is a rare autosomal dominant connective tissue disorder that is primarily characterized by skin hyperextensibility, abnormal wound healing/atrophic scars, and joint hypermobility. A recent study demonstrated that more than 90% of patients who satisfy all of these major criteria harbor a type V collagen (COLLV) defect. Methods This cohort included 40 patients with cEDS who were clinically diagnosed according to the Villefranche nosology. The flowchart that was adopted for mutation detection consisted of sequencing the COL5A1 gene and, if no mutation was detected, COL5A2 analysis. In the negative patients the presence of large genomic rearrangements in COL5A1 was investigated using MLPA, and positive results were confirmed via SNP-array analysis. Results We report the clinical and molecular characterization of 40 patients from 28 families, consisting of 14 pediatric patients and 26 adults. A family history of cEDS was present in 9 patients. The majority of the patients fulfilled all the major diagnostic criteria for cEDS; atrophic scars were absent in 2 females, skin hyperextensibility was not detected in a male and joint hypermobility was negative in 8 patients (20% of the entire cohort). Wide inter- and intra-familial phenotypic heterogeneity was observed. We identified causal mutations with a detection rate of approximately 93%. In 25/28 probands, COL5A1 or COL5A2 mutations were detected. Twenty-one mutations were in the COL5A1 gene, 18 of which were novel (2 recurrent). Of these, 16 mutations led to nonsense-mediated mRNA decay (NMD) and to COLLV haploinsufficiency and 5 mutations were structural. Two novel COL5A2 splice mutations were detected in patients with the most severe phenotypes. The known p. (Arg312Cys) mutation in the COL1A1 gene was identified in one patient with vascular-like cEDS. Conclusions Our findings highlight that the three major criteria for cEDS are useful and sufficient for cEDS clinical diagnosis in the large majority of the patients. The borderline patients for whom these criteria fail can be diagnosed when minor signs of connective tissue diseases and family history are present and when genetic testing reveals a defect in COLLV. Our data also confirm that COL5A1 and COL5A2 are the major, if not the only, genes involved in cEDS. PMID:23587214

Convection-enhanced delivery of a topoisomerase I inhibitor (nanoliposomal topotecan) and a topoisomerase II inhibitor (pegylated liposomal doxorubicin) in intracranial brain tumor xenografts1

PubMed Central

Yamashita, Yoji; Krauze, Michal T.; Kawaguchi, Tomohiro; Noble, Charles O.; Drummond, Daryl C.; Park, John W.; Bankiewicz, Krystof S.

2007-01-01

Despite multimodal treatment options, the response and survival rates for patients with malignant gliomas remain dismal. Clinical trials with convection-enhanced delivery (CED) have recently opened a new window in neuro-oncology to the direct delivery of chemotherapeutics to the CNS, circumventing the blood-brain barrier and reducing systemic side effects. Our previous CED studies with liposomal chemotherapeutics have shown promising antitumor activity in rodent brain tumor models. In this study, we evaluated a combination of nanoliposomal topotecan (nLs-TPT) and pegylated liposomal doxorubicin (PLD) to enhance efficacy in our brain tumor models, and to establish a CED treatment capable of improving survival from malignant brain tumors. Both liposomal drugs decreased key enzymes involved in tumor cell replication in vitro. Synergistic effects of nLs-TPT and PLD on U87MG cell death were found. The combination displayed excellent efficacy in a CED-based survival study 10 days after tumor cell implantation. Animals in the control group and those in single-agent groups had a median survival of less than 30 days, whereas the combination group experienced a median survival of more than 90 days. We conclude that CED of two liposomal chemotherapeutics (nLs-TPT and PLD) may be an effective treatment option for malignant gliomas. PMID:17018695

Gonadal and Sexual Dysfunction in Childhood Cancer Survivors.

PubMed

Yoon, Ju Young; Park, Hyeon Jin; Ju, Hee Young; Yoon, Jong Hyung; Chung, Jin Soo; Hwang, Sang Hyun; Lee, Dong Ock; Shim, Hye Young; Park, Byung-Kiu

2017-10-01

Few studies have addressed gonadal and sexual dysfunctions in childhood cancer survivors. We evaluated the prevalence rates and risk factors for gonadal failure among adolescent/young adult childhood cancer survivors and their sexual function. Subjects were childhood cancer survivors aged 15-29 years who had completed therapy more than 2 years ago. Demographic and medical characteristics were obtained from the patients' medical records. In addition, hormonal evaluation and semen analysis were performed and sexual function was evaluated via questionnaire. The study included 105 survivors (57 males, 48 females), of which 61 were adults (age > 19 years) and 44 were adolescents. In both males and females, the proportion of survivors with low sex hormone levels did not differ among age groups or follow-up period. Thirteen female subjects (27.1%) needed sex hormone replacement, while five males subjects (8.8%) were suspected of having hypogonadism, but none were receiving sex hormone replacement. Of 27 semen samples, 14 showed azospermia or oligospermia. The proportion of normospermia was lower in the high cyclophosphamide equivalent dose (CED) group (CED ≥ 8,000 mg/m2) than the low CED group (27.3% vs. 62.5%, p=0.047). Among adults, none were married and only 10 men (35.7%) and eight women (34.3%) were in a romantic relationship. Though a significant proportion (12.0% of males and 5.3% of females) of adolescent survivors had experienced sexual activity, 13.6% had not experienced sex education. The childhood cancer survivors in this study showed a high prevalence of gonadal/sexual dysfunction; accordingly, proper strategies are needed to manage these complications.

7 CFR 1221.227 - Canvassing voting ballots.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Director (CED) and a county or State FSA office employee to canvass the ballots and report the results... INFORMATION ORDER Procedures for the Conduct of Referenda Procedures § 1221.227 Canvassing voting ballots. (a..., and designate the CED and/or another county or State FSA office employee to canvass requests in any...

7 CFR 1221.227 - Canvassing voting ballots.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Director (CED) and a county or State FSA office employee to canvass the ballots and report the results... INFORMATION ORDER Procedures for the Conduct of Referenda Procedures § 1221.227 Canvassing voting ballots. (a..., and designate the CED and/or another county or State FSA office employee to canvass requests in any...

7 CFR 1221.227 - Canvassing voting ballots.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Director (CED) and a county or State FSA office employee to canvass the ballots and report the results... INFORMATION ORDER Procedures for the Conduct of Referenda Procedures § 1221.227 Canvassing voting ballots. (a..., and designate the CED and/or another county or State FSA office employee to canvass requests in any...

7 CFR 1280.627 - Canvassing voting ballots.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Executive Director (CED) and a county or State FSA office employee to canvass the ballots and report the... INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.627 Canvassing voting ballots. (a... impractical, and designate the CED and/or another county or State FSA office employee to canvass requests in...

7 CFR 1280.627 - Canvassing voting ballots.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Executive Director (CED) and a county or State FSA office employee to canvass the ballots and report the... INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.627 Canvassing voting ballots. (a... impractical, and designate the CED and/or another county or State FSA office employee to canvass requests in...

7 CFR 1280.627 - Canvassing voting ballots.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Executive Director (CED) and a county or State FSA office employee to canvass the ballots and report the... INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.627 Canvassing voting ballots. (a... impractical, and designate the CED and/or another county or State FSA office employee to canvass requests in...

7 CFR 1221.227 - Canvassing voting ballots.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Director (CED) and a county or State FSA office employee to canvass the ballots and report the results... INFORMATION ORDER Procedures for the Conduct of Referenda Procedures § 1221.227 Canvassing voting ballots. (a..., and designate the CED and/or another county or State FSA office employee to canvass requests in any...

7 CFR 1280.627 - Canvassing voting ballots.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Executive Director (CED) and a county or State FSA office employee to canvass the ballots and report the... INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.627 Canvassing voting ballots. (a... impractical, and designate the CED and/or another county or State FSA office employee to canvass requests in...

7 CFR 1280.627 - Canvassing voting ballots.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Executive Director (CED) and a county or State FSA office employee to canvass the ballots and report the... INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.627 Canvassing voting ballots. (a... impractical, and designate the CED and/or another county or State FSA office employee to canvass requests in...

Models, Measurements, and Local Decisions: Assessing and ...

EPA Pesticide Factsheets

This presentation includes a combination of modeling and measurement results to characterize near-source air quality in Newark, New Jersey with consideration of how this information could be used to inform decision making to reduce risk of health impacts. Decisions could include either exposure or emissions reduction, and a host of stakeholders, including residents, academics, NGOs, local and federal agencies. This presentation includes results from the C-PORT modeling system, and from a citizen science project from the local area. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-support tools, and models to be applied to media-specific or receptor-specific problem areas. CED uses modeling-based approaches to characterize exposures, evaluate fate and transport, and support environmental diagnostics/forensics with input from multiple data sources. It also develops media- and receptor-specific models, process models, and decision support tools for use both within and outside of EPA.

WRF/CMAQ AQMEII3 Simulations of US Regional-Scale ...

EPA Pesticide Factsheets

Chemical boundary conditions are a key input to regional-scale photochemical models. In this study, performed during the third phase of the Air Quality Model Evaluation International Initiative (AQMEII3), we perform annual simulations over North America with chemical boundary conditions prepared from four different global models. Results indicate that the impacts of different boundary conditions are significant for ozone throughout the year and most pronounced outside the summer season. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-support tools, and models to be applied to media-specific or receptor-specific problem areas. CED uses modeling-based approaches to characterize exposures, evaluate fate and transport, and support environmental diagnostics/forensics with input from multiple data sources. It also develops media- and receptor-specific models, process models, and decision support tools for use both within and outside of EPA.

7 CFR 1220.629 - Disposition of records.

Code of Federal Regulations, 2011 CFR

2011-01-01

... records will be placed in a secure location under the custody of the FSA CED for a period of not less than... CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.629 Disposition of records. Each FSA CED will place in sealed containers marked with the identification of the “Request for Soybean...

7 CFR 1230.637 - Disposition of ballots and records.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Disposition of ballots and records. (a) Producer ballots and records. Each FSA CED will place in sealed... summaries. Such records will be placed under lock in a safe place under the custody of the FSA CED for a..., South Agriculture Building, 1400 Independence Avenue, SW., Washington, DC. A Marketing Programs Branch...

7 CFR 1230.637 - Disposition of ballots and records.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Disposition of ballots and records. (a) Producer ballots and records. Each FSA CED will place in sealed... summaries. Such records will be placed under lock in a safe place under the custody of the FSA CED for a..., South Agriculture Building, 1400 Independence Avenue, SW., Washington, DC. A Marketing Programs Branch...

7 CFR 1230.637 - Disposition of ballots and records.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Disposition of ballots and records. (a) Producer ballots and records. Each FSA CED will place in sealed... summaries. Such records will be placed under lock in a safe place under the custody of the FSA CED for a..., South Agriculture Building, 1400 Independence Avenue, SW., Washington, DC. A Marketing Programs Branch...

7 CFR 1220.629 - Disposition of records.

Code of Federal Regulations, 2013 CFR

2013-01-01

... records will be placed in a secure location under the custody of the FSA CED for a period of not less than... CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.629 Disposition of records. Each FSA CED will place in sealed containers marked with the identification of the “Request for Soybean...

7 CFR 1220.629 - Disposition of records.

Code of Federal Regulations, 2010 CFR

2010-01-01

... records will be placed in a secure location under the custody of the FSA CED for a period of not less than... CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.629 Disposition of records. Each FSA CED will place in sealed containers marked with the identification of the “Request for Soybean...

7 CFR 1230.637 - Disposition of ballots and records.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Disposition of ballots and records. (a) Producer ballots and records. Each FSA CED will place in sealed... summaries. Such records will be placed under lock in a safe place under the custody of the FSA CED for a..., South Agriculture Building, 1400 Independence Avenue, SW., Washington, DC. A Marketing Programs Branch...

7 CFR 1230.637 - Disposition of ballots and records.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Disposition of ballots and records. (a) Producer ballots and records. Each FSA CED will place in sealed... summaries. Such records will be placed under lock in a safe place under the custody of the FSA CED for a..., South Agriculture Building, 1400 Independence Avenue, SW., Washington, DC. A Marketing Programs Branch...

7 CFR 1220.629 - Disposition of records.

Code of Federal Regulations, 2014 CFR

2014-01-01

... records will be placed in a secure location under the custody of the FSA CED for a period of not less than... CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.629 Disposition of records. Each FSA CED will place in sealed containers marked with the identification of the “Request for Soybean...

7 CFR 1280.632 - Disposition of records.

Code of Federal Regulations, 2013 CFR

2013-01-01

... records will be placed in a secure location under the custody of FSA CED for a period of not less than 12... INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.632 Disposition of records. Each FSA CED will place in sealed containers marked with the identification of the “Lamb Checkoff Program...

7 CFR 1280.632 - Disposition of records.

Code of Federal Regulations, 2012 CFR

2012-01-01

... records will be placed in a secure location under the custody of FSA CED for a period of not less than 12... INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.632 Disposition of records. Each FSA CED will place in sealed containers marked with the identification of the “Lamb Checkoff Program...

7 CFR 1220.629 - Disposition of records.

Code of Federal Regulations, 2012 CFR

2012-01-01

... records will be placed in a secure location under the custody of the FSA CED for a period of not less than... CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.629 Disposition of records. Each FSA CED will place in sealed containers marked with the identification of the “Request for Soybean...

7 CFR 1280.632 - Disposition of records.

Code of Federal Regulations, 2011 CFR

2011-01-01

... records will be placed in a secure location under the custody of FSA CED for a period of not less than 12... INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.632 Disposition of records. Each FSA CED will place in sealed containers marked with the identification of the “Lamb Checkoff Program...

7 CFR 1280.632 - Disposition of records.

Code of Federal Regulations, 2010 CFR

2010-01-01

... records will be placed in a secure location under the custody of FSA CED for a period of not less than 12... INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.632 Disposition of records. Each FSA CED will place in sealed containers marked with the identification of the “Lamb Checkoff Program...

7 CFR 1280.632 - Disposition of records.

Code of Federal Regulations, 2014 CFR

2014-01-01

... records will be placed in a secure location under the custody of FSA CED for a period of not less than 12... INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.632 Disposition of records. Each FSA CED will place in sealed containers marked with the identification of the “Lamb Checkoff Program...

78 FR 5176 - CED White River Solar, LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-24

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ER13-764-000] CED White River Solar, LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes Request for Blanket... River Solar, LLC's application for market-based rate authority, with an accompanying rate schedule...

Humility pills: building an ethics of cognitive enhancement.

PubMed

Goodman, Rob

2014-06-01

The use of cognition-enhancing drugs (CEDs) appears to be increasingly common in both academic and workplace settings. But many universities and businesses have not yet engaged with the ethical challenges raised by CED use. This paper considers criticisms of CED use with a particular focus on the Accomplishment Argument: an influential set of claims holding that enhanced work is less dignified, valuable, or authentic, and that cognitive enhancement damages our characters. While the Accomplishment Argument assumes a view of authorship based on individual credit-taking, an impersonal or collaborative view is just as possible. This paper considers the benefits of this view-including humility, a value often claimed by critics of enhancement-and argues that such a view is consistent with open CED use. It proposes an ethics of cognitive enhancement based on toleration, transparency, and humility, and it discusses how institutions and individuals can build a culture of open cognitive enhancement. © The Author 2014. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Effect of Less-Lethal Weapons on Injuries in Police Use-of-Force Events

PubMed Central

Kaminski, Robert J.; Smith, Michael R.

2009-01-01

Objectives. We investigated the effect of the use of less-lethal weapons, conductive energy devices (CEDs), and oleoresin capsicum (OC) spray on the prevalence and incidence of injuries to police officers and civilians in encounters involving the use of force. Methods. We analyzed data from 12 police departments that documented injuries to officers and civilians in 24 380 cases. We examined monthly injury rates for 2 police departments before and after their adoption of CEDs. Results. Odds of injury to civilians and officers were significantly lower when police used CED weapons, after control for differences in case attributes and departmental policies restricting use of these weapons. Monthly incidence of injury in 2 police departments declined significantly, by 25% to 62%, after adoption of CED devices. Conclusions. Injuries sustained during police use-of-force events affect thousands of police officers and civilians in the United States each year. Incidence of these injuries can be reduced dramatically when law enforcement agencies responsibly employ less-lethal weapons in lieu of physical force. PMID:19846686

Consumption of Probiotic Lactobacillus fermentum MTCC: 5898-Fermented Milk Attenuates Dyslipidemia, Oxidative Stress, and Inflammation in Male Rats Fed on Cholesterol-Enriched Diet.

PubMed

Yadav, Radha; Khan, Suhail Hakeem; Mada, Sanusi Bello; Meena, Sunita; Kapila, Rajeev; Kapila, Suman

2018-05-13

There is a growing and alarming prevalence that increased serum cholesterol is closely related to increased cardiovascular disease risk. Probiotic consumption could be a safe and natural strategy to combat. Therefore, we sought to examine the cholesterol-lowering potential of co-supplementation of probiotic bacteria Lactobacillus fermentum MTCC: 5898-fermented buffalo milk (2.5% fat) in rats fed cholesterol-enriched diet. Male Wistar rats were divided into three groups on the basis of feed, viz. group 1, fed standard diet (SD); group 2, fed cholesterol-enriched diet (CED); and group 3, fed cholesterol-enriched diet along with L. fermentum MTCC: 5898-fermented milk (CED+LF) for 90 days. At the endpoint, significantly higher levels of serum total cholesterol, low-density lipoprotein cholesterol, triacylglycerols, very low density lipoprotein cholesterol, atherogenic index, coronary artery risk index, hepatic lipids, lipid peroxidation, and mRNA expression of inflammatory cytokines (TNF-α and IL-6) in the liver while significantly lower levels of serum high-density lipoprotein cholesterol and anti-oxidative enzyme activities, catalase, superoxide dismutase, and glutathione peroxidase in the liver and kidney were observed in the CED group compared to the SD group. Compared to the CED group, these adverse physiological alterations were found significantly improved in the CED+LF group. Hence, this study proposes that L. fermentum MTCC: 5898 is a potential probiotic bacteria that can be consumed to tackle hypercholesterolemia. Graphical Abstract ᅟ.

Cell Death in C. elegans Development.

PubMed

Malin, Jennifer Zuckerman; Shaham, Shai

2015-01-01

Cell death is a common and important feature of animal development, and cell death defects underlie many human disease states. The nematode Caenorhabditis elegans has proven fertile ground for uncovering molecular and cellular processes controlling programmed cell death. A core pathway consisting of the conserved proteins EGL-1/BH3-only, CED-9/BCL2, CED-4/APAF1, and CED-3/caspase promotes most cell death in the nematode, and a conserved set of proteins ensures the engulfment and degradation of dying cells. Multiple regulatory pathways control cell death onset in C. elegans, and many reveal similarities with tumor formation pathways in mammals, supporting the idea that cell death plays key roles in malignant progression. Nonetheless, a number of observations suggest that our understanding of developmental cell death in C. elegans is incomplete. The interaction between dying and engulfing cells seems to be more complex than originally appreciated, and it appears that key aspects of cell death initiation are not fully understood. It has also become apparent that the conserved apoptotic pathway is dispensable for the demise of the C. elegans linker cell, leading to the discovery of a previously unexplored gene program promoting cell death. Here, we review studies that formed the foundation of cell death research in C. elegans and describe new observations that expand, and in some cases remodel, this edifice. We raise the possibility that, in some cells, more than one death program may be needed to ensure cell death fidelity. © 2015 Elsevier Inc. All rights reserved.

Traditional food consumption and nutritional status of Dalit mothers in rural Andhra Pradesh, South India.

PubMed

Schmid, M A; Egeland, G M; Salomeyesudas, B; Satheesh, P V; Kuhnlein, H V

2006-11-01

To describe prevalence of malnutrition and their correlates of nutrient and traditional food consumption in rural Dalit mothers. In a cross-sectional study, we used socio-cultural questionnaires, anthropometric measurements and clinical eye examinations during the rainy season in 2003. Food frequency questionnaires and 24-h recalls were conducted during both summer and rainy seasons. Dalit mothers with young children were recruited from 37 villages in the Medak District of rural Andhra Pradesh, India. Dalit mothers (n = 220) participated. The prevalence of chronic energy-deficient (CED) mothers (body mass index <18.5 kg/m2) was 58%. Illiterate women and active women were more likely to have CED than those literate and non-active (relative risks (RR) = 1.6 and 1.4, respectively, P < or = 0.05), but literacy and activity level were not significant in multivariable analyses including sanitation and number of children < or =5 years of age. Increasing levels of fat intake, as a percent of total energy, was significantly associated with lower risk of CED (RR of the lowest 25th percentile compared to those in the 75th percentile or above was 1.6, P < or = 0.05), findings that remained significant in multivariable analyses. Consumption of pulses (g/day) was also inversely related to CED in univariate and multivariable analyses. Carbohydrate intake, as a percent of total energy, was inversely related to percent energy from fat (r = -0.96, P < or = 0.01), and, although positively related to CED in univariate analyses, carbohydrate consumption was not significant in multivariable analyses. Mothers' age in years and income was positively related to vitamin A deficiency. These results confirm that CED and vitamin A malnutrition among Dalit women are predominant problems in this area. Increased consumption of local traditional Dalit food (particularly sorghum, pulses, vegetables and animal source food) should be incorporated as an important component of intervention strategies to improve nutritional status.

Poor drug distribution as a possible explanation for the results of the PRECISE trial.

PubMed

Sampson, John H; Archer, Gary; Pedain, Christoph; Wembacher-Schröder, Eva; Westphal, Manfred; Kunwar, Sandeep; Vogelbaum, Michael A; Coan, April; Herndon, James E; Raghavan, Raghu; Brady, Martin L; Reardon, David A; Friedman, Allan H; Friedman, Henry S; Rodríguez-Ponce, M Inmaculada; Chang, Susan M; Mittermeyer, Stephan; Croteau, David; Puri, Raj K

2010-08-01

Convection-enhanced delivery (CED) is a novel intracerebral drug delivery technique with considerable promise for delivering therapeutic agents throughout the CNS. Despite this promise, Phase III clinical trials employing CED have failed to meet clinical end points. Although this may be due to inactive agents or a failure to rigorously validate drug targets, the authors have previously demonstrated that catheter positioning plays a major role in drug distribution using this technique. The purpose of the present work was to retrospectively analyze the expected drug distribution based on catheter positioning data available from the CED arm of the PRECISE trial. Data on catheter positioning from all patients randomized to the CED arm of the PRECISE trial were available for analyses. BrainLAB iPlan Flow software was used to estimate the expected drug distribution. Only 49.8% of catheters met all positioning criteria. Still, catheter positioning score (hazard ratio 0.93, p = 0.043) and the number of optimally positioned catheters (hazard ratio 0.72, p = 0.038) had a significant effect on progression-free survival. Estimated coverage of relevant target volumes was low, however, with only 20.1% of the 2-cm penumbra surrounding the resection cavity covered on average. Although tumor location and resection cavity volume had no effect on coverage volume, estimations of drug delivery to relevant target volumes did correlate well with catheter score (p < 0.003), and optimally positioned catheters had larger coverage volumes (p < 0.002). Only overall survival (p = 0.006) was higher for investigators considered experienced after adjusting for patient age and Karnofsky Performance Scale score. The potential efficacy of drugs delivered by CED may be severely constrained by ineffective delivery in many patients. Routine use of software algorithms and alternative catheter designs and infusion parameters may improve the efficacy of drugs delivered by CED.

Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model

PubMed Central

Singleton, WG; Collins, AM; Bienemann, AS; Killick-Cole, CL; Haynes, HR; Asby, DJ; Butts, CP; Wyatt, MJ; Barua, NU; Gill, SS

2017-01-01

Background The pan-histone deacetylase inhibitor panobinostat is a potential therapy for malignant glioma, but it is water insoluble and does not cross the blood–brain barrier when administered systemically. In this article, we describe the in vitro and in vivo efficacy of a novel water-soluble nano-micellar formulation of panobinostat designed for administration by convection enhanced delivery (CED). Materials and methods The in vitro efficacy of panobinostat-loaded nano-micelles against rat F98, human U87-MG and M059K glioma cells and against patient-derived glioma stem cells was measured using a cell viability assay. Nano-micelle distribution in rat brain was analyzed following acute CED using rhodamine-labeled nano-micelles, and toxicity was assayed using immunofluorescent microscopy and synaptophysin enzyme-linked immunosorbent assay. We compared the survival of the bioluminescent syngenic F98/Fischer344 rat glioblastoma model treated by acute CED of panobinostat-loaded nano-micelles with that of untreated and vehicle-only-treated controls. Results Nano-micellar panobinostat is cytotoxic to rat and human glioma cells in vitro in a dose-dependent manner following short-time exposure to drug. Fluorescent rhodamine-labelled nano-micelles distribute with a volume of infusion/volume of distribution (Vi/Vd) ratio of four and five respectively after administration by CED. Administration was not associated with any toxicity when compared to controls. CED of panobinostat-loaded nano-micelles was associated with significantly improved survival when compared to controls (n=8 per group; log-rank test, P<0.001). One hundred percent of treated animals survived the 60-day experimental period and had tumour response on post-mortem histological examination. Conclusion CED of nano-micellar panobinostat represents a potential novel therapeutic option for malignant glioma and warrants translation into the clinic. PMID:28260886

Necrotic Cells Actively Attract Phagocytes through the Collaborative Action of Two Distinct PS-Exposure Mechanisms

PubMed Central

Li, Zao; Venegas, Victor; Nagaoka, Yuji; Morino, Eri; Raghavan, Prashant; Audhya, Anjon; Nakanishi, Yoshinobu; Zhou, Zheng

2015-01-01

Necrosis, a kind of cell death closely associated with pathogenesis and genetic programs, is distinct from apoptosis in both morphology and mechanism. Like apoptotic cells, necrotic cells are swiftly removed from animal bodies to prevent harmful inflammatory and autoimmune responses. In the nematode Caenorhabditis elegans, gain-of-function mutations in certain ion channel subunits result in the excitotoxic necrosis of six touch neurons and their subsequent engulfment and degradation inside engulfing cells. How necrotic cells are recognized by engulfing cells is unclear. Phosphatidylserine (PS) is an important apoptotic-cell surface signal that attracts engulfing cells. Here we observed PS exposure on the surface of necrotic touch neurons. In addition, the phagocytic receptor CED-1 clusters around necrotic cells and promotes their engulfment. The extracellular domain of CED-1 associates with PS in vitro. We further identified a necrotic cell-specific function of CED-7, a member of the ATP-binding cassette (ABC) transporter family, in promoting PS exposure. In addition to CED-7, anoctamin homolog-1 (ANOH-1), the C. elegans homolog of the mammalian Ca2+-dependent phospholipid scramblase TMEM16F, plays an independent role in promoting PS exposure on necrotic cells. The combined activities from CED-7 and ANOH-1 ensure efficient exposure of PS on necrotic cells to attract their phagocytes. In addition, CED-8, the C. elegans homolog of mammalian Xk-related protein 8 also makes a contribution to necrotic cell-removal at the first larval stage. Our work indicates that cells killed by different mechanisms (necrosis or apoptosis) expose a common “eat me” signal to attract their phagocytic receptor(s); furthermore, unlike what was previously believed, necrotic cells actively present PS on their outer surfaces through at least two distinct molecular mechanisms rather than leaking out PS passively. PMID:26061275

Probabilistic evaluation of on-line checks in fault-tolerant multiprocessor systems

NASA Technical Reports Server (NTRS)

Nair, V. S. S.; Hoskote, Yatin V.; Abraham, Jacob A.

1992-01-01

The analysis of fault-tolerant multiprocessor systems that use concurrent error detection (CED) schemes is much more difficult than the analysis of conventional fault-tolerant architectures. Various analytical techniques have been proposed to evaluate CED schemes deterministically. However, these approaches are based on worst-case assumptions related to the failure of system components. Often, the evaluation results do not reflect the actual fault tolerance capabilities of the system. A probabilistic approach to evaluate the fault detecting and locating capabilities of on-line checks in a system is developed. The various probabilities associated with the checking schemes are identified and used in the framework of the matrix-based model. Based on these probabilistic matrices, estimates for the fault tolerance capabilities of various systems are derived analytically.

Medical regulation of cognitive enhancement devices: some concerns

PubMed Central

King, Mike; Gavaghan, Colin; McMillan, John

2014-01-01

The authors present a cogent and detailed case for altering the Medical Devices Directive to allow regulation of cognitive enhancement devices (CEDs). Protection against significant risk of harm, especially for the vulnerable, and promotion of benefit through informed use of CEDs are all good features of the proposal. However, the pre-market approval process has limitations, which we explore. We raise the possibility of ‘risk compensation’ in response to the introduction of safety measures, which could alter its effectiveness. The proposal alludes to use of ‘formally trained practitioners,’ which provide a further tier of regulation for CEDs within the proposal. We consider some positive and negative implications of this aspect of the proposal that might warrant further consideration. PMID:27774173

Biomedical study on combined effects of simulated weightlessness and emergent depressurization of spacecraft

NASA Astrophysics Data System (ADS)

Yang, T. D.; Zhang, R. G.; Wang, C. M.; Fu, H. W.; Zhang, B. L.; Zhang, J. X.

1999-01-01

Cabin emergent depressurization (CED) may occur in spacecraft during manned space flight. The purpose of this paper was to study the combined effects of simulated weightlessness (SW) and CED factors on humans and animals. It was found that the amplitude of T wave of human electrocardiograms (ECG) significantly decreased in bed rest and hypoxia compared with the control condition (P<0.05), and that suspension with pure O2 induced severer edema in the lungs of rats than that in only a pure O2 environment. SW and pure O2 caused middle ear congestion and decreased the barofunction during pressure changes. These results indicate that human response to CED factors become more serious under SW because of the blood redistribution.

[Pay attention to the corneal epithelial cell dysfunction after cataract surgery].

PubMed

Sun, Xuguang; Wang, Sen

2015-03-01

Corneal epithelial dysfunction ( CED ) is the abnormality of the regeneration, conjunction, adhesion and immigration of the corneal epithelium cells without the decompensation of the corneal limbal cells. Due to the affection resulting from the systemic problems of patients and the management in the preoperative period, some of the patients at one to two weeks after cataract surgery will present the edema and fluorescein staining of the corneal epithelium. Without correct therapy, the defect of the epithelium, or even persisting ulceration of the cornea will occur. The key points of the management for CED are the early diagnosis and reasonable therapy. We suggest paying special attention to CED in the patients with metabolism diseases, abnormality of the tear film and long-term blepharitis.

Socio-economic and demographic factors influencing nutritional status among early childbearing young mothers in Bangladesh.

PubMed

Islam, Ashraful; Islam, Nurul; Bharati, Premananda; Aik, Saw; Hossain, Golam

2016-08-26

Early childbearing influences women's health. This study aims to examine the effects of socio-demographic factors on nutritional status of early childbearing mothers in Bangladesh based on Body Mass Index (BMI) as the indicator. Data was extracted from Bangladesh Demographic and Health Survey (BDHS)-2011. The survey was performed on 17,842 married women aged 15-49. We focused on early childbearing mothers (age ≤ 24, and who had delivered their first child ≤ 20). Mothers who were underweight (BMI ≤ 18.5 kg/m(2)) would be further classified into various grades of chronic energy deficiency (CED): mild (17.0 ≤ BMI < 18.5 kg/m(2)), moderate (16.0 ≤ BMI <17.0 kg/m(2)), and severe (BMI < 16.0 kg/m(2)). Multiple logistic regression model was used to examine the effect of socio-demographic factors on nutritional status. Mean age of the mothers was 20.49 ± 2.37 years (ranged 15-24 years). The prevalence of underweight among early childbearing mothers was 32.1 % (urban 25 % and rural 35.1 %). Most of the underweight mothers had mild (62.2 %) CED, while the remaining had either moderate (25.9 %) or severe (11.9 %) CED. Multiple logistic regression analysis demonstrated that young mothers from rural areas, poor families, and those who were illiterate or with low level of education, working, and married to unemployed husband were at higher risk for being underweight. Young mothers who had non-caesarean delivered, delivered at home, or married at early age and had more than two children were also at higher risk for being underweight. The prevalence of underweight among early childbearing mothers in Bangladesh is very high (32.1 %), associated with the still common practice of teenage marriage. Education level, wealth index, occupation, place of residence, age at first marriage and parity were important predictors for their nutritional status. The government and non-government organizations should take initiatives to reduce the prevalence of underweight mothers in Bangladesh.

13 CFR 303.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... INVESTMENTS AND COMPREHENSIVE ECONOMIC DEVELOPMENT STRATEGIES § 303.2 Definitions. In addition to the defined... following meanings: Planning Investment means the award of EDA Investment Assistance under section 203 of... CEDS for a specific EDA-approved Region under section 203 of PWEDA. Strategy Committee means the...

The perspective of celiac disease patients on emerging treatment options and non-celiac gluten sensitivity.

PubMed

Greuter, Thomas; Schmidlin, Sandra; Lattmann, Jaqueline; Stotz, Matthias; Lehmann, Romina; Zeitz, Jonas; Scharl, Michael; Misselwitz, Benjamin; Pohl, Daniel; Fried, Michael; Tutuian, Radu; Fasano, Alessio; Schoepfer, Alain M; Rogler, Gerhard; Biedermann, Luc; Vavricka, Stephan R

2017-03-01

Non-celiac gluten sensitivity (NCGS) and emerging treatment options are hot topics in the celiac disease (CeD) scientific literature. However, very little is known about the perspective on these issues of CeD patients. We performed a large patient survey among unselected CeD patients in Switzerland. A total of 1689 patients were analyzed. 57.5% have previously heard of NCGS. 64.5% believe in the existence of this entity. Regarding a potential influence of NCGS on CeD awareness, 31.7% show a positive and 27.5% a negative perception. Patients with prior use of alternative medicine and women more often have heard of and believe in the existence of NCGS vs. those never having used alternative methods and men, respectively (66.9 vs. 56.9%, p=0.001 and 78.5 vs. 69.0%, p=0.001; 60.7 vs. 44.2%, p<0.001 and 71.0 vs. 60.8%, p=0.002). Women and patients ≥30 years more often show a negative attitude towards NCGS (32.2% vs. 24.8%, p=0.024 and 32.2% vs. 24.2%, p=0.018). With regard to emerging treatment options for CeD, 43.3% have previously heard of novel agents, more women than men (46.0 vs. 38.0%, p=0.019). Perception of and attitude towards NCGS differ depending on sex, age and prior use of alternative medicine. Knowledge of the progress towards emerging treatment options is currently limited. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

New insights into apoptosome structure and function.

PubMed

Dorstyn, Loretta; Akey, Christopher W; Kumar, Sharad

2018-05-15

The apoptosome is a platform that activates apical procaspases in response to intrinsic cell death signals. Biochemical and structural studies in the past two decades have extended our understanding of apoptosome composition and structure, while illuminating the requirements for initiator procaspase activation. A number of studies have now provided high-resolution structures for apoptosomes from C. elegans (CED-4), D. melanogaster (Dark), and H. sapiens (Apaf-1), which define critical protein interfaces, including intra and interdomain interactions. This work also reveals interactions of apoptosomes with their respective initiator caspases, CED-3, Dronc and procaspase-9. Structures of the human apoptosome have defined the requirements for cytochrome c binding, which triggers the conversion of inactive Apaf-1 molecules to an extended, assembly competent state. While recent data have provided a detailed understanding of apoptosome formation and procaspase activation, they also highlight important evolutionary differences with functional implications for caspase activation. CARD/CARD interactions in the CED-4, Dark and Apaf-1 apoptosomes. Type I, II and III interfaces that stabilize CARD-CARD interactions are indicated (left column). Note that the Type I interface appears to be unique to Apaf-1/pc-9 CARD interactions. Middle column shows cartoons of the active states of the CARD-CARD disks, illustrating the two CED-4 tetrameric ring layers (top) and the recruitment of 8 Dronc CARDs and between 3-4 pc-9 CARDs, to the Dark and Apaf-1 apoptosomes respectively (middle and lower panels). Ribbon diagrams of the CED-4, Dark and Apaf-1 apoptosomes are shown (right column).

Synthesis and photocatalytic studies of ZnS nanoparticles from heteroleptic complex of Zn(II) 1-cyano-1-carboethoxy-2,-2-ethylenedithiolato diisopropylthiourea and its adducts with N-donor ligands

NASA Astrophysics Data System (ADS)

Osuntokun, Jejenija; Ajibade, Peter A.; Onwudiwe, Damian C.

2016-12-01

Zinc complexes of the type [Zn(diptu)2(ced)] (1), [Zn(diptu)2(ced)py] (2), [Zn(diptu)2(ced)bpy] (3), and [Zn(diptu)2(ced)phen] (4), (where (diptu)2(ced) = 1-cyano-1-carboethoxyethylene-2,2-dithiolato-κS,S‧-bis(N,N-diisopropyllthiourea), py = pyridine, bpy = 2, 2‧ bipyridine and phen = 1, 10 phenanthroline have been synthesized and characterized by elemental analyses, Fourier transform infra-red (FTIR) and Nuclear magnetic resonance (NMR) spectroscopies. The parent complex (1) was formulated as four coordinate species, which gave rise to 5 coordinate complex in (2) and six coordinate compounds in (3) and (4), with the dithiolate acting as bidentate chelating ligand. The complexes were used as single-source precursors for the synthesis of HDA-capped ZnS nanoparticles. The nanoparticles gave different morphologies with sizes in the range of 1.92-4.72 nm as observed from the TEM analysis and supported by XRD. The UV-vis spectroscopy showed that all the ZnS nanoparticles are blue shifted, with respect to the bulk, which confirmed quantum confinement. The photoluminescence spectra showed narrow and broad emission peaks around 290 and 360 nm which are ascribed to spontaneous emission peaks from band to band transition and surface states respectively. Photocatalytic activities of all the nanoparticles were investigated with methylene blue (MB) acting as the organic dye, and the UV-vis spectral revealed a gradual decrease in absorption peak that confirmed the degradation of the MB.

Perspectives on a Policy That Never Was: Trying To Enhance Multiculturalism in a University Setting.

ERIC Educational Resources Information Center

Greenwald, Beatrice

This paper discusses the failure of the University of Washington to formulate a policy regarding the establishment of a Cultural and Ethnic Diversity (CED) course requirement for undergraduates despite nine years of efforts to do so, tracing the efforts to establish a CED requirement, along with the arguments for and against such a requirement. It…

Correlated electronic decay in expanding clusters triggered by intense XUV pulses from a Free-Electron-Laser

PubMed Central

Oelze, Tim; Schütte, Bernd; Müller, Maria; Müller, Jan P.; Wieland, Marek; Frühling, Ulrike; Drescher, Markus; Al-Shemmary, Alaa; Golz, Torsten; Stojanovic, Nikola; Krikunova, Maria

2017-01-01

Irradiation of nanoscale clusters and large molecules with intense laser pulses transforms them into highly-excited non- equilibrium states. The dynamics of intense laser-cluster interaction is encoded in electron kinetic energy spectra, which contain signatures of direct photoelectron emission as well as emission of thermalized nanoplasma electrons. In this work we report on a so far not observed spectrally narrow bound state signature in the electron kinetic energy spectra from mixed Xe core - Ar shell clusters ionized by intense extreme-ultraviolet (XUV) pulses from a free-electron-laser. This signature is attributed to the correlated electronic decay (CED) process, in which an excited atom relaxes and the excess energy is used to ionize the same or another excited atom or a nanoplasma electron. By applying the terahertz field streaking principle we demonstrate that CED-electrons are emitted at least a few picoseconds after the ionizing XUV pulse has ended. Following the recent finding of CED in clusters ionized by intense near-infrared laser pulses, our observation of CED in the XUV range suggests that this process is of general relevance for the relaxation dynamics in laser produced nanoplasmas. PMID:28098175

Convection-enhanced delivery for the treatment of brain tumors

PubMed Central

Debinski, Waldemar; Tatter, Stephen B

2013-01-01

The brain is highly accessible for nutrients and oxygen, however delivery of drugs to malignant brain tumors is a very challenging task. Convection-enhanced delivery (CED) has been designed to overcome some of the difficulties so that pharmacological agents that would not normally cross the BBB can be used for treatment. Drugs are delivered through one to several catheters placed stereotactically directly within the tumor mass or around the tumor or the resection cavity. Several classes of drugs are amenable to this technology including standard chemotherapeutics or novel experimental targeted drugs. The first Phase III trial for CED-delivered, molecularly targeted cytotoxin in the treatment of recurrent glioblastoma multiforme has been accomplished and demonstrated objective clinical efficacy. The lessons learned from more than a decade of attempts at exploiting CED for brain cancer treatment weigh critically for its future clinical applications. The main issues center around the type of catheters used, number of catheters and their exact placement; pharmacological formulation of drugs, prescreening patients undergoing treatment and monitoring the distribution of drugs in tumors and the tumor-infiltrated brain. It is expected that optimizing CED will make this technology a permanent addition to clinical management of brain malignancies. PMID:19831841

Drug-carrying microbubbles as a theranostic tool in convection-enhanced delivery for brain tumor therapy.

PubMed

Chen, Pin-Yuan; Yeh, Chih-Kuang; Hsu, Po-Hung; Lin, Chung-Yin; Huang, Chiung-Yin; Wei, Kuo-Chen; Liu, Hao-Li

2017-06-27

Convection-enhanced delivery (CED) is a promising technique for infusing a therapeutic agent through a catheter with a pressure gradient to create bulk flow for improving drug spread into the brain. So far, gadopentetate dimeglumine (Gd-DTPA) is the most commonly applied surrogate agent for predicting drug distribution through magnetic resonance imaging (MRI). However, Gd-DTPA provides only a short observation duration, and concurrent infusion provides an indirect measure of the exact drug distribution. In this study, we propose using microbubbles as a contrast agent for MRI monitoring, and evaluate their use as a drug-carrying vehicle to directly monitor the infused drug. Results show that microbubbles can provide excellent detectability through MRI relaxometry and accurately represent drug distribution during CED infusion. Compared with the short half-life of Gd-DTPA (1-2 hours), microbubbles allow an extended observation period of up to 12 hours. Moreover, microbubbles provide a sufficiently high drug payload, and glioma mice that underwent a CED infusion of microbubbles carrying doxorubicin presented considerable tumor growth suppression and a significantly improved survival rate. This study recommends microbubbles as a new theranostic tool for CED procedures.

The CEBAF Element Database

DOE Office of Scientific and Technical Information (OSTI.GOV)

Theodore Larrieu, Christopher Slominski, Michele Joyce

2011-03-01

With the inauguration of the CEBAF Element Database (CED) in Fall 2010, Jefferson Lab computer scientists have taken a step toward the eventual goal of a model-driven accelerator. Once fully populated, the database will be the primary repository of information used for everything from generating lattice decks to booting control computers to building controls screens. A requirement influencing the CED design is that it provide access to not only present, but also future and past configurations of the accelerator. To accomplish this, an introspective database schema was designed that allows new elements, types, and properties to be defined on-the-fly withmore » no changes to table structure. Used in conjunction with Oracle Workspace Manager, it allows users to query data from any time in the database history with the same tools used to query the present configuration. Users can also check-out workspaces to use as staging areas for upcoming machine configurations. All Access to the CED is through a well-documented Application Programming Interface (API) that is translated automatically from original C++ source code into native libraries for scripting languages such as perl, php, and TCL making access to the CED easy and ubiquitous.« less

Periodic Application of Concurrent Error Detection in Processor Array Architectures. PhD. Thesis -

NASA Technical Reports Server (NTRS)

Chen, Paul Peichuan

1993-01-01

Processor arrays can provide an attractive architecture for some applications. Featuring modularity, regular interconnection and high parallelism, such arrays are well-suited for VLSI/WSI implementations, and applications with high computational requirements, such as real-time signal processing. Preserving the integrity of results can be of paramount importance for certain applications. In these cases, fault tolerance should be used to ensure reliable delivery of a system's service. One aspect of fault tolerance is the detection of errors caused by faults. Concurrent error detection (CED) techniques offer the advantage that transient and intermittent faults may be detected with greater probability than with off-line diagnostic tests. Applying time-redundant CED techniques can reduce hardware redundancy costs. However, most time-redundant CED techniques degrade a system's performance.

Development of a new Clinical Engineering Management Tool & Information System (CLE-MANTIS).

PubMed

Panousis, S G; Malataras, P; Patelodimou, C; Kolitsi, Z; Pallikarakis, N

1997-01-01

The evolution of the field of biomedical technology has led to the diffusion of an impressive number of medical devices into healthcare institutions. In this environment, Clinical Engineering Departments (CEDs) are expanding their role in healthcare technology management, by changing their structure and introducing quality systems in order to improve their services and monitor the outcomes. In the framework of the national project BIOTECHNET II, a software tool for the management of biomedical technology, named CLE-MANTIS, has been developed, with the aim to assist CEDs in their tasks. CLE-MANTIS functions include the upkeep of an inventory, the support and monitoring of scheduled maintenance, corrective maintenance, vigilance, equipment acquisition and replacement, service contract management and user training. The system offers clinical engineers the possibility to monitor and evaluate the quality and cost-effectiveness of their departments through the monitoring of quality and cost indicators. This paper presents the main features and functions of the system.

Nuclear Rocket Test Facility Decommissioning Including Controlled Explosive Demolition of a Neutron-Activated Shield Wall

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michael Kruzic

2007-09-01

Located in Area 25 of the Nevada Test Site, the Test Cell A Facility was used in the 1960s for the testing of nuclear rocket engines, as part of the Nuclear Rocket Development Program. The facility was decontaminated and decommissioned (D&D) in 2005 using the Streamlined Approach For Environmental Restoration (SAFER) process, under the Federal Facilities Agreement and Consent Order (FFACO). Utilities and process piping were verified void of contents, hazardous materials were removed, concrete with removable contamination decontaminated, large sections mechanically demolished, and the remaining five-foot, five-inch thick radiologically-activated reinforced concrete shield wall demolished using open-air controlled explosive demolitionmore » (CED). CED of the shield wall was closely monitored and resulted in no radiological exposure or atmospheric release.« less

Projected 2050 Model Simulations for the Chesapeake Bay ...

EPA Pesticide Factsheets

The Chesapeake Bay Program as has been tasked with assessing how changes in climate systems are expected to alter key variables and processes within the Watershed in concurrence with land use changes. EPA’s Office of Research and Development will be conducting historic and future, 2050, Weather Research and Forecast (WRF) metrological and Community Multiscale Air Quality (CMAQ) chemical transport model simulations to provide meteorological and nutrient deposition estimates for inclusion of the Chesapeake Bay Program’s assessment of how climate and land use change may impact water quality and ecosystem health. This presentation will present the timeline and research updates. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-support tools, and models to be applied to media-specific or receptor-specific problem areas. CED uses modeling-based approaches to characterize exposures, evaluate fate and transport, and support environmental diagnostics/forensics with input from multiple data sources. It also develops media- and receptor-specific models, process models, and decision support tools for use both within and outside of EPA.

A Data-Driven Framework for Incorporating New Tools for ...

EPA Pesticide Factsheets

This talk was given during the “Exposure-Based Toxicity Testing” session at the annual meeting of the International Society for Exposure Science. It provided an update on the state of the science and tools that may be employed in risk-based prioritization efforts. It outlined knowledge gained from the data provided using these high-throughput tools to assess chemical bioactivity and to predict chemical exposures and also identified future needs. It provided an opportunity to showcase ongoing research efforts within the National Exposure Research Laboratory and the National Center for Computational Toxicology within the Office of Research and Development to an international audience. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-support tools, and models to be applied to media-specific or receptor-specific problem areas. CED uses modeling-based approaches to characterize exposures, evaluate fate and transport, and support environmental diagnostics/forensics with input from multiple data sources. It also develops media- and receptor-specific models, process models, and decision support tools for use both within and outside of EPA.

A Five- Year CMAQ Model Performance for Wildfires and ...

EPA Pesticide Factsheets

Biomass burning has been identified as an important contributor to the degradation of air quality because of its impact on ozone and particulate matter. Two components of the biomass burning inventory, wildfires and prescribed fires are routinely estimated in the national emissions inventory. However, there is a large amount of uncertainty in the development of these emission inventory sectors. We have completed a 5 year set of CMAQ model simulations (2008-2012) in which we have simulated regional air quality with and without the wildfire and prescribed fire inventory. We will examine CMAQ model performance over regions with significant PM2.5 and Ozone contribution from prescribed fires and wildfires. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-support tools, and models to be applied to media-specific or receptor-specific problem areas. CED uses modeling-based approaches to characterize exposures, evaluate fate and transport, and support environmental diagnostics/forensics with input from multiple data sources. It also develops media- and receptor-specific models, process models, and decision support tools for use both within and outside of EPA.

Determination of Chromium(III), Chromium(VI), and Chromium(III) acetylacetonate in water by ion-exchange disk extraction/metal furnace atomic absorption spectrometry

NASA Astrophysics Data System (ADS)

Kamakura, Nao; Inui, Tetsuo; Kitano, Masaru; Nakamura, Toshihiro

A new method for the separate determination of Chromium(III) (Cr(III)), Chromium(VI) (Cr(VI)), and Cr(III) acetylacetonate (Cr(acac)3) in water was developed using a cation-exchange extraction disk (CED) and an anion-exchange extraction disk (AED) combined with metal furnace atomic absorption spectrometry (MFAAS). A 100-mL water sample was adjusted to pH 5.6 and passed through the CED placed on the AED. Cr(acac)3 and Cr(III) were adsorbed on the CED, and Cr(VI) was adsorbed on the AED. The adsorbed Cr(acac)3 was eluted with 50 mL of carbon tetrachloride, followed by the elution of Cr(III) with 50 mL of 3 mol L- 1 nitric acid. Cr(VI) was eluted with 50 mL of 3 mol L- 1 nitric acid. The chemical species of Cr eluted from the CED with carbon tetrachloride was identified as Cr(acac)3 using infrared spectroscopy. The eluate of Cr(acac)3 was diluted to 100 mL with carbon tetrachloride, and those of Cr(III) and Cr(VI) were diluted to 100 mL with deionized water. All of the solutions were subsequently analyzed by MFAAS. The calibration curve for the Cr(acac)3 aqueous solutions exhibited good linearity in the range of 0.1 to 1 ng. The detection limit of Cr, which corresponded to three times the standard deviation (n = 10) of the blank values, was 20 pg. The recovery test for Cr(III), Cr(VI), and Cr(acac)3 exhibited desirable results (96.0%-107%) when 5 μg of each species (50 μg L- 1) was added to 100 mL water samples (i.e., tap water, rainwater, and bottled drinking water). In a humic acid solution, Cr(acac)3 was quantitatively recovered (103%), but Cr(III) and Cr(VI) exhibited poor recoveries (i.e., 84.8% and 78.4%, respectively).

Cumulative radiation dose caused by radiologic studies in critically ill trauma patients.

PubMed

Kim, Patrick K; Gracias, Vicente H; Maidment, Andrew D A; O'Shea, Michael; Reilly, Patrick M; Schwab, C William

2004-09-01

Critically ill trauma patients undergo many radiologic studies, but the cumulative radiation dose is unknown. The purpose of this study was to estimate the cumulative effective dose (CED) of radiation resulting from radiologic studies in critically ill trauma patients. The study group was composed of trauma patients at an urban Level I trauma center with surgical intensive care unit length of stay (LOS) greater than 30 days. The radiology records were reviewed. A typical effective dose per study for each type of plain film radiograph, computed tomographic scan, fluoroscopic study, and nuclear medicine study was used to calculate CED. Forty-six patients met criteria. The mean surgical intensive care unit and hospital LOS were 42.7 +/- 14.0 and 59.5 +/- 28.5 days, respectively. The mean Injury Severity Score was 32.2 +/- 15.0. The mean number of studies per patient was 70.1 +/- 29.0 plain film radiographs, 7.8 +/- 4.1 computed tomographic scans, 2.5 +/- 2.6 fluoroscopic studies, and 0.065 +/- 0.33 nuclear medicine study. The mean CED was 106 +/- 59 mSv per patient (range, 11-289 mSv; median, 104 mSv). Among age, mechanism, Injury Severity Score, and LOS, there was no statistically significant predictor of high CED. The mean CED in the study group was 30 times higher than the average yearly radiation dose from all sources for individuals in the United States. The theoretical additional morbidity attributable to radiologic studies was 0.78%. From a radiobiologic perspective, risk-to-benefit ratios of radiologic studies are favorable, given the importance of medical information obtained. Current practice patterns regarding use of radiologic studies appear to be acceptable.

Infusion-line pressure as a real-time monitor of convection-enhanced delivery in pre-clinical models.

PubMed

Lam, Miu Fei; Foo, Stacy W L; Thomas, Meghan G; Lind, Christopher R P

2014-01-15

Acute convection-enhanced delivery (CED) is a neurosurgical delivery technique that allows for precise and uniform distribution of an infusate to a brain structure. It remains experimental due to difficulties in ensuring successful delivery. Real-time monitoring is able to provide immediate feedback on cannula placement, infusate distribution, and if the infusion is proceeding as planned or is failing due to reflux or catheter obstruction. Pressure gradient is the driving force behind CED, with the infusion pressure being directly proportional to the flow-rate. The aim of this study was to assess the feasibility of using infusion-line pressure profiling to distinguish in real-time between succeeding and failing CED infusions. To do so we delivered cresyl violet dye at 0.5, 1.0 and 2.0 μl/min via CED in vitro using 0.6% agarose gel and in vivo to the rat striatum. Infusions that failed in agarose gel models could only be differentiated late during the procedures. In the rat in vivo model, the infusion-line profiles of obstructed infusions were not distinctive from those of successful infusions. Intraoperative magnetic resonance imaging (MRI) is used for real-time visualisation of cannula placement and infusate distribution. Particularly for animal pre-clinical work, it would be advantageous to supplement MRI with a cheap, accessible technique to monitor infusions and provide a real-time measure of infusion success or failure. Infusion-line pressure monitoring was of limited value in identifying successful CED with small volume infusions, whilst its utility for large volume infusion remains unknown. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Convection-enhanced delivery of sorafenib and suppression of tumor progression in a murine model of brain melanoma through the inhibition of signal transducer and activator of transcription 3.

PubMed

Zou, Zhaoxia; Yin, Yufang; Lin, Jenny; Hsu, Li-Chen J; Brandon, Vanessa L; Yang, Fan; Jove, Richard; Jandial, Rahul; Li, Gang; Chen, Mike Y

2016-05-01

OBJECT Despite recent advances, metastatic melanoma remains a terminal disease, in which life-threatening brain metastasis occurs in approximately half of patients. Sorafenib is a multikinase inhibitor that induces apoptosis of melanoma cells in vitro. However, systemic administration has been ineffective because adequate tissue concentrations cannot be achieved. This study investigated if convection-enhanced delivery (CED) of sorafenib would enhance tumor control and survival via inhibition of the signal transducer and activator of transcription 3 (Stat3) pathway in a murine model of metastatic brain melanoma. METHODS Melanoma cells treated with sorafenib in vitro were examined for signaling and survival changes. The effect of sorafenib given by CED was assessed by bioluminescent imaging and animal survival. RESULTS The results showed that sorafenib induced cell death in the 4 established melanoma cell lines and in 1 primary cultured melanoma cell line. Sorafenib inhibited Stat3 phosphorylation in HTB65, WYC1, and B16 cells. Accordingly, sorafenib treatment also decreased expression of Mcl-1 mRNA in melanoma cell lines. Because sorafenib targets multiple pathways, the present study demonstrated the contribution of the Stat3 pathway by showing that mouse embryonic fibroblast (MEF) Stat3 +/+ cells were significantly more sensitive to sorafenib than MEF Stat3 -/- cells. In the murine model of melanoma brain metastasis used in this study, CED of sorafenib increased survival by 150% in the treatment group compared with animals receiving the vehicle control (p < 0.01). CED of sorafenib also significantly abrogated tumor growth. CONCLUSIONS The data from this study indicate that local delivery of sorafenib effectively controls brain melanoma. These findings validate further investigation of the use of CED to distribute molecularly targeted agents.

Mutagenesis and repair induced by the DNA advanced glycation end product N2-1-(carboxyethyl)-2'-deoxyguanosine in human cells.

PubMed

Tamae, Daniel; Lim, Punnajit; Wuenschell, Gerald E; Termini, John

2011-03-29

Glycation of biopolymers by glucose-derived α-oxo-aldehydes such as methylglyoxal (MG) is believed to play a major role in the complex pathologies associated with diabetes and metabolic disease. In contrast to the extensive literature detailing the formation and physiological consequences of protein glycation, there is little information about the corresponding phenomenon for DNA. To assess the potential contribution of DNA glycation to genetic instability, we prepared shuttle vectors containing defined levels of the DNA glycation adduct N(2)-(1-carboxyethyl)-2'-deoxyguanosine (CEdG) and transfected them into isogenic human fibroblasts that differed solely in the capacity to conduct nucleotide excision repair (NER). In the NER-compromised fibroblasts, the induced mutation frequencies increased up to 18-fold relative to background over a range of ∼10-1400 CEdG adducts/10(5) dG, whereas the same substrates transfected into NER-competent cells induced a response that was 5-fold over background at the highest adduct density. The positive linear correlation (R(2) = 0.998) of mutation frequency with increasing CEdG level in NER-defective cells suggested that NER was the primary if not exclusive mechanism for repair of this adduct in human fibroblasts. Consistent with predictions from biochemical studies using CEdG-substituted oligonucleotides, guanine transversions were the predominant mutation resulting from replication of MG-modified plasmids. At high CEdG levels, significant increases in the number of AT → GC transitions were observed exclusively in NER-competent cells (P < 0.0001). This suggested the involvement of an NER-dependent mutagenic process in response to critical levels of DNA damage, possibly mediated by error-prone Y-family polymerases.

The roles of DNA damage-dependent signals and MAPK cascades in tributyltin-induced germline apoptosis in Caenorhabditis elegans.

PubMed

Wang, Yun; Wang, Shunchang; Luo, Xun; Yang, Yanan; Jian, Fenglei; Wang, Xuemin; Xie, Lucheng

2014-08-01

The induction of apoptosis is recognized to be a major mechanism of tributyltin (TBT) toxicity. However, the underlying signaling pathways for TBT-induced apoptosis remain unclear. In this study, using the nematode Caenorhabditis elegans, we examined whether DNA damage response (DDR) pathway and mitogen-activated protein kinase (MAPK) signaling cascades are involved in TBT-induced germline apoptosis and cell cycle arrest. Our results demonstrated that exposing worms to TBT at the dose of 10nM for 6h significantly increased germline apoptosis in N2 strain. Germline apoptosis was absent in strains that carried ced-3 or ced-4 loss-of-function alleles, indicating that both caspase protein CED-3 and Apaf-1 protein CED-4 were required for TBT-induced apoptosis. TBT-induced apoptosis was blocked in the Bcl-2 gain-of-function strain ced-9(n1950), whereas TBT induced a minor increase in the BH3-only protein EGL-1 mutated strain egl-1(n1084n3082). Checkpoint proteins HUS-1 and CLK-2 exerted proapoptotic effects, and the null mutation of cep-1, the homologue of tumor suppressor gene p53, significantly inhibited TBT-induced apoptosis. Apoptosis in the loss-of-function strains of ERK, JNK and p38 MAPK signaling pathways were completely or mildly suppressed under TBT stress. These results were supported by the results of mRNA expression levels of corresponding genes. The present study indicated that TBT-induced apoptosis required the core apoptotic machinery, and that DDR genes and MAPK pathways played essential roles in signaling the processes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Benchmarking the ERG valve tip and MRI Interventions Smart Flow neurocatheter convection-enhanced delivery system's performance in a gel model of the brain: employing infusion protocols proposed for gene therapy for Parkinson's disease

NASA Astrophysics Data System (ADS)

Sillay, Karl; Schomberg, Dominic; Hinchman, Angelica; Kumbier, Lauren; Ross, Chris; Kubota, Ken; Brodsky, Ethan; Miranpuri, Gurwattan

2012-04-01

Convection-enhanced delivery (CED) is an advanced infusion technique used to deliver therapeutic agents into the brain. CED has shown promise in recent clinical trials. Independent verification of published parameters is warranted with benchmark testing of published parameters in applicable models such as gel phantoms, ex vivo tissue and in vivo non-human animal models to effectively inform planned and future clinical therapies. In the current study, specific performance characteristics of two CED infusion catheter systems, such as backflow, infusion cloud morphology, volume of distribution (mm3) versus the infused volume (mm3) (Vd/Vi) ratios, rate of infusion (µl min-1) and pressure (mmHg), were examined to ensure published performance standards for the ERG valve-tip (VT) catheter. We tested the hypothesis that the ERG VT catheter with an infusion protocol of a steady 1 µl min-1 functionality is comparable to the newly FDA approved MRI Interventions Smart Flow (SF) catheter with the UCSF infusion protocol in an agarose gel model. In the gel phantom models, no significant difference was found in performance parameters between the VT and SF catheter. We report, for the first time, such benchmark characteristics in CED between these two otherwise similar single-end port VT with stylet and end-port non-stylet infusion systems. Results of the current study in agarose gel models suggest that the performance of the VT catheter is comparable to the SF catheter and warrants further investigation as a tool in the armamentarium of CED techniques for eventual clinical use and application.

Caspase-8 Deficiency Presenting as Late-Onset Multi-Organ Lymphocytic Infiltration with Granulomas in two Adult Siblings.

PubMed

Niemela, Julie; Kuehn, Hye Sun; Kelly, Corin; Zhang, Mingchang; Davies, Joie; Melendez, Jose; Dreiling, Jennifer; Kleiner, David; Calvo, Katherine; Oliveira, João B; Rosenzweig, Sergio D

2015-05-01

Caspase-8 deficiency (CED) was originally described in 2002 in two pediatric patients presenting with clinical manifestations resembling autoimmune lymphoproliferative syndrome (ALPS) accompanied by infections, and T, B and NK cell defects. Since then, no new CED patients were published. Here we report two adult siblings (Pt1 and Pt2) presenting in their late thirties with pulmonary hypertension leading to lung transplant (Pt1), and a complex neurological disease leading to multiple cranial nerves palsies (Pt2) as their main manifestations. A thorough clinical and immunological evaluation was performed at the Primary Immunodeficiency Clinic at NIH, followed by whole exome sequencing. The patients had multiorgan lymphocytic infiltration and granulomas, as well as clinical signs of immune deficiency/ immune dysregulation. Both siblings carried homozygous mutations in CASP8, c.1096C > T, p.248R > W. This was the same mutation described on the previously published CED patients, to whom these new patients were likely distantly related. We report two new CED patients presenting during adulthood with life-threatening end-organ lymphocyte infiltrates affecting the lungs, liver, spleen, bone marrow and central nervous system. This phenotype broadens the clinical spectrum of manifestations associated with this disease and warrants the search of CASP8 mutations in other cohorts of patients.

Determinants of Cancer Early Detection Behaviors:Application of Protection Motivation Theory.

PubMed

Rahaei, Zohreh; Ghofranipour, Fazlollah; Morowatisharifabad, Mohammad Ali; Mohammadi, Eesa

2015-01-01

Cancer is account for 13% of all deaths around the world and is the third cause of mortality in Iran. More than one third of these cases are pre-ventable and about 33% are curable with early detection. The aim of this study was to determine the predictors of cancer early detection (CED) behaviors applying Protection Motivation Theory (PMT). In this cross-sectional study, cluster sampling method was employed to recruit 260 individuals of above 20 years old in Yazd, Iran and a researcher designed questionnaire was completed through interviews for each of the respondents. PMT theoretical variables and CED behaviors were the basis of data collection procedure. Participants acquired 64.47% of the protection motivation, 30.97% of the passive and 45.64% of the active behaviors‟ possible scores. Theory constructs predicted 19.8%, 15.6% and 9.6% of the variations for protection motivation, passive and active behavior respectively. Protection motivation was responsible for 3.6% of passive and 8% of active behaviors‟ variations. Considering the scarceness of CED behaviors and the applicability of PMT in predicting these behaviors, utilization of the PMT‟s constructs in any interventional programs to accelerate CED behaviors could be an alternate methodological choice in the cancer control initiatives.

Distribution of polymer nanoparticles by convection-enhanced delivery to brain tumors.

PubMed

Saucier-Sawyer, Jennifer K; Seo, Young-Eun; Gaudin, Alice; Quijano, Elias; Song, Eric; Sawyer, Andrew J; Deng, Yang; Huttner, Anita; Saltzman, W Mark

2016-06-28

Glioblastoma multiforme (GBM) is a fatal brain tumor characterized by infiltration beyond the margins of the main tumor mass and local recurrence after surgery. The blood-brain barrier (BBB) poses the most significant hurdle to brain tumor treatment. Convection-enhanced delivery (CED) allows for local administration of agents, overcoming the restrictions of the BBB. Recently, polymer nanoparticles have been demonstrated to penetrate readily through the healthy brain when delivered by CED, and size has been shown to be a critical factor for nanoparticle penetration. Because these brain-penetrating nanoparticles (BPNPs) have high potential for treatment of intracranial tumors since they offer the potential for cell targeting and controlled drug release after administration, here we investigated the intratumoral CED infusions of PLGA BPNPs in animals bearing either U87 or RG2 intracranial tumors. We demonstrate that the overall volume of distribution of these BPNPs was similar to that observed in healthy brains; however, the presence of tumors resulted in asymmetric and heterogeneous distribution patterns, with substantial leakage into the peritumoral tissue. Together, our results suggest that CED of BPNPs should be optimized by accounting for tumor geometry, in terms of location, size and presence of necrotic regions, to determine the ideal infusion site and parameters for individual tumors. Copyright © 2016 Elsevier B.V. All rights reserved.

ISO observations of the reflection nebula Ced 201: evolution of carbonaceous dust

NASA Astrophysics Data System (ADS)

Cesarsky, D.; Lequeux, J.; Ryter, C.; Gérin, M.

2000-02-01

We present spectrophotometric imaging mid-IR observations of the reflection nebula Ced 201. Ced 201 is a part of a molecular cloud illuminated by a B9.5V star moving through it at more than 12 km s-1. The spectra of Ced 201 give evidence for transformation of very small carbonaceous grains into the carriers of the Aromatic Infrared Bands (AIBs), due to the radiation field of the illuminating star and/or to shock waves created by its motion. These very small grains emit mainly very broad bands and a continuum. We suggest that they are present everywhere in the interstellar medium but can only be detected in the mid-IR under special circumstances such as those prevailing in this reflection nebula. The efficiency of energy conversion of stellar light into mid-infrared emission is 7.5% for both the very small grains and the AIB carriers, and the fraction of interstellar carbon locked in these emitters is approximately 15%. Based on observations at the Cal Tech submillimeter observatory (CSO) and with ISO, an ESA project with instruments funded by ESA member states (especially the PI countries: France, Germany, the Netherlands and the United Kingdom) and with the participation of ISAS and NASA.

Real-time imaging of perivascular transport of nanoparticles during convection-enhanced delivery in the rat cortex.

PubMed

Foley, Conor P; Nishimura, Nozomi; Neeves, Keith B; Schaffer, Chris B; Olbricht, William L

2012-02-01

Convection-enhanced delivery (CED) is a promising technique for administering large therapeutics that do not readily cross the blood brain barrier to neural tissue. It is of vital importance to understand how large drug constructs move through neural tissue during CED to optimize construct and delivery parameters so that drugs are concentrated in the targeted tissue, with minimal leakage outside the targeted zone. Experiments have shown that liposomes, viral vectors, high molecular weight tracers, and nanoparticles infused into neural tissue localize in the perivascular spaces of blood vessels within the brain parenchyma. In this work, we used two-photon excited fluorescence microscopy to monitor the real-time distribution of nanoparticles infused in the cortex of live, anesthetized rats via CED. Fluorescent nanoparticles of 24 and 100 nm nominal diameters were infused into rat cortex through microfluidic probes. We found that perivascular spaces provide a high permeability path for rapid convective transport of large nanoparticles through tissue, and that the effects of perivascular spaces on transport are more significant for larger particles that undergo hindered transport through the extracellular matrix. This suggests that the vascular topology of the target tissue volume must be considered when delivering large therapeutic constructs via CED.

Women and Community Economic Development--Changing Knowledge, Changing Practice: A Summary of Research Results. NALL Working Paper #12.

ERIC Educational Resources Information Center

Stratton, Mary; Levine, Barbara

A preliminary study explored how Canadian practitioners who are engaged in community economic development (CED) that includes or is specific to women gain new information relevant to their work and how they incorporate that new learning into their daily practice. Interview questions focused on sources of information, learning opportunities and…

Detecting points as developmental delay based on the life-history development and urosome deformity of the harpacticoid copepod, Tigriopus japonicus sensu lato, following exposure to benzo(a)pyrene.

PubMed

Bang, Hyun Woo; Lee, Wonchoel; Kwak, Inn-Sil

2009-09-01

To identify ecotoxicological responses to an endocrine disrupter, benzo(a)pyrene, we examined the life-history of the harpacticoid copepod, Tigriopus japonicus sensu lato. Based on the life-history of copepods, survival rate of nauplii (NSR) and copepodites (CSR), copepodite emergence day (CED) and adult male emergence day (AMED), sex ratio (MER), brooding success rate (BSR), and first brooding day of adult females (FBD) were measured. Significant differences were observed in the survival and development of nauplii (NSR and CED) and sex ratio (MER) of exposed and non-exposed copepods. Moreover, high concentration of BaP can be lethal to copepodite and exhibited a delay of growth. In this study, the CED and AMED among ecotoxicological response based on life-history developments were delayed and the body characteristics decreased in response to exposure to benzo(a)pyrene. The dwarfism and urosome deformity of the T. japonicus s.l. was exhibited in response to chemical exposure. Specifically, the body characteristics and biomass of dwarf copepods that had been exposed to benzo(a)pyrene were 30% and 50% lower than the control group, respectively. The incidence of abnormal urosomes was divided into two types. The first deformity type was signs of shrinkage in the middle of the urosome or the entire urosome was narrower than those of the control organisms. In the second type, the anal somite and the distal side of the urosome had abnormally swelled. Taken together, the nauplii and copepodid development of T. japonicus s.l. can be used as a useful biomaker for detecting developmental delay based on their entire life-history. In addition, the urosome deformity was used a good potential monitoring tool invading various chemicals and environmental contamination into water system.

Convection-Enhanced Delivery of Carboplatin PLGA Nanoparticles for the Treatment of Glioblastoma.

PubMed

Arshad, Azeem; Yang, Bin; Bienemann, Alison S; Barua, Neil U; Wyatt, Marcella J; Woolley, Max; Johnson, Dave E; Edler, Karen J; Gill, Steven S

2015-01-01

We currently use Convection-Enhanced Delivery (CED) of the platinum-based drug, carboplatin as a novel treatment strategy for high grade glioblastoma in adults and children. Although initial results show promise, carboplatin is not specifically toxic to tumour cells and has been associated with neurotoxicity at high infused concentrations in pre-clinical studies. Our treatment strategy requires intermittent infusions due to rapid clearance of carboplatin from the brain. In this study, carboplatin was encapsulated in lactic acid-glycolic acid copolymer (PLGA) to develop a novel drug delivery system. Neuronal and tumour cytotoxicity were assessed in primary neuronal and glioblastoma cell cultures. Distribution, tissue clearance and toxicity of carboplatin nanoparticles following CED was assessed in rat and porcine models. Carboplatin nanoparticles conferred greater tumour cytotoxicity, reduced neuronal toxicity and prolonged tissue half-life. In conclusion, this drug delivery system has the potential to improve the prognosis for patients with glioblastomas.

Convection-Enhanced Delivery of Carboplatin PLGA Nanoparticles for the Treatment of Glioblastoma

PubMed Central

Arshad, Azeem; Yang, Bin; Bienemann, Alison S.; Barua, Neil U.; Wyatt, Marcella J.; Woolley, Max; Johnson, Dave E.; Edler, Karen J.; Gill, Steven S.

2015-01-01

We currently use Convection-Enhanced Delivery (CED) of the platinum-based drug, carboplatin as a novel treatment strategy for high grade glioblastoma in adults and children. Although initial results show promise, carboplatin is not specifically toxic to tumour cells and has been associated with neurotoxicity at high infused concentrations in pre-clinical studies. Our treatment strategy requires intermittent infusions due to rapid clearance of carboplatin from the brain. In this study, carboplatin was encapsulated in lactic acid-glycolic acid copolymer (PLGA) to develop a novel drug delivery system. Neuronal and tumour cytotoxicity were assessed in primary neuronal and glioblastoma cell cultures. Distribution, tissue clearance and toxicity of carboplatin nanoparticles following CED was assessed in rat and porcine models. Carboplatin nanoparticles conferred greater tumour cytotoxicity, reduced neuronal toxicity and prolonged tissue half-life. In conclusion, this drug delivery system has the potential to improve the prognosis for patients with glioblastomas. PMID:26186224

Current status of intratumoral therapy for glioblastoma.

PubMed

Mehta, Ankit I; Linninger, Andreas; Lesniak, Maciej S; Engelhard, Herbert H

2015-10-01

With emerging drug delivery technologies becoming accessible, more options are expected to become available to patients with glioblastoma (GBM) in the near future. It is important for clinicians to be familiar with the underlying mechanisms and limitations of intratumoral drug delivery, and direction of recent research efforts. Tumor-adjacent brain is an extremely complex living matrix that creates challenges with normal tissue intertwining with tumor cells. For convection-enhanced delivery (CED), the role of tissue anisotropy for better predicting the biodistribution of the infusate has recently been studied. Computational predictive methods are now available to better plan CED therapy. Catheter design and placement—in addition to the agent being used—are critical components of any protocol. This paper overviews intratumoral therapies for GBM, highlighting key anatomic and physiologic perspectives, selected agents (especially immunotoxins), and some new developments such as the description of the glymphatic system.

The regulation of cognitive enhancement devices: extending the medical model

PubMed Central

Maslen, Hannah; Douglas, Thomas; Cohen Kadosh, Roi; Levy, Neil; Savulescu, Julian

2014-01-01

This article presents a model for regulating cognitive enhancement devices (CEDs). Recently, it has become very easy for individuals to purchase devices which directly modulate brain function. For example, transcranial direct current stimulators are increasingly being produced and marketed online as devices for cognitive enhancement. Despite posing risks in a similar way to medical devices, devices that do not make any therapeutic claims do not have to meet anything more than basic product safety standards. We present the case for extending existing medical device legislation to cover CEDs. Medical devices and CEDs operate by the same or similar mechanisms and pose the same or similar risks. This fact coupled with the arbitrariness of the line between treatment and enhancement count in favour of regulating these devices in the same way. In arguing for this regulatory model, the paper highlights potential challenges to its implementation, and suggests solutions. PMID:25243073

Ramped-rate vs continuous-rate infusions: An in vitro comparison of convection enhanced delivery protocols.

PubMed

Schomberg, Dominic; Wang, Anyi; Marshall, Hope; Miranpuri, Gurwattan; Sillay, Karl

2013-04-01

Convection enhanced delivery (CED) is a technique using infusion convection currents to deliver therapeutic agents into targeted regions of the brain. Recently, CED is gaining significant acceptance for use in gene therapy of Parkinson's disease (PD) employing direct infusion into the brain. CED offers advantages in that it targets local areas of the brain, bypasses the blood-brain barrier (BBB), minimizes systemic toxicity of the therapeutics, and allows for delivery of larger molecules that diffusion driven methods cannot achieve. Investigating infusion characteristics such as backflow and morphology is important in developing standard and effective protocols in order to successfully deliver treatments into the brain. Optimizing clinical infusion protocols may reduce backflow, improve final infusion cloud morphology, and maximize infusate penetrance into targeted tissue. The purpose of the current study was to compare metrics during ramped-rate and continuous-rate infusions using two different catheters in order to optimize current infusion protocols. Occasionally, the infusate refluxes proximally up the catheter tip, known as backflow, and minimizing this can potentially reduce undesirable effects in the clinical setting. Traditionally, infusions are performed at a constant rate throughout the entire duration, and backflow is minimized only by slow infusion rates, which increases the time required to deliver the desired amount of infusate. In this study, we investigate the effects of ramping and various infusion rates on backflow and infusion cloud morphology. The independent parameters in the study are: ramping, maximum infusion rate, time between rate changes, and increments of rate changes. Backflow was measured using two methods: i) at the point of pressure stabilization within the catheter, and ii) maximum backflow as shown by video data. Infusion cloud morphology was evaluated based on the height-to-width ratio of each infusion cloud at the end of each experiment. Results were tabulated and statistically analyzed to identify any significant differences between protocols. The experimental results show that CED rampedrate infusion protocols result in smaller backflow distances and more spherical cloud morphologies compared to continuous-rate infusion protocols ending at the same maximum infusion rate. Our results also suggest internal-line pressure measurements can approximate the time-point at which backflow ceases. Our findings indicate that ramping CED infusion protocols can potentially minimize backflow and produce more spherical infusion clouds. However, further research is required to determine the strength of this correlation, especially in relation to maximum infusion rates.

Convection enhanced delivery of boronated EGF as a molecular targeting agent for neutron capture therapy of brain tumors

PubMed Central

Yang, Weilian; Wu, Gong; Huo, Tianyao; Tjarks, Werner; Ciesielski, Michael; Fenstermaker, Robert A.; Ross, Brain D.; Wikstrand, Carol J.; Riley, Kent J.; Binns, Peter J.

2010-01-01

In the present study, we have evaluated a boronated dendrimer-epidermal growth factor (BD-EGF) bioconjugate as a molecular targeting agent for boron neutron capture therapy (BNCT) of the human EGFR gene-transfected F98 rat glioma, designated F98EGFR. EGF was chemically linked to a heavily boronated polyamidoamine dendrimer (BD) by means of the heterobifunctional reagent, mMBS. Biodistribution studies were carried out at 6 h and 24 h following intratumoral (i.t.) injection or intracerebral (i.c.) convection enhanced delivery (CED) of 125I-labeled or unlabeled BD-EGF (40 μg 10B/10 μg EGF) to F98 glioma bearing rats. At 24 h. there was 43% more radioactivity in EGFR(+) tumors following CED compared to i.t. injection, and a doubling of the tumor boron concentration (22.3 μg/g vs. 11.7 μg/g). CED of BD-EGF resulted in a 7.2× increase in the volume of distribution within the infused cerebral hemisphere and a 1.9× increase in tumor uptake of BD-EGF compared with i.t. injection. Based on these favorable bio-distribution data, BNCT was carried out at the Massachusetts Institute of Technology nuclear reactor 14 days following i.c. tumor implantation and 24 h. after CED of BD-EGF. These animals had a MST of 54.1 ± 4.7 days compared to 43.0 ± 2.8 days following i.t. injection. Rats that received BD-EGF by CED in combination with i.v. boronophenylalanine (BPA), which has been used in both experimental and clinical studies, had a MST of 86.0 ± 28.1 days compared to 39.8 ± 1.6 days for i.v. BPA alone (P < 0.01), 30.9 ± 1.4 days for irradiated controls and 25.1 ± 1.0 days for untreated controls (overall P < 0.0001). These data have demonstrated that the efficacy of BNCT was significantly increased (P < 0.006), following i.c CED of BD-EGF compared to i.t injection, and that the survival data were equivalent to those previously reported by us using the boronated anti-human-EGF mAb, C225 (cetuximab). PMID:19588228

Preclinical evaluation of convection-enhanced delivery of liposomal doxorubicin to treat pediatric diffuse intrinsic pontine glioma and thalamic high-grade glioma.

PubMed

Sewing, A Charlotte P; Lagerweij, Tonny; van Vuurden, Dannis G; Meel, Michaël H; Veringa, Susanna J E; Carcaboso, Angel M; Gaillard, Pieter J; Peter Vandertop, W; Wesseling, Pieter; Noske, David; Kaspers, Gertjan J L; Hulleman, Esther

2017-05-01

OBJECTIVE Pediatric high-grade gliomas (pHGGs) including diffuse intrinsic pontine gliomas (DIPGs) are primary brain tumors with high mortality and morbidity. Because of their poor brain penetrance, systemic chemotherapy regimens have failed to deliver satisfactory results; however, convection-enhanced delivery (CED) may be an alternative mode of drug delivery. Anthracyclines are potent chemotherapeutics that have been successfully delivered via CED in preclinical supratentorial glioma models. This study aims to assess the potency of anthracyclines against DIPG and pHGG cell lines in vitro and to evaluate the efficacy of CED with anthracyclines in orthotopic pontine and thalamic tumor models. METHODS The sensitivity of primary pHGG cell lines to a range of anthracyclines was tested in vitro. Preclinical CED of free doxorubicin and pegylated liposomal doxorubicin (PLD) to the brainstem and thalamus of naïve nude mice was performed. The maximum tolerated dose (MTD) was determined based on the observation of clinical symptoms, and brains were analyzed after H & E staining. Efficacy of the MTD was tested in adult glioma E98-FM-DIPG and E98-FM-thalamus models and in the HSJD-DIPG-007-Fluc primary DIPG model. RESULTS Both pHGG and DIPG cells were sensitive to anthracyclines in vitro. Doxorubicin was selected for further preclinical evaluation. Convection-enhanced delivery of the MTD of free doxorubicin and PLD in the pons was 0.02 mg/ml, and the dose tolerated in the thalamus was 10 times higher (0.2 mg/ml). Free doxorubicin or PLD via CED was ineffective against E98-FM-DIPG or HSJD-DIPG-007-Fluc in the brainstem; however, when applied in the thalamus, 0.2 mg/ml of PLD slowed down tumor growth and increased survival in a subset of animals with small tumors. CONCLUSIONS Local delivery of doxorubicin to the brainstem causes severe toxicity, even at doxorubicin concentrations that are safe in the thalamus. As a consequence, the authors could not establish a therapeutic window for treating orthotopic brainstem tumors in mice. For tumors in the thalamus, therapeutic concentrations to slow down tumor growth could be reached. These data suggest that anatomical location determines the severity of toxicity after local delivery of therapeutic agents and that caution should be used when translating data from supratentorial CED studies to treat infratentorial tumors.

Next-generation concurrent engineering: developing models to complement point designs

NASA Technical Reports Server (NTRS)

Morse, Elizabeth; Leavens, Tracy; Cohanim, Barbak; Harmon, Corey; Mahr, Eric; Lewis, Brian

2006-01-01

Concurrent Engineering Design teams have made routine the rapid development of point designs for space missions. The Jet Propulsion Laboratory's Team X is now evolving into a next generation CED; nin addition to a point design, the team develops a model of the local trade space. The process is a balance between the power of model-developing tools and the creativity of human experts, enabling the development of a variety of trade models for any space mission.

America's Basic Research: Prosperity Through Discovery. A Policy Statement by the Research and Policy Committee of the Committee for Economic Development

ERIC Educational Resources Information Center

Committee for Economic Development, 1998

1998-01-01

This policy statement looks at America's basic research enterprise and lays out the processes and systematic reforms needed to meet emerging risks to the outcomes from investments in basic research. The Committee for Economic Development (CED) undertook this project in the belief that significant progress with many of society's problems and new…

Expression of animal anti-apoptotic gene Ced-9 enhances tolerance during Glycine max L.-Bradyrhizobium japonicum interaction under saline stress but reduces nodule formation.

PubMed

Robert, Germán; Muñoz, Nacira; Melchiorre, Mariana; Sánchez, Federico; Lascano, Ramiro

2014-01-01

The mechanisms by which the expression of animal cell death suppressors in economically important plants conferred enhanced stress tolerance are not fully understood. In the present work, the effect of expression of animal antiapoptotic gene Ced-9 in soybean hairy roots was evaluated under root hairs and hairy roots death-inducing stress conditions given by i) Bradyrhizobium japonicum inoculation in presence of 50 mM NaCl, and ii) severe salt stress (150 mM NaCl), for 30 min and 3 h, respectively. We have determined that root hairs death induced by inoculation in presence of 50 mM NaCl showed characteristics of ordered process, with increased ROS generation, MDA and ATP levels, whereas the cell death induced by 150 mM NaCl treatment showed non-ordered or necrotic-like characteristics. The expression of Ced-9 inhibited or at least delayed root hairs death under these treatments. Hairy roots expressing Ced-9 had better homeostasis maintenance, preventing potassium release; increasing the ATP levels and controlling the oxidative damage avoiding the increase of reactive oxygen species production. Even when our results demonstrate a positive effect of animal cell death suppressors in plant cell ionic and redox homeostasis under cell death-inducing conditions, its expression, contrary to expectations, drastically inhibited nodule formation even under control conditions.

The Plant Cuticle Is Required for Osmotic Stress Regulation of Abscisic Acid Biosynthesis and Osmotic Stress Tolerance in Arabidopsis[W

PubMed Central

Wang, Zhen-Yu; Xiong, Liming; Li, Wenbo; Zhu, Jian-Kang; Zhu, Jianhua

2011-01-01

Osmotic stress activates the biosynthesis of abscisic acid (ABA). One major step in ABA biosynthesis is the carotenoid cleavage catalyzed by a 9-cis epoxycarotenoid dioxygenase (NCED). To understand the mechanism for osmotic stress activation of ABA biosynthesis, we screened for Arabidopsis thaliana mutants that failed to induce the NCED3 gene expression in response to osmotic stress treatments. The ced1 (for 9-cis epoxycarotenoid dioxygenase defective 1) mutant isolated in this study showed markedly reduced expression of NCED3 in response to osmotic stress (polyethylene glycol) treatments compared with the wild type. Other ABA biosynthesis genes are also greatly reduced in ced1 under osmotic stress. ced1 mutant plants are very sensitive to even mild osmotic stress. Map-based cloning revealed unexpectedly that CED1 encodes a putative α/β hydrolase domain-containing protein and is allelic to the BODYGUARD gene that was recently shown to be essential for cuticle biogenesis. Further studies discovered that other cutin biosynthesis mutants are also impaired in osmotic stress induction of ABA biosynthesis genes and are sensitive to osmotic stress. Our work demonstrates that the cuticle functions not merely as a physical barrier to minimize water loss but also mediates osmotic stress signaling and tolerance by regulating ABA biosynthesis and signaling. PMID:21610183

The mammalian Ced-1 ortholog MEGF10/KIAA1780 displays a novel adhesion pattern

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Emiko; Nakayama, Manabu

2007-07-01

Ced-1 protein is a Caenorhabditis elegans cell surface receptor involved in phagocytosis of dead cells. The gene encoding the mammalian ortholog of Ced-1 is yet to be identified. Here, we describe a potential candidate: human MEGF10. MEGF10 has the overall domain organization of Ced-1, containing a signal peptide, a EMI domain, 17 atypical EGF-like repeats, a transmembrane domain, and a cytoplasmic domain with NPXY and YXXL motifs. MEGF10-EGFP fusion protein expressed in HEK293 cells produced an irregular, mosaic-like pattern on the surface of coated glass. Protruded MEGF10 bound tightly to the glass, in effect 'pinning' the cytoplasmic membrane firmly ontomore » the glass, thereby restricting cell motility. These cells also took on a flat appearance. Although MEGF10-EGFP localized throughout the cytoplasmic membrane, no MEGF10-EGFP was found in lamellipodia. The MEGF10-EGFP signal was surrounded by a 1-2-{mu}m-wide dark strip lacking EGFP. Expression analyses of various MEGF10 deletion mutants revealed that the irregular, mosaic-like adhesion pattern characteristic of MEGF10 family members is due to concerted interactions between the EMI and 17 atypical EGF-like domains. Co-culturing of MEGF10-EGFP-expressing cells with apoptotic cells revealed that MEGF10 protein accumulated around the contact region during engulfment of apoptotic cells.« less

Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease.

PubMed

Croese, John; Giacomin, Paul; Navarro, Severine; Clouston, Andrew; McCann, Leisa; Dougall, Annette; Ferreira, Ivana; Susianto, Atik; O'Rourke, Peter; Howlett, Mariko; McCarthy, James; Engwerda, Christian; Jones, Dianne; Loukas, Alex

2015-02-01

Celiac disease (CeD) is a common gluten-sensitive autoimmune enteropathy. A gluten-free diet is an effective treatment, but compliance is demanding; hence, new treatment strategies for CeD are required. Parasitic helminths hold promise for treating inflammatory disorders, so we examined the influence of experimental hookworm infection on the predicted outcomes of escalating gluten challenges in CeD subjects. A 52-week study was conducted involving 12 adults with diet-managed CeD. Subjects were inoculated with 20 Necator americanus larvae, and escalating gluten challenges consumed as pasta were subsequently administered: (1) 10 to 50 mg for 12 weeks (microchallenge); (2) 25 mg daily + 1 g twice weekly for 12 weeks (GC-1g); and (3) 3 g daily (60-75 straws of spaghetti) for 2 weeks (GC-3g). Symptomatic, serologic, and histological outcomes evaluated gluten toxicity. Regulatory and inflammatory T cell populations in blood and mucosa were examined. Two gluten-intolerant subjects were withdrawn after microchallenge. Ten completed GC-1g, 8 of whom enrolled in and completed GC-3g. median villous height-to-crypt depth ratios (2.60-2.63; P = .98) did not decrease as predicted after GC-1g, and the mean IgA-tissue transglutaminase titers declined, contrary to the predicted rise after GC-3g. quality of life scores improved (46.3-40.6; P = .05); celiac symptom indices (24.3-24.3; P = .53), intra-epithelial lymphocyte percentages (32.5-35.0; P = .47), and Marsh scores were unchanged by gluten challenge. Intestinal T cells expressing IFNγ were reduced following hookworm infection (23.9%-11.5%; P = .04), with corresponding increases in CD4(+) Foxp3(+) regulatory T cells (0.19%-1.12%; P = .001). Necator americanus and gluten microchallenge promoted tolerance and stabilized or improved all tested indices of gluten toxicity in CeD subjects. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Intrinsic and scattering attenuation of high-frequency S-waves in the central part of the External Dinarides

NASA Astrophysics Data System (ADS)

Majstorović, Josipa; Belinić, Tena; Namjesnik, Dalija; Dasović, Iva; Herak, Davorka; Herak, Marijan

2017-09-01

The central part of the External Dinarides (CED) is a geologically and tectonically complex region formed in the collision between the Adriatic microplate and the European plate. In this study, the contributions of intrinsic and scattering attenuation ( Q i - 1 and Q sc - 1 , respectively) to the total S-wave attenuation were calculated for the first time. The multiple lapse-time window analysis (MLTWA method), based on the assumptions of multiple isotropic scattering in a homogeneous medium with uniformly distributed scatterers, was applied to seismograms of 450 earthquakes recorded at six seismic stations. Selected events have hypocentral distances between 40 and 90 km with local magnitudes between 1.5 and 4.7. The analysis was performed over 11 frequency bands with central frequencies between 1.5 and 16 Hz. Results show that the seismic albedo of the studied area is less than 0.5 and Q i - 1 > Q sc - 1 at all central frequencies and for all stations. These imply that the intrinsic attenuation dominates over scattering attenuation in the whole study area. Calculated total S-wave and expected coda wave attenuation for CED are in a very good agreement with the ones measured in previous studies using the coda normalization and the coda-Q methods. All estimated attenuation factors decrease with increasing frequency. The intrinsic attenuation for CED is among the highest observed elsewhere, which could be due to the highly fractured and fluid-filled carbonates in the upper crust. The scattering and the total S-wave attenuation for CED are close to the average values obtained in other studies performed worldwide. In particular, good agreement of frequency dependence of total attenuation in CED and in the regions that contributed most strong-motion records for ground motion prediction equations used in PSHA in Croatia indicates that those were well chosen and applicable to this area as far as their attenuation properties are concerned.

Prolonged Attenuation of Amygdala-Kindled Seizure Measures in Rats by Convection-Enhanced Delivery of the N-Type Calcium Channel Antagonists ω-Conotoxin GVIA and ω-Conotoxin MVIIA

PubMed Central

Gasior, Maciej; White, Natalie A.; Rogawski, Michael A.

2008-01-01

Convection-enhanced delivery (CED) permits the homogeneous distribution of therapeutic agents throughout localized regions of the brain parenchyma without causing tissue damage as occurs with bolus injection. Here, we examined whether CED infusion of the N-type calcium channel antagonists ω-conotoxin GVIA (ω-CTX-G) and ω-conotoxin MVIIA (ω-CTX-M) can attenuate kindling measures in fully amygdala-kindled rats. Rats were implanted with a combination infusion cannula-stimulating electrode assembly into the right basolateral amygdala. Fully kindled animals received infusions of vehicle, ω-CTX-G (0.005, 0.05, and 0.5 nmol), ω-CTX-M (0.05, 0.15, and 0.5 nmol), proteolytically inactivated ω-CTX-M (0.5 nmol), or carbamazepine (500 nmol) into the stimulation site. CED of ω-CTX-G and ω-CTX-M over a 20-min period resulted in a dose-dependent increase in the afterdischarge threshold and a decrease in the afterdischarge duration and behavioral seizure score and duration during a period of 20 min to 1 week after the infusion, indicating an inhibitory effect on the triggering and expression of kindled seizures. The protective effects of ω-conotoxins reached a maximum at 48 h postinfusion, and then they gradually resolved over the next 5 days. In contrast, carbamazepine was active at 20 min but not at 24 h after the infusion, whereas CED of vehicle or inactivated ω-CTX-M had no effect. Except for transient tremor in some rats receiving the highest toxin doses, no adverse effects were observed. These results indicate that local CED of high-molecular-weight presynaptic N-type calcium channel blockers can produce long-lasting inhibition of brain excitability and that they may provide prolonged seizure protection in focal seizure disorders. PMID:17717191

Convection-enhanced delivery of an anti-miR is well-tolerated, preserves anti-miR stability and causes efficient target de-repression: a proof of concept.

PubMed

Halle, Bo; Marcusson, Eric G; Aaberg-Jessen, Charlotte; Jensen, Stine S; Meyer, Morten; Schulz, Mette K; Andersen, Claus; Kristensen, Bjarne W

2016-01-01

Over-expressed microRNAs (miRs) are promising new targets in glioblastoma (GBM) therapy. Inhibition of over-expressed miRs has been shown to diminish GBM proliferation, invasion and angiogenesis, indicating a significant therapeutic potential. However, the methods utilized for miR inhibition have had low translational potential. In clinical trials convection-enhanced delivery (CED) has been applied for local delivery of compounds in the brain. The aim of this study was to determine if safe and efficient miR inhibition was possible by CED of an anti-miR. We used a highly invasive GBM orthotopic xenograft model and targeted a well-validated miR, let-7a, with a 2'-O-methoxyethyl anti-miR with a combined phosphodiester/phosphorothioate backbone to establish an initial proof of concept. In vitro, anti-let-7a was delivered unassisted to the patient-derived T87 glioblastoma spheroid culture. In vivo, anti-let-7a or saline were administered by CED into orthotopic T87-derived tumors. After 1 month of infusion, tumors were removed and tumor mRNA levels of the target-gene High-mobility group AT-hook 2 (HMGA2) were determined. In vitro, 5 days inhibition was superior to 1 day at de-repressing the let-7a target HMGA2 and the inhibition was stable for 24 h. In vivo, anti-miR integrity was preserved in the pumps and no animals showed signs of severe adverse effects attributable to the anti-miR treatment. HMGA2 tumor level was significantly de-repressed in the anti-miR treated animals. The results showed-as an initial proof of concept-that miRs can be efficiently inhibited using CED delivery of anti-miR. The next step is to apply CED for anti-miR delivery focusing on key oncogenic miRs.

Combined prevalence of inherited skeletal disorders in dog breeds in Belgium.

PubMed

Coopman, F; Broeckx, B; Verelst, E; Deforce, D; Saunders, J; Duchateau, L; Verhoeven, G

2014-01-01

Canine hip dysplasia (CHD), canine elbow dysplasia (CED), and humeral head osteochondrosis (HHOC) are inherited traits with uneven incidence in dog breeds. Knowledge of the combined prevalence of these three disorders is necessary to estimate the effect of the currently applied breeding strategies, in order to improve the genetic health of the population. Official screening results of the Belgian National Committee for Inherited Skeletal Disorders (NCSID) revealed that an average of 31.8% (CHD, CED, or both; n = 1273 dogs) and 47.2% (CHD, CED, HHOC, or a combination of these three diseases; n = 250 dogs) of dogs are mildly to severely affected by at least one skeletal disorder. According to the current breeding recommendations in some dog breeds in Belgium, these animals should be restricted (mild signs) or excluded (moderate to severe signs) from breeding. The introduction of genetic parameters, such as estimated breeding values, might create a better approach to gradually reduce the incidence of these complex inherited joint disorders, without compromising genetic population health.

IER-297 CED-2: Final Design for Thermal/Epithermal eXperiments with Jemima Plates with Polyethylene and Hafnium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, A. J.; Percher, C. M.; Zywiec, W. J.

This report presents the final design (CED-2) for IER-297, and focuses on 15 critical configurations using highly enriched uranium (HEU) Jemima plates moderated by polyethylene with and without hafnium diluent. The goal of the U.S. Nuclear Criticality Safety Program’s Thermal/Epithermal eXperiments (TEX) is to design and conduct new critical experiments to address high priority nuclear data needs from the nuclear criticality safety and nuclear data communities, with special emphasis on intermediate energy (0.625 eV – 100 keV) assemblies that can be easily modified to include various high priority diluent materials. The TEX (IER 184) CED-1 Report [1], completed in 2012,more » demonstrated the feasibility of meeting the TEX goals with two existing NCSP fissile assets, plutonium Zero Power Physics Reactor (ZPPR) plates and highly enriched uranium (HEU) Jemima plates. The first set of TEX experiments will focus on using the plutonium ZPPR plates with polyethylene moderator and tantalum diluents.« less

Design and Implementation of the CEBAF Element Database

DOE Office of Scientific and Technical Information (OSTI.GOV)

Theodore Larrieu, Christopher Slominski, Michele Joyce

2011-10-01

With inauguration of the CEBAF Element Database (CED) in Fall 2010, Jefferson Lab computer scientists have taken a first step toward the eventual goal of a model-driven accelerator. Once fully populated, the database will be the primary repository of information used for everything from generating lattice decks to booting front-end computers to building controls screens. A particular requirement influencing the CED design is that it must provide consistent access to not only present, but also future, and eventually past, configurations of the CEBAF accelerator. To accomplish this, an introspective database schema was designed that allows new elements, element types, andmore » element properties to be defined on-the-fly without changing table structure. When used in conjunction with the Oracle Workspace Manager, it allows users to seamlessly query data from any time in the database history with the exact same tools as they use for querying the present configuration. Users can also check-out workspaces and use them as staging areas for upcoming machine configurations. All Access to the CED is through a well-documented API that is translated automatically from original C++ into native libraries for script languages such as perl, php, and TCL making access to the CED easy and ubiquitous. Notice: Authored by Jefferson Science Associates, LLC under U.S. DOE Contract No. DE-AC05-06OR23177. The U.S. Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce this manuscript for U.S. Government purposes.« less

Induction of cap-independent BiP (hsp-3) and Bcl-2 (ced-9) translation in response to eIF4G (IFG-1) depletion in C. elegans

PubMed Central

Morrison, J Kaitlin; Friday, Andrew J; Henderson, Melissa A; Hao, Enhui; Keiper, Brett D

2014-01-01

During apoptosis, activated caspases cleave the translation initiation factor eIF4G. This cleavage disrupts cap-dependent mRNA translation initiation within the cell. However, a specific subset of mRNAs can still be recruited for protein synthesis in a cap-independent manner by the residual initiation machinery. Many of these mRNAs, including cell death related mRNAs, contain internal ribosome entry sites (IRESes) that promote their enhanced translation during apoptosis. Still other mRNAs have little dependence on the cap recognition mechanism. The expression of the encoded proteins, both anti- and pro-apoptotic, allows for an initial period of attempted cell survival, then commitment to cell death when damage is extensive. In this study we address the translational regulation of the stress and apoptosis-related mRNAs in C. elegans: BiP (hsp-3) (hsp-4), Hif-1 (hif-1), p53 (cep-1), Bcl-2 (ced-9) and Apaf-1 (ced-4). Altered translational efficiency of these messages was observed upon depletion of cap-dependent translation and induction of apoptosis within the C. elegans gonad. Our findings suggest a physiological link between the cap-independent mechanism and the enhanced translation of hsp-3 and ced-9. This increase in the efficiency of translation may be integral to the stress response during the induction of physiological apoptosis. PMID:26779406

Deficiency and sources of nutrition among an Indian tribal population.

PubMed

Ghosh, Sudipta

2014-09-01

This paper is an attempt to explore the relationship between protein consumption and BMI for the adult Santhals, a tribal community of West Bengal, India. For this purpose, a cross sectional sample of 1262 adult Santhals were mea- sured. A high incidence (46.9%) of chronic energy deficiency (CED) is observed. A low production of protein rich food items such as pulses, poultry and fishing within their own economy reveal that the barter system fails to provide enough protein rich food items for the community. Along with this, low income earning opportunities lead to a low consumption of protein rich food and hence a high incidence of undernutrition. The occupational pattern reveals that the Santhals who derive livelihood by the means of hard physical activities are more prone to develop CED. The study suggests that the overdependence on forests and their own economy for consumption needs may not be helping this community in attaining a better health status.

A System Approach to Navy Medical Education and Training. Appendix 11. Advanced General Duty Corpsman.

DTIC Science & Technology

1974-08-31

PILONIDAL CYST /ABSCESS TURN PAGE LEFT PtS7 OF & CED GENERAL TASK BC(KLET TASK N-. I ENTEO RESPONSES TO STATEmENTS PELOo I’! LEFT SIIE ’F Oij, 03 ( fF PESP7...NSE BrKLET I IPRESCPIBE TREATMENT FOR PILO\\IOAL CYST /49SCESS 2 IOBSEQVE FrC/REPORT SYMPTOMS OF INTESTINAL wCtS 3 IMAKE PRELIMINARY DIEGNOSIS CF A4EIC...INGROWN NAIL 45 IEXTRACT SEBACEOUS MATERIAL FROM COMEDO 46 ITRIM CORNS/CALLUSES 47 IEXCISE SEBACEOUS CYST /LIPOMA 48 IEXCISE POLYP 49 IGIVE CARE TO BURN

Convection Enhanced Delivery: A Comparison of infusion characteristics in ex vivo and in vivo non-human primate brain tissue.

PubMed

Miranpuri, Gurwattan; Hinchman, Angelica; Wang, Anyi; Schomberg, Dominic; Kubota, Ken; Brady, Martin; Raghavan, Raghu; Bruner, Kevin; Brodsky, Ethan; Block, Walter; Grabow, Ben; Raschke, Jim; Alexander, Andrew; Ross, Chris; Simmons, Heather; Sillay, Karl

2013-07-01

Convection enhanced delivery (CED) is emerging as a promising infusion toolto facilitate delivery of therapeutic agents into the brain via mechanically controlled pumps. Infusion protocols and catheter design have an important impact on delivery. CED is a valid alternative for systemic administration of agents in clinical trials for cell and gene therapies. Where gel and ex vivo models are not sufficient in modeling the disease, in vivo models allow researchers to better understand the underlying mechanisms of neuron degeneration, which is helpful in finding novel approaches to control the process or reverse the progression. Determining the risks, benefits, and efficacy of new gene therapies introduced via CED will pave a way to enter human clinical trial. The objective of this study is to compare volume distribution (Vd)/ volume infused (Vi) ratios and backflow measurements following CED infusions in ex vivo versus in vivo non-human primate brain tissue, based on infusion protocols developed in vitro. In ex vivo infusions, the first brain received 2 infusions using a balloon catheter at rates of 1 μL/min and 2 μL/min for 30 minutes. The second and third brains received infusions using a valve-tip (VT) catheter at 1 μL/min for 30 minutes. The fourth brain received a total of 45 μL infused at a rate of 1 μL/min for 15 minutes followed by 2 μL/min for 15 minutes. Imaging was performed (SPGR FA34) every 3 minutes. In the in vivo group, 4 subjects received a total of 8 infusions of 50 μL. Subjects 1 and 2 received infusions at 1.0 μL/min using a VT catheter in the left hemisphere and a smart-flow (SF) catheter in the right hemisphere. Subjects 3 and 4 each received 1 infusion in the left and right hemisphere at 1.0 μL/min. MRI calculations of Vd/Vi did not significantly differ from those obtained on post-mortem pathology. The mean measured Vd/Vi of in vivo (5.23 + /-1.67) compared to ex vivo (2.17 + /-1.39) demonstrated a significantly larger Vd/Vi for in vivo by 2.4 times (p = 0.0017). We detected higher ratios in the in vivo subjects than in ex vivo. This difference could be explained by the extra cellular space volume fraction. Studies evaluating backflow and morphology use in vivo tissue as a medium are recommended. Further investigation is warranted to evaluate the role blood pressure and heart rate may play in human CED clinical trials.

Widespread suppression of huntingtin with convection-enhanced delivery of siRNA.

PubMed

Stiles, David K; Zhang, Zhiming; Ge, Pei; Nelson, Brian; Grondin, Richard; Ai, Yi; Hardy, Peter; Nelson, Peter T; Guzaev, Andrei P; Butt, Mark T; Charisse, Klaus; Kosovrasti, Verbena; Tchangov, Lubomir; Meys, Michael; Maier, Martin; Nechev, Lubomir; Manoharan, Muthiah; Kaemmerer, William F; Gwost, Douglas; Stewart, Gregory R; Gash, Don M; Sah, Dinah W Y

2012-01-01

Huntington's disease is an autosomal dominant neurodegenerative disease caused by a toxic gain of function mutation in the huntingtin gene (Htt). Silencing of Htt with RNA interference using direct CNS delivery in rodent models of Huntington's disease has been shown to reduce pathology and promote neuronal recovery. A key translational step for this approach is extension to the larger non-human primate brain, achieving sufficient distribution of small interfering RNA targeting Htt (siHtt) and levels of Htt suppression that may have therapeutic benefit. We evaluated the potential for convection enhanced delivery (CED) of siHtt to provide widespread and robust suppression of Htt in nonhuman primates. siHtt was infused continuously for 7 or 28 days into the nonhuman primate putamen to analyze effects of infusion rate and drug concentration on the volume of effective suppression. Distribution of radiolabeled siHtt and Htt suppression were quantified by autoradiography and PCR, respectively, in tissue punches. Histopathology was evaluated and Htt suppression was also visualized in animals treated for 28 days. Seven days of CED led to widespread distribution of siHtt and significant Htt silencing throughout the nonhuman primate striatum in an infusion rate and dose dependent manner. Htt suppression at therapeutic dose levels was well tolerated by the brain. A model developed from these results predicts that continuous CED of siHtt can achieve significant coverage of the striatum of Huntington's disease patients. These findings suggest that this approach may provide an important therapeutic strategy for treating Huntington's disease. Copyright © 2011 Elsevier Inc. All rights reserved.

JPRS Report, Latin America

DTIC Science & Technology

1988-04-28

vision en Chile : un desafio nacional" [Television in Chile : a National Challenge], which was published by the Development Studies Center (CED) and...through its subsid- iary’ Minera Utah dc Chile , Inc.; Rio Tinto Zinc ( En - glish), with 30 percent of the rights through its subsidiary RTZ Escondida...19 CHILE Undecided Voters in Plebiscite Analyzed 21 Television Election Programming, Reporting Viewed Critically 22 Latest Inflation Figures

Dynamic Evaluation of Two Decades of CMAQ Simulations ...

EPA Pesticide Factsheets

This presentation focuses on the dynamic evaluation of the CMAQ model over the continental United States using multi-decadal simulations for the period from 1990 to 2010 to examine how well the changes in observed ozone air quality induced by variations in meteorology and/or emissions are simulated by the model. We applied spectral decomposition of the ozone time-series using the KZ filter to assess the variations in the strengths of synoptic (weather-induced variations) and baseline (long-term variation) forcings, embedded in the simulated and observed concentrations. The results reveal that CMAQ captured the year-to-year variability (more so in the later years than the earlier years) and the synoptic forcing in accordance with what the observations are showing. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-support tools, and models to be applied to media-specific or receptor-specific problem areas. CED uses modeling-based approaches to characterize exposures, evaluate fate and transport, and support environmental diagnostics/forensics with input from multiple data sources. It also develops media- and receptor-specific models, process models, and decision support tools for use both within and outside of EPA.

Delineation of Ehlers-Danlos syndrome phenotype due to the c.934C>T, p.(Arg312Cys) mutation in COL1A1: Report on a three-generation family without cardiovascular events, and literature review.

PubMed

Colombi, Marina; Dordoni, Chiara; Venturini, Marina; Zanca, Arianna; Calzavara-Pinton, Piergiacomo; Ritelli, Marco

2017-02-01

Classical Ehlers-Danlos syndrome (cEDS) is a rare connective tissue disorder primarily characterized by hyperextensible skin, defective wound healing, abnormal scars, easy bruising, and generalized joint hypermobility; arterial dissections are rarely observed. Mutations in COL5A1 and COL5A2 encoding type V collagen account for more than 90% of the patients so far characterized. In addition, cEDS phenotype was reported in a small number of patients carrying the c.934C>T mutation in COL1A1 that results in an uncommon substitution of a non-glycine residue in one Gly-Xaa-Yaa repeat of the pro-α1(I)-chain p.(Arg312Cys), which leads to disturbed collagen fibrillogenesis due to delayed removal of the type I procollagen N-propeptide. This specific mutation has been associated with propensity to arterial rupture in early adulthood; indeed, in literature the individuals harboring this mutation are also referred to as "(classic) vascular-like" EDS patients. Herein, we describe a three-generation cEDS family with six adults carrying the p.(Arg312Cys) substitution, which show a variable and prevalent cutaneous involvement without any major vascular event. These data, together with those available in literature, suggest that vascular events are not a diagnostic handle to differentiate patients with the p.(Arg312Cys) COL1A1 mutation from those with COL5A1 and COL5A2 defects, and highlight that during the diagnostic process the presence of at least the p.(Arg312Cys) substitution in COL1A1 should be investigated in cEDS patients without type V collagen mutations. Nevertheless, for these patients, as well as for those affected with cEDS, a periodical vascular surveillance should be carried out together with cardiovascular risk factors monitoring. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

188Re-loaded lipid nanocapsules as a promising radiopharmaceutical carrier for internal radiotherapy of malignant gliomas

PubMed Central

Allard, Emilie; Hindré, François; Passirani, Catherine; Lemaire, Laurent; Lepareur, Nicolas; Noiret, Nicolas; Menei, Philippe; Benoit, Jean-Pierre

2008-01-01

Purpose Lipid nanocapsules (LNC) entrapping lipophilic complexes of 188Re (188Re(S3CPh)2(S2CPh) [188Re-SSS]) were investigated as a novel radiopharmaceutical carrier for internal radiation therapy of malignant gliomas. The present study was designed to evaluate the efficacy of intracerebral administration of 188Re-SSS LNC by means of convection-enhanced delivery (CED) on a 9L rat brain tumour model. Methods Female Fischer rats with 9L glioma were treated with a single injection of 188Re-SSS LNC by CED 6 days after cell implantation. Rats were put into random groups according to the dose infused: 12, 10, 8, and 3 Gy in comparison with blank LNC, perrhenate solution (4Gy) and non-treated animals. The radionuclide brain retention level was evaluated by measuring 188Re elimination in faeces and urine over 72h after the CED injection. The therapeutic effect of 188Re-SSS LNC was assessed based on animal survival. Results CED of 188Re perrhenate solution resulted in rapid drug clearance with a brain T1/2 of 7h. In contrast, when administered in LNC, 188Re tissue retention was greatly prolonged, with only 10% of the injected dose being eliminated at 72h. Rat median survival was significantly improved for the group treated with 8Gy 188Re-SSS LNC compared to the control group and blank-LNC treated animals. The increase in the median survival time (ISTmedian) was about 80% compared to the control group; 33% of the animals were long-term survivors. The dose of 8Gy proved to be a very effective dose, between toxic (10–12Gy) and ineffective (3–4Gy) doses. Conclusions These findings show that CED of Rhenium-188-loaded lipid nanocapsules is a safe and potent antitumour system for treating malignant gliomas. Our data are the first to show the in vivo efficacy of Rhenium-188 internal radiotherapy for the treatment of brain malignancy. PMID:18465130

DPL-1 DP, LIN-35 Rb and EFL-1 E2F act with the MCD-1 zinc-finger protein to promote programmed cell death in Caenorhabditis elegans.

PubMed

Reddien, Peter W; Andersen, Erik C; Huang, Michael C; Horvitz, H Robert

2007-04-01

The genes egl-1, ced-9, ced-4, and ced-3 play major roles in programmed cell death in Caenorhabditis elegans. To identify genes that have more subtle activities, we sought mutations that confer strong cell-death defects in a genetically sensitized mutant background. Specifically, we screened for mutations that enhance the cell-death defects caused by a partial loss-of-function allele of the ced-3 caspase gene. We identified mutations in two genes not previously known to affect cell death, dpl-1 and mcd-1 (modifier of cell death). dpl-1 encodes the C. elegans homolog of DP, the human E2F-heterodimerization partner. By testing genes known to interact with dpl-1, we identified roles in cell death for four additional genes: efl-1 E2F, lin-35 Rb, lin-37 Mip40, and lin-52 dLin52. mcd-1 encodes a novel protein that contains one zinc finger and that is synthetically required with lin-35 Rb for animal viability. dpl-1 and mcd-1 act with efl-1 E2F and lin-35 Rb to promote programmed cell death and do so by regulating the killing process rather than by affecting the decision between survival and death. We propose that the DPL-1 DP, MCD-1 zinc finger, EFL-1 E2F, LIN-35 Rb, LIN-37 Mip40, and LIN-52 dLin52 proteins act together in transcriptional regulation to promote programmed cell death.

Feasibility of liquid nitrogen cryotherapy after failed radiofrequency ablation for Barrett's esophagus.

PubMed

Trindade, Arvind J; Inamdar, Sumant; Kothari, Shivangi; Berkowitz, Joshua; McKinley, Matthew; Kaul, Vivek

2017-09-01

Radiofrequency ablation (RFA) for dysplastic Barrett's esophagus (BE) is highly effective. RFA failures are infrequent but can be a challenging cohort to manage. There are limited data on the feasibility of liquid nitrogen cryospray ablation for complete eradication of dysplasia (CE-D) and/or intestinal metaplasia (CE-IM) after RFA has failed to achieve CE-IM in patients with dysplastic BE. This is a retrospective review from two medical centers of prospectively maintained databases looking at patients that underwent liquid nitrogen cryospray ablation for refractory intestinal metaplasia post failed RFA. Eighteen patients were identified that met inclusion criteria. Eleven patients had persistent dysplasia and IM following RFA and seven had persistent non-dysplastic IM. More than 80% of patients were male with long-segment BE (median length 8 cm). Seventy two percent of patients with dysplasia achieved CE-D after cryotherapy. Fifty percent (9/18) of all RFA failures achieved CE-IM with cryotherapy. In comparison, RFA has a CE-IM of 78% in a less challenging treatment naïve cohort from a large-scale meta-analysis of 3802 patients. No adverse events occurred in our cohort. Cryospray ablation is feasible and safe for achieving CE-D and CE-IM after RFA failure. The CE-D rates are high with cryotherapy in this population. CE-IM with cryotherapy is acceptable in this difficult-to-treat cohort when compared to CE-IM rates with RFA in dysplastic BE treatment naïve patients (50% vs 78%). © 2017 Japan Gastroenterological Endoscopy Society.

Intraneural convection enhanced delivery of AAVrh20 for targeting primary sensory neurons.

PubMed

Pleticha, Josef; Jeng-Singh, Christian; Rezek, Rahaf; Zaibak, Manal; Beutler, Andreas S

2014-05-01

Gene therapy using adeno-associated virus (AAV) is an attractive strategy to treat disorders of the peripheral nervous system (PNS), such as chronic pain or peripheral neuropathies. Although intrathecal (IT) administration of AAV has been the standard in the field for targeting the PNS, it lacks anatomical specificity and results in wide rostro-caudal distribution of the vector. An alternative approach is to deliver AAV directly to the peripheral nerve axon. The present study employed convection-enhanced delivery (CED) of a novel AAV serotype, AAVrh20, expressing enhanced green fluorescent protein (EGFP) into rat sciatic nerve investigating its efficacy, anatomical selectivity, and safety, compared to the IT route. Intraneural CED resulted in transduction confined to the ipsilateral L4 and L5 DRG while IT administration led to promiscuous DRG transduction encompassing the entire lumbar region bilaterally. The transduction rate for intraneural AAV administration was similar to IT delivery (24% for L4 and 31.5% for L5 DRG versus 50% for L4 and 19.5% for L5 DRG). The use of hyperosmotic diluent did not further improve the transduction efficiency. AAVrh20 was superior to reference serotypes previously described to be most active for each route. Intraneural CED of AAV was associated with transient allodynia that resolved spontaneously. These findings establish intraneural CED as an alternative to IT administration for AAV mediated gene transfer to the PNS and, based on a reference rodent model, suggest AAVrh20 as a superior serotype for targeting the PNS. Copyright © 2014 Elsevier Inc. All rights reserved.

The cyclophosphamide equivalent dose as an approach for quantifying alkylating agent exposure: a report from the Childhood Cancer Survivor Study.

PubMed

Green, Daniel M; Nolan, Vikki G; Goodman, Pamela J; Whitton, John A; Srivastava, DeoKumar; Leisenring, Wendy M; Neglia, Joseph P; Sklar, Charles A; Kaste, Sue C; Hudson, Melissa M; Diller, Lisa R; Stovall, Marilyn; Donaldson, Sarah S; Robison, Leslie L

2014-01-01

Estimation of the risk of adverse long-term outcomes such as second malignant neoplasms and infertility often requires reproducible quantification of exposures. The method for quantification should be easily utilized and valid across different study populations. The widely used Alkylating Agent Dose (AAD) score is derived from the drug dose distribution of the study population and thus cannot be used for comparisons across populations as each will have a unique distribution of drug doses. We compared the performance of the Cyclophosphamide Equivalent Dose (CED), a unit for quantifying alkylating agent exposure independent of study population, to the AAD. Comparisons included associations from three Childhood Cancer Survivor Study (CCSS) outcome analyses, receiver operator characteristic (ROC) curves and goodness of fit based on the Akaike's Information Criterion (AIC). The CED and AAD performed essentially identically in analyses of risk for pregnancy among the partners of male CCSS participants, risk for adverse dental outcomes among all CCSS participants and risk for premature menopause among female CCSS participants, based on similar associations, lack of statistically significant differences between the areas under the ROC curves and similar model fit values for the AIC between models including the two measures of exposure. The CED is easily calculated, facilitating its use for patient counseling. It is independent of the drug dose distribution of a particular patient population, a characteristic that will allow direct comparisons of outcomes among epidemiological cohorts. We recommend the use of the CED in future research assessing cumulative alkylating agent exposure. © 2013 Wiley Periodicals, Inc.

A Pilot Study: Cardiac Parameters in Children Receiving New-Generation Antidepressants.

PubMed

Uchida, Mai; Spencer, Andrea E; Kenworthy, Tara; Chan, James; Fitzgerald, Maura; Rosales, Ana Maria; Kagan, Elana; Saunders, Alexandra; Biederman, Joseph

2017-06-01

Because of concerns about potential associations between high doses of citalopram and QTc prolongation in adults, this study examined whether such associations are operant in children. We hypothesized that therapeutic doses of nontricyclic antidepressant medications (non-TCAs) prescribed to children would be cardiovascularly safe. The sample consisted of 49 psychiatrically referred children and adolescents 6 to 17 years old of both sexes treated with a non-TCA (citalopram, escitalopram, fluoxetine, paroxetine, sertraline, bupropion, duloxetine, venlafaxine, mirtazapine). To standardize the doses of different antidepressants, we converted doses of individual medicines into "citalopram equivalent doses" (CEDs) based on dosing recommendation for individual antidepressants. Correlation analysis was carried out to compare the continuous and weight-based CED to variables of interest. A QTc grouping was defined as normal, borderline, or abnormal, and CED was compared across QTc groupings using linear regression. An antidepressant dosage group was defined as low or high dose, and a t test compared variables of interest across dosage groups. No significant associations were found between total or weight-corrected CEDs of any antidepressant examined and QTc or any other electrocardiogram or blood pressure parameters. In patients taking citalopram or escitalopram, a significant correlation was found between PR interval and total daily dose, which disappeared when weight-based doses were used or when corrected by age. Although limited by a relatively small sample size, these results suggest that therapeutic doses of non-TCA antidepressants when used in children do not seem to be associated with prolonged QTc interval or other adverse cardiovascular effects.

Guidance for Using Formal Methods in a Certification Context

NASA Technical Reports Server (NTRS)

Brown, Duncan; Delseny, Herve; Hayhurst, Kelly; Wiels, Virginie

2010-01-01

This paper discusses some of the challenges to using formal methods in a certification context and describes the effort by the Formal Methods Subgroup of RTCA SC-205/EUROCAE WG-71 to propose guidance to make the use of formal methods a recognized approach. This guidance, expected to take the form of a Formal Methods Technical Supplement to DO-178C/ED-12C, is described, including the activities that are needed when using formal methods, new or modified objectives with respect to the core DO-178C/ED-12C document, and evidence needed for meeting those objectives.

Internal dosimetry of inhaled iodine-131.

PubMed

Kiani Nasab, Mitra; Rafat Motavalli, Laleh; Miri Hakimabad, Hashem

2018-01-01

In this paper, the dose assessment for the iodine inhalation exposure in 19 aerosol sizes and three gas/vapor forms at three levels of thyroid uptake, was performed. Two different modes of work (light vs. heavy) and breathing (nose vs. mouth) for aerosol inhalation were investigated. In order to calculate the cumulated activities per unit of inhaled activity, a combined model which included the latest models of both human respiratory and alimentary tract was developed. The S values for 131 I were computed based on the ICRP adult male and female reference voxel phantoms by the Monte Carlo method. Then, the committed equivalent and committed effective dose coefficients were obtained (The data are available at http://www.um.ac.ir/∼mirihakim). In general, for the nonzero thyroid uptakes, the maximum cumulated activity was found in the thyroid. When the thyroid is blocked, however, the maximum depends on the work and breathing mode and radioisotope form. Overall, the maximum CED coefficient was evaluated for the inhalation of elemental iodine at thyroid uptake of ∼27% (2.8 × 10 -8 Sv/Bq). As for the particle inhalation per se, mouth breathing of 0.6 nm and 0.2 μm AMTD particles showed to have the maximum (2.8 × 10 -8 Sv/Bq) and minimum (6.4 × 10 -9 Sv/Bq) CED coefficients, respectively. Compared to the reference CED coefficients, the authors found an increase of about 58% for inhalation of the aerosols with AMAD of 1 μm and 70% for 5 μm. Copyright © 2017 Elsevier Ltd. All rights reserved.

Offering integrated medical equipment management in an application service provider model.

PubMed

Cruz, Antonio Miguel; Barr, Cameron; Denis, Ernesto Rodríguez

2007-01-01

With the advancement of medical technology and thus the complexity of the equipment under their care, clinical engineering departments (CEDs) must continue to make use of computerized tools in the management of departmental activities. Authors of this paper designed, installed, and implemented an application service provider (ASP) model at the laboratory level to offer value added management tools in an online format to CEDs. The project, designed to investigate how to help meet demands across multiple healthcare organizations and provide a means of access for organizations that otherwise might not be able to take advantage of the benefits of those tools, has been well received. Ten hospitals have requested the service, and five of those are ready to proceed with the implementation of the ASP. With the proposed centralized system architecture, the model has shown promise in reducing network infrastructure labor and equipment costs, benchmarking of equipment performance indicators, and developing avenues for proper and timely problem reporting. The following is a detailed description of the design process from conception to implementation of the five main software modules and supporting system architecture.

Regional convection-enhanced delivery of gadolinium-labeled albumin in the rat hippocampus in vivo.

PubMed

Astary, Garrett W; Kantorovich, Svetlana; Carney, Paul R; Mareci, Thomas H; Sarntinoranont, Malisa

2010-03-15

Convection-enhanced delivery (CED) has emerged as a promising method of targeted drug delivery for treating central nervous system (CNS) disorders, but the influence of brain structure on infusate distribution is unclear. We have utilized this approach to study extracellular transport and distribution of a contrast agent in the hippocampus, a complex structure susceptible to CNS disorders. The magnetic resonance (MR) contrast agent diethylene triamene penta-acetic acid chelated gadolinium-labeled albumin (Gd-albumin), tagged with Evans blue dye, was directly infused (V(i)=5 microl) into the dorsal and ventral hippocampus of seven male Sprague-Dawley rats. The final distribution profile of the contrast agent, a product of CED and limited diffusion, was observed in vivo using high-resolution T1-weighted MR imaging at 11.1T. Dense cell layers, such as the granule cell layer of the dentate gyrus and the pyramidal cell layer of CA1, appeared to be barriers to transport of the tracer. Three-dimensional distribution shape and volume (V(d)) differences, between the dorsal and ventral hippocampus infusions, were determined from the MR images using a semi-automatic segmentation routine (dorsal V(d)=23.4+/-1.8 microl, ventral V(d)=36.4+/-5.1 microl). Finer structural detail of the hippocampus was obtained using a combination of histological analysis and fluorescence imaging. This study demonstrates that CED has the potential to target all regions of the hippocampus and that tracer distribution is influenced by infusion site, underlying structure and circuitry, and extent of backflow. Therefore, CED, combined with high-resolution MR imaging, may be a useful strategy for delivering therapeutics for the treatment of CNS disorders affecting the hippocampus. Published by Elsevier B.V.

Cumulative effective dose associated with computed tomography examinations in adolescent trauma patients.

PubMed

Choi, Seung Joon; Kim, Eun Young; Kim, Hyung Sik; Choi, Hye-Young; Cho, Jinseong; Yang, Hyuk Jun; Chung, Yong Eun

2014-07-01

The aims of this study were to analyze cumulative effective dose (cED) and to assess lifetime attributable risk (LAR) of cancer due to radiation exposure during computed tomography (CT) examinations in adolescent trauma patients. Between January 2010 and May 2011, the adolescent patients with trauma were enrolled in this study. Numbers of CT examinations and body regions examined were collated, and cEDs were calculated using dose-length product values and conversion factors. Lifetime attributable risk for cancer incidence and cancer-associated mortality were quantified based on the studies of survivors of the atomic bombs on Japan. Data were stratified according to severity of trauma: minor trauma, injury severity score of less than 16; and major trauma, injury severity score of 16 or greater. A total of 698 CT scans were obtained on the following regions of 484 adolescent patients: head CT, n = 647; rest of the body, n = 41; and thorax, n = 10. Mean cED per patient was 3.4 mSv, and mean LARs for cancer incidence and mortality were 0.05% and 0.02%, respectively. The majority of patients (98.4%) experienced minor trauma, and their mean cED and LARs for cancer incidence and mortality (3.0 mSv and 0.04% and 0.02%, respectively) were significantly lower than those of patients with major trauma (24.3 mSv and 0.31% and 0.15%, respectively, all P values < 0.001). The overall radiation-induced cancer risk due to CT examinations performed for the initial assessment of minor trauma was found to be relatively low in adolescent patients. However, adolescent patients with major trauma were exposed to a substantial amount of radiation during multiple CT examinations.

Frameless multimodal image guidance of localized convection-enhanced delivery of therapeutics in the brain

PubMed Central

van der Bom, Imramsjah M J; Moser, Richard P; Gao, Guanping; Sena-Esteves, Miguel; Aronin, Neil

2013-01-01

Introduction Convection-enhanced delivery (CED) has been shown to be an effective method of administering macromolecular compounds into the brain that are unable to cross the blood-brain barrier. Because the administration is highly localized, accurate cannula placement by minimally invasive surgery is an important requisite. This paper reports on the use of an angiographic c-arm system which enables truly frameless multimodal image guidance during CED surgery. Methods A microcannula was placed into the striatum of five sheep under real-time fluoroscopic guidance using imaging data previously acquired by cone beam computed tomography (CBCT) and MRI, enabling three-dimensional navigation. After introduction of the cannula, high resolution CBCT was performed and registered with MRI to confirm the position of the cannula tip and to make adjustments as necessary. Adeno-associated viral vector-10, designed to deliver small-hairpin micro RNA (shRNAmir), was mixed with 2.0 mM gadolinium (Gd) and infused at a rate of 3 μl/min for a total of 100 μl. Upon completion, the animals were transferred to an MR scanner to assess the approximate distribution by measuring the volume of spread of Gd. Results The cannula was successfully introduced under multimodal image guidance. High resolution CBCT enabled validation of the cannula position and Gd-enhanced MRI after CED confirmed localized administration of the therapy. Conclusion A microcannula for CED was introduced into the striatum of five sheep under multimodal image guidance. The non-alloy 300 μm diameter cannula tip was well visualized using CBCT, enabling confirmation of the position of the end of the tip in the area of interest. PMID:22193239

Additive Neuroprotective Effects of the Multifunctional Iron Chelator M30 with Enriched Diet in a Mouse Model of Amyotrophic Lateral Sclerosis.

PubMed

Golko-Perez, Sagit; Mandel, Silvia; Amit, Tamar; Kupershmidt, Lana; Youdim, Moussa B H; Weinreb, Orly

2016-02-01

Amyotrophic lateral sclerosis (ALS) is the most common degenerative disease of the motoneuron system, involving various abnormalities, such as mitochondrial dysfunction, oxidative stress, transitional metal accumulation, neuroinflammation, glutamate excitotoxicity, apoptosis, decreased supply of trophic factors, cytoskeletal abnormalities, and extracellular superoxide dismutase (SOD)-1 toxicity. These multiple disease etiologies implicated in ALS gave rise to the perception that future therapeutic approaches for the disease should be aimed at targeting multiple pathological pathways. In line with this view, we have evaluated in the current study the therapeutic effects of low doses of the novel multifunctional monoamine oxidase (MAO) inhibitor/iron-chelating compound, M30 in combination with high Calorie Energy supplemented Diet (CED) in the SOD1-G93A transgenic mouse model of ALS. Our results demonstrated that the combined administration of M30 with CED produced additive neuroprotective effects on motor performance and increased survival of SOD1-G93A mice. We also found that both M30 and M30/CED regimens caused a significant inhibition of MAO-A and -B activities and decreased the turnover of dopamine in the brain of SOD1-G93A mice. In addition, M30/CED combined treatment resulted in a significant increase in mRNA expression levels of various mitochondrial biogenesis and metabolism regulators, such as peroxisome proliferator-activated receptor-γ (PPARγ)-co activator 1 alpha (PGC-1α), PPARγ, uncoupling protein 1, and insulin receptor in the gastrocnemius muscle of SOD1-G93A mice. These results suggest that a combination of drug/agents with different, but complementary mechanisms may be beneficial in the treatment of ALS.

Poor diagnostic accuracy of a single fasting plasma citrulline concentration to assess intestinal energy absorption capacity.

PubMed

Peters, Job H C; Wierdsma, Nicolette J; Teerlink, Tom; van Leeuwen, Paul A M; Mulder, Chris J J; van Bodegraven, Ad A

2007-12-01

Our aim was to explore the diagnostic value of fasting citrulline concentrations to detect decreased intestinal energy absorption in patients with recently diagnosed celiac disease (CeD), refractory celiac disease (RCeD), and short bowel syndrome (SBS). Decreased intestinal energy absorption is regarded a marker of intestinal failure. Fasting plasma citrulline concentrations were determined by high performance liquid chromatography (HPLC) in a prospective study of 30 consecutive adult patients (15 CeD, 9 RCeD, and 16 SBS) and 21 healthy subjects. Intestinal energy absorption capacity using bomb calorimetry was determined in all patients and healthy subjects and was regarded as the gold standard for intestinal energy absorption function. The mean fasting plasma citrulline concentration was lower in RCeD patients than in healthy subjects (28.5+/-9.9 vs 38.1+/-8.0 micromol/L, P<0.05) and CeD patients (28.5+/-9.9 vs 38.1+/-6.4 micromol/L, P<0.05), however, clearly within reference values. The mean intestinal energy absorption capacity was lower in SBS patients than in healthy subjects (64.3+/-18.2 vs 90.3+/-3.5%, P<0.001), CeD patients (64.3+/-18.2 vs 89.2+/-3.4%, P<0.001), and the RCeD group (64.3+/-18.2 vs 82.3+/-11.7%, P<0.01). No relation was observed between fasting plasma citrulline concentration and intestinal energy absorption capacity (Pearson r=0.09, P=0.56). The area under the ROC curve for fasting plasma citrulline to detect decreased intestinal energy absorption capacity (i.e., <85%) was 0.50. Fasting plasma citrulline concentrations have poor test characteristics for detection of decreased intestinal energy absorption capacity in patients with enterocyte damage.

A new physically-based windblown dust emission ...

EPA Pesticide Factsheets

Dust has significant impacts on weather and climate, air quality and visibility, and human health; therefore, it is important to include a windblown dust emission module in atmospheric and air quality models. In this presentation, we summarize our efforts in development of a physics-based windblown dust emission scheme and its implementation in the CMAQ modeling system. The new model incorporates the effect of the surface wind speed, soil texture, soil moisture, and surface roughness in a physically sound manner. Specifically, a newly developed dynamic relation for the surface roughness length in this model is believed to adequately represent the physics of the surface processes involved in the dust generation. Furthermore, careful attention is paid in integrating the new windblown dust module within the CMAQ to ensure that the required input parameters are correctly configured. The new model is evaluated for the case studies including the continental United States and the Northern hemisphere, and is shown to be able to capture the occurrence of the dust outbreak and the level of the soil concentration. We discuss the uncertainties and limitations of the model and briefly describe our path forward for further improvements. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-support tools, and models to be applied to media-specific or receptor-specific problem areas. CED uses modeling-based

AmeriFlux US-Ced Cedar Bridge

DOE Data Explorer

Clark, Ken [USDA Forest Service

2016-01-01

This is the AmeriFlux version of the carbon flux data for the site US-Ced Cedar Bridge. Site Description - Wildfires and prescribed fires are a common occurrence in the NJ Pinelands. Prior to a 1995 nonstand replacing wildfire, the stand was last burned in the very large wildfire in 1963. Plow lines were installed for fire control in December of 2007, followed by a prescribed burns in 2008 and 2013, conducted by the New Jersey Forest Fire Service. Pine looper defoliated the stand in 1998, and Gypsy moth defoliated the understory and deciduos oaks in 2007. Pitch Pines are largely unaffected by defoliation by Gypsy moth.

Reaction of. beta. -propiolactone with derivatives of adenine and with DNA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, R.; Mieyal, J.J.; Goldthwait, D.A.

1982-01-01

The reaction of deoxyadenosine with ..beta..-propiolactone produces two derivatives. One is 1-(2-carboxyethyl)-2-deoxyadenosine (CEdA). The proposed structure for the other is 3-(..beta..-D-2-deoxyribosyl)-7,8-dihydropyrimido-(2,l-i)purine-9-one (dDPP). Spectral characteristics of both compounds are presented. These include u.v. spectra of each in acidic, neutral and alkaline solutions, i.r. spectra, fluorescence spectra, and n.m.r. spectra. The dDPP can be converted to CEdA by mild acid hydrolysis, and the CEdA can be converted to dDPP by reaction with a carbodiimide derivative. When poly A was reacted with ..beta..-propiolactone, the yield of dDPP in the polymer was 7-9%. When double-stranded DNA was alkylated by (/sup 3/H)..beta..-propiolactone at relatively highmore » concentrations and then acid hydrolyzed to separate 1-(2-carboxyethyl)adenine (CEA) and 7-(2-carboxyethyl)guanine (CEG), and CEA to CEG ratio of up to 0.62 was obtained. With relatively low concentrations of (/sup 3/H)..beta..-propiolactone, the yield of CEA was low with double-stranded DNA but was 5-6 fold greater with single-stranded DNA.« less

Toxicity evaluation of convection-enhanced delivery of small-molecule kinase inhibitors in naïve mouse brainstem.

PubMed

Zhou, Zhiping; Ho, Sharon L; Singh, Ranjodh; Pisapia, David J; Souweidane, Mark M

2015-04-01

Diffuse intrinsic pontine gliomas (DIPGs) are inoperable and lethal high-grade gliomas lacking definitive therapy. Platelet-derived growth factor receptor (PDGFR) and its downstream signaling molecules are the most commonly overexpressed oncogenes in DIPG. This study tested the effective concentration of PDGFR pathway inhibitors in cell culture and then toxicity of these small-molecule kinase inhibitors delivered to the mouse brainstem via convection-enhanced delivery (CED) for potential clinical application. Effective concentrations of small-molecule kinase inhibitors were first established in cell culture from a mouse brainstem glioma model. Sixteen mice underwent CED, a local drug delivery technique, of saline or of single and multidrug combinations of dasatinib (2 M), everolimus (20 M), and perifosine (0.63 mM) in the pons. Animals were kept alive for 3 days following the completion of infusion. No animals displayed any immediate or delayed neurological deficits postoperatively. Histological analysis revealed edema, microgliosis, acute inflammation, and/or axonal injury in the experimental animals consistent with mild acute drug toxicity. Brainstem CED of small-molecule kinase inhibitors in the mouse did not cause serious acute toxicities. Future studies will be necessary to evaluate longer-term safety to prepare for potential clinical application.

Using additional external inputs to forecast water quality with an artificial neural network for contamination event detection in source water

NASA Astrophysics Data System (ADS)

Schmidt, F.; Liu, S.

2016-12-01

Source water quality plays an important role for the safety of drinking water and early detection of its contamination is vital to taking appropriate countermeasures. However, compared to drinking water, it is more difficult to detect contamination events because its environment is less controlled and numerous natural causes contribute to a high variability of the background values. In this project, Artificial Neural Networks (ANNs) and a Contamination Event Detection Process (CED Process) were used to identify events in river water. The ANN models the response of basic water quality sensors obtained in laboratory experiments in an off-line learning stage and continuously forecasts future values of the time line in an on-line forecasting step. During this second stage, the CED Process compares the forecast to the measured value and classifies it as regular background or event value, which modifies the ANN's continuous learning and influences its forecasts. In addition to this basic setup, external information is fed to the CED Process: A so-called Operator Input (OI) is provided to inform about unusual water quality levels that are unrelated to the presence of contamination, for example due to cooling water discharge from a nearby power plant. This study's primary goal is to evaluate how well the OI fits into the design of the combined forecasting ANN and CED Process and to understand its effects on the online forecasting stage. To test this, data from laboratory experiments conducted previously at the School of Environment, Tsinghua University, have been used to perform simulations highlighting features and drawbacks of this method. Applying the OI has been shown to have a positive influence on the ANN's ability to handle a sudden change in background values, which is unrelated to contamination. However, it might also mask the presence of an event, an issue that underlines the necessity to have several instances of the algorithm run in parallel. Other difficulties addressed in this study include the source and the format of the OI. This project tries to add to the ongoing research into algorithms for CED. It provides ideas for how results from the binary classification of time series could be evaluated in a more realistic fashion and shows what the advantages and limitations of such a method would be.

Computational electrodynamics in material media with constraint-preservation, multidimensional Riemann solvers and sub-cell resolution - Part II, higher order FVTD schemes

NASA Astrophysics Data System (ADS)

Balsara, Dinshaw S.; Garain, Sudip; Taflove, Allen; Montecinos, Gino

2018-02-01

The Finite Difference Time Domain (FDTD) scheme has served the computational electrodynamics community very well and part of its success stems from its ability to satisfy the constraints in Maxwell's equations. Even so, in the previous paper of this series we were able to present a second order accurate Godunov scheme for computational electrodynamics (CED) which satisfied all the same constraints and simultaneously retained all the traditional advantages of Godunov schemes. In this paper we extend the Finite Volume Time Domain (FVTD) schemes for CED in material media to better than second order of accuracy. From the FDTD method, we retain a somewhat modified staggering strategy of primal variables which enables a very beneficial constraint-preservation for the electric displacement and magnetic induction vector fields. This is accomplished with constraint-preserving reconstruction methods which are extended in this paper to third and fourth orders of accuracy. The idea of one-dimensional upwinding from Godunov schemes has to be significantly modified to use the multidimensionally upwinded Riemann solvers developed by the first author. In this paper, we show how they can be used within the context of a higher order scheme for CED. We also report on advances in timestepping. We show how Runge-Kutta IMEX schemes can be adapted to CED even in the presence of stiff source terms brought on by large conductivities as well as strong spatial variations in permittivity and permeability. We also formulate very efficient ADER timestepping strategies to endow our method with sub-cell resolving capabilities. As a result, our method can be stiffly-stable and resolve significant sub-cell variation in the material properties within a zone. Moreover, we present ADER schemes that are applicable to all hyperbolic PDEs with stiff source terms and at all orders of accuracy. Our new ADER formulation offers a treatment of stiff source terms that is much more efficient than previous ADER schemes. The computer algebra system scripts for generating ADER time update schemes for any general PDE with stiff source terms are also given in the electronic supplements to this paper. Second, third and fourth order accurate schemes for numerically solving Maxwell's equations in material media are presented in this paper. Several stringent tests are also presented to show that the method works and meets its design goals even when material permittivity and permeability vary by an order of magnitude over just a few zones. Furthermore, since the method is unconditionally stable and sub-cell-resolving in the presence of stiff source terms (i.e. for problems involving giant variations in conductivity over just a few zones), it can accurately handle such problems without any reduction in timestep. We also show that increasing the order of accuracy offers distinct advantages for resolving sub-cell variations in material properties. Most importantly, we show that when the accuracy requirements are stringent the higher order schemes offer the shortest time to solution. This makes a compelling case for the use of higher order, sub-cell resolving schemes in CED.

Approximating dose and risk for contaminants in groundwater from the underground nuclear test areas of the Nevada National Security Site (NNSS)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daniels, Jeffrey I.; Chapman, Jenny; Pohlmann, Karl F.

As part of the Environmental Management Program at the Nevada National Security Site (NNSS), the Underground Test Area (UGTA) Activity investigates the potential impacts of radionuclides that were introduced into groundwater from the underground nuclear tests conducted near or below the NNSS water table between 1951 and 1992. Groundwater models are being used to simulate contaminant transport and forecast contaminant boundaries that encompass areas where the groundwater has a five percent or greater probability of containing contaminants above the Safe Drinking Water Act Maximum Contaminant Levels (SDWA MCLs) at any time during the next 1,000 years. Transport modeling conducted formore » the Frenchman Flat Corrective Action Unit (CAU) at the NNSS identified the beta/photon-emitting radionuclides tritium (3H), carbon-14 (14C), chlorine-36 (36Cl), technetium-99 (99Tc), and iodine-129 (129I) as having the greatest influence in defining the farthest extent of the modeled CAU contaminant boundary. These same radionuclides are assumed here as the contaminants of concern (COCs) for all underground nuclear tests at the NNSS because models are not yet complete for the other CAUs.Potential public exposure to the COCs will only occur and be of concern if the COCs migrate into the groundwater beneath public or private lands at levels that exceed either individual SDWA MCLs or dose and risk limits. Groundwater flow directions strongly suggest that any contaminant boundary predicted by contaminant fate and transport modeling to overlap public or private lands is more likely to occur to the west and/or southwest of the NNSS and the adjacent Nevada Test and Training Range (NTTR). Well-established, rural communities exist in these directions. Estimates of representative activity concentrations at the applicable SDWA MCL were developed for the five COCs. It is assumed that these COC concentrations may collectively occur at some public or private location in the future, but that situation does not exist today. These representative activity concentrations are evaluated with respect to conforming collectively to a modern annual committed effective dose (CED) and lifetime excess cancer morbidity risk for a hypothetical reasonably maximally exposed individual (RMEI). This approach goes beyond the SDWA MCL focus of the contaminant boundary because individual COC concentrations may comply with the SDWA MCL but not collectively meet the modern health-protection metrics and the SDWA language, especially if future modeling studies or monitoring activities show multiple radionuclides from different SDWA MCL categories to be COCs. For the drinking water exposure pathway alone, the annual committed effective dose (CED) for the RMEI from all five COCs that are collectively at estimated activity concentrations equal to their SDWA MCL is well below the U.S. Department of Energy health-protective CED limit of 100 millirem (mrem)/yr. This is consistent using both the NNSS unclassified, 1992 decay-corrected radionuclide atom inventory and the atom inventory based on radionuclides measured in groundwater obtained from the ALMENDRO cavity in 2009 to calculate the SDWA MCL activity concentrations in groundwater. The RMEI’s total lifetime excess cancer risk from the drinking water exposure pathway for both atom inventories is within the range of 1 × 10 -4 to ≤ 1 × 10 -6, which is considered health protective according to modern SDWA MCL regulatory language. The biosphere exposure pathways are drinking water, garden produce, animal products, inadvertent soil ingestion, and indoor and outdoor air inhalation. The exposure parameters for communities west and southwest of the NNSS were developed when the Yucca Mountain high-level, nuclear-waste disposal facility was under consideration. For all biosphere exposure pathways, calculations of the annual CED and lifetime excess cancer morbidity risk for the RMEI revealed that: 1) The annual CED is well within health-protective guidance (<< 100 mrem CED/yr) for the COC activity concentrations at the SDWA MCL, regardless of the atom inventory used. 2) The calculated 70-year lifetime excess cancer morbidity risk (6 x 10 -5) is within the health-protective range when the five COC activity concentrations are derived using the NNSS 1992 atom inventory, but it is at the upper limit of the acceptable range (1 x 10 -4) using the ALMENDRO 2009 atom inventory. 3) Tritium (3H) is the principal COC for producing annual dose and lifetime excess cancer risk, regardless of the atom inventory used. 4) Overall, the drinking water ingestion pathway is the dominant exposure pathway contributing to the total annual CED and lifetime excess cancer risk, followed by eating locally grown produce and animal products. 5) When tritium completely decays (after about 100 years), the RMEI’s lifetime risk will fall well within the health-protective range (i.e., 1 × 10-4 to ≤ 1 × 10 -6) and 36Cl will then become the most important contributor to the RMEI’s total annual CED and lifetime excess cancer morbidity risk from eating local produce and animal products. In the event that radionuclide concentrations begin to approach SDWA MCLs, a reasonable risk-management strategy for keeping lifetime risk more in compliance with regulatory guidance would be to use local sources of groundwater that are below SDWA MCLs or to limit the consumption of local produce and animal products that have ingested COC-contaminated groundwater. The viability of the latter strategy increases where the annual CED due to 36Cl approaches that of 3H.The dose and risk values calculated here for an RMEI are specific to the assumption that the five COCs occur in groundwater beneath public or private lands at concentrations that are collectively at the SDWA MCL. Currently, these COCs are essentially absent from groundwater beneath public or private lands beyond the boundaries of the NNSS and NTTR other than at very low, naturally occurring concentrations. The analyses presented here can be readily applied to determine dose and risk for COC concentrations actually measured in future monitoring samples.« less

Historical (1750–2014) anthropogenic emissions of reactive gases and aerosols from the Community Emissions Data System (CEDS)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoesly, Rachel M.; Smith, Steven J.; Feng, Leyang

Here, we present a new data set of annual historical (1750–2014) anthropogenic chemically reactive gases (CO, CH 4, NH 3, NO x, SO 2, NMVOCs), carbonaceous aerosols (black carbon – BC, and organic carbon – OC), and CO 2 developed with the Community Emissions Data System (CEDS). We improve upon existing inventories with a more consistent and reproducible methodology applied to all emission species, updated emission factors, and recent estimates through 2014. The data system relies on existing energy consumption data sets and regional and country-specific inventories to produce trends over recent decades. All emission species are consistently estimated using the samemore » activity data over all time periods. Emissions are provided on an annual basis at the level of country and sector and gridded with monthly seasonality. These estimates are comparable to, but generally slightly higher than, existing global inventories. Emissions over the most recent years are more uncertain, particularly in low- and middle-income regions where country-specific emission inventories are less available. Future work will involve refining and updating these emission estimates, estimating emissions' uncertainty, and publication of the system as open-source software.« less

Historical (1750–2014) anthropogenic emissions of reactive gases and aerosols from the Community Emissions Data System (CEDS)

DOE PAGES

Hoesly, Rachel M.; Smith, Steven J.; Feng, Leyang; ...

2018-01-29

Here, we present a new data set of annual historical (1750–2014) anthropogenic chemically reactive gases (CO, CH 4, NH 3, NO x, SO 2, NMVOCs), carbonaceous aerosols (black carbon – BC, and organic carbon – OC), and CO 2 developed with the Community Emissions Data System (CEDS). We improve upon existing inventories with a more consistent and reproducible methodology applied to all emission species, updated emission factors, and recent estimates through 2014. The data system relies on existing energy consumption data sets and regional and country-specific inventories to produce trends over recent decades. All emission species are consistently estimated using the samemore » activity data over all time periods. Emissions are provided on an annual basis at the level of country and sector and gridded with monthly seasonality. These estimates are comparable to, but generally slightly higher than, existing global inventories. Emissions over the most recent years are more uncertain, particularly in low- and middle-income regions where country-specific emission inventories are less available. Future work will involve refining and updating these emission estimates, estimating emissions' uncertainty, and publication of the system as open-source software.« less

Effectiveness of an interpersonal relationship program on interpersonal relationships, self-esteem, and depression in nursing students.

PubMed

Yoon, Hee Sang; Kim, Gyung Hee; Kim, Jiyoung

2011-12-01

The purpose of this study was to examine the effectiveness of an interpersonal relationship program on interpersonal relationships, self-esteem, and depression in nursing students. This was a quasi-experiment with a nonequivalent control group pre-posttest design. Sixty-four nursing students participated in the study with 31 in the experimental group and 33 in the control group. They were from 3 different colleges of nursing located in Seoul. The interpersonal relationship program was held 10 times over 10 weeks, taking 90 minutes per session. The interpersonal relationship change scale developed by Schlein and Guemey, Rosenberg's self-esteem scale, and CED-S for depression were the instruments used in the study. The data collection period was from January 4 to March 8, 2011, and the collected data were analyzed with SPSS 14.0 using the Χ(2)-test, t-test, and paired t-test. The results showed a significant difference between the experimental group and the control group in terms of the degree of interpersonal relationships, self-esteem, and depression. The results indicate that interpersonal relationship programs have positive effects for improving interpersonal relationships and self-esteem, and decreasing depression in nursing students.

Historical (1750-2014) anthropogenic emissions of reactive gases and aerosols from the Community Emissions Data System (CEDS)

NASA Astrophysics Data System (ADS)

Hoesly, Rachel M.; Smith, Steven J.; Feng, Leyang; Klimont, Zbigniew; Janssens-Maenhout, Greet; Pitkanen, Tyler; Seibert, Jonathan J.; Vu, Linh; Andres, Robert J.; Bolt, Ryan M.; Bond, Tami C.; Dawidowski, Laura; Kholod, Nazar; Kurokawa, June-ichi; Li, Meng; Liu, Liang; Lu, Zifeng; Moura, Maria Cecilia P.; O'Rourke, Patrick R.; Zhang, Qiang

2018-01-01

We present a new data set of annual historical (1750-2014) anthropogenic chemically reactive gases (CO, CH4, NH3, NOx, SO2, NMVOCs), carbonaceous aerosols (black carbon - BC, and organic carbon - OC), and CO2 developed with the Community Emissions Data System (CEDS). We improve upon existing inventories with a more consistent and reproducible methodology applied to all emission species, updated emission factors, and recent estimates through 2014. The data system relies on existing energy consumption data sets and regional and country-specific inventories to produce trends over recent decades. All emission species are consistently estimated using the same activity data over all time periods. Emissions are provided on an annual basis at the level of country and sector and gridded with monthly seasonality. These estimates are comparable to, but generally slightly higher than, existing global inventories. Emissions over the most recent years are more uncertain, particularly in low- and middle-income regions where country-specific emission inventories are less available. Future work will involve refining and updating these emission estimates, estimating emissions' uncertainty, and publication of the system as open-source software.

A community-based event delivery protocol in publish/subscribe systems for delay tolerant sensor networks.

PubMed

Liu, Nianbo; Liu, Ming; Zhu, Jinqi; Gong, Haigang

2009-01-01

The basic operation of a Delay Tolerant Sensor Network (DTSN) is to finish pervasive data gathering in networks with intermittent connectivity, while the publish/subscribe (Pub/Sub for short) paradigm is used to deliver events from a source to interested clients in an asynchronous way. Recently, extension of Pub/Sub systems in DTSNs has become a promising research topic. However, due to the unique frequent partitioning characteristic of DTSNs, extension of a Pub/Sub system in a DTSN is a considerably difficult and challenging problem, and there are no good solutions to this problem in published works. To ad apt Pub/Sub systems to DTSNs, we propose CED, a community-based event delivery protocol. In our design, event delivery is based on several unchanged communities, which are formed by sensor nodes in the network according to their connectivity. CED consists of two components: event delivery and queue management. In event delivery, events in a community are delivered to mobile subscribers once a subscriber comes into the community, for improving the data delivery ratio. The queue management employs both the event successful delivery time and the event survival time to decide whether an event should be delivered or dropped for minimizing the transmission overhead. The effectiveness of CED is demonstrated through comprehensive simulation studies.

Immunocontraceptive efficacy of synthetic peptides corresponding to major antigenic determinants of chicken riboflavin carrier protein in the female rats.

PubMed

Subramanian, S; Karande, A A; Adiga, P R

2000-09-01

Earlier studies have demonstrated that antibodies directed towards the N-terminal (residues 10-17) and C-terminal (residues 200-207) regions on chicken riboflavin carrier protein (RCP; 219 AA) are effective in pregnancy termination in rodents and sub-human primates. In the present study, the immunocontraceptive potential of three additional immunodominant sequences comprising of residues 33-49, 64 83 and 130-147 (CYA, CED and CGE peptides, respectively) of chicken RCP was investigated. The three antigenic peptides were synthesized by using Fmoc chemistry. Oligoclonal antibodies were generated in rabbits. Bioneutralizing capacity of these peptides was assessed by passive and active immunoneutralization studies. All the three peptides-specific antisera recognized their cognate epitopes on native RCP. When the affinity purified peptide IgG were administered on three consecutive days to pregnant rats (on days 10, 11 and 12), it was observed that the rats injected with CED and CGE-IgG failed to deliver any pups whereas the animals which received CYA IgG delivered normal pups. Active immunization of fertile female rats with CED or CGE peptide conferred protection from pregnancy. These results demonstrate the presence of two additional stretches in chicken RCP which can serve as mini-vaccines.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klumpp, John Allan; Bertelli, Luiz; Waters, Tom L.

For radionuclides such as plutonium and americium, detection of removable activity in the nose (i.e., nasal swab measurements) are frequently used to determine whether follow-up bioassay measurements are warranted following a potential intake. For this paper, the authors analyzed 429 nasal swab measurements taken following incidents or suspicious circumstances (such as an air monitor alarming) at Los Alamos National Laboratory (LANL) for which the dose was later evaluated using in vitro bioassay. Nasal swab measurements were found to be very poor predictors of dose and should not be used as such in the field. However, nasal swab measurements can bemore » indicative of whether a reliably detectable committed effective dose (CED) occurred. About 14% of nasal swab measurements between 1.25 and 16.7 Bq corresponded to CEDs greater than 1 mSv, so in general, positive nasal swabs always indicate that follow-up bioassay should be performed (positive nasal swabs less than 1.25 Bq are considered separately). This probability increased significantly for nasal swabs greater than 16.7 Bq. Only about 3% of nasal swabs with no detectable activity (NDA) corresponded to reliably detectable CEDs. As a result, a nasal swab with NDA is therefore necessary, but not sufficient, to negate the need for a follow-up bioassay if it was collected following other workplace indicators of a potential intake.« less

IER 203 CED-2 Report: LLNL Final Design for BERP Ball With a Composite Reflector of Thin Polyethylene Backed by Nickel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Percher, C. M.; Heinrichs, D. P.; Kim, S. K.

2016-07-18

This report documents the results of final design (CED-2) for IER 203, BERP Ball Composite Reflection, and focuses on critical configurations with a 4.5 kg α-phase plutonium sphere reflected by a combination of thin high-density polyethylene (HDPE) backed by a thick nickel reflector. The Lawrence Livermore National Laboratory’s (LLNL’s) Nuclear Criticality Safety Division, in support of fissile material operations, calculated surprisingly reactive configurations when a fissile core was surrounded by a thin, moderating reflector backed by a thick metal reflector. These composite reflector configurations were much more reactive than either of the single reflector materials separately. The calculated findings havemore » resulted in a stricter-than-anticipated criticality control set, impacting programmatic work. IER 203 was requested in response to these seemingly anomalous calculations to see if the composite reflection effect could be shown experimentally. This report focuses on the Beryllium Reflected Plutonium (BERP) ball as a fissile material core reflected by polyethylene and nickel. A total of four critical configurations were designed as part of CED-2. Fabrication costs are estimated to be $98,500, largely due to the cost of the large nickel reflectors. The IER 203 experiments could reasonably be expected to begin in early FY2017.« less

Cumulative effective radiation dose received by blunt trauma patients arriving to a military level I trauma center from point of injury and interhospital transfers.

PubMed

Van Arnem, Kerri A; Supinski, David P; Tucker, Jonathan E; Varney, Shawn

2016-12-01

Trauma patients sustaining blunt injuries are exposed to multiple radiologic studies. Evidence indicates that the risk of cancer from exposure to ionizing radiation rises in direct proportion to the cumulative effective dose (CED) received. The purpose of this study is to quantify the amount of ionizing radiation accumulated when arriving directly from point of injury to San Antonio Military Medical Center (SAMMC), a level I trauma center, compared with those transferred from other facilities. A retrospective record review was conducted from 1st January 2010 through 31st December 2012. The SAMMC trauma registry, electronic medical records, and the digital radiology imaging system were searched for possible candidates. The medical records were then analyzed for sex, age, mechanism of injury, received directly from point of injury (direct group), transfer from another medical facility (transfer group), computed tomographic scans received, dose-length product, CED of radiation, and injury severity score. A diagnostic imaging physicist then calculated the estimated CED each subject received based on the dose-length product of each computed tomographic scan. A total of 300 patients were analyzed, with 150 patients in the direct group and 150 patients in the transfer group. Both groups were similar in age and sex. Patients in the transfer group received a significantly greater CED of radiation compared with the direct group (mean, 37.6 mSv vs 28 mSv; P=.001). The radiation received in the direct group correlates with a lifetime attributable risk (LAR) of 1 in 357 compared with the transfer group with an increase in LAR to 1 in 266. Patients transferred to our facility received a 34% increase in ionizing radiation compared with patients brought directly from the injury scene. This increased dose of ionizing radiation contributes to the LAR of cancer and needs to be considered before repeating imaging studies. III. Published by Elsevier Inc.

Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial.

PubMed

Leffler, Daniel A; Kelly, Ciaran P; Green, Peter H R; Fedorak, Richard N; DiMarino, Anthony; Perrow, Wendy; Rasmussen, Henrik; Wang, Chao; Bercik, Premysl; Bachir, Natalie M; Murray, Joseph A

2015-06-01

Celiac disease (CeD) is a prevalent autoimmune condition. Recurrent signs and symptoms are common despite treatment with a gluten-free diet (GFD), yet no approved or proven nondietary treatment is available. In this multicenter, randomized, double-blind, placebo-controlled study, we assessed larazotide acetate 0.5, 1, or 2 mg 3 times daily to relieve ongoing symptoms in 342 adults with CeD who had been on a GFD for 12 months or longer and maintained their current GFD during the study. The study included a 4-week placebo run-in, 12 weeks of treatment, and a 4-week placebo run-out phase. The primary end point was the difference in average on-treatment Celiac Disease Gastrointestinal Symptom Rating Scale score. The primary end point was met with the 0.5-mg dose of larazotide acetate, with fewer symptoms compared with placebo by modified intention to treat (n = 340) (analysis of covariance, P = .022; mixed model for repeated measures, P = .005). The 0.5-mg dose showed an effect on exploratory end points including a 26% decrease in celiac disease patient-reported outcome symptomatic days (P = .017), a 31% increase in improved symptom days (P = .034), a 50% or more reduction from baseline of the weekly average abdominal pain score for 6 or more of 12 weeks of treatment (P = .022), and a decrease in the nongastrointestinal symptoms of headache and tiredness (P = .010). The 1- and 2-mg doses were no different than placebo for any end point. Safety was comparable with placebo. Larazotide acetate 0.5 mg reduced signs and symptoms in CeD patients on a GFD better than a GFD alone. Although results were mixed, this study was a successful trial of a novel therapeutic agent targeting tight junction regulation in patients with CeD who are symptomatic despite a GFD. Clinicaltrials.gov: NCT01396213. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Minimally invasive convection-enhanced delivery of biologics into dorsal root ganglia: validation in the pig model and prospective modeling in humans. Technical note.

PubMed

Pleticha, Josef; Maus, Timothy P; Christner, Jodie A; Marsh, Michael P; Lee, Kendall H; Hooten, W Michael; Beutler, Andreas S

2014-10-01

Dorsal root ganglia (DRG) are critical anatomical structures involved in nociception. Intraganglionic (IG) drug delivery is therefore an important route of administration for novel analgesic therapies. Although IG injection in large animal models is highly desirable for preclinical biodistribution and toxicology studies of new drugs, no method to deliver pharmaceutical agents into the DRG has been reported in any large species. The present study describes a minimally invasive technique of IG agent delivery in domestic swine, one of the most common large animal models. The technique utilizes CT guidance for DRG targeting and a custom-made injection assembly for convection enhanced delivery (CED) of therapeutic agents directly into DRG parenchyma. The DRG were initially visualized by CT myelography to determine the optimal access route to the DRG. The subsequent IG injection consisted of 3 steps. First, a commercially available guide needle was advanced to a position dorsolateral to the DRG, and the dural root sleeve was punctured, leaving the guide needle contiguous with, but not penetrating, the DRG. Second, the custom-made stepped stylet was inserted through the guide needle into the DRG parenchyma. Third, the stepped stylet was replaced by the custom-made stepped needle, which was used for the IG CED. Initial dye injections performed in pig cadavers confirmed the accuracy of DRG targeting under CT guidance. Intraganglionic administration of adeno-associated virus in vivo resulted in a unilateral transduction of the injected DRG, with 33.5% DRG neurons transduced. Transgene expression was also found in the dorsal root entry zones at the corresponding spinal levels. The results thereby confirm the efficacy of CED by the stepped needle and a selectivity of DRG targeting. Imaging-based modeling of the procedure in humans suggests that IG CED may be translatable to the clinical setting.

Convection-enhanced drug delivery of interleukin-4 Pseudomonas exotoxin (PRX321): increased distribution and magnetic resonance monitoring.

PubMed

Mardor, Y; Last, D; Daniels, D; Shneor, R; Maier, S E; Nass, D; Ram, Z

2009-08-01

Convection-enhanced drug delivery (CED) enables achieving a drug concentration within brain tissue and brain tumors that is orders of magnitude higher than by systemic administration. Previous phase I/II clinical trials using intratumoral convection of interleukin-4 Pseudomonas exotoxin (PRX321) have demonstrated an acceptable safety and toxicity profile with promising signs of therapeutic activity. The present study was designed to assess the distribution efficiency and toxicity of this PRX321 using magnetic resonance imaging (MRI) and to test whether reformulation with increased viscosity could enhance drug distribution. Convection of low- [0.02% human serum albumin (HSA)] and high-viscosity (3% HSA) infusates mixed with gadolinium-diethylenetriamine pentaacetic acid and PRX321 were compared with low- and high-viscosity infusates without the drug, in normal rat brains. MRI was used for assessment of drug distribution and detection of early and late toxicity. Representative brain samples were subjected to histological examination. Distribution volumes calculated from the magnetic resonance images showed that the average distribution of 0.02% HSA was larger than that of 0.02% HSA with PRX321 by a factor of 1.98 (p < 0.02). CED of 3.0% HSA, with or without PRX321, tripled the volume of distribution compared with 0.02% HSA with PRX321 (p < 0.015). No drug-related toxicity was detected. These results suggest that the impeded convection of the PRX321 infusate used in previous clinical trials can be reversed by increasing infusate viscosity and lead to tripling of the volume of distribution. This effect was not associated with any detectable toxicity. A similar capability to reverse impeded convection was also demonstrated in a CED model using acetic acid. These results will be implemented in an upcoming phase IIb PRX321 CED trial with a high-viscosity infusate.

Earthquake Energy Dissipation in Light of High-Velocity, Slip-Pulse Shear Experiments

NASA Astrophysics Data System (ADS)

Reches, Z.; Liao, Z.; Chang, J. C.

2014-12-01

We investigated the energy dissipation during earthquakes by analysis of high-velocity shear experiments conducted on room-dry, solid samples of granite, tonalite, and dolomite sheared at slip-velocity of 0.0006-1m/s, and normal stress of 1-11.5MPa. The experimental fault were loaded in one of three modes: (1) Slip-pulse of abrupt, intense acceleration followed by moderate deceleration; (2) Impact by a spinning, heavy flywheel (225 kg); and (3) Constant velocity loading. We refer to energy dissipation in terms of power-density (PD=shear stress*slip-velocity; units of MW/m^2), and Coulomb-energy-density (CED= mechanical energy/normal stress; units of m). We present two aspects: Relative energy dissipation of the above loading modes, and relative energy dissipation between impact experiments and moderate earthquakes. For the first aspect, we used: (i) the lowest friction coefficient of the dynamic weakening; (ii) the work dissipated before reaching the lowest friction; and (iii) the cumulative mechanical work during the complete run. The results show that the slip-pulse/impact modes are energy efficient relatively to the constant-velocity mode as manifested by faster, more intense weakening and 50-90% lower energy dissipation. Thus, for a finite amount of pre-seismic crustal energy, the efficiency of slip-pulse would amplify earthquake instability. For the second aspect, we compare the experimental CED of the impact experiments to the reported breakdown energy (EG) of moderate earthquakes, Mw = 5.6 to 7.2 (Chang et al., 2012). In is commonly assumed that the seismic EG is a small fraction of the total earthquake energy, and as expected in 9 out of 11 examined earthquakes, EG was 0.005 to 0.07 of the experimental CED. We thus speculate that the experimental relation of Coulomb-energy-density to total slip distance, D, CED = 0.605 × D^0.933, is a reasonable estimate of total earthquake energy, a quantity that cannot be determined from seismic data.

Adding Four- Dimensional Data Assimilation (aka grid ...

EPA Pesticide Factsheets

Adding four-dimensional data assimilation (a.k.a. grid nudging) to MPAS.The U.S. Environmental Protection Agency is investigating the use of MPAS as the meteorological driver for its next-generation air quality model. To function as such, MPAS needs to operate in a diagnostic mode in much the same manner as the current meteorological driver, the Weather Research and Forecasting (WRF) model. The WRF operates in diagnostic mode using Four-Dimensional Data Assimilation, also known as "grid nudging". MPAS version 4.0 has been modified with the addition of an FDDA routine to the standard physics drivers to nudge the state variables for wind, temperature and water vapor towards MPAS initialization fields defined at 6-hour intervals from GFS-derived data. The results to be shown demonstrate the ability to constrain MPAS simulations to known historical conditions and thus provide the U.S. EPA with a practical meteorological driver for global-scale air quality simulations. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-support tools, and models to be applied to media-specific or receptor-specific problem areas. CED uses modeling-based approaches to characterize exposures, evaluate fate and transport, and support environmental diagnostics/forensics with input from multiple data sources. It also develops media- and receptor-specific models, process models, and decision support tools for use bo

Canine spontaneous glioma: A translational model system for convection-enhanced delivery

PubMed Central

Dickinson, Peter J.; LeCouteur, Richard A.; Higgins, Robert J.; Bringas, John R.; Larson, Richard F.; Yamashita, Yoji; Krauze, Michal T.; Forsayeth, John; Noble, Charles O.; Drummond, Daryl C.; Kirpotin, Dmitri B.; Park, John W.; Berger, Mitchel S.; Bankiewicz, Krystof S.

2010-01-01

Canine spontaneous intracranial tumors bear striking similarities to their human tumor counterparts and have the potential to provide a large animal model system for more realistic validation of novel therapies typically developed in small rodent models. We used spontaneously occurring canine gliomas to investigate the use of convection-enhanced delivery (CED) of liposomal nanoparticles, containing topoisomerase inhibitor CPT-11. To facilitate visualization of intratumoral infusions by real-time magnetic resonance imaging (MRI), we included identically formulated liposomes loaded with Gadoteridol. Real-time MRI defined distribution of infusate within both tumor and normal brain tissues. The most important limiting factor for volume of distribution within tumor tissue was the leakage of infusate into ventricular or subarachnoid spaces. Decreased tumor volume, tumor necrosis, and modulation of tumor phenotype correlated with volume of distribution of infusate (Vd), infusion location, and leakage as determined by real-time MRI and histopathology. This study demonstrates the potential for canine spontaneous gliomas as a model system for the validation and development of novel therapeutic strategies for human brain tumors. Data obtained from infusions monitored in real time in a large, spontaneous tumor may provide information, allowing more accurate prediction and optimization of infusion parameters. Variability in Vd between tumors strongly suggests that real-time imaging should be an essential component of CED therapeutic trials to allow minimization of inappropriate infusions and accurate assessment of clinical outcomes. PMID:20488958

Camurati-Engelmann disease: unique variant featuring a novel mutation in TGFβ1 encoding transforming growth factor beta 1 and a missense change in TNFSF11 encoding RANK ligand.

PubMed

Whyte, Michael P; Totty, William G; Novack, Deborah V; Zhang, Xiafang; Wenkert, Deborah; Mumm, Steven

2011-05-01

We report a 32-year-old man and his 59-year-old mother with a unique and extensive variant of Camurati-Engelmann disease (CED) featuring histopathological changes of osteomalacia and alterations within TGFβ1 and TNFSF11 encoding TGFβ1 and RANKL, respectively. He suffered leg pain and weakness since childhood and reportedly grew until his late 20s, reaching 7 feet in height. He had deafness, perforated nasal septum, torus palatinus, disproportionately long limbs with knock-knees, low muscle mass, and pseudoclubbing. Radiographs revealed generalized skeletal abnormalities, including wide bones and cortical and trabecular bone thickening in keeping with CED, except that long bone ends were also affected. Lumbar spine and hip BMD Z-scores were + 7.7 and + 4.4, respectively. Biochemical markers of bone turnover were elevated. Hypocalciuria accompanied low serum 25-hydroxyvitamin D (25[OH]D) levels. Pituitary hypogonadism and low serum insulin-like growth factor (IGF)-1 were present. Karyotype was normal. Despite vitamin D repletion, iliac crest histology revealed severe osteomalacia. Exon 1 of TNFRSF11A (RANK), exons 2, 3, and 4 of LRP5, and all coding exons and adjacent mRNA splice junctions of TNFRSF11B (OPG), SQSTM1 (sequestosome 1), and TNSALP (tissue nonspecific alkaline phosphatase) were intact. His asymptomatic and less dysmorphic 5'11″ mother, also with low serum 25(OH)D, had milder clinical, radiological, biochemical, and histopathological findings. Both individuals were heterozygous for a novel 12-bp duplication (c.27_38dup, p.L10_L13dup) in exon 1 of TGFβ1, predicting four additional leucine residues in the latency-associated-peptide segment of TGFβ1, consistent with CED. The son was also homozygous for a single base transversion in TNFSF11, predicting a nonconservative amino acid change (c.107C > G, p.Pro36Arg) in the intracellular domain of RANKL that was heterozygous in his nonconsanguineous parents. This TNFSF11 variant was not found in the SNP Database, nor in published TNFSF11 association studies, but it occurred in four of the 134 TNFSF11 alleles (3.0%) we tested randomly among individuals without CED. Perhaps the unique phenotype of this CED family is conditioned by altered RANKL activity. Copyright © 2011 American Society for Bone and Mineral Research.

A model for optimizing delivery of targeted radionuclide therapies into resection cavity margins for the treatment of primary brain cancers.

PubMed

Raghavan, Raghu; Howell, Roger W; Zalutsky, Michael R

2017-06-01

Radionuclides conjugated to molecules that bind specifically to cancer cells are of great interest as a means to increase the specificity of radiotherapy. Currently, the methods to disseminate these targeted radiotherapeutics have been either systemic delivery or by bolus injection into the tumor or tumor resection cavity. Herein we model a potentially more efficient method of delivery, namely pressure-driven fluid flow, called convection-enhanced delivery (CED), where a device infuses the molecules in solution (or suspension) directly into the tissue of interest. In particular, we focus on the setting of primary brain cancer after debulking surgery, where the tissue margins surrounding the surgical resection cavity are infiltrated with tumor cells and the most frequent sites of tumor recurrence. We develop the combination of fluid flow, chemical kinetics, and radiation dose models needed to examine such protocols. We focus on Auger electron-emitting radionuclides (e.g. 67 Ga, 77 Br, 111 In, 125 I, 123 I, 193m Pt, 195m Pt) whose short range makes them ideal for targeted therapy in this setting of small foci of tumor spread within normal tissue. By solving these model equations, we confirm that a CED protocol is promising in allowing sufficient absorbed dose to destroy cancer cells with minimal absorbed dose to normal cells at clinically feasible activity levels. We also show that Auger emitters are ideal for this purpose while the longer range alpha particle emitters fail to meet criteria for effective therapy (as neither would energetic beta particle emitters). The model is used with simplified assumptions on the geometry and homogeneity of brain tissue to allow semi-analytic solutions to be displayed, and with the purpose of a first examination of this new delivery protocol proposed for radionuclide therapy. However, we emphasize that it is immediately extensible to personalized therapy treatment planning as we have previously shown for conventional CED, at the price of requiring a fully numerical computerized approach.

Therapeutic Ultrasound Enhancement of Drug Delivery to Soft Tissues

NASA Astrophysics Data System (ADS)

Lewis, George; Wang, Peng; Lewis, George; Olbricht, William

2009-04-01

Effects of exposure to 1.58 MHz focused ultrasound on transport of Evans Blue Dye (EBD) in soft tissues are investigated when an external pressure gradient is applied to induce convective flow through the tissue. The magnitude of the external pressure gradient is chosen to simulate conditions in brain parenchyma during convection-enhanced drug delivery (CED) to the brain. EBD uptake and transport are measured in equine brain, avian muscle and agarose brain-mimicking phantoms. Results show that ultrasound enhances EBD uptake and transport, and the greatest enhancement occurs when the external pressure gradient is applied. The results suggest that exposure of the brain parenchyma to ultrasound could enhance penetration of material infused into the brain during CED therapy.

M.H.D. Diagnostics - Gas Temperature and Emittance

DTIC Science & Technology

1960-04-06

AD-A280 700 DTIC $ELECTE M.H.D. DIAGNOSTICS - GAS TEMPERATURE AND EMITTANCE by W. E. HILL REPORT NO. 60GL63 APRIL 6, 1960t i T i n n e iii, ic ie. n ...Accesion For NTIS CRA&I DTIC TAB Una;Olow;ced Justification Distribution y Availability C,.. Avail ard C.A Dist Special GENERAL* ELECTRIC _ l I SCHOWCTADY...from the Instrumen- tation viewpoint. Some of the instrumentation techniques developed $ n the allied field of combustion instrumentation can be expected

Interpretation of nasal swab measurements following suspected releases of actinide aerosols

DOE PAGES

Klumpp, John Allan; Bertelli, Luiz; Waters, Tom L.

2017-05-01

For radionuclides such as plutonium and americium, detection of removable activity in the nose (i.e., nasal swab measurements) are frequently used to determine whether follow-up bioassay measurements are warranted following a potential intake. For this paper, the authors analyzed 429 nasal swab measurements taken following incidents or suspicious circumstances (such as an air monitor alarming) at Los Alamos National Laboratory (LANL) for which the dose was later evaluated using in vitro bioassay. Nasal swab measurements were found to be very poor predictors of dose and should not be used as such in the field. However, nasal swab measurements can bemore » indicative of whether a reliably detectable committed effective dose (CED) occurred. About 14% of nasal swab measurements between 1.25 and 16.7 Bq corresponded to CEDs greater than 1 mSv, so in general, positive nasal swabs always indicate that follow-up bioassay should be performed (positive nasal swabs less than 1.25 Bq are considered separately). This probability increased significantly for nasal swabs greater than 16.7 Bq. Only about 3% of nasal swabs with no detectable activity (NDA) corresponded to reliably detectable CEDs. As a result, a nasal swab with NDA is therefore necessary, but not sufficient, to negate the need for a follow-up bioassay if it was collected following other workplace indicators of a potential intake.« less

Engineering a vascularized collagen-β-tricalcium phosphate graft using an electrochemical approach.

PubMed

Kang, Yunqing; Mochizuki, Naoto; Khademhosseini, Ali; Fukuda, Junji; Yang, Yunzhi

2015-01-01

Vascularization of three-dimensional large synthetic grafts for tissue regeneration remains a significant challenge. Here we demonstrate an electrochemical approach, named the cell electrochemical detachment (CED) technique, to form an integral endothelium and use it to prevascularize a collagen-β-tricalcium phosphate (β-TCP) graft. The CED technique electrochemically detached an integral endothelium from a gold-coated glass rod to a collagen-infiltrated, channeled, macroporous β-TCP scaffold, forming an endothelium-lined microchannel containing graft upon removal of the rod. The in vitro results from static and perfusion culture showed that the endothelium robustly emanated microvascular sprouting and prevascularized the entire collagen/β-TCP integrated graft. The in vivo subcutaneous implantation studies showed that the prevascularized collagen/β-TCP grafts established blood flow originating from the endothelium-lined microchannel within a week, and the blood flow covered more areas in the graft over time. In addition, many blood vessels invaded the prevascularized collagen/β-TCP graft and the in vitro preformed microvascular networks anastomosed with the host vasculature, while collagen alone without the support of rigid ceramic scaffold showed less blood vessel invasion and anastomosis. These results suggest a promising strategy for effectively vascularizing large tissue-engineered grafts by integrating multiple hydrogel-based CED-engineered endothelium-lined microchannels into a rigid channeled macroporous scaffold. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Life cycle assessment of a power tower concentrating solar plant and the impacts of key design alternatives.

PubMed

Whitaker, Michael B; Heath, Garvin A; Burkhardt, John J; Turchi, Craig S

2013-06-04

A hybrid life cycle assessment (LCA) is used to evaluate four sustainability metrics over the life cycle of a power tower concentrating solar power (CSP) facility: greenhouse gas (GHG) emissions, water consumption, cumulative energy demand (CED), and energy payback time (EPBT). The reference design is for a dry-cooled, 106 MW(net) power tower facility located near Tucson, AZ that uses a mixture of mined nitrate salts as the heat transfer fluid and storage medium, a two-tank thermal energy storage system designed for six hours of full load-equivalent storage, and receives auxiliary power from the local electric grid. A thermocline-based storage system, synthetically derived salts, and natural gas auxiliary power are evaluated as design alternatives. Over its life cycle, the reference plant is estimated to have GHG emissions of 37 g CO2eq/kWh, consume 1.4 L/kWh of water and 0.49 MJ/kWh of energy, and have an EPBT of 15 months. Using synthetic salts is estimated to increase GHG emissions by 12%, CED by 7%, and water consumption by 4% compared to mined salts. Natural gas auxiliary power results in greater than 10% decreases in GHG emissions, water consumption, and CED. The thermocline design is most advantageous when coupled with the use of synthetic salts.

Galectins in Intestinal Inflammation: Galectin-1 Expression Delineates Response to Treatment in Celiac Disease Patients

PubMed Central

Sundblad, Victoria; Quintar, Amado A.; Morosi, Luciano G.; Niveloni, Sonia I.; Cabanne, Ana; Smecuol, Edgardo; Mauriño, Eduardo; Mariño, Karina V.; Bai, Julio C.; Maldonado, Cristina A.; Rabinovich, Gabriel A.

2018-01-01

Galectins, a family of animal lectins characterized by their affinity for N-acetyllactosamine-enriched glycoconjugates, modulate several immune cell processes shaping the course of innate and adaptive immune responses. Through interaction with a wide range of glycosylated receptors bearing complex branched N-glycans and core 2-O-glycans, these endogenous lectins trigger distinct signaling programs thereby controling immune cell activation, differentiation, recruitment and survival. Given the unique features of mucosal inflammation and the differential expression of galectins throughout the gastrointestinal tract, we discuss here key findings on the role of galectins in intestinal inflammation, particularly Crohn’s disease, ulcerative colitis, and celiac disease (CeD) patients, as well as in murine models resembling these inflammatory conditions. In addition, we present new data highlighting the regulated expression of galectin-1 (Gal-1), a proto-type member of the galectin family, during intestinal inflammation in untreated and treated CeD patients. Our results unveil a substantial upregulation of Gal-1 accompanying the anti-inflammatory and tolerogenic response associated with gluten-free diet in CeD patients, suggesting a major role of this lectin in favoring resolution of inflammation and restoration of mucosal homeostasis. Thus, a coordinated network of galectins and their glycosylated ligands, exerting either anti-inflammatory or proinflammatory responses, may influence the interplay between intestinal epithelial cells and the highly specialized gut immune system in physiologic and pathologic settings. PMID:29545799

Galectins in Intestinal Inflammation: Galectin-1 Expression Delineates Response to Treatment in Celiac Disease Patients.

PubMed

Sundblad, Victoria; Quintar, Amado A; Morosi, Luciano G; Niveloni, Sonia I; Cabanne, Ana; Smecuol, Edgardo; Mauriño, Eduardo; Mariño, Karina V; Bai, Julio C; Maldonado, Cristina A; Rabinovich, Gabriel A

2018-01-01

Galectins, a family of animal lectins characterized by their affinity for N-acetyllactosamine-enriched glycoconjugates, modulate several immune cell processes shaping the course of innate and adaptive immune responses. Through interaction with a wide range of glycosylated receptors bearing complex branched N-glycans and core 2-O-glycans, these endogenous lectins trigger distinct signaling programs thereby controling immune cell activation, differentiation, recruitment and survival. Given the unique features of mucosal inflammation and the differential expression of galectins throughout the gastrointestinal tract, we discuss here key findings on the role of galectins in intestinal inflammation, particularly Crohn's disease, ulcerative colitis, and celiac disease (CeD) patients, as well as in murine models resembling these inflammatory conditions. In addition, we present new data highlighting the regulated expression of galectin-1 (Gal-1), a proto-type member of the galectin family, during intestinal inflammation in untreated and treated CeD patients. Our results unveil a substantial upregulation of Gal-1 accompanying the anti-inflammatory and tolerogenic response associated with gluten-free diet in CeD patients, suggesting a major role of this lectin in favoring resolution of inflammation and restoration of mucosal homeostasis. Thus, a coordinated network of galectins and their glycosylated ligands, exerting either anti-inflammatory or proinflammatory responses, may influence the interplay between intestinal epithelial cells and the highly specialized gut immune system in physiologic and pathologic settings.

Convection-enhanced delivery of AAV2 in white matter--a novel method for gene delivery to cerebral cortex.

PubMed

Barua, N U; Woolley, M; Bienemann, A S; Johnson, D; Wyatt, M J; Irving, C; Lewis, O; Castrique, E; Gill, S S

2013-10-30

Convection-enhanced delivery (CED) is currently under investigation for delivering therapeutic agents to subcortical targets in the brain. Direct delivery of therapies to the cerebral cortex, however, remains a significant challenge. We describe a novel method of targeting adeno-associated viral vector (AAV) mediated gene therapies to specific cerebral cortical regions by performing high volume, high flow rate infusions into underlying white matter in a large animal (porcine) model. Infusion volumes of up to 700 μl at flow rates as high as 10 μl/min were successfully performed in white matter without adverse neurological sequelae. Co-infusion of AAV2/5-GFP with 0.2% Gadolinium in artificial CSF confirmed transgene expression in the deep layers of cerebral cortex overlying the infused areas of white matter. AAV-mediated gene therapies have been previously targeted to the cerebral cortex by performing intrathalamic CED and exploiting axonal transport. The novel method described in this study facilitates delivery of gene therapies to specific regions of the cerebral cortex without targeting deep brain structures. AAV-mediated gene therapies can be targeted to specific cortical regions by performing CED into underlying white matter. This technique could be applied to the treatment of neurological disorders characterised by cerebral cortical degeneration. Copyright © 2013 Elsevier B.V. All rights reserved.

Convection-enhanced delivery of MANF--volume of distribution analysis in porcine putamen and substantia nigra.

PubMed

Barua, N U; Bienemann, A S; Woolley, M; Wyatt, M J; Johnson, D; Lewis, O; Irving, C; Pritchard, G; Gill, S

2015-10-15

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a 20kDa human protein which has both neuroprotective and neurorestorative activity on dopaminergic neurons and therefore may have application for the treatment of Parkinson's Disease. The aims of this study were to determine the translational potential of convection-enhanced delivery (CED) of MANF for the treatment of PD by studying its distribution in porcine putamen and substantia nigra and to correlate histological distribution with co-infused gadolinium-DTPA using real-time magnetic resonance imaging. We describe the distribution of MANF in porcine putamen and substantia nigra using an implantable CED catheter system using co-infused gadolinium-DTPA to allow real-time MRI tracking of infusate distribution. The distribution of gadolinium-DTPA on MRI correlated well with immunohistochemical analysis of MANF distribution. Volumetric analysis of MANF IHC staining indicated a volume of infusion (Vi) to volume of distribution (Vd) ratio of 3 in putamen and 2 in substantia nigra. This study confirms the translational potential of CED of MANF as a novel treatment strategy in PD and also supports the co-infusion of gadolinium as a proxy measure of MANF distribution in future clinical studies. Further study is required to determine the optimum infusion regime, flow rate and frequency of infusions in human trials. Copyright © 2015 Elsevier B.V. All rights reserved.

Distribution of AAV-TK following intracranial convection-enhanced delivery into rats.

PubMed

Cunningham, J; Oiwa, Y; Nagy, D; Podsakoff, G; Colosi, P; Bankiewicz, K S

2000-01-01

Adeno-associated virus (AAV)-based vectors are being tested in animal models as viable treatments for glioma and neurodegenerative disease and could potentially be employed to target a variety of central nervous system disorders. The relationship between dose of injected vector and its resulting distribution in brain tissue has not been previously reported nor has the most efficient method of delivery been determined. Here we report that convection-enhanced delivery (CED) of 2.5 x 10(8), 2.5 x 10(9), or 2.5 x 10(10) particles of AAV-thymidine kinase (AAV-TK) into rat brain revealed a clear dose response. In the high-dose group, a volume of 300 mm3 of brain tissue was partially transduced. Results showed that infusion pump and subcutaneous osmotic pumps were both capable of delivering vector via CED and that total particle number was the most important determining factor in obtaining efficient expression. Results further showed differences in histopathology between the delivery groups. While administration of vector using infusion pump had relatively benign effects, the use of osmotic pumps resulted in notable toxicity to the surrounding brain tissue. To determine tissue distribution of vector following intracranial delivery, PCR analysis was performed on tissues from rats that received high doses of AAV-TK. Three weeks following CED, vector could be detected in both hemispheres of the brain, spinal cord, spleen, and kidney.

15 CFR 995.14 - Auditing.

Code of Federal Regulations, 2011 CFR

2011-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA HYDROGRAPHIC PRODUCTS Certification and Procedures § 995.14 Auditing. NOAA reserves the right to audit CED or...

15 CFR 995.14 - Auditing.

Code of Federal Regulations, 2014 CFR

2014-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA HYDROGRAPHIC PRODUCTS Certification and Procedures § 995.14 Auditing. NOAA reserves the right to audit CED or...

15 CFR 995.14 - Auditing.

Code of Federal Regulations, 2012 CFR

2012-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA HYDROGRAPHIC PRODUCTS Certification and Procedures § 995.14 Auditing. NOAA reserves the right to audit CED or...

15 CFR 995.14 - Auditing.

Code of Federal Regulations, 2013 CFR

2013-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA HYDROGRAPHIC PRODUCTS Certification and Procedures § 995.14 Auditing. NOAA reserves the right to audit CED or...

Academic Achievement in Physics-Chemistry: The Predictive Effect of Attitudes and Reasoning Abilities.

PubMed

Vilia, Paulo N; Candeias, Adelinda A; Neto, António S; Franco, Maria Da Glória S; Melo, Madalena

2017-01-01

Science education plays a critical role as political priority due to its fundamental importance in engaging students to pursue technological careers considered essential in modern societies, in order to face scientific development challenges. High-level achievement on science education and positive attitudes toward science constitutes a crucial challenge for formal education. Several studies indicate close relationships between students' attitudes, cognitive abilities, and academic achievement. The main purpose of this study is to analyze the impact of student's attitudes toward the school discipline of Physics and Chemistry and their reasoning abilities on academic achievement on that school subject, among Portuguese 9th grade students using the data collected during the Project Academic Performance and Development: a longitudinal study on the effects of school transitions in Portuguese students (PTDC/CPE-CED/104884/2008). The participants were 470 students (267 girls - 56.8% and 203 boys - 43.2%), aged 14-16 years old (μ = 14.3 ± 0.58). The attitude data were collected using the Attitude toward Physics-Chemistry Questionnaire (ATPCQ) and, the Reasoning Test Battery (RTB) was used to assess the students reasoning abilities. Achievement was measured using the students' quarterly (9-week) grades in the physics and chemistry subject. The relationships between the attitude dimensions toward Physics-chemistry and the reasoning dimensions and achievement in each of the three school terms were assessed by multiple regression stepwise analyses and standardized regression coefficients (β), calculated with IBM SPSS Statistics 21 software. Both variables studied proved to be significant predictor variables of school achievement. The models obtained from the use of both variables were always stronger accounting for higher proportions of student's grade variations. The results show that ATPCQ and RTB had a significantly positive relationship with student's achievement in Physics-chemistry, indicating that both attitudinal and cognitive variables should be taken into account on science education as well as in educative intervention.

Academic Achievement in Physics-Chemistry: The Predictive Effect of Attitudes and Reasoning Abilities

PubMed Central

Vilia, Paulo N.; Candeias, Adelinda A.; Neto, António S.; Franco, Maria Da Glória S.; Melo, Madalena

2017-01-01

Science education plays a critical role as political priority due to its fundamental importance in engaging students to pursue technological careers considered essential in modern societies, in order to face scientific development challenges. High-level achievement on science education and positive attitudes toward science constitutes a crucial challenge for formal education. Several studies indicate close relationships between students’ attitudes, cognitive abilities, and academic achievement. The main purpose of this study is to analyze the impact of student’s attitudes toward the school discipline of Physics and Chemistry and their reasoning abilities on academic achievement on that school subject, among Portuguese 9th grade students using the data collected during the Project Academic Performance and Development: a longitudinal study on the effects of school transitions in Portuguese students (PTDC/CPE-CED/104884/2008). The participants were 470 students (267 girls – 56.8% and 203 boys – 43.2%), aged 14–16 years old (μ = 14.3 ± 0.58). The attitude data were collected using the Attitude toward Physics-Chemistry Questionnaire (ATPCQ) and, the Reasoning Test Battery (RTB) was used to assess the students reasoning abilities. Achievement was measured using the students’ quarterly (9-week) grades in the physics and chemistry subject. The relationships between the attitude dimensions toward Physics-chemistry and the reasoning dimensions and achievement in each of the three school terms were assessed by multiple regression stepwise analyses and standardized regression coefficients (β), calculated with IBM SPSS Statistics 21 software. Both variables studied proved to be significant predictor variables of school achievement. The models obtained from the use of both variables were always stronger accounting for higher proportions of student’s grade variations. The results show that ATPCQ and RTB had a significantly positive relationship with student’s achievement in Physics-chemistry, indicating that both attitudinal and cognitive variables should be taken into account on science education as well as in educative intervention. PMID:28701978

Imaging of convection enhanced delivery of toxins in humans.

PubMed

Mehta, Ankit I; Choi, Bryan D; Raghavan, Raghu; Brady, Martin; Friedman, Allan H; Bigner, Darell D; Pastan, Ira; Sampson, John H

2011-03-01

Drug delivery of immunotoxins to brain tumors circumventing the blood brain barrier is a significant challenge. Convection-enhanced delivery (CED) circumvents the blood brain barrier through direct intracerebral application using a hydrostatic pressure gradient to percolate therapeutic compounds throughout the interstitial spaces of infiltrated brain and tumors. The efficacy of CED is determined through the distribution of the therapeutic agent to the targeted region. The vast majority of patients fail to receive a significant amount of coverage of the area at risk for tumor recurrence. Understanding this challenge, it is surprising that so little work has been done to monitor the delivery of therapeutic agents using this novel approach. Here we present a review of imaging in convection enhanced delivery monitoring of toxins in humans, and discuss future challenges in the field.

Imaging of Convection Enhanced Delivery of Toxins in Humans

PubMed Central

Mehta, Ankit I.; Choi, Bryan D.; Raghavan, Raghu; Brady, Martin; Friedman, Allan H.; Bigner, Darell D.; Pastan, Ira; Sampson, John H.

2011-01-01

Drug delivery of immunotoxins to brain tumors circumventing the blood brain barrier is a significant challenge. Convection-enhanced delivery (CED) circumvents the blood brain barrier through direct intracerebral application using a hydrostatic pressure gradient to percolate therapeutic compounds throughout the interstitial spaces of infiltrated brain and tumors. The efficacy of CED is determined through the distribution of the therapeutic agent to the targeted region. The vast majority of patients fail to receive a significant amount of coverage of the area at risk for tumor recurrence. Understanding this challenge, it is surprising that so little work has been done to monitor the delivery of therapeutic agents using this novel approach. Here we present a review of imaging in convection enhanced delivery monitoring of toxins in humans, and discuss future challenges in the field. PMID:22069706

Enhanced representation of soil NO emissions in the ...

EPA Pesticide Factsheets

Modeling of soil nitric oxide (NO) emissions is highly uncertain and may misrepresent its spatial and temporal distribution. This study builds upon a recently introduced parameterization to improve the timing and spatial distribution of soil NO emission estimates in the Community Multiscale Air Quality (CMAQ) model. The parameterization considers soil parameters, meteorology, land use, and mineral nitrogen (N) availability to estimate NO emissions. We incorporate daily year-specific fertilizer data from the Environmental Policy Integrated Climate (EPIC) agricultural model to replace the annual generic data of the initial parameterization, and use a 12 km resolution soil biome map over the continental USA. CMAQ modeling for July 2011 shows slight differences in model performance in simulating fine particulate matter and ozone from Interagency Monitoring of Protected Visual Environments (IMPROVE) and Clean Air Status and Trends Network (CASTNET) sites and NO2 columns from Ozone Monitoring Instrument (OMI) satellite retrievals. We also simulate how the change in soil NO emissions scheme affects the expected O3 response to projected emissions reductions. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-support tools, and models to be applied to media-specific or receptor-specific problem areas. CED uses modeling-based approaches to characterize exposures, evaluate fate and transport, and

The Impact of Iodide-Mediated Ozone Deposition and ...

EPA Pesticide Factsheets

The air quality of many large coastal areas in the United States is affected by the confluence of polluted urban and relatively clean marine airmasses, each with distinct atmospheric chemistry. In this context, the role of iodide-mediated ozone (O3) deposition over seawater and marine halogen chemistry accounted for in both the lateral boundary conditions and coastal waters surrounding the continental U.S. is examined using the Community Multiscale Air Quality (CMAQ) model. Several nested simulations are conducted in which these halogen processes are implemented separately in the continental U.S. and hemispheric CMAQ domains, the latter providing lateral boundary conditions for the former. Overall, it is the combination of these processes within both the continental U.S. domain and from lateral boundary conditions that lead to the largest reductions in modeled surface O3 concentrations. Predicted reductions in surface O3 concentrations occur mainly along the coast where CMAQ typically has large overpredictions. These results suggest that a realistic representation of halogen processes in marine regions can improve model prediction of O3 concentrations near the coast. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-support tools, and models to be applied to media-specific or receptor-specific problem areas. CED uses modeling-based approaches to characterize exposures, evaluate fate and

Quantifying and tracing sediment mobilized during the 20th century in the South River watershed, western Massachusetts

NASA Astrophysics Data System (ADS)

Dow, S.; Snyder, N. P.; Ouimet, W. B.; Martini, A. M.; Yellen, B.; Woodruff, J. D.; Newton, R. M.

2016-12-01

New England has a long history of anthropogenic activity affecting the landscape, including deforestation, land use changes, and the construction of dams. Dams in particular have the ability to impound vast quantities of sediment eroded off the landscape. The South River in western Massachusetts is an example of a watershed where mill dam construction coincided with deforestation during the 17th-19th centuries, leading to the impoundment of legacy sediment. Along the river, these deposits act as a source of sediment being released back into the river. The Conway Electric Dam (CED), a 17 m tall dam built in 1906, is located downstream of the mill dams (most of which are no longer intact), and provides a 20th century depositional record for the watershed. The purpose of this study is to quantify sedimentation behind the CED and link this to erosion of upstream mill pond and glacial sediment sources using aerial photography, sediment cores, grainsize, and geochemical analyses. We used aerial photographs to map areal changes of the reservoir from 1940-1980, and topographic profiles generated from LiDAR to estimate a volume of 244,000 m3 of sediment stored behind the CED. We dated layers in cores collected at the site with Hg and 137Cs analyses. Overall, the reservoir exhibits a decreasing rate of sediment infilling occurring from 1940-1980, except for a potentially anomalous increase from 1940-1952. Discharge data containing large storm events were compared to sediment infilling rates to identify if a frequency of large storms could account for high rates of erosion and sediment transport; however, sedimentation at the site does not appear to be solely dependent on these large storm events. Preliminary Hg analyses of deposits from the watershed upstream of the CED indicate higher concentrations in mill pond sediment than glacial sediment. Ongoing work with geochemical tracers can potentially provide a robust understanding of sources and 20th century sediment mobilization in the South River watershed, allowing us to quantify the influence of two cycles of dam construction on watershed sediment transport rates.

The DNA damage response of C. elegans affected by gravity sensing and radiosensitivity during the Shenzhou-8 spaceflight.

PubMed

Gao, Ying; Xu, Dan; Zhao, Lei; Sun, Yeqing

2017-01-01

Space radiation and microgravity are recognized as primary and inevitable risk factors for humans traveling in space, but the reports regarding their synergistic effects remain inconclusive and vary across studies due to differences in the environmental conditions and intrinsic biological sensitivity. Thus, we studied the synergistic effects on transcriptional changes in the global genome and DNA damage response (DDR) by using dys-1 mutant and ced-1 mutant of C. elegans, which respectively presented microgravity-insensitivity and radiosensitivity when exposure to spaceflight condition (SF) and space radiation (SR). The dys-1 mutation induced similar transcriptional changes under both conditions, including the transcriptional distribution and function of altered genes. The majority of alterations were related to metabolic shift under both conditions, including transmembrane transport, lipid metabolic processes and proteolysis. Under SF and SR conditions, 12/14 and 10/13 altered pathways, respectively, were both grouped in the metabolism category. Out of the 778 genes involved in DDR, except eya-1 and ceh-34, 28 altered genes in dys-1 mutant showed no predicted protein interactions, or anti-correlated miRNAs during spaceflight. The ced-1 mutation induced similar changes under SF and SR; however, these effects were stronger than those of the dys-1 mutant. The additional genes identified were related to phosphorous/phosphate metabolic processes and growth rather than, metabolism, especially for environmental information processing under SR. Although the DDR profiles were significantly changed under both conditions, the ced-1 mutation favored DNA repair under SF and apoptosis under SR. Notably, 37 miRNAs were predicted to be involved in the DDR. Our study indicates that, the dys-1 mutation reduced the transcriptional response to SF, and the ced-1 mutation increased the response to SR, when compared with the wild type C. elegans. Although some effects were due to radiosensitivity, microgravity, depending on the dystrophin, exerts predominant effects on transcription in C. elegans during short-duration spaceflight. Copyright © 2017 Elsevier B.V. All rights reserved.

Arctigenin Treatment Protects against Brain Damage through an Anti-Inflammatory and Anti-Apoptotic Mechanism after Needle Insertion

PubMed Central

Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-feng; Kong, Liang; Yao, Ying-Jia; Jiao, Ya-Nan; Yan, Yu-Hui; Li, Shao-Heng; Tao, Zhen-Yu; Lian, Guan; Yang, Jing-Xian; Kang, Ting-Guo

2016-01-01

Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in a stab wound injury (SWI). Subsequent secondary injury involves the release of inflammatory and apoptotic cytokines, which have dramatic consequences on the integrity of damaged tissue, leading to the evolution of a pericontusional-damaged area minutes to days after in the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary brain injury and the determination of the underlying mechanism of action in a mouse model of SWI that mimics the process of CED. After CED, mice received a gavage of ARC from 30 min to 14 days. Neurological severity scores (NSS) and wound closure degree were assessed after the injury. Histological analysis and immunocytochemistry were used to evaluated the extent of brain damage and neuroinflammation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to detect universal apoptosis. Enzyme-linked immunosorbent assays (ELISA) was used to test the inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10) and lactate dehydrogenase (LDH) content. Gene levels of inflammation (TNF-α, IL-6, and IL-10) and apoptosis (Caspase-3, Bax and Bcl-2) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Using these, we analyzed ARC’s efficacy and mechanism of action. Results: ARC treatment improved neurological function by reducing brain water content and hematoma and accelerating wound closure relative to untreated mice. ARC treatment reduced the levels of TNF-α and IL-6 and the number of allograft inflammatory factor (IBA)- and myeloperoxidase (MPO)-positive cells and increased the levels of IL-10. ARC-treated mice had fewer TUNEL+ apoptotic neurons and activated caspase-3-positive neurons surrounding the lesion than controls, indicating increased neuronal survival. Conclusions: ARC treatment confers neuroprotection of brain tissue through anti-inflammatory and anti-apoptotic effects in a mouse model of SWI. These results suggest a new strategy for promoting neuronal survival and function after CED to improve long-term patient outcome. PMID:27445818

7 CFR 1220.605 - Farm Service Agency County Executive Director.

Code of Federal Regulations, 2014 CFR

2014-01-01

... SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Procedures To Request a Referendum Definitions..., also referred to as “CED,” means the person employed by the FSA County Committee to execute the...

7 CFR 1220.605 - Farm Service Agency County Executive Director.

Code of Federal Regulations, 2012 CFR

2012-01-01

... SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Procedures To Request a Referendum Definitions..., also referred to as “CED,” means the person employed by the FSA County Committee to execute the...

7 CFR 1220.605 - Farm Service Agency County Executive Director.

Code of Federal Regulations, 2013 CFR

2013-01-01

... SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Procedures To Request a Referendum Definitions..., also referred to as “CED,” means the person employed by the FSA County Committee to execute the...

7 CFR 1220.605 - Farm Service Agency County Executive Director.

Code of Federal Regulations, 2011 CFR

2011-01-01

... SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Procedures To Request a Referendum Definitions..., also referred to as “CED,” means the person employed by the FSA County Committee to execute the...

7 CFR 1220.605 - Farm Service Agency County Executive Director.

Code of Federal Regulations, 2010 CFR

2010-01-01

... SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Procedures To Request a Referendum Definitions..., also referred to as “CED,” means the person employed by the FSA County Committee to execute the...

Imaging the delivery of brain-penetrating PLGA nanoparticles in the brain using magnetic resonance.

PubMed

Strohbehn, Garth; Coman, Daniel; Han, Liang; Ragheb, Ragy R T; Fahmy, Tarek M; Huttner, Anita J; Hyder, Fahmeed; Piepmeier, Joseph M; Saltzman, W Mark; Zhou, Jiangbing

2015-02-01

Current therapy for glioblastoma multiforme (GBM) is largely ineffective, with nearly universal tumor recurrence. The failure of current therapy is primarily due to the lack of approaches for the efficient delivery of therapeutics to diffuse tumors in the brain. In our prior study, we developed brain-penetrating nanoparticles that are capable of penetrating brain tissue and distribute over clinically relevant volumes when administered via convection-enhanced delivery (CED). We demonstrated that these particles are capable of efficient delivery of chemotherapeutics to diffuse tumors in the brain, indicating that they may serve as a groundbreaking approach for the treatment of GBM. In the original study, nanoparticles in the brain were imaged using positron emission tomography (PET). However, clinical translation of this delivery platform can be enabled by engineering a non-invasive detection modality using magnetic resonance imaging (MRI). For this purpose, we developed chemistry to incorporate superparamagnetic iron oxide (SPIO) into the brain-penetrating nanoparticles. We demonstrated that SPIO-loaded nanoparticles, which retain the same morphology as nanoparticles without SPIO, have an excellent transverse (T(2)) relaxivity. After CED, the distribution of nanoparticles in the brain (i.e., in the vicinity of injection site) can be detected using MRI and the long-lasting signal attenuation of SPIO-loaded brain-penetrating nanoparticles lasted over a one-month timecourse. Development of these nanoparticles is significant as, in future clinical applications, co-administration of SPIO-loaded nanoparticles will allow for intraoperative monitoring of particle distribution in the brain to ensure drug-loaded nanoparticles reach tumors as well as for monitoring the therapeutic benefit with time and to evaluate tumor relapse patterns.

Evaluation of Roadmap to Achieve Energy Delivery Systems Cybersecurity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chavez, Adrian R.

The Department of Energy/Office of Electricity Delivery and Energy Reliability (DOE/OE) Cybersecurity for Energy Delivery Systems (CEDS) program is currently evaluating the Roadmap to Achieve Energy Delivery Systems Cybersecurity document that sets a vision and outlines a set of milestones. The milestones are divided into five strategic focus areas that include: 1. Build a Culture of Security; 2. Assess and Monitor Risk; 3. Develop and Implement New Protective Measures to Reduce Risk; 4. Manage Incidents; and 5. Sustain Security Improvements. The most current version of the roadmap was last updated in September of 2016. Sandia National Laboratories (SNL) has beenmore » tasked with revisiting the roadmap to update the current state of energy delivery systems cybersecurity protections. SNL is currently working with previous and current partners to provide feedback on which of the roadmap milestones have been met and to identify any preexisting or new gaps that are not addressed by the roadmap. The specific focus areas SNL was asked to evaluate are: 1. Develop and Implement New Protective Measures to Reduce Risk and 2. Sustain Security Improvements. SNL has formed an Industry Advisory Board (IAB) to assist in answering these questions. The IAB consists of previous partners on past CEDS funded efforts as well as new collaborators that have unique insights into the current state of cybersecurity within energy delivery systems. The IAB includes asset owners, utilities and vendors of control systems. SNL will continue to maintain regular communications with the IAB to provide various perspectives on potential future updates to further improve the breadth of cybersecurity coverage of the roadmap.« less

7 CFR 1280.607 - Farm Service Agency County Executive Director.

Code of Federal Regulations, 2010 CFR

2010-01-01

... LAMB PROMOTION, RESEARCH, AND INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280... referred to as “CED,” means the person employed by the FSA County Committee to execute the policies of the...

7 CFR 1280.607 - Farm Service Agency County Executive Director.

Code of Federal Regulations, 2013 CFR

2013-01-01

... LAMB PROMOTION, RESEARCH, AND INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280... referred to as “CED,” means the person employed by the FSA County Committee to execute the policies of the...

7 CFR 1280.607 - Farm Service Agency County Executive Director.

Code of Federal Regulations, 2012 CFR

2012-01-01

... LAMB PROMOTION, RESEARCH, AND INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280... referred to as “CED,” means the person employed by the FSA County Committee to execute the policies of the...

7 CFR 1280.607 - Farm Service Agency County Executive Director.

Code of Federal Regulations, 2014 CFR

2014-01-01

... LAMB PROMOTION, RESEARCH, AND INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280... referred to as “CED,” means the person employed by the FSA County Committee to execute the policies of the...

7 CFR 1280.607 - Farm Service Agency County Executive Director.

Code of Federal Regulations, 2011 CFR

2011-01-01

... LAMB PROMOTION, RESEARCH, AND INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280... referred to as “CED,” means the person employed by the FSA County Committee to execute the policies of the...

Intraparenchymal ultrasound application and improved distribution of infusate with convection-enhanced delivery in rodent and nonhuman primate brain.

PubMed

Mano, Yui; Saito, Ryuta; Haga, Yoichi; Matsunaga, Tadao; Zhang, Rong; Chonan, Masashi; Haryu, Shinya; Shoji, Takuhiro; Sato, Aya; Sonoda, Yukihiko; Tsuruoka, Noriko; Nishiyachi, Keisuke; Sumiyoshi, Akira; Nonaka, Hiroi; Kawashima, Ryuta; Tominaga, Teiji

2016-05-01

OBJECT Convection-enhanced delivery (CED) is an effective drug delivery method that delivers high concentrations of drugs directly into the targeted lesion beyond the blood-brain barrier. However, the drug distribution attained using CED has not satisfactorily covered the entire targeted lesion in tumors such as glioma. Recently, the efficacy of ultrasound assistance was reported for various drug delivery applications. The authors developed a new ultrasound-facilitated drug delivery (UFD) system that enables the application of ultrasound at the infusion site. The purpose of this study was to demonstrate the efficacy of the UFD system and to examine effective ultrasound profiles. METHODS The authors fabricated a steel bar-based device that generates ultrasound and enables infusion of the aqueous drug from one end of the bar. The volume of distribution (Vd) after infusion of 10 ml of 2% Evans blue dye (EBD) into rodent brain was tested with different frequencies and applied voltages: 252 kHz/30 V; 252 kHz/60 V; 524 kHz/13 V; 524 kHz/30 V; and 524 kHz/60 V. In addition, infusion of 5 mM gadopentetate dimeglumine (Gd-DTPA) was tested with 260 kHz/60 V, the distribution of which was evaluated using a 7-T MRI unit. In a nonhuman primate (Macaca fascicularis) study, 300 μl of 1 mM Gd-DTPA/EBD was infused. The final distribution was evaluated using MRI. Two-sample comparisons were made by Student t-test, and 1-way ANOVA was used for multiple comparisons. Significance was set at p < 0.05. RESULTS After infusion of 10 μl of EBD into the rat brain using the UFD system, the Vds of EBD in the UFD groups were significantly larger than those of the control group. When a frequency of 252 kHz was applied, the Vd of the group in which 60 V was applied was significantly larger than that of the group in which 30 V was used. When a frequency of 524 kHz was applied, the Vd tended to increase with application of a higher voltage; however, the differences were not significant (1-way ANOVA). The Vd of Gd-DTPA was also significantly larger in the UFD group than in the control group (p < 0.05, Student t-test). The volume of Gd-DTPA in the nonhuman primate used in this study was 1209.8 ± 193.6 mm(3). This volume was much larger than that achieved by conventional CED (568.6 ± 141.0 mm(3)). CONCLUSIONS The UFD system facilitated the distribution of EBD and Gd-DTPA more effectively than conventional CED. Lower frequency and higher applied voltage using resonance frequencies might be more effective to enlarge the Vd. The UFD system may provide a new treatment approach for CNS disorders.

Contribution of health motive to cannabis use among high-school students.

PubMed

Chabrol, Henri; Beck, Charline; Laconi, Stéphanie

2017-01-01

The Marijuana Motives Measure (MMM), which is derived from a scale measuring alcohol use motives, has been the main instrument used to explore the role of motives in cannabis use and related problems. Two studies attempted to developed specific cannabis use motives but none of them showed a unique association to cannabis use and problems when controlling for MMM motives. The aim of our study was to examine if additional motives contributed to problematic use beyond MMM motives and psychopathological symptoms. Participants were 249 high-school students who completed the Cannabis Use Disorder Identification Test-Revised (CUDIT-R) assessing cannabis use and problematic use, the MMM and a new scale measuring motives derived from clinical experience with adolescents using cannabis (CED motives), and scales measuring anxiety and depressive symptoms and borderline personality traits. Among the 107 participants using cannabis, 39 reached the cut-off score for problematic cannabis use. Hierarchical multiple regression analyses controlling for psychopathological variables showed that only one CED motives, Health (sleep, form, energy, appetite, health), was a significant predictor of both frequency of use and problematic use symptoms. The importance of Health motive may be linked to the role of depressive symptoms and may have implication for treatment. We suggest to add the Health subscale to the MMM and to further study the role of health motive in both use and dependence. Copyright © 2016. Published by Elsevier Ltd.

Dynamic Contrast-Enhanced MRI of Gd-albumin Delivery to the Rat Hippocampus In Vivo by Convection-Enhanced Delivery

PubMed Central

Kim, Jung Hwan; Astary, Garrett W.; Nobrega, Tatiana L.; Kantorovich, Svetlana; Carney, Paul R.; Mareci, Thomas H.; Sarntinoranont, Malisa

2013-01-01

Convection enhanced delivery (CED) shows promise in treating neurological diseases due to its ability to circumvent the blood-brain barrier (BBB) and deliver therapeutics directly to the parenchyma of the central nervous system (CNS). Such a drug delivery method may be useful in treating CNS disorders involving the hippocampus such temporal lobe epilepsy and gliomas; however, the influence of anatomical structures on infusate distribution is not fully understood. As a surrogate for therapeutic agents, we used gadolinium-labeled-albumin (Gd-albumin) tagged with Evans blue dye to observe the time dependence of CED infusate distributions into the rat dorsal and ventral hippocampus in vivo with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). For finer anatomical detail, final distribution volumes (Vd) of the infusate were observed with high-resolution T1-weighted MR imaging and light microscopy of fixed brain sections. Dynamic images demonstrated that Gd-albumin preferentially distributed within the hippocampus along neuroanatomical structures with less fluid resistance and less penetration was observed in dense cell layers. Furthermore, significant leakage into adjacent cerebrospinal fluid (CSF) spaces such as the hippocampal fissure, velum interpositum and midbrain cistern occurred toward the end of infusion. Vd increased linearly with infusion volume (Vi) at a mean Vd/Vi ratio of 5.51 ± 0.55 for the dorsal hippocampus infusion and 5.30 ± 0.83 for the ventral hippocampus infusion. This study demonstrated the significant effects of tissue structure and CSF space boundaries on infusate distribution during CED. PMID:22687936

Assessment of Committed Effective Dose due to consumption of Red Sea coral reef fishes collected from the local market (Sudan).

PubMed

Hassona, Rifaat K; Sam, A K; Osman, O I; Sirelkhatim, D A; LaRosa, J

2008-04-15

An assessment of Committed Effective Dose (CED) due to consumption of Red Sea fish containing (210)Po and (137)Cs was performed for 23 different marine fish samples collected from the local market at Port Sudan. The fish were classified according to their feeding habits into three categories: carnivores, herbivores, and omnivores. Measured activity concentrations of (210)Po were found in the ranges 0.25-6.42 (carnivores), 0.7-5 (omnivores) and 1.5-3.8 (herbivores) Bq/kg fresh weight. In the same study, activity concentrations of Cs-137 were determined to be in the ranges 0.1-0.46 (carnivores), 0.09-0.35 (omnivores) and 0.09-0.32 (herbivores) Bq/kg fresh weight, which were several times lower than those of (210)Po. Appropriate conversion factors were used to derive the CED, which was found to be 0.012, 0.01 and 0.01 (microSv/yr) in carnivores, omnivores and herbivores, respectively, for (137)Cs. This contributes about 0.4% of the total dose exclusively by ingestion of fish. For (210)Po, it was found to be 3.47, 4.81 and 4.14 (microSv/yr) in carnivores, omnivores and herbivores, respectively, which represents 99.6% of the total dose (exclusively by ingestion of fish). The results of CED calculations suggest that the dose received by the Sudanese population from the consumption of marine fish is rather small and that the contribution of (137)Cs is negligible compared to (210)Po.

Consumption of Caffeinated Energy Drinks Among Youth and Young Adults in Canada.

PubMed

Reid, Jessica L; McCrory, Cassondra; White, Christine M; Martineau, Chantal; Vanderkooy, Pat; Fenton, Nancy; Hammond, David

2017-03-01

The growing market for caffeinated energy drinks (CEDs) has caused concern about excessive caffeine intake and potential adverse effects, particularly among young people. The current study examined patterns of CED consumption among youth and young adults in Canada, using data from a national online survey conducted in October 2014. Data from a non-probability sample of 2040 respondents aged 12-24 from a consumer panel was weighted to national proportions; measures of CED consumption were estimated, including prevalence, excessive daily consumption, and context for use (locations and reasons). Separate logistic regression models for two outcomes, past-week consumption and "ever" exceeding two energy drinks in a day (as per common guidance), were conducted to examine associations with demographic variables (sex, age, geographic region, race/ethnicity, and language). Overall, 73.6% of respondents reported "ever" consuming energy drinks; 15.6% had done so in the past week. Any consumption of energy drinks in the past week was more prevalent among males, Aboriginal respondents (vs. white only or mixed/other), and residents of British Columbia. Among "ever-consumers," 16.0% reported ever consuming more than two energy drinks in a day. Exceeding two in a day was more prevalent among older respondents (young adults aged 18-24), aboriginal respondents (vs. white only), and British Columbia residents. While the majority of youth and young adults had consumed energy drinks, about half were "experimental" consumers (i.e., consumed ≤ 5 drinks in their lifetime). Approximately one in six consumers had exceeded the usual guidance for maximum daily consumption, potentially increasing their risk of experiencing adverse effects.

Aerospace Sensor Component and Subsystem Investigation and Innovation-2 Component Exploration and Development (ASCSII-2 CED) Delivery Order 0003: Hermetically Sealed Cavities in 3-D GaAs-Silicon and Silicon-Silicon Packages for Microelectromechanical System (MEMS) Devices Using Selective and Large-Scale Bonding

DTIC Science & Technology

2003-03-01

and silicon-to-silicon to produce cavities for 3-D assembly of MEMS devices has been demonstrated using SnAgCu and eutectic SnPb solders. Laser and...of GaAs-to-silicon and silicon-to-silicon to produce cavities for 3-D assembly of MEMS devices has been demonstrated using SnAgCu and euctectic...research_images/ 3.2 Solder Reflow The reflow profile for SnAgCu solder was developed on the Sikama convection/ conduction reflow oven using a continuous

15 CFR 995.20 - General.

Code of Federal Regulations, 2014 CFR

2014-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA HYDROGRAPHIC PRODUCTS Requirements for Certified Distributors and Value Added Distributors of NOAA ENC Products § 995.20 General. The requirements for certification as a “Certified NOAA ENC Distributor” (CED) and...

15 CFR 995.20 - General.

Code of Federal Regulations, 2012 CFR

2012-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA HYDROGRAPHIC PRODUCTS Requirements for Certified Distributors and Value Added Distributors of NOAA ENC Products § 995.20 General. The requirements for certification as a “Certified NOAA ENC Distributor” (CED) and...

15 CFR 995.20 - General.

Code of Federal Regulations, 2013 CFR

2013-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA HYDROGRAPHIC PRODUCTS Requirements for Certified Distributors and Value Added Distributors of NOAA ENC Products § 995.20 General. The requirements for certification as a “Certified NOAA ENC Distributor” (CED) and...

15 CFR 995.20 - General.

Code of Federal Regulations, 2011 CFR

2011-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA HYDROGRAPHIC PRODUCTS Requirements for Certified Distributors and Value Added Distributors of NOAA ENC Products § 995.20 General. The requirements for certification as a “Certified NOAA ENC Distributor” (CED) and...

15 CFR 995.20 - General.

Code of Federal Regulations, 2010 CFR

2010-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA HYDROGRAPHIC PRODUCTS Requirements for Certified Distributors and Value Added Distributors of NOAA ENC Products § 995.20 General. The requirements for certification as a “Certified NOAA ENC Distributor” (CED) and...

78 FR 42082 - Proposed Information Collection Activity; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-15

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Administration for Children and Families Proposed Information Collection Activity; Comment Request Proposed Projects: Title: Renewal of Office of Community... through the CED program. Since grantees are already familiar with the current format and elements, and all...

The Cell-CT 3D Cell Imaging Technology Platform Enables the Detection of Lung Cancer Using the Non-Invasive LuCED Sputum Test

PubMed Central

Meyer, Michael G.; Hayenga, Jon; Neumann, Thomas; Katdare, Rahul; Presley, Chris; Steinhauer, David; Bell, Timothy; Lancaster, Christy; Nelson, Alan C.

2015-01-01

The war against cancer has yielded important advances in the early diagnosis and treatment of certain cancer types, but the poor detection rate and 5-year survival rate for lung cancer remains little changed over the past 40 years. Early detection through emerging lung cancer screening programs promises the most reliable means of improving mortality. Sputum cytology has been tried without success because sputum contains few malignant cells that are difficult for cytologists to detect. However, research has shown that sputum contains diagnostic malignant cells and could serve as a means of lung cancer detection if those cells could be detected and correctly characterized. Recently, the National Lung Cancer Screening Trial reported that screening by three consecutive low-dose X-ray CT scans provides a 20% reduction in lung cancer mortality compared to chest X-ray. This reduction in mortality, however, comes with an unacceptable false positive rate that increases patient risks and the overall cost of lung cancer screening. This article reviews the LuCED® test for detecting early lung cancer. LuCED is based on patient sputum that is enriched for bronchial epithelial cells. The enriched sample is then processed on the Cell-CT®, which images cells in three dimensions with sub-micron resolution. Algorithms are applied to the 3D cell images to extract morphometric features that drive a classifier to identify cells that have abnormal characteristics. The final status of these candidate abnormal cells is established by the pathologist's manual review. LuCED promotes accurate cell classification which could enable cost effective detection of lung cancer. PMID:26148817

The C. elegans TIA-1/TIAR homolog TIAR-1 is required to induce germ cell apoptosis.

PubMed

Silva-García, Carlos Giovanni; Estela Navarro, Rosa

2013-10-01

In Caenorhabditis elegans, physiological germ cell apoptosis eliminates more than half of the cells in the hermaphrodite gonad to support gamete quality and germline homeostasis by a still unidentified mechanism. External factors can also affect germ cell apoptosis. The BH3-only protein EGL-1 induces germ cell apoptosis when animals are exposed to pathogens or agents that produce DNA damage. DNA damage-induced apoptosis also requires the nematode p53 homolog CEP-1. Previously, we found that heat shock, oxidative, and osmotic stresses induce germ cell apoptosis through an EGL-1 and CEP-1 independent mechanism that requires the MAPKK pathway. However, we observed that starvation increases germ cell apoptosis by an unknown pathway. Searching for proteins that participate in stress-induced apoptosis, we found the RNA-binding protein TIAR-1 (a homolog of the mammalian TIA-1/TIAR family of proteins). Here, we show that TIAR-1 in C. elegans is required to induce apoptosis in the germline under several conditions. We also show that TIAR-1 acts downstream of CED-9 (a BCL2 homolog) to induce apoptosis under stress conditions, and apparently does not seem to regulate ced-4 or ced-3 mRNAs accumulation directly. TIAR-1 is expressed ubiquitously in the cytoplasm of the soma as well as the germline, where it sometimes associates with P granules. We show that animals lacking TIAR-1 expression are temperature sensitive sterile due to oogenesis and spermatogenesis defects. Our work shows that TIAR-1 is required for proper germline function and demonstrates that this protein is important to induce germ cell apoptosis under several conditions. Copyright © 2013 Wiley Periodicals, Inc.

Highly Effective Auger-Electron Therapy in an Orthotopic Glioblastoma Xenograft Model using Convection-Enhanced Delivery

PubMed Central

Thisgaard, Helge; Halle, Bo; Aaberg-Jessen, Charlotte; Olsen, Birgitte Brinkmann; Therkelsen, Anne Sofie Nautrup; Dam, Johan Hygum; Langkjær, Niels; Munthe, Sune; Någren, Kjell; Høilund-Carlsen, Poul Flemming; Kristensen, Bjarne Winther

2016-01-01

Glioblastoma, the most common and malignant primary brain tumor, always recurs after standard treatment. Therefore, promising new therapeutic approaches are needed. Short-range Auger-electron-emitters carry the ability of causing highly damaging radiation effects in cells. The aim of this study was to test the effect of [125I]5-Iodo-2'-deoxyuridine (125I-UdR, a radioactive Auger-electron-emitting thymidine analogue) Auger-therapy on immature glioblastoma spheroid cultures and orthotopic xenografted glioblastoma-bearing rats, the latter by means of convection-enhanced delivery (CED). Moreover, we aimed to determine if the therapeutic effect could be enhanced when combining 125I-UdR therapy with the currently used first-line chemotherapeutic agent temozolomide. 125I-UdR significantly decreased glioblastoma cell viability and migration in vitro and the cell viability was further decreased by co-treatment with methotrexate and/or temozolomide. Intratumoral CED of methotrexate and 125I-UdR with and without concomitant systemic temozolomide chemotherapy significantly reduced the tumor burden in orthotopically xenografted glioblastoma-bearing nude rats. Thus, 100% (8/8) of the animals survived the entire observation period of 180 days when subjected to the combined Auger-chemotherapy while 57% (4/7) survived after the Auger-therapy alone. No animals (0/8) treated with temozolomide alone survived longer than 50 days. Blood samples and post-mortem histology showed no signs of dose-limiting adverse effects. In conclusion, the multidrug approach consisting of CED of methotrexate and 125I-UdR with concomitant systemic temozolomide was safe and very effective leading to 100% survival in an orthotopic xenograft glioblastoma model. Therefore, this therapeutic strategy may be a promising option for future glioblastoma therapy. PMID:27924163

Highly Effective Auger-Electron Therapy in an Orthotopic Glioblastoma Xenograft Model using Convection-Enhanced Delivery.

PubMed

Thisgaard, Helge; Halle, Bo; Aaberg-Jessen, Charlotte; Olsen, Birgitte Brinkmann; Therkelsen, Anne Sofie Nautrup; Dam, Johan Hygum; Langkjær, Niels; Munthe, Sune; Någren, Kjell; Høilund-Carlsen, Poul Flemming; Kristensen, Bjarne Winther

2016-01-01

Glioblastoma, the most common and malignant primary brain tumor, always recurs after standard treatment. Therefore, promising new therapeutic approaches are needed. Short-range Auger-electron-emitters carry the ability of causing highly damaging radiation effects in cells. The aim of this study was to test the effect of [ 125 I]5-Iodo-2'-deoxyuridine ( 125 I-UdR, a radioactive Auger-electron-emitting thymidine analogue) Auger-therapy on immature glioblastoma spheroid cultures and orthotopic xenografted glioblastoma-bearing rats, the latter by means of convection-enhanced delivery (CED). Moreover, we aimed to determine if the therapeutic effect could be enhanced when combining 125 I-UdR therapy with the currently used first-line chemotherapeutic agent temozolomide. 125 I-UdR significantly decreased glioblastoma cell viability and migration in vitro and the cell viability was further decreased by co-treatment with methotrexate and/or temozolomide. Intratumoral CED of methotrexate and 125 I-UdR with and without concomitant systemic temozolomide chemotherapy significantly reduced the tumor burden in orthotopically xenografted glioblastoma-bearing nude rats. Thus, 100% (8/8) of the animals survived the entire observation period of 180 days when subjected to the combined Auger-chemotherapy while 57% (4/7) survived after the Auger-therapy alone. No animals (0/8) treated with temozolomide alone survived longer than 50 days. Blood samples and post-mortem histology showed no signs of dose-limiting adverse effects. In conclusion, the multidrug approach consisting of CED of methotrexate and 125 I-UdR with concomitant systemic temozolomide was safe and very effective leading to 100% survival in an orthotopic xenograft glioblastoma model. Therefore, this therapeutic strategy may be a promising option for future glioblastoma therapy.

Effect of needle insertion speed on tissue injury, stress, and backflow distribution for convection-enhanced delivery in the rat brain.

PubMed

Casanova, Fernando; Carney, Paul R; Sarntinoranont, Malisa

2014-01-01

Flow back along a needle track (backflow) can be a problem during direct infusion, e.g. convection-enhanced delivery (CED), of drugs into soft tissues such as brain. In this study, the effect of needle insertion speed on local tissue injury and backflow was evaluated in vivo in the rat brain. Needles were introduced at three insertion speeds (0.2, 2, and 10 mm/s) followed by CED of Evans blue albumin (EBA) tracer. Holes left in tissue slices were used to reconstruct penetration damage. These measurements were also input into a hyperelastic model to estimate radial stress at the needle-tissue interface (pre-stress) before infusion. Fast insertion speeds were found to produce more tissue bleeding and disruption; average hole area at 10 mm/s was 1.87-fold the area at 0.2 mm/s. Hole measurements also differed at two fixation time points after needle retraction, 10 and 25 min, indicating that pre-stresses are influenced by time-dependent tissue swelling. Calculated pre-stresses were compressive (0 to 485 Pa) and varied along the length of the needle with smaller average values within white matter (116 Pa) than gray matter (301 Pa) regions. Average pre-stress at 0.2 mm/s (351.7 Pa) was calculated to be 1.46-fold the value at 10 mm/s. For CED backflow experiments (0.5, 1, and 2 µL/min), measured EBA backflow increased as much as 2.46-fold between 10 and 0.2 mm/s insertion speeds. Thus, insertion rate-dependent damage and changes in pre-stress were found to directly contribute to the extent of backflow, with slower insertion resulting in less damage and improved targeting.

Fine mapping of the celiac disease-associated LPP locus reveals a potential functional variant.

PubMed

Almeida, Rodrigo; Ricaño-Ponce, Isis; Kumar, Vinod; Deelen, Patrick; Szperl, Agata; Trynka, Gosia; Gutierrez-Achury, Javier; Kanterakis, Alexandros; Westra, Harm-Jan; Franke, Lude; Swertz, Morris A; Platteel, Mathieu; Bilbao, Jose Ramon; Barisani, Donatella; Greco, Luigi; Mearin, Luisa; Wolters, Victorien M; Mulder, Chris; Mazzilli, Maria Cristina; Sood, Ajit; Cukrowska, Bozena; Núñez, Concepción; Pratesi, Riccardo; Withoff, Sebo; Wijmenga, Cisca

2014-05-01

Using the Immunochip for genotyping, we identified 39 non-human leukocyte antigen (non-HLA) loci associated to celiac disease (CeD), an immune-mediated disease with a worldwide frequency of ∼1%. The most significant non-HLA signal mapped to the intronic region of 70 kb in the LPP gene. Our aim was to fine map and identify possible functional variants in the LPP locus. We performed a meta-analysis in a cohort of 25 169 individuals from six different populations previously genotyped using Immunochip. Imputation using data from the Genome of the Netherlands and 1000 Genomes projects, followed by meta-analysis, confirmed the strong association signal on the LPP locus (rs2030519, P = 1.79 × 10(-49)), without any novel associations. The conditional analysis on this top SNP-indicated association to a single common haplotype. By performing haplotype analyses in each population separately, as well as in a combined group of the four populations that reach the significant threshold after correction (P < 0.008), we narrowed down the CeD-associated region from 70 to 2.8 kb (P = 1.35 × 10(-44)). By intersecting regulatory data from the ENCODE project, we found a functional SNP, rs4686484 (P = 3.12 × 10(-49)), that maps to several B-cell enhancer elements and a highly conserved region. This SNP was also predicted to change the binding motif of the transcription factors IRF4, IRF11, Nkx2.7 and Nkx2.9, suggesting its role in transcriptional regulation. We later found significantly low levels of LPP mRNA in CeD biopsies compared with controls, thus our results suggest that rs4686484 is the functional variant in this locus, while LPP expression is decreased in CeD.

Evaluation of European coeliac disease risk variants in a north Indian population

PubMed Central

Senapati, Sabyasachi; Gutierrez-Achury, Javier; Sood, Ajit; Midha, Vandana; Szperl, Agata; Romanos, Jihane; Zhernakova, Alexandra; Franke, Lude; Alonso, Santos; Thelma, B K; Wijmenga, Cisca; Trynka, Gosia

2015-01-01

Studies in European populations have contributed to a better understanding of the genetics of complex diseases, for example, in coeliac disease (CeD), studies of over 23 000 European samples have reported association to the HLA locus and another 39 loci. However, these associations have not been evaluated in detail in other ethnicities. We sought to better understand how disease-associated loci that have been mapped in Europeans translate to a disease risk for a population with a different ethnic background. We therefore performed a validation of European risk loci for CeD in 497 cases and 736 controls of north Indian origin. Using a dense-genotyping platform (Immunochip), we confirmed the strong association to the HLA region (rs2854275, P=8.2 × 10−49). Three loci showed suggestive association (rs4948256, P=9.3 × 10−7, rs4758538, P=8.6 × 10−5 and rs17080877, P=2.7 × 10−5). We directly replicated five previously reported European variants (P<0.05; mapping to loci harbouring FASLG/TNFSF18, SCHIP1/IL12A, PFKFB3/PRKCQ, ZMIZ1 and ICOSLG). Using a transferability test, we further confirmed association at PFKFB3/PRKCQ (rs2387397, P=2.8 × 10−4) and PTPRK/THEMIS (rs55743914, P=3.4 × 10−4). The north Indian population has a higher degree of consanguinity than Europeans and we therefore explored the role of recessively acting variants, which replicated the HLA locus (rs9271850, P=3.7 × 10−23) and suggested a role of additional four loci. To our knowledge, this is the first replication study of CeD variants in a non-European population. PMID:25052311

Magnetic Resonance Imaging-Based Assessment of Gadolinium-Conjugated Diethylenetriamine Penta-Acetic Acid Test-Infusion in Detecting Dysfunction of Convection-Enhanced Delivery Catheters.

PubMed

van Putten, Erik H P; Wembacher-Schröder, Eva; Smits, Marion; Dirven, Clemens M F

2016-05-01

In a phase 1 trial conducted at our institute, convection-enhanced delivery (CED) was used to administrate the Delta-24-RGD adenovirus in patients with a recurrent glioblastoma multiforme. Infusion of the virus was preceded by a gadolinium-conjugated diethylenetriamine penta-acetic acid (Gd-DTPA) test-infusion. In the present study, we analyzed the results of Gd-DTPA test infusion through 50 catheters. Thirteen adults with a recurrent glioblastoma multiforme were enrolled in a larger phase 1 multicenter, dose-finding study, in which a conditionally replication-competent adenovirus was administered by CED. Up to 4 infusion catheters per patient were placed intra- and/or peritumorally. Before infusion of the virus, a Gd-DTPA infusion was performed for 6 hours, directly followed by a MRI scan. The MRIs were evaluated for catheter position, Gd-DTPA distribution outcome, and contrast leakage. Leakage of Gd-DTPA into the cerebrospinal fluid was detected in 17 of the 50 catheters (34%). Sulcus crossing was the most frequent cause of leakage. In 8 cases, leakage could only be detected on the fluid-attenuated inversion recovery sequence. Nonleaking catheters showed a significantly larger Gd-DTPA distribution fraction (volume of distribution/volume of infusion) than leaking catheters (P = 0.009). A significantly lower volume of distribution/volume of infusion was observed in intratumoral catheters, compared with peritumoral catheters (P = 0.004). Gd-DTPA test infusion did not result in significant changes in Karnofsky Performance Score and Neurological Status. Pre-CED treatment infusion of Gd-DTPA is an adequate and safe method to identify dysfunctional catheters. The use of an optimized drug delivery catheter is necessary to reduce leakage and improve the efficacy of intracerebral drug infusion. Copyright © 2016 Elsevier Inc. All rights reserved.

Continuous intraputamenal convection-enhanced delivery in adult rhesus macaques.

PubMed

Fan, Xiaotong; Nelson, Brian D; Ai, Yi; Stiles, David K; Gash, Don M; Hardy, Peter A; Zhang, Zhiming

2015-12-01

Assessing the safety and feasibility of chronic delivery of compounds to the brain using convection-enhanced delivery (CED) is important for the further development of this important therapeutic technology. The objective of this study was to follow and model the distribution of a compound delivered by CED into the putamen of rhesus monkeys. The authors sequentially implanted catheters into 4 sites spanning the left and right putamen in each of 6 rhesus monkeys. The catheters were connected to implanted pumps, which were programmed to deliver a 5-mM solution of the MRI contrast agent Gd-DTPA at 0.1 μl/minute for 7 days and 0.3 μl/minute for an additional 7 days. The animals were followed for 28 days per implant cycle during which they were periodically examined with MRI. All animals survived the 4 surgeries with no deficits in behavior. Compared with acute infusion, the volume of distribution (Vd) increased 2-fold with 7 days of chronic infusion. Increasing the flow rate 3-fold over the next week increased the Vd an additional 3-fold. Following withdrawal of the compound, the half-life of Gd-DTPA in the brain was estimated as 3.1 days based on first-order pharmacokinetics. Histological assessment of the brain showed minimal tissue damage limited to the insertion site. These results demonstrate several important features in the development of a chronically implanted pump and catheter system: 1) the ability to place catheters accurately in a predetermined target; 2) the ability to deliver compounds in a chronic fashion to the putamen; and 3) the use of MRI and MR visible tracers to follow the evolution of the infusion volume over time.

Spatial, seasonal and diurnal patterns in physicochemical characteristics and sources of PM2.5 in both inland and coastal regions within a megacity in China.

PubMed

Tian, Yingze; Liu, Jiayuan; Han, Suqin; Shi, Xurong; Shi, Guoliang; Xu, Hong; Yu, Haofei; Zhang, Yufen; Feng, Yinchang; Russell, Armistead G

2018-01-15

Day and night PM 2.5 samples were collected at coastal and inland stations in a megacity in China. Temporal, spatial, and directional characteristics of PM 2.5 concentrations and compositions were investigated. Average PM 2.5 concentration was higher at inland (153.28μg/m 3 ) than at coastal (114.46μg/m 3 ). PM 2.5 were significantly influenced by season and site but insignificantly by diurnal pattern. Sources were quantified by a two-way and a newly developed three-way receptor models conducted using ME2. Secondary sulfate and SOC (SS&SOC, 25% and 23%), coal and biomass burning (CC&BB, 20% and 21%), crustal and cement dust (CRD&CED, 19% and 21%), secondary nitrate (SN, 13% and 18%), vehicular exhaust (VE, 14% and 17%), and sea salt (SEA, 6% and 2%) were major sources for coastal and inland. Different mechanisms of heavy pollution were observed: heavy PM 2.5 caused by primary sources and secondary sources showed similar frequency at coast, while most of heavy pollutions at inland site might be associated with the elevation of secondary particles. For spatial characteristics, SS&SOC, CRD&CED contributions were higher at coastal; SN and VE presented higher fractions at inland. Higher SS&SOC, SN and CC&BB in winter might be attributed to intensive coal combustion for residential warming and to stable meteorological conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

15 CFR 995.15 - Termination of certification.

Code of Federal Regulations, 2011 CFR

2011-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA... NOAA determines that a CED or CEVAD is not meeting the requirements described in this part, the Office of Coast Survey, NOAA (OCS) will provide initial written notification of potential termination to the...

15 CFR 995.15 - Termination of certification.

Code of Federal Regulations, 2014 CFR

2014-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA... NOAA determines that a CED or CEVAD is not meeting the requirements described in this part, the Office of Coast Survey, NOAA (OCS) will provide initial written notification of potential termination to the...

15 CFR 995.15 - Termination of certification.

Code of Federal Regulations, 2013 CFR

2013-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA... NOAA determines that a CED or CEVAD is not meeting the requirements described in this part, the Office of Coast Survey, NOAA (OCS) will provide initial written notification of potential termination to the...

15 CFR 995.15 - Termination of certification.

Code of Federal Regulations, 2012 CFR

2012-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA... NOAA determines that a CED or CEVAD is not meeting the requirements described in this part, the Office of Coast Survey, NOAA (OCS) will provide initial written notification of potential termination to the...

13 CFR 307.4 - Award requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... ECONOMIC ADJUSTMENT ASSISTANCE INVESTMENTS General § 307.4 Award requirements. (a) General. EDA will select... criteria provided in paragraphs (b) and (c) of this section, as applicable. (b) Strategy Grants. EDA will review Strategy Grant proposals to ensure that the proposed activities conform to the CEDS requirements...

15 CFR 995.15 - Termination of certification.

Code of Federal Regulations, 2010 CFR

2010-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA... NOAA determines that a CED or CEVAD is not meeting the requirements described in this part, the Office of Coast Survey, NOAA (OCS) will provide initial written notification of potential termination to the...

Ionizing radiation exposure as a result of diagnostic imaging in patients with lymphoma.

PubMed

Crowley, M P; O'Neill, S B; Kevane, B; O'Neill, D C; Eustace, J A; Cahill, M R; Bird, B; Maher, M M; O'Regan, K; O'Shea, D

2016-05-01

Survival rates among patients with lymphoma continue to improve. Strategies aimed at reducing potential treatment-related toxicity are increasingly prioritized. While radiological procedures play an important role, ionizing radiation exposure has been linked to an increased risk of malignancy, particularly among individuals whose cumulative radiation exposure exceeds a specific threshold (75 millisieverts). Within this retrospective study, the cumulative radiation exposure dose was quantified for 486 consecutive patients with lymphoma. The median estimated total cumulative effective dose (CED) of ionizing radiation per subject was 69 mSv (42-118). However, younger patients (under 40 years) had a median CED of 89 mSv (55-124). This study highlights the considerable radiation exposure occurring among patients with lymphoma as a result of diagnostic imaging. To limit the risk of secondary carcinogenesis, consideration should be given to monitoring cumulative radiation exposure in individual patients as well as considering imaging modalities, which do not impart an ionizing radiation dose.

Restriction enzyme analysis of Indian isolates of egg drop syndrome 1976 virus recovered from chicken, duck and quail.

PubMed

Senthilkumar, N; Kataria, J M; Koti, M; Dhama, K; Dash, B B

2004-07-01

Egg drop syndrome 1976 (EDS-76) is caused by a haemagglutinating adenovirus belonging to group III of the genus Aviadenovirus in the family Adenoviridae. All isolates are serologically identical, but have been divided into three groups based on restriction endonuclease (RE) analysis. In this study the viral DNA of various Indian EDS-76 viral isolates (CEDS-A, CEDS-B, EDS-M, EDS-ML, EDS-1/AD/86, EDS-KC and QEDS) obtained from different avian species and different geographical regions were digested with restriction endonucleases viz., EcoRI, BamHI, HindIII and PstI. The results showed that one Indian isolate obtained from duck (DEDS-KC) was different from all other chicken and quail counterparts. All other isolates were identical to the reference viral strain BC-14, which belong to group I of EDS-76 viruses. The duck isolate EDS-KC could not be placed in any of the three groups reported earlier.

Evaluation of the Community Multiscale Air Quality (CMAQ) Model Version 5.2

EPA Science Inventory

The Community Multiscale Air Quality (CMAQ) model is a state-of-the-science air quality model that simulates the emission, transport and fate of numerous air pollutants, including ozone and particulate matter. The Computational Exposure Division (CED) of the U.S. Environmental Pr...

Evaluation of the Community Multi-scale Air Quality Model Version 5.2

EPA Science Inventory

The Community Multiscale Air Quality (CMAQ) model is a state-of-the-science air quality model that simulates the emission, transport and fate of numerous air pollutants, including ozone and particulate matter. The Computational Exposure Division (CED) of the U.S. Environmental Pr...

15 CFR 995.21 - Registry of data users.

Code of Federal Regulations, 2012 CFR

2012-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA HYDROGRAPHIC PRODUCTS Requirements for Certified Distributors and Value Added Distributors of NOAA ENC Products § 995.21 Registry of data users. (a) CED or CEVAD shall maintain a registry of customers receiving NOAA...

15 CFR 995.21 - Registry of data users.

Code of Federal Regulations, 2014 CFR

2014-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA HYDROGRAPHIC PRODUCTS Requirements for Certified Distributors and Value Added Distributors of NOAA ENC Products § 995.21 Registry of data users. (a) CED or CEVAD shall maintain a registry of customers receiving NOAA...

15 CFR 995.21 - Registry of data users.

Code of Federal Regulations, 2013 CFR

2013-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA HYDROGRAPHIC PRODUCTS Requirements for Certified Distributors and Value Added Distributors of NOAA ENC Products § 995.21 Registry of data users. (a) CED or CEVAD shall maintain a registry of customers receiving NOAA...

7 CFR 1230.633 - Canvassing ballots.

Code of Federal Regulations, 2014 CFR

2014-01-01

... CONSUMER INFORMATION Procedures for the Conduct of Referendum Referendum § 1230.633 Canvassing ballots. (a) Producers. (1) Counting the ballots. Under the supervision of FSA CED, acting on behalf of the Administrator... spoiled ballots. (2) Invalid ballots. Ballots will be declared invalid if a producer voting in-person has...

7 CFR 1230.633 - Canvassing ballots.

Code of Federal Regulations, 2013 CFR

2013-01-01

... CONSUMER INFORMATION Procedures for the Conduct of Referendum Referendum § 1230.633 Canvassing ballots. (a) Producers. (1) Counting the ballots. Under the supervision of FSA CED, acting on behalf of the Administrator... spoiled ballots. (2) Invalid ballots. Ballots will be declared invalid if a producer voting in-person has...

7 CFR 1230.633 - Canvassing ballots.

Code of Federal Regulations, 2010 CFR

2010-01-01

... CONSUMER INFORMATION Procedures for the Conduct of Referendum Referendum § 1230.633 Canvassing ballots. (a) Producers. (1) Counting the ballots. Under the supervision of FSA CED, acting on behalf of the Administrator... spoiled ballots. (2) Invalid ballots. Ballots will be declared invalid if a producer voting in-person has...

7 CFR 1230.633 - Canvassing ballots.

Code of Federal Regulations, 2011 CFR

2011-01-01

... CONSUMER INFORMATION Procedures for the Conduct of Referendum Referendum § 1230.633 Canvassing ballots. (a) Producers. (1) Counting the ballots. Under the supervision of FSA CED, acting on behalf of the Administrator... spoiled ballots. (2) Invalid ballots. Ballots will be declared invalid if a producer voting in-person has...

7 CFR 1230.633 - Canvassing ballots.

Code of Federal Regulations, 2012 CFR

2012-01-01

... CONSUMER INFORMATION Procedures for the Conduct of Referendum Referendum § 1230.633 Canvassing ballots. (a) Producers. (1) Counting the ballots. Under the supervision of FSA CED, acting on behalf of the Administrator... spoiled ballots. (2) Invalid ballots. Ballots will be declared invalid if a producer voting in-person has...

Evaluation of the Community Multi-scale Air Quality (CMAQ) Model Version 5.1

EPA Science Inventory

The Community Multiscale Air Quality (CMAQ) model is a state-of-the-science air quality model that simulates the emission, transport and fate of numerous air pollutants, including ozone and particulate matter. The Computational Exposure Division (CED) of the U.S. Environmental Pr...

Overview and Evaluation of the Community Multiscale Air Quality Model Version 5.2

EPA Science Inventory

The Community Multiscale Air Quality (CMAQ) model is a state-of-the-science air quality model that simulates the emission, transport and fate of numerous air pollutants, including ozone and particulate matter. The Computational Exposure Division (CED) of the U.S. Environmental Pr...

Evaluation of the Community Multi-scale Air Quality (CMAQ) Model Version 5.2

EPA Science Inventory

The Community Multiscale Air Quality (CMAQ) model is a state-of-the-science air quality model that simulates the emission, transport and fate of numerous air pollutants, including ozone and particulate matter. The Computational Exposure Division (CED) of the U.S. Environmental Pr...

15 CFR 995.12 - Certification designation.

Code of Federal Regulations, 2012 CFR

2012-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA... been certified by NOAA as a CED may use the phrase “Certified NOAA ENC Distributor” on products and marketing materials. An Applicant that has been certified by NOAA as a CEVAD may use the phrase “Certified...

15 CFR 995.12 - Certification designation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA... been certified by NOAA as a CED may use the phrase “Certified NOAA ENC Distributor” on products and marketing materials. An Applicant that has been certified by NOAA as a CEVAD may use the phrase “Certified...

15 CFR 995.12 - Certification designation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA... been certified by NOAA as a CED may use the phrase “Certified NOAA ENC Distributor” on products and marketing materials. An Applicant that has been certified by NOAA as a CEVAD may use the phrase “Certified...

15 CFR 995.12 - Certification designation.

Code of Federal Regulations, 2013 CFR

2013-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA... been certified by NOAA as a CED may use the phrase “Certified NOAA ENC Distributor” on products and marketing materials. An Applicant that has been certified by NOAA as a CEVAD may use the phrase “Certified...

7 CFR 1220.626 - FSA county office report.

Code of Federal Regulations, 2010 CFR

2010-01-01

... CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.626 FSA county office report. The county FSA office report shall be certified as accurate and complete by the CED or designee... county summary of requests on a form provided by the Administrator, FSA. Each county FSA office shall...

12 CFR 28.18 - Recordkeeping and reporting.

Code of Federal Regulations, 2011 CFR

2011-01-01

... deposit. A foreign bank with a consolidated CED shall maintain a book entry accounting of assets... ACTIVITIES Federal Branches and Agencies of Foreign Banks § 28.18 Recordkeeping and reporting. (a) General. A... to national banks and with any additional requirements that may be prescribed by the OCC. A Federal...

7 CFR 1220.626 - FSA county office report.

Code of Federal Regulations, 2013 CFR

2013-01-01

... CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.626 FSA county office report. The county FSA office report shall be certified as accurate and complete by the CED or designee... county summary of requests on a form provided by the Administrator, FSA. Each county FSA office shall...

12 CFR 28.18 - Recordkeeping and reporting.

Code of Federal Regulations, 2012 CFR

2012-01-01

... deposit. A foreign bank with a consolidated CED shall maintain a book entry accounting of assets... ACTIVITIES Federal Branches and Agencies of Foreign Banks § 28.18 Recordkeeping and reporting. (a) General. A... to national banks and with any additional requirements that may be prescribed by the OCC. A Federal...

7 CFR 1220.626 - FSA county office report.

Code of Federal Regulations, 2014 CFR

2014-01-01

... CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.626 FSA county office report. The county FSA office report shall be certified as accurate and complete by the CED or designee... county summary of requests on a form provided by the Administrator, FSA. Each county FSA office shall...

12 CFR 28.18 - Recordkeeping and reporting.

Code of Federal Regulations, 2013 CFR

2013-01-01

... deposit. A foreign bank with a consolidated CED shall maintain a book entry accounting of assets... ACTIVITIES Federal Branches and Agencies of Foreign Banks § 28.18 Recordkeeping and reporting. (a) General. A... to national banks and with any additional requirements that may be prescribed by the OCC. A Federal...

12 CFR 28.18 - Recordkeeping and reporting.

Code of Federal Regulations, 2014 CFR

2014-01-01

... deposit. A foreign bank with a consolidated CED shall maintain a book entry accounting of assets... ACTIVITIES Federal Branches and Agencies of Foreign Banks § 28.18 Recordkeeping and reporting. (a) General. A... to national banks and with any additional requirements that may be prescribed by the OCC. A Federal...

7 CFR 1220.626 - FSA county office report.

Code of Federal Regulations, 2012 CFR

2012-01-01

... CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.626 FSA county office report. The county FSA office report shall be certified as accurate and complete by the CED or designee... county summary of requests on a form provided by the Administrator, FSA. Each county FSA office shall...

7 CFR 1220.626 - FSA county office report.

Code of Federal Regulations, 2011 CFR

2011-01-01

... CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.626 FSA county office report. The county FSA office report shall be certified as accurate and complete by the CED or designee... county summary of requests on a form provided by the Administrator, FSA. Each county FSA office shall...

15 CFR 995.12 - Certification designation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... REQUIREMENTS FOR NOAA HYDROGRAPHIC PRODUCTS AND SERVICES CERTIFICATION REQUIREMENTS FOR DISTRIBUTORS OF NOAA... been certified by NOAA as a CED may use the phrase “Certified NOAA ENC Distributor” on products and marketing materials. An Applicant that has been certified by NOAA as a CEVAD may use the phrase “Certified...

MRI-Based Computational Model of Heterogeneous Tracer Transport following Local Infusion into a Mouse Hind Limb Tumor

PubMed Central

Magdoom, Kulam Najmudeen; Pishko, Gregory L.; Rice, Lori; Pampo, Chris; Siemann, Dietmar W.; Sarntinoranont, Malisa

2014-01-01

Systemic drug delivery to solid tumors involving macromolecular therapeutic agents is challenging for many reasons. Amongst them is their chaotic microvasculature which often leads to inadequate and uneven uptake of the drug. Localized drug delivery can circumvent such obstacles and convection-enhanced delivery (CED) - controlled infusion of the drug directly into the tissue - has emerged as a promising delivery method for distributing macromolecules over larger tissue volumes. In this study, a three-dimensional MR image-based computational porous media transport model accounting for realistic anatomical geometry and tumor leakiness was developed for predicting the interstitial flow field and distribution of albumin tracer following CED into the hind-limb tumor (KHT sarcoma) in a mouse. Sensitivity of the model to changes in infusion flow rate, catheter placement and tissue hydraulic conductivity were investigated. The model predictions suggest that 1) tracer distribution is asymmetric due to heterogeneous porosity; 2) tracer distribution volume varies linearly with infusion volume within the whole leg, and exponentially within the tumor reaching a maximum steady-state value; 3) infusion at the center of the tumor with high flow rates leads to maximum tracer coverage in the tumor with minimal leakage outside; and 4) increasing the tissue hydraulic conductivity lowers the tumor interstitial fluid pressure and decreases the tracer distribution volume within the whole leg and tumor. The model thus predicts that the interstitial fluid flow and drug transport is sensitive to porosity and changes in extracellular space. This image-based model thus serves as a potential tool for exploring the effects of transport heterogeneity in tumors. PMID:24619021

15 CFR 995.23 - Acquisition of data.

Code of Federal Regulations, 2010 CFR

2010-01-01

... HYDROGRAPHIC PRODUCTS Requirements for Certified Distributors and Value Added Distributors of NOAA ENC Products... process. (2) In the event that said CRC checksum value does not match that in the CATALOG.031 file, CED or CEVAD agrees to: (i) Repeat the download process; (ii) In the event that said CRC checksum value for the...

15 CFR 995.23 - Acquisition of data.

Code of Federal Regulations, 2014 CFR

2014-01-01

... HYDROGRAPHIC PRODUCTS Requirements for Certified Distributors and Value Added Distributors of NOAA ENC Products... process. (2) In the event that said CRC checksum value does not match that in the CATALOG.031 file, CED or CEVAD agrees to: (i) Repeat the download process; (ii) In the event that said CRC checksum value for the...

15 CFR 995.23 - Acquisition of data.

Code of Federal Regulations, 2012 CFR

2012-01-01

... HYDROGRAPHIC PRODUCTS Requirements for Certified Distributors and Value Added Distributors of NOAA ENC Products... process. (2) In the event that said CRC checksum value does not match that in the CATALOG.031 file, CED or CEVAD agrees to: (i) Repeat the download process; (ii) In the event that said CRC checksum value for the...

15 CFR 995.23 - Acquisition of data.

Code of Federal Regulations, 2011 CFR

2011-01-01

... HYDROGRAPHIC PRODUCTS Requirements for Certified Distributors and Value Added Distributors of NOAA ENC Products... process. (2) In the event that said CRC checksum value does not match that in the CATALOG.031 file, CED or CEVAD agrees to: (i) Repeat the download process; (ii) In the event that said CRC checksum value for the...

15 CFR 995.23 - Acquisition of data.

Code of Federal Regulations, 2013 CFR

2013-01-01

... HYDROGRAPHIC PRODUCTS Requirements for Certified Distributors and Value Added Distributors of NOAA ENC Products... process. (2) In the event that said CRC checksum value does not match that in the CATALOG.031 file, CED or CEVAD agrees to: (i) Repeat the download process; (ii) In the event that said CRC checksum value for the...

15 CFR 995.21 - Registry of data users.

Code of Federal Regulations, 2010 CFR

2010-01-01

... do so by the CED or CEVAD). (b)(1) The registry shall include, but not be limited to: (i) Which NOAA ENC ® cells were provided to each customer; (ii) Edition number of each cell provided; (iii) Updates provided for each cell; (iv) Method of distribution for each customer. (2) The registry may also include...

Methods of treating Parkinson's disease using viral vectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bankiewicz, Krystof; Cunningham, Janet

Methods of delivering viral vectors, particularly recombinant adeno-associated virus (rAAV) virions, to the central nervous system (CNS) using convection enhanced delivery (CED) are provided. The rAAV virions include a nucleic acid sequence encoding a therapeutic polypeptide. The methods can be used for treating CNS disorders such as for treating Parkinson's Disease.

7 CFR 1221.229 - FSA county office report.

Code of Federal Regulations, 2014 CFR

2014-01-01

... county FSA office report shall be certified as accurate and complete by the CED or designee, acting on... released by the Secretary. A copy of the report shall be posted for 30 calendar days following the date of notification by the Administrator, FSA, in the county FSA office in a conspicuous place accessible to the...

7 CFR 1221.229 - FSA county office report.

Code of Federal Regulations, 2012 CFR

2012-01-01

... county FSA office report shall be certified as accurate and complete by the CED or designee, acting on... released by the Secretary. A copy of the report shall be posted for 30 calendar days following the date of notification by the Administrator, FSA, in the county FSA office in a conspicuous place accessible to the...

7 CFR 1221.229 - FSA county office report.

Code of Federal Regulations, 2011 CFR

2011-01-01

... county FSA office report shall be certified as accurate and complete by the CED or designee, acting on... released by the Secretary. A copy of the report shall be posted for 30 calendar days following the date of notification by the Administrator, FSA, in the county FSA office in a conspicuous place accessible to the...

7 CFR 1280.629 - FSA county office report.

Code of Federal Regulations, 2014 CFR

2014-01-01

... INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.629 FSA county office report. The county FSA office report shall be certified as accurate and complete by the CED or designee, acting on... released by the Secretary. A copy of the report shall be posted for 30 calendar days following the date of...

7 CFR 1280.629 - FSA county office report.

Code of Federal Regulations, 2010 CFR

2010-01-01

... INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.629 FSA county office report. The county FSA office report shall be certified as accurate and complete by the CED or designee, acting on... released by the Secretary. A copy of the report shall be posted for 30 calendar days following the date of...

7 CFR 1280.629 - FSA county office report.

Code of Federal Regulations, 2013 CFR

2013-01-01

... INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.629 FSA county office report. The county FSA office report shall be certified as accurate and complete by the CED or designee, acting on... released by the Secretary. A copy of the report shall be posted for 30 calendar days following the date of...

7 CFR 1280.629 - FSA county office report.

Code of Federal Regulations, 2011 CFR

2011-01-01

... INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.629 FSA county office report. The county FSA office report shall be certified as accurate and complete by the CED or designee, acting on... released by the Secretary. A copy of the report shall be posted for 30 calendar days following the date of...

7 CFR 1221.229 - FSA county office report.

Code of Federal Regulations, 2013 CFR

2013-01-01

... county FSA office report shall be certified as accurate and complete by the CED or designee, acting on... released by the Secretary. A copy of the report shall be posted for 30 calendar days following the date of notification by the Administrator, FSA, in the county FSA office in a conspicuous place accessible to the...

7 CFR 1280.629 - FSA county office report.

Code of Federal Regulations, 2012 CFR

2012-01-01

... INFORMATION ORDER Procedures To Request a Referendum Definitions § 1280.629 FSA county office report. The county FSA office report shall be certified as accurate and complete by the CED or designee, acting on... released by the Secretary. A copy of the report shall be posted for 30 calendar days following the date of...

Probing the Mechanism of LAL-32, a Gold Nanoparticle-Based Antibiotic Discovered through Small Molecule Variable Ligand Display.

PubMed

Byrne-Nash, Rose; Lucero, Danielle M; Osbaugh, Niki A; Melander, Roberta J; Melander, Christian; Feldheim, Daniel L

2017-07-19

The unrelenting rise of antimicrobial-resistant bacteria has necessitated the search for novel antibiotic solutions. Herein we describe further mechanistic studies on a 2.0-nm-diameter gold nanoparticle-based antibiotic (designated LAL-32). This antibiotic exhibits bactericidal activity against the Gram-negative bacterium Escherichia coli at 1.0 μM, a concentration significantly lower than several clinically available antibiotics (such as ampicillin and gentamicin), and acute treatment with LAL-32 does not give rise to spontaneous resistant mutants. LAL-32 treatment inhibits cellular division, daughter cell separation, and twin-arginine translocation (Tat) pathway dependent shuttling of proteins to the periplasm. Furthermore, we have found that the cedA gene imparts increased resistance to LAL-32, and shown that an E. coli cedA transposon mutant exhibits increased susceptibility to LAL-32. Taken together, these studies further implicate cell division pathways as the target for this nanoparticle-based antibiotic and demonstrate that there may be inherently higher barriers for resistance evolution against nanoscale antibiotics in comparison to their small molecule counterparts.

High performance electrode material for supercapacitors based on α-Co(OH)2 nano-sheets prepared through pulse current cathodic electro-deposition (PC-CED)

NASA Astrophysics Data System (ADS)

Aghazadeh, Mustafa; Rashidi, Amir; Ganjali, Mohammad Reza

2018-01-01

In this paper, the well-defined nano-sheets of α-Co(OH)2 were prepared through the cathodic electrosynthesis from an additive-free aqueous cobalt nitrate bath. The pulse current cathodic electro-deposition (PC-CED) was used as the means for the controlling the OH- electrogeneration on the cathode surface. The characteristics and electrochemical behavior of the prepared cobalt hydroxide were also assessed through SEM, TEM, XRD, BET, and IR. The results proved the product to be composed of crystalline pure α phase of cobalt hydroxide with sheet-like morphology at nanoscale. Evaluations of the electrochemical behaviour of the α-Co(OH)2 nano-sheets revealed that they are capable to delivering the specific capacitance of 1122 F g-1 at a discharge load of 3 A g-1 and SC retention of 84% after 4000 continues discharging cycles, suggesting the nano-sheets as promising candidates for use in electrochemical supercapacitors. Further, the method used for the preparation of the compounds enjoys the capability of being scaled up. [Figure not available: see fulltext.

Botryomycosis presenting as nasal cutaneous fistulas caused by Prevotella melaninogenica.

PubMed

Huang, C-F; Liaw, F-Y; Dai, N-T; Ou, K-W; Wang, C-C; Wang, W-M

2012-07-01

Botryomycosis is an uncommon chronic suppurative granulomatous bacterial infection that can affect the skin and viscera. Clinically, lesions typically consist of small tender nodules from which draining sinuses may develop to expel a purulent discharge. Histopathological features include characteristic aggregation of microorganisms (grain) within the inflammatory infiltrate. The commonest causative organisms are Staphylococcus aureus and Pseudomonas aeruginosa, of others. Botryomycosis resulting from Prevotella melaninogenica has not been reported previously. We report the case of a middle-aged patient with botryomycosis presenting as nasal cutaneous fistulas caused by P. melaninogenica, which was successfully treated with surgical intervention combined with systemic antibiotic treatment. © The Author(s). CED © 2011 British Association of Dermatologists.

Inhibition of Ced-3/ICE-related Proteases Does Not Prevent Cell Death Induced by Oncogenes, DNA Damage, or the Bcl-2 Homologue Bak

PubMed Central

McCarthy, Nicola J.; Whyte, Moira K.B.; Gilbert, Christopher S.; Evan, Gerard I.

1997-01-01

There is increasing evidence for a central role in mammalian apoptosis of the interleukin-1β– converting enzyme (ICE) family of cysteine proteases, homologues of the product of the nematode “death” gene, ced-3. Ced-3 is thought to act as an executor rather than a regulator of programmed cell death in the nematode. However, it is not known whether mammalian ICE-related proteases (IRPs) are involved in the execution or the regulation of mammalian apoptosis. Moreover, an absolute requirement for one or more IRPs for mammalian apoptosis has yet to be established. We have used two cell-permeable inhibitors of IRPs, Z-Val-Ala-Asp.fluoromethylketone (ZVAD.fmk) and t-butoxy carbonyl-Asp.fluoromethylketone (BD.fmk), to demonstrate a critical role for IRPs in mammalian apoptosis induced by several disparate mechanisms (deregulated oncogene expression, ectopic expression of the Bcl-2 relative Bak, and DNA damage–induced cell death). In all instances, ZVAD.fmk and BD.fmk treatment inhibits characteristic biochemical and morphological events associated with apoptosis, including cleavage of nuclear lamins and poly-(ADP-ribose) polymerase, chromatin condensation and nucleosome laddering, and external display of phosphatidylserine. However, neither ZVAD.fmk nor BD.fmk inhibits the onset of apoptosis, as characterized by the onset of surface blebbing; rather, both act to delay completion of the program once initiated. In complete contrast, IGF-I and Bcl-2 delay the onset of apoptosis but have no effect on the kinetics of the program once initiated. Our data indicate that IRPs constitute part of the execution machinery of mammalian apoptosis induced by deregulated oncogenes, DNA damage, or Bak but that they act after the point at which cells become committed to apoptosis or can be rescued by survival factors. Moreover, all such blocked cells have lost proliferative potential and all eventually die by a process involving cytoplasmic blebbing. PMID:9008715

Tasers and Community Controversy: Investigating Training Officer Perceptions of Public Concern over Conducted Energy Weapons

ERIC Educational Resources Information Center

De Angelis, Joseph; Wolf, Brian

2013-01-01

Over the last several decades, "Tasers," "stun guns" and other conducted energy devices (CEDs) have become a widely adopted, though publicly controversial, form of police restraint technology. While there is a growing body of research on the physiological effects of these types of weapons, less attention has been devoted to the…

Integrated modeling to assess the ecological and air quality trade-offs of agricultural burning in the Flint Hills of eastern Kansas

EPA Science Inventory

The Flint Hills of eastern Kansas and northern Oklahoma is home to the largest remaining contiguous grassland prairie in the United States. Throughout the prairie, burning is a common practice used to preserve the prairie from encroachment of woody species such as eastern Red Ced...

Integrated software system for improving medical equipment management.

PubMed

Bliznakov, Z; Pappous, G; Bliznakova, K; Pallikarakis, N

2003-01-01

The evolution of biomedical technology has led to an extraordinary use of medical devices in health care delivery. During the last decade, clinical engineering departments (CEDs) turned toward computerization and application of specific software systems for medical equipment management in order to improve their services and monitor outcomes. Recently, much emphasis has been given to patient safety. Through its Medical Device Directives, the European Union has required all member nations to use a vigilance system to prevent the reoccurrence of adverse events that could lead to injuries or death of patients or personnel as a result of equipment malfunction or improper use. The World Health Organization also has made this issue a high priority and has prepared a number of actions and recommendations. In the present workplace, a new integrated, Windows-oriented system is proposed, addressing all tasks of CEDs but also offering a global approach to their management needs, including vigilance. The system architecture is based on a star model, consisting of a central core module and peripheral units. Its development has been based on the integration of 3 software modules, each one addressing specific predefined tasks. The main features of this system include equipment acquisition and replacement management, inventory archiving and monitoring, follow up on scheduled maintenance, corrective maintenance, user training, data analysis, and reports. It also incorporates vigilance monitoring and information exchange for adverse events, together with a specific application for quality-control procedures. The system offers clinical engineers the ability to monitor and evaluate the quality and cost-effectiveness of the service provided by means of quality and cost indicators. Particular emphasis has been placed on the use of harmonized standards with regard to medical device nomenclature and classification. The system's practical applications have been demonstrated through a pilot evaluation trial.

Disease activity indices in coeliac disease: systematic review and recommendations for clinical trials.

PubMed

Hindryckx, Pieter; Levesque, Barrett G; Holvoet, Tom; Durand, Serina; Tang, Ceen-Ming; Parker, Claire; Khanna, Reena; Shackelton, Lisa M; D'Haens, Geert; Sandborn, William J; Feagan, Brian G; Lebwohl, Benjamin; Leffler, Daniel A; Jairath, Vipul

2018-01-01

Although several pharmacological agents have emerged as potential adjunctive therapies to a gluten-free diet for coeliac disease, there is currently no widely accepted measure of disease activity used in clinical trials. We conducted a systematic review of coeliac disease activity indices to evaluate their operating properties and potential as outcome measures in registration trials. MEDLINE, EMBASE and the Cochrane central library were searched from 1966 to 2015 for eligible studies in adult and/or paediatric patients with coeliac disease that included coeliac disease activity markers in their outcome measures. The operating characteristics of histological indices, patient-reported outcomes (PROs) and endoscopic indices were evaluated for content and construct validity, reliability, responsiveness and feasibility using guidelines proposed by the US Food and Drug Administration (FDA). Of 19 123 citations, 286 studies were eligible, including 24 randomised-controlled trials. Three of five PROs identified met most key evaluative criteria but only the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient-Reported Outcome (CeD PRO) have been approved by the FDA. All histological and endoscopic scores identified lacked content validity. Quantitative morphometric histological analysis had better reliability and responsiveness compared with qualitative scales. Endoscopic indices were infrequently used, and only one index demonstrated responsiveness to effective therapy. Current best evidence suggests that the CDSD and the CeD PRO are appropriate for use in the definition of primary end points in coeliac disease registration trials. Morphometric histology should be included as a key secondary or co-primary end point. Further work is needed to optimise end point configuration to inform efficient drug development. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Redox-Responsive Magnetic Nanoparticle for Targeted Convection-Enhanced Delivery of O6-Benzylguanine to Brain Tumors

PubMed Central

2015-01-01

Resistance to temozolomide (TMZ) based chemotherapy in glioblastoma multiforme (GBM) has been attributed to the upregulation of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). Inhibition of MGMT using O6-benzylguanine (BG) has shown promise in these patients, but its clinical use is hindered by poor pharmacokinetics that leads to unacceptable toxicity. To improve BG biodistribution and efficacy, we developed superparamagnetic iron oxide nanoparticles (NP) for targeted convection-enhanced delivery (CED) of BG to GBM. The nanoparticles (NPCP-BG-CTX) consist of a magnetic core coated with a redox-responsive, cross-linked, biocompatible chitosan-PEG copolymer surface coating (NPCP). NPCP was modified through covalent attachment of BG and tumor targeting peptide chlorotoxin (CTX). Controlled, localized BG release was achieved under reductive intracellular conditions and NPCP-BG-CTX demonstrated proper trafficking of BG in human GBM cells in vitro. NPCP-BG-CTX treated cells showed a significant reduction in MGMT activity and the potentiation of TMZ toxicity. In vivo, CED of NPCP-BG-CTX produced an excellent volume of distribution (Vd) within the brain of mice bearing orthotopic human primary GBM xenografts. Significantly, concurrent treatment with NPCP-BG-CTX and TMZ showed a 3-fold increase in median overall survival in comparison to NPCP-CTX/TMZ treated and untreated animals. Furthermore, NPCP-BG-CTX mitigated the myelosuppression observed with free BG in wild-type mice when administered concurrently with TMZ. The combination of favorable physicochemical properties, tumor cell specific BG delivery, controlled BG release, and improved in vivo efficacy demonstrates the great potential of these NPs as a treatment option that could lead to improved clinical outcomes. PMID:25247850

Redox-responsive magnetic nanoparticle for targeted convection-enhanced delivery of O6-benzylguanine to brain tumors.

PubMed

Stephen, Zachary R; Kievit, Forrest M; Veiseh, Omid; Chiarelli, Peter A; Fang, Chen; Wang, Kui; Hatzinger, Shelby J; Ellenbogen, Richard G; Silber, John R; Zhang, Miqin

2014-10-28

Resistance to temozolomide (TMZ) based chemotherapy in glioblastoma multiforme (GBM) has been attributed to the upregulation of the DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT). Inhibition of MGMT using O(6)-benzylguanine (BG) has shown promise in these patients, but its clinical use is hindered by poor pharmacokinetics that leads to unacceptable toxicity. To improve BG biodistribution and efficacy, we developed superparamagnetic iron oxide nanoparticles (NP) for targeted convection-enhanced delivery (CED) of BG to GBM. The nanoparticles (NPCP-BG-CTX) consist of a magnetic core coated with a redox-responsive, cross-linked, biocompatible chitosan-PEG copolymer surface coating (NPCP). NPCP was modified through covalent attachment of BG and tumor targeting peptide chlorotoxin (CTX). Controlled, localized BG release was achieved under reductive intracellular conditions and NPCP-BG-CTX demonstrated proper trafficking of BG in human GBM cells in vitro. NPCP-BG-CTX treated cells showed a significant reduction in MGMT activity and the potentiation of TMZ toxicity. In vivo, CED of NPCP-BG-CTX produced an excellent volume of distribution (Vd) within the brain of mice bearing orthotopic human primary GBM xenografts. Significantly, concurrent treatment with NPCP-BG-CTX and TMZ showed a 3-fold increase in median overall survival in comparison to NPCP-CTX/TMZ treated and untreated animals. Furthermore, NPCP-BG-CTX mitigated the myelosuppression observed with free BG in wild-type mice when administered concurrently with TMZ. The combination of favorable physicochemical properties, tumor cell specific BG delivery, controlled BG release, and improved in vivo efficacy demonstrates the great potential of these NPs as a treatment option that could lead to improved clinical outcomes.

15 CFR 995.21 - Registry of data users.

Code of Federal Regulations, 2011 CFR

2011-01-01

... information about the type and size of vessel that the NOAA ENC data has been provided for as well as an... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Registry of data users. 995.21 Section... § 995.21 Registry of data users. (a) CED or CEVAD shall maintain a registry of customers receiving NOAA...

Design of the Detector II: A CMOS Gate Array for the Study of Concurrent Error Detection Techniques.

DTIC Science & Technology

1987-07-01

detection schemes and temporary failures. The circuit consists- or of six different adders with concurrent error detection schemes . The error detection... schemes are - simple duplication, duplication with functional dual implementation, duplication with different &I [] .6implementations, two-rail encoding...THE SYSTEM. .. .... ...... ...... ...... 5 7. DESIGN OF CED SCHEMES .. ... ...... ...... ........ 7 7.1 Simple Duplication

The CEBAF Element Database and Related Operational Software

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larrieu, Theodore; Slominski, Christopher; Keesee, Marie

The newly commissioned 12GeV CEBAF accelerator relies on a flexible, scalable and comprehensive database to define the accelerator. This database delivers the configuration for CEBAF operational tools, including hardware checkout, the downloadable optics model, control screens, and much more. The presentation will describe the flexible design of the CEBAF Element Database (CED), its features and assorted use case examples.

Comparative life cycle assessment of battery storage systems for stationary applications.

PubMed

Hiremath, Mitavachan; Derendorf, Karen; Vogt, Thomas

2015-04-21

This paper presents a comparative life cycle assessment of cumulative energy demand (CED) and global warming potential (GWP) of four stationary battery technologies: lithium-ion, lead-acid, sodium-sulfur, and vanadium-redox-flow. The analyses were carried out for a complete utilization of their cycle life and for six different stationary applications. Due to its lower CED and GWP impacts, a qualitative analysis of lithium-ion was carried out to assess the impacts of its process chains on 17 midpoint impact categories using ReCiPe-2008 methodology. It was found that in general the use stage of batteries dominates their life cycle impacts significantly. It is therefore misleading to compare the environmental performance of batteries only on a mass or capacity basis at the manufacturing outlet ("cradle-to-gate analyses") while neglecting their use stage impacts, especially when they have different characteristic parameters. Furthermore, the relative ranking of batteries does not show a significant dependency on the investigated stationary application scenarios in most cases. Based on the results obtained, the authors go on to recommend the deployment of batteries with higher round-trip efficiency, such as lithium-ion, for stationary grid operation in the first instance.

Strategies for improving the intratumoral distribution of liposomal drugs in cancer therapy

PubMed Central

Goins, Beth; Phillips, William T.; Bao, Ande

2016-01-01

Introduction A major limitation of current liposomal cancer therapies is the inability of liposome therapeutics to penetrate throughout the entire tumor mass. This inhomogeneous distribution of liposome therapeutics within the tumor has been linked to treatment failure and drug resistance. Both liposome particle transport properties and tumor microenvironment characteristics contribute to this challenge in cancer therapy. This limitation is relevant to both intravenously and intratumorally administered liposome therapeutics. Areas covered Strategies to improve the intratumoral distribution of liposome therapeutics are described. Combination therapies of intravenous liposome therapeutics with pharmacologic agents modulating abnormal tumor vasculature, interstitial fluid pressure, extracellular matrix components, and tumor associated macrophages are discussed. Combination therapies using external stimuli (hyperthermia, radiofrequency ablation, magnetic field, radiation, and ultrasound) with intravenous liposome therapeutics are discussed. Intratumoral convection-enhanced delivery (CED) of liposomal therapeutics is reviewed. Expert opinion Optimization of the combination therapies and drug delivery protocols are necessary. Further research should be conducted in appropriate cancer types with consideration of physiochemical features of liposomes and their timing sequence. More investigation of the role of tumor associated macrophages in intratumoral distribution is warranted. Intratumoral infusion of liposomes using CED is a promising approach to improve their distribution within the tumor mass. PMID:26981891

Environmental Impacts of Plant-Based Diets: How Does Organic Food Consumption Contribute to Environmental Sustainability?

PubMed

Lacour, Camille; Seconda, Louise; Allès, Benjamin; Hercberg, Serge; Langevin, Brigitte; Pointereau, Philippe; Lairon, Denis; Baudry, Julia; Kesse-Guyot, Emmanuelle

2018-01-01

Studies investigating diet-related environmental impacts have rarely considered the production method of the foods consumed. The objective of the present study, based on the NutriNet-Santé cohort, was to investigate the relationship between a provegetarian score and diet-related environmental impacts. We also evaluated potential effect modifications on the association between a provegetarian score and the environmental impacts of organic food consumption. Food intake and organic food consumption ratios were obtained from 34,442 French adults using a food frequency questionnaire, which included information on organic food consumption for each group. To characterize the overall structure of the diets, a provegetarian score was used to identify preferences for plant-based products as opposed to animal-based products. Moreover, three environmental indicators were used to assess diet-related environmental impacts: greenhouse gas (GHG) emissions, cumulative energy demand (CED), and land occupation. Environmental impacts were assessed using production life cycle assessment (LCA) at the farm level. Associations between provegetarian score quintiles, the level of organic food consumption, and environmental indicators were analyzed using ANCOVAs adjusted for energy, sex, and age. Participants with diets rich in plant-based foods (fifth quintile) were more likely to be older urban dwellers, to hold a higher degree in education, and to be characterized by an overall healthier lifestyle and diet. A higher provegetarian score was associated with lower environmental impacts (GHG emissions Q5vsQ1  = 838/1,664 kg CO 2eq /year, -49.6%, P  < 0.0001; CED Q5vsQ1  = 4,853/6,775 MJ/year, -26.9%, P  < 0.0001; land occupation Q5vsQ1  = 2,420/4,138 m 2 /year, -41.5%, P  < 0.0001). Organic food consumption was also an important modulator of the relationship between provegetarian dietary patterns and environmental impacts but only among participants with diets rich in plant-based products. Future field studies should endeavor to integrate all the components of a sustainable diet, i.e., both diet composition and production methods.

Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies.

PubMed

Broce, Iris; Karch, Celeste M; Wen, Natalie; Fan, Chun C; Wang, Yunpeng; Tan, Chin Hong; Kouri, Naomi; Ross, Owen A; Höglinger, Günter U; Muller, Ulrich; Hardy, John; Momeni, Parastoo; Hess, Christopher P; Dillon, William P; Miller, Zachary A; Bonham, Luke W; Rabinovici, Gil D; Rosen, Howard J; Schellenberg, Gerard D; Franke, Andre; Karlsen, Tom H; Veldink, Jan H; Ferrari, Raffaele; Yokoyama, Jennifer S; Miller, Bruce L; Andreassen, Ole A; Dale, Anders M; Desikan, Rahul S; Sugrue, Leo P

2018-01-01

Converging evidence suggests that immune-mediated dysfunction plays an important role in the pathogenesis of frontotemporal dementia (FTD). Although genetic studies have shown that immune-associated loci are associated with increased FTD risk, a systematic investigation of genetic overlap between immune-mediated diseases and the spectrum of FTD-related disorders has not been performed. Using large genome-wide association studies (GWASs) (total n = 192,886 cases and controls) and recently developed tools to quantify genetic overlap/pleiotropy, we systematically identified single nucleotide polymorphisms (SNPs) jointly associated with FTD-related disorders-namely, FTD, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS)-and 1 or more immune-mediated diseases including Crohn disease, ulcerative colitis (UC), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CeD), and psoriasis. We found up to 270-fold genetic enrichment between FTD and RA, up to 160-fold genetic enrichment between FTD and UC, up to 180-fold genetic enrichment between FTD and T1D, and up to 175-fold genetic enrichment between FTD and CeD. In contrast, for CBD and PSP, only 1 of the 6 immune-mediated diseases produced genetic enrichment comparable to that seen for FTD, with up to 150-fold genetic enrichment between CBD and CeD and up to 180-fold enrichment between PSP and RA. Further, we found minimal enrichment between ALS and the immune-mediated diseases tested, with the highest levels of enrichment between ALS and RA (up to 20-fold). For FTD, at a conjunction false discovery rate < 0.05 and after excluding SNPs in linkage disequilibrium, we found that 8 of the 15 identified loci mapped to the human leukocyte antigen (HLA) region on Chromosome (Chr) 6. We also found novel candidate FTD susceptibility loci within LRRK2 (leucine rich repeat kinase 2), TBKBP1 (TBK1 binding protein 1), and PGBD5 (piggyBac transposable element derived 5). Functionally, we found that the expression of FTD-immune pleiotropic genes (particularly within the HLA region) is altered in postmortem brain tissue from patients with FTD and is enriched in microglia/macrophages compared to other central nervous system cell types. The main study limitation is that the results represent only clinically diagnosed individuals. Also, given the complex interconnectedness of the HLA region, we were not able to define the specific gene or genes on Chr 6 responsible for our pleiotropic signal. We show immune-mediated genetic enrichment specifically in FTD, particularly within the HLA region. Our genetic results suggest that for a subset of patients, immune dysfunction may contribute to FTD risk. These findings have potential implications for clinical trials targeting immune dysfunction in patients with FTD.

Convection-enhanced delivery of M13 bacteriophage to the brain

PubMed Central

Ksendzovsky, Alexander; Walbridge, Stuart; Saunders, Richard C.; Asthagiri, Ashok R.; Heiss, John D.; Lonser, Russell R.

2013-01-01

Object Recent studies indicate that M13 bacteriophage, a very large nanoparticle, binds to β-amyloid and α-synuclein proteins, leading to plaque disaggregation in models of Alzheimer and Parkinson disease. To determine the feasibility, safety, and characteristics of convection-enhanced delivery (CED) of M13 bacteriophage to the brain, the authors perfused primate brains with bacteriophage. Methods Four nonhuman primates underwent CED of M13 bacteriophage (900 nm) to thalamic gray matter (4 infusions) and frontal white matter (3 infusions). Bacteriophage was coinfused with Gd-DTPA (1 mM), and serial MRI studies were performed during infusion. Animals were monitored for neurological deficits and were killed 3 days after infusion. Tissues were analyzed for bacteriophage distribution. Results Real-time T1-weighted MRI studies of coinfused Gd-DTPA during infusion demonstrated a discrete region of perfusion in both thalamic gray and frontal white matter. An MRI-volumetric analysis revealed that the mean volume of distribution (Vd) to volume of infusion (Vi) ratio of M13 bacteriophage was 2.3 ± 0.2 in gray matter and 1.9 ± 0.3 in white matter. The mean values are expressed ± SD. Immunohistochemical analysis demonstrated mean Vd:Vi ratios of 2.9 ± 0.2 in gray matter and 2.1 ± 0.3 in white matter. The Gd-DTPA accurately tracked M13 bacteriophage distribution (the mean difference between imaging and actual bacteriophage Vd was insignificant [p > 0.05], and was −2.2% ± 9.9% in thalamic gray matter and 9.1% ± 9.5% in frontal white matter). Immunohistochemical analysis revealed evidence of additional spread from the initial delivery site in white matter (mean Vd:Vi, 16.1 ± 9.1). All animals remained neurologically intact after infusion during the observation period, and histological studies revealed no evidence of toxicity. Conclusions The CED method can be used successfully and safely to distribute M13 bacteriophage in the brain. Furthermore, additional white matter spread after infusion cessation enhances distribution of this large nanoparticle. Real-time MRI studies of coinfused Gd-DTPA (1 mM) can be used for accurate tracking of distribution during infusion of M13 bacteriophage. PMID:22606981

Convection-enhanced delivery of M13 bacteriophage to the brain.

PubMed

Ksendzovsky, Alexander; Walbridge, Stuart; Saunders, Richard C; Asthagiri, Ashok R; Heiss, John D; Lonser, Russell R

2012-08-01

Recent studies indicate that M13 bacteriophage, a very large nanoparticle, binds to β-amyloid and α-synuclein proteins, leading to plaque disaggregation in models of Alzheimer and Parkinson disease. To determine the feasibility, safety, and characteristics of convection-enhanced delivery (CED) of M13 bacteriophage to the brain, the authors perfused primate brains with bacteriophage. Four nonhuman primates underwent CED of M13 bacteriophage (900 nm) to thalamic gray matter (4 infusions) and frontal white matter (3 infusions). Bacteriophage was coinfused with Gd-DTPA (1 mM), and serial MRI studies were performed during infusion. Animals were monitored for neurological deficits and were killed 3 days after infusion. Tissues were analyzed for bacteriophage distribution. Real-time T1-weighted MRI studies of coinfused Gd-DTPA during infusion demonstrated a discrete region of perfusion in both thalamic gray and frontal white matter. An MRI-volumetric analysis revealed that the mean volume of distribution (Vd) to volume of infusion (Vi) ratio of M13 bacteriophage was 2.3 ± 0.2 in gray matter and 1.9 ± 0.3 in white matter. The mean values are expressed ± SD. Immunohistochemical analysis demonstrated mean Vd:Vi ratios of 2.9 ± 0.2 in gray matter and 2.1 ± 0.3 in white matter. The Gd-DTPA accurately tracked M13 bacteriophage distribution (the mean difference between imaging and actual bacteriophage Vd was insignificant [p > 0.05], and was -2.2% ± 9.9% in thalamic gray matter and 9.1% ± 9.5% in frontal white matter). Immunohistochemical analysis revealed evidence of additional spread from the initial delivery site in white matter (mean Vd:Vi, 16.1 ± 9.1). All animals remained neurologically intact after infusion during the observation period, and histological studies revealed no evidence of toxicity. The CED method can be used successfully and safely to distribute M13 bacteriophage in the brain. Furthermore, additional white matter spread after infusion cessation enhances distribution of this large nanoparticle. Real-time MRI studies of coinfused Gd-DTPA (1 mM) can be used for accurate tracking of distribution during infusion of M13 bacteriophage.

Warm Water Entrainment Impacts and Environmental Life Cycle Assessment of a Proposed Ocean Thermal Energy Conversion Pilot Plant Offshore Oahu, Hawaii

NASA Astrophysics Data System (ADS)

Hauer, Whitney Blanchard

Ocean thermal energy conversion (OTEC) is a marine renewable energy technology that uses the temperature difference of large volumes of cold deep and warm surface seawater in tropical regions to generate electricity. One anticipated environmental impact of OTEC operations is the entrainment and subsequent mortality of ichthyoplankton (fish eggs and larvae) from the withdrawal of cold and warm seawater. The potential ichthyoplankton loss from the warm water intake was estimated for a proposed 10 MW OTEC pilot plant offshore Oahu, HI based on ambient vertical distribution data. The estimated losses due to entrainment from the warm water intake were 8.418E+02 larvae/1000 m3, 3.26E+06 larvae/day, and 1.19E+09 larvae/year. The potential entrained larvae/year is 1.86 X greater than at the Kahe Generating Station (Kapolei, HI), a 582 MW oil-fired power plant. Extrapolating to age-1 equivalence (9.2E+02 and 2.9E+02 yellowfin and skipjack tuna, respectively), the estimated yearly losses from warm water entrainment of yellowfin and skipjack tuna fish eggs and larvae represent 0.25-0.26 % and 0.09-0.11 % of Hawaii's commercial yellowfin and skipjack tuna industry in 2011 and 2012. An environmental life cycle assessment (LCA) was developed for the proposed OTEC plant operating for 20 and 40 years with availability factors of 0.85, 0.95, and 1.0 to determine the global warming potential (GWP) and cumulative energy demand (CED) impacts. For a 20 year operational OTEC plant, the GWP, CED, energy return on investment (EROI), and energy payback time (EPBT) ranged from 0.047 to 0.055 kg CO2eq/kWh, 0.678 to 0.798 MJ/kWh, 4.51 to 5.31 (unitless), and 3.77 to 4.43 years, respectively. For a 40 year operational OTEC plant, the GWP, CED, EROI, and EBPT ranged from 0.036 to 0.043 kg CO2eq/kWh, 0.527 to 0.620 MJ/kWh, 5.81 to 6.83 (unitless), and 5.85 to 6.89 years, respectively. The GWP impacts are within the range of renewable energy technologies and less than conventional electricity generation, with the exception of nuclear power. As part of the LCA, an ichthyoplankton entrainment impact assessment method was developed to estimate potential loss from the warm water intake for the proposed OTEC plant and for six coastal nuclear power facilities that use once-through cooling technology. Larval fish entrainment (#/kWh) was significantly greater (p<0.026) for the proposed OTEC facility, ranging from 10.0 to 11.7 larvae/kWh due to different capacity factors, than for the six nuclear power facilities that ranged from 0.08 to 0.78 larvae/kWh. While this research did not investigate OTEC technology development and economics, OTEC would be a favorable option for reducing the GWP and the reliance on fossil fuels for electricity generation in HI. The impact of ichthyoplankton mortality due to warm water entrainment for a 10 MW OTEC plant offshore Oahu, HI would likely be acceptable as there are examples of similar water withdrawals for electricity generation. Biological monitoring of a 10 MW facility would verify estimated environmental impacts of the warm water withdrawal and provide new information on the cold water withdrawal before advancing to a commercial (e.g., 100 MW) scale facility.

Reducing uncertainty in value-based pricing using evidence development agreements: the case of continuous intraduodenal infusion of levodopa/carbidopa (Duodopa®) in Sweden.

PubMed

Willis, Michael; Persson, Ulf; Zoellner, York; Gradl, Birgit

2010-01-01

Value-based pricing (VBP), whereby prices are set according to the perceived benefits offered to the consumer at a time when costs and benefits are characterized by considerable uncertainty and are then reviewed ex post, is a much discussed topic in pharmaceutical reimbursement. It is usually combined with coverage with evidence development (CED), a tool in which manufacturers are granted temporary reimbursement but are required to collect and submit additional health economic data at review. Many countries, including the UK, are signalling shifts in this direction. Several countries, including Sweden, have already adopted this approach and offer good insight into the benefits and pitfalls in actual practice. To describe VBP reimbursement decision making using CED in actual practice in Sweden. Decision making by The Dental and Pharmaceutical Benefits Agency (TLV) in Sweden was reviewed using a case study of continuous intraduodenal infusion of levodopa/carbidopa (Duodopa®) in the treatment of advanced Parkinson's disease (PD) with severe motor fluctuations. The manufacturer of Duodopa® applied for reimbursement in late 2003. While the proper economic data were not included in the submission, TLV granted reimbursement until early 2005 to provide time for the manufacturer to submit a formal economic evaluation. The re-submission with economic data was considered inadequate to judge cost effectiveness, so TLV granted an additional extension of reimbursement until August 2007, at which time conclusive data were expected. The manufacturer initiated a 3-year, prospective health economic study and a formal economic model. Data from a pre-planned interim analysis of the data were loaded into the model and the cost-effectiveness ratio was the basis of the next re-submission. TLV concluded that the data were suitable for making a definite decision and that the drug was not cost effective, deciding to discontinue reimbursement for any new patients (current patients were unaffected). The manufacturer continued to collect data and to improve the economic model and re-submitted in 2008. New data and the improved model resulted in reduced uncertainty and a lower cost-effectiveness ratio in the range of Swedish kronor (SEK)430,000 per QALY gained in the base-case analysis, ranging up to SEK900,000 in the most conservative sensitivity analysis, resulting in reimbursement being granted. The case of Duodopa® provides excellent insight into VBP reimbursement decision making in combination with CED and ex post review in actual practice. Publicly available decisions document the rigorous, time-consuming process (four iterations were required before a final decision could be reached). The data generated as part of the risk-sharing agreement proved correct the initial decision to grant limited coverage despite lack of economic data. Access was provided to 100 patients while evidence was generated. Economic appraisal differs from clinical assessment, and decision makers benefit from analysis of naturalistic, actual practice data. Despite reviewing the initial trial-based, 'piggy-back' economic analysis, TLV was uncertain of the cost effectiveness in actual practice and deferred a final decision until observational data from the DAPHNE study became available. Second, acceptance of economic modelling and use of temporary reimbursement conditional on additional evidence development provide a mechanism for risk sharing between TLV and manufacturers, which enabled patient access to a drug with proven clinical benefit while necessary evidence to support claims of cost effectiveness could be generated.

Wind - Ceiling - Visibility Data at Selected Airports. Volume X. Part B. Alaskan and Pacific Regions.

DTIC Science & Technology

1981-06-01

Aviation Administration Final Report office of Aviation Policy and Plans_______________ 800 Independence Avenue, S.W. 14. $gronsoei Aenc Ced* Washington...D0C> 00 0 0 0 - - Q cO O O Q Q O -0 LiL LiO Li CL CDC 7DK cnCD - .~ .z .~u . . . . . . . inn AD Ln co . . . . . . . ... .- .7i - C; CCD 0 C; C0 T CC C

Convection-enhanced delivery and in vivo imaging of polymeric nanoparticles for the treatment of malignant glioma.

PubMed

Bernal, Giovanna M; LaRiviere, Michael J; Mansour, Nassir; Pytel, Peter; Cahill, Kirk E; Voce, David J; Kang, Shijun; Spretz, Ruben; Welp, Ulrich; Noriega, Sandra E; Nunez, Luis; Larsen, Gustavo F; Weichselbaum, Ralph R; Yamini, Bakhtiar

2014-01-01

A major obstacle to the management of malignant glioma is the inability to effectively deliver therapeutic agent to the tumor. In this study, we describe a polymeric nanoparticle vector that not only delivers viable therapeutic, but can also be tracked in vivo using MRI. Nanoparticles, produced by a non-emulsion technique, were fabricated to carry iron oxide within the shell and the chemotherapeutic agent, temozolomide (TMZ), as the payload. Nanoparticle properties were characterized and subsequently their endocytosis-mediated uptake by glioma cells was demonstrated. Convection-enhanced delivery (CED) can disperse nanoparticles through the rodent brain and their distribution is accurately visualized by MRI. Infusion of nanoparticles does not result in observable animal toxicity relative to control. CED of TMZ-bearing nanoparticles prolongs the survival of animals with intracranial xenografts compared to control. In conclusion, the described nanoparticle vector represents a unique multifunctional platform that can be used for image-guided treatment of malignant glioma. GBM remains one of the most notoriously treatment-unresponsive cancer types. In this study, a multifunctional nanoparticle-based temozolomide delivery system was demonstrated to possess enhanced treatment efficacy in a rodent xenograft GBM model, with the added benefit of MRI-based tracking via the incorporation of iron oxide as a T2* contrast material in the nanoparticles. © 2014.

The role of ARK in stress-induced apoptosis in Drosophila cells

PubMed Central

Zimmermann, Katja C.; Ricci, Jean-Ehrland; Droin, Nathalie M.; Green, Douglas R.

2002-01-01

The molecular mechanisms of apoptosis are highly conserved throughout evolution. The homologs of genes essential for apoptosis in Caenorhabditis elegans and Drosophila melanogaster have been shown to be important for apoptosis in mammalian systems. Although a homologue for CED-4/apoptotic protease-activating factor (Apaf)-1 has been described in Drosophila, its exact function and the role of the mitochondrial pathway in its activation remain unclear. Here, we used the technique of RNA interference to dissect apoptotic signaling pathways in Drosophila cells. Inhibition of the Drosophila CED-4/Apaf-1–related killer (ARK) homologue resulted in pronounced inhibition of stress-induced apoptosis, whereas loss of ARK did not protect the cells from Reaper- or Grim-induced cell death. Reduction of DIAP1 induced rapid apoptosis in these cells, whereas the inhibition of DIAP2 expression did not but resulted in increased sensitivity to stress-induced apoptosis; apoptosis in both cases was prevented by inhibition of ARK expression. Cells in which cytochrome c expression was decreased underwent apoptosis induced by stress stimuli, Reaper or Grim. These results demonstrate the central role of ARK in stress-induced apoptosis, which appears to act independently of cytochrome c. Apoptosis induced by Reaper or Grim can proceed via a distinct pathway, independent of ARK. PMID:11901172

Association of Anxiety, Depression, and Somatization with Menstrual Problems among North Korean Women Defectors in South Korea.

PubMed

Kim, Hyun Kyoung; Kim, Hee Sook; Kim, Seog Ju

2017-11-01

North Korean women defectors have suffered from anxiety, depression, and somatization after defection. Also they have had many menstrual problems like amenorrhea. This study was done to identify the correlations of anxiety, depression, and somatization to menstrual problems among North Korean woman defectors in South Korea. The participants in this study were 126 women from 5 government resettlement centers throughout South Korea. Questionnaires which included State-Trait Anxiety Inventory (STAI), Center for Epidemiological studies-Depression Scale (CED-S), and Symptom Checklist-90-Revised (SCL-90-R) were used to identify anxiety and somatization. Data were collected between June and September, 2012. The women reported the following problems; amenorrhea (9.5%), hypomenorrhea (13.6%), menorrhagia (19.8%), polymenorrhea (13.5%), oligomenorrhea (4.8%), changes in amount of menstrual discharge (4.0%), and changes in amount of blood clot (9.5%). Anxiety (r=0.20, p=0.002), depression (r=0.25, p=0.005), and Somatization (r=0.35, p<0.001) were correlated with number of menstrual problems. The results of this study indicate that mental health services need to be taken into account in interventions for North Korean woman defectors to improve their reproductive health including addressing menstrual problems.

The effect of workplace smoking bans on heart rate variability and pulse wave velocity of non-smoking hospitality workers.

PubMed

Rajkumar, Sarah; Schmidt-Trucksäss, Arno; Wellenius, Gregory A; Bauer, Georg F; Huynh, Cong Khanh; Moeller, Alexander; Röösli, Martin

2014-08-01

To investigate the effect of a change in second-hand smoke (SHS) exposure on heart rate variability (HRV) and pulse wave velocity (PWV), this study utilized a quasi-experimental setting when a smoking ban was introduced. HRV, a quantitative marker of autonomic activity of the nervous system, and PWV, a marker of arterial stiffness, were measured in 55 non-smoking hospitality workers before and 3-12 months after a smoking ban and compared to a control group that did not experience an exposure change. SHS exposure was determined with a nicotine-specific badge and expressed as inhaled cigarette equivalents per day (CE/d). PWV and HRV parameters significantly changed in a dose-dependent manner in the intervention group as compared to the control group. A one CE/d decrease was associated with a 2.3% (95% CI 0.2-4.4; p = 0.031) higher root mean square of successive differences (RMSSD), a 5.7% (95% CI 0.9-10.2; p = 0.02) higher high-frequency component and a 0.72% (95% CI 0.40-1.05; p < 0.001) lower PWV. PWV and HRV significantly improved after introducing smoke-free workplaces indicating a decreased cardiovascular risk.

The effect of workplace smoking bans on heart rate variability and pulse wave velocity of non-smoking hospitality workers

PubMed Central

Rajkumar, Sarah; Schmidt-Trucksäss, Arno; Wellenius, Gregory A.; Bauer, Georg F.; Huynh, Cong Khanh; Moeller, Alexander; Röösli, Martin

2014-01-01

Objectives To investigate the effect of a change in second hand smoke (SHS) exposure on heart rate variability (HRV) and pulse wave velocity (PWV), this study utilized a quasi-experimental setting when a smoking ban was introduced. Methods HRV, a quantitative marker of autonomic activity of the nervous system, and PWV, a marker of arterial stiffness, were measured in 55 non-smoking hospitality workers before and 3 to 12 months after a smoking ban and compared to a control group that did not experience an exposure change. SHS exposure was determined with a nicotine specific badge and expressed as inhaled cigarette equivalents per day (CE/d). Results PWV and HRV parameters significantly changed in a dose dependent manner in the intervention group compared to the control group. A one CE/d decrease was associated with a 2.3% (95% CI: 0.2, 4.4; p=0.031) higher root mean square of successive differences (RMSSD), a 5.7 % (95% CI: 0.9, 10.2; p=0.02) higher high frequency component and a 0.72% (95 % CI: 0.40–1.05; p<0.001) lower PWV. Conclusions PWV and HRV significantly improved after introducing smoke-free workplaces indicating a decreased cardiovascular risk. PMID:24504155

The new Section 23 of DO160C/ED14C lightning testing of externally mounted electrical equipment

NASA Astrophysics Data System (ADS)

Burrows, B. J. C.

1991-08-01

The new Section 23 is introduced which has only very recently been fully approved by the RTCA for incorporation into the first revision of DO160C/ED14C. Full threat lightning direct effects testing of equipment is entirely new to DO160, the only existing lightning testing is transient testing for LRU's (Line Replaceable Units) by pin or cable bundle injection methods, for equipment entirely contained within the airframe and assumed to be unaffected by direct effects. This testing required transients of very low amplitude compared with lightning itself, whereas the tests now to be described involve full threat lightning testing, that is using the previously established severe parameters of lightning appropriate to the Zone, such as 200 kA for Zone 1A as in AC20-136. Direct effects (i.e., damage) testing involves normally the lightning current arc attaching to the object under test (or very near to it) so submitting it to full potential for the electric, mechanical, thermal and shock damage which is caused by high current arcing. Since equipment for any part of the airframe require qualification, tests to demonstrate safety of equipment in fuel vapor regions of the airframe are also included.

Novel functions for the RNA-binding protein ETR-1 in Caenorhabditis elegans reproduction and engulfment of germline apoptotic cell corpses

PubMed Central

Boateng, Ruby; Nguyen, Ken C.Q.; Hall, David H.; Golden, Andy; Allen, Anna K.

2017-01-01

RNA-binding proteins (RBPs) are essential regulators of gene expression that act through a variety of mechanisms to ensure the proper post-transcriptional regulation of their target RNAs. RBPs in multiple species have been identified as playing crucial roles during development and as having important functions in various adult organ systems, including the heart, nervous, muscle, and reproductive systems. ETR-1, a highly conserved ELAV-Type RNA-binding protein belonging to the CELF/Bruno protein family, has been previously reported to be involved in C. elegans muscle development. Animals depleted of ETR-1 have been previously characterized as arresting at the two-fold stage of embryogenesis. In this study, we show that ETR-1 is expressed in the hermaphrodite somatic gonad and germ line, and that reduction of ETR-1 via RNA interference (RNAi) results in reduced hermaphrodite fecundity. Detailed characterization of this fertility defect indicates that ETR-1 is required in both the somatic tissue and the germ line to ensure wild-type reproductive levels. Additionally, the ability of ETR-1 depletion to suppress the published WEE-1.3-depletion infertility phenotype is dependent on ETR-1 being reduced in the soma. Within the germline of etr-1(RNAi) hermaphrodite animals, we observe a decrease in average oocyte size and an increase in the number of germline apoptotic cell corpses as evident by an increased number of CED-1::GFP and acridine orange positive apoptotic germ cells. Transmission Electron Microscopy (TEM) studies confirm the significant increase in apoptotic cells in ETR-1-depleted animals, and reveal a failure of the somatic gonadal sheath cells to properly engulf dying germ cells in etr-1(RNAi) animals. Through investigation of an established engulfment pathway in C. elegans, we demonstrate that co-depletion of CED-1 and ETR-1 suppresses both the reduced fecundity and the increase in the number of apoptotic cell corpses observed in etr-1(RNAi) animals. Combined, this data identifies a novel role for ETR-1 in hermaphrodite gametogenesis and in the process of engulfment of germline apoptotic cell corpses. PMID:28648844

A new approach to equipment testing

NASA Technical Reports Server (NTRS)

Hardwick, C. J.; Dunkley, V. P.; Burrows, B. J. C.; Darney, I.

1991-01-01

Considerable controversy has arisen during the recent discussions over a new version of the RTCA DO160C/ED 14C Section 22 document at the European Committee for Aviation Electronics. Section 22 is concerned with lightning waveform tests to equipment. Investigations of some of these controversies with circuit analysis and measurements indicate the impedance characteristics required of the transient generators and the possibility of testing to a voltage limit even for current waveforms.

Medical Civic Action Programs (MEDCAPS) and Medical Readiness Training Exercises (MEDRETES) as Instruments of Foreign Policy

DTIC Science & Technology

1988-05-24

term for their program, namely GUARDE, which stands for Guiar de Assistancia Resistancia De Enfermedades (Guided Assistance to Resistance to Sickness...Measles, Tetanus, Toxoid,- BCG). 2. Tuberculosis 3. C.E.D. (Control de Enfermedades Diarreicas) Control of Diarrhea (Oral Rehidration) 4. I.R.A...Infecciones Respiratorias Agudas) Acute Respiratory Infections ,. 5. Rabia . Rabies -control " 6.. .T. S.-.( Enfermedades de Transmisi6n Sexual) S ", -T

A Study of Pilots’ Value Systems and Their Effect on Career Intentions

DTIC Science & Technology

1978-09-01

needs, Maslow’s need-hierarchy comes into play3 Maslow stated that there are five basic needs: physiological, safety, love. estt:em, and self ...then again direct his atttention to the next higher level need (10370-396). Maslow also asse-ced that man strives for eventual self -actualization...life) (affectionate, tender) SELF -RESPECT 0 BEDIENT ( self - esteem ) (dutiful, respectful) SOCIAL RECOGNITION PO LITE (respect, admiration) (courteous, well

Comprehensive Final Report for the Marine Seismic System Program

DTIC Science & Technology

1985-08-01

Executive summary g ■ -■• < ".• v>:.* From 1981 through 1983, the Defense Advanced Research Projects Agency funded the National Science...S. Government. Per Mr. J. A. Ballard, NORDA/Code 360 Accesion For NTIS CRA&I DUG TAB Unannou.iCed Justification G D By Distib...n>r" Analysis of Ambient Seismic Noise Recorded by Downhole and Ocean-Bottom Seismometers on Dee: Sea Drilling Project Leg 78B Richard G

A new approach to equipment testing

NASA Astrophysics Data System (ADS)

Hardwick, C. J.; Dunkley, V. P.; Burrows, B. J. C.; Darney, I.

1991-08-01

Considerable controversy has arisen during the recent discussions over a new version of the RTCA DO160C/ED 14C Section 22 document at the European Committee for Aviation Electronics. Section 22 is concerned with lightning waveform tests to equipment. Investigations of some of these controversies with circuit analysis and measurements indicate the impedance characteristics required of the transient generators and the possibility of testing to a voltage limit even for current waveforms.

Sunnier European countries have lower melanoma mortality.

PubMed

Shipman, A R; Clark, A B; Levell, N J

2011-07-01

Doubt has been cast on sunlight as the major causative factor for malignant melanoma. We performed statistical analysis of the average annual sunlight hours in 36 European capital cities compared with the country's melanoma mortality rate. A significant inverse proportionality was identified in both men and women, indicating that sun exposure is unlikely to be the strongest factor affecting mortality from malignant melanoma. © The Author(s). CED © 2011 British Association of Dermatologists.

Geoenvironmental and structural studies for developing new water resources in arid and semi-arid regions using remote sensing and GIS

NASA Astrophysics Data System (ADS)

Amer, Reda Mohammed

2011-12-01

Water crises are rising with increasing world population and decreasing of freshwater resources. This problem is magnified in the arid and semi-arid regions because surface water resources are very limited and highly unreliable and therefore groundwater is the primary source of water supply in these regions. This study presents an integrated approach for the identification of groundwater occurrences using remote sensing, geological, and geophysical data, and establishing sustainable paths to groundwater management. The Central Eastern Desert (CED) of Egypt was selected as a test site for this study because its climate is arid and there is an urgent need to identify potential areas for groundwater accumulations. Field investigations indicated that the CED has three types of aquifers; shallow alluvial (SA), and fracture zone (FZ) aquifers in the valley depressions, and deep aquifers in the sedimentary succession that range in age from Late Cretaceous to Recent in the marginal extensional sub-basins (ESB) along the Red Sea coast. I developed three models: (1) a Geographic Information System (GIS) model for groundwater potential in the SA and FZ shallow aquifers; (2) a kinematic model for the development of the ESB; and (3) a groundwater budget model for the ESB aquifers. The GIS model is based on the analysis of remote sensing data of the Phased Array L-band Synthetic Aperture Radar, the Landsat Enhanced Thematic Mapper Plus, and the Advanced Spaceborne Thermal Emission and Reflection Radiometer digital elevation model. The model was evaluated and proven successful against the existing shallow water wells, and by geophysical surveys using Ground Penetrating Radar and Geoelectric methods. The kinematic model indicated that the ESB were formed in the orthogonal rifting phase in the late Oligocene that is followed by oblique rifting phase during the early Miocene which resulted to the en-echelon pattern of the inland ESB and nucleation of the rift depression into segments separated by oblique-slip accommodation zones. The groundwater budget model shows that the ESB aquifers have considerable amounts of paleowater that can be purified and used for drinking. The renewable groundwater of SA and FZ aquifers can be used for herding, irrigation, and ore dressing in the mining zones.

Improved distribution of small molecules and viral vectors in the murine brain using a hollow fiber catheter

PubMed Central

Seunguk, Oh; Odland, Rick; Wilson, Scott R.; Kroeger, Kurt M.; Liu, Chunyan; Lowenstein, Pedro R.; Castro, Maria G.; Hall, Walter A.; Ohlfest, John R.

2008-01-01

Object A hollow fiber catheter was developed to improve the distribution of drugs administered via direct infusion into the central nervous system (CNS). It is a porous catheter that significantly increases the surface area of brain tissue into which a drug is infused. Methods Dye was infused into the mouse brain through convection-enhanced delivery (CED) using a 28-gauge needle compared with a 3-mm-long hollow fiber catheter. To determine whether a hollow fiber catheter could increase the distribution of gene therapy vectors, a recombinant adenovirus expressing the firefly luciferase reporter was injected into the mouse striatum. Gene expression was monitored using in vivo bioluminescent imaging. To assess the distribution of gene transfer, an adenovirus expressing green fluorescent protein was injected into the striatum using a hollow fiber catheter or a needle. Results Hollow fiber catheter—mediated infusion increased the volume of brain tissue labeled with dye by 2.7 times relative to needle-mediated infusion. In vivo imaging revealed that catheter-mediated infusion of adenovirus resulted in gene expression that was 10 times greater than that mediated by a needle. The catheter appreciably increased the area of brain transduced with adenovirus relative to a needle, affecting a significant portion of the injected hemisphere. Conclusions The miniature hollow fiber catheter used in this study significantly increased the distribution of dye and adenoviral-mediated gene transfer in the mouse brain compared with the levels reached using a 28-gauge needle. Compared with standard single-port clinical catheters, the hollow fiber catheter has the advantage of millions of nanoscale pores to increase surface area and bulk flow in the CNS. Extending the scale of the hollow fiber catheter for the large mammalian brain shows promise in increasing the distribution and efficacy of gene therapy and drug therapy using CED. PMID:17886557

A novel in situ permeation system and its utility in cancer tissue ablation

PubMed Central

WATANABE, MASAMI

2015-01-01

Focal ablation therapy is an emerging treatment modality for localized cancer lesions. It is an attractive strategy for inhibiting tumor progression and preventing morbidity associated with open surgery. As for intratissue drug delivery systems for use in local therapy, the convection-enhanced delivery (CED) of liquid drugs has been utilized, particularly for the treatment of malignant brain tumors. Although the conventional CED system is useful for providing drug/vehicle-based local therapy, there are several reported disadvantages in terms of the ability to control the extent of drug diffusion. We herein developed and validated a novel in situ permeation (ISP)-MW-1 system for achieving intratissue drug diffusion. The ISP system includes a perfusion catheter connected to an injector and aspirator, which enables intratissue perfusion of the solute diluted in the vehicle in the tip-inserted cavity. We subsequently evaluated the utility of the ISP-MW-1 system for in situ permeation in a subcutaneous tumor model in hamsters. Dehydrated ethanol, saline and 50% acetic acid were evaluated as the vehicle, and methylene blue was used as a dissolved substance for evaluating the diffusion of the agent. As a result, almost all of the tumor tissue within the capsule (tumor size: ~3 cm) was permeated with the dehydrated ethanol and 50% acetic acid and partially with the saline. We further demonstrated that ISP treatment with 50% acetic acid completely ablated the subcutaneous tumors in all of the treated hamsters (n=3). Therefore, the ISP-MW-1 system is a promising approach for controlling the intratissue diffusion of therapeutic agents and for providing local ablation therapy for cancer lesions. We believe that this system may be applicable to a broad range of medicinal and industrial fields, such as regenerative medicine, drug delivery systems, biochemistry and material technologies as well as cancer therapy. PMID:26134633

Determination of diphenylarsinic acid, phenylarsonic acid and inorganic arsenic in drinking water by graphite-furnace atomic-absorption spectrometry after simultaneous separation and preconcentration with solid-phase extraction disks.

PubMed

Hagiwara, Kenta; Inui, Tetsuo; Koike, Yuya; Nakamura, Toshihiro

2013-01-01

A simple method of graphite-furnace atomic-absorption spectrometry (GFAAS) after solid-phase extraction (SPE) was developed for the determination of diphenylarsinic acid (DPAA), phenylarsonic acid (PAA), and inorganic arsenic (iAs) in drinking water. This method involves the simultaneous collection of DPAA, PAA, and iAs using three stacked SPE disks, i.e., an Empore SDB-XD disk (the upper layer), an activated carbon disk (the middle layer), and a Cation-SR disk loaded with Zr and Ca (ZrCa-CED; the lower layer). A 200-mL aqueous sample was adjusted to pH 3 with nitric acid and passed through the SPE disks at a flow rate of 15 mL min(-1), to concentrate DPAA on the SDB-XD disk, PAA on the activated carbon disk, and iAs on the ZrCa-CED. The As compounds were eluted from the disks with 10 mL of ethanol containing 0.5 mol L(-1) ammonia solution for DPAA, 20 mL of 1 mol L(-1) ammonia solution for PAA, and 20 mL of 6 mol L(-1) hydrochloric acid for iAs. The eluates of DPAA, PAA, and iAs were diluted to 20, 25, and 25 mL, respectively, with deionized water, and then analyzed by GFAAS. The detection limits of As (three-times the standard deviation (n = 3) of the blank values) were 0.13 and 0.16 μg L(-1) at enrichment factors of 10 and 8, respectively, using a 200-mL water sample. Spike tests with 2 μg (10 μg L(-1)) of DPAA, PAA, and iAs in 200 mL of tap water and bottled drinking water showed good recoveries (96.1-103.8%).

T2-weighted images are superior to other MR image types for the determination of diffuse intrinsic pontine glioma intratumoral heterogeneity.

PubMed

Harward, Stephen; Harrison Farber, S; Malinzak, Michael; Becher, Oren; Thompson, Eric M

2018-03-01

Diffuse intrinsic pontine glioma (DIPG) remains the main cause of death in children with brain tumors. Given the inefficacy of numerous peripherally delivered agents to treat DIPG, convection enhanced delivery (CED) of therapeutic agents is a promising treatment modality. The purpose of this study was to determine which MR imaging type provides the best discrimination of intratumoral heterogeneity to guide future stereotactic implantation of CED catheters into the most cellular tumor regions. Patients ages 18 years or younger with a diagnosis of DIPG from 2000 to 2015 were included. Radiographic heterogeneity index (HI) of the tumor was calculated by measuring the standard deviation of signal intensity of the tumor (SD Tumor ) normalized to the genu of the corpus callosum (SD Corpus Callosum ). Four MR image types (T2-weighted, contrast-enhanced T1-weighted, FLAIR, and ADC) were analyzed at several time points both before and after radiotherapy and chemotherapy. HI values across these MR image types were compared and correlated with patient survival. MR images from 18 patients with DIPG were evaluated. The mean survival ± standard deviation was 13.8 ± 13.7 months. T2-weighted images had the highest HI (mean ± SD, 5.1 ± 2.5) followed by contrast-enhanced T1-weighted images (3.7 ± 1.5), FLAIR images (3.0 ± 1.1), and ADC maps (1.6 ± 0.4). ANOVA demonstrated that HI values were significantly higher for T2-weighted images than FLAIR (p < 0.01) and ADC (p < 0.0001). Following radiotherapy, T2-weighted and contrast-enhanced T1-weighted image HI values increased, while FLAIR and ADC HI values decreased. Univariate and multivariate analyses did not reveal a relationship between HI values and patient survival (p > 0.05). For children with DIPG, T2-weighted MRI demonstrates the greatest signal intensity variance suggesting tumor heterogeneity. Within this heterogeneity, T2-weighted signal hypointensity is known to correlate with increased cellularity and thus may represent a putative target for CED catheter placement in future clinical trials.

The Procurement of Non Developmental Items: Pros and Cons

DTIC Science & Technology

1994-09-01

commercial way of procurement will bring more advantages than disadvantages to DOD. The list of the pros greatly outweighs the cons . There is practically...AD-A285 009 MH PROCUREMENT OF NON DEVELOPMENTAL ITEMS: PROS AND CONS THES IS Giorgio Scappaticci. Lt. Col., Italian Air Force AFIT/GLMILALj94S-3 I...PROS AND CONS U;narmou,.ced 0 Justification THESIS Giorgio Scappaticci, Lt. Col., Italian Air Force Dist’ibution f Availability Codes AFIT/GLM/LAL

Ex vivo multiscale quantitation of skin biomechanics in wild-type and genetically-modified mice using multiphoton microscopy

NASA Astrophysics Data System (ADS)

Bancelin, Stéphane; Lynch, Barbara; Bonod-Bidaud, Christelle; Ducourthial, Guillaume; Psilodimitrakopoulos, Sotiris; Dokládal, Petr; Allain, Jean-Marc; Schanne-Klein, Marie-Claire; Ruggiero, Florence

2015-12-01

Soft connective tissues such as skin, tendon or cornea are made of about 90% of extracellular matrix proteins, fibrillar collagens being the major components. Decreased or aberrant collagen synthesis generally results in defective tissue mechanical properties as the classic form of Elhers-Danlos syndrome (cEDS). This connective tissue disorder is caused by mutations in collagen V genes and is mainly characterized by skin hyperextensibility. To investigate the relationship between the microstructure of normal and diseased skins and their macroscopic mechanical properties, we imaged and quantified the microstructure of dermis of ex vivo murine skin biopsies during uniaxial mechanical assay using multiphoton microscopy. We used two genetically-modified mouse lines for collagen V: a mouse model for cEDS harboring a Col5a2 deletion (a.k.a. pN allele) and the transgenic K14-COL5A1 mice which overexpress the human COL5A1 gene in skin. We showed that in normal skin, the collagen fibers continuously align with stretch, generating the observed increase in mechanical stress. Moreover, dermis from both transgenic lines exhibited altered collagen reorganization upon traction, which could be linked to microstructural modifications. These findings show that our multiscale approach provides new crucial information on the biomechanics of dermis that can be extended to all collagen-rich soft tissues.

Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC): application for photodynamic therapy and boron neutron capture therapy.

PubMed

Hiramatsu, Ryo; Kawabata, Shinji; Tanaka, Hiroki; Sakurai, Yoshinori; Suzuki, Minoru; Ono, Koji; Miyatake, Shin-ichi; Kuroiwa, Toshihiko; Hao, Erhong; Vicente, M Graça H

2015-03-01

Carboranyl-containing chlorins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and their strong absorptions in the red region of the optical spectrum. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl-containing chlorin of high boron content (24% by weight). To evaluate TPFC's applicability as sensitizer for both PDT and BNCT, we performed an in vitro and in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is currently used in clinical BNCT studies, via intravenous administration (i.v.) and/or used TPFC via convection-enhanced delivery (CED), a method for local drug infusion directly into the brain. In the in vitro PDT study, the cell surviving fraction following laser irradiation (9 J/cm(2) ) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 10(12) n/cm(2) ) was 0.04. In the in vivo BNCT study, the median survival time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42 days (95% confidence interval; 37-43 days). © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Tetrakis(p-Carboranylthio-Tetrafluorophenyl)Chlorin (TPFC): Application for Photodynamic Therapy and Boron Neutron Capture Therapy

PubMed Central

HIRAMATSU, RYO; KAWABATA, SHINJI; TANAKA, HIROKI; SAKURAI, YOSHINORI; SUZUKI, MINORU; ONO, KOJI; MIYATAKE, SHIN-ICHI; KUROIWA, TOSHIHIKO; HAO, ERHONG; VICENTE, M. GRAÇA H.

2015-01-01

Carboranyl-containing chlorins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and their strong absorptions in the red region of the optical spectrum. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl-containing chlorin of high boron content (24% by weight). To evaluate TPFC’s applicability as sensitizer for both PDT and BNCT, we performed an in vitro and in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is currently used in clinical BNCT studies, via intravenous administration (i.v.) and/or used TPFC via convection-enhanced delivery (CED), a method for local drug infusion directly into the brain. In the in vitro PDT study, the cell surviving fraction following laser irradiation (9 J/cm2) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 1012 n/cm2) was 0.04. In the in vivo BNCT study, the median survival time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42 days (95% confidence interval; 37–43 days). PMID:25546823

Epitope mapping and evaluation of specificity of T-helper sites in four major antigenic peptides of chicken riboflavin carrier protein in outbred rats.

PubMed

Subramanian, Sarada; Andal, S; Karande, Anjali A; Radhakantha Adiga, P

2003-11-07

This paper reviews our studies on synthetic peptides spanning the major antigenic determinants of the chicken riboflavin carrier protein (RCP; 219 AA). These determinants are composed of residues 4-24 (YGC), 64-83 (CED), 130-147 (GEN), and 200-219 (HAC) and function as minivaccines in terms of eliciting anti-peptide antibodies which recognize the native protein and are particularly promising contraceptive vaccine candidates. We have used 15-residue synthetic peptides to define short sequences involved in interaction with antibody and with T-cells. We have mapped the boundaries of T-cell epitopes of these peptides in outbred rats by immunizing the animals with each peptide and assaying the popliteal lymph node cell proliferation against a series of overlapping synthetic 15-mers covering the entire length of the individual peptides. The peptides YGC, GEN, and HAC harboured a single T-cell epitope each whereas the peptide CED exhibited bimodal response possessing two epitopes, one at N-terminus and the other at the C-terminus. These studies provide insight into the way in which an immunogen is viewed by the immune system. In addition, preferential T-cell helper function for B cells recognizing unique determinants on the same molecule was demonstrated. This information helps in exploiting synthetic peptides in the construction of designer immunogens which have potential as candidate vaccines.

The archaeal Ced system imports DNA

PubMed Central

van Wolferen, Marleen; Wagner, Alexander; van der Does, Chris; Albers, Sonja-Verena

2016-01-01

The intercellular transfer of DNA is a phenomenon that occurs in all domains of life and is a major driving force of evolution. Upon UV-light treatment, cells of the crenarchaeal genus Sulfolobus express Ups pili, which initiate cell aggregate formation. Within these aggregates, chromosomal DNA, which is used for the repair of DNA double-strand breaks, is exchanged. Because so far no clear homologs of bacterial DNA transporters have been identified among the genomes of Archaea, the mechanisms of archaeal DNA transport have remained a puzzling and underinvestigated topic. Here we identify saci_0568 and saci_0748, two genes from Sulfolobus acidocaldarius that are highly induced upon UV treatment, encoding a transmembrane protein and a membrane-bound VirB4/HerA homolog, respectively. DNA transfer assays showed that both proteins are essential for DNA transfer between Sulfolobus cells and act downstream of the Ups pili system. Our results moreover revealed that the system is involved in the import of DNA rather than the export. We therefore propose that both Saci_0568 and Saci_0748 are part of a previously unidentified DNA importer. Given the fact that we found this transporter system to be widely spread among the Crenarchaeota, we propose to name it the Crenarchaeal system for exchange of DNA (Ced). In this study we have for the first time to our knowledge described an archaeal DNA transporter. PMID:26884154

Spectrum of mucocutaneous, ocular and facial features and delineation of novel presentations in 62 classical Ehlers-Danlos syndrome patients.

PubMed

Colombi, M; Dordoni, C; Venturini, M; Ciaccio, C; Morlino, S; Chiarelli, N; Zanca, A; Calzavara-Pinton, P; Zoppi, N; Castori, M; Ritelli, M

2017-12-01

Classical Ehlers-Danlos syndrome (cEDS) is characterized by marked cutaneous involvement, according to the Villefranche nosology and its 2017 revision. However, the diagnostic flow-chart that prompts molecular testing is still based on experts' opinion rather than systematic published data. Here we report on 62 molecularly characterized cEDS patients with focus on skin, mucosal, facial, and articular manifestations. The major and minor Villefranche criteria, additional 11 mucocutaneous signs and 15 facial dysmorphic traits were ascertained and feature rates compared by sex and age. In our cohort, we did not observe any mandatory clinical sign. Skin hyperextensibility plus atrophic scars was the most frequent combination, whereas generalized joint hypermobility according to the Beighton score decreased with age. Skin was more commonly hyperextensible on elbows, neck, and knees. The sites more frequently affected by abnormal atrophic scarring were knees, face (especially forehead), pretibial area, and elbows. Facial dysmorphism commonly affected midface/orbital areas with epicanthal folds and infraorbital creases more commonly observed in young patients. Our findings suggest that the combination of ≥1 eye dysmorphism and facial/forehead scars may support the diagnosis in children. Minor acquired traits, such as molluscoid pseudotumors, subcutaneous spheroids, and signs of premature skin aging are equally useful in adults. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

let-7 miRNA controls CED-7 homotypic adhesion and EFF-1–mediated axonal self-fusion to restore touch sensation following injury

PubMed Central

Basu, Atrayee; Dey, Shirshendu; Puri, Dharmendra; Das Saha, Nilanjana; Sabharwal, Vidur; Thyagarajan, Pankajam; Srivastava, Prerna; Koushika, Sandhya Padmanabhan

2017-01-01

Neuronal injury often leads to devastating consequences such as loss of senses or locomotion. Restoration of function after injury relies on whether the injured axons can find their target cells. Although fusion between injured proximal axon and distal fragment has been observed in many organisms, its functional significance is not clear. Here, using Caenorhabditis elegans mechanosensory neurons, we address this question. Using two femtosecond lasers simultaneously, we could scan and sever posterior lateral microtubule neurons [posterior lateral microtubules (PLMs)] on both sides of the worm. We showed that axotomy of both PLMs leads to a dramatic loss of posterior touch sensation. During the regenerative phase, only axons that fuse to their distal counterparts contribute to functional recovery. Loss of let-7 miRNA promotes functional restoration in both larval and adult stages. In the L4 stage, loss of let-7 increases fusion events by increasing the mRNA level of one of the cell-recognition molecules, CED-7. The ability to establish cytoplasmic continuity between the proximal and distal ends declines with age. Loss of let-7 overcomes this barrier by promoting axonal transport and enrichment of the EFF-1 fusogen at the growing tip of cut processes. Our data reveal the functional property of a regenerating neuron. PMID:29109254

Chronic, intermittent convection-enhanced delivery devices.

PubMed

Lewis, Owen; Woolley, Max; Johnson, David; Rosser, Anne; Barua, Neil U; Bienemann, Alison S; Gill, Steven S; Evans, Sam

2016-02-01

Intraparenchymal convection-enhanced delivery (CED) of therapeutics directly into the brain has long been endorsed as a medium through which meaningful concentrations of drug can be administered to patients, bypassing the blood brain barrier. The translation of the technology to clinic has been hindered by poor distribution not previously observed in smaller pre-clinical models. In part this was due to the larger volumes of target structures found in humans but principally the poor outcome was linked to reflux (backflow) of infusate proximally along the catheter track. Over the past 10 years, improvements have been made to the technology in the field which has led to a small number of commercially available devices containing reflux inhibiting features. While these devices are currently suitable for acute or short term use, several indications would benefit from longer term repeated, intermittent administration of therapeutics (Parkinson's, Alzheimer's, Amyotrophic lateral sclerosis, Brain tumours such as Glioblastoma Multiforme (GBM) and Diffuse intrinsic Pontine Glioma (DIPG), etc.). Despite the need for a chronically accessible platform for such indications, limited experience exists in this part of the field. At the time of writing no commercially available clinical platform, indicated for chronic, intermittent or continuous delivery to the brain exists. Here we review the improvements that have been made to CED devices over recent years and current state of the art for chronic infusion systems. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Life cycle assessment of a parabolic trough concentrating solar power plant and the impacts of key design alternatives.

PubMed

Burkhardt, John J; Heath, Garvin A; Turchi, Craig S

2011-03-15

Climate change and water scarcity are important issues for today's power sector. To inform capacity expansion decisions, hybrid life cycle assessment is used to evaluate a reference design of a parabolic trough concentrating solar power (CSP) facility located in Daggett, CA, along four sustainability metrics: life cycle (LC) greenhouse gas (GHG) emissions, water consumption, cumulative energy demand (CED), and energy payback time (EPBT). This wet-cooled, 103 MW plant utilizes mined nitrates salts in its two-tank, thermal energy storage (TES) system. Design alternatives of dry-cooling, a thermocline TES, and synthetically derived nitrate salt are evaluated. During its LC, the reference CSP plant is estimated to emit 26 g of CO(2eq) per kWh, consume 4.7 L/kWh of water, and demand 0.40 MJ(eq)/kWh of energy, resulting in an EPBT of approximately 1 year. The dry-cooled alternative is estimated to reduce LC water consumption by 77% but increase LC GHG emissions and CED by 8%. Synthetic nitrate salts may increase LC GHG emissions by 52% compared to mined. Switching from two-tank to thermocline TES configuration reduces LC GHG emissions, most significantly for plants using synthetically derived nitrate salts. CSP can significantly reduce GHG emissions compared to fossil-fueled generation; however, dry-cooling may be required in many locations to minimize water consumption.

Brain Tumor Diagnostics and Therapeutics with Superparamagnetic Ferrite Nanoparticles.

PubMed

Hyder, Fahmeed; Manjura Hoque, S

2017-01-01

Ferrite nanoparticles (F-NPs) can transform both cancer diagnostics and therapeutics. Superparamagnetic F-NPs exhibit high magnetic moment and susceptibility such that in presence of a static magnetic field transverse relaxation rate of water protons for MRI contrast is augmented to locate F-NPs (i.e., diagnostics) and exposed to an alternating magnetic field local temperature is increased to induce tissue necrosis (i.e., thermotherapy). F-NPs are modified by chemical synthesis of mixed spinel ferrites as well as their size, shape, and coating. Purposely designed drug-containing nanoparticles (D-NPs) can slowly deliver drugs (i.e., chemotherapy). Convection-enhanced delivery (CED) of D-NPs with MRI guidance improves glioblastoma multiforme (GBM) treatment. MRI monitors the location of chemotherapy when D-NPs and F-NPs are coadministered with CED. However superparamagnetic field gradients produced by F-NPs complicate MRI readouts (spatial distortions) and MRS (extensive line broadening). Since extracellular pH (pH e ) is a cancer hallmark, pH e imaging is needed to screen cancer treatments. Biosensor imaging of redundant deviation in shifts (BIRDS) extrapolates pH e from paramagnetically shifted signals and the pH e accuracy remains unaffected by F-NPs. Hence effect of both chemotherapy and thermotherapy can be monitored (by BIRDS), whereas location of F-NPs is revealed (by MRI). Smarter tethering of nanoparticles and agents will impact GBM theranostics.

Evaluation of the antioxidant property and effects in Caenorhabditis elegans of Xiangxi flavor vinegar, a Hunan local traditional vinegar*

PubMed Central

HUANG, Run-ting; HUANG, Qing; WU, Gen-liang; CHEN, Chun-guang; LI, Zong-jun

2017-01-01

Xiangxi flavor vinegar (XV) is one of Hunan Province’s traditional fermented vinegars. It is produced from herb, rice, and spring water with spontaneous liquid-state fermentation techniques. In this study, we investigated the antioxidant property of XV by analyzing its antioxidant compounds, its free radical scavenging property in vitro and in vivo, and its effects on antioxidant enzyme activity and apoptosis in Caenorhabditis elegans. The results showed that XV is rich in antioxidants. In particular, ligustrazine reached 6.431 μg/ml. The in vitro 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH•), hydroxyl radical (•OH), and superoxide anion radical (O2 •−) scavenging rates of XV were 95.85%, 97.22%, and 63.33%, respectively. The reactive oxygen species (ROS) content in XV-treated C. elegans decreased significantly (P<0.01) compared to the control group. Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities were remarkably increased (P<0.01) in C. elegans after XV treatment. In addition, XV could upregulate CED-9 protein expression and downregulate CED-3 protein expression in C. elegans. These results prove that XV is rich in antioxidants and scavenges radicals in vitro efficiently. XV inhibits apoptosis in C. elegans probably by scavenging ROS and increasing the activities of its antioxidant enzymes. PMID:28378570

Intelligence and Electronic Warfare (IEW) Streamlining Project. Volume 1. Sustainment Analysis Report. Revision

DTIC Science & Technology

1992-10-30

I Sustainment Analysis Report Accesion For NTIS CRA&I DTIC 1 AP- U. an-;o u,ced [] jj ~~~Y INSPECTED 5 Js~~~o By.......... ............ Dit Ib ’tiot...ELECTRONIC WARFARE (1EW) STREAMUNING PROJECT Vohune I Sustainment Analysis Report Revised October 30, 1992 93-29047 The views, opinions, and findings...Streamlining Project, C OPM-91-2964 Volume I, Sustainment Analysis Report PR 02TO2K 6. AUTHORIS) David P. Nicholas, Robert E. Klebo. Wolodymyr J. Mokey

Influence of Embedded Optical Fibers on Compressive Strength of Advanced Composites

DTIC Science & Technology

1993-12-01

Aeronautial Engineering Accesion For NTIS CRA&,j DTIC TAB 13 Unawlou:,ced Justification Stefan B. Dosedel, B.S.M.E. By _i l b i...aircraft weight can yield an increase in specific excess power of 1%, an increase in subsonic sustained turn rate of 1%, and an increase in supersonic... sustained turn rate of .5% [2]. Composite materials can achieve mass savings on the order of 9-30 percent [2]. It is expected that composite materials will

Design of a Microprogram Control Unit with Concurrent Error Detection.

DTIC Science & Technology

1984-08-01

I fxoot Office of Naval Research N/A N00039-80-C-0556 ta. ADDRESS (City. St.. and ZIP Cod 10. SOURCE OF FUNOING N0. -PROGRAM PROJECT TASK WORK UNIT...However, the CED concept is mainly applied to various codes data transmission, and simple functional units, such as arithmetic units. Little work has...been done in the control unit area. Previous work is primarily in the use of clanical self-checking circuits, using bit slicin& parity, and m-out-of-n

Requirements for radiation emergency urine bioassay techniques for the public and first responders.

PubMed

Li, Chunsheng; Vlahovich, Slavica; Dai, Xiongxin; Richardson, Richard B; Daka, Joseph N; Kramer, Gary H

2010-11-01

Following a radiation emergency, the affected public and the first responders may need to be quickly assessed for internal contamination by the radionuclides involved. Urine bioassay is one of the most commonly used methods for assessing radionuclide intake and radiation dose. This paper attempts to derive the sensitivity requirements (from inhalation exposure) for the urine bioassay techniques for the top 10 high-risk radionuclides that might be used in a terrorist attack. The requirements are based on a proposed reference dose to adults of 0.1 Sv (CED, committed effective dose). In addition, requirements related to sample turnaround time and field deployability of the assay techniques are also discussed. A review of currently available assay techniques summarized in this paper reveals that method development for ²⁴¹Am, ²²⁶Ra, ²³⁸Pu, and ⁹⁰Sr urine bioassay is needed.

Idiopathic pure sudomotor failure and cholinergic urticaria in a patient after acute infectious mononucleosis infection.

PubMed

Chin, Y-Y; Chang, T C-C; Chang, C-H

2013-03-01

Idiopathic pure sudomotor failure (IPSF) is a subgroup of acquired idiopathic generalized anhidrosis, which is characterized by early age of onset, acute or sudden onset, concomitant sharp pain or cholinergic urticaria over the entire body, absence of autonomic dysfunction other than generalized anhidrosis, raised serum IgE level, and marked response to steroid. The aetiology of IPSF is still not well understood, but is thought to be caused by interference in cholinergic transmission in the eccrine glands of skin. IPSF after viral infection has rarely been reported in the literature. We describe a patient who developed generalized anhidrosis and cholinergic urticaria accompanied by heat intolerance after infectious mononucleosis infection. This is the first such case, to our knowledge, and the patient was successfully treated with steroid pulse therapy. © The Author(s). CED © 2012 British Association of Dermatologists.

Modeling of magnitude distributions by the generalized truncated exponential distribution

NASA Astrophysics Data System (ADS)

Raschke, Mathias

2015-01-01

The probability distribution of the magnitude can be modeled by an exponential distribution according to the Gutenberg-Richter relation. Two alternatives are the truncated exponential distribution (TED) and the cutoff exponential distribution (CED). The TED is frequently used in seismic hazard analysis although it has a weak point: when two TEDs with equal parameters except the upper bound magnitude are mixed, then the resulting distribution is not a TED. Inversely, it is also not possible to split a TED of a seismic region into TEDs of subregions with equal parameters except the upper bound magnitude. This weakness is a principal problem as seismic regions are constructed scientific objects and not natural units. We overcome it by the generalization of the abovementioned exponential distributions: the generalized truncated exponential distribution (GTED). Therein, identical exponential distributions are mixed by the probability distribution of the correct cutoff points. This distribution model is flexible in the vicinity of the upper bound magnitude and is equal to the exponential distribution for smaller magnitudes. Additionally, the exponential distributions TED and CED are special cases of the GTED. We discuss the possible ways of estimating its parameters and introduce the normalized spacing for this purpose. Furthermore, we present methods for geographic aggregation and differentiation of the GTED and demonstrate the potential and universality of our simple approach by applying it to empirical data. The considerable improvement by the GTED in contrast to the TED is indicated by a large difference between the corresponding values of the Akaike information criterion.

Polymeric nanoparticles for nonviral gene therapy extend brain tumor survival in vivo.

PubMed

Mangraviti, Antonella; Tzeng, Stephany Yi; Kozielski, Kristen Lynn; Wang, Yuan; Jin, Yike; Gullotti, David; Pedone, Mariangela; Buaron, Nitsa; Liu, Ann; Wilson, David R; Hansen, Sarah K; Rodriguez, Fausto J; Gao, Guo-Dong; DiMeco, Francesco; Brem, Henry; Olivi, Alessandro; Tyler, Betty; Green, Jordan J

2015-02-24

Biodegradable polymeric nanoparticles have the potential to be safer alternatives to viruses for gene delivery; however, their use has been limited by poor efficacy in vivo. In this work, we synthesize and characterize polymeric gene delivery nanoparticles and evaluate their efficacy for DNA delivery of herpes simplex virus type I thymidine kinase (HSVtk) combined with the prodrug ganciclovir (GCV) in a malignant glioma model. We investigated polymer structure for gene delivery in two rat glioma cell lines, 9L and F98, to discover nanoparticle formulations more effective than the leading commercial reagent Lipofectamine 2000. The lead polymer structure, poly(1,4-butanediol diacrylate-co-4-amino-1-butanol) end-modified with 1-(3-aminopropyl)-4-methylpiperazine, is a poly(β-amino ester) (PBAE) and formed nanoparticles with HSVtk DNA that were 138 ± 4 nm in size and 13 ± 1 mV in zeta potential. These nanoparticles containing HSVtk DNA showed 100% cancer cell killing in vitro in the two glioma cell lines when combined with GCV exposure, while control nanoparticles encoding GFP maintained robust cell viability. For in vivo evaluation, tumor-bearing rats were treated with PBAE/HSVtk infusion via convection-enhanced delivery (CED) in combination with systemic administration of GCV. These treated animals showed a significant benefit in survival (p = 0.0012 vs control). Moreover, following a single CED infusion, labeled PBAE nanoparticles spread completely throughout the tumor. This study highlights a nanomedicine approach that is highly promising for the treatment of malignant glioma.

Cumulative energy demand and global warming potential of a building-integrated solar thermal system with/without phase change material.

PubMed

Lamnatou, Chr; Motte, F; Notton, G; Chemisana, D; Cristofari, C

2018-04-15

Building-integrated solar thermal (BIST) systems are a specific type of solar thermal systems which are integrated into the building and they participate in building functionality. The present article is about the life-cycle assessment of different options of a BIST system (Mediterranean climatic conditions: Ajaccio, France). The environmental profile of the studied configurations is assessed by means of CED (cumulative energy demand), GWP (global warming potential) and EPBT (energy payback time). The proposed configurations (for the collector) include: i) a system without PCM (phase change material) using only rock wool as insulation and ii) a system with PCM (myristic acid) and rock wool. Concerning life-cycle results based on CED and GWP 100a (scenario without recycling), the configuration without PCM shows 0.67 MJ prim /kWh and 0.06 kg CO 2.eq /kWh while the configuration with PCM presents 0.74 MJ prim /kWh and 0.08 kg CO 2.eq /kWh. Regarding EPBT, if the inputs for pumping/auxiliary heating are not taken into account, both configurations (with/without PCM) have almost the same EPBT (about 1.3 years). On the other hand, if the inputs for pumping/auxiliary heating are considered, EPBT is lower for the system with PCM. In addition, scenarios with recycling have been examined and the results demonstrate that recycling considerably improves the environmental profile of the studied configurations. Copyright © 2018 Elsevier Ltd. All rights reserved.

MetaCRAST: reference-guided extraction of CRISPR spacers from unassembled metagenomes.

PubMed

Moller, Abraham G; Liang, Chun

2017-01-01

Clustered regularly interspaced short palindromic repeat (CRISPR) systems are the adaptive immune systems of bacteria and archaea against viral infection. While CRISPRs have been exploited as a tool for genetic engineering, their spacer sequences can also provide valuable insights into microbial ecology by linking environmental viruses to their microbial hosts. Despite this importance, metagenomic CRISPR detection remains a major challenge. Here we present a reference-guided CRISPR spacer detection tool ( Meta genomic C RISPR R eference- A ided S earch T ool-MetaCRAST) that constrains searches based on user-specified direct repeats (DRs). These DRs could be expected from assembly or taxonomic profiles of metagenomes. We compared the performance of MetaCRAST to those of two existing metagenomic CRISPR detection tools-Crass and MinCED-using both real and simulated acid mine drainage (AMD) and enhanced biological phosphorus removal (EBPR) metagenomes. Our evaluation shows MetaCRAST improves CRISPR spacer detection in real metagenomes compared to the de novo CRISPR detection methods Crass and MinCED. Evaluation on simulated metagenomes show it performs better than de novo tools for Illumina metagenomes and comparably for 454 metagenomes. It also has comparable performance dependence on read length and community composition, run time, and accuracy to these tools. MetaCRAST is implemented in Perl, parallelizable through the Many Core Engine (MCE), and takes metagenomic sequence reads and direct repeat queries (FASTA or FASTQ) as input. It is freely available for download at https://github.com/molleraj/MetaCRAST.

Inhibition of GLO1 in Glioblastoma Multiforme Increases DNA-AGEs, Stimulates RAGE Expression, and Inhibits Brain Tumor Growth in Orthotopic Mouse Models.

PubMed

Jandial, Rahul; Neman, Josh; Lim, Punnajit P; Tamae, Daniel; Kowolik, Claudia M; Wuenschell, Gerald E; Shuck, Sarah C; Ciminera, Alexandra K; De Jesus, Luis R; Ouyang, Ching; Chen, Mike Y; Termini, John

2018-01-30

Cancers that exhibit the Warburg effect may elevate expression of glyoxylase 1 (GLO1) to detoxify the toxic glycolytic byproduct methylglyoxal (MG) and inhibit the formation of pro-apoptotic advanced glycation endproducts (AGEs). Inhibition of GLO1 in cancers that up-regulate glycolysis has been proposed as a therapeutic targeting strategy, but this approach has not been evaluated for glioblastoma multiforme (GBM), the most aggressive and difficult to treat malignancy of the brain. Elevated GLO1 expression in GBM was established in patient tumors and cell lines using bioinformatics tools and biochemical approaches. GLO1 inhibition in GBM cell lines and in an orthotopic xenograft GBM mouse model was examined using both small molecule and short hairpin RNA (shRNA) approaches. Inhibition of GLO1 with S -( p -bromobenzyl) glutathione dicyclopentyl ester ( p- BrBzGSH(Cp)₂) increased levels of the DNA-AGE N ²-1-(carboxyethyl)-2'-deoxyguanosine (CEdG), a surrogate biomarker for nuclear MG exposure; substantially elevated expression of the immunoglobulin-like receptor for AGEs (RAGE); and induced apoptosis in GBM cell lines. Targeting GLO1 with shRNA similarly increased CEdG levels and RAGE expression, and was cytotoxic to glioma cells. Mice bearing orthotopic GBM xenografts treated systemically with p -BrBzGSH(Cp)₂ exhibited tumor regression without significant off-target effects suggesting that GLO1 inhibition may have value in the therapeutic management of these drug-resistant tumors.

Inhibition of GLO1 in Glioblastoma Multiforme Increases DNA-AGEs, Stimulates RAGE Expression, and Inhibits Brain Tumor Growth in Orthotopic Mouse Models

PubMed Central

Jandial, Rahul; Neman, Josh; Tamae, Daniel; Kowolik, Claudia M.; Wuenschell, Gerald E.; Ciminera, Alexandra K.; De Jesus, Luis R.; Ouyang, Ching; Chen, Mike Y.

2018-01-01

Cancers that exhibit the Warburg effect may elevate expression of glyoxylase 1 (GLO1) to detoxify the toxic glycolytic byproduct methylglyoxal (MG) and inhibit the formation of pro-apoptotic advanced glycation endproducts (AGEs). Inhibition of GLO1 in cancers that up-regulate glycolysis has been proposed as a therapeutic targeting strategy, but this approach has not been evaluated for glioblastoma multiforme (GBM), the most aggressive and difficult to treat malignancy of the brain. Elevated GLO1 expression in GBM was established in patient tumors and cell lines using bioinformatics tools and biochemical approaches. GLO1 inhibition in GBM cell lines and in an orthotopic xenograft GBM mouse model was examined using both small molecule and short hairpin RNA (shRNA) approaches. Inhibition of GLO1 with S-(p-bromobenzyl) glutathione dicyclopentyl ester (p-BrBzGSH(Cp)2) increased levels of the DNA-AGE N2-1-(carboxyethyl)-2′-deoxyguanosine (CEdG), a surrogate biomarker for nuclear MG exposure; substantially elevated expression of the immunoglobulin-like receptor for AGEs (RAGE); and induced apoptosis in GBM cell lines. Targeting GLO1 with shRNA similarly increased CEdG levels and RAGE expression, and was cytotoxic to glioma cells. Mice bearing orthotopic GBM xenografts treated systemically with p-BrBzGSH(Cp)2 exhibited tumor regression without significant off-target effects suggesting that GLO1 inhibition may have value in the therapeutic management of these drug-resistant tumors. PMID:29385725

Insights from molecular modeling and dynamics simulation of pathogen resistance (R) protein from brinjal.

PubMed

Shrivastava, Dipty; Nain, Vikrant; Sahi, Shakti; Verma, Anju; Sharma, Priyanka; Sharma, Prakash Chand; Kumar, Polumetla Ananda

2011-01-22

Resistance (R) protein recognizes molecular signature of pathogen infection and activates downstream hypersensitive response signalling in plants. R protein works as a molecular switch for pathogen defence signalling and represent one of the largest plant gene family. Hence, understanding molecular structure and function of R proteins has been of paramount importance for plant biologists. The present study is aimed at predicting structure of R proteins signalling domains (CC-NBS) by creating a homology model, refining and optimising the model by molecular dynamics simulation and comparing ADP and ATP binding. Based on sequence similarity with proteins of known structures, CC-NBS domains were initially modelled using CED- 4 (cell death abnormality protein) and APAF-1 (apoptotic protease activating factor) as multiple templates. The final CC-NBS structural model was built and optimized by molecular dynamic simulation for 5 nanoseconds (ns). Docking of ADP and ATP at active site shows that both ligand bind specifically with same residues and with minor difference (1 Kcal/mol) in binding energy. Sharing of binding site by ADP and ATP and low difference in their binding site makes CC-NBS suitable for working as molecular switch. Furthermore, structural superimposition elucidate that CC-NBS and CARD (caspase recruitment domains) domain of CED-4 have low RMSD value of 0.9 A° Availability of 3D structural model for both CC and NBS domains will . help in getting deeper insight in these pathogen defence genes.

Computational electrodynamics in material media with constraint-preservation, multidimensional Riemann solvers and sub-cell resolution - Part I, second-order FVTD schemes

NASA Astrophysics Data System (ADS)

Balsara, Dinshaw S.; Taflove, Allen; Garain, Sudip; Montecinos, Gino

2017-11-01

While classic finite-difference time-domain (FDTD) solutions of Maxwell's equations have served the computational electrodynamics (CED) community very well, formulations based on Godunov methodology have begun to show advantages. We argue that the formulations presented so far are such that FDTD schemes and Godunov-based schemes each have their own unique advantages. However, there is currently not a single formulation that systematically integrates the strengths of both these major strains of development. While an early glimpse of such a formulation was offered in Balsara et al. [16], that paper focused on electrodynamics in plasma. Here, we present a synthesis that integrates the strengths of both FDTD and Godunov-based schemes into a robust single formulation for CED in material media. Three advances make this synthesis possible. First, from the FDTD method, we retain (but somewhat modify) a spatial staggering strategy for the primal variables. This provides a beneficial constraint preservation for the electric displacement and magnetic induction vector fields via reconstruction methods that were initially developed in some of the first author's papers for numerical magnetohydrodynamics (MHD). Second, from the Godunov method, we retain the idea of upwinding, except that this idea, too, has to be significantly modified to use the multi-dimensionally upwinded Riemann solvers developed by the first author. Third, we draw upon recent advances in arbitrary derivatives in space and time (ADER) time-stepping by the first author and his colleagues. We use the ADER predictor step to endow our method with sub-cell resolving capabilities so that the method can be stiffly stable and resolve significant sub-cell variation in the material properties within a zone. Overall, in this paper, we report a new scheme for numerically solving Maxwell's equations in material media, with special attention paid to a second-order-accurate formulation. Several numerical examples are presented to show that the proposed technique works. Because of its sub-cell resolving ability, the new method retains second-order accuracy even when material permeability and permittivity vary by an order-of-magnitude over just one or two zones. Furthermore, because the new method is also unconditionally stable in the presence of stiff source terms (i.e., in problems involving giant conductivity variations), it can handle several orders-of-magnitude variation in material conductivity over just one or two zones without any reduction of the time-step. Consequently, the CFL depends only on the propagation speed of light in the medium being studied.

A Centralized Source of Information for the Military Working Dog Program

DTIC Science & Technology

1990-06-01

USA B.S., Purdue University, 1975 MS., Oklahoma State University, 1978 D TIC D.V.M., Colorado State University, 1982 NOV2 6 1990 SI D Fort...FROST, MAJ, USA D A"C "BU~n ancno un ced i B.S., Purdue University, 1975 aUsti c tio M.S., Oklahoma State University, 1978 - D.V.M., Colorado State...19-35: 2, 11-27; Thorton). Narcotic Detector Dog - A MWD trained specifically to detect the presence of marijuana and its derivatives. They are also

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heinrichs, Dave; Beller, Tim; Burch, Jennifer

This document is the Final Design (CED-2) Report for IER-148, “International Inter-comparison Exercise for Nuclear Accident Dosimetry at the DAF Using Godiva-IV.” The report describes the structure of the exercise consisting of three irradiations; identifies the participating laboratories and their points of contact; provides the details of all dosimetry elements and their placement in proximity to Godiva-IV on support stands or phantoms ; and lists the counting and spectroscopy equipment each laboratory will utilize in the Mercury NAD Lab. The exercise is tentatively scheduled for one week in August 2015.

The Art and Science of Operational Maneuver,

DTIC Science & Technology

1988-05-04

Classification) The Art and Science of Operational Maneuver (U) 12. PERSONAL AUTHOR(S) MAJ Joseph Schroedel 13a. TYPE OF REPORT 13b. TIME COVERED 14...CLASSIFICATION OF THIS PAGE VA) CL LA S F1 EP {fJE ART ANQ SCIENCE OlF OPERAIl NAL MANUVER By6 Mal or Josepi~ Schroeci, L U. S. Arm~y H Aciv -darILC Ced M ili t...Studies ,nIgz’raph ApprovwA. Name of Student: Major Jonevh Schroedel. U.S. Army Title ot Monograph: The Art and Science of Operational Maneuver Approved By

A novel magnetic resonance imaging segmentation technique for determining diffuse intrinsic pontine glioma tumor volume.

PubMed

Singh, Ranjodh; Zhou, Zhiping; Tisnado, Jamie; Haque, Sofia; Peck, Kyung K; Young, Robert J; Tsiouris, Apostolos John; Thakur, Sunitha B; Souweidane, Mark M

2016-11-01

OBJECTIVE Accurately determining diffuse intrinsic pontine glioma (DIPG) tumor volume is clinically important. The aims of the current study were to 1) measure DIPG volumes using methods that require different degrees of subjective judgment; and 2) evaluate interobserver agreement of measurements made using these methods. METHODS Eight patients from a Phase I clinical trial testing convection-enhanced delivery (CED) of a therapeutic antibody were included in the study. Pre-CED, post-radiation therapy axial T2-weighted images were analyzed using 2 methods requiring high degrees of subjective judgment (picture archiving and communication system [PACS] polygon and Volume Viewer auto-contour methods) and 1 method requiring a low degree of subjective judgment (k-means clustering segmentation) to determine tumor volumes. Lin's concordance correlation coefficients (CCCs) were calculated to assess interobserver agreement. RESULTS The CCCs of measurements made by 2 observers with the PACS polygon and the Volume Viewer auto-contour methods were 0.9465 (lower 1-sided 95% confidence limit 0.8472) and 0.7514 (lower 1-sided 95% confidence limit 0.3143), respectively. Both were considered poor agreement. The CCC of measurements made using k-means clustering segmentation was 0.9938 (lower 1-sided 95% confidence limit 0.9772), which was considered substantial strength of agreement. CONCLUSIONS The poor interobserver agreement of PACS polygon and Volume Viewer auto-contour methods highlighted the difficulty in consistently measuring DIPG tumor volumes using methods requiring high degrees of subjective judgment. k-means clustering segmentation, which requires a low degree of subjective judgment, showed better interobserver agreement and produced tumor volumes with delineated borders.

A shape-preserving oriented partial differential equation based on a new fidelity term for electronic speckle pattern interferometry fringe patterns denoising

NASA Astrophysics Data System (ADS)

Xu, Wenjun; Tang, Chen; Zheng, Tingyue; Qiu, Yue

2018-07-01

Oriented partial differential equations (OPDEs) have been demonstrated to be a powerful tool for preserving the integrity of fringes while filtering electronic speckle pattern interferometry (ESPI) fringe patterns. However, the main drawback of OPDEs-based methods is that many iterations are often needed, which causes the change in the shape of fringes. Change in the shape of fringes will affect the accuracy of subsequent fringe analysis. In this paper, we focus on preserving the shape of fringes while filtering, suggested here for the first time. We propose a shape-preserving OPDE for ESPI fringe patterns denoising by introducing a new fidelity term to the previous second-order single oriented PDE (SOOPDE). In our proposed fidelity term, the evolution image is subtracted from the shrinkage result of original noisy image by shearlet transform. Our proposed shape-preserving OPDE is capable of eliminating noise effectively, keeping the integrity of fringes, and more importantly, preserving the shape of fringes. We test the proposed shape-preserving OPDE on three computer-simulated and three experimentally obtained ESPI fringe patterns with poor quality. Furthermore, we compare our model with three representative filtering methods, including the widely used SOOPDE, shearlet transform and coherence-enhancing diffusion (CED). We also compare our proposed fidelity term with the traditional fidelity term. Experimental results show that the proposed shape-preserving OPDE not only yields filtered images with visual quality on par with those by CED which is the state-of-the-art method for ESPI fringe patterns denoising, but also keeps the shape of ESPI fringe patterns.

Interactions of UNC-34 Enabled With Rac GTPases and the NIK Kinase MIG-15 in Caenorhabditis elegans Axon Pathfinding and Neuronal Migration

PubMed Central

Shakir, M. Afaq; Gill, Jason S.; Lundquist, Erik A.

2006-01-01

Many genes that affect axon pathfinding and cell migration have been identified. Mechanisms by which these genes and the molecules they encode interact with one another in pathways and networks to control developmental events are unclear. Rac GTPases, the cytoskeletal signaling molecule Enabled, and NIK kinase have all been implicated in regulating axon pathfinding and cell migration. Here we present evidence that, in Caenorhabditis elegans, three Rac GTPases, CED-10, RAC-2, and MIG-2, define three redundant pathways that each control axon pathfinding, and that the NIK kinase MIG-15 acts in each Rac pathway. Furthermore, we show that the Enabled molecule UNC-34 defines a fourth partially redundant pathway that acts in parallel to Rac/MIG-15 signaling in axon pathfinding. Enabled and the three Racs also act redundantly to mediate AQR and PQR neuronal cell migration. The Racs and UNC-34 Ena might all control the formation of actin-based protrusive structures (lamellipodia and filopodia) that mediate growth cone outgrowth and cell migration. MIG-15 does not act with the three Racs in execution of cell migration. Rather, MIG-15 affects direction of PQR neuronal migration, similar to UNC-40 and DPY-19, which control initial Q cell polarity, and Wnt signaling, which acts later to control Q cell-directed migration. MIG-2 Rac, which acts with CED-10 Rac, RAC-2 Rac, and UNC-34 Ena in axon pathfinding and cell migration, also acts with MIG-15 in PQR directional migration. PMID:16204220

Time-dependent Variation in Life Cycle Assessment of Microalgal Biorefinery Co-products

NASA Astrophysics Data System (ADS)

Montazeri, Mahdokht

Microalgae can serve as a highly productive biological feedstock for fuels and chemicals. The lipid fraction of algal seeds has been the primary target of research for biofuel production. However, numerous assessments have found that valorization of co-products is essential to achieve economic and environmental goals. The relative proportion of co-products depends on the biomolecular composition of algae at the time of harvesting. In the present study the productivity of lipid, starch, and protein fractions were shown through growth experiments to vary widely with species, feeding regime, and harvesting time. Four algae species were cultivated under nitrogen-replete and -deplete conditions and analyzed at regular harvesting intervals. Dynamic growth results were then used for life cycle assessment using the U.S. Department of Energy's GREET model to determine optimal growth scenarios that minimize life cycle greenhouse gas (GHG) emissions, eutrophication, and cumulative energy demand (CED), while aiming for an energy return on investment (EROI) greater than unity. Per kg of biodiesel produced, C. sorokiniana in N-replete conditions harvested at 12 days was most favorable for GHG emissions and CED, despite having a lipid content of <20%. N. oculata under the same conditions had the lowest life cycle eutrophication impacts, driven by efficient nutrient cycling and valorization of microalgal protein and anaerobic digester residue co-products. The results indicate that growth cycle times that maximize a single fraction do not necessarily result in the most favorable environmental performance on a life cycle basis, underscoring the importance of designing biorefinery systems that simultaneously optimize for lipid and non-lipid fractions.

A pilot study of silver-loaded cellulose fabric with incorporated seaweed for the treatment of atopic dermatitis.

PubMed

Park, K Y; Jang, W S; Yang, G W; Rho, Y H; Kim, B J; Mun, S K; Kim, C W; Kim, M N

2012-07-01

Because clothing has the longest and most direct contact with human skin, it is important to carefully choose suitable fabrics for atopic patients who have disrupted skin. To evaluate the clinical effectiveness and biophysical properties of a newly developed silver-loaded cellulose fabric with incorporated seaweed, we enrolled 12 subjects with mild to moderate atopic dermatitis into a clinical control study. The subjects wore a two-piece garment (top and leggings), each piece of which was divided into two parts: one side was made of SkinDoctor(®) fabric, and the other of 100% cotton. Treatment efficacy was measured with the modified SCORing Atopic Dermatitis (mSCORAD) index, transepidermal water loss (TEWL) and the patients' subjective impressions. All three of these measures had significantly better scores on the side covered with SkinDoctor. These results suggest that SkinDoctor is a beneficial fabric that can improve the comfort of patients with AD. © The Author(s). CED © 2012 British Association of Dermatologists.

Isospin symmetry breaking and large-scale shell-model calculations with the Sakurai-Sugiura method

NASA Astrophysics Data System (ADS)

Mizusaki, Takahiro; Kaneko, Kazunari; Sun, Yang; Tazaki, Shigeru

2015-05-01

Recently isospin symmetry breaking for mass 60-70 region has been investigated based on large-scale shell-model calculations in terms of mirror energy differences (MED), Coulomb energy differences (CED) and triplet energy differences (TED). Behind these investigations, we have encountered a subtle problem in numerical calculations for odd-odd N = Z nuclei with large-scale shell-model calculations. Here we focus on how to solve this subtle problem by the Sakurai-Sugiura (SS) method, which has been recently proposed as a new diagonalization method and has been successfully applied to nuclear shell-model calculations.

Comparison of Retention Patterns for Army National Guard and Army Reserve Units Participating in National Training Center, Reforger and Blazing Trails Exercises

DTIC Science & Technology

1990-01-01

Department of the Army RAND Corp. Accesion Fo, NTIS CRA&I Technical review by DTIC ! A6 0Undnno s: ced 0 David K. Home tl IC I Robert W. Tinney By Dist...changes to the Sixth Quadrennial Review of Military Compensation. viii COMPARISON OF RETENTION PATTERNS FOR NATIONAL GUARD AND ARMY RESERVE UNITS...duty time-- movies , volleyball, and time to go to the PX at Big Bear. Because of the work schedule, the soldiers did not have any free time in the

The Consequences of Metric Production for Small Manufacturers. Volume II. Case Studies of Large Business-Small Business Interaction,

DTIC Science & Technology

1982-02-08

II 00 CASE STUDIES OF LARGE BUSINESS - SMALL BUSINESS INTERACTION ’C- DTIC. Henry H1. Hitchcock dlELECTE7 Joseph F. Coates Marcy M. Canavan AUGG261982...J wis&omWWS1ARET N W WASIINGTOW. OC NO$I THE CONSEQUENCES OF METRIC PRODUCTION FOR SMALL MANUFACTURERS Volume 11 CASE STUDIES OF LARGE BUSINESS ... SMALL BUSINESS INTERACTION Accesqi~r, For NTIS GRA&t DTIC TAB Unannoun~ced J’htiI’ctof _ Henry H. Hitchcock vi 1ribr i t o aes Joseph F. Coates Avail arid

Exploring the Human Fabric through an Analyst's Eyes

NASA Astrophysics Data System (ADS)

Belov, Nadya; Patti, Jeff; Wilcox, Saki; Almanzar, Rafael; Kim, Janet; Kellogg, Jennifer; Dang, Steven

The nature and type of conflicts drastically changed in the last half of the twentieth century. Wars are no longer limited to the field; they are supplemented with guerrilla warfare and other asymmetric warfare tactics including domestic terrorism. Domestic terrorism has demonstrated a need for improved homeland security capabilities. Establishing and maintaining the understanding of the key players and the underlying social networks is essential to combating asynchronous warfare tactics. Herein, we identify the key challenges addressed by our Collection/Exploitation Decision System (CEDS) that assist analysts in maintaining an up-to-date understanding of dynamic human networks.

Particle Detectors and Data Analysis for Cusp Transient Features Campaign

NASA Technical Reports Server (NTRS)

Sharber, J. R.

1998-01-01

Grant NAG5-5084 was awarded to support the participation of South West Research Institute (SwRI) in building the energy per unit charge particle detectors for the Cusp Transient Features Campaign and analysis of flight data from these instruments. The detectors are part of an instrumented payload (Rocket 36.152, Dr. R. Pfaff, P.I.) launched from Svalbard on December 3, 1997, into the dark cusp. The particle instruments, a Cusp Electron Detector (CED) and a Cusp Ion Detector (CID), built on this project, provided differential energy and angular measurements along the rocket trajectory throughout the flight.

Nexus of Poverty, Energy Balance and Health

PubMed Central

Mishra, C. P.

2012-01-01

Since the inception of planning process in India, health planning was an integral component of socio-economic planning. Recommendations of several committees, policy documents and Millennium development goals were instrumental in development of impressive health infrastructure. Several anti-poverty and employment generation programmes were instituted to remove poverty. Spectacular achievements took place in terms of maternal and child health indicators and expectancy of life at birth. However, communicable diseases and undernutrition remain cause of serious concern and non-communicable diseases are imposing unprecedented challenge to planners and policy makers. Estimates of poverty based on different criteria point that it has remained a sustained problem in the country and emphasizes on revisiting anti-poverty programmes, economic policies and social reforms. Poverty affects purchasing power and thereby, food consumption. Energy intake data has inherent limitations. It must be assessed in terms of energy expenditure. Energy balance has been least explored area of research. The studies conducted in three different representative population group of Eastern Uttar Pradesh revealed that 69.63% rural adolescent girls (10-19 years), 79.9% rural reproductive age group females and 62.3% rural geriatric subjects were in negative energy balance. Negative energy balance was significantly less in adolescent girls belonging to high SES (51.37%), having main occupation of family as business (55.3%), and highest per capita income group (57.1%) with respect to their corresponding sub-categories. In case of rural reproductive age groups, this was maximum (93.0%) in SC/ST category and least (65.7%) in upper caste group. In case of geriatric group, higher adjusted Odd's Ratio for negative energy balance for subjects not cared by family members (AOR 23.43, CI 3.93-139.56), not kept money (AOR 5.27, CI 1.58-17.56), belonging to lower and upper middle SES by Udai Pareekh Classification (AOR 3.73, CI 1.22-11.41), with lowest per capita income (AOR 15.14, CI 2.44-94.14) and in age group >80 years (AOR 5.76, CI 1.03-32.39). Of those in negative energy balance, 70.21% rural adolescent girls and 7 out of 10 geriatric subjects (activity based) were victims of CED. Extent of undernutrition and CED in rural reproductive age group females were more in those caste groups where energy deficit was also of higher magnitude. Energy balance must be visualized giving due consideration to the importance of exercise on human health. The evidence thus generated needs to be translated to the masses based on principles of translational research. PMID:22654278

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

PubMed Central

Tosi, Umberto; Marnell, Christopher S.; Chang, Raymond; Cho, William C.; Ting, Richard; Maachani, Uday B.; Souweidane, Mark M.

2017-01-01

Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents. PMID:28208698

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors.

PubMed

Tosi, Umberto; Marnell, Christopher S; Chang, Raymond; Cho, William C; Ting, Richard; Maachani, Uday B; Souweidane, Mark M

2017-02-08

Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood-brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a "wait-and-see" approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents.

Late Neoproterozoic basement rocks of Meatiq area, Central Eastern Desert, Egypt: Petrography and remote sensing characterizations

NASA Astrophysics Data System (ADS)

Hassan, Safaa M.; El kazzaz, Yahiya A.; Taha, Maysa M. N.; Mohammad, Abdullah T.

2017-07-01

Meatiq dome is one of the mysteries of the basement rocks in Central Eastern Desert (CED) of Egypt. Its mode of formation, and tectonic evolution are still controversial and not fully understood. Satellite remote sensing is a powerful tool for geologic applications, especially in inaccessible regions of the Earth's surface. In this study, three proposed Landsat-8 band ratios (6/2, 6/7, (6/4*4/3)), (6/7, 6/4, 4/2), and (7/5, 7/6, 5/3) are successfully used for detailed geological mapping of the different lithological rock units exposed in Meatiq dome area in the CED. Landsat-8 Principal component (PC) images is also used for refinement the boundaries between the widely-exposed rock units in the study area. Fourteen spectral bands of Advanced Space borne Thermal Emission and Reflection Radiometer (ASTER) data are successfully used to emphasize the distribution of some rock forming minerals (i.e. muscovite, quartz, ferrous oxides, ferrous silicates and hydroxyl-bearing minerals) in the lithological rock units of Meatiq dome area. ASTER muscovite index (B7/B6) and quartz index (B14/B12), ferrous iron index (B5/B3), ferrous silicates index (B5/B4), mafic index (B12/B13) and hydroxyl-bearing minerals index ((B7/B6)*(B4/B6)) discriminate muscovite bearing rocks, Granitoids, and other felsic rocks, amphibolite and other mafic rocks. The proposed image processing methods effectively discriminates between four granitic varieties existed in Meatiq area. They are namely; Abu Ziran, Ariki, Fawakhir and Atalla Plutons. This study reveals that the applied data of ASTER and Landsat-8 enhanced images produced a modified geological map with well emphasized rock units which are verified with field observations, and petrographic study.

A novel magnetic resonance imaging segmentation technique for determining diffuse intrinsic pontine glioma tumor volume

PubMed Central

Singh, Ranjodh; Zhou, Zhiping; Tisnado, Jamie; Haque, Sofia; Peck, Kyung K.; Young, Robert J.; Tsiouris, Apostolos John; Thakur, Sunitha B.; Souweidane, Mark M.

2017-01-01

OBJECTIVE Accurately determining diffuse intrinsic pontine glioma (DIPG) tumor volume is clinically important. The aims of the current study were to 1) measure DIPG volumes using methods that require different degrees of subjective judgment; and 2) evaluate interobserver agreement of measurements made using these methods. METHODS Eight patients from a Phase I clinical trial testing convection-enhanced delivery (CED) of a therapeutic antibody were included in the study. Pre-CED, post–radiation therapy axial T2-weighted images were analyzed using 2 methods requiring high degrees of subjective judgment (picture archiving and communication system [PACS] polygon and Volume Viewer auto-contour methods) and 1 method requiring a low degree of subjective judgment (k-means clustering segmentation) to determine tumor volumes. Lin’s concordance correlation coefficients (CCCs) were calculated to assess interobserver agreement. RESULTS The CCCs of measurements made by 2 observers with the PACS polygon and the Volume Viewer auto-contour methods were 0.9465 (lower 1-sided 95% confidence limit 0.8472) and 0.7514 (lower 1-sided 95% confidence limit 0.3143), respectively. Both were considered poor agreement. The CCC of measurements made using k-means clustering segmentation was 0.9938 (lower 1-sided 95% confidence limit 0.9772), which was considered substantial strength of agreement. CONCLUSIONS The poor interobserver agreement of PACS polygon and Volume Viewer auto-contour methods high-lighted the difficulty in consistently measuring DIPG tumor volumes using methods requiring high degrees of subjective judgment. k-means clustering segmentation, which requires a low degree of subjective judgment, showed better interob-server agreement and produced tumor volumes with delineated borders. PMID:27391980

In vitro and in vivo testing of a novel recessed-step catheter for reflux-free convection-enhanced drug delivery to the brain.

PubMed

Gill, T; Barua, N U; Woolley, M; Bienemann, A S; Johnson, D E; S O'Sullivan; Murray, G; Fennelly, C; Lewis, O; Irving, C; Wyatt, M J; Moore, P; Gill, S S

2013-09-30

The optimisation of convection-enhanced drug delivery (CED) to the brain is fundamentally reliant on minimising drug reflux. The aim of this study was to evaluate the performance of a novel reflux-resistant CED catheter incorporating a recessed-step and to compare its performance to previously described stepped catheters. The in vitro performance of the recessed-step catheter was compared to a conventional "one-step" catheter with a single transition in outer diameter (OD) at the catheter tip, and a "two-step" design comprising two distal transitions in OD. The volumes of distribution and reflux were compared by performing infusions of Trypan blue into agarose gels. The in vivo performance of the recessed-step catheter was then analysed in a large animal model by performing infusions of 0.2% Gadolinium-DTPA in Large White/Landrace pigs. The recessed-step catheter demonstrated significantly higher volumes of distribution than the one-step and two-step catheters (p=0.0001, one-way ANOVA). No reflux was detected until more than 100 ul had been delivered via the recessed-step catheter, whilst reflux was detected after infusion of only 25 ul via the 2 non-recessed catheters. The recessed-step design also showed superior reflux resistance to a conventational one-step catheter in vivo. Reflux-free infusions were achieved in the thalamus, putamen and white matter at a maximum infusion rate of 5 ul/min using the recessed-step design. The novel recessed-step catheter described in this study shows significant potential for the achievement of predictable high volume, high flow rate infusions whilst minimising the risk of reflux. Copyright © 2013 Elsevier B.V. All rights reserved.

Regulation of gene expression in autoimmune disease loci and the genetic basis of proliferation in CD4+ effector memory T cells.

PubMed

Hu, Xinli; Kim, Hyun; Raj, Towfique; Brennan, Patrick J; Trynka, Gosia; Teslovich, Nikola; Slowikowski, Kamil; Chen, Wei-Min; Onengut, Suna; Baecher-Allan, Clare; De Jager, Philip L; Rich, Stephen S; Stranger, Barbara E; Brenner, Michael B; Raychaudhuri, Soumya

2014-06-01

Genome-wide association studies (GWAS) and subsequent dense-genotyping of associated loci identified over a hundred single-nucleotide polymorphism (SNP) variants associated with the risk of rheumatoid arthritis (RA), type 1 diabetes (T1D), and celiac disease (CeD). Immunological and genetic studies suggest a role for CD4-positive effector memory T (CD+ TEM) cells in the pathogenesis of these diseases. To elucidate mechanisms of autoimmune disease alleles, we investigated molecular phenotypes in CD4+ effector memory T cells potentially affected by these variants. In a cohort of genotyped healthy individuals, we isolated high purity CD4+ TEM cells from peripheral blood, then assayed relative abundance, proliferation upon T cell receptor (TCR) stimulation, and the transcription of 215 genes within disease loci before and after stimulation. We identified 46 genes regulated by cis-acting expression quantitative trait loci (eQTL), the majority of which we detected in stimulated cells. Eleven of the 46 genes with eQTLs were previously undetected in peripheral blood mononuclear cells. Of 96 risk alleles of RA, T1D, and/or CeD in densely genotyped loci, eleven overlapped cis-eQTLs, of which five alleles completely explained the respective signals. A non-coding variant, rs389862A, increased proliferative response (p=4.75 × 10-8). In addition, baseline expression of seventeen genes in resting cells reliably predicted proliferative response after TCR stimulation. Strikingly, however, there was no evidence that risk alleles modulated CD4+ TEM abundance or proliferation. Our study underscores the power of examining molecular phenotypes in relevant cells and conditions for understanding pathogenic mechanisms of disease variants.

Uncommon runs of homozygosity disclose homozygous missense mutations in two ciliopathy-related genes (SPAG17 and WDR35) in a patient with multiple brain and skeletal anomalies.

PubMed

Córdova-Fletes, Carlos; Becerra-Solano, Luis E; Rangel-Sosa, Martha M; Rivas-Estilla, Ana María; Alberto Galán-Huerta, Kame; Ortiz-López, Rocío; Rojas-Martínez, Augusto; Juárez-Vázquez, Clara I; García-Ortiz, José E

2018-03-01

We describe a patient severely affected with multiple congenital anomalies, including brain malformations and skeletal dysplasia suggestive of cranioectodermal dysplasia (CED) ciliopathy, who unusually carries several homozygosity tracts involving homozygous missense mutations in SPAG17 (exon 8; c.1069G > C; p.Asp357His) and WDR35 (exon 13; c.1415G > A; p.Arg472Gln) as revealed by homozygosity mapping and next generation sequencing. SPAG17 is essential for the function and structure of motile cilia, while WDR35 belongs to the same intraflagellar transport (IFT) gene family whose protein products are part of functional IFT A and B complexes. Formerly, SPAG17 was related - through polymorphic variants - to an influence on individuals' height; more recently, Spag17-/- mice models were reported to present skeletal and bone defects, reduced mucociliary clearance, respiratory distress, and cerebral ventricular enlargement. Homozygous or compound heterozygous mutations in WDR35 have mainly been related to CED2 or short-rib thoracic dysplasia 7, with only three cases showing some brain anomalies. Given that our patient presents these clinical features and the close functional relationship between SPAG17 and WDR35, it is feasible that the combined effects from both mutations contribute to his phenotype. To our knowledge, this patient is the first to harbor a likely pathogenic homozygous mutation in both genes at the same time. Thus, the resulting complex phenotype of this patient illustrates the heterogeneity associated with ciliopathies and further expands the clinical and mutational spectrum of these diseases. Finally, we highlight the combined use of high-throughput tools to diagnose and support the proper handling of this and other patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A composite experimental dynamic substructuring method based on partitioned algorithms and localized Lagrange multipliers

NASA Astrophysics Data System (ADS)

Abbiati, Giuseppe; La Salandra, Vincenzo; Bursi, Oreste S.; Caracoglia, Luca

2018-02-01

Successful online hybrid (numerical/physical) dynamic substructuring simulations have shown their potential in enabling realistic dynamic analysis of almost any type of non-linear structural system (e.g., an as-built/isolated viaduct, a petrochemical piping system subjected to non-stationary seismic loading, etc.). Moreover, owing to faster and more accurate testing equipment, a number of different offline experimental substructuring methods, operating both in time (e.g. the impulse-based substructuring) and frequency domains (i.e. the Lagrange multiplier frequency-based substructuring), have been employed in mechanical engineering to examine dynamic substructure coupling. Numerous studies have dealt with the above-mentioned methods and with consequent uncertainty propagation issues, either associated with experimental errors or modelling assumptions. Nonetheless, a limited number of publications have systematically cross-examined the performance of the various Experimental Dynamic Substructuring (EDS) methods and the possibility of their exploitation in a complementary way to expedite a hybrid experiment/numerical simulation. From this perspective, this paper performs a comparative uncertainty propagation analysis of three EDS algorithms for coupling physical and numerical subdomains with a dual assembly approach based on localized Lagrange multipliers. The main results and comparisons are based on a series of Monte Carlo simulations carried out on a five-DoF linear/non-linear chain-like systems that include typical aleatoric uncertainties emerging from measurement errors and excitation loads. In addition, we propose a new Composite-EDS (C-EDS) method to fuse both online and offline algorithms into a unique simulator. Capitalizing from the results of a more complex case study composed of a coupled isolated tank-piping system, we provide a feasible way to employ the C-EDS method when nonlinearities and multi-point constraints are present in the emulated system.

Escherichia coli W as a new platform strain for the enhanced production of L-valine by systems metabolic engineering.

PubMed

Park, Jin Hwan; Jang, Yu-Sin; Lee, Jeong Wook; Lee, Sang Yup

2011-05-01

A less frequently employed Escherichia coli strain W, yet possessing useful metabolic characteristics such as less acetic acid production and high L-valine tolerance, was metabolically engineered for the production of L-valine. The ilvA gene was deleted to make more pyruvate, a key precursor for L-valine, available for enhanced L-valine biosynthesis. The lacI gene was deleted to allow constitutive expression of genes under the tac or trc promoter. The ilvBN(mut) genes encoding feedback-resistant acetohydroxy acid synthase (AHAS) I and the L-valine biosynthetic ilvCED genes encoding acetohydroxy acid isomeroreductase, dihydroxy acid dehydratase, and branched chain amino acid aminotransferase, respectively, were amplified by plasmid-based overexpression. The global regulator Lrp and L-valine exporter YgaZH were also amplified by plasmid-based overexpression. The engineered E. coli W (ΔlacI ΔilvA) strain overexpressing the ilvBN(mut) , ilvCED, ygaZH, and lrp genes was able to produce an impressively high concentration of 60.7 g/L L-valine by fed-batch culture in 29.5 h, resulting in a high volumetric productivity of 2.06 g/L/h. The most notable finding is that there was no other byproduct produced during L-valine production. The results obtained in this study suggest that E. coli W can be a good alternative to Corynebacterium glutamicum and E. coli K-12, which have so far been the most efficient L-valine producer. Furthermore, it is expected that various bioproducts including other amino acids might be more efficiently produced by this revisited platform strain of E. coli. Copyright © 2010 Wiley Periodicals, Inc.

Methodological Guidelines on Net Energy Analysis of Photovoltaic Electricity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raugei, Marco; Frischknecht, Rolf; Olson, Carol

Net Energy Analysis (NEA) is a structured, comprehensive method of quantifying the extent to which a given energy source is able to provide a net energy gain (i.e., an energy surplus) to the end user, after accounting for all the energy losses occurring along the chain of processes that are required to exploit it (i.e., for its extraction, processing and transformation into a usable energy carrier, and delivery to the end user), as well as for all the additional energy 'investments' that are required in order to carry out the same chain of processes. However, this general framework leaves themore » individual practitioner with a range of choices that can affect the results and thus, the conclusions of a NEA study. The current IEA PVPS guidelines were developed to provide guidance on assuring consistency, balance, and quality to enhance the credibility and reliability of the results from photovoltaic (PV) NEAs. The guidelines represent a consensus among the authors -- PV NEA experts in North America, Europe, and Asia -- for assumptions made on PV performance, process inputs and outputs, methods of analysis, and reporting of the results. Guidance is given on photovoltaic-specific parameters used as inputs in NEA and on choices and assumptions in inventory data analysis and on implementation of modelling approaches. A consistent approach towards system modelling, the functional unit, the system boundaries and allocation aspects enhances the credibility of PV electricity NEA studies and enables balanced NEA-based comparisons of different electricity producing technologies. This document provides an in-depth discussion of a common metric of NEA, namely the energy return on investment (EROI), and how this is to be interpreted vis-a-vis the deceptively similar-sounding metrics in the field of Life Cycle Assessment (LCA): cumulative energy demand (CED) and non-renewable cumulative energy demand (nr-CED) per unit output. Specifically, a number of key differences are highlighted between these metrics as applied to electricity production systems. Transparency in reporting is of the utmost importance as parameters vary with geographical zones, and a system's boundary conditions and modelling approach can affect the findings significantly. This guideline lists 16 items that should be reported in every NEA study of PV electricity.« less

Word Frequency Analysis. MOS: 62E. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

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