Transient receptor potential melastatin 8 (TRPM8) channels are involved in body temperature regulation

PubMed Central

2012-01-01

Background Transient receptor potential cation channel subfamily M member 8 (TRPM8) is activated by cold temperature in vitro and has been demonstrated to act as a ‘cold temperature sensor’ in vivo. Although it is known that agonists of this ‘cold temperature sensor’, such as menthol and icilin, cause a transient increase in body temperature (Tb), it is not known if TRPM8 plays a role in Tb regulation. Since TRPM8 has been considered as a potential target for chronic pain therapeutics, we have investigated the role of TRPM8 in Tb regulation. Results We characterized five chemically distinct compounds (AMG0635, AMG2850, AMG8788, AMG9678, and Compound 496) as potent and selective antagonists of TRPM8 and tested their effects on Tb in rats and mice implanted with radiotelemetry probes. All five antagonists used in the study caused a transient decrease in Tb (maximum decrease of 0.98°C). Since thermoregulation is a homeostatic process that maintains Tb about 37°C, we further evaluated whether repeated administration of an antagonist attenuated the decrease in Tb. Indeed, repeated daily administration of AMG9678 for four consecutive days showed a reduction in the magnitude of the Tb decrease Day 2 onwards. Conclusions The data reported here demonstrate that TRPM8 channels play a role in Tb regulation. Further, a reduction of magnitude in Tb decrease after repeated dosing of an antagonist suggests that TRPM8’s role in Tb maintenance may not pose an issue for developing TRPM8 antagonists as therapeutics. PMID:22571355

Rapid preparation of functional polysaccharides from Pyropia yezoensis by microwave-assistant rapid enzyme digest system.

PubMed

Lee, Ji-Hyeok; Kim, Hyung-Ho; Ko, Ju-Young; Jang, Jun-Ho; Kim, Gwang-Hoon; Lee, Jung-Suck; Nah, Jae-Woon; Jeon, You-Jin

2016-11-20

This study describes a simple preparation of functional polysaccharides from Pyropia yezoensis using a microwave-assistant rapid enzyme digest system (MAREDS) with various carbohydrases, and evaluates their antioxidative effects. Polysaccharide hydrolysates were prepared using MAREDS under different hydrolytic conditions of the carbohydrases and microwave powers. Polysaccharides less than 10kDa (Low molecular weight polysaccharides, LMWP, ≤10kDa) were efficiently obtained using an ultrafiltration (molecular weight cut-off of 10kDa). MAREDS increases AMG activation via an increased degree of hydrolysis; the best AMG hydrolysate was prepared using a 10:1 ratio of substrate to enzyme for 2h in MAREDS with 400W. LMWP consisted of galactose (27.3%), glucose (64.5%), and mannose (8.3%) from the AMG hydrolysate had stronger antioxidant effects than the high molecular weight polysaccharides (>10kDa). We rapidly prepared functional LMWPs by using MAREDS with carbohydrases, and suggest that LMWP might be potentially a valuable algal polysaccharide antioxidant. Copyright © 2016 Elsevier Ltd. All rights reserved.

TRPV1 receptor-mediated expression of Toll-like receptors 2 and 4 following permanent middle cerebral artery occlusion in rats

PubMed Central

Hakimizadeh, Elham; Shamsizadeh, Ali; Roohbakhsh, Ali; Arababadi, Mohammad Kazemi; Hajizadeh, Mohammad Reza; Shariati, Mehdi; Fatemi, Iman; Moghadam-ahmadi, Amir; Bazmandegan, Gholamreza; Rezazadeh, Hossein; Allahtavakoli, Mohammad

2017-01-01

Objective(s): Stroke is known as a main cause of mortality and prolonged disability in adults. Both transient receptor potential V1 (TRPV1) channels and toll-like receptors (TLRs) are involved in mediating the inflammatory responses. In the present study, the effects of TRPV1 receptor activation and blockade on stroke outcome and gene expression of TLR2 and TLR4 were assessed following permanent middle cerebral artery occlusion in rats Materials and Methods: Eighty male Wistar rats were divided into four groups as follows: sham, vehicle, AMG9810 (TRPV1 antagonist) -treated and capsaicin (TRPV1 agonist) -treated. For Stroke induction, the middle cerebral artery was permanently occluded and then behavioral functions were evaluated 1, 3 and 7 days after stroke. Results: TRPV1 antagonism significantly reduced the infarct volume compared to the stroke group. Also, neurological deficits were decreased by AMG9810 seven days after cerebral ischemia. In the ledged beam-walking test, the slip ratio was enhanced following ischemia. AMG9810 decreased this index in stroke animals. However, capsaicin improved the ratio 3 and 7 days after cerebral ischemia. Compared to the sham group, the mRNA expression of TLR2 and TLR4 was significantly increased in the stroke rats. AMG9810 Administration significantly reduced the mRNA expression of TLR2 and TLR4. However, capsaicin did not significantly affect the gene expression of TLR2 and TLR4. Conclusion: Our results demonstrated that TRPV1 antagonism by AMG9810 attenuates behavioral function and mRNA expression of TLR2 and TLR4. Thus, it might be useful to shed light on future therapeutic strategies for the treatment of ischemic stroke. PMID:29085577

Demonstration of vessels in CNS and other organs by AMG silver enhancement of colloidal gold particles dispersed in gelatine.

PubMed

Danscher, G; Andreasen, A

1997-12-01

We present a new autometallographic technique for demonstrating vessels and other small cavities at light microscopy (LM) and electron microscopy (EM) levels. It is possible to obtain detailed knowledge of the 3-D appearance of the vascular system by exchanging blood with a 40 degrees C, 8% gelatine solution containing colloidal gold particles (gold gelatine solution, GGS) and ensuing silver enhancement of the gold particles by autometallography (AMG). The GGS-AMG technique demonstrates the vascular system as a dark web that can be studied in cryostat, vibratome, methacrylate, paraffin and Epon sections at all magnifications. The infused GGS becomes increasingly viscous and finally becomes rigid when the temperature falls below 20 degrees C. An additional advantage of this technique is the fact that none of the tested counterstains or immunotechniques interfere with this AMG approach. The GGS-AMG technique is demonstrated on rat brains but can be applied to any organ. We believe that the present technique is valuable for both experimental studies and routine pathology.

Midgut of the non-hematophagous mosquito Toxorhynchites theobaldi (Diptera, Culicidae).

PubMed

Godoy, Raquel S M; Fernandes, Kenner M; Martins, Gustavo F

2015-10-30

In most mosquito species, the females require a blood-feeding for complete egg development. However, in Toxorhynchites mosquitoes, the eggs develop without blood-feeding, and both females and males exclusively feed on sugary diets. The midgut is a well-understood organ in blood-feeding mosquitoes, but little is known about it in non-blood-feeding ones. In the present study, the detailed morphology of the midgut of Toxorhynchites theobaldi were investigated using histochemical and ultrastructural methods. The midgut of female and male T. theobaldi adults consists of a long, slender anterior midgut (AMG), and a short, dilated posterior midgut (PMG). The AMG is subdivided into AMG1 (short, with folds) and AMG2 (long, without folds). Nerve branches and enteroendocrine cells are present in AMG and PMG, respectively. Compared with the PMG of blood-feeding female mosquitoes, the PMG of T. theobaldi is smaller; however, in both mosquitoes, PMG seems be the main region of food digestion and absorption, and protein secretion. The epithelial folds present in the AMG of T. theobaldi have not been reported in other mosquitoes; however, the midgut muscle organization and endocrine control of the digestion process are conserved in both T. theobaldi and blood-feeding mosquitoes.

Glycation inhibitors extend yeast chronological lifespan by reducing advanced glycation end products and by back regulation of proteins involved in mitochondrial respiration.

PubMed

Kazi, Rubina S; Banarjee, Reema M; Deshmukh, Arati B; Patil, Gouri V; Jagadeeshaprasad, Mashanipalya G; Kulkarni, Mahesh J

2017-03-06

Advanced Glycation End products (AGEs) are implicated in aging process. Thus, reducing AGEs by using glycation inhibitors may help in attenuating the aging process. In this study using Saccharomyces cerevisiae yeast system, we show that Aminoguanidine (AMG), a well-known glycation inhibitor, decreases the AGE modification of proteins in non-calorie restriction (NR) (2% glucose) and extends chronological lifespan (CLS) similar to that of calorie restriction (CR) condition (0.5% glucose). Proteomic analysis revealed that AMG back regulates the expression of differentially expressed proteins especially those involved in mitochondrial respiration in NR condition, suggesting that it switches metabolism from fermentation to respiration, mimicking CR. AMG induced back regulation of differentially expressed proteins could be possibly due to its chemical effect or indirectly by glycation inhibition. To delineate this, Metformin (MET), a structural analog of AMG and a mild glycation inhibitor and Hydralazine (HYD), another potent glycation inhibitor but not structural analog of AMG were used. HYD was more effective than MET in mimicking AMG suggesting that glycation inhibition was responsible for restoration of differentially expressed proteins. Thus glycation inhibitors particularly AMG, HYD and MET extend yeast CLS by reducing AGEs, modulating the expression of proteins involved in mitochondrial respiration and possibly by scavenging glucose. This study reports the role of glycation in aging process. In the non-caloric restriction condition, carbohydrates such as glucose promote protein glycation and reduce CLS. While, the inhibitors of glycation such as AMG, HYD, MET mimic the caloric restriction condition by back regulating deregulated proteins involved in mitochondrial respiration which could facilitate shift of metabolism from fermentation to respiration and extend yeast CLS. These findings suggest that glycation inhibitors can be potential molecules that can be used in management of aging. Copyright © 2017 Elsevier B.V. All rights reserved.

Amyloglucosidase enzymatic reactivity inside lipid vesicles

PubMed Central

Li, Mian; Hanford, Michael J; Kim, Jin-Woo; Peeples, Tonya L

2007-01-01

Efficient functioning of enzymes inside liposomes would open new avenues for applications in biocatalysis and bioanalytical tools. In this study, the entrapment of amyloglucosidase (AMG) (EC 3.2.1.3) from Aspergillus niger into dipalmitoylphosphatidylcholine (DPPC) multilamellar vesicles (MLVs) and large unilamellar vesicles (LUVs) was investigated. Negative-stain, freeze-fracture, and cryo-transmission electron microscopy images verified vesicle formation in the presence of AMG. Vesicles with entrapped AMG were isolated from the solution by centrifugation, and vesicle lamellarity was identified using fluorescence laser confocal microscopy. The kinetics of starch hydrolysis by AMG was modeled for two different systems, free enzyme in aqueous solution and entrapped enzyme within vesicles in aqueous suspension. For the free enzyme system, intrinsic kinetics were described by a Michaelis-Menten kinetic model with product inhibition. The kinetic constants, Vmax and Km, were determined by initial velocity measurements, and Ki was obtained by fitting the model to experimental data of glucose concentration-time curves. Predicted concentration-time curves using these kinetic constants were in good agreement with experimental measurements. In the case of the vesicles, the time-dependence of product (glucose) formation was experimentally determined and simulated by considering the kinetic behavior of the enzyme and the permeation of substrate into the vesicle. Experimental results demonstrated that entrapped enzymes were much more stable than free enyzme. The entrapped enzyme could be recycled with retention of 60% activity after 3 cycles. These methodologies can be useful in evaluating other liposomal catalysis operations. PMID:18271982

Nonclinical Pharmacokinetics, Disposition, and Drug-Drug Interaction Potential of a Novel d-Amino Acid Peptide Agonist of the Calcium-Sensing Receptor AMG 416 (Etelcalcetide).

PubMed

Subramanian, Raju; Zhu, Xiaochun; Kerr, Savannah J; Esmay, Joel D; Louie, Steven W; Edson, Katheryne Z; Walter, Sarah; Fitzsimmons, Michael; Wagner, Mylo; Soto, Marcus; Pham, Roger; Wilson, Sarah F; Skiles, Gary L

2016-08-01

AMG 416 (etelcalcetide) is a novel synthetic peptide agonist of the calcium-sensing receptor composed of a linear chain of seven d-amino acids (referred to as the d-amino acid backbone) with a d-cysteine linked to an l-cysteine via a disulfide bond. AMG 416 contains four basic d-arginine residues and is a +4 charged peptide at physiologic pH with a mol. wt. of 1048.3 Da. The pharmacokinetics (PK), disposition, and potential of AMG 416 to cause drug-drug interaction were investigated in nonclinical studies with two single (14)C-labels placed either at a potentially metabolically labile acetyl position or on the d-alanine next to d-cysteine in the interior of the d-amino acid backbone. After i.v. dosing, the PK and disposition of AMG 416 were similar in male and female rats. Radioactivity rapidly distributed to most tissues in rats with intact kidneys, and renal elimination was the predominant clearance pathway. No strain-dependent differences were observed. In bilaterally nephrectomized rats, minimal radioactivity (1.2%) was excreted via nonrenal pathways. Biotransformation occurred primarily via disulfide exchange with endogenous thiol-containing molecules in whole blood rather than metabolism by enzymes, such as proteases or cytochrome P450s; the d-amino acid backbone remained unaltered. A substantial proportion of the plasma radioactivity was covalently conjugated to albumin. AMG 416 presents a low risk for P450 or transporter-mediated drug-drug interactions because it showed no interactions in vitro. These studies demonstrated a (14)C label on either the acetyl or the d-alanine in the d-amino acid backbone would be appropriate for clinical studies. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Sexually dimorphic functional connectivity in response to high vs. low energy-dense food cues in obese humans: an fMRI study.

PubMed

Atalayer, Deniz; Pantazatos, Spiro P; Gibson, Charlisa D; McOuatt, Haley; Puma, Lauren; Astbury, Nerys M; Geliebter, Allan

2014-10-15

Sexually-dimorphic behavioral and biological aspects of human eating have been described. Using psychophysiological interaction (PPI) analysis, we investigated sex-based differences in functional connectivity with a key emotion-processing region (amygdala, AMG) and a key reward-processing area (ventral striatum, VS) in response to high vs. low energy-dense (ED) food images using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in obese persons in fasted and fed states. When fed, in response to high vs. low-ED food cues, obese men (vs. women) had greater functional connectivity with AMG in right subgenual anterior cingulate, whereas obese women had greater functional connectivity with AMG in left angular gyrus and right primary motor areas. In addition, when fed, AMG functional connectivity with pre/post-central gyrus was more associated with BMI in women (vs. men). When fasted, obese men (vs. women) had greater functional connectivity with AMG in bilateral supplementary frontal and primary motor areas, left precuneus, and right cuneus, whereas obese women had greater functional connectivity with AMG in left inferior frontal gyrus, right thalamus, and dorsomedial prefrontal cortex. When fed, greater functional connectivity with VS was observed in men in bilateral supplementary and primary motor areas, left postcentral gyrus, and left precuneus. These sex-based differences in functional connectivity in response to visual food cues may help partly explain differential eating behavior, pathology prevalence, and outcomes in men and women. Published by Elsevier Inc.

The Features of Fracture Behavior of an Aluminum-Magnesium Alloy AMg6 Under High-Rate Straining

NASA Astrophysics Data System (ADS)

Skripnyak, N. V.

2015-09-01

The results of investigation of fracture dynamics of rolled sheet specimens of an AMg6 alloy are presented for the range of strain rates from 10-3 to 103 s-1. It is found out that the presence of nanostructured surface layers on the thin AMg6 rolled sheets results in improved strength characteristics within the above range of strain rates. A modified model of a deforming medium is proposed to describe the plastic flow and fracture of the AMg6 alloy.

Continuous monitoring of arthritis in animal models using optical imaging modalities

NASA Astrophysics Data System (ADS)

Son, Taeyoon; Yoon, Hyung-Ju; Lee, Saseong; Jang, Won Seuk; Jung, Byungjo; Kim, Wan-Uk

2014-10-01

Given the several difficulties associated with histology, including difficulty in continuous monitoring, this study aimed to investigate the feasibility of optical imaging modalities-cross-polarization color (CPC) imaging, erythema index (EI) imaging, and laser speckle contrast (LSC) imaging-for continuous evaluation and monitoring of arthritis in animal models. C57BL/6 mice, used for the evaluation of arthritis, were divided into three groups: arthritic mice group (AMG), positive control mice group (PCMG), and negative control mice group (NCMG). Complete Freund's adjuvant, mineral oil, and saline were injected into the footpad for AMG, PCMG, and NCMG, respectively. LSC and CPC images were acquired from 0 through 144 h after injection for all groups. EI images were calculated from CPC images. Variations in feet area, EI, and speckle index for each mice group over time were calculated for quantitative evaluation of arthritis. Histological examinations were performed, and the results were found to be consistent with those from optical imaging analysis. Thus, optical imaging modalities may be successfully applied for continuous evaluation and monitoring of arthritis in animal models.

Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors

NASA Astrophysics Data System (ADS)

Lloyd, David J.; St Jean, David J.; Kurzeja, Robert J. M.; Wahl, Robert C.; Michelsen, Klaus; Cupples, Rod; Chen, Michelle; Wu, John; Sivits, Glenn; Helmering, Joan; Komorowski, Renée; Ashton, Kate S.; Pennington, Lewis D.; Fotsch, Christopher; Vazir, Mukta; Chen, Kui; Chmait, Samer; Zhang, Jiandong; Liu, Longbin; Norman, Mark H.; Andrews, Kristin L.; Bartberger, Michael D.; van, Gwyneth; Galbreath, Elizabeth J.; Vonderfecht, Steven L.; Wang, Minghan; Jordan, Steven R.; Véniant, Murielle M.; Hale, Clarence

2013-12-01

Glucose homeostasis is a vital and complex process, and its disruption can cause hyperglycaemia and type II diabetes mellitus. Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate in pancreatic β-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes. In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production, and is subject to the endogenous inhibitor GK regulatory protein (GKRP). During fasting, GKRP binds, inactivates and sequesters GK in the nucleus, which removes GK from the gluconeogenic process and prevents a futile cycle of glucose phosphorylation. Compounds that directly hyperactivate GK (GK activators) lower blood glucose levels and are being evaluated clinically as potential therapeutics for the treatment of type II diabetes mellitus. However, initial reports indicate that an increased risk of hypoglycaemia is associated with some GK activators. To mitigate the risk of hypoglycaemia, we sought to increase GK activity by blocking GKRP. Here we describe the identification of two potent small-molecule GK-GKRP disruptors (AMG-1694 and AMG-3969) that normalized blood glucose levels in several rodent models of diabetes. These compounds potently reversed the inhibitory effect of GKRP on GK activity and promoted GK translocation both in vitro (isolated hepatocytes) and in vivo (liver). A co-crystal structure of full-length human GKRP in complex with AMG-1694 revealed a previously unknown binding pocket in GKRP distinct from that of the phosphofructose-binding site. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus.

Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors.

PubMed

Lloyd, David J; St Jean, David J; Kurzeja, Robert J M; Wahl, Robert C; Michelsen, Klaus; Cupples, Rod; Chen, Michelle; Wu, John; Sivits, Glenn; Helmering, Joan; Komorowski, Renée; Ashton, Kate S; Pennington, Lewis D; Fotsch, Christopher; Vazir, Mukta; Chen, Kui; Chmait, Samer; Zhang, Jiandong; Liu, Longbin; Norman, Mark H; Andrews, Kristin L; Bartberger, Michael D; Van, Gwyneth; Galbreath, Elizabeth J; Vonderfecht, Steven L; Wang, Minghan; Jordan, Steven R; Véniant, Murielle M; Hale, Clarence

2013-12-19

Glucose homeostasis is a vital and complex process, and its disruption can cause hyperglycaemia and type II diabetes mellitus. Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate in pancreatic β-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes. In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production, and is subject to the endogenous inhibitor GK regulatory protein (GKRP). During fasting, GKRP binds, inactivates and sequesters GK in the nucleus, which removes GK from the gluconeogenic process and prevents a futile cycle of glucose phosphorylation. Compounds that directly hyperactivate GK (GK activators) lower blood glucose levels and are being evaluated clinically as potential therapeutics for the treatment of type II diabetes mellitus. However, initial reports indicate that an increased risk of hypoglycaemia is associated with some GK activators. To mitigate the risk of hypoglycaemia, we sought to increase GK activity by blocking GKRP. Here we describe the identification of two potent small-molecule GK-GKRP disruptors (AMG-1694 and AMG-3969) that normalized blood glucose levels in several rodent models of diabetes. These compounds potently reversed the inhibitory effect of GKRP on GK activity and promoted GK translocation both in vitro (isolated hepatocytes) and in vivo (liver). A co-crystal structure of full-length human GKRP in complex with AMG-1694 revealed a previously unknown binding pocket in GKRP distinct from that of the phosphofructose-binding site. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus.

Preclinical characterization of AMG 330, a CD3/CD33-bispecific T-cell-engaging antibody with potential for treatment of acute myelogenous leukemia.

PubMed

Friedrich, Matthias; Henn, Anja; Raum, Tobias; Bajtus, Monika; Matthes, Katja; Hendrich, Larissa; Wahl, Joachim; Hoffmann, Patrick; Kischel, Roman; Kvesic, Majk; Slootstra, Jerry W; Baeuerle, Patrick A; Kufer, Peter; Rattel, Benno

2014-06-01

There is high demand for novel therapeutic options for patients with acute myelogenous leukemia (AML). One possible approach is the bispecific T-cell-engaging (BiTE, a registered trademark of Amgen) antibody AMG 330 with dual specificity for CD3 and the sialic acid-binding lectin CD33 (SIGLEC-3), which is frequently expressed on the surface of AML blasts and leukemic stem cells. AMG 330 binds with low nanomolar affinity to CD33 and CD3ε of both human and cynomolgus monkey origin. Eleven human AML cell lines expressing between 14,400 and 56,700 CD33 molecules per cell were all potently lysed with EC(50) values ranging between 0.4 pmol/L and 3 pmol/L (18-149 pg/mL) by previously resting, AMG 330-redirected T cells. Complete lysis was achieved after 40 hours of incubation. In the presence of AML cells, AMG 330 specifically induced expression of CD69 and CD25 as well as release of IFN-γ, TNF, interleukin (IL)-2, IL-10, and IL-6. Ex vivo, AMG 330 mediated autologous depletion of CD33-positive cells from cynomolgous monkey bone marrow aspirates. Soluble CD33 at concentrations found in bone marrow of patients with AML did not significantly affect activities of AMG 330. Neoexpression of CD33 on newly activated T cells was negligible as it was limited to 6% of T cells in only three out of ten human donors tested. Daily intravenous administration with as low as 0.002 mg/kg AMG 330 significantly prolonged survival of immunodeficient mice adoptively transferred with human MOLM-13 AML cells and human T cells. AMG 330 warrants further development as a potential therapy for AML. ©2014 American Association for Cancer Research.

Algebraic multigrid methods applied to problems in computational structural mechanics

NASA Technical Reports Server (NTRS)

Mccormick, Steve; Ruge, John

1989-01-01

The development of algebraic multigrid (AMG) methods and their application to certain problems in structural mechanics are described with emphasis on two- and three-dimensional linear elasticity equations and the 'jacket problems' (three-dimensional beam structures). Various possible extensions of AMG are also described. The basic idea of AMG is to develop the discretization sequence based on the target matrix and not the differential equation. Therefore, the matrix is analyzed for certain dependencies that permit the proper construction of coarser matrices and attendant transfer operators. In this manner, AMG appears to be adaptable to structural analysis applications.

An algebraic multigrid method for Q2-Q1 mixed discretizations of the Navier-Stokes equations

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

Prokopenko, Andrey; Tuminaro, Raymond S.

Algebraic multigrid (AMG) preconditioners are considered for discretized systems of partial differential equations (PDEs) where unknowns associated with different physical quantities are not necessarily co-located at mesh points. Speci cally, we investigate a Q 2-Q 1 mixed finite element discretization of the incompressible Navier-Stokes equations where the number of velocity nodes is much greater than the number of pressure nodes. Consequently, some velocity degrees-of-freedom (dofs) are defined at spatial locations where there are no corresponding pressure dofs. Thus, AMG approaches lever- aging this co-located structure are not applicable. This paper instead proposes an automatic AMG coarsening that mimics certain pressure/velocitymore » dof relationships of the Q 2-Q 1 discretization. The main idea is to first automatically define coarse pressures in a somewhat standard AMG fashion and then to carefully (but automatically) choose coarse velocity unknowns so that the spatial location relationship between pressure and velocity dofs resembles that on the nest grid. To define coefficients within the inter-grid transfers, an energy minimization AMG (EMIN-AMG) is utilized. EMIN-AMG is not tied to specific coarsening schemes and grid transfer sparsity patterns, and so it is applicable to the proposed coarsening. Numerical results highlighting solver performance are given on Stokes and incompressible Navier-Stokes problems.« less

An algebraic multigrid method for Q2-Q1 mixed discretizations of the Navier-Stokes equations

DOE PAGES

Prokopenko, Andrey; Tuminaro, Raymond S.

2016-07-01

Algebraic multigrid (AMG) preconditioners are considered for discretized systems of partial differential equations (PDEs) where unknowns associated with different physical quantities are not necessarily co-located at mesh points. Speci cally, we investigate a Q 2-Q 1 mixed finite element discretization of the incompressible Navier-Stokes equations where the number of velocity nodes is much greater than the number of pressure nodes. Consequently, some velocity degrees-of-freedom (dofs) are defined at spatial locations where there are no corresponding pressure dofs. Thus, AMG approaches lever- aging this co-located structure are not applicable. This paper instead proposes an automatic AMG coarsening that mimics certain pressure/velocitymore » dof relationships of the Q 2-Q 1 discretization. The main idea is to first automatically define coarse pressures in a somewhat standard AMG fashion and then to carefully (but automatically) choose coarse velocity unknowns so that the spatial location relationship between pressure and velocity dofs resembles that on the nest grid. To define coefficients within the inter-grid transfers, an energy minimization AMG (EMIN-AMG) is utilized. EMIN-AMG is not tied to specific coarsening schemes and grid transfer sparsity patterns, and so it is applicable to the proposed coarsening. Numerical results highlighting solver performance are given on Stokes and incompressible Navier-Stokes problems.« less

Targeting anxiety to improve quality of life in patients with schizophrenia.

PubMed

Buonocore, M; Bosia, M; Bechi, M; Spangaro, M; Cavedoni, S; Cocchi, F; Bianchi, L; Guglielmino, C; Mastromatteo, A R; Cavallaro, R

2017-09-01

Several studies suggested that anxiety can significantly affect the outcome of schizophrenia. Despite this evidence, non-pharmacological interventions targeting anxiety are still heterogenous. This study aims to test the efficacy of a novel training specifically designed to target anxiety in patients with schizophrenia. Innovatively, this training, beyond psychoeducation and problem solving, also targets Theory of Mind, as it provides coping strategies. Twenty-seven outpatients with schizophrenia received a novel rehabilitative training targeting anxiety (Anxiety Management Group [AMG]) combined with a Computer-Assisted Cognitive Remediation (CACR), and twenty received CACR plus a control intervention (Control Newspaper discussion Group [CNG]). All patients were assessed at baseline and after treatment for quality of life, neurocognition and anxiety. After training, patients treated with AMG+CACR showed significantly greater improvements on anxiety. A significant increase in quality of life was observed only for AMG+CACR group. Moreover, the participants' appraisal showed a significant difference between treatment groups with higher ratings among patients who received the AMG+CACR. This study thus suggests feasibility and efficacy of the proposed intervention, that could be implemented in rehabilitative programs for patients with schizophrenia with potential benefits also on disease course and outcome. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Gene Expression and Molecular Characterization of a Xylanase from Chicken Cecum Metagenome

PubMed Central

AL-Darkazali, Hind; Meevootisom, Vithaya

2017-01-01

A xylanase gene xynAMG1 with a 1,116-bp open reading frame, encoding an endo-β-1,4-xylanase, was cloned from a chicken cecum metagenome. The translated XynAMG1 protein consisted of 372 amino acids including a putative signal peptide of 23 amino acids. The calculated molecular mass of the mature XynAMG1 was 40,013 Da, with a theoretical pI value of 5.76. The amino acid sequence of XynAMG1 showed 59% identity to endo-β-1,4-xylanase from Prevotella bryantii and Prevotella ruminicola and 58% identity to that from Prevotella copri. XynAMG1 has two conserved motifs, DVVNE and TEXD, containing two active site glutamates and an invariant asparagine, characteristic of GH10 family xylanase. The xynAMG1 gene without signal peptide sequence was cloned and fused with thioredoxin protein (Trx.Tag) in pET-32a plasmid and overexpressed in Escherichia coli Tuner™(DE3)pLysS. The purified mature XynAMG1 was highly salt-tolerant and stable and displayed higher than 96% of its catalytic activity in the reaction containing 1 to 4 M NaCl. It was only slightly affected by common organic solvents added in aqueous solution to up to 5 M. This chicken cecum metagenome-derived xylanase has potential applications in animal feed additives and industrial enzymatic processes requiring exposure to high concentrations of salt and organic solvents. PMID:28751915

Comparative sensory and proximate evaluation of spontaneously fermenting kunu-zaki made from germinated and ungerminated composite cereal grains

PubMed Central

Oluwajoba, Solakunmi O; Akinyosoye, Felix A; Oyetayo, Olusegun V

2013-01-01

This study evaluated the sensory properties, proximate composition, and overall consumer acceptability of kunu-zaki using germinated and ungerminated Sorghum bicolor (sorghum), Pennisetum americanum (millet), and Digitaria exilis (acha) cereal grains. The three cereal grains were used in nongerminated and germinated composite and noncomposite proportions coded A (Acha), S (Sorghum), M (Millet), AS (Acha–Sorghum), AM (Acha–Millet), SM (Sorghum–Millet), ASG (Acha–Sorghum Germinated), AMG (Acha–Millet Germinated), and SMG (Sorghum–Millet Germinated). Proximate analysis determined the moisture content, ash, crude fiber, fat, and crude protein content of the fermented grains. The 9-point hedonic scale was used to judge the sensory parameters of taste, color, and aroma. The paired comparison test was used to judge consumer preference between kunu-zaki made from germinated grains and the ungerminated counterpart. Scores were statistically analyzed using the Kruskal–Wallis test in the SPSS analytical software package. Panelists ranked the ASG-coded drink highest in terms of taste and aroma, the AMG-coded drink highest in terms of color. SM ranked least in terms of taste; SMG ranked least in terms of aroma; and AM ranked the least in terms of color. Preference for each parameter was significantly different (P < 0.001). Panelists ranked overall preference for the drinks from the most liked to the least liked in the order ASG>AMG>A>AS>S>M>SMG>AM>SM. The overall preference for the drinks was also significantly different (P < 0.001). Panelists pairing both ungerminated drinks with the germinated drinks ranked the ungerminated drink AS as most preferred in terms of taste, color, and aroma above its germinated counterpart ASG with preference not significantly dependent on the parameters (P = 0.065 > 0.05). Ungerminated AM was also preferred above the germinated counterpart AMG in terms of taste, color, and aroma with preference not significantly dependent on parameters (P = 0.055 > 0.05). However, panelists showed preference for the taste and aroma of the germinated drink SMG but more preference for the color of the ungerminated drink SM with preference significantly dependent on the parameters (P = 0.028 < 0.05). Crude fiber values were higher – 11.3%, 13.1%, and 17.37% for SMG, AMG and ASG, respectively. Germination increased %Fat values slightly but the %Ash was relatively stable in both germinated and ungerminated drinks. Addition of germinated acha cereal grains to either sorghum or millet prior to fermentation offers desirable sensory and nutritional quality attributes in kunu-zaki. PMID:24804038

Comparative sensory and proximate evaluation of spontaneously fermenting kunu-zaki made from germinated and ungerminated composite cereal grains.

PubMed

Oluwajoba, Solakunmi O; Akinyosoye, Felix A; Oyetayo, Olusegun V

2013-07-01

This study evaluated the sensory properties, proximate composition, and overall consumer acceptability of kunu-zaki using germinated and ungerminated Sorghum bicolor (sorghum), Pennisetum americanum (millet), and Digitaria exilis (acha) cereal grains. The three cereal grains were used in nongerminated and germinated composite and noncomposite proportions coded A (Acha), S (Sorghum), M (Millet), AS (Acha-Sorghum), AM (Acha-Millet), SM (Sorghum-Millet), ASG (Acha-Sorghum Germinated), AMG (Acha-Millet Germinated), and SMG (Sorghum-Millet Germinated). Proximate analysis determined the moisture content, ash, crude fiber, fat, and crude protein content of the fermented grains. The 9-point hedonic scale was used to judge the sensory parameters of taste, color, and aroma. The paired comparison test was used to judge consumer preference between kunu-zaki made from germinated grains and the ungerminated counterpart. Scores were statistically analyzed using the Kruskal-Wallis test in the SPSS analytical software package. Panelists ranked the ASG-coded drink highest in terms of taste and aroma, the AMG-coded drink highest in terms of color. SM ranked least in terms of taste; SMG ranked least in terms of aroma; and AM ranked the least in terms of color. Preference for each parameter was significantly different (P < 0.001). Panelists ranked overall preference for the drinks from the most liked to the least liked in the order ASG>AMG>A>AS>S>M>SMG>AM>SM. The overall preference for the drinks was also significantly different (P < 0.001). Panelists pairing both ungerminated drinks with the germinated drinks ranked the ungerminated drink AS as most preferred in terms of taste, color, and aroma above its germinated counterpart ASG with preference not significantly dependent on the parameters (P = 0.065 > 0.05). Ungerminated AM was also preferred above the germinated counterpart AMG in terms of taste, color, and aroma with preference not significantly dependent on parameters (P = 0.055 > 0.05). However, panelists showed preference for the taste and aroma of the germinated drink SMG but more preference for the color of the ungerminated drink SM with preference significantly dependent on the parameters (P = 0.028 < 0.05). Crude fiber values were higher - 11.3%, 13.1%, and 17.37% for SMG, AMG and ASG, respectively. Germination increased %Fat values slightly but the %Ash was relatively stable in both germinated and ungerminated drinks. Addition of germinated acha cereal grains to either sorghum or millet prior to fermentation offers desirable sensory and nutritional quality attributes in kunu-zaki.

Turkish Adaptation of the Educational-Learning Capital Questionnaire: Results for Gifted and Non-Gifted Students

ERIC Educational Resources Information Center

Leana-Tascilar, Marilena Z.

2016-01-01

The Actiotope Model of Giftedness (AMG) focuses on person--environment interactions to define giftedness. The development of the Questionnaire of Educational and Learning Capital (QELC) was based on the AMG. The first aim of this study was to present the reliability and validity of a Turkish version of the QELC for 10th grade students. The second…

Synthesis of adenine-modified reduced graphene oxide nanosheets.

PubMed

Cao, Huaqiang; Wu, Xiaoming; Yin, Gui; Warner, Jamie H

2012-03-05

We report here a facile strategy to synthesize the nanocomposite of adenine-modified reduced graphene oxide (AMG) via reaction between adenine and GOCl which is generated from SOCl(2) reacted with graphite oxide (GO). The as-synthesized AMG was characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), UV-vis absorption spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, Raman spectroscopy, thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV), and galvanostatic discharge analysis. The AMG owns about one adenine group per 53 carbon atoms on a graphene sheet, which improves electronic conductivity compared with reduced graphene oxide (RGO). The AMG displays enhanced supercapacitor performance compared with RGO accompanying good stability and good cycling behavior in the supercapacitor.

Activity of some aminoglycoside antibiotics against true fungi, Phytophthora and Pythium species.

PubMed

Lee, H B; Kim, Y; Kim, J C; Choi, G J; Park, S-H; Kim, C-J; Jung, H S

2005-01-01

To investigate the in vitro antifungal and antioomycete activities of some aminoglycosides against true fungi and Phytophthora and Pythium species and to evaluate the potential of the antibiotics against Phytophthora late blight on plants. Antifungal and antioomycete activities of aminoglycoside antibiotics (neomycin, paromomycin, ribostamycin and streptomycin) and a paromomycin-producing strain (Streptomyces sp. AMG-P1) against Phytophthora and Pythium species and 10 common fungi were measured in potato dextrose broth (PDB) and on seedlings in pots. Paromomycin was the most active against Phytophthora and Pythium species with a minimal inhibitory concentration of 1-10 microg ml(-1) in PDB, but displayed low to moderate activities towards other common fungi at the same concentration. Paromomycin also showed potent in vivo activity against red pepper and tomato late blight diseases with 80 and 99% control value, respectively, at 100 microg ml(-1). In addition, culture broth of Streptomyces sp. AMG-P1 as a paromomycin producer exhibited high in vivo activity against late blight at 500 microg freeze-dried weight per millilitre. Among tested aminoglycoside antibiotics, paromomycin was the most active against oomycetes both in vitro and in vivo. Data from this study show that aminoglycoside antibiotics have in vitro and in vivo activities against oomycetes, suggesting that Streptomyces sp. AMG-P1 may be used as a biocontrol agent against oomycete diseases.

Polymeric composites on the basis of Martian ground for building future mars stations

NASA Astrophysics Data System (ADS)

Mukbaniani, O. V.; Aneli, J. N.; Markarashvili, E. G.; Tarasashvili, M. V.; Aleksidze, N. D.

2016-04-01

The colonization of Mars will require obtaining building materials which can be put in place and processed into buildings via various constructive technologies. We tried to use artificial Martian ground - AMG (GEO PAT 11-234 (2015)) and special resins for the preparation of building block prototypes. The composite material has been obtained based on the AMG as filler, epoxy resin (type ED-20) and tetraethoxysilane - TEOS. We have studied strengthening - softening temperatures and water absorption of the AMG polymer composites that are determined by epoxy resin and TEOS modification. Comparison of the experimental results shows that composites containing modified filler have higher values of the maximum ultimate strength, resistance and flexibility parameters than unmodified composites with definite loading. Modified composites also have a higher softening temperature and lower water absorption.

Comparison of an algebraic multigrid algorithm to two iterative solvers used for modeling ground water flow and transport

USGS Publications Warehouse

Detwiler, R.L.; Mehl, S.; Rajaram, H.; Cheung, W.W.

2002-01-01

Numerical solution of large-scale ground water flow and transport problems is often constrained by the convergence behavior of the iterative solvers used to solve the resulting systems of equations. We demonstrate the ability of an algebraic multigrid algorithm (AMG) to efficiently solve the large, sparse systems of equations that result from computational models of ground water flow and transport in large and complex domains. Unlike geometric multigrid methods, this algorithm is applicable to problems in complex flow geometries, such as those encountered in pore-scale modeling of two-phase flow and transport. We integrated AMG into MODFLOW 2000 to compare two- and three-dimensional flow simulations using AMG to simulations using PCG2, a preconditioned conjugate gradient solver that uses the modified incomplete Cholesky preconditioner and is included with MODFLOW 2000. CPU times required for convergence with AMG were up to 140 times faster than those for PCG2. The cost of this increased speed was up to a nine-fold increase in required random access memory (RAM) for the three-dimensional problems and up to a four-fold increase in required RAM for the two-dimensional problems. We also compared two-dimensional numerical simulations of steady-state transport using AMG and the generalized minimum residual method with an incomplete LU-decomposition preconditioner. For these transport simulations, AMG yielded increased speeds of up to 17 times with only a 20% increase in required RAM. The ability of AMG to solve flow and transport problems in large, complex flow systems and its ready availability make it an ideal solver for use in both field-scale and pore-scale modeling.

Attenuation of TRPV1 by AMG-517 after nerve injury promotes peripheral axonal regeneration in rats.

PubMed

Bai, Juan; Liu, Fu; Wu, Li-Fei; Wang, Ya-Fang; Li, Xia-Qing

2018-01-01

Aims The main objective was to investigate the effects of the transient receptor potential cation channel subfamily V member 1 (TRPV1) on nerve regeneration following sciatic transection injury by functional blockage of TRPV1 using AMG-517, a specific blocker of TRPV1. Methods AMG-517 was injected into the area surrounding ipsilateral lumbar dorsal root ganglia 30 min after unilateral sciatic nerve transection. The number of sciatic axons and the expression of growth-associated protein-43 (GAP-43) and glial fibrillary acidic protein was examined using semithin sections, Western blot, and immunofluorescence analyses. Results Blockage of TRPV1 with AMG-517 markedly promoted axonal regeneration, especially at two weeks after sciatic injury; the number of axons was similar to the uninjured control group. After sciatic nerve transection, expression of glial fibrillary acidic protein was decreased and GAP-43 was increased at the proximal stump. However, the expression of both glial fibrillary acidic protein and GAP-43 increased significantly in AMG-517-treated groups. Conclusions TRPV1 may be an important therapeutic target to promote peripheral nerve regeneration after injury.

Application of DBS sampling in combination with LC-MS/MS for pharmacokinetic evaluation of a compound with species-specific blood-to-plasma partitioning.

PubMed

Xu, Guifen; Chen, Jiyun S; Phadnis, Ruta; Huang, Tom; Uyeda, Craig; Soto, Marcus; Stouch, Brian; Wells, Mary C; James, Christopher A; Carlson, Timothy J

2012-08-01

Dried blood spot (DBS) sampling in combination with LC-MS/MS has been used increasingly in drug discovery for quantitative analysis to support pharmacokinetic (PK) studies. In this study, we assessed the effect of blood-to-plasma (B:P) partitioning on the bioanalytical performance and PK data acquired by DBS for a compound AMG-1 with species and concentration-dependent B:P ratio. B:P partitioning did not adversely affect bioanalytical performance of DBS for AMG-1. For rat, (B:P ratio of 0.63), PK profiles from DBS and plasma methods were comparable. For dog, concentration-dependence of B:P ratio was observed both in vivo and in vitro. Additional studies demonstrated concentration-dependence of the compound's unbound fraction in plasma, which may contribute to the concentration-dependence of the B:P ratio. DBS is a promising sampling technique for preclinical pharmacokinetic studies. For compounds with high B:P ratio, caution needs to be applied for data comparison and interpretation between matrices.

Air Conditioning Modifications to AMG Buses

DOT National Transportation Integrated Search

1983-12-01

This report presents the documentation and evaluation of air conditioning system modifications devised by Miami (Florida) Metrobus and Los Angeles SCRTD for the AM General Model B bus. The objective of these modifications was to reduce the frequency ...

NONLINEAR MULTIGRID SOLVER EXPLOITING AMGe COARSE SPACES WITH APPROXIMATION PROPERTIES

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

Christensen, Max La Cour; Villa, Umberto E.; Engsig-Karup, Allan P.

The paper introduces a nonlinear multigrid solver for mixed nite element discretizations based on the Full Approximation Scheme (FAS) and element-based Algebraic Multigrid (AMGe). The main motivation to use FAS for unstruc- tured problems is the guaranteed approximation property of the AMGe coarse spaces that were developed recently at Lawrence Livermore National Laboratory. These give the ability to derive stable and accurate coarse nonlinear discretization problems. The previous attempts (including ones with the original AMGe method, [5, 11]), were less successful due to lack of such good approximation properties of the coarse spaces. With coarse spaces with approximation properties, ourmore » FAS approach on un- structured meshes should be as powerful/successful as FAS on geometrically re ned meshes. For comparison, Newton's method and Picard iterations with an inner state-of-the-art linear solver is compared to FAS on a nonlinear saddle point problem with applications to porous media ow. It is demonstrated that FAS is faster than Newton's method and Picard iterations for the experiments considered here. Due to the guaranteed approximation properties of our AMGe, the coarse spaces are very accurate, providing a solver with the potential for mesh-independent convergence on general unstructured meshes.« less

On the scalability of the Albany/FELIX first-order Stokes approximation ice sheet solver for large-scale simulations of the Greenland and Antarctic ice sheets

DOE PAGES

Tezaur, Irina K.; Tuminaro, Raymond S.; Perego, Mauro; ...

2015-01-01

We examine the scalability of the recently developed Albany/FELIX finite-element based code for the first-order Stokes momentum balance equations for ice flow. We focus our analysis on the performance of two possible preconditioners for the iterative solution of the sparse linear systems that arise from the discretization of the governing equations: (1) a preconditioner based on the incomplete LU (ILU) factorization, and (2) a recently-developed algebraic multigrid (AMG) preconditioner, constructed using the idea of semi-coarsening. A strong scalability study on a realistic, high resolution Greenland ice sheet problem reveals that, for a given number of processor cores, the AMG preconditionermore » results in faster linear solve times but the ILU preconditioner exhibits better scalability. In addition, a weak scalability study is performed on a realistic, moderate resolution Antarctic ice sheet problem, a substantial fraction of which contains floating ice shelves, making it fundamentally different from the Greenland ice sheet problem. We show that as the problem size increases, the performance of the ILU preconditioner deteriorates whereas the AMG preconditioner maintains scalability. This is because the linear systems are extremely ill-conditioned in the presence of floating ice shelves, and the ill-conditioning has a greater negative effect on the ILU preconditioner than on the AMG preconditioner.« less

Simultaneous Production of Amyloglucosidase and Exo-Polygalacturonase by Aspergillus niger in a Rotating Drum Reactor.

PubMed

Colla, Eliane; Santos, Lucielen Oliveira; Deamici, Kricelle; Magagnin, Glênio; Vendruscolo, Mauricio; Costa, Jorge Alberto Vieira

2017-02-01

Simultaneous production of amyloglucosidase (AMG) and exo-polygalacturonase (exo-PG) was carried out by Aspergillus niger in substrate of defatted rice bran in a rotating drum bioreactor (RDB) and studied by a 3 1  × 2 2 factorial experimental design. Variables under study were A. niger strains (A. niger NRRL 3122 and A. niger t0005/007-2), types of inoculum (spore suspension and fermented bran), and types of inducer (starch, pectin, and a mix of both). Solid-state fermentation process (SSF) was conducted at 30 °C under 60-vvm aeration for 96 h in a pilot scale. Production of AMG and exo-PG was significantly affected by the fungal strain and the type of inoculum, but inducers did not trigger any significant effect, an evidence of the fact that these enzymes are constitutive. The maximum activity of exo-PG was 84 U g dm -1 whereas the maximum yield of AMG was 886.25 U g dm -1 .

Layout optimization with algebraic multigrid methods

NASA Technical Reports Server (NTRS)

Regler, Hans; Ruede, Ulrich

1993-01-01

Finding the optimal position for the individual cells (also called functional modules) on the chip surface is an important and difficult step in the design of integrated circuits. This paper deals with the problem of relative placement, that is the minimization of a quadratic functional with a large, sparse, positive definite system matrix. The basic optimization problem must be augmented by constraints to inhibit solutions where cells overlap. Besides classical iterative methods, based on conjugate gradients (CG), we show that algebraic multigrid methods (AMG) provide an interesting alternative. For moderately sized examples with about 10000 cells, AMG is already competitive with CG and is expected to be superior for larger problems. Besides the classical 'multiplicative' AMG algorithm where the levels are visited sequentially, we propose an 'additive' variant of AMG where levels may be treated in parallel and that is suitable as a preconditioner in the CG algorithm.

Parallel Solver for H(div) Problems Using Hybridization and AMG

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

Lee, Chak S.; Vassilevski, Panayot S.

2016-01-15

In this paper, a scalable parallel solver is proposed for H(div) problems discretized by arbitrary order finite elements on general unstructured meshes. The solver is based on hybridization and algebraic multigrid (AMG). Unlike some previously studied H(div) solvers, the hybridization solver does not require discrete curl and gradient operators as additional input from the user. Instead, only some element information is needed in the construction of the solver. The hybridization results in a H1-equivalent symmetric positive definite system, which is then rescaled and solved by AMG solvers designed for H1 problems. Weak and strong scaling of the method are examinedmore » through several numerical tests. Our numerical results show that the proposed solver provides a promising alternative to ADS, a state-of-the-art solver [12], for H(div) problems. In fact, it outperforms ADS for higher order elements.« less

Modification to AOAC official methods 2009.01 and 2011.25 to allow for minor overestimation of low molecular weight soluble dietary fiber in samples containing starch.

PubMed

Mccleary, Barry V

2014-01-01

AOAC Official Methods 2009.01 and 2011.25 have been modified to allow removal of resistant maltodextrins produced on hydrolysis of various starches by the combination of pancreatic alpha-amylase and amyloglucosidase (AMG) used in these assay procedures. The major resistant maltodextrin, 6(3),6(5)-di-alpha-D-glucosyl maltopentaose, is highly resistant to hydrolysis by microbial alpha-glucosidases, isoamylase, pullulanase, pancreatic, bacterial and fungal alpha-amylase and AMG. However, this oligosaccharide is hydrolyzed by the mucosal alpha-glucosidase complex of the pig small intestine (which is similar to the human small intestine), and thus must be removed in the analytical procedure. Hydrolysis of these oligosaccharides has been by incubation with a high concentration of a purified AMG at 60 degrees C. This incubation results in no hydrolysis or loss of other resistant oligosaccharides such as FOS, GOS, XOS, resistant maltodextrins (e.g., Fibersol 2) or polydextrose. The effect of this additional incubation with AMG on the measured level of low molecular weight soluble dietary fiber (SDFS) and of total dietary fiber in a broad range of samples is reported. Results from this study demonstrate that the proposed modification can be used with confidence in the measurement of dietary fiber.

Investigation of the midgut structure and ultrastructure in Cimex lectularius and Cimex pipistrelli (Hemiptera: Cimicidae).

PubMed

Rost-Roszkowska, M M; Vilimova, J; Włodarczyk, A; Sonakowska, L; Kamińska, K; Kaszuba, F; Marchewka, A; Sadílek, D

2017-02-01

Cimicidae are temporary ectoparasites, which means that they cannot obtain food continuously. Both Cimex species examined here, Cimex lectularius (Linnaeus 1758) and Cimex pipistrelli (Jenyns 1839), can feed on a non-natal host, C. lectularius from humans on bats, C. pipistrelli on humans, but never naturally. The midgut of C. lectularius and C. pipistrelli is composed of three distinct regions-the anterior midgut (AMG), which has a sack-like shape, the long tube-shaped middle midgut (MMG), and the posterior midgut (PMG). The different ultrastructures of the AMG, MMG, and PMG in both of the species examined suggest that these regions must fulfill different functions in the digestive system. Ultrastructural analysis showed that the AMG fulfills the role of storing food and synthesizing and secreting enzymes, while the MMG is the main organ for the synthesis of enzymes, secretion, and the storage of the reserve material. Additionally, both regions, the AMG and MMG, are involved in water absorption in the digestive system of both Cimex species. The PMG is the part of the midgut in which spherites accumulate. The results of our studies confirm the suggestion of former authors that the structure of the digestive tract of insects is not attributed solely to diet but to the basic adaptation of an ancestor.

75 FR 65515 - Shieldalloy Metallurgical Corporation, A Subsidiary of AMG, Newfield, NJ; Notice of Affirmative...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-25

... finding that a shift of production to Canada in 2006 did not contribute importantly to separations at the...; rather, the subject firm provided storage services for other subsidiaries of AMG, the parent company, and...

89Zr-DFO-AMG102 Immuno-PET to Determine Local Hepatocyte Growth Factor Protein Levels in Tumors for Enhanced Patient Selection.

PubMed

Price, Eric W; Carnazza, Kathryn E; Carlin, Sean D; Cho, Andrew; Edwards, Kimberly J; Sevak, Kuntal K; Glaser, Jonathan M; de Stanchina, Elisa; Janjigian, Yelena Y; Lewis, Jason S

2017-09-01

The hepatocyte growth factor (HGF) binding antibody rilotumumab (AMG102) was modified for use as a 89 Zr-based immuno-PET imaging agent to noninvasively determine the local levels of HGF protein in tumors. Because recent clinical trials of HGF-targeting therapies have been largely unsuccessful in several different cancers (e.g., gastric, brain, lung), we have synthesized and validated 89 Zr-DFO-AMG102 as a companion diagnostic for improved identification and selection of patients having high local levels of HGF in tumors. To date, patient selection has not been performed using the local levels of HGF protein in tumors. Methods: The chelator p -SCN-Bn-DFO was conjugated to AMG102, radiolabeling with 89 Zr was performed in high radiochemical yields and purity (>99%), and binding affinity of the modified antibody was confirmed using an enzyme-linked immunosorbent assay (ELISA)-type binding assay. PET imaging, biodistribution, autoradiography and immunohistochemistry, and ex vivo HGF ELISA experiments were performed on murine xenografts of U87MG (HGF-positive, MET-positive) and MKN45 (HGF-negative, MET-positive) and 4 patient-derived xenografts (MET-positive, HGF unknown). Results: Tumor uptake of 89 Zr-DFO-AMG102 at 120 h after injection in U87MG xenografts (HGF-positive) was high (36.8 ± 7.8 percentage injected dose per gram [%ID/g]), whereas uptake in MKN45 xenografts (HGF-negative) was 5.0 ± 1.3 %ID/g and a control of nonspecific human IgG 89 Zr-DFO-IgG in U87MG tumors was 11.5 ± 3.3 %ID/g, demonstrating selective uptake in HGF-positive tumors. Similar experiments performed in 4 different gastric cancer patient-derived xenograft models showed low uptake of 89 Zr-DFO-AMG102 (∼4-7 %ID/g), which corresponded with low HGF levels in these tumors (ex vivo ELISA). Autoradiography, immunohistochemical staining, and HGF ELISA assays confirmed that elevated levels of HGF protein were present only in U87MG tumors and that 89 Zr-DFO-AMG102 uptake was closely correlated with HGF protein levels in tumors. Conclusion: The new immuno-PET imaging agent 89 Zr-DFO-AMG102 was successfully synthesized, radiolabeled, and validated in vitro and in vivo to selectively accumulate in tumors with high local levels of HGF protein. These results suggest that 89 Zr-DFO-AMG102 would be a valuable companion diagnostic tool for the noninvasive selection of patients with elevated local concentrations of HGF in tumors for planning any HGF-targeted therapy, with the potential to improve clinical outcomes. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

αAMG based on Weighted Matching for Systems of Elliptic PDEs Arising From Displacement and Mixed Methods

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

D'Ambra, P.; Vassilevski, P. S.

2014-05-30

Adaptive Algebraic Multigrid (or Multilevel) Methods (αAMG) are introduced to improve robustness and efficiency of classical algebraic multigrid methods in dealing with problems where no a-priori knowledge or assumptions on the near-null kernel of the underlined matrix are available. Recently we proposed an adaptive (bootstrap) AMG method, αAMG, aimed to obtain a composite solver with a desired convergence rate. Each new multigrid component relies on a current (general) smooth vector and exploits pairwise aggregation based on weighted matching in a matrix graph to define a new automatic, general-purpose coarsening process, which we refer to as “the compatible weighted matching”. Inmore » this work, we present results that broaden the applicability of our method to different finite element discretizations of elliptic PDEs. In particular, we consider systems arising from displacement methods in linear elasticity problems and saddle-point systems that appear in the application of the mixed method to Darcy problems.« less

INSULIN-LIKE GROWTH FACTOR-1 RECEPTOR INHIBITOR, AMG-479, IN CETUXIMAB-REFRACTORY HEAD AND NECK SQUAMOUS CELL CARCINOMA

PubMed Central

Pohlmann, Paula R.; Rothenberg, Mace L.; Burkey, Brian B.; Parker, Joel; Palka, Kevin; Aulino, Joseph; Puzanov, Igor; Murphy, Barbara

2011-01-01

Background Recurrent head and neck squamous cell carcinoma (HNSCC) remains a difficult cancer to treat. Here, we describe a patient with HNSCC who had complete response to methotrexate (MTX) after progressing on multiple cytotoxic agents, cetuximab, and AMG-479 (monoclonal antibody against insulin-like growth factor-1 receptor [IGF-1R]). Methods The clinical information was collected by a retrospective medical record review under an Institutional Review Board–approved protocol. From 4 tumors and 2 normal mucosal epithelia, global gene expression, and IGF-1R and dihydrofolate reductase (DHFR) protein levels were determined. Results Effective target inhibition in the tumor was confirmed by the decreased protein levels of total and phospho-IGF-1R after treatment with AMG-479. Decreased level of DHFR and conversion of a gene expression profile associated with cetuximab-resistance to cetuximab-sensitivity were also observed. Conclusion This suggests that the combination of AMG- 479 and MTX or cetuximab may be a promising therapeutic approach in refractory HNSCC. PMID:20652976

A novel mechanism for antiglycative action of limonene through stabilization of protein conformation.

PubMed

Joglekar, Madhav M; Panaskar, Shrimant N; Chougale, Ashok D; Kulkarni, Mahesh J; Arvindekar, Akalpita U

2013-10-01

Inhibition of protein glycation is known to ameliorate secondary complications in diabetes. In the present study antiglycative properties of limonene, a natural product, were evaluated using BSA as a model protein. AMG (aminoguanidine) was used as a positive control. Measurement of total AGEs (Advanced Glycation End-products) and specific AGEs revealed that limonene could inhibit protein glycation to the extent of 56.3% and 75.1% respectively at 50 μM concentration as against 54.4% and 82.2% by AMG at 1 mM. Congo red binding and CD (Circular Dichroism) analysis revealed inhibition of α-helix to β-sheet transition wherein 18.5% β-sheet structures were observed in glycated BSA (bovine serum albumin) as against 4.9% with limonene. Glycation of protein in the presence of urea was enhanced by 18%, while in the presence of limonene it was reduced by 23% revealing the stabilizing effect of limonene. Electrophoretic mobility was similar to the normal control and a zeta potential value of -12.1 mV as against -15.1 mV in diabetic control was observed. Inhibition of glycation in limonene treated samples was confirmed through LC-MS analysis wherein AGEs such as pentosidine, CML (N(ε)-(carboxymethyl)lysine), CEL (N(ε)-(carboxyethyl)lysine), MOLD (methylglyoxal-lysine dimer) and imidazolone observed in glycated samples were absent in limonene treated samples. PatchDock studies revealed that limonene could bind to the major glycation sites IB, IIA and IIB sub domains and AMG to the IIIA sub domain. Thus limonene is a potent protein glycation inhibitor that prevents protein glycation through a novel mechanism of stabilization of protein structure through hydrophobic interactions.

E4206: AMG 706 and Octreotide in Patients with Low-Grade Neuroendocrine Tumors.

PubMed

Lubner, Sam; Feng, Yang; Mulcahy, Mary; O'Dwyer, Peter; Giang, Guang-Yu; Louis Hinshaw, J; Deming, Dustin; Klein, Leonard; Teitelbaum, Ursina; Payne, Jennifer; Engstrom, Paul; Stella, Philip; Meropol, Neal; Benson, Al

2018-05-31

Rate of progression-free survival at a particular point in time, i.e., a landmark analysis, is a difficult endpoint for a heterogenous malignancy such as neuroendocrine cancer.Landmark analyses can also be complicated by evolution in the standard of care during the conduct of a clinical trial.Improvements in biomarker development would be useful in developing future clinical trials in NET to better tailor individualized therapies and assess for possible efficacy endpoints. Neuroendocrine tumors (NETs) are rare malignancies of the gastrointestinal (GI) tract that are highly vascularized and overexpress vascular-endothelial growth factor (VEGF). Sunitinib has demonstrated efficacy in the pancreatic subset of NET. This study explored the activity of another oral VEGF inhibitor, AMG 706 or motesanib, a multikinase inhibitor that targets receptor tyrosine kinases, including VEGFR1, VEGFR2, VEGFR3, KIT, RET, and PDGFR (IC50s = 2, 3, 6, 8, 59, and 84 nM, respectively). This was a single-arm, first-line, phase II study run through the Eastern Cooperative Oncology Group. Patients with low-grade NET (as defined by central confirmation of Ki-67 of 0%-2%) were administered a flat dose of 125 mg per day orally combined with octreotide long acting-repeatable (LAR) for patients who had been on a stable dose. The primary objective was to determine the 4-month progression-free survival (PFS). Forty-four patients were evaluated per protocol. The 4-month PFS was 78.5%. The partial response rate was 13.6% (6/44), stable disease was 54.5% (24/44), 9.1% (4/44) had progressive disease, and 10/44 were not evaluable for response. Common toxicities included fatigue, hypertension, nausea, and headache, and most were grade 1-2. Median PFS was 8.7 months, and overall survival was 27.5 months. Motesanib (AMG 706) demonstrated a 4-month PFS that met the per-protocol definition of efficacy. Fatigue and hypertension were the most common toxicities, and few grade 3-4 toxicities were encountered. The progression-free survival of 8.7 months in all NETs merits further study. The Oncologist 2018. © AlphaMed Press 2018.

Aging management guideline for commercial nuclear power plants - heat exchangers

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

Booker, S.; Lehnert, D.; Daavettila, N.

1994-06-01

This Aging Management Guideline (AMG) describes recommended methods for effective detection and mitigation of age-related degradation mechanisms in commercial nuclear power plant heat exchangers important to license renewal. The intent of this AMG is to assist plant maintenance and operations personnel in maximizing the safe, useful life of these components. It also supports the documentation of effective aging management programs required under the License Renewal Rule 10 CFR 54. This AMG is presented in a manner that allows personnel responsible for performance analysis and maintenance to compare their plant-specific aging mechanisms (expected or already experienced) and aging management program activitiesmore » to the more generic results and recommendations presented herein.« less

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

Lin, Paul T.; Shadid, John N.; Tsuji, Paul H.

Here, this study explores the performance and scaling of a GMRES Krylov method employed as a smoother for an algebraic multigrid (AMG) preconditioned Newton- Krylov solution approach applied to a fully-implicit variational multiscale (VMS) nite element (FE) resistive magnetohydrodynamics (MHD) formulation. In this context a Newton iteration is used for the nonlinear system and a Krylov (GMRES) method is employed for the linear subsystems. The efficiency of this approach is critically dependent on the scalability and performance of the AMG preconditioner for the linear solutions and the performance of the smoothers play a critical role. Krylov smoothers are considered inmore » an attempt to reduce the time and memory requirements of existing robust smoothers based on additive Schwarz domain decomposition (DD) with incomplete LU factorization solves on each subdomain. Three time dependent resistive MHD test cases are considered to evaluate the method. The results demonstrate that the GMRES smoother can be faster due to a decrease in the preconditioner setup time and a reduction in outer GMRESR solver iterations, and requires less memory (typically 35% less memory for global GMRES smoother) than the DD ILU smoother.« less

76 FR 14104 - Shieldalloy Metallurgical Corporation, a Subsidiary of AMG; Newfield, NJ; Notice of Negative...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-15

... the decision. The petition states that the workers' separations occurred between October 2009 and... Canada in 2006 did not contribute importantly to workers' separations because, during the period of the... for other subsidiaries of AMG (the parent company) and those storage services were shifted to an...

Pharmacokinetic-Pharmacodynamic Relationship of Erenumab (AMG 334) and Capsaicin-Induced Dermal Blood Flow in Healthy and Migraine Subjects.

PubMed

Vu, Thuy; Ma, Peiming; Chen, Jiyun Sunny; de Hoon, Jan; Van Hecken, Anne; Yan, Lucy; Wu, Liviawati Sutjandra; Hamilton, Lisa; Vargas, Gabriel

2017-09-01

Capsaicin-induced dermal blood flow (CIDBF) is a validated biomarker used to evaluate the target engagement of potential calcitonin gene-related peptide-blocking therapeutics for migraine. To characterize the pharmacokinetics (PK) and quantify the inhibitory effects of erenumab (AMG 334) on CIDBF, CIDBF data were pooled from a single- and a multiple-dose study in healthy and migraine subjects. Repeated capsaicin challenges and DBF measurements were performed and serum erenumab concentrations determined. A population analysis was conducted using a nonlinear mixed-effects modeling approach. Effects of body weight, gender, and age on model parameters were evaluated. Two-compartment target-mediated drug disposition (TMDD) model assuming binding of erenumab in the central compartment best described the nonlinear PK of erenumab. Subcutaneous absorption half-life was 1.6 days and bioavailability was 74%. Erenumab produced a maximum inhibition of 89% (95% confidence interval: 87-91%). Erenumab concentrations required for 50% and 99% of maximum inhibition were 255 ng/mL and 1134 ng/mL, respectively. Increased body weight was associated with increased erenumab clearance but had no effect on the inhibitory effect on CIDBF. Our results show that erenumab pharmacokinetics was best characterized by a TMDD model and resulted in potent inhibition of CIDBF.

Dcm methylation is detrimental to plasmid transformation in Clostridium thermocellum

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

Guss, Adam M; Olson, Daniel G.; Caiazza, Nicky

2012-01-01

BACKGROUND: Industrial production of biofuels and other products by cellulolytic microorganisms is of interest but hindered by the nascent state of genetic tools. Although a genetic system for Clostridium thermocellum DSM1313 has recently been developed, available methods achieve relatively low efficiency and similar plasmids can transform C. thermocellum at dramatically different efficiencies. RESULTS: We report an increase in transformation efficiency of C. thermocellum for a variety of plasmids by using DNA that has been methylated by Escherichia coli Dam but not Dcm methylases. When isolated from a dam+ dcm+ E. coli strain, pAMG206 transforms C. thermocellum 100-fold better than themore » similar plasmid pAMG205, which contains an additional Dcm methylation site in the pyrF gene. Upon removal of Dcm methylation, transformation with pAMG206 showed a four- to seven-fold increase in efficiency; however, transformation efficiency of pAMG205 increased 500-fold. Removal of the Dcm methylation site from the pAM205 pyrF gene via silent mutation resulted in increased transformation efficiencies equivalent to that of pAMG206. Upon proper methylation, transformation efficiency of plasmids bearing the pMK3 and pB6A origins of replication increased ca. three orders of magnitude. CONCLUSION: E. coli Dcm methylation decreases transformation efficiency in C. thermocellum DSM1313. The use of properly methylated plasmid DNA should facilitate genetic manipulation of this industrially relevant bacterium.« less

Algebraic multigrid preconditioning within parallel finite-element solvers for 3-D electromagnetic modelling problems in geophysics

NASA Astrophysics Data System (ADS)

Koldan, Jelena; Puzyrev, Vladimir; de la Puente, Josep; Houzeaux, Guillaume; Cela, José María

2014-06-01

We present an elaborate preconditioning scheme for Krylov subspace methods which has been developed to improve the performance and reduce the execution time of parallel node-based finite-element (FE) solvers for 3-D electromagnetic (EM) numerical modelling in exploration geophysics. This new preconditioner is based on algebraic multigrid (AMG) that uses different basic relaxation methods, such as Jacobi, symmetric successive over-relaxation (SSOR) and Gauss-Seidel, as smoothers and the wave front algorithm to create groups, which are used for a coarse-level generation. We have implemented and tested this new preconditioner within our parallel nodal FE solver for 3-D forward problems in EM induction geophysics. We have performed series of experiments for several models with different conductivity structures and characteristics to test the performance of our AMG preconditioning technique when combined with biconjugate gradient stabilized method. The results have shown that, the more challenging the problem is in terms of conductivity contrasts, ratio between the sizes of grid elements and/or frequency, the more benefit is obtained by using this preconditioner. Compared to other preconditioning schemes, such as diagonal, SSOR and truncated approximate inverse, the AMG preconditioner greatly improves the convergence of the iterative solver for all tested models. Also, when it comes to cases in which other preconditioners succeed to converge to a desired precision, AMG is able to considerably reduce the total execution time of the forward-problem code-up to an order of magnitude. Furthermore, the tests have confirmed that our AMG scheme ensures grid-independent rate of convergence, as well as improvement in convergence regardless of how big local mesh refinements are. In addition, AMG is designed to be a black-box preconditioner, which makes it easy to use and combine with different iterative methods. Finally, it has proved to be very practical and efficient in the parallel context.

Seeking Space Aliens and the Strong Approximation Property: A (disjoint) Study in Dust Plumes on Planetary Satellites and Nonsymmetric Algebraic Multigrid

NASA Astrophysics Data System (ADS)

Southworth, Benjamin Scott

PART I: One of the most fascinating questions to humans has long been whether life exists outside of our planet. To our knowledge, water is a fundamental building block of life, which makes liquid water on other bodies in the universe a topic of great interest. In fact, there are large bodies of water right here in our solar system, underneath the icy crust of moons around Saturn and Jupiter. The NASA-ESA Cassini Mission spent two decades studying the Saturnian system. One of the many exciting discoveries was a "plume" on the south pole of Enceladus, emitting hundreds of kg/s of water vapor and frozen water-ice particles from Enceladus' subsurface ocean. It has since been determined that Enceladus likely has a global liquid water ocean separating its rocky core from icy surface, with conditions that are relatively favorable to support life. The plume is of particular interest because it gives direct access to ocean particles from space, by flying through the plume. Recently, evidence has been found for similar geological activity occurring on Jupiter's moon Europa, long considered one of the most likely candidate bodies to support life in our solar system. Here, a model for plume-particle dynamics is developed based on studies of the Enceladus plume and data from the Cassini Cosmic Dust Analyzer. A C++, OpenMP/MPI parallel software package is then built to run large scale simulations of dust plumes on planetary satellites. In the case of Enceladus, data from simulations and the Cassini mission provide insight into the structure of emissions on the surface, the total mass production of the plume, and the distribution of particles being emitted. Each of these are fundamental to understanding the plume and, for Europa and Enceladus, simulation data provide important results for the planning of future missions to these icy moons. In particular, this work has contributed to the Europa Clipper mission and proposed Enceladus Life Finder. PART II: Solving large, sparse linear systems arises often in the modeling of biological and physical phenomenon, data analysis through graphs and networks, and other scientific applications. This work focuses primarily on linear systems resulting from the discretization of partial differential equations (PDEs). Because solving linear systems is the bottleneck of many large simulation codes, there is a rich field of research in developing "fast" solvers, with the ultimate goal being a method that solves an n x n linear system in O(n) operations. One of the most effective classes of solvers is algebraic multigrid (AMG), which is a multilevel iterative method based on projecting the problem into progressively smaller spaces, and scales like O(n) or O(nlog n) for certain classes of problems. The field of AMG is well-developed for symmetric positive definite matrices, and is typically most effective on linear systems resulting from the discretization of scalar elliptic PDEs, such as the heat equation. Systems of PDEs can add additional difficulties, but the underlying linear algebraic theory is consistent and, in many cases, an elliptic system of PDEs can be handled well by AMG with appropriate modifications of the solver. Solving general, nonsymmetric linear systems remains the wild west of AMG (and other fast solvers), lacking significant results in convergence theory as well as robust methods. Here, we develop new theoretical motivation and practical variations of AMG to solve nonsymmetric linear systems, often resulting from the discretization of hyperbolic PDEs. In particular, multilevel convergence of AMG for nonsymmetric systems is proven for the first time. A new nonsymmetric AMG solver is also developed based on an approximate ideal restriction, referred to as AIR, which is able to solve advection-dominated, hyperbolic-type problems that are outside the scope of existing AMG solvers and other fast iterative methods. AIR demonstrates scalable convergence on unstructured meshes, in multiple dimensions, and with high-order finite elements, expanding the applicability of AMG to a new class of problems.

Synthesis, crystal structure and spectroscopy properties of Na 3AZr(PO 4) 3 ( A=Mg, Ni) and Li 2.6Na 0.4NiZr(PO 4) 3 phosphates

NASA Astrophysics Data System (ADS)

Chakir, M.; El Jazouli, A.; de Waal, D.

2006-06-01

Na 3AZr(PO 4) 3 ( A=Mg, Ni) phosphates were prepared at 750 °C by coprecipitation route. Their crystal structures have been refined at room temperature from X-ray powder diffraction data using Rietveld method. Li 2.6Na 0.4NiZr(PO 4) 3 was synthesized through ion exchange from the sodium analog. These materials belong to the Nasicon-type structure. Raman spectra of Na 3AZr(PO 4) 3 ( A=Mg, Ni) phosphates present broad peaks in favor of the statistical distribution in the sites around PO 4 tetrahedra. Diffuse reflectance spectra indicate the presence of octahedrally coordinated Ni 2+ ions.

Conditioned effects of ethanol on the immune system.

PubMed

Gano, Anny; Pautassi, Ricardo Marcos; Doremus-Fitzwater, Tamara L; Deak, Terrence

2017-04-01

Several studies indicate that the immune system can be subjected to classical conditioning. Acute ethanol intoxication significantly modulates several pro-inflammatory cytokines (e.g. interleukins-1 and 6 [IL-1β and IL-6, respectively] and tumor necrosis factor alpha [TNFα])) in several brain areas, including amygdala (AMG), paraventricular nucleus (PVN), and hippocampus (HPC). It is unknown, however, whether cues associated with ethanol can elicit conditioned alterations in cytokine expression. The present study analyzed, in male Sprague-Dawley rats, whether ethanol-induced changes in the central cytokine response may be amenable to conditioning. In Experiments 1 and 2, the rats were given one or two pairings between a distinctive odor (conditional stimulus, CS) and the post-absorptive effects of a high (3.0 or 4.0 g/kg, Experiments 1 and 2, respectively) ethanol dose. Neither of these experiments revealed conditioning of IL-6, IL-1β, or TNFα, as measured via mRNA levels. Yet, re-exposure to the lemon-odor CS in Experiment 1 significantly increased C-Fos levels in the PVN. In Experiment 3, the rats were given four pairings between an odor CS and a moderate ethanol dose (2.0 g/kg), delivered intraperitoneally (i.p.) or intragastrically (i.g.). Re-exposure to the odor CS significantly increased IL-6 levels in HPC and AMG, an effect only evident in paired rats administered ethanol i.p. Overall, this study suggests that ethanol exposure can regulate the levels of IL-6 at HPC and AMG via classical conditioning mechanisms. These ethanol-induced, conditioned alterations in cytokine levels may ultimately affect the intake and motivational effects of ethanol. Impact statement This study examines, across three experiments, whether odor cues associated with ethanol exposure can condition changes in cytokine expression. The analysis of ethanol-induced conditioning of immune responses is a novel niche that can help understand the transition from social drinking to alcohol abuse and dependence. Ethanol-induced conditioning of the immune system could likely exacerbate neuroinflammation and drug-related toxicity, which in turn may facilitate further engagement in ethanol intake. The main new finding of the present study was that, after four pairings of ethanol's unconditioned effects and a distinctive odor, the latter CS increased IL-6 levels in HPC and AMG. This suggests that ethanol's effects upon IL-6 in HPC and AMG may come under conditioned control, particularly after repeated pairings between distinctive odor cues and ethanol's effects. This article advances our knowledge of conditioned increases in cytokine responses, which should help understand the mechanisms underlying alcohol use, abuse, and relapse.

Aging Management Guideline for commercial nuclear power plants: Motor control centers; Final report

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

Toman, G.; Gazdzinski, R.; O`Hearn, E.

1994-02-01

This Aging Management Guideline (AMG) provides recommended methods for effective detection and mitigation of age-related degradation mechanisms in Boiling Water Reactor (BWR) and Pressurized Water Reactor (PWR) commercial nuclear power plant motor control centers important to license renewal. The intent of this AMG is to assist plant maintenance and operations personnel in maximizing the safe, useful life of these components. It also supports the documentation of effective aging management programs required under the License Renewal Rule 10 CFR Part 54. This AMG is presented in a manner that allows personnel responsible for performance analysis and maintenance to compare their plant-specificmore » aging mechanisms (expected or already experienced) and aging management program activities to the more generic results and recommendations presented herein.« less

[A model of multiple organ injury induced by Klebsiella pneumoniae pneumonia in aged rats].

PubMed

Li, Jian-sheng; Wang, Shou-fu; Qin, Jin-li; Zhang, Hui-jian; Li, Su-yun; Yu, Hai-bin; Wang, Feng; Liu, Si-hua; Li, Ya

2009-04-01

To reproduce a model of bacterial multiple organ injury (MOI) in aged rats. Male Sprague-Dawley (SD) rats were used. The young rats were divided into young control group (YCG, n=10) and young model group (YMG, n=15), and the elderly, aged control group (ACG, n=10) and aged model group (AMG, n=25). The model of rats with Klebsiella pneumoniae pneumonia was produced by tracheal instillation of the bacteria, and injury to various organs was observed and evaluated with changes in biochemical parameters, pathological pictures and mortality. Between YMG and AMG, the mortality rates were 33.33% (5/15) and 60.00% (15/25), respectively, at 24 hours after instillation of the bacteria. Compared with YCG and ACG, the neutrophil percentage and white blood cell (WBC) counts in peripheral blood increased significantly in YMG and AMG groups (all P<0.01), the rates of dysfunction of the lungs, the heart and the liver, were 60%-100%. The respiratory dysfunction was evidenced by an increase in the arterial partial pressure of carbon dioxide (PaCO(2), P<0.01), and a decrease in the arterial partial pressure of oxygen (PaO(2), P<0.05 or P<0.01). Myocardial dysfunction was shown by a the sharp increase in creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB) and lactate dehydrogenase (LDH), and that of the liver by changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST, P<0.05 or P<0.01). The pathological changes under light and electronic microscopy were obvious, and the main feature was infiltration of the inflammatory cells. Compared with YMG, PaO(2) in AMG dropped significantly, PaCO(2) increased, CK, CK-MB, LDH, ALT and AST also increased significantly (P<0.05 or P<0.01). The scores of pathological injury in the lungs, the heart and the small intestine in the AMG were obviously higher than that in YMG group (all P<0.05), and the same was trend in the liver and the kidney. The model of bacterial MOI in aged rats is reproduced successfully, and it mimics the pathogenesis of multiple organ dysfunction syndrome (MODS) which initiates from infection in the lungs. The model is simple and convenient to replicate with a high success rate. The MOI in the aged rats is characterized by the severity of the organ injury and a high mortality rate.

Final report for''FOSPACK''

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

Ruge, J W; Dean, D

2000-11-20

The goal of this subcontract was to modify the FOSPACK code, developed by John Ruge, to call the BoomerAMG solver developed at LLNL through the HYPRE interface. FOSPACK is a package developed for the automatic discretization and solution of First-Order System Least-Squares (FOSLS) formulations of 2D partial differential equations (c.f [3-9]). FOSPACK takes a user-specified mesh (which can be an unstructured combination of triangular and quadrilateral elements) and specification of the first-order system, and produces the discretizations needed for solution. Generally, all specifications are contained in data files, so no re-compilation is necessary when changing domains, mesh sizes, problems, etc.more » Much of the work in FOSPACK has gone into an interpreter that allows for simple, intuitive specification of the equations. The interpreter reads the equations, processes them, and stores them as instruction lists needed to apply the operators involved to finite element basis functions, allowing assembly of the discrete system. Quite complex equations may be specified, including variable coefficients, user defined functions, and vector notation. The first-order systems may be nonlinear, with linearizations either performed automatically, or specified in a convenient way by the user. The program also includes global/local refinement capability. FOSLS formulations are very well suited for solution by algebraic multigrid (AMG) (c.f. [10-13]). The original version uses a version of algebraic multigrid written by John Ruge in FORTRAN 77, and modified somewhat for use with FOSPACK. BoomerAMG, a version of AMG developed at CASC, has a number of advantages over the FORTRAN version, including dynamic memory allocation and parallel capability. This project was to benefit both FRSC and CASC, giving FOSPACK the advantages of BoomerAMG, while giving CASC a tool for testing FOSLS as a discretization method for problems of interest there. The major parts of this work were implementation and testing of the HYPRE package on our computers, writing a C wrapper/driver for the FOSPACK code, and modifying the wrapper to call BoomerAMG through the HYPRE interface.« less

Impact of Diverse Immune Evasion Mechanisms of Cancer Cells on T Cells Engaged by EpCAM/CD3-Bispecific Antibody Construct AMG 110

PubMed Central

Deisting, Wibke; Raum, Tobias; Kufer, Peter; Baeuerle, Patrick A.; Münz, Markus

2015-01-01

Background Bispecific T cell engager (BiTE®) are single-chain bispecific antibody constructs with dual specificity for CD3 on T cells and a surface antigen on target cells. They can elicit a polyclonal cytotoxic T cell response that is not restricted by T cell receptor (TCR) specificity, and surface expression of MHC class I/peptide antigen complexes. Using human EpCAM/CD3-bispecific BiTE® antibody construct AMG 110, we here assessed to what extent surface expression of PD-L1, cytoplasmic expression of indoleamine-2,3-deoxygenase type 1, Bcl-2 and serpin PI-9, and the presence of transforming growth factor beta (TGF-β), interleukin-10 (IL-10) and adenosine in culture medium can impact redirected lysis by AMG 110-engaged T cells. Methods The seven factors, which are all involved in inhibiting T cell functions by cancer cells, were tested with human EpCAM-expressing Chinese hamster ovary (CHO) target cells at levels that in most cases exceeded those observed in a number of human cancer cell lines. Co-culture experiments were used to determine the impact of the evasion mechanisms on EC50 values and amplitude of redirected lysis by AMG 110, and on BiTE®-induced proliferation of previously resting human peripheral T cells. Findings An inhibitory effect on redirected lysis by AMG 110-engaged T cells was seen upon overexpression of serpin PI-9, Bcl-2, TGF-βand PD-L1. An inhibitory effect on induction of T cell proliferation was only seen with CHO cells overexpressing IDO. In no case, a single evasion mechanism rendered target cells completely resistant to BiTE®-induced lysis, and even various combinations could not. Conclusions Our data suggest that diverse mechanisms employed by cancer cells to fend off T cells cannot inactivate AMG 110-engaged T cells, and that inhibitory effects observed in vitro may be overcome by increased concentrations of the BiTE® antibody construct. PMID:26510188

The freshwater artisanal fishery of Patos Lagoon.

PubMed

Ceni, G; Fontoura, N F; Cabral, H N

2016-07-01

In this study data relative to the fishery in the freshwater area of the Patos Lagoon are analysed, and the dynamics, fishing gears used and catches evaluated. The results reveal the existence of two fishery strategies: forbidden mesh size gillnets (FMG; <35 mm; square measure) and allowed mesh size gillnets (AMG; ≥35 mm; square measure). In total, 31 species were caught (AMG = 27 and FMG = 24), but selectivity due to mesh size was significant (P < 0·001). The FMG may be very harmful since it captures individuals of most species below size at first maturity, including the target species, the armoured catfish Loricariichthys anus (61% of the total catch). In addition, this gear is used throughout the year, including the closed season (CS; November to January), when the target species is reproducing. Target species for the AMG are larger in size, comprising mainly the mullet Mugil liza, the marine catfish Genidens barbus and the whitemouth croaker Micropogonias furnieri. AMS gillnets were not used during the CS. The use of FMG reveals the need for effective fishery law enforcement and the need for additional studies to assess the status of populations of the exploited species. © 2016 The Fisheries Society of the British Isles.

Effective connectivity during processing of facial affect: evidence for multiple parallel pathways.

PubMed

Dima, Danai; Stephan, Klaas E; Roiser, Jonathan P; Friston, Karl J; Frangou, Sophia

2011-10-05

The perception of facial affect engages a distributed cortical network. We used functional magnetic resonance imaging and dynamic causal modeling to characterize effective connectivity during explicit (conscious) categorization of affective stimuli in the human brain. Specifically, we examined the modulation of connectivity from posterior regions of the face-processing network to the lateral ventral prefrontal cortex (VPFC) during affective categorization and we tested for a potential role of the amygdala (AMG) in mediating this modulation. We found that explicit processing of facial affect led to prominent modulation (increase) in the effective connectivity from the inferior occipital gyrus (IOG) to the VPFC, while there was less evidence for modulation of the afferent connections from fusiform gyrus and AMG to VPFC. More specifically, the forward connection from IOG to the VPFC exhibited a selective increase under anger (as opposed to fear or sadness). Furthermore, Bayesian model comparison suggested that the modulation of afferent connections to the VPFC was mediated directly by facial affect, as opposed to an indirect modulation mediated by the AMG. Our results thus suggest that affective information is conveyed to the VPFC along multiple parallel pathways and that AMG activity is not sufficient to account for the gating of information transfer to the VPFC during explicit emotional processing.

Effect of Intensive Plastic Deformation on Microstructure and Mechanical Properties of Aluminum Alloys

NASA Astrophysics Data System (ADS)

Rakhadilov, Bauyrzhan; Uazyrkhanova, Gulzhaz; Myakinin, Alexandr; Uazyrkhanova, Zhuldyz

2016-08-01

In work it was studied the influence of intensive plastic deformation on structure and mechanical properties of aluminum alloys. Intensive plastic deformation was carried out by using equal-channel angular extrusion. It is shown that the most efficient angle of intersection of the channels is the angle of Φ=120°, which ensures defect-free parts at the highest possible level of accumulated strain (e=8). It is established that the intensive milling grain structures in aluminum alloys AMG6 and AMC occurs at ECAE-12 passes, while the intersection angle of the channels of 120°. After ECAE-12 in aluminum alloys the grain refinement reaches to the size of ∼⃒1.0-1.5 gm. It is determined that as a result of equal channel angular pressing, the microhardness of alloy AMG6 increases almost 4 times in comparison with the initial state, the microhardness of alloy AMC increases by almost 4.5 times in comparison with the initial state. It is shown that ECAE-12 mass loss is reduced to 5.4 and 5.6 mg, which shows an increase in wear-resistance of aluminum alloys AMG6 and AMC 13-14 %.

Aniracetam enhances glutamatergic transmission in the prefrontal cortex of stroke-prone spontaneously hypertensive rats.

PubMed

Togashi, Hiroko; Nakamura, Kazuo; Matsumoto, Machiko; Ueno, Ken-ichi; Ohashi, Satoshi; Saito, Hideya; Yoshioka, Mitsuhiro

2002-03-08

The effects of aniracetam, a cognition enhancer, on extracellular levels of glutamate (Glu), gamma-aminobutyric acid (GABA) and nitric oxide metabolites (NOx) were examined in the prefrontal cortex (PFC) and the basolateral amygdala (AMG) in stroke-prone spontaneously hypertensive rats (SHRSP) using in vivo microdialysis. Basal release of Glu, was lower in the AMG of SHRSP than in normotensive Wistar Kyoto rats, whereas no difference in GABA and NOx was noted. Aniracetam (100 mg/kg, p.o.) significantly increased the area under the curve of Glu levels in the PFC, but not in the AMG, of SHRSP. Aniracetam failed to exert any remarkable effects on GABA or NOx levels in either brain region. Our findings suggest that aniracetam enhances cortical glutamatergic release, which may be the mechanism involved in the ameliorating effects of aniracetam on various neuronal dysfunctions.

Protective effect of enzymatic hydrolysates from highbush blueberry (Vaccinium corymbosum L.) against hydrogen peroxide-induced oxidative damage in Chinese hamster lung fibroblast cell line

PubMed Central

Senevirathne, Mahinda; Kim, Soo-Hyun

2010-01-01

Blueberry was enzymatically hydrolyzed using selected commercial food grade carbohydrases (AMG, Celluclast, Termamyl, Ultraflo and Viscozyme) and proteases (Alcalase, Flavourzyme, Kojizyme, Neutrase and Protamex) to obtain water soluble compounds, and their protective effect was investigated against H2O2-induced damage in Chinese hamster lung fibroblast cell line (V79-4) via various published methods. Both AMG and Alcalase hydrolysates showed higher total phenolic content as well as higher cell viability and ROS scavenging activities, and hence, selected for further antioxidant assays. Both AMG and Alcalase hydrolysates also showed higher protective effects against lipid peroxidation, DNA damage and apoptotic body formation in a dose-dependent fashion. Thus, the results indicated that water soluble compounds obtained by enzymatic hydrolysis of blueberry possess good antioxidant activity against H2O2-induced cell damage in vitro. PMID:20607062

Protective effect of enzymatic hydrolysates from highbush blueberry (Vaccinium corymbosum L.) against hydrogen peroxide-induced oxidative damage in Chinese hamster lung fibroblast cell line.

PubMed

Senevirathne, Mahinda; Kim, Soo-Hyun; Jeon, You-Jin

2010-06-01

Blueberry was enzymatically hydrolyzed using selected commercial food grade carbohydrases (AMG, Celluclast, Termamyl, Ultraflo and Viscozyme) and proteases (Alcalase, Flavourzyme, Kojizyme, Neutrase and Protamex) to obtain water soluble compounds, and their protective effect was investigated against H(2)O(2)-induced damage in Chinese hamster lung fibroblast cell line (V79-4) via various published methods. Both AMG and Alcalase hydrolysates showed higher total phenolic content as well as higher cell viability and ROS scavenging activities, and hence, selected for further antioxidant assays. Both AMG and Alcalase hydrolysates also showed higher protective effects against lipid peroxidation, DNA damage and apoptotic body formation in a dose-dependent fashion. Thus, the results indicated that water soluble compounds obtained by enzymatic hydrolysis of blueberry possess good antioxidant activity against H(2)O(2)-induced cell damage in vitro.

First principle study of structural, elastic and electronic properties of APt3 (A=Mg, Sc, Y and Zr)

NASA Astrophysics Data System (ADS)

Benamer, A.; Roumili, A.; Medkour, Y.; Charifi, Z.

2018-02-01

We report results obtained from first principle calculations on APt3 compounds with A=Mg, Sc, Y and Zr. Our results of the lattice parameter a are in good agreement with experimental data, with deviations less than 0.8%. Single crystal elastic constants are calculated, then polycrystalline elastic moduli (bulk, shear and Young moduli, Poisson ration, anisotropy factor) are presented. Based on Debye model, Debye temperature ϴD is calculated from the sound velocities Vl, Vt and Vm. Band structure results show that the studied compounds are electrical conductors, the conduction mechanism is assured by Pt-d electrons. Different hybridisation states are observed between Pt-d and A-d orbitals. The study of the charge density distribution and the population analysis shows the coexistence of ionic, covalent and metallic bonds.

The influence of carbon nanotubes on enzyme activity and structure: investigation of different immobilization procedures through enzyme kinetics and circular dichroism studies.

PubMed

Cang-Rong, Jason Teng; Pastorin, Giorgia

2009-06-24

In the last decade, many environmental organizations have devoted their efforts to identifying renewable biosystems, which could provide sustainable fuels and thus enhance energy security. Amidst the myriad of possibilities, some biofuels make use of different types of waste biomasses, and enzymes are often employed to hydrolyze these biomasses and produce sugars that will be subsequently converted into ethanol. In this project, we aimed to bridge nanotechnology and biofuel production: here we report on the activity and structure of the enzyme amyloglucosidase (AMG), physically adsorbed or covalently immobilized onto single-walled carbon nanotubes (SWNTs) and multi-walled carbon nanotubes (MWNTs). In fact, carbon nanotubes (CNTs) present several properties that render them ideal support systems, without the diffusion limitations displayed by porous material and with the advantage of being further functionalizable at their surface. Chemical ligation was achieved both on oxidized nanotubes (via carbodiimide chemistry), as well as on amino-functionalized nanotubes (via periodate-oxidized AMG). Results showed that AMG retained a certain percentage of its specific activity for all enzyme-carbon nanotubes complexes prepared, with the physically adsorbed samples displaying better catalytic efficiency than the covalently immobilized samples. Analysis of the enzyme's structure through circular dichroism (CD) spectroscopy revealed significant structural changes in all samples, the degree of change being consistent with the activity profiles. This study proves that AMG interacts differently with carbon nanotubes depending on the method employed. Due to the higher activity reported by the enzyme physically adsorbed onto CNTs, these samples demonstrated a vast potential for further development. At the same time, the possibility of inducing magnetic properties into CNTs offers the opportunity to easily separate them from the original solution. Hence, substances to which they have been attached can be separated from a reaction medium, or directed by an external magnetic field to achieve efficient biofuel production. This paves the way for future design of efficient CNT-enzyme nanostructure bioreactors.

The influence of carbon nanotubes on enzyme activity and structure: investigation of different immobilization procedures through enzyme kinetics and circular dichroism studies

NASA Astrophysics Data System (ADS)

Cang-Rong, Jason Teng; Pastorin, Giorgia

2009-06-01

In the last decade, many environmental organizations have devoted their efforts to identifying renewable biosystems, which could provide sustainable fuels and thus enhance energy security. Amidst the myriad of possibilities, some biofuels make use of different types of waste biomasses, and enzymes are often employed to hydrolyze these biomasses and produce sugars that will be subsequently converted into ethanol. In this project, we aimed to bridge nanotechnology and biofuel production: here we report on the activity and structure of the enzyme amyloglucosidase (AMG), physically adsorbed or covalently immobilized onto single-walled carbon nanotubes (SWNTs) and multi-walled carbon nanotubes (MWNTs). In fact, carbon nanotubes (CNTs) present several properties that render them ideal support systems, without the diffusion limitations displayed by porous material and with the advantage of being further functionalizable at their surface. Chemical ligation was achieved both on oxidized nanotubes (via carbodiimide chemistry), as well as on amino-functionalized nanotubes (via periodate-oxidized AMG). Results showed that AMG retained a certain percentage of its specific activity for all enzyme-carbon nanotubes complexes prepared, with the physically adsorbed samples displaying better catalytic efficiency than the covalently immobilized samples. Analysis of the enzyme's structure through circular dichroism (CD) spectroscopy revealed significant structural changes in all samples, the degree of change being consistent with the activity profiles. This study proves that AMG interacts differently with carbon nanotubes depending on the method employed. Due to the higher activity reported by the enzyme physically adsorbed onto CNTs, these samples demonstrated a vast potential for further development. At the same time, the possibility of inducing magnetic properties into CNTs offers the opportunity to easily separate them from the original solution. Hence, substances to which they have been attached can be separated from a reaction medium, or directed by an external magnetic field to achieve efficient biofuel production. This paves the way for future design of efficient CNT-enzyme nanostructure bioreactors.

Conditioned effects of ethanol on the immune system

PubMed Central

Gano, Anny; Doremus-Fitzwater, Tamara L; Deak, Terrence

2017-01-01

Several studies indicate that the immune system can be subjected to classical conditioning. Acute ethanol intoxication significantly modulates several pro-inflammatory cytokines (e.g. interleukins-1 and 6 [IL-1β and IL-6, respectively] and tumor necrosis factor alpha [TNFα])) in several brain areas, including amygdala (AMG), paraventricular nucleus (PVN), and hippocampus (HPC). It is unknown, however, whether cues associated with ethanol can elicit conditioned alterations in cytokine expression. The present study analyzed, in male Sprague-Dawley rats, whether ethanol-induced changes in the central cytokine response may be amenable to conditioning. In Experiments 1 and 2, the rats were given one or two pairings between a distinctive odor (conditional stimulus, CS) and the post-absorptive effects of a high (3.0 or 4.0 g/kg, Experiments 1 and 2, respectively) ethanol dose. Neither of these experiments revealed conditioning of IL-6, IL-1β, or TNFα, as measured via mRNA levels. Yet, re-exposure to the lemon-odor CS in Experiment 1 significantly increased C-Fos levels in the PVN. In Experiment 3, the rats were given four pairings between an odor CS and a moderate ethanol dose (2.0 g/kg), delivered intraperitoneally (i.p.) or intragastrically (i.g.). Re-exposure to the odor CS significantly increased IL-6 levels in HPC and AMG, an effect only evident in paired rats administered ethanol i.p. Overall, this study suggests that ethanol exposure can regulate the levels of IL-6 at HPC and AMG via classical conditioning mechanisms. These ethanol-induced, conditioned alterations in cytokine levels may ultimately affect the intake and motivational effects of ethanol. Impact statement This study examines, across three experiments, whether odor cues associated with ethanol exposure can condition changes in cytokine expression. The analysis of ethanol-induced conditioning of immune responses is a novel niche that can help understand the transition from social drinking to alcohol abuse and dependence. Ethanol-induced conditioning of the immune system could likely exacerbate neuroinflammation and drug-related toxicity, which in turn may facilitate further engagement in ethanol intake. The main new finding of the present study was that, after four pairings of ethanol’s unconditioned effects and a distinctive odor, the latter CS increased IL-6 levels in HPC and AMG. This suggests that ethanol’s effects upon IL-6 in HPC and AMG may come under conditioned control, particularly after repeated pairings between distinctive odor cues and ethanol’s effects. This article advances our knowledge of conditioned increases in cytokine responses, which should help understand the mechanisms underlying alcohol use, abuse, and relapse. PMID:28201924

Development of a novel non-radioactive cell-based method for the screening of SGLT1 and SGLT2 inhibitors using 1-NBDG.

PubMed

Chang, Hung-Chi; Yang, Su-Fu; Huang, Ching-Chun; Lin, Tzung-Sheng; Liang, Pi-Hui; Lin, Chun-Jung; Hsu, Lih-Ching

2013-08-01

Sodium-coupled glucose co-transporters SGLT1 and SGLT2 play important roles in intestinal absorption and renal reabsorption of glucose, respectively. Blocking SGLT2 is a novel mechanism for lowering the blood glucose level by inhibiting renal glucose reabsorption and selective SGLT2 inhibitors are under development for treatment of type 2 diabetes. Furthermore, it has been reported that perturbation of SGLT1 is associated with cardiomyopathy and cancer. Therefore, both SGLT1 and SGLT2 are potential therapeutic targets. Here we report the development of a non-radioactive cell-based method for the screening of SGLT inhibitors using COS-7 cells transiently expressing human SGLT1 (hSGLT1), CHO-K1 cells stably expressing human SGLT2 (hSGLT2), and a novel fluorescent d-glucose analogue 1-NBDG as a substrate. Our data indicate that 1-NBDG can be a good replacement for the currently used isotope-labeled SGLT substrate, (14)C-AMG. The Michaelis constant of 1-NBDG transport (0.55 mM) is similar to that of d-glucose (0.51 mM) and AMG (0.40 mM) transport through hSGLT1. The IC50 values of a SGLT inhibitor phlorizin for hSGLT1 obtained using 1-NBDG and (14)C-AMG were identical (0.11 μM) in our cell-based system. The IC50 values of dapagliflozin, a well-known selective SGLT2 inhibitor, for hSGLT2 and hSGLT1 determined using 1-NBDG were 1.86 nM and 880 nM, respectively, which are comparable to the published results obtained using (14)C-AMG. Compared to (14)C-AMG, the use of 1-NBDG is cost-effective, convenient and potentially more sensitive. Taken together, a non-radioactive system using 1-NBDG has been validated as a rapid and reliable method for the screening of SGLT1 and SGLT2 inhibitors.

Chronic nicotine-induced changes in gene expression of delta and kappa-opioid receptors and their endogenous ligands in the mesocorticolimbic system of the rat.

PubMed

Ugur, Muzeyyen; Kaya, Egemen; Gozen, Oguz; Koylu, Ersin O; Kanit, Lutfiye; Keser, Aysegul; Balkan, Burcu

2017-09-01

Delta and kappa opioid receptors (DOR and KOR, respectively) and their endogenous ligands, proenkephalin (PENK) and prodynorphin (PDYN)-derived opioid peptides are proposed as important mediators of nicotine reward. This study investigated the regulatory effect of chronic nicotine treatment on the gene expression of DOR, KOR, PENK and PDYN in the mesocorticolimbic system. Three groups of rats were injected subcutaneously with nicotine at doses of 0.2, 0.4, or 0.6 mg/kg/day for 6 days. Rats were decapitated 1 hr after the last dose on day six, as this timing coincides with increased dopamine release in the mesocorticolimbic system. mRNA levels in the ventral tegmental area (VTA), lateral hypothalamic area (LHA), amygdala (AMG), dorsal striatum (DST), nucleus accumbens, and medial prefrontal cortex were measured by quantitative real-time PCR. Our results showed that nicotine upregulated DOR mRNA in the VTA at all of the doses employed, in the AMG at the 0.4 and 0.6 mg/kg doses, and in the DST at the 0.4 mg/kg dose. Conversely, PDYN mRNA was reduced in the LHA with 0.6 mg/kg nicotine and in the AMG with 0.4 mg/kg nicotine. KOR mRNA was also decreased in the DST with 0.6 mg/kg nicotine. Nicotine did not regulate PENK mRNA in any brain region studied. © 2017 Wiley Periodicals, Inc.

Discovery of Phosphodiesterase 10A (PDE10A) PET Tracer AMG 580 to Support Clinical Studies.

PubMed

Hu, Essa; Chen, Ning; Kunz, Roxanne K; Hwang, Dah-Ren; Michelsen, Klaus; Davis, Carl; Ma, Ji; Shi, Jianxia; Lester-Zeiner, Dianna; Hungate, Randall; Treanor, James; Chen, Hang; Allen, Jennifer R

2016-07-14

We report the discovery of PDE10A PET tracer AMG 580 developed to support proof of concept studies with PDE10A inhibitors in the clinic. To find a tracer with higher binding potential (BPND) in NHP than our previously reported tracer 1, we implemented a surface plasmon resonance assay to measure the binding off-rate to identify candidates with slower washout rate in vivo. Five candidates (2-6) from two structurally distinct scaffolds were identified that possessed both the in vitro characteristics that would favor central penetration and the structural features necessary for PET isotope radiolabeling. Two cinnolines (2, 3) and one keto-benzimidazole (5) exhibited PDE10A target specificity and brain uptake comparable to or better than 1 in the in vivo LC-MS/MS kinetics distribution study in SD rats. In NHP PET imaging study, [(18)F]-5 produced a significantly improved BPND of 3.1 and was nominated as PDE10A PET tracer clinical candidate for further studies.

DD-αAMG on QPACE 3

NASA Astrophysics Data System (ADS)

Georg, Peter; Richtmann, Daniel; Wettig, Tilo

2018-03-01

We describe our experience porting the Regensburg implementation of the DD-αAMG solver from QPACE 2 to QPACE 3. We first review how the code was ported from the first generation Intel Xeon Phi processor (Knights Corner) to its successor (Knights Landing). We then describe the modifications in the communication library necessitated by the switch from InfiniBand to Omni-Path. Finally, we present the performance of the code on a single processor as well as the scaling on many nodes, where in both cases the speedup factor is close to the theoretical expectations.

The roles of the amygdala in the affective regulation of body, brain, and behaviour

NASA Astrophysics Data System (ADS)

Mirolli, Marco; Mannella, Francesco; Baldassarre, Gianluca

2010-09-01

Despite the great amount of knowledge produced by the neuroscientific literature on affective phenomena, current models tackling non-cognitive aspects of behaviour are often bio-inspired but rarely bio-constrained. This paper presents a theoretical account of affective systems centred on the amygdala (Amg). This account aims to furnish a general framework and specific pathways to implement models that are more closely related to biological evidence. The Amg, which receives input from brain areas encoding internal states, innately relevant stimuli, and innately neutral stimuli, plays a fundamental role in the motivational and emotional processes of organisms. This role is based on the fact that Amg implements the two associative processes at the core of Pavlovian learning (conditioned stimulus (CS)-unconditioned stimulus (US) and CS-unconditioned response (UR) associations), and that it has the capacity of modulating these associations on the basis of internal states. These functionalities allow the Amg to play an important role in the regulation of the three fundamental classes of affective responses (namely, the regulation of body states, the regulation of brain states via neuromodulators, and the triggering of a number of basic behaviours fundamental for adaptation) and in the regulation of three high-level cognitive processes (namely, the affective labelling of memories, the production of goal-directed behaviours, and the performance of planning and complex decision-making). Our analysis is conducted within a methodological approach that stresses the importance of understanding the brain within an evolutionary/adaptive framework and with the aim of isolating general principles that can potentially account for the wider possible empirical evidence in a coherent fashion.

Distinct representations of configural and part information across multiple face-selective regions of the human brain

PubMed Central

Golarai, Golijeh; Ghahremani, Dara G.; Eberhardt, Jennifer L.; Gabrieli, John D. E.

2015-01-01

Several regions of the human brain respond more strongly to faces than to other visual stimuli, such as regions in the amygdala (AMG), superior temporal sulcus (STS), and the fusiform face area (FFA). It is unclear if these brain regions are similar in representing the configuration or natural appearance of face parts. We used functional magnetic resonance imaging of healthy adults who viewed natural or schematic faces with internal parts that were either normally configured or randomly rearranged. Response amplitudes were reduced in the AMG and STS when subjects viewed stimuli whose configuration of parts were digitally rearranged, suggesting that these regions represent the 1st order configuration of face parts. In contrast, response amplitudes in the FFA showed little modulation whether face parts were rearranged or if the natural face parts were replaced with lines. Instead, FFA responses were reduced only when both configural and part information were reduced, revealing an interaction between these factors, suggesting distinct representation of 1st order face configuration and parts in the AMG and STS vs. the FFA. PMID:26594191

Characterization and Application of BiLA, a Psychrophilic α-Amylase from Bifidobacterium longum.

PubMed

Lee, Hye-Won; Jeon, Hye-Yeon; Choi, Hye-Jeong; Kim, Na-Ri; Choung, Woo-Jae; Koo, Ye-Seul; Ko, Dam-Seul; You, SangGuan; Shim, Jae-Hoon

2016-04-06

In this study, a novel α-amylase was cloned from Bifidobacterium longum and named BiLA. The enzyme exhibited optimal activity at 20 °C and a pH value of 5.0. Kinetic analysis using various carbohydrate substrates revealed that BiLA had the highest k(cat/)K(m) value for amylose. Interestingly, analysis of the enzymatic reaction products demonstrated that BiLA specifically catalyzed the hydrolysis of oligosaccharides and starches up to G5 from the nonreducing ends. To determine whether BiLA can be used to generate slowly digestible starch (SDS), starch was treated with BiLA, and the kinetic parameters were analyzed using porcine pancreatic α-amylase (PPA) and amyloglucosidase (AMG). Compared to normal starch, BiLA-treated starch showed lower k(cat)/K(m) values with PPA and AMG, suggesting that BiLA is a potential candidate for the production of SDS.

The consolidation of inhibitory avoidance memory in mice depends on the intensity of the aversive stimulus: The involvement of the amygdala, dorsal hippocampus and medial prefrontal cortex.

PubMed

Canto-de-Souza, L; Mattioli, R

2016-04-01

Several studies using inhibitory avoidance models have demonstrated the importance of limbic structures, such as the amygdala, dorsal hippocampus and medial prefrontal cortex, in the consolidation of emotional memory. However, we aimed to investigate the role of the amygdala (AMG), dorsal hippocampus (DH) and medial prefrontal cortex (mPFC) of mice in the consolidation of step-down inhibitory avoidance and whether this avoidance would be conditioned relative to the intensity of the aversive stimulus. To test this, we bilaterally infused anisomycin (ANI-40μg/μl, a protein synthesis inhibitor) into one of these three brain areas in mice. These mice were then exposed to one of two different intensities (moderate: 0.5mA or intense: 1.5mA) in a step-down inhibitory avoidance task. We found that consolidation of both of the aversive experiences was mPFC dependent, while the AMG and DH were only required for the consolidation of the intense experience. We suggest that in moderately aversive situations, which do not represent a severe physical risk to the individual, the consolidation of aversive experiences does not depend on protein synthesis in the AMG or the DH, but only the mPFC. However, for intense aversive stimuli all three of these limbic structures are essential for the consolidation of the experience. Copyright © 2016 Elsevier Inc. All rights reserved.

Reducing Communication in Algebraic Multigrid Using Additive Variants

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

Vassilevski, Panayot S.; Yang, Ulrike Meier

Algebraic multigrid (AMG) has proven to be an effective scalable solver on many high performance computers. However, its increasing communication complexity on coarser levels has shown to seriously impact its performance on computers with high communication cost. Moreover, additive AMG variants provide not only increased parallelism as well as decreased numbers of messages per cycle but also generally exhibit slower convergence. Here we present various new additive variants with convergence rates that are significantly improved compared to the classical additive algebraic multigrid method and investigate their potential for decreased communication, and improved communication-computation overlap, features that are essential for goodmore » performance on future exascale architectures.« less

Reducing Communication in Algebraic Multigrid Using Additive Variants

DOE PAGES

Vassilevski, Panayot S.; Yang, Ulrike Meier

2014-02-12

Algebraic multigrid (AMG) has proven to be an effective scalable solver on many high performance computers. However, its increasing communication complexity on coarser levels has shown to seriously impact its performance on computers with high communication cost. Moreover, additive AMG variants provide not only increased parallelism as well as decreased numbers of messages per cycle but also generally exhibit slower convergence. Here we present various new additive variants with convergence rates that are significantly improved compared to the classical additive algebraic multigrid method and investigate their potential for decreased communication, and improved communication-computation overlap, features that are essential for goodmore » performance on future exascale architectures.« less

On the Performance of an Algebraic MultigridSolver on Multicore Clusters

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

Baker, A H; Schulz, M; Yang, U M

2010-04-29

Algebraic multigrid (AMG) solvers have proven to be extremely efficient on distributed-memory architectures. However, when executed on modern multicore cluster architectures, we face new challenges that can significantly harm AMG's performance. We discuss our experiences on such an architecture and present a set of techniques that help users to overcome the associated problems, including thread and process pinning and correct memory associations. We have implemented most of the techniques in a MultiCore SUPport library (MCSup), which helps to map OpenMP applications to multicore machines. We present results using both an MPI-only and a hybrid MPI/OpenMP model.

Application of twin screw extrusion to the manufacture of cocrystals: scale-up of AMG 517-sorbic acid cocrystal production.

PubMed

Daurio, Dominick; Nagapudi, Karthik; Li, Lan; Quan, Peter; Nunez, Fernando-Alvarez

2014-01-01

The application of twin screw extrusion (TSE) in the scale-up of cocrystal production was investigated by using AMG 517-sorbic acid as a model system. Extrusion parameters that influenced conversion to the cocrystal such as temperature, feed rate and screw speed were investigated. Extent of conversion to the cocrystal was found to have a strong dependence on temperature and a moderate dependence on feed rate and screw speed. Cocrystals made by the TSE process were found to have superior mechanical properties than solution grown cocrystals. Additionally, moving to a TSE process eliminated the need for solvent.

Conatumumab (AMG 655) coated nanoparticles for targeted pro-apoptotic drug delivery.

PubMed

Fay, Francois; McLaughlin, Kirsty M; Small, Donna M; Fennell, Dean A; Johnston, Patrick G; Longley, Daniel B; Scott, Christopher J

2011-11-01

Colloidal nanoparticle drug delivery systems have attracted much interest for their ability to enable effective formulation and delivery of therapeutic agents. The selective delivery of these nanoparticles to the disease site can be enhanced by coating the surface of the nanoparticles with targeting moieties, such as antibodies. In this current work, we demonstrate that antibodies on the surface of the particles can also elicit key biological effects. Specifically, we demonstrate the induction of apoptosis in colorectal HCT116 cancer cells using PLGA nanoparticles coated with Conatumumab (AMG 655) death receptor 5-specific antibodies (DR5-NP). We show that DR5-NP preferentially target DR5-expressing cells and present a sufficient density of antibody paratopes to induce apoptosis via DR5, unlike free AMG 655 or non-targeted control nanoparticles. We also demonstrate that DR5-targeted nanoparticles encapsulating the cytotoxic drug camptothecin are effectively targeted to the tumour cells, thereby producing enhanced cytotoxic effects through simultaneous drug delivery and apoptosis induction. These results demonstrate that antibodies on nanoparticulate surfaces can be exploited for dual modes of action to enhance the therapeutic utility of the modality. Copyright © 2011 Elsevier Ltd. All rights reserved.

The chemistry of aminoguanidine derivatives - preparation, crystal structure, thermal properties, and molecular docking studies of aminoguanidinium salts of several carboxylic acids

NASA Astrophysics Data System (ADS)

Selvakumar, Rajendran; Geib, Steven J.; Muthu Sankar, Aathi; Premkumar, Thathan; Govindarajan, Subbaiah

2015-11-01

The reaction of aminoguanidine bicarbonate (Amg) with oxamic, oxalic, malonic and sulfoacetic acids yielded (AmgH)H2NOC-COO (1), OOC-CONHNHC(NH2)NH2 (2) (AmgH)HOOC-CH2-COO (3) and O3S-CH2-CONHNHC(NH2)NH2 (4), respectively. For the first time, we studied the salt-forming ability of aminoguanidine with several carboxylic acids, such as oxamic, oxalic, malonic and sulphoacetic acids. We also compared the structural and thermal properties of these salts. Oxamic and malonic acids form only mono-aminoguanidinium salts, whereas oxalic acid mainly forms di-aminoguanidinium oxalate. In addition, oxalic acid forms guanylhydrazido-oxalic acid which exists as zwitter ion. Unlike other acids, sulfoacetic acid readily forms only the zwitter ionic salts (2-guanylhydrazido-oxo-methanesulfonic acid) rather than the usual simple salt. This result may be a result of the highly acidic nature of the sulfonic group, which favors acid catalyzed condensation. More significantly, for the first time, the ability guanylhydrazido-oxalic acid (2) and 2-guanylhydrazido-oxo-methanesulfonic acid (4) to inhibit human butyrylcholinesterase (human BChE) receptor has been studied with a molecular docking approach. The binding of the compounds to human BChE was examined as it is crucial to understanding the biological significance of aminoguanidine derivatives. The compounds were identified and characterized by analytical, FT-IR spectroscopic and thermal studies. Furthermore, the structures of compounds 1, 2 and 4 were confirmed by single X-ray diffraction studies. Compounds 1 and 2 crystallized in a monoclinic crystal system with P21/c and Cc space groups, respectively, whereas compound 4 crystalized in an orthorhombic system with a Pbca space group. All the compounds (1-4) underwent endo- followed by exothermic decomposition in the temperature range from 130 to 600 °C to yield gaseous products.

Performance of Granular Starch with Controlled Pore Size during Hydrolysis with Digestive Enzymes.

PubMed

Benavent-Gil, Yaiza; Rosell, Cristina M

2017-12-01

Studies on porous starch have been directed to explore different industrial applications as bio-adsorbents of a variety of compounds. However, the analysis of starch digestibility is essential for food application. The objective of this study was to determine the impact of porous structure on in vitro starch digestibility. Porous starches were obtained using a range of concentrations of amyloglucosidase (AMG), α-amylase (AM), cyclodextrin-glycosyltransferase (CGTase) or branching enzyme (BE). Porous starches exhibited major content of digestible starch (DS) that increased with the intensity of the enzymatic treatment, and very low amount of resistant starch (RS). Porous starches behaved differently during in vitro hydrolysis depending on their enzymatic treatment. AMG was the unique treatment that increased the digestive amylolysis and estimated glycemic index, whereas AM, CGTase and BE reduced them. A significant relationship was found between the pore size and the severity of the amylolysis, suggesting that a specific pore size is required for the accessibility of the digestive amylase. Therefore, pore size in the starch surface was a limiting factor for digestion of starch granules.

Selective inhibition of receptor activator of NF-κB ligand (RANKL) in hematopoietic cells improves outcome after experimental myocardial infarction.

PubMed

Slavic, Svetlana; Andrukhova, Olena; Ford, Kristopher; Handschuh, Stephan; Latic, Nejla; Reichart, Ursula; Sasgary, Soleman; Bergow, Claudia; Hofbauer, Lorenz C; Kostenuik, Paul J; Erben, Reinhold G

2018-05-08

The RANK (receptor activator of nuclear factor κB)/RANKL (RANK ligand)/OPG (osteoprotegerin) axis is activated after myocardial infarction (MI), but its pathophysiological role is not well understood. Here, we investigated how global and cell compartment-selective inhibition of RANKL affects cardiac function and remodeling after MI in mice. Global RANKL inhibition was achieved by treatment of human RANKL knock-in (huRANKL-KI) mice with the monoclonal antibody AMG161. huRANKL-KI mice express a chimeric RANKL protein wherein part of the RANKL molecule is humanized. AMG161 inhibits human and chimeric but not murine RANKL. To dissect the pathophysiological role of RANKL derived from hematopoietic and mesenchymal cells, we selectively exchanged the hematopoietic cell compartment by lethal irradiation and across-genotype bone marrow transplantation between wild-type and huRANKL-KI mice, exploiting the specificity of AMG161. After permanent coronary artery ligation, mice were injected with AMG161 or an isotype control antibody over 4 weeks post-MI. MI increased RANKL expression mainly in cardiomyocytes and scar-infiltrating cells 4 weeks after MI. Only inhibition of RANKL derived from hematopoietic cellular sources, but not global or mesenchymal RANKL inhibition, improved post-infarct survival and cardiac function. Mechanistically, hematopoietic RANKL inhibition reduced expression of the pro-inflammatory cytokine IL-1ß in the cardiac cellular infiltrate. In conclusion, inhibition of RANKL derived from hematopoietic cellular sources is beneficial to maintain post-ischemic cardiac function by reduction of pro-inflammatory cytokine production. Experimental myocardial infarction (MI) augments cardiac RANKL expression in mice. RANKL expression is increased in cardiomyocytes and scar-infiltrating cells after MI. Global or mesenchymal cell RANKL inhibition has no influence on cardiac function after MI. Inhibition of RANKL derived from hematopoietic cells improves heart function post-MI. Hematopoietic RANKL inhibition reduces pro-inflammatory cytokines in scar-infiltrating cells.

Oxidative stress and nitrosative stress are involved in different stages of proteolytic pulmonary emphysema.

PubMed

Lanzetti, Manuella; da Costa, Cristiane Aguiar; Nesi, Renata Tiscoski; Barroso, Marina Valente; Martins, Vanessa; Victoni, Tatiana; Lagente, Vincent; Pires, Karla Maria Pereira; e Silva, Patrícia Machado Rodrigues; Resende, Angela Castro; Porto, Luis Cristóvão; Benjamim, Cláudia Farias; Valença, Samuel Santos

2012-12-01

Our aim was to investigate the role of oxidative stress in elastase-induced pulmonary emphysema. C57BL/6 mice were subjected to pancreatic porcine elastase (PPE) instillation (0.05 or 0.5 U per mouse, i.t.) to induce pulmonary emphysema. Lungs were collected on days 7, 14, and 21 after PPE instillation. The control group was sham injected. Also, mice treated with 1% aminoguanidine (AMG) and inducible NO synthase (iNOS) knockout mice received 0.5 U PPE (i.t.), and lungs were analyzed 21 days after. We performed bronchoalveolar lavage, biochemical analyses of oxidative stress, and lung stereology and morphometry assays. Emphysema was observed histologically at 21 days after 0.5 U PPE treatment; tissues from these mice exhibited increased alveolar linear intercept and air-space volume density in comparison with the control group. TNF-α was elevated at 7 and 14 days after 0.5 U PPE treatment, concomitant with a reduction in the IL-10 levels at the same time points. Myeloperoxidase was elevated in all groups treated with 0.5 U PPE. Oxidative stress was observed during early stages of emphysema, with increased nitrite levels and malondialdehyde and superoxide dismutase activity at 7 days after 0.5 U PPE treatment. Glutathione peroxidase activity was increased in all groups treated with 0.5 U PPE. The emphysema was attenuated when iNOS was inhibited using 1% AMG and in iNOS knockout mice. Furthermore, proteolytic stimulation by PPE enhanced the expression of nitrotyrosine and iNOS, whereas the PPE+AMG group showed low expression of iNOS and nitrotyrosine. PPE stimulus also induced endothelial (e) NOS expression, whereas AMG reduced eNOS. Our results suggest that the oxidative and nitrosative stress pathways are triggered by nitric oxide production via iNOS expression in pulmonary emphysema. Copyright © 2012 Elsevier Inc. All rights reserved.

[Non-commercial clinical trials--who will be the legal sponsor? Sponsorship of investigator-initiated clinical trials according to the German Drug Law].

PubMed

Benninger-Döring, G; Boos, J

2006-07-01

Non-commercial clinical trials may be of great benefit to the patients concerned. The 12th amendment to the German Drug Law (AMG) changed legal liability of the initiators of investigator-initiated clinical trials with extensive consequences for traditional project leaders. The central point under discussion is the sponsor's responsibility according to the AMG. Presently leading management divisions of university hospitals and universities are developing proceedings to assume sponsor responsibility by institutions (institutional sponsorship), which should enable investigator-initiated clinical trials to be conducted according to legal requirements in the future. Detailed problems and special questions can only be resolved in a single-minded fashion, and if necessary political processes should be catalyzed.

Differential Effects of Inescapable Stress on Locus Coeruleus GRK3, Alpha2-Adrenoceptor and CRF1 Receptor Levels in Learned Helpless and Non-Helpless Rats: A potential link to stress resilience

PubMed Central

Taneja, Manish; Salim, Samina; Saha, Kaustuv; Happe, H. Kevin; Qutna, Nidal; Petty, Frederick; Bylund, David B.; Eikenburg, Douglas C.

2011-01-01

Exposure of rats to unpredictable, inescapable stress results in two distinct behaviors during subsequent escape testing. One behavior, suggestive of lack of stress resilience, is prolonged escape latency compared to non-stressed rats and is labeled learned helplessness (LH). The other behavior suggestive of stress resilience is normal escape latency and is labeled non-helpless (NH). This study examines the effects of unpredictable, inescapable tail-shock stress (TSS) on alpha2-adrenoceptor (α2-AR) and corticotropin-releasing factor 1 receptor (CRF1) regulation as well as protein levels of G protein-coupled receptor kinase 3 (GRK3), GRK2, tyrosine hydroxylase (TH) plus carbonylated protein levels in locus coeruleus (LC), amygdala (AMG), cortex (COR) and striatum (STR). In NH rats, α2-AR and CRF1 receptors were significantly down-regulated in LC after TSS. No changes in these receptor levels were observed in the LC of LH rats. GRK3, which phosphorylates receptors and thereby contributes to α2-AR and CRF1 receptor down-regulation, was reduced in the LC of LH but not NH rats. GRK2 levels were unchanged. In AMG, GRK3 but not GRK2 levels were reduced in LH but not NH rats, and receptor regulation was impaired in LH rats. In STR, no changes in GRK3 or GRK2 levels were observed. Finally, protein carbonylation, an index of oxidative stress, was increased in the LC and AMG of LH but not NH rats. We suggest that reduced stress resilience after TSS may be related to oxidative stress, depletion of GRK3 and impaired regulation of α2-AR and CRF1 receptor in LC. PMID:21333691

Development of an instant coffee enriched with chlorogenic acids.

PubMed

Corso, Marinês Paula; Vignoli, Josiane Alessandra; Benassi, Marta de Toledo

2016-03-01

The objective of this study was to present possible formulations for an instant coffee product enriched with chlorogenic acids for the Brazilian market. Formulations were prepared with different concentrations of freeze dried extracts of green Coffea canephora beans (G) added to freeze dried extracts of roasted Coffea arabica (A) and Coffea canephora (C). Medium (M) and dark (D) roasting degrees instant coffee were produced (AM, AD, CM and CD) to obtain four formulations with green extract addition (AMG, ADG, CMG and CDG). Chlorogenic acids were determined by HPLC, with average contents of 7.2 %. Roasted extracts and formulations were evaluated for 5-CQA and caffeine contents (by HPLC), browned compounds (absorbance 420 nm), and antioxidant activity (ABTS and Folin). Coffee brews of the four formulations were also assessed in a lab-scale test by 42 consumers for acceptance of the color, aroma, flavor and body, overall acceptance and purchase intent, using a 10 cm hybrid scale. The formulations obtained acceptance scores of 6.6 and 7.7 for all attributes, thus they were equally acceptable. Greater purchase intent was observed for ADG, CDG and CMG (6.9) in comparison to AMG (6.1). The formulations had, on average, 2.5 times more 5-CQA than the average obtained from conventional commercial instant coffees. In addition to being more economically viable, the formulations developed with C. canephora (CDG and CMG) showed greater antioxidant potential (32.5 g of Trolox/100 g and 13.8 g of gallic acid equivalent/100 g) due to a balance in the amount of bioactive compounds.

Upscaling of Mixed Finite Element Discretization Problems by the Spectral AMGe Method

DOE PAGES

Kalchev, Delyan Z.; Lee, C. S.; Villa, U.; ...

2016-09-22

Here, we propose two multilevel spectral techniques for constructing coarse discretization spaces for saddle-point problems corresponding to PDEs involving a divergence constraint, with a focus on mixed finite element discretizations of scalar self-adjoint second order elliptic equations on general unstructured grids. We use element agglomeration algebraic multigrid (AMGe), which employs coarse elements that can have nonstandard shape since they are agglomerates of fine-grid elements. The coarse basis associated with each agglomerated coarse element is constructed by solving local eigenvalue problems and local mixed finite element problems. This construction leads to stable upscaled coarse spaces and guarantees the inf-sup compatibility ofmore » the upscaled discretization. Also, the approximation properties of these upscaled spaces improve by adding more local eigenfunctions to the coarse spaces. The higher accuracy comes at the cost of additional computational effort, as the sparsity of the resulting upscaled coarse discretization (referred to as operator complexity) deteriorates when we introduce additional functions in the coarse space. We also provide an efficient solver for the coarse (upscaled) saddle-point system by employing hybridization, which leads to a symmetric positive definite (s.p.d.) reduced system for the Lagrange multipliers, and to solve the latter s.p.d. system, we use our previously developed spectral AMGe solver. Numerical experiments, in both two and three dimensions, are provided to illustrate the efficiency of the proposed upscaling technique.« less

Upscaling of Mixed Finite Element Discretization Problems by the Spectral AMGe Method

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

Kalchev, Delyan Z.; Lee, C. S.; Villa, U.

Here, we propose two multilevel spectral techniques for constructing coarse discretization spaces for saddle-point problems corresponding to PDEs involving a divergence constraint, with a focus on mixed finite element discretizations of scalar self-adjoint second order elliptic equations on general unstructured grids. We use element agglomeration algebraic multigrid (AMGe), which employs coarse elements that can have nonstandard shape since they are agglomerates of fine-grid elements. The coarse basis associated with each agglomerated coarse element is constructed by solving local eigenvalue problems and local mixed finite element problems. This construction leads to stable upscaled coarse spaces and guarantees the inf-sup compatibility ofmore » the upscaled discretization. Also, the approximation properties of these upscaled spaces improve by adding more local eigenfunctions to the coarse spaces. The higher accuracy comes at the cost of additional computational effort, as the sparsity of the resulting upscaled coarse discretization (referred to as operator complexity) deteriorates when we introduce additional functions in the coarse space. We also provide an efficient solver for the coarse (upscaled) saddle-point system by employing hybridization, which leads to a symmetric positive definite (s.p.d.) reduced system for the Lagrange multipliers, and to solve the latter s.p.d. system, we use our previously developed spectral AMGe solver. Numerical experiments, in both two and three dimensions, are provided to illustrate the efficiency of the proposed upscaling technique.« less

Porting AMG2013 to Heterogeneous CPU+GPU Nodes

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

Samfass, Philipp

LLNL's future advanced technology system SIERRA will feature heterogeneous compute nodes that consist of IBM PowerV9 CPUs and NVIDIA Volta GPUs. Conceptually, the motivation for such an architecture is quite straightforward: While GPUs are optimized for throughput on massively parallel workloads, CPUs strive to minimize latency for rather sequential operations. Yet, making optimal use of heterogeneous architectures raises new challenges for the development of scalable parallel software, e.g., with respect to work distribution. Porting LLNL's parallel numerical libraries to upcoming heterogeneous CPU+GPU architectures is therefore a critical factor for ensuring LLNL's future success in ful lling its national mission. Onemore » of these libraries, called HYPRE, provides parallel solvers and precondi- tioners for large, sparse linear systems of equations. In the context of this intern- ship project, I consider AMG2013 which is a proxy application for major parts of HYPRE that implements a benchmark for setting up and solving di erent systems of linear equations. In the following, I describe in detail how I ported multiple parts of AMG2013 to the GPU (Section 2) and present results for di erent experiments that demonstrate a successful parallel implementation on the heterogeneous ma- chines surface and ray (Section 3). In Section 4, I give guidelines on how my code should be used. Finally, I conclude and give an outlook for future work (Section 5).« less

Clinical and analytical evaluation of the new Aptima Mycoplasma genitalium assay, with data on M. genitalium prevalence and antimicrobial resistance in M. genitalium in Denmark, Norway and Sweden in 2016.

PubMed

Unemo, M; Salado-Rasmussen, K; Hansen, M; Olsen, A O; Falk, M; Golparian, D; Aasterød, M; Ringlander, J; Nilsson, C Stezckó; Sundqvist, M; Schønning, K; Moi, H; Westh, H; Jensen, J S

2018-05-01

Mycoplasma genitalium (MG) causes urethritis and cervicitis, potentially causing reproductive complications. Resistance in MG to first-line (azithromycin) and second-line (moxifloxacin) treatment has increased. We examined the clinical and analytical performance of the new Conformité Européene (CE)/in vitro diagnostics (IVD) Aptima Mycoplasma genitalium assay (CE/IVD AMG; Hologic); the prevalence of MG, Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); and MG resistance to azithromycin and moxifloxacin in Denmark, Norway and Sweden in 2016. From February 2016 to February 2017, urogenital and extragenital (only in Denmark) specimens from consecutive attendees at three sexually transmitted disease clinics were tested with the CE/IVD AMG, the research-use-only MG Alt TMA-1 assay (Hologic), Aptima Combo 2 (CT/NG) assay and a laboratory-developed TaqMan real-time mgpB quantitative real-time PCR (qPCR). Resistance-associated mutations were determined by sequencing. Strains of MG and other mycoplasma species in different concentrations were also tested. In total 5269 patients were included. The prevalence of MG was 7.2% (382/5269; 4.9-9.8% in the countries). The sensitivity of the CE/IVD AMG, MG Alt TMA-1 and mgpB qPCR ranged 99.13-100%, 99.13-100% and 73.24-81.60%, respectively, in the countries. The specificity ranged 99.57-99.96%, 100% and 99.69-100%, respectively. The prevalence of resistance-associated mutations for azithromycin and moxifloxacin was 41.4% (120/290; 17.7-56.6%) and 6.6% (18/274; 4.1-10.2%), respectively. Multidrug resistance was found in all countries (2.7%; 1.1-4.2%). Both transcription-mediated amplification (TMA)-based MG assays had a highly superior sensitivity compared to the mgpB qPCR. The prevalence of MG and azithromycin resistance was high. Validated and quality-assured molecular tests for MG, routine resistance testing of MG-positive samples and antimicrobial resistance surveillance are crucial. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Humidity induced phase transformation of poloxamer 188 and its effect on physical stability of amorphous solid dispersion of AMG 579, a PDE10A inhibitor.

PubMed

Wu, Qiong; Kennedy, Michael T; Nagapudi, Karthik; Kiang, Y-H

2017-04-15

Poloxamer 188, a commonly used emulsifying and solubilizing agent, was found to be the cause of crystallization of an investigational drug, AMG 579, from its amorphous solid dispersion at accelerated storage conditions. Investigation of this physical stability issue included thorough characterization of poloxamer 188 at non-ambient conditions. At 40°C, poloxamer 188 becomes deliquescent above relative humidity of 75%. Upon returning to ambient conditions, the deliquescent poloxamer 188 loses water and re-solidifies. The reversible phase transformation of poloxamer 188 may cause physical and chemical stability issues and this risk should be assessed when selecting it as an excipient for formulation development. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of Proxy Application Performance on Advanced Architectures. UMT2013, MCB, AMG2013

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

Howell, Louis H.; Gunney, Brian T.; Bhatele, Abhinav

2015-10-09

Three codes were tested at LLNL as part of a Tri-Lab effort to make detailed assessments of several proxy applications on various advanced architectures, with the eventual goal of extending these assessments to codes of programmatic interest running more realistic simulations. Teams from Sandia and Los Alamos tested proxy apps of their own. The focus in this report is on the LLNL codes UMT2013, MCB, and AMG2013. We present weak and strong MPI scaling results and studies of OpenMP efficiency on a large BG/Q system at LLNL, with comparison against similar tests on an Intel Sandy Bridge TLCC2 system. Themore » hardware counters on BG/Q provide detailed information on many aspects of on-node performance, while information from the mpiP tool gives insight into the reasons for the differing scaling behavior on these two different architectures. Results from three more speculative tests are also included: one that exploits NVRAM as extended memory, one that studies performance under a power bound, and one that illustrates the effects of changing the torus network mapping on BG/Q.« less

Effect of aminoguanidine and albendazole on inducible nitric oxide synthase (iNOS) activity in T. spiralis-infected mice muscles.

PubMed

Zeromski, Jan; Boczoń, Krystyna; Wandurska-Nowak, Elzbieta; Mozer-Lisewska, Iwona

2005-01-01

The aim of this study was to provide evidence for the expression of iNOS in the cells of inflammatory infiltrates around larvae in skeletal muscles of T. spiralis infected mice. The BALB/c mice (n = 8) divided into subgroups, received either aminoguanidine (AMG)--a specific iNOS inhibitor or albendazole (ALB)--an antiparasitic drug of choice in trichinellosis treatment. Control animals (n = 2 in each subgroup) were either uninfected and treated or uninfected and untreated. Frozen sections of hind leg muscles from mice sacrificed at various time intervals after infection were cut and subjected to immunohistochemistry, using monoclonal anti-iNOS antibody. The ALB-treated mice revealed stronger iNOS staining in the infiltrating cells around larvae than the infected and untreated animals. On the contrary, in the AMG-treated animals, the infiltrating cells did not show any specific iNOS reaction. These data confirm the specificity of iNOS staining in the cellular infiltrates around T. spiralis larvae and shed some light on the role of nitric oxide during ALB treatment in experimental trichinellosis.

Multigrid accelerated simulations for Twisted Mass fermions

NASA Astrophysics Data System (ADS)

Bacchio, Simone; Alexandrou, Constantia; Finkerath, Jacob

2018-03-01

Simulations at physical quark masses are affected by the critical slowing down of the solvers. Multigrid preconditioning has proved to deal effectively with this problem. Multigrid accelerated simulations at the physical value of the pion mass are being performed to generate Nf = 2 and Nf = 2 + 1 + 1 gauge ensembles using twisted mass fermions. The adaptive aggregation-based domain decomposition multigrid solver, referred to as DD-αAMG method, is employed for these simulations. Our simulation strategy consists of an hybrid approach of different solvers, involving the Conjugate Gradient (CG), multi-mass-shift CG and DD-αAMG solvers. We present an analysis of the multigrid performance during the simulations discussing the stability of the method. This significant speeds up the Hybrid Monte Carlo simulation by more than a factor 4 at physical pion mass compared to the usage of the CG solver.

Shedding new light on viral photosynthesis.

PubMed

Puxty, Richard J; Millard, Andrew D; Evans, David J; Scanlan, David J

2015-10-01

Viruses infecting the environmentally important marine cyanobacteria Prochlorococcus and Synechococcus encode 'auxiliary metabolic genes' (AMGs) involved in the light and dark reactions of photosynthesis. Here, we discuss progress on the inventory of such AMGs in the ever-increasing number of viral genome sequences as well as in metagenomic datasets. We contextualise these gene acquisitions with reference to a hypothesised fitness gain to the phage. We also report new evidence with regard to the sequence and predicted structural properties of viral petE genes encoding the soluble electron carrier plastocyanin. Viral copies of PetE exhibit extensive modifications to the N-terminal signal peptide and possess several novel residues in a region responsible for interaction with redox partners. We also highlight potential knowledge gaps in this field and discuss future opportunities to discover novel phage-host interactions involved in the photosynthetic process.

Pressure broadening and frequency shift of the D 1 and D 2 lines of K in the presence of Ne and Kr

NASA Astrophysics Data System (ADS)

Wang, Xulin; Chen, Yao; Quan, Wei; Chi, Haotian; Fang, Jiancheng

2018-02-01

We present the results of pressure broadening and frequency shift of K D 1 and D 2 lines in presence of 1-4 amg of Neon gas and 1-5 amg of Krypton gas by laser absorption spectroscopy. Both pressure broadening and frequency shift are linearly related to gas density with high accuracy. The asymmetry of the absorption line shape caused by van der Waals potential was first found in the near-line wings of large density Kr in the experiment. We have also investigated the temperature dependence of the pressure broadening and frequency shift in a range of 353-403 K in Neon and 373-417 K in Krypton and compared the results of the pressure broadening and frequency shift with previous values.

Energy limitation of cyanophage development: implications for marine carbon cycling.

PubMed

Puxty, Richard J; Evans, David J; Millard, Andrew D; Scanlan, David J

2018-05-01

Marine cyanobacteria are responsible for ~25% of the fixed carbon that enters the ocean biosphere. It is thought that abundant co-occurring viruses play an important role in regulating population dynamics of cyanobacteria and thus the cycling of carbon in the oceans. Despite this, little is known about how viral infections 'play-out' in the environment, particularly whether infections are resource or energy limited. Photoautotrophic organisms represent an ideal model to test this since available energy is modulated by the incoming light intensity through photophosphorylation. Therefore, we exploited phototrophy of the environmentally relevant marine cyanobacterium Synechococcus and monitored growth of a cyanobacterial virus (cyanophage). We found that light intensity has a marked effect on cyanophage infection dynamics, but that this is not manifest by a change in DNA synthesis. Instead, cyanophage development appears energy limited for the synthesis of proteins required during late infection. We posit that acquisition of auxiliary metabolic genes (AMGs) involved in light-dependent photosynthetic reactions acts to overcome this limitation. We show that cyanophages actively modulate expression of these AMGs in response to light intensity and provide evidence that such regulation may be facilitated by a novel mechanism involving light-dependent splicing of a group I intron in a photosynthetic AMG. Altogether, our data offers a mechanistic link between diurnal changes in irradiance and observed community level responses in metabolism, i.e., through an irradiance-dependent, viral-induced release of dissolved organic matter (DOM).

Personality characteristics and attributes of international medical graduates in general practice training: Implications for supporting this valued Australian workforce.

PubMed

Laurence, Caroline O; Eley, Diann S; Walters, Lucie; Elliott, Taryn; Cloninger, Claude Robert

2016-10-01

To describe the personality profiles of International Medical Graduates (IMGs) undertaking General Practice (GP) training in Australia. A better understanding of the personal characteristics of IMGs may inform their training and enhance support for their vital contribution to the Australian rural workforce. Cross-sectional self-report questionnaires. Independent variables included socio-demographics, prior training, the Temperament and Character Inventory, and the Resilience Scale. GP registrars (IMGs = 102; AMGs = 350) training in the Australian General Practice Training rural and general pathway and the Australian College of Rural and Remote Medicine independent pathway. Univariate analysis explored the differences in levels of traits between IMG and AMG registrars. Compared to the general population both groups have moderately high resilience, and well-organised characters with high Self-directedness, high Cooperativeness and low Self-transcendence, supported by temperaments which were high in Persistence and Reward Dependence. IMGs were different than AMGs in two temperament traits, Novelty Seeking and Persistence and two character traits, Self-directedness and Cooperativeness. Factors such as cultural and training backgrounds, personal and professional expectations, and adjustments necessary to assimilate to a new lifestyle and health system are likely to be responsible for differences found between groups. Understanding the personality profiles of IMGs provides opportunities for targeted training and support which may in turn impact on their retention in rural areas. © 2016 National Rural Health Alliance Inc.

Denosumab: an investigational drug for the management of postmenopausal osteoporosis

PubMed Central

Lewiecki, E Michael

2008-01-01

Denosumab (AMG 162) is an investigational fully human monoclonal antibody with a high affinity and specificity for receptor activator of nuclear factor-κB ligand (RANKL), a cytokine member of the tumor necrosis factor family. RANKL, the principal mediator of osteoclastic bone resorption, plays a major role in the pathogenesis of postmenopausal osteoporosis and other skeletal disorders associated with bone loss. Denosumab inhibits the action of RANKL, thereby reducing the differentiation, activity, and survival of osteoclasts, and lowering the rate of bone resorption. Clinical trials have shown that denosumab increases bone mineral density (BMD) and reduces bone turnover in postmenopausal women with low BMD. Studies to evaluate the fracture risk benefit and long-term safety of denosumab in women with postmenopausal osteoporosis (PMO) are ongoing. Denosumab is a potential treatment for PMO and other skeletal disorders. PMID:19707445

Characterization of amygdalin-degrading Lactobacillus species.

PubMed

Menon, R; Munjal, N; Sturino, J M

2015-02-01

Cyanogenic glycosides are phytotoxic secondary metabolites produced by some crop plants. The aim of this study was to identify lactic acid bacteria (LAB) capable of catabolizing amygdalin, a model cyanogenic glycoside, for use in the biodetoxification of amygdalin-containing foods and feeds. Amygdalin-catabolizing lactobacilli were characterized using a combination of cultivation-dependent and molecular assays. Lactobacillus paraplantarum and Lactobacillus plantarum grew robustly on amygdalin (Amg(+)), while other LAB species typically failed to catabolize amygdalin (Amg(-)). Interestingly, high concentrations of amygdalin and two of its metabolic derivatives (mandelonitrile and benzaldehyde) inhibited the growth of Lact. plantarum RENO 0093. The differential regulation of genes tentatively involved in cyanohydrin metabolism illustrated that the metabolism of amygdalin- and glucose-grown cultures also differed significantly. Amygdalin fermentation was a relatively uncommon phenotype among the LAB and generally limited to strains from the Lact. plantarum group. Phenotype microarrays (PM) enabled strain-level discrimination between closely related strains within a species and suggested that phenotypic differences might affect niche specialization. Amygdalin-degrading lactobacilli with practical application in the biodetoxification of amygdalin were characterized. These strains show potential for use as starter cultures to improve the safety of foods and feeds. © 2014 The Society for Applied Microbiology.

Thermoelectric properties of AMg 2X 2, AZn 2Sb 2 (A = Ca, Sr, Ba; X = Sb, Bi), and Ba 2ZnX 2 (X = Sb, Bi) Zintl compounds

DOE PAGES

Sun, Jifeng; Singh, David J.

2017-04-03

In this paper, we report a theoretical investigation of the electronic structure and transport properties of eleven Zintl compounds including nine 122 phases (AMg 2X 2, AZn 2Sb 2 (A = Ca, Sr, Ba; X = Sb, Bi)) and two 212 phases (Ba 2ZnX 2 (X = Sb, Bi)). The electronic structures and electrical transport properties are studied using ab initio calculations and semi-classical Boltzmann theory within the constant relaxation time approximation. All the compounds are semiconducting. We find that the n-type 122 phases with the CaAl 2Si 2 structure type show better performance than p-type materials due to themore » multi-valley degeneracy with anisotropic carrier pockets at and near the conduction band minimum. The pocket anisotropy is beneficial in achieving high conductivity and Seebeck coefficient simultaneously. This mechanism yields substantial improvement in the power factor. Finally, the general performance of 212 phases is inferior to that of the 122 phases, with the Ba 2ZnSb 2 compound showing better performance.« less

Pd@Pt core-shell concave decahedra: A class of catalysts for the oxygen reduction reaction with enhanced activity and durability

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

Wang, Xue; Vera, Madeline; Chi, Miaofang

Here, we report a facile synthesis of multiply twinned Pd@Pt core shell concave decahedra by controlling the deposition of Pt on preformed Pd decahedral seeds. The Pt atoms are initially deposited on the vertices of a decahedral seed, followed by surface diffusion to other regions along the edges/ridges and then across the faces. Different from the coating of a Pd icosahedral seed, the Pt atoms prefer to stay at the vertices and edges/ridges of a decahedral seed even when the deposition is conducted at 200 degrees C, naturally generating a core shell structure covered by concave facets. The nonuniformity inmore » the Pt coating can be attributed to the presence of twin boundaries at the vertices, as well as the {100} facets and twin defects along the edges/ridges of a decahedron, effectively trapping the Pt adatoms at these high-energy sites. As compared to a commercial Pt/C catalyst, the Pd@Pt concave decahedra show substantial enhancement in both catalytic activity and durability toward the oxygen reduction reaction (ORR). For the concave decahedra with 29.6% Pt by weight, their specific (1.66 mA/cm 2 pt) and mass (1.60 A/mg/ 2 pt) ORR activities are enhanced by 4.4 and 6.6 times relative to those of the Pt/C catalyst (0.36 mA/cm 2 pt and 0.32 A/mg pt, respectively). After 10 000 cycles of accelerated durability test, the concave decahedra still exhibit a mass activity of 0.69 A/mg pt, more than twice that of the pristine Pt/C catalyst.« less

Pd@Pt core-shell concave decahedra: A class of catalysts for the oxygen reduction reaction with enhanced activity and durability

DOE PAGES

Wang, Xue; Vera, Madeline; Chi, Miaofang; ...

2015-11-13

Here, we report a facile synthesis of multiply twinned Pd@Pt core shell concave decahedra by controlling the deposition of Pt on preformed Pd decahedral seeds. The Pt atoms are initially deposited on the vertices of a decahedral seed, followed by surface diffusion to other regions along the edges/ridges and then across the faces. Different from the coating of a Pd icosahedral seed, the Pt atoms prefer to stay at the vertices and edges/ridges of a decahedral seed even when the deposition is conducted at 200 degrees C, naturally generating a core shell structure covered by concave facets. The nonuniformity inmore » the Pt coating can be attributed to the presence of twin boundaries at the vertices, as well as the {100} facets and twin defects along the edges/ridges of a decahedron, effectively trapping the Pt adatoms at these high-energy sites. As compared to a commercial Pt/C catalyst, the Pd@Pt concave decahedra show substantial enhancement in both catalytic activity and durability toward the oxygen reduction reaction (ORR). For the concave decahedra with 29.6% Pt by weight, their specific (1.66 mA/cm 2 pt) and mass (1.60 A/mg/ 2 pt) ORR activities are enhanced by 4.4 and 6.6 times relative to those of the Pt/C catalyst (0.36 mA/cm 2 pt and 0.32 A/mg pt, respectively). After 10 000 cycles of accelerated durability test, the concave decahedra still exhibit a mass activity of 0.69 A/mg pt, more than twice that of the pristine Pt/C catalyst.« less

Roles of TRPV1 and TRPA1 in Spontaneous Pain from Inflamed Masseter Muscle.

PubMed

Wang, Sheng; Brigoli, Benjamin; Lim, Jongseuk; Karley, Alisha; Chung, Man-Kyo

2018-06-08

Craniofacial muscle pain, such as spontaneous pain and bite-evoked pain, are major symptoms in patients with temporomandibular disorders and infection. However, the underlying mechanisms of muscle pain, especially mechanisms of highly prevalent spontaneous pain, are poorly understood. Recently, we reported that transient receptor potential vanilloid 1 (TRPV1) contributes to spontaneous pain but only marginally contributes to bite-evoked pain during masseter inflammation. Here, we investigated the role of transient receptor potential ankyrin 1 (TRPA1) in spontaneous and bite-evoked pain during masseter inflammation, and dissected the relative contributions of TRPA1 and TRPV1. Masseter inflammation increased mouse grimace scale (MGS) scores and face wiping behaviors. Pharmacological or genetic inhibition of TRPA1 significantly attenuated MGS but not face wiping behaviors. MGS scores were also attenuated by scavenging putative endogenous ligands for TRPV1 or TRPA1. Simultaneous inhibition of TRPA1 by AP18 and TRPV1 by AMG9810 in masseter muscle resulted in robust inhibition of both MGS and face wiping behaviors. Administration of AP18 or AMG9810 to masseter muscle induced conditioned place preference (CPP). The extent of CPP following simultaneous administration of AP18 and AMG9810 was greater than that induced by the individual antagonists. In contrast, inflammation-induced reduction of bite force was not affected by the inhibition of TRPA1 alone or in combination with TRPV1. These results suggest that simultaneous inhibition of TRPV1 and TRPA1 produces additive relief of spontaneous pain, but does not ameliorate bite-evoked pain during masseter inflammation. Our results provide further evidence that distinct mechanisms underlie spontaneous and bite-evoked pain from inflamed masseter muscle. Copyright © 2018. Published by Elsevier Ltd.

Cavitation Fracture of the Typical Materials Used in Hydraulic Machines and Units

NASA Astrophysics Data System (ADS)

Kovalev, A. A.; Kuznetsov, N. N.

2017-12-01

The cavitation fracture of AMg6, BrAZh9-4, grade 20 steel, 12Kh18N10T, 20Kh13, and VT1-0 alloys, which are used in hydraulic machines and units, is studied. In tests, the materials are subjected to ultrasonic waves and the sample mass loss and the microhardness are measured. It is shown that new cavitation- resistant materials, which have a sufficient strength and plasticity, should be designed.

Sodium transport through the cerebral sodium-glucose transporter exacerbates neuron damage during cerebral ischaemia.

PubMed

Yamazaki, Yui; Harada, Shinichi; Wada, Tetsuyuki; Yoshida, Shigeru; Tokuyama, Shogo

2016-07-01

We recently demonstrated that the cerebral sodium-glucose transporter (SGLT) is involved in postischaemic hyperglycaemia-induced exacerbation of cerebral ischaemia. However, the associated SGLT-mediated mechanisms remain unclear. Thus, we examined the involvement of cerebral SGLT-induced excessive sodium ion influx in the development of cerebral ischaemic neuronal damage. [Na+]i was estimated according to sodium-binding benzofuran isophthalate fluorescence. In the in vitro study, primary cortical neurons were prepared from fetuses of ddY mice. Primary cortical neurons were cultured for 5 days before each treatment with reagents, and these survival rates were assessed using biochemical assays. In in vivo study, a mouse model of focal ischaemia was generated using middle cerebral artery occlusion (MCAO). In these experiments, treatment with high concentrations of glucose induced increment in [Na+]i, and this phenomenon was suppressed by the SGLT-specific inhibitor phlorizin. SGLT-specific sodium ion influx was induced using a-methyl-D-glucopyranoside (a-MG) treatments, which led to significant concentration-dependent declines in neuronal survival rates and exacerbated hydrogen peroxide-induced neuronal cell death. Moreover, phlorizin ameliorated these effects. Finally, intracerebroventricular administration of a-MG exacerbated the development of neuronal damage induced by MCAO, and these effects were ameliorated by the administration of phlorizin. Hence, excessive influx of sodium ions into neuronal cells through cerebral SGLT may exacerbate the development of cerebral ischaemic neuronal damage. © 2016 Royal Pharmaceutical Society.

The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature.

PubMed

Alawi, Khadija M; Aubdool, Aisah A; Liang, Lihuan; Wilde, Elena; Vepa, Abhinav; Psefteli, Maria-Paraskevi; Brain, Susan D; Keeble, Julie E

2015-10-01

Transient receptor potential vanilloid 1 (TRPV1) is involved in sensory nerve nociceptive signaling. Recently, it has been discovered that TRPV1 receptors also regulate basal body temperature in multiple species from mice to humans. In the present study, we investigated whether TRPV1 modulates basal sympathetic nervous system (SNS) activity. C57BL6/J wild-type (WT) mice and TRPV1 knockout (KO) mice were implanted with radiotelemetry probes for measurement of core body temperature. AMG9810 (50 mg/kg) or vehicle (2% DMSO/5% Tween 80/10 ml/kg saline) was injected intraperitoneally. Adrenoceptor antagonists or vehicle (5 ml/kg saline) was injected subcutaneously. In WT mice, the TRPV1 antagonist, AMG9810, caused significant hyperthermia, associated with increased noradrenaline concentrations in brown adipose tissue. The hyperthermia was significantly attenuated by the β-adrenoceptor antagonist propranolol, the mixed α-/β-adrenoceptor antagonist labetalol, and the α1-adrenoceptor antagonist prazosin. TRPV1 KO mice have a normal basal body temperature, indicative of developmental compensation. d-Amphetamine (potent sympathomimetic) caused hyperthermia in WT mice, which was reduced in TRPV1 KO mice, suggesting a decreased sympathetic drive in KOs. This study provides new evidence that TRPV1 controls thermoregulation upstream of the SNS, providing a potential therapeutic target for sympathetic hyperactivity thermoregulatory disorders. © FASEB.

Morphological and physicochemical characterization of porous starches obtained from different botanical sources and amylolytic enzymes.

PubMed

Benavent-Gil, Yaiza; Rosell, Cristina M

2017-10-01

Porous starches might offer an attractive alternative as bio-adsorbents of a variety of compounds. However, morphology and physicochemical properties of starches must be understood before exploring their applications. Objective was to study the action of different amylolytic enzymes for producing porous starches. Wheat, rice, potato and cassava starches were treated with Amyloglucosidase (AMG), α-amylase (AM) and cyclodextrin-glycosyltransferase (CGTase). Morphological characteristics, chemical composition, adsorptive capacity and pasting/thermal properties were assessed. Scanning Electron Microscopy (SEM) showed porous structures with diverse pore size distribution, which was dependent on the enzyme type and starch source, but no differences were observed in the total granule surface occupied by pores. The adsorptive capacity analysis revealed that modified starches had high water absorptive capacity and showed different oil adsorptive capacity depending on the enzyme type. Amylose content analysis revealed different hydrolysis pattern of the amylases, suggesting that AMG mainly affected crystalline region meanwhile AM and CGTase attacked amorphous area. A heatmap illustrated the diverse pasting properties of the different porous starches, which also showed significant different thermal properties, with different behavior between cereal and tuber starches. Therefore, it is possible to modulate the properties of starches through the use of different enzymes. Copyright © 2017 Elsevier B.V. All rights reserved.

[Validity of adjusted morbidity groups with respect to clinical risk groups in the field of primary care].

PubMed

Monterde, David; Vela, Emili; Clèries, Montse; García Eroles, Luis; Pérez Sust, Pol

2018-02-09

To compare the performance in terms of goodness of fit and explanatory power of 2morbidity groupers in primary care (PC): adjusted morbidity groups (AMG) and clinical risk groups (CRG). Cross-sectional study. PC in the Catalan Institute for the Health (CIH), Catalonia, Spain. Population allocated in primary care centers of the CIH for the year 2014. Three indicators of interest are analyzed such as urgent hospitalization, number of visits and spending in pharmacy. A stratified analysis by centers is applied adjusting generalized lineal models from the variables age, sex and morbidity grouping to explain each one of the 3variables of interest. The statistical measures to analyze the performance of the different models applied are the Akaike index, the Bayes index and the pseudo-variability explained by deviance change. The results show that in the area of the primary care the explanatory power of the AMGs is higher to that offered by the CRGs, especially for the case of the visits and the pharmacy. The performance of GMAs in the area of the CIH PC is higher than that shown by the CRGs. Copyright © 2018 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.

MDM2 Inhibitor AMG-232 and Decitabine in Treating Patients With Relapsed, Refractory, or Newly-Diagnosed Acute Myeloid Leukemia

ClinicalTrials.gov

2018-06-18

Acute Myeloid Leukemia; Blasts 5 Percent or More of Bone Marrow Nucleated Cells; Recurrent Adult Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; TP53 wt Allele; Untreated Adult Acute Myeloid Leukemia

75 FR 1455 - Custody of Funds or Securities of Clients by Investment Advisers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-11

... the internal controls relating to the custody of those assets from an independent public accountant... must obtain or receive an internal control report within six months of the effective date. Section III... securities (SIFMA(AMG) Letter), requiring an internal control report only instead of both the report and a...

TRPV1 and PLC Participate in Histamine H4 Receptor-Induced Itch.

PubMed

Jian, Tunyu; Yang, Niuniu; Yang, Yan; Zhu, Chan; Yuan, Xiaolin; Yu, Guang; Wang, Changming; Wang, Zhongli; Shi, Hao; Tang, Min; He, Qian; Lan, Lei; Wu, Guanyi; Tang, Zongxiang

2016-01-01

Histamine H4 receptor has been confirmed to play a role in evoking peripheral pruritus. However, the ionic and intracellular signaling mechanism of activation of H4 receptor on the dorsal root ganglion (DRG) neurons is still unknown. By using cell culture and calcium imaging, we studied the underlying mechanism of activation of H4 receptor on the DRG neuron. Immepip dihydrobromide (immepip)-a histamine H4 receptor special agonist under cutaneous injection-obviously induced itch behavior of mice. Immepip-induced scratching behavior could be blocked by TRPV1 antagonist AMG9810 and PLC pathway inhibitor U73122. Application of immepip (8.3-50 μM) could also induce a dose-dependent increase in intracellular Ca(2+) ([Ca(2+)]i) of DRG neurons. We found that 77.8% of the immepip-sensitized DRG neurons respond to the TRPV1 selective agonist capsaicin. U73122 could inhibit immepip-induced Ca(2+) responses. In addition, immepip-induced [Ca(2+)]i increase could be blocked by ruthenium red, capsazepine, and AMG9810; however it could not be blocked by TRPA1 antagonist HC-030031. These results indicate that TRPV1 but not TRPA1 is the important ion channel to induce the DRG neurons' responses in the downstream signaling pathway of histamine H4 receptor and suggest that TRPV1 may be involved in the mechanism of histamine-induced itch response by H4 receptor activation.

What's Cooler Than Being Cool? Ice-Sheet Models Using a Fluidity-Based FOSLS Approach to Nonlinear-Stokes Flow

NASA Astrophysics Data System (ADS)

Allen, Jeffery M.

This research involves a few First-Order System Least Squares (FOSLS) formulations of a nonlinear-Stokes flow model for ice sheets. In Glen's flow law, a commonly used constitutive equation for ice rheology, the viscosity becomes infinite as the velocity gradients approach zero. This typically occurs near the ice surface or where there is basal sliding. The computational difficulties associated with the infinite viscosity are often overcome by an arbitrary modification of Glen's law that bounds the maximum viscosity. The FOSLS formulations developed in this thesis are designed to overcome this difficulty. The first FOSLS formulation is just the first-order representation of the standard nonlinear, full-Stokes and is known as the viscosity formulation and suffers from the problem above. To overcome the problem of infinite viscosity, two new formulation exploit the fact that the deviatoric stress, the product of viscosity and strain-rate, approaches zero as the viscosity goes to infinity. Using the deviatoric stress as the basis for a first-order system results in the the basic fluidity system. Augmenting the basic fluidity system with a curl-type equation results in the augmented fluidity system, which is more amenable to the iterative solver, Algebraic MultiGrid (AMG). A Nested Iteration (NI) Newton-FOSLS-AMG approach is used to solve the nonlinear-Stokes problems. Several test problems from the ISMIP set of benchmarks is examined to test the effectiveness of the various formulations. These test show that the viscosity based method is more expensive and less accurate. The basic fluidity system shows optimal finite-element convergence. However, there is not yet an efficient iterative solver for this type of system and this is the topic of future research. Alternatively, AMG performs better on the augmented fluidity system when using specific scaling. Unfortunately, this scaling results in reduced finite-element convergence.

New series of triple molybdates AgA{sub 3}R(MoO{sub 4}){sub 5} (A=Mg, R=Cr, Fe; A=Mn, R=Al, Cr, Fe, Sc, In) with framework structures and mobile silver ion sublattices

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

Kotova, Irina Yu.; Buryat State University, Smolin St. 24a, Ulan-Ude 670000, Buryat Republic; Solodovnikov, Sergey F.

Triple molybdates AgA{sub 3}R(MoO{sub 4}){sub 5} (A=Mg, R=Cr, Fe; A=Mn, R=Al, Cr, Fe, Sc, In) of the NaMg{sub 3}In(MoO{sub 4}){sub 5} type were synthesized and single crystals of AgMg{sub 3}R(MoO{sub 4}){sub 5} (R=Cr, Fe) were grown. In their structures, the MoO{sub 4} tetrahedra, pairs and trimers of edge-shared (Mg, R)O{sub 6} octahedra are connected by common vertices to form a 3D framework. Large framework cavities involve Ag{sup +} cations disordered on three nearby positions with CN=3+1 or 4+1. Alternating (Mg, R)O{sub 6} octahedra and MoO{sub 4} tetrahedra in the framework form quadrangular windows penetrable for Ag{sup +} at elevated temperatures.more » Above 653–673 K, the newly obtained molybdates demonstrate abrupt reduction of the activation energy to 0.4–0.6 eV. At 773 K, AgMg{sub 3}Al(MoO{sub 4}){sub 5} shows electric conductivity 2.5·10{sup −2} S/cm and E{sub a}=0.39 eV compatible with characteristics of the best ionic conductors of the NASICON type. - Graphical abstract: Triple molybdates AgA{sub 3}R(MoO{sub 4}){sub 5} (A=Mg, R=Cr, Fe; A=Mn, R=Al, Cr, Fe, Sc, In) of the NaMg{sub 3}In(MoO{sub 4}){sub 5} type were synthesized, AgMg{sub 3}R(MoO{sub 4}){sub 5} (R=Cr, Fe) were structurally characterized, ion-conductive properties of AgMg{sub 3}Al(MoO{sub 4}){sub 5} were measured. Display Omitted - Highlights: • Triple molybdates AgA{sub 3}R(MoO{sub 4}){sub 5} (A=Mg, R=Cr, Fe; A=Mn, R=Al, Cr, Fe, Sc, In) of the NaMg{sub 3}In(MoO{sub 4}){sub 5} type were synthesized. • Single crystals of AgMg{sub 3}R(MoO{sub 4}){sub 5} (R=Cr, Fe) were grown and their crystal structures were determined. • Disordering Ag{sup +} ions and penetrable framework structures of AgMg{sub 3}R(MoO{sub 4}){sub 5} (R=Cr, Fe) suggest 2D-character of silver-ion mobility. • Measured ion-conductive properties of AgMg{sub 3}Al(MoO{sub 4}){sub 5} are compatible with characteristics of the best ionic conductors of the NASICON type.« less

[Safety monitoring of cell-based medicinal products (CBMPs)].

PubMed

Funk, Markus B; Frech, Marion; Spranger, Robert; Keller-Stanislawski, Brigitte

2015-11-01

Cell-based medicinal products (CBMPs), a category of advanced-therapy medicinal products (ATMPs), are authorised for the European market by the European Commission by means of the centralized marketing authorisation. By conforming to the German Medicinal Products Act (Sec. 4b AMG), national authorisation can be granted by the Paul-Ehrlich-Institut in Germany exclusively for ATMPs not based on a routine manufacturing procedure. In both procedures, quality, efficacy, and safety are evaluated and the risk-benefit balance is assessed. For the centralised procedure, mainly controlled clinical trial data must be submitted, whereas the requirements for national procedures could be modified corresponding to the stage of development of the ATMP. After marketing authorization, the marketing authorization/license holder is obligated to report all serious adverse reactions to the competent authority and to provide periodic safety update reports. If necessary, post-authorization safety studies could be imposed. On the basis of these regulatory measures, the safety of advanced therapies can be monitored and improved.

Antihyperlipidemic therapies targeting PCSK9.

PubMed

Weinreich, Michael; Frishman, William H

2014-01-01

Hyperlipidemia is a major cause of cardiovascular disease despite the availability of first-line cholesterol-lowering agents such as statins. A new therapeutic approach to lowering low-density lipoprotein-cholesterol (LDL-C) acts by blocking LDL-receptor degradation by serum proprotein convertase subtilisin kexin 9 (PCSK9). Human monoclonal antibodies that target PCSK9 and its interaction with the LDL receptor are now in clinical trials (REGN727/SAR23653, AMG145, and RN316). These agents are administered by either subcutaneous or intravenous routes, and have been shown to have major LDL-C and apolipoprotein B effects when combined with statins. A phase III clinical trial program evaluating clinical endpoints is now in progress. Other PCSK9-targeted approaches are in early stages of investigation, including natural inhibitors of PCSK9, RNA interference, and antisense inhibitors.

Connectedness and Life Skills Development for All Children

ERIC Educational Resources Information Center

Yuen, Mantak; Fong, Ricci W.

2012-01-01

A. Ziegler and S. N. Phillipson draw upon the Actiotope Model of Giftedness (AMG) to give an overview of a systemic approach to gifted education. They argue the value of such a systemic approach for understanding the development of exceptionality. The reviewers certainly agree that the achievement of excellent performance is not only the result of…

The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature

PubMed Central

Alawi, Khadija M.; Aubdool, Aisah A.; Liang, Lihuan; Wilde, Elena; Vepa, Abhinav; Psefteli, Maria-Paraskevi; Brain, Susan D.; Keeble, Julie E.

2015-01-01

Transient receptor potential vanilloid 1 (TRPV1) is involved in sensory nerve nociceptive signaling. Recently, it has been discovered that TRPV1 receptors also regulate basal body temperature in multiple species from mice to humans. In the present study, we investigated whether TRPV1 modulates basal sympathetic nervous system (SNS) activity. C57BL6/J wild-type (WT) mice and TRPV1 knockout (KO) mice were implanted with radiotelemetry probes for measurement of core body temperature. AMG9810 (50 mg/kg) or vehicle (2% DMSO/5% Tween 80/10 ml/kg saline) was injected intraperitoneally. Adrenoceptor antagonists or vehicle (5 ml/kg saline) was injected subcutaneously. In WT mice, the TRPV1 antagonist, AMG9810, caused significant hyperthermia, associated with increased noradrenaline concentrations in brown adipose tissue. The hyperthermia was significantly attenuated by the β-adrenoceptor antagonist propranolol, the mixed α-/β-adrenoceptor antagonist labetalol, and the α1-adrenoceptor antagonist prazosin. TRPV1 KO mice have a normal basal body temperature, indicative of developmental compensation. d-Amphetamine (potent sympathomimetic) caused hyperthermia in WT mice, which was reduced in TRPV1 KO mice, suggesting a decreased sympathetic drive in KOs. This study provides new evidence that TRPV1 controls thermoregulation upstream of the SNS, providing a potential therapeutic target for sympathetic hyperactivity thermoregulatory disorders.—Alawi, K. M., Aubdool, A. A., Liang, L., Wilde, E., Vepa, A., Psefteli, M.-P., Brain, S. D., Keeble, J. E. The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature. PMID:26136480

Investigation of Phase Mixing in Amorphous Solid Dispersions of AMG 517 in HPMC-AS Using DSC, Solid-State NMR, and Solution Calorimetry.

PubMed

Calahan, Julie L; Azali, Stephanie C; Munson, Eric J; Nagapudi, Karthik

2015-11-02

Intimate phase mixing between the drug and the polymer is considered a prerequisite to achieve good physical stability for amorphous solid dispersions. In this article, spray dried amorphous dispersions (ASDs) of AMG 517 and HPMC-as were studied by differential scanning calorimetry (DSC), solid-state NMR (SSNMR), and solution calorimetry. DSC analysis showed a weakly asymmetric (ΔTg ≈ 13.5) system with a single glass transition for blends of different compositions indicating phase mixing. The Tg-composition data was modeled using the BKCV equation to accommodate the observed negative deviation from ideality. Proton spin-lattice relaxation times in the laboratory and rotating frames ((1)H T1 and T1ρ), as measured by SSNMR, were consistent with the observation that the components of the dispersion were in intimate contact over a 10-20 nm length scale. Based on the heat of mixing calculated from solution calorimetry and the entropy of mixing calculated from the Flory-Huggins theory, the free energy of mixing was calculated. The free energy of mixing was found to be positive for all ASDs, indicating that the drug and polymer are thermodynamically predisposed to phase separation at 25 °C. This suggests that miscibility measured by DSC and SSNMR is achieved kinetically as the result of intimate mixing between drug and polymer during the spray drying process. This kinetic phase mixing is responsible for the physical stability of the ASD.

The Actiotope Model of Giftedness: Its Relationship with Motivation, and the Prediction of Academic Achievement among Turkish Students

ERIC Educational Resources Information Center

Leana-Tascilar, Marilena Z.

2015-01-01

The Actiotope Model of Giftedness (AMG) focuses on person-environment interactions instead of on the personality traits associated with actions. Motivation is a combination of intrinsic and extrinsic forces that are fundamental to the production of actions. Therefore, the resources provided by the environment or person are important for the…

Method of orbit sums in the theory of modular vector invariants

NASA Astrophysics Data System (ADS)

Stepanov, S. A.

2006-12-01

Let F be a field, V a finite-dimensional F-vector space, G\\leqslant \\operatorname{GL}_F(V) a finite group, and V^m=V\\oplus\\dots\\oplus V the m-fold direct sum with the diagonal action of G. The group G acts naturally on the symmetric graded algebra A_m=F \\lbrack V^m \\rbrack as a group of non-degenerate linear transformations of the variables. Let A_m^G be the subalgebra of invariants of the polynomial algebra A_m with respect to G. A classical result of Noether [1] says that if \\operatorname{char}F=0, then A_m^G is generated as an F-algebra by homogeneous polynomials of degree at most \\vert G\\vert, no matter how large m can be. On the other hand, it was proved by Richman [2], [3] that this result does not hold when the characteristic of F is positive and divides the order \\vert G\\vert of G. Let p, p>2, be a prime number, F=F_p a finite field of p elements, V a linear F_p-vector space of dimension n, and H\\leqslant \\operatorname{GL}_{F_p}(V) a cyclic group of order p generated by a matrix \\gamma of a certain special form. In this paper we describe explicitly (Theorem 1) one complete set of generators of A_m^H. After that, for an arbitrary complete set of generators of this algebra we find a lower bound for the highest degree of the generating elements of this algebra. This is a significant extension of the corresponding result of Campbell and Hughes [4] for the particular case of n=2. As a consequence we show (Theorem 3) that if m>n and G\\ge H is an arbitrary finite group, then each complete set of generators of A_m^G contains an element of degree at least 2(m-n+2r)(p-1)/r, where r=r(H) is a positive integer dependent on the structure of the generating matrix \\gamma of the group H. This result refines considerably the earlier lower bound obtained by Richman [3].

International Medical Graduates in Radiation Oncology: Historical Trends and Comparison With Other Medical Specialties

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

Verma, Vivek, E-mail: vivek333@gmail.com; Shah, Chirag; Lautenschlaeger, Tim

Purpose: This is the first National Resident Matching Program analysis evaluating historical patterns of international medical graduates (IMGs) in radiation oncology (RO) and providing comparison with American (MD) medical graduates (AMGs), osteopathic students (DOs), unfilled positions, and other specialties. Methods and Materials: National Resident Matching Program data for IMGs were available from 2003 to 2015, with limited data for other specialty matches. The following RO-specific figures were obtained per year: total positions available; total matched positions; number of unfilled positions; and number of IMG, AMG, and DO matches. In addition, the number of IMG matches and total matched positions weremore » obtained for 19 other specialties. Fisher exact tests and χ{sup 2} tests were considered significant at α <.05. Results: From 2010 to 2015, 0.8% of RO matches were IMGs, a decline from 2.4% in 2003 to 2009 (P=.006). Proportions of DO matches during these intervals increased by 40% (from 1.0% to 1.4%), significantly lower than IMGs for 2003 to 2009 (P=.03) but not 2010 to 2015 (P=.26). From 2003 to 2015, the percentage of IMG matches, at 1.5%, was significantly lower than the percentage of unfilled seats, at 3.5% (P<.001). In comparison with other specialties (2003-2015), RO had the fewest IMG matches (1.5%), followed by otolaryngology (1.9%) and orthopedics (2.2%); specialties with the highest IMG proportions were internal medicine (37.1%), family medicine (35.7%), and neurology (31.1%). Conclusions: Presently, IMGs represent <1% of RO matches, the lowest among major specialties. There are several speculative factors associated with this low proportion. There are significantly more unfilled positions than those filled by IMGs; programs at risk of not matching could weigh the advantages and disadvantages of interviewing IMGs.« less

Civil Affairs and Military Government Operations in Post-Fascist Italy

DTIC Science & Technology

2014-05-22

Fascist influence and control. A Joint Intelligence Assessment on the fall of Mussolini, dated July 27, 1943, addressed the full significance of this...119Murphy, 186. 120Message to AFHQ Algiers G2 FREEDOM for Joint Intelligence Committee from Joint Intelligence , 29 July, 1943, Eisenhower Pre...northward. Food stores and banks were emptied, and hoarding was a continual problem for AMG personnel. Malnutrition and hunger was rampant as the

C-Met Inhibitor AMG 337, Oxaliplatin, Leucovorin Calcium, and Fluorouracil in Treating Patients With Advanced Stomach or Esophageal Cancer

ClinicalTrials.gov

2017-10-17

Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Gastrointestinal Cancer; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

Changing recruitment outcomes: the 'why' and the 'how'.

PubMed

MacLean, Lisa; Pato, Michèle T

2011-01-01

Residency programs compete for applicants and commit extensive resources to the recruitment process. After failing to fill in the match for 5 years (1999-2004), this program decided to make changes in its recruitment process. The authors describe one program's experience in improving recruitment outcomes. The new training director surveyed other program directors, reviewed medical student feedback, and evaluated previous recruitment processes, developing and implementing a new plan. Tracked outcome measures included USMLE scores, COMLEX scores, match results, and American graduate ratios. After implementation of the new process in 2004-2005, the program has filled all six positions every year. Average median COMLEX 1 and 2 scores increased from 35.0 to 77.5 (p<0.012). The American graduate-to-International medical graduate ratio (AMG/IMG ratio) for the program changed from 7/16 in 1999 to 19/5 for Years 2006-2009. Changes in the recruitment process can favorably alter match outcomes.

USSR and Eastern Europe Scientific Abstracts, Materials Science and Metallurgy, Number 47

DTIC Science & Technology

1977-09-27

temperature intervals may vary and depends on the composition and previous heat treatment history of the alloy. Figures 2; references 13: 1 Russian, 12... HISTORY OF AMg6 ALLOY INTERMEDIATE WORKPIECES ON THE TIGHTNESS AND MECHANICAL PROPERTIES OF WELDS Kiev AVTOMATICHESKAYA SVARKA In Russian No 5(290), May...of Sciences Ukrainian SSR [Abstract] The effect of flux composition during argon-arc welding of titani - um with a nonconsumable electrode on melting

Development of Novel Instrumentation to Characterize Aerosol Insets and Cloud Particles

DTIC Science & Technology

2007-07-01

Wks Ic 1O m~s upwind of .03w a3~ I~ "We"~ 2D-C & -w4 km .1amg~hu upwind of CPI- =108 swa 4.0 *let k.03.8 km -"PO~m Distibuton -s. Mall MEM Mean~~ Snz...1226,1999. Goldfarb, L., Keckhut, P., Chanin, M.-L., and References Hauchecome, A.: Cirrus climatological results from lidar measurements at OHP (44_ N

Cinacalcet: AMG 073, Calcimimetics--Amgen/NPS Pharmaceuticals, KRN 1493, NPS 1493.

PubMed

2003-01-01

Cinacalcet [AMG 073, KRN 1493, NPS 1493] is an orally active, second-generation calcimimetic compound licensed by NPS Pharmaceuticals to Amgen in the US for potential treatment of hyperparathyroidism (HPT). Cinacalcet modulates (increases the sensitivity of) calcium receptors on the surface of parathyroid cells thereby inhibiting the oversecretion of parathyroid hormone, which characterises HPT. It also represents a potentially significant advance for chronic kidney disease patients diagnosed with secondary HPT, a common yet serious metabolic disorder where parathyroid hormone levels are elevated. Patients with this disease can suffer from bone disease, bone pain and fractures, soft tissue calcification, vascular calcification and cardiovascular complications. Amgen has rights to develop and sell cinacalcet throughout the world except in Japan, Taiwan and China, where the compound was licensed to Kirin Brewery. Kirin is developing it as KRN 1493 in phase II clinical studies in Japan. In December 2001, commencement of a phase III clinical trial with cinacalcet for the treatment of secondary HPT, triggered a 3 million US dollars milestone payment to NPS Pharmaceuticals. In September 2003, submission of an NDA to the US FDA for cinacalcet for secondary HPT will be followed by a milestone payment of 6 million US dollars to NPS. NPS, Kirin and Amgen were also developing another compound, tecalcet, for HPT, but that project has been discontinued in favour of cinacalcet. In September 2003, Amgen submitted an NDA to the US FDA for secondary HPT in patients with chronic kidney disease. In April 2003, Amgen announced positive results from a phase III clinical trial with cinacalcet in patients with secondary HPT. In a clinical study in patients on dialysis suffering from the effects of chronically elevated levels parathyroid hormone, cinacalcet appeared to be safe and well tolerated and was significantly more effective than placebo. Two more additional efficacy studies with cinacalcet have also been completed. Phase II trials of cinacalcet in dialysis patients with secondary HPT and in patients with primary HPT were successfully completed.

Investigational CD33-targeted therapeutics for acute myeloid leukemia.

PubMed

Walter, Roland B

2018-04-01

There is long-standing interest in drugs targeting the myeloid differentiation antigen CD33 in acute myeloid leukemia (AML). Positive results from randomized trials with the antibody-drug conjugate (ADC) gemtuzumab ozogamicin (GO) validate this approach. Partly stimulated by the success of GO, several CD33-targeted therapeutics are currently in early phase testing. Areas covered: CD33-targeted therapeutics in clinical development include Fc-engineered unconjugated antibodies (BI 836858 [mAb 33.1]), ADCs (SGN-CD33A [vadastuximab talirine], IMGN779), radioimmunoconjugates ( 225 Ac-lintuzumab), bi- and trispecific antibodies (AMG 330, AMG 673, AMV564, 161533 TriKE fusion protein), and chimeric antigen receptor (CAR)-modified immune effector cells. Besides limited data on 225 Ac-lintuzumab showing modest single-agent activity, clinical data are so far primarily available for SGN-CD33A. SGN-CD33A has single-agent activity and has shown encouraging results when combined with an azanucleoside or standard chemotherapeutics. However, concerns about toxicity to the liver and normal hematopoietic cells - the latter leading to early termination of a phase 3 trial - have derailed the development of SGN-CD33A, and its future is uncertain. Expert opinion: Early results from a new generation of CD33-targeted therapeutics are anticipated in the next 2-3 years. Undoubtedly, re-approval of GO in 2017 has changed the landscape and rendered clinical development for these agents more challenging.

Design and Rationale of the LAPLACE-TIMI 57 Trial: A Phase II, Double-Blind, Placebo-Controlled Study of the Efficacy and Tolerability of a Monoclonal Antibody Inhibitor of PCSK9 in Subjects With Hypercholesterolemia on Background Statin Therapy

PubMed Central

Kohli, Payal; Desai, Nihar R.; Giugliano, Robert P.; Kim, Jae B.; Somaratne, Ransi; Huang, Fannie; Knusel, Beat; McDonald, Shannon; Abrahamsen, Timothy; Wasserman, Scott M.; Scott, Robert; Sabatine, Marc S.

2013-01-01

Lowering low-density lipoprotein cholesterol (LDL-C) is a cornerstone for the prevention of atherosclerotic heart disease, improving clinical outcomes and reducing vascular mortality in patients with hypercholesterolemia. The clinical benefits of LDL-C reduction appear to extend even to patients starting with LDL-C as low as 60–80 mg/dL prior to initiating therapy. Statins are the first-line agents for treating hypercholesterolemia and are effective in reducing LDL-C, but many patients are unable to achieve their optimal lipid targets despite intensive statin therapy. Therefore, there has been a strong impetus for the development of novel pharmacologic agents designed to lower LDL-C further in patients already on statin therapy. Genetic mutations resulting in altered cholesterol homeostasis provide valuable information regarding novel approaches for treating hypercholesterolemia. To that end, mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) were linked to altered levels of LDL-C, illustrating this protein’s role in lipid metabolism. PCSK9 promotes degradation of the LDL receptor, preventing its transport back to the cell surface and thereby increasing circulating LDL-C. Conversely, inhibition of PCSK9 can profoundly decrease circulating LDL-C, and thus is an attractive new target for LDL-C–lowering therapy. AMG 145 is a fully human monoclonal immunoglobulin G2 antibody that binds specifically to human PCSK9 and inhibits its interaction with the low-density lipoprotein receptor. In this manuscript, we describe the rationale and design of LDL-C Assessment with PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy–Thrombolysis In Myocardial Infarction 57 (LAPLACE-TIMI 57; NCT01380730), a 12-week, randomized, double-blind, dose-ranging, placebo-controlled study designed to assess the safety and efficacy of AMG 145 when added to statin therapy in patients with hypercholesterolemia. PMID:22714699

American Academy of Allergy, Asthma and Immunology (AAAAI)-2010 annual meeting. 26 February-2 March 2010, New Orleans, LA, USA.

PubMed

Bielory, Leonard

2010-05-01

The 2010 American Academy of Allergy, Asthma and Immunology (AAAAI) meeting, held in New Orleans, included topics covering new therapeutic developments in the fields of allergy, asthma and immunological diseases. This conference report highlights selected presentations on potential treatments for food and other allergies, as well as therapies for asthma and other immunological diseases. Investigational drugs discussed include Oralair Mites (Stallergenes SA/Paladin Labs Inc), PF-03654746 (Pfizer Inc) and AMG-853 (Amgen Inc).

The effect of surface oxide layer on the rate of hydrogen emission from aluminum and its alloys in a high vacuum

NASA Technical Reports Server (NTRS)

Makarova, V. I.; Zyabrev, A. A.

1979-01-01

The influence of surface oxide layers on the kinetics of hydrogen emission at the high vacuum of 10 to the minus 8th power torr was investigated at temperatures from 20 to 450 C using samples of pure AB00 aluminum and the cast alloy AMg. Cast and deformed samples of AMts alloy were used to study the effect of oxide film thickness on the rate of hydrogen emission. Thermodynamic calculations of the reactions of the generation and dissociation of aluminum oxide show that degasification at elevated temperatures (up to 600 C) and high vacuum will not reduce the thickness of artificially-generated surface oxide layers on aluminum and its alloys.

Two Days' Sleep Debt Causes Mood Decline During Resting State Via Diminished Amygdala-Prefrontal Connectivity.

PubMed

Motomura, Yuki; Katsunuma, Ruri; Yoshimura, Michitaka; Mishima, Kazuo

2017-10-01

Sleep debt (SD) has been suggested to evoke emotional instability by diminishing the suppression of the amygdala by the medial prefrontal cortex (MPFC). Here, we investigated how short-term SD affects resting-state functional connectivity between the amygdala and MPFC, self-reported mood, and sleep parameters. Eighteen healthy adult men aged 29 ± 8.24 years participated in a 2-day sleep control session (SC; time in bed [TIB], 9 hours) and 2-day SD session (TIB, 3 hours). On day 2 of each session, resting-state functional magnetic resonance imaging was performed, followed immediately by measuring self-reported mood on the State-Trait Anxiety Inventory-State subscale (STAI-S). STAI-S score was significantly increased, and functional connectivity between the amygdala and MPFC was significantly decreased in SD compared with SC. Significant correlations were observed between reduced rapid eye movement (REM) sleep and reduced left amygdala-MPFC functional connectivity (FCL_amg-MPFC) and between reduced FCL_amg-MPFC and increased STAI-S score in SD compared with SC. These findings suggest that reduced MPFC functional connectivity of amygdala activity is involved in mood deterioration under SD, and that REM sleep reduction is involved in functional changes in the corresponding brain regions. Having adequate REM sleep may be important for mental health maintenance. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Molecular Epidemiology of Mutations in Antimicrobial Resistance Loci of Pseudomonas aeruginosa Isolates from Airways of Cystic Fibrosis Patients.

PubMed

Greipel, Leonie; Fischer, Sebastian; Klockgether, Jens; Dorda, Marie; Mielke, Samira; Wiehlmann, Lutz; Cramer, Nina; Tümmler, Burkhard

2016-11-01

The chronic airway infections with Pseudomonas aeruginosa in people with cystic fibrosis (CF) are treated with aerosolized antibiotics, oral fluoroquinolones, and/or intravenous combination therapy with aminoglycosides and β-lactam antibiotics. An international strain collection of 361 P. aeruginosa isolates from 258 CF patients seen at 30 CF clinics was examined for mutations in 17 antimicrobial susceptibility and resistance loci that had been identified as hot spots of mutation by genome sequencing of serial isolates from a single CF clinic. Combinatorial amplicon sequencing of pooled PCR products identified 1,112 sequence variants that were not present in the genomes of representative strains of the 20 most common clones of the global P. aeruginosa population. A high frequency of singular coding variants was seen in spuE, mexA, gyrA, rpoB, fusA1, mexZ, mexY, oprD, ampD, parR, parS, and envZ (amgS), reflecting the pressure upon P. aeruginosa in lungs of CF patients to generate novel protein variants. The proportion of nonneutral amino acid exchanges was high. Of the 17 loci, mexA, mexZ, and pagL were most frequently affected by independent stop mutations. Private and de novo mutations seem to play a pivotal role in the response of P. aeruginosa populations to the antimicrobial load and the individual CF host. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Pharmacological evaluation of NSAID-induced gastropathy as a "Translatable" model of referred visceral hypersensitivity.

PubMed

Hummel, Michele; Knappenberger, Terri; Reilly, Meghan; Whiteside, Garth T

2017-09-07

To evaluate whether non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral hypersensitivity. Gastric ulcer pain was induced by the oral administration of indomethacin to male, CD1 mice ( n = 10/group) and then assessed by measuring referred abdominal hypersensitivity to tactile application. A diverse range of pharmacological mechanisms contributing to the pain were subsequently investigated. These mechanisms included: transient receptor potential (TRP), sodium and acid-sensing ion channels (ASICs) as well as opioid receptors and guanylate cyclase C (GC-C). Results showed that two opioids and a GC-C agonist, morphine, asimadoline and linaclotide, respectively, the TRP antagonists, AMG9810 and HC-030031 and the sodium channel blocker, carbamazepine, elicited a dose- and/or time-dependent attenuation of referred visceral hypersensitivity, while the ASIC blocker, amiloride, was ineffective at all doses tested. Together, these findings implicate opioid receptors, GC-C, and sodium and TRP channel activation as possible mechanisms associated with visceral hypersensitivity. More importantly, these findings also validate NSAID-induced gastropathy as a sensitive and clinically predictive mouse model suitable for assessing novel molecules with potential pain-attenuating properties.

Pharmacological evaluation of NSAID-induced gastropathy as a "Translatable" model of referred visceral hypersensitivity

PubMed Central

Hummel, Michele; Knappenberger, Terri; Reilly, Meghan; Whiteside, Garth T

2017-01-01

AIM To evaluate whether non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral hypersensitivity. METHODS Gastric ulcer pain was induced by the oral administration of indomethacin to male, CD1 mice (n = 10/group) and then assessed by measuring referred abdominal hypersensitivity to tactile application. A diverse range of pharmacological mechanisms contributing to the pain were subsequently investigated. These mechanisms included: transient receptor potential (TRP), sodium and acid-sensing ion channels (ASICs) as well as opioid receptors and guanylate cyclase C (GC-C). RESULTS Results showed that two opioids and a GC-C agonist, morphine, asimadoline and linaclotide, respectively, the TRP antagonists, AMG9810 and HC-030031 and the sodium channel blocker, carbamazepine, elicited a dose- and/or time-dependent attenuation of referred visceral hypersensitivity, while the ASIC blocker, amiloride, was ineffective at all doses tested. CONCLUSION Together, these findings implicate opioid receptors, GC-C, and sodium and TRP channel activation as possible mechanisms associated with visceral hypersensitivity. More importantly, these findings also validate NSAID-induced gastropathy as a sensitive and clinically predictive mouse model suitable for assessing novel molecules with potential pain-attenuating properties. PMID:28970722

Anatomically accurate high resolution modeling of human whole heart electromechanics: A strongly scalable algebraic multigrid solver method for nonlinear deformation

NASA Astrophysics Data System (ADS)

Augustin, Christoph M.; Neic, Aurel; Liebmann, Manfred; Prassl, Anton J.; Niederer, Steven A.; Haase, Gundolf; Plank, Gernot

2016-01-01

Electromechanical (EM) models of the heart have been used successfully to study fundamental mechanisms underlying a heart beat in health and disease. However, in all modeling studies reported so far numerous simplifications were made in terms of representing biophysical details of cellular function and its heterogeneity, gross anatomy and tissue microstructure, as well as the bidirectional coupling between electrophysiology (EP) and tissue distension. One limiting factor is the employed spatial discretization methods which are not sufficiently flexible to accommodate complex geometries or resolve heterogeneities, but, even more importantly, the limited efficiency of the prevailing solver techniques which is not sufficiently scalable to deal with the incurring increase in degrees of freedom (DOF) when modeling cardiac electromechanics at high spatio-temporal resolution. This study reports on the development of a novel methodology for solving the nonlinear equation of finite elasticity using human whole organ models of cardiac electromechanics, discretized at a high para-cellular resolution. Three patient-specific, anatomically accurate, whole heart EM models were reconstructed from magnetic resonance (MR) scans at resolutions of 220 μm, 440 μm and 880 μm, yielding meshes of approximately 184.6, 24.4 and 3.7 million tetrahedral elements and 95.9, 13.2 and 2.1 million displacement DOF, respectively. The same mesh was used for discretizing the governing equations of both electrophysiology (EP) and nonlinear elasticity. A novel algebraic multigrid (AMG) preconditioner for an iterative Krylov solver was developed to deal with the resulting computational load. The AMG preconditioner was designed under the primary objective of achieving favorable strong scaling characteristics for both setup and solution runtimes, as this is key for exploiting current high performance computing hardware. Benchmark results using the 220 μm, 440 μm and 880 μm meshes demonstrate efficient scaling up to 1024, 4096 and 8192 compute cores which allowed the simulation of a single heart beat in 44.3, 87.8 and 235.3 minutes, respectively. The efficiency of the method allows fast simulation cycles without compromising anatomical or biophysical detail.

Anatomically accurate high resolution modeling of human whole heart electromechanics: A strongly scalable algebraic multigrid solver method for nonlinear deformation

PubMed Central

Augustin, Christoph M.; Neic, Aurel; Liebmann, Manfred; Prassl, Anton J.; Niederer, Steven A.; Haase, Gundolf; Plank, Gernot

2016-01-01

Electromechanical (EM) models of the heart have been used successfully to study fundamental mechanisms underlying a heart beat in health and disease. However, in all modeling studies reported so far numerous simplifications were made in terms of representing biophysical details of cellular function and its heterogeneity, gross anatomy and tissue microstructure, as well as the bidirectional coupling between electrophysiology (EP) and tissue distension. One limiting factor is the employed spatial discretization methods which are not sufficiently flexible to accommodate complex geometries or resolve heterogeneities, but, even more importantly, the limited efficiency of the prevailing solver techniques which are not sufficiently scalable to deal with the incurring increase in degrees of freedom (DOF) when modeling cardiac electromechanics at high spatio-temporal resolution. This study reports on the development of a novel methodology for solving the nonlinear equation of finite elasticity using human whole organ models of cardiac electromechanics, discretized at a high para-cellular resolution. Three patient-specific, anatomically accurate, whole heart EM models were reconstructed from magnetic resonance (MR) scans at resolutions of 220 μm, 440 μm and 880 μm, yielding meshes of approximately 184.6, 24.4 and 3.7 million tetrahedral elements and 95.9, 13.2 and 2.1 million displacement DOF, respectively. The same mesh was used for discretizing the governing equations of both electrophysiology (EP) and nonlinear elasticity. A novel algebraic multigrid (AMG) preconditioner for an iterative Krylov solver was developed to deal with the resulting computational load. The AMG preconditioner was designed under the primary objective of achieving favorable strong scaling characteristics for both setup and solution runtimes, as this is key for exploiting current high performance computing hardware. Benchmark results using the 220 μm, 440 μm and 880 μm meshes demonstrate efficient scaling up to 1024, 4096 and 8192 compute cores which allowed the simulation of a single heart beat in 44.3, 87.8 and 235.3 minutes, respectively. The efficiency of the method allows fast simulation cycles without compromising anatomical or biophysical detail. PMID:26819483

Urocortin1-induced anorexia is regulated by activation of the serotonin 2C receptor in the brain.

PubMed

Harada, Yumi; Takayama, Kiyoshige; Ro, Shoki; Ochiai, Mitsuko; Noguchi, Masamichi; Iizuka, Seiichi; Hattori, Tomohisa; Yakabi, Koji

2014-01-01

This study was conducted to determine the mechanisms by which serotonin (5-hydroxytryptamine, 5-HT) receptors are involved in the suppression of food intake in a rat stress model and to observe the degree of activation in the areas of the brain involved in feeding. In the stress model, male Sprague-Dawley rats (8 weeks old) were given intracerebroventricular injections of urocortin (UCN) 1. To determine the role of the 5-HT2c receptor (5-HT2cR) in the decreased food intake in UCN1-treated rats, specific 5-HT2cR or 5-HT2b receptor (5-HT2bR) antagonists were administered. Food intake was markedly reduced in UCN1-injected rats compared with phosphate buffered saline treated control rats. Intraperitoneal administration of a 5-HT2cR antagonist, but not a 5-HT2bR antagonist, significantly inhibited the decreased food intake. To assess the involvement of neural activation, we tracked the expression of c-fos mRNA as a neuronal activation marker. Expression of the c-fos mRNA in the arcuate nucleus, ventromedial hypothalamic nucleus (VMH) and rostral ventrolateral medulla (RVLM) in UNC1-injected rats showed significantly higher expression than in the PBS-injected rats. Increased c-fos mRNA was also observed in the paraventricular nucleus (PVN), the nucleus of the solitary tract (NTS), and the amygdala (AMG) after injection of UCN1. Increased 5-HT2cR protein expression was also observed in several areas. However, increased coexpression of 5-HT2cR and c-fos was observed in the PVN, VMH, NTS, RVLM and AMG. Whereas, pro-opiomelanocortin mRNA expression was not changed. In an UNC1-induced stress model, 5-HT2cR expression and activation was found in brain areas involved in feeding control. Copyright © 2013 Elsevier Inc. All rights reserved.

[Measurement of atomic number of alkali vapor and pressure of buffer gas based on atomic absorption].

PubMed

Zheng, Hui-jie; Quan, Wei; Liu, Xiang; Chen, Yao; Lu, Ji-xi

2015-02-01

High sensitivitymagnetic measurementscanbe achieved by utilizing atomic spinmanipulation in the spin-exchange-relaxation-free (SERF) regime, which uses an alkali cell as a sensing element. The atomic number density of the alkali vapor and the pressure of the buffer gasare among the most important parameters of the cell andrequire accurate measurement. A method has been proposed and developedto measure the atomic number density and the pressure based on absorption spectroscopy, by sweeping the absorption line and fittingthe experiment data with a Lorentzian profile to obtainboth parameters. Due to Doppler broadening and pressure broadening, which is mainly dominated by the temperature of the cell and the pressure of buffer gas respectively, this work demonstrates a simulation of the errorbetween the peaks of the Lorentzian profile and the Voigt profile caused by bothfactors. The results indicates that the Doppler broadening contribution is insignificant with an error less than 0.015% at 313-513 K for a 4He density of 2 amg, and an error of 0.1% in the presence of 0.6-5 amg at 393 K. We conclude that the Doppler broadening could be ignored under above conditions, and that the Lorentzianprofile is suitably applied to fit the absorption spectrumobtainingboth parameters simultaneously. In addition we discuss the resolution and the instability due to thelight source, wavelength and the temperature of the cell. We find that the cell temperature, whose uncertainty is two orders of magnitude larger than the instability of the light source and the wavelength, is one of the main factors which contributes to the error.

Generalization of mixed multiscale finite element methods with applications

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

Lee, C S

Many science and engineering problems exhibit scale disparity and high contrast. The small scale features cannot be omitted in the physical models because they can affect the macroscopic behavior of the problems. However, resolving all the scales in these problems can be prohibitively expensive. As a consequence, some types of model reduction techniques are required to design efficient solution algorithms. For practical purpose, we are interested in mixed finite element problems as they produce solutions with certain conservative properties. Existing multiscale methods for such problems include the mixed multiscale finite element methods. We show that for complicated problems, the mixedmore » multiscale finite element methods may not be able to produce reliable approximations. This motivates the need of enrichment for coarse spaces. Two enrichment approaches are proposed, one is based on generalized multiscale finte element metthods (GMsFEM), while the other is based on spectral element-based algebraic multigrid (rAMGe). The former one, which is called mixed GMsFEM, is developed for both Darcy’s flow and linear elasticity. Application of the algorithm in two-phase flow simulations are demonstrated. For linear elasticity, the algorithm is subtly modified due to the symmetry requirement of the stress tensor. The latter enrichment approach is based on rAMGe. The algorithm differs from GMsFEM in that both of the velocity and pressure spaces are coarsened. Due the multigrid nature of the algorithm, recursive application is available, which results in an efficient multilevel construction of the coarse spaces. Stability, convergence analysis, and exhaustive numerical experiments are carried out to validate the proposed enrichment approaches. iii« less

Immune checkpoints PVR and PVRL2 are prognostic markers in AML and their blockade represents a new therapeutic option.

PubMed

Stamm, Hauke; Klingler, Felix; Grossjohann, Eva-Maria; Muschhammer, Jana; Vettorazzi, Eik; Heuser, Michael; Mock, Ulrike; Thol, Felicitas; Vohwinkel, Gabi; Latuske, Emily; Bokemeyer, Carsten; Kischel, Roman; Dos Santos, Cedric; Stienen, Sabine; Friedrich, Matthias; Lutteropp, Michael; Nagorsen, Dirk; Wellbrock, Jasmin; Fiedler, Walter

2018-05-31

Immune checkpoints are promising targets in cancer therapy. Recently, poliovirus receptor (PVR) and poliovirus receptor-related 2 (PVRL2) have been identified as novel immune checkpoints. In this investigation we show that acute myeloid leukemia (AML) cell lines and AML patient samples highly express the T-cell immunoreceptor with Ig and ITIM domains (TIGIT) ligands PVR and PVRL2. Using two independent patient cohorts, we could demonstrate that high PVR and PVRL2 expression correlates with poor outcome in AML. We show for the first time that antibody blockade of PVR or PVRL2 on AML cell lines or primary AML cells or TIGIT blockade on immune cells increases the anti-leukemic effects mediated by PBMCs or purified CD3 + cells in vitro. The cytolytic activity of the BiTE® antibody construct AMG 330 against leukemic cells could be further enhanced by blockade of the TIGIT-PVR/PVRL2 axis. This increased immune reactivity is paralleled by augmented secretion of Granzyme B by immune cells. Employing CRISPR/Cas9-mediated knockout of PVR and PVRL2 in MV4-11 cells, the cytotoxic effects of antibody blockade could be recapitulated in vitro. In NSG mice reconstituted with human T cells and transplanted with either MV4-11 PVR/PVRL2 knockout or wildtype cells, prolonged survival was observed for the knockout cells. This survival benefit could be further extended by treating the mice with AMG 330. Therefore, targeting the TIGIT-PVR/PVRL2 axis with blocking antibodies might represent a promising future therapeutic option in AML.

Electrical Resistivity Tomography using a finite element based BFGS algorithm with algebraic multigrid preconditioning

NASA Astrophysics Data System (ADS)

Codd, A. L.; Gross, L.

2018-03-01

We present a new inversion method for Electrical Resistivity Tomography which, in contrast to established approaches, minimizes the cost function prior to finite element discretization for the unknown electric conductivity and electric potential. Minimization is performed with the Broyden-Fletcher-Goldfarb-Shanno method (BFGS) in an appropriate function space. BFGS is self-preconditioning and avoids construction of the dense Hessian which is the major obstacle to solving large 3-D problems using parallel computers. In addition to the forward problem predicting the measurement from the injected current, the so-called adjoint problem also needs to be solved. For this problem a virtual current is injected through the measurement electrodes and an adjoint electric potential is obtained. The magnitude of the injected virtual current is equal to the misfit at the measurement electrodes. This new approach has the advantage that the solution process of the optimization problem remains independent to the meshes used for discretization and allows for mesh adaptation during inversion. Computation time is reduced by using superposition of pole loads for the forward and adjoint problems. A smoothed aggregation algebraic multigrid (AMG) preconditioned conjugate gradient is applied to construct the potentials for a given electric conductivity estimate and for constructing a first level BFGS preconditioner. Through the additional reuse of AMG operators and coarse grid solvers inversion time for large 3-D problems can be reduced further. We apply our new inversion method to synthetic survey data created by the resistivity profile representing the characteristics of subsurface fluid injection. We further test it on data obtained from a 2-D surface electrode survey on Heron Island, a small tropical island off the east coast of central Queensland, Australia.

Heavy metals in locus ceruleus and motor neurons in motor neuron disease.

PubMed

Pamphlett, Roger; Kum Jew, Stephen

2013-12-12

The causes of sporadic amyotrophic lateral sclerosis (SALS) and other types of motor neuron disease (MND) remain largely unknown. Heavy metals have long been implicated in MND, and it has recently been shown that inorganic mercury selectively enters human locus ceruleus (LC) and motor neurons. We therefore used silver nitrate autometallography (AMG) to look for AMG-stainable heavy metals (inorganic mercury and bismuth) in LC and motor neurons of 24 patients with MND (18 with SALS and 6 with familial MND) and in the LC of 24 controls. Heavy metals in neurons were found in significantly more MND patients than in controls when comparing: (1) the presence of any versus no heavy metal-containing LC neurons (MND 88%, controls 42%), (2) the median percentage of heavy metal-containing LC neurons (MND 9.5%, control 0.0%), and (3) numbers of individuals with heavy metal-containing LC neurons in the upper half of the percentage range (MND 75%, controls 25%). In MND patients, 67% of remaining spinal motor neurons contained heavy metals; smaller percentages were found in hypoglossal, nucleus ambiguus and oculomotor neurons, but none in cortical motor neurons. The majority of MND patients had heavy metals in both LC and spinal motor neurons. No glia or other neurons, including neuromelanin-containing neurons of the substantia nigra, contained stainable heavy metals. Uptake of heavy metals by LC and lower motor neurons appears to be fairly common in humans, though heavy metal staining in the LC, most likely due to inorganic mercury, was seen significantly more often in MND patients than in controls. The LC innervates many cell types that are affected in MND, and it is possible that MND is triggered by toxicant-induced interactions between LC and motor neurons.

Inter-species prediction of protein phosphorylation in the sbv IMPROVER species translation challenge

PubMed Central

Biehl, Michael; Sadowski, Peter; Bhanot, Gyan; Bilal, Erhan; Dayarian, Adel; Meyer, Pablo; Norel, Raquel; Rhrissorrakrai, Kahn; Zeller, Michael D.; Hormoz, Sahand

2015-01-01

Motivation: Animal models are widely used in biomedical research for reasons ranging from practical to ethical. An important issue is whether rodent models are predictive of human biology. This has been addressed recently in the framework of a series of challenges designed by the systems biology verification for Industrial Methodology for Process Verification in Research (sbv IMPROVER) initiative. In particular, one of the sub-challenges was devoted to the prediction of protein phosphorylation responses in human bronchial epithelial cells, exposed to a number of different chemical stimuli, given the responses in rat bronchial epithelial cells. Participating teams were asked to make inter-species predictions on the basis of available training examples, comprising transcriptomics and phosphoproteomics data. Results: Here, the two best performing teams present their data-driven approaches and computational methods. In addition, post hoc analyses of the datasets and challenge results were performed by the participants and challenge organizers. The challenge outcome indicates that successful prediction of protein phosphorylation status in human based on rat phosphorylation levels is feasible. However, within the limitations of the computational tools used, the inclusion of gene expression data does not improve the prediction quality. The post hoc analysis of time-specific measurements sheds light on the signaling pathways in both species. Availability and implementation: A detailed description of the dataset, challenge design and outcome is available at www.sbvimprover.com. The code used by team IGB is provided under http://github.com/uci-igb/improver2013. Implementations of the algorithms applied by team AMG are available at http://bhanot.biomaps.rutgers.edu/wiki/AMG-sc2-code.zip. Contact: meikelbiehl@gmail.com PMID:24994890

Heavy metals in locus ceruleus and motor neurons in motor neuron disease

PubMed Central

2013-01-01

Background The causes of sporadic amyotrophic lateral sclerosis (SALS) and other types of motor neuron disease (MND) remain largely unknown. Heavy metals have long been implicated in MND, and it has recently been shown that inorganic mercury selectively enters human locus ceruleus (LC) and motor neurons. We therefore used silver nitrate autometallography (AMG) to look for AMG-stainable heavy metals (inorganic mercury and bismuth) in LC and motor neurons of 24 patients with MND (18 with SALS and 6 with familial MND) and in the LC of 24 controls. Results Heavy metals in neurons were found in significantly more MND patients than in controls when comparing: (1) the presence of any versus no heavy metal-containing LC neurons (MND 88%, controls 42%), (2) the median percentage of heavy metal-containing LC neurons (MND 9.5%, control 0.0%), and (3) numbers of individuals with heavy metal-containing LC neurons in the upper half of the percentage range (MND 75%, controls 25%). In MND patients, 67% of remaining spinal motor neurons contained heavy metals; smaller percentages were found in hypoglossal, nucleus ambiguus and oculomotor neurons, but none in cortical motor neurons. The majority of MND patients had heavy metals in both LC and spinal motor neurons. No glia or other neurons, including neuromelanin-containing neurons of the substantia nigra, contained stainable heavy metals. Conclusions Uptake of heavy metals by LC and lower motor neurons appears to be fairly common in humans, though heavy metal staining in the LC, most likely due to inorganic mercury, was seen significantly more often in MND patients than in controls. The LC innervates many cell types that are affected in MND, and it is possible that MND is triggered by toxicant-induced interactions between LC and motor neurons. PMID:24330485

Lecture Notes on Multigrid Methods

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

Vassilevski, P S

The Lecture Notes are primarily based on a sequence of lectures given by the author while been a Fulbright scholar at 'St. Kliment Ohridski' University of Sofia, Sofia, Bulgaria during the winter semester of 2009-2010 academic year. The notes are somewhat expanded version of the actual one semester class he taught there. The material covered is slightly modified and adapted version of similar topics covered in the author's monograph 'Multilevel Block-Factorization Preconditioners' published in 2008 by Springer. The author tried to keep the notes as self-contained as possible. That is why the lecture notes begin with some basic introductory matrix-vectormore » linear algebra, numerical PDEs (finite element) facts emphasizing the relations between functions in finite dimensional spaces and their coefficient vectors and respective norms. Then, some additional facts on the implementation of finite elements based on relation tables using the popular compressed sparse row (CSR) format are given. Also, typical condition number estimates of stiffness and mass matrices, the global matrix assembly from local element matrices are given as well. Finally, some basic introductory facts about stationary iterative methods, such as Gauss-Seidel and its symmetrized version are presented. The introductory material ends up with the smoothing property of the classical iterative methods and the main definition of two-grid iterative methods. From here on, the second part of the notes begins which deals with the various aspects of the principal TG and the numerous versions of the MG cycles. At the end, in part III, we briefly introduce algebraic versions of MG referred to as AMG, focusing on classes of AMG specialized for finite element matrices.« less

Total mercury levels in hair, toenail, and urine among women free from occupational exposure and their relations to renal tubular function

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

Ohno, Tomoko; Sakamoto, Mineshi; Kurosawa, Tomoko

2007-02-15

To investigate the relations among total mercury levels in hair, toenail, and urine, together with potential effects of methylmercury intake on renal tubular function, we determined their levels, and urinary N-acetyl-{beta}-d-glucosaminidase activity (NAG) and {alpha}{sub 1}-microglobulin (AMG) in 59 women free from occupational exposures, and estimated daily mercury intakes from fish and other seafood using a food frequency questionnaire. Mercury levels (mean+/-SD) in the women were 1.51+/-0.91{mu}g/g in hair, 0.59+/-0.32{mu}g/g in toenail, and 0.86+/-0.66{mu}g/g creatinine in urine; and, there were positive correlations among them (P<0.001). The daily mercury intake of 9.15+/-7.84{mu}g/day was significantly correlated with total mercury levels in hair,more » toenail, and urine (r=0.551, 0.537, and 0.604, P<0.001). Among the women, the NAG and AMG were positively correlated with both the daily mercury intake and mercury levels in hair, toenail, and urine (P<0.01); and, these relations were almost similar when using multiple regression analysis to adjust for possible confounders such as urinary cadmium (0.47+/-0.28{mu}g/g creatinine) and smoking status. In conclusion, mercury resulting from fish consumption can explain total mercury levels in hair, toenail, and urine to some degree (about 30%), partly through the degradation into the inorganic form, and it may confound the renal tubular effect of other nephrotoxic agents. Also, the following equation may be applicable to the population neither with dental amalgam fillings nor with occupational exposures: [hair mercury ({mu}g/g)]=2.44x[toenail mercury ({mu}g/g)].« less

MAPK pathway inhibition induces MET and GAB1 levels, priming BRAF mutant melanoma for rescue by hepatocyte growth factor

PubMed Central

Caenepeel, Sean; Cooke, Keegan; Wadsworth, Sarah; Huang, Guo; Robert, Lidia; Moreno, Blanca Homet; Parisi, Giulia; Cajulis, Elaina; Kendall, Richard; Beltran, Pedro; Ribas, Antoni; Coxon, Angela; Hughes, Paul E.

2017-01-01

Therapeutic resistance is a major obstacle to achieving durable clinical responses with targeted therapies, highlighting a need to elucidate the underlying mechanisms responsible for resistance and identify strategies to overcome this challenge. An emerging body of data implicates the tyrosine kinase MET in mediating resistance to BRAF inhibitors in BRAFV600E mutant melanoma. In this study we observed a dominant role for the HGF/MET axis in mediating resistance to BRAF and MEK inhibitors in models of BRAFV600E and NRAS mutant melanoma. In addition, we showed that MAPK pathway inhibition induced rapid increases in MET and GAB1 levels, providing novel mechanistic insight into how BRAFV600E mutant melanoma is primed for HGF-mediated rescue. We also determined that tumor-derived HGF, not systemic HGF, may be required to convey resistance to BRAF inhibition in vivo and that resistance could be reversed following treatment with AMG 337, a selective MET inhibitor. In summary, these findings support the clinical evaluation of MET-directed targeted therapy to circumvent resistance to BRAF and MEK inhibitors in BRAFV600E mutant melanoma. In addition, the induction of MET following treatment with BRAF and MEK inhibitors has the potential to serve as a predictive biomarker for identifying patients best suited for MET inhibitor combination therapy. PMID:28147313

[Phenotypic variations of susceptibility in Klebsiella pneumoniae strains of nosocomial origin and their association with biofilm formation].

PubMed

Barreto, Silvio; Zambrano, María; Araque, María

2009-06-01

Klebsiella pneumoniae is the principal opportunist pathogen associated with nosocomial infections. The morbidity and mortality produced by this microorganism is related mostly to antimicrobial resistance and its capacity to form biofilms. In this study, the phenotypic variations of susceptibility in 50 Klebsiella pneumoniae strains (26 betaLEE-producer and 24 no betaLEE-producer) isolated from pediatric patients with nosocomial septicemia at the High-risk Neonatal Unit of the Instituto Aut6nomo Hospital Universitario de Los Andes, Mérida, Venezuela and their associations with biofilm formation were analyzed. These strains were biochemically identified by standard microbiology methods. Antimicrobial susceptibility was determined by minimal inhibitory concentration and biofilm formation was detected by spectrophotometric techniques. Most of betaLEE strains were frequently associated with resistance markers such as tobramycin, kanamycin, tetracycline, chloramphenicol (38% each), streptomycin (36%) and netilmicin (34%). The predominant multiresistent phenotype was composed of betaLEE+ -AMG-TET-CLF (30%). 18% of K. pneumoniae strains were sensible to the antibiotics tested. Formation of biofilm was observed in 77.8% and 96.2% of sensible and resistent strains, respectively. There was no statistic relation between phenotipic variations of susceptibility and biofilm formation (p > = 0.05). However, both characteristics of K. pneumoniae should be evaluated to determine the therapeutic conduct to treat patients with nosocomial infection.

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

Jones, J E; Vassilevski, P S; Woodward, C S

This paper provides extensions of an element agglomeration AMG method to nonlinear elliptic problems discretized by the finite element method on general unstructured meshes. The method constructs coarse discretization spaces and corresponding coarse nonlinear operators as well as their Jacobians. We introduce both standard (fairly quasi-uniformly coarsened) and non-standard (coarsened away) coarse meshes and respective finite element spaces. We use both kind of spaces in FAS type coarse subspace correction (or Schwarz) algorithms. Their performance is illustrated on a number of model problems. The coarsened away spaces seem to perform better than the standard spaces for problems with nonlinearities inmore » the principal part of the elliptic operator.« less

Progress on the Development of the hPIC Particle-in-Cell Code

NASA Astrophysics Data System (ADS)

Dart, Cameron; Hayes, Alyssa; Khaziev, Rinat; Marcinko, Stephen; Curreli, Davide; Laboratory of Computational Plasma Physics Team

2017-10-01

Advancements were made in the development of the kinetic-kinetic electrostatic Particle-in-Cell code, hPIC, designed for large-scale simulation of the Plasma-Material Interface. hPIC achieved a weak scaling efficiency of 87% using the Algebraic Multigrid Solver BoomerAMG from the PETSc library on more than 64,000 cores of the Blue Waters supercomputer at the University of Illinois at Urbana-Champaign. The code successfully simulates two-stream instability and a volume of plasma over several square centimeters of surface extending out to the presheath in kinetic-kinetic mode. Results from a parametric study of the plasma sheath in strongly magnetized conditions will be presented, as well as a detailed analysis of the plasma sheath structure at grazing magnetic angles. The distribution function and its moments will be reported for plasma species in the simulation domain and at the material surface for plasma sheath simulations. Membership Pending.

Magnetically induced phonon splitting in A Cr 2 O 4 spinels from first principles

DOE PAGES

Wysocki, Aleksander L.; Birol, Turan

2016-04-22

We study the magnetically-induced phonon splitting in cubic ACr 2O 4 (A=Mg, Zn, Cd) spinels from first principles and demonstrate that the sign of the splitting, which is experimentally observed to be opposite in CdCr 2O 4 compared to ZnCr 2O 4 and MgCr 2O 4, is determined solely by the particular magnetic ordering pattern observed in these compounds. We further show that this interaction between magnetism and phonon frequencies can be fully described by the previously proposed spin-phonon coupling model [C. J. Fennie and K. M. Rabe, Phys. Rev. Lett. 96, 205505 (2006)] that includes only the nearest neighbormore » exchange. In conclusion, using this model with materials specific parameters calculated from first principles, we provide additional insights into the physics of spin-phonon coupling in this intriguing family of compounds.« less

Marginal adaptation of lithium disilicate ceramic crowns cemented with three different resin cements.

PubMed

Peroz, Ingrid; Mitsas, Triantafyllos; Erdelt, Kurt; Kopsahilis, Niko

2018-04-17

The cementation process and cementation materials have an influence on the marginal adaptation of restorations. The gap could be affected by thermal and mechanical loading (TCML). The computerized x-ray microtomography (μCT) method offers the possibility of measuring the marginal gap without destruction of the restoration. The aim of this study was to evaluate the marginal gap (MG) and the absolute marginal discrepancy (AMD) before and after TCML. Thirty-nine human premolars were prepared for full ceramic crowns made of lithium disilicate. The crowns were cemented by three different resins-Panavia F 2.0, Variolink II, and Relyx Unicem. The MG and AMD were evaluated by μCT before and after TCML. Panavia F 2.0 had the lowest MG (before 118 μm-after TMCL 124 μm) and AMD (before 145 μm-after TMCL 154 μm), followed by Relyx Unicem (MG: before 164 μm-after TCML 155 μm; AMD: before 213 μm-after TMCL 209 μm) and Variolink II (MG: before 317 μm-after TMCL 320 μm; AMD: before 412 μm-after TMCL 406 μm). The differences were statistically significant before and after TCML. Rather than TCML, it appeared the resin cement was responsible for differences between the MG and AMD before and after TCML. μCT is an accurate technique for assessing cemented restorations. Panavia F 2.0 has the lowest MG and AMD before and after TCML. The resin material that features a three-step protocol (Variolink II) produced higher MG and AMG values than the Panavia or Relyx Unicem varieties with less or no intermediate steps at all.

The effect of ICT on CO2 emissions in emerging economies: does the level of income matters?

PubMed

Danish; Khan, Noheed; Baloch, Muhammad Awais; Saud, Shah; Fatima, Tehreem

2018-05-31

In the modern era of globalization, the rapid increase in information and telecommunication technologies (ICTs) contributes in various sectors of an economy; however, the environmental consequences of ICTs cannot be ignored. Therefore, the study investigates the nexus between ICTs, economic growth, financial development, and environmental quality in emerging economies. The novel feature of the study is that the interaction term of ICT is introduced with economic growth and financial development. The empirical findings of the study are based on panel mean group (MG) and augmented mean group (AMG) estimation methods from 1990 to 2015. The following empirical results are established: first the ICTs significantly affect CO 2 emissions. Second, the moderating effect of ICT and financial development stimulate the level of CO 2 emissions. Third, economic growth contributes CO 2 emission; however, the interaction between ICT and GDP mitigates the level of pollution. Policy thresholds with the R&D in ICT sector are required to mitigate the level of CO 2 emission. Introduction of green ICTs projects in the financial sector is a better choice to improve the energy efficiency.

New therapies targeting apoB metabolism for high-risk patients with inherited dyslipidaemias: what can the clinician expect?

PubMed

Sahebkar, Amirhossein; Watts, Gerald F

2013-12-01

Apolipoprotein B (apoB) has a key role in the assembly and secretion of very low-density lipoprotein (VLDL) from the liver. Plasma apoB concentration affects the number of circulating atherogenic particles, and serves as an independent predictor of the risk of atherosclerotic cardiovascular disease. While statins are the most potent apoB-lowering agents currently prescribed, their efficacy in achieving therapeutic targets for low-density lipoprotein cholesterol (LDL-C) in high-risk patients, such as those with familial hypercholesterolaemia (FH), is limited. Resistance and intolerance to statins also occurs in a significant number of patients, necessitating new types of lipid-lowering therapies. Monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9; AMG 145 and REGN727), a sequence-specific antisense oligonucleotide against apoB mRNA (mipomersen) and a synthetic inhibitor of microsomal triglyceride transfer protein (MTTP; lomitapide) have been tested in phase III clinical trials, particularly in patients with FH. The trials demonstrated the efficacy of these agents in lowering apoB, LDL-C, non-high-density lipoprotein cholesterol and lipoprotein(a) by 32-55 %, 37-66 %, 38-61 % and 22-50 % (AMG 145), 21-68 %, 29-72 %, 16-60 % and 8-36 % (REGN727), 16-71 %, 15-71 %, 12-66 % and 23-49 % (mipomersen) and 24-55 %, 25-51 %, 27-50 % and 15-19 % (lomitapide), respectively. Monoclonal antibodies against PCSK9 have an excellent safety profile and may be indicated not only in heterozygous FH, but also in statin-intolerant patients and those with other inherited dyslipidemias, such as familial combined hyperlipidaemia and familial elevation in Lp(a). Mipomersen and lomitapide increase hepatic fat content and are at present indicated for treating adult patients with homozygous FH alone.

Evaluation of the efficacy, safety and glycaemic effects of evolocumab (AMG 145) in hypercholesterolaemic patients stratified by glycaemic status and metabolic syndrome.

PubMed

Blom, Dirk J; Koren, Michael J; Roth, Eli; Monsalvo, Maria Laura; Djedjos, C Stephen; Nelson, Patric; Elliott, Mary; Wasserman, Scott M; Ballantyne, Christie M; Holman, Rury R

2017-01-01

To examine the lipid and glycaemic effects of 52 weeks of treatment with evolocumab. The Durable Effect of PCSK9 Antibody Compared with Placebo Study (DESCARTES) was a 52-week placebo-controlled trial of evolocumab that randomized 905 patients from 88 study centres in 9 countries, with 901 receiving at least one dose of study drug. For this post-hoc analysis, DESCARTES patients were categorized by baseline glycaemic status: type 2 diabetes, impaired fasting glucose (IFG), metabolic syndrome (MetS) or none of these. Monthly subcutaneous evolocumab (420 mg) or placebo was administered. The main outcomes measured were percentage change in LDL-cholesterol (LDL-C) at week 52 and safety. A total of 413 patients had dysglycaemia (120, type 2 diabetes; 293, IFG), 289 had MetS (194 also had IFG) and 393 had none of these conditions. At week 52, evolocumab reduced LDL-C by >50% in all subgroups, with favourable effects on other lipids. No significant differences in fasting plasma glucose, HbA1c, insulin, C-peptide or HOMA indices were seen in any subgroup between evolocumab and placebo at week 52. The overall incidence of new-onset diabetes mellitus did not differ between placebo (6.6%) and evolocumab (5.6%); in those with baseline normoglycaemia, the incidences were 1.9% and 2.7%, respectively. Incidences of AEs were similar in evolocumab- and placebo-treated patients. Evolocumab showed encouraging safety and efficacy at 52 weeks in patients with or without dysglycaemia or MetS. Changes in glycaemic parameters did not differ between evolocumab- and placebo-treated patients within the glycaemic subgroups examined. © 2016 John Wiley & Sons Ltd.

Development of a combustor liner composed of ceramic matrix composite (CMC)

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

Nishio, K.; Igashira, K.I.; Take, K.

The Research Institute of Advanced Materials Gas-Generator (AMG), which is a joint effort by the Japan Key Technology Center and 14 firms in Japan, has, since fiscal year 1992, been conducting technological studies on an innovative gas generator that will use 20% less fuel, weight 50% less, and emit 70% less NO{sub x} than the conventional gas generator through the use of advanced materials. Within this project, there is an R and D program for applying ceramic matrix composite (CMC) liners to the combustor, which is a major component of the gas generator. In the course of R and D,more » continuous SiC fiber-reinforced SiC composite (SiC{sup F}/SiC) was selected as the most suitable CMD for the combustor liner because of its thermal stability and formability. An evaluation of the applicability of the SiC{sup F}/SiC composite to the combustor liner on the basis of an evaluation of its mechanical properties and stress analysis of a SiC{sup F}/SiC combustor liner was carried out, and trial SiC{sup F}/SiC combustor liners, the largest of which was 500-mm in diameter, were fabricated by the filament winding and PIP (polymer impregnation and pyrolysis) method. Using a SiC{sup F}/SiC liner built to the actual dimensions, a noncooling combustion test was carried out and even when the gas temperature was raised to 1873K at outlet of the liner, no damage was observed after the test. Through their studies, the authors have confirmed the applicability of the selected SiC{sup F}/SiC composite as a combustor liner. In this paper, the authors describe the present state of the R and D of a CMC combustor liner.« less

Prenatal identification of i(Yp) by molecular cytogenetic analysis

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

Wang, B.T.; Peng, W.; Williams, J. III

1994-09-01

An isochromosome derived from the short arm of the Y chromosome, i(Yp), is a rare marker chromosome. Its de novo presence prenatally represents a diagnostic dilemna since its impact on fetal development is difficult to predict. We present a case of 46,X,+i(Yp) de novo detected in an amniotic fluid specimen received for karyotype analysis. Fluorescence in situ hybridization (FISH) studies using a panel of Y-specific biotinylated DNA probes including a Y-centromere probe, a Y whole chromosome painting probe, and a lambda HAM2 probe containing 19 kb of AMG-Y sequence, located to Yp11.2, have identified the marker chromosome as i(Yp). Themore » breakpoint on this marker chromosome is tentatively assigned to Yq11.1 which is close to the centromere. The present report illustrates the importance of FISH techniques as a complement to cytogenetic methods for accurate identification of chromosome rearrangements in prenatal diagnosis and genetic counseling.« less

Effect of friction stir welding parameters on defect formation

NASA Astrophysics Data System (ADS)

Tarasov, S. Yu.; Rubtsov, V. E.; Eliseev, A. A.; Kolubaev, E. A.; Filippov, A. V.; Ivanov, A. N.

2015-10-01

Friction stir welding is a perspective method for manufacturing automotive parts, aviation and space technology. One of the major problems is the formation of welding defects and weld around the welding zone. The formation of defect is the main reason failure of the joint. A possible way to obtain defect-free welded joints is the selection of the correct welding parameters. Experimental results describing the effect of friction stir welding process parameters on the defects of welded joints on aluminum alloy AMg5M have been shown. The weld joint defects have been characterized using the non-destructive radioscopic and ultrasound phase array methods. It was shown how the type and size of defects determine the welded joint strength.

["Legal highs" from the German internet--"bath salt drugs" on the rise].

PubMed

Musshoff, Frank; Hottmann, Lidia; Hess, Cornelius; Madea, Burkhard

2013-01-01

The appearance of dangerous and insufficiently studied designer drugs has increased substantially within the last few years. Mixtures containing centrally active compounds are often declared as "bath salt", "incense", "plant food", "bong cleaners" and are marketed in head shops and on the Internet. As the majority of the ingredients of such products are not subject to regulations of the German Narcotics Law (Betäubungsmittelgesetz, BtMG), the vendors and consumers mistake the sale of such products for legal. An alternative possibility to prosecute the distribution of so-called "legal highs" arises from the regulations of the German Medicinal Products Act (Arzneimittelgesetz, AMG). Indicating a private address, several products were purchased via the Internet. The products were analyzed by gas chromatography- mass spectrometry using computer-assisted database search and potential hits were checked for plausibility. The analysis of 100 samples revealed centrally acting compounds (including caffeine) in 98 % (75 % of all samples positive for caffeine). In 16 % of the samples, drugs subject to the BtMG at the time of purchase (end of 2011) were found including 2,5-dimethoxy-4-methylamphetamine, amphetamine, etilamphetamine, N-benzylpiperazine, mephedrone, methcathinone, and phenobarbital. In 55 % of the samples, drugs subject to the current BtMG were found (after its amendment on 20 July 2012). In 37 % of the samples, substances subject to the AMG were found (e.g. ephedrine). In 35 % of the samples, drugs with a potential psychotropic effect were found. In 57.3 % of the positive samples, more than one active ingredient was determined and in some cases up to five active components were found. Other interesting pharmacologically active ingredients found were 4-methylcathinone (n=13), flephedrone (n=8), trifluoromethylphenyl-piperazine (n=7), methylone (n=5), butylone (n=2), hordenine (n=2), and harmane (n=2). Most of the substances not covered by the BtMG can be classified as "unsafe" drugs. The distribution of unsafe drugs is illegal in Germany. However, the easy availability of real or potential drugs has to be seen critically. Little is known about the toxicological and pharmacological effects of those single substances, let alone of interactions in mixtures of such substances. In chat rooms, users advertise such drugs and blaze abroad their own experiences.

High-throughput 96-well solvent mediated sonic blending synthesis and on-plate solid/solution stability characterization of pharmaceutical cocrystals.

PubMed

Luu, Van; Jona, Janan; Stanton, Mary K; Peterson, Matthew L; Morrison, Henry G; Nagapudi, Karthik; Tan, Helming

2013-01-30

A 96-well high-throughput cocrystal screening workflow has been developed consisting of solvent-mediated sonic blending synthesis and on-plate solid/solution stability characterization by XRPD. A strategy of cocrystallization screening in selected blend solvents including water mixtures is proposed to not only manipulate solubility of the cocrystal components but also differentiate physical stability of the cocrystal products. Caffeine-oxalic acid and theophylline-oxalic acid cocrystals were prepared and evaluated in relation to saturation levels of the cocrystal components and stability of the cocrystal products in anhydrous and hydrous solvents. AMG 517 was screened with a number of coformers, and solid/solution stability of the resulting cocrystals on the 96-well plate was investigated. A stability trend was observed and confirmed that cocrystals comprised of lower aqueous solubility coformers tended to be more stable in water. Furthermore, cocrystals which could be isolated under hydrous solvent blending condition exhibited superior physical stability to those which could only be obtained under anhydrous condition. This integrated HTS workflow provides an efficient route in an API-sparing approach to screen and identify cocrystal candidates with proper solubility and solid/solution stability properties. Copyright © 2012 Elsevier B.V. All rights reserved.

Phase 1, randomized, parallel-group, double-blind, placebo-controlled trial to evaluate the effects of erenumab (AMG 334) and concomitant sumatriptan on blood pressure in healthy volunteers.

PubMed

de Hoon, Jan; Van Hecken, Anne; Vandermeulen, Corinne; Herbots, Marissa; Kubo, Yumi; Lee, Ed; Eisele, Osa; Vargas, Gabriel; Gabriel, Kristin

2018-01-01

Objectives The aim of this study was to assess the effects of concomitant administration of erenumab and sumatriptan on resting blood pressure, pharmacokinetics, safety, and tolerability in healthy subjects. Methods In this phase 1, parallel-group, one-way crossover, double-blind, placebo-controlled study, healthy adult subjects were randomized (1:2) to receive either intravenous placebo and subcutaneous sumatriptan 12 mg (i.e. two 6-mg injections separated by 1 hour) or intravenous erenumab 140 mg and subcutaneous sumatriptan 12 mg. Blood pressure was measured pre-dose and at prespecified times post-dose. The primary endpoint was individual time-weighted averages of mean arterial pressure, measured from 0 hours to 2.5 hours after the first dose of sumatriptan. Pharmacokinetic parameters for sumatriptan were evaluated by calculating geometric mean ratios (erenumab and sumatriptan/placebo and sumatriptan). Adverse events and anti-erenumab antibodies were also evaluated. Results A total of 34 subjects were randomized and included in the analysis. Least squares mean (standard error) time-weighted averages of mean arterial pressure were 87.4 (1.0) mmHg for the placebo and sumatriptan group and 87.4 (1.2) mmHg for the erenumab and sumatriptan group. Mean difference in mean arterial pressure between groups was -0.04 mmHg (90% confidence interval: -2.2, 2.1). Geometric mean ratio estimates for maximum plasma concentration of sumatriptan was 0.95 (90% confidence interval: 0.82, 1.09), area under the plasma concentration-time curve (AUC) from time 0 to 6 hours was 0.98 (90% confidence interval: 0.93, 1.03), and AUC from time 0 to infinity was 1.00 (90% confidence interval: 0.96, 1.05). No clinically relevant safety findings for co-administration of sumatriptan and erenumab were identified. Conclusion Co-administration of erenumab and sumatriptan had no additional effect on resting blood pressure or on pharmacokinetics of sumatriptan. ClinicalTrials.gov, NCT02741310.

Antibody-based therapeutics to watch in 2011

PubMed Central

2011-01-01

This overview of 25 monoclonal antibody (mAb) and five Fc fusion protein therapeutics provides brief descriptions of the candidates, recently published clinical study results and on-going Phase 3 studies. In alphanumeric order, the 2011 therapeutic antibodies to watch list comprises AIN-457, bapineuzumab, brentuximab vedotin, briakinumab, dalotuzumab, epratuzumab, farletuzumab, girentuximab (WX-G250), naptumomab estafenatox, necitumumab, obinutuzumab, otelixizumab, pagibaximab, pertuzumab, ramucirumab, REGN88, reslizumab, solanezumab, T1h, teplizumab, trastuzumab emtansine, tremelimumab, vedolizumab, zalutumumab and zanolimumab. In alphanumeric order, the 2011 Fc fusion protein therapeutics to watch list comprises aflibercept, AMG-386, atacicept, Factor VIII-Fc and Factor IX-Fc. Commercially-sponsored mAb and Fc fusion therapeutics that have progressed only as far as Phase 2/3 or 3 were included. Candidates undergoing regulatory review or products that have been approved may also be in Phase 3 studies, but these were excluded. Due to the large body of primary literature about the candidates, only selected references are given and results from recent publications and articles that were relevant to Phase 3 studies are emphasized. Current as of September 2010, the information presented here will serve as a baseline against which future progress in the development of antibody-based therapeutics can be measured. PMID:21051951

Erenumab (AMG 334) in episodic migraine: Interim analysis of an ongoing open-label study.

PubMed

Ashina, Messoud; Dodick, David; Goadsby, Peter J; Reuter, Uwe; Silberstein, Stephen; Zhang, Feng; Gage, Julia R; Cheng, Sunfa; Mikol, Daniel D; Lenz, Robert A

2017-09-19

To assess long-term safety and efficacy of anti-calcitonin gene-related peptide receptor erenumab in patients with episodic migraine (EM). Patients enrolled in a 12-week, double-blind, placebo-controlled clinical trial (NCT01952574) who continued in an open-label extension (OLE) study will receive erenumab 70 mg every 4 weeks for up to 5 years. This preplanned interim analysis, conducted after all participants had completed the 1-year open-label follow-up, evaluated changes in monthly migraine days (MMD), achievement of ≥50%, ≥75%, and 100% reductions, Headache Impact Test (HIT-6) score, Migraine-Specific Quality of Life (MSQ), Migraine Disability Assessment (MIDAS), and safety. Data reported as observed without imputation for missing data. Of 472 patients enrolled in the parent study, 383 continued in the OLE with a median exposure to erenumab of 575 days (range 28-822 days). Mean (SD) MMD were 8.8 (2.6) at parent study baseline, 6.3 (4.2) at week 12 (beginning of OLE), and 3.7 (4.0) at week 64 (mean change from baseline [reduction] of 5.0 days). At week 64, 65%, 42%, and 26% achieved ≥50%, ≥75%, and 100% reduction in MMD, respectively. Mean HIT-6 scores were 60.2 (6.3) at baseline and 51.7 (9.2) at week 64. MSQ and MIDAS improvements from baseline were maintained through week 64. Safety profiles during the OLE were similar to those in the double-blind phase, which overall were similar to placebo. One-year efficacy, supported by functional improvements and favorable safety and tolerability profiles, supports further investigation of erenumab as a preventive treatment in patients with EM. NCT01952574. This study provides Class IV evidence that for patients with episodic migraine, erenumab reduces long-term MMD and improves headache-related disability and migraine-specific quality of life. © 2017 American Academy of Neurology.

Viral impacts on microbial carbon cycling in thawing permafrost soils

NASA Astrophysics Data System (ADS)

Trubl, G. G.; Roux, S.; Bolduc, B.; Jang, H. B.; Emerson, J. B.; Solonenko, N.; Li, F.; Solden, L. M.; Vik, D. R.; Wrighton, K. C.; Saleska, S. R.; Sullivan, M. B.; Rich, V. I.

2017-12-01

Permafrost contains 30-50% of global soil carbon (C) and is rapidly thawing. While the fate of this C is unknown, it will be shaped in part by microbes and their associated viruses, which modulate host activities via mortality and metabolic control. To date, viral research in soils has been outpaced by that in aquatic environments, due to the technical challenges of accessing viruses as well as the dramatic physicochemical heterogeneity in soils. Here, we describe advances in soil viromics from our research on permafrost-associated soils, and their implications for associated terrestrial C cycling. First, we optimized viral resuspension-DNA extraction methods for a range of soil types. Second, we applied cutting-edge viral-specific informatics methods to recover viral populations, define their gene content, connect them to potential hosts, and analyze their relationships to environmental parameters. A total of 781 viral populations were recovered from size-fractionated virus samples of three soils along a permafrost thaw gradient. Ecological analyses revealed endemism as recovered viral populations were largely unique to each habitat and unlike those in aquatic communities. Genome- and network-based classification assigned these viruses into 226 viral clusters (VCs; genus-level taxonomy), 55% of which were novel. This increases the number of VCs by a third and triples the number of soil viral populations in the RefSeq database (currently contains 256 VCs and 316 soil viral populations). Genomic analyses revealed 85% of the genes were functionally unknown, though 5% of the annotatable genes contained C-related auxiliary metabolic genes (AMGs; e.g. glycoside hydrolases). Using sequence-based features and microbial population genomes, we were able to in silico predict hosts for 30% of the viral populations. The identified hosts spanned 3 phyla and 6 genera but suggested these viruses have species-specific host ranges as >80% of hosts for a given virus were in the same species. Several identified hosts (e.g. Acidobacterium) are dominant community members that play major roles in C cycling through organic matter degradation. Together these findings show that permafrost viruses play a major role in the fate of soil C through infection of key hosts and metabolic reprogramming using specific C cycling AMGs.

Fabrication and Characterization of New Composite Tio2 Carbon Nanofiber Anodic Catalyst Support for Direct Methanol Fuel Cell via Electrospinning Method

NASA Astrophysics Data System (ADS)

Abdullah, N.; Kamarudin, S. K.; Shyuan, L. K.; Karim, N. A.

2017-12-01

Platinum (Pt) is the common catalyst used in a direct methanol fuel cell (DMFC). However, Pt can lead towards catalyst poisoning by carbonaceous species, thus reduces the performance of DMFC. Thus, this study focuses on the fabrication of a new composite TiO2 carbon nanofiber anodic catalyst support for direct methanol fuel cells (DMFCs) via electrospinning technique. The distance between the tip and the collector (DTC) and the flow rate were examined as influencing parameters in the electrospinning technique. To ensure that the best catalytic material is fabricated, the nanofiber underwent several characterizations and electrochemical tests, including FTIR, XRD, FESEM, TEM, and cyclic voltammetry. The results show that D18, fabricated with a flow rate of 0.1 mLhr-1 and DTC of 18 cm, is an ultrafine nanofiber with the smallest average diameter, 136.73 ± 39.56 nm. It presented the highest catalyst activity and electrochemical active surface area value as 274.72 mAmg-1 and 226.75m2 g-1 PtRu, respectively, compared with the other samples.

Calcimimetic and Calcilytic Drugs: Feats, Flops, and Futures.

PubMed

Nemeth, E F; Goodman, W G

2016-04-01

The actions of extracellular Ca(2+) in regulating parathyroid gland and kidney functions are mediated by the extracellular calcium receptor (CaR), a G protein-coupled receptor. The CaR is one of the essential molecules maintaining systemic Ca(2+) homeostasis and is a molecular target for drugs useful in treating bone and mineral disorders. Ligands that activate the CaR are termed calcimimetics and are classified as either agonists (type I) or positive allosteric modulators (type II); calcimimetics inhibit the secretion of parathyroid hormone (PTH). Cinacalcet is a type II calcimimetic that is used to treat secondary hyperparathyroidism in patients receiving dialysis and to treat hypercalcemia in some forms of primary hyperparathyroidism. The use of cinacalcet among patients with secondary hyperparathyroidism who are managed with dialysis effectively lowers circulating PTH levels, reduces serum phosphorus and FGF23 concentrations, improves bone histopathology, and may diminish skeletal fracture rates and the need for parathyroidectomy. A second generation type II calcimimetic (AMG 416) is currently under regulatory review. Calcilytics are CaR antagonists that stimulate the secretion of PTH. Several calcilytic compounds have been evaluated as orally active anabolic therapies for postmenopausal osteoporosis but clinical development of all of them has been abandoned because they lacked clinical efficacy. Calcilytics might be repurposed for new indications like autosomal dominant hypocalcemia or other disorders beyond those involving systemic Ca(2+) homeostasis.

[Consequences of the 12th AMG amendment on the conduct of non-commercial clinical trials].

PubMed

Rossion, I

2005-12-01

In 2004, the German Drug Law was reformed substantially putting into effect the European directive 2001/20/EG on Good Clinical Practice (GCP). Investigator initiated trials have to comply with the same requirements as clinical trials for drug development. When registered drugs are used in non-commercial clinical trials some simplifications are possible.Currently, all essential elements of GCP, such as financing of the trial, laying-down of sponsor responsibilities, establishing an extensive quality assurance system as well as immediate reporting of unexpected serious drug reactions, are stipulated by law. Since regulatory authorities and ethics committees have to approve every clinical trial, surveillance is reinforced. The new requirements cannot be met without sufficient financing, qualified personnel and professional structures for clinical trials. Compared to European partners, the research location Germany is at a disadvantage due to high administrative workload and costs.

Diagnosis and treatment of gastroesophageal reflux disease: recommendations of the Asociación Mexicana de Gastroenterología.

PubMed

Huerta-Iga, F; Bielsa-Fernández, M V; Remes-Troche, J M; Valdovinos-Díaz, M A; Tamayo-de la Cuesta, J L

Emerging concepts in the pathophysiology of gastroesophageal reflux disease (GERD) and the constant technologic advances in the diagnosis and treatment of this clinical condition make it necessary to frequently review and update the clinical guidelines, recommendations, and official statements from the leading academic groups worldwide. The Asociación Mexicana de Gastroenterología (AMG), aware of this responsibility, brought together national experts in this field to analyze the most recent scientific evidence and formulate a series of practical recommendations to guide and facilitate the diagnostic process and efficacious treatment of these patients. The document includes algorithms, figures, and tables for convenient consultation, along with opinions on GERD management in sensitive populations, such as pregnant women and older adults. Copyright © 2016 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Co/NHPI-mediated aerobic oxygenation of benzylic C–H bonds in pharmaceutically relevant molecules

DOE PAGES

Hruszkewycz, Damian P.; Miles, Kelsey C.; Thiel, Oliver R.; ...

2016-10-07

A simple cobalt(II)/N-hydroxyphthalimide catalyst system has been identified for selective conversion of benzylic methylene groups in pharmaceutically relevant (hetero)arenes to the corresponding (hetero)aryl ketones. The radical reaction pathway tolerates electronically diverse benzylic C–H bonds, contrasting recent oxygenation reactions that are initiated by deprotonation of a benzylic C–H bond. The reactions proceed under practical reaction conditions (1 M substrate in BuOAc or EtOAc solvent, 12 h, 90–100 °C), and they tolerate common heterocycles, such as pyridines and imidazoles. A cobalt-free, electrochemical, NHPI-catalyzed oxygenation method overcomes challenges encountered with chelating substrates that inhibit the chemical reaction. The utility of the aerobic oxidationmore » method is showcased in the multigram synthesis of a key intermediate towards a drug candidate (AMG 579) under process-relevant reaction conditions.« less

Transrapid (the first high-speed Maglev train system certified ready for application): Development status and prospects for deployment

NASA Technical Reports Server (NTRS)

Luerken, Reinhard F.

1994-01-01

The Transrapid maglev technology is at the threshold of commercial deployment and technologically all prerequisites for the successful operation of the system in public service are given. In post unification Germany the domestic maglev technology is envisioned to be applied in the Berlin-Hamburg project. At present, a public-private funding concept is being prepared and the lengthy planning process is about to be initiated. In the USA the AMG has presented a program to Americanize the technology and to make it available for commercial use in the U.S. in the very near future. The paramount features of this program are to generate economic development, provide a basis for transportation technology development, create opportunities for U.S. industry, improve the U.S. transportation infrastructure, and improve the environment and traveler safety. Maglev is ready for the U.S.; is the U.S. ready for maglev?

[Failure of a study in forensic psychiatric hospitals : Clinical trial to investigate the additive effect of triptorelin on the efficacy of psychotherapy].

PubMed

Briken, Peer; Müller, Jürgen L; Berner, Wolfgang; Bödeker, Rolf-Hasso; Vollmann, Jochen; Kasperk, Christian; Koller, Matthias

2017-05-01

A testosterone-lowering medication is relatively commonly used as a form of treatment for sexual offenders with severe paraphilic disorders in German forensic psychiatric hospitals; however, a double-blind, controlled and randomized study, which investigates the efficacy of this medication, is still lacking. This article describes the process from the planning to the rejection of a clinical trial over the period from 2009 to 2015. Despite the careful planning with an interdisciplinary team and giving special consideration to the complex legal situation, the Federal Institute for Drugs and Medical Devices (BfArM) rejected the proposed trial in a brief formal letter with reference to the German Drug Law (§ 40 para. 1 p. 3 nr. 4 AMG). The ethics committee of the Hamburg Medical Association considered that clinical research is basically not possible with patients detained in a forensic psychiatric hospital. In the opinion of the authors, the described facts illustrate how legal regulations that should protect vulnerable groups in medical research, in a specific case can lead to the fact that a therapy form relevant to the corresponding patient group cannot be scientifically investigated.

Gateways to clinical trials.

PubMed

Tomillero, A; Moral, M A

2010-06-01

[¹¹C]RAC; (18)F-Fluoromisonidazole; 89-12; 9-[¹⁸F]Fluoropropyl-(+)-dihydrotetrabenazine; Adalimumab, Adecatumumab, ADMVA, ADXS-11-001, Aflibercept, Agatolimod sodium, AGS-004, Alglucosidase alfa, Aliskiren fumarate, Alvocidib hydrochloride, AMG-108, AMG-853, Apixaban, Aripiprazole, Armodafinil, Atazanavir sulfate, Atomoxetine hydrochloride; Bevacizumab, BioMatrix Flex drug eluting stent, Biphasic insulin aspart, Bortezomib, Bosentan; Caspofungin acetate, Cediranib, Cetuximab, ChimeriVax-Dengue, Choriogonadotropin alfa, Cinacalcet hydrochloride, Cizolirtine citrate, Clofarabine, Cocaine conjugate vaccine, CX-717; Darbepoetin alfa, Dasatinib, Decitabine, Denosumab, Desvenlafaxine succinate, Dexamethasone sodium phosphate, Dienogest, Diphencyprone, Doripenem, DTaP-HepB-IPV, Dutasteride; E-7010, Ecallantide, Ecstasy, Eicosapentaenoic acid/docosahexaenoic acid, Emtricitabine, Enfuvirtide, Erlotinib hydrochloride, Eszopiclone, Etonogestrel/ethinyl estradiol, Etoricoxib, Everolimus, Everolimus-eluting coronary stent EVT-201, Ezetimibe, Ezetimibe/simvastatin; Ferumoxytol, Fesoterodine fumavate, Figitumumab, Filgrastim, Fingolimod hydrochloride, Fluticasone furoate, Fluval P, Fluzone, Fondaparinux sodium, Fulvestrant, Fungichromin; Gamma-hydroxybutyrate sodium, Gefitinib, GHB-01L1, GLY-230, GSK-1349572; Hib-MenCY-TT, Hib-TT, HPV-6/11/16/18, Hydrocodone bitartrate; IC-51, Icatibant acetate, Imatinib mesylate, Immunoglobulin intravenous (human), Indetanib, Influenza A (H1N1) 2009 Monovalent Vaccine, Inhalable human insulin, Insulin glargine, Insulin glulisine, Interferon-beta, Ispinesib mesylate, Ixabepilone; Laromustine, Latanoprost/timolol maleate, L-Citrulline, Lenalidomide, Lexatumumab, Linezolid, Lopinavir/ritonavir, Lutropin alfa; Mapatumumab, MDX-066, MDX-1388, Mepolizumab, Methoxy polyethylene glycol-epoetin-beta, Metreleptin, Micafungin sodium, Mometasone furoate/oxymetazoline hydrochloride, Mx-dnG1, Mycophenolic acid sodium salt; Nabiximols, Natalizumab, Nemonoxacin, Norelgestromin/ethinyl estradiol; Oblimersen sodium, Ocriplasmin, Olmesartan medoxomil, Omacetaxine mepesuccinate; Paclitaxel-eluting stent, Pagoclone, Paliperidone, Panitumumab, Pazopanib hydrochloride, PCV7, Pegaptanib octasodium, Peginterferon alfa-2a, Peginterferon alfa-2b/ ribavirin, Pegvisomant, Pemetrexed disodium, Perifosine, Pimecrolimus, Pitavastatin calcium, Plerixafor hydrochloride, Plitidepsin, Posaconazole, Pregabalin, Progesterone capriate; Raltegravir potassium, Ramucirumab, Ranelic acid distrontium salt, Rasburicase, Recombinant Bet V1, Recombinant human insulin, rhFSH, Rolofylline, Romidepsin, Romiplostim, Rosuvastatin calcium; Sapacitabine, Sevelamer carbonate, Sinecatechins, Sirolimus-eluting stent, Sitagliptin phosphate monohydrate, SN-29244, Sorafenib, Sugammadex sodium, Sunitinib malate; Tadalafil, Tafenoquine, Talnetant, Tanezumab, Tapentadol hydrochloride, Tasocitinib citrate, Technosphere/Insulin, Telcagepant, Tenofovir disoproxil fumarate, Teriparatide, Ticagrelor, Tigecycline, Tiotropium bromide, Tipifarnib, Tocilizumab, TS-041; Ulipristal acetate, Urtoxazumab, Ustekinumab; Vandetanib, Varenicline tartrate, Vicriviroc, Voriconazole, Vorinostat, VRC-HIVADV014-00-VP, VRC-HIVDNA016-00-VP; Zoledronic acid monohydrate. Copyright 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

Fabrication and Characterization of New Composite Tio2 Carbon Nanofiber Anodic Catalyst Support for Direct Methanol Fuel Cell via Electrospinning Method.

PubMed

Abdullah, N; Kamarudin, S K; Shyuan, L K; Karim, N A

2017-12-06

Platinum (Pt) is the common catalyst used in a direct methanol fuel cell (DMFC). However, Pt can lead towards catalyst poisoning by carbonaceous species, thus reduces the performance of DMFC. Thus, this study focuses on the fabrication of a new composite TiO 2 carbon nanofiber anodic catalyst support for direct methanol fuel cells (DMFCs) via electrospinning technique. The distance between the tip and the collector (DTC) and the flow rate were examined as influencing parameters in the electrospinning technique. To ensure that the best catalytic material is fabricated, the nanofiber underwent several characterizations and electrochemical tests, including FTIR, XRD, FESEM, TEM, and cyclic voltammetry. The results show that D18, fabricated with a flow rate of 0.1 mLhr -1 and DTC of 18 cm, is an ultrafine nanofiber with the smallest average diameter, 136.73 ± 39.56 nm. It presented the highest catalyst activity and electrochemical active surface area value as 274.72 mAmg -1 and 226.75m 2  g -1 PtRu , respectively, compared with the other samples.

Telegenetics: application of a tele-education program in genetic syndromes for Brazilian students

PubMed Central

MAXIMINO, Luciana Paula; PICOLINI-PEREIRA, Mirela Machado; CARVALHO, José Luiz Brito

2014-01-01

With the high occurrence of genetic anomalies in Brazil and the manifestations of communication disorders associated with these conditions, the development of educative actions that comprise these illnesses can bring unique benefits in the identification and appropriate treatment of these clinical pictures. Objective The aim of this study was to develop and analyze an educational program in genetic syndromes for elementary students applied in two Brazilian states, using an Interactive Tele-education model. Material and Methods The study was carried out in 4 schools: two in the state of São Paulo, Southeast Region, Brazil, and two in the state of Amazonas, North Region, Brazil. Forty-five students, both genders, aged between 13 and 14 years, of the 9th grade of the basic education of both public and private system, were divided into two groups: 21 of São Paulo Group (SPG) and 24 of Amazonas Group (AMG). The educational program lasted about 3 months and was divided into two stages including both classroom and distance activities on genetic syndromes. The classroom activity was carried out separately in each school, with expository lessons, graphs and audiovisual contents. In the activity at a distance the educational content was presented to students by means of the Interactive Tele-education model. In this stage, the students had access a Cybertutor, using the Young Doctor Project methodology. In order to measure the effectiveness of the educational program, the Problem Situation Questionnaire (PSQ) and the Web Site Motivational Analysis Checklist adapted (FPM) were used. Results The program developed was effective for knowledge acquisition in 80% of the groups. FPM showed a high satisfaction index from the participants in relation to the Interactive Tele-education, evaluating the program as "awesome course". No statistically significant differences between the groups regarding type of school or state were observed. Conclusion Thus, the Tele-Education Program can be used as a tool for educational purposes in genetic syndromes of other populations, in several regions of Brazil. PMID:25591016

Estimating conformation content of a protein using citrate-stabilized Au nanoparticles

NASA Astrophysics Data System (ADS)

Deka, Jashmini; Paul, Anumita; Chattopadhyay, Arun

2010-08-01

Herein we report the use of the optical properties of citrate-stabilized gold nanoparticles (Au NPs) for estimation of native or denatured conformation content in a mixture of a protein in solution. The UV-vis extinction spectrum of citrate-stabilized Au NPs is known to broaden differently in the presence of native and denatured states of α-amylase, bovine serum albumin (BSA) or amyloglucosidase (AMG). On the other hand, herein we show that when a mixture of native and denatured protein was present in the medium, the broadening of the spectrum differed for different fractional content of the conformations. Also, the total area under the extinction spectrum varied linearly with the change in the mole fraction content of a state and for a constant total protein concentration. Transmission electron microscopy (TEM) measurements revealed different levels of agglomeration for different fractional contents of the native or denatured state of a protein. In addition, time-dependent denaturation of a protein could be followed using the present method. The rate constants calculated for denaturation indicated a possible fast change in conformation of a protein before complete thermal denaturation. The observations have been explained based on the changes in extinction coefficient (thereby oscillator strength) upon interaction of citrate-stabilized NPs with proteins being in different states and levels of agglomeration.Herein we report the use of the optical properties of citrate-stabilized gold nanoparticles (Au NPs) for estimation of native or denatured conformation content in a mixture of a protein in solution. The UV-vis extinction spectrum of citrate-stabilized Au NPs is known to broaden differently in the presence of native and denatured states of α-amylase, bovine serum albumin (BSA) or amyloglucosidase (AMG). On the other hand, herein we show that when a mixture of native and denatured protein was present in the medium, the broadening of the spectrum differed for different fractional content of the conformations. Also, the total area under the extinction spectrum varied linearly with the change in the mole fraction content of a state and for a constant total protein concentration. Transmission electron microscopy (TEM) measurements revealed different levels of agglomeration for different fractional contents of the native or denatured state of a protein. In addition, time-dependent denaturation of a protein could be followed using the present method. The rate constants calculated for denaturation indicated a possible fast change in conformation of a protein before complete thermal denaturation. The observations have been explained based on the changes in extinction coefficient (thereby oscillator strength) upon interaction of citrate-stabilized NPs with proteins being in different states and levels of agglomeration. Electronic supplementary information (ESI) available: Additional UV-vis and fluorescence spectra and graphs based on UV-vis studies. See DOI: 10.1039/c0nr00154f

High-performance transition metal-doped Pt 3Ni octahedra for oxygen reduction reaction

DOE PAGES

Huang, Xiaoqing; Zhao, Zipeng; Cao, Liang; ...

2015-06-11

Bimetallic platinum-nickel (Pt-Ni) nanostructures represent an emerging class of electrocatalysts for oxygen reduction reaction (ORR) in fuel cells, but practical applications have been limited by catalytic activity and durability. We surface-doped Pt 3Ni octahedra supported on carbon with transition metals, termed M-Pt 3Ni/C, where M is vanadium, chromium, manganese, iron, cobalt, molybdenum (Mo), tungsten, or rhenium. The Mo-Pt 3Ni/C showed the best ORR performance, with a specific activity of 10.3 mA/cm2 and mass activity of 6.98 A/mgPt, which are 81- and 73-fold enhancements compared with the commercial Pt/C catalyst (0.127 mA/cm 2 and 0.096 A/mg Pt). In conclusion, theoretical calculationsmore » suggest that Mo prefers subsurface positions near the particle edges in vacuum and surface vertex/edge sites in oxidizing conditions, where it enhances both the performance and the stability of the Pt3Ni catalyst.« less

Improved Regolith-Landform and Geological Mapping using AIRSAR Data as an Aid to Mineral Exploration in the North-Eastern Goldfields Region, Western Australia

NASA Technical Reports Server (NTRS)

Tapley, Ian J.

1996-01-01

The distinctive contribution of AIRSAR data in characterizing the regolith-landforms in a relatively vegetation free environment are discussed. AIRSAR frame processed data were initially MAF-cleaned to enhance the signal content of the data before geocoding to AMG coordinates. Colors in a three frequency single polarization combination image C-, L- P- bands, and in an enhancement of pedestal height, relate directly to the scale of surface roughness of the various regolith units Examination of the AIRSAR enhancements reveals that in mafic terrain, and to a lesser extent, in felsic terrain, AIRSAR data provides discrimination between the principle geomorphic regimes, relict, erosional and depositional. A multivariate statistical technique called an all-possible subsets calculation was used to examine the degree of polarimetric separation between selected regolith-landforms for all combinations of the nine band AIRSAR radar. An unanticipated aspect of the research was the identification on the AIRSAR imagery of previously unmapped structural features.

Anticonvulsive effects of endocannabinoids; an investigation to determine the role of regulatory components of endocannabinoid metabolism in the Pentylenetetrazol induced tonic- clonic seizures.

PubMed

Zareie, Parisa; Sadegh, Mehdi; Palizvan, Mohammad Reza; Moradi-Chameh, Homeira

2018-06-01

2-Arachidonoylglycerol (2-AG) and anandamide are two major endocannabinoids produced, released and eliminated by metabolic pathways. Anticonvulsive effect of 2-AG and CB1 receptor is well-established. Herein, we designed to investigate the anticonvulsive influence of key components of the 2-AG and anandamide metabolism. Tonic-clonic seizures were induced by an injection of Pentylenetetrazol (80 mg/kg, i.p.) in adult male Wistar rats. Delay and duration for the seizure stages were considered for analysis. Monoacylglycerol lipase blocker (JJKK048; 1 mg/kg) or alpha/beta hydroxylase domain 6 blocker (WWL70; 5 mg/kg) were administrated alone or with 2-AG to evaluate the anticonvulsive potential of these enzymes. To determine the CB1 receptor involvement, its blocker (MJ15; 3 mg/kg) was administrated associated with JJKK048 or WWL70. To assess anandamide anticonvulsive effect, anandamide membrane transporter blocker (LY21813240; 2.5 mg/kg) was used alone or associated with MJ15. Also, fatty acid amide hydrolase blocker (URB597; 1 mg/kg; to prevent intracellular anandamide hydrolysis) were used alone or with AMG21629 (transient receptor potential vanilloid; TRPV1 antagonist; 3 mg/kg). All compounds were dissolved in DMSO and injected i.p., before the Pentylenetetrazol. Both JJKK048 and WWL70 revealed anticonvulsive effect. Anticonvulsive effect of JJKK048 but not WWL70 was CB1 receptor dependent. LY2183240 showed CB1 receptor dependent anticonvulsive effect. However, URB597 revealed a TRPV1 dependent proconvulsive effect. It seems extracellular accumulation of 2-AG or anandamide has anticonvulsive effect through the CB1 receptor, while intracellular anandamide accumulation is proconvulsive through TRPV1.

Development and application of a fluorescent glucose uptake assay for the high-throughput screening of non-glycoside SGLT2 inhibitors.

PubMed

Wu, Szu-Huei; Yao, Chun-Hsu; Hsieh, Chieh-Jui; Liu, Yu-Wei; Chao, Yu-Sheng; Song, Jen-Shin; Lee, Jinq-Chyi

2015-07-10

Sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors are of current interest as a treatment for type 2 diabetes. Efforts have been made to discover phlorizin-related glycosides with good SGLT2 inhibitory activity. To increase structural diversity and better understand the role of non-glycoside SGLT2 inhibitors on glycemic control, we initiated a research program to identify non-glycoside hits from high-throughput screening. Here, we report the development of a novel, fluorogenic probe-based glucose uptake system based on a Cu(I)-catalyzed [3+2] cycloaddition. The safer processes and cheaper substances made the developed assay our first priority for large-scale primary screening as compared to the well-known [(14)C]-labeled α-methyl-D-glucopyranoside ([(14)C]-AMG) radioactive assay. This effort culminated in the identification of a benzimidazole, non-glycoside SGLT2 hit with an EC50 value of 0.62 μM by high-throughput screening of 41,000 compounds. Copyright © 2015 Elsevier B.V. All rights reserved.

Recent advances in nephrology: highlights from the 35th annual meeting of the American society of nephrology.

PubMed

Cases, Aleix

2002-12-01

The 35th Annual Meeting of the American Society of Nephrology, held in Philadelphia, Pennsylvania, United States (October 30 to November 4, 2002) presented the newest advances in basic and clinical nephrology science. Several presentations and symposia discussed the effects of various interventions and risk factors in clinical outcomes in dialysis patients. The recent evidences of pure red cell aplasia secondary to neutralizing antibodies against erythropoietin were also extensively discussed in a special symposium. Recent advances in the management of calcium phosphorus metabolism and secondary hyperparathyroidism, such as the clinical efficacy and safety of AMG-073, a new calcimimetic agent in the control of hyperparathyroidism in chronic kidney disease patients, or the use of sevelamer or lanthanum carbonate as phosphate binders, were presented. The results in animal models on improved sparing of renal function with rapamycin versus cyclosporin A represent a promising advance in renal transplantation. Finally, the recent discoveries with the newly identified disease gene PKHD1, which causes autosomal recessive polycystic kidney disease, were also presented at the meeting. (c) 2002 Prous Science. All rights reserved.

[Manufacture of autologous serum eye drops for out-patient therapy : cooperation between ophthalmic clinic and transfusion medicine department].

PubMed

Dietrich, T; Weisbach, V; Seitz, B; Jacobi, C; Kruse, F E; Eckstein, R; Cursiefen, C

2008-11-01

Autologous serum eye drops are an important therapy option in severe ocular surface disorders and the therapeutic effectiveness has been demonstrated in many clinical studies. The production and use of autologous serum eye drops is strictly controlled by legal regulations in Germany: Both the German Medicines Act (AMG) and the Blood Transfusion Act regulate production, distribution and application, unless it is carried out by one person under controlled conditions in a hospital setting. In cooperation with the ophthalmic clinic and the department of transfusion medicine, a standard operating procedure (SOP) was developed and a license for production and delivery of autologous serum eye drops was obtained from the appropriate local authorities. The experiences of the first two years of practice were analyzed. By an interfaculty cooperation, the possibility of legal and feasible out-patient treatment with autologous eye drops has been established at the University Hospital Erlangen. From 07/2005 to 07/2007, there ware 240 prescriptions for autologous serum eye drops. Unexpectedly, a relatively high rate (3.3%) of patients with primarily unknown viral or bacterial infectious diseases were found, which were diagnosed during the screening. These patients had to be excluded from autologous serum eye drop therapy. The treatment with autologous serum eye drops in an out-patient setting is possible, when the infrastructure for manufacture and delivery is provided in accordance with existing regulations.

Equilibrium unfolding of A. niger RNase: pH dependence of chemical and thermal denaturation.

PubMed

Kumar, Gundampati Ravi; Sharma, Anurag; Kumari, Moni; Jagannadham, Medicherla V; Debnath, Mira

2011-08-01

Equilibrium unfolding of A. niger RNase with chemical denaturants, for example GuHCl and urea, and thermal unfolding have been studied as a function of pH using fluorescence, far-UV, near-UV, and absorbance spectroscopy. Because of their ability to affect electrostatic interactions, pH and chemical denaturants have a marked effect on the stability, structure, and function of many globular proteins. ANS binding studies have been conducted to enable understanding of the folding mechanism of the protein in the presence of the denaturants. Spectroscopic studies by absorbance, fluorescence, and circular dichroism and use of K2D software revealed that the enzyme has α + β type secondary structure with approximately 29% α-helix, 24% β-sheet, and 47% random coil. Under neutral conditions the enzyme is stable in urea whereas GuHCl-induced equilibrium unfolding was cooperative. A. niger RNase has little ANS binding even under neutral conditions. Multiple intermediates were populated during the pH-induced unfolding of A. niger RNase. Urea and temperature-induced unfolding of A. niger RNase into the molten globule-like state is non-cooperative, in contrast to the cooperativity seen with the native protein, suggesting the presence of two parts/domains, in the molecular structure of A. niger RNase, with different stability that unfolds in steps. Interestingly, the GuHCl-induced unfolding of the A state (molten globule state) of A. niger RNase is unique, because a low concentration of denaturant not only induces structural change but also facilitates transition from one molten globule like state (A(MG1)) into another (I(MG2)).

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

Schnur, R.E.; Wick, P.A.; Louis, A.

MLS and FDHG syndromes have overlapping phenotypes, including linear skin defects or erosions that heal in cribiform patterns of atrophy and pigmentary change and asymmetric ocular defects. It has been postulated that MLS and FDHG phenotypes reflect changes in the same gene(s) as well as variable X-inactivation patterns. In order to explore this, we studied one new MLS and 2 FDHG patients at clinical, cytogenetic, and molecular levels. Phenotype comparison: We observed a greater variety and wider distribution of cutaneous lesions in FDHG. Only the MLS patient had microphthalmia and sclerocornea with other ocular changes. Skeletal lesions were seen inmore » only one FDHG patient who also had additional problems. Cytogenetics: The MLS patient demonstrated a 46,XX,del(X)(p22) karyotype. We excluded a cryptic Y-translocation by FISH using a Y-chromosome paint. Both FDHG patients had 46,XX karyotypes. Molecular studies: For deletion analysis, somatic cell hybrids containing separated X homologues were made from EBV-transformed LBL lines of all 3 patients. Of 20 hybrids obtained from the MLS patient, only one contained the deleted X, but we recognize that a culture artifact may have occurred in LBL cells prior to fusion. There was also a suggestion of partial skewing of X-homologue representation in FDHG hybrids. The breakpoint for the MLS deletion, which arose on the paternally-derived homologue (by RFLPs), was between DXS16 and AMG; DXS70 and DXS85 were also deleted. This is consistent with reported breakpoints in other MLS patients. Neither FDHG patient was deleted at any of these loci. Our study provides a basis for additional testing in FDHG patients via somatic cell hybrids with new markers and candidate genes from the MLS critical region to confirm or negate the proposed mapping of FDHG to Xp22.3.« less

Current and novel therapeutic strategies in celiac disease.

PubMed

Kurada, Satya; Yadav, Abhijeet; Leffler, Daniel A

2016-09-01

A gluten free diet (GFD) is the only available treatment for celiac disease (CD). However many patients fail to respond fully clinically or histologically. Several surveys highlight the psychosocial implications of adherence to a GFD. Hence, efforts are ongoing to develop therapeutic strategies beyond a GFD. We conducted a search of PubMed and clinicaltrials.gov to extract articles on CD using keywords including 'celiac disease' and 'refractory celiac disease' (RCD) and focused on articles conducting pathophysiologic and therapeutic research in/ex-vivo models and human trials. We highlight novel therapeutics that manipulate these mechanisms including tight junction regulators, glutenases, gluten sequestrants and immunotherapy using vaccines, nanoparticles that may serve as adjuncts to a GFD or more ambitiously to allow for gluten consumption. We also highlight the role of anti-inflammatories, immunosuppressants and monoclonal antibodies in RCD. Expert commentary: Therapeutics including tight junction regulators, glutenases have the potential to be approved for non-responsive CD or as gluten adjuncts. We expect results of various phase 1/2 trials using AMG 714, BL 7010, IgY antibodies to be published. In the interim, off-label use of 5 amino-salicylates, budesonide, nucleoside analogues and newer biologics developed for other inflammatory diseases will be used in RCD.

Formation of Heterogeneous Powder Coatings with a Two-Level Micro-and Nanocomposite Structure under Gas-Dynamic Spraying Conditions

NASA Astrophysics Data System (ADS)

Aborkin, A. V.; Alymov, M. I.; Arkhipov, V. E.; Khrenov, D. S.

2018-02-01

Heterogeneous coatings have been deposited by the cold gas-dynamic spraying of mechanically synthesized AMg2/graphite + Al2O3 powders. A specific feature of the coatings formed is the existence of a two-level micro-and nanocomposite structure. It has been established that an increase in the content of microsized Al2O3 particles in the mixture from 10 to 30 wt % produces a twofold increase in the thickness of the coating deposited for the same time period from 140 to 310 μm. A further growth in the content of microsized Al2O3 particles in the mixture up to 50 wt % leads to a decrease in the thickness of the coating formed to 40 μm. The manufactured coatings have a high microhardness ranging from 1.7 to 3.2 GPa depending on their composition. The high microhardness of these coatings is caused by an increase in the hardness of the matrix material due to the creation of a nanocomposite structure, which strengthens the immobilization of microsized Al2O3 particles in it, thus improving the properties of the heterogeneous coating as a whole.

The role of TRPV1 in different subtypes of dorsal root ganglion neurons in rat chronic inflammatory nociception induced by complete Freund's adjuvant

PubMed Central

Yu, Lu; Yang, Fei; Luo, Hao; Liu, Feng-Yu; Han, Ji-Sheng; Xing, Guo-Gang; Wan, You

2008-01-01

Background The present study aims to investigate the role of transient receptor potential vanilloid 1 (TRPV1) in dorsal root ganglion (DRG) neurons in chronic pain including thermal hyperalgesia and mechanical allodynia. Chronic inflammatory nociception of rats was produced by intraplantar injection of complete Freund's adjuvant (CFA) and data was collected until day 28 following injection. Results Thermal hyperalgesia was evident from day 1 to day 28 with peak at day 7, while mechanical allodynia persisted from day 1 to day 14 and was greatest at day 7. Intrathecal administration of AMG 9810 at day 7, a selective TRPV1 antagonist, significantly reduced thermal hyperalgesia and mechanical allodynia. TRPV1 expression in DRG detected by Western blotting was increased relative to baseline throughout the observation period. Double labeling of TRPV1 with neuronal marker neurofilament 200 (NF200), calcitonin gene-related peptide (CGRP) or isolectin B4 (IB4) was used to distinguish different subtypes of DRG neurons. TRPV1 expression was increased in the medium-sized myelinated A fiber (NF200 positive) neurons and in small non-peptidergic (IB4 positive) neurons from day 1 to day 14 and was increased in small peptidergic (CGRP positive) neurons from day 1 to day 28. Conclusion TRPV1 expression increases in all three types of DRG neurons after CFA injection and plays a role in CFA-induced chronic inflammatory pain including thermal hyperalgesia and mechanical allodynia. PMID:19055783

Algebraic multigrid preconditioners for two-phase flow in porous media with phase transitions

NASA Astrophysics Data System (ADS)

Bui, Quan M.; Wang, Lu; Osei-Kuffuor, Daniel

2018-04-01

Multiphase flow is a critical process in a wide range of applications, including oil and gas recovery, carbon sequestration, and contaminant remediation. Numerical simulation of multiphase flow requires solving of a large, sparse linear system resulting from the discretization of the partial differential equations modeling the flow. In the case of multiphase multicomponent flow with miscible effect, this is a very challenging task. The problem becomes even more difficult if phase transitions are taken into account. A new approach to handle phase transitions is to formulate the system as a nonlinear complementarity problem (NCP). Unlike in the primary variable switching technique, the set of primary variables in this approach is fixed even when there is phase transition. Not only does this improve the robustness of the nonlinear solver, it opens up the possibility to use multigrid methods to solve the resulting linear system. The disadvantage of the complementarity approach, however, is that when a phase disappears, the linear system has the structure of a saddle point problem and becomes indefinite, and current algebraic multigrid (AMG) algorithms cannot be applied directly. In this study, we explore the effectiveness of a new multilevel strategy, based on the multigrid reduction technique, to deal with problems of this type. We demonstrate the effectiveness of the method through numerical results for the case of two-phase, two-component flow with phase appearance/disappearance. We also show that the strategy is efficient and scales optimally with problem size.

The Effects of Bismuth Oxide on Microstructures and Magnetic Properties of Mn-Mg-Al Ferrites

NASA Astrophysics Data System (ADS)

Nekouee, Kh. A.; Rahimi, A. H.; Haghighi, M. Alineghad; Ehsani, N.

2018-04-01

In the present paper, the effects of bismuth oxide as an additive on microstructure and magnetic properties of Mg0.9Mn0.1Al0.4Fe1.6O4 were investigated. Mg-Mn-Al ferrite powders were prepared by the conventional solid state synthesis method. Two different amounts of bismuth oxide (2.5 wt.% and 5 wt.%) were utilized as the sintering aid and their microstructure and physical properties were compared to those of the sample without additives. X-ray diffraction (XRD) analysis indicated that crystal lattice distortion due to the microstructural constraints as the result from incorporation of bismuth oxide into the microstructure was developed by adding bismuth oxide. XRD Rietveld refinement was used to define the cation distribution and to refine the lattice parameter and oxygen parameter for the sample without bismuth oxide as (Mg0.16Mn0.02Al0.15Fe0.77)A(Mg0.74Mn0.08Al0.25Fe0.83)BO4 and 8.3308 Å and 0.2542, respectively. Microstructure studies show that a bismuth rich liquid phase forms during the sintering at 1250°C, which enhances the densification of sintered bodies up to 13% (a relative density of 93%). Magnetization of sintered samples were increased from 21.1 emu/g to 26.2 emu/g upon addition of 2.5 wt.% bismuth oxide and then decreased to 24.9 emu/g when 5 wt.% bismuth oxide was added.

A disease-specific measure of health-related quality of life in adults with chronic immune thrombocytopenic purpura: psychometric testing in an open-label clinical trial.

PubMed

Mathias, Susan D; Bussel, James B; George, James N; McMillan, Robert; Okano, Gary J; Nichol, Janet L

2007-05-01

The Immune Thrombocytopenic Purpura Patient Assessment Questionnaire (ITP-PAQ) was developed to assess disease-specific quality of life (QoL) in adults with ITP. It is a 44-item questionnaire that includes scales for physical health (symptoms, fatigue/sleep, bother, and activity), emotional health (psychological and fear), overall QoL, social activity, women's reproductive health, and work. A previous study reported preliminary evidence of its reliability and validity. The present study was conducted to ascertain the responsiveness (ability to detect a clinically important treatment effect), reliability, and validity of the ITP-PAQ and to corroborate the earlier findings. The women's reproductive health scale was evaluated for psychometric evidence of the existence of separate menstrual symptoms and fertility subscales. The ITP-PAQ was evaluated in the context of an ongoing open-label extension study assessing the tolerability and durability of increases in the platelet count with AMG 531 (a thrombopoiesis peptibody that increases platelet production by targeting the thrombopoietin receptor) administered by subcutaneous injection once weekly in adult patients with ITP It was self-administered at baseline and at weeks 4, 12, and 24. The responsiveness of the questionnaire was evaluated by calculating and comparing the change scores of patients who showed clinical improvement-categorized as platelet responders (those with a platelet count > or =50 x 10(9) cells/L and a doubling of baseline values at week 24) and durable platelet responders (those with a platelet count > or =50 x 10(9) cells/L and a doubling of baseline values on > or =6 occasions during weeks 17-24)-with the change scores of patients wh did not show clinical improvement. The reliability (internal consistency and test-retest) and validity (convergent, discriminant, and known groups) of the questionnaire were also evaluated. Validity was examined in terms of correlations between the ITP-PAQ and the 36-item Short-Form Health Survey (SF-36), a generic measure of health-related QoL. Thirty-four patients completed the ITP-PAQ. Most of the scales were found capable of detecting clinically important treatment effects, with the scales for symptoms, fatigue/sleep, bother, and activity being particularly responsive. All scales were found to have internal consistency reliability (Cronbach's alpha, 0.700-0.950), with the exceptions of the menstrual symptoms subscale (0.988 and 0.959 at weeks 12 and 24, respectively) and the work scale (0.691 at week 24). Test-retest reliability was acceptable (intraclass correlation coefficient, 0.725-0.867), with the exceptions of the scales for symptoms (0.677) and women's reproductive health (0.592) and the fertility subscale (0.171). Construct validity was supported by correlations between specific ITP-PAQ and SF-36 scales, with the exceptions of the menstrual symptoms and fertility subscales. Discriminant validity was reported for the symptoms, fatigue/sleep, bother, and activity scales. Durable platelet responders had significantly better scores than nonresponders on the symptoms (P = 0.022), bother (P = 0.008), psychological (P = 0.033), and overall QoL scales (P = 0.032). Compared with those who had undergone splenectomy, patients without splenectomy had significantly higher scores on the women's reproductive health scale (P = 0.03). The results of this analysis indicate that the ITP-PAQ has acceptable responsiveness, reliability, and validity. Further study of the minimal clinically important difference in ITP-PAQ scale scores is needed.

Alterations in endocannabinoid tone following chemotherapy-induced peripheral neuropathy: effects of endocannabinoid deactivation inhibitors targeting fatty-acid amide hydrolase and monoacylglycerol lipase in comparison to reference analgesics following cisplatin treatment.

PubMed

Guindon, Josée; Lai, Yvonne; Takacs, Sara M; Bradshaw, Heather B; Hohmann, Andrea G

2013-01-01

Cisplatin, a platinum-derived chemotherapeutic agent, produces mechanical and coldallodynia reminiscent of chemotherapy-induced neuropathy in humans. The endocannabinoid system represents a novel target for analgesic drug development. The endocannabinoid signaling system consists of endocannabinoids (e.g. anandamide (AEA) and 2-arachidonoylglycerol (2-AG)), cannabinoid receptors (e.g. CB(1) and CB(2)) and the enzymes controlling endocannabinoid synthesis and degradation. AEA is hydrolyzed by fatty-acid amide hydrolase (FAAH) whereas 2-AG is hydrolyzed primarily by monoacylglycerol lipase (MGL). We compared effects of brain permeant (URB597) and impermeant (URB937) inhibitors of FAAH with an irreversible inhibitor of MGL (JZL184) on cisplatin-evoked behavioral hypersensitivities. Endocannabinoid modulators were compared with agents used clinically to treat neuropathy (i.e. the opioid analgesic morphine, the anticonvulsant gabapentin and the tricyclic antidepressant amitriptyline). Cisplatin produced robust mechanical and cold allodynia but did not alter responsiveness to heat. After neuropathy was fully established, groups received acute intraperitoneal (i.p.) injections of vehicle, amitriptyline (30 mg/kg), gabapentin (100 mg/kg), morphine (6 mg/kg), URB597 (0.1 or 1 mg/kg), URB937 (0.1 or 1 mg/kg) or JZL184 (1, 3 or 8 mg/kg). Pharmacological specificity was assessed by coadministering each endocannabinoid modulator with either a CB(1) (AM251 3 mg/kg), CB(2) (AM630 3 mg/kg), TRPV1 (AMG9810 3 mg/kg) or TRPA1 (HC030031 8 mg/kg) antagonist. Effects of cisplatin on endocannabinoid levels and transcription of receptors (CB(1), CB(2), TRPV1, TRPA1) and enzymes (FAAH, MGL) linked to the endocannabinoid system were also assessed. URB597, URB937, JZL184 and morphine reversed cisplatin-evoked mechanical and cold allodynia to pre-cisplatin levels. By contrast, gabapentin only partially reversed the observed allodynia while amitriptyline, administered acutely, was ineffective. CB(1) or CB(2) antagonists completely blocked the anti-allodynic effects of both FAAH (URB597, URB937) and MGL (JZL184) inhibitors to mechanical and cold stimulation. By contrast, the TRPV1 antagonist AMG9810 blocked the anti-allodynic efficacy of both FAAH inhibitors, but not the MGL inhibitor. By contrast, the TRPA1 antagonist HC30031 did not attenuate anti-allodynic efficacy of any endocannabinoid modulator. When the levels of endocannabinoids were examined, cisplatin increased both anandamide (AEA) and 2-arachidonoylglycerol (2-AG) levels in the lumbar spinal cord and decreased 2-AG levels (but not AEA) in dorsal hind paw skin. RT-PCR showed that mRNA for FAAH, but not other markers, was upregulated by cisplatin treatment in lumbar spinal cord. The present studies demonstrate that cisplatin alters endocannabinoid tone and that inhibition of endocannabinoid hydrolysis alleviates chemotherapy-induced mechanical and cold allodynia. The anti-allodynic effects of FAAH and MGL inhibitors are mediated by CB(1) and CB(2) cannabinoid receptors, whereas TRPV1, but not TRPA1, -dependent mechanisms contribute to the anti-allodynic efficacy of FAAH (but not MGL) inhibitors. Strikingly, endocannabinoid modulators potently suppressed cisplatin-evoked allodynia with a rapid onset and showed efficacy that equaled or exceeded that of major classes of anti-neuropathic pain medications used clinically. Thus, inhibition of endocannabinoid hydrolysis, via FAAH or MGL inhibitors, represents an efficacious pharmacological approach for suppressing chemotherapy-induced neuropathic pain. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Recording and reporting adverse reactions in clinical trials. New legal provisions according to the 12th Law Amending the German Drug Law (AMG) and the Ordinance on GCP (GCP-V)].

PubMed

Eckhardt, K; Cremer-Schaeffer, P; König, J; Paeschke, N

2005-02-01

With the 12th Law Amending the German Drug Law and the Ordinance on GCP (GCPV), new legal provisions for clinical trials came into force in August 2004. These include specific definitions and differentiated reporting obligations affecting investigators, sponsors, authorities and ethics committees concerning pharmacovigilance in clinical trials. The definitions according to section sign3 (6-8) GCP-V make clear that these provisions focus on those adverse events and adverse drug reactions, which are related to investigational medicinal products. In the GCP-V for the first time legally binding provisions for investigators are laid down defining obligations to report all serious adverse events to the sponsor. The sponsor of clinical trials plays a decisive role concerning the evaluation, documentation and reporting to the competent higher authorities, ethics committees and investigators involved in the clinical trial. In the GCP-V different time limits concerning the reporting for sponsors are laid down. The requirements concerning expedited reporting focus on suspected unexpected serious adverse reactions (SUSARs), i. e. those adverse serious reactions, which are not described in the information on the investigational medicinal product. The time limit for reporting SUSARs leading to death or life-threatening SUSARs is 7 days, while for other SUSARs the time limit is 15 days. Besides the responsibilities on expedited reporting the sponsor has to submit a line listing of all serious adverse reactions which occurred during the clinical trial and a report on the safety of the trial subjects on an annual basis or on request. On the European level the harmonisation concerning the provisions on pharmacovigilance in clinical trials according to the Directive 2001/20/EC and the Eudravigilance database should contribute to reach a faster and more effective exchange of safety information related to clinical trials between the different competent authorities of the EU member states.

A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer.

PubMed

Body, Jean-Jacques; Facon, Thierry; Coleman, Robert E; Lipton, Allan; Geurs, Filip; Fan, Michelle; Holloway, Donna; Peterson, Mark C; Bekker, Pirow J

2006-02-15

Receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for the differentiation, function, and survival of osteoclasts, which play a key role in establishment and propagation of skeletal disease in patients with multiple myeloma or bone metastases as well as many other skeletal diseases. Denosumab (AMG 162), a fully human monoclonal antibody to RANKL, was developed to treat patients with skeletal diseases. This was a randomized, double-blind, double-dummy, active-controlled, multicenter study to determine the safety and efficacy of denosumab in patients with breast cancer (n = 29) or multiple myeloma (n = 25) with radiologically confirmed bone lesions. Patients received a single dose of either denosumab (0.1, 0.3, 1.0, or 3.0 mg/kg s.c.) or pamidronate (90 mg i.v.). Bone antiresorptive effect was assessed by changes in urinary and serum N-telopeptide levels. Pharmacokinetics of denosumab also were assessed. Following a single s.c. dose of denosumab, levels of urinary and serum N-telopeptide decreased within 1 day, and this decrease lasted through 84 days at the higher denosumab doses. Pamidronate also decreased bone turnover, but the effect diminished progressively through follow-up. Denosumab injections were well tolerated. Mean half-lives of denosumab were 33.3 and 46.3 days for the two highest dosages. A single s.c. dose of denosumab given to patients with multiple myeloma or bone metastases from breast cancer was well tolerated and reduced bone resorption for at least 84 days. The decrease in bone turnover markers was similar in magnitude but more sustained than with i.v. pamidronate.

The role of the GABAergic and dopaminergic systems in the brain response to an intragastric load of alcohol in conscious rats.

PubMed

Tsurugizawa, T; Uematsu, A; Uneyama, H; Torii, K

2010-12-01

The brain's response to ethanol intake has been extensively investigated using electrophysiological recordings, brain lesion techniques, and c-Fos immunoreactivity. However, few studies have investigated this phenomenon using functional magnetic resonance imaging (fMRI). In the present study, we used fMRI to investigate the blood oxygenation level-dependent (BOLD) signal response to an intragastric (IG) load of ethanol in conscious, ethanol-naive rats. An intragastrically infused 10% ethanol solution induced a significant decrease in the intensity of the BOLD signal in several regions of the brain, including the bilateral amygdala (AMG), nucleus accumbens (NAc), hippocampus, ventral pallidum, insular cortex, and cingulate cortex, and an increase in the BOLD signal in the ventral tegmental area (VTA) and hypothalamic regions. Treatment with bicuculline, which is an antagonist of the gamma-aminobutyric acid A (GABA(A)) receptor, increased the BOLD signal intensity in the regions that had shown decreases in the BOLD signal after the IG infusion of 10% ethanol solution, but it did not affect the BOLD signal increase in the hypothalamus. Treatment with SCH39166, which is an antagonist of D1-like receptors, eliminated the increase in the BOLD signal intensity in the hypothalamic areas but did not affect the BOLD signal decrease following the 10% ethanol infusion. These results indicate that an IG load of ethanol caused both a GABA(A) receptor-mediated BOLD decrease in the limbic system and the cortex and a D1-like receptor-mediated BOLD increase in the hypothalamic regions in ethanol-naive rats. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

MICROSCOPIC USES OF NANOGOLD.

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

HAINFELD,J.F.POWELL,R.D.FURUYA,F.R.

2003-04-17

Gold has been used for immunocytochemistry since 1971 when Faulk and Taylor discovered adsorption of antibodies to colloidal gold. It is an ideal label for electron microscopy (EM) due to its high atomic number, which scatters electrons efficiently, and the fact that preparative methods have been developed to make uniform particles in the appropriate size range of 5 to 30 nm. Use in light microscopy (LM) generally requires silver enhancement (autometallography; AMG) of these small gold particles. Significant advances in this field since that time have included a better understanding of the conditions for best antibody adsorption, more regular goldmore » size production, adsorption of other useful molecules, like protein A, and advances in silver enhancement. Many studies have also been accomplished showing the usefulness of these techniques to cell biology and biomedical research. A further advance in this field was the development of Nanogold{trademark}, a 1.4 nm gold cluster. A significant difference from colloidal gold is that Nanogold is actually a coordination compound containing a gold core covalently linked to surface organic groups. These in turn may be covalently attached to antibodies. This approach to immunolabeling has several advantages compared to colloidal gold such as vastly better penetration into tissues, generally greater sensitivity, and higher density of labeling. Since Nanogold is covalently coupled to antibodies, it may also be directly coupled to almost any protein, peptide, carbohydrate, or molecule of interest, including molecules which do not adsorb to colloidal gold. This increases the range of probes possible, and expands the applications of gold labeling.« less

Afferent Drive Elicits Ongoing Pain in a Model of Advanced Osteoarthritis

PubMed Central

Okun, Alec; Liu, Ping; Davis, Peg; Ren, Jiyang; Remeniuk, Bethany; Brion, Triza; Ossipov, Michael H.; Xie, Jennifer; Dussor, Gregory O.; King, Tamara; Porreca, Frank

2012-01-01

Osteoarthritis (OA) is a chronic condition characterized by pain during joint movement. Additionally, patients with advanced disease experience pain at rest (i.e., ongoing pain)that is generally resistant to non-steroidal anti-inflammatory drugs (NSAIDs). Injection of monosodium iodoacetate (MIA) into the intra-articular space of the rodent knee is a well-established model of OA that elicits weight-bearing asymmetry and referred tactile and thermal hypersensitivity. Whether ongoing pain is present in this model is unknown. Additionally, the possible relationship of ongoing pain to MIA dose is not known. MIA produced weight asymmetry, joint osteolysis, and cartilage erosion across a range of doses (1, 3, and 4.8 mg). However, only rats treated with the highest dose of MIA showed conditioned place preference to a context paired with intra-articular lidocaine, indicating relief from ongoing pain. Diclofenac blocked the MIA-induced weight asymmetry but failed to block MIA-induced ongoing pain. Systemic AMG9810, a TRPV1 antagonist, effectively blocked thermal hypersensitivity, but failed to block high dose MIA-induced weight asymmetry or ongoing pain. Additionally, systemic or intra-articular HC030031, a TRPA1 antagonist, failed to block high dose MIA-induced weight asymmetry or ongoing pain. Our studies suggest that a high dose of intra-articular MIA induces ongoing pain originating from the site of injury that is dependent on afferent fiber activity but apparently independent of TRPV1 or TRPA1 activation. Identification of mechanisms driving ongoing pain may enable development of improved treatments for patients with severe OA pain and diminish the need for joint replacement surgery. PMID:22387095

Algebraic multigrid preconditioners for two-phase flow in porous media with phase transitions [Algebraic multigrid preconditioners for multiphase flow in porous media with phase transitions

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

Bui, Quan M.; Wang, Lu; Osei-Kuffuor, Daniel

Multiphase flow is a critical process in a wide range of applications, including oil and gas recovery, carbon sequestration, and contaminant remediation. Numerical simulation of multiphase flow requires solving of a large, sparse linear system resulting from the discretization of the partial differential equations modeling the flow. In the case of multiphase multicomponent flow with miscible effect, this is a very challenging task. The problem becomes even more difficult if phase transitions are taken into account. A new approach to handle phase transitions is to formulate the system as a nonlinear complementarity problem (NCP). Unlike in the primary variable switchingmore » technique, the set of primary variables in this approach is fixed even when there is phase transition. Not only does this improve the robustness of the nonlinear solver, it opens up the possibility to use multigrid methods to solve the resulting linear system. The disadvantage of the complementarity approach, however, is that when a phase disappears, the linear system has the structure of a saddle point problem and becomes indefinite, and current algebraic multigrid (AMG) algorithms cannot be applied directly. In this study, we explore the effectiveness of a new multilevel strategy, based on the multigrid reduction technique, to deal with problems of this type. We demonstrate the effectiveness of the method through numerical results for the case of two-phase, two-component flow with phase appearance/disappearance. In conclusion, we also show that the strategy is efficient and scales optimally with problem size.« less

Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.

PubMed

Xiao, Xing; Zhao, Xiao-Tao; Xu, Ling-Chi; Yue, Lu-Peng; Liu, Feng-Yu; Cai, Jie; Liao, Fei-Fei; Kong, Jin-Ge; Xing, Guo-Gang; Yi, Ming; Wan, You

2015-04-01

Transient receptor potential vanilloid 1 (TRPV1) receptors are expressed in nociceptive neurons of rat dorsal root ganglions (DRGs) and mediate inflammatory pain. Nonspecific inhibition of protein-tyrosine phosphatases (PTPs) increases the tyrosine phosphorylation of TRPV1 and sensitizes TRPV1. However, less is known about tyrosine phosphorylation's implication in inflammatory pain, compared with that of serine/threonine phosphorylation. Src homology 2 domain-containing tyrosine phosphatase 1 (Shp-1) is a key phosphatase dephosphorylating TRPV1. In this study, we reported that Shp-1 colocalized with and bound to TRPV1 in nociceptive DRG neurons. Shp-1 inhibitors, including sodium stibogluconate and PTP inhibitor III, sensitized TRPV1 in cultured DRG neurons. In naive rats, intrathecal injection of Shp-1 inhibitors increased both TRPV1 and tyrosine-phosphorylated TRPV1 in DRGs and induced thermal hyperalgesia, which was abolished by pretreatment with TRPV1 antagonists capsazepine, BCTC, or AMG9810. Complete Freund's adjuvant (CFA)-induced inflammatory pain in rats significantly increased the expression of Shp-1, TRPV1, and tyrosine-phosphorylated TRPV1, as well as the colocalization of Shp-1 and TRPV1 in DRGs. Intrathecal injection of sodium stibogluconate aggravated CFA-induced inflammatory pain, whereas Shp-1 overexpression in DRG neurons alleviated it. These results suggested that Shp-1 dephosphorylated and inhibited TRPV1 in DRG neurons, contributing to maintain thermal nociceptive thresholds in normal rats, and as a compensatory mechanism, Shp-1 increased in DRGs of rats with CFA-induced inflammatory pain, which was involved in protecting against excessive thermal hyperalgesia.

Brain activity correlates with emotional perception induced by dynamic avatars.

PubMed

Goldberg, Hagar; Christensen, Andrea; Flash, Tamar; Giese, Martin A; Malach, Rafael

2015-11-15

An accurate judgment of the emotional state of others is a prerequisite for successful social interaction and hence survival. Thus, it is not surprising that we are highly skilled at recognizing the emotions of others. Here we aimed to examine the neuronal correlates of emotion recognition from gait. To this end we created highly controlled dynamic body-movement stimuli based on real human motion-capture data (Roether et al., 2009). These animated avatars displayed gait in four emotional (happy, angry, fearful, and sad) and speed-matched neutral styles. For each emotional gait and its equivalent neutral gait, avatars were displayed at five morphing levels between the two. Subjects underwent fMRI scanning while classifying the emotions and the emotional intensity levels expressed by the avatars. Our results revealed robust brain selectivity to emotional compared to neutral gait stimuli in brain regions which are involved in emotion and biological motion processing, such as the extrastriate body area (EBA), fusiform body area (FBA), superior temporal sulcus (STS), and the amygdala (AMG). Brain activity in the amygdala reflected emotional awareness: for visually identical stimuli it showed amplified stronger response when the stimulus was perceived as emotional. Notably, in avatars gradually morphed along an emotional expression axis there was a parametric correlation between amygdala activity and emotional intensity. This study extends the mapping of emotional decoding in the human brain to the domain of highly controlled dynamic biological motion. Our results highlight an extensive level of brain processing of emotional information related to body language, which relies mostly on body kinematics. Copyright © 2015. Published by Elsevier Inc.

Algebraic multigrid preconditioners for two-phase flow in porous media with phase transitions [Algebraic multigrid preconditioners for multiphase flow in porous media with phase transitions

DOE PAGES

Bui, Quan M.; Wang, Lu; Osei-Kuffuor, Daniel

2018-02-06

Multiphase flow is a critical process in a wide range of applications, including oil and gas recovery, carbon sequestration, and contaminant remediation. Numerical simulation of multiphase flow requires solving of a large, sparse linear system resulting from the discretization of the partial differential equations modeling the flow. In the case of multiphase multicomponent flow with miscible effect, this is a very challenging task. The problem becomes even more difficult if phase transitions are taken into account. A new approach to handle phase transitions is to formulate the system as a nonlinear complementarity problem (NCP). Unlike in the primary variable switchingmore » technique, the set of primary variables in this approach is fixed even when there is phase transition. Not only does this improve the robustness of the nonlinear solver, it opens up the possibility to use multigrid methods to solve the resulting linear system. The disadvantage of the complementarity approach, however, is that when a phase disappears, the linear system has the structure of a saddle point problem and becomes indefinite, and current algebraic multigrid (AMG) algorithms cannot be applied directly. In this study, we explore the effectiveness of a new multilevel strategy, based on the multigrid reduction technique, to deal with problems of this type. We demonstrate the effectiveness of the method through numerical results for the case of two-phase, two-component flow with phase appearance/disappearance. In conclusion, we also show that the strategy is efficient and scales optimally with problem size.« less

Hemocompatible ɛ-polylysine-heparin microparticles: A platform for detecting triglycerides in whole blood.

PubMed

Xu, Tingting; Chi, Bo; Chu, Meilin; Zhang, Qicheng; Zhan, Shuyue; Shi, Rongjia; Xu, Hong; Mao, Chun

2018-01-15

Triglycerides are clinically important marker for atherosclerosis, heart disease and hypertension. Here, a platform for detecting triglycerides in whole blood directly was developed based on hemocompatible ɛ-polylysine-heparin microparticles. The obtained products of ɛ-polylysine-heparin microparticles were characterized by fourier transform infrared (FT-IR) spectra, transmission electron microscopy (TEM) and ζ-potential. Moreover, the blood compatibility of ɛ-polylysine-heparin microparticles was characterized by in vitro coagulation tests, hemolysis assay and whole blood adhesion tests. Considering of uniform particle size, good dispersibility and moderate long-term anticoagulation capability of the microparticles, a Lipase-(ɛ-polylysine-heparin)-glassy carbon electrode (GCE) was constructed to detect triglycerides. The proposed biosensor had good electrocatalytic activity towards triglycerides, in which case the sensitivity was 0.40μAmg -1 dLcm -2 and the detection limit was 4.67mgdL -1 (S/N = 3). Meanwhile, the Lipase-(ɛ-polylysine-heparin)-GCE electrode had strong anti-interference ability as well as a long shelf-life. Moreover, for the detection of triglycerides in whole blood directly, the detection limit was as low as 5.18mgdL -1 . The new constructed platform is suitable for detecting triglycerides in whole blood directly, which provides new analytical systems for clinical illness diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Patient-specific blood flow simulation to improve intracranial aneurysm diagnosis

NASA Astrophysics Data System (ADS)

Fenz, Wolfgang; Dirnberger, Johannes

2011-03-01

We present a novel simulation system of blood flow through intracranial aneurysms including the interaction between blood lumen and vessel tissue. It provides the means to estimate rupture risks by calculating the distribution of pressure and shear stresses in the aneurysm, in order to support the planning of clinical interventions. So far, this has only been possible with commercial simulation packages originally targeted at industrial applications, whereas our implementation focuses on the intuitive integration into clinical workflow. Due to the time-critical nature of the application, we exploit most efficient state-of-the-art numerical methods and technologies together with high performance computing infrastructures (Austrian Grid). Our system builds a three-dimensional virtual replica of the patient's cerebrovascular system from X-ray angiography, CT or MR images. The physician can then select a region of interest which is automatically transformed into a tetrahedral mesh. The differential equations for the blood flow and the wall elasticity are discretized via the finite element method (FEM), and the resulting linear equation systems are handled by an algebraic multigrid (AMG) solver. The wall displacement caused by the blood pressure is calculated using an iterative fluid-structure interaction (FSI) algorithm, and the fluid mesh is deformed accordingly. First simulation results on measured patient geometries show good medical relevance for diagnostic decision support.

Enhanced activity of Pt/CNTs anode catalyst for direct methanol fuel cells using Ni2P as co-catalyst

NASA Astrophysics Data System (ADS)

Li, Xiang; Luo, Lanping; Peng, Feng; Wang, Hongjuan; Yu, Hao

2018-03-01

The direct methanol fuel cell is a promising energy conversion device because of the utilization of the state-of-the-art platinum (Pt) anode catalyst. In this work, novel Pt/Ni2P/CNTs catalysts were prepared by the H2 reduction method. It was found that the activity and stability of Pt for methanol oxidation reaction (MOR) could be significantly enhanced while using nickel phosphide (Ni2P) nanoparticles as co-catalyst. X-ray photoelectron spectroscopy revealed that the existence of Ni2P affected the particle size and electronic distribution of Pt obviously. Pt/CNTs catalyst, Pt/Ni2P/CNTs catalysts with different Ni2P amount were synthesized, among which Pt/6%Ni2P/CNTs catalyst exhibited the best MOR activity of 1400 mAmg-1Pt, which was almost 2.5 times of the commercial Pt/C-JM catalyst. Moreover, compared to other Pt-based catalysts, this novel Pt/Ni2P/CNTs catalyst also exhibited higher onset current density and better steady current density. The result of this work may provide positive guidance to the research on high efficiency and stability of Pt-based catalyst for direct methanol fuel cells.

[(68)Ga-labeled peptides for clinical trials - production according to the German Drug Act: the Göttingen experience].

PubMed

Meller, Birgit; Angerstein, C; Liersch, T; Ghadimi, M; Sahlmann, C-O; Meller, J

2012-01-01

The AMG implies far-reaching implications for the synthesis of new radiopharmaceuticals for clinical trials. As a part of the DFG-funded Clinical Research Group (KFO 179) a project designated "Immuno-PET for assessment of early response to radiochemotherapy of advanced rectal cancer" was initiated. This trial is focused on a trivalent bispecific humanized monoclonal antibody, and a 68Ga-labeled peptide. Following the new regulatory framework we established a GMP-compliant cleanroom laboratory and applied for a manufacturing permission. During the project constructural, personnel and organizational conditions for a successful application were established, including a quality management system. A GMP-conform cleanroom laboratory class C was constructed, equipped with a two-chamber lock. The actual manufacturing is performed in a closed system with subsequent sterile filtration. The manufacturing processes have been automatised and validated as well as the necessary quality controls. The manufacturing permission was granted after an official inspection. The new German Drug Act is considered as a break in the production practice of nuclear medicine. The early involvement and communication with the authorities avoids time-consuming and costly planning errors. It is much to be hoped that the new legal situation in Germany will not cause serious impairments in the realization of clinical trials in German nuclear medicine.

Staphylococcal superantigen-specific IgE antibodies: degree of sensitization and association with severity of asthma.

PubMed

Elabras, José; Mello, Fernanda Carvalho de Queiroz; Lupi, Omar; Bica, Blanca Elena Rios Gomes; Papi, José Angelo de Souza; França, Alfeu Tavares

2016-01-01

To determine the presence of staphylococcal superantigen-specific IgE antibodies and degree of IgE-mediated sensitization, as well as whether or not those are associated with the severity of asthma in adult patients. This was a cross-sectional study involving outpatients with asthma under treatment at a tertiary care university hospital in the city of Rio de Janeiro, Brazil. Consecutive patients were divided into two groups according to the severity of asthma based on the Global Initiative for Asthma criteria: mild asthma (MA), comprising patients with mild intermittent or persistent asthma; and moderate or severe asthma (MSA). We determined the serum levels of staphylococcal toxin-specific IgE antibodies, comparing the results and performing a statistical analysis. The study included 142 patients: 72 in the MA group (median age = 46 years; 59 females) and 70 in the MSA group (median age = 56 years; 60 females). In the sample as a whole, 62 patients (43.7%) presented positive results for staphylococcal toxin-specific IgE antibodies: staphylococcal enterotoxin A (SEA), in 29 (20.4%); SEB, in 35 (24.6%); SEC, in 33 (23.2%); and toxic shock syndrome toxin (TSST), in 45 (31.7%). The mean serum levels of IgE antibodies to SEA, SEB, SEC, and TSST were 0.96 U/L, 1.09 U/L, 1.21 U/L, and 1.18 U/L, respectively. There were no statistically significant differences between the two groups in terms of the qualitative or quantitative results. Serum IgE antibodies to SEA, SEB, SEC, and TSST were detected in 43.7% of the patients in our sample. However, neither the qualitative nor quantitative results showed a statistically significant association with the clinical severity of asthma. Determinar a presença de anticorpos IgE específicos para superantígenos estafilocócicos e o grau de sensibilização mediada por esses, assim como se esses estão associados à gravidade da asma em pacientes adultos. Estudo transversal incluindo asmáticos adultos em acompanhamento ambulatorial em um hospital universitário terciário no Rio de Janeiro (RJ). Os pacientes foram alocados consecutivamente em dois grupos de gravidade da asma segundo critérios da Global Initiative for Asthma: asma leve (AL), com asmáticos leves intermitentes ou persistentes, e asma moderada ou grave (AMG). Foram determinados os níveis séricos de anticorpos IgE antitoxinas estafilocócicas, e os resultados foram comparados por análise estatística. Foram incluídos 142 pacientes no estudo: 72 no grupo AL (mediana de idade = 46 anos; 59 do sexo feminino) e 70 do grupo AMG (mediana de idade = 56 anos; 60 do sexo feminino). Na amostra geral, 62 pacientes (43,7%) apresentaram resultados positivos para dosagens de anticorpos IgE antitoxinas estafilocócicas: enterotoxina (TX) A, em 29 (20,4%); TXB, em 35 (24,6%); TXC, em 33 (23,2%); e toxic shock syndrome toxin (TSST), em 45 (31,7%). As médias das dosagens séricas de anticorpos IgE específicos anti-TXA, TXB, TXC e TSST foram, respectivamente, de 0,96 U/l, 1,09 U/l, 1,21 U/l, e 1,18 U/l. Não houve diferença estatisticamente significativa dos resultados qualitativos ou quantitativos entre os grupos. A presença de anticorpos IgE séricos anti-TXA, TXB, TXC e TSST, foi detectada em 43,7% nessa amostra de pacientes, mas não houve associação estatisticamente significativa entre seus resultados qualitativos ou quantitativos e gravidade clínica da asma.

Anti-inflammatory activity of a sulfated polysaccharide isolated from an enzymatic digest of brown seaweed Sargassum horneri in RAW 264.7 cells.

PubMed

Sanjeewa, Kalu Kapuge Asanka; Fernando, Ilekkuttige Priyan Shanura; Kim, Eun-A; Ahn, Ginnae; Jee, Youngheun; Jeon, You-Jin

2017-02-01

Sargassum horneri is an edible brown alga that grows in the subtidal zone as an annual species along the coasts of South Korea, China, and Japan. Recently, an extreme amount of S. horneri moved into the coasts of Jeju Island from the east coast of China, which made huge economic and environmental loss to the Jeju Island. Thus, utilization of this biomass becomes a big issue with the local authorities. Therefore, the present study was performed to evaluate the anti-inflammatory potential of crude polysaccharides (CPs) extracted from S. horneri China strain in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. CPs were precipitated from S. horneri digests prepared by enzyme assistant extraction using four food-grade enzymes (AMG, Celluclast, Viscozyme, and Alcalase). The production levels of nitric oxide (NO) and pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-1β were measured by Griess assay and enzyme-linked immunosorbent assay, respectively. The levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPKs) were measured by using western blot. The IR spectrums of the CPs were recorded using a fourier transform infrared spectroscopy (FT-IR) spectrometer. The polysaccharides from the Celluclast enzyme digest (CCP) showed the highest inhibition of NO production in LPS-stimulated RAW 264.7 cells (IC 50 value: 95.7 µg/mL). Also, CCP dose-dependently down-regulated the protein expression levels of iNOS and COX-2 as well as the production of inflammatory cytokines, including TNF-α and IL-1β, compared to the only LPS-treated cells. In addition, CCP inhibited the activation of NF-κB p50 and p65 and the phosphorylation of MAPKs, including p38 and extracellular signal-regulated kinase, in LPS-stimulated RAW 264.7 cells. Furthermore, FT-IR analysis showed that the FT-IR spectrum of CCP is similar to that of commercial fucoidan. Our results suggest that CCP has anti-inflammatory activities and is a potential candidate for the formulation of a functional food ingredient or/and drug to treat inflammatory diseases.

Anti-inflammatory activity of a sulfated polysaccharide isolated from an enzymatic digest of brown seaweed Sargassum horneri in RAW 264.7 cells

PubMed Central

Sanjeewa, Kalu Kapuge Asanka; Fernando, Ilekkuttige Priyan Shanura; Kim, Eun-A; Jee, Youngheun

2017-01-01

BACKGROUND/OBJECTIVES Sargassum horneri is an edible brown alga that grows in the subtidal zone as an annual species along the coasts of South Korea, China, and Japan. Recently, an extreme amount of S. horneri moved into the coasts of Jeju Island from the east coast of China, which made huge economic and environmental loss to the Jeju Island. Thus, utilization of this biomass becomes a big issue with the local authorities. Therefore, the present study was performed to evaluate the anti-inflammatory potential of crude polysaccharides (CPs) extracted from S. horneri China strain in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. MATERIALS/METHODS CPs were precipitated from S. horneri digests prepared by enzyme assistant extraction using four food-grade enzymes (AMG, Celluclast, Viscozyme, and Alcalase). The production levels of nitric oxide (NO) and pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-1β were measured by Griess assay and enzyme-linked immunosorbent assay, respectively. The levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPKs) were measured by using western blot. The IR spectrums of the CPs were recorded using a fourier transform infrared spectroscopy (FT-IR) spectrometer. RESULTS The polysaccharides from the Celluclast enzyme digest (CCP) showed the highest inhibition of NO production in LPS-stimulated RAW 264.7 cells (IC50 value: 95.7 µg/mL). Also, CCP dose-dependently down-regulated the protein expression levels of iNOS and COX-2 as well as the production of inflammatory cytokines, including TNF-α and IL-1β, compared to the only LPS-treated cells. In addition, CCP inhibited the activation of NF-κB p50 and p65 and the phosphorylation of MAPKs, including p38 and extracellular signal-regulated kinase, in LPS-stimulated RAW 264.7 cells. Furthermore, FT-IR analysis showed that the FT-IR spectrum of CCP is similar to that of commercial fucoidan. CONCLUSIONS Our results suggest that CCP has anti-inflammatory activities and is a potential candidate for the formulation of a functional food ingredient or/and drug to treat inflammatory diseases. PMID:28194259

Study of collisional deactivation of O{sub 2}(b{sup 1}{Sigma}{sub g}{sup +}) molecules in a hydrogen-oxygen mixture at high temperatures using laser-induced gratings

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

Kozlov, D. N., E-mail: dnk@kapella.gpi.ru; Kobtsev, V. D.; Stel'makh, O. M.

2013-07-15

Collisional deactivation of O{sub 2}(b{sup 1}{Sigma}{sub g}{sup +}) molecules resonantly excited by a 10 ns pulse of laser radiation with a wavelength of 762 nm in H{sub 2}/O{sub 2} mixtures is experimentally studied. The radiation intensity and hence the molecule excitation efficiency have a spatially periodic modulation that leads to the formation of laser-induced gratings (LIGs) of the refractive index. The study of LIG temporal evolution allows collisional relaxation rates of molecular excited states and gas temperature to be determined. In this work, the b{sup 1}{Sigma}{sub g}{sup +} state of O{sub 2} molecules deactivation rates are measured in a 4.3more » vol % H{sub 2} mixture at the number density of 2 amg in the temperature range 291-850 K. The physical deactivation is shown to dominate in the collisions of H{sub 2} with O{sub 2}(b{sup 1}{Sigma}{sub g}{sup +}) and O{sub 2}(a{sup 1}{Delta}{sub g}) up to temperatures of 780-790 K at time delays up to 10 {mu}s after the excitation pulse. The parameters of the obtained temperature dependence of the (b{sup 1}{Sigma}{sub g}{sup +} state deactivation rate agree well with the data of independent measurements performed earlier at lower temperatures (200-400 K). Tunable diode laser absorption spectroscopy is used to measure the temperature dependence of the number density of the H{sub 2}O molecules which appear as the mixture, as the result of the dark gross reaction with O{sub 2} molecules in the ground state, O{sub 2} + 2H{sub 2} {yields} 2H{sub 2}O. The measurements show that this reaction results in complete transformation of H{sub 2} into H{sub 2}O at temperatures of 790-810 K.« less

Fe Stabilization by Intermetallic L1 0-FePt and Pt Catalysis Enhancement in L1 0-FePt/Pt Nanoparticles for Efficient Oxygen Reduction Reaction in Fuel Cells

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

Li, Junrui; Xi, Zheng; Pan, Yung -Tin

We report in this article a detailed study on how to stabilize a first-row transition metal (M) in an intermetallic L1 0-MPt alloy nanoparticle (NP) structure and how to surround the L1 0-MPt with an atomic layer of Pt to enhance the electrocatalysis of Pt for oxygen reduction reaction (ORR) in fuel cell operation conditions. Using 8 nm FePt NPs as an example, we demonstrate that Fe can be stabilized more efficiently in a core/shell structured L1 0-FePt/Pt with a 5 Å Pt shell. The presence of Fe in the alloy core induces the desired compression of the thin Ptmore » shell, especially the 2 atomic layers of Pt shell, further improving the ORR catalysis. This leads to much enhanced Pt catalysis for ORR in 0.1 M HClO 4 solution (both at room temperature and 60°C) and in the membrane electrode assembly (MEA) at 80°C. The L1 0-FePt/Pt catalyst has a mass activity of 0.7 A/mg Pt from the half-cell ORR test and shows no obvious mass activity loss after 30,000 potential cycles between 0.6 V and 0.95 V at 80°C in the MEA, meeting the DOE 2020 target (<40% loss in mass activity). Here, we are extending the concept and preparing other L1 0-MPt/Pt NPs, such as L1 0-CoPt/Pt NPs, with reduced NP size as a highly efficient ORR catalyst for automotive fuel cell applications.« less

Neuroinflammatory contributions to pain after SCI: roles for central glial mechanisms and nociceptor-mediated host defense.

PubMed

Walters, Edgar T

2014-08-01

Neuropathic pain after spinal cord injury (SCI) is common, often intractable, and can be severely debilitating. A number of mechanisms have been proposed for this pain, which are discussed briefly, along with methods for revealing SCI pain in animal models, such as the recently applied conditioned place preference test. During the last decade, studies of animal models have shown that both central neuroinflammation and behavioral hypersensitivity (indirect reflex measures of pain) persist chronically after SCI. Interventions that reduce neuroinflammation have been found to ameliorate pain-related behavior, such as treatment with agents that inhibit the activation states of microglia and/or astroglia (including IL-10, minocycline, etanercept, propentofylline, ibudilast, licofelone, SP600125, carbenoxolone). Reversal of pain-related behavior has also been shown with disruption by an inhibitor (CR8) and/or genetic deletion of cell cycle-related proteins, deletion of a truncated receptor (trkB.T1) for brain-derived neurotrophic factor (BDNF), or reduction by antisense knockdown or an inhibitor (AMG9810) of the activity of channels (TRPV1 or Nav1.8) important for electrical activity in primary nociceptors. Nociceptor activity is known to drive central neuroinflammation in peripheral injury models, and nociceptors appear to be an integral component of host defense. Thus, emerging results suggest that spinal and systemic effects of SCI can activate nociceptor-mediated host defense responses that interact via neuroinflammatory signaling with complex central consequences of SCI to drive chronic pain. This broader view of SCI-induced neuroinflammation suggests new targets, and additional complications, for efforts to develop effective treatments for neuropathic SCI pain. Copyright © 2014 Elsevier Inc. All rights reserved.

Fe Stabilization by Intermetallic L1 0-FePt and Pt Catalysis Enhancement in L1 0-FePt/Pt Nanoparticles for Efficient Oxygen Reduction Reaction in Fuel Cells

DOE PAGES

Li, Junrui; Xi, Zheng; Pan, Yung -Tin; ...

2018-02-07

We report in this article a detailed study on how to stabilize a first-row transition metal (M) in an intermetallic L1 0-MPt alloy nanoparticle (NP) structure and how to surround the L1 0-MPt with an atomic layer of Pt to enhance the electrocatalysis of Pt for oxygen reduction reaction (ORR) in fuel cell operation conditions. Using 8 nm FePt NPs as an example, we demonstrate that Fe can be stabilized more efficiently in a core/shell structured L1 0-FePt/Pt with a 5 Å Pt shell. The presence of Fe in the alloy core induces the desired compression of the thin Ptmore » shell, especially the 2 atomic layers of Pt shell, further improving the ORR catalysis. This leads to much enhanced Pt catalysis for ORR in 0.1 M HClO 4 solution (both at room temperature and 60°C) and in the membrane electrode assembly (MEA) at 80°C. The L1 0-FePt/Pt catalyst has a mass activity of 0.7 A/mg Pt from the half-cell ORR test and shows no obvious mass activity loss after 30,000 potential cycles between 0.6 V and 0.95 V at 80°C in the MEA, meeting the DOE 2020 target (<40% loss in mass activity). Here, we are extending the concept and preparing other L1 0-MPt/Pt NPs, such as L1 0-CoPt/Pt NPs, with reduced NP size as a highly efficient ORR catalyst for automotive fuel cell applications.« less

Cannabidiol enhances microglial phagocytosis via transient receptor potential (TRP) channel activation

PubMed Central

Hassan, Samia; Eldeeb, Khalil; Millns, Paul J; Bennett, Andrew J; Alexander, Stephen P H; Kendall, David A

2014-01-01

Background and Purpose Microglial cells are important mediators of the immune response in the CNS. The phytocannabinoid, cannabidiol (CBD), has been shown to have central anti-inflammatory properties, and the purpose of the present study was to investigate the effects of CBD and other phytocannabinoids on microglial phagocytosis. Experimental Approach Phagocytosis was assessed by measuring ingestion of fluorescently labelled latex beads by cultured microglial cells. Drug effects were probed using single-cell Ca2+ imaging and expression of mediator proteins by immunoblotting and immunocytochemistry. Key Results CBD (10 μM) enhanced bead phagocytosis to 175 ± 7% control. Other phytocannabinoids, synthetic and endogenous cannabinoids were without effect. The enhancement was dependent upon Ca2+ influx and was abolished in the presence of EGTA, the Ca2+ channel inhibitor SKF96365, the transient receptor potential (TRP) channel blocker ruthenium red, and the TRPV1 antagonists capsazepine and AMG9810. CBD produced a sustained increase in intracellular Ca2+ concentration in BV-2 microglia and this was abolished by ruthenium red. CBD rapidly increased the expression of TRPV2 and TRPV1 proteins and caused a translocation of TRPV2 to the cell membrane. Wortmannin blocked CBD enhancement of BV-2 cell phagocytosis, suggesting that it is mediated by PI3K signalling downstream of the Ca2+ influx. Conclusions and Implications The TRPV-dependent phagocytosis-enhancing effect of CBD suggests that pharmacological modification of TRPV channel activity could be a rational approach to treating neuroinflammatory disorders involving changes in microglial function and that CBD is a potential starting point for future development of novel therapeutics acting on the TRPV receptor family. PMID:24641282

Structural Biology Insight for the Design of Sub-type Selective Aurora Kinase Inhibitors.

PubMed

Sarvagalla, Sailu; Coumar, Mohane Selvaraj

2015-01-01

Aurora kinase A, B and C, are key regulators of mitosis and are over expressed in many of the human cancers, making them an ideal drug target for cancer chemotherapy. Currently, over a dozen of Aurora kinase inhibitors are in various phases of clinical development. The majority of the inhibitors (VX-680/MK-0457, PHA-739358, CYC116, SNS-314, AMG 900, AT-9283, SCH- 1473759, ABT-348, PF-03814735, R-763/AS-703569, KW-2449 and TAK-901) are pan-selective (isoform non-selective) and few are Aurora A (MLN8054, MLN8237, VX-689/MK5108 and ENMD 2076) and Aurora B (AZD1152 and GSK1070916) sub-type selective. Despite the intensive research efforts in the past decade, no Aurora kinase inhibitor has reached the market. Recent evidence suggests that the sub-type selective Aurora kinase A inhibitor could possess advantages over pan-selective Aurora inhibitors, by avoiding Aurora B mediated neutropenia. However, sub-type selective Aurora kinase A inhibitor design is very challenging due to the similarity in the active site among the isoforms. Structural biology and computational aspects pertaining to the design of Aurora kinase inhibitors were analyzed and found that a possible means to develop sub-type selective inhibitor is by targeting Aurora A specific residues (Leu215, Thr217 and Arg220) or Aurora B specific residues (Arg159, Glu161 and Lys164), near the solvent exposed region of the protein. Particularly, a useful strategy for the design of sub-type selective Aurora A inhibitor could be by targeting Thr217 residue as in the case of MLN8054. Further preclinical and clinical studies with the sub-type selective Aurora inhibitors could help bring them to the market for the treatment of cancer.

TRPM8 is the Principal Mediator of Menthol-induced Analgesia of Acute and Inflammatory Pain

PubMed Central

Liu, Boyi; Fan, Lu; Balakrishna, Shrilatha; Sui, Aiwei; Morris, John B.; Jordt, Sven-Eric

2013-01-01

Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis and other painful conditions. Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. It remains unclear which of these targets contribute to menthol-induced analgesia, or to the irritating side effects associated with menthol therapy. Here, we use genetic and pharmacological approaches in mice to probe the role of TRPM8 in analgesia induced by L-menthol, the predominant analgesic menthol isomer in medicinal preparations. L-menthol effectively diminished pain behavior elicited by chemical stimuli (capsaicin, acrolein, acetic acid), noxious heat and inflammation (complete Freund's adjuvant). Genetic deletion of TRPM8 completely abolished analgesia by L-menthol in all these models, while other analgesics (acetaminophen) remained effective. Loss of L-menthol-induced analgesia was recapitulated in mice treated with a selective TRPM8 inhibitor, AMG2850. Selective activation of TRPM8 with WS-12, a menthol derivative we characterized as a specific TRPM8 agonist in cultured sensory neurons and in vivo, also induced TRPM8-dependent analgesia of acute and inflammatory pain. L-menthol and WS-12 induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively with diminished side effects. PMID:23820004

Targeting interferons in systemic lupus erythematosus: current and future prospects.

PubMed

Mathian, Alexis; Hie, Miguel; Cohen-Aubart, Fleur; Amoura, Zahir

2015-05-01

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown aetiology that can be debilitating and life threatening. As new insights are gained into the underlying pathology of SLE, there have been an unprecedented number of new agents under development to treat the disease via a diverse range of targets. One such class of emerging agents target interferon (IFN) signalling. In this article, we review the preclinical evidence that the inhibition of the secretion and downstream effectors of both IFN-α and IFN-γ may be effective for the treatment of SLE. The primary agents that are currently in clinical development to treat SLE via the targeting of interferon pathways are monoclonal neutralising antibodies (Mab) that bind to and neutralise IFN-γ (AMG 811), IFN-α (sifalimumab, rontalizumab and AGS-009) or its receptor (anifrolumab), and IFN-α kinoid, which is a drug composed of inactivated IFN-α molecules coupled to the keyhole limpet haemocyanin protein. Phase I and II trials have demonstrated acceptable short-term safety with no increase in severe viral infections or reactivation, favourable pharmacokinetic profiles and an inhibition of IFN-associated gene overexpression; however, the impact of these drugs on disease activity must still be assessed in phase III clinical trials. This review concludes with a summary of the challenges that are inherent to this approach to managing SLE.

Multi-modal intelligent seizure acquisition (MISA) system--a new approach towards seizure detection based on full body motion measures.

PubMed

Conradsen, Isa; Beniczky, Sandor; Wolf, Peter; Terney, Daniella; Sams, Thomas; Sorensen, Helge B D

2009-01-01

Many epilepsy patients cannot call for help during a seizure, because they are unconscious or because of the affection of their motor system or speech function. This can lead to injuries, medical complications and at worst death. An alarm system setting off at seizure onset could help to avoid hazards. Today no reliable alarm systems are available. A Multi-modal Intelligent Seizure Acquisition (MISA) system based on full body motion data seems as a good approach towards detection of epileptic seizures. The system is the first to provide a full body description for epilepsy applications. Three test subjects were used for this pilot project. Each subject simulated 15 seizures and in addition performed some predefined normal activities, during a 4-hour monitoring with electromyography (EMG), accelerometer, magnetometer and gyroscope (AMG), electrocardiography (ECG), electroencephalography (EEG) and audio and video recording. The results showed that a non-subject specific MISA system developed on data from the modalities: accelerometer (ACM), gyroscope and EMG is able to detect 98% of the simulated seizures and at the same time mistakes only 4 of the normal movements for seizures. If the system is individualized (subject specific) it is able to detect all simulated seizures with a maximum of 1 false positive. Based on the results from the simulated seizures and normal movements the MISA system seems to be a promising approach to seizure detection.

Architecting the Finite Element Method Pipeline for the GPU.

PubMed

Fu, Zhisong; Lewis, T James; Kirby, Robert M; Whitaker, Ross T

2014-02-01

The finite element method (FEM) is a widely employed numerical technique for approximating the solution of partial differential equations (PDEs) in various science and engineering applications. Many of these applications benefit from fast execution of the FEM pipeline. One way to accelerate the FEM pipeline is by exploiting advances in modern computational hardware, such as the many-core streaming processors like the graphical processing unit (GPU). In this paper, we present the algorithms and data-structures necessary to move the entire FEM pipeline to the GPU. First we propose an efficient GPU-based algorithm to generate local element information and to assemble the global linear system associated with the FEM discretization of an elliptic PDE. To solve the corresponding linear system efficiently on the GPU, we implement a conjugate gradient method preconditioned with a geometry-informed algebraic multi-grid (AMG) method preconditioner. We propose a new fine-grained parallelism strategy, a corresponding multigrid cycling stage and efficient data mapping to the many-core architecture of GPU. Comparison of our on-GPU assembly versus a traditional serial implementation on the CPU achieves up to an 87 × speedup. Focusing on the linear system solver alone, we achieve a speedup of up to 51 × versus use of a comparable state-of-the-art serial CPU linear system solver. Furthermore, the method compares favorably with other GPU-based, sparse, linear solvers.

The punishment of gene doping - The relation between WADA prohibited lists, German Medicinal Products Act, German Doping Agents Amounts Ordinance, and Basic Law of the Federal Republic of Germany.

PubMed

Parzeller, Markus

2011-10-01

The genetic constitution of athletes influences efficiency. Knowledge of genetic influences provides an opportunity for medical diagnostic and therapeutic attempts. Beside risks and therapeutic aspects, however, the possibilities of abuse for gene doping purposes in sports also exist. Genetic screening or gene therapy may have an advantage for athletes who use these methods. In juridical comments, it is pointed out that gene doping so far plays no role in sports, but that the legislator must consider a development in this area. Preventing abuse requires legal regulations. These regulations can include sanctions. This paper deals with the gene doping prohibition of the World Anti-Doping Agency (WADA) as confirmed and accepted by the monitoring group according to Articles 10 and 11 of the European Anti-Doping Convention by the Council of Europe, the prohibition of (gene) doping in sports of the German Medicinal Products Act (Arzneimittelgesetz - AMG) and the German Doping Agents Amounts Ordinance (Dopingmittel-Mengen-Verordnung-DmMV) of the German Federal Ministry of Health (BMG). The comprehensibility of the doping ban on the norm addressee was tested with a questionnaire. In connection with legal regulations of the German constitution, gene doping is discussed and problems which may arise by a state doping prohibition are pointed out. Copyright © 2011 John Wiley & Sons, Ltd.

Development of Ultra-Low Platinum Alloy Cathode Catalysts for PEM Fuel Cells

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

Popov, Branko N.; Weidner, John

2016-01-07

The goal of this project is to synthesize a low cost PEM fuel cell cathode catalyst and support with optimized average mass activity, stability of mass activity, initial high current density performance under H 2/air (power density), and catalyst and support stability able to meet 2017 DOE targets for electrocatalysts for transportation applications. Pt*/ACCS-2 catalyst was synthesized according to a novel methodology developed at USC through: (i) surface modification, (ii) metal catalyzed pyrolysis and (iii) chemical leaching to remove excess meal used to dope the support. Pt* stands for suppressed platinum catalyst synthesized with Co doped platinum. The procedure resultsmore » in increasing carbon graphitization, inclusion of cobalt in the bulk and formation of non-metallic active sites on the carbon surface. Catalytic activity of the support shows an onset potential of 0.86 V for the oxygen reduction reaction (ORR) with well-defined kinetic and mass transfer regions and 2.5% H 2O 2 production. Pt*/ACCS-2 catalyst durability under 0.6-1.0 V potential cycling and support stability under 1.0-1.5 V potential cycling was evaluated. The results indicated excellent catalyst and support performance under simulated start-up/shut down operating conditions (1.0 – 1.5 V, 5000 cycles) which satisfy DOE 2017 catalyst and support durability and activity. The 30% Pt*/ACCS-2 catalyst showed high initial mass activity of 0.34 A/mg PGM at 0.9 ViR-free and loss of mass activity of 45% after 30,000 cycles (0.6-1.0 V). The catalyst performance under H 2-air fuel cell operating conditions showed only 24 mV (iR-free) loss at 0.8 A/cm 2 with an ECSA loss of 42% after 30,000 cycles (0.6-1.0 V). The support stability under 1.0-1.5 V potential cycling showed mass activity loss of 50% and potential loss of 8 mV (iR-free) at 1.5 A/cm 2. The ECSA loss was 22% after 5,000 cycles. Furthermore, the Pt*/ACCS-2 catalyst showed an initial power density (rated) of 0.174 g PGM/kW. Excellent activity and stability of the catalyst are due to synergistic effect of the catalytic activity and stability of ACCS-2, its enhanced hydrophobicity as well as activity of compressive Pt* lattice catalysts. For the first time, we report a carbon based support which is stable under simulated start-up/shut down operating conditions. Five 25cm 2 MEA’s were fabricated at USC using Pt*/ACCS-2 cathode catalyst for independent evaluation at National Renewable Energy. In the Final NREL report they summarize their results as follow: (1) Initial ORR activity and performance of the USC MEA’s Pt*/ACCS-2 under oxygen air, evaluated at NREL were comparable to that measured and reported by USC in their report: (2) Cyclic durability studies indicate that Pt*/ACCS-2 catalysts has minimal losses in activity and performant under 1-1.5 V potential cycling indicating a robust corrosion resistant support.« less

Scalable implicit incompressible resistive MHD with stabilized FE and fully-coupled Newton–Krylov-AMG

DOE PAGES

Shadid, J. N.; Pawlowski, R. P.; Cyr, E. C.; ...

2016-02-10

Here, we discuss that the computational solution of the governing balance equations for mass, momentum, heat transfer and magnetic induction for resistive magnetohydrodynamics (MHD) systems can be extremely challenging. These difficulties arise from both the strong nonlinear, nonsymmetric coupling of fluid and electromagnetic phenomena, as well as the significant range of time- and length-scales that the interactions of these physical mechanisms produce. This paper explores the development of a scalable, fully-implicit stabilized unstructured finite element (FE) capability for 3D incompressible resistive MHD. The discussion considers the development of a stabilized FE formulation in context of the variational multiscale (VMS) method,more » and describes the scalable implicit time integration and direct-to-steady-state solution capability. The nonlinear solver strategy employs Newton–Krylov methods, which are preconditioned using fully-coupled algebraic multilevel preconditioners. These preconditioners are shown to enable a robust, scalable and efficient solution approach for the large-scale sparse linear systems generated by the Newton linearization. Verification results demonstrate the expected order-of-accuracy for the stabilized FE discretization. The approach is tested on a variety of prototype problems, that include MHD duct flows, an unstable hydromagnetic Kelvin–Helmholtz shear layer, and a 3D island coalescence problem used to model magnetic reconnection. Initial results that explore the scaling of the solution methods are also presented on up to 128K processors for problems with up to 1.8B unknowns on a CrayXK7.« less

Gateways to clinical trials.

PubMed

Tomillero, A; Moral, M A

2009-03-01

ABT-869, Acadesine, Acetylsalicylic acid/omeprazole, Adefovir, Adefovir dipivoxil, AEG-35156, Agatolimod sodium, Albiglutide, Alemtuzumab, Alipogene tiparvovec, Alogliptin benzoate, AMG-386, Amrubicin hydrochloride, Apremilast, Aripiprazole, Asoprisnil, Atorvastatin/fenofibrate, AVN-944, Axitinib; Belinostat, Bevacizumab, BHT-3021, BI-2536, Biapenem, Bilastine, Biphasic insulin aspart, Blinatumomab, Bortezomib, Bosentan; Catumaxomab, CD-NP, Cediranib, Certolizumab pegol, Cetuximab, Choline fenofibrate, Ciclesonide, CK-1827452,Clevudine, Clofarabine, CSL-360, CYT-997; Dapagliflozin, Darinaparsin, Denosumab, Densiron 68, Desloratadine, Dulanermin; Edoxaban tosilate, Emtricitabine, Entecavir, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Fidaxomicintiacumiv, Fulvestrant; G-207, GCR-8015, Gefitinib, Ghrelin (human), Glufosfamide; HPV16L1E7CVLP; Ibutamoren mesilate, Imatinib mesylate, Insulin detemir, Insulin glargine, Iodine (I131) tositumomab, Istaroxime, ITMN-191, Ixabepilone; JZP-4, Lenalidomide; Levetiracetam, Linaclotide acetate, Liposomal cytarabine/daunorubicin, Liposomal doxorubicin, Liraglutide, LY-518674; Milatuzumab, MMR-V, Motesanib diphosphate, Mycophenolic acid sodium salt; Niacin/simvastatin; Obatoclax mesylate, Odanacatib; Paclitaxel nanoparticles, Paclitaxel-eluting stent, Pazufloxacin, PBT-2, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pemetrexed disodium, Perampanel, PfCP2.9, Pitavastatin calcium, Poly I:CLC, Pomalidomide, Pralatrexate, Pramlintide acetate, Prucalopride; rhGAD65, Roflumilast; RTS,S/AS02D; SCH-530348, Semagacestat, Sirolimus-eluting coronary stent, Sirolimus-Eluting Stent, SIR-Spheres, Sivelestat sodium hydrate, Sorafenib, Sunitinib malate; Tadalafil, Tafluprost, Tanespimycin, Teduglutide, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tiotropium bromide, TMC-435350, Tositumomab/iodine (I131) tositumomab, Travoprost/timolol, Triciribine phosphate; Vandetanib, VIA-2291, Vinflunine, Vorinostat; XL-019; Yttrium 90 (90Y) ibritumomab tiuxetan. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

[Consequence of European Directive 2004/23/EC for bone banks in Germany].

PubMed

Pruss, A; Knaepler, H; Katthagen, B-D; Frommelt, L

2005-11-01

Allogenic bone grafting is an established method in revision surgery of artificial joint replacement and spinal surgery in case of bone defects. In Germany, femoral heads from living donors undergoing total hip replacement are frequently used. These grafts are processed according to the "Guidelines for the management of bone banking" issued by the Federal Medical Board. Bone grafts are drugs according to German law. Local bone banks are excluded from the regulations of the federal law on drugs [Arzneimittelgesetz (AMG) section sign 4a (4)] if certain requirements are fulfilled. The Directive 2004/23/EC of the European Parliament and of The Council on Setting Standards of Quality and Safety for the Donation, Procurement, Testing, Processing, Preservation, Storage and Distribution of Human Tissues and Cells has to be implemented into national law within 2 years. The exception of section sign 4a (4) will no longer be possible. Thus a legal construction has to be found which allows running local bone banks in compliance with the new legal settings. Three conditions will be possible: (1) a single physician procures a graft for another patient of his, (2) grafts are procured in one hospital and are used exclusively in this hospital: a license from the local authorities and a strict quality assessment according to GMP-rules is required, (3) if the grafts are distributed to other hospitals, a license from the local authorities and registration as a drug by the federal authorities are necessary.

Upgrading weld quality of a friction stir welded aluminum alloys AMG6

NASA Astrophysics Data System (ADS)

Chernykh, I. K.; Vasil'ev, E. V.; Matuzko, E. N.; Krivonos, E. V.

2018-01-01

In the course of introduction of FSW technology into the industry there is a keen interest in this process; there are issues such as how does joining take place, what is the structure of the joint, and where there are dangerous zones. The objective of this research is to obtain information about the structure of the joint, what are the temperatures that arise during the joining, what strength is apply to the tool when joining the material, what tensile strength of joint, and where fracture tended to occur. Specimens were produced at different modes of welding at a tool rotation speed of 315 to 625 rpm and tool travel speed of 40 to 125 mm/min. During the experiment, the strength applied to the tool was measured, which reached 800016000 N (Fz) and 400-1400 N (Fx) and the temperature on the surface of the tool, which is in the range 250-400°C. Before the welding process the tool was heated to a temperature in the range of 100-250 degrees, but the tensile strength is not had a tangible impact. The tensile strength is about 80 % of that of the aluminum alloy base metal tensile strength, and fracture tended is occur not at the line of joint but follow the shape of the tool. In the transverse cross section of a FSW material there is a microstructural regions such as weld nugget, thermomechanically affected zone and heat-affected zone with parent material.

Studying plastic shear localization in aluminum alloys under dynamic loading

NASA Astrophysics Data System (ADS)

Bilalov, D. A.; Sokovikov, M. A.; Chudinov, V. V.; Oborin, V. A.; Bayandin, Yu. V.; Terekhina, A. I.; Naimark, O. B.

2016-12-01

An experimental and theoretical study of plastic shear localization mechanisms observed under dynamic deformation using the shear-compression scheme on a Hopkinson-Kolsky bar has been carried out using specimens of AMg6 alloy. The mechanisms of plastic shear instability are associated with collective effects in the microshear ensemble in spatially localized areas. The lateral surface of the specimens was photographed in the real-time mode using a CEDIP Silver 450M high-speed infrared camera. The temperature distribution obtained at different times allowed us to trace the evolution of the localization of the plastic strain. Based on the equations that describe the effect of nonequilibrium transitions on the mechanisms of structural relaxation and plastic flow, numerical simulation of plastic shear localization has been performed. A numerical experiment relevant to the specimen-loading scheme was carried out using a system of constitutive equations that reflect the part of the structural relaxation mechanisms caused by the collective behavior of microshears with the autowave modes of the evolution of the localized plastic flow. Upon completion of the experiment, the specimens were subjected to microstructure analysis using a New View-5010 optical microscope-interferometer. After the dynamic deformation, the constancy of the Hurst exponent, which reflects the relationship between the behavior of defects and roughness induced by the defects on the surfaces of the specimens is observed in a wider range of spatial scales. These investigations revealed the distinctive features in the localization of the deformation followed by destruction to the script of the adiabatic shear. These features may be caused by the collective multiscale behavior of defects, which leads to a sharp decrease in the stress-relaxation time and, consequently, a localized plastic flow and generation of fracture nuclei in the form of adiabatic shear. Infrared scanning of the localization zone of the plastic strain in situ and the subsequent study of the defect structure corroborated the hypothesis about the decisive role of non-equilibrium transitions in defect ensembles during the evolution of a localized plastic flow.

Carbonate mineralization via an amorphous calcium carbonate (ACC) pathway: Tuning polymorph selection by Mg, pH, and mixing environment

NASA Astrophysics Data System (ADS)

Dove, P. M.; Blue, C.; Mergelsberg, S. T.; Giuffre, A. J.; Han, N.; De Yoreo, J. J.

2017-12-01

Mineral formation by nonclassical processes is widespread with many pathways that include aggregation of nanoparticles, oriented attachment of fully formed crystals, and sequential nucleation/transformation of amorphous phases (De Yoreo et al., 2015, Science). Field observations indicate amorphous calcium carbonate (ACC) can be the initial precipitate when local conditions promote high supersaturations for short time periods. Examples include microbial mats, marine porewaters that undergo pulses of increased alkalinity, closed basin lakes, and sabkhas. The crystalline products exhibit diverse morphologies and complex elemental and isotopic signatures. This study quantifies relationships between solution composition and the crystalline polymorphs that transform from ACC (Blue et al., GCA, 2017). Our experimental design synthesized ACC under controlled conditions for a suite of compositions by tuning input pH, Mg/Ca, and total carbonate concentration. ACC products were allowed to transform within output suspensions under stirred or quiescent mixing while characterizing the polymorph and composition of evolving solutions and solids. We find that ACC transforms to crystalline polymorphs with a systematic relationship to solution composition to give a quantitative framework based upon solution aMg2+/aCa2+ and aCO32-/aCa2+. We also measure a polymorph-specific evolution of pH and Mg/Ca during the transformation that indicates the initial polymorph to form. Pathway is further modulated by stirring versus quiescent conditions. The findings reconcile discrepancies among previous studies of ACC to crystalline products and supports claims that monohydrocalcite may be an overlooked, transient phase during formation of some aragonite and calcite deposits. Organic additives and extreme pH are not required to tune composition and polymorph. Insights from this study reiterate the need to revisit long-standing dogmas regarding controls on CaCO3 polymorph selection. Classical models assume thermodynamic equilibria but cannot provide a reliable predictor of compositions when kinetic factors are driving mineralization. Nonclassical pathways to mineralization may be the missing link to interpreting unusual CaCO3 polymorphs, compositions and textures in modern and ancient carbonates.

Ectopic expression of bacterial amylopullulanase enhances bioethanol production from maize grain.

PubMed

Nahampun, Hartinio N; Lee, Chang Joo; Jane, Jay-Lin; Wang, Kan

2013-09-01

Heterologous expression of amylopullulanase in maize seeds leads to partial starch degradation into fermentable sugars, which enhances direct bioethanol production from maize grain. Utilization of maize in bioethanol industry in the United States reached ±13.3 billion gallons in 2012, most of which was derived from maize grain. Starch hydrolysis for bioethanol industry requires the addition of thermostable alpha amylase and amyloglucosidase (AMG) enzymes to break down the α-1,4 and α-1,6 glucosidic bonds of starch that limits the cost effectiveness of the process on an industrial scale due to its high cost. Transgenic plants expressing a thermostable starch-degrading enzyme can overcome this problem by omitting the addition of exogenous enzymes during the starch hydrolysis process. In this study, we generated transgenic maize plants expressing an amylopullulanase (APU) enzyme from the bacterium Thermoanaerobacter thermohydrosulfuricus. A truncated version of the dual functional APU (TrAPU) that possesses both alpha amylase and pullulanase activities was produced in maize endosperm tissue using a seed-specific promoter of 27-kD gamma zein. A number of analyses were performed at 85 °C, a temperature typically used for starch processing. Firstly, enzymatic assay and thin layer chromatography analysis showed direct starch hydrolysis into glucose. In addition, scanning electron microscopy illustrated porous and broken granules, suggesting starch autohydrolysis. Finally, bioethanol assay demonstrated that a 40.2 ± 2.63 % (14.7 ± 0.90 g ethanol per 100 g seed) maize starch to ethanol conversion was achieved from the TrAPU seeds. Conversion efficiency was improved to reach 90.5 % (33.1 ± 0.66 g ethanol per 100 g seed) when commercial amyloglucosidase was added after direct hydrolysis of TrAPU maize seeds. Our results provide evidence that enzymes for starch hydrolysis can be produced in maize seeds to enhance bioethanol production.

Global Cicada Sound Collection I: Recordings from South Africa and Malawi by B. W. Price & M. H. Villet and harvesting of BioAcoustica data by GBIF

PubMed Central

Price, Benjamin Wills; Rycroft, Simon; Villet, Martin H.

2015-01-01

Abstract Background Sound collections for singing insects provide important repositories that underpin existing research (e.g. Price et al. 2007 at http://bio.acousti.ca/node/11801; Price et al. 2010) and make bioacoustic collections available for future work, including insect communication (Ordish 1992), systematics (e.g. David et al. 2003), and automated identification (Bennett et al. 2015). The BioAcoustica platform (Baker et al. 2015) is both a repository and analysis platform for bioacoustic collections: allowing collections to be available in perpetuity, and also facilitating complex analyses using the BioVeL cloud infrastructure (Vicario et al. 2011). The Global Cicada Sound Collection is a project to make recordings of the world's cicadas (Hemiptera: Cicadidae) available using open licences to maximise their potential for study and reuse. This first component of the Global Cicada Sound Collection comprises recordings made between 2006 and 2008 of Cicadidae in South Africa and Malawi. New information This collection of sounds includes 219 recordings of 133 voucher specimens, comprising 42 taxa (25 identified to species, all identified to genus) from South Africa and Malawi. The recordings have been used to underpin work on the species limits of cicadas in southern Africa, including Price et al. (2007) and Price et al. (2010). The specimens are deposited in the Albany Museum, Grahamstown, South Africa (AMGS). The harvesting of acoustic data as occurrence records by GBIF has been implemented by the Scratchpads Team at the Natural History Museum, London. This link increases the value of individual recordings and the BioAcoustica platform within the global infrastructure of biodiversity informatics by making specimen/occurence records from BioAcoustica available to a wider audience, and allowing their integration with other occurence datasets that also contribute to GBIF. PMID:26379465

Feasibility of using Big Area Additive Manufacturing to Directly Manufacture Boat Molds

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

Post, Brian K.; Chesser, Phillip C.; Lind, Randall F.

The goal of this project was to explore the feasibility of using Big Area Additive Manufacturing (BAAM) to directly manufacture a boat mold without the need for coatings. All prior tooling projects with BAAM required the use to thick coatings to overcome the surface finish limitations of the BAAM process. While the BAAM process significantly lowers the cost of building the mold, the high cost element rapidly became the coatings (cost of the material, labor on coating, and finishing). As an example, the time and cost to manufacture the molds for the Wind Turbine project with TPI Composites Inc. andmore » the molds for the submarine project with Carderock Naval Warfare Systems was a fraction of the time and cost of the coatings. For this project, a catamaran boat hull mold was designed, manufactured, and assembled with an additional 0.15” thickness of material on all mold surfaces. After printing, the mold was immediately machined and assembled. Alliance MG, LLC (AMG), the industry partner of this project, experimented with mold release agents on the carbon-fiber reinforced acrylonitrile butadiene styrene (CF ABS) to verify that the material can be directly used as a mold (rather than needing a coating). In addition, for large molds (such as the wind turbine mold with TPI Composites Inc.), the mold only provided the target surface. A steel subframe had to be manufactured to provide structural integrity. If successful, this will significantly reduce the time and cost necessary for manufacturing large resin infusion molds using the BAAM process.« less

Pharmacokinetics, Biotransformation, and Excretion of [14C]Etelcalcetide (AMG 416) Following a Single Microtracer Intravenous Dose in Patients with Chronic Kidney Disease on Hemodialysis.

PubMed

Subramanian, Raju; Zhu, Xiaochun; Hock, M Benjamin; Sloey, Bethlyn J; Wu, Benjamin; Wilson, Sarah F; Egbuna, Ogo; Slatter, J Greg; Xiao, Jim; Skiles, Gary L

2017-02-01

Etelcalcetide (AMG 416) is a novel synthetic peptide calcium-sensing receptor activator in clinical development as an intravenous calcimimetic for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on hemodialysis. Etelcalcetide is composed of seven D-aminoacids with an L-cysteine linked to a D-cysteine by a disulfide bond. A single intravenous dose of [ 14 C]etelcalcetide (10 mg; 26.3 kBq; 710 nCi) was administered to patients with CKD on hemodialysis to elucidate the pharmacokinetics, biotransformation, and excretion of etelcalcetide in this setting. Blood, dialysate, urine, and feces were collected to characterize the pharmacokinetics, biotransformation product profiles, mass balance, and formation of anti-etelcalcetide antibodies. Accelerator mass spectrometry was necessary to measure the microtracer quantities of C-14 excreted in the large volumes of dialysate and other biomatrices. An estimated 67 % of the [ 14 C]etelcalcetide dose was recovered in dialysate, urine, and feces 176 days after dose administration. Etelcalcetide was primarily cleared by hemodialysis, with approximately 60 % of the administered dose eliminated in dialysate. Minor excretion was observed in urine and feces. Biotransformation resulted from disulfide exchange with endogenous thiols, and preserved the etelcalcetide D-amino acid backbone. Drug-related radioactivity circulated primarily as serum albumin peptide conjugate (SAPC). Following removal of plasma etelcalcetide by hemodialysis, re-equilibration occurred between SAPC and L-cysteine present in blood to partially restore the etelcalcetide plasma concentrations between dialysis sessions. No unanticipated safety signals or anti-etelcalcetide or anti-SAPC antibodies were detected.

[European Marketing Authorisation: a long process. Experiences of small biotech companies with the ATMP regulation].

PubMed

Buljovčić, Z

2011-07-01

On 30 December 2008, the Regulation (EC) 1394/2007 on advanced therapy medicinal products (ATMPs) entered into force. Herewith the first EU-wide regulatory framework for ATMPs was established. It requires a central marketing authorisation application to the EMA (European Medicinal Agency). This new framework especially changes the code of regulatory practice for tissue engineered products (TEPs), as no registration procedure had been previously required for autologous TEPs. This also meant that no clinical proof of efficacy achieved by a pivotal clinical trial was necessary. Difficulties and their background as well as the vast requirements for product development that have to be addressed by small companies within a very short time frame are presented. Hereby, it is obvious that regulatory experience which is required to identify and implement the resulting implications was not in place yet and still had to be established. The lack of regulatory experience also resulted in difficulties with scientific advice preparation, expectations toward regulatory agencies, consultants, and transformation of regulatory requirements. Addressing the regulatory requirements within the transition period is even more difficult for entrepreneurs with products which are assigned for indications resulting in complex challenges to the trial design. Due to the enormous time pressure to generate data and due to the implied financial pressure, different adaptation strategies are evolving. In Germany the "hospital exemption" according to §4b AMG (German Medicinal Products Law) is of major importance. A reorientation toward acellular products and a slow down in development of new ATMP products is expected.

Neurokinin-1 receptor antagonism attenuates neuronal activity triggered by stress-induced reinstatement of alcohol seeking.

PubMed

Schank, J R; Nelson, B S; Damadzic, R; Tapocik, J D; Yao, M; King, C E; Rowe, K E; Cheng, K; Rice, K C; Heilig, M

2015-12-01

Substance P (SP) and its cognate neurokinin-1 receptor (NK1R) are involved in alcohol-related behaviors. We have previously reported that NK1R antagonism attenuates stress-induced reinstatement of alcohol seeking and suppresses escalated alcohol self-administration, but does not affect primary reinforcement or cue-induced reinstatement. Here, we administered an NK1R antagonist or vehicle prior to footshock-induced reinstatement of alcohol seeking, and mapped the resulting neuronal activation using Fos immunohistochemistry. As expected, vehicle treated animals exposed to footshock showed induction of Fos immunoreactivity in several regions of the brain stress circuitry, including the amygdala (AMG), nucleus accumbens (NAC), dorsal raphe nucleus (DR), prefrontal cortex (PFC), and bed nucleus of the stria terminalis (BNST). NK1R antagonism selectively suppressed the stress-induced increase in Fos in the DR and NAC shell. In the DR, Fos-induction by stress largely overlapped with tryptophan hydroxylase (TrpH), indicating activation of serotonergic neurons. Of NAC shell neurons activated during stress-induced reinstatement of alcohol seeking, about 30% co-expressed dynorphin (DYN), while 70% co-expressed enkephalin (ENK). Few (<1%) activated NAC shell neurons coexpressed choline acetyltransferase (ChAT), which labels the cholinergic interneurons of this region. Infusion of the NK1R antagonist L822429 into the NAC shell blocked stress-induced reinstatement of alcohol seeking. In contrast, L822429 infusion into the DR had no effect, suggesting that the influence of NK1R signaling on neuronal activity in the DR is indirect. Taken together, our results outline a potential pathway through which endogenous NK1R activation mediates stress-induced alcohol seeking. Copyright © 2015 Elsevier Ltd. All rights reserved.

Crystal structure and optical property of complex perovskite oxynitrides ALi0.2Nb0.8O2.8N0.2, ANa0.2Nb0.8O2.8N0.2, and AMg0.2Nb0.8O2.6N0.4 (A = Sr, Ba)

NASA Astrophysics Data System (ADS)

Moon, Keon Ho; Avdeev, Maxim; Kim, Young-Il

2017-10-01

Oxynitride type complex perovskites AM0.2Nb0.8O3-xNx (A = Sr, Ba; M = Li, Na, Mg) were newly synthesized by the solid state diffusion of Li+, Na+, or Mg2+ into the layered oxide, A5Nb4O15, with concurrent O/N substitution. Neutron and synchrotron X-ray Rietveld refinement showed that SrLi0.2Nb0.8O2.8N0.2, SrNa0.2Nb0.8O2.8N0.2, and SrMg0.2Nb0.8O2.6N0.4 had body-centered tetragonal symmetry (I4/mcm), while those with A = Ba had simple cubic symmetry (Pm 3 ̅ m). In the tetragonal Sr-compounds, the nitrogen atoms were localized on the c-axial 4a site. However, the octahedral cations, M/Nb (M = Li, Na, Mg) were distributed randomly in all six compounds. The lattice volume of AM0.2Nb0.8O3-xNx was dependent on various factors including the type of A and the electronegativity of M. Compared to the simple perovskites, ANbO2N (A = Sr, Ba), AM0.2Nb0.8O3-xNx had wider band gaps (1.76-2.15 eV for A = Sr and 1.65-2.10 eV for A = Ba), but significantly lower sub-gap absorption.

Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate

PubMed Central

2011-01-01

Background The study investigated the distribution of silver after 28 days repeated oral administration of silver nanoparticles (AgNPs) and silver acetate (AgAc) to rats. Oral administration is a relevant route of exposure because of the use of silver nanoparticles in products related to food and food contact materials. Results AgNPs were synthesized with a size distribution of 14 ± 4 nm in diameter (90% of the nanoparticle volume) and stabilized in aqueous suspension by the polymer polyvinylpyrrolidone (PVP). The AgNPs remained stable throughout the duration of the 28-day oral toxicity study in rats. The organ distribution pattern of silver following administration of AgNPs and AgAc was similar. However the absolute silver concentrations in tissues were lower following oral exposure to AgNPs. This was in agreement with an indication of a higher fecal excretion following administration of AgNPs. Besides the intestinal system, the largest silver concentrations were detected in the liver and kidneys. Silver was also found in the lungs and brain. Autometallographic (AMG) staining revealed a similar cellular localization of silver in ileum, liver, and kidney tissue in rats exposed to AgNPs or AgAc. Using transmission electron microscopy (TEM), nanosized granules were detected in the ileum of animals exposed to AgNPs or AgAc and were mainly located in the basal lamina of the ileal epithelium and in lysosomes of macrophages within the lamina propria. Using energy dispersive x-ray spectroscopy it was shown that the granules in lysosomes consisted of silver, selenium, and sulfur for both AgNP and AgAc exposed rats. The diameter of the deposited granules was in the same size range as that of the administered AgNPs. No silver granules were detected by TEM in the liver. Conclusions The results of the present study demonstrate that the organ distribution of silver was similar when AgNPs or AgAc were administered orally to rats. The presence of silver granules containing selenium and sulfur in the intestinal wall of rats exposed to either of the silver forms suggests a common mechanism of their formation. Additional studies however, are needed to gain further insight into the underlying mechanisms of the granule formation, and to clarify whether AgNPs dissolve in the gastrointestinal system and/or become absorbed and translocate as intact nanoparticles to organs and tissues. PMID:21631937

Peripheral Receptor Mechanisms Underlying Orofacial Muscle Pain and Hyperalgesia

NASA Astrophysics Data System (ADS)

Saloman, Jami L.

Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) are severely debilitating and affect approximately 12% of the population. Identifying peripheral nociceptive mechanisms underlying mechanical hyperalgesia, a prominent feature of persistent muscle pain, could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. This study provides evidence of functional interactions between ligand-gated channels, P2X3 and TRPV1/TRPA1, in trigeminal sensory neurons, and proposes that these interactions underlie the development of mechanical hyperalgesia. In the masseter muscle, direct P2X3 activation, via the selective agonist αβmeATP, induced a dose- and time-dependent hyperalgesia. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810, or the TRPA1 antagonist, AP18. P2X3 was co-expressed with both TRPV1 and TRPA1 in masseter muscle afferents confirming the possibility for intracellular interactions. Moreover, in a subpopulation of P2X3 /TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly potentiated following P2X3 activation. Inhibition of Ca2+-dependent kinases, PKC and CaMKII, prevented P2X3-mechanical hyperalgesia whereas blockade of Ca2+-independent PKA did not. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal sensory neurons. Significant phosphorylation was observed at 15 minutes, the time point at which behavioral hyperalgesia was prominent. Similar data were obtained regarding another nonselective cation channel, the NMDA receptor (NMDAR). Our data propose P2X3 and NMDARs interact with TRPV1 in a facilitatory manner, which could contribute to the peripheral sensitization underlying masseter hyperalgesia. This study offers novel mechanisms by which individual pro-nociceptive ligand gated ion channels form functional complexes in nociceptors. It is also important to further elucidate peripheral anti-nociceptive mechanisms to improve clinical utilization of currently available analgesics and uncover additional therapeutic targets. A side project examined the mechanisms underlying sex differences in the anti-hyperalgesic effects of delta opioid receptors (DORs). This study provides evidence of a sex difference in the potency at DORs that is mediated by differences in the expression of ATP-sensitive potassium channels. Collectively, understanding detailed molecular events that underlie the development of pathological pain conditions could benefit future pharmacotherapies.

On the implementation of an accurate and efficient solver for convection-diffusion equations

NASA Astrophysics Data System (ADS)

Wu, Chin-Tien

In this dissertation, we examine several different aspects of computing the numerical solution of the convection-diffusion equation. The solution of this equation often exhibits sharp gradients due to Dirichlet outflow boundaries or discontinuities in boundary conditions. Because of the singular-perturbed nature of the equation, numerical solutions often have severe oscillations when grid sizes are not small enough to resolve sharp gradients. To overcome such difficulties, the streamline diffusion discretization method can be used to obtain an accurate approximate solution in regions where the solution is smooth. To increase accuracy of the solution in the regions containing layers, adaptive mesh refinement and mesh movement based on a posteriori error estimations can be employed. An error-adapted mesh refinement strategy based on a posteriori error estimations is also proposed to resolve layers. For solving the sparse linear systems that arise from discretization, goemetric multigrid (MG) and algebraic multigrid (AMG) are compared. In addition, both methods are also used as preconditioners for Krylov subspace methods. We derive some convergence results for MG with line Gauss-Seidel smoothers and bilinear interpolation. Finally, while considering adaptive mesh refinement as an integral part of the solution process, it is natural to set a stopping tolerance for the iterative linear solvers on each mesh stage so that the difference between the approximate solution obtained from iterative methods and the finite element solution is bounded by an a posteriori error bound. Here, we present two stopping criteria. The first is based on a residual-type a posteriori error estimator developed by Verfurth. The second is based on an a posteriori error estimator, using local solutions, developed by Kay and Silvester. Our numerical results show the refined mesh obtained from the iterative solution which satisfies the second criteria is similar to the refined mesh obtained from the finite element solution.

Resolving TRPV1 and TNF-α Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1

PubMed Central

Park, Chul-Kyu; Lü, Ning; Xu, Zhen-Zhong; Liu, Tong; Serhan, Charles N.; Ji, Ru-Rong

2011-01-01

Mechanisms of inflammatory pain are not fully understood. We investigated the role of TRPV1 and TNF-α, two critical mediators for inflammatory pain, in regulating spinal cord synaptic transmission. We found in mice lacking Trpv1 the frequency but not the amplitude of spontaneous EPSCs (sEPSCs) in lamina II neurons of spinal cord slices is reduced. Further, C-fiber-induced spinal long-term potentiation (LTP) in vivo is abolished in Trpv1 knockout mice. TNF-α also increases sEPSC frequency but not amplitude in spinal lamina IIo neurons, and this increase is abolished in Trpv1 knockout mice. Single-cell PCR analysis revealed that TNF-α-responding neurons in lamina IIo are exclusively excitatory (vGluT2+) neurons. Notably, neuroprotectin-1 (NPD1), an anti-inflammatory lipid mediator derived from omega-3 polyunsaturated fatty acid (docosahexaenoic acid) blocks TNF-α- and capsaicin-evoked sEPSC frequency increases but has no effect on basal synaptic transmission. Strikingly, NPD1 potently inhibits capsaicin-induced TRPV1 current (IC50=0.4 nM) in dissociated dorsal root ganglion neurons, and this IC50 is ≈ 500 times lower than that of AMG9810, a commonly used TRPV1 antagonist. NPD1 inhibition of TRPV1 is mediated by GPCRs, since the effects were blocked by pertussis toxin. In contrast, NPD1 had not effect on mustard oil-induced TRPA1 currents. Spinal injection of NPD1, at very low doses (0.1–10 ng), blocks spinal LTP and reduces TRPV1-dependent inflammatory pain, without affecting baseline pain. NPD1 also reduces TRPV1-independent but TNF-α-dependent pain hypersensitivity. Our findings demonstrate a novel role of NPD1 in regulating TRPV1/TNF-α-mediated spinal synaptic plasticity and identify NPD1 as a novel analgesic for treating inflammatory pain. PMID:22016541

[Future supply of tuberculin in Germany].

PubMed

Sagebiel, D; Hauer, B; Haas, W; Magdorf, K; Priwitzer, M; Loddenkemper, R

2005-04-01

The manufacturers of the only tuberculin available up to now in Germany for intradermal TB tests according to Mantoux, Chiron Vaccines Behring, in 2004 unexpectedly stopped the production of the tuberculin Behring GT (GT="gereinigtes Tuberkulin"-purified protein derivative tuberculin). Only residual stocks were sold during the preceding months. The stocks of GT 10 were already depleted at the beginning of 2005, while there are small supplies left of GT 100 and GT 1000. As a temporary solution, Chiron Vaccines Behring is offering to import the Italian tuberculin Biocine PPD 5 IE lyophil produced by Chiron S.r.l. in Siena. As this is not licensed for sale in Germany, it is necessary to obtain an exceptional prescription (Einzelverordnung) according to section sign 73 (3) of the Federal Law Relating to the Manufacture and Distribution of Medicine (Arzneimittelgesetz, AMG). In the long term, Chiron Vaccines Behring plan to secure the supply of tuberculin in Germany by importing, starting in the summer of 2006, the tuberculin produced by Chiron Vaccines Evans in the UK (PPD Evans). However, these plans involve changing over to a different type of tuberculin twice within a very short period of time. Another problem is the unresolved issue of bioequivalence. Besides the above-mentioned tuberculins produced by Chiron Vaccines, a further possibility would be the import of the tuberculin PPD RT23 SSI of the Statens Serums Institute (Copenhagen/Denmark), which is recommended by the World Health Organization (WHO) as the standard tuberculin and which has already been introduced in several European countries, or of other tuberculins such as Tubersol (PPD CT68), which is used in the US. Together with the Robert Koch Institute (RKI) and the Paul Ehrlich Institute (PEI), the German Central Committee against Tuberculosis (DZK) is striving to find a solution, in view of the urgent need for an uninterrupted supply of tuberculin in Germany for diagnostic purposes and contact tracing. A uniform tuberculin should be used in all German regions as a basis to secure a standardized testing procedure and national comparability of test results. The estimated annual requirement for Germany is two million tuberculin test doses. The Statens Serum Institute is currently evaluating the possibility of licensing PPD RT23 SSI in Germany. Chiron Vaccines Behring communicated that it is not aiming to have the Biocine tuberculin licensed for Germany but intends to apply for a license for the tuberculin PPD Evans. Sanofi Pasteur MSD at this point does not intend to have a tuberculin like Tubersol (PPD CT68) licensed for Germany. Until a licensed tuberculin is again available in Germany, it would be very useful if, especially in settings where stocks of tuberculin are essential (e.g. public health services or hospital dispensaries), an exceptional import license could be obtained.

Chemical and physical controls on the transformation of amorphous calcium carbonate into crystalline CaCO3 polymorphs

NASA Astrophysics Data System (ADS)

Blue, C. R.; Giuffre, A.; Mergelsberg, S.; Han, N.; De Yoreo, J. J.; Dove, P. M.

2017-01-01

Calcite and other crystalline polymorphs of CaCO3 can form by pathways involving amorphous calcium carbonate (ACC). Apparent inconsistencies in the literature indicate the relationships between ACC composition, local conditions, and the subsequent crystalline polymorphs are not yet established. This experimental study quantifies the control of solution composition on the transformation of ACC into crystalline polymorphs in the presence of magnesium. Using a mixed flow reactor to control solution chemistry, ACC was synthesized with variable Mg contents by tuning input pH, Mg/Ca, and total carbonate concentration. ACC products were allowed to transform within the output suspension under stirred or quiescent conditions while characterizing the evolving solutions and solids. As the ACC transforms into a crystalline phase, the solutions record a polymorph-specific evolution of pH and Mg/Ca. The data provide a quantitative framework for predicting the initial polymorph that forms from ACC based upon the solution aMg2+/aCa2+ and aCO32-/aCa2+ and stirring versus quiescent conditions. This model reconciles discrepancies among previous studies that report on the nature of the polymorphs produced from ACC and supports the previous claim that monohydrocalcite may be an important, but overlooked, transient phase on the way to forming some aragonite and calcite deposits. By this construct, organic additives and extreme pH are not required to tune the composition and nature of the polymorph that forms. Our measurements show that the Mg content of ACC is recorded in the resulting calcite with a ≈1:1 dependence. By correlating composition of these calcite products with the Mgtot/Catot of the initial solutions, we find a ≈3:1 dependence that is approximately linear and general to whether calcite is formed via an ACC pathway or by the classical step-propagation process. Comparisons to calcite grown in synthetic seawater show a ≈1:1 dependence. The relationships suggest that the local Mg2+/Ca2+ at the time of precipitation determines the calcite composition, independent of whether growth occurs via an amorphous intermediate or classical pathway for a range of supersaturations and pH conditions. The findings reiterate the need to revisit the traditional picture of chemical and physical controls on CaCO3 polymorph selection. Mineralization by pathways involving ACC can lead to the formation of crystalline phases whose polymorphs and compositions are out of equilibrium with local growth media. As such, classical thermodynamic equilibria may not provide a reliable predictor of observed compositions.

Mapping the changing pattern of local climate as an observed distribution

NASA Astrophysics Data System (ADS)

Chapman, Sandra; Stainforth, David; Watkins, Nicholas

2013-04-01

It is at local scales that the impacts of climate change will be felt directly and at which adaptation planning decisions must be made. This requires quantifying the geographical patterns in trends at specific quantiles in distributions of variables such as daily temperature or precipitation. Here we focus on these local changes and on the way observational data can be analysed to inform us about the pattern of local climate change. We present a method[1] for analysing local climatic timeseries data to assess which quantiles of the local climatic distribution show the greatest and most robust trends. We demonstrate this approach using E-OBS gridded data[2] timeseries of local daily temperature from specific locations across Europe over the last 60 years. Our method extracts the changing cumulative distribution function over time and uses a simple mathematical deconstruction of how the difference between two observations from two different time periods can be assigned to the combination of natural statistical variability and/or the consequences of secular climate change. This deconstruction facilitates an assessment of the sensitivity of different quantiles of the distributions to changing climate. Geographical location and temperature are treated as independent variables, we thus obtain as outputs the pattern of variation in sensitivity with temperature (or occurrence likelihood), and with geographical location. We find as an output many regionally consistent patterns of response of potential value in adaptation planning. We discuss methods to quantify and map the robustness of these observed sensitivities and their statistical likelihood. This also quantifies the level of detail needed from climate models if they are to be used as tools to assess climate change impact. [1] S C Chapman, D A Stainforth, N W Watkins, 2013, On Estimating Local Long Term Climate Trends, Phil. Trans. R. Soc. A, in press [2] Haylock, M.R., N. Hofstra, A.M.G. Klein Tank, E.J. Klok, P.D. Jones and M. New. 2008: A European daily high-resolution gridded dataset of surface temperature and precipitation. J. Geophys. Res (Atmospheres), 113, D20119, doi:10.1029/2008JD10201

7-tert-Butyl-6-(4-chloro-phenyl)-2-thioxo-2,3-dihydro-1H-pyrido[2,3-d]pyrimidin-4-one, a classic polymodal inhibitor of transient receptor potential vanilloid type 1 with a reduced liability for hyperthermia, is analgesic and ameliorates visceral hypersensitivity.

PubMed

Nash, Mark S; McIntyre, Peter; Groarke, Alex; Lilley, Elliot; Culshaw, Andrew; Hallett, Allan; Panesar, Moh; Fox, Alyson; Bevan, Stuart

2012-08-01

The therapeutic potential of transient receptor potential vanilloid type 1 (TRPV1) antagonists for chronic pain has been recognized for more than a decade. However, preclinical and clinical data revealed that acute pharmacological blockade of TRPV1 perturbs thermoregulation, resulting in hyperthermia, which is a major hurdle for the clinical development of these drugs. Here, we describe the properties of 7-tert-butyl-6-(4-chloro-phenyl)-2-thioxo-2,3-dihydro-1H-pyrido[2,3-d]pyrimidin-4-one (BCTP), a TRPV1 antagonist with excellent analgesic properties that does not induce significant hyperthermia in rodents at doses providing maximal analgesia. BCTP is a classic polymodal inhibitor of TRPV1, blocking activation of the human channel by capsaicin and low pH with IC(50) values of 65.4 and 26.4 nM, respectively. Similar activity was observed with rat TRPV1, and the inhibition by BCTP was competitive and reversible. BCTP also blocked heat-induced activation of TRPV1. In rats, the inhibition of capsaicin-induced mechanical hyperalgesia was observed with a D(50) value of 2 mg/kg p.o. BCTP also reversed visceral hypersensitivity and somatic inflammatory pain, and using a model of neuropathic pain in TRPV1 null mice we confirmed that its analgesic properties were solely through the inhibition of TRPV1. We were surprised to find that BCTP administered orally induced only a maximal 0.6°C increase in core body temperature at the highest tested doses (30 and 100 mg/kg), contrasting markedly with N-[4-({6-[4-(trifluoromethyl)phenyl]pyrimidin-4-yl}oxy)-1,3-benzothiazol-2-yl]acetamide (AMG517), a clinically tested TRPV1 antagonist, which induced marked hyperthermia (>1°C) at doses eliciting submaximal reversal of capsaicin-induced hyperalgesia. The combined data indicate that TRPV1 antagonists with a classic polymodal inhibition profile can be identified where the analgesic action is separated from the effects on body temperature.

Expression and Function of Chemokines CXCL9-11 in Micturition Pathways in Cyclophosphamide (CYP)-Induced Cystitis and Somatic Sensitivity in Mice

PubMed Central

Guo, Michael; Chang, Phat; Hauke, Eric; Girard, Beatrice M.; Tooke, Katharine; Ojala, Jacqueline; Malley, Susan M.; Hsiang, Harrison; Vizzard, Margaret A.

2018-01-01

Changes in urinary bladder function and somatic sensation may be mediated, in part, by inflammatory changes in the urinary bladder including the expression of chemokines. Male and female C57BL/6 mice were treated with cyclophosphamide (CYP; 75 mg/kg, 200 mg/kg, i.p.) to induce bladder inflammation (4 h, 48 h, chronic). We characterized the expression of CXC chemokines (CXCL9, CXCL10 and CXCL11) in the urinary bladder and determined the effects of blockade of their common receptor, CXCR3, at the level urinary bladder on bladder function and somatic (hindpaw and pelvic) sensation. qRT-PCR and Enzyme-Linked Immunoassays (ELISAs) were used to determine mRNA and protein expression of CXCL9, CXCL10 and CXCL11 in urothelium and detrusor. In urothelium of female mice treated with CYP, CXCL9 and CXCL10 mRNA significantly (p ≤ 0.01) increased with CYP treatment whereas CXC mRNA expression in the detrusor exhibited both increases and decreases in expression with CYP treatment. CXC mRNA expression urothelium and detrusor of male mice was more variable with both significant (p ≤ 0.01) increases and decreases in expression depending on the specific CXC chemokine and CYP treatment. CXCL9 and CXCL10 protein expression was significantly (p ≤ 0.01) increased in the urinary bladder with 4 h CYP treatment in female mice whereas CXC protein expression in the urinary bladder of male mice did not exhibit an overall change in expression. CXCR3 blockade with intravesical instillation of AMG487 (5 mg/kg) significantly (p ≤ 0.01) increased bladder capacity, reduced voiding frequency and reduced non-voiding contractions in female mice treated with CYP (4 h, 48 h). CXCR3 blockade also reduced (p ≤ 0.01) hindpaw and pelvic sensitivity in female mice treated with CYP (4 h, 48 h). CXC chemokines may be novel targets for treating urinary bladder dysfunction and somatic sensitization resulting from urinary bladder inflammation. PMID:29681802

An observationally centred method to quantify local climate change as a distribution

NASA Astrophysics Data System (ADS)

Stainforth, David; Chapman, Sandra; Watkins, Nicholas

2013-04-01

For planning and adaptation, guidance on trends in local climate is needed at the specific thresholds relevant to particular impact or policy endeavours. This requires quantifying trends at specific quantiles in distributions of variables such as daily temperature or precipitation. These non-normal distributions vary both geographically and in time. The trends in the relevant quantiles may not simply follow the trend in the distribution mean. We present a method[1] for analysing local climatic timeseries data to assess which quantiles of the local climatic distribution show the greatest and most robust trends. We demonstrate this approach using E-OBS gridded data[2] timeseries of local daily temperature from specific locations across Europe over the last 60 years. Our method extracts the changing cumulative distribution function over time and uses a simple mathematical deconstruction of how the difference between two observations from two different time periods can be assigned to the combination of natural statistical variability and/or the consequences of secular climate change. This deconstruction facilitates an assessment of the sensitivity of different quantiles of the distributions to changing climate. Geographical location and temperature are treated as independent variables, we thus obtain as outputs how the trend or sensitivity varies with temperature (or occurrence likelihood), and with geographical location. These sensitivities are found to be geographically varying across Europe; as one would expect given the different influences on local climate between, say, Western Scotland and central Italy. We find as an output many regionally consistent patterns of response of potential value in adaptation planning. We discuss methods to quantify the robustness of these observed sensitivities and their statistical likelihood. This also quantifies the level of detail needed from climate models if they are to be used as tools to assess climate change impact. [1] S C Chapman, D A Stainforth, N W Watkins, 2013, On Estimating Local Long Term Climate Trends, Phil. Trans. R. Soc. A, in press [2] Haylock, M.R., N. Hofstra, A.M.G. Klein Tank, E.J. Klok, P.D. Jones and M. New. 2008: A European daily high-resolution gridded dataset of surface temperature and precipitation. J. Geophys. Res (Atmospheres), 113, D20119, doi:10.1029/2008JD10201

A data centred method to estimate and map how the local distribution of daily precipitation is changing

NASA Astrophysics Data System (ADS)

Chapman, Sandra; Stainforth, David; Watkins, Nick

2014-05-01

Estimates of how our climate is changing are needed locally in order to inform adaptation planning decisions. This requires quantifying the geographical patterns in changes at specific quantiles in distributions of variables such as daily temperature or precipitation. Here we focus on these local changes and on a method to transform daily observations of precipitation into patterns of local climate change. We develop a method[1] for analysing local climatic timeseries to assess which quantiles of the local climatic distribution show the greatest and most robust changes, to specifically address the challenges presented by daily precipitation data. We extract from the data quantities that characterize the changes in time of the likelihood of daily precipitation above a threshold and of the relative amount of precipitation in those days. Our method is a simple mathematical deconstruction of how the difference between two observations from two different time periods can be assigned to the combination of natural statistical variability and/or the consequences of secular climate change. This deconstruction facilitates an assessment of how fast different quantiles of precipitation distributions are changing. This involves both determining which quantiles and geographical locations show the greatest change but also, those at which any change is highly uncertain. We demonstrate this approach using E-OBS gridded data[2] timeseries of local daily precipitation from specific locations across Europe over the last 60 years. We treat geographical location and precipitation as independent variables and thus obtain as outputs the pattern of change at a given threshold of precipitation and with geographical location. This is model- independent, thus providing data of direct value in model calibration and assessment. Our results show regionally consistent patterns of systematic increase in precipitation on the wettest days, and of drying across all days which is of potential value in adaptation planning. [1] S C Chapman, D A Stainforth, N W Watkins, 2013, On Estimating Local Long Term Climate Trends, Phil. Trans. R. Soc. A, 371 20120287; D. A. Stainforth, 2013, S. C. Chapman, N. W. Watkins, Mapping climate change in European temperature distributions, Environ. Res. Lett. 8, 034031 [2] Haylock, M.R., N. Hofstra, A.M.G. Klein Tank, E.J. Klok, P.D. Jones and M. New. 2008: A European daily high-resolution gridded dataset of surface temperature and precipitation. J. Geophys. Res (Atmospheres), 113, D20119

Near-UV and blue wavelength excitable Mg{sub 0.6}Ca{sub 2.16}Mo{sub 0.2}W{sub 0.8}O{sub 6}: Eu{sub 0.12}{sup 3+}/Na{sub 0.12}{sup +} high efficiency red phosphors

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

Khanna, A.; Electrical Computer and Systems Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180; Dutta, P.S., E-mail: duttap@rpi.edu

Red phosphors with narrow emission around 615 nm (with FWHM~5–10 nm) having chemical compositions of A{sub 0.6}Ca{sub 2.16}Mo{sub 0.2}W{sub 0.8}O{sub 6}: Eu{sub 0.12}{sup 3+}/Na{sub 0.12}{sup +} (A=Mg, Sr) have been found to exhibit the highest luminescence amongst the molybdate–tungstate family when excited by sources in the 380–420 nm wavelength range. Thus they are most suitable for enhancing color rendering index and lowering color temperature in phosphor converted white LEDs (pc-WLEDs) with near-UV/blue LED excitation sources. The excitation band edge in the near UV/blue wavelength in the reported phosphor has been attributed to the coordination environment of the transition metal ionmore » (Mo{sup 6+}, W{sup 6+}) and host crystal structure. Furthermore the quantum efficiency of the phosphors has been enhanced by adjusting activator concentration, suitable compositional alloying using substitutional alkaline earth metal cations and charge compensation mechanisms. - Graphical abstract: The charge transfer excitation of orthorhombic Mg{sub 0.6}Ca{sub 2.16}Mo{sub 0.2}W{sub 0.8}O{sub 6}: Eu{sub 0.12}{sup 3+}/Na{sub 0.12}{sup +} is significantly higher than tetragonal CaMoO{sub 4}: Eu{sup 3+} phosphors making Mg{sub 0.6}Ca{sub 2.16}Mo{sub 0.2}W{sub 0.8}O{sub 6}: Eu{sub 0.12}{sup 3+}/Na{sub 0.12}{sup +} prime candidates for fabrication of warm white phosphor-converted LEDs. - Highlights: • LED excitable Mg{sub 0.6}Ca{sub 2.16}Mo{sub 0.2}W{sub 0.8}O{sub 6}: Eu{sub 0.12}{sup 3+}/Na{sub 0.12}{sup +} phosphors were synthesized. • These phosphors are 10 times more intense than CaMoO{sub 4}: Eu{sup 3+} red phosphors. • Their intensity and efficiency were enhanced by materials optimization techniques. • Such techniques include compositional alloying, charge compensation, etc.« less

From daily to sub-daily time steps - Creating a high temporal and spatial resolution climate reference data set for hydrological modeling and bias-correction of RCM data

NASA Astrophysics Data System (ADS)

Willkofer, Florian; Wood, Raul R.; Schmid, Josef; von Trentini, Fabian; Ludwig, Ralf

2016-04-01

The ClimEx project (Climate change and hydrological extreme events - risks and perspectives for water management in Bavaria and Québec) focuses on the effects of climate change on hydro-meteorological extreme events and their implications for water management in Bavaria and Québec. It builds on the conjoint analysis of a large ensemble of the CRCM5, driven by 50 members of the CanESM2, and the latest information provided through the CORDEX-initiative, to better assess the influence of natural climate variability and climatic change on the dynamics of extreme events. A critical point in the entire project is the preparation of a meteorological reference dataset with the required temporal (1-6h) and spatial (500m) resolution to be able to better evaluate hydrological extreme events in mesoscale river basins. For Bavaria a first reference data set (daily, 1km) used for bias-correction of RCM data was created by combining raster based data (E-OBS [1], HYRAS [2], MARS [3]) and interpolated station data using the meteorological interpolation schemes of the hydrological model WaSiM [4]. Apart from the coarse temporal and spatial resolution, this mosaic of different data sources is considered rather inconsistent and hence, not applicable for modeling of hydrological extreme events. Thus, the objective is to create a dataset with hourly data of temperature, precipitation, radiation, relative humidity and wind speed, which is then used for bias-correction of the RCM data being used as driver for hydrological modeling in the river basins. Therefore, daily data is disaggregated to hourly time steps using the 'Method of fragments' approach [5], based on available training stations. The disaggregation chooses fragments of daily values from observed hourly datasets, based on similarities in magnitude and behavior of previous and subsequent events. The choice of a certain reference station (hourly data, provision of fragments) for disaggregating daily station data (application of fragments) is crucial and several methods will be tested to achieve a profound spatial interpolation. This entire methodology shall be applicable for existing or newly developed datasets. References [1] Haylock, M.R., N. Hofstra, A.M.G. Klein Tank, E.J. Klok, P.D. Jones and M. New. A European daily high-resolution gridded dataset of surface temperature and precipitation. J. Geophys. Res (Atmospheres) (2008), 113, D20119, doi:10.1029/2008JD10201. [2] Rauthe, M., Steiner, H., Riediger, U., Mazurkiewicz, A. and A. Gratzki. A Central European precipitation climatology - Part I: Generation and validation of a high-resolution gridded daily data set (HYRAS). Meteorologische Zeitschrift (2013), 22/3, p.238-256. [3] MARS-AGRI4CAST. AGRI4CAST Interpolated Meteorological Data. http://mars.jrc.ec.europa.eu/mars/ About-us/AGRI4CAST/Data-distribution/AGRI4CAST-Interpolated-Meteorological-Data. 2007, last accessed May 10th, 2013. [4] Schulla, J. Model Description WaSiM - Water balance Simulation Model. 2015, available at: http://wasim.ch/en/products/wasim_description.htm. [5] Sharma, A. and S. Srikanthan. Continuous Rainfall Simulation: A Nonparametric Alternative. 30th Hydrology and Water Resources Symposium, Launceston, Tasmania, 4-7 December, 2006.

Sharing hydrological knowledge: an international comparison of hydrological models in the Meuse River Basin

NASA Astrophysics Data System (ADS)

Bouaziz, Laurène; Sperna Weiland, Frederiek; Drogue, Gilles; Brauer, Claudia; Weerts, Albrecht

2015-04-01

International collaboration between institutes and universities working and studying the same transboundary basin is needed for consensus building around possible effects of climate change and climate adaptation measures. Education, experience and expert knowledge of the hydrological community have resulted in the development of a great variety of model concepts, calibration and analysis techniques. Intercomparison could be a first step into consensus modeling or an ensemble based modeling strategy. Besides these practical objectives, such an intercomparison offers the opportunity to explore different ranges of models and learn from each other, hopefully increasing the insight into the hydrological processes that play a role in the transboundary basin. In this experiment, different international research groups applied their rainfall-runoff model in the Ourthe, a Belgium sub-catchment of the Meuse. Data preparation involved the interpolation of hourly precipitation station data collected and owned by the Service Public de Wallonie1 and the freely available E-OBS dataset for daily temperature (Haylock et al., 2008). Daily temperature was disaggregated to hourly values and potential evaporation was derived with the Hargreaves formula. The data was made available to the researchers through an FTP server. The protocol for the modeling involved a split-sample calibration and validation for pre-defined periods. Objective functions for calibration were fixed but the calibration algorithm was a free choice of the research groups. The selection of calibration algorithm was considered model dependent because lumped as well as computationally less efficient distributed models were used. For each model, an ensemble of best performing parameter sets was selected and several performance metrics enabled to assess the models' abilities to simulate discharge. The aim of this experiment is to identify those model components and structures that increase model performance and may best represent the catchment's hydrological behavior. Further steps in the collaboration may include (1) repeating the experiment for other sub-catchments of the Meuse River Basin where different hydrological processes may be relevant and where other models may perform better; and (2) the comparison of hydrological model results obtained by forcing the model with daily local measured precipitation and lower resolution gridded precipitation from the E-OBS (Haylock et at., 2008) dataset to estimate the value of high-resolution data versus lower resolution gridded products. 1 Service Publique de Wallonie, Direction générale opérationnelle de la Mobilité et des Voies hydrauliques, Département des Etudes et de l'Appui à la Gestion, Direction de la Gestion hydrologique intégrée, Boulevard du Nord 8 - 5000 Namur "Haylock, M.R., N. Hofstra, A.M.G. Klein Tank, E.J. Klok, P.D. Jones and M. New. 2008: A European daily high-resolution gridded dataset of surface temperature and precipitation. J. Geophys. Res (Atmospheres), 113, D20119, doi:10.1029/2008JD10201"

Gridded precipitation fields at high temporal and spatial resolution for operational flood forecasting in the Rhine basin

NASA Astrophysics Data System (ADS)

van Osnabrugge, Bart; Weerts, Albrecht; Uijlenhoet, Remko

2017-04-01

Gridded areal precipitation, as one of the most important hydrometeorological input variables for initial state estimation in operational hydrological forecasting, is available in the form of raster data sets (e.g. HYRAS and EOBS) for the River Rhine basin. These datasets are compiled off-line on a daily time step using station data with the highest possible spatial density. However, such a product is not available operationally and at an hourly discretisation. Therefore, we constructed an hourly gridded precipitation dataset at 1.44 km2 resolution for the Rhine basin for the period from 1998 to present using a REGNIE-like interpolation procedure (Weerts et al., 2008) using a low and a high density rain gauge network. The datasets were validated against daily HYRAS (Rauthe, 2013) and EOBS (Haylock, 2008) data. The main goal of the operational procedure is to emulate the HYRAS dataset as good as possible, as the daily HYRAS dataset is used in the off-line calibration of the hydrological model. Our main findings are that even with low station density, the spatial patterns found in the HYRAS data set are well reproduced. With low station density (years 1999-2006) our dataset underestimates precipitation compared to HYRAS and EOBS, notably during the winter. However, interpolation based on the same set of stations overestimates precipitation compared to EOBS for the years 2006-2014. This discrepancy disappears when switching to the high station density. We also analyze the robustness of the hourly precipitation fields by comparing with stations not used during interpolation. Specific issues regarding the data when creating the gridded precipitation fields will be highlighted. Finally, the datasets are used to drive an hourly and daily gridded WFLOW_HBV model of the Rhine at the same spatial resolution. Haylock, M.R., N. Hofstra, A.M.G. Klein Tank, E.J. Klok, P.D. Jones and M. New. 2008: A European daily high-resolution gridded dataset of surface temperature and precipitation. J. Geophys. Res (Atmospheres), 113, D20119, doi:10.1029/2008JD10201 Rauthe, M., Steiner, H., Riediger, U., Mazurkiewicz, A., Gratzki, A. 2013: A Central European precipitation climatology - Part 1: Generation and validation of a high-resolution gridded daily data set (HYRAS). Meteorologische Zeitschrift, 22(3), 235 256 Weerts, A.H., D. Meißner, and S. Rademacher, 2008. Input data rainfall-runoff model operational system FEWS-NL & FEWS-DE. Technical report, Deltares.

Rates of mineral dissolution and carbonation in peridotite and basalt

NASA Astrophysics Data System (ADS)

Kelemen, P. B.; Matter, J. M.

2009-12-01

We study natural rates and processes of mineral carbonation in peridotite (olivine-rich rock) in mantle rocks exposed to weathering in northern Oman to learn effective mechanisms from natural processes, and seek ways to accelerate them to achieve significant CO2 capture and storage via mineral carbonation at the lowest possible cost. In our first paper (1), we fit data on mantle olivine carbonation from the DOE Albany Research Center (2,3, ARC). These data, and data from Arizona State University (4, ASU) suggest that a peridotite rock volume heated to 185°C and infused with H2O+CO2 at PCO2 > 75 bars could consume ~ 1 ton CO2 per cubic meter of rock per year. Because it is more abundant than peridotite, other workers focus on carbonation of the most common type of lava on Earth, basalt, whose main mineral constituent is generally labradorite, part of the plagioclase feldspar solid solution series. Our intuition is that labradorite carbonation is much slower than mantle olivine carbonation. To quantify this, we compiled data on dissolution of mantle olivine, labradorite, crystalline basalt, and basaltic glass in aqueous fluids, as well as data on mantle olivine carbonation. The dissolution data are calibrated as a function of surface area (i.e., grain size and shape) and pH, as well as temperature, whereas most of the ARC and ASU experiments were done at a single pH and grain size. Thus, for comparison, we calculated dissolution rates for 70 micron spheres at pH 8, close to the ARC and ASU experimental conditions. At these conditions, olivine carbonation observed by ARC and ASU is 100 to 1000 times faster than labradorite and crystalline basalt, and faster than conventionally measured olivine dissolution rates. The ARC and ASU experiments were different from conventional dissolution experiments in several ways that could lead to an enhancement in olivine reaction rates: (a) they may have lower a(Mg) in fluid due to solid MgCO3 (magnesite) precipitation, (b) they used a relatively high ratio of olivine:fluid (1:4), (c) they generally used high fluid NaCl contents, and (d) they consistently used high NaHCO3 and/or KHCO3 (alkali-bicarbonate) concentrations. In agreement with the ASU group, we consider that alkali-bicarbonate is the crucial catalyst, provided PCO2 is high.This raises the question of whether alkali-carbonate could also catalyze labradorite and basalt carbonation. ARC and ASU data extrapolated to low T and low PCO2 agree with natural carbonation rates in Oman. Our geological observations suggest that higher temperature peridotite carbonation went to completion (all Mg as MgCO3, all Si as quartz), perhaps because reaction-driven cracking maintained reactive surface area and permeability despite formation of reaction products in pore space and armoring of remaining olivine reactants. We are not aware of comparable observations on present-day carbonation of basalt. (1) Kelemen & Matter, PNAS 2008 (2) O’Connor et al., DOE Final Report ARC-TR-04-002, 2004 (3) Gerdemann et al., Environ. Sci. Technol. 2007 (4) Chizmeshya et al., DOE Final Report 924162, 2007

User-relevant, threshold-specific observations of climate change

NASA Astrophysics Data System (ADS)

Stainforth, Dave; Chapman, Sandra; Watkins, Nicholas

2014-05-01

Users of climate information look for details of changing climate at local scales (to inform specific activities) and on the geographical patterns of such changes (to prioritise adaptation investments). They often have user-specific thresholds of vulnerability so the changes of interest must refer to such thresholds or to the related quantile of the climatic distribution. A method for providing such information from timeseries of temperature data has recently been published [1] along with maps of changes at thresholds and quantiles [2] derived from the European Observational dataset E-Obs [3]. In this presentation we will do two things. First we will discuss the opportunities to tailor such methods to provide user-specific information through climate services, using illustrations from the existing methodology applied to daily maximum and minimum temperatures [1,2]. Second we will present new results on threshold specific observed changes in precipitation. The methodology for precipitation is related to that which has been applied to temperature but has been developed to handle the characteristics of precipitation distributions. The results identify some regions with systematic increases in precipitation on the seasonally wettest days and others which show drying across all days, on a seasonal basis. We will present the geographic locations and precipitation thresholds where strong signals of changes are seen across Europe. The coherency of such results and the methodology used to process the observational data will be discussed. We will also highlight the justifications for having confidence in the results in some regions and at some thresholds while having a lack of confidence in others. Such information should be an important element of any climate services. It is worth noting that here "wettest days" refers to events which are uncommon within a season (e.g. one in ~20 wet days). This is in contrast and complementary to, for instance, the one in a hundred year extreme event. Users can be vulnerable to one or the other or both of these event types and climate services are required which are sufficiently flexible to provide tailored information in either situation. It is common to focus on the latter while the former is relatively understudied. [1] Chapman, S C, Stainforth, D A, Watkins, N W. 2013 On Estimating Local Long Term Climate Trends, Phil. Trans. R. Soc. A, 371 20120287; [2] Stainforth, D A, Chapman, S. C. & Watkins, N. W. 2013. Mapping climate change in European temperature distributions Environ. Res. Lett. 8 034031 [3] Haylock, M.R., N. Hofstra, A.M.G. Klein Tank, E.J. Klok, P.D. Jones and M. New. 2008: A European daily high-resolution gridded dataset of surface temperature and precipitation. J. Geophys. Res (Atmospheres), 113, D20119

Large Scale, High Resolution, Mantle Dynamics Modeling

NASA Astrophysics Data System (ADS)

Geenen, T.; Berg, A. V.; Spakman, W.

2007-12-01

To model the geodynamic evolution of plate convergence, subduction and collision and to allow for a connection to various types of observational data, geophysical, geodetical and geological, we developed a 4D (space-time) numerical mantle convection code. The model is based on a spherical 3D Eulerian fem model, with quadratic elements, on top of which we constructed a 3D Lagrangian particle in cell(PIC) method. We use the PIC method to transport material properties and to incorporate a viscoelastic rheology. Since capturing small scale processes associated with localization phenomena require a high resolution, we spend a considerable effort on implementing solvers suitable to solve for models with over 100 million degrees of freedom. We implemented Additive Schwartz type ILU based methods in combination with a Krylov solver, GMRES. However we found that for problems with over 500 thousend degrees of freedom the convergence of the solver degraded severely. This observation is known from the literature [Saad, 2003] and results from the local character of the ILU preconditioner resulting in a poor approximation of the inverse of A for large A. The size of A for which ILU is no longer usable depends on the condition of A and on the amount of fill in allowed for the ILU preconditioner. We found that for our problems with over 5×105 degrees of freedom convergence became to slow to solve the system within an acceptable amount of walltime, one minute, even when allowing for considerable amount of fill in. We also implemented MUMPS and found good scaling results for problems up to 107 degrees of freedom for up to 32 CPU¡¯s. For problems with over 100 million degrees of freedom we implemented Algebraic Multigrid type methods (AMG) from the ML library [Sala, 2006]. Since multigrid methods are most effective for single parameter problems, we rebuild our model to use the SIMPLE method in the Stokes solver [Patankar, 1980]. We present scaling results from these solvers for 3D spherical models. We also applied the above mentioned method to a high resolution (~ 1 km) 2D mantle convection model with temperature, pressure and phase dependent rheology including several phase transitions. We focus on a model of a subducting lithospheric slab which is subject to strong folding at the bottom of the mantle's D" region which includes the postperovskite phase boundary. For a detailed description of this model we refer to poster [Mantel convection models of the D" region, U17] [Saad, 2003] Saad, Y. (2003). Iterative methods for sparse linear systems. [Sala, 2006] Sala. M (2006) An Object-Oriented Framework for the Development of Scalable Parallel Multilevel Preconditioners. ACM Transactions on Mathematical Software, 32 (3), 2006 [Patankar, 1980] Patankar, S. V.(1980) Numerical Heat Transfer and Fluid Flow, Hemisphere, Washington.

Gateways to clinical trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2005-06-01

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abiraterone acetate, acyline, adalimumab, adenosine triphosphate, AEE-788, AIDSVAX gp120 B/B, AK-602, alefacept, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, alprazolam, amdoxovir, AMG-162, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, aminophylline hydrate, anakinra, anecortave acetate, anti-CTLA-4 MAb, APC-8015, aripiprazole, aspirin, atazanavir sulfate, atomoxetine hydrochloride, atorvastatin calcium, atrasentan, AVE-5883, AZD-2171; Betamethasone dipropionate, bevacizumab, bimatoprost, biphasic human insulin (prb), bortezomib, BR-A-657, BRL-55730, budesonide, busulfan; Calcipotriol, calcipotriol/betamethasone dipropionate, calcium folinate, capecitabine, capravirine, carmustine, caspofungin acetate, cefdinir, certolizumab pegol, CG-53135, chlorambucil, ciclesonide, ciclosporin, cisplatin, clofarabine, clopidogrel hydrogensulfate, clozapine, co-trimoxazole, CP-122721, creatine, CY-2301, cyclophosphamide, cypher, cytarabine, cytolin; D0401, darbepoetin alfa, darifenacin hydrobromide, DASB, desipramine hydrochloride, desloratadine, desvenlafaxine succinate, dexamethasone, didanosine, diquafosol tetrasodium, docetaxel, doxorubicin hydrochloride, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecallantide, efalizumab, efavirenz, eletriptan, emtricitabine, enfuvirtide, enoxaparin sodium, estramustine phosphate sodium, etanercept, ethinylestradiol, etonogestrel, etonogestrel/ethinylestradiol, etoposide, exenatide; Famciclovir, fampridine, febuxostat, filgrastim, fludarabine phosphate, fluocinolone acetonide, fluorouracil, fluticasone propionate, fluvastatin sodium, fondaparinux sodium; Gaboxadol, gamma-hydroxybutyrate sodium, gefitinib, gelclair, gemcitabine, gemfibrozil, glibenclamide, glyminox; Haloperidol, heparin sodium, HPV 16/HPV 18 vaccine, human insulin, human insulin; Icatibant, imatinib mesylate, indium 111 (111In) ibritumomab tiuxetan, infliximab, INKP-100, iodine (I131) tositumomab, IoGen, ipratropium bromide, ixabepilone; L-870810, lamivudine, lapatinib, laquinimod, latanoprost, levonorgestrel, licochalcone a, liposomal doxorubicin, lopinavir, lopinavir/ritonavir, lorazepam, lovastatin; Maraviroc, maribavir, matuzumab, MDL-100907, melphalan, methotrexate, methylprednisolone, mitomycin, mitoxantrone hydrochloride, MK-0431, MN-001, MRKAd5 HIV-1 gag/pol/nef, MRKAd5gag, MVA.HIVA, MVA-BN Nef, MVA-Muc1-IL-2, mycophenolate mofetil; Nelfinavir mesilate, nesiritide, NSC-330507; Olanzapine, olmesartan medoxomil, omalizumab, oral insulin, osanetant; PA-457, paclitaxel, paroxetine, paroxetine hydrochloride, PCK-3145, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, perillyl alcohol, pexelizumab, pimecrolimus, pitavastatin calcium, porfiromycin, prasterone, prasugrel, pravastatin sodium, prednisone, pregabalin, prinomastat, PRO-2000, propofol, prostate cancer vaccine; Rasagiline mesilate, rhBMP-2/ACS, rhBMP-2/BCP, rhC1, ribavirin, rilpivirine, ritonavir, rituximab, Ro-26-9228, rosuvastatin calcium, rosuvastatin sodium, rubitecan; Selodenoson, simvastatin, sirolimus, sitaxsentan sodium, sorafenib, SS(dsFv)-PE38, St. John's Wort extract, stavudine; Tacrolimus, tadalafil, tafenoquine succinate, talaglumetad, tanomastat, taxus, tegaserod maleate, telithromycin, tempol, tenofovir, tenofovir disoproxil fumarate, testosterone enanthate, TH-9507, thalidomide, tigecycline, timolol maleate, tiotropium bromide, tipifarnib, torcetrapib, trabectedin, travoprost, travoprost/timolol, treprostinil sodium; Valdecoxib, vardenafil hydrochloride hydrate, varenicline, VEGF-2 gene therapy, venlafaxine hydrochloride, vildagliptin, vincristine sulfate, voriconazole, VRX-496, VX-385; Warfarin sodium; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, zidovudine. Copyright (c) 2005 Prous Science. All rights reserved.

Evaluating Evaluation Systems: Policy Levers and Strategies for Studying Implementation of Educator Evaluation. Policy Snapshot

ERIC Educational Resources Information Center

Matlach, Lauren

2015-01-01

Evaluation studies can provide feedback on implementation, support continuous improvement, and increase understanding of evaluation systems' impact on teaching and learning. Despite the importance of educator evaluation studies, states often need support to prioritize and fund them. Successful studies require expertise, time, and a shared…

Educational Evaluation: The State of the Field.

ERIC Educational Resources Information Center

Wolf, Richard M., Ed.

1987-01-01

Educational evaluation is discussed. Topics include: an evaluation framework, educational objectives and study design from a 20-year perspective, a sample study, educational evaluation for local school improvement, decision-oriented evaluation studies, reporting study results, and professional standards for assuring the quality of educational…

42 CFR 456.243 - Content of medical care evaluation studies.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 4 2011-10-01 2011-10-01 false Content of medical care evaluation studies. 456.243... Ur Plan: Medical Care Evaluation Studies § 456.243 Content of medical care evaluation studies. Each medical care evaluation study must— (a) Identify and analyze medical or administrative factors related to...

42 CFR 456.143 - Content of medical care evaluation studies.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 4 2011-10-01 2011-10-01 false Content of medical care evaluation studies. 456.143...: Medical Care Evaluation Studies § 456.143 Content of medical care evaluation studies. Each medical care evaluation study must— (a) Identify and analyze medical or administrative factors related to the hospital's...

Do economic evaluation studies inform effective healthcare resource allocation in Iran? A critical review of the literature.

PubMed

Haghparast-Bidgoli, Hassan; Kiadaliri, Aliasghar Ahmad; Skordis-Worrall, Jolene

2014-01-01

To aid informed health sector decision-making, data from sufficient high quality economic evaluations must be available to policy makers. To date, no known study has analysed the quantity and quality of available Iranian economic evaluation studies. This study aimed to assess the quantity, quality and targeting of economic evaluation studies conducted in the Iranian context. The study systematically reviewed full economic evaluation studies (n = 30) published between 1999 and 2012 in international and local journals. The findings of the review indicate that although the literature on economic evaluation in Iran is growing, these evaluations were of poor quality and suffer from several major methodological flaws. Furthermore, the review reveals that economic evaluation studies have not addressed the major health problems in Iran. While the availability of evidence is no guarantee that it will be used to aid decision-making, the absence of evidence will certainly preclude its use. Considering the deficiencies in the data identified by this review, current economic evaluations cannot be a useful source of information for decision makers in Iran. To improve the quality and overall usefulness of economic evaluations we would recommend; 1) developing clear national guidelines for the conduct of economic evaluations, 2) highlighting priority areas where information from such studies would be most useful and 3) training researchers and policy makers in the calculation and use of economic evaluation data.

Do economic evaluation studies inform effective healthcare resource allocation in Iran? A critical review of the literature

PubMed Central

2014-01-01

To aid informed health sector decision-making, data from sufficient high quality economic evaluations must be available to policy makers. To date, no known study has analysed the quantity and quality of available Iranian economic evaluation studies. This study aimed to assess the quantity, quality and targeting of economic evaluation studies conducted in the Iranian context. The study systematically reviewed full economic evaluation studies (n = 30) published between 1999 and 2012 in international and local journals. The findings of the review indicate that although the literature on economic evaluation in Iran is growing, these evaluations were of poor quality and suffer from several major methodological flaws. Furthermore, the review reveals that economic evaluation studies have not addressed the major health problems in Iran. While the availability of evidence is no guarantee that it will be used to aid decision-making, the absence of evidence will certainly preclude its use. Considering the deficiencies in the data identified by this review, current economic evaluations cannot be a useful source of information for decision makers in Iran. To improve the quality and overall usefulness of economic evaluations we would recommend; 1) developing clear national guidelines for the conduct of economic evaluations, 2) highlighting priority areas where information from such studies would be most useful and 3) training researchers and policy makers in the calculation and use of economic evaluation data. PMID:25050084

Attitudes toward evaluation: An exploratory study of students' and stakeholders' social representations.

PubMed

Schultes, Marie-Therese; Kollmayer, Marlene; Mejeh, Mathias; Spiel, Christiane

2018-06-15

Positive attitudes toward evaluation among stakeholders are an important precondition for successful evaluation processes. However, empirical studies focusing on stakeholders' attitudes toward evaluation are scarce. The present paper explores the approach of assessing social representations as indicators of people's attitudes toward evaluation. In an exploratory study, two groups were surveyed: University students (n = 60) with rather theoretical knowledge of evaluation and stakeholders (n = 61) who had shortly before taken part in participatory evaluation studies. Both groups were asked to name their free associations with the term "evaluation", which were subsequently analyzed lexicographically. The results indicate different social representations of evaluation in the two groups. The student group primarily saw evaluation as an "appraisal", whereas the stakeholders emphasized the "improvement" resulting from evaluation. Implications for further evaluation research and practice are discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Integrating Human Factors into Crew Exploration Vehicle (CEV) Design

NASA Technical Reports Server (NTRS)

Whitmore, Mihriban; Holden, Kritina; Baggerman, Susan; Campbell, Paul

2007-01-01

The purpose of this design process is to apply Human Engineering (HE) requirements and guidelines to hardware/software and to provide HE design, analysis and evaluation of crew interfaces. The topics include: 1) Background/Purpose; 2) HE Activities; 3) CASE STUDY: Net Habitable Volume (NHV) Study; 4) CASE STUDY: Human Modeling Approach; 5) CASE STUDY: Human Modeling Results; 6) CASE STUDY: Human Modeling Conclusions; 7) CASE STUDY: Human-in-the-Loop Evaluation Approach; 8) CASE STUDY: Unsuited Evaluation Results; 9) CASE STUDY: Suited Evaluation Results; 10) CASE STUDY: Human-in-the-Loop Evaluation Conclusions; 11) Near-Term Plan; and 12) In Conclusion

Standardizing the evaluation criteria on treatment outcomes of mandibular implant overdentures: a systematic review

PubMed Central

Kim, Ha-Young; Shin, Sang-Wan

2014-01-01

PURPOSE The aim of this review was to analyze the evaluation criteria on mandibular implant overdentures through a systematic review and suggest standardized evaluation criteria. MATERIALS AND METHODS A systematic literature search was conducted by PubMed search strategy and hand-searching of relevant journals from included studies considering inclusion and exclusion criteria. Randomized clinical trials (RCT) and clinical trial studies comparing attachment systems on mandibular implant overdentures until December, 2011 were selected. Twenty nine studies were finally selected and the data about evaluation methods were collected. RESULTS Evaluation criteria could be classified into 4 groups (implant survival, peri-implant tissue evaluation, prosthetic evaluation, and patient satisfaction). Among 29 studies, 21 studies presented implant survival rate, while any studies reporting implant failure did not present cumulative implant survival rate. Seventeen studies evaluating peri-implant tissue status presented following items as evaluation criteria; marginal bone level (14), plaque Index (13), probing depth (8), bleeding index (8), attachment gingiva level (8), gingival index (6), amount of keratinized gingiva (1). Eighteen studies evaluating prosthetic maintenance and complication also presented following items as evaluation criteria; loose matrix (17), female detachment (15), denture fracture (15), denture relining (14), abutment fracture (14), abutment screw loosening (11), and occlusal adjustment (9). Atypical questionnaire (9), Visual analog scales (VAS) (4), and Oral Health Impact Profile (OHIP) (1) were used as the format of criteria to evaluate patients satisfaction in 14 studies. CONCLUSION For evaluation of implant overdenture, it is necessary to include cumulative survival rate for implant evaluation. It is suggested that peri-implant tissue evaluation criteria include marginal bone level, plaque index, bleeding index, probing depth, and attached gingiva level. It is also suggested that prosthetic evaluation criteria include loose matrix, female detachment, denture fracture, denture relining, abutment fracture, abutment screw loosening, and occlusal adjustment. Finally standardized criteria like OHIP-EDENT or VAS are required for patient satisfaction. PMID:25352954

Rapid estimate of earthquake source duration: application to tsunami warning.

NASA Astrophysics Data System (ADS)

Reymond, Dominique; Jamelot, Anthony; Hyvernaud, Olivier

2016-04-01

We present a method for estimating the source duration of the fault rupture, based on the high-frequency envelop of teleseismic P-Waves, inspired from the original work of (Ni et al., 2005). The main interest of the knowledge of this seismic parameter is to detect abnormal low velocity ruptures that are the characteristic of the so called 'tsunami-earthquake' (Kanamori, 1972). The validation of the results of source duration estimated by this method are compared with two other independent methods : the estimated duration obtained by the Wphase inversion (Kanamori and Rivera, 2008, Duputel et al., 2012) and the duration calculated by the SCARDEC process that determines the source time function (M. Vallée et al., 2011). The estimated source duration is also confronted to the slowness discriminant defined by Newman and Okal, 1998), that is calculated routinely for all earthquakes detected by our tsunami warning process (named PDFM2, Preliminary Determination of Focal Mechanism, (Clément and Reymond, 2014)). Concerning the point of view of operational tsunami warning, the numerical simulations of tsunami are deeply dependent on the source estimation: better is the source estimation, better will be the tsunami forecast. The source duration is not directly injected in the numerical simulations of tsunami, because the cinematic of the source is presently totally ignored (Jamelot and Reymond, 2015). But in the case of a tsunami-earthquake that occurs in the shallower part of the subduction zone, we have to consider a source in a medium of low rigidity modulus; consequently, for a given seismic moment, the source dimensions will be decreased while the slip distribution increased, like a 'compact' source (Okal, Hébert, 2007). Inversely, a rapid 'snappy' earthquake that has a poor tsunami excitation power, will be characterized by higher rigidity modulus, and will produce weaker displacement and lesser source dimensions than 'normal' earthquake. References: CLément, J. and Reymond, D. (2014). New Tsunami Forecast Tools for the French Polynesia Tsunami Warning System. Pure Appl. Geophys, 171. DUPUTEL, Z., RIVERA, L., KANAMORI, H. and HAYES, G. (2012). Wphase source inversion for moderate to large earthquakes. Geophys. J. Intl.189, 1125-1147. Kanamori, H. (1972). Mechanism of tsunami earthquakes. Phys. Earth Planet. Inter. 6, 246-259. Kanamori, H. and Rivera, L. (2008). Source inversion of W phase : speeding up seismic tsunami warning. Geophys. J. Intl. 175, 222-238. Newman, A. and Okal, E. (1998). Teleseismic estimates of radiated seismic energy : The E=M0 discriminant for tsunami earthquakes. J. Geophys. Res. 103, 26885-26898. Ni, S., H. Kanamori, and D. Helmberger (2005), Energy radiation from the Sumatra earthquake, Nature, 434, 582. Okal, E.A., and H. Hébert (2007), Far-field modeling of the 1946 Aleutian tsunami, Geophys. J. Intl., 169, 1229-1238. Vallée, M., J. Charléty, A.M.G. Ferreira, B. Delouis, and J. Vergoz, SCARDEC : a new technique for the rapid determination of seismic moment magnitude, focal mechanism and source time functions for large earthquakes using body wave deconvolution, Geophys. J. Int., 184, 338-358, 2011.

Evaluation of the National Assessment of Educational Progress. Study Reports

ERIC Educational Resources Information Center

Buckendahl, Chad W.; Davis, Susan L.; Plake, Barbara S.; Sireci, Stephen G.; Hambleton, Ronald K.; Zenisky, April L.; Wells, Craig S.

2009-01-01

The "Evaluation of the National Assessment of Educational Progress: Study Reports" describes the special studies that comprised the design of the evaluation. In the Final Report, the authors presented a practical discussion of the evaluation studies to its primary, intended audience, namely policymakers. On this accompanying CD, readers…

A methodology for evaluating the usability of audiovisual consumer electronic products.

PubMed

Kwahk, Jiyoung; Han, Sung H

2002-09-01

Usability evaluation is now considered an essential procedure in consumer product development. Many studies have been conducted to develop various techniques and methods of usability evaluation hoping to help the evaluators choose appropriate methods. However, planning and conducting usability evaluation requires considerations of a number of factors surrounding the evaluation process including the product, user, activity, and environmental characteristics. In this perspective, this study suggested a new methodology of usability evaluation through a simple, structured framework. The framework was outlined by three major components: the interface features of a product as design variables, the evaluation context consisting of user, product, activity, and environment as context variables, and the usability measures as dependent variables. Based on this framework, this study established methods to specify the product interface features, to define evaluation context, and to measure usability. The effectiveness of this methodology was demonstrated through case studies in which the usability of audiovisual products was evaluated by using the methods developed in this study. This study is expected to help the usability practitioners in consumer electronics industry in various ways. Most directly, it supports the evaluators' plan and conduct usability evaluation sessions in a systematic and structured manner. In addition, it can be applied to other categories of consumer products (such as appliances, automobiles, communication devices, etc.) with minor modifications as necessary.

School Evaluation and Accreditation: A Bibliography of Research Studies.

ERIC Educational Resources Information Center

Diamond, Joan

1982-01-01

This 97-item bibliography cites research in the following categories: purposes and structures of school accreditation/evaluation; the school evaluation process, involving self-study, team visits, and implementation; evaluation of the accreditation/evaluation process; external factors influencing school accreditation/evaluation; and objectivity in…

A Scoping Review of Peer-led Education in Patient Safety Training

PubMed Central

McLachlan, Andrew J.; Chen, Timothy F.

2018-01-01

Objective. To examine the literature pertaining to the use of peer-led education in patient safety. Findings. Four studies met the inclusion criteria: two were conducted in health care students and two in medical practitioners. Three studies used pre-post evaluation, with one containing a comparator group. One study a post-intervention evaluation only. All studies undertook Kirkpatrick Level 2 evaluations, showing significant improvements in attitudes and knowledge. One study undertook Level 3 and 4 evaluations, showing improvement in self-reported behaviors and engagement in quality improvement initiatives. Summary. There are few studies evaluating peer-led education in patient safety and formal and high-quality evaluations are lacking. PMID:29606704

Researching evaluation influence: a review of the literature.

PubMed

Herbert, James Leslie

2014-10-01

The impact of an evaluation is an important consideration in designing and carrying out evaluations. Evaluation influence is a way of thinking about the effect that an evaluation can have in the broadest possible terms, which its proponents argue will lead to a systematic body of evidence about influential evaluation practices. This literature review sets out to address three research questions: How have researchers defined evaluation influence; how is this reflected in the research; and what does the research suggest about the utility of evaluation influence as a conceptual framework. Drawing on studies that had cited one of the key evaluation influence articles and conducted original research on some aspect of influence this article reviewed the current state of the literature toward the goal of developing a body of evidence about how to practice influential evaluation. Twenty-eight studies were found that have drawn on evaluation influence, which were categorized into (a) descriptive studies, (b) analytical studies, and (c) hypothesis testing. Despite the prominence of evaluation influence in the literature, there is slow progress toward a persuasive body of literature. Many of the studies reviewed offered vague and inconsistent definitions and have applied influence in an unspecified way in the research. It is hoped that this article will stimulate interest in the systematic study of influence mechanisms, leading to improvements in the potential for evaluation to affect positive social change. © The Author(s) 2014.

Reported Influence of Evaluation Data on Decision Makers' Actions: An Empirical Examination

ERIC Educational Resources Information Center

Christie, Christina A.

2007-01-01

Using a set of scenarios derived from actual evaluation studies, this simulation study examines the reported influence of evaluation information on decision makers' potential actions. Each scenario described a context where one of three types of evaluation information (large-scale study data, case study data, or anecdotal accounts) is presented…

42 CFR 456.143 - Content of medical care evaluation studies.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Content of medical care evaluation studies. 456.143...: Medical Care Evaluation Studies § 456.143 Content of medical care evaluation studies. Each medical care... patient care; (b) Include analysis of at least the following: (1) Admissions; (2) Durations of stay; (3...

Evaluation methods used on health information systems (HISs) in Iran and the effects of HISs on Iranian healthcare: a systematic review.

PubMed

Ahmadian, Leila; Nejad, Simin Salehi; Khajouei, Reza

2015-06-01

The most important goal of a health information system (HIS) is improvement of quality, effectiveness and efficiency of health services. To achieve this goal, health care systems should be evaluated continuously. The aim of this paper was to study the impacts of HISs in Iran and the methods used for their evaluation. We systematically searched all English and Persian papers evaluating health information systems in Iran that were indexed in SID, Magiran, Iran medex, PubMed and Embase databases until June 2013. A data collection form was designed to extract required data such as types of systems evaluated, evaluation methods and tools. In this study, 53 out of 1103 retrieved articles were selected as relevant and reviewed by the authors. This study indicated that 28 studies used questionnaires to evaluate the system and in 27 studies the study instruments were distributed within a research population. In 26 papers the researchers collected the information by means of interviews, observations, heuristic evaluation and the review of documents and records. The main effects of the evaluated systems in health care settings were improving quality of services, reducing time, increasing accessibility to information, reducing costs and decreasing medical errors. Evaluation of health information systems is central to their development and enhancement, and to understanding their effect on health and health services. Despite numerous evaluation methods available, the reviewed studies used a limited number of methods to evaluate HIS. Additionally, the studies mainly discussed the positive effects of HIS on health care services. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evaluation research in occupational health services: general principles and a systematic review of empirical studies.

PubMed

Hulshof, C T; Verbeek, J H; van Dijk, F J; van der Weide, W E; Braam, I T

1999-06-01

To study the nature and extent of evaluation research in occupational health services (OHSs). Literature review of evaluation research in OHSs. On the basis of a conceptual model of OHS evaluation, empirical studies are categorised into aspects of input, process, output, outcome, and OHS core activities. Many methods to evaluate OHSs or OHS activities exist, depending on the objective and object of evaluation. The amount of empirical studies on evaluation of OHSs or OHS activities that met the non-restrictive inclusion criteria, was remarkably limited. Most of the 52 studies were more descriptive than evaluative. The methodological quality of most studies was not high. A differentiated picture of the evidence of effectiveness of OHSs arises. Occupational health consultations and occupational rehabilitation are hardly studied despite much time spent on the consultation by occupational physicians in most countries. The lack of effectiveness and efficiency of the pre-employment examination should lead to its abandonment as a means of selection of personnel by OHSs. Periodic health monitoring or surveillance, and education on occupational health hazards can be carried out with reasonable process quality. Identification and evaluation of occupational health hazards by a workplace survey can be done with a high output quality, which, however, does not guarantee a favourable outcome. Although rigorous study designs are not always applicable or feasible in daily practice, much more effort should be directed at the scientific evaluation of OHSs and OHS instruments. To develop evidence-based occupational health care the quality of evaluation studies should be improved. In particular, process and outcome of consultation and rehabilitation activities of occupational physicians need to be studied more.

Evaluation and communication: using a communication audit to evaluate organizational communication.

PubMed

Hogard, Elaine; Ellis, Roger

2006-04-01

This article identifies a surprising dearth of studies that explicitly link communication and evaluation at substantive, theoretical, and methodological levels. A three-fold typology of evaluation studies referring to communication is proposed and examples given. The importance of organizational communication in program delivery is stressed and illustrative studies reviewed. It is proposed that organizational communication should be considered in all program evaluations and that this should be approached through communication audit. Communication audits are described with particular reference to established survey questionnaire instruments. Two case studies exemplify the use of such instruments in the evaluation of educational and social programs.

Study Sensitivity: Evaluating the Ability to Detect Effects in Systematic Reviews of Chemical Exposures

PubMed Central

Cooper, Glinda S.; Lunn, Ruth M.; Ågerstrand, Marlene; Glenn, Barbara S.; Kraft, Andrew D.; Luke, April M.; Ratcliffe, Jennifer M.

2016-01-01

A critical step in systematic reviews of potential health hazards is the structured evaluation of the strengths and weaknesses of the included studies; risk of bias is a term often used to represent this process, specifically with respect to the evaluation of systematic errors that can lead to inaccurate (biased) results (i.e. focusing on internal validity). Systematic review methods developed in the clinical medicine arena have been adapted for use in evaluating environmental health hazards; this expansion raises questions about the scope of risk of bias tools and the extent to which they capture the elements that can affect the interpretation of results from environmental and occupational epidemiology studies and in vivo animal toxicology studies, (the studies typically available for assessment of risk of chemicals). One such element, described here as “sensitivity”, is a measure of the ability of a study to detect a true effect or hazard. This concept is similar to the concept of the sensitivity of an assay; an insensitive study may fail to show a difference that truly exists, leading to a false conclusion of no effect. Factors relating to study sensitivity should be evaluated in a systematic manner with the same rigor as the evaluation of other elements within a risk of bias framework. We discuss the importance of this component for the interpretation of individual studies, examine approaches proposed or in use to address it, and describe how it relates to other evaluation components. The evaluation domains contained within a risk of bias tool can include, or can be modified to include, some features relating to study sensitivity; the explicit inclusion of these sensitivity criteria with the same rigor and at the same stage of study evaluation as other bias-related criteria can improve the evaluation process. In some cases, these and other features may be better addressed through a separate sensitivity domain. The combined evaluation of risk of bias and sensitivity can be used to identify the most informative studies, to evaluate the confidence of the findings from individual studies and to identify those study elements that may help to explain heterogeneity across the body of literature. PMID:27156196

Evaluating radiographers' diagnostic accuracy in screen-reading mammograms: what constitutes a quality study?

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

Debono, Josephine C, E-mail: josephine.debono@bci.org.au; Poulos, Ann E; Westmead Breast Cancer Institute, Westmead, New South Wales

The aim of this study was to first evaluate the quality of studies investigating the diagnostic accuracy of radiographers as mammogram screen-readers and then to develop an adapted tool for determining the quality of screen-reading studies. A literature search was used to identify relevant studies and a quality evaluation tool constructed by combining the criteria for quality of Whiting, Rutjes, Dinnes et al. and Brealey and Westwood. This constructed tool was then applied to the studies and subsequently adapted specifically for use in evaluating quality in studies investigating diagnostic accuracy of screen-readers. Eleven studies were identified and the constructed toolmore » applied to evaluate quality. This evaluation resulted in the identification of quality issues with the studies such as potential for bias, applicability of results, study conduct, reporting of the study and observer characteristics. An assessment of the applicability and relevance of the tool for this area of research resulted in adaptations to the criteria and the development of a tool specifically for evaluating diagnostic accuracy in screen-reading. This tool, with further refinement and rigorous validation can make a significant contribution to promoting well-designed studies in this important area of research and practice.« less

Social Studies. MicroSIFT Courseware Evaluations.

ERIC Educational Resources Information Center

Northwest Regional Educational Lab., Portland, OR.

This compilation of 11 courseware evaluations gives a general overview of available social studies microcomputer courseware for students in grades 3-12. Each evaluation lists title, date, producer, date of evaluation, evaluating institution, cost, ability level, topic, medium of transfer, required hardware, required software, instructional…

Social Studies. Microsift Courseware Evaluations.

ERIC Educational Resources Information Center

Northwest Regional Educational Lab., Portland, OR.

This compilation of 17 courseware evaluations gives a general overview of available social studies microcomputer courseware for students in grades 1-12. Each evaluation lists title, date, producer, date of evaluation, evaluating institution, cost, ability level, topic, medium of transfer, required hardware, required software, instructional…

Challenges of teacher-based clinical evaluation from nursing students' point of view: Qualitative content analysis.

PubMed

Sadeghi, Tabandeh; Seyed Bagheri, Seyed Hamid

2017-01-01

Clinical evaluation is very important in the educational system of nursing. One of the most common methods of clinical evaluation is evaluation by the teacher, but the challenges that students would face in this evaluation method, have not been mentioned. Thus, this study aimed to explore the experiences and views of nursing students about the challenges of teacher-based clinical evaluation. This study was a descriptive qualitative study with a qualitative content analysis approach. Data were gathered through semi-structured focused group sessions with undergraduate nursing students who were passing their 8 th semester at Rafsanjan University of Medical Sciences. Date were analyzed using Graneheim and Lundman's proposed method. Data collection and analysis were concurrent. According to the findings, "factitious evaluation" was the main theme of study that consisted of three categories: "Personal preferences," "unfairness" and "shirking responsibility." These categories are explained using quotes derived from the data. According to the results of this study, teacher-based clinical evaluation would lead to factitious evaluation. Thus, changing this approach of evaluation toward modern methods of evaluation is suggested. The finding can help nursing instructors to get a better understanding of the nursing students' point of view toward this evaluation approach and as a result could be planning for changing of this approach.

Cautions on the Use of Investigative Case Studies in Meta-Evaluation.

ERIC Educational Resources Information Center

Smith, Nick L.

1990-01-01

A meta-analysis combining expert evaluation with naturalistic case study methods indicates that such investigations must use special methods to render evaluative judgments of worth. It is demonstrated that descriptive, interpretive, and evaluative aspects of such a study must be combined to yield justifiable conclusions. (TJH)

Formative and Summative Evaluation: Related Issues in Performance Measurement.

ERIC Educational Resources Information Center

Wholey, Joseph S.

1996-01-01

Performance measurement can serve both formative and summative evaluation functions. Formative evaluation is typically more useful for government purposes whereas performance measurement is more useful than one-shot evaluations of either formative or summative nature. Evaluators should study performance measurement through case studies and…

Economic evaluations of clinical pharmacy services: 2006-2010.

PubMed

Touchette, Daniel R; Doloresco, Fred; Suda, Katie J; Perez, Alexandra; Turner, Stuart; Jalundhwala, Yash; Tangonan, Maria C; Hoffman, James M

2014-08-01

Studies have consistently evidenced the positive clinical, economic, and humanistic benefits of pharmacist-directed patient care in a variety of settings. Given the vast differences in clinical outcomes associated with evaluated clinical pharmacy services (CPS), more detail as to the nature of the CPS is needed to better understand observed differences in economic outcomes. With the growing trend of outpatient pharmacy services, these economic evaluations serve as viable decision-making tools in choosing the most effective and cost-effective pharmacy programs. We previously conducted three systematic reviews to evaluate the economic impact of CPS from 1988 to 2005. In this systematic review, our objectives were to describe and evaluate the quality of economic evaluations of CPS published between 2006 and 2010, with the goal of informing administrators and practitioners as to their cost-effectiveness. We searched the scientific literature by using the Medline, International Pharmaceutical Abstracts, Embase, and Cumulative Index to Nursing and Allied Health Literature databases to identify studies describing CPS published from 2006 to 2010. Studies meeting our inclusion criteria (original research articles that evaluated CPS and described economic and clinical outcomes) were reviewed by two investigators. Methodology used, economic evaluation type, CPS setting and type, and clinical and economic outcome results were extracted. Results were informally compared with previous systematic reviews. Of 3587 potential studies identified, 25 met inclusion criteria. Common CPS settings were hospital (36%), community (32%), and clinic or hospital-based ambulatory practices (28%). CPS types were disease state management (48%), general pharmacotherapeutic monitoring (24%), target drug programs (8%), and patient education (4%). Two studies (8%) listed CPS as medication therapy management. Costs were evaluated in 24 studies (96%) and sufficiently described in 13 (52%). Clinical or humanistic outcomes were evaluated in 20 studies (80%) and were sufficiently described in 18 (72%). Control groups were included in 16 (70%) of 23 studies not involving modeling. Study assumptions and limitations were stated and justified in eight studies (32%). Conclusions and recommendations were considered justified and based on results in 24 studies (96%). Eighteen studies (72%) involved full economic evaluation. The mean ± SD study quality score for full economic evaluations (18 studies) was 60.4 ± 22.3 of a possible 100 points. Benefit-cost ratios from three studies ranged from 1.05:1 to 25.95:1, and incremental cost-effectiveness ratios of five studies were calculated and reported. Fewer studies documented the economic impact of CPS from 2006-2010 than from 2001-2005, although a higher proportion involved controlled designs and were full economic evaluations. Evaluations of ambulatory practices were increasingly common. CPS were generally considered cost-effective or provided a good benefit-cost ratio. © 2014 Pharmacotherapy Publications, Inc.

Arts Integration and Students' Reading Achievement: A Formative Evaluation Study

ERIC Educational Resources Information Center

Hosfelt, Patricia D.

2017-01-01

The purpose of this dissertation was to evaluate essential components of an arts-integration program that may contribute to improved student achievement in elementary reading at the school of study through a formative evaluation. Stufflebeam's CIPP model of program evaluation served as the conceptual framework for the study's findings. Creative…

Evaluation Policy in a Nonprofit Foundation: A Case Study Exploration of the Robert Wood Johnson Foundation

ERIC Educational Resources Information Center

Dillman, Lisa M.; Christie, Christina A.

2017-01-01

This study explores the relationship between evaluation policies and evaluation practice. Through document analysis, interviews, and a multiple case study, the research examined the explicit and implicit policies overarching the evaluation work commissioned by the Robert Wood Johnson Foundation (RWJF) and explored how these policies are…

Evaluation systems for clinical governance development: a comparative study.

PubMed

Hooshmand, Elaheh; Tourani, Sogand; Ravaghi, Hamid; Ebrahimipour, Hossein

2014-01-01

Lack of scientific and confirmed researches and expert knowledge about evaluation systems for clinical governance development in Iran have made studies on different evaluation systems for clinical governance development a necessity. These studies must provide applied strategies to design criteria of implementing clinical governance for hospital's accreditation. This is a descriptive and comparative study on development of clinical governance models all over the world. Data have been gathered by reviewing related articles. Models have been studied in comprehensive review method. The evaluated models of clinical governance development were Australian, NHS, SPOCK and OPTIGOV. The final aspects extracted from these models were Responsiveness, Policies and Strategies, Organizational Structure, Allocating Resources, Education and Occupational Development, Performance Evaluation, External Evaluation, Patient Oriented Approach, Risk Management, Personnel's Participation, Information Technology, Human Resources, Research and Development, Evidence Based Medicine, Clinical Audit, Health Technology Assessment and Quality. These results are applicable for completing the present criteria which evaluating clinical governance application and provide practical framework to evaluate country's hospital on the basis of clinical governance elements.

Students Evaluation of Faculty

ERIC Educational Resources Information Center

Thawabieh, Ahmad M.

2017-01-01

This study aimed to investigate how students evaluate their faculty and the effect of gender, expected grade, and college on students' evaluation. The study sample consisted of 5291 students from Tafila Technical University Faculty evaluation scale was used to collect data. The results indicated that student evaluation of faculty was high (mean =…

An Analysis of State and Local Alignment of Teacher Evaluation in Maryland

ERIC Educational Resources Information Center

Peterson, Serene N.

2014-01-01

This study explored the components of Maryland's newly-implemented teacher evaluation framework and compared state requirements with evaluations to three local school systems' evaluation procedures. The study sought to investigate the relationship between three evaluation protocols in comparison to the state requirements. Three local school…

Study sensitivity: Evaluating the ability to detect effects in systematic reviews of chemical exposures.

PubMed

Cooper, Glinda S; Lunn, Ruth M; Ågerstrand, Marlene; Glenn, Barbara S; Kraft, Andrew D; Luke, April M; Ratcliffe, Jennifer M

2016-01-01

A critical step in systematic reviews of potential health hazards is the structured evaluation of the strengths and weaknesses of the included studies; risk of bias is a term often used to represent this process, specifically with respect to the evaluation of systematic errors that can lead to inaccurate (biased) results (i.e. focusing on internal validity). Systematic review methods developed in the clinical medicine arena have been adapted for use in evaluating environmental health hazards; this expansion raises questions about the scope of risk of bias tools and the extent to which they capture the elements that can affect the interpretation of results from environmental and occupational epidemiology studies and in vivo animal toxicology studies, (the studies typically available for assessment of risk of chemicals). One such element, described here as "sensitivity", is a measure of the ability of a study to detect a true effect or hazard. This concept is similar to the concept of the sensitivity of an assay; an insensitive study may fail to show a difference that truly exists, leading to a false conclusion of no effect. Factors relating to study sensitivity should be evaluated in a systematic manner with the same rigor as the evaluation of other elements within a risk of bias framework. We discuss the importance of this component for the interpretation of individual studies, examine approaches proposed or in use to address it, and describe how it relates to other evaluation components. The evaluation domains contained within a risk of bias tool can include, or can be modified to include, some features relating to study sensitivity; the explicit inclusion of these sensitivity criteria with the same rigor and at the same stage of study evaluation as other bias-related criteria can improve the evaluation process. In some cases, these and other features may be better addressed through a separate sensitivity domain. The combined evaluation of risk of bias and sensitivity can be used to identify the most informative studies, to evaluate the confidence of the findings from individual studies and to identify those study elements that may help to explain heterogeneity across the body of literature. Copyright © 2016. Published by Elsevier Ltd.

Presenting an Evaluation Model for the Cancer Registry Software.

PubMed

Moghaddasi, Hamid; Asadi, Farkhondeh; Rabiei, Reza; Rahimi, Farough; Shahbodaghi, Reihaneh

2017-12-01

As cancer is increasingly growing, cancer registry is of great importance as the main core of cancer control programs, and many different software has been designed for this purpose. Therefore, establishing a comprehensive evaluation model is essential to evaluate and compare a wide range of such software. In this study, the criteria of the cancer registry software have been determined by studying the documents and two functional software of this field. The evaluation tool was a checklist and in order to validate the model, this checklist was presented to experts in the form of a questionnaire. To analyze the results of validation, an agreed coefficient of %75 was determined in order to apply changes. Finally, when the model was approved, the final version of the evaluation model for the cancer registry software was presented. The evaluation model of this study contains tool and method of evaluation. The evaluation tool is a checklist including the general and specific criteria of the cancer registry software along with their sub-criteria. The evaluation method of this study was chosen as a criteria-based evaluation method based on the findings. The model of this study encompasses various dimensions of cancer registry software and a proper method for evaluating it. The strong point of this evaluation model is the separation between general criteria and the specific ones, while trying to fulfill the comprehensiveness of the criteria. Since this model has been validated, it can be used as a standard to evaluate the cancer registry software.

Attitudes of affiliate faculty members toward medical student summative evaluation for clinical clerkships: a qualitative analysis.

PubMed

Wang, Karen E; Fitzpatrick, Caroline; George, David; Lane, Lindsey

2012-01-01

Summative evaluation of medical students is a critical component of the educational process. Despite extensive literature on evaluation, few studies have centered on affiliate faculty members' attitudes toward summative evaluation of students, though it has been suggested that these attitudes influence their effectiveness as evaluators. The objective is to examine affiliate faculty members' attitudes toward clinical clerkship evaluation using primarily qualitative research methods. The study used a nonexperimental research design and employed mixed methods. Data were collected through interviews, focus groups, and a questionnaire from 11 affiliate faculty members. Themes emerging from the data fell into three broad categories: (a) factors that influence grading, (b) consequences of negative evaluations, and (c) disconnections in the grading process. The quantitative portion of the study revealed important discrepancies supporting the use of qualitative methods. The study highlights faculty members' struggles with the evaluative process and emphasizes the need for improvements in evaluation tools and faculty development.

A systematic review of economic evaluations of health and health-related interventions in Bangladesh

PubMed Central

2011-01-01

Background Economic evaluation is used for effective resource allocation in health sector. Accumulated knowledge about economic evaluation of health programs in Bangladesh is not currently available. While a number of economic evaluation studies have been performed in Bangladesh, no systematic investigation of the studies has been done to our knowledge. The aim of this current study is to systematically review the published articles in peer-reviewed journals on economic evaluation of health and health-related interventions in Bangladesh. Methods Literature searches was carried out during November-December 2008 with a combination of key words, MeSH terms and other free text terms as suitable for the purpose. A comprehensive search strategy was developed to search Medline by the PubMed interface. The first specific interest was mapping the articles considering the areas of exploration by economic evaluation and the second interest was to scrutiny the methodological quality of studies. The methodological quality of economic evaluation of all articles has been scrutinized against the checklist developed by Evers Silvia and associates. Result Of 1784 potential articles 12 were accepted for inclusion. Ten studies described the competing alternatives clearly and only two articles stated the perspective of their articles clearly. All studies included direct cost, incurred by the providers. Only one study included the cost of community donated resources and volunteer costs. Two studies calculated the incremental cost effectiveness ratio (ICER). Six of the studies applied some sort of sensitivity analysis. Two of the studies discussed financial affordability of expected implementers and four studies discussed the issue of generalizability for application in different context. Conclusion Very few economic evaluation studies in Bangladesh are found in different areas of health and health-related interventions, which does not provide a strong basis of knowledge in the area. The most frequently applied economic evaluation is cost-effectiveness analysis. The majority of the studies did not follow the scientific method of economic evaluation process, which consequently resulted into lack of robustness of the analyses. Capacity building on economic evaluation of health and health-related programs should be enhanced. PMID:21771343

Impact of a Major National Evaluation Study: Israel's Van Leer Report.

ERIC Educational Resources Information Center

Alkin, Marvin C.; Lewy, Arieh

This investigation documents the impact of the Van Leer Study, a large-scale evaluation study of achievement in the primary schools of Israel. It is intended to increase understanding of the process of evaluation utilization, showing how evaluation findings and other kinds of information can work together, over time and in a variety of ways, to…

Strategies for Evaluating a Freshman Studies Program.

ERIC Educational Resources Information Center

Ketkar, Kusum; Bennett, Shelby D.

1989-01-01

The study developed an economic model for the evaluation of Seaton Hall University's freshman studies program. Two techniques used to evaluate the economic success of the program are break-even analysis and elasticity coefficient. (Author/MLW)

Rebooting Kirkpatrick: Integrating Information System Theory Into the Evaluation of Web-based Continuing Professional Development Interventions for Interprofessional Education.

PubMed

Shen, Nelson; Yufe, Shira; Saadatfard, Omid; Sockalingam, Sanjeev; Wiljer, David

2017-01-01

Information system research has stressed the importance of theory in understanding how user perceptions can motivate the use and adoption of technology such as web-based continuing professional development programs for interprofessional education (WCPD-IPE). A systematic review was conducted to provide an information system perspective on the current state of WCPD-IPE program evaluation and how current evaluations capture essential theoretical constructs in promoting technology adoption. Six databases were searched to identify studies evaluating WCPD-IPE. Three investigators determined eligibility of the articles. Evaluation items extracted from the studies were assessed using the Kirkpatrick-Barr framework and mapped to the Benefits Evaluation Framework. Thirty-seven eligible studies yielded 362 evaluation items for analysis. Most items (n = 252) were assessed as Kirkpatrick-Barr level 1 (reaction) and were mainly focused on the quality (information, service, and quality) and satisfaction dimensions of the Benefits Evaluation. System quality was the least evaluated quality dimension, accounting for 26 items across 13 studies. WCPD-IPE use was reported in 17 studies and its antecedent factors were evaluated in varying degrees of comprehensiveness. Although user reactions were commonly evaluated, greater focus on user perceptions of system quality (ie, functionality and performance), usefulness, and usability of the web-based platform is required. Surprisingly, WCPD-IPE use was reported in less than half of the studies. This is problematic as use is a prerequisite to realizing any individual, organizational, or societal benefit of WCPD-IPE. This review proposes an integrated framework which accounts for these factors and provides a theoretically grounded guide for future evaluations.

Insight into Evaluation Practice: A Content Analysis of Designs and Methods Used in Evaluation Studies Published in North American Evaluation-Focused Journals

ERIC Educational Resources Information Center

Christie, Christina A.; Fleischer, Dreolin Nesbitt

2010-01-01

To describe the recent practice of evaluation, specifically method and design choices, the authors performed a content analysis on 117 evaluation studies published in eight North American evaluation-focused journals for a 3-year period (2004-2006). The authors chose this time span because it follows the scientifically based research (SBR)…

Course Evaluation in Sweden--When, How, What and Why

ERIC Educational Resources Information Center

Cronholm, Stefan

2010-01-01

This study is about course evaluation in Swedish higher education. Performing course evaluation is regulated in Swedish law. Despite this, only half of the courses are evaluated. The aim of this study is to understand why satisfactory course evaluations not are performed. Problems are identified from a student perspective and the paper provides…

Textbook Evaluation for the Students of Speech Therapy

ERIC Educational Resources Information Center

Jamshidi, Tahereh; Soori, Afshin

2013-01-01

This study aimed to evaluate an ESP textbook in terms of McDonough and Shaw (2003) based on external and internal evaluation. The ESP textbook was "Special English for Computer Sciences" (2010) by Hojjat Baghban. This study also discussed the external evaluation and a detailed evaluation of a chapter of the ESP textbook. This ESP…

Economic evaluation of diagnostic methods used in dentistry. A systematic review.

PubMed

Christell, Helena; Birch, Stephen; Horner, Keith; Lindh, Christina; Rohlin, Madeleine

2014-11-01

To review the literature of economic evaluations regarding diagnostic methods used in dentistry. Four databases (MEDLINE, Web of Science, The Cochrane library, the NHS Economic Evaluation Database) were searched for studies, complemented by hand search, until February 2013. Two authors independently screened all titles or abstracts and then applied inclusion and exclusion criteria to select full-text publications published in English, which reported an economic evaluation comparing at least two alternative methods. Studies of diagnostic methods were assessed by four reviewers using a protocol based on the QUADAS tool regarding diagnostic methods and a check-list for economic evaluations. The results of the data extraction were summarized in a structured table and as a narrative description. From 476 identified full-text publications, 160 were considered to be economic evaluations. Only 12 studies (7%) were on diagnostic methods, whilst 78 studies (49%) were on prevention and 70 (40%) on treatment. Among studies on diagnostic methods, there was between-study heterogeneity methodologically, regarding the diagnostic method analysed and type of economic evaluation addressed. Generally, the choice of economic evaluation method was not justified and the perspective of the study not stated. Costing of diagnostic methods varied. A small body of literature addresses economic evaluation of diagnostic methods in dentistry. Thus, there is a need for studies from various perspectives with well defined research questions and measures of the cost and effectiveness. Economic resources in healthcare are finite. For diagnostic methods, an understanding of efficacy provides only part of the information needed for evidence-based practice. This study highlighted a paucity of economic evaluations of diagnostic methods used in dentistry, indicating that much of what we practise lacks sufficient evidence.

Simulation studies for the evaluation of health information technologies: experiences and results.

PubMed

Ammenwerth, Elske; Hackl, Werner O; Binzer, Kristine; Christoffersen, Tue E H; Jensen, Sanne; Lawton, Kitta; Skjoet, Peter; Nohr, Christian

It is essential for new health information technologies (IT) to undergo rigorous evaluations to ensure they are effective and safe for use in real-world situations. However, evaluation of new health IT is challenging, as field studies are often not feasible when the technology being evaluated is not sufficiently mature. Laboratory-based evaluations have also been shown to have insufficient external validity. Simulation studies seem to be a way to bridge this gap. The aim of this study was to evaluate, using a simulation methodology, the impact of a new prototype of an electronic medication management system on the appropriateness of prescriptions and drug-related activities, including laboratory test ordering or medication changes. This article presents the results of a controlled simulation study with 50 simulation runs, including ten doctors and five simulation patients, and discusses experiences and lessons learnt while conducting the study. Although the new electronic medication management system showed tendencies to improve medication safety when compared with the standard system, this tendency was not significant. Altogether, five distinct situations were identified where the new medication management system did help to improve medication safety. This simulation study provided a good compromise between internal validity and external validity. However, several challenges need to be addressed when undertaking simulation evaluations including: preparation of adequate test cases; training of participants before using unfamiliar applications; consideration of time, effort and costs of conducting the simulation; technical maturity of the evaluated system; and allowing adequate preparation of simulation scenarios and simulation setting. Simulation studies are an interesting but time-consuming approach, which can be used to evaluate newly developed health IT systems, particularly those systems that are not yet sufficiently mature to undergo field evaluation studies.

Revisioning the Process: A Case Study in Feminist Program Evaluation.

ERIC Educational Resources Information Center

Beardsley, Rebecca M.; Miller, Michelle Hughes

2002-01-01

Conducted a case study of the evaluation of a women's substance abuse prevention program and identified three key aspects of negotiated evaluation. Discusses the processes involved in feminist evaluation, including collaborative agenda setting and cooperative teamwork. (SLD)

Evaluating Voucher Programs: The Milwaukee Parental Choice Program

ERIC Educational Resources Information Center

Witte, John F.

2016-01-01

This paper is the first summary of two studies and 10 years of evaluating the Milwaukee Parental Choice (voucher) Program (MPCP). This paper discusses school voucher evaluations in general terms and how these studies are carried out. The paper outlines the types of studies completed in "Study I" and "Study II" and the results…

An Evaluative Case Study on Professional Competency of Preservice Information Technology Teachers

ERIC Educational Resources Information Center

Kabakci Yurdakul, Isil

2011-01-01

The purpose of this study is to evaluate preservice Information Technology (IT) teachers' professional competency in the teaching process. The study was designed on the basis of evaluative case study. The participants of the study consisted of seven preservice IT teachers attending the department of Computer Education and Instructional…

A systematic review of economic evaluations of population-based sodium reduction interventions.

PubMed

Hope, Silvia F; Webster, Jacqui; Trieu, Kathy; Pillay, Arti; Ieremia, Merina; Bell, Colin; Snowdon, Wendy; Neal, Bruce; Moodie, Marj

2017-01-01

To summarise evidence describing the cost-effectiveness of population-based interventions targeting sodium reduction. A systematic search of published and grey literature databases and websites was conducted using specified key words. Characteristics of identified economic evaluations were recorded, and included studies were appraised for reporting quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Twenty studies met the study inclusion criteria and received a full paper review. Fourteen studies were identified as full economic evaluations in that they included both costs and benefits associated with an intervention measured against a comparator. Most studies were modelling exercises based on scenarios for achieving salt reduction and assumed effects on health outcomes. All 14 studies concluded that their specified intervention(s) targeting reductions in population sodium consumption were cost-effective, and in the majority of cases, were cost saving. Just over half the studies (8/14) were assessed as being of 'excellent' reporting quality, five studies fell into the 'very good' quality category and one into the 'good' category. All of the identified evaluations were based on modelling, whereby inputs for all the key parameters including the effect size were either drawn from published datasets, existing literature or based on expert advice. Despite a clear increase in evaluations of salt reduction programs in recent years, this review identified relatively few economic evaluations of population salt reduction interventions. None of the studies were based on actual implementation of intervention(s) and the associated collection of new empirical data. The studies universally showed that population-based salt reduction strategies are likely to be cost effective or cost saving. However, given the reliance on modelling, there is a need for the effectiveness of new interventions to be evaluated in the field using strong study designs and parallel economic evaluations.

Michigan English Study of Structure for Curriculum Evaluation (MESSAGE).

ERIC Educational Resources Information Center

Taylor, Vi Marie

The Michigan English Study of Structure for Curriculum Evaluation (MESSAGE) training session involved 40 leaders of English curriculum study in a 7-day intensive program. They studied objective evaluation in terms of behavior, instruction, and institution; approaches to the English curriculum through instructional objectives that include…

How social context moderates the self-evaluative emotions experienced due to health risk behaviour.

PubMed

Grob, Judith D M; Dijkstra, Arie; de Groot, Carla

2011-10-01

When people are confronted with the potential negative physical outcomes of their own health risk behaviour, they experience a self-threat. This threat is felt as negative self-evaluative emotions. We hypothesise that the threat will lead to more private self-evaluative emotions (e.g. regret) in a private social context, whereas more public self-evaluative emotions (e.g. embarrassment) will be felt in a public social context with negative norms. Consistent with our hypotheses, we show that participants anticipate feeling more private self-evaluative emotions when confronted with the negative consequences of their unhealthy behaviour when alone, and more public self-evaluative emotions when in a group (Study 1). They further anticipate more public self-evaluative emotions in response to a health self-threat when the group norm is negative, and more private self-evaluative emotions when the group norm is lenient (Study 2). Finally, in a cross-sectional study amongst smokers, we show that private but not public negative self-evaluative emotions concerning their own smoking habits are positively correlated with the intent to quit smoking (Study 3). These studies show that a distinction needs to be made between public and private self-evaluative emotions, in terms of their antecedents and effects. Theoretical implications and further lines of research are discussed.

Head-camera video recordings of trauma core competency procedures can evaluate surgical resident's technical performance as well as colocated evaluators.

PubMed

Mackenzie, Colin F; Pasley, Jason; Garofalo, Evan; Shackelford, Stacy; Chen, Hegang; Longinaker, Nyaradzo; Granite, Guinevere; Pugh, Kristy; Hagegeorge, George; Tisherman, Samuel A

2017-07-01

Unbiased evaluation of trauma core competency procedures is necessary to determine if residency and predeployment training courses are useful. We tested whether a previously validated individual procedure score (IPS) for individual procedure vascular exposure and fasciotomy (FAS) performance skills could discriminate training status by comparing IPS of evaluators colocated with surgeons to blind video evaluations. Performance of axillary artery (AA), brachial artery (BA), and femoral artery (FA) vascular exposures and lower extremity FAS on fresh cadavers by 40 PGY-2 to PGY-6 residents was video-recorded from head-mounted cameras. Two colocated trained evaluators assessed IPS before and after training. One surgeon in each pretraining tertile of IPS for each procedure was randomly identified for blind video review. The same 12 surgeons were video-recorded repeating the procedures less than 4 weeks after training. Five evaluators independently reviewed all 96 randomly arranged deidentified videos. Inter-rater reliability/consistency, intraclass correlation coefficients were compared by colocated versus video review of IPS, and errors. Study methodology and bias were judged by Medical Education Research Study Quality Instrument and the Quality Assessment of Diagnostic Accuracy Studies criteria. There were no differences (p ≥ 0.5) in IPS for AA, FA, FAS, whether evaluators were colocated or reviewed video recordings. Evaluator consistency was 0.29 (BA) - 0.77 (FA). Video and colocated evaluators were in total agreement (p = 1.0) for error recognition. Intraclass correlation coefficient was 0.73 to 0.92, dependent on procedure. Correlations video versus colocated evaluations were 0.5 to 0.9. Except for BA, blinded video evaluators discriminated (p < 0.002) whether procedures were performed before training versus after training. Study methodology by Medical Education Research Study Quality Instrument criteria scored 15.5/19, Quality Assessment of Diagnostic Accuracy Studies 2 showed low bias risk. Video evaluations of AA, FA, and FAS procedures with IPS are unbiased, valid, and have potential for formative assessments of competency. Prognostic study, level II.

Developing Statistical Physics Course Handout on Distribution Function Materials Based on Science, Technology, Engineering, and Mathematics

NASA Astrophysics Data System (ADS)

Riandry, M. A.; Ismet, I.; Akhsan, H.

2017-09-01

This study aims to produce a valid and practical statistical physics course handout on distribution function materials based on STEM. Rowntree development model is used to produce this handout. The model consists of three stages: planning, development and evaluation stages. In this study, the evaluation stage used Tessmer formative evaluation. It consists of 5 stages: self-evaluation, expert review, one-to-one evaluation, small group evaluation and field test stages. However, the handout is limited to be tested on validity and practicality aspects, so the field test stage is not implemented. The data collection technique used walkthroughs and questionnaires. Subjects of this study are students of 6th and 8th semester of academic year 2016/2017 Physics Education Study Program of Sriwijaya University. The average result of expert review is 87.31% (very valid category). One-to-one evaluation obtained the average result is 89.42%. The result of small group evaluation is 85.92%. From one-to-one and small group evaluation stages, averagestudent response to this handout is 87,67% (very practical category). Based on the results of the study, it can be concluded that the handout is valid and practical.

Exploring Organizational Evaluation Capacity and Evaluation Capacity Building: A Delphi Study of Taiwanese Elementary and Junior High Schools

ERIC Educational Resources Information Center

Cheng, Shu-Huei; King, Jean A.

2017-01-01

Researchers have conducted numerous empirical studies on evaluation capacity (EC) and evaluation capacity building (ECB) in Western cultural settings. However, little is known about these practices in non-Western contexts. To that end, this study identified the major dimensions of EC and feasible ECB approaches in Taiwanese elementary and junior…

An Evaluation Study of Youth Participation in Youth Work: A Case Study in Southern Italy

ERIC Educational Resources Information Center

Morciano, Daniele; Scardigno, Anna Fausta; Manuti, Amelia; Pastore, Serafina

2014-01-01

In this paper an evaluation study of a public programme financing a regional network of 157 youth centres in the South of Italy is presented. A theory-based evaluation model was adopted to explore the causal links between different types of participation experience. Evaluation questions focused on three main issues are: the perception of…

Evaluating Work-Based Learning: Insights from an Illuminative Evaluation Study of Work-Based Learning in a Vocational Qualification

ERIC Educational Resources Information Center

van Rensburg, Estelle

2008-01-01

This article outlines an illuminative evaluation study of the work-based module in a vocational qualification in Animal Health offered for the paraveterinary industry by a distance education institution in South Africa. In illuminative evaluation, a programme is studied by qualitative methods to gain an in-depth understanding of its…

Critical appraisal of published economic evaluations of home care for the elderly.

PubMed

Ramos, Maria Lucia Teixeira; Ferraz, Marcos Bosi; Sesso, Ricardo

2004-01-01

The goal of the study was to appraise the economic evaluations published between 1980 and 2004 of "home care" for the elderly, focusing on the methodological aspects. MEDLINE was searched to identify and assess economic evaluations (defined as an analysis comparing two or more strategies, involving the assessment of both costs and consequences) related to "home care" exclusively for the elderly (65 years or more) and to critically appraise the methodology using five accepted principles used worldwide for conducting economic evaluations. Twenty-four economic evaluations of "home care" for the elderly were identified and the articles were assessed. All five principles were satisfactorily addressed in two studies (8.3%), four principles in four studies (16.7%), three principles in five studies (20.8%), two principles in eight studies (33.3%) and only one principle in five studies (20.8%). A disparity in the methodology of writing economic evaluations compromises the comparisons among outcomes and lately jeopardizes decisions on the choice of the most appropriate healthcare interventions. The methodological principles represent important guidelines but the discussion of the context of the economic evaluation and the special characteristics of some services and populations should be considered for the appropriate use of economic evaluations.

Performing well in an evaluative situation: the roles of perceived competence and task-irrelevant interfering thoughts.

PubMed

Van Yperen, Nico W

2007-12-01

This research expands on previous research by arguing and demonstrating that high perceived competence buffers the detrimental effects of an evaluative situation. In Study 1 (n=75, 38.7% male), the situation (evaluative vs. non-evaluative) and perceived competence (high vs. low) were manipulated, whereas in Study 2 (n=42, 33.3% male), perceived competence relied on naturally occurring differences in perceived competence. The results of Study 1 indicate that people may underachieve in an evaluative situation. More importantly, in Study 2 it was demonstrated that such an evaluative situation had only a negative effect on test performance among individuals low in perceived competence. The occurrence of task-irrelevant interfering thoughts during task completion accounted for this inimical effect of an evaluative situation on test performance among these individuals.

Economic analysis of the health impacts of housing improvement studies: a systematic review.

PubMed

Fenwick, Elisabeth; Macdonald, Catriona; Thomson, Hilary

2013-10-01

Economic evaluation of public policies has been advocated but rarely performed. Studies from a systematic review of the health impacts of housing improvement included data on costs and some economic analysis. Examination of these data provides an opportunity to explore the difficulties and the potential for economic evaluation of housing. Data were extracted from all studies included in the systematic review of housing improvement which had reported costs and economic analysis (n=29/45). The reported data were assessed for their suitability to economic evaluation. Where an economic analysis was reported the analysis was described according to pre-set definitions of various types of economic analysis used in the field of health economics. 25 studies reported cost data on the intervention and/or benefits to the recipients. Of these, 11 studies reported data which was considered amenable to economic evaluation. A further four studies reported conducting an economic evaluation. Three of these studies presented a hybrid 'balance sheet' approach and indicated a net economic benefit associated with the intervention. One cost-effectiveness evaluation was identified but the data were unclearly reported; the cost-effectiveness plane suggested that the intervention was more costly and less effective than the status quo. Future studies planning an economic evaluation need to (i) make best use of available data and (ii) ensure that all relevant data are collected. To facilitate this, economic evaluations should be planned alongside the intervention with input from health economists from the outset of the study. When undertaken appropriately, economic evaluation provides the potential to make significant contributions to housing policy.

Analyzing the School Evaluation Use Process To Make Evaluation Worth the Effort.

ERIC Educational Resources Information Center

Pechman, Ellen M.; King, Jean A.

This paper describes a structure for assessing the school evaluation use process developed from a longitudinal case study of districtwide and school level evaluation procedures in a large urban school district. Two fundamental questions guided the study: (1) Why isn't the evaluation process more useful to decision-makers and practitioners? and (2)…

Learning from Evaluation by Peer Team: A Case Study of a Family Counselling Organization

ERIC Educational Resources Information Center

Muniute-Cobb, Eivina I.; Alfred, Mary V.

2010-01-01

This qualitative study explores how employees learn from Team Primacy Concept-based employee evaluation and how they use the feedback in performing their jobs. Team Primacy Concept-based evaluation is a type of multirater evaluation. The distinctive characteristic of such evaluation is its peer feedback component during which the employee's…

Products for Improving Educational Evaluation. Center for the Study of Evaluation. Fifth Annual Report.

ERIC Educational Resources Information Center

Alkin, Marvin C.

This publication provides background information on the functions and operations of the Center for the Study of Evaluation and reports on such center products as Insructional Objectives Exchange (IOX), CSE Elementary School Test Evaluations, and Evaluation Workshop I. Appendixes include: a summary of center accomplishments; a list of the center's…

Examining Teacher Evaluation Validity and Leadership Decision Making within a Standards-Based Evaluation System

ERIC Educational Resources Information Center

Kimball, Steven M.; Milanowski, Anthony

2009-01-01

Purpose: The article reports on a study of school leader decision making that examined variation in the validity of teacher evaluation ratings in a school district that has implemented a standards-based teacher evaluation system. Research Methods: Applying mixed methods, the study used teacher evaluation ratings and value-added student achievement…

User Experience Evaluations in Rehabilitation Video Games for Children: A Systematic Mapping of the Literature.

PubMed

Rico-Olarte, Carolina; López, Diego M; Blobel, Bernd; Kepplinger, Sara

2017-01-01

In recent years, the interest in user experience (UX) evaluation methods for assessing technology solutions, especially in health systems for children with special needs like cognitive disabilities, has increased. Conduct a systematic mapping study to provide an overview in the field of UX evaluations in rehabilitation video games for children. The definition of research questions, the search for primary studies and the extraction of those studies by inclusion and exclusion criteria lead to the mapping of primary papers according to a classification scheme. Main findings from this study include the detection of the target population of the selected studies, the recognition of two different ways of evaluating UX: (i) user evaluation and (ii) system evaluation, and UX measurements and devices used. This systematic mapping specifies the research gaps identified for future research works in the area.

On the importance of cognitive evaluation as a determinant of interpersonal attraction.

PubMed

Montoya, R Matthew; Horton, Robert S

2004-05-01

Three studies examined a model of attraction in which the cognitive evaluation of the target individual was the primary determinant of interpersonal attraction. In Study 1, the cognitive evaluation of the target individual mediated the influence of attitude similarity on interpersonal attraction. In Study 2, a path analysis revealed significant indirect effects of (a) similarity on cognitive evaluation via the valence of information implied by attitudes and (b) the valence of information implied by attitudes on attraction via cognitive evaluation of the target. Study 3 provided empirical and theoretical support for the uniqueness of interpersonal attraction from cognitive evaluation. The implications of these data for existing attraction theory are discussed, and a new model of interpersonal attraction is described.

Economic evaluation of vaccines in Canada: A systematic review.

PubMed

Chit, Ayman; Lee, Jason K H; Shim, Minsup; Nguyen, Van Hai; Grootendorst, Paul; Wu, Jianhong; Van Exan, Robert; Langley, Joanne M

2016-05-03

Economic evaluations should form part of the basis for public health decision making on new vaccine programs. While Canada's national immunization advisory committee does not systematically include economic evaluations in immunization decision making, there is increasing interest in adopting them. We therefore sought to examine the extent and quality of economic evaluations of vaccines in Canada. We conducted a systematic review of economic evaluations of vaccines in Canada to determine and summarize: comprehensiveness across jurisdictions, studied vaccines, funding sources, study designs, research quality, and changes over time. Searches in multiple databases were conducted using the terms "vaccine," "economics" and "Canada." Descriptive data from eligible manuscripts was abstracted and three authors independently evaluated manuscript quality using a 7-point Likert-type scale scoring tool based on criteria from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). 42/175 articles met the search criteria. Of these, Canada-wide studies were most common (25/42), while provincial studies largely focused on the three populous provinces of Ontario, Quebec and British Columbia. The most common funding source was industry (17/42), followed by government (7/42). 38 studies used mathematical models estimating expected economic benefit while 4 studies examined post-hoc data on established programs. Studies covered 10 diseases, with 28/42 addressing pediatric vaccines. Many studies considered cost-utility (22/42) and the majority of these studies reported favorable economic results (16/22). The mean quality score was 5.9/7 and was consistent over publication date, funding sources, and disease areas. We observed diverse approaches to evaluate vaccine economics in Canada. Given the increased complexity of economic studies evaluating vaccines and the impact of results on public health practice, Canada needs improved, transparent and consistent processes to review and assess the findings of the economic evaluations of vaccines.

Objective evaluation of acute adverse events and image quality of gadolinium-based contrast agents (gadobutrol and gadobenate dimeglumine) by blinded evaluation. Pilot study.

PubMed

Semelka, Richard C; Hernandes, Mateus de A; Stallings, Clifton G; Castillo, Mauricio

2013-01-01

The purpose was to objectively evaluate a recently FDA-approved gadolinium-based contrast agent (GBCA) in comparison to our standard GBCA for acute adverse events and image quality by blinded evaluation. Evaluation was made of a recently FDA-approved GBCA, gadobutrol (Gadavist; Bayer), in comparison to our standard GBCA, gadobenate dimeglumine (MultiHance; Bracco), in an IRB- and HIPAA-compliant study. Both the imaging technologist and patient were not aware of the brand of the GBCA used. A total of 59 magnetic resonance studies were evaluated (59 patients, 31 men, 28 women, age range of 5-85 years, mean age of 52 years). Twenty-nine studies were performed with gadobutrol (22 abdominal and 7 brain studies), and 30 studies were performed with gadobenate dimeglumine (22 abdominal and 8 brain studies). Assessment was made of acute adverse events focusing on objective observations of vomiting, hives, and moderate and severe reactions. Adequacy of enhancement was rated as poor, fair and good by one of two experienced radiologists who were blinded to the type of agent evaluated. No patient experienced acute adverse events with either agent. The target minor adverse events of vomiting or hives, and moderate and severe reactions were not observed in any patient. Adequacy of enhancement was rated as good for both agents in all patients. Objective, blinded evaluation is feasible and readily performable for the evaluation of GBCAs. This proof-of-concept study showed that both GBCAs evaluated exhibited consistent good image quality and no noteworthy adverse events. Copyright © 2013 Elsevier Inc. All rights reserved.

Unintended outcomes evaluation approach: A plausible way to evaluate unintended outcomes of social development programmes.

PubMed

Jabeen, Sumera

2018-06-01

Social development programmes are deliberate attempts to bring about change and unintended outcomes can be considered as inherent to any such intervention. There is now a solid consensus among the international evaluation community regarding the need to consider unintended outcomes as a key aspect in any evaluative study. However, this concern often equates to nothing more than false piety. Exiting evaluation theory suffers from overlap of terminology, inadequate categorisation of unintended outcomes and lack of guidance on how to study them. To advance the knowledge of evaluation theory, methods and practice, the author has developed an evaluation approach to study unintended effects using a theory building, testing and refinement process. A comprehensive classification of unintended outcomes on the basis of knowability, value, distribution and temporality helped specify various type of unintended outcomes for programme evaluation. Corresponding to this classification, a three-step evaluation process was proposed including a) outlining programme intentions b) forecasting likely unintended effects c) mapping the anticipated and understanding unanticipated unintended outcomes. This unintended outcomes evaluation approach (UOEA) was then trialled by undertaking a multi-site and multi-method case study of a poverty alleviation programme in Pakistan and refinements were made to the approach.The case study revealed that this programme was producing a number of unintended effects, mostly negative, affecting those already disadvantaged such as the poorest, women and children. The trialling process demonstrated the effectiveness of the UOEA and suggests that this can serve as a useful guide for future evaluation practice. It also provides the discipline of evaluation with an empirically-based reference point for further theoretical developments in the study of unintended outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Barriers to and Facilitators of the Evaluation of Integrated Community-Wide Overweight Intervention Approaches: A Qualitative Case Study in Two Dutch Municipalities

PubMed Central

van Koperen, Tessa M.; de Kruif, Anja; van Antwerpen, Lisa; Hendriks, Anna-Marie; Seidell, Jacob C.; Schuit, Albertine J.; Renders, Carry M.

2016-01-01

To prevent overweight and obesity the implementation of an integrated community-wide intervention approach (ICIA) is often advocated. Evaluation can enhance implementation of such an approach and demonstrate the extent of effectiveness. To be able to support professionals in the evaluation of ICIAs we studied barriers to and facilitators of ICIA evaluation. In this study ten professionals of two Dutch municipalities involved in the evaluation of an ICIA participated. We conducted semi-structured interviews (n = 12), observed programme meetings (n = 4) and carried out document analysis. Data were analyzed using a thematic content approach. We learned that evaluation is hampered when it is perceived as unfeasible due to limited time and budget, a lack of evaluation knowledge or a negative evaluation attitude. Other barriers are a poor understanding of the evaluation process and its added value to optimizing the programme. Sufficient communication between involved professionals on evaluation can facilitate evaluation, as does support for evaluation of ICIAs together with stakeholders at a strategic and tactical level. To stimulate the evaluation of ICIAs, we recommend supporting professionals in securing evaluation resources, providing tailored training and tools to enhance evaluation competences and stimulating strategic communication on evaluation. PMID:27043600

Barriers to and Facilitators of the Evaluation of Integrated Community-Wide Overweight Intervention Approaches: A Qualitative Case Study in Two Dutch Municipalities.

PubMed

van Koperen, Tessa M; de Kruif, Anja; van Antwerpen, Lisa; Hendriks, Anna-Marie; Seidell, Jacob C; Schuit, Albertine J; Renders, Carry M

2016-03-31

To prevent overweight and obesity the implementation of an integrated community-wide intervention approach (ICIA) is often advocated. Evaluation can enhance implementation of such an approach and demonstrate the extent of effectiveness. To be able to support professionals in the evaluation of ICIAs we studied barriers to and facilitators of ICIA evaluation. In this study ten professionals of two Dutch municipalities involved in the evaluation of an ICIA participated. We conducted semi-structured interviews (n = 12), observed programme meetings (n = 4) and carried out document analysis. Data were analyzed using a thematic content approach. We learned that evaluation is hampered when it is perceived as unfeasible due to limited time and budget, a lack of evaluation knowledge or a negative evaluation attitude. Other barriers are a poor understanding of the evaluation process and its added value to optimizing the programme. Sufficient communication between involved professionals on evaluation can facilitate evaluation, as does support for evaluation of ICIAs together with stakeholders at a strategic and tactical level. To stimulate the evaluation of ICIAs, we recommend supporting professionals in securing evaluation resources, providing tailored training and tools to enhance evaluation competences and stimulating strategic communication on evaluation.

A Study of the Correlation of the Improvement of Teaching Evaluation Scores Based on Student Performance Grades

ERIC Educational Resources Information Center

Chen, Chi Yuan; Wang, Shu-Yin; Yang, Yi-Fang

2017-01-01

The purpose of the study is to explore the influence of teaching evaluations on teachers in that they might try to please their students by giving higher grades in order to get higher teaching evaluation scores. To achieve this purpose, the study analyzed the correlations between teaching evaluation scores, student's final grades and course fail…

An Interprofessional Program Evaluation Case Study: Utilizing Multiple Measures To Assess What Matters. AIR 1997 Annual Forum Paper.

ERIC Educational Resources Information Center

Delaney, Anne Marie

This paper reviews the first two years of a model program-evaluation case study which is intended to show: (1) how program evaluation can contribute to academic and professional degree programs; (2) how qualitative and quantitative techniques can be used to produce reliable measures for evaluation studies; and (3) how the role of the institutional…

Early economic evaluation of emerging health technologies: protocol of a systematic review

PubMed Central

2014-01-01

Background The concept of early health technology assessment, discussed well over a decade, has now been collaboratively implemented by industry, government, and academia to select and expedite the development of emerging technologies that may address the needs of patients and health systems. Early economic evaluation is essential to assess the value of emerging technologies, but empirical data to inform the current practice of early evaluation is limited. We propose a systematic review of early economic evaluation studies in order to better understand the current practice. Methods/design This protocol describes a systematic review of economic evaluation studies of regulated health technologies in which the evaluation is conducted prior to regulatory approval and when the technology effectiveness is not well established. Included studies must report an economic evaluation, defined as the comparative analysis of alternatives with respect to their associated costs and health consequences, and must evaluate some regulated health technology such as pharmaceuticals, biologics, high-risk medical devices, or biomarkers. We will conduct the literature search on multiple databases, including MEDLINE, EMBASE, the Centre for Reviews and Dissemination Databases, and EconLit. Additional citations will be identified via scanning reference lists and author searching. We suspect that many early economic evaluation studies are unpublished, especially those conducted for internal use only. Additionally, we use a chain-referral sampling approach to identify authors of unpublished studies who work in technology discovery and development, starting out with our contact lists and authors who published relevant studies. Citation screening and full-text review will be conducted by pairs of reviewers. Abstracted data will include those related to the decision context and decision problem of the early evaluation, evaluation methods (e.g., data sources, methods, and assumptions used to identify, measure, and value the likely effectiveness and the costs and consequences of the new technology, handling of uncertainty), and whether the study results adequately address the main study question or objective. Data will be summarized overall and stratified by publication status. Discussion This study is timely to inform early economic evaluation practice, given the international trend in early health technology assessment initiatives. PMID:25055987

Early economic evaluation of emerging health technologies: protocol of a systematic review.

PubMed

Pham, Ba'; Tu, Hong Anh Thi; Han, Dolly; Pechlivanoglou, Petros; Miller, Fiona; Rac, Valeria; Chin, Warren; Tricco, Andrea C; Paulden, Mike; Bielecki, Joanna; Krahn, Murray

2014-07-23

The concept of early health technology assessment, discussed well over a decade, has now been collaboratively implemented by industry, government, and academia to select and expedite the development of emerging technologies that may address the needs of patients and health systems. Early economic evaluation is essential to assess the value of emerging technologies, but empirical data to inform the current practice of early evaluation is limited. We propose a systematic review of early economic evaluation studies in order to better understand the current practice. This protocol describes a systematic review of economic evaluation studies of regulated health technologies in which the evaluation is conducted prior to regulatory approval and when the technology effectiveness is not well established. Included studies must report an economic evaluation, defined as the comparative analysis of alternatives with respect to their associated costs and health consequences, and must evaluate some regulated health technology such as pharmaceuticals, biologics, high-risk medical devices, or biomarkers. We will conduct the literature search on multiple databases, including MEDLINE, EMBASE, the Centre for Reviews and Dissemination Databases, and EconLit. Additional citations will be identified via scanning reference lists and author searching. We suspect that many early economic evaluation studies are unpublished, especially those conducted for internal use only. Additionally, we use a chain-referral sampling approach to identify authors of unpublished studies who work in technology discovery and development, starting out with our contact lists and authors who published relevant studies. Citation screening and full-text review will be conducted by pairs of reviewers. Abstracted data will include those related to the decision context and decision problem of the early evaluation, evaluation methods (e.g., data sources, methods, and assumptions used to identify, measure, and value the likely effectiveness and the costs and consequences of the new technology, handling of uncertainty), and whether the study results adequately address the main study question or objective. Data will be summarized overall and stratified by publication status. This study is timely to inform early economic evaluation practice, given the international trend in early health technology assessment initiatives.

Teacher Evaluation Models: Compliance or Growth Oriented?

ERIC Educational Resources Information Center

Clenchy, Kelly R.

2017-01-01

This research study reviewed literature specific to the evolution of teacher evaluation models and explored the effectiveness of standards-based evaluation models' potential to facilitate professional growth. The researcher employed descriptive phenomenology to conduct a study of teachers' perceptions of a standard-based evaluation model's…

Factors Underlying the Public's Credibility Perceptions in Educational Evaluations

ERIC Educational Resources Information Center

Jacobson, Miriam R.

2016-01-01

Understanding how evaluation audiences perceive credibility can help evaluators design evaluations and reports that support appropriate use. While researchers have studied credibility assessment among various educational stakeholders, little research has been conducted with the broader public. This study explored potential factors affecting the…

Do State Pre-K Programs Improve Children's Pre-Literacy and Math Learning? Evaluation Science Brief

ERIC Educational Resources Information Center

National Forum on Early Childhood Program Evaluation, 2008

2008-01-01

"Evaluation Science Briefs" summarize the findings and implications of a recent study evaluating the effects of an early childhood program or environment. This Brief evaluates the study "An Effectiveness-Based Evaluation of Five State Pre-Kindergarten Programs" (V. C. Wong, T. D. Cook, W. S. Barnett, and K. Jung.) States have high aspirations for…

Empirically evaluating decision-analytic models.

PubMed

Goldhaber-Fiebert, Jeremy D; Stout, Natasha K; Goldie, Sue J

2010-08-01

Model-based cost-effectiveness analyses support decision-making. To augment model credibility, evaluation via comparison to independent, empirical studies is recommended. We developed a structured reporting format for model evaluation and conducted a structured literature review to characterize current model evaluation recommendations and practices. As an illustration, we applied the reporting format to evaluate a microsimulation of human papillomavirus and cervical cancer. The model's outputs and uncertainty ranges were compared with multiple outcomes from a study of long-term progression from high-grade precancer (cervical intraepithelial neoplasia [CIN]) to cancer. Outcomes included 5 to 30-year cumulative cancer risk among women with and without appropriate CIN treatment. Consistency was measured by model ranges overlapping study confidence intervals. The structured reporting format included: matching baseline characteristics and follow-up, reporting model and study uncertainty, and stating metrics of consistency for model and study results. Structured searches yielded 2963 articles with 67 meeting inclusion criteria and found variation in how current model evaluations are reported. Evaluation of the cervical cancer microsimulation, reported using the proposed format, showed a modeled cumulative risk of invasive cancer for inadequately treated women of 39.6% (30.9-49.7) at 30 years, compared with the study: 37.5% (28.4-48.3). For appropriately treated women, modeled risks were 1.0% (0.7-1.3) at 30 years, study: 1.5% (0.4-3.3). To support external and projective validity, cost-effectiveness models should be iteratively evaluated as new studies become available, with reporting standardized to facilitate assessment. Such evaluations are particularly relevant for models used to conduct comparative effectiveness analyses.

Student Self-evaluation After Nursing Examinations: That's a Wrap.

PubMed

Butzlaff, Alice; Gaylle, Debrayh; O'Leary Kelley, Colleen

2018-04-13

Examination wrappers are a self-evaluation tool that uses metacognition to help students reflect on test performance. After examinations, rather than focus on points earned, students learn to self-identify study strategies and recognize methods of test preparation. The purpose of the study was to determine if the use of an examination wrapper after each test would encourage students to self-evaluate performance and adjust study strategies. A total of 120 undergraduate nursing students completed self-evaluations after each examination, which were analyzed using content analysis. Three general patterns emerged from student self-evaluation: effective and ineffective study strategies, understanding versus memorization of content, and nurse educator assistance.

Nuclear density evaluation on asphaltic concrete: final report.

DOT National Transportation Integrated Search

1967-04-01

This study was one of two studies designated as Research Project 62-1SB to evaluate the use of nuclear devices in highway construction. (1) The primary objective of this study was to evaluate a nuclear density device for obtaining densities on asphal...

An Evaluation System for the Online Training Programs in Meteorology and Hydrology

ERIC Educational Resources Information Center

Wang, Yong; Zhi, Xiefei

2009-01-01

This paper studies the current evaluation system for the online training program in meteorology and hydrology. CIPP model that includes context evaluation, input evaluation, process evaluation and product evaluation differs from Kirkpatrick model including reactions evaluation, learning evaluation, transfer evaluation and results evaluation in…

A Collection of Papers on Self-Study and Institutional Improvement, 2003. Volume 4: The Self-Study Process for Commission Evaluation. 2003 Edition.

ERIC Educational Resources Information Center

Van Kollenburg, Susan E., Ed.

Papers in this collection were prepared for the annual meeting of the North Central Association of Colleges and Schools. This volume contains papers related to the self-study process for Commission evaluation. Papers in chapters 1, "Self-Study and Commission Evaluation: Coordinating the Self-Study," are: (1) "Initiating the…

Evaluating Creative Thinking of Rn-Bsn Students in the Course of Clinical Case Study and Practicum

ERIC Educational Resources Information Center

Ku, Ya-Lie

2015-01-01

This case study evaluated creative thinking of RN-BSN students in the course of clinical case study and practicum. Study design used quantitative and qualitative evaluations of creative thinking of RN-BSN students by triangulation method in the course of clinical case study and practicum. Sixty RN-BSN students self-perceived the changing levels of…

Issues in evaluation: evaluating assessments of elderly people using a combination of methods.

PubMed

McEwan, R T

1989-02-01

In evaluating a health service, individuals will give differing accounts of its performance, according to their experiences of the service, and the evaluative perspective they adopt. The value of a service may also change through time, and according to the particular part of the service studied. Traditional health care evaluations have generally not accounted for this variability because of the approaches used. Studies evaluating screening or assessment programmes for the elderly have focused on programme effectiveness and efficiency, using relatively inflexible quantitative methods. Evaluative approaches must reflect the complexity of health service provision, and methods must vary to suit the particular research objective. Under these circumstances, this paper presents the case for the use of multiple triangulation in evaluative research, where differing methods and perspectives are combined in one study. Emphasis is placed on the applications and benefits of subjectivist approaches in evaluation. An example of combined methods is provided in the form of an evaluation of the Newcastle Care Plan for the Elderly.

Status and the evaluation of workplace deviance.

PubMed

Bowles, Hannah Riley; Gelfand, Michele

2010-01-01

Bias in the evaluation of workplace misbehavior is hotly debated in courts and corporations, but it has received little empirical attention. Classic sociological literature suggests that deviance by lower-status actors will be evaluated more harshly than deviance by higher-status actors. However, more recent psychological literature suggests that discrimination in the evaluation of misbehavior may be moderated by the relative status of the evaluator because status influences both rule observance and attitudes toward social hierarchy. In Study 1, the psychological experience of higher status decreased rule observance and increased preferences for social hierarchy, as we theorized. In three subsequent experiments, we tested the hypothesis that higher-status evaluators would be more discriminating in their evaluations of workplace misbehavior, evaluating fellow higher-status deviants more leniently than lower-status deviants. Results supported the hypothesized interactive effect of evaluator status and target status on the evaluation of workplace deviance, when both achieved status characteristics (Studies 2a and 2b) and ascribed status characteristics (i.e., race and gender in Study 3) were manipulated.

[Self-acceptance as adaptively resigning the self to low self-evaluation].

PubMed

Ueda, T

1996-10-01

In past studies, the concept of self-acceptance has often been confused with self-evaluation or self-esteem. The purpose of this study was to distinguish these concepts, and operationally define self-acceptance as Carl Rogers proposed: feeling all right toward the self when self-evaluation was low. Self-acceptance as adaptive resignation, a moderating variable, therefore should raise self-esteem of only those people with low self-evaluation. Self-acceptance was measured in the study as affirmative evaluation of own self-evaluation. Two hundred and forty college students, 120 each for men and women, completed a questionnaire of self-evaluative consciousness and self-esteem scales. Results of statistical analyses showed that among subjects with low self-evaluation, the higher self-acceptance, the higher the person's self-esteem. The same relation was not observed among those with high self-evaluation. Thus, it may be concluded that self-acceptance was adaptive resignation, and therefore meaningful to only those with low self-evaluation.

Principals' Experiences of Being Evaluated: A Phenomenological Study

ERIC Educational Resources Information Center

Parylo, Oksana; Zepeda, Sally J.; Bengtson, Ed

2012-01-01

This phenomenological study sought to understand principals' lived experiences of being evaluated with reliance on the principles of developmental supervision and adult learning theory. Analysis of interview data from 16 principals revealed 3 major constructs in principal evaluation: evaluation is a complex, constantly changing system; principal…

Economic analysis of the health impacts of housing improvement studies: a systematic review

PubMed Central

Fenwick, Elisabeth; Macdonald, Catriona; Thomson, Hilary

2013-01-01

Background Economic evaluation of public policies has been advocated but rarely performed. Studies from a systematic review of the health impacts of housing improvement included data on costs and some economic analysis. Examination of these data provides an opportunity to explore the difficulties and the potential for economic evaluation of housing. Methods Data were extracted from all studies included in the systematic review of housing improvement which had reported costs and economic analysis (n=29/45). The reported data were assessed for their suitability to economic evaluation. Where an economic analysis was reported the analysis was described according to pre-set definitions of various types of economic analysis used in the field of health economics. Results 25 studies reported cost data on the intervention and/or benefits to the recipients. Of these, 11 studies reported data which was considered amenable to economic evaluation. A further four studies reported conducting an economic evaluation. Three of these studies presented a hybrid ‘balance sheet’ approach and indicated a net economic benefit associated with the intervention. One cost-effectiveness evaluation was identified but the data were unclearly reported; the cost-effectiveness plane suggested that the intervention was more costly and less effective than the status quo. Conclusions Future studies planning an economic evaluation need to (i) make best use of available data and (ii) ensure that all relevant data are collected. To facilitate this, economic evaluations should be planned alongside the intervention with input from health economists from the outset of the study. When undertaken appropriately, economic evaluation provides the potential to make significant contributions to housing policy. PMID:23929616

Review of health information technology usability study methodologies

PubMed Central

Bakken, Suzanne

2011-01-01

Usability factors are a major obstacle to health information technology (IT) adoption. The purpose of this paper is to review and categorize health IT usability study methods and to provide practical guidance on health IT usability evaluation. 2025 references were initially retrieved from the Medline database from 2003 to 2009 that evaluated health IT used by clinicians. Titles and abstracts were first reviewed for inclusion. Full-text articles were then examined to identify final eligibility studies. 629 studies were categorized into the five stages of an integrated usability specification and evaluation framework that was based on a usability model and the system development life cycle (SDLC)-associated stages of evaluation. Theoretical and methodological aspects of 319 studies were extracted in greater detail and studies that focused on system validation (SDLC stage 2) were not assessed further. The number of studies by stage was: stage 1, task-based or user–task interaction, n=42; stage 2, system–task interaction, n=310; stage 3, user–task–system interaction, n=69; stage 4, user–task–system–environment interaction, n=54; and stage 5, user–task–system–environment interaction in routine use, n=199. The studies applied a variety of quantitative and qualitative approaches. Methodological issues included lack of theoretical framework/model, lack of details regarding qualitative study approaches, single evaluation focus, environmental factors not evaluated in the early stages, and guideline adherence as the primary outcome for decision support system evaluations. Based on the findings, a three-level stratified view of health IT usability evaluation is proposed and methodological guidance is offered based upon the type of interaction that is of primary interest in the evaluation. PMID:21828224

What We Do and Do Not Know about Teaching Medical Image Interpretation.

PubMed

Kok, Ellen M; van Geel, Koos; van Merriënboer, Jeroen J G; Robben, Simon G F

2017-01-01

Educators in medical image interpretation have difficulty finding scientific evidence as to how they should design their instruction. We review and comment on 81 papers that investigated instructional design in medical image interpretation. We distinguish between studies that evaluated complete offline courses and curricula, studies that evaluated e-learning modules, and studies that evaluated specific educational interventions. Twenty-three percent of all studies evaluated the implementation of complete courses or curricula, and 44% of the studies evaluated the implementation of e-learning modules. We argue that these studies have encouraging results but provide little information for educators: too many differences exist between conditions to unambiguously attribute the learning effects to specific instructional techniques. Moreover, concepts are not uniformly defined and methodological weaknesses further limit the usefulness of evidence provided by these studies. Thirty-two percent of the studies evaluated a specific interventional technique. We discuss three theoretical frameworks that informed these studies: diagnostic reasoning, cognitive schemas and study strategies. Research on diagnostic reasoning suggests teaching students to start with non-analytic reasoning and subsequently applying analytic reasoning, but little is known on how to train non-analytic reasoning. Research on cognitive schemas investigated activities that help the development of appropriate cognitive schemas. Finally, research on study strategies supports the effectiveness of practice testing, but more study strategies could be applicable to learning medical image interpretation. Our commentary highlights the value of evaluating specific instructional techniques, but further evidence is required to optimally inform educators in medical image interpretation.

[The methods within the evaluation of disease management programmes in control-group designs using the example of diabetes mellitus - a systematic literature review].

PubMed

Drabik, A; Sawicki, P T; Müller, D; Passon, A; Stock, S

2012-08-01

Disease management programmes (DMPs) were implemented in Germany in 2002. Their evaluation is required by law. Beyond the mandatory evaluation, a growing number of published studies evaluate the DMP for diabetes mellitus type 2 in a control-group design. As patients opt into the programme on a voluntary basis it is necessary to adjust the inherent selection bias between groups. The aim of this study is to review published studies which evaluate the diabetes DMP using a control-group design with respect to the methods used. A systematic literature review of electronic databases (PUBMED, Cochrane Library, EMBASE, MEDPILOT) and a hand search of reference lists of the relevant publications was conducted to identify studies evaluating the DMP diabetes mellitus in a control-group design. 8 studies were included in the systematic literature review. 4 studies gathered retrospective claims data from sickness funds, one from physician's records, one study used prospective data from ambulatory care, and 2 studies were based on one patient survey. Methods used for adjustment of selection bias included exact matching, matching using propensity score methods, age-adjusted and sex-separated analysis, and adjustment in a regression model/analysis of covariance. One study did not apply adjustment methods. The intervention period ranged from 1 day to 4 years. Considered outcomes of studies (surrogate parameter, diabetes complications, mortality, quality of life, and claim data) depended on the database. In the evaluation of the DMP diabetes mellitus based on a control-group design neither the database nor the methods used for selection bias adjustment were consistent in the available studies. Effectiveness of DMPs cannot be judged based on this review due to heterogeneity of study designs. To allow for a comprehensive programme evaluation standardised minimum requirements for the evaluation of DMPs in the control group design are required. © Georg Thieme Verlag KG Stuttgart · New York.

A Tentative Study on the Evaluation of Community Health Service Quality*

NASA Astrophysics Data System (ADS)

Ma, Zhi-qiang; Zhu, Yong-yue

Community health service is the key point of health reform in China. Based on pertinent studies, this paper constructed an indicator system for the community health service quality evaluation from such five perspectives as visible image, reliability, responsiveness, assurance and sympathy, according to service quality evaluation scale designed by Parasuraman, Zeithaml and Berry. A multilevel fuzzy synthetical evaluation model was constructed to evaluate community health service by fuzzy mathematics theory. The applicability and maneuverability of the evaluation indicator system and evaluation model were verified by empirical analysis.

The evaluability bias in charitable giving: Saving administration costs or saving lives?

PubMed Central

Caviola, Lucius; Faulmüller, Nadira; Everett, Jim. A. C.; Savulescu, Julian; Kahane, Guy

2014-01-01

We describe the “evaluability bias”: the tendency to weight the importance of an attribute in proportion to its ease of evaluation. We propose that the evaluability bias influences decision making in the context of charitable giving: people tend to have a strong preference for charities with low overhead ratios (lower administrative expenses) but not for charities with high cost-effectiveness (greater number of saved lives per dollar), because the former attribute is easier to evaluate than the latter. In line with this hypothesis, we report the results of four studies showing that, when presented with a single charity, people are willing to donate more to a charity with low overhead ratio, regardless of cost-effectiveness. However, when people are presented with two charities simultaneously—thereby enabling comparative evaluation—they base their donation behavior on cost-effectiveness (Study 1). This suggests that people primarily value cost-effectiveness but manifest the evaluability bias in cases where they find it difficult to evaluate. However, people seem also to value a low overhead ratio for its own sake (Study 2). The evaluability bias effect applies to charities of different domains (Study 3). We also show that overhead ratio is easier to evaluate when its presentation format is a ratio, suggesting an inherent reference point that allows meaningful interpretation (Study 4). PMID:25279024

Veterinary and human vaccine evaluation methods

PubMed Central

Knight-Jones, T. J. D.; Edmond, K.; Gubbins, S.; Paton, D. J.

2014-01-01

Despite the universal importance of vaccines, approaches to human and veterinary vaccine evaluation differ markedly. For human vaccines, vaccine efficacy is the proportion of vaccinated individuals protected by the vaccine against a defined outcome under ideal conditions, whereas for veterinary vaccines the term is used for a range of measures of vaccine protection. The evaluation of vaccine effectiveness, vaccine protection assessed under routine programme conditions, is largely limited to human vaccines. Challenge studies under controlled conditions and sero-conversion studies are widely used when evaluating veterinary vaccines, whereas human vaccines are generally evaluated in terms of protection against natural challenge assessed in trials or post-marketing observational studies. Although challenge studies provide a standardized platform on which to compare different vaccines, they do not capture the variation that occurs under field conditions. Field studies of vaccine effectiveness are needed to assess the performance of a vaccination programme. However, if vaccination is performed without central co-ordination, as is often the case for veterinary vaccines, evaluation will be limited. This paper reviews approaches to veterinary vaccine evaluation in comparison to evaluation methods used for human vaccines. Foot-and-mouth disease has been used to illustrate the veterinary approach. Recommendations are made for standardization of terminology and for rigorous evaluation of veterinary vaccines. PMID:24741009

Economic evaluations in gastroenterology in Brazil: A systematic review.

PubMed

de Paiva Haddad, Luciana Bertocco; Decimoni, Tassia Cristina; Turri, Jose Antonio; Leandro, Roseli; de Soárez, Patrícia Coelho

2016-02-06

To systematically review economic evaluations in gastroenterology, relating to Brazil, published between 1980 and 2013. We selected full and partial economic evaluations from among those retrieved by searching the following databases: MEDLINE (PubMed); Excerpta Medica; the Latin American and Caribbean Health Sciences Literature database; the Scientific Electronic Library Online; the database of the Centre for Reviews and Dissemination; the National Health Service (NHS) Economic Evaluation Database; the NHS Health Technology Assessment database; the Health Economics database of the Brazilian Virtual Library of Health; Scopus; Web of Science; and the Brazilian Network for the Evaluation of Health Technologies. Two researchers, working independently, selected the studies and extracted the data. We identified 535 health economic evaluations relating to Brazil and published in the 1980-2013 period. Of those 535 articles, only 40 dealt with gastroenterology. Full and partial economic evaluations respectively accounted for 23 (57.5%) and 17 (42.5%) of the 40 studies included. Among the 23 full economic evaluations, there were 11 cost-utility analyses, seven cost-effectiveness analyses, four cost-consequence analyses, and one cost-minimization analysis. Of the 40 studies, 25 (62.5%) evaluated medications; 7 (17.5%) evaluated procedures; and 3 (7.5%) evaluated equipment. Most (55%) of the studies were related to viral hepatitis, and most (63.4%) were published after 2010. Other topics included gastrointestinal cancer, liver transplantation, digestive diseases and hernias. Over the 33-year period examined, the number of such economic evaluations relating to Brazil, especially of those evaluating medications for the treatment of hepatitis, increased considerably. Further studies are needed in order to ensure that expenditures on health care in Brazil are made as fairly and efficiently as possible.

Economic evaluations in gastroenterology in Brazil: A systematic review

PubMed Central

de Paiva Haddad, Luciana Bertocco; Decimoni, Tassia Cristina; Turri, Jose Antonio; Leandro, Roseli; de Soárez, Patrícia Coelho

2016-01-01

AIM: To systematically review economic evaluations in gastroenterology, relating to Brazil, published between 1980 and 2013. METHODS: We selected full and partial economic evaluations from among those retrieved by searching the following databases: MEDLINE (PubMed); Excerpta Medica; the Latin American and Caribbean Health Sciences Literature database; the Scientific Electronic Library Online; the database of the Centre for Reviews and Dissemination; the National Health Service (NHS) Economic Evaluation Database; the NHS Health Technology Assessment database; the Health Economics database of the Brazilian Virtual Library of Health; Scopus; Web of Science; and the Brazilian Network for the Evaluation of Health Technologies. Two researchers, working independently, selected the studies and extracted the data. RESULTS: We identified 535 health economic evaluations relating to Brazil and published in the 1980-2013 period. Of those 535 articles, only 40 dealt with gastroenterology. Full and partial economic evaluations respectively accounted for 23 (57.5%) and 17 (42.5%) of the 40 studies included. Among the 23 full economic evaluations, there were 11 cost-utility analyses, seven cost-effectiveness analyses, four cost-consequence analyses, and one cost-minimization analysis. Of the 40 studies, 25 (62.5%) evaluated medications; 7 (17.5%) evaluated procedures; and 3 (7.5%) evaluated equipment. Most (55%) of the studies were related to viral hepatitis, and most (63.4%) were published after 2010. Other topics included gastrointestinal cancer, liver transplantation, digestive diseases and hernias. Over the 33-year period examined, the number of such economic evaluations relating to Brazil, especially of those evaluating medications for the treatment of hepatitis, increased considerably. CONCLUSION: Further studies are needed in order to ensure that expenditures on health care in Brazil are made as fairly and efficiently as possible. PMID:26855823

78 FR 41926 - Proposed Information Collection Request; Comment Request; Performance Evaluation Studies on...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-12

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OECA-2013-0413; FRL--9832-8] Proposed Information Collection Request; Comment Request; Performance Evaluation Studies on Wastewater Laboratories (Renewal); EPA... request (ICR), ``Performance Evaluation Studies on Wastewater Laboratories'' (EPA ICR No. 0234.11, OMB...

Economic Evaluation of Obesity Prevention in Early Childhood: Methods, Limitations and Recommendations.

PubMed

Döring, Nora; Mayer, Susanne; Rasmussen, Finn; Sonntag, Diana

2016-09-13

Despite methodological advances in the field of economic evaluations of interventions, economic evaluations of obesity prevention programmes in early childhood are seldom conducted. The aim of the present study was to explore existing methods and applications of economic evaluations, examining their limitations and making recommendations for future cost-effectiveness assessments. A systematic literature search was conducted using PubMed, Cochrane Library, the British National Health Service Economic Evaluation Databases and EconLit. Eligible studies included trial-based or simulation-based cost-effectiveness analyses of obesity prevention programmes targeting preschool children and/or their parents. The quality of included studies was assessed. Of the six studies included, five were intervention studies and one was based on a simulation approach conducted on secondary data. We identified three main conceptual and methodological limitations of their economic evaluations: Insufficient conceptual approach considering the complexity of childhood obesity, inadequate measurement of effects of interventions, and lack of valid instruments to measure child-related quality of life and costs. Despite the need for economic evaluations of obesity prevention programmes in early childhood, only a few studies of varying quality have been conducted. Moreover, due to methodological and conceptual weaknesses, they offer only limited information for policy makers and intervention providers. We elaborate reasons for the limitations of these studies and offer guidance for designing better economic evaluations of early obesity prevention.

Economic Evaluation of Obesity Prevention in Early Childhood: Methods, Limitations and Recommendations

PubMed Central

Döring, Nora; Mayer, Susanne; Rasmussen, Finn; Sonntag, Diana

2016-01-01

Despite methodological advances in the field of economic evaluations of interventions, economic evaluations of obesity prevention programmes in early childhood are seldom conducted. The aim of the present study was to explore existing methods and applications of economic evaluations, examining their limitations and making recommendations for future cost-effectiveness assessments. A systematic literature search was conducted using PubMed, Cochrane Library, the British National Health Service Economic Evaluation Databases and EconLit. Eligible studies included trial-based or simulation-based cost-effectiveness analyses of obesity prevention programmes targeting preschool children and/or their parents. The quality of included studies was assessed. Of the six studies included, five were intervention studies and one was based on a simulation approach conducted on secondary data. We identified three main conceptual and methodological limitations of their economic evaluations: Insufficient conceptual approach considering the complexity of childhood obesity, inadequate measurement of effects of interventions, and lack of valid instruments to measure child-related quality of life and costs. Despite the need for economic evaluations of obesity prevention programmes in early childhood, only a few studies of varying quality have been conducted. Moreover, due to methodological and conceptual weaknesses, they offer only limited information for policy makers and intervention providers. We elaborate reasons for the limitations of these studies and offer guidance for designing better economic evaluations of early obesity prevention. PMID:27649218

Understanding of evaluation capacity building in practice: a case study of a national medical education organization.

PubMed

Sarti, Aimee J; Sutherland, Stephanie; Landriault, Angele; DesRosier, Kirk; Brien, Susan; Cardinal, Pierre

2017-01-01

Evaluation capacity building (ECB) is a topic of great interest to many organizations as they face increasing demands for accountability and evidence-based practices. ECB is about building the knowledge, skills, and attitudes of organizational members, the sustainability of rigorous evaluative practices, and providing the resources and motivations to engage in ongoing evaluative work. There exists a solid foundation of theoretical research on ECB, however, understanding what ECB looks like in practice is relatively thin. Our purpose was to investigate what ECB looks like firsthand within a national medical educational organization. The context for this study was the Acute Critical Events Simulation (ACES) organization in Canada, which has successfully evolved into a national educational program, driven by physicians. We conducted an exploratory qualitative study to better understand and describe ECB in practice. In doing so, interviews were conducted with program leaders and instructors so as to gain a richer understanding of evaluative processes and practices. A total of 21 individuals participated in the semistructured interviews. Themes from our qualitative data analysis included the following: evaluation knowledge, skills, and attitudes, use of evaluation findings, shared evaluation beliefs and commitment, evaluation frameworks and processes, and resources dedicated to evaluation. The national ACES organization was a useful case study to explore ECB in practice. The ECB literature provided a solid foundation to understand the purpose and nuances of ECB. This study added to the paucity of studies focused on examining ECB in practice. The most important lesson learned was that the organization must have leadership who are intrinsically motivated to employ and use evaluation data to drive ongoing improvements within the organization. Leaders who are intrinsically motivated will employ risk taking when evaluation practices and processes may be somewhat unfamiliar. Creating and maintaining a culture of data use and ongoing inquiry have enabled national ACES to achieve a sustainable evaluation practice.

Addressing Enterprise-Level Information System Deficiencies

DTIC Science & Technology

2015-03-26

goals and effectiveness. This case study evaluates the Depot Source of Repair (DSOR) team and how it has addressed the USAF’s enterprise- level IS...deficiencies. A framework created from the literature review is used to evaluate the DSOR team’s IS called DSOR II. The case study evaluation ...7 IS Design Evaluation

Teacher Evaluation Reform: Focus, Feedback, and Fear

ERIC Educational Resources Information Center

Donaldson, Morgaen L.

2016-01-01

How are teachers experiencing the more rigorous teacher evaluation systems that many states have mandated in recent years? Donaldson, who has studied teacher evaluation reform over the past eight years, shares insights from a study of 14 Connecticut districts that have implemented the state's 2012 teacher evaluation reforms. In surveys and…

A Database Evaluation Based on Information Needs of Academic Social Scientists.

ERIC Educational Resources Information Center

Buterbaugh, Nancy Toth

This study evaluates two databases, "Historical Abstracts" and REESWeb, to determine their effectiveness in supporting academic social science research. While many performance evaluations gather quantitative data from isolated query and response transactions, this study is a qualitative evaluation of the databases in the context of…

Evaluation and Communication: Using a Communication Audit to Evaluate Organizational Communication

ERIC Educational Resources Information Center

Hogard, Elaine; Ellis, Roger

2006-01-01

This article identifies a surprising dearth of studies that explicitly link communication and evaluation at substantive, theoretical, and methodological levels. A three-fold typology of evaluation studies referring to communication is proposed and examples given. The importance of organizational communication in program delivery is stressed and…

Inside the Black Box--An Implementation Evaluation Case Study

ERIC Educational Resources Information Center

Rector, Patricia; Bakacs, Michele; Rowe, Amy; Barbour, Bruce

2016-01-01

The case study presented in this article is an example of an implementation evaluation. The evaluation investigated significant components of the implementation of a long-term environmental educational program. Direct observation, evaluation-specific survey data, and historical data were used to determine program integrity as identified by…

Research Governance and the Role of Evaluation: A Comparative Study

ERIC Educational Resources Information Center

Molas-Gallart, Jordi

2012-01-01

Through a comparative study of the United Kingdom and Spain, this article addresses the effect of different research governance structures on the functioning and uses of research evaluation. It distinguishes three main evaluation uses: distributive, improvement, and controlling. Research evaluation in the United Kingdom plays important…

Practical Considerations in Evaluating Patient/Consumer Health Education Programs.

ERIC Educational Resources Information Center

Bryant, Nancy H.

This report contains brief descriptions of seven evaluative efforts and outcomes of health education programs, some considerations of problems encountered in evaluating the programs, and detailed descriptions of two case studies: (1) a process evaluation of preoperative teaching and (2) a retrospective study of visiting nurse association use by…

The Effect of Evaluation on Performance: Evidence from Longitudinal Student Achievement Data of Mid-Career Teachers. NBER Working Paper No. 16877

ERIC Educational Resources Information Center

Taylor, Eric S.; Tyler, John H.

2011-01-01

The effect of evaluation on employee performance is traditionally studied in the context of the principal-agent problem. Evaluation can, however, also be characterized as an investment in the evaluated employee's human capital. We study a sample of mid-career public school teachers where we can consider these two types of evaluation effect…

A Comparison of the Autism Treatment Evaluation Checklist (ATEC) and the Childhood Autism Rating Scale (CARS) for the Quantitative Evaluation of Autism

ERIC Educational Resources Information Center

Geier, David A.; Kern, Janet K.; Geier, Mark R.

2013-01-01

The purpose of this study was to evaluate scores generated from the Autism Treatment Evaluation Checklist (ATEC), a parent-rated measure, and those derived from professionally completed Childhood Autism Rating Scale (CARS) evaluations. A cohort of 56 participants diagnosed with an autism spectrum disorder was used for the study, and each child was…

The scope of costs in alcohol studies: Cost-of-illness studies differ from economic evaluations.

PubMed

van Gils, Paul F; Hamberg-van Reenen, Heleen H; van den Berg, Matthijs; Tariq, Luqman; de Wit, G Ardine

2010-07-06

Alcohol abuse results in problems on various levels in society. In terms of health, alcohol abuse is not only an important risk factor for chronic disease, but it is also related to injuries. Social harms which can be related to drinking include interpersonal problems, work problems, violent and other crimes. The scope of societal costs related to alcohol abuse in principle should be the same for both economic evaluations and cost-of-illness studies. In general, economic evaluations report a small part of all societal costs. To determine the cost- effectiveness of an intervention it is necessary that all costs and benefits are included. The purpose of this study is to describe and quantify the difference in societal costs incorporated in economic evaluations and cost-of-illness studies on alcohol abuse. To investigate the economic costs attributable to alcohol in cost-of-illness studies we used the results of a recent systematic review (June 2009). We performed a PubMed search to identify economic evaluations on alcohol interventions. Only economic evaluations in which two or more interventions were compared from a societal perspective were included. The proportion of health care costs and the proportion of societal costs were estimated in both type of studies. The proportion of healthcare costs in cost-of-illness studies was 17% and the proportion of societal costs 83%. In economic evaluations, the proportion of healthcare costs was 57%, and the proportion of societal costs was 43%. The costs included in economic evaluations performed from a societal perspective do not correspond with those included in cost-of-illness studies. Economic evaluations on alcohol abuse underreport true societal cost of alcohol abuse. When considering implementation of alcohol abuse interventions, policy makers should take into account that economic evaluations from the societal perspective might underestimate the total effects and costs of interventions.

Automatic Evaluations and Exercising: Systematic Review and Implications for Future Research.

PubMed

Schinkoeth, Michaela; Antoniewicz, Franziska

2017-01-01

The general purpose of this systematic review was to summarize, structure and evaluate the findings on automatic evaluations of exercising. Studies were eligible for inclusion if they reported measuring automatic evaluations of exercising with an implicit measure and assessed some kind of exercise variable. Fourteen nonexperimental and six experimental studies (out of a total N = 1,928) were identified and rated by two independent reviewers. The main study characteristics were extracted and the grade of evidence for each study evaluated. First, results revealed a large heterogeneity in the applied measures to assess automatic evaluations of exercising and the exercise variables. Generally, small to large-sized significant relations between automatic evaluations of exercising and exercise variables were identified in the vast majority of studies. The review offers a systematization of the various examined exercise variables and prompts to differentiate more carefully between actually observed exercise behavior (proximal exercise indicator) and associated physiological or psychological variables (distal exercise indicator). Second, a lack of transparent reported reflections on the differing theoretical basis leading to the use of specific implicit measures was observed. Implicit measures should be applied purposefully, taking into consideration the individual advantages or disadvantages of the measures. Third, 12 studies were rated as providing first-grade evidence (lowest grade of evidence), five represent second-grade and three were rated as third-grade evidence. There is a dramatic lack of experimental studies, which are essential for illustrating the cause-effect relation between automatic evaluations of exercising and exercise and investigating under which conditions automatic evaluations of exercising influence behavior. Conclusions about the necessity of exercise interventions targeted at the alteration of automatic evaluations of exercising should therefore not be drawn too hastily.

Automatic Evaluations and Exercising: Systematic Review and Implications for Future Research

PubMed Central

Schinkoeth, Michaela; Antoniewicz, Franziska

2017-01-01

The general purpose of this systematic review was to summarize, structure and evaluate the findings on automatic evaluations of exercising. Studies were eligible for inclusion if they reported measuring automatic evaluations of exercising with an implicit measure and assessed some kind of exercise variable. Fourteen nonexperimental and six experimental studies (out of a total N = 1,928) were identified and rated by two independent reviewers. The main study characteristics were extracted and the grade of evidence for each study evaluated. First, results revealed a large heterogeneity in the applied measures to assess automatic evaluations of exercising and the exercise variables. Generally, small to large-sized significant relations between automatic evaluations of exercising and exercise variables were identified in the vast majority of studies. The review offers a systematization of the various examined exercise variables and prompts to differentiate more carefully between actually observed exercise behavior (proximal exercise indicator) and associated physiological or psychological variables (distal exercise indicator). Second, a lack of transparent reported reflections on the differing theoretical basis leading to the use of specific implicit measures was observed. Implicit measures should be applied purposefully, taking into consideration the individual advantages or disadvantages of the measures. Third, 12 studies were rated as providing first-grade evidence (lowest grade of evidence), five represent second-grade and three were rated as third-grade evidence. There is a dramatic lack of experimental studies, which are essential for illustrating the cause-effect relation between automatic evaluations of exercising and exercise and investigating under which conditions automatic evaluations of exercising influence behavior. Conclusions about the necessity of exercise interventions targeted at the alteration of automatic evaluations of exercising should therefore not be drawn too hastily. PMID:29250022

Evaluating For-Profit Higher Education: Evidence from the Education Longitudinal Study. A CAPSEE Working Paper

ERIC Educational Resources Information Center

Liu, Yuen Ting; Belfield, Clive

2014-01-01

This study evaluates the postsecondary and labor market outcomes of students who attended for-profit colleges. The evaluation complements a similar study by Deming, Goldin, and Katz (2012) that found significant differences in outcomes between students in for-profit colleges and those in other sectors. In this study we use the Education…

Study design considerations in evaluating environmental impacts

Treesearch

Stan T. Lebow; Paul A. Cooper; Patricia Lebow

2006-01-01

The purpose of this chapter is to make the reader aware of how choices in study parameters may influence the outcome of treated-wood environmental impact evaluations. Evaluation of the leaching and environmental accumulation of preservatives from treated wood is a complex process. and many factors can influence the results of such studies. In laboratory studies, the...

Evaluation and Assessment Processes in Nebraska Public Schools. A Staff Report. Education Interim Study LR 181.

ERIC Educational Resources Information Center

Nebraska Legislative Council, Lincoln. Legislative Research Div.

During the spring of 1987, the National Conference of State Legislatures awarded the Nebraska Legislature a cost-sharing award to study local school evaluation processes. Embodied in Legislative Resolution 181, which has the purpose of studying school evaluation procedures, the study attempts to provide legislators, educators, local school…

Design and Implementation of a Multi-Strategy, Collegewide Program of Evaluation and Planning: The Mercy College Self-Study Project.

ERIC Educational Resources Information Center

Kraetzer, Mary C.; And Others

The rationale, strategies, and methods of The Mercy College Self-Study Project are considered, and evaluation instruments are provided. This program of institutional evaluation and planning was initiated in 1980 and consists of: standardized surveys, a 10-year longitudinal (panel) study, and academic department self-studies. Questionnaires…

Evaluation Studies of Robotic Rollators by the User Perspective: A Systematic Review.

PubMed

Werner, Christian; Ullrich, Phoebe; Geravand, Milad; Peer, Angelika; Hauer, Klaus

2016-01-01

Robotic rollators enhance the basic functions of established devices by technically advanced physical, cognitive, or sensory support to increase autonomy in persons with severe impairment. In the evaluation of such ambient assisted living solutions, both the technical and user perspectives are important to prove usability, effectiveness and safety, and to ensure adequate device application. The aim of this systematic review is to summarize the methodology of studies evaluating robotic rollators with focus on the user perspective and to give recommendations for future evaluation studies. A systematic literature search up to December 31, 2014, was conducted based on the Cochrane Review methodology using the electronic databases PubMed and IEEE Xplore. Articles were selected according to the following inclusion criteria: evaluation studies of robotic rollators documenting human-robot interaction, no case reports, published in English language. Twenty-eight studies were identified that met the predefined inclusion criteria. Large heterogeneity in the definitions of the target user group, study populations, study designs and assessment methods was found across the included studies. No generic methodology to evaluate robotic rollators could be identified. We found major methodological shortcomings related to insufficient sample descriptions and sample sizes, and lack of appropriate, standardized and validated assessment methods. Long-term use in habitual environment was also not evaluated. Apart from the heterogeneity, methodological deficits in most of the identified studies became apparent. Recommendations for future evaluation studies include: clear definition of target user group, adequate selection of subjects, inclusion of other assistive mobility devices for comparison, evaluation of the habitual use of advanced prototypes, adequate assessment strategy with established, standardized and validated methods, and statistical analysis of study results. Assessment strategies may additionally focus on specific functionalities of the robotic rollators allowing an individually tailored assessment of innovative features to document their added value. © 2016 S. Karger AG, Basel.

A systematic review of economic evaluations of population-based sodium reduction interventions

PubMed Central

Hope, Silvia F.; Webster, Jacqui; Trieu, Kathy; Pillay, Arti; Ieremia, Merina; Bell, Colin; Snowdon, Wendy; Neal, Bruce; Moodie, Marj

2017-01-01

Objective To summarise evidence describing the cost-effectiveness of population-based interventions targeting sodium reduction. Methods A systematic search of published and grey literature databases and websites was conducted using specified key words. Characteristics of identified economic evaluations were recorded, and included studies were appraised for reporting quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Results Twenty studies met the study inclusion criteria and received a full paper review. Fourteen studies were identified as full economic evaluations in that they included both costs and benefits associated with an intervention measured against a comparator. Most studies were modelling exercises based on scenarios for achieving salt reduction and assumed effects on health outcomes. All 14 studies concluded that their specified intervention(s) targeting reductions in population sodium consumption were cost-effective, and in the majority of cases, were cost saving. Just over half the studies (8/14) were assessed as being of ‘excellent’ reporting quality, five studies fell into the ‘very good’ quality category and one into the ‘good’ category. All of the identified evaluations were based on modelling, whereby inputs for all the key parameters including the effect size were either drawn from published datasets, existing literature or based on expert advice. Conclusion Despite a clear increase in evaluations of salt reduction programs in recent years, this review identified relatively few economic evaluations of population salt reduction interventions. None of the studies were based on actual implementation of intervention(s) and the associated collection of new empirical data. The studies universally showed that population-based salt reduction strategies are likely to be cost effective or cost saving. However, given the reliance on modelling, there is a need for the effectiveness of new interventions to be evaluated in the field using strong study designs and parallel economic evaluations. PMID:28355231

Women's Studies Collections: A Checklist Evaluation

ERIC Educational Resources Information Center

Bolton, Brooke A.

2009-01-01

A checklist evaluation on thirty-seven Women's Studies programs conducted using the individual institutions' online public access catalogs (OPACs) is presented. Although Women's Studies collections are very difficult to build, an evaluation of existing programs shows that collections, for the most part, have managed substantial coverage of the…

Online Continuing Professional Education: An Evaluative Case Study

ERIC Educational Resources Information Center

Pullen, Darren L.

2005-01-01

An evaluation study, assessing the pedagogical and instructional design (e-pedagogy) effectiveness of online continuing professional education (CPE) courses offered by a large Australasian CPE provider to health care professionals (HCPs). The study used a naturalistic theory approach in conjunction with a multilevel evaluation to examine the…

77 FR 15370 - Agency Information Collection Request. 60-Day Public Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-15

.... Proposed Project: Teen Pregnancy Prevention Replication Evaluation Study: Follow-up Data Collection--OMB No... Evaluation (ASPE), the Centers for Disease Control and Prevention (CDC), and the Administration for Children... with ASPE the Teen Pregnancy Prevention Replication Evaluation Study (TPP Replication Study). The TPP...

7 CFR 295.4 - Program evaluation status reports.

Code of Federal Regulations, 2011 CFR

2011-01-01

... completed studies may be obtained by writing the Director, Office of Analysis and Evaluation, Food and... evaluation status reports. FNS also publishes summaries of objectives and findings of completed studies and...

Expression of Cyclin d1 protein and CCND1 та PNKP genes in peripheral blood mononuclear cells in clean up worker of Chornobyl accident with different state of immune system.

PubMed

Bazyka, D A; Kubashko, A V; Ilyenko, I M; Belyaev, O A; Pleskach, O J

2015-12-01

to investigate the Cyclin D1+ cells levels changes, associated CCND1 and PNKP genes in peripheral blood mononuclear cells in clean up workers of Chornobyl accident with different state of immune system in depends on the dose irradiation. Relative level of Cyclin D1+cells in peripheral blood mononuclears of 39 clean up workers, men, irradiated in dose range (0,01-2,00) Gy have been analyzed. Immunological status of examinee' subjects was determined by CD3/19, CD4/8, CD3/HLA DR, СD3/16/56 testing using flow cytometry method and Ig A,M,G testing by immunoenzymatic assay in blood. CCND1 та PNKP gene expression, which associated with Cyclin D1 metabolism, was conducted using PCR real time method. The obtained results were compared in relation to data from 18 healthy men, who had no contact with ionizing radiation over then nature background. Аnalyzed data of the nuclear controller of cell cycle - Cyclin D1 protein expression changes and related CCND1 та PNKP genes in peripheral blood mononuclear cells in clean up workers Chornobyl accident with different status of immune system in remote period after exposure is represented. It is shown, that in examinees' subjects exposed in dose > 0,1 Gy percentage of Суclin D1+ cells is elevated against normal range and correlates with dose of radiation (rs = 0,417, p = 0,048). Normal range deflation of relative amount of Cyclin D1+cells connects with changes in cellular and humoral immunity. Decline of relative amount of Cyclin D1+ cells below the control level following CD3+ lymphocytes decrease and CD3 16+56+ elevation in clean up workers exposed in dose < 0,35 Gy. Increase of relative amount of Cyclin D1+ cells above the control range associates with CD3+ fall together with tendency of CD3+16+56+ lymphocytes fall that attends the IgG elevation in examinees' subjects with dose > 0,35 Gy. Percentage of Cyclin D1+ cells correlates with CD3 16+56+ (rs = 0,872, p = 0,049), CD8+ and IgG (rs = 0,683, p = 0,042; rs = 0,809, p = 0,014), CD4+ (rs = 0,602, p = 0,029), CD19+ and IgM (rs = 0,604, p = 0,017; rs = 0,538, p = 0,038) under condition of increased level CD4+, CD19+, Іreg. and IgG accordantly. Reviled decrease the CCND1 and PNKP gene expression in clean up workers exposed in dose > 0,1 Gy following appearance of correlation between (relative quantification) RQ PNKP and irradiation dose (rs = 0,638, p = 0,035) and also with RQ PNKP and percentage of Cyclin D1+ cells (rs = 0,792, p = 0,034).Concusions. Reveled changes in expression of Cyclin D1+ cells and regulation of related genes may point on possi ble radiation associated firm molecular disturbances occurred during elimination of consequences of Chornobyl accident, that could be a potential basis for cell and humoral communicative links breach in immune system result ing in elevation of stochastic effects like oncopathology in clean up workers of Chornobyl accident in remote peri od after exposure. D. A. Bazyka, A. V. Kubashko, I. M. Ilyenko, O. A. Belyaev, O. J. Pleskach.

Evaluation of a proposed expert system development methodology: Two case studies

NASA Technical Reports Server (NTRS)

Gilstrap, Lewey

1990-01-01

Two expert system development projects were studied to evaluate a proposed Expert Systems Development Methodology (ESDM). The ESDM was developed to provide guidance to managers and technical personnel and serve as a standard in the development of expert systems. It was agreed that the proposed ESDM must be evaluated before it could be adopted; therefore a study was planned for its evaluation. This detailed study is now underway. Before the study began, however, two ongoing projects were selected for a retrospective evaluation. They were the Ranging Equipment Diagnostic Expert System (REDEX) and the Backup Control Mode Analysis and Utility System (BCAUS). Both projects were approximately 1 year into development. Interviews of project personnel were conducted, and the resulting data was used to prepare the retrospective evaluation. Decision models of the two projects were constructed and used to evaluate the completeness and accuracy of key provisions of ESDM. A major conclusion reached from these case studies is that suitability and risk analysis should be required for all AI projects, large and small. Further, the objectives of each stage of development during a project should be selected to reduce the next largest area of risk or uncertainty on the project.

Usability Study and Heuristic Evaluation of the Applied Robotics for Installations and Base Operations (ARIBO) Driverless Vehicle Reservation Application ARIBO Mobile

DTIC Science & Technology

2017-03-01

ARL-TN-0814 ● MAR 2017 US Army Research Laboratory Usability Study and Heuristic Evaluation of the Applied Robotics for...ARL-TN-0814 ● MAR 2017 US Army Research Laboratory Usability Study and Heuristic Evaluation of the Applied Robotics for...Heuristic Evaluation of the Applied Robotics for Installations and Base Operations (ARIBO) Driverless Vehicle Reservation Application ARIBO Mobile 5a

Evaluation of STD/AIDS prevention programs: a review of approaches and methodologies.

PubMed

da Cruz, Marly Marques; dos Santos, Elizabeth Moreira; Monteiro, Simone

2007-05-01

The article presents a review of approaches and methodologies in the evaluation of STD/AIDS prevention programs, searching for theoretical and methodological support for the institutionalization of evaluation and decision-making. The review included the MEDLINE, SciELO, and ISI Web of Science databases and other sources like textbooks and congress abstracts from 1990 to 2005, with the key words: "evaluation", "programs", "prevention", "STD/AIDS", and similar terms. The papers showed a predominance of quantitative outcome or impact evaluative studies with an experimental or quasi-experimental design. The main use of evaluation is accountability, although knowledge output and program improvement were also identified in the studies. Only a few evaluative studies contemplate process evaluation and its relationship to the contexts. The review aimed to contribute to the debate on STD/AIDS, which requires more effective, consistent, and sustainable decisions in the field of prevention.

75 FR 68829 - Agency Information Collection Activities: Comment Request; Generic Survey Clearance for the...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-09

... evaluation studies. In order to conduct program- or portfolio-level evaluations, however, both experimental and quasi-experimental evaluation research studies on STEM education interventions require researchers...

Evaluation and impact of cardiotocography training programmes: a systematic review.

PubMed

Pehrson, C; Sorensen, J L; Amer-Wåhlin, I

2011-07-01

The interpretation and management of cardiotocography (CTG) tracings are often criticised in obstetric malpractice cases. As a consequence, regular CTG training has been recommended, even though little is known about the effect of CTG training. To perform a systematic review of the existing literature on studies on CTG training in order to assess educational strategies, evaluation of training programmes, and impact of training programmes. The Medline database was searched to identify studies describing and/or evaluating CTG training programmes. The literature search resulted in 409 citations. Twenty studies describing and evaluating CTG training programmes were included. There was no restriction on study design. Data regarding study design, study quality, educational strategies used for training in CTG interpretation and decision making, target groups, number of participants, methods used for evaluation, quality of evaluation, level of evaluation and results of training was extracted from 20 articles, and analysed using Kirkpatrick's four-level model for the evaluation of education. Training was associated with improvements on all Kirkpatrick levels, resulting in increased CTG knowledge and interpretive skills, higher interobserver agreement, better management of intrapartum CTG, and improved quality of care. Computer-based training (CBT) might be less time-consuming than classroom teaching. Clinical skills seem to decrease faster than theoretical knowledge. Training can improve CTG competence and clinical practise. Further research on CBT, test-enhanced learning and long-term retention, evaluation of training and impact on clinical outcomes is recommended. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

Health Science students' evaluation of courses and Instructors: the effect of response rate and class size interaction.

PubMed

Kuwaiti, Ahmed Al

2015-01-01

This study aims at investigating the effect of response rate and class size interaction on students' evaluation of instructors and the courses offered at heath science colleges in Saudi Arabia. A retrospective study design was adapted to ascertain Course Evaluation Surveys (CES) conducted at the health science colleges of the University of Dammam [UOD] in the academic year 2013-2014. Accordingly, the CES data which was downloaded from an exclusive online application 'UDQUEST' which includes 337 different courses and 15,264 surveys were utilized in this study. Two-way analysis of variance was utilized to test whether there is any significant interaction between the class size and the response rate on the students' evaluation of courses and instructors. The study showed that high response rate is required for student evaluation of instructors at Health Science colleges when the class size is small whereas a medium response rate is required for students' evaluation of courses. On the other hand, when the class size is medium, a medium or high response rate is needed for students' evaluation of both instructors and courses. The results of this study recommend that the administrators of the health science colleges to be aware of the interpretation of students' evaluations of courses and instructors. The study also suggests that the interaction between response rate and class size is a very important factor that needs to be taken into consideration while interpreting the findings of the students' evaluation of instructors and courses.

42 CFR 456.242 - UR plan requirements for medical care evaluation studies.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Utilization Control: Mental Hospitals Ur Plan: Medical Care Evaluation Studies § 456.242 UR plan requirements for medical care... evaluation studies in the mental hospital; (2) Documents for each study— (i) Its results; and (ii) How the...

Evaluation of Virtual Laboratory Package on Nigerian Secondary School Physics Concepts

ERIC Educational Resources Information Center

Falode, Oluwole Caleb; Gambari, Amosa Isiaka

2017-01-01

The study evaluated accessibility, flexibility, cost and learning effectiveness of researchers-developed virtual laboratory package for Nigerian secondary school physics. Based on these issues, four research questions were raised and answered. The study was a quantitative-based evaluation research. Sample for the study included 24 physics…

77 FR 61789 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Workforce...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-11

... Programs Gold Standard Evaluation Follow-Up Surveys, Veterans Study, and Cost Data,'' to the Office of... Standard Evaluation Follow-Up Surveys, Veterans Study, and Cost Data ACTION: Notice. SUMMARY: The... Worker Programs Gold Standard Evaluation Follow-Up Surveys, Veterans Study, and Cost Data. OMB ICR...

Handbook of Evaluated Materials for Secondary Social Studies.

ERIC Educational Resources Information Center

Mount Diablo Unified School District, Concord, CA.

The handbook contains teacher evaluations of secondary social studies materials used in the Mt. Diablo Unified School District (MDUSD), Orinda, California. The Materials Testing Program of MDUSD is an effort to involve secondary teachers in the process of evaluating social studies materials in certain concept areas: conflict, social change, man's…

Teacher Evaluations in Leisure Studies Programs: An Old Issue with a New Slant.

ERIC Educational Resources Information Center

Butts, Frank B.; Swearingen, Tommy

1994-01-01

This paper examines teacher evaluation practices in leisure studies programs, noting the perceived effectiveness of rating instruments. Surveys of leisure studies professors nationwide indicated many institutions used evaluation instruments and processes that were not statistically validated; key decisions were often made on the basis of these…

An Evaluation of Digital Stories Created for Social Studies Teaching

ERIC Educational Resources Information Center

Seker, Burcu Sezginsoy

2016-01-01

Digital stories are useful tools for combining technology with education, in terms of the preparation stage, practicality, availability and usability as an evaluation instrument. In this study, digital stories created in a social studies teaching class were evaluated and the opinions of primary school teacher candidates were obtained concerning…

The Principal's Role in the Post-Evaluation Process.--How Does the Principal Engage in the Work Carried out after the Schools Self-Evaluation?

ERIC Educational Resources Information Center

Emstad, Anne Berit

2011-01-01

This article refers to a study on how the school principal engaged in the process after a school self-evaluation. The study examined how two primary schools followed up the evaluation. Although they both used the same evaluation tool, the schools' understanding and application of results differed greatly. This paper describes and discusses the…

A qualitative case study of evaluation use in the context of a collaborative program evaluation strategy in Burkina Faso.

PubMed

D'Ostie-Racine, Léna; Dagenais, Christian; Ridde, Valéry

2016-05-26

Program evaluation is widely recognized in the international humanitarian sector as a means to make interventions and policies more evidence based, equitable, and accountable. Yet, little is known about the way humanitarian non-governmental organizations (NGOs) actually use evaluations. The current qualitative evaluation employed an instrumental case study design to examine evaluation use (EU) by a humanitarian NGO based in Burkina Faso. This organization developed an evaluation strategy in 2008 to document the implementation and effects of its maternal and child healthcare user fee exemption program. Program evaluations have been undertaken ever since, and the present study examined the discourses of evaluation partners in 2009 (n = 15) and 2011 (n = 17). Semi-structured individual interviews and one group interview were conducted to identify instances of EU over time. Alkin and Taut's (Stud Educ Eval 29:1-12, 2003) conceptualization of EU was used as the basis for thematic qualitative analyses of the different forms of EU identified by stakeholders of the exemption program in the two data collection periods. Results demonstrated that stakeholders began to understand and value the utility of program evaluations once they were exposed to evaluation findings and then progressively used evaluations over time. EU was manifested in a variety of ways, including instrumental and conceptual use of evaluation processes and findings, as well as the persuasive use of findings. Such EU supported planning, decision-making, program practices, evaluation capacity, and advocacy. The study sheds light on the many ways evaluations can be used by different actors in the humanitarian sector. Conceptualizations of EU are also critically discussed.

Evaluating Teachers' Professional Development Initiatives: Towards an Extended Evaluative Framework

ERIC Educational Resources Information Center

Merchie, Emmelien; Tuytens, Melissa; Devos, Geert; Vanderlinde, Ruben

2018-01-01

Evaluating teachers' professional development initiatives (PDI) is one of the main challenges for the teacher professionalisation field. Although different studies have focused on the effectiveness of PDI, the obtained effects and evaluative methods have been found to be widely divergent. By means of a narrative review, this study provides an…

Can Principals Promote Teacher Development as Evaluators? A Case Study of Principals' Views and Experiences

ERIC Educational Resources Information Center

Kraft, Matthew A.; Gilmour, Allison F.

2016-01-01

Purpose: New teacher evaluation systems have expanded the role of principals as instructional leaders, but little is known about principals' ability to promote teacher development through the evaluation process. We conducted a case study of principals' perspectives on evaluation and their experiences implementing observation and feedback cycles to…

76 FR 78670 - Draft Guidance for Industry and Food and Drug Administration Staff; Evaluation of Sex Differences...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-19

...] Draft Guidance for Industry and Food and Drug Administration Staff; Evaluation of Sex Differences in... entitled ``Evaluation of Sex Differences in Medical Device Clinical Studies.'' This document provides guidance on the study and evaluation of sex differences in medical device clinical trials, with a specific...

Summative Evaluation on the Hospital Wards. What Do Faculty Say to Learners?

ERIC Educational Resources Information Center

Hasley, Peggy B.; Arnold, Robert M.

2009-01-01

No previous studies have described how faculty give summative evaluations to learners on the medical wards. The aim of this study was to describe summative evaluations on the medical wards. Participants were students, house staff and faculty at the University of Pittsburgh. Ward rotation evaluative sessions were tape recorded. Feedback was…

Evaluating the Assessment Models for Young Children with Special Needs in Taiwan

ERIC Educational Resources Information Center

Ho, Hua-Kuo

2009-01-01

The purpose of this study was intended to evaluate the assessment models of two representative centers of team evaluation for children's development in Taiwan. Documentary analysis and phone interview were employed in the study to collect the research data needed. Two centers of team evaluation for children's development were selected and…

Evaluation of Turkish and Mathematics Curricula According to Value-Based Evaluation Model

ERIC Educational Resources Information Center

Duman, Serap Nur; Akbas, Oktay

2017-01-01

This study evaluated secondary school seventh-grade Turkish and mathematics programs using the Context-Input-Process-Product Evaluation Model based on student, teacher, and inspector views. The convergent parallel mixed method design was used in the study. Student values were identified using the scales for socio-level identification, traditional…

A Study To Evaluate the Effectiveness of the Montana Functional Vision Assessment for Multihandicapped Persons.

ERIC Educational Resources Information Center

Marks, Ron

The study evaluated the validity, reliability, and effectiveness in providing needed information of the Montana Functional Vision Assessment (MFVA) Instrument by comparing it with the Texas Education Agency Functional Vision Assessment and field testing the instrument in evaluations of nine multihandicapped students (ages 3-11). Evaluation led to…

Questionnaire Evaluating Teaching Competencies in the University Environment. Evaluation of Teaching Competencies in the University

ERIC Educational Resources Information Center

Moreno-Murcia, Juan Antonio; Silveira Torregrosa, Yolanda; Belando Pedreño, Noelia

2015-01-01

The objective of this study was to design and validate a measuring instrument to evaluate the performance of university professors. The Evaluation of Teaching Performance (CEID [Centro de Estudios e Investigaciones Docentes (Center for Teaching Studies and Research)]) questionnaire was administered to 1297 university students. Various factor…

An Analysis of Critical Issues in Korean Teacher Evaluation Systems

ERIC Educational Resources Information Center

Choi, Hee Jun; Park, Ji-Hye

2016-01-01

Korea has used three different teacher evaluation systems since the 1960s: teacher performance rating, teacher performance-based pay and teacher evaluation for professional development. A number of studies have focused on an analysis of each evaluation system in terms of its advent, development, advantages and disadvantages, but these studies have…

Measuring Spontaneous and Instructed Evaluation Processes during Web Search: Integrating Concurrent Thinking-Aloud Protocols and Eye-Tracking Data

ERIC Educational Resources Information Center

Gerjets, Peter; Kammerer, Yvonne; Werner, Benita

2011-01-01

Web searching for complex information requires to appropriately evaluating diverse sources of information. Information science studies identified different criteria applied by searchers to evaluate Web information. However, the explicit evaluation instructions used in these studies might have resulted in a distortion of spontaneous evaluation…

An Evaluation of the Private High School Curriculum in Turkey

ERIC Educational Resources Information Center

Aslan, Dolgun

2016-01-01

This study aims at evaluating curricula of private high schools in line with opinions of teachers working at the related high schools, and identifying any related problems. Screening model is used as a quantitative research method in the study. The "element-based curriculum evaluation model" is taken as basis for evaluation of the…

Understanding Expertise-Based Training Effects on the Software Evaluation Process of Mathematics Education Teachers

ERIC Educational Resources Information Center

Incikabi, Lutfi; Sancar Tokmak, Hatice

2012-01-01

This case study examined the educational software evaluation processes of pre-service teachers who attended either expertise-based training (XBT) or traditional training in conjunction with a Software-Evaluation checklist. Forty-three mathematics teacher candidates and three experts participated in the study. All participants evaluated educational…

[The development of evaluation capacity in primary healthcare management: a case study in Santa Catarina State, Brazil, 2008-2011].

PubMed

Nickel, Daniela Alba; Calvo, Maria Cristina Marino; Natal, Sonia; Freitas, Sérgio Fernando Torres de; Hartz, Zulmira Maria de Araújo

2014-04-01

This article analyzes evaluation capacity-building based on the case study of a State Health Secretariat participating in the Project to Strengthen the Technical Capacity of State Health Secretariats in Monitoring and Evaluating Primary Healthcare. The case study adopted a mixed design with information from documents, semi-structured interviews, and evaluation of primary care by the State Health Secretariat in 2008-2011. Process analysis was used to identify the logical events that contributed to evaluation capacity-building, with two categories: evaluation capacity-building events and events for building organizational structure. The logical chain of events was formed by negotiation and agreement on the decision-making levels for the continuity of evaluation, data collection and analysis by the State Health Secretariat, a change in key indicators, restructuring of the evaluation matrix, and communication of the results to the municipalities. The three-way analysis showed that the aim of developing evaluation capacity was achieved.

User Interface Problems of a Nationwide Inpatient Information System: A Heuristic Evaluation.

PubMed

Atashi, Alireza; Khajouei, Reza; Azizi, Amirabbas; Dadashi, Ali

2016-01-01

While studies have shown that usability evaluation could uncover many design problems of health information systems, the usability of health information systems in developing countries using their native language is poorly studied. The objective of this study was to evaluate the usability of a nationwide inpatient information system used in many academic hospitals in Iran. Three trained usability evaluators independently evaluated the system using Nielsen's 10 usability heuristics. The evaluators combined identified problems in a single list and independently rated the severity of the problems. We statistically compared the number and severity of problems identified by HIS experienced and non-experienced evaluators. A total of 158 usability problems were identified. After removing duplications 99 unique problems were left. The highest mismatch with usability principles was related to "Consistency and standards" heuristic (25%) and the lowest related to "Flexibility and efficiency of use" (4%). The average severity of problems ranged from 2.4 (Major problem) to 3.3 (Catastrophe problem). The experienced evaluator with HIS identified significantly more problems and gave higher severities to problems (p<0.02). Heuristic Evaluation identified a high number of usability problems in a widely used inpatient information system in many academic hospitals. These problems, if remain unsolved, may waste users' and patients' time, increase errors and finally threaten patient's safety. Many of them can be fixed with simple redesign solutions such as using clear labels and better layouts. This study suggests conducting further studies to confirm the findings concerning effect of evaluator experience on the results of Heuristic Evaluation.

User Interface Problems of a Nationwide Inpatient Information System: A Heuristic Evaluation

PubMed Central

Atashi, Alireza; Azizi, Amirabbas; Dadashi, Ali

2016-01-01

Summary Introduction While studies have shown that usability evaluation could uncover many design problems of health information systems, the usability of health information systems in developing countries using their native language is poorly studied. The objective of this study was to evaluate the usability of a nationwide inpatient information system used in many academic hospitals in Iran. Material and Methods Three trained usability evaluators independently evaluated the system using Nielsen’s 10 usability heuristics. The evaluators combined identified problems in a single list and independently rated the severity of the problems. We statistically compared the number and severity of problems identified by HIS experienced and non-experienced evaluators. Results A total of 158 usability problems were identified. After removing duplications 99 unique problems were left. The highest mismatch with usability principles was related to “Consistency and standards” heuristic (25%) and the lowest related to “Flexibility and efficiency of use” (4%). The average severity of problems ranged from 2.4 (Major problem) to 3.3 (Catastrophe problem). The experienced evaluator with HIS identified significantly more problems and gave higher severities to problems (p<0.02). Discussion Heuristic Evaluation identified a high number of usability problems in a widely used inpatient information system in many academic hospitals. These problems, if remain unsolved, may waste users’ and patients’ time, increase errors and finally threaten patient’s safety. Many of them can be fixed with simple redesign solutions such as using clear labels and better layouts. This study suggests conducting further studies to confirm the findings concerning effect of evaluator experience on the results of Heuristic Evaluation. PMID:27081409

Evaluation Criteria of Noninvasive Telemonitoring for Patients With Heart Failure: Systematic Review.

PubMed

Farnia, Troskah; Jaulent, Marie-Christine; Steichen, Olivier

2018-01-16

Telemonitoring can improve heart failure (HF) management, but there is no standardized evaluation framework to comprehensively evaluate its impact. Our objectives were to list the criteria used in published evaluations of noninvasive HF telemonitoring projects, describe how they are used in the evaluation studies, and organize them into a consistent scheme. Articles published from January 1990 to August 2015 were obtained through MEDLINE, Web of Science, and EMBASE. Articles were eligible if they were original reports of a noninvasive HF telemonitoring evaluation study in the English language. Studies of implantable telemonitoring devices were excluded. Each selected article was screened to extract the description of the telemonitoring project and the evaluation process and criteria. A qualitative synthesis was performed. We identified and reviewed 128 articles leading to 52 evaluation criteria classified into 6 dimensions: clinical, economic, user perspective, educational, organizational, and technical. The clinical and economic impacts were evaluated in more than 70% of studies, whereas the educational, organizational, and technical impacts were studied in fewer than 15%. User perspective was the most frequently covered dimension in the development phase of telemonitoring projects, whereas clinical and economic impacts were the focus of later phases. Telemonitoring evaluation frameworks should cover all 6 dimensions appropriately distributed along the telemonitoring project lifecycle. Our next goal is to build such a comprehensive evaluation framework for telemonitoring and test it on an ongoing noninvasive HF telemonitoring project. ©Troskah Farnia, Marie-Christine Jaulent, Olivier Steichen. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 16.01.2018.

A Model and Method of Evaluative Accounts: Development Impact of the National Literacy Mission (NLM of India).

ERIC Educational Resources Information Center

Bhola, H. S.

2002-01-01

Studied the developmental impact of the National Literacy Mission of India, providing an evaluative account based on 97 evaluation studies. Compared findings with those from a 27-study synthesis of studies of effects of adult literacy efforts in Africa. Findings show the impact of literacy on the development of nations. (SLD)

Evaluation of the Professional Development Program on Web Based Content Development

ERIC Educational Resources Information Center

Yurdakul, Bünyamin; Uslu, Öner; Çakar, Esra; Yildiz, Derya G.

2014-01-01

The aim of this study is to evaluate the professional development program on web based content development (WBCD) designed by the Ministry of National Education (MoNE). Based on the theoretical CIPP model by Stufflebeam and Guskey's levels of evaluation, the study was carried out as a case study. The study group consisted of the courses that…

40 CFR Appendix A to Subpart H of... - Requirements for Diagnostic-Feasibility Studies and Environmental Evaluations

Code of Federal Regulations, 2010 CFR

2010-07-01

... Studies and Environmental Evaluations A Appendix A to Subpart H of Part 35 Protection of Environment... to Subpart H of Part 35—Requirements for Diagnostic-Feasibility Studies and Environmental Evaluations... officer as specified in §§ 35.1650-3(b)(1) and 35.1650-3(c)(1). (a) A diagnostic study consisting of: (1...

40 CFR Appendix A to Subpart H of... - Requirements for Diagnostic-Feasibility Studies and Environmental Evaluations

Code of Federal Regulations, 2012 CFR

2012-07-01

... Studies and Environmental Evaluations A Appendix A to Subpart H of Part 35 Protection of Environment... to Subpart H of Part 35—Requirements for Diagnostic-Feasibility Studies and Environmental Evaluations... officer as specified in §§ 35.1650-3(b)(1) and 35.1650-3(c)(1). (a) A diagnostic study consisting of: (1...

40 CFR Appendix A to Subpart H of... - Requirements for Diagnostic-Feasibility Studies and Environmental Evaluations

Code of Federal Regulations, 2014 CFR

2014-07-01

... Studies and Environmental Evaluations A Appendix A to Subpart H of Part 35 Protection of Environment... to Subpart H of Part 35—Requirements for Diagnostic-Feasibility Studies and Environmental Evaluations... officer as specified in §§ 35.1650-3(b)(1) and 35.1650-3(c)(1). (a) A diagnostic study consisting of: (1...

40 CFR Appendix A to Subpart H of... - Requirements for Diagnostic-Feasibility Studies and Environmental Evaluations

Code of Federal Regulations, 2013 CFR

2013-07-01

... Studies and Environmental Evaluations A Appendix A to Subpart H of Part 35 Protection of Environment... to Subpart H of Part 35—Requirements for Diagnostic-Feasibility Studies and Environmental Evaluations... officer as specified in §§ 35.1650-3(b)(1) and 35.1650-3(c)(1). (a) A diagnostic study consisting of: (1...

40 CFR Appendix A to Subpart H of... - Requirements for Diagnostic-Feasibility Studies and Environmental Evaluations

Code of Federal Regulations, 2011 CFR

2011-07-01

... Studies and Environmental Evaluations A Appendix A to Subpart H of Part 35 Protection of Environment... to Subpart H of Part 35—Requirements for Diagnostic-Feasibility Studies and Environmental Evaluations... officer as specified in §§ 35.1650-3(b)(1) and 35.1650-3(c)(1). (a) A diagnostic study consisting of: (1...

Evaluating the utility of two gestural discomfort evaluation methods

PubMed Central

Son, Minseok; Jung, Jaemoon; Park, Woojin

2017-01-01

Evaluating physical discomfort of designed gestures is important for creating safe and usable gesture-based interaction systems; yet, gestural discomfort evaluation has not been extensively studied in HCI, and few evaluation methods seem currently available whose utility has been experimentally confirmed. To address this, this study empirically demonstrated the utility of the subjective rating method after a small number of gesture repetitions (a maximum of four repetitions) in evaluating designed gestures in terms of physical discomfort resulting from prolonged, repetitive gesture use. The subjective rating method has been widely used in previous gesture studies but without empirical evidence on its utility. This study also proposed a gesture discomfort evaluation method based on an existing ergonomics posture evaluation tool (Rapid Upper Limb Assessment) and demonstrated its utility in evaluating designed gestures in terms of physical discomfort resulting from prolonged, repetitive gesture use. Rapid Upper Limb Assessment is an ergonomics postural analysis tool that quantifies the work-related musculoskeletal disorders risks for manual tasks, and has been hypothesized to be capable of correctly determining discomfort resulting from prolonged, repetitive gesture use. The two methods were evaluated through comparisons against a baseline method involving discomfort rating after actual prolonged, repetitive gesture use. Correlation analyses indicated that both methods were in good agreement with the baseline. The methods proposed in this study seem useful for predicting discomfort resulting from prolonged, repetitive gesture use, and are expected to help interaction designers create safe and usable gesture-based interaction systems. PMID:28423016

Economic evaluation of vaccines in Canada: A systematic review

PubMed Central

Chit, Ayman; Lee, Jason K. H.; Shim, Minsup; Nguyen, Van Hai; Grootendorst, Paul; Wu, Jianhong; Van Exan, Robert; Langley, Joanne M.

2016-01-01

ABSTRACT Background: Economic evaluations should form part of the basis for public health decision making on new vaccine programs. While Canada's national immunization advisory committee does not systematically include economic evaluations in immunization decision making, there is increasing interest in adopting them. We therefore sought to examine the extent and quality of economic evaluations of vaccines in Canada. Objective: We conducted a systematic review of economic evaluations of vaccines in Canada to determine and summarize: comprehensiveness across jurisdictions, studied vaccines, funding sources, study designs, research quality, and changes over time. Methods: Searches in multiple databases were conducted using the terms “vaccine,” “economics” and “Canada.” Descriptive data from eligible manuscripts was abstracted and three authors independently evaluated manuscript quality using a 7-point Likert-type scale scoring tool based on criteria from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Results: 42/175 articles met the search criteria. Of these, Canada-wide studies were most common (25/42), while provincial studies largely focused on the three populous provinces of Ontario, Quebec and British Columbia. The most common funding source was industry (17/42), followed by government (7/42). 38 studies used mathematical models estimating expected economic benefit while 4 studies examined post-hoc data on established programs. Studies covered 10 diseases, with 28/42 addressing pediatric vaccines. Many studies considered cost-utility (22/42) and the majority of these studies reported favorable economic results (16/22). The mean quality score was 5.9/7 and was consistent over publication date, funding sources, and disease areas. Conclusions: We observed diverse approaches to evaluate vaccine economics in Canada. Given the increased complexity of economic studies evaluating vaccines and the impact of results on public health practice, Canada needs improved, transparent and consistent processes to review and assess the findings of the economic evaluations of vaccines. PMID:26890128

Student perceptions of evaluation in undergraduate medical education: A qualitative study from one medical school.

PubMed

Schiekirka, Sarah; Reinhardt, Deborah; Heim, Susanne; Fabry, Götz; Pukrop, Tobias; Anders, Sven; Raupach, Tobias

2012-06-22

Evaluation is an integral part of medical education. Despite a wide use of various evaluation tools, little is known about student perceptions regarding the purpose and desired consequences of evaluation. Such knowledge is important to facilitate interpretation of evaluation results. The aims of this study were to elicit student views on the purpose of evaluation, indicators of teaching quality, evaluation tools and possible consequences drawn from evaluation data. This qualitative study involved 17 undergraduate medical students in Years 3 and 4 participating in 3 focus group interviews. Content analysis was conducted by two different researchers. Evaluation was viewed as a means to facilitate improvements within medical education. Teaching quality was believed to be dependent on content, process, teacher and student characteristics as well as learning outcome, with an emphasis on the latter. Students preferred online evaluations over paper-and-pencil forms and suggested circulating results among all faculty and students. Students strongly favoured the allocation of rewards and incentives for good teaching to individual teachers. In addition to assessing structural aspects of teaching, evaluation tools need to adequately address learning outcome. The use of reliable and valid evaluation methods is a prerequisite for resource allocation to individual teachers based on evaluation results.

Student perceptions of evaluation in undergraduate medical education: A qualitative study from one medical school

PubMed Central

2012-01-01

Background Evaluation is an integral part of medical education. Despite a wide use of various evaluation tools, little is known about student perceptions regarding the purpose and desired consequences of evaluation. Such knowledge is important to facilitate interpretation of evaluation results. The aims of this study were to elicit student views on the purpose of evaluation, indicators of teaching quality, evaluation tools and possible consequences drawn from evaluation data. Methods This qualitative study involved 17 undergraduate medical students in Years 3 and 4 participating in 3 focus group interviews. Content analysis was conducted by two different researchers. Results Evaluation was viewed as a means to facilitate improvements within medical education. Teaching quality was believed to be dependent on content, process, teacher and student characteristics as well as learning outcome, with an emphasis on the latter. Students preferred online evaluations over paper-and-pencil forms and suggested circulating results among all faculty and students. Students strongly favoured the allocation of rewards and incentives for good teaching to individual teachers. Conclusions In addition to assessing structural aspects of teaching, evaluation tools need to adequately address learning outcome. The use of reliable and valid evaluation methods is a prerequisite for resource allocation to individual teachers based on evaluation results. PMID:22726271

Guidelines for reporting evaluations based on observational methodology.

PubMed

Portell, Mariona; Anguera, M Teresa; Chacón-Moscoso, Salvador; Sanduvete-Chaves, Susana

2015-01-01

Observational methodology is one of the most suitable research designs for evaluating fidelity of implementation, especially in complex interventions. However, the conduct and reporting of observational studies is hampered by the absence of specific guidelines, such as those that exist for other evaluation designs. This lack of specific guidance poses a threat to the quality and transparency of these studies and also constitutes a considerable publication hurdle. The aim of this study thus was to draw up a set of proposed guidelines for reporting evaluations based on observational methodology. The guidelines were developed by triangulating three sources of information: observational studies performed in different fields by experts in observational methodology, reporting guidelines for general studies and studies with similar designs to observational studies, and proposals from experts in observational methodology at scientific meetings. We produced a list of guidelines grouped into three domains: intervention and expected outcomes, methods, and results. The result is a useful, carefully crafted set of simple guidelines for conducting and reporting observational studies in the field of program evaluation.

The role of affect and cognition in health decision making.

PubMed

Keer, Mario; van den Putte, Bas; Neijens, Peter

2010-03-01

Both affective and cognitive evaluations of behaviours have been allocated various positions in theoretical models of decision making. Most often, they have been studied as direct determinants of either intention or overall evaluation, but these two possible positions have never been compared. The aim of this study was to determine whether affective and cognitive evaluations influence intention directly, or whether their influence is mediated by overall evaluation. A sample of 300 university students filled in questionnaires on their affective, cognitive, and overall evaluations in respect of 20 health behaviours. The data were interpreted using mediation analyses with the application of path modelling. Both affective and cognitive evaluations were found to have significantly predicted intention. The influence of affective evaluation was largely direct for each of the behaviours studied, whereas that of cognitive evaluation was partially direct and partially mediated by overall evaluation. These results indicate that decisions regarding the content of persuasive communication (affective vs. cognitive) are highly dependent on the theoretical model chosen. It is suggested that affective evaluation should be included as a direct determinant of intention in theories of decision making when predicting health behaviours.

Escalator Design Features Evaluation

DOT National Transportation Integrated Search

1982-05-01

This study provides an evaluation of the effectiveness of several special design features associated with escalators in rail transit systems. The objective of the study was to evaluate the effectiveness of three escalator design features: (1) mat ope...

STARE-HI – Statement on Reporting of Evaluation Studies in Health Informatics

PubMed Central

Brender, J.; Talmon, J.; de Keizer, N.; Nykänen, P.; Rigby, M.; Ammenwerth, E.

2013-01-01

Summary Background Improving the quality of reporting of evaluation studies in health informatics is an important requirement towards the vision of evidence-based health informatics. The STARE-HI – Statement on Reporting of Evaluation Studies in health informatics, published in 2009, provides guidelines on the elements to be contained in an evaluation study report. Objectives To elaborate on and provide a rationale for the principles of STARE-HI and to guide authors and readers of evaluation studies in health informatics by providing explanatory examples of reporting. Methods A group of methodologists, researchers and editors prepared the present elaboration of the STARE-HI statement and selected examples from the literature. Results The 35 STARE-HI items to be addressed in evaluation papers describing health informatics interventions are discussed one by one and each is extended with examples and elaborations. Conclusion The STARE-HI statement and this elaboration document should be helpful resources to improve reporting of both quantitative and qualitative evaluation studies. Evaluation manuscripts adhering to the principles will enable readers of such papers to better place the studies in a proper context and judge their validity and generalizability, and thus in turn optimize the exploitation of the evidence contained therein. Limitations This paper is based on experiences of a group of editors, reviewers, authors of systematic reviews and readers of the scientific literature. The applicability of the details of these principles has to evolve as a function of their use in practice. PMID:24155788

Evaluating the Feasibility of RESCUE: An Adjunctive HAI-Based Intervention for Veterans with PTSD

DTIC Science & Technology

2017-05-01

with clinicians on study 9/14/16 – 9/16/16. c) Independent evaluators completed 1-day Clinician Administered PTSD Scale (CAPS) training 10/31/16. d...therapists Recruit, facilitate hiring, and train study independent evaluators (IEs) 0-6 100% Facilitate and coordinate training and PE certification...developed referral stream for study 6 - 8 100% Major Task 3: Conduct pre-treatment evaluations for case series Screen, obtain consent, assess, and

Consensus-based cross-European recommendations for the identification, measurement and valuation of costs in health economic evaluations: a European Delphi study.

PubMed

van Lier, Lisanne I; Bosmans, Judith E; van Hout, Hein P J; Mokkink, Lidwine B; van den Hout, Wilbert B; de Wit, G Ardine; Dirksen, Carmen D; Nies, Henk L G R; Hertogh, Cees M P M; van der Roest, Henriëtte G

2017-12-19

Differences between country-specific guidelines for economic evaluations complicate the execution of international economic evaluations. The aim of this study was to develop cross-European recommendations for the identification, measurement and valuation of resource use and lost productivity in economic evaluations using a Delphi procedure. A comprehensive literature search was conducted to identify European guidelines on the execution of economic evaluations or costing studies as part of economic evaluations. Guideline recommendations were extracted by two independent reviewers and formed the basis for the first round of the Delphi study, which was conducted among European health economic experts. During three written rounds, consensus (agreement of 67% or higher) was sought on items concerning the identification, measurement and valuation of costs. Recommendations from 18 guidelines were extracted. Consensus among 26 panellists from 17 European countries was reached on 61 of 68 items. The recommendations from the Delphi study are to adopt a societal perspective, to use patient report for measuring resource use and lost productivity, to value both constructs with use of country-specific standardized/unit costs and to use country-specific discounting rates. This study provides consensus-based cross-European recommendations on how to measure and value resource use and lost productivity in economic evaluations. These recommendations are expected to support researchers, healthcare professionals, and policymakers in executing and appraising economic evaluations performed in international contexts.

Methodological convergence of program evaluation designs.

PubMed

Chacón-Moscoso, Salvador; Anguera, M Teresa; Sanduvete-Chaves, Susana; Sánchez-Martín, Milagrosa

2014-01-01

Nowadays, the confronting dichotomous view between experimental/quasi-experimental and non-experimental/ethnographic studies still exists but, despite the extensive use of non-experimental/ethnographic studies, the most systematic work on methodological quality has been developed based on experimental and quasi-experimental studies. This hinders evaluators and planners' practice of empirical program evaluation, a sphere in which the distinction between types of study is changing continually and is less clear. Based on the classical validity framework of experimental/quasi-experimental studies, we carry out a review of the literature in order to analyze the convergence of design elements in methodological quality in primary studies in systematic reviews and ethnographic research. We specify the relevant design elements that should be taken into account in order to improve validity and generalization in program evaluation practice in different methodologies from a practical methodological and complementary view. We recommend ways to improve design elements so as to enhance validity and generalization in program evaluation practice.

Non-formal educator use of evaluation results.

PubMed

Baughman, Sarah; Boyd, Heather H; Franz, Nancy K

2012-08-01

Increasing demands for accountability in educational programming have resulted in increasing calls for program evaluation in educational organizations. Many organizations include conducting program evaluations as part of the job responsibilities of program staff. Cooperative Extension is a complex organization offering non-formal educational programs through land grant universities. Many Extension services require non-formal educational program evaluations be conducted by field-based Extension educators. Evaluation research has focused primarily on the efforts of professional, external evaluators. The work of program staff with many responsibilities including program evaluation has received little attention. This study examined how field based Extension educators (i.e. program staff) in four Extension services use the results of evaluations of programs that they have conducted themselves. Four types of evaluation use are measured and explored; instrumental use, conceptual use, persuasive use and process use. Results indicate that there are few programmatic changes as a result of evaluation findings among the non-formal educators surveyed in this study. Extension educators tend to use evaluation results to persuade others about the value of their programs and learn from the evaluation process. Evaluation use is driven by accountability measures with very little program improvement use as measured in this study. Practical implications include delineating accountability and program improvement tasks within complex organizations in order to align evaluation efforts and to improve the results of both. There is some evidence that evaluation capacity building efforts may be increasing instrumental use by educators evaluating their own programs. Copyright © 2011 Elsevier Ltd. All rights reserved.

Case study of evaluations that go beyond clinical outcomes to assess quality improvement diabetes programmes using the Diabetes Evaluation Framework for Innovative National Evaluations (DEFINE).

PubMed

Paquette-Warren, Jann; Harris, Stewart B; Naqshbandi Hayward, Mariam; Tompkins, Jordan W

2016-10-01

Investments in efforts to reduce the burden of diabetes on patients and health care are critical; however, more evaluation is needed to provide evidence that informs and supports future policies and programmes. The newly developed Diabetes Evaluation Framework for Innovative National Evaluations (DEFINE) incorporates the theoretical concepts needed to facilitate the capture of critical information to guide investments, policy and programmatic decision making. The aim of the study is to assess the applicability and value of DEFINE in comprehensive real-world evaluation. Using a critical and positivist approach, this intrinsic and collective case study retrospectively examines two naturalistic evaluations to demonstrate how DEFINE could be used when conducting real-world comprehensive evaluations in health care settings. The variability between the cases and the evaluation designs are described and aligned to the DEFINE goals, steps and sub-steps. The majority of the theoretical steps of DEFINE were exemplified in both cases, although limited for knowledge translation efforts. Application of DEFINE to evaluate diverse programmes that target various chronic diseases is needed to further test the inclusivity and built-in flexibility of DEFINE and its role in encouraging more comprehensive knowledge translation. This case study shows how DEFINE could be used to structure or guide comprehensive evaluations of programmes and initiatives implemented in health care settings and support scale-up of successful innovations. Future use of the framework will continue to strengthen its value in guiding programme evaluation and informing health policy to reduce the burden of diabetes and other chronic diseases. © 2016 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons, Ltd.

Outcome Reporting Bias in Government-Sponsored Policy Evaluations: A Qualitative Content Analysis of 13 Studies

PubMed Central

2016-01-01

The reporting of evaluation outcomes can be a point of contention between evaluators and policy-makers when a given reform fails to fulfil its promises. Whereas evaluators are required to report outcomes in full, policy-makers have a vested interest in framing these outcomes in a positive light–especially when they previously expressed a commitment to the reform. The current evidence base is limited to a survey of policy evaluators, a study on reporting bias in education research and several studies investigating the influence of industry sponsorship on the reporting of clinical trials. The objective of this study was twofold. Firstly, it aimed to assess the risk of outcome reporting bias (ORB or ‘spin’) in pilot evaluation reports, using seven indicators developed by clinicians. Secondly, it sought to examine how the government’s commitment to a given reform may affect the level of ORB found in the corresponding evaluation report. To answer these questions, 13 evaluation reports were content-analysed, all of which found a non-significant effect of the intervention on its stated primary outcome. These reports were systematically selected from a dataset of 233 pilot and experimental evaluations spanning three policy areas and 13 years of government-commissioned research in the UK. The results show that the risk of ORB is real. Indeed, all studies reviewed here resorted to at least one of the presentational strategies associated with a risk of spin. This study also found a small, negative association between the seniority of the reform’s champion and the risk of ORB in the evaluation of that reform. The publication of protocols and the use of reporting guidelines are recommended. PMID:27690131

Helping Students Evaluate the Validity of a Research Study.

ERIC Educational Resources Information Center

Morgan, George A.; Gliner, Jeffrey A.

Students often have difficulty in evaluating the validity of a study. A conceptually and linguistically meaningful framework for evaluating research studies is proposed that is based on the discussion of internal and external validity of T. D. Cook and D. T. Campbell (1979). The proposal includes six key dimensions, three related to internal…

Evaluation of Core Vocabulary Intervention for Treatment of Inconsistent Phonological Disorder: Three Treatment Case Studies

ERIC Educational Resources Information Center

McIntosh, Beth; Dodd, Barbara

2009-01-01

Children with unintelligible speech differ in severity, underlying deficit, type of surface error patterns and response to treatment. Detailed treatment case studies, evaluating specific intervention protocols for particular diagnostic groups, can identify best practice for children with speech disorder. Three treatment case studies evaluated the…

How to Critically Evaluate Case Studies in Social Work

ERIC Educational Resources Information Center

Lee, Eunjung; Mishna, Faye; Brennenstuhl, Sarah

2010-01-01

The purpose of this article is to develop guidelines to assist practitioners and researchers in evaluating and developing rigorous case studies. The main concern in evaluating a case study is to accurately assess its quality and ultimately to offer clients social work interventions informed by the best available evidence. To assess the quality of…

The evaluation of complex interventions in palliative care: an exploration of the potential of case study research strategies.

PubMed

Walshe, Catherine

2011-12-01

Complex, incrementally changing, context dependent and variable palliative care services are difficult to evaluate. Case study research strategies may have potential to contribute to evaluating such complex interventions, and to develop this field of evaluation research. This paper explores definitions of case study (as a unit of study, a process, and a product) and examines the features of case study research strategies which are thought to confer benefits for the evaluation of complex interventions in palliative care settings. Ten features of case study that are thought to be beneficial in evaluating complex interventions in palliative care are discussed, drawing from exemplars of research in this field. Important features are related to a longitudinal approach, triangulation, purposive instance selection, comprehensive approach, multiple data sources, flexibility, concurrent data collection and analysis, search for proving-disproving evidence, pattern matching techniques and an engaging narrative. The limitations of case study approaches are discussed including the potential for subjectivity and their complex, time consuming and potentially expensive nature. Case study research strategies have great potential in evaluating complex interventions in palliative care settings. Three key features need to be exploited to develop this field: case selection, longitudinal designs, and the use of rival hypotheses. In particular, case study should be used in situations where there is interplay and interdependency between the intervention and its context, such that it is difficult to define or find relevant comparisons.

Application of an organizational evaluation capacity self-assessment instrument to different organizations: similarities and lessons learned.

PubMed

Bourgeois, Isabelle; Whynot, Jane; Thériault, Étienne

2015-06-01

Organizational evaluation capacity (EC) has received significant attention in the evaluation research literature in the past decade. Much of the focus has been on defining organizational evaluation capacity, which can be thought of as the competencies and structures required to conduct high-quality evaluation studies (capacity to do), as well as the organization's ability to integrate evaluation findings into its decision-making processes (capacity to use). This paper seeks to contribute to this growing body of knowledge through a multiple case study of EC across three different organizations (e.g., non-profit, provincial government and federal government, herein named sectors); the novelty of this particular study is that each case study is based on the use of a common measurement tool developed by Bourgeois, Toews, Whynot and Lamarche (2013). The cross-case analysis presented in the paper reveals that evaluation capacity tends to be higher, both in terms of capacity to do and capacity to use, in organizations that have developed systematic mechanisms to institute an evaluation culture within their walls. Interestingly, however, we also found that capacity to use does not first require capacity to do, as evidenced in the non-profit organization under study. Copyright © 2015 Elsevier Ltd. All rights reserved.

Do Early Childhood Programs Have Lasting Effects on Children? Evaluation Science Brief

ERIC Educational Resources Information Center

National Forum on Early Childhood Program Evaluation, 2008

2008-01-01

"Evaluation Science Briefs" summarize the findings and implications of a recent study evaluating the effects of an early childhood program or environment. This Brief evaluates the study "Early Intervention in Low Birthweight Premature Infants: Results at 18 Years of Age for the Infant Health and Development Program (IHDP)" (M.C. McCormick, J.…

The Utility of Pitch Elevation in the Evaluation of Oropharyngeal Dysphagia: Preliminary Findings

ERIC Educational Resources Information Center

Malandraki, Georgia A.; Hind, Jacqueline A.; Gangnon, Ronald; Logemann, Jeri A.; Robbins, JoAnne

2011-01-01

Purpose: To evaluate the utility of a pitch elevation task in the assessment of oropharyngeal dysphagia. Method: This study was a pilot prospective cohort study including 40 consecutive patients (16 male and 24 female) who were referred by their physician for a swallowing evaluation. Patients were evaluated with a noninstrumental clinical…

Redesigning Teacher Evaluation: Lessons Learned from a Pilot Implementation in New Hampshire

ERIC Educational Resources Information Center

Riordan, Julie; Lacireno-Paquet, Natalie; Shakman, Karen; Bocala, Candice

2016-01-01

Many studies have called attention to the limitations of current teacher evaluation systems and the need for reform nationwide. This study addresses three research questions: (1) What are the features of the new teacher evaluation systems in New Hampshire's districts with SIG schools?; (2) To what extent did schools implement the evaluation system…

Using Student Evaluations at a Cambodian University to Improve Teaching Effectiveness

ERIC Educational Resources Information Center

Nash, John Lysne

2012-01-01

This is the first study done in Cambodia wherein students used the Student Evaluations of Educational Quality (SEEQ) evaluation tool to evaluate the teaching quality of their instructors. Respondents were instructors and students from the English Language Support Unit at the Royal University of Phnom Penh. This study generated data from mid- and…

Formative Evaluation of the No-Fee Teacher Education Program from the Students' Standpoint

ERIC Educational Resources Information Center

Han, Yumei; Hu, Meizhong; Li, Ling

2013-01-01

This exploratory case study applied a formative evaluation framework to evaluate the no-fee teacher education program at Southwest University. The study focused on the students' perspective and their perceptions of the program, both intrinsic and extrinsic. A self-evaluation checklist and a questionnaire were the instruments used to collect data.…

Evaluating the Evaluators: Comparative Study of High School Newspaper Critique Services.

ERIC Educational Resources Information Center

Davis, Nancy

High school publication staffs depend on national critique services as a major means of evaluation and recognition, but most have no measure of how one critique service compares to the others, because they can afford the entry fee for only one evaluation. Thus, a study was conducted to test the validity of three major national critique…

EVALUATION OF THE REAL-TIME AIR-QUALITY MODEL USING THE RAPS (REGIONAL AIR POLLUTION STUDY) DATA BASE. VOLUME 4. EVALUATION GUIDE

EPA Science Inventory

The theory and programming of statistical tests for evaluating the Real-Time Air-Quality Model (RAM) using the Regional Air Pollution Study (RAPS) data base are fully documented in four volumes. Moreover, the tests are generally applicable to other model evaluation problems. Volu...

[Valences of self-evaluation and approach-avoidance tendencies: research based on regulatory focus theory].

PubMed

Ozaki, Yuka; Karasawa, Kaori

2011-12-01

Four studies were conducted to investigate the relationship between valences of self-evaluation and approach-avoidance tendencies. Based on regulatory focus theory (Higgins, 1997, 1998), we predicted that positivity of self-evaluation is related to the tendency to approach gains, while negativity of self-evaluation is related to the tendency to avoid losses. In Study 1, a self-report measure of behavioral tendencies for approaching gains and avoiding losses was developed. In Studies 2 to 4, correlations between these approach/avoidance tendencies and various kinds of self-evaluations were examined. Overall, the authors' predictions were supported. The results suggest that the self-evaluation system and the self-regulation system work in close cooperation with each other in controlling human behavior.

Moving away from exhaustion: how core self-evaluations influence academic burnout.

PubMed

Lian, Penghu; Sun, Yunfeng; Ji, Zhigang; Li, Hanzhong; Peng, Jiaxi

2014-01-01

Academic burnout refers to students who have low interest, lack of motivation, and tiredness in studying. Studies concerning how to prevent academic burnout are rare. The present study aimed to investigate the impact of core self-evaluations on the academic burnout of university students, and mainly focused on the confirmation of the mediator role of life satisfaction. A total of 470 university students accomplished the core self-evaluation scale, Satisfaction with Life, and academic burnout scale. Both core self-evaluations and life satisfaction were significantly correlated with academic burnout. Structural equation modeling indicated that life satisfaction partially mediated the relationship between core self-evaluations and academic burnout. Core self-evaluations significantly influence academic burnout and are partially mediated by life satisfaction.

Review of economic evaluations of mask and respirator use for protection against respiratory infection transmission.

PubMed

Mukerji, Shohini; MacIntyre, C Raina; Newall, Anthony T

2015-10-13

There has been increasing debate surrounding mask and respirator interventions to control respiratory infection transmission in both healthcare and community settings. As decision makers are considering the recommendations they should evaluate how to provide the most efficient protection strategies with minimum costs. The aim of this review is to identify and evaluate the existing economic evaluation literature in this area and to offer advice on how future evaluations on this topic should be conducted. We searched the Scopus database for all literature on economic evaluation of mask or respirator use to control respiratory infection transmission. Reference lists from the identified studies were also manually searched. Seven studies met our inclusion criteria from the initial 806 studies identified by the search strategy and our manual search. Five studies considered interventions for seasonal and/or pandemic influenza, with one also considering SARS (Severe Acute Respiratory Syndrome). The other two studies focussed on tuberculosis transmission control interventions. The settings and methodologies of the studies varied greatly. No low-middle income settings were identified. Only one of the reviewed studies cited clinical evidence to inform their mask/respirator intervention effectiveness parameters. Mask and respirator interventions were generally reported by the study authors to be cost saving or cost-effective when compared to no intervention or other control measures, however the evaluations had important limitations. Given the large cost differential between masks and respirators, there is a need for more comprehensive economic evaluations to compare the relative costs and benefits of these interventions in situations and settings where alternative options are potentially applicable. There are at present insufficient well conducted cost-effectiveness studies to inform decision-makers on the value for money of alternative mask/respirator options.

Mastering moral misery: Emotional and coping responses to intragroup morality (vs. competence) evaluations.

PubMed

van der Lee, Romy; Ellemers, Naomi; Scheepers, Daan

2016-01-01

In social groups, individuals are often confronted with evaluations of their behaviour by other group members and are motivated to adapt their own behaviour accordingly. In two studies we examine emotional responses towards, and perceived coping abilities with, morality vs. competence evaluations individuals receive from other in-group members. In Study 1, we show that evaluations of one's immoral behaviour primarily induce guilt, whereas evaluations of incompetent behaviour raise anger. In Study 2, we elaborate on the psychological process associated with these emotional responses, and demonstrate that evaluations of immorality, compared to incompetence, diminish group members' perceived coping abilities, which in turn intensifies feelings of guilt. However, when anticipating an opportunity to restore one's self-image as a moral group member, perceived coping abilities are increased and the experience of guilt is alleviated. Together these studies demonstrate how group members can overcome their moral misery when restoring their self-image.

Impact of Educational Level on Study Attrition and Evaluation of Web-Based Computer-Tailored Interventions: Results From Seven Randomized Controlled Trials.

PubMed

Reinwand, Dominique A; Crutzen, Rik; Elfeddali, Iman; Schneider, Francine; Schulz, Daniela Nadine; Smit, Eline Suzanne; Stanczyk, Nicola Esther; Tange, Huibert; Voncken-Brewster, Viola; Walthouwer, Michel Jean Louis; Hoving, Ciska; de Vries, Hein

2015-10-07

Web-based computer-tailored interventions have shown to be effective in improving health behavior; however, high dropout attrition is a major issue in these interventions. The aim of this study is to assess whether people with a lower educational level drop out from studies more frequently compared to people with a higher educational level and to what extent this depends on evaluation of these interventions. Data from 7 randomized controlled trials of Web-based computer-tailored interventions were used to investigate dropout rates among participants with different educational levels. To be able to compare higher and lower educated participants, intervention evaluation was assessed by pooling data from these studies. Logistic regression analysis was used to assess whether intervention evaluation predicted dropout at follow-up measurements. In 3 studies, we found a higher study dropout attrition rate among participants with a lower educational level, whereas in 2 studies we found that middle educated participants had a higher dropout attrition rate compared to highly educated participants. In 4 studies, no such significant difference was found. Three of 7 studies showed that participants with a lower or middle educational level evaluated the interventions significantly better than highly educated participants ("Alcohol-Everything within the Limit": F2,376=5.97, P=.003; "My Healthy Behavior": F2,359=5.52, P=.004; "Master Your Breath": F2,317=3.17, P=.04). One study found lower intervention evaluation by lower educated participants compared to participants with a middle educational level ("Weight in Balance": F2,37=3.17, P=.05). Low evaluation of the interventions was not a significant predictor of dropout at a later follow-up measurement in any of the studies. Dropout attrition rates were higher among participants with a lower or middle educational level compared with highly educated participants. Although lower educated participants evaluated the interventions better in approximately half of the studies, evaluation did not predict dropout attrition. Further research is needed to find other explanations for high dropout rates among lower educated participants.

Shuttle Ground Operations Efficiencies/Technologies (SGOE/T) study. Volume 2: Ground Operations evaluation

NASA Technical Reports Server (NTRS)

Scholz, A. L.; Hart, M. T.; Lowry, D. J.

1987-01-01

The Ground Operations Evaluation describes the breath and depth of the various study elements selected as a result of an operational analysis conducted during the early part of the study. Analysis techniques used for the evaluation are described in detail. Elements selected for further evaluation are identified; the results of the analysis documented; and a follow-on course of action recommended. The background and rationale for developing recommendations for the current Shuttle or for future programs is presented.

Health services research evaluation principles. Broadening a general framework for evaluating health information technology.

PubMed

Sockolow, P S; Crawford, P R; Lehmann, H P

2012-01-01

Our forthcoming national experiment in increased health information technology (HIT) adoption funded by the American Recovery and Reinvestment Act of 2009 will require a comprehensive approach to evaluating HIT. The quality of evaluation studies of HIT to date reveals a need for broader evaluation frameworks that limits the generalizability of findings and the depth of lessons learned. Develop an informatics evaluation framework for health information technology (HIT) integrating components of health services research (HSR) evaluation and informatics evaluation to address identified shortcomings in available HIT evaluation frameworks. A systematic literature review updated and expanded the exhaustive review by Ammenwerth and deKeizer (AdK). From retained studies, criteria were elicited and organized into classes within a framework. The resulting Health Information Technology Research-based Evaluation Framework (HITREF) was used to guide clinician satisfaction survey construction, multi-dimensional analysis of data, and interpretation of findings in an evaluation of a vanguard community health care EHR. The updated review identified 128 electronic health record (EHR) evaluation studies and seven evaluation criteria not in AdK: EHR Selection/Development/Training; Patient Privacy Concerns; Unintended Consequences/ Benefits; Functionality; Patient Satisfaction with EHR; Barriers/Facilitators to Adoption; and Patient Satisfaction with Care. HITREF was used productively and was a complete evaluation framework which included all themes that emerged. We can recommend to future EHR evaluators that they consider adding a complete, research-based HIT evaluation framework, such as HITREF, to their evaluation tools suite to monitor HIT challenges as the federal government strives to increase HIT adoption.

Consider the source: persuasion of implicit evaluations is moderated by source credibility.

PubMed

Smith, Colin Tucker; De Houwer, Jan; Nosek, Brian A

2013-02-01

The long history of persuasion research shows how to change explicit, self-reported evaluations through direct appeals. At the same time, research on how to change implicit evaluations has focused almost entirely on techniques of retraining existing evaluations or manipulating contexts. In five studies, we examined whether direct appeals can change implicit evaluations in the same way as they do explicit evaluations. In five studies, both explicit and implicit evaluations showed greater evidence of persuasion following information presented by a highly credible source than a source low in credibility. Whereas cognitive load did not alter the effect of source credibility on explicit evaluations, source credibility had an effect on the persuasion of implicit evaluations only when participants were encouraged and able to consider information about the source. Our findings reveal the relevance of persuasion research for changing implicit evaluations and provide new ideas about the processes underlying both types of evaluation.

Evaluative judgments are based on evaluative information: Evidence against meaning change in evaluative context effects.

PubMed

Kaplan, M F

1975-07-01

Trait adjectives commonly employed in person perception studies have both evaluative and denotative meanings. Evaluative ratings of single traits shift with variations in the context of other traits ascribed to the stimulus person; the extent to which denotative changes underlie these evaluative context effects has been a theoretical controversy. In the first experiment, it was shown that context effects on quantitative ratings of denotation can be largely accounted for by evaluative halo effects. In the second experiment, increasing the denotative relatedness of context traits to the test trait didnot increase the effect of the context. Only the evaluative meaning of the context affected evaluation of the rated test trait. These studies suggest that the denotative relationship between a test adjective and its context has little influence on context effects in person perception, and that denotative meaning changes do not mediate context effects. Instead, evaluative judgments appear to be based on evaluative meaning.

A Systematic Review of the Level of Evidence in Economic Evaluations of Medical Devices: The Example of Vertebroplasty and Kyphoplasty

PubMed Central

van den Brink, Hélène; Pineau, Judith; Prognon, Patrice; Borget, Isabelle

2015-01-01

Context Economic evaluations are far less frequently reported for medical devices than for drugs. In addition, little is known about the quality of existing economic evaluations, particularly for innovative devices, such as those used in vertebroplasty and kyphoplasty. Objective To assess the level of evidence provided by the available economic evaluations for vertebroplasty and kyphoplasty. Data Sources A systematic review of articles in English or French listed in the MEDLINE, PASCAL, COCHRANE and National Health Service Economic Evaluation databases, with limits on publication date (up to the date of the review, March 2014). Study Selection We included only economic evaluations of vertebroplasty or kyphoplasty. Editorial and methodological articles were excluded. Data Extraction Data were extracted from articles by two authors working independently and using two analysis grids to measure the quality of economic evaluations. Data Synthesis Twenty-one studies met our inclusion criteria. All were published between 2008 and 2014. Eighteen (86%) were full economic evaluations. Cost-effectiveness analysis (CEA) was the most frequent type of economic evaluation, and was present in 11 (52%) studies. Only three CEAs complied fully with the British Medical Journal checklist. The quality of the data sources used in the 21 studies was high, but the CEAs conforming to methodological guidelines did not use high-quality data sources for all components of the analysis. Conclusions This systematic review shows that the level of evidence in economic evaluations of vertebroplasty and kyphoplasty is low, despite the recent publication of a large number of studies. This finding highlights the challenges to be faced to improve the quality of economic evaluations of medical devices. PMID:26661078

Are cardiovascular disease risk assessment and management programmes cost effective? A systematic review of the evidence.

PubMed

Lee, John Tayu; Lawson, Kenny D; Wan, Yizhou; Majeed, Azeem; Morris, Stephen; Soljak, Michael; Millett, Christopher

2017-06-01

The World Health Organization recommends that countries implement population-wide cardiovascular disease (CVD) risk assessment and management programmes. The aim of this study was to conduct a systematic review to evaluate whether this recommendation is supported by cost-effectiveness evidence. Published economic evaluations were identified via electronic medical and social science databases (including Medline, Web of Science, and the NHS Economic Evaluation Database) from inception to March 2016. Study quality was evaluated using a modified version of the Consolidated Health Economic Evaluation Reporting Standards. Fourteen economic evaluations were included: five studies based on randomised controlled trials, seven studies based on observational studies and two studies using hypothetical modelling synthesizing secondary data. Trial based studies measured CVD risk factor changes over 1 to 3years, with modelled projections of longer term events. Programmes were either not, or only, cost-effective under non-verified assumptions such as sustained risk factor changes. Most observational and hypothetical studies suggested programmes were likely to be cost-effective; however, study deigns are subject to bias and subsequent empirical evidence has contradicted key assumptions. No studies assessed impacts on inequalities. In conclusion, recommendations for population-wide risk assessment and management programmes lack a robust, real world, evidence basis. Given implementation is resource intensive there is a need for robust economic evaluation, ideally conducted alongside trials, to assess cost effectiveness. Further, the efficiency and equity impact of different delivery models should be investigated, and also the combination of targeted screening with whole population interventions recognising that there multiple approaches to prevention. Copyright © 2017. Published by Elsevier Inc.

Crescent Evaluation : appendix B : state case study evaluation report

DOT National Transportation Integrated Search

1994-02-01

The state case study evaluation approach uniquely captured an understanding of the potential of such a system by documenting the experiences, issues, and opportunities of selected key state government personnel from a cross-section of involved agenci...

NORTHERN OHIO AEROSOL STUDY: STAPHYLOCOCCUS AUREUS EVALUATION

EPA Science Inventory

A consortium of Universities, located in northwest Ohio have received funds to conduct a comprehensive evaluation of land applied biosolids in that state. This USDA funded study includes observing land application practices and evaluating biosolids, soils, runoff water and bioaer...

Anticipating evaluative social interactions involving persons with disabilities.

PubMed

Santuzzi, Alecia M

2011-08-01

Similar to other types of social interactions, the expected outcomes of interactions between persons with and without disabilities likely are influenced by global self-esteem such that individuals with high self-esteem should fare better than those with low self-esteem. The present set of laboratory studies examined whether simple and complex evaluative situations affect the role of self-esteem when anticipating interactions with individuals who have a physical disability. In Study 1, participants completed a measure of global self-esteem and then were randomly assigned to expect either a brief (5 minutes) or extended (45 minutes) interaction with a confederate in a wheelchair. Participants then completed measures of state affect and meta-evaluations (expected evaluations from the partner). Study 2 replicated the design of Study 1 and additionally randomly assigned participants to be outcome-dependent on the partner or not. Study 1 found that individuals reported affective experiences and expected meta-evaluations that were consistent with global self-esteem when expecting a brief interaction but not an extended interaction with the partner. Study 2 replicated and extended the results from Study 1, demonstrating that self-esteem resumed a priority when participants expected an extended interaction that also placed the participant in an outcome-dependent role. Taken together, the results seem to support a dilution of the role of self-esteem in simple evaluative situations but not in situations that are nonevaluative or situations with combined evaluative factors.

Descriptive analysis of context evaluation instrument for technical oral presentation skills evaluation: A case study in English technical communication course

NASA Astrophysics Data System (ADS)

Mohamed, Abdullah-Adnan; Asmawi, Adelina; Hamid, Mohd Rashid Ab; Mustafa, Zainol bin

2015-02-01

This paper reports a pilot study of Context Evaluation using a self-developed questionnaire distributed among engineering undergraduates at a university under study. The study aims to validate the self-developed questionnaires used in the Context evaluation, a component in the CIPP Model. The Context evaluation assesses background information for needs, assets, problems and opportunities relevant to beneficiaries of the study in a defined environment. Through the questionnaire, background information for the assessment of needs, assets and problems related to the engineering undergraduates' perceptions on the teaching and learning of technical oral presentation skills was collected and analysed. The questionnaire was developed using 5-points Likert scale to measure the constructs under study. They were distributed to 100 respondents with 79 returned. The respondents consisted of engineering undergraduates studied at various faculties at one technical university in Malaysia. The descriptive analysis of data for each item which makes up the construct for Context evaluation is found to be high. This implied that engineering undergraduates showed high interest in teaching and learning of technical oral presentation skills, thus their needs are met. Also, they agreed that assets and facilities are conducive to their learning. In conclusion, the context evaluation involving needs and assets factors are both considerably important; their needs are met and the assets and facilities do support their technical oral presentation skills learning experience.

Integrating service development with evaluation in telehealthcare: an ethnographic study.

PubMed

Finch, Tracy; May, Carl; Mair, Frances; Mort, Maggie; Gask, Linda

2003-11-22

To identify issues that facilitate the successful integration of evaluation and development of telehealthcare services. Ethnographic study using various qualitative research techniques to obtain data from several sources, including in-depth semistructured interviews, project steering group meetings, and public telehealthcare meetings. Seven telehealthcare evaluation projects (four randomised controlled trials and three pragmatic service evaluations) in the United Kingdom, studied over two years. Projects spanned a range of specialties-dermatology, psychiatry, respiratory medicine, cardiology, and oncology. Clinicians, managers, technical experts, and researchers involved in the projects. Key problems in successfully integrating evaluation and service development in telehealthcare are, firstly, defining existing clinical practices (and anticipating changes) in ways that permit measurement; secondly, managing additional workload and conflicting responsibilities brought about by combining clinical and research responsibilities (including managing risk); and, thirdly, understanding various perspectives on effectiveness and the limitations of evaluation results beyond the context of the research study. Combined implementation and evaluation of telehealthcare systems is complex, and is often underestimated. The distinction between quantitative outcomes and the workability of the system is important for producing evaluative knowledge that is of practical value. More pragmatic approaches to evaluation, that permit both quantitative and qualitative methods, are required to improve the quality of such research and its relevance for service provision in the NHS.

Effect of odour on multisensory environmental evaluations of road traffic

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

Jiang, Like, E-mail: jianglike@yahoo.com; Masullo, Massimiliano, E-mail: Massimiliano.MASULLO@unina2.it; Maffei, Luigi, E-mail: luigi.maffei@unina2.it

This study investigated the effect of odour on multisensory environmental evaluations of road traffic. The study aimed to answer: (1) Does odour have any effect on evaluations on noise, landscape and the overall environment? (2) How different are participants' responses to odour stimuli and are these differences influential on the evaluations? Experimental scenarios varied in three Traffic levels, three Tree screening conditions and two Odour presence conditions were designed, and presented to participants in virtual reality. Perceived Loudness, Noise Annoyance, Landscape Quality and Overall Pleasantness of each scenario were evaluated and the results were analysed. It shows that Odour presencemore » did not have significant main effect on any of the evaluations, but has significant interactions with Traffic level on Noise Annoyance and with Tree screening on Landscape Quality, indicating the potential of odour to modulate noise and visual landscape perceptions in specific environmental content. Concerning participants' responses to odour stimuli, large differences were found in this study. However, the differences did not seem to be influential on environmental evaluations in this study. Larger samples of participants may benefit this study for more significant results of odour effect.« less

The Influence of Evaluators' Principles on Evaluation Resource Decisions

ERIC Educational Resources Information Center

Crohn, Kara Shea Davis

2009-01-01

This study examines ways in which evaluators' principles influence decisions about evaluation resources. Evaluators must seek-out and allocate (often scarce) resources (e.g., money, time, data, people, places) in a way that allows them to conduct the best possible evaluation given clients' and evaluation participants' constraints. Working within…

Health information systems evaluation frameworks: A systematic review.

PubMed

Eslami Andargoli, Amirhossein; Scheepers, Helana; Rajendran, Diana; Sohal, Amrik

2017-01-01

Evaluation of health information systems (HISs) is complicated because of the complex nature of the health care domain. Various studies have proposed different frameworks to reduce the complexity in the assessment of these systems. The aim of these frameworks is to provide a set of guidelines for the evaluation of the adequacy of health care information systems. This paper aims to analyse studies on the evaluation of HISs by applying a content, context and process (CCP) framework to address the 'who', 'what', 'how', 'when', and 'why' of the evaluation processes used. This will allow for a better understanding of the relative strengths and weaknesses of various HISs evaluation frameworks, and will pave the way for developing a more complete framework for HISs. A systematic literature review on HIS evaluation studies was undertaken to identify the currently available HIS evaluation frameworks. Five academic databases were selected to conduct this systematic literature review. Most of the studies only address some, but not all, of the five main questions, i.e. the who, what, how, when, why, and that there was a lack of consensus in the way these questions were addressed. The critical role of context was also largely neglected in these studies. Evaluation of HISs is complex. The health care domain is highly context sensitive and in order to have a complete assessment of HISs, consideration of contextual factors is necessary. Specifically, to have the right set of criteria to measure the 'what', the answer to the 'who' of the evaluation is necessary. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Measurement and Design Issues in the Study of Adolescent Sexual Behavior and the Evaluation of Adolescent Sexual Health Behavior Interventions

ERIC Educational Resources Information Center

Young, Michael; Palacios, Rebecca; Penhollow, Tina M.

2012-01-01

To improve the quality of research and commentary concerning adolescent sexuality and evaluation of both comprehensive sexuality education and abstinence education programs, this article aims to help readers (1) select appropriate measures to study adolescent sexual behavior, (2) develop appropriate study designs to evaluate adolescent sexual…

A Qualitative Evaluation of the Use of Multimedia Case Studies in an Introductory Engineering Course at Two Southeastern Universities

ERIC Educational Resources Information Center

Huett, Kim C.; Kawulich, Barbara

2015-01-01

Collaborating at two universities to improve teaching and learning in undergraduate engineering, an interdisciplinary team of researchers, instructors, and evaluators planned and implemented the use of multimedia case studies with students enrolled in an introductory engineering course. This qualitative action evaluation study focuses on results…

An Evaluation of the Relationship between Classroom Practices and Mathematics Motivation from Student and Teacher Perspectives

ERIC Educational Resources Information Center

Chen, Jinsong

2011-01-01

This study evaluated the relationships between classroom practices and mathematics motivation. The evaluation was given in a specific context, namely eighth grade in U.S. middle schools. Using quantitative methods, the study adopted data from the Trends in International Mathematics and Science Study (TIMSS) 2007 and compared classroom practices…

Evaluation of Turkish Education Programs

ERIC Educational Resources Information Center

Durmuscelebi, Mustafa

2010-01-01

The aim of this study is to evaluate the new Turkish education program that has been being implemented since 2005 gradually in light of teacher suggestions. The study has been done in scanning model. In this study which has been conducted with the purpose of evaluating the newly prepared Turkish education programs, the program has been tried to be…

Case Studies of Teacher Satisfaction with Three Plans for Evaluation and Supervision

ERIC Educational Resources Information Center

Arp, Jeb-Stuart Bennett

2013-01-01

The purpose of this study was to identify which plans for evaluation and supervision are most satisfactory to teachers. The study's participants come from three school systems in northwest Georgia. Each school district uses a different plan for evaluation and supervision; each claiming that the end goal is to improve teacher performance. Prior…

78 FR 68461 - Guidance for Industry: Studies To Evaluate the Utility of Anti-Salmonella Chemical Food Additives...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-14

...] Guidance for Industry: Studies To Evaluate the Utility of Anti- Salmonella Chemical Food Additives in Feeds... Industry: Studies to Evaluate the Utility of Anti-Salmonella Chemical Food Additives in Feeds,'' and is... of Anti-Salmonella Chemical Food Additives in Feeds (GFI 80) is to help sponsors design efficacy...

A Multi-Stage Longitudinal Comparative Design Stage II Evaluation of the Changing Lives Program: The Life Course Interview (RDA-LCI)

ERIC Educational Resources Information Center

Arango, Lisa Lewis; Kurtines, William M.; Montgomery, Marilyn J.; Ritchie, Rachel

2008-01-01

The study reported in this article, a Multi-Stage Longitudinal Comparative Design Stage II evaluation conducted as a planned preliminary efficacy evaluation (psychometric evaluation of measures, short-term controlled outcome studies, etc.) of the Changing Lives Program (CLP), provided evidence for the reliability and validity of the qualitative…

The Impact of Disciplinary Background and Teaching Experience on the Use of Evaluative Language in Teacher Feedback

ERIC Educational Resources Information Center

Hu, Guangwei; Choo, Lilin

2016-01-01

This study was designed to examine secondary teachers' use of evaluative language resources in their qualitative written feedback on student work and factors shaping the deployment of such resources. Drawing on appraisal theory as an analytic framework for the language of evaluation, the study analyzed 84 teachers' evaluative reports on their…

Use and Non-use of Evaluation Results: Case Study of Environmental Influences in the Private Sector.

ERIC Educational Resources Information Center

Russ-Eft, Darlene; Atwood, Regina; Egherman, Tori

2002-01-01

Studied the evaluation of a sale program within a business services organization. Interviewed 23 sales people, 10 implementation specialists, 9 consultants, and 40 clients of the business. Results show the use and nonuse of evaluation results and point out the factors contributing to use or nonuse of evaluation results in this private sector…

An Examination of Performance-Based Teacher Evaluation Systems in Five States. Summary. Issues & Answers. REL 2012-No. 129

ERIC Educational Resources Information Center

Shakman, Karen; Riordan, Julie; Sanchez, Maria Teresa; Cook, Kyle DeMeo; Fournier, Richard; Brett, Jessica

2012-01-01

This study reports on performance-based teacher evaluation systems in five states that have implemented such systems. It investigates two primary research questions: (1) What are the key characteristics of state-level performance-based teacher evaluation systems in the study states?; and (2) How do state teacher evaluation measures, the teaching…

Teaching Evaluation: Antecedents of Teachers' Perceived Usefulness of Follow-Up Sessions and Perceived Stress Related to the Evaluation Process

ERIC Educational Resources Information Center

Lejonberg, Eli; Elstad, Eyvind; Christophersen, Knut Andreas

2018-01-01

This study examines teaching evaluation based on student feedback which is intended to contribute to teachers' professional development. Although studies have highlighted that teaching evaluation is a potential source of professional development and that follow-up sessions are crucial to this benefit, little attention has been paid to the…

Teacher Attitudes as Related to the Implementation of the New Jersey Teacher Evaluation System

ERIC Educational Resources Information Center

Gallo, Donna

2016-01-01

The focus of this qualitative case study is on an attitudinal change of teachers towards teacher evaluation with the implementation of a new evaluation system. The goal of this qualitative case study was to gain an understanding of how the implementation of the new New Jersey teacher evaluation system relates to teachers' attitudes toward…

Software Quality Evaluation Models Applicable in Health Information and Communications Technologies. A Review of the Literature.

PubMed

Villamor Ordozgoiti, Alberto; Delgado Hito, Pilar; Guix Comellas, Eva María; Fernandez Sanchez, Carlos Manuel; Garcia Hernandez, Milagros; Lluch Canut, Teresa

2016-01-01

Information and Communications Technologies in healthcare has increased the need to consider quality criteria through standardised processes. The aim of this study was to analyse the software quality evaluation models applicable to healthcare from the perspective of ICT-purchasers. Through a systematic literature review with the keywords software, product, quality, evaluation and health, we selected and analysed 20 original research papers published from 2005-2016 in health science and technology databases. The results showed four main topics: non-ISO models, software quality evaluation models based on ISO/IEC standards, studies analysing software quality evaluation models, and studies analysing ISO standards for software quality evaluation. The models provide cost-efficiency criteria for specific software, and improve use outcomes. The ISO/IEC25000 standard is shown as the most suitable for evaluating the quality of ICTs for healthcare use from the perspective of institutional acquisition.

ENGINEERING STUDY FOR THE 200 AREA EFFLUENT TREATMENT FACILITY (ETF) SECONDARY WASTE TREATMENT OF PROJECTED FUTURE WASTE FEEDS

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

LUECK, K.J.

2004-10-18

This report documents an engineering study conducted to evaluate alternatives for treating secondary waste in the secondary treatment train (STT) of the Hanford Site 200 Area Effluent Treatment Facility (ETF). The study evaluates ETF STT treatment alternatives and recommends preferred alternatives for meeting the projected future missions of the ETF. The preferred alternative(s) will process projected future ETF influents to produce a solid waste acceptable for final disposal on the Hanford Site. The main text of this report summarizes the ETF past and projected operations, lists the assumptions about projected operations that provide the basis for the engineering evaluation, andmore » summarizes the evaluation process. The evaluation process includes identification of available modifications to the current ETF process, screens those modifications for technical viability, evaluates the technically viable alternatives, and provides conclusions and recommendations based on that evaluation.« less

Diagnosing Alzheimer's disease: a systematic review of economic evaluations.

PubMed

Handels, Ron L H; Wolfs, Claire A G; Aalten, Pauline; Joore, Manuela A; Verhey, Frans R J; Severens, Johan L

2014-03-01

The objective of this study is to systematically review the literature on economic evaluations of interventions for the early diagnosis of Alzheimer's disease (AD) and related disorders and to describe their general and methodological characteristics. We focused on the diagnostic aspects of the decision models to assess the applicability of existing decision models for the evaluation of the recently revised diagnostic research criteria for AD. PubMed and the National Institute for Health Research Economic Evaluation database were searched for English-language publications related to economic evaluations on diagnostic technologies. Trial-based economic evaluations were assessed using the Consensus on Health Economic Criteria list. Modeling studies were assessed using the framework for quality assessment of decision-analytic models. The search retrieved 2109 items, from which eight decision-analytic modeling studies and one trial-based economic evaluation met all eligibility criteria. Diversity among the study objective and characteristics was considerable and, despite considerable methodological quality, several flaws were indicated. Recommendations were focused on diagnostic aspects and the applicability of existing models for the evaluation of recently revised diagnostic research criteria for AD. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Evaluating quantity and quality of literature focusing on health economics and pharmacoeconomics in Gulf Cooperation Council countries.

PubMed

Eljilany, Islam; El-Dahiyat, Faris; Curley, Louise Elizabeth; Babar, Zaheer-Ud-Din

2018-05-30

The importance of pharmacoeconomics and health economics has been augmented. It has the potential to provide evidence to aid in optimal decision-making in the funding of cost-effective medicines and services in Gulf Cooperation Council countries (G.C.C). To evaluate the quality and quantity of health economic researches published until the end of 2017 in G.C.C. and to identify the factors that affect the quality of studies. Studies were included according to predefined inclusion and exclusion criteria. The quantity was recorded, and the quality was assessed using the Quality of Health Economic Studies (QHES) instrument. Forty-nine studies were included. The mean (SD) quality score of all studies was 57.83 (25.05), and a high number of reviewed studies (47%) were evaluated as either poor or extremely poor quality. The factors that affect the quality of studies with statistical significance were, the type and method of economic evaluation, the economic outcome was the objective of the research, author`s background, the perspective of the study, health intervention and source of funding. The use of economic evaluation studies in G.C.C was limited. Different factors that affect the quality of articles such as performing a full economic evaluation and choosing societal perspective were identified. Strategies to improve the quality of future studies were recommended.

Current status of quality evaluation of nursing care through director review and reflection from the Nursing Quality Control Centers

PubMed Central

Duan, Xia; Shi, Yan

2014-01-01

Background: The quality evaluation of nursing care is a key link in medical quality management. It is important and worth studying for the nursing supervisors to know the disadvantages during the process of quality evaluation of nursing care and then to improve the whole nursing quality. This study was to provide director insight on the current status of quality evaluation of nursing care from Nursing Quality Control Centers (NQCCs). Material and Methods: This qualitative study used a sample of 12 directors from NQCCs who were recruited from 12 provinces in China to evaluate the current status of quality evaluation of nursing care. Data were collected by in-depth interviews. Content analysis method was used to analyze the data. Results: Four themes emerged from the data: 1) lag of evaluation index; 2) limitations of evaluation content; 3) simplicity of evaluation method; 4) excessive emphasis on terminal quality. Conclusion: It is of great realistic significance to ameliorate nursing quality evaluation criteria, modify the evaluation content based on patient needs-oriented idea, adopt scientific evaluation method to evaluate nursing quality, and scientifically and reasonably draw horizontal comparisons of nursing quality between hospitals, as well as longitudinal comparisons of a hospital’s nursing quality. These methods mentioned above can all enhance a hospital’s core competitiveness and benefit more patients. PMID:25419427

Case study of evaluations that go beyond clinical outcomes to assess quality improvement diabetes programmes using the Diabetes Evaluation Framework for Innovative National Evaluations (DEFINE)

PubMed Central

Harris, Stewart B.; Naqshbandi Hayward, Mariam; Tompkins, Jordan W.

2016-01-01

Abstract Rationale, aims and objectives Investments in efforts to reduce the burden of diabetes on patients and health care are critical; however, more evaluation is needed to provide evidence that informs and supports future policies and programmes. The newly developed Diabetes Evaluation Framework for Innovative National Evaluations (DEFINE) incorporates the theoretical concepts needed to facilitate the capture of critical information to guide investments, policy and programmatic decision making. The aim of the study is to assess the applicability and value of DEFINE in comprehensive real‐world evaluation. Method Using a critical and positivist approach, this intrinsic and collective case study retrospectively examines two naturalistic evaluations to demonstrate how DEFINE could be used when conducting real‐world comprehensive evaluations in health care settings. Results The variability between the cases and the evaluation designs are described and aligned to the DEFINE goals, steps and sub‐steps. The majority of the theoretical steps of DEFINE were exemplified in both cases, although limited for knowledge translation efforts. Application of DEFINE to evaluate diverse programmes that target various chronic diseases is needed to further test the inclusivity and built‐in flexibility of DEFINE and its role in encouraging more comprehensive knowledge translation. Conclusions This case study shows how DEFINE could be used to structure or guide comprehensive evaluations of programmes and initiatives implemented in health care settings and support scale‐up of successful innovations. Future use of the framework will continue to strengthen its value in guiding programme evaluation and informing health policy to reduce the burden of diabetes and other chronic diseases. PMID:26804339

Evaluating markers for the early detection of cancer: overview of study designs and methods.

PubMed

Baker, Stuart G; Kramer, Barnett S; McIntosh, Martin; Patterson, Blossom H; Shyr, Yu; Skates, Steven

2006-01-01

The field of cancer biomarker development has been evolving rapidly. New developments both in the biologic and statistical realms are providing increasing opportunities for evaluation of markers for both early detection and diagnosis of cancer. To review the major conceptual and methodological issues in cancer biomarker evaluation, with an emphasis on recent developments in statistical methods together with practical recommendations. We organized this review by type of study: preliminary performance, retrospective performance, prospective performance and cancer screening evaluation. For each type of study, we discuss methodologic issues, provide examples and discuss strengths and limitations. Preliminary performance studies are useful for quickly winnowing down the number of candidate markers; however their results may not apply to the ultimate target population, asymptomatic subjects. If stored specimens from cohort studies with clinical cancer endpoints are available, retrospective studies provide a quick and valid way to evaluate performance of the markers or changes in the markers prior to the onset of clinical symptoms. Prospective studies have a restricted role because they require large sample sizes, and, if the endpoint is cancer on biopsy, there may be bias due to overdiagnosis. Cancer screening studies require very large sample sizes and long follow-up, but are necessary for evaluating the marker as a trigger of early intervention.

A framework for evaluating e-health: Systematic review of studies assessing the quality of health information and services for patients on the Internet

PubMed Central

Eysenbach, Gunther

2000-01-01

Context A recent concern and topic of many publications in the last three years has been the quality of health information and services for the public on the Internet. Objectives To identify and summarize studies published in the peer-reviewed literature evaluating the quality of information and services for consumers on the Internet, including information published on web sites, information on newsgroups and mailing lists and other venues such as email contacts with doctors, as well as studies evaluating the quality of ehealth services such as cyberdoctors and cyberpharmacies. Data Sources MEDLINE and PREMEDLINE (1966 - May 2000), Science Citation Index (1992-May 2000), Social Sciences Citation Index (1992- May 2000), Arts and Humanities Citation Index (1992-May 2000) and a personal bibliographic database. Study Selection We included empirical studies where investigators searched the Internet systematically for specific health information or clearly define a set of specific services to be included, evaluated the quality of information or services found, and reported quantitative data. Data Extraction Study characteristics, medical domain, search strategies used, quality criteria and methodology of quality assessment, results (number of sites rated as sufficient pertaining to a quality), quality and rigor of study methodology and reporting. Data Synthesis A total of 41 studies met the inclusion criteria, dealing either with content of websites, information on e-commerce sites, quality of online-care or community venues. A) Content: 29 evaluated information on websites, of those 5 evaluated information on websites from the field of pediatrics, 3 from oncology, 3 pharmacology information, 2 nutrition information, 4 general clinical information and 12 specific information from other clinical disciplines. Studies varied widely in methodology, quality and results. Among the 29 studies dealing with quality of health information on websites, one study evaluated the authority of source, 19 studies checked sites for presence or absences of technical criteria (such as disclosure of sponsorship, authorship, presence of references or last update), three evaluated readability, 20 evaluated the accuracy of information, and 12 content completeness. B) E-Commerce: Three studies dealt with drug information on e-commerce sites. To evaluate the quality authors extracted prices, checked for completeness of online-history taking and/or information provided on the site e.g. pertaining to contraindications or the presence/absence of disclaimers and/or liability waivers. Only one of these three studies actually used the service by ordering drugs, allowing to evaluate quality of online-advice, qualification of cyberdocs, delivery time, reasons for non-delivery. C) Care: Five studies dealt with the quality of online consultations, of them one dealt with advice given by ordinary physicians in response to a unsolicited fictionous patient request, two evaluated the responses of cyberdocs soliciting patient requests, and two evaluated advice given in response to a request for an online prescription directed to drug e-commerce sites. D) Community: Seven studies evaluated messages on mailing lists or usenet newsgroups. Two studies collected messages from a venue and evaluated them for accuracy, two studies posted a "test" message on a newsgroup and evaluated the accuracy of responses. In three studies authors used the cumulative impact factor of the published research of the mailing list contributors as an indicator for the qualification of the authors and thus as quality indicator of the mailing list. Of the 23 studies evaluating accuracy and/or completeness of information provided on websites, 10 used guidelines as gold standard (all of the to extract a-priori criteria), five used peer-reviewed literature (all to compare information a posteriori), two used textbooks, one used consensus among the raters and three used the personal experience or opinion of the author. All three studies which compared information against personal opinion came to a positive conclusion regarding the accuracy of information, while all of the more rigorous studies comparing information against guidelines concluded that much of the information found on the web were of low quality. In two cases it was not reported where the gold standard comes from. 9 studies used more than one rater to assess a website, 6 of them provided some sort of information on inter-observer variability. Conclusions Methodology, results and conclusions of investigators vary widely. There is a wide variability even regarding the evaluation of formal criteria such as authorship and references. Differences in study conclusions regarding the quality of Internet information are likely a result of difference in study rigor, evaluation criteria and topic chosen. All but five studies concluded that quality is a problem on the Internet. The rigor of these five studies coming to a more positive conclusion as expressed in a "assessment quality score" was significantly inferior to the remaining studies. Although there were two comparative studies of the quality of information on the Internet compared with information found outside of the Internet, there is little evidence that health information found on the Internet is worse than health information in traditional media. A conceptual and methodological framework is presented for describing, comparing, and analyzing the structure and quality of e-health, based on Donabedians quality measures of structure, process and outcome.

A Critical Review of Methods to Evaluate the Impact of FDA Regulatory Actions

PubMed Central

Briesacher, Becky A.; Soumerai, Stephen B.; Zhang, Fang; Toh, Sengwee; Andrade, Susan E.; Wagner, Joann L.; Shoaibi, Azadeh; Gurwitz, Jerry H.

2013-01-01

Purpose To conduct a synthesis of the literature on methods to evaluate the impacts of FDA regulatory actions, and identify best practices for future evaluations. Methods We searched MEDLINE for manuscripts published between January 1948 and August 2011 that included terms related to FDA, regulatory actions, and empirical evaluation; the review additionally included FDA-identified literature. We used a modified Delphi method to identify preferred methodologies. We included studies with explicit methods to address threats to validity, and identified designs and analytic methods with strong internal validity that have been applied to other policy evaluations. Results We included 18 studies out of 243 abstracts and papers screened. Overall, analytic rigor in prior evaluations of FDA regulatory actions varied considerably; less than a quarter of studies (22%) included control groups. Only 56% assessed changes in the use of substitute products/services, and 11% examined patient health outcomes. Among studies meeting minimal criteria of rigor, 50% found no impact or weak/modest impacts of FDA actions and 33% detected unintended consequences. Among those studies finding significant intended effects of FDA actions, all cited the importance of intensive communication efforts. There are preferred methods with strong internal validity that have yet to be applied to evaluations of FDA regulatory actions. Conclusions Rigorous evaluations of the impact of FDA regulatory actions have been limited and infrequent. Several methods with strong internal validity are available to improve trustworthiness of future evaluations of FDA policies. PMID:23847020

Urban pedestrian accident countermeasures experimental evaluation. Volume 1, Behavioral evaluation studies

DOT National Transportation Integrated Search

1975-02-01

A series of site and accident specific pedestrian safety countermeasures had been developed in a previous study, but the effectiveness of these countermeasures had not been empirically evaluated. This project focused on the determination of the effec...

78 FR 6329 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-30

... announced below concerns Birth Defects Study to Evaluate Pregnancy exposureS (BD-STEPS), FOA DD13-003... evaluation of applications received in response to ``Birth Defects Study to Evaluate Pregnancy exposureS (BD...

Safety evaluation of STOP AHEAD pavement markings

DOT National Transportation Integrated Search

2007-12-01

The Federal Highway Administration (FHWA) organized a Pooled Fund Study of 26 States to evaluate low-cost safety strategies as part of its strategic highway safety effort. One of the strategies chosen to be evaluated for this study was STOP AHEAD pav...