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

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

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.

Self-reported dietary adherence, disease-specific symptoms, and quality of life are associated with healthcare provider follow-up in celiac disease.

PubMed

Hughey, Jacob J; Ray, Bonnie K; Lee, Anne R; Voorhees, Kristin N; Kelly, Ciaran P; Schuppan, Detlef

2017-12-11

The only treatment for celiac disease (CeD) is a lifelong gluten-free diet (GFD). The restrictive nature of the GFD makes adherence a challenge. As an integral part of CeD management, multiple professional organizations recommend regular follow-up with a healthcare provider (HCP). Many CeD patients also participate in patient advocacy groups (PAGs) for education and support. Previous work found that follow-up of CeD patients is highly variable. Here we investigated the self-reported factors associated with HCP follow-up among individuals diagnosed with CeD who participate in a PAG. We conducted a survey of members of Beyond Celiac (a PAG), collecting responses from 1832 U.S. adults ages 19-65 who reported having CeD. The survey queried HCP follow-up related to CeD and included validated instruments for dietary adherence (CDAT), disease-specific symptoms (CSI), and quality of life (CD-QOL). Overall, 27% of respondents diagnosed with CeD at least five years ago reported that they had not visited an HCP about CeD in the last five years. The most frequent reason for not visiting an HCP was "doing fine on my own" (47.6%). Using multiple logistic regression, we identified significant associations between whether a respondent reported visiting an HCP about CeD in the last five years and the scores for all three validated instruments. In particular, as disease-specific symptoms and quality of life worsened, the probability of having visited an HCP increased. Conversely, as dietary adherence worsened, the probability decreased. Our results suggest that many individuals with CeD manage their disease without ongoing support from an HCP. Our results thus emphasize the need for greater access to high quality CeD care, and highlight an opportunity for PAGs to bring together patients and HCPs to improve management of CeD.

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

CEDS Addresses: Rubric Elements

ERIC Educational Resources Information Center

US Department of Education, 2015

2015-01-01

Common Education Data Standards (CEDS) Version 4 introduced a common data vocabulary for defining rubrics in a data system. The CEDS elements support digital representations of both holistic and analytic rubrics. This document shares examples of holistic and analytic project rubrics, available CEDS Connections, and a logical model showing the…

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.

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.

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.

Energy and sports drinks in children and adolescents.

PubMed

Pound, Catherine M; Blair, Becky

2017-10-01

Sports drinks and caffeinated energy drinks (CEDs) are commonly consumed by youth. Both sports drinks and CEDs pose potential risks for the health of children and adolescents and may contribute to obesity. Sports drinks are generally unnecessary for children engaged in routine or play-based physical activity. CEDs may affect children and adolescents more than adults because they weigh less and thus experience greater exposure to stimulant ingredients per kilogram of body weight. Paediatricians need to recognize and educate patients and families on the differences between sport drinks and CEDs. Screening for the consumption of CEDs, especially when mixed with alcohol, should be done routinely. The combination of CEDs and alcohol may be a marker for higher risk of substance use or abuse and for other health-compromising behaviours.

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.

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

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.

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

Perceptions and Knowledge of Caffeinated Energy Drinks: Results of Focus Groups With Canadian Youth.

PubMed

McCrory, Cassondra; White, Christine M; Bowman, Carolyn; Fenton, Nancy; Reid, Jessica L; Hammond, David

2017-04-01

To examine use, knowledge, and perceptions of caffeinated energy drinks (CEDs) among youth. Qualitative research using focus group discussions (n = 4). Two Canadian cities (Toronto and Montreal). Youth aged 12-18 years (n = 41). Perceived definitions of CEDs, reasons for use, knowledge of health effects, use with alcohol, marketing perceptions, and use and understanding of cautionary statements on packaging. Data were analyzed using a modified grounded-theory approach. Youth identified CEDs as products that provide energy and contain caffeine and sugar. Compared with mainstream CED brands and energy shots, youth were less likely to perceive Gatorade, Coca-Cola, and a Starbucks beverage as energy drinks, despite some ambiguity. The majority of participants believed that CEDs, including mixed with alcohol, were not necessarily harmful in moderation and that marketing was targeted toward older youth and young adults. Awareness of cautionary statements on CEDs was low; cautionary statements were perceived as difficult to find and read owing to the design and small font. Findings suggest a need to increase public education regarding the potential risks of CED consumption, including enhancements to the mandated cautionary statements, with greater attention to the impact of CED marketing on youth. Copyright © 2016 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

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.

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.

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.

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.

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.

Coverage with Evidence Development: applications and issues.

PubMed

Trueman, Paul; Grainger, David L; Downs, Kristen E

2010-01-01

The aim of this study was to describe the current issues surrounding Coverage with Evidence Development (CED). CED is characterized by restricted coverage for a new technology in parallel with targeted research when the stated goal of the research or data collection is to provide definitive evidence for the clinical or cost-effectiveness impact of the new technology. Presented here is information summarized and interpreted from presentations and discussions at the 2008 Health Technology Assessment International (HTAi) meeting and additional information from the medical literature. This study describes the differences between CED and other conditional coverage agreements, provides a brief history of CED, describes real-world examples of CED, describes the areas of consensus between the stakeholders, discusses the areas for future negotiation between stakeholders, and proposes criteria to assist stakeholders in determining when CED could be appropriate. Payers could interpret the evidence obtained from a CED program either positively or negatively, and a range of possible changes to the reimbursement status of the new technology may result. Striking an appropriate balance between the demands for prompt access to new technology and acknowledging that some degree of uncertainty will always exist is a critical challenge to the uptake of this innovative form of conditional coverage. When used selectively for innovative procedures, pharmaceuticals, or devices in the appropriate disease areas, CED may provide patients access to promising medicines or technologies while data to minimize uncertainty are collected.

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 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.

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

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.

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.

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.

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

13 CFR 303.6 - EDA-funded CEDS process.

Code of Federal Regulations, 2010 CFR

2010-01-01

... PLANNING INVESTMENTS AND COMPREHENSIVE ECONOMIC DEVELOPMENT STRATEGIES § 303.6 EDA-funded CEDS process. If EDA awards Investment Assistance to a Planning Organization to develop, revise or replace a CEDS, the... must appoint a Strategy Committee. The Strategy Committee must represent the main economic interests of...

Instructional Design Issues in a Distributed Collaborative Engineering Design (CED) Instructional Environment

ERIC Educational Resources Information Center

Koszalka, Tiffany A.; Wu, Yiyan

2010-01-01

Changes in engineering practices have spawned changes in engineering education and prompted the use of distributed learning environments. A distributed collaborative engineering design (CED) course was designed to engage engineering students in learning about and solving engineering design problems. The CED incorporated an advanced interactive…

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...

CEDS Addresses: Virtual and Blended Learning

ERIC Educational Resources Information Center

US Department of Education, 2015

2015-01-01

The Common Education Data Standards (CEDS) common data vocabulary supports the collection and use of information about virtual and blended learning. The data element "Virtual Indicator", introduced in version 3 of CEDS, supports a range of virtual learning-related use cases. The Virtual Indicator element may be related to a Course…

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

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...

Fiscal Models as Reflections of Institutional Philosophies toward Continuing Education.

ERIC Educational Resources Information Center

Thompson, Gordon

Throughout the existence of the Continuing Education Division (CED) at the University of Manitoba, three different fiscal models were applied by University Administration to the CED: the traditional model; the income-target model; and the subsidy model. (1) The traditional model paralleled that applied to faculties and schools. The CED was…

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.

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.

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...

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

Factors associated with nutritional status among adult women in urban India, 1998-2006.

PubMed

Rai, Rajesh Kumar

2015-03-01

This study attempts to understand the factors associated with chronic energy deficiency (CED) and overweight/obesity together with change in CED and overweight/obesity among urban Indian women during 1998-2006. Both National Family Health Survey (NFHS) 1998-1999 and NFHS 2005-2006 data sets were used. The standard cutoff points for both CED (BMI < 18.5 kg/m(2)) and overweight/obesity (BMI ≥ 23 kg/m(2)) were considered. The Phi and Cramer's V tests and predicted probabilities were used to fulfill the study objective. Results indicate an almost 3% reduction in CED and a 6% increase in overweight/obesity during 1998-2006. The probability of CED has reduced among nonliterate women and women belonging to the poorest wealth quintile; on the other hand, the likelihood of being overweight/obese has increased among women with high school education and above and women belonging to the richest wealth quintile. Interventions to promote physical activities and nutritional awareness programs, which are effective in addressing nutritional problems, have been proposed. © 2012 APJPH.

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.

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.

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.

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

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.

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.

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.

Undernutrition among adult Bengalees of Dearah, Hooghly District, West Bengal, India: relationship with educational status and food habit.

PubMed

Bose, Kaushik; Bisai, Samiran; Sadhukhan, Sanjay; Mukhopadhyay, Ashish; Bhadra, Mithu

2009-06-01

A cross-sectional study of 1203 adult (> 18 years of age) Bengalees of Dearah, Hooghly District, West Bengal, India, was undertaken to evaluate the prevalence of undernutrition and the relationship of educational level and food habit with undernutrition. Height and weight were measured and body mass index (BMI) computed following the standard equation. A BMI < 18.5 kg/m2 was classified as undernutrition or chronic energy deficiency (CED) as per World Health Organization (WHO) recommendations. The public health problem of low BMI in this population was classified according to the WHO criteria. Educational status was coded as: no formal education, 1-8 years of schooling and > 8 years of schooling. Food habit was recorded as vegetarian or non-vegetarian. The mean ages of males and females were (39.6 +/- 15.0 years) and (39.6 +/- 15.0 years), respectively. There were significant (p < 0.001) sex differences in mean height and weight; both sexes had a similar BMI. The overall (sex combined) prevalence of undernutrition was 27.7%. The frequency of undernutrition was significantly (p < 0.001) higher among females (31.7%) compared to males (23.6%). According to the WHO classification of low BMI, the prevalence of CED was high (20-39%) indicating a serious situation. There existed a significant (p < 0.001) relationship between the level of formal education and nutritional status. Overall, the frequencies of CED (43.5%) were much higher than overweight (7.0%) among subjects with no formal education. The frequencies of CED and overweight among subjects with 1-8 years of formal education were 25.7% and 9.7%, respectively. Similarly, significantly (p < 0.001) higher rates of CED were found among subjects with no formal education in both sexes (males = 39.5%; females = 45.6%) compared to the presence of overweight (males = 1.8%; females = 9.8%). Sex-combined frequency of undernutrition was significantly (p < 0.001) higher among vegetarians (48.3%) compared with non-vegetarians (25.5%). The respective frequencies of overweight were 1.7% and 12.8%. This significant (p < 0.001) trend existed in both sexes with 46.9% male and 49.3% female vegetarians having CED. The corresponding figures for overweight among vegetarians were 0.0% and 2.9%, respectively. The rates of CED were significantly (p < 0.001) lower among non-vegetarians (males = 21.5%; females = 29.6%). Non-vegetarians had significantly higher rates of overweight in both males (8.7%) and females (16.9%). Multiple regression analysis revealed that both educational status as well as food habit had significant effect on BMI in both sexes. In general, the educational status had a stronger impact (males: t = 6.356, females: t = 5.017) than food habit (males: t = 3.373; females: t = 2.763) on BMI. This significant impact remained even after controlling for the effect of age. In conclusion, this study demonstrated that adult Bengalees of Dearah were under serious nutritional stress indicating a public health problem. In addition, a strong inverse relationship existed between educational level and CED. Moreover, vegetarianism was significantly associated with CED. Urgent public health measures are required, particularly among females, to reduce the high prevalence of CED in this population. Similar studies should be conducted in other parts of West Bengal before any general conclusions can be inferred about the relationship between educational status, food habit and CED in the state.

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

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

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.

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

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...

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.

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.

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...

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.

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

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.

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.

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.

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...

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...

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

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...

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

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.

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.

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.

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

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.

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

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.

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.

A New Partnership: Reshaping the Federal and State Commitment to Need-Based Aid

ERIC Educational Resources Information Center

Doyle, William R.

2013-01-01

The Committee for Economic Development (CED) is pleased to present these research findings regarding ways to reform student financial aid. In 2012, CED released "Boosting Postsecondary Education Performance"--calling on business to become active advocates at the state level for broad-access institutions that are so vital to the nation's…

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

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.

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.

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 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

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.

Unfinished Business: Continued Investment in Child Care and Early Education is Critical to Business and America's Future

ERIC Educational Resources Information Center

Committee for Economic Development, 2012

2012-01-01

The Committee for Economic Development (CED) has a decades-old commitment to quality early childhood education. CED Trustees have always been in the forefront of the effort to promote early learning and development for all children. Over recent years, the case for investment in the early years of childhood has become stronger and more urgent.…

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

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.

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

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.

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.

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.

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.

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

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.

Hearing loss: terminology and classification. Joint Committee of the American Speech-Language-Hearing Association and the Council on Education of the Deaf.

PubMed

1998-01-01

The following position statement and technical report were developed by the Joint Committee of the American Speech-Language-Hearing Association (ASHA) and the Council on Education of the Deaf (CED) and approved as Association policy by the ASHA Legislative Council in November 1997 (LC 6-97). CED member organizations are reviewing the document for approval in 1998. Joint Committee members responsible for the development of this document include (from ASHA) Joan Marttila, chair 1996-97; Linda Seestedt-Stanford, chair 1994-95; Evelyn Cherow, ex official; Donald Goldberg; Dawna Lewis; Leslie Ann McMillian; Jane Seaton; Alicia Stewart; and Larry Higdon, vice president for professional practices in audiology and monitoring vice president; and (from CED) Kathee Christensen; Steve Nover; Marilyn Sass-Lehrer; and Patrick Stone. This document supersedes ASHA policy: Definitions of Communication Disorders and Variations: Hearing Disorders section.

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

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.

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.

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.

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 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.

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

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

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

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

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

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

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.

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.

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.

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).

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.

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.

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.

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

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.

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.

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%).

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.

Supporting clinical engineering in Italy: results of a survey conducted by the AIIC.

PubMed

Faggiano, Francesco; Ritrovato, Matteo; Freda, Paola; Vivo, Liliana; D'Alessandro, Luigi; Derrico, Pietro

2012-01-01

This article presents the outcomes of a survey developed and conducted by the Italian Association of Clinical Engineers (AIIC) in 2010 [1]. The AIIC, affiliated with the International Federation for Medical and Biological Engineering (IFMBE) since 2003, conducted this in-depth survey to investigate the educational profile of clinical engineers (CEs) as well as the activities and organization of clinical engineering departments (CEDs) in Italy. The survey consisted of a six-section questionnaire designed by the AIIC Board, which was based on other previous international surveys of CEDs. The questionnaire was sent to the AIIC members and to the most important Italian health-care organizations.

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.

Analysis of phase II studies on targeted agents and subsequent phase III trials: what are the predictors for success?

PubMed

Chan, John K; Ueda, Stefanie M; Sugiyama, Valerie E; Stave, Christopher D; Shin, Jacob Y; Monk, Bradley J; Sikic, Branimir I; Osann, Kathryn; Kapp, Daniel S

2008-03-20

To identify the characteristics of phase II studies that predict for subsequent "positive" phase III trials (those that reached the proposed primary end points of study or those wherein the study drug was superior to the standard regimen investigating targeted agents in advanced tumors. We identified all phase III clinical trials of targeted therapies against advanced cancers published from 1985 to 2005. Characteristics of the preceding phase II studies were reviewed to identify predictive factors for success of the subsequent phase III trial. Data were analyzed using the chi(2) test and logistic regression models. Of 351 phase II studies, 167 (47.6%) subsequent phase III trials were positive and 184 (52.4%) negative. Phase II studies from multiple rather than single institutions were more likely to precede a successful trial (60.4% v 39.4%; P < .001). Positive phase II results were more likely to lead to a successful phase III trial (50.8% v 22.5%; P = .003). The percentage of successful trials from pharmaceutical companies was significantly higher compared with academic, cooperative groups, and research institutes (89.5% v 44.2%, 45.2%, and 46.3%, respectively; P = .002). On multivariate analysis, these factors and shorter time interval between publication of phase II results and III study publication were independent predictive factors for a positive phase III trial. In phase II studies of targeted agents, multiple- versus single-institution participation, positive phase II trial, pharmaceutical company-based trials, and shorter time period between publication of phase II to phase III trial were independent predictive factors of success in a phase III trial. Investigators should be cognizant of these factors in phase II studies before designing phase III trials.

Phase III of Early Restoration | NOAA Gulf Spill Restoration

Science.gov Websites

information about this phase of Early Restoration, including fact sheets on each project. The final Phase III 44 projects are documented in a final Record of Decision. Information about Phase III of Early Archive Home Phase III of Early Restoration Phase III of Early Restoration Beach habitat would be restored

NCSP IER 422 CED-3b Documentation

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

Hutchinson, Jesson D.; Cutler, Theresa Elizabeth; Bahran, Rian Mustafa

2017-11-22

A Subcritical Copper-Reflected α-phase Plutonium (SCRαP) integral benchmark experiment has been designed and measured. In this experiment, multiplication is approximated using correlated neutron data from a detector system consisting of 3He tubes inside high density polyethylene (HDPE). Measurements were performed on various subcritical experimental configurations consisting of a weapons-grade plutonium sphere surrounded by different Cu thicknesses. In addition to the proposed base experimental configurations with Cu, additional configurations were performed with the plutonium ball nested in various thicknesses of interleaved HDPE spherical shells mixed in with the Cu shells. The HDPE is intended to provide fast neutron moderation and reflection,more » resulting in additional measurements with differing multiplication, spectra, and nuclear data sensitivity.« less

Environmental Life Cycle Assessment Model for Soil Bioengineering Measures on Infrastructure Slopes

NASA Astrophysics Data System (ADS)

Hoerbinger, Stephan; Obriejetan, Michael

2015-04-01

Soil bioengineering techniques can be a helpful instrument for civil engineers taking into account not only technical but also ecological, socio-economic and sustainability aspects. Environmental Life Cycle Assessment (LCA) models can serve as supplementary evaluation methods to economic analyses, taking into account the resource demand and environmental burdens of engineering structures. The presented LCA model includes the functional grade of structures in addition to environmental aspects. When using vegetation as living construction material, several factors have to be considered. There is the provision of ecosystem services of plants, such as the stabilization of the slope through its root-system, CO2 sequestration through biomass production et cetera. However, it must be noted that vegetation can cause security issues on infrastructure facilities and entail costs through the necessity of maintenance works. For this reason, it is necessary to already define the target systems during the planning phase of a soil bioengineering structure. In this way, necessary measures can be adapted in all life cycles of a structure. The objective of the presented LCA model is to serve as a basis for the definition of target systems. In the designed LCA model the soil bioengineering structures are divided into four life phases; construction phase, operational phase, end of life phase and subsequent use phase. A main objective of the LCA model is the understanding of the "Cumulative Energy Demand" (CED) and "Global Warming Potential" (GWP) of soil bioengineering structures during all life cycle phases. Additionally, the biomass production and the CO2 sequestration potential of the used plants are regarded as well as the functional integrity of the soil bioengineering system. In the life phase of soil bioengineering structures, a major part of the energy input is required during the construction phase. This is mainly due to the cumulative energy demand of the inert materials used. The principle of biological engineering constructions is based on the combination of dead and living materials and the emerging positive synergistic effects. The dead auxiliaries (stone, wood, etc.) protect the living plants until they undertake technical functions. During the operational phase of the structure, maintenance work has to be done in order to maintain the protective properties of the used plants. Through measures like cutting the vegetation back to the trunk, energy will be put into the system (e.g. through machine use), but will also be put out in form of biomass. Additionally, carbon is sequestered by the biomass production of the plants. The end of life phase is reached after the projected lifetime of a structure. Outside of zones with plant growth restrictions like within a clearance gauge, soil bioengineering approaches are designed to have a subsequent use phase. That means, that after the actual lifespan of the construction, a forest should have developed and maintain its balance by natural succession. The LCA model aims at supporting sustainable management strategies for CED and GWP as a base for Green Public Procurement and eco- friendly implementation and maintenance of soil bioengineering structures on infrastructure slopes.

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.

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.

Multifaced Roles of the αvβ3 Integrin in Ehlers–Danlos and Arterial Tortuosity Syndromes’ Dermal Fibroblasts

PubMed Central

Zoppi, Nicoletta; Chiarelli, Nicola; Ritelli, Marco; Colombi, Marina

2018-01-01

The αvβ3 integrin, an endothelial cells’ receptor-binding fibronectin (FN) in the extracellular matrix (ECM) of blood vessels, regulates ECM remodeling during migration, invasion, angiogenesis, wound healing and inflammation, and is also involved in the epithelial mesenchymal transition. In vitro-grown human control fibroblasts organize a fibrillar network of FN, which is preferentially bound on the entire cell surface to its canonical α5β1 integrin receptor, whereas the αvβ3 integrin is present only in rare patches in focal contacts. We report on the preferential recruitment of the αvβ3 integrin, due to the lack of FN–ECM and its canonical integrin receptor, in dermal fibroblasts from Ehlers–Danlos syndromes (EDS) and arterial tortuosity syndrome (ATS), which are rare multisystem connective tissue disorders. We review our previous findings that unraveled different biological mechanisms elicited by the αvβ3 integrin in fibroblasts derived from patients affected with classical (cEDS), vascular (vEDS), hypermobile EDS (hEDS), hypermobility spectrum disorders (HSD), and ATS. In cEDS and vEDS, respectively, due to defective type V and type III collagens, αvβ3 rescues patients’ fibroblasts from anoikis through a paxillin-p60Src-mediated cross-talk with the EGF receptor. In hEDS and HSD, without a defined molecular basis, the αvβ3 integrin transduces to the ILK-Snail1-axis inducing a fibroblast-to-myofibroblast-transition. In ATS cells, the deficiency of the dehydroascorbic acid transporter GLUT10 leads to redox imbalance, ECM disarray together with the activation of a non-canonical αvβ3 integrin-TGFBRII signaling, involving p125FAK/p60Src/p38MAPK. The characterization of these different biological functions triggered by αvβ3 provides insights into the multifaced nature of this integrin, at least in cultured dermal fibroblasts, offering future perspectives for research in this field. PMID:29587413

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

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.

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.

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.

Phase III Early Restoration Public Meetings | NOAA Gulf Spill Restoration

Science.gov Websites

Archive Home Phase III Early Restoration Public Meetings Phase III Early Restoration Public Meetings share Posted on December 6, 2013 | Assessment and Early Restoration Restoration Area Title: Phase III Early on the draft plan for the third phase of Early Restoration, which proposes more than $625 million in

Using phase II data for the analysis of phase III studies: An application in rare diseases.

PubMed

Wandel, Simon; Neuenschwander, Beat; Röver, Christian; Friede, Tim

2017-06-01

Clinical research and drug development in orphan diseases are challenging, since large-scale randomized studies are difficult to conduct. Formally synthesizing the evidence is therefore of great value, yet this is rarely done in the drug-approval process. Phase III designs that make better use of phase II data can facilitate drug development in orphan diseases. A Bayesian meta-analytic approach is used to inform the phase III study with phase II data. It is particularly attractive, since uncertainty of between-trial heterogeneity can be dealt with probabilistically, which is critical if the number of studies is small. Furthermore, it allows quantifying and discounting the phase II data through the predictive distribution relevant for phase III. A phase III design is proposed which uses the phase II data and considers approval based on a phase III interim analysis. The design is illustrated with a non-inferiority case study from a Food and Drug Administration approval in herpetic keratitis (an orphan disease). Design operating characteristics are compared to those of a traditional design, which ignores the phase II data. An analysis of the phase II data reveals good but insufficient evidence for non-inferiority, highlighting the need for a phase III study. For the phase III study supported by phase II data, the interim analysis is based on half of the patients. For this design, the meta-analytic interim results are conclusive and would justify approval. In contrast, based on the phase III data only, interim results are inconclusive and require further evidence. To accelerate drug development for orphan diseases, innovative study designs and appropriate methodology are needed. Taking advantage of randomized phase II data when analyzing phase III studies looks promising because the evidence from phase II supports informed decision-making. The implementation of the Bayesian design is straightforward with public software such as R.

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.

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.

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.

Efficacy and safety of rifaximin in Japanese patients with hepatic encephalopathy: A phase II/III, multicenter, randomized, evaluator-blinded, active-controlled trial and a phase III, multicenter, open trial.

PubMed

Suzuki, Kazuyuki; Endo, Ryujin; Takikawa, Yasuhiro; Moriyasu, Fuminori; Aoyagi, Yutaka; Moriwaki, Hisataka; Terai, Shuji; Sakaida, Isao; Sakai, Yoshiyuki; Nishiguchi, Shuhei; Ishikawa, Toru; Takagi, Hitoshi; Naganuma, Atsushi; Genda, Takuya; Ichida, Takafumi; Takaguchi, Koichi; Miyazawa, Katsuhiko; Okita, Kiwamu

2018-05-01

The efficacy and safety of rifaximin in the treatment of hepatic encephalopathy (HE) are widely known, but they have not been confirmed in Japanese patients with HE. Thus, two prospective, randomized studies (a phase II/III study and a phase III study) were carried out. Subjects with grade I or II HE and hyperammonemia were enrolled. The phase II/III study, which was a randomized, evaluator-blinded, active-comparator, parallel-group study, was undertaken at 37 institutions in Japan. Treatment periods were 14 days. Eligible patients were randomized to the rifaximin group (1200 mg/day) or the lactitol group (18-36 g/day). The phase III study was carried out in the same patients previously enrolled in the phase II/III study, and they were all treated with rifaximin (1200 mg/day) for 10 weeks. In the phase II/III study, 172 patients were enrolled. Blood ammonia (B-NH 3 ) concentration was significantly improved in the rifaximin group, but the difference between the two groups was not significant. The portal systemic encephalopathy index (PSE index), including HE grade, was significantly improved in both groups. In the phase III study, 87.3% of enrolled patients completed the treatment. The improved B-NH 3 concentration and PSE index were well maintained from the phase II/III study during the treatment period of the phase III study. Adverse drug reactions (ADRs) were seen in 13.4% of patients who received rifaximin, but there were no severe ADRs leading to death. The efficacy of rifaximin is sufficient and treatment is well tolerated in Japanese patients with HE and hyperammonemia. © 2017 The Japan Society of Hepatology.

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

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

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...

Los Angeles International Airport Runway Incursion Studies: Phase III--Center-Taxiway Simulation

NASA Technical Reports Server (NTRS)

Madson, Michael D.

2004-01-01

Phase III of the Los Angeles International Airport Runway Incursion Studies was conducted, under an agreement with HNTB Corporation, at the NASA Ames FutureFlight Central (FFC) facility in June 2003. The objective of the study was the evaluation of a new center-taxiway concept at LAX. This study is an extension of the Phase I and Phase II studies previously conducted at FFC. This report presents results from Phase III of the study, in which a center-taxiway concept between runways 25L and 25R was simulated and evaluated. Phase III data were compared objectively against the Baseline data. Subjective evaluations by participating LAX controllers were obtained with regard to workload, efficiency, and safety criteria. To facilitate a valid comparison between Baseline and Phase III data, the same scenarios were used for Phase III that were tested during Phases I and II. This required briefing participating controllers on differences in airport and airline operations between 2001 and today.

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.

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

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.

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.

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

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.

Installation Restoration Program. Phase II: Stage 1 Problem Confirmation Study, Duluth International Airport, Duluth, Minnesota.

DTIC Science & Technology

1984-10-01

8 iii "i t-. Table of Contents (cont.) Section Title Page -APPENDIX A Acronyms, Definitions, Nomenclature and Units of Measure B Scope of Work, Task...Identification/Records Search Phase II - Problem Confirmation and Quantification Phase III - Technology Base Development Phase IV - Corrective Action Only...Problem Identification/Records Search Phase II - Problem Confirmation and Quantification Phase III - Technology Base Development Phase IV - Corrective

Motilin-induced gastric contractions signal hunger in man.

PubMed

Tack, J; Deloose, E; Ang, D; Scarpellini, E; Vanuytsel, T; Van Oudenhove, L; Depoortere, I

2016-02-01

Hunger is controlled by the brain, which receives input from signals of the GI tract (GIT). During fasting, GIT displays a cyclical motor pattern, the migrating motor complex (MMC), regulated by motilin. To study the relationship between hunger and MMC phases (I-III), focusing on spontaneous and pharmacologically induced phase III and the correlation with plasma motilin and ghrelin levels. The role of phase III was also studied in the return of hunger after a meal in healthy individuals and in patients with loss of appetite. In fasting healthy volunteers, mean hunger ratings during a gastric (62.5±7.5) but not a duodenal (40.4±5.4) phase III were higher (p<0.0005) than during phase I (27.4±4.7) and phase II (37±4.5). The motilin agonist erythromycin, but not the cholinesterase inhibitor neostigmine, induced a premature gastric phase III, which coincided with an increase in hunger scores from 29.2±7 to 61.7±8. The somatostatin analogue octreotide induced a premature intestinal phase III without a rise in hunger scores. Hunger ratings significantly correlated (β=0.05; p=0.01) with motilin plasma levels, and this relationship was lost after erythromycin administration. Motilin, but not ghrelin administration, induced a premature gastric phase III and a rise in hunger scores. In contrast to octreotide, postprandial administration of erythromycin induced a premature gastric phase III accompanied by an early rise in hunger ratings. In patients with unexplained loss of appetite, gastric phase III was absent and hunger ratings were lower. Motilin-induced gastric phase III is a hunger signal from GIT in man. 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/

Initiation of phase III contractions in the jejunum by atropine, hexamethonium and xylocaine in conscious dogs.

PubMed

Tohara, K; Uchida, Y; Suzuki, H; Itoh, Z

2000-02-01

Mechanisms of initiation of phase III contractions in the jejunum during the digestive state are not well understood. To test whether phase III can be induced by a local injection of various agents in a jejunal segment, a polyethylene tube was chronically placed in a branch of the jejunal artery, and force transducers were chronically placed in the upper jejunum. Local injection of atropine, hexamethonium and xylocaine induced caudal-migrating phase III in the injected segment only in the digestive state, and simultaneous intra-arterial infusions of L-arginine, an NK-1 antagonist, or 5-hydroxytryptamine (5-HT) 1P and 3 antagonists inhibited the induced phase III. Intravenous atropine and hexamethonium also inhibited xylocaine-induced phase III contractions. Atropine and hexamethonium-induced phase III were brought about by inhibition of neural transmission at nicotinic receptors in the inhibitory pathway to NO neurones. NK-1, 5-HT1P and 5-HT3 receptors are present in the excitatory but not the inhibitory pathway to NO neurones. Xylocaine appears to stop neuronal transmission from mechanoreceptors to NO neurones. Thus, the initiation of spontaneous occurrence of phase III in the digestive jejunum is likely to be brought about by transient cessation of postprandial contractions in a segment of the jejunum.

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

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...

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...

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

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.

Quantifying Acoustic Impacts on Marine Mammals and Sea Turtles: Methods and Analytical Approach for Phase III Training and Testing

DTIC Science & Technology

2017-06-16

Acoustic Impacts on Marine Mammals and Sea Turtles: Methods and Analytical Approach for Phase III Training and Testing Sarah A. Blackstock Joseph O...December 2017 4. TITLE AND SUBTITLE Quantifying Acoustic Impacts on Marine Mammals and Sea Turtles: Methods and Analytical Approach for Phase III...Navy’s Phase III Study Areas as described in each Environmental Impact Statement/ Overseas Environmental Impact Statement and describes the methods

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...

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.

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.

77 FR 40936 - 60-Day Notice of Proposed Information Collection: Passport Demand Forecasting Study Phase III

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-11

...: Passport Demand Forecasting Study Phase III ACTION: Notice of request for public comments. SUMMARY: The... of 1995. Title of Information Collection: Passport Demand Forecasting Study Phase III. OMB Control... Consular Affairs/Passport Services (CA/PPT) Form Number: SV-2012-0006. Respondents: A national...

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.

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

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.

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.

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...

Phenomenology of Polymorphism, III: p, TDiagram and Stability of Piracetam Polymorphs

NASA Astrophysics Data System (ADS)

Céolin, R.; Agafonov, V.; Louër, D.; Dzyabchenko, V. A.; Toscani, S.; Cense, J. M.

1996-02-01

The nootropic drug Piracetam is known to crystallize in three phases. In order to obtain their stability hierarchy from sublimation pressure inequalities, the drawing of a topologicalp,Tdiagram was attempted. For such a purpose and also for quality control, crystallographic and thermodynamic data were required. Powder X-ray diffractometry (XRD) and differential scanning calorimetry (DSC) were used. Molecular energy calculations were performed. Phase I melts at 426 K (ΔfusH(I) = +180 J·g-1). Phase II transforms into Phase I at 399 K (Δ(II→I)H= +24 J·g-1). Phase III transforms into phase I at 392 K (Δ(III→I)H= +28 J·g-1) or melts at 412 K (ΔfusH(III) = +210 J·g-1). Thep,Tdiagram shows that phase I is stable at higher temperature and phase II at lower temperature, like phase III, which is stable under high pressure. At room temperature, phase II is the more stable form, and phase I the less stable one. This agrees with the spontaneous I → II transformation observed at 298 K within a few hours, and with lattice energies, calculated previously. Molecular energy calculations and crystal structure comparison show how intermolecular hydrogen bonds and H-bonded dimers, in phases II and III, may stabilize conformations higher in energy than those of the isolated molecule and of phase I.

Security Quality Requirements Engineering (SQUARE): Case Study Phase III

DTIC Science & Technology

2006-05-01

Security Quality Requirements Engineering (SQUARE): Case Study Phase III Lydia Chung Frank Hung Eric Hough Don Ojoko-Adams Advisor...Engineering (SQUARE): Case Study Phase III CMU/SEI-2006-SR-003 Lydia Chung Frank Hung Eric Hough Don Ojoko-Adams Advisor Nancy R. Mead...1 1.1 The SQUARE Process ............................................................................... 1 1.2 Case Study Clients

Suboptimal Dosing Parameters as Possible Factors in the Negative Phase III Clinical Trials of Progesterone for Traumatic Brain Injury.

PubMed

Howard, Randy B; Sayeed, Iqbal; Stein, Donald G

2017-06-01

To date, outcomes for all Phase III clinical trials for traumatic brain injury (TBI) have been negative. The recent disappointing results of the Progesterone for the Treatment of Traumatic Brain Injury (ProTECT) and Study of a Neuroprotective Agent, Progesterone, in Severe Traumatic Brain Injury (SyNAPSe) Phase III trials for progesterone in TBI have triggered considerable speculation about the reasons for the negative outcomes of these two studies in particular and for those of all previous Phase III TBI clinical trials in general. Among the factors proposed to explain the ProTECT III and SyNAPSe results, the investigators themselves and others have cited: 1) the pathophysiological complexity of TBI itself; 2) issues with the quality and clinical relevance of the preclinical animal models; 3) insufficiently sensitive clinical endpoints; and 4) inappropriate clinical trial designs and strategies. This paper highlights three critical trial design factors that may have contributed substantially to the negative outcomes: 1) suboptimal doses and treatment durations in the Phase II studies; 2) the strategic decision not to perform Phase IIB studies to optimize these variables before initiating Phase III; and 3) the lack of incorporation of the preclinical and Chinese Phase II results, as well as allometric scaling principles, into the Phase III designs. Given these circumstances and the exceptional pleiotropic potential of progesterone as a TBI (and stroke) therapeutic, we are advocating a return to Phase IIB testing. We advocate the incorporation of dose and schedule optimization focused on lower doses and a longer duration of treatment, combined with the addressing of other potential trial design problems raised by the authors in the recently published trial results.

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...

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...

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...

Enhanced Night Visibility Series, Volume XII : Overview of Phase II and Development of Phase III Experimental Plan

DOT National Transportation Integrated Search

2005-12-01

This volume provides an overview of the six studies that compose Phase II of the Enhanced Night Visibility project and the experimental plan for its third and final portion, Phase III. The Phase II studies evaluated up to 12 vision enhancement system...

Lot-to-lot consistency of a tetravalent dengue vaccine in healthy adults in Australia: a randomised study.

PubMed

Torresi, Joseph; Heron, Leon G; Qiao, Ming; Marjason, Joanne; Chambonneau, Laurent; Bouckenooghe, Alain; Boaz, Mark; van der Vliet, Diane; Wallace, Derek; Hutagalung, Yanee; Nissen, Michael D; Richmond, Peter C

2015-09-22

The recombinant yellow fever-17D-dengue virus, live, attenuated, tetravalent dengue vaccine (CYD-TDV) has undergone extensive clinical trials. Here safety and consistency of immunogenicity of phase III manufacturing lots of CYD-TDV were evaluated and compared with a phase II lot and placebo in a dengue-naïve population. Healthy 18-60 year-olds were randomly assigned in a 3:3:3:3:1 ratio to receive three subcutaneous doses of either CYD-TDV from any one of three phase III lots or a phase II lot, or placebo, respectively in a 0, 6, 12 month dosing schedule. Neutralising antibody geometric mean titres (PRNT50 GMTs) for each of the four dengue serotypes were compared in sera collected 28 days after the third vaccination-equivalence among lots was demonstrated if the lower and upper limits of the two-sided 95% CIs of the GMT ratio were ≥0.5 and ≤2.0, respectively. 712 participants received vaccine or placebo and 614 (86%) completed the study; 17 (2.4%) participants withdrew after adverse events. Equivalence of phase III lots was demonstrated for 11 of 12 pairwise comparisons. One of three comparisons for serotype 2 was not statistically equivalent. GMTs for serotype 2 in phase III lots were close to each other (65.9, 44.1 and 58.1, respectively). Phase III lots can be produced in a consistent manner with predictable immune response and acceptable safety profile similar to previously characterised phase II lots. The phase III lots may be considered as not clinically different as statistical equivalence was shown for serotypes 1, 3 and 4 across the phase III lots. For serotype 2, although equivalence was not shown between two lots, the GMTs observed in the phase III lots were consistently higher than those for the phase II lot. As such, in our view, biological equivalence for all serotypes was demonstrated. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effects of step-feeding and intermittent aeration on organics and nitrogen removal in a horizontal subsurface flow constructed wetland.

PubMed

Patil, Sagar; Chakraborty, Saswati

2017-03-21

The effect of step feed strategy and intermittent aeration on removal of chemical oxygen demand (COD) and nitrogen was investigated in a laboratory scale horizontal subsurface flow constructed wetland (HSSFCW). Wetland was divided into four zones along the length (zone I to IV), and influent was introduced into first and third zones by step feeding. Continuous study was carried out in four phases. In phases I to III, 30% of influent was bypassed to zone III for denitrification along with organics removal. Intermittent aeration was provided only in zone II at 2.5 L/min for 4 h/day, during phases II, III and IV. In phase I, 87% COD and 43% NH 4 + -N (ammonia-nitrogen) removal were obtained from influents of 331 and 30 mg/L, respectively. In phase II study, external aeration resulted in 97% COD and 71% NH 4 + -N removal in the wetland. In phase IV, 40% of feed was delivered to zone III. Higher supply of organic in zone III resulted in higher denitrification, and total nitrogen removal rate increased to 70% from 56%. In the final effluent, concentration of NO 3 - -N was 9-11 mg/L in phase I to III and decreased to 4 mg/L in phase IV. Batch study showed that COD and NH 4 + -N removal followed first order kinetics in different zones of wetland.

Unraveling the Mystery of the Blue Fog: Structure, Properties, and Applications of Amorphous Blue Phase III.

PubMed

Gandhi, Sahil Sandesh; Chien, Liang-Chy

2017-12-01

The amorphous blue phase III of cholesteric liquid crystals, also known as the "blue fog," are among the rising stars in materials science that can potentially be used to develop next-generation displays with the ability to compete toe-to-toe with disruptive technologies like organic light-emitting diodes. The structure and properties of the practically unobservable blue phase III have eluded scientists for more than a century since it was discovered. This progress report reviews the developments in this field from both fundamental and applied research perspectives. The first part of this progress report gives an overview of the 130-years-long scientific tour-de-force that very recently resulted in the revelation of the mysterious structure of blue phase III. The second part reviews progress made in the past decade in developing electrooptical, optical, and photonic devices based on blue phase III. The strong and weak aspects of the development of these devices are underlined and criticized, respectively. The third- and-final part proposes ideas for further improvement in blue phase III technology to make it feasible for commercialization and widespread use. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Conceptional Considerations to Energy Balance and Global Warming Potential of Soil Bioengineering Structures

NASA Astrophysics Data System (ADS)

von der Thannen, Magdalena; Paratscha, Roman; Smutny, Roman; Lampalzer, Thomas; Strauss, Alfred; Rauch, Hans Peter

2016-04-01

Nowadays there is a high demand on engineering solutions considering not only technical aspects but also ecological and aesthetic values. In this context soil bioengineering techniques are often used as standalone solutions or in combination with conventional engineering structures. It is a construction technique that uses biological components for hydraulic and civil engineering solutions. In general it pursues the same objectives as conventional civil engineering structures. Currently the used assessment methods for soil bioengineering structures are referencing technically, ecologically and socio-economically. In a modern engineering approach additionally, environmental impacts and potential added values should be considered. The research project E-Protect aims at developing Environmental Life Cycle Assessment (LCA) models for this special field of alpine protective constructions. Both, the Cumulative Energy Demand (CED) and the Global Warming Potential (GWP) should be considered in an Environmental LCA over the whole life cycle of an engineering structure. The life cycle itself can be divided into three phases: the construction phase, the use phase and the end of life phase. The paper represents a concept to apply an Environmental LCA model for soil bioengineering structures. Beside the construction phase of these structures particular attention will be given to the use phase. It is not only important in terms of engineering effects but also plays an important role for positive carbon footprint due to the growing plants of soil bioengineering structures in contrast to conventional structures. Innovative Environmental LCA models will be applied to soil bioengineering structures which provide a new transparency for the responsible planners and stakeholders, by pointing out the total consumption of resources in all construction phases and components.

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.

Failures in Phase III: Causes and Consequences.

PubMed

Seruga, Bostjan; Ocana, Alberto; Amir, Eitan; Tannock, Ian F

2015-10-15

Phase III randomized controlled trials (RCT) in oncology fail to lead to registration of new therapies more often than RCTs in other medical disciplines. Most RCTs are sponsored by the pharmaceutical industry, which reflects industry's increasing responsibility in cancer drug development. Many preclinical models are unreliable for evaluation of new anticancer agents, and stronger evidence of biologic effect should be required before a new agent enters the clinical development pathway. Whenever possible, early-phase clinical trials should include pharmacodynamic studies to demonstrate that new agents inhibit their molecular targets and demonstrate substantial antitumor activity at tolerated doses in an enriched population of patients. Here, we review recent RCTs and found that these conditions were not met for most of the targeted anticancer agents, which failed in recent RCTs. Many recent phase III RCTs were initiated without sufficient evidence of activity from early-phase clinical trials. Because patients treated within such trials can be harmed, they should not be undertaken. The bar should also be raised when making decisions to proceed from phase II to III and from phase III to marketing approval. Many approved agents showed only better progression-free survival than standard treatment in phase III trials and were not shown to improve survival or its quality. Introduction of value-based pricing of new anticancer agents would dissuade the continued development of agents with borderline activity in early-phase clinical trials. When collaborating with industry, oncologists should be more critical and better advocates for cancer patients. ©2015 American Association for Cancer Research.

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...

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...

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...

Statistical aspects of the TNK-S2B trial of tenecteplase versus alteplase in acute ischemic stroke: an efficient, dose-adaptive, seamless phase II/III design.

PubMed

Levin, Bruce; Thompson, John L P; Chakraborty, Bibhas; Levy, Gilberto; MacArthur, Robert; Haley, E Clarke

2011-08-01

TNK-S2B, an innovative, randomized, seamless phase II/III trial of tenecteplase versus rt-PA for acute ischemic stroke, terminated for slow enrollment before regulatory approval of use of phase II patients in phase III. (1) To review the trial design and comprehensive type I error rate simulations and (2) to discuss issues raised during regulatory review, to facilitate future approval of similar designs. In phase II, an early (24-h) outcome and adaptive sequential procedure selected one of three tenecteplase doses for phase III comparison with rt-PA. Decision rules comparing this dose to rt-PA would cause stopping for futility at phase II end, or continuation to phase III. Phase III incorporated two co-primary hypotheses, allowing for a treatment effect at either end of the trichotomized Rankin scale. Assuming no early termination, four interim analyses and one final analysis of 1908 patients provided an experiment-wise type I error rate of <0.05. Over 1,000 distribution scenarios, each involving 40,000 replications, the maximum type I error in phase III was 0.038. Inflation from the dose selection was more than offset by the one-half continuity correction in the test statistics. Inflation from repeated interim analyses was more than offset by the reduction from the clinical stopping rules for futility at the first interim analysis. Design complexity and evolving regulatory requirements lengthened the review process. (1) The design was innovative and efficient. Per protocol, type I error was well controlled for the co-primary phase III hypothesis tests, and experiment-wise. (2a) Time must be allowed for communications with regulatory reviewers from first design stages. (2b) Adequate type I error control must be demonstrated. (2c) Greater clarity is needed on (i) whether this includes demonstration of type I error control if the protocol is violated and (ii) whether simulations of type I error control are acceptable. (2d) Regulatory agency concerns that protocols for futility stopping may not be followed may be allayed by submitting interim analysis results to them as these analyses occur.

Methods for synthesizing semiconductor quality chalcopyrite crystals for nonlinear optical and radiation detection applications and the like

DOEpatents

Stowe, Ashley; Burger, Arnold

2016-05-10

A method for synthesizing I-III-VI.sub.2 compounds, including: melting a Group III element; adding a Group I element to the melted Group III element at a rate that allows the Group I and Group III elements to react thereby providing a single phase I-III compound; and adding a Group VI element to the single phase I-III compound under heat, with mixing, and/or via vapor transport. The Group III element is melted at a temperature of between about 200 degrees C. and about 700 degrees C. Preferably, the Group I element consists of a neutron absorber and the group III element consists of In or Ga. The Group VI element and the single phase I-III compound are heated to a temperature of between about 700 degrees C. and about 1000 degrees C. Preferably, the Group VI element consists of S, Se, or Te. Optionally, the method also includes doping with a Group IV element activator.

Enantioselective separation of racemic juvenile hormone III by normal-phase high-performance liquid chromatography and preparation of [(2)H(3)]juvenile hormone III as an internal standard for liquid chromatography-mass spectrometry quantification.

PubMed

Ichikawa, Akio; Ono, Hiroshi; Furuta, Kenjiro; Shiotsuki, Takahiro; Shinoda, Tetsuro

2007-08-17

Juvenile hormone III (JH III) racemate was prepared from methyl (2E,6E)-farnesoate via epoxidation with 3-chloroperbenzoic acid (mCPBA). Enantioselective separation of JH III was conducted using normal-phase high-performance liquid chromatography (HPLC) on a chiral stationary phase. [(2)H(3)]Methyl (2E,6E)-farnesoate was also prepared from (2E,6E)-farnesoic acid and [(2)H(4)]methanol (methanol-d(4)) using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and 4-dimethylaminopyridine (DMAP); the conjugated double bond underwent isomerization to some degree. Epoxidation of [(2)H(3)]methyl (2E,6E)-farnesoate with mCPBA gave a novel deuterium-substituted internal standard [(2)H(3)]JH III (JH III-d(3)). The standard curve was produced by linear regression using the peak area ratios of JH III and JH III-d(3) in liquid chromatography-mass spectrometry (LC-MS).

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.

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

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...

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.

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.

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.

Unusual Enhancement of Magnetization by Pressure in the Antiferro-Quadrupole-Ordered Phase in CeB6

NASA Astrophysics Data System (ADS)

Ikeda, Suguru; Sera, Masafumi; Hane, Shingo; Uwatoko, Yoshiya; Kosaka, Masashi; Kunii, Satoru

2007-06-01

The effect of pressure on CeB6 was investigated by the measurement of the magnetization (M) under pressure, and we obtained the following results. The effect of pressure on M in phase I is very small. By applying pressure, TQ is enhanced, but TN and the critical field from the antiferromagnetic (AFM) phase III to the antiferro-quadrupole (AFQ) phase II (HcIII--II) are suppressed, as previously reported. The magnetization curve in phase III shows the characteristic shoulder at H˜ HcIII--II/2 at ambient pressure. This shoulder becomes much more pronounced by applying pressure. Both HcIII--II and the magnetic field, where a shoulder is seen in the magnetization curve in phase III, are largely suppressed by pressure. In phase II, the M-T curve at a low magnetic field exhibits an unusual concave temperature dependence below TQ down to TN. Thus, we found that the lower the magnetic field, the larger the enhancement of M in both phases III and II. To clarify the origin of the unusual pressure effect of M, we performed a mean-field calculation for the 4-sublattice model using the experimental results of dTQ/dP>0 and dTN/dP<0 and assuming the positive pressure dependence of the Txyz-antiferro-octupole (AFO) interaction. The characteristic features of the pressure effect of M obtained by the experiments could be reproduced well by the mean-field calculation. We found that the origin of the characteristic effect of pressure on CeB6 is the change in the subtle balance between the AFM interaction and the magnetic field-induced-effective FM interaction induced by the coexistence of the Oxy-AFQ and Txyz-AFO interactions under pressure.

Pore-scale characterization of biogeochemical controls on iron and uranium speciation under flow conditions.

PubMed

Pearce, Carolyn I; Wilkins, Michael J; Zhang, Changyong; Heald, Steve M; Fredrickson, Jim K; Zachara, John M

2012-08-07

Etched silicon microfluidic pore network models (micromodels) with controlled chemical and redox gradients, mineralogy, and microbiology under continuous flow conditions are used for the incremental development of complex microenvironments that simulate subsurface conditions. We demonstrate the colonization of micromodel pore spaces by an anaerobic Fe(III)-reducing bacterial species (Geobacter sulfurreducens) and the enzymatic reduction of a bioavailable Fe(III) phase within this environment. Using both X-ray microprobe and X-ray absorption spectroscopy, we investigate the combined effects of the precipitated Fe(III) phases and the microbial population on uranium biogeochemistry under flow conditions. Precipitated Fe(III) phases within the micromodel were most effectively reduced in the presence of an electron shuttle (AQDS), and Fe(II) ions adsorbed onto the precipitated mineral surface without inducing any structural change. In the absence of Fe(III), U(VI) was effectively reduced by the microbial population to insoluble U(IV), which was precipitated in discrete regions associated with biomass. In the presence of Fe(III) phases, however, both U(IV) and U(VI) could be detected associated with biomass, suggesting reoxidation of U(IV) by localized Fe(III) phases. These results demonstrate the importance of the spatial localization of biomass and redox active metals, and illustrate the key effects of pore-scale processes on contaminant fate and reactive transport.

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

Safety and tolerability review of lorcaserin in clinical trials.

PubMed

Greenway, F L; Shanahan, W; Fain, R; Ma, T; Rubino, D

2016-10-01

Lorcaserin is a novel selective serotonin 2C receptor agonist indicated by the US Food and Drug Administration for chronic weight management in adults with obesity or overweight with ≥1 comorbidity. The safety and efficacy of lorcaserin were established during two Phase III clinical trials in patients without diabetes (BLOOM and BLOSSOM) and one Phase III clinical trial in patients with type 2 diabetes (BLOOM-DM). Headache was the most common adverse event experienced by patients during all Phase III trials. Additional adverse events occurring in >5% of patients receiving lorcaserin included dizziness, fatigue, nausea, dry mouth and constipation in patients without diabetes, and hypoglycaemia, back pain, cough and fatigue in patients with diabetes. In a pooled analysis of echocardiographic data collected during the three lorcaserin Phase III trials, the incidence of FDA-defined valvulopathy was similar in patients taking lorcaserin and the placebo. Here, the safety profile of lorcaserin at the FDA-approved dose of 10 mg twice daily is reviewed using data from the lorcaserin Phase III programme, with a focus on theoretical adverse events commonly associated with agonists of the serotonin receptor family. Based on the lorcaserin Phase III clinical trial data, lorcaserin is safe and well tolerated in the indicated patient populations. © 2016 World Obesity.

Simulating Aqueous-Phase Isoprene-Epoxydiol (IEPOX) ...

EPA Pesticide Factsheets

The lack of statistically robust relationships between IEPOX (isoprene epoxydiol)-derived SOA (IEPOX SOA) and aerosol liquid water and pH observed during the 2013 Southern Oxidant and Aerosol Study (SOAS) emphasizes the importance of modeling the whole system to understand the controlling factors governing IEPOX SOA formation. We present a mechanistic modeling investigation predicting IEPOX SOA based on Community Multiscale Air Quality (CMAQ) model algorithms and a recently introduced photochemical box model, simpleGAMMA. We aim to (1) simulate IEPOX SOA tracers from the SOAS Look Rock ground site, (2) compare the two model formulations, (3) determine the limiting factors in IEPOX SOA formation, and (4) test the impact of a hypothetical sulfate reduction scenario on IEPOX SOA. The estimated IEPOX SOA mass variability is in similar agreement (r2 ∼ 0.6) with measurements. Correlations of the estimated and measured IEPOX SOA tracers with observed aerosol surface area (r2 ∼ 0.5–0.7), rate of particle-phase reaction (r2 ∼ 0.4–0.7), and sulfate (r2 ∼ 0.4–0.5) suggest an important role of sulfate in tracer formation via both physical and chemical mechanisms. A hypothetical 25% reduction of sulfate results in ∼70% reduction of IEPOX SOA formation, reaffirming the importance of aqueous phase chemistry in IEPOX SOA production. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, decision-suppor

The motilin receptor agonist erythromycin stimulates hunger and food intake through a cholinergic pathway.

PubMed

Deloose, Eveline; Vos, Rita; Janssen, Pieter; Van den Bergh, Omer; Van Oudenhove, Lukas; Depoortere, Inge; Tack, Jan

2016-03-01

Motilin-induced phase III contractions have been identified as a hunger signal. These phase III contractions occur as part of the migrating motor complex (MMC), a contractility pattern of the gastrointestinal tract during fasting. The mechanism involved in this association between subjective hunger feelings and gastrointestinal motility during the MMC is largely unknown, however, as is its ability to stimulate food intake. We sought to 1) investigate the occurrence of hunger peaks and their relation to phase III contractions, 2) evaluate whether this relation was cholinergically driven, and 3) assess the ability of the motilin receptor agonist erythromycin to induce food intake. An algorithm was developed to detect hunger peaks. The association with phase III contractions was studied in 14 healthy volunteers [50% men; mean ± SEM age: 25 ± 2 y; mean ± SEM body mass index (BMI; in kg/m(2)): 23 ± 1]. The impact of pharmacologically induced phase III contractions on the occurrence of hunger peaks and the involvement of a cholinergic pathway were assessed in 14 healthy volunteers (43% men; age: 29 ± 3 y; BMI: 23 ± 1). Last, the effect of erythromycin administration on food intake was examined in 15 healthy volunteers (40% men; age: 28 ± 3 y; BMI: 22 ± 1). The occurrence of hunger peaks and their significant association with phase III contractions was confirmed (P < 0.0001). Pharmacologically induced phase III contractions were also significantly associated with hunger peaks (P < 0.05), and this association involved a cholinergic pathway. Administering erythromycin significantly stimulated food intake compared with placebo (53% ± 13% compared with 10% ± 5%; P < 0.05). Motilin-induced phase III contractions induced hunger feelings through a cholinergic pathway. Moreover, erythromycin stimulated food intake, suggesting a physiologic role of motilin as an orexigenic signal from the gastrointestinal tract. This trial was registered at www.clinicaltrials.gov as NCT02633579. © 2016 American Society for Nutrition.

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…

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...

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...

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...

Professional Identity Development of Counselor Education Doctoral Students: A Qualitative Investigation

ERIC Educational Resources Information Center

Limberg, Dodie; Bell, Hope; Super, John T.; Jacobson, Lamerial; Fox, Jesse; DePue, M. Kristina; Christmas, Chris; Young, Mark E.; Lambie, Glenn W.

2013-01-01

The professional identity of a counselor educator develops primarily during the individual's doctoral preparation program. This study employed consensual qualitative research methodology to examine the phenomenon of professional identity development in counselor education doctoral students (CEDS) in a cohort model. Cross-sectional focus groups…

Monterey-Salinas Transit ITS Augmentation Project : Phase III Evaluation Report

DOT National Transportation Integrated Search

2009-12-01

The purpose of this document is to present the findings from Phase II and Phase III of the Evaluation of the Intelligent Transportation Systems (ITS) Augmentation Project that was implemented at the Monterey-Salinas Transit (MST) in Monterey, Califor...

The Mississippi Catalog of Competencies for Public Elementary and Secondary Physical Education.

ERIC Educational Resources Information Center

Mississippi State Dept. of Education, Jackson.

Phase III of a five-phase project which has implications for the improvement of instructional programs in Mississippi's elementary and secondary schools is described. In phase III, specifically stated objectives or competencies in physical education, designed to accomplish the objectives stated in phase II, are cataloged. The competencies are…

The use of dihexyldithiocarbamate in reverse-phase HPLC of metal chelates

NASA Astrophysics Data System (ADS)

Fatimah, S. S.; Bahti, H. H.; Hastiawan, I.; Permanasari, A.

2018-05-01

Dialkyldithiocarbamates have long been used as chelating agents in reverse-phase HPLC of transition metals. In the previous study, an alkyl homolog of this type of ligand, namely dihexyldithiocarbamate (DHDTC), was synthesized and characterized. The use of this particular ligand in the revese-phase HPLC of some selected transition metal ions is now reported for the first time. The mobile phase comprising of the flow rate and of the detection, in the separation of the metal chelates of Cd (II), Fe (III), Cu (II), and Co (III), were investigated on a C-18 column. The results showed that dihexylditiocarbamate could be used for separating Cd (II), Fe(III), Cu(II), and Co(III). Therefore, it could be used in simultaneous analysis.

A new trial design to accelerate tuberculosis drug development: the Phase IIC Selection Trial with Extended Post-treatment follow-up (STEP).

PubMed

Phillips, Patrick P J; Dooley, Kelly E; Gillespie, Stephen H; Heinrich, Norbert; Stout, Jason E; Nahid, Payam; Diacon, Andreas H; Aarnoutse, Rob E; Kibiki, Gibson S; Boeree, Martin J; Hoelscher, Michael

2016-03-23

The standard 6-month four-drug regimen for the treatment of drug-sensitive tuberculosis has remained unchanged for decades and is inadequate to control the epidemic. Shorter, simpler regimens are urgently needed to defeat what is now the world's greatest infectious disease killer. We describe the Phase IIC Selection Trial with Extended Post-treatment follow-up (STEP) as a novel hybrid phase II/III trial design to accelerate regimen development. In the Phase IIC STEP trial, the experimental regimen is given for the duration for which it will be studied in phase III (presently 3 or 4 months) and patients are followed for clinical outcomes of treatment failure and relapse for a total of 12 months from randomisation. Operating characteristics of the trial design are explored assuming a classical frequentist framework as well as a Bayesian framework with flat and sceptical priors. A simulation study is conducted using data from the RIFAQUIN phase III trial to illustrate how such a design could be used in practice. With 80 patients per arm, and two (2.5 %) unfavourable outcomes in the STEP trial, there is a probability of 0.99 that the proportion of unfavourable outcomes in a potential phase III trial would be less than 12 % and a probability of 0.91 that the proportion of unfavourable outcomes would be less than 8 %. With six (7.5 %) unfavourable outcomes, there is a probability of 0.82 that the proportion of unfavourable outcomes in a potential phase III trial would be less than 12 % and a probability of 0.41 that it would be less than 8 %. Simulations using data from the RIFAQUIN trial show that a STEP trial with 80 patients per arm would have correctly shown that the Inferior Regimen should not proceed to phase III and would have had a high chance (0.88) of either showing that the Successful Regimen could proceed to phase III or that it might require further optimisation. Collection of definitive clinical outcome data in a relatively small number of participants over only 12 months provides valuable information about the likelihood of success in a future phase III trial. We strongly believe that the STEP trial design described herein is an important tool that would allow for more informed decision-making and accelerate regimen development.

Cloud point extraction: an alternative to traditional liquid-liquid extraction for lanthanides(III) separation.

PubMed

Favre-Réguillon, Alain; Draye, Micheline; Lebuzit, Gérard; Thomas, Sylvie; Foos, Jacques; Cote, Gérard; Guy, Alain

2004-06-17

Cloud point extraction (CPE) was used to extract and separate lanthanum(III) and gadolinium(III) nitrate from an aqueous solution. The methodology used is based on the formation of lanthanide(III)-8-hydroxyquinoline (8-HQ) complexes soluble in a micellar phase of non-ionic surfactant. The lanthanide(III) complexes are then extracted into the surfactant-rich phase at a temperature above the cloud point temperature (CPT). The structure of the non-ionic surfactant, and the chelating agent-metal molar ratio are identified as factors determining the extraction efficiency and selectivity. In an aqueous solution containing equimolar concentrations of La(III) and Gd(III), extraction efficiency for Gd(III) can reach 96% with a Gd(III)/La(III) selectivity higher than 30 using Triton X-114. Under those conditions, a Gd(III) decontamination factor of 50 is obtained.

School Improvement Efforts: Qualitative Data from Four Naturally Occurring Experiments in Phase III of the Louisiana School Effectiveness Study.

ERIC Educational Resources Information Center

Stringfield, Sam; And Others

Phase III of the Louisiana School Effectiveness Study (LSES-III) was designed in part to obtain rich, qualitative data on the characteristics of more and less effective schools in the Gulf South. Data were gathered on eight matched outlier pairs of schools during the 1984-1985 school year. Of the eight historically ineffective schools in LSES-III,…

Fe(II) sorption on pyrophyllite: Effect of structural Fe(III) (impurity) in pyrophyllite on nature of layered double hydroxide (LDH) secondary mineral formation

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

Starcher, Autumn N.; Li, Wei; Kukkadapu, Ravi K.

Fe(II)-Al(III)-LDH (layered double hydroxide) phases have been shown to form from reactions of aqueous Fe(II) with Fe-free Al-bearing minerals (phyllosilicate/clays and Al-oxides). To our knowledge, the effect of small amounts of structural Fe(III) impurities in “neutral” clays on such reactions, however, were not studied. In this study to understand the role of structural Fe(III) impurity in clays, laboratory batch studies with pyrophyllite (10 g/L), an Al-bearing phyllosilicate, containing small amounts of structural Fe(III) impurities and 0.8 mM and 3 mM Fe(II) (both natural and enriched in 57Fe) were carried out at pH 7.5 under anaerobic conditions (4% H2 – 96%more » N2 atmosphere). Samples were taken up to 4 weeks for analysis by Fe-X-ray absorption spectroscopy and 57Fe Mössbauer spectroscopy. In addition to the precipitation of Fe(II)-Al(III)-LDH phases as observed in earlier studies with pure minerals (no Fe(III) impurities in the minerals), the analyses indicated formation of small amounts of Fe(III) containing solid(s), most probably hybrid a Fe(II)-Al(III)/Fe(III)-LDH phase. The mechanism of Fe(II) oxidation was not apparent but most likely was due to interfacial electron transfer from the sorbed Fe(II) to the structural Fe(III) and/or surface-sorption-induced electron-transfer from the sorbed Fe(II) to the clay lattice. Increase in the Fe(II)/Al ratio of the LDH with reaction time further indicated the complex nature of the samples. This research provides evidence for the formation of both Fe(II)-Al(III)-LDH and Fe(II)-Fe(III)/Al(III)-LDH-like phases during reactions of Fe(II) in systems that mimic the natural environments. Better understanding Fe phase formation in complex laboratory studies will improve models of natural redox systems.« less

Methodology of clinical trials evaluating the incorporation of new drugs in the first-line treatment of patients with diffuse large B-cell lymphoma (DLBCL): a critical review.

PubMed

Iacoboni, G; Zucca, E; Ghielmini, M; Stathis, A

2018-05-01

The first-line treatment of diffuse large B-cell lymphoma (DLBCL) is the combination of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, curing approximately 60% of patients. Many clinical trials have been carried out over the last 10 years trying to improve the results of this treatment, but the appropriateness of their planning strategies could be rediscussed. Reports of phase III trials evaluating the addition of molecularly targeted agents or new monoclonal antibodies to the classic R-CHOP backbone in first-line induction or maintenance treatment were reviewed. The trial design, primary end point, number of patients enrolled, patient selection criteria, treatment schedule and results were registered for each one. In addition, the phases I and II trials which preceded these phase III trials were also reviewed. Among six phase III trials with results, only one trial evaluating lenalidomide maintenance after response to R-CHOP induction was positive and reached its primary end point. The other five trials did not show an improved outcome with the addition of the new agent. The preceding phases I and II trials were very heterogeneous in their end points and design. Even though most of these trials were considered positive, thus encouraging further investigation, so far they failed to predict the results of the subsequent phase III trials. The standard of care for DLBCL is still R-CHOP. Phase I/II trials failed to predict the results of subsequent phase III trials evaluating non-chemotherapeutic agents added to R-CHOP. The methodology of phase II trials evaluating new agents in DLBCL needs to be better defined in the future.

76 FR 52658 - State Program Requirements; Approval of Application for Program Revision to the National...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-23

... (ADEC) in four phases. Phases I-III have been transferred from the EPA to ADEC. In March 2011, ADEC made a submission for approval for a one year extension of the transfer of Phase IV of the APDES program... facilities not previously transferred in Phases I-III. The EPA approved the one year extension for Phase IV...

Pore-Scale Characterization of Biogeochemical Controls on Iron and Uranium Speciation under Flow Conditions

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

Pearce, Carolyn I.; Wilkins, Michael J.; Zhang, Changyong

2012-09-17

Etched silicon microfluidic pore network models (micromodels) with controlled chemical and redox gradients, mineralogy, and microbiology under continuous flow conditions are used for the incremental development of complex microenvironments that simulate subsurface conditions. We demonstrate the colonization of micromodel pore spaces by an anaerobic Fe(III)-reducing bacterial species (Geobacter sulfurreducens) and the enzymatic reduction of a bioavailable Fe(III) phase within this environment. Using both X-ray Microprobe and X-ray Absorption Spectroscopy, we investigate the combined effects of the precipitated Fe(III) phases and the microbial population on uranium biogeochemistry under flow conditions. Precipitated Fe(III) phases within the micromodel were most effectively reduced inmore » the presence of an electron shuttle (AQDS), and Fe(II) ions adsorbed onto the precipitated mineral surface without inducing any structural change. In the absence of Fe(III), U(VI) was effectively reduced by the microbial population to insoluble U(IV), which was precipitated in discrete regions associated with biomass. In the presence of Fe(III) phases, however, both U(IV) and U(VI) could be detected associated with biomass, suggesting re-oxidation of U(IV) by localized Fe(III) phases. These results demonstrate the importance of the spatial localization of biomass and redox active metals, and illustrate the key effects of pore-scale processes on contaminant fate and reactive transport.« less

Changing interdigestive migrating motor complex in rats under acute liver injury.

PubMed

Liu, Mei; Zheng, Su-Jun; Xu, Weihong; Zhang, Jianying; Chen, Yu; Duan, Zhongping

2014-01-01

Gastrointestinal motility disorder is a major clinical manifestation of acute liver injury, and interdigestive migrating motor complex (MMC) is an important indicator. We investigated the changes and characteristics of MMC in rats with acute liver injury. Acute liver injury was created by d-galactosamine, and we recorded the interdigestive MMC using a multichannel physiological recorder and compared the indexes of interdigestive MMC. Compared with normal controls, antral MMC Phase I duration was significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The duodenal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The jejunal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury compared with normal controls. Compared with the normal controls, rats with acute liver injury had a significantly prolonged interdigestive MMC cycle, related mainly to longer MMC Phases I and IV, shortened MMC Phase III, and MMC Phase II characterized by increased migrating clustered contractions, which were probably major contributors to the gastrointestinal motility disorders.

Effects of Combined Phase III and Phase II Cardiac Exercise Therapy for Middle-aged Male Patients with Acute Myocardial Infarction

PubMed Central

Lee, Chih-Wei; Wang, Ji-Hung; Hsieh, Jen-Che; Hsieh, Tsung-Cheng; Huang, Chien-Hui

2013-01-01

[Purpose] To investigate the effects of cardiac exercise therapy (CET) on exercise capacity and coronary risk factors (CRFs) of patients with acute myocardial infarction (AMI). [Methods] Patients who participated in an 8-week supervised, hospital-based phase II and 6-month home-based phase III CET with monthly telephone and/or home visits were defined as the exercise group (EG) (n=20), while those who did not receive phase II or phase III CET were defined as the no-exercise group (NEG) (n=10). CRFs were evaluated pre- and post-phase II and eight months after discharge. One and two-way repeated measures ANOVA were used to perform intra- and inter-group comparisons. [Results] Thirty men with AMI aged 49.3 ± 8.3 years were studied. EG increased their exercise capacity (METs) (6.8 ± 1.6 vs.10.0 ± 1.9) after phase II CET and was able to maintain it at 8-month follow-up. Both groups had significantly fewer persons who kept on smoking compared to the first examination. High density lipoprotein cholesterol (HDL-C) increased from 38.1 ± 11.0 to 43.7 ± 8.7 mg/dl at follow-up in EG while no significant difference was noted in NEG. [Conclusion] After phase III CET subjects had maintained the therapeutic effects of smoking cessation, and increasing exercise capacity obtained in phase II CET. HDL-C in EG continued to improve during phase III CET. PMID:24396201

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...

Creative Retirement: Survey of Older Adults' Educational Interests and Motivations

ERIC Educational Resources Information Center

Sloane-Seale, Atlanta; Kops, Bill

2004-01-01

The University of Manitoba's Continuing Education Division (CED) and Creative Retirement Manitoba (CRM) formed a partnership to promote applied research on lifelong learning and older adults, to develop new and to complement existing educational activities, and to explore new program models and instructional methods to meet the educational needs…

"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…

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...

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…

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...

Phase III Simplified Integrated Test (SIT) results - Space Station ECLSS testing

NASA Technical Reports Server (NTRS)

Roberts, Barry C.; Carrasquillo, Robyn L.; Dubiel, Melissa Y.; Ogle, Kathryn Y.; Perry, Jay L.; Whitley, Ken M.

1990-01-01

During 1989, phase III testing of Space Station Freedom Environmental Control and Life Support Systems (ECLSS) began at Marshall Space Flight Center (MSFC) with the Simplified Integrated Test. This test, conducted at the MSFC Core Module Integration Facility (CMIF), was the first time the four baseline air revitalization subsystems were integrated together. This paper details the results and lessons learned from the phase III SIT. Future plans for testing at the MSFC CMIF are also discussed.

Review of phase III trial data on IL-23 inhibitors tildrakizumab and guselkumab for psoriasis.

PubMed

Amin, M; Darji, K; No, D J; Wu, J J

2017-10-01

The development of monoclonal antibodies targeting IL-12 and IL-23 has enhanced the therapeutic options available for psoriasis patients. Recent research suggests that IL-23 alone plays a role in the pathogenesis of psoriasis. The objective was to review the phase III clinical trial data for the anti-IL-23 agents to evaluate the safety and efficacy profile of each agent. We reviewed the results of the phase III clinical trials for the anti-IL-23 agents tildrakizumab and guselkumab. The results of phase III trials on risankizumab have not yet been reported. By week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was >60% among the most efficacious dose of each agent. The percentage of patients achieving PASI 90 at week 16 was the primary endpoint for the phase III trials for guselkumab, which was above 70%. The safety profiles of the agents were comparable, with the most commonly reported adverse events of nasopharyngitis and upper respiratory tract infections. The anti-IL-23 agents demonstrated a rapid clinical improvement that is similar or superior to the improvement seen with currently marketed IL-17 inhibitors with a favourable short-term safety profile. The results of the phase III trials support the notion that IL-23 is a potential target in psoriasis treatment. © 2017 European Academy of Dermatology and Venereology.

Confirmation of model-based dose selection for a Japanese phase III study of rivaroxaban in non-valvular atrial fibrillation patients.

PubMed

Kaneko, Masato; Tanigawa, Takahiko; Hashizume, Kensei; Kajikawa, Mariko; Tajiri, Masahiro; Mueck, Wolfgang

2013-01-01

This study was designed to confirm the appropriateness of the dose setting for a Japanese phase III study of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF), which had been based on model simulation employing phase II study data. The previously developed mixed-effects pharmacokinetic/pharmacodynamic (PK-PD) model, which consisted of an oral one-compartment model parameterized in terms of clearance, volume and a first-order absorption rate, was rebuilt and optimized using the data for 597 subjects from the Japanese phase III study, J-ROCKET AF. A mixed-effects modeling technique in NONMEM was used to quantify both unexplained inter-individual variability and inter-occasion variability, which are random effect parameters. The final PK and PK-PD models were evaluated to identify influential covariates. The empirical Bayes estimates of AUC and C(max) from the final PK model were consistent with the simulated results from the Japanese phase II study. There was no clear relationship between individual estimated exposures and safety-related events, and the estimated exposure levels were consistent with the global phase III data. Therefore, it was concluded that the dose selected for the phase III study with Japanese NVAF patients by means of model simulation employing phase II study data had been appropriate from the PK-PD perspective.

Benzocaine polymorphism: pressure-temperature phase diagram involving forms II and III.

PubMed

Gana, Inès; Barrio, Maria; Do, Bernard; Tamarit, Josep-Lluís; Céolin, René; Rietveld, Ivo B

2013-11-18

Understanding the phase behavior of an active pharmaceutical ingredient in a drug formulation is required to avoid the occurrence of sudden phase changes resulting in decrease of bioavailability in a marketed product. Benzocaine is known to possess three crystalline polymorphs, but their stability hierarchy has so far not been determined. A topological method and direct calorimetric measurements under pressure have been used to construct the topological pressure-temperature diagram of the phase relationships between the solid phases II and III, the liquid, and the vapor phase. In the process, the transition temperature between solid phases III and II and its enthalpy change have been determined. Solid phase II, which has the highest melting point, is the more stable phase under ambient conditions in this phase diagram. Surprisingly, solid phase I has not been observed during the study, even though the scarce literature data on its thermal behavior appear to indicate that it might be the most stable one of the three solid phases. Copyright © 2013 Elsevier B.V. All rights reserved.

Studies on the Inhalation Toxicity of Dyes Present in Colored Smoke Munitions. Phase III, Studies: Four-Week Inhalation Exposures of Rats to Dye Aerosols.

DTIC Science & Technology

1984-09-10

0") AD STUDIES ON THE INHALATION TOXICITY CO• OF DYES PRESENT IN COLORED Ln SMOKE MUNIlIONS U FINAL REPORT FOR PHASE III STUDIES : SFOUR- ELK...3 RECIIEPIT’S CATA6.0G NUMBE.• 4. TITLE (and ,ubiltI.e) S. TYPE OF REPORT & PERIOD COygC r., Studies on the Inhalation Toxicity of Dyes Final: Phase...III Present in Colored Smoke Munitions. Final Report Fh for Phase 111 Studies : FoLr-Week Inhalation G. PERFORMING ORO. REPORT N,’,ER Exposures of Rats

PLCO Ovarian Phase III Validation Study — EDRN Public Portal

Cancer.gov

Our preliminary data indicate that the performance of CA 125 as a screening test for ovarian cancer can be improved upon by additional biomarkers. With completion of one additional validation step, we will be ready to test the performance of a consensus marker panel in a phase III validation study. Given the original aims of the PLCO trial, we believe that the PLCO represents an ideal longitudinal cohort offering specimens for phase III validation of ovarian cancer biomarkers.

Preparation of cerium halide solvate complexes

DOEpatents

Vasudevan, Kalyan V; Smith, Nickolaus A; Gordon, John C; McKigney, Edward A; Muenchaussen, Ross E

2013-08-06

Crystals of a solvated cerium(III) halide solvate complex resulted from a process of forming a paste of a cerium(III) halide in an ionic liquid, adding a solvent to the paste, removing any undissolved solid, and then cooling the liquid phase. Diffusing a solvent vapor into the liquid phase also resulted in crystals of a solvated cerium(III) halide complex.

Effect of amoxicillin/clavulanate on gastrointestinal motility in children.

PubMed

Gomez, Roberto; Fernandez, Sergio; Aspirot, Ann; Punati, Jaya; Skaggs, Beth; Mousa, Hayat; Di Lorenzo, Carlo

2012-06-01

The aim of the present study was to evaluate the effect of amoxicillin/clavulanate (A/C) on gastrointestinal motility. Twenty consecutive pediatric patients referred for antroduodenal manometry received 20 mg/kg of A/C into the small bowel lumen. In 10 patients (group A), A/C was given 1 hour after and in 10 (group B), 1 hour before ingestion of a meal. Characteristics of the migrating motor complex, including presence, frequency, amplitude, and propagation of duodenal phase III and phase I duration and phase II motility index (MI), were evaluated 30 minutes before and after A/C administration. There were no statistically significant differences in age and sex between the 2 groups. Manometry studies were considered normal in 8 patients in each group. In group A, 2 patients developed duodenal phase III after receiving A/C, and no significant difference was found in the MI before and after the drug administration. In group B, 9 patients developed duodenal phase III (P <0.05 vs group A). All phase III occurred within a few minutes from the medication administration. Most duodenal phase III contractions were preceded by an antral component during fasting but never after the medication was administered in either of the 2 groups (P<0.001 vs fasting). In group B, the duration of duodenal phase I was shorter after drug administration (P<0.05). There was no significant difference in duodenal phase II MI before and after A/C administration for the 2 study groups. In children, administration of A/C directly into the small bowel before a meal induces phase III-type contractions in the duodenum, with characteristics similar to those present in the fasting state. These data suggest the possible use of A/C as a prokinetic agent. Further studies are needed to clarify its specific mechanism of action and the group of patients most likely to benefit from its use.

Neutron imaging systems utilizing lithium-containing semiconductor crystals

DOEpatents

Stowe, Ashley C.; Burger, Arnold

2017-04-25

A neutron imaging system, including: a plurality of Li-III-VI.sub.2 semiconductor crystals arranged in an array, wherein III represents a Group III element and VI represents a Group VI element; and electronics operable for detecting and a charge in each of the plurality of crystals in the presence of neutrons and for imaging the neutrons. Each of the crystals is formed by: melting the Group III element; adding the Li to the melted Group III element at a rate that allows the Li and Group III element to react, thereby providing a single phase Li-III compound; and adding the Group VI element to the single phase Li-III compound and heating. Optionally, each of the crystals is also formed by doping with a Group IV element activator.

75 FR 30385 - Defense Transportation Regulation, Part IV

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-01

... extensions will be considered due to the timelines associated with funding and programming future Phase III... extensions will be considered due to the timelines associated with funding and programming future Phase III...

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...

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...

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…

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...

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…

Owen Bradford Butler: Corporate America's Evangelist for the Educationally Disadvantaged.

ERIC Educational Resources Information Center

Matthews, Frank L.

1989-01-01

The retired Procter & Gamble corporate leader and member of the Committee for Economic Development (CED) discusses the crisis in the American education system and his efforts for reform. Subjects covered include implications for business and the nation, business and federal reform initiatives, and the mandate for community-wide involvement.…

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.

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.

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.

Individualized Inservice Teacher Education (Project In-Step). Evaluation Report. Phase III.

ERIC Educational Resources Information Center

Thurber, John C.

This is a report on the third phase of Project IN-STEP, which was intended to develop a viable model for individualized, multi-media in-service teacher education programs. (Phase I and II are reported in ED 033 905, and ED 042 709). The rationale for Phase III was to see if the model could be successfully transferred to an area other than teaching…

Rotator Phases of n-Heptane under High Pressure: Raman Scattering and X-ray Diffraction Studies

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

C Ma; Q Zhou; F Li

2011-12-31

We performed high-pressure Raman scattering and angle-dispersive synchrotron X-ray diffraction measurements on n-heptane at room temperature. It has been found that n-heptane undergoes a liquid to rotator phase III (R{sub III}) transition at 1.2 GPa and then transforms into another rotator phase R{sub IV} at about 3 GPa. As the pressure reaches 7.5 GPa, a transition from an orientationally disordered R{sub IV} phase to an ordered crystalline state starts and is completed around 14.5 GPa. Our results clearly present the high-pressure phase transition sequence (liquid-R{sub III}-R{sub IV}-crystal) of n-heptane, similar to that of normal alkanes.

Phase transformation in the alumina-titania system during flash sintering experiments

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

Jha, S. K.; Lebrun, J. M.; Raj, R.

2016-02-01

We show that phase transformation in the alumina–titania system, which produces aluminum-titanate, follows an unusual trajectory during flash sintering. The experiments begin with mixed powders of alumina–titania and end in dense microstructures that are transformed into aluminum-titanate. The sintering and the phase transformation are separated in time, with the sintering occurs during Stage II, and phase transformation during Stage III of the flash sintering experiment. Stage III is the steady-state condition of flash activated state that is established under current control, while Stage II is the period of transition from voltage to current control. The extent of phase transformation increasesmore » with the current density and the hold time in Stage III.« less

Imprinted magnetic graphene oxide for the mini-solid phase extraction of Eu (III) from coal mine area

NASA Astrophysics Data System (ADS)

Patra, Santanu; Roy, Ekta; Madhuri, Rashmi; Sharma, Prashant K.

2017-05-01

The present work represents the preparation of imprinted magnetic reduced graphene oxide and applied it for the selective removal of Eu (III) from local coal mines area. A simple solid phase extraction method was used for this purpose. The material shows a very high adsorption as well as removal efficiency towards Eu (III), which suggest that the material have potential to be used in future for their real time applications in removal of Eu (III) from complex matrices.

Job Aids: Descriptive Authoring Flowcharts for Phase III--DEVELOP of the Instructional Systems Development Model.

ERIC Educational Resources Information Center

Schulz, Russel E.; Farrell, Jean R.

This resource guide for the use of job aids ("how-to-do-it" guidance) for activities identified in the third phase of the Instructional Systems Development Model (ISD) contains an introduction to the use of job aids, as well as descriptive authoring flowcharts for Blocks III.1 through III.5. The introduction includes definitions;…

Development and testing of responder : phase III.

DOT National Transportation Integrated Search

2017-06-28

This report documents the research project Development and Testing of Responder Phase III. Under previous research, a Responder system has been developed to provide relevant and timely information to first responders, allow responders to provid...

Phase III Early Restoration Meeting | NOAA Gulf Spill Restoration

Science.gov Websites

Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News Publications Press Releases Story programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

Phase III Early Restoration Meeting - Corpus Christi, TX | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

Phase III Early Restoration Meeting - Pensacola, FL (rescheduled) | NOAA

Science.gov Websites

Restoration Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

Motivation and participation in a phase III cardiac rehabilitation programme: an application of the health action process approach.

PubMed

Dohnke, Birte; Nowossadeck, Enno; Müller-Fahrnow, Werner

2010-10-01

This longitudinal study extends the previous research on low participation rates and high dropout rates in phase III cardiac rehabilitation (CR) exercise programmes. It examines the correlates of motivation and participation 6 months after inpatient phase II CR (T1) and the predictors of dropout 6 months later (T2) using the health action process approach (HAPA). Risk perception, outcome expectancies, self-efficacy, intention (at T1), and participation (at T1 and T2) in relation to phase III CR programmes was assessed in 456 patients. Based on intention and participation at T1, patients were classified as nonintenders (56%), intenders (13%), or actors (31%). Group differences were confirmed in outcome expectancies and self-efficacy. By T2, 21% of T1 actors had dropped out. Dropouts and maintainers differed in intention and self-efficacy (at T1). Results are in line with the HAPA and suggest a perspective for tailoring motivational counselling to improve participation in phase III CR programmes.

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

Wu, T.; Griffin, A. M.; Gorski, C. A.

Dissimilatory microbial reduction of solid-phase Fe(III)-oxides and Fe(III)-bearing phyllosilicates (Fe(III)-phyllosilicates) is an important process in anoxic soils, sediments, and subsurface materials. Although various studies have documented the relative extent of microbial reduction of single-phase Fe(III)-oxides and Fe(III)-phyllosilicates, detailed information is not available on interaction between these two processes in situations where both phases are available for microbial reduction. The goal of this research was to use the model dissimilatory iron-reducing bacterium (DIRB) Geobacter sulfurreducens to study Fe(III)-oxide vs. Fe(III)-phyllosilicate reduction in a range of subsurface materials and Fe(III)-oxide stripped versions of the materials. Low temperature (12K) Mossbauer spectroscopy was usedmore » to infer changes in the relative abundances of Fe(III)-oxide, Fe(III)-phyllosilicate, and phyllosilicate-associated Fe(II) (Fe(II)-phyllosilicate). A Fe partitioning model was employed to analyze the fate of Fe(II) and assess the potential for abiotic Fe(II)-catalyzed reduction of Fe(III)-phyllosilicates. The results showed that in most cases Fe(III)- oxide utilization dominated (70-100 %) bulk Fe(III) reduction activity, and that electron transfer from oxide-derived Fe(II) played only a minor role (ca. 10-20 %) in Fe partitioning. In addition, the extent of Fe(III)-oxide reduction was positively correlated to surface area-normalized cation exchange capacity and the phyllosilicate-Fe(III)/total Fe(III) ratio, which suggests that the phyllosilicates in the natural sediments promoted Fe(III)-oxide reduction by binding of oxide-derived Fe(II), thereby enhancing Fe(III)-oxide reduction by reducing or delaying the inhibitory effect that Fe(II) accumulation on oxide and DIRB cell surfaces has on Fe(III)-oxide reduction. In general our results suggest that although Fe(III)-oxide reduction is likely to dominate bulk Fe(III) reduction in most subsurface sediments, Fe(II) binding by phyllosilicates is likely to play a key role in controlling the long-term kinetics of Fe(III)-oxide reduction.« less

Installation Restoration Program. Phase II--Confirmation/Quantification. Stage 1.

DTIC Science & Technology

1985-03-01

four phases. Phase I, Initial Assessment/ Records Search, is designed to identify possible hazardous waste contami- nated sites and potential...7 71 -. - - IL’ -, 1% 33 AihlIII Is 33 n~iL t iiC UII! ii CL C LU 1-3, Phase II, Confirmation and Quantification, is designed to confirm the...additional monitoring data upon which design of mitigative actions are based. In Phase III, Technology Base Development, appropriate technology is selected and

Electronic monitoring and voice prompts improve hand hygiene and decrease nosocomial infections in an intermediate care unit.

PubMed

Swoboda, Sandra M; Earsing, Karen; Strauss, Kevin; Lane, Stephen; Lipsett, Pamela A

2004-02-01

To determine whether electronic monitoring of hand hygiene and voice prompts can improve hand hygiene and decrease nosocomial infection rates in a surgical intermediate care unit. Three-phase quasi-experimental design. Phase I was electronic monitoring and direct observation; phase II was electronic monitoring and computerized voice prompts for failure to perform hand hygiene on room exit; and phase III was electronic monitoring only. Nine-room, 14-bed intermediate care unit in a university, tertiary-care institution. All patient rooms, utility room, and staff lavatory were monitored electronically. All healthcare personnel including physicians, nurses, nursing support personnel, ancillary staff, all visitors and family members, and any other personnel interacting with patients on the intermediate care unit. All patients with an intermediate care unit length of stay >48 hrs were followed for nosocomial infection. Electronic monitoring during all phases, computerized voice prompts during phase II only. We evaluated a total of 283,488 electronically monitored entries into a patient room with 251,526 exits for 420 days (10,080 hrs and 3,549 patient days). Compared with phase I, hand hygiene compliance in patient rooms improved 37% during phase II (odds ratio, 1.38; 95% confidence interval, 1.04-1.83) and 41% in phase III (odds ratio, 1.41; 95% confidence interval, 1.07-1.84). When adjusting for patient admissions during each phase, point estimates of nosocomial infections decreased by 22% during phase II and 48% during phase III; when adjusting for patient days, the number of infections decreased by 10% during phase II and 40% during phase III. Although the overall rate of nosocomial infections significantly decreased when combining phases II and III, the association between nosocomial infection and individual phase was not significant. Electronic monitoring provided effective ongoing feedback about hand hygiene compliance. During both the voice prompt phase and post-intervention phase, hand hygiene compliance and nosocomial infection rates improved suggesting that ongoing monitoring and feedback had both a short-term and, perhaps, a longer-term effect.

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.

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

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.

Raman spectroscopic study of calcite III to aragonite transformation under high pressure and high temperature

NASA Astrophysics Data System (ADS)

Liu, Chuanjiang; Zheng, Haifei; Wang, Duojun

2017-10-01

In our study, a series of Raman experiments on the phase transition of calcite at high pressure and high temperature were investigated using a hydrothermal diamond anvil cell and Raman spectroscopy technique. It was found that calcite I transformed to calcite II and calcite III at pressures of 1.62 and 2.12 GPa and room temperature. With increasing temperature, the phase transition of calcite III to aragonite occurred. Aragonite was retained upon slowly cooling of the system, indicating that the transition of calcite III to aragonite was irreversible. Based on the available data, the phase boundary between calcite III and aragonite was determined by the following relation: P(GPa) = 0.013 × T(°C) + 1.22 (100°C ≤ T ≤ 170°C). It showed that the transition pressure linearly rose with increasing temperature. A better understanding of the stability of calcite III and aragonite is of great importance to further explore the thermodynamic behavior of carbonates and carbon cycling in the mantle.

Trends in heteroepitaxy of III-Vs on silicon for photonic and photovoltaic applications

NASA Astrophysics Data System (ADS)

Lourdudoss, Sebastian; Junesand, Carl; Kataria, Himanshu; Metaferia, Wondwosen; Omanakuttan, Giriprasanth; Sun, Yan-Ting; Wang, Zhechao; Olsson, Fredrik

2017-02-01

We present and compare the existing methods of heteroepitaxy of III-Vs on silicon and their trends. We focus on the epitaxial lateral overgrowth (ELOG) method as a means of achieving good quality III-Vs on silicon. Initially conducted primarily by near-equilibrium epitaxial methods such as liquid phase epitaxy and hydride vapour phase epitaxy, nowadays ELOG is being carried out even by non-equilibrium methods such as metal organic vapour phase epitaxy. In the ELOG method, the intermediate defective seed and the mask layers still exist between the laterally grown purer III-V layer and silicon. In a modified ELOG method called corrugated epitaxial lateral overgrowth (CELOG) method, it is possible to obtain direct interface between the III-V layer and silicon. In this presentation we exemplify some recent results obtained by these techniques. We assess the potentials of these methods along with the other existing methods for realizing truly monolithic photonic integration on silicon and III-V/Si heterojunction solar cells.

Effect of 60 degrees head-down tilt on peripheral gas mixing in the human lung.

PubMed

Olfert, I Mark; Prisk, G Kim

2004-09-01

The phase III slope of sulfur hexafluoride (SF6) in a single-breath washout (SBW) is greater than that of helium (He) under normal gravity (i.e., 1G), thus resulting in a positive SF6-He slope difference. In microgravity (microG), SF6-He slope difference is smaller because of a greater fall in the phase III slope of SF6 than He. We sought to determine whether increasing thoracic fluid volume using 60 degrees head-down tilt (HDT) in 1G would produce a similar effect to microG on phase III slopes of SF6 and He. Single-breath vital capacity (SBW) and multiple-breath washout (MBW) tests were performed before, during, and 60 min after 1 h of HDT. Compared with baseline (SF6 1.050 +/- 0.182%/l, He 0.670 +/- 0.172%/l), the SBW phase III slopes for both SF6 and He tended to decrease during HDT, reaching nadir at 30 min (SF6 0.609 +/- 0.211%/l, He 0.248 +/- 0.138%/l; P = 0.08 and P = 0.06, respectively). In contrast to microG, the magnitude of the phase III slope decrease was similar for both SF6 and He; therefore, no change in SF6-He slope difference was observed. MBW analysis revealed a decrease in normalized phase III slopes at all time points during HDT, for both SF6 (P < 0.01) and He (P < 0.01). This decrease was due to changes in the acinar, and not the conductive, component of the normalized phase III slope. These findings support the notion that changes in thoracic fluid volume alter ventilation distribution in the lung periphery but also demonstrate that the effect during HDT does not wholly mimic that observed in microG.

Phase III Early Restoration Meeting - Lake Charles, LA | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News early restoration planning for Phase III and future early restoration plans. Open House: 5:30pm Public

Extraction equilibrium of indium(III) from nitric acid solutions by di(2-ethylhexyl)phosphoric acid dissolved in kerosene.

PubMed

Tsai, Hung-Sheng; Tsai, Teh-Hua

2012-01-04

The extraction equilibrium of indium(III) from a nitric acid solution using di(2-ethylhexyl) phosphoric acid (D2EHPA) as an acidic extractant of organophosphorus compounds dissolved in kerosene was studied. By graphical and numerical analysis, the compositions of indium-D2EHPA complexes in organic phase and stoichiometry of the extraction reaction were examined. Nitric acid solutions with various indium concentrations at 25 °C were used to obtain the equilibrium constant of InR₃ in the organic phase. The experimental results showed that the extraction distribution ratios of indium(III) between the organic phase and the aqueous solution increased when either the pH value of the aqueous solution and/or the concentration of the organic phase extractant increased. Finally, the recovery efficiency of indium(III) in nitric acid was measured.

Influence of Al(III) on biofilm and its extracellular polymeric substances in sequencing batch biofilm reactors.

PubMed

Hu, Xuewei; Yang, Lei; Lai, Xinke; Yao, Qi; Chen, Kai

2017-10-03

This paper presented the influence of Al(III) on biodegradability, micromorphology, composition and functional groups characteristics of the biofilm extracellular polymeric substances (EPS) during different growth phases. The sequencing batch biofilm reactors were developed to cultivate biofilms under different Al(III) dosages. The results elucidated that Al(III) affected biofilm development adversely at the beginning of biofilm growth, but promoted the biofilm mass and improved the biofilm activity with the growth of the biofilm. The micromorphological observation indicated that Al(III) led to a reduction of the filaments and promotion of the EPS secretion in growth phases of the biofilm, also Al(III) could promote microorganisms to form larger colonies for mature biofilm. Then, the analysis of EPS contents and components suggested that Al(III) could increase the protein (PN) of tightly bound EPS (TB-EPS) which alleviated the metal toxicity inhibition on the biofilm during the initial phases of biofilm growth. The biofilm could gradually adapt to the inhibition caused by Al(III) at the biofilm maturation moment. Finally, through the Fourier transform infrared spectroscopy, it was found that Al(III) was beneficial for the proliferation and secretion of TB-EPS functional groups, especially the functional groups of protein and polysaccharides.

40 CFR 63.163 - Standards: Pumps in light liquid service.

Code of Federal Regulations, 2013 CFR

2013-07-01

... later than 1 year after the compliance date; and (C) Phase III, beginning no later than 21/2 years after... requirements; and (B) Beginning no later than 1 year after initial start-up, comply with the Phase III... parts per million or greater. (ii) For Phase II, an instrument reading of 5,000 parts per million or...

40 CFR 63.163 - Standards: Pumps in light liquid service.

Code of Federal Regulations, 2012 CFR

2012-07-01

... later than 1 year after the compliance date; and (C) Phase III, beginning no later than 21/2 years after... requirements; and (B) Beginning no later than 1 year after initial start-up, comply with the Phase III... parts per million or greater. (ii) For Phase II, an instrument reading of 5,000 parts per million or...

40 CFR 63.163 - Standards: Pumps in light liquid service.

Code of Federal Regulations, 2014 CFR

2014-07-01

... later than 1 year after the compliance date; and (C) Phase III, beginning no later than 21/2 years after... requirements; and (B) Beginning no later than 1 year after initial start-up, comply with the Phase III... parts per million or greater. (ii) For Phase II, an instrument reading of 5,000 parts per million or...

Phase II and III Clinical Studies of Diphtheria-Tetanus-Acellular Pertussis Vaccine Containing Inactivated Polio Vaccine Derived from Sabin Strains (DTaP-sIPV).

PubMed

Okada, Kenji; Miyazaki, Chiaki; Kino, Yoichiro; Ozaki, Takao; Hirose, Mizuo; Ueda, Kohji

2013-07-15

Phase II and III clinical studies were conducted to evaluate immunogenicity and safety of a novel DTaP-IPV vaccine consisting of Sabin inactivated poliovirus vaccine (sIPV) and diphtheria-tetanus-acellular pertussis vaccine (DTaP). A Phase II study was conducted in 104 healthy infants using Formulation H of the DTaP-sIPV vaccine containing high-dose sIPV (3, 100, and 100 D-antigen units for types 1, 2, and 3, respectively), and Formulations M and L, containing half and one-fourth of the sIPV in Formulation H, respectively. Each formulation was administered 3 times for primary immunization and once for booster immunization. A Phase III study was conducted in 342 healthy infants who received either Formulation M + oral polio vaccine (OPV) placebo or DTaP + OPV. The OPV or OPV placebo was orally administered twice between primary and booster immunizations. Formulation M was selected as the optimum dose. In the Phase III study, the seropositive rate was 100% for all Sabin strains after primary immunization, and the neutralizing antibody titer after booster immunization was higher than in the control group (DTaP + OPV). All adverse reactions were clinically acceptable. DTaP-sIPV was shown to be a safe and immunogenic vaccine. JapicCTI-121902 for Phase II study, JapicCTI-101075 for Phase III study (http://www.clinicaltrials.jp/user/cte_main.jsp).

Structures and phase transitions in a new ferroelectric -- pyridinium chlorochromate -- studied by X-ray diffraction, DSC and dielectric methods.

PubMed

Małuszyńska, Hanna; Czarnecki, Piotr; Czarnecka, Anna; Pająk, Zdzisław

2012-04-01

Pyridinium chlorochromate, [C(5)H(5)NH](+)[ClCrO(3)](-) (hereafter referred to as PyClCrO(3)), was studied by X-ray diffraction, differential scanning calorimetry (DSC) and dielectric methods. Studies reveal three reversible phase transitions at 346, 316 and 170 K with the following phase sequence: R ̅3m (I) → R3m (II) → Cm (III) → Cc (IV), c' = 2c. PyClCrO(3) is the first pyridinium salt in which all four phases have been successfully characterized by a single-crystal X-ray diffraction method. Structural results together with dielectric and calorimetric studies allow the classification of the two intermediate phases (II) and (III) as ferroelectric with the Curie point at 346 K, and the lowest phase (IV) as most probably ferroelectric. The ferroelectric hysteresis loop was observed only in phase (III). The high ionic conductivity hindered its observation in phase (II).

Effect of weak magnetic field on arsenate and arsenite removal from water by zerovalent iron: an XAFS investigation.

PubMed

Sun, Yuankui; Guan, Xiaohong; Wang, Jianmin; Meng, Xiaoguang; Xu, Chunhua; Zhou, Gongming

2014-06-17

In this study, a weak magnetic field (WMF), superimposed with a permanent magnet, was utilized to improve ZVI corrosion and thereby enhance As(V)/As(III) removal by ZVI at pHini 3.0-9.0. The experiment with real arsenic-bearing groundwater revealed that WMF could greatly improve arsenic removal by ZVI even in the presence of various cations and anions. The WMF-induced improvement in As(V)/As(III) removal by ZVI should be primarily associated with accelerated ZVI corrosion, as evidenced by the pH variation, Fe(2+) release, and the formation of corrosion products as characterized with X-ray absorption fine structure spectroscopy. The arsenic species analysis in solution/solid phases at pHini 3.0 revealed that As(III) oxidation to As(V) in aqueous phase preceded its subsequent sequestration by the newly formed iron (hydr)oxides. However, both As(V) adsorption following As(III) oxidation to As(V) in solution and As(III) adsorption preceding its conversion to As(V) in solid phase were observed at pHini 5.0-9.0. The application of WMF accelerated the transformation of As(III) to As(V) in both aqueous and solid phases at pHini 5.0-9.0 and enhanced the oxidation of As(III) to As(V) in solution at pHini 3.0.

The Systems Approach to Functional Job Analysis. Task Analysis of the Physician's Assistant: Volume II--Curriculum and Phase I Basic Core Courses and Volume III--Phases II and III--Clinical Clerkships and Assignments.

ERIC Educational Resources Information Center

Wake Forest Univ., Winston Salem, NC. Bowman Gray School of Medicine.

This publication contains a curriculum developed through functional job analyses for a 24-month physician's assistant training program. Phase 1 of the 3-phase program is a 6-month basic course program in clinical and bioscience principles and is required of all students regardless of their specialty interest. Phase 2 is a 6 to 10 month period of…

Joint probability of statistical success of multiple phase III trials.

PubMed

Zhang, Jianliang; Zhang, Jenny J

2013-01-01

In drug development, after completion of phase II proof-of-concept trials, the sponsor needs to make a go/no-go decision to start expensive phase III trials. The probability of statistical success (PoSS) of the phase III trials based on data from earlier studies is an important factor in that decision-making process. Instead of statistical power, the predictive power of a phase III trial, which takes into account the uncertainty in the estimation of treatment effect from earlier studies, has been proposed to evaluate the PoSS of a single trial. However, regulatory authorities generally require statistical significance in two (or more) trials for marketing licensure. We show that the predictive statistics of two future trials are statistically correlated through use of the common observed data from earlier studies. Thus, the joint predictive power should not be evaluated as a simplistic product of the predictive powers of the individual trials. We develop the relevant formulae for the appropriate evaluation of the joint predictive power and provide numerical examples. Our methodology is further extended to the more complex phase III development scenario comprising more than two (K > 2) trials, that is, the evaluation of the PoSS of at least k₀ (k₀≤ K) trials from a program of K total trials. Copyright © 2013 John Wiley & Sons, Ltd.

Chattanooga SmartBus Project : phase III evaluation report

DOT National Transportation Integrated Search

2009-12-01

This report presents the results of Phase III of the national evaluation of the Chattanooga Area Regional Transportation Authoritys (CARTA) SmartBus Project. The SmartBus Project is a comprehensive transit ITS program for the city of Chattanooga, ...

Phase III Early Restoration Meeting - Galveston, TX | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

Phase III Early Restoration Meeting - Port Arthur, TX | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

Phase III Early Restoration Meeting - Panama City, FL | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

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…

Austin, Texas: An Educator/Business Collaboration in Support of Teacher Compensation Reform. Teacher Compensation and Teacher Quality: Policy Brief

ERIC Educational Resources Information Center

Committee for Economic Development, 2013

2013-01-01

In its 2009 report "Teacher Compensation and Teacher Quality," the Committee for Economic Development urged business leaders to be active participants in school district deliberations about teacher compensation policies. The Committee for Economic Development (CED) noted that "business leaders can make the case to the public that…

Hiring and Higher Education: Business Executives Talk about the Costs and Benefits of College

ERIC Educational Resources Information Center

Farkas, Steve

2011-01-01

The Committee for Economic Development (CED), in collaboration with Public Agenda, launched this qualitative research effort to explore the attitudes of business leaders toward higher education. The goal is to understand the starting point of business executives: What are their views on the purposes, importance, strengths and weaknesses of the…

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…

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...

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,…

North Carolina "Sealed Corridor" Phase I, II, and III Assessment

DOT National Transportation Integrated Search

2009-10-01

The Federal Railroad Administration (FRA) tasked the John A. Volpe National Transportation Systems Center to document the further success of the North Carolina DOT "Sealed Corridor" project through Phases I, II, and III. The Sealed Corridor is the se...

Phase III gross solids removal devices pilot study, 2002-2005.

DOT National Transportation Integrated Search

2005-12-01

The objective of the Phase III Gross Solids Removal Devices (GSRDs) Pilot study was to : evaluate the performance of non-proprietary devices that can capture gross solids and that can be : incorporated into existing highway drainage systems or implem...

Improvement of conspicuity of trailblazing signs, Phase III : evaluation of fluorescent colors.

DOT National Transportation Integrated Search

2001-01-01

This report represents a Phase III effort to design and evaluate a new sign design for incident route trailblazing. The colors evaluated were fluorescent coral, fluorescent purple, fluorescent yellow-green, and non-fluorescent purple. The results ind...

Clinical Investigation Program Report, RCS MED-300 (R-1).

DTIC Science & Technology

1985-10-31

Patients with Locally Advanced Gastric Adenocarcinoma, Phase III. (C) 63 1982 SWOG 8006, Preoperative Reductive Chemotherapy for Stage III or IV Operable...Mesothelioma Localized to One Hemithorax, Phase III. (C) 81 1984 SWOG 8104, Treatment of Advanced Seminoma (Stage cII (4) + clII) with Combined...of Locally or Regionally Recurrent but Surgically Resectable Breast Cancer. (C) 99 1984 SWOG 8300, Treatment of Limited Non-Small Cell Lung Cancer

Growth-differentiation factor-15, endoglin and N-terminal pro-brain natriuretic peptide induction in athletes participating in an ultramarathon foot race.

PubMed

Tchou, Isabelle; Margeli, Alexandra; Tsironi, Maria; Skenderi, Katerina; Barnet, Marc; Kanaka-Gantenbein, Christina; Papassotiriou, Ioannis; Beris, Photis

2009-09-01

We investigated the actions of growth-differentiation factor (GDF)-15, endoglin and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in 15 male athletes who participated in the ultradistance foot race of the 246 km 'Sparthathlon'. Measurements were performed before (phase I), at the end of the race (phase II) and 48 h post-race (phase III). GDF-15 and endoglin serum concentrations were determined with enzyme-linked immunosorbent assay and NT-pro-BNP plasma levels by electrochemiluminescence. GDF-15 levels were increased from phase I (563.9 +/- 57.1 pg ml(-1)) to phase II (2311.1 +/- 462.3 pg ml(-1)) and decreased at phase III (862.0 +/- 158.0 pg ml(-1)) (p < 0.0002). NT-pro-BNP levels followed a similar pattern to that of GDF-15 from 38.1 +/- 4.8 pg ml(-1) at phase I to 1280.6 +/- 259.0 pg ml(-1) at phase II and 89.8 +/- 13.6 pg ml(-1) at phase III (p < 0.0001) and at the same time points, endoglin levels were 4.7 +/- 0.2 ng ml(-1) at phase I, 5.8 +/- 0.2 ng ml(-1) at phase II and 4.3 +/- 0.2 ng ml(-1) at phase III (p < 0.002). These findings indicate that circulating GDF-15, endoglin and NT-pro-BNP levels reflect a transient endothelial dysfunction in these athletes who participated in a foot race consisting of continuous, prolonged and brisk exercise.

Development of an EORTC quality of life phase III module measuring cancer-related fatigue (EORTC QLQ-FA13).

PubMed

Weis, Joachim; Arraras, Juan Ignacio; Conroy, Thierry; Efficace, Fabio; Fleissner, Claudia; Görög, Attila; Hammerlid, Eva; Holzner, Bernhard; Jones, Louise; Lanceley, Anne; Singer, Susanne; Wirtz, Markus; Flechtner, Henning; Bottomley, Andrew

2013-05-01

European Organisation for Research and Treatment of Cancer (EORTC) has developed a new multidimensional instrument measuring cancer-related fatigue that can be used in conjunction with the quality of life core questionnaire, EORTC QLQ-C30. The paper focuses on the development of the phase III module, collaborating with seven European countries, including a patient sample of 318 patients. The methodology followed the EORTC guidelines for developing phase III modules. Patients were assessed by questionnaires (EORTC QLQ-C30 with the EORTC Fatigue Module FA15) followed by an interview, asking for their opinions on the difficulty in understanding, on annoyance and on intrusiveness. The phase II FA15 was revised on the basis of qualitative analyses (comments of the patients), quantitative results (descriptive statistics) as well as the multi-item response theory analyses. The three dimensions (physical, emotional and cognitive) of the scale could be confirmed. As a result, EORTC QLQ-FA13 is now available as a valid phase III module measuring cancer-related fatigue in clinical trials and will be psychometrically improved in the upcoming phase IV. Copyright © 2012 John Wiley & Sons, Ltd.

40 CFR 86.109-94 - Exhaust gas sampling system; Otto-cycle vehicles not requiring particulate emission measurements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... detection for the HPLC analyzer. Sampling systems for all phases shall be identical. (iii) The methanol and... detection for the HPLC analyzer. Sampling systems for all phases shall be identical. (iii) The methanol and...

40 CFR 86.109-94 - Exhaust gas sampling system; Otto-cycle vehicles not requiring particulate emission measurements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... detection for the HPLC analyzer. Sampling systems for all phases shall be identical. (iii) The methanol and... detection for the HPLC analyzer. Sampling systems for all phases shall be identical. (iii) The methanol and...

40 CFR 86.109-94 - Exhaust gas sampling system; Otto-cycle vehicles not requiring particulate emission measurements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... detection for the HPLC analyzer. Sampling systems for all phases shall be identical. (iii) The methanol and... detection for the HPLC analyzer. Sampling systems for all phases shall be identical. (iii) The methanol and...

Benzyl and Methyl Fatty Hydroxamic Acids Based on Palm Kernel Oil as Chelating Agent for Liquid-Liquid Iron(III) Extraction

PubMed Central

Haron, Md Jelas; Jahangirian, Hossein; Silong, Sidik; Yusof, Nor Azah; Kassim, Anuar; Rafiee-Moghaddam, Roshanak; Mahdavi, Behnam; Peyda, Mazyar; Abdollahi, Yadollah; Amin, Jamileh

2012-01-01

Liquid-liquid iron(III) extraction was investigated using benzyl fatty hydroxamic acids (BFHAs) and methyl fatty hydroxamic acids (MFHAs) as chelating agents through the formation of iron(III) methyl fatty hydroxamate (Fe-MFHs) or iron(III) benzyl fatty hydroxamate (Fe-BFHs) in the organic phase. The results obtained under optimized conditions, showed that the chelating agents in hexane extract iron(III) at pH 1.9 were realized effectively with a high percentage of extraction (97.2% and 98.1% for MFHAs and BFHAs, respectively). The presence of a large amount of Mg(II), Ni(II), Al(III), Mn(II) and Co(II) ions did affect the iron(III) extraction. Finally stripping studies for recovering iron(III) from organic phase (Fe-MFHs or Fe-BFHs dissolved in hexane) were carried out at various concentrations of HCl, HNO3 and H2SO4. The results showed that the desired acid for recovery of iron(III) was 5 M HCl and quantitative recovery of iron(III) was achieved from Fe(III)-MFHs and Fe(III)-BFHs solutions in hexane containing 5 mg/L of Fe(III). PMID:22408444

Secukinumab in the Treatment of Psoriasis and Psoriatic Arthritis: A Review of the Literature.

PubMed

Abrouk, M; Gandy, J; Nakamura, M; Lee, K; Brodsky, M; Singh, R; Zhu, H; Farahnik, B; Bhutani, T; Koo, J

2017-07-01

While there are several commercially available treatment options for psoriasis and psoriatic arthritis, there remains a large number of individuals who are refractory to current modalities. In the recent past, there has been increasing evidence that interleukin (IL)-17 plays a vital role in the pathophysiology of psoriasis. Preclinical, phase II, and phase III studies of secukinumab (Cosentyx®) targeting IL-17 and its receptor have thus far proved to be promising. We reviewed the results of phase II and phase III clinical trials for secukinumab in the treatment of psoriasis and psoriatic arthritis. Only published studies were considered in the present review. We also performed an English language literature search from January 2003 to September 2015 using PubMed with any of the following key words: (secukinumab OR AIN457) AND (psoriasis OR psoriatic arthritis). In our review of the literature, seven phase III and five phase II clinical trials, as well as open-label extension studies with unpublished findings were found. Results from phase III clinical trials indicated secukinumab to be efficacious and safe for the treatment of psoriasis and psoriatic arthritis according to Psoriasis Area and Severity Index (PASI) and American College of Rheumatology (ACR) scores. The safety profile of this agent was similar across all studies, with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, headache, and injection site reaction. Secukinumab demonstrates rapid and robust clinical improvement accompanied by a favorable short- term safety profile. The results of the phase III trials continue to reinforce the theory that the IL-17 pathway is an essential target in psoriasis and psoriatic arthritis treatment. Additional extension studies of lower level evidence are needed to further understand the safety profile of the drug.

Remedial Action Report for Operable Units 6-05 and 10-04, Phase III

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

R. P. Wells

2007-08-15

This Phase III remedial action report addresses the remediation of lead-contaminated soils found at the Security Training Facility STF-02 Gun Range at the Idaho National Laboratory Site. Phase I, consisting of developing and implementing institutional controls at Operble Unit 10-04 sites and developing and implementing Idaho National Laboratory Site-wide plans for both institutional controls and ecological monitoring, was addressed in a previous report. Phase II will remediate sites contaminated with trinitrotoluene and Royal Demolition Explosive. Phase IV will remediate hazards from unexploded ordnance.

New Round of Studies Begin in Phase 0/I/II Cancer Prevention Clinical Trials Program | Division of Cancer Prevention

Cancer.gov

The NCI Division of Cancer Prevention’s Phase 0/I/II Cancer Prevention Clinical Trials Program, also known as the Consortia for Early Phase Prevention Trials, is beginning a new round of studies in the effort toward systematic early clinical development of promising preventive agents for people at increased risk of developing cancer. |

Student Perceptions of Elementary School Climates in the Louisiana School Effectiveness Study: A Comparison of Phase III and Phase IV.

ERIC Educational Resources Information Center

Roberts, Sharon Pol; Heroman, Deborah S.

A 5-year study examined third-graders' perceptions of school climate in 16 Louisiana schools. Part of the Louisiana School Effectiveness Study (LSES), Phase III and IV examined student perceptions in 1984-85 and 1989-90, respectively, and also gathered demographic data and multiple measures of student outcomes through student surveys and classroom…

Unbiased estimation in seamless phase II/III trials with unequal treatment effect variances and hypothesis-driven selection rules.

PubMed

Robertson, David S; Prevost, A Toby; Bowden, Jack

2016-09-30

Seamless phase II/III clinical trials offer an efficient way to select an experimental treatment and perform confirmatory analysis within a single trial. However, combining the data from both stages in the final analysis can induce bias into the estimates of treatment effects. Methods for bias adjustment developed thus far have made restrictive assumptions about the design and selection rules followed. In order to address these shortcomings, we apply recent methodological advances to derive the uniformly minimum variance conditionally unbiased estimator for two-stage seamless phase II/III trials. Our framework allows for the precision of the treatment arm estimates to take arbitrary values, can be utilised for all treatments that are taken forward to phase III and is applicable when the decision to select or drop treatment arms is driven by a multiplicity-adjusted hypothesis testing procedure. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

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...

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…

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…

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.

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

Practice versus knowledge when it comes to pressure ulcer prevention.

PubMed

Provo, B; Piacentine, L; Dean-Baar, S

1997-09-01

This study was completed to determine the current knowledge and documentation patterns of nursing staff in the prevention of pressure ulcers and to identify the prevalence of pressure ulcers. This pre-post intervention study was carried out in three phases. In phase 1, 67 nursing staff members completed a modified version of Bostrom's Patient Skin Integrity Survey. A Braden Scale score, the presence of actual skin breakdown, and the presence of nursing documentation were collected for each patient (n = 43). Phase II consisted of a 20-minute educational session to all staff. In phase III, 51 nursing staff completed a second questionnaire similar to that completed in phase I. Patient data (n = 49) were again collected using the same procedure as phase I. Twenty-seven staff members completed questionnaires in both phase I and phase III of the study. No statistically significant differences were found in the knowledge of the staff before or after the educational session. The number of patients with a documented plan of care showed a statistically significant difference from phase I to phase III. The number of patients with pressure ulcers or at risk for pressure ulcer development (determined by a Braden Scale score of 16 or less) did not differ statistically from phase I to phase III. Knowledge about pressure ulcers in this sample of staff nurses was for the most part current and consistent with the recommendations in the Agency for Health Care Policy and Research guideline. Documentation of pressure ulcer prevention and treatment improved after the educational session. Although a significant change was noted in documentation, it is unclear whether it reflected an actual change in practice.

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