Quality by Design (QbD) Approach for Development of Co-Processed Excipient Pellets (MOMLETS) By Extrusion-Spheronization Technique.

Science.gov (United States)

Patel, Hetal; Patel, Kishan; Tiwari, Sanjay; Pandey, Sonia; Shah, Shailesh; Gohel, Mukesh

2016-01-01

Microcrystalline cellulose (MCC) is an excellent excipient for the production of pellets by extrusion spheronization. However, it causes slow release rate of poorly water soluble drugs from pellets. Co-processed excipient prepared by spray drying (US4744987; US5686107; WO2003051338) and coprecipitation technique (WO9517831) are patented. The objective of present study was to develop co-processed MCC pellets (MOMLETS) by extrusion-spheronization technique using the principle of Quality by Design (QbD). Co-processed excipient core pellets (MOMLETS) were developed by extrusion spheronization technique using Quality by Design (QbD) approach. BCS class II drug (telmisartan) was layered onto it in a fluidized bed processor. Quality Target Product Profile (QTPP) and Critical Quality Attributes (CQA) for pellets were identified. Risk assessment was reported using Ishikawa diagram. Plackett Burman design was used to check the effect of seven independent variables; superdisintegrant, extruder speed, ethanol: water, spheronizer speed, extruder screen, pore former and MCC: lactose; on percentage drug release at 30 min. Pareto chart and normal probability plot was constructed to identify the significant factors. Box-Behnken design (BBD) using three most significant factors (Extruder screen size, type of superdisintegrant and type of pore former) was used as an optimization design. The control space was identified in which desired quality of the pellets can be obtained. Co-processed excipient core pellets (MOMLETS) were successfully developed by QbD approach. Versatility, Industrial scalability and simplicity are the main features of the proposed research. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The binding of quinone to the photosynthetic reaction centers: kinetics and thermodynamics of reactions occurring at the QB-site in zwitterionic and anionic liposomes.

Science.gov (United States)

Mavelli, Fabio; Trotta, Massimo; Ciriaco, Fulvio; Agostiano, Angela; Giotta, Livia; Italiano, Francesca; Milano, Francesco

2014-07-01

Liposomes represent a versatile biomimetic environment for studying the interaction between integral membrane proteins and hydrophobic ligands. In this paper, the quinone binding to the QB-site of the photosynthetic reaction centers (RC) from Rhodobacter sphaeroides has been investigated in liposomes prepared with either the zwitterionic phosphatidylcholine (PC) or the negatively charged phosphatidylglycerol (PG) to highlight the role of the different phospholipid polar heads. Quinone binding (K Q) and interquinone electron transfer (L AB) equilibrium constants in the two type of liposomes were obtained by charge recombination reaction of QB-depleted RC in the presence of increasing amounts of ubiquinone-10 over the temperature interval 6-35 °C. The kinetic of the charge recombination reactions has been fitted by numerically solving the ordinary differential equations set associated with a detailed kinetic scheme involving electron transfer reactions coupled with quinone release and uptake. The entire set of traces at each temperature was accurately fitted using the sole quinone release constants (both in a neutral and a charge separated state) as adjustable parameters. The temperature dependence of the quinone exchange rate at the QB-site was, hence, obtained. It was found that the quinone exchange regime was always fast for PC while it switched from slow to fast in PG as the temperature rose above 20 °C. A new method was introduced in this paper for the evaluation of constant K Q using the area underneath the charge recombination traces as the indicator of the amount of quinone bound to the QB-site.

Strategic framework for education and training in Quality by Design (QbD) and process analytical technology (PAT).

Science.gov (United States)

de Matas, Marcel; De Beer, Thomas; Folestad, Staffan; Ketolainen, Jarkko; Lindén, Hans; Lopes, João Almeida; Oostra, Wim; Weimer, Marco; Öhrngren, Per; Rantanen, Jukka

2016-07-30

The regulatory and technical landscape of the pharmaceutical field is rapidly evolving from one focused predominantly on development of small molecules, using well established manufacturing technologies towards an environment in which biologicals and complex modalities are being developed using advanced science and technology coupled with the application of modern Quality by Design (QbD) principles. In order that Europe keeps pace with these changes and sustains its position as major player in the development and commercialization of medicines, it is essential that measures are put in place to maintain a highly skilled workforce. A number of challenges however exist to equipping academic, industrial and health agency staff with the requisite knowledge, skills and experience to develop the next generation of medicines. In this regard, the EUFEPS QbD and PAT Sciences Network has proposed a structured framework for education, training and continued professional development, which comprises a number of pillars covering the fundamental principles of modern pharmaceutical development including the underpinning aspects of science, engineering and technology innovation. The framework is not prescriptive and is not aimed at describing specific course content in detail. It should however be used as a point of reference for those institutions delivering pharmaceutical based educational courses, to ensure that the necessary skills, knowledge and experience for successful pharmaceutical development are maintained. A positive start has been made and a number of examples of formal higher education courses and short training programs containing elements of this framework have been described. The ultimate vision for this framework however, is to see widespread adoption and proliferation of this curriculum with it forming the backbone of QbD and PAT science based skills development. Copyright © 2016 Elsevier B.V. All rights reserved.

Knowledge management in a waste based biorefinery in the QbD paradigm.

Science.gov (United States)

Rathore, Anurag S; Chopda, Viki R; Gomes, James

2016-09-01

Shifting resource base from fossil feedstock to renewable raw materials for production of chemical products has opened up an area of novel applications of industrial biotechnology-based process tools. This review aims to provide a concise and focused discussion on recent advances in knowledge management to facilitate efficient and optimal operation of a biorefinery. Application of quality by design (QbD) and process analytical technology (PAT) as tools for knowledge creation and management at different levels has been highlighted. Role of process integration, government policies, knowledge exchange through collaboration, and use of databases and computational tools have also been touched upon. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tuning cofactor redox potentials: the 2-methoxy dihedral angle generates a redox potential difference of >160 mV between the primary (Q(A)) and secondary (Q(B)) quinones of the bacterial photosynthetic reaction center.

Science.gov (United States)

Taguchi, Alexander T; Mattis, Aidas J; O'Malley, Patrick J; Dikanov, Sergei A; Wraight, Colin A

2013-10-15

Only quinones with a 2-methoxy group can act simultaneously as the primary (QA) and secondary (QB) electron acceptors in photosynthetic reaction centers from Rhodobacter sphaeroides. (13)C hyperfine sublevel correlation measurements of the 2-methoxy in the semiquinone states, SQA and SQB, were compared with quantum mechanics calculations of the (13)C couplings as a function of the dihedral angle. X-ray structures support dihedral angle assignments corresponding to a redox potential gap (ΔEm) between QA and QB of ~180 mV. This is consistent with the failure of a ubiquinone analogue lacking the 2-methoxy to function as QB in mutant reaction centers with a ΔEm of ≈160-195 mV.

Infrared speckle observations of the binary Ross 614 AB - combined shift-and-add and zero-and-add analysis

International Nuclear Information System (INIS)

Davey, B.L.K.; Bates, R.H.T.; Cocke, W.J.; Mccarthy, D.W. Jr.; Christou, J.C.

1989-01-01

One-dimensional infrared speckle scans of Ross 614 AB were recorded at a wavelength of 2.2 microns, and the three bins corresponding to the three best seeing conditions were further processed by applying a shift-and-add algorithm to the set of images contained within each bin, generating three shift-and-add images with differing shift-and-add point-spread functions. A zero-and-add technique was used to deconvolve the three shift-and-add images in order to obtain parameters corresponding to the separation and the brightness ratio of a two-component model of Ross 614 Ab. Least-squares analysis results reveal a separation of 1.04 arcsec and a brightness ratio of 4.3 for the binary system at this wavelength. 31 refs

Transcriptome profiling of whole blood cells identifies PLEK2 and C1QB in human melanoma.

Directory of Open Access Journals (Sweden)

Yuchun Luo

Full Text Available Developing analytical methodologies to identify biomarkers in easily accessible body fluids is highly valuable for the early diagnosis and management of cancer patients. Peripheral whole blood is a "nucleic acid-rich" and "inflammatory cell-rich" information reservoir and represents systemic processes altered by the presence of cancer cells.We conducted transcriptome profiling of whole blood cells from melanoma patients. To overcome challenges associated with blood-based transcriptome analysis, we used a PAXgene™ tube and NuGEN Ovation™ globin reduction system. The combined use of these systems in microarray resulted in the identification of 78 unique genes differentially expressed in the blood of melanoma patients. Of these, 68 genes were further analyzed by quantitative reverse transcriptase PCR using blood samples from 45 newly diagnosed melanoma patients (stage I to IV and 50 healthy control individuals. Thirty-nine genes were verified to be differentially expressed in blood samples from melanoma patients. A stepwise logit analysis selected eighteen 2-gene signatures that distinguish melanoma from healthy controls. Of these, a 2-gene signature consisting of PLEK2 and C1QB led to the best result that correctly classified 93.3% melanoma patients and 90% healthy controls. Both genes were upregulated in blood samples of melanoma patients from all stages. Further analysis using blood fractionation showed that CD45(- and CD45(+ populations were responsible for the altered expression levels of PLEK2 and C1QB, respectively.The current study provides the first analysis of whole blood-based transcriptome biomarkers for malignant melanoma. The expression of PLEK2, the strongest gene to classify melanoma patients, in CD45(- subsets illustrates the importance of analyzing whole blood cells for biomarker studies. The study suggests that transcriptome profiling of blood cells could be used for both early detection of melanoma and monitoring of patients

Gray QB-sing-faced version 2 (SF2) open environment test report

Energy Technology Data Exchange (ETDEWEB)

Plummer, J. [Savannah River Site (SRS), Aiken, SC (United States); Immel, D. [Savannah River Site (SRS), Aiken, SC (United States); Bobbitt, J. [Savannah River Site (SRS), Aiken, SC (United States); Negron, M. [Savannah River Site (SRS), Aiken, SC (United States)

2015-02-16

This report details the design upgrades incorporated into the new version of the GrayQbTM SF2 device and the characterization testing of this upgraded device. Results from controlled characterization testing in the Savannah River National Laboratory (SRNL) R&D Engineering Imaging and Radiation Lab (IRL) and the Savannah River Site (SRS) Health Physics Instrument Calibration Laboratory (HPICL) is presented, as well as results from the open environment field testing performed in the E-Area Low Level Waste Storage Area. Resultant images presented in this report were generated using the SRNL developed Radiation Analyzer (RAzerTM) software program which overlays the radiation contour images onto the visual image of the location being surveyed.

The rate of second electron transfer to QB(-) in bacterial reaction center of impaired proton delivery shows hydrogen-isotope effect.

Science.gov (United States)

Maróti, Ágnes; Wraight, Colin A; Maróti, Péter

2015-02-01

The 2nd electron transfer in reaction center of photosynthetic bacterium Rhodobacter sphaeroides is a two step process in which protonation of QB(-) precedes interquinone electron transfer. The thermal activation and pH dependence of the overall rate constants of different RC variants were measured and compared in solvents of water (H2O) and heavy water (D2O). The electron transfer variants where the electron transfer is rate limiting (wild type and M17DN, L210DN and H173EQ mutants) do not show solvent isotope effect and the significant decrease of the rate constant of the second electron transfer in these mutants is due to lowering the operational pKa of QB(-)/QBH: 4.5 (native), 3.9 (L210DN), 3.7 (M17DN) and 3.1 (H173EQ) at pH7. On the other hand, the proton transfer variants where the proton transfer is rate limiting demonstrate solvent isotope effect of pH-independent moderate magnitude (2.11±0.26 (WT+Ni(2+)), 2.16±0.35 (WT+Cd(2+)) and 2.34±0.44 (L210DN/M17DN)) or pH-dependent large magnitude (5.7 at pH4 (L213DN)). Upon deuteration, the free energy and the enthalpy of activation increase in all proton transfer variants by about 1 kcal/mol and the entropy of activation becomes negligible in L210DN/M17DN mutant. The results are interpreted as manifestation of equilibrium and kinetic solvent isotope effects and the structural, energetic and kinetic possibility of alternate proton delivery pathways are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

Mechanisms with discrete nitrene species

Indian Academy of Sciences (India)

identifying a dissociation path involving singlet acyl- nitrene. However, CCSD(T) and CBS-QB3 studies62 predicted acetyl azide decomposes by methyl group migration to give methyl isocyanate and N2 with a bar- rier of 27 kcal/mol. Experimentally, photolysis of pival- oyl azide gives singlet pivaloyl nitrene,45 which adds to.

Structural consequences of disease-causing mutations in the ATRX-DNMT3-DNMT3L (ADD) domain of the chromatin-associated protein ATRX.

Science.gov (United States)

Argentaro, Anthony; Yang, Ji-Chun; Chapman, Lynda; Kowalczyk, Monika S; Gibbons, Richard J; Higgs, Douglas R; Neuhaus, David; Rhodes, Daniela

2007-07-17

The chromatin-associated protein ATRX was originally identified because mutations in the ATRX gene cause a severe form of syndromal X-linked mental retardation associated with alpha-thalassemia. Half of all of the disease-associated missense mutations cluster in a cysteine-rich region in the N terminus of ATRX. This region was named the ATRX-DNMT3-DNMT3L (ADD) domain, based on sequence homology with a family of DNA methyltransferases. Here, we report the solution structure of the ADD domain of ATRX, which consists of an N-terminal GATA-like zinc finger, a plant homeodomain finger, and a long C-terminal alpha-helix that pack together to form a single globular domain. Interestingly, the alpha-helix of the GATA-like finger is exposed and highly basic, suggesting a DNA-binding function for ATRX. The disease-causing mutations fall into two groups: the majority affect buried residues and hence affect the structural integrity of the ADD domain; another group affects a cluster of surface residues, and these are likely to perturb a potential protein interaction site. The effects of individual point mutations on the folding state and stability of the ADD domain correlate well with the levels of mutant ATRX protein in patients, providing insights into the molecular pathophysiology of ATR-X syndrome.

Process for Biotransformation of Androsta-4-ene-3, 17-Dione (4-AD) to Androsta-1,4-Diene-3,17-Dione (ADD).

Science.gov (United States)

Prakash, Surya; Bajaj, Abhay

2017-01-01

Androsta-1,4-diene-3,17-dione (androstadienedione, ADD) is key intermediate for the organic synthesis of a variety of female sex hormones such as estrone, estradiol, estriol and other related derivatives. De novo synthesis of this molecule is not yet reported in any form of living system, i.e., microbial, plant, and animal. The structural complexities due to presence of several chiral carbon centers create significant hurdles in chemical synthesis of such molecules. Microbe-mediated biotransformation offer a highly reliable, cost-effective, and relatively non hazardous way for commercial manufacturing of steroidal key intermediates. Currently microbial biotransformations are extensively being exploited for large-scale production of basic intermediates such as androstenedione (AD), ADD, and several types of hydroxylated derivatives of androstane compounds. In this chapter several aspects of microbial biotransformation process of AD to ADD are discussed.

46 CFR 57.04-1 - Test specimen requirements and definition of ranges (modifies QW 202, QW 210, QW 451, and QB 202).

Science.gov (United States)

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Test specimen requirements and definition of ranges... HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING WELDING AND BRAZING Procedure Qualification Range § 57.04-1 Test specimen requirements and definition of ranges (modifies QW 202, QW 210, QW 451, and QB 202...

Conformational differences between the methoxy groups of QA and QB site ubisemiquinones in bacterial reaction centers: a key role for methoxy group orientation in modulating ubiquinone redox potential.

Science.gov (United States)

Taguchi, Alexander T; O'Malley, Patrick J; Wraight, Colin A; Dikanov, Sergei A

2013-07-09

Ubiquinone is an almost universal, membrane-associated redox mediator. Its ability to accept either one or two electrons allows it to function in critical roles in biological electron transport. The redox properties of ubiquinone in vivo are determined by its environment in the binding sites of proteins and by the dihedral angle of each methoxy group relative to the ring plane. This is an attribute unique to ubiquinone among natural quinones and could account for its widespread function with many different redox complexes. In this work, we use the photosynthetic reaction center as a model system for understanding the role of methoxy conformations in determining the redox potential of the ubiquinone/semiquinone couple. Despite the abundance of X-ray crystal structures for the reaction center, quinone site resolution has thus far been too low to provide a reliable measure of the methoxy dihedral angles of the primary and secondary quinones, QA and QB. We performed 2D ESEEM (HYSCORE) on isolated reaction centers with ubiquinones (13)C-labeled at the headgroup methyl and methoxy substituents, and have measured the (13)C isotropic and anisotropic components of the hyperfine tensors. Hyperfine couplings were compared to those derived by DFT calculations as a function of methoxy torsional angle allowing estimation of the methoxy dihedral angles for the semiquinones in the QA and QB sites. Based on this analysis, the orientation of the 2-methoxy groups are distinct in the two sites, with QB more out of plane by 20-25°. This corresponds to an ≈50 meV larger electron affinity for the QB quinone, indicating a substantial contribution to the experimental difference in redox potentials (60-75 mV) of the two quinones. The methods developed here can be readily extended to ubiquinone-binding sites in other protein complexes.

Multivariate Approaches for Simultaneous Determination of Avanafil and Dapoxetine by UV Chemometrics and HPLC-QbD in Binary Mixtures and Pharmaceutical Product.

Science.gov (United States)

2016-04-07

Multivariate UV-spectrophotometric methods and Quality by Design (QbD) HPLC are described for concurrent estimation of avanafil (AV) and dapoxetine (DP) in the binary mixture and in the dosage form. Chemometric methods have been developed, including classical least-squares, principal component regression, partial least-squares, and multiway partial least-squares. Analytical figures of merit, such as sensitivity, selectivity, analytical sensitivity, LOD, and LOQ were determined. QbD consists of three steps, starting with the screening approach to determine the critical process parameter and response variables. This is followed by understanding of factors and levels, and lastly the application of a Box-Behnken design containing four critical factors that affect the method. From an Ishikawa diagram and a risk assessment tool, four main factors were selected for optimization. Design optimization, statistical calculation, and final-condition optimization of all the reactions were Carried out. Twenty-five experiments were done, and a quadratic model was used for all response variables. Desirability plot, surface plot, design space, and three-dimensional plots were calculated. In the optimized condition, HPLC separation was achieved on Phenomenex Gemini C18 column (250 × 4.6 mm, 5 μm) using acetonitrile-buffer (ammonium acetate buffer at pH 3.7 with acetic acid) as a mobile phase at flow rate of 0.7 mL/min. Quantification was done at 239 nm, and temperature was set at 20°C. The developed methods were validated and successfully applied for simultaneous determination of AV and DP in the dosage form.

Applying quality by design (QbD) concept for fabrication of chitosan coated nanoliposomes.

Science.gov (United States)

Pandey, Abhijeet P; Karande, Kiran P; Sonawane, Raju O; Deshmukh, Prashant K

2014-03-01

In the present investigation, a quality by design (QbD) strategy was successfully applied to the fabrication of chitosan-coated nanoliposomes (CH-NLPs) encapsulating a hydrophilic drug. The effects of the processing variables on the particle size, encapsulation efficiency (%EE) and coating efficiency (%CE) of CH-NLPs (prepared using a modified ethanol injection method) were investigated. The concentrations of lipid, cholesterol, drug and chitosan; stirring speed, sonication time; organic:aqueous phase ratio; and temperature were identified as the key factors after risk analysis for conducting a screening design study. A separate study was designed to investigate the robustness of the predicted design space. The particle size, %EE and %CE of the optimized CH-NLPs were 111.3 nm, 33.4% and 35.2%, respectively. The observed responses were in accordance with the predicted response, which confirms the suitability and robustness of the design space for CH-NLP formulation. In conclusion, optimization of the selected key variables will help minimize the problems related to size, %EE and %CE that are generally encountered when scaling up processes for NLP formulations. The robustness of the design space will help minimize both intra-batch and inter-batch variations, which are quite common in the pharmaceutical industry.

Risk Assessment Integrated QbD Approach for Development of Optimized Bicontinuous Mucoadhesive Limicubes for Oral Delivery of Rosuvastatin.

Science.gov (United States)

Javed, Md Noushad; Kohli, Kanchan; Amin, Saima

2018-04-01

Statins are widely prescribed for hyperlipidemia, cancer, and Alzheimer's disease but are facing some inherent challenges such as low solubility and drug loading, higher hepatic metabolism, as well as instability at gastric pH. So, relatively higher circulating dose, required for exerting the therapeutic benefits, leads to dose-mediated severe toxicity. Furthermore, due to low biocompatibility, high toxicity, and other regulatory caveats such as product conformity, reproducibility, and stability of conventional formulations as well as preferentially higher bioabsorption of lipids in their favorable cuboidal geometry, enhancement in in vivo biopharmaceutical performance of Rosuvastatin could be well manifested in Quality by Design (QbD) integrated cuboidal-shaped mucoadhesive microcrystalline delivery systems (Limicubes). Here, quality-target-product-profile (QTPPs), critical quality attributes (CQAs), Ishikawa fishbone diagram, and integration of risk management through risk assessment matrix for failure mode and effects analysis (FMEA) followed by processing of Plackett-Burman design matrix using different statistical test for the first time established an approach to substantiate the claims that controlling levels of only these three screened out independent process variables, i.e., Monoolein (B = 800-1100 μL), Poloxamer (C = 150-200 mg), and stirring speed (F = 700-1000 rpm) were statistically significant to modulate and improve the biopharmaceutical performance affecting key attributes, viz., average particle size (Y 1  = 1.40-2.70 μ), entrapment efficiency (Y 2  = 62.60-88.80%), and drug loading (Y 3  = 0.817-1.15%), in QbD-enabled process. The optimal performance of developed Limicubes exhibited an average particle size of 1.8 ± 0.2 μ, entrapment efficiency 80.32 ± 2.88%, and drug loading 0.93 ± 0.08% at the level of 1100 μL (+ 1), 200 mg (+ 1), and 700 rpm (- 1) for Monoolein, Poloxamer, and stirring

Add Value

DEFF Research Database (Denmark)

Kobbelgaard, Cecilie Elisabeth

2016-01-01

"Add Value – kend din kunde" er et brætspil, som giver både offentlige og private virksomheder unikke muligheder for at forbedre deres service overfor kunderne. Spillet giver, på en alternativ og handlingsorienteret måde, mulighed for at blive skarpere på kundeoplevelsen – hvor er der værdi...... at hente, og hvor kan der spares på tid og ressourcer? Dette samtidig med, at kunderne får den oplevelse og service, de forventer. Når I spiller "Add Value – kend din kunde" sættes der fokus på Jeres kundeservice ud fra kundens perspektiv, og det er i alle Jeres kontaktflader med kunden. Lige fra kunden...

QbD-enabled systematic development of gastroretentive multiple-unit microballoons of itopride hydrochloride.

Science.gov (United States)

Bansal, Sanjay; Beg, Sarwar; Asthana, Abhay; Garg, Babita; Asthana, Gyati Shilakari; Kapil, Rishi; Singh, Bhupinder

2016-01-01

The objectives of present studies were to develop the systematically optimized multiple-unit gastroretentive microballoons, i.e. hollow microspheres of itopride hydrochloride (ITH) employing quality by design (QbD)-based approach. Initially, the patient-centric QTPP and CQAs were earmarked, and preliminary studies were conducted to screen the suitable polymer, solvent, solvent ratio, pH and temperature conditions. Microspheres were prepared by non-aqueous solvent evaporation method employing Eudragit S-100. Risk assessment studies carried out by constructing Ishikawa cause-effect fish-bone diagram, and techniques like risk estimation matrix (REM) and failure mode effect analysis (FMEA) facilitated the selection of plausible factors affecting the drug product CQAs, i.e. percent yield, entrapment efficiency (EE) and percent buoyancy. A 3(3) Box-Behnken design (BBD) was employed for optimizing CMAs and CPPs selected during factor screening studies employing Taguchi design, i.e. drug-polymer ratio (X1), stirring temperature (X2) and stirring speed (X3). The hollow microspheres, as per BBD, were evaluated for EE, particle size and drug release characteristics. The optimum formulation was embarked upon using numerical desirability function yielding excellent floatation characteristics along with adequate drug release control. Drug-excipient compatibility studies employing FT-IR, DSC and powder XRD revealed absence of significant interaction among the formulation excipients. The SEM studies on the optimized formulation showed hollow and spherical nature of the prepared microspheres. In vivo X-ray imaging studies in rabbits confirmed the buoyant nature of the hollow microspheres for 8 h in the upper GI tract. In a nutshell, the current investigations report the successful development of gastroretentive floating microspheres for once-a-day administration of ITH.

Embedding objects during 3D printing to add new functionalities.

Science.gov (United States)

Yuen, Po Ki

2016-07-01

A novel method for integrating and embedding objects to add new functionalities during 3D printing based on fused deposition modeling (FDM) (also known as fused filament fabrication or molten polymer deposition) is presented. Unlike typical 3D printing, FDM-based 3D printing could allow objects to be integrated and embedded during 3D printing and the FDM-based 3D printed devices do not typically require any post-processing and finishing. Thus, various fluidic devices with integrated glass cover slips or polystyrene films with and without an embedded porous membrane, and optical devices with embedded Corning(®) Fibrance™ Light-Diffusing Fiber were 3D printed to demonstrate the versatility of the FDM-based 3D printing and embedding method. Fluid perfusion flow experiments with a blue colored food dye solution were used to visually confirm fluid flow and/or fluid perfusion through the embedded porous membrane in the 3D printed fluidic devices. Similar to typical 3D printed devices, FDM-based 3D printed devices are translucent at best unless post-polishing is performed and optical transparency is highly desirable in any fluidic devices; integrated glass cover slips or polystyrene films would provide a perfect optical transparent window for observation and visualization. In addition, they also provide a compatible flat smooth surface for biological or biomolecular applications. The 3D printed fluidic devices with an embedded porous membrane are applicable to biological or chemical applications such as continuous perfusion cell culture or biocatalytic synthesis but without the need for any post-device assembly and finishing. The 3D printed devices with embedded Corning(®) Fibrance™ Light-Diffusing Fiber would have applications in display, illumination, or optical applications. Furthermore, the FDM-based 3D printing and embedding method could also be utilized to print casting molds with an integrated glass bottom for polydimethylsiloxane (PDMS) device replication

Early Implementation of QbD in Biopharmaceutical Development: A Practical Example

Directory of Open Access Journals (Sweden)

Jesús Zurdo

2015-01-01

Full Text Available In drug development, the “onus” of the low R&D efficiency has been put traditionally onto the drug discovery process (i.e., finding the right target or “binding” functionality. Here, we show that manufacturing is not only a central component of product success, but also that, by integrating manufacturing and discovery activities in a “holistic” interpretation of QbD methodologies, we could expect to increase the efficiency of the drug discovery process as a whole. In this new context, early risk assessment, using developability methodologies and computational methods in particular, can assist in reducing risks during development in a cost-effective way. We define specific areas of risk and how they can impact product quality in a broad sense, including essential aspects such as product efficacy and patient safety. Emerging industry practices around developability are introduced, including some specific examples of applications to biotherapeutics. Furthermore, we suggest some potential workflows to illustrate how developability strategies can be introduced in practical terms during early drug development in order to mitigate risks, reduce drug attrition and ultimately increase the robustness of the biopharmaceutical supply chain. Finally, we also discuss how the implementation of such methodologies could accelerate the access of new therapeutic treatments to patients in the clinic.

Firefox add-ons for medical reference.

Science.gov (United States)

Hoy, Matthew B

2010-07-01

Firefox is a Web browser created by the Mozilla project, an open-source software group. Features of the browser include automated updates, advanced security and standards compliance, and the ability to add functionality through add-ons and extensions. First introduced in 2004, Firefox now accounts for roughly 30% of the browser market. This article will focus primarily on add-ons and extensions available for the browser that are useful to medical researchers.

The unusually strong hydrogen bond between the carbonyl of Q(A) and His M219 in the Rhodobacter sphaeroides reaction center is not essential for efficient electron transfer from Q(A)(-) to Q(B).

Science.gov (United States)

Breton, Jacques; Lavergne, Jérôme; Wakeham, Marion C; Nabedryk, Eliane; Jones, Michael R

2007-06-05

In native reaction centers (RCs) from photosynthetic purple bacteria the primary quinone (QA) and the secondary quinone (QB) are interconnected via a specific His-Fe-His bridge. In Rhodobacter sphaeroides RCs the C4=O carbonyl of QA forms a very strong hydrogen bond with the protonated Npi of His M219, and the Ntau of this residue is in turn coordinated to the non-heme iron atom. The second carbonyl of QA is engaged in a much weaker hydrogen bond with the backbone N-H of Ala M260. In previous work, a Trp side chain was introduced by site-directed mutagenesis at the M260 position in the RC of Rb. sphaeroides, resulting in a complex that is completely devoid of QA and therefore nonfunctional. A photochemically competent derivative of the AM260W mutant was isolated that contains a Cys side chain at the M260 position (denoted AM260(W-->C)). In the present work, the interactions between the carbonyl groups of QA and the protein in the AM260(W-->C) suppressor mutant have been characterized by light-induced FTIR difference spectroscopy of the photoreduction of QA. The QA-/QA difference spectrum demonstrates that the strong interaction between the C4=O carbonyl of QA and His M219 is lost in the mutant, and the coupled CO and CC modes of the QA- semiquinone are also strongly perturbed. In parallel, a band assigned to the perturbation of the C5-Ntau mode of His M219 upon QA- formation in the native RC is lacking in the spectrum of the mutant. Furthermore, a positive band between 2900 and 2400 cm-1 that is related to protons fluctuating within a network of highly polarizable hydrogen bonds in the native RC is reduced in amplitude in the mutant. On the other hand, the QB-/QB FTIR difference spectrum is essentially the same as for the native RC. The kinetics of electron transfer from QA- to QB were measured by the flash-induced absorption changes at 780 nm. Compared to native RCs the absorption transients are slowed by a factor of about 2 for both the slow phase (in the

Hydrogen bonding between the QB site ubisemiquinone and Ser-L223 in the bacterial reaction centre – a combined spectroscopic and computational perspective^

OpenAIRE

Martin, Erik; Baldansuren, Amgalanbaatar; Lin, Tzu-Jen; Samoilova, Rimma I.; Wraight, Colin A.; Dikanov, Sergei A.; O’Malley, Patrick J.

2012-01-01

In the QB site of the Rba. sphaeroides photosynthetic reaction centre the donation of a hydrogen bond from the hydroxyl group of Ser-L223 to the ubisemiquinone formed after the first flash is debatable. In this study we use a combination of spectroscopy and quantum mechanics/molecular mechanics (QM/MM) calculations to comprehensively explore this topic. We show that ENDOR, ESEEM and HYSCORE spectroscopic differences between the mutant L223SA and the wild type sample (WT) are negligible, indic...

QbD-Based Development and Validation of a Stability-Indicating HPLC Method for Estimating Ketoprofen in Bulk Drug and Proniosomal Vesicular System.

Science.gov (United States)

Yadav, Nand K; Raghuvanshi, Ashish; Sharma, Gajanand; Beg, Sarwar; Katare, Om P; Nanda, Sanju

2016-03-01

The current studies entail systematic quality by design (QbD)-based development of simple, precise, cost-effective and stability-indicating high-performance liquid chromatography method for estimation of ketoprofen. Analytical target profile was defined and critical analytical attributes (CAAs) were selected. Chromatographic separation was accomplished with an isocratic, reversed-phase chromatography using C-18 column, pH 6.8, phosphate buffer-methanol (50 : 50v/v) as a mobile phase at a flow rate of 1.0 mL/min and UV detection at 258 nm. Systematic optimization of chromatographic method was performed using central composite design by evaluating theoretical plates and peak tailing as the CAAs. The method was validated as per International Conference on Harmonization guidelines with parameters such as high sensitivity, specificity of the method with linearity ranging between 0.05 and 250 µg/mL, detection limit of 0.025 µg/mL and quantification limit of 0.05 µg/mL. Precision was demonstrated using relative standard deviation of 1.21%. Stress degradation studies performed using acid, base, peroxide, thermal and photolytic methods helped in identifying the degradation products in the proniosome delivery systems. The results successfully demonstrated the utility of QbD for optimizing the chromatographic conditions for developing highly sensitive liquid chromatographic method for ketoprofen. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Omega-3 fatty acids decreased irritability of patients with bipolar disorder in an add-on, open label study

Directory of Open Access Journals (Sweden)

Baldassano Claudia F

2005-02-01

Full Text Available Abstract This is a report on a 37-patient continuation study of the open ended, Omega-3 Fatty Acid (O-3FA add-on study. Subjects consisted of the original 19 patients, along with 18 new patients recruited and followed in the same fashion as the first nineteen. Subjects carried a DSM-IV-TR diagnosis of Bipolar Disorder and were visiting a Mood Disorder Clinic regularly through the length of the study. At each visit, patients' clinical status was monitored using the Clinical Monitoring Form. Subjects reported on the frequency and severity of irritability experienced during the preceding ten days; frequency was measured by way of percentage of days in which subjects experienced irritability, while severity of that irritability was rated on a Likert scale of 1 – 4 (if present. The irritability component of Young Mania Rating Scale (YMRS was also recorded quarterly on 13 of the 39 patients consistently. Patients had persistent irritability despite their ongoing pharmacologic and psychotherapy. Omega-3 Fatty Acid intake helped with the irritability component of patients suffering from bipolar disorder with a significant presenting sign of irritability. Low dose (1 to 2 grams per day, add-on O-3FA may also help with the irritability component of different clinical conditions, such as schizophrenia, borderline personality disorder and other psychiatric conditions with a common presenting sign of irritability.

A quality by design (QbD case study on enteric-coated pellets: Screening of critical variables and establishment of design space at laboratory scale

Directory of Open Access Journals (Sweden)

Shuling Kan

2014-10-01

Full Text Available The study aims to prepare naproxen enteric-coated pellets (NAP-ECPs by fluid-bed coating using QbD principle. Risk assessment was firstly performed by using failure mode and effect analysis (FMEA methodology. A Plackett–Burman design was then used for assessment of the most important variables affecting enteric-coated pellets characteristics. A Box–Behnken design was subsequently used for investigating the main, interactive, and quadratic effects of these variables on the response. By FMEA we discovered that eight factors should be considered to be high/important risk variables as compared with others. The responses of acid resistance and cumulative drug release were taken as critical quality attributes (CQAs. Pareto ranking analyses indicated that the coating weight gain (X7, triethyl citrate percentage (X1 and glycerol monostearate percentage (X2 were the most significant factors affecting the selected responses out of the eight high-risk variables. Optimization with response surface method (RSM further fully clarified the relationship between X7, X1, X2 and CQAs, and design space was established based on the constraints set on the responses. Due to the extreme coincidence of the predicted value generated by model with the observed value, the accuracy and robustness of the model were confirmed. It could be concluded that a promising NAP-ECPs was successfully designed using QbD approach in a laboratory scale.

ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome

Energy Technology Data Exchange (ETDEWEB)

Iwase, Shigeki; Xiang, Bin; Ghosh, Sharmistha; Ren, Ting; Lewis, Peter W.; Cochrane, Jesse C.; Allis, C. David; Picketts, David J.; Patel, Dinshaw J.; Li, Haitao; Shi, Yang (Harvard-Med); (Ottawa Hosp.); (MSKCC); (Rockefeller); (CH-Boston); (Tsinghua); (Mass. Gen. Hosp.)

2011-07-19

ATR-X (alpha-thalassemia/mental retardation, X-linked) syndrome is a human congenital disorder that causes severe intellectual disabilities. Mutations in the ATRX gene, which encodes an ATP-dependent chromatin-remodeler, are responsible for the syndrome. Approximately 50% of the missense mutations in affected persons are clustered in a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, ADD{sub ATRX}), whose function has remained elusive. Here we identify ADD{sub ATRX} as a previously unknown histone H3-binding module, whose binding is promoted by lysine 9 trimethylation (H3K9me3) but inhibited by lysine 4 trimethylation (H3K4me3). The cocrystal structure of ADD{sub ATRX} bound to H3{sub 1-15}K9me3 peptide reveals an atypical composite H3K9me3-binding pocket, which is distinct from the conventional trimethyllysine-binding aromatic cage. Notably, H3K9me3-pocket mutants and ATR-X syndrome mutants are defective in both H3K9me3 binding and localization at pericentromeric heterochromatin; thus, we have discovered a unique histone-recognition mechanism underlying the ATR-X etiology.

ATRX ADD Domain Links an Atypical Histone Methylation Recognition Mechanism to Human Mental-Retardation Syndrome

Energy Technology Data Exchange (ETDEWEB)

S Iwase; B Xiang; S Ghosh; T Ren; P Lewis; J Cochrane; C Allis; D Picketts; D Patel; et al.

2011-12-31

ATR-X (alpha-thalassemia/mental retardation, X-linked) syndrome is a human congenital disorder that causes severe intellectual disabilities. Mutations in the ATRX gene, which encodes an ATP-dependent chromatin-remodeler, are responsible for the syndrome. Approximately 50% of the missense mutations in affected persons are clustered in a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, ADD{sub ATRX}), whose function has remained elusive. Here we identify ADD{sub ATRX} as a previously unknown histone H3-binding module, whose binding is promoted by lysine 9 trimethylation (H3K9me3) but inhibited by lysine 4 trimethylation (H3K4me3). The cocrystal structure of ADD{sub ATRX} bound to H3{sub 1-15}K9me3 peptide reveals an atypical composite H3K9me3-binding pocket, which is distinct from the conventional trimethyllysine-binding aromatic cage. Notably, H3K9me3-pocket mutants and ATR-X syndrome mutants are defective in both H3K9me3 binding and localization at pericentromeric heterochromatin; thus, we have discovered a unique histone-recognition mechanism underlying the ATR-X etiology.

Association between genetic variants of the ADD1 and GNB3 genes and blood pressure response to the cold pressor test in a Chinese Han population: the GenSalt Study.

Science.gov (United States)

Wang, Laiyuan; Chen, Shufeng; Zhao, Qi; Hixson, James E; Rao, Dabeeru C; Jaquish, Cashell E; Huang, Jianfeng; Lu, Xiangfeng; Chen, Jichun; Cao, Jie; Li, Jianxin; Li, Hongfan; He, Jiang; Liu, De-Pei; Gu, Dongfeng

2012-08-01

Genetic factors influence blood pressure (BP) response to the cold pressor test (CPT), which is a phenotype related to hypertension risk. We examined the association between variants of the α-adducin (ADD1) and guanine nucleotide binding protein (G protein) β-polypeptide 3 (GNB3) genes and BP response to the CPT. A total of 1998 Han Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity completed the CPT. The area under the curve (AUC) above the baseline BP during the CPT was used to measure the BP response. Twelve single-nucleotide polymorphisms (SNPs) of the ADD1 and GNB3 genes were selected and genotyped. Both single-marker and haplotype association analyses were conducted using linear mixed models. The rs17833172 and rs3775067 SNPs of the ADD1 gene and the rs4963516 SNP of the GNB3 gene were significantly associated with the BP response to CPT, even after adjusting for multiple testing. For the ADD1 gene, the AA genotype of SNP rs17833172 was associated with lower systolic BP (SBP) reactivity (PAUC (P=0.003). Haplotype analysis indicated that the CCGC haplotype of ADD1 constructed by rs1263359, rs3775067, rs4961 and rs4963 was significantly associated with the BP response to CPT. These data suggest that genetic variants of the ADD1 and GNB3 genes may have important roles in BP response to the CPT. Future studies aimed at replicating these novel findings are warranted.

Quality by Design (QbD) approach to optimize the formulation of a bilayer combination tablet (Telmiduo®) manufactured via high shear wet granulation.

Science.gov (United States)

Lee, Ah Ram; Kwon, Seok Young; Choi, Du Hyung; Park, Eun Seok

2017-12-20

A bilayer tablet, which consisted of telmisartan and amlodipine besylate, was formulated based on a Quality by Design (QbD) approach. The control and response factors were determined based on primary knowledge and the target values of the control tablet (Twynsta ® ). A D-optimal mixture design was used to obtain the optimal formulations in terms of D-mannitol, crospovidone, and MCC for the telmisartan layer, and CCM-Na, PVP K25, and Prosolv for the amlodipine layer. The quantitative effects of the different formulation factors on the response factors were accurately predicted using the equations of best fit and a strong linearity was observed between the predicted and actual values of the response factors. The optimized bilayer tablet was obtained using a numeric optimization technique and was characterized compared with a control (Twynsta ® ) by using various physical evaluations and in vivo pharmacokinetic parameters. The physical stability of Telmiduo ® was greater than that of Twynsta ® owing to the improvement of formulation factors. The in vivo pharmacokinetic parameters suggested that Telmiduo ® might have pharmaceutical equivalence and bioequivalence with Twynsta ® . Therefore, the bilayer tablet that consisted of telmisartan and amlodipine besylate could be produced using a more economical and simpler method than that used to produce Twynsta ® . Moreover, the suitability of QbD for effective product development in the pharmaceutical industry was shown. Copyright © 2017 Elsevier B.V. All rights reserved.

A multiply-add engine with monolithically integrated 3D memristor crossbar/CMOS hybrid circuit.

Science.gov (United States)

Chakrabarti, B; Lastras-Montaño, M A; Adam, G; Prezioso, M; Hoskins, B; Payvand, M; Madhavan, A; Ghofrani, A; Theogarajan, L; Cheng, K-T; Strukov, D B

2017-02-14

Silicon (Si) based complementary metal-oxide semiconductor (CMOS) technology has been the driving force of the information-technology revolution. However, scaling of CMOS technology as per Moore's law has reached a serious bottleneck. Among the emerging technologies memristive devices can be promising for both memory as well as computing applications. Hybrid CMOS/memristor circuits with CMOL (CMOS + "Molecular") architecture have been proposed to combine the extremely high density of the memristive devices with the robustness of CMOS technology, leading to terabit-scale memory and extremely efficient computing paradigm. In this work, we demonstrate a hybrid 3D CMOL circuit with 2 layers of memristive crossbars monolithically integrated on a pre-fabricated CMOS substrate. The integrated crossbars can be fully operated through the underlying CMOS circuitry. The memristive devices in both layers exhibit analog switching behavior with controlled tunability and stable multi-level operation. We perform dot-product operations with the 2D and 3D memristive crossbars to demonstrate the applicability of such 3D CMOL hybrid circuits as a multiply-add engine. To the best of our knowledge this is the first demonstration of a functional 3D CMOL hybrid circuit.

76 FR 47240 - ``Add Us In'' Initiative

Science.gov (United States)

2011-08-04

... DEPARTMENT OF LABOR Office of Disability Employment Policy ``Add Us In'' Initiative AGENCY: Office of Disability Employment Policy, Department of Labor. Announcement Type: New Notice of Availability... Add Us In initiative is to identify and develop strategies to increase the capacity of small...

Inviting Calm Within: ADD, Neurology, and Mindfulness

Science.gov (United States)

Riner, Phillip S.; Tanase, Madalina

2014-01-01

The fourth edition of the "Diagnostic and Statistical Manual of Mental Disorders" ("DSM IV") describes ADD as behaviorally observed impairments in attention, impulsivity, and hyperactivity. Officially known as AD/HD, we use ADD here because we are dealing primarily with attention, organizational, and impulsivity issues. A more…

AcEST: DK952789 [AcEST

Lifescience Database Archive (English)

Full Text Available 9BRYO Photosystem Q(B) protein OS=Brachymenium ... 359 9e-98 tr|Q8HRC4|Q8HRC4_9BRYO Photosystem Q(B) protein OS=Plagio...9BRYO Photosystem Q(B) protein OS=Plagiobryum c... 359 9e-98 tr|Q8HRB3|Q8HRB3_9BRYO Photosystem Q(B) protein OS=Plagio...|Q8HRB0|Q8HRB0_9BRYO Photosystem Q(B) protein OS=Plagiobryum l... 359 9e-98 >tr|Q5YGB0|Q5YGB0_9MARC Photosys

WITHDRAWN: Oxcarbazepine add-on for drug-resistant partial epilepsy.

Science.gov (United States)

Castillo, Sergio M; Schmidt, Dieter B; White, Sarah; Shukralla, Arif

2016-11-15

Most people with epilepsy have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic drug, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarize the current evidence regarding oxcarbazepine when used as an add-on treatment for drug-resistant partial epilepsy. To evaluate the effects of oxcarbazepine when used as an add-on treatment for drug-resistant partial epilepsy. We searched the Cochrane Epilepsy Group's Specialized Register (28 March 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to March 2006). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies. We also contacted Novartis (manufacturers of oxcarbazepine) and experts in the field. Randomized, placebo-controlled, double-blinded, add-on trials of oxcarbazepine in patients with drug-resistant partial epilepsy. Two review authors independently assessed trials for inclusion and extracted the relevant data. The following outcomes were assessed : (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention-to-treat. Summary odds ratios were estimated for each outcome. Two trials were included representing 961 randomized patients.Overall Odds Ratio (OR) (95% Confidence Interval (CIs)) for 50% or greater reduction in seizure frequency compared to placebo 2.96 (2.20, 4.00).Treatment withdrawal OR (95% CIs) compared to placebo 2.17 (1.59, 2.97).Side effects: OR (99% CIs) compared to placebo, ataxia 2.93 (1.72, 4.99); dizziness 3.05 (1.99, 4.67); fatigue 1.80 (1.02, 3.19); nausea 2.88 (1.77, 4.69); somnolence 2.55 (1.84, 3.55); diplopia 4.32 (2.65, 7.04), were significantly associated with oxcarbazepine. Oxcarbazepine has efficacy as an add-on treatment in patients with drug

Nanostructured lipid carriers employing polyphenols as promising anticancer agents: Quality by design (QbD) approach.

Science.gov (United States)

Bhise, Ketki; Kashaw, Sushil Kumar; Sau, Samaresh; Iyer, Arun K

2017-06-30

Cancer is one of the leading causes of death worldwide. There are several hurdles in cancer therapy because of side-effects which limits its usage. Nanoparticulate drug delivery systems have been tested against cancer in a range of scientific studies. In the recent years, advanced research on Nanostructured Lipid Carriers (NLCs) has garnered considerable attention owing to the advantages over their first-generation counterparts, Solid Lipid Nanoparticles (SLN). NLCs facilitate efficient loading of poorly water soluble drugs with simple methods of drug loading. Recently, there is an increased interest in polyphenols because of the evidence of their promising role in prevention of cancer. Polyphenols are produced as secondary metabolites by plants. Their role in prevention of development of tumors through variety of mechanisms and reduction of tumor cell mass has been reported. This article aims to review the science behind development of NLCs and role of polyphenols as promising anticancer agents. Principles of Quality by Design (QbD) have also been explained which are used in formulation-development of many nanoparticles, including NLCs, as reported in literature. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of omega-3 fatty acids versus 5-hydroxytryptophan as add on therapy to sertraline in controlling suicidal ideation in patients with depression: A comparative study

Directory of Open Access Journals (Sweden)

Jyoti Prakash Sahoo

2016-04-01

Full Text Available Background: Omega-3 fatty acids and 5-hydroxytryptophan have been gaining attention as promising alternative treatment for depressive illness. These agents are given as as add on treatment to conventional antidepressant drugs. The present study was carried out to evaluate efficacy of omega-3 fatty acids versus 5-hydroxytryptophan as add on therapy in controlling suicidal ideation in depressive patients on sertraline.Methods: This was a prospective, open label, randomized, parallel group study conducted in department of Psychiatry. Ninety treatment naïve patients (18-65 years age were divided into 3 groups of 30 each. Group I: Sertraline, Group II: Sertraline plus omega-3 fatty acids, Group III: Sertraline plus 5-hydroxytryptophan. Suicidal ideations were assessed with Beck’s scale for suicidal ideation (BSI at weeks 0, 4 and 8. Data were analyzed using repeated measures ANOVA (SPSS version 20.0. Post hoc analysis was done using Bonferroni test.Results: Baseline parameters in patients of all groups were comparable. Administration of sertraline resulted in reduction of Beck’s scale for suicidal ideation scores as compared to baseline. Addition of omega-3 fatty acids and 5-hydroxytryptophan also showed reduction in BSI scores. Effect of sertraline monotherapy was more as compared to omega-3 fatty acids or 5-hydroxytryptophan as add on therapy, which was statistically significant (p value < 0.05.Conclusion: Both omega-3 fatty acids and 5-hydroxytryptophan produce significant effect in controlling suicidal ideations in patients with depression.

Application of Quality by Design (QbD) Principles to Extractables/Leachables Assessment. Establishing a Design Space for Terminally Sterilized Aqueous Drug Products Stored in a Plastic Packaging System.

Science.gov (United States)

Jenke, Dennis

2010-01-01

The concept of quality by design (QbD) reflects the current global regulatory thinking related to pharmaceutical products. A cornerstone of the QbD paradigm is the concept of a design space, where the design space is a multidimensional combination of input variables and process parameters that have been demonstrated to provide the assurance of product quality. If a design space can be established for a pharmaceutical process or product, then operation within the design space confirms that the product or process output possesses the required quality attributes. This concept of design space can be applied to the safety (leachables) assessment of drug products manufactured and stored in packaging systems. Critical variables in such a design space would include those variables that affect the interaction of the drug product and its packaging, including (a) composition of the drug product, (b) composition of the packaging system, (c) configuration of the packaging system, and (d) the conditions of contact. This paper proposes and justifies such a leachables design space for aqueous drug products packaged in a specific plastic packaging system. Such a design space has the following boundaries:Aqueous drug products with a pH in the range of 2 to 8 and that contain no polarity-impacting agents such as organic solubilizers and stabilizers (addressing variable a). Packaging systems manufactured from materials that meet the system's existing material specifications (addressing variable b). Nominal fill volumes from 50 to 1000 mL (addressing variable c). Products subjected to terminal sterilization and then stored at room temperature for a period of up to 24 months (addressing variable d). The ramification of such a design space is that any drug product that falls within these boundaries is deemed to be compatible with the packaging system, from the perspective of safety, without the requirement of supporting drug product testing. When drug products are packaged in plastic

Add Audio and Video to Your Site

CERN Document Server

MacDonald, Matthew

2010-01-01

Nothing spices up websites like cool sound effects (think ker-thunk as visitors press a button) or embedded videos. Think you need a programmer to add sizzle to your site? Think again. This hands-on guide gives you the techniques you need to add video, music, animated GIFs, and sound effects to your site. This Mini Missing Manual is excerpted from Creating a Web Site: The Missing Manual.

Southeast Economic Add-on 1997

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — To collect data on an angler's last trip for revealed preference models and economic valuation purposes. Typically done as an add-on to the MRIP intercept survey and...

Southeast Economic Add-on 2004

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — To collect data on an angler's last trip for revealed preference models and economic valuation purposes. Typically done as an add-on to the MRIP intercept survey and...

40 CFR 75.34 - Units with add-on emission controls.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Units with add-on emission controls... add-on emission controls. (a) The owner or operator of an affected unit equipped with add-on SO2 and... assurance/quality control program for the unit, required by section 1 in appendix B of this part. To provide...

QbD for pediatric oral lyophilisates development: risk assessment followed by screening and optimization.

Science.gov (United States)

Casian, Tibor; Iurian, Sonia; Bogdan, Catalina; Rus, Lucia; Moldovan, Mirela; Tomuta, Ioan

2017-12-01

This study proposed the development of oral lyophilisates with respect to pediatric medicine development guidelines, by applying risk management strategies and DoE as an integrated QbD approach. Product critical quality attributes were overviewed by generating Ishikawa diagrams for risk assessment purposes, considering process, formulation and methodology related parameters. Failure Mode Effect Analysis was applied to highlight critical formulation and process parameters with an increased probability of occurrence and with a high impact on the product performance. To investigate the effect of qualitative and quantitative formulation variables D-optimal designs were used for screening and optimization purposes. Process parameters related to suspension preparation and lyophilization were classified as significant factors, and were controlled by implementing risk mitigation strategies. Both quantitative and qualitative formulation variables introduced in the experimental design influenced the product's disintegration time, mechanical resistance and dissolution properties selected as CQAs. The optimum formulation selected through Design Space presented ultra-fast disintegration time (5 seconds), a good dissolution rate (above 90%) combined with a high mechanical resistance (above 600 g load). Combining FMEA and DoE allowed the science based development of a product with respect to the defined quality target profile by providing better insights on the relevant parameters throughout development process. The utility of risk management tools in pharmaceutical development was demonstrated.

Error-free 320 Gb/s simultaneous add-drop multiplexing

DEFF Research Database (Denmark)

Mulvad, Hans Christian Hansen; Oxenløwe, Leif Katsuo; Clausen, Anders

2007-01-01

We report on the first demonstration of error-free time-division add-drop multiplexing at 320 Gb/s. The add- and drop-operations are performed simultaneously in a non-linear optical loop mirror with only 100 m of highly non-linear fibre....

Application of quality by design for 3D printed bone prostheses and scaffolds.

Science.gov (United States)

Martinez-Marquez, Daniel; Mirnajafizadeh, Ali; Carty, Christopher P; Stewart, Rodney A

2018-01-01

3D printing is an emergent manufacturing technology recently being applied in the medical field for the development of custom bone prostheses and scaffolds. However, successful industry transformation to this new design and manufacturing approach requires technology integration, concurrent multi-disciplinary collaboration, and a robust quality management framework. This latter change enabler is the focus of this study. While a number of comprehensive quality frameworks have been developed in recent decades to ensure that the manufacturing of medical devices produces reliable products, they are centred on the traditional context of standardised manufacturing techniques. The advent of 3D printing technologies and the prospects for mass customisation provides significant market opportunities, but also presents a serious challenge to regulatory bodies tasked with managing and assuring product quality and safety. Before 3D printing bone prostheses and scaffolds can gain traction, industry stakeholders, such as regulators, clients, medical practitioners, insurers, lawyers, and manufacturers, would all require a high degree of confidence that customised manufacturing can achieve the same quality outcomes as standardised manufacturing. A Quality by Design (QbD) approach to custom 3D printed prostheses can help to ensure that products are designed and manufactured correctly from the beginning without errors. This paper reports on the adaptation of the QbD approach for the development process of 3D printed custom bone prosthesis and scaffolds. This was achieved through the identification of the Critical Quality Attributes of such products, and an extensive review of different design and fabrication methods for 3D printed bone prostheses. Research outcomes include the development of a comprehensive design and fabrication process flow diagram, and categorised risks associated with the design and fabrication processes of such products. An extensive systematic literature review

Application of quality by design for 3D printed bone prostheses and scaffolds

Science.gov (United States)

Martinez-Marquez, Daniel; Mirnajafizadeh, Ali; Carty, Christopher P.

2018-01-01

3D printing is an emergent manufacturing technology recently being applied in the medical field for the development of custom bone prostheses and scaffolds. However, successful industry transformation to this new design and manufacturing approach requires technology integration, concurrent multi-disciplinary collaboration, and a robust quality management framework. This latter change enabler is the focus of this study. While a number of comprehensive quality frameworks have been developed in recent decades to ensure that the manufacturing of medical devices produces reliable products, they are centred on the traditional context of standardised manufacturing techniques. The advent of 3D printing technologies and the prospects for mass customisation provides significant market opportunities, but also presents a serious challenge to regulatory bodies tasked with managing and assuring product quality and safety. Before 3D printing bone prostheses and scaffolds can gain traction, industry stakeholders, such as regulators, clients, medical practitioners, insurers, lawyers, and manufacturers, would all require a high degree of confidence that customised manufacturing can achieve the same quality outcomes as standardised manufacturing. A Quality by Design (QbD) approach to custom 3D printed prostheses can help to ensure that products are designed and manufactured correctly from the beginning without errors. This paper reports on the adaptation of the QbD approach for the development process of 3D printed custom bone prosthesis and scaffolds. This was achieved through the identification of the Critical Quality Attributes of such products, and an extensive review of different design and fabrication methods for 3D printed bone prostheses. Research outcomes include the development of a comprehensive design and fabrication process flow diagram, and categorised risks associated with the design and fabrication processes of such products. An extensive systematic literature review

Add-on unidirectional elastic metamaterial plate cloak

Science.gov (United States)

Lee, Min Kyung; Kim, Yoon Young

2016-02-01

Metamaterial cloaks control the propagation of waves to make an object invisible or insensible. To manipulate elastic waves in space, a metamaterial cloak is typically embedded in a base system that includes or surrounds a target object. The embedding is undesirable because it structurally weakens or permanently alters the base system. In this study, we propose a new add-on metamaterial elastic cloak that can be placed over and mechanically coupled with a base structure without embedding. We designed an add-on type annular metamaterial plate cloak through conformal mapping, fabricated it and performed cloaking experiments in a thin-plate with a hole. Experiments were performed in a thin plate by using the lowest symmetric Lamb wave centered at 100 kHz. As a means to check the cloaking performance of the add-on elastic plate cloak, possibly as a temporary stress reliever or a so-called “stress bandage”, the degree of stress concentration mitigation and the recovery from the perturbed wave field due to a hole were investigated.

Quality-by-Design (QbD): An integrated process analytical technology (PAT) approach for a dynamic pharmaceutical co-precipitation process characterization and process design space development.

Science.gov (United States)

Wu, Huiquan; White, Maury; Khan, Mansoor A

2011-02-28

The aim of this work was to develop an integrated process analytical technology (PAT) approach for a dynamic pharmaceutical co-precipitation process characterization and design space development. A dynamic co-precipitation process by gradually introducing water to the ternary system of naproxen-Eudragit L100-alcohol was monitored at real-time in situ via Lasentec FBRM and PVM. 3D map of count-time-chord length revealed three distinguishable process stages: incubation, transition, and steady-state. The effects of high risk process variables (slurry temperature, stirring rate, and water addition rate) on both derived co-precipitation process rates and final chord-length-distribution were evaluated systematically using a 3(3) full factorial design. Critical process variables were identified via ANOVA for both transition and steady state. General linear models (GLM) were then used for parameter estimation for each critical variable. Clear trends about effects of each critical variable during transition and steady state were found by GLM and were interpreted using fundamental process principles and Nyvlt's transfer model. Neural network models were able to link process variables with response variables at transition and steady state with R(2) of 0.88-0.98. PVM images evidenced nucleation and crystal growth. Contour plots illustrated design space via critical process variables' ranges. It demonstrated the utility of integrated PAT approach for QbD development. Published by Elsevier B.V.

Evolutionary diversification of protein-protein interactions by interface add-ons.

Science.gov (United States)

Plach, Maximilian G; Semmelmann, Florian; Busch, Florian; Busch, Markus; Heizinger, Leonhard; Wysocki, Vicki H; Merkl, Rainer; Sterner, Reinhard

2017-10-03

Cells contain a multitude of protein complexes whose subunits interact with high specificity. However, the number of different protein folds and interface geometries found in nature is limited. This raises the question of how protein-protein interaction specificity is achieved on the structural level and how the formation of nonphysiological complexes is avoided. Here, we describe structural elements called interface add-ons that fulfill this function and elucidate their role for the diversification of protein-protein interactions during evolution. We identified interface add-ons in 10% of a representative set of bacterial, heteromeric protein complexes. The importance of interface add-ons for protein-protein interaction specificity is demonstrated by an exemplary experimental characterization of over 30 cognate and hybrid glutamine amidotransferase complexes in combination with comprehensive genetic profiling and protein design. Moreover, growth experiments showed that the lack of interface add-ons can lead to physiologically harmful cross-talk between essential biosynthetic pathways. In sum, our complementary in silico, in vitro, and in vivo analysis argues that interface add-ons are a practical and widespread evolutionary strategy to prevent the formation of nonphysiological complexes by specializing protein-protein interactions.

GnRH-Analoga und Add-back-Verfahren

Directory of Open Access Journals (Sweden)

Kleinstein J

2008-01-01

Full Text Available GnRH-Analoga haben eine große Bedeutung in der medikamentösen Therapie der Endometriose erlangt. Sie sind in der Lage, Endometrioseassoziierte Schmerzen zu beseitigen und sind Bestandteil der Therapie der endometriosebedingten Infertilität. Aufgrund der Chronizität der Endometriose bedarf es in vielen Fällen der Prolongation der GnRH-A-Therapie über den Zeitraum von 6 Monaten hinaus. Für diese Fälle eignet sich eine Add-back- Therapie nach dem Format von Hormonersatztherapien, um vasomotorischen Nebeneffekten und dem Knochensubstanzverlust entgegenwirken zu können. Dabei wird der Estrogenanteil niedrig dosiert eingesetzt, um innerhalb eines "therapeutischen Fensters" den Hypoestrogenismus auszugleichen, ohne das Endometriosewachstum zu fördern. Prinzipiell kann dazu das Estrogen oral, aber auch transdermal appliziert werden. Die Effektivität der Kombination aus GnRH-A plus Add-back bezüglich der Knochenprotektion konnte bereits für einen Zeitraum von bis zu 10 Jahren bestätigt werden, sodass damit eine Langzeitkonzeption für Frauen mit rezidivierender Endometriose und wiederholten operativen Eingriffen existiert. Alternativen zur klassischen Add-back mit Sexualsteroiden existieren vielfältig, aber ihr Einsatz ist durch Partialwirkungen und eigene Nebenwirkungen limitiert.

Add-on perampanel in Lance-Adams syndrome.

Science.gov (United States)

Steinhoff, Bernhard J; Bacher, Matthias; Kurth, Christoph; Staack, Anke M; Kornmeier, Reinhold

2016-01-01

Perampanel (PER) is the first-in-class selective, noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist that has been licensed and marketed as antiepileptic drug (AED) indicated for patients with partial-onset and primary generalized tonic-clonic seizures. A positive effect was reported in some patients with epileptic myoclonic jerks in idiopathic generalized epilepsy and in progressive myoclonic epilepsy. We treated a male patient with posthypoxic nonepileptic myoclonus (Lance-Adams syndrome) with add-on PER and achieved an almost complete cessation of jerks. This effect was reproducible and, therefore, we suggest that it might be worth trying PER in comparable cases.

More notions of forcing add a Souslin tree

OpenAIRE

Brodsky, Ari Meir; Rinot, Assaf

2016-01-01

An $\\aleph_1$-Souslin tree is a complicated combinatorial object whose existence cannot be decided on the grounds of ZFC alone. But 15 years after Tennenbaum and independently Jech devised notions of forcing for introducing such a tree, Shelah proved that already the simplest forcing notion --- Cohen forcing --- adds an $\\aleph_1$-Souslin tree. In this paper, we identify a rather large class of notions of forcing that, assuming a GCH-type assumption, add a $\\lambda^+$-Souslin tree. This class...

AcEST: BP912159 [AcEST

Lifescience Database Archive (English)

Full Text Available 9ROSA Photosystem Q(B) protein OS=Prunus spinul... 60 1e-16 tr|Q95B38|Q95B38_9ROSA Photosystem Q(B) protein OS=Prunus grayan...em Q(B) protein OS=Prunus grayana GN=psbA PE=3 SV=1 Length = 353 Score = 60.1 bit

Non-invasive beamforming add-on module

KAUST Repository

Bader, Ahmed; Alouini, Mohamed-Slim

2017-01-01

An embodiment of a non-invasive beamforming add-on apparatus couples to an existing antenna port and rectifies the beam azimuth in the upstream and downstream directions. The apparatus comprises input circuitry that is configured to receive one

Add-on deep Transcranial Magnetic Stimulation (dTMS) for the treatment of chronic migraine: A preliminary study.

Science.gov (United States)

Rapinesi, Chiara; Del Casale, Antonio; Scatena, Paola; Kotzalidis, Georgios D; Di Pietro, Simone; Ferri, Vittoria Rachele; Bersani, Francesco Saverio; Brugnoli, Roberto; Raccah, Ruggero Nessim; Zangen, Abraham; Ferracuti, Stefano; Orzi, Francesco; Girardi, Paolo; Sette, Giuliano

2016-06-03

Deep Transcranial Magnetic Stimulation (dTMS) can be an alternative treatment to relieve pain in chronic migraine (CM). The aim of this study was to evaluate the effect of high-frequency dTMS in add-on to standard treatment for CM in patients not responding to effective abortive or preventive drug treatment. We randomized 14 patients with International Classification of Headache Disorders, 3rd Edition (ICHD-3) treatment-resistant CM to add-on dTMS (n=7) or standard abortive or preventive antimigraine treatment (n=7). Three sessions of alternate day 10Hz dTMS consisting of 600 pulses in 10 trains were delivered to the dorsolateral prefrontal cortex (DLPFC), bilaterally, but with left hemisphere prevalence, for 12 sessions spread over one month. The add-on dTMS treatment was well tolerated. Patients treated with dTMS showed significant reduction of pain intensity, frequency of attacks, analgesic overuse, and depressive symptoms during treatment and one month later, compared to the month preceding treatment and at the same time-points compared to the control group. As compared to standard pharmacological treatment alone, add-on high-frequency dTMS of the bilateral DLPFC reduced the frequency and intensity of migraine attack, drug overuse, and depressive symptoms. This study supports the add-on dTMS treatment in treatment-resistant CM. Copyright © 2016. Published by Elsevier Ireland Ltd.

[Discussion on research and development of new traditional Chinese medicine preparation process based on idea of QbD].

Science.gov (United States)

Feng, Yi; Hong, Yan-Long; Xian, Jie-Chen; Du, Ruo-Fei; Zhao, Li-Jie; Shen, Lan

2014-09-01

Traditional processes are mostly adopted in traditional Chinese medicine (TCM) preparation production and the quality of products is mostly controlled by terminal. Potential problems of the production in the process are unpredictable and is relied on experience in most cases. Therefore, it is hard to find the key points affecting the preparation process and quality control. A pattern of research and development of traditional Chinese medicine preparation process based on the idea of Quality by Design (QbD) was proposed after introducing the latest research achievement. Basic theories of micromeritics and rheology were used to characterize the physical property of TCM raw material. TCM preparation process was designed in a more scientific and rational way by studying the correlation among enhancing physical property of raw material, preparation process and product quality of preparation. So factors affecting the quality of TCM production would be found out and problems that might occur in the pilot process could be predicted. It would be a foundation for the R&D and production of TCM preparation as well as support for the "process control" of TCMIs gradually realized in the future.

Birefringence Bragg Binary (3B) grating, quasi-Bragg grating and immersion gratings

Science.gov (United States)

Ebizuka, Noboru; Morita, Shin-ya; Yamagata, Yutaka; Sasaki, Minoru; Bianco, Andorea; Tanabe, Ayano; Hashimoto, Nobuyuki; Hirahara, Yasuhiro; Aoki, Wako

2014-07-01

A volume phase holographic (VPH) grating achieves high angular dispersion and very high diffraction efficiency for the first diffraction order and for S or P polarization. However the VPH grating could not achieve high diffraction efficiency for non-polarized light at a large diffraction angle because properties of diffraction efficiencies for S and P polarizations are different. Furthermore diffraction efficiency of the VPH grating extinguishes toward a higher diffraction order. A birefringence binary Bragg (3B) grating is a thick transmission grating with optically anisotropic material such as lithium niobate or liquid crystal. The 3B grating achieves diffraction efficiency up to 100% for non-polarized light by tuning of refractive indices for S and P polarizations, even in higher diffraction orders. We fabricated 3B grating with liquid crystal and evaluated the performance of the liquid crystal grating. A quasi-Bragg (QB) grating, which consists long rectangle mirrors aligned in parallel precisely such as a window shade, also achieves high diffraction efficiency toward higher orders. We fabricated QB grating by laminating of silica glass substrates and glued by pressure fusion of gold films. A quasi-Bragg immersion (QBI) grating has smooth mirror hypotenuse and reflector array inside the hypotenuse, instead of step-like grooves of a conventional immersion grating. An incident beam of the QBI grating reflects obliquely at a reflector, then reflects vertically at the mirror surface and reflects again at the same reflector. We are going to fabricate QBI gratings by laminating of mirror plates as similar to fabrication of the QB grating. We will also fabricate silicon and germanium immersion gratings with conventional step-like grooves by means of the latest diamond machining methods. We introduce characteristics and performance of these gratings.

SiPM and ADD as advanced detectors for astro-particle physics

International Nuclear Information System (INIS)

Mirzoyan, Razmick; Dolgoshein, Boris; Holl, Peter; Klemin, Sergei; Merck, Christine; Moser, Hans-Guenther; Otte, Adam Nepomuk; Ninkovic, Jelena; Popova, Elena; Richter, Rainer; Teshima, Masahiro

2007-01-01

In recent years, a few scientific groups are developing a novel type light sensor. These so-called silicon photo multipliers (SiPM) operate at relatively low bias voltage of 20-60 V, show unprecedented amplitude resolution and already now can provide photon detection efficiencies (PDE) comparable to or better than that of classical photo multipliers (PMT). We are developing the novel sensors for the astro-particle physics experiments MAGIC [J. Albert, et al., Astrophys. Lett. 642 (2006) L119. ] and also for EUSO [M. Teshima, et al., EUSO (The Extreme Universe Space Observatory), in: Scientific Objectives Proceedings ICRC, 2003, p. 10690. ]. The front-illuminated SiPM are developing with the group from MEPhI in Moscow and the back-illuminated Avalanche Drift Diodes (ADD) with the semiconductor laboratory (HLL) attached to the MPI for Physics. Our goal is to produce 5-10 mm size ultra-fast, low-noise and very high PDE (60-80%) sensors operating in the wavelength range 300-600 nm. Together with MEPhI, we have already produced and successfully tested 1.3x1.3, 3x3 and 5x5 mm 2 size SiPMs. Very recently, the first ADD test structures were produced and are under evaluation at the HLL. In this report, we want to outline the main parameters of the new sensors for the needs of astro-particle physics experiments

A role for α-adducin (ADD-1) in nematode and human memory.

Science.gov (United States)

Vukojevic, Vanja; Gschwind, Leo; Vogler, Christian; Demougin, Philippe; de Quervain, Dominique J-F; Papassotiropoulos, Andreas; Stetak, Attila

2012-03-21

Identifying molecular mechanisms that underlie learning and memory is one of the major challenges in neuroscience. Taken the advantages of the nematode Caenorhabditis elegans, we investigated α-adducin (add-1) in aversive olfactory associative learning and memory. Loss of add-1 function selectively impaired short- and long-term memory without causing acquisition, sensory, or motor deficits. We showed that α-adducin is required for consolidation of synaptic plasticity, for sustained synaptic increase of AMPA-type glutamate receptor (GLR-1) content and altered GLR-1 turnover dynamics. ADD-1, in a splice-form- and tissue-specific manner, controlled the storage of memories presumably through actin-capping activity. In support of the C. elegans results, genetic variability of the human ADD1 gene was significantly associated with episodic memory performance in healthy young subjects. Finally, human ADD1 expression in nematodes restored loss of C. elegans add-1 gene function. Taken together, our findings support a role for α-adducin in memory from nematodes to humans. Studying the molecular and genetic underpinnings of memory across distinct species may be helpful in the development of novel strategies to treat memory-related diseases.

Quality by design (QbD), Process Analytical Technology (PAT), and design of experiment applied to the development of multifunctional sunscreens.

Science.gov (United States)

Peres, Daniela D'Almeida; Ariede, Maira Bueno; Candido, Thalita Marcilio; de Almeida, Tania Santos; Lourenço, Felipe Rebello; Consiglieri, Vladi Olga; Kaneko, Telma Mary; Velasco, Maria Valéria Robles; Baby, André Rolim

2017-02-01

Multifunctional formulations are of great importance to ensure better skin protection from harm caused by ultraviolet radiation (UV). Despite the advantages of Quality by Design and Process Analytical Technology approaches to the development and optimization of new products, we found in the literature only a few studies concerning their applications in cosmetic product industry. Thus, in this research work, we applied the QbD and PAT approaches to the development of multifunctional sunscreens containing bemotrizinol, ethylhexyl triazone, and ferulic acid. In addition, UV transmittance method was applied to assess qualitative and quantitative critical quality attributes of sunscreens using chemometrics analyses. Linear discriminant analysis allowed classifying unknown formulations, which is useful for investigation of counterfeit and adulteration. Simultaneous quantification of ethylhexyl triazone, bemotrizinol, and ferulic acid presented at the formulations was performed using PLS regression. This design allowed us to verify the compounds in isolation and in combination and to prove that the antioxidant action of ferulic acid as well as the sunscreen actions, since the presence of this component increased 90% of antioxidant activity in vitro.

Simultaneous all-optical add and drop multiplexing of 40-Gbit/s OTDM signals using monolithically integrated Mach-Zehnder interferometer

DEFF Research Database (Denmark)

Jepsen, Kim Stokholm; Mikkelsen, Benny; Vaa, Michael

1998-01-01

Simultaneous all-optical add and drop multiplexing of a 40-Gbit/s OTDM signal using a monolithically integrated semiconductor optical amplifier/Mach Zehnder interferometer (SOA-MZI) is demonstrated. While maintaining a penalty of 1.3 dB for the add operation the sensitivity for the demultiplexed ...... signal is -34.4 dBm...

Neural biomarkers for dyslexia, ADHD and ADD in the auditory cortex of children

Directory of Open Access Journals (Sweden)

Bettina Serrallach

2016-07-01

Full Text Available Dyslexia, attention deficit hyperactivity disorder (ADHD, and attention deficit disorder (ADD show distinct clinical profiles that may include auditory and language-related impairments. Currently, an objective brain-based diagnosis of these developmental disorders is still unavailable. We investigated the neuro-auditory systems of dyslexic, ADHD, ADD, and age-matched control children (N=147 using neuroimaging, magnet-encephalography and psychoacoustics. All disorder subgroups exhibited an oversized left planum temporale and an abnormal interhemispheric asynchrony (10-40 ms of the primary auditory evoked P1-response. Considering right auditory cortex morphology, bilateral P1 source waveform shapes, and auditory performance, the three disorder subgroups could be reliably differentiated with outstanding accuracies of 89-98%. We therefore for the first time provide differential biomarkers for a brain-based diagnosis of dyslexia, ADHD, and ADD. The method allowed not only a clear discrimination between two subtypes of attentional disorders (ADHD and ADD, a topic controversially discussed for decades in the scientific community, but also revealed the potential for objectively identifying comorbid cases. Noteworthy, in children playing a musical instrument, after three and a half years of training the observed interhemispheric asynchronies were reduced by about 2/3, thus suggesting a strong beneficial influence of music experience on brain development. These findings might have far-reaching implications for both research and practice and enable a profound understanding of the brain-related etiology, diagnosis, and musically based therapy of common auditory-related developmental disorders and learning disabilities.

Implementation of computerized add-on testing for hospitalized patients in a large academic medical center.

Science.gov (United States)

Kim, Ji Yeon; Kamis, Irina K; Singh, Balaji; Batra, Shalini; Dixon, Roberta H; Dighe, Anand S

2011-05-01

Physician requests for additional testing on an existing laboratory specimen (add-ons) are resource intensive and generally require a phone call to the laboratory. Verbal orders such as these have been noted to be associated with errors in accuracy. The aim of this study was to compare a novel computerized system for add-on requests to the prior verbal system. We compare the computerized add-on request system to the verbal system with respect to order completeness and workflow. We demonstrate that the computerized add-on system resulted in the complete in-laboratory documentation of the add-on request 100% of the time, compared to 58% with the verbal add-on system. In addition, we show that documentation of a verbal add-on request in the electronic medical record (EMR) occurred for 4% of requests, while in the computerized system EMR documentation occurred 100% of the time. We further demonstrate that the computerized add-on request process was well accepted by providers and did not significantly change the test mix of the add-on requests. In computerized physician order entry (CPOE) implementations, add-on order functionality should be considered so these orders are documented in the EMR.

Polarization-independent rapidly tunable optical add-drop multiplexer utilizing non-polarizing beam splitters in Ti:LiNbO3

Science.gov (United States)

Shin, Yong-Wook; Sung, Won Ju; Eknoyan, O.; Madsen, C. K.; Taylor, H. F.

2012-04-01

A polarization-independent four-port wavelength-tunable optical add drop multiplexer (OADM) that utilizes non-polarizing relaxed beam splitters has been analyzed and demonstrated in Ti:LiNbO3 at the 1530 nm wavelength regime. The design utilizes an asymmetric interferometer configuration with strain induced index grating for polarization coupling along its arms that are shifted in position relative to each other. Experimental results of the filter response agree with theoretical predictions. Electrooptic tuning over a range of 15.7 nm at a rate of 0.08 nm/V has been measured. A temporal response < 46 ns to a 20 V step change in tuning voltage has been demonstrated. Fiber-to-fiber insertion loss is ~ 6.5 dB.

PC add on card for processing of LSC signals

International Nuclear Information System (INIS)

Jadhav, S.R.; Nikhare, D.M.; Gurna, R.K.; Paulson, Molly; Kulkarni, C.P.; Vaidya, P.P.

2001-01-01

This paper describes PC- add on card developed at Electronics Division for processing of LSC signals. This card uses highly integrated digital and analog circuits, for entire processing of signals available from preamplifiers to get complete beta energy spectrum corresponding to coincident events in Liquid Scintillation Counting. LSC card along with High Voltage PC-add on card gives complete electronics required for LSC system. This card is also used in automatic LSC system along with interface circuits, which are used to control mechanical movements. (author)

QbD based approach for optimization of Tenofovir disoproxil fumarate loaded liquid crystal precursor with improved permeability

Directory of Open Access Journals (Sweden)

Sharvil Patil

2017-11-01

Full Text Available BCS class III drugs suffer from a drawback of low permeability even though they have high aqueous solubility. The objective of current work was to screen the suitability of glyceryl monooleate (GMO/Pluronic F127 cubic phase liquid crystals precursors for permeation enhancement and in turn the bioavailability of tenofovir disoproxil fumarate (TDF, a BCS class III drug. Spray-drying method was used for preparation of TDF loaded liquid crystal precursors (LCP consisting of GMO/Pluronic F127 and lactose monohydrate with an ability to in situ transform into stable cubic phases upon hydration. The quality by design (QbD approach (Factorial design was used for batch optimization. Spherical TDF loaded LCP as revealed by scanning electron microscopy photographs when hydrated and analyzed by small angle X-ray scattering confirmed formation of cubic phase. Differential scanning calorimetry and X-ray diffraction studies confirmed the molecular dispersion of TDF in polymer matrix and also suggested the conversion of TDF from crystalline to amorphous form. In vitro TDF release from prepared LCP showed controlled drug release over a period of 10 h. Further ex vivo studies revealed permeation enhancing activity of prepared LCP, which was highest when tested in presence of digestive enzyme extract. Thus, formulation of stable liquid crystal powder precursor can serve as an alternative for designing oral delivery system for drugs with low permeability.

Cognitive Control and Attentional Selection in Adolescents with ADHD versus ADD

Science.gov (United States)

Carr, Laurie; Henderson, John; Nigg, Joel T.

2010-01-01

An important research question is whether Attention Deficit Hyperactivity Disorder (ADHD) is related to early- or late-stage attentional control mechanisms and whether this differentiates a nonhyperactive subtype (ADD). This question was addressed in a sample of 145 ADD/ADHD and typically developing comparison adolescents (aged 13-17). Attentional…

76 FR 49508 - ``Add Us In'' Initiative

Science.gov (United States)

2011-08-10

... DEPARTMENT OF LABOR Office of Disability Employment Program ``Add Us In'' Initiative AGENCY: Office of Disability Employment Policy, Department of Labor. ACTION: Correction to the Funding Opportunity Number and Closing Date. SUMMARY: The Office of Disability Employment Policy, Department of Labor...

Low-dose add-back therapy during postoperative GnRH agonist treatment

Directory of Open Access Journals (Sweden)

Hsiao-Wen Tsai

2016-02-01

Conclusion: Low dose add-back therapy could effectively ameliorate hypoestrogenic side effects and simultaneously maintain the therapeutic response of GnRH agonist treatment. The treatment dropout was lower compared with a regular dose. Therefore, low dose add-back therapy can be considered a treatment choice during postoperative GnRH agonist treatment.

Arterial line pressure control enhanced extracorporeal blood flow prescription in hemodialysis patients

Directory of Open Access Journals (Sweden)

Rosales Laura

2008-11-01

Full Text Available Abstract Background In hemodialysis, extracorporeal blood flow (Qb recommendation is 300–500 mL/min. To achieve the best Qb, we based our prescription on dynamic arterial line pressure (DALP. Methods This prospective study included 72 patients with catheter Group 1 (G1, 1877 treatments and 35 arterio-venous (AV fistulae Group 2 (G2, 1868 treatments. The dialysis staff was trained to prescribe Qb sufficient to obtain DALP between -200 to -250 mmHg. We measured ionic clearance (IK: mL/min, access recirculation, DALP (mmHg and Qb (mL/min. Six prescription zones were identified: from an optimal A zone (Qb > 400, DALP -200 to -250 to zones with lower Qb E (Qb -199. Results Treatments distribution in A was 695 (37% in G1 vs. 704 (37.7% in G2 (P = 0.7. In B 150 (8% in G1 vs. 458 (24.5% in G2 (P P = 0.62. IK in A was 214 ± 34 (G1 vs. 213 ± 35 (G2 (P = 0.65. IK Anova between G2 zones was: A vs. C and D (P P = 0.02. Conclusion In conclusion, an optimal Qb can de prescribed with DALP of -200 mmHg. Staff adherence to DLAP treatment prescription could be reached up to 81.3% in catheters and 84.1% in AV fistulae.

Development of an add-on kit for scanning confocal microscopy (Conference Presentation)

Science.gov (United States)

Guo, Kaikai; Zheng, Guoan

2017-03-01

Scanning confocal microscopy is a standard choice for many fluorescence imaging applications in basic biomedical research. It is able to produce optically sectioned images and provide acquisition versatility to address many samples and application demands. However, scanning a focused point across the specimen limits the speed of image acquisition. As a result, scanning confocal microscope only works well with stationary samples. Researchers have performed parallel confocal scanning using digital-micromirror-device (DMD), which was used to project a scanning multi-point pattern across the sample. The DMD based parallel confocal systems increase the imaging speed while maintaining the optical sectioning ability. In this paper, we report the development of an add-on kit for high-speed and low-cost confocal microscopy. By adapting this add-on kit to an existing regular microscope, one can convert it into a confocal microscope without significant hardware modifications. Compared with current DMD-based implementations, the reported approach is able to recover multiple layers along the z axis simultaneously. It may find applications in wafer inspection and 3D metrology of semiconductor circuit. The dissemination of the proposed add-on kit under $1000 budget could also lead to new types of experimental designs for biological research labs, e.g., cytology analysis in cell culture experiments, genetic studies on multicellular organisms, pharmaceutical drug profiling, RNA interference studies, investigation of microbial communities in environmental systems, and etc.

Mode-routed fiber-optic add-drop filter

Science.gov (United States)

Moslehi, Behzad (Inventor); Black, Richard James (Inventor); Shaw, Herbert John (Inventor)

2000-01-01

New elements mode-converting two-mode grating and mode-filtering two-mode coupler are disclosed and used as elements in a system for communications, add-drop filtering, and strain sensing. Methods of fabrication for these new two-mode gratings and mode-filtering two-mode couplers are also disclosed.

Add-on effect of Brahmi in the management of schizophrenia

Directory of Open Access Journals (Sweden)

Sukanto Sarkar

2012-01-01

Full Text Available Brahmi(Bacopa monnieri, an Ayurvedic herb has primarily been used to enhance cognitive ability, memory and learning skills. We present a case study of schizophrenia in which add-on Brahmi extracts 500 mg/day for a period of one month resulted in reduction in psychopathology without any treatment-emergent adverse effect. Although preliminary, our case study suggests therapeutic efficacy of add-on Brahmi in schizophrenia, thus opening up a new dimension of its role in alternative medicines.

NPS Adds Another Astronaut Alumnus With NASA’s Newest Class

OpenAIRE

Kuska, Dale M.

2013-01-01

Article taken from the NPS website: http://www.nps.edu/About/News/NPS-Adds-Another-Astronaut-Alumnus-With-NASAs-Newest-Class.html When NASA Administrator Charles Bolden announced the latest class of NASA’s eight astronaut candidates, June 17, the Naval Postgraduate School (NPS) was able to add yet another space-traveling alumnus to its ranks, now totaling 41 and counting. Lt. Cmdr. Victor Glover, an F/A-18 combat pilot currently serving as a Legislative Fellow in the office of Senat...

Word add-in for ontology recognition: semantic enrichment of scientific literature

Directory of Open Access Journals (Sweden)

Naim Oscar

2010-02-01

Full Text Available Abstract Background In the current era of scientific research, efficient communication of information is paramount. As such, the nature of scholarly and scientific communication is changing; cyberinfrastructure is now absolutely necessary and new media are allowing information and knowledge to be more interactive and immediate. One approach to making knowledge more accessible is the addition of machine-readable semantic data to scholarly articles. Results The Word add-in presented here will assist authors in this effort by automatically recognizing and highlighting words or phrases that are likely information-rich, allowing authors to associate semantic data with those words or phrases, and to embed that data in the document as XML. The add-in and source code are publicly available at http://www.codeplex.com/UCSDBioLit. Conclusions The Word add-in for ontology term recognition makes it possible for an author to add semantic data to a document as it is being written and it encodes these data using XML tags that are effectively a standard in life sciences literature. Allowing authors to mark-up their own work will help increase the amount and quality of machine-readable literature metadata.

Word add-in for ontology recognition: semantic enrichment of scientific literature.

Science.gov (United States)

Fink, J Lynn; Fernicola, Pablo; Chandran, Rahul; Parastatidis, Savas; Wade, Alex; Naim, Oscar; Quinn, Gregory B; Bourne, Philip E

2010-02-24

In the current era of scientific research, efficient communication of information is paramount. As such, the nature of scholarly and scientific communication is changing; cyberinfrastructure is now absolutely necessary and new media are allowing information and knowledge to be more interactive and immediate. One approach to making knowledge more accessible is the addition of machine-readable semantic data to scholarly articles. The Word add-in presented here will assist authors in this effort by automatically recognizing and highlighting words or phrases that are likely information-rich, allowing authors to associate semantic data with those words or phrases, and to embed that data in the document as XML. The add-in and source code are publicly available at http://www.codeplex.com/UCSDBioLit. The Word add-in for ontology term recognition makes it possible for an author to add semantic data to a document as it is being written and it encodes these data using XML tags that are effectively a standard in life sciences literature. Allowing authors to mark-up their own work will help increase the amount and quality of machine-readable literature metadata.

radEq Add-On Module for CFD Solver Loci-CHEM

Science.gov (United States)

McCloud, Peter

2013-01-01

Loci-CHEM to be applied to flow velocities where surface radiation due to heating from compression and friction becomes significant. The module adds a radiation equilibrium boundary condition to the computational fluid dynamics (CFD) code to produce accurate results. The module expanded the upper limit for accurate CFD solutions of Loci-CHEM from Mach 4 to Mach 10 based on Space Shuttle Orbiter Re-Entry trajectories. Loci-CHEM already has a very promising architecture and performance, but absence of radiation equilibrium boundary condition limited the application of Loci-CHEM to below Mach 4. The immediate advantage of the add-on module is that it allows Loci-CHEM to work with supersonic flows up to Mach 10. This transformed Loci-CHEM from a rocket engine- heritage CFD code with general subsonic and low-supersonic applications, to an aeroheating code with hypersonic applications. The follow-on advantage of the module is that it is a building block for additional add-on modules that will solve for the heating generated at Mach numbers higher than 10.

40 CFR 63.4566 - How do I determine the add-on control device emission destruction or removal efficiency?

Science.gov (United States)

2010-07-01

... by volume (ppmv), dry basis. Qsd = Volumetric flow rate of gases entering or exiting the add-on...). 0.0416 = Conversion factor for molar volume, kg-moles per cubic meter (mol/m3) (@ 293 Kelvin (K) and... to 40 CFR part 60, as appropriate, to measure gas volumetric flow rate. (3) Use Method 3, 3A, or 3B...

Add Control: plant virtualization for control solutions in WWTP.

Science.gov (United States)

Maiza, M; Bengoechea, A; Grau, P; De Keyser, W; Nopens, I; Brockmann, D; Steyer, J P; Claeys, F; Urchegui, G; Fernández, O; Ayesa, E

2013-01-01

This paper summarizes part of the research work carried out in the Add Control project, which proposes an extension of the wastewater treatment plant (WWTP) models and modelling architectures used in traditional WWTP simulation tools, addressing, in addition to the classical mass transformations (transport, physico-chemical phenomena, biological reactions), all the instrumentation, actuation and automation & control components (sensors, actuators, controllers), considering their real behaviour (signal delays, noise, failures and power consumption of actuators). Its ultimate objective is to allow a rapid transition from the simulation of the control strategy to its implementation at full-scale plants. Thus, this paper presents the application of the Add Control simulation platform for the design and implementation of new control strategies at the WWTP of Mekolalde.

The application of the Accelerated Stability Assessment Program (ASAP) to quality by design (QbD) for drug product stability.

Science.gov (United States)

Waterman, Kenneth Craig

2011-09-01

An isoconversion paradigm, where times in different temperature and humidity-controlled stability chambers are set to provide a fixed degradant level, is shown to compensate for the complex, non-single order kinetics of solid drug products. A humidity-corrected Arrhenius equation provides reliable estimates for temperature and relative humidity effects on degradation rates. A statistical protocol is employed to determine best fits for chemical stability data, which in turn allows for accurate estimations of shelf life (with appropriate confidence intervals) at any storage condition including inside packaging (based on the moisture vapor transmission rate of the packaging and moisture sorption isotherms of the internal components). These methodologies provide both faster results and far better predictions of chemical stability limited shelf life (expiry) than previously possible. Precise shelf-life estimations are generally determined using a 2-week, product-specific protocol. Once the model for a product is developed, it can play a critical role in providing the product understanding necessary for a quality by design (QbD) filing for product approval and enable rational control strategies to assure product stability. Moreover, this Accelerated Stability Assessment Program (ASAP) enables the coupling of product attributes (e.g., moisture content, packaging options) to allow for flexibility in how control strategies are implemented to provide a balance of cost, speed, and other factors while maintaining adequate stability.

Optimization of a Coupling Process for Insulin Degludec According to a Quality by Design (QbD) Paradigm.

Science.gov (United States)

Nie, Lei; Hu, Mingming; Yan, Xu; Guo, Tingting; Wang, Haibin; Zhang, Sheng; Qu, Haibin

2018-05-03

This case study described a successful application of the quality by design (QbD) principles to a coupling process development of insulin degludec. Failure mode effects analysis (FMEA) risk analysis was first used to recognize critical process parameters (CPPs). Five CPPs, including coupling temperature (Temp), pH of desB30 solution (pH), reaction time (Time), desB30 concentration (Conc), and molar equivalent of ester per mole of desB30 insulin (MolE), were then investigated using a fractional factorial design. The curvature effect was found significant, indicating the requirement of second-order models. Afterwards, a central composite design was built with an augmented star and center points study. Regression models were developed for the CPPs to predict the purity and yield of predegludec using above experimental data. The R 2 and adjusted R 2 were higher than 96 and 93% for the two models respectively. The Q 2 values were more than 80% indicating a good predictive ability of models. MolE was found to be the most significant factor affecting both yield and purity of predegludec. Temp, pH, and Conc were also significant for predegludec purity, while Time appeared to remarkably influence the yield model. The multi-dimensional design space and normal operating region (NOR) with a robust setpoint were determined using a probability-based Monte-Carlo simulation method. The verified experimental results showed that the design space was reliable and effective. This study enriches the understanding of acetylation process and is instructional to other complicated operations in biopharmaceutical engineering.

Silicon-Based Asymmetric Add-Drop Microring Resonators with Ultra-Large Through-Port Extinctions

International Nuclear Information System (INIS)

Xi, Xiao; Yun-Tao, Li; Yu-De, Yu; Jin-Zhong, Yu

2010-01-01

We theoretically simulate and experimentally demonstrate ultra-large through-port extinctions in silicon-based asymmetrically-coupled add-drop microring resonators (MRs). Through-port responses in an add-drop MR are analyzed by simulations and large extinctions are found when the MR is near-critically coupled. Accurate fabrication techniques are applied in producing a series of 20 μm-radii add-drop microrings with drop-side gap-widths in slight differences. A through-port extinction of about 42.7 dB is measured in an MR with through- and drop-side gap-width to be respectively 280nm and 295nm. The large extinction suggests about a 20.5 dB improvement from the symmetrical add-drop MR of the same size and the through-side gap-width. The experimental results are finally compared with the post-fabrication simulations, which show a gap-width tolerance of > 30 am for the through-port extinction enhancement

Eslicarbazepine acetate add-on for drug-resistant partial epilepsy.

Science.gov (United States)

Chang, Xian-Chao; Yuan, Hai; Wang, Yi; Xu, Hui-Qin; Hong, Wen-Ke; Zheng, Rong-Yuan

2017-10-25

(RR 2.90, 95% CI 1.49 to 5.68). Participants were more likely to have ESL withdrawn for adverse effects (RR 2.66, 95% CI 1.42 to 4.96) but not for any reason (RR 1.19, 95% CI 0.86 to 1.64). The following adverse effects were significantly associated with ESL: dizziness (RR 2.81, 99% CI 1.86 to 4.27); nausea (RR 2.61, 99% CI 1.36 to 5.01); diplopia (RR 4.14, 99% CI 1.74 to 9.84); somnolence (RR 1.71, 99% CI 1.11 to 2.63) and vomiting (RR 3.30, 99% CI 1.34 to 8.13). Overall the quality of the evidence was rated as moderate to high. ESL reduces seizure frequency when used as an add-on treatment for people with drug-resistant partial epilepsy. The trials included in this review were of short-term duration and focused on adults. One new trial has been included in this update, but the conclusions are unchanged.

24 CFR 983.206 - HAP contract amendments (to add or substitute contract units).

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false HAP contract amendments (to add or... Contract § 983.206 HAP contract amendments (to add or substitute contract units). (a) Amendment to substitute contract units. At the discretion of the PHA and subject to all PBV requirements, the HAP contract...

Measuring Narcissism within Add Health: The Development and Validation of a New Scale

Science.gov (United States)

Davis, Mark S.; Brunell, Amy B.

2012-01-01

This study reports the development of a measure of narcissism within the National Longitudinal Study of Adolescent Health (Add Health) data set. In Study 1, items were selected from Wave III to form the Add Health Narcissism Scale (AHNS). These were factor analyzed, yielding a single factor comprised of five subscales. We correlated the AHNS and…

Avoidant personality disorder in individuals with generalized social anxiety disorder: what does it add?

Science.gov (United States)

Marques, Luana; Porter, Eliora; Keshaviah, Aparna; Pollack, Mark H; Van Ameringen, Michael; Stein, Murray B; Simon, Naomi M

2012-08-01

Avoidant personality disorder (AvPD) has a high level of symptom overlap and comorbidity with generalized social anxiety disorder (GSAD). We examined whether the presence of comorbid AvPD adds significant clinically relevant information for individuals seeking treatment for GSAD. Results suggested that AvPD was significantly associated with poorer quality of life and greater disability in univariate, but not multivariate analyses. Endorsement of more AvPD symptoms was associated with increased disability, increased risk of intimacy, and lower social support, even after covariate adjustment. Specifically, AvPD item 3, hard to be "open" even with people you are close to, was most strongly correlated with quality of life and disability. A binary diagnosis of AvPD alone adds little beyond a marker of greater GSAD severity and depression among patients with GSAD, while a specific feature of AvPD not captured by the GSAD diagnosis, namely emotional guardedness, may be associated with greater impairment. Published by Elsevier Ltd.

An add-in implementation of the RESAMPLING syntax under Microsoft EXCEL.

Science.gov (United States)

Meineke, I

2000-10-01

The RESAMPLING syntax defines a set of powerful commands, which allow the programming of probabilistic statistical models with few, easily memorized statements. This paper presents an implementation of the RESAMPLING syntax using Microsoft EXCEL with Microsoft WINDOWS(R) as a platform. Two examples are given to demonstrate typical applications of RESAMPLING in biomedicine. Details of the implementation with special emphasis on the programming environment are discussed at length. The add-in is available electronically to interested readers upon request. The use of the add-in facilitates numerical statistical analyses of data from within EXCEL in a comfortable way.

SINGLE-FACED GRAYQB{trademark} - A RADIATION MAPPING DEVICE

Energy Technology Data Exchange (ETDEWEB)

Mayer, J.; Farfan, E.; Immel, D.; Phillips, M.; Bobbitt, J.; Plummer, J.

2013-12-12

GrayQb{trademark} is a novel technology that has the potential to characterize radioactively contaminated areas such as hot cells, gloveboxes, small and large rooms, hallways, and waste tanks. The goal of GrayQb{trademark} is to speed the process of decontaminating these areas, which reduces worker exposures and promotes ALARA considerations. The device employs Phosphorous Storage Plate (PSP) technology as its primary detector material. PSPs, commonly used for medical applications and non-destructive testing, can be read using a commercially available scanner. The goal of GrayQb{trademark} technology is to locate, quantify, and identify the sources of contamination. The purpose of the work documented in this report was to better characterize the performance of GrayQb{trademark} in its ability to present overlay images of the PSP image and the associated visual image of the location being surveyed. The results presented in this report are overlay images identifying the location of hot spots in both controlled and field environments. The GrayQb{trademark} technology has been mainly tested in a controlled environment with known distances and source characteristics such as specific known radionuclides, dose rates, and strength. The original concept for the GrayQb{trademark} device involved utilizing the six faces of a cube configuration and was designed to be positioned in the center of a contaminated area for 3D mapping. A smaller single-faced GrayQb{trademark}, dubbed GrayQb SF, was designed for the purpose of conducting the characterization testing documented in this report. This lighter 2D version is ideal for applications where entry ports are too small for a deployment of the original GrayQb™ version or where only a single surface is of interest. The shape, size, and weight of these two designs have been carefully modeled to account for most limitations encountered in hot cells, gloveboxes, and contaminated areas. GrayQb{trademark} and GrayQb{trademark} SF

THE SLOAN DIGITAL SKY SURVEY CO-ADD: A GALAXY PHOTOMETRIC REDSHIFT CATALOG

International Nuclear Information System (INIS)

Reis, Ribamar R. R.; Soares-Santos, Marcelle; Annis, James; Dodelson, Scott; Hao Jiangang; Johnston, David; Kubo, Jeffrey; Lin Huan; Seo, Hee-Jong; Simet, Melanie

2012-01-01

We present and describe a catalog of galaxy photometric redshifts (photo-z) for the Sloan Digital Sky Survey (SDSS) Co-add Data. We use the artificial neural network (ANN) technique to calculate the photo-z and the nearest neighbor error method to estimate photo-z errors for ∼13 million objects classified as galaxies in the co-add with r 68 = 0.031. After presenting our results and quality tests, we provide a short guide for users accessing the public data.

Exploiting mAb structure characteristics for a directed QbD implementation in early process development.

Science.gov (United States)

Karlberg, Micael; von Stosch, Moritz; Glassey, Jarka

2018-03-07

decision tool can help to enhance the risk assessment to better aid process development and thereby overcome some of the limitations and challenges present in QbD implementation today.

Neural biomarkers for dyslexia, ADHD and ADD in the auditory cortex of children

OpenAIRE

Bettina Serrallach; Christine Gross; Valdis Bernhofs; Dorte Engelmann; Jan Benner; Jan Benner; Nadine Gündert; Maria Blatow; Martina Wengenroth; Angelika Seitz; Monika Brunner; Stefan Seither; Stefan Seither; Richard Parncutt; Peter Schneider

2016-01-01

Dyslexia, attention deficit hyperactivity disorder (ADHD), and attention deficit disorder (ADD) show distinct clinical profiles that may include auditory and language-related impairments. Currently, an objective brain-based diagnosis of these developmental disorders is still unavailable. We investigated the neuro-auditory systems of dyslexic, ADHD, ADD, and age-matched control children (N=147) using neuroimaging, magnet-encephalography and psychoacoustics. All disorder subgroups exhibited an ...

The healing effect of combined hydroalcoholic extract of Teocurium polium and the seed hull of Quercus brantii on burn wounds in rats

Directory of Open Access Journals (Sweden)

Mohammadi Jamshid

2016-10-01

Full Text Available Plants and their extracts have considerable potential for wound healing. So, The aim of this study was to evaluate the wound healing effect of combined hydroalcoholic extract of Teocurium Polium (TP and the seed hull of Quercus brantii (Persian oak (QB and comparing with silver sulfadiazine (SSD ointment (1% in rats. Animals were divided into six groups consist of normal (untreated, physiologic serum, TP, seed hulls of Quercus brantii (QB, combination of TP and QB and the other group was SSD. Burn area size, epidermal and dermal diameter, number of hair follicle, histopathology of the burn skin and concentration of plasma malondialdehide (MDA were determined in different groups. Animals treated with QB and TP, SSD and combination of two extracts (QB +TP showed a significant reduction in the burn area. Serum MDA decreased significantly in animals treated with QB, TP and QB+TP. Histological comparison has shown that TP, QB and combination of them significantly increased reepithelialization in burn wounds, as compared to normal group. In conclusion, our results demonstrated that topical application of TP and QB has a significant effect on the burn wound healing.

12 CFR 502.60 - When will OTS adjust, add, waive, or eliminate a fee?

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false When will OTS adjust, add, waive, or eliminate a fee? 502.60 Section 502.60 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY ASSESSMENTS AND FEES Fees § 502.60 When will OTS adjust, add, waive, or eliminate a fee? Under...

Nanosystem trends in drug delivery using quality-by-design concept.

Science.gov (United States)

Li, Jing; Qiao, Yanjiang; Wu, Zhisheng

2017-06-28

Quality by design (QbD) has become an inevitable trend because of its benefits for product quality and process understanding. Trials have been conducted using QbD in nanosystems' optimization. This paper reviews the application of QbD for processing nanosystems and summarizes the application procedure. It provides prospective guidelines for future investigations that apply QbD to nanosystem manufacturing processes. Employing the QbD concept in this way is a novel area in nanosystem quality. Copyright © 2017 Elsevier B.V. All rights reserved.

Estimating the postmortem interval (PMI) using accumulated degree-days (ADD) in a temperate region of South Africa.

Science.gov (United States)

Myburgh, Jolandie; L'Abbé, Ericka N; Steyn, Maryna; Becker, Piet J

2013-06-10

The validity of the method in which total body score (TBS) and accumulated degree-days (ADD) are used to estimate the postmortem interval (PMI) is examined. TBS and ADD were recorded for 232 days in northern South Africa, which has temperatures between 17 and 28 °C in summer and 6 and 20 °C in winter. Winter temperatures rarely go below 0°C. Thirty pig carcasses, which weighed between 38 and 91 kg, were used. TBS was scored using the modified method of Megyesi et al. [1]. Temperature was acquired from an on site data logger and the weather station bureau; differences between these two sources were not statistically significant. Using loglinear random-effects maximum likelihood regression, an r(2) value for ADD (0.6227) was produced and linear regression formulae to estimate PMI from ADD with a 95% prediction interval were developed. The data of 16 additional pigs that were placed a year later were then used to validate the accuracy of this method. The actual PMI and ADD were compared to the estimated PMI and ADD produced by the developed formulae as well as the estimated PMIs within the 95% prediction interval. A validation of the study produced poor results as only one pig of 16 fell within the 95% interval when using the formulae, showing that ADD has limited use in the prediction of PMI in a South African setting. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Stereotaxic core needle biopsy of breast microcalcifications obtained using a standard mammography table with an add-on unit

International Nuclear Information System (INIS)

Ward, S.E.; Taves, D.H.; McCurdy, L.I.

2000-01-01

To demonstrate the reliability of stereotaxic biopsy of indeterminate microcalcifications using a standard mammography table with an add-on unit. In 121 cases of indeterminate microcalcifications, core biopsy was performed using a standard mammography table with an add-on stereotaxic unit. Microcalcifications were identified on radiography of core specimens. Microcalcifications and a definitive histologic diagnosis were obtained in 112 core biopsies (92.6%), with no significant complications. In 23 lesions frank malignancy was diagnosed, and all of these diagnoses were confirmed on surgery. Pathologic examination suggested carcinoma in 4 lesions, and open biopsy confirmed malignancy in 3 of these cases. Four lesions showed atypical ductal hyperplasia. Benign disease was diagnosed in 81 lesions, of which 78 remained stable on mammographic follow-up (mean 16 months later) and 3 were subjected to surgical biopsy (of which 1 was malignant and 2 were benign). Nine cases were technically unsatisfactory because microcalcifications were not sampled. Stereotaxic core biopsy performed with an add-on unit is a safe and reliable technique for biopsy of indeterminate microcalcifications. For successful biopsy, microcalcifications must be harvested. Pathologic results should be correlated with mammographic findings. The accuracy rate compares favourably with results reported using prone biopsy tables. In an era of cost containment, this alternative to prone biopsy tables could result m significant savings in terms of capital investment and use of hospital rooms. In this study, surgical biopsy could have been avoided in 64.5% of cases. (author)

Non-invasive beamforming add-on module

KAUST Repository

Bader, Ahmed

2017-02-23

An embodiment of a non-invasive beamforming add-on apparatus couples to an existing antenna port and rectifies the beam azimuth in the upstream and downstream directions. The apparatus comprises input circuitry that is configured to receive one or more signals from a neighboring node of the linear wireless sensor network; first amplifier circuitry configured to adjust an amplitude of a respective received signal in accordance with a weighting coefficient and invoke a desired phase to a carrier frequency of the received signal thereby forming a first amplified signal; and second amplifier circuitry configured to adjust a gain of the first amplified signal towards upstream and downstream neighbors of the linear wireless sensor in the linear wireless sensor network.

Rate and associated factors of solifenacin add-on after tamsulosin monotherapy in men with voiding and storage lower urinary tract symptoms.

Science.gov (United States)

Lee, H N; Lee, K-S; Kim, J C; Chung, B H; Kim, C-S; Lee, J G; Kim, D K; Park, C H; Park, J K; Hong, S J

2015-04-01

To explore the rate of add-on therapy with solifenacin in men with voiding and storage lower urinary tract symptoms (LUTS) after tamsulosin monotherapy and to explore predictive factors for starting solifenacin add-on therapy. Men aged ≥ 45 years with IPSS ≥ 12 and symptoms of OAB (OAB-V8 ≥ 8, micturition ≥ 8/24 h, urgency ≥ 2/24 h) were enrolled to receive tamsulosin 0.2 mg once daily. After 4 weeks, men with residual symptoms of OAB and reported 'dissatisfied' or 'a little satisfied' were received solifenacin 5 mg in combination with tamsulosin monotherapy. Subjects completed an IPSS, a Quality of life (QoL) index, OAB V8, and an International Consultation of Incontinence Questionnaire (ICIQ)-Male LUTS, and patient perception of bladder condition (PPBC) at baseline and week 4. Of a total of 305 patients, 254 patients completed 4 weeks of tamsulosin treatment. For 176 patients, solifenacin was added (69.3%). Significant predictive factors of solifenacin add-on therapy included long LUTS duration, high IPSS, number of micturitions per 24 h, more urgency episodes, high urgency severity score in a voiding diary and high OAB V8 score. Based on multivariable analysis, potential predictive factors of solifenacin add-on therapy included long LUTS duration (OR = 1.008, 95% CI: 1.001-1.014), high serum PSA (OR = 1.543, 95% CI: 1.136-2.095) and small prostate size (OR = 0.970, 95% CI: 0.947-0.994) (p tamsulosin monotherapy. Two thirds of men with voiding and storage LUTS needed to add anticholinergics after 4 weeks of tamsulosin monotherapy. Patients with longer lasting symptoms and storage symptoms with small prostate volume may require the anticholinergic add-on. © 2014 John Wiley & Sons Ltd.

Sensitivity and specificity of the amer dizziness diagnostic scale (adds) for patients with vestibular disorders.

Science.gov (United States)

Al Saif, Amer; Alsenany, Samira

2015-01-01

[Purpose] To investigate the sensitivity and specificity of a newly developed diagnostic tool, the Amer Dizziness Diagnostic Scale (ADDS), to evaluate and differentially diagnose vestibular disorder and to identify the strengths and weaknesses of the scale and its usefulness in clinical practice. [Subjects and Methods] Two hundred subjects of both genders (72 males, 128 females) aged between 18 to 60 (49.5±7.8) who had a history of vertigo and/or dizziness symptoms for this previous two weeks or less were recruited for the study. All subjects were referred by otolaryngologists, neurologists or family physicians in and around Jeddah, Kingdom of Saudi Arabia. On the first clinic visit, all the patients were evaluated once using the ADDS, following which they underwent routine testing of clinical signs and symptoms, audiometry, and a neurological examination, coupled with tests of Vestibulo-Ocular Reflex function, which often serves as the "gold standard" for determining the probability of a vestibular deficit. [Results] The results show that the ADDS strongly correlated with "true-positive" and "true-negative" responses for determining the probability of a vestibular disorder (r =0.95). A stepwise linear regression was conducted and the results indicate that the ADDS was a significant predictor of "true-positive" and "true-negative" responses in vestibular disorders (R(2) =0.90). Approximately 90% of the variability in the vestibular gold standard test was explained by its relationship to the ADDS. Moreover, the ADDS was found to have a sensitivity of 96% and a specificity of 96%. [Conclusion] This study showed that the Amer Dizziness Diagnostic Scale has high sensitivity and specificity and that it can be used as a method of differential diagnosis for patients with vestibular disorders.

Assessment of the optimal operating parameters during extracorporeal CO2 removal with the Abylcap® system.

Science.gov (United States)

Eloot, Sunny; Peperstraete, Harlinde; De Somer, Filip; Hoste, Eric

2017-01-13

Lung protective ventilation is recommended in patients with acute respiratory distress syndrome (ARDS) needing mechanical ventilation. This can however be associated with hypercapnia and respiratory acidosis, such that extracorporeal CO2 removal (ECCO2R) can be applied. The aim of this study was to derive optimal operating parameters for the ECCO2R Abylcap® system (Bellco, Italy). We included 4 ARDS patients with a partial arterial oxygen tension over the fraction of inspired oxygen (PaO2/FiO2) lower than 150 mmHg, receiving lung-protective ventilation and treated with the Abylcap® via a double lumen 13.5-Fr dialysis catheter in the femoral vein. Every 24 hours during 5 consecutive days, blood was sampled at the Abylcap® inlet and outlet for different blood flows (QB:200-300-400 mL/min) with 100% O2 gas flow (QG) of 7 L/min, and for different QG (QG: 0.5-1-1.5-3-6-8 L/min) with QB400 mL/min. CO2 and O2 transfer remained constant over 5 days for a fixed QB. We found that, for a fixed QG of 7 L/min, CO2 transfer linearly and significantly increased with QB (i.e. from 58 ± 8 to 98 ± 16 mL/min for QB 200 to 400 mL/min). For a fixed QB of 400 mL/min, CO2 transfer non-linearly increased with QG (i.e. from 39 ± 9 to 98 ± 16 mL/min for QG 0.5 to 8 L/min) reaching a plateau at QG of 6 L/min. Hence, when using the Abylcap® ECCO2R in the treatment of ARDS patients the O2 flow should be at least 6 L/min while QB should be set at its maximum.

Application of Edible Films Containing Oregano (Origanum vulgare) Essential Oil on Queso Blanco Cheese Prepared with Flaxseed (Linum usitatissimum) Oil.

Science.gov (United States)

Gurdian, Cristhiam; Chouljenko, Alexander; Solval, Kevin Mis; Boeneke, Charles; King, Joan M; Sathivel, Subramaniam

2017-06-01

Fortification of queso blanco (QB) with flaxseed oil (FO) containing omega-3 polyunsaturated fatty acids may provide a functional food with health benefits such as improved cell, brain, and retina functionality, and protection against cardiovascular and immune-inflammatory diseases. However, QB experiences a short shelf life because of the early development of yeasts and molds and addition of FO may increase susceptibility to lipid oxidation. Oregano essential oil (OEO) is known for its antimicrobial and antioxidant properties, but due to its intense flavor compounds it may not be suitable for direct incorporation into QB. Thus, incorporation of OEO into an edible film prepared with whey protein isolate (WPI) may improve the shelf life of QB. Scanning electron microscopy (SEM) micrographs revealed that FO was successfully retained by the cheese after homogenization. The thiobarbituric-acid-reactive-substances (TBARS) and yeast and mold counts (YMC) of the wrapped cheeses were analyzed during 60 d of refrigerated storage. The oxidation rate increased significantly for nonwrapped QB containing FO (QBFO) during storage, however wrapping with WPI edible films containing OEO (WOF) significantly limited lipid oxidation and prevented growth of yeasts and molds. This study demonstrated the antioxidant and antimicrobial properties of WOF for preservation of QBFO during refrigerated storage. © 2017 Institute of Food Technologists®.

Role of the PufX protein in photosynthetic growth of Rhodobacter sphaeroides. 2. PufX is required for efficient ubiquinone/ubiquinol exchange between the reaction center QB site and the cytochrome bc1 complex.

Science.gov (United States)

Barz, W P; Verméglio, A; Francia, F; Venturoli, G; Melandri, B A; Oesterhelt, D

1995-11-21

The PufX membrane protein is essential for photosynthetic growth of Rhodobacter sphaeroides because it is required for multiple-turnover electron transfer under anaerobic conditions [see accompanying article; Barz, W. P., Francia, F., Venturoli, G., Melandri, B. A., Verméglio, A., & Oesterhelt, D. (1995) Biochemistry 34, 15235-15247]. In order to understand the molecular role of PufX, light-induced absorption spectroscopy was performed using a pufX- mutant, a pufX+ strain, and two suppressor mutants. We show that the reaction center (RC) requires PufX for its functionality under different redox conditions than the cytochrome bc1 complex: When the kinetics of flash-induced reduction of cytochrome b561 were monitored in chromatophores, we observed a requirement of PufX for turnover of the cytochrome bc1 complex only at high redox potential (Eh > 140 mV), suggesting a function of PufX in lateral ubiquinol transfer from the RC. In contrast, PufX is required for multiple turnover of the RC only under reducing conditions: When the Q pool was partially oxidized in vivo using oxygen or electron acceptors like dimethyl sulfoxide or trimethylamine N-oxide, the deletion of PufX had no effect on light-driven electron flow through the RC. Flash train experiments under anaerobic in vivo conditions revealed that RC photochemistry does not depend on PufX for the first two flash excitations. Following the third and subsequent flashes, however, efficient charge separation requires PufX, indicating an important role of PufX for fast Q/QH2 exchange at the QB site of the RC. We show that the Q/QH2 exchange rate is reduced approximately 500-fold by the deletion of PufX when the Q pool is nearly completely reduced, demonstrating an essential role of PufX for the access of ubiquinone to the QB site. The fast ubiquinone/ubiquinol exchange is partially restored by suppressor mutations altering the macromolecular antenna structure. These results suggest an indirect role of PufX in

Effects of Vildagliptin Add-on Insulin Therapy on Nocturnal Glycemic Variations in Uncontrolled Type 2 Diabetes.

Science.gov (United States)

Li, Feng-Fei; Shen, Yun; Sun, Rui; Zhang, Dan-Feng; Jin, Xing; Zhai, Xiao-Fang; Chen, Mao-Yuan; Su, Xiao-Fei; Wu, Jin-Dan; Ye, Lei; Ma, Jian-Hua

2017-10-01

To investigate whether vildagliptin add-on insulin therapy improves glycemic variations in patients with uncontrolled type 2 diabetes (T2D) compared to patients with placebo therapy. This was a 24-week, single-center, double-blind, placebo-controlled trial. Inadequately controlled T2D patients treated with insulin therapy were recruited between June 2012 and April 2013. The trial included a 2-week screening period and a 24-week randomized period. Subjects were randomly assigned to a vildagliptin add-on insulin therapy group (n = 17) or a matched placebo group (n = 16). Scheduled visits occurred at weeks 4, 8, 12, 16, 20, and 24. Continuous glucose monitoring (CGM) was performed before and at the endpoint of the study. A total of 33 subjects were admitted, with 1 patient withdrawing from the placebo group. After 24 weeks of therapy, HbA1c values were significantly reduced at the endpoint in the vildagliptin add-on group. CGM data showed that patients with vildagliptin add-on therapy had a significantly lower 24-h mean glucose concentration and mean amplitude of glycemic excursion (MAGE). At the endpoint of the study, patients in the vildagliptin add-on group had a significantly lower MAGE and standard deviation compared to the control patients during the nocturnal period (0000-0600). A severe hypoglycemic episode was not observed in either group. Vildagliptin add-on therapy to insulin has the ability to improve glycemic variations, especially during the nocturnal time period, in patients with uncontrolled T2D.

QbD-Enabled Development of Novel Stimuli-Responsive Gastroretentive Systems of Acyclovir for Improved Patient Compliance and Biopharmaceutical Performance.

Science.gov (United States)

Singh, Bhupinder; Kaur, Anterpreet; Dhiman, Shashi; Garg, Babita; Khurana, Rajneet Kaur; Beg, Sarwar

2016-04-01

The current studies entail systematic quality by design (QbD)-based development of stimuli-responsive gastroretentive drug delivery systems (GRDDS) of acyclovir using polysaccharide blends for attaining controlled drug release profile and improved patient compliance. The patient-centric quality target product profile was defined and critical quality attributes (CQAs) earmarked. Risk assessment studies, carried out through Ishikawa fish bone diagram and failure mode, effect, and criticality analysis, helped in identifying the plausible risks or failure modes affecting the quality attributes of the drug product. A face-centered cubic design was employed for systematic development and optimization of the concentration of sodium alginate (X 1) and gellan (X 2) as the critical material attributes (CMAs) in the stimuli-responsive formulations, which were evaluated for CQAs viz. viscosity, gel strength, onset of floatation, and drug release characteristics. Mathematical modeling was carried out for generation of design space, and optimum formulation was embarked upon, exhibiting formulation characteristics marked by excellent floatation and bioadhesion characteristics along with promising drug release control up to 24 h. Drug-excipient compatibility studies through FTIR and DSC revealed absence of any interaction(s) among the formulation excipients. In vivo pharmacokinetic studies in Wistar rats corroborated extension in the drug absorption profile from the optimized stimuli-responsive GR formulations vis-à-vis the marketed suspension (ZOVIRAX®). Establishment of in vitro/in vivo correlation (IVIVC) revealed a high degree of correlation between the in vitro and in vivo data. In a nutshell, the present investigations report the successful development of stimuli-responsive GRDDS of acyclovir, which can be applicable as a platform approach for other drugs too.

Humor adds the creative touch to CQI teams.

Science.gov (United States)

Balzer, J W

1994-07-01

The health care industry is looking to continuous quality improvement as a process to both improve patient care and promote cost effectiveness. Interdisciplinary teams are learning to work together and to use data-driven problem solving. Humor adds a creative and welcome touch to the process that makes it easier and more fun to work in teams. The team leader or facilitator who uses humor along the journey sanctions the risk-taking behavior that accompanies creative solutions to tough problems.

Pharmaceutical quality by design: product and process development, understanding, and control.

Science.gov (United States)

Yu, Lawrence X

2008-04-01

The purpose of this paper is to discuss the pharmaceutical Quality by Design (QbD) and describe how it can be used to ensure pharmaceutical quality. The QbD was described and some of its elements identified. Process parameters and quality attributes were identified for each unit operation during manufacture of solid oral dosage forms. The use of QbD was contrasted with the evaluation of product quality by testing alone. The QbD is a systemic approach to pharmaceutical development. It means designing and developing formulations and manufacturing processes to ensure predefined product quality. Some of the QbD elements include: Defining target product quality profile; Designing product and manufacturing processes; Identifying critical quality attributes, process parameters, and sources of variability; Controlling manufacturing processes to produce consistent quality over time. Using QbD, pharmaceutical quality is assured by understanding and controlling formulation and manufacturing variables. Product testing confirms the product quality. Implementation of QbD will enable transformation of the chemistry, manufacturing, and controls (CMC) review of abbreviated new drug applications (ANDAs) into a science-based pharmaceutical quality assessment.

Pharmaceutical product development: A quality by design approach

Science.gov (United States)

Pramod, Kannissery; Tahir, M. Abu; Charoo, Naseem A.; Ansari, Shahid H.; Ali, Javed

2016-01-01

The application of quality by design (QbD) in pharmaceutical product development is now a thrust area for the regulatory authorities and the pharmaceutical industry. International Conference on Harmonization and United States Food and Drug Administration (USFDA) emphasized the principles and applications of QbD in pharmaceutical development in their guidance for the industry. QbD attributes are addressed in question-based review, developed by USFDA for chemistry, manufacturing, and controls section of abbreviated new drug applications. QbD principles, when implemented, lead to a successful product development, subsequent prompt regulatory approval, reduce exhaustive validation burden, and significantly reduce post-approval changes. The key elements of QbD viz., target product quality profile, critical quality attributes, risk assessments, design space, control strategy, product lifecycle management, and continual improvement are discussed to understand the performance of dosage forms within design space. Design of experiments, risk assessment tools, and process analytical technology are also discussed for their role in QbD. This review underlines the importance of QbD in inculcating science-based approach in pharmaceutical product development. PMID:27606256

Pharmaceutical product development: A quality by design approach.

Science.gov (United States)

Pramod, Kannissery; Tahir, M Abu; Charoo, Naseem A; Ansari, Shahid H; Ali, Javed

2016-01-01

The application of quality by design (QbD) in pharmaceutical product development is now a thrust area for the regulatory authorities and the pharmaceutical industry. International Conference on Harmonization and United States Food and Drug Administration (USFDA) emphasized the principles and applications of QbD in pharmaceutical development in their guidance for the industry. QbD attributes are addressed in question-based review, developed by USFDA for chemistry, manufacturing, and controls section of abbreviated new drug applications. QbD principles, when implemented, lead to a successful product development, subsequent prompt regulatory approval, reduce exhaustive validation burden, and significantly reduce post-approval changes. The key elements of QbD viz., target product quality profile, critical quality attributes, risk assessments, design space, control strategy, product lifecycle management, and continual improvement are discussed to understand the performance of dosage forms within design space. Design of experiments, risk assessment tools, and process analytical technology are also discussed for their role in QbD. This review underlines the importance of QbD in inculcating science-based approach in pharmaceutical product development.

Does gesture add to the comprehensibility of people with aphasia?

NARCIS (Netherlands)

van Nispen, Karin; Sekine, Kazuki; Rose, Miranda; Ferré, Gaëlle; Tutton, Mark

2015-01-01

Gesture can convey information co-occurring with and in the absence of speech. As such, it seems a useful strategy for people with aphasia (PWA) to compensate for their impaired speech. To find out whether gestures used by PWA add to the comprehensibility of their communication we looked at the

Weight gain with add-on second-generation antipsychotics in bipolar disorder: a naturalistic study.

Science.gov (United States)

Najar, H; Joas, E; Kardell, M; Pålsson, E; Landén, M

2017-06-01

Our aim was to investigate the prevalence and magnitude of weight gain in-patients with bipolar disorder when treated with a second-generation antipsychotic as an add-on treatment to a mood stabilizer in routine clinical practice. Data were derived from the quality register for bipolar disorder in Sweden (BipoläR). Patients with bipolar disorder who started add-on treatment with a SGA (n = 575) were compared at next yearly follow-up with age and sex matched patients who were only treated with a mood stabilizer (n = 566). The primary outcome measure was change in body weight and body mass index (BMI). We also assessed the prevalence of clinically significant weight gain defined as ≥7% gain in body weight. The group that received add-on treatment with antipsychotics neither gained more weight nor were at higher risk for a clinically significant weight gain than the reference group. Instead, factors associated with clinically significant weight gain were female sex, young age, low-baseline BMI, and occurrence of manic/hypomanic episodes. We found no evidence of an overall increased risk of weight gain for patients with bipolar disorder after receiving add-on SGA to a mood stabilizer in a routine clinical setting. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High optical label switching add-drop multiplexer nodes with nanoseconds latency for 5G metro/access networks

NARCIS (Netherlands)

Calabretta, N.; Miao, W.; De Waardt, H.

2016-01-01

We present a novel optical add-drop multiplexer for next-generation metro/access networks by exploiting optical label switching technology. Experimental results of a ring network show nanoseconds add/drop operation including multicasting and power equalization of 50Gb/s data.

Project DyAdd: Visual Attention in Adult Dyslexia and ADHD

Science.gov (United States)

Laasonen, Marja; Salomaa, Jonna; Cousineau, Denis; Leppamaki, Sami; Tani, Pekka; Hokkanen, Laura; Dye, Matthew

2012-01-01

In this study of the project DyAdd, three aspects of visual attention were investigated in adults (18-55 years) with dyslexia (n = 35) or attention deficit/hyperactivity disorder (ADHD, n = 22), and in healthy controls (n = 35). Temporal characteristics of visual attention were assessed with Attentional Blink (AB), capacity of visual attention…

40 CFR 63.4567 - How do I establish the emission capture system and add-on control device operating limits during...

Science.gov (United States)

2010-07-01

... system and add-on control device operating limits during the performance test? 63.4567 Section 63.4567... Emission Rate with Add-on Controls Option § 63.4567 How do I establish the emission capture system and add-on control device operating limits during the performance test? During the performance test required...

Which thiazide to choose as add-on therapy for hypertension?

Directory of Open Access Journals (Sweden)

Barrios V

2014-07-01

Full Text Available Vivencio Barrios,1 Carlos Escobar2 1Department of Cardiology, Hospital Ramon y Cajal, 2Department of Cardiology, Hospital La Paz, Madrid, Spain Abstract: Combined therapy is required in the majority of patients with hypertension to achieve blood pressure (BP targets. Although different antihypertensive drugs can be combined, not all combinations are equally effective and safe. In this context, the combination of a renin angiotensin system inhibitor with a diuretic, usually a thiazide, particularly hydrochlorothiazide (HCTZ or thiazide-like diuretics, such as chlorthalidone or indapamide, is recommended. However, not all diuretics are equal. Although HCTZ, chlorthalidone, and indapamide as add-on therapy effectively reduce BP levels, the majority of studies have obtained greater BP reductions with chlorthalidone or indapamide than with HCTZ. Moreover, there are data showing benefits with chlorthalidone or indapamide beyond BP. Thus, chlorthalidone seems to have pleiotropic effects beyond BP reduction. Moreover, compared with placebo, chlorthalidone has small effects on fasting glucose and total cholesterol, and compared with HCTZ, chlorthalidone achieves significantly lower total cholesterol and low-density lipoprotein cholesterol levels. Similarly, indapamide has demonstrated no negative impact on glucose or lipid metabolism. More importantly, although head-to-head clinical trials comparing the effects of indapamide or chlorthalidone with HCTZ are not available, indirect comparisons and post hoc analyses suggest that the use of chlorthalidone or indapamide is associated with a reduction in cardiovascular events. Despite this, the most frequent diuretic used in clinical practice as add-on therapy for hypertension is HCTZ. The purpose of this review is to update the published data on the efficacy and safety of HCTZ, chlorthalidone, and indapamide as add-on therapy in patients with hypertension. Keywords: blood pressure control, hydrochlorothiazide

40 CFR 63.3546 - How do I establish the emission capture system and add-on control device operating limits during...

Science.gov (United States)

2010-07-01

... system and add-on control device operating limits during the performance test? 63.3546 Section 63.3546... device or system of multiple capture devices. The average duct static pressure is the maximum operating... Add-on Controls Option § 63.3546 How do I establish the emission capture system and add-on control...

40 CFR 63.4767 - How do I establish the emission capture system and add-on control device operating limits during...

Science.gov (United States)

2010-07-01

... system and add-on control device operating limits during the performance test? 63.4767 Section 63.4767... Rate with Add-on Controls Option § 63.4767 How do I establish the emission capture system and add-on control device operating limits during the performance test? During the performance test required by § 63...

40 CFR 63.4167 - How do I establish the emission capture system and add-on control device operating limits during...

Science.gov (United States)

2010-07-01

... system and add-on control device operating limits during the performance test? 63.4167 Section 63.4167... with Add-on Controls Option § 63.4167 How do I establish the emission capture system and add-on control device operating limits during the performance test? During the performance test required by § 63.4160...

40 CFR 63.4966 - How do I establish the emission capture system and add-on control device operating limits during...

Science.gov (United States)

2010-07-01

... system and add-on control device operating limits during the performance test? 63.4966 Section 63.4966... outlet gas temperature is the maximum operating limit for your condenser. (e) Emission capture system... with Add-on Controls Option § 63.4966 How do I establish the emission capture system and add-on control...

An Analysis of Aviation Maintenance Operations and Supporting Costs, and Cost Capturing Systems

Science.gov (United States)

2012-12-04

the La Mesa Parent Teacher Association. = ^Åèìáëáíáçå=oÉëÉ~êÅÜ=mêçÖê~ã= do^ar^qb=p`elli=lc=_rpfkbpp=C=mr_if`=mlif`v= = - vii -= k^s^i=mlpqdo^ar^qb=p...host.uniroma3.it/facolta/ economia /db/materiali/insegnamenti/588_3930.pdf Cost Analysis Improvement Group (CAIG). (2007). Office of the Secretary of

Qualidade por concepção: uma nova abordagem para acelerar o desenvolvimento tecnológico e inovação na área da saúde | Quality by design: A new approach to accelerate the technological development in health

Directory of Open Access Journals (Sweden)

Martha Maria de Oliveira

2017-02-01

Full Text Available O presente artigo pretende apresentar um modelo de gestão de qualidade sistemático e proativo, baseado no rigor científico e em análise e gerenciamento de risco, conhecido como Quality by Design (QbD ou Qualidade por Concepção (QpC. Desde 2012, as agências reguladoras dos Estados Unidos e União Europeia têm sugerido a aplicação das diretrizes da QpC para o desenvolvimento de processos e produtos. No Brasil, a nova abordagem tem recebido atenção crescente da comunidade farmacêutica/biotecnológica, assim como da Anvisa, e é vista hoje como uma inciativa regulatória global que visa garantir o desenvolvimento racional dos produtos, reduzindo o tempo de disponibilização ao mercado, incrementando a elaboração de protocolos clínicos, controlando os custos e aumentando as chances de sucesso do setor farmacêutico. Nesse contexto, a adoção dos princípios da QpC pretende agregar valor à política de qualidade já existente nas organizações, propiciando não apenas mais agilidade e assertividade, como também mais confiança nos novos produtos desenvolvidos. =============================== This article seeks to present a systematic and proactive quality management model based on scientific rigor, as well as on analysis and risk management, known as Quality by Design (QbD. Since 2012, regulatory agencies from the United States and the European Union have pressed the manufactures to speed the adoption of QbD principles for processes and products development. In Brazil, the new approach has received increasing attention from the pharmaceutical∕biotechnological community, as well as from Anvisa, and it is now seen as a global regulatory initiative to assure the rational development of products, reducing the lead and launch time to market, incrementing the elaboration of clinical protocols, controlling costs and increasing success chances of the pharmaceutical sector. In this context, the adoption of the QbD concepts aims to add

Comparative study of muscarinic acetylcholine receptors of human and rat cortical glial cells

International Nuclear Information System (INIS)

Demushkin, V.P.; Burbaeva, G.S.; Dzhaliashvili, T.A.; Plyashkevich, Y.G.

1985-01-01

The aim of the present investigation was a comparative studyof muscarinic acetylcholine receptors in human and rat glial cells. ( 3 H)Quinuclidinyl-benzylate (( 3 H)-QB), atropine, platiphylline, decamethonium, carbamylcholine, tubocurarine, and nicotine were used. The glial cell fraction was obtained from the cerebral cortex of rats weighing 130-140 g and from the frontal pole of the postmortem brain from men aged 60-70 years. The use of the method of radioimmune binding of ( 3 H)-QB with human and rat glial cell membranes demonstrated the presence of a muscarinic acetylcholine receptor in the glial cells

Erythropoietin as an add-on treatment for cognitive side effects of electroconvulsive therapy

DEFF Research Database (Denmark)

Schmidt, Lejla Sjanic; Petersen, Jeff Zarp; Vinberg, Maj

2018-01-01

trial investigates (1) whether short-term add-on treatment with erythropoietin (EPO) can reduce the cognitive side -effects of ECT and (2) whether such effects are long-lasting. Further, structural and functional magnetic resonance imaging (MRI) will be used to explore the neural underpinnings...... cognitive benefits of EPO are investigated with structural and functional MRI after the final EPO/saline infusion. The primary outcome is change from baseline to after EPO treatment (3 days after eight ECT sessions) in a cognitive composite score spanning attention, psychomotor speed, and executive...... of covariance. Functional MRI data will be preprocessed and analyzed using the FMRIB Software Library....

Evaluation of add-on devices for the prevention of phlebitis and other complications associated with the use of peripheral catheters in hospitalised adults: a randomised controlled study.

Science.gov (United States)

Martínez, J A; Piazuelo, M; Almela, M; Blecua, P; Gallardo, R; Rodríguez, S; Escalante, Z; Robau, M; Trilla, A

2009-10-01

The aim of this study was to assess the role of add-on devices for the prevention of phlebitis and other complications associated with the use of peripheral catheters. Patients admitted to an infectious diseases ward and requiring the insertion of a peripheral catheter for at least 24h were randomly allocated to be managed with or without add-on devices. Incidence of phlebitis and all complications were the primary outcomes. Extravasation, inadvertent withdrawal, obstruction and rupture were considered to be mechanical complications, and analysis was performed using survival methods. Of 683 evaluated catheters, 351 were allocated to the add-on device arm and 332 to the control arm. Despite randomisation, patients in the add-on device group were older (P=0.048), less likely to have human immunodeficiency virus (P=0.02) and more likely to have received antibiotics (P=0.05). After adjustment for these variables, the hazard ratio for phlebitis remained non-significant (hazard ratio: 0.95; 95% confidence interval: 0.7-1.3), but the risk of mechanical complications became lower in the add-on device arm (0.68; 0.5-0.94). This translated into a trend towards a lower risk of any complication (0.83; 0.67-1.01). The beneficial effect on mechanical or all complications was noticeable after six days of catheterisation. Add-on devices do not reduce the incidence of phlebitis but may prevent mechanical complications. However, the impact of add-on devices on the incidence of all complications is at most small and only apparent after the sixth day of catheter use.

Dimensional enrichment of statistical linked open data

DEFF Research Database (Denmark)

Varga, Jovan; Vaisman, Alejandro; Romero, Oscar

2016-01-01

On-Line Analytical Processing (OLAP) is a data analysis technique typically used for local and well-prepared data. However, initiatives like Open Data and Open Government bring new and publicly available data on the web that are to be analyzed in the same way. The use of semantic web technologies...... for this context is especially encouraged by the Linked Data initiative. There is already a considerable amount of statistical linked open data sets published using the RDF Data Cube Vocabulary (QB) which is designed for these purposes. However, QB lacks some essential schema constructs (e.g., dimension levels......) to support OLAP. Thus, the QB4OLAP vocabulary has been proposed to extend QB with the necessary constructs and be fully compliant with OLAP. In this paper, we focus on the enrichment of an existing QB data set with QB4OLAP semantics. We first thoroughly compare the two vocabularies and outline the benefits...

dAdd1 and dXNP prevent genome instability by maintaining HP1a localization at Drosophila telomeres.

Science.gov (United States)

Chavez, Joselyn; Murillo-Maldonado, Juan Manuel; Bahena, Vanessa; Cruz, Ana Karina; Castañeda-Sortibrán, América; Rodriguez-Arnaiz, Rosario; Zurita, Mario; Valadez-Graham, Viviana

2017-12-01

Telomeres are important contributors to genome stability, as they prevent linear chromosome end degradation and contribute to the avoidance of telomeric fusions. An important component of the telomeres is the heterochromatin protein 1a (HP1a). Mutations in Su(var)205, the gene encoding HP1a in Drosophila, result in telomeric fusions, retrotransposon regulation loss and larger telomeres, leading to chromosome instability. Previously, it was found that several proteins physically interact with HP1a, including dXNP and dAdd1 (orthologues to the mammalian ATRX gene). In this study, we found that mutations in the genes encoding the dXNP and dAdd1 proteins affect chromosome stability, causing chromosomal aberrations, including telomeric defects, similar to those observed in Su(var)205 mutants. In somatic cells, we observed that dXNP and dAdd1 participate in the silencing of the telomeric HTT array of retrotransposons, preventing anomalous retrotransposon transcription and integration. Furthermore, the lack of dAdd1 results in the loss of HP1a from the telomeric regions without affecting other chromosomal HP1a binding sites; mutations in dxnp also affected HP1a localization but not at all telomeres, suggesting a specialized role for dAdd1 and dXNP proteins in locating HP1a at the tips of the chromosomes. These results place dAdd1 as an essential regulator of HP1a localization and function in the telomere heterochromatic domain.

Renal function preservation with pioglitazone or with basal insulin as an add-on therapy for patients with type 2 diabetes mellitus.

Science.gov (United States)

Chang, Yu-Hung; Hwu, Der-Wei; Chang, Dao-Ming; An, Ling-Wang; Hsieh, Chang-Hsun; Lee, Yau-Jiunn

2017-06-01

Clinical outcome may differ owing to the distinct pharmacological characteristics of insulin sensitizers and insulin. This study was performed to compare the metabolic and renal function changes with add-on pioglitazone treatment versus basal insulin in patients with type 2 diabetes mellitus (DM) in whom sulfonylurea and metformin regimens failed. Patients who were consecutively managed in the diabetes comprehensive program with add-on pioglitazone or detemir/glargine treatment for at least 2 years following sulfonylurea and metformin treatment failure were included. A total of 1002 patients were enrolled (pioglitazone: 559, detemir: 264, glargine: 179). After propensity score matching, there were 105 patients with matchable baseline characteristics in each group. After a mean of 3.5 years of follow-up, the pioglitazone group showed a greater HbA1c reduction than the detemir group and the glargine group. Despite patients in all three groups exhibiting significant body weight gain, those in the pioglitazone group and the glargine group showed greater body weight increases than the patients in the detemir group (2.1, 1.6 and 0.8 kg, respectively, p 1.79-3.88) and 3.13 (95% CI 2.01-4.87), respectively. Our study first showed that treatment with both pioglitazone and basal insulin improved glycemic control, while only pioglitazone treatment was observed to be advantageous in terms of preserving renal function when used as an add-on therapy for patients with type 2 DM in whom sulfonylurea and metformin regimens failed.

Add/drop filters based on SiC technology for optical interconnects

International Nuclear Information System (INIS)

Vieira, M; Vieira, M A; Louro, P; Fantoni, A; Silva, V

2014-01-01

In this paper we demonstrate an add/drop filter based on SiC technology. Tailoring of the channel bandwidth and wavelength is experimentally demonstrated. The concept is extended to implement a 1 by 4 wavelength division multiplexer with channel separation in the visible range. The device consists of a p-i'(a-SiC:H)-n/p-i(a-Si:H)-n heterostructure. Several monochromatic pulsed lights, separately or in a polychromatic mixture illuminated the device. Independent tuning of each channel is performed by steady state violet bias superimposed either from the front and back sides. Results show that, front background enhances the light-to-dark sensitivity of the long and medium wavelength channels and quench strongly the others. Back violet background has the opposite behaviour. This nonlinearity provides the possibility for selective removal or addition of wavelengths. An optoelectronic model is presented and explains the light filtering properties of the add/drop filter, under different optical bias conditions

Relationship between ADD1 Gly460Trp gene polymorphism and essential hypertension in Madeira Island.

Science.gov (United States)

Sousa, Ana Célia; Palma Dos Reis, Roberto; Pereira, Andreia; Borges, Sofia; Freitas, Ana Isabel; Guerra, Graça; Góis, Teresa; Rodrigues, Mariana; Henriques, Eva; Freitas, Sónia; Ornelas, Ilídio; Pereira, Décio; Brehm, António; Mendonça, Maria Isabel

2017-10-01

Essential hypertension (EH) is a complex disease in which physiological, environmental, and genetic factors are involved in its genesis. The genetic variant of the alpha-adducin gene (ADD1) has been described as a risk factor for EH, but with controversial results.The objective of this study was to evaluate the association of ADD1 (Gly460Trp) gene polymorphism with the EH risk in a population from Madeira Island.A case-control study with 1614 individuals of Caucasian origin was performed, including 817 individuals with EH and 797 controls. Cases and controls were matched for sex and age, by frequency-matching method. All participants collected blood for biochemical and genotypic analysis for the Gly460Trp polymorphism. We further investigated which variables were independently associated to EH, and, consequently, analyzed their interactions.In our study, we found a significant association between the ADD1 gene polymorphism and EH (odds ratio 2.484, P = .01). This association remained statistically significant after the multivariate analysis (odds ratio 2.548, P = .02).The ADD1 Gly460Trp gene polymorphism is significantly and independently associated with EH risk in our population. The knowledge of genetic polymorphisms associated with EH is of paramount importance because it leads to a better understanding of the etiology and pathophysiology of this pathology.

How to Add Philosophy Dimensions in Your Basic International Business Course

Science.gov (United States)

Thanopoulos, John

2010-01-01

This article aims to assist professors in introducing concepts of self, philosophy, religions, the universe, existential dilemmas, etc., in their basic international business classes. Using active learning and five-member student teams, a student organized and administered conference adds a very useful dimension of knowledge sacrificing only one…

Development of a colonoscopy add-on device for improvement of the intubation process

Directory of Open Access Journals (Sweden)

Litten JD

2011-12-01

Full Text Available Jonathan D Litten1, JungHun Choi2, David Drozek31Department of Mechanical Engineering; 2Department of Mechanical Engineering and Biomedical Engineering Program; 3College of Osteopathic Medicine, Department of Specialty Medicine, Ohio University, Athens, OH, USAAbstract: A colonoscopy add-on device has been developed to reduce intubation time without modification of the current colonoscope and peripheral devices. One of the main purposes of the system is to minimize trauma caused by the distal tip of the colonoscope. The detachable sensory fixture at the end of the distal tip measures the distance between the distal tip and the colon wall in three directions, and the actuation system attached at the base of the colonoscope controls the distal tip by rotating two dial knobs. The device controls the distal tip to minimize contact between the distal tip and the colon wall, and the distal tip ideally points out the next possible lumen. A compatibility test of the infrared sensory system was carried out, and the design of the actuation system was accomplished. The system is integrated and controlled by a microprocessor. The device was tested in a silicon colon and porcine intestine. The results showed that a colonoscopist successfully reached the cecum with the aid of the colonoscopy add-on device without significant contact between the colon wall and the distal tip. The colonoscopy aid device was very helpful for the novice colonoscopist.Keywords: colonoscope, infrared sensors, intubation, trauma, colonoscopy training model

The freedom to choose, eat, add and gain weight

Directory of Open Access Journals (Sweden)

D.A. Cabrera-Gaytán

2018-04-01

Full Text Available The Federal Commission for Protection Against Health Risks (COFEPRIS launched a regulation for new front nutritional labelling for food and non-alcoholic beverages, recommending that consumers add up their consumptions throughout the day without exceeding a hundred percentage points. The campaign has therefore been called “Add up and do not exceed 100%”. The policy established by the Federal Government is based on assumptions that encourage consumption and will not solve the problem in depth. Following is a descriptive and critical argument against said policy. Resumen: La Comisión Federal para la Protección Contra Riesgos Sanitarios (COFEPRIS, lanzó una regulación del nuevo etiquetado frontal nutrimental en los alimentos y bebidas no alcohólicas, con la recomendación al consumidor sumar a lo largo del día los consumos sin exceder de cien puntos porcentuales, por lo que a la campaña se le ha denominado “Suma y no te pases de 100%”. La política instaurada por el Gobierno Federal, se basa en supuestos que fomentan el consumo y no resolverán de fondo el problema, por lo que se hace una argumentación descriptiva y crítica de esa política. Keywords: Obesity, Public policy, Consumption, Palabras clave: Obesidad, Política pública, Consumo

QB1 - Stochastic Gene Regulation

Energy Technology Data Exchange (ETDEWEB)

Munsky, Brian [Los Alamos National Laboratory

2012-07-23

Summaries of this presentation are: (1) Stochastic fluctuations or 'noise' is present in the cell - Random motion and competition between reactants, Low copy, quantization of reactants, Upstream processes; (2) Fluctuations may be very important - Cell-to-cell variability, Cell fate decisions (switches), Signal amplification or damping, stochastic resonances; and (3) Some tools are available to mode these - Kinetic Monte Carlo simulations (SSA and variants), Moment approximation methods, Finite State Projection. We will see how modeling these reactions can tell us more about the underlying processes of gene regulation.

Elevated removal of middle molecules without significant albumin loss with mixed-dilution hemodiafiltration for patients unable to provide sufficient blood flow rates.

Science.gov (United States)

Potier, Jacky; Le Roy, Frank; Faucon, Jean Paul; Besselièvre, Thibault; Renaudineau, Eric; Farquet, Christian; Soihan, Pascale; Touzard, Dominique; Djema, Asia; Ilinca, Toma

2013-01-01

We examined the hypothesis that mixed-dilution online hemodiafiltration (MIXED) rather than predilution online hemodiafiltration (PRE) could enable patients with low blood flow rate (Qb) to benefit from advantages of convective therapies. Thirty-eight patients were included in a prospective, randomized, crossover and multicenter study conducted with a view to comparing the equilibrated Kt/V, reduction ratio (RR) of phosphates, β2-microglobulin (β2-M) and myoglobin (myo) between PRE and MIXED, each at two Qb values of 250 and 300 ml/min during 4 h sessions with a FX1000HDF dialyzer. Albumin losses (Alb) were also measured in 12 patients. MIXED was always found to be more efficient compared to PRE notably for middle molecules (MM). RRβ2-M: MIX250: 81.3 ± 3.6 vs. PRE250: 75.2 ± 5.9; MIX300: 82.7 ± 3.6 vs. PRE300: 78.1 ± 5.4; RRmyo: MIX250: 70.2 ± 3.6 vs. PRE250: 42.6 ± 2.6; MIX300: 70.6 ± 3.6 vs. PRE300: 45.7 ± 3.6 and with Alb <3.0 g/session. MIXED allows patients unable to provide sufficiently high Qb to achieve high levels of MM removal. © 2013 S. Karger AG, Basel.

Development of FQ-PCR method to determine the level of ADD1 expression in fatty and lean pigs.

Science.gov (United States)

Cui, J X; Chen, W; Zeng, Y Q

2015-10-30

To determine how adipocyte determination and differentiation factor 1 (ADD1), a gene involved in the determination of pork quality, is regulated in Laiwu and Large pigs, we used TaqMan fluorescence quantitative real-time polymerase chain reaction (FQ-PCR) to detect differential expression in the longissimus muscle of Laiwu (fatty) and Large White (lean) pigs. In this study, the ADD1 and GAPDH cDNA sequences were cloned using a T-A cloning assay, and the clone sequences were consistent with those deposited in GenBank. Thus, the target fragment was successfully recombined into the vector, and its integrity was maintained. The standard curve and regression equation were established through the optimized FQ-PCR protocol. The standard curve of porcine ADD1 and GAPDH cDNA was determined, and its linear range extension could reach seven orders of magnitudes. The results showed that this method was used to quantify ADD1 expression in the longissimus muscle of two breeds of pig, and was found to be accurate, sensitive, and convenient. These results provide information regarding porcine ADD1 mRNA expression and the mechanism of adipocyte differentiation, and this study could help in the effort to meet the demands of consumers interested in the maintenance of health and prevention of obesity. Furthermore, it could lead to new approaches in the prevention and clinical treatment of this disease.

Feasibility study of veterinary antibiotic consumption in Germany--comparison of ADDs and UDDs by animal production type, antimicrobial class and indication.

Science.gov (United States)

Merle, Roswitha; Robanus, Matthias; Hegger-Gravenhorst, Christine; Mollenhauer, Yvonne; Hajek, Peter; Käsbohrer, Annemarie; Honscha, Walther; Kreienbrock, Lothar

2014-01-08

Within a feasibility study the use of antibiotics in pigs and cattle was determined in 24 veterinary practices in Lower Saxony and on 66 farms in North Rhine-Westphalia in Germany. Focus was laid on the comparison of the Used Daily Doses (UDD) (dose per animal and day prescribed by the veterinarians) with the Defined Animal Daily Doses (ADD) (dose per animal and day calculated by means of recommended dosages and estimated live weights). For piglets and calves most of the UDD (50% and 46% of nUDD, respectively) were above the ADD (i.e. UDD/ADD-ratio above 1.25). Regarding sows, fattening pigs, dairy and beef cattle, most of the UDDs (49% to 65% of nUDD) were lower than the respective ADD (i.e. UDD/ADD-ratio below 0.8). In pigs, the UDDs of beta-lactams, fluoroquinolones and cephalosporins, and in cattle, those of macrolides and beta-lactams were often below the ADDs. Tetracyclines were frequently used above the recommended dose.Enteric diseases were more often treated below the recommended dose than respiratory diseases, possibly due to overestimation of the live weight (diarrhea in young animals, respiratory diseases in elder animals) and consequently overestimation of the recommended dose. Comparisons between UDD and ADD can be used to observe differences between antimicrobials and trends in the usage of antibiotics. But individual treatment comparisons of UDD and ADD must be interpreted carefully, because they may be due to lower live weights than estimated. Correlating such data with data on the occurrence of resistant bacteria in future may help to improve resistance prevention and control.

Effect of “add-on” interventions on exercise training in individuals with COPD: a systematic review

Directory of Open Access Journals (Sweden)

Carlos A. Camillo

2016-03-01

Full Text Available The aim of this review was to identify the effectiveness of therapies added on to conventional exercise training to maximise exercise capacity in patients with chronic obstructive pulmonary disease (COPD. Electronic databases were searched, identifying trials comparing exercise training with exercise training plus “add-on” therapy. Outcomes included peak oxygen uptake (V′O2peak, work rate and incremental/endurance cycle and field walking tests. Individual trial effects on exercise capacity were extracted and collated into eight subgroups and pooled for meta-analysis. Sensitivity analyses were conducted to explore the stability of effect estimates across studies employing patient-centred designs and those deemed to be of “high” quality (PEDro score >5 out of 10. 74 studies (2506 subjects met review inclusion criteria. Interventions spanned a broad scope of clinical practice and were most commonly evaluated via the 6-min walking distance and V′O2peak. Meta-analysis revealed few clinically relevant and statistically significant benefits of “add-on” therapies on exercise performance compared with exercise training. Benefits favouring “add-on” therapies were observed across six different interventions (additional exercise training, noninvasive ventilation, bronchodilator therapy, growth hormone, vitamin D and nutritional supplementation. The sensitivity analyses included considerably fewer studies, but revealed minimal differences to the primary analysis. The lack of systematic benefits of “add-on” interventions is a probable reflection of methodological limitations, such as “one size fits all” eligibility criteria, that are inherent in many of the included studies of “add-on” therapies. Future clarification regarding the exact value of such therapies may only arise from adequately powered, multicentre clinical trials of tailored interventions for carefully selected COPD patient subgroups defined according to distinct

40 CFR 63.3169 - What are the requirements for a capture system or add-on control device which is not taken into...

Science.gov (United States)

2010-07-01

... systems or add-on control devices which you choose not to take into account when demonstrating compliance... system or add-on control device which is not taken into account when demonstrating compliance with the....3169 What are the requirements for a capture system or add-on control device which is not taken into...

IMPLEMENTASI PROGRAM ALOKASI DANA DESA (ADD DALAM PEMBERDAYAAN MASYARAKAT DI DESA PUNAGAYA KECAMATAN BANGKALA KABUPATEN JENEPONTO

Directory of Open Access Journals (Sweden)

Octrian TSL

2013-04-01

Full Text Available Punagaya village through the village fund allocation (ADD will allocate a budget for community development in the areas of sugar production business, the study aims to look at the implementation of the allocation of funds in the rural community empowerment programs and the factors that affect the implementation of the implementation of the allocation of funds within the village community empowerment program in the Village Punagaya sub Bangkala Jeneponto district. This research is descriptive qualitative research sampling technique used was purposive sampling. This study uses data analysis techniques interviews and observations, after which the data collected are then analyzed using frequency tables later be described qualitatively. Number of samples 33 people consisting of 1 person village head, village secretary 1 person, a member of the Committee seminar 5 people, local people 7 people, 4 people Ibu PKK, brown sugar 6 people Makers, Executive Team Live Help ADD 3orang, public figures 6 people. Penelitaian showed that 52% of people believe that the implementation of the Village punagaya village fund allocation in the village punagaya poorly this happens because people do not see the program conducted by the local government to improve the empowerment and increased repair services performed by local governments to use allocation of village funds. Based on the research I did it, it can be concluded that the public has not been empowered by optimal utilization of ADD in the Village District Punagaya Bangkala Jeneponto. It is caused due to problems such as the allocation of funds provided inadequate to meningatkan empowerment, besides the allocation of funds is often given too late and village officials rendahmya influence on the development and management of the allocation of funds is a factor inhibiting village program implementation in the village of village fund allocation Punagaya Sub Bangkala Jeneponto but from the village fund allocation is

Strategies for Successfully Teaching Students with ADD or ADHD in Instrumental Lessons

Science.gov (United States)

Melago, Kathleen A.

2014-01-01

Teachers can easily encounter students with Attention Deficit Disorder (ADD) or Attention Deficit Hyperactivity Disorder (ADHD) in the instrumental lesson setting. Applicable to instrumental lesson settings in the public or private schools, private studios, or college studios, this article focuses on specific strategies ranging from the…

N -annulated perylene-based push-pull-type sensitizers

KAUST Repository

Qi, Qingbiao; Wang, Xingzhu; Fan, Li; Zheng, Bin; Zeng, Wangdong; Luo, Jie; Huang, Kuo-Wei; Wang, Qing; Wu, Jishan

2015-01-01

Alkoxy-wrapped N-annulated perylene (NP) was synthesized and used as a rigid and coplanar π-linker for three push-pull type metal-free sensitizers QB1-QB3. Their optical and electrochemical properties were tuned by varying the structure of acceptor. These new dyes were applied in Co(II)/(III) based dye-sensitized solar cells, and power conversion efficiency up to 6.95% was achieved, indicating that NP could be used as a new building block for the design of high-performance sensitizers in the future.

N -annulated perylene-based push-pull-type sensitizers

KAUST Repository

Qi, Qingbiao

2015-02-06

Alkoxy-wrapped N-annulated perylene (NP) was synthesized and used as a rigid and coplanar π-linker for three push-pull type metal-free sensitizers QB1-QB3. Their optical and electrochemical properties were tuned by varying the structure of acceptor. These new dyes were applied in Co(II)/(III) based dye-sensitized solar cells, and power conversion efficiency up to 6.95% was achieved, indicating that NP could be used as a new building block for the design of high-performance sensitizers in the future.

Development of a radiometer based on an Add-ON card for PC

International Nuclear Information System (INIS)

Bolanos, L.; Lopez, B.; Fernandez, J.L.; Laria, J.

1997-01-01

The design of an add-on card for PC that enables it to record nuclear pulses provided by two channels is described in this paper. This card carries acts as a pulse discriminator, and according to the software it finds many appliances in radioimmunoassay, nuclear medicine, industry and other fields

36 CFR 1011.5 - What interest, penalty charges and administrative costs will the Presidio Trust add to a debt?

Science.gov (United States)

2010-07-01

... charges and administrative costs will the Presidio Trust add to a debt? 1011.5 Section 1011.5 Parks... § 1011.5 What interest, penalty charges and administrative costs will the Presidio Trust add to a debt? (a) Interest. (1) The Presidio Trust will assess interest on all delinquent debts unless prohibited...

The MMPI-168(L) and ADD in Assessing Psychopathology in Individuals with Mental Retardation: Between and within Instrument Associations.

Science.gov (United States)

McDaniel, William F.; Passmore, Corie E.; Sewell, Hollie M.

2003-01-01

A study involving 58 adults with mental retardation and mental disorders found few correlations between the Minnesota Multiphasic Personality Inventory (MMPI) and the Assessment of Dual Diagnosis (ADD). The major exception was the Mania scale of the MMPI, which correlated moderately well with the ADD Schizophrenia and Dementia scales. (Contains…

Using patient lists to add value to integrated data repositories.

Science.gov (United States)

Wade, Ted D; Zelarney, Pearlanne T; Hum, Richard C; McGee, Sylvia; Batson, Deborah H

2014-12-01

Patient lists are project-specific sets of patients that can be queried in integrated data repositories (IDR's). By allowing a set of patients to be an addition to the qualifying conditions of a query, returned results will refer to, and only to, that set of patients. We report a variety of use cases for such lists, including: restricting retrospective chart review to a defined set of patients; following a set of patients for practice management purposes; distributing "honest-brokered" (deidentified) data; adding phenotypes to biosamples; and enhancing the content of study or registry data. Among the capabilities needed to implement patient lists in an IDR are: capture of patient identifiers from a query and feedback of these into the IDR; the existence of a permanent internal identifier in the IDR that is mappable to external identifiers; the ability to add queryable attributes to the IDR; the ability to merge data from multiple queries; and suitable control over user access and de-identification of results. We implemented patient lists in a custom IDR of our own design. We reviewed capabilities of other published IDRs for focusing on sets of patients. The widely used i2b2 IDR platform has various ways to address patient sets, and it could be modified to add the low-overhead version of patient lists that we describe. Copyright © 2014 Elsevier Inc. All rights reserved.

5 CFR 591.227 - What adjustment factors does OPM add to the price indexes?

Science.gov (United States)

2010-01-01

... CIVIL SERVICE REGULATIONS ALLOWANCES AND DIFFERENTIALS Cost-of-Living Allowance and Post Differential-Nonforeign Areas Cost-Of-Living Allowances § 591.227 What adjustment factors does OPM add to the price...

40 CFR Table 1 to Subpart Ssss of... - Operating Limits if Using Add-on Control Devices and Capture System

Science.gov (United States)

2010-07-01

... Using Add-on Control Devices and Capture System If you are required to comply with operating limits by... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Operating Limits if Using Add-on Control Devices and Capture System 1 Table 1 to Subpart SSSS of Part 63 Protection of Environment...

40 CFR Table 1 to Subpart Jjjj of... - Operating Limits if Using Add-On Control Devices and Capture System

Science.gov (United States)

2010-07-01

... Limits if Using Add-On Control Devices and Capture System If you are required to comply with operating... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Operating Limits if Using Add-On Control Devices and Capture System 1 Table 1 to Subpart JJJJ of Part 63 Protection of Environment...

Evaluation of homoeopathic medicines as add-on to institutional management protocol in Acute Encephalitis Syndrome: An exploratory observational comparative study

Directory of Open Access Journals (Sweden)

Raj K Manchanda

2015-01-01

Conclusion: This exploratory observational study suggests reduction of mortality and morbidity with add-on homoeopathic medicine. Further randomized controlled trial study with comparable groups is desirable. If findings are confirmed by subsequent research, add-on Homoeopathy might have relevant implication for its management.

40 CFR Table 2 to Subpart Oooo of... - Operating Limits if Using Add-On Control Devices and Capture System

Science.gov (United States)

2010-07-01

... OOOO of Part 63—Operating Limits if Using Add-On Control Devices and Capture System If you are required... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Operating Limits if Using Add-On Control Devices and Capture System 2 Table 2 to Subpart OOOO of Part 63 Protection of Environment...

A television in the bedroom is associated with higher weekday screen time among youth with attention deficit hyperactivity disorder (ADD/ADHD)

OpenAIRE

Lo, Charmaine B.; Waring, Molly E.; Pagoto, Sherry L.; Lemon, Stephenie C.

2015-01-01

Objective: A TV in the bedroom has been associated with screen time in youth. Youth with attention deficit hyperactivity disorder (ADD/ADHD) have higher rates of screen time, but associations with bedroom TVs are unknown in this population. We examined the association of having a bedroom TV with screen time among youth with ADD/ADHD. Methods: Data were from the 2007 National Survey of Children's Health. Youth 6–17 years whose parent/guardian reported a physician's diagnosis of ADD/ADHD (n ...

40 CFR 63.3967 - How do I establish the emission capture system and add-on control device operating limits during...

Science.gov (United States)

2010-07-01

... system and add-on control device operating limits during the performance test? 63.3967 Section 63.3967... capture system and add-on control device operating limits during the performance test? During the... the operating limits required by § 63.3892 according to this section, unless you have received...

Improving Content and Technology Skills in ADD/ADHD via a Web Enhanced Course

Science.gov (United States)

Jordan, LuAnn; Smith, Sean; Dillon, Ann S.; Algozzine, Bob; Beattie, John; Spooner, Fred; Fisher, Ashlee L.

2004-01-01

Attention Deficit Disorder and Attention Deficit Hyperactivity Disorder (ADD/ADHD) create concerns in public education and in teacher education programs. Because of continuous advances in technology, distance learning is a viable option for delivering coursework to preservice and inservice teacher education students challenged by geography, time…

40 CFR 63.9324 - How do I establish the emission capture system and add-on control device operating limits during...

Science.gov (United States)

2010-07-01

... capture system and add-on control device operating limits during the performance test? 63.9324 Section 63... Requirements § 63.9324 How do I establish the emission capture system and add-on control device operating... the operating limits required by § 63.9302 according to this section, unless you have received...

40 CFR 63.3556 - How do I establish the emission capture system and add-on control device operating limits during...

Science.gov (United States)

2010-07-01

... system and add-on control device operating limits during the performance test? 63.3556 Section 63.3556... of key parameters of the valve operating system (e.g., solenoid valve operation, air pressure.../outlet Concentration Option § 63.3556 How do I establish the emission capture system and add-on control...

Med-records: an ADD database of AAEC medical records since 1966

International Nuclear Information System (INIS)

Barry, J.M.; Pollard, J.P.; Tucker, A.D.

1986-08-01

Since its inception in 1958 most of the staff of the AAEC Research Establishment at Lucas Heights have had annual medical examinations. Medical information accrued since 1966 has been collected as an ADD database to allow ad hoc enquiries to be made against the data. Details are given of the database schema and numerous support routines ranging from the integrity checking of input data to analysis and plotting of the summary results

Spatio-temporal variability of NDVI-precipitation over southernmost South America: possible linkages between climate signals and epidemics

Energy Technology Data Exchange (ETDEWEB)

Tourre, Y M [METEO-France, Meteopole, 42 Avenue Coriolis, 31057 Toulouse Cedex 1 (France); Jarlan, L [Centre d' Etudes Spatiales de la Biosphere (CESBIO), 18 avenue Edouard Belin, F-31401 Toulouse Cedex 4 (France); Lacaux, J-P [Universite Paul Sabatier (UPS), Observatoire Midi Pyrenees (OMP), 12 Avenue Edouard Belin, 31400 Toulouse (France); Rotela, C H [Instituto de Altos Estudios Espaciales ' Mario Gulich' , Comision Nacional de Actividades Espaciales (CONAE), Universidad Nacional de Cordoba (Argentina); Lafaye, M [CNES, DSP/ARP/AV, 18 Avenue Edouard Belin, F-31401 Toulouse Cedex 4 (France)

2008-10-15

Climate-environment variability affects the rates of incidence of vector-borne and zoonotic diseases and is possibly associated with epidemics outbreaks. Over southernmost South America the joint spatio-temporal evolution of climate-environment is analyzed for the 1982-2004 period. Detailed mapping of normalized difference vegetation index (NDVI) and rainfall variability are then compared to zones with preliminary epidemiological reports. A significant quasi-biennial signal (2.2- to 2.4-year periods, or QB) for joint NDVI-rainfall variability is revealed. From rotated EOFs, dominant NDVI patterns are partitioned according to their lead frequencies: (1) the 'QB group' (2.1-to 3-year periods) includes six modes over southern Brazil, Uruguay, northern-central Argentina (two modes), the southern Paraguay-northern Argentina border, and the Santa Cruz Province; (2) the QB1 (2.4- to 3-year periods) + quasi-quadrennial (QQ) mode over the Misiones Province; and (3) the QB2 (2.1- to 2.5-year periods) + QQ + inter-annual (IA) (3- to 7-year periods) two modes over south-eastern Argentina. Modes within the 'QB group' are positively correlated with global climate signals and SST. The Uruguayan mode is correlated with global ENSO (8-month lag) whilst the southern Entre-Rios/northern Buenos Aires provinces are correlated with central equatorial Pacific SSTs (3-month lag). The Santa Cruz (Patagonia) Province is most correlated with the Pacific South America (PSA) index and SST patterns (3-month lag) along the Antarctica circumpolar current. The spatial distribution of lead NDVI modes includes the Formosa, Misiones, Chaco and Buenos Aires provinces among others, known for being prone to vector-borne epidemics such as dengue fever, malaria, leishmaniasis (American cutaneous leishmaniasis or ACL), hantivirus, chagas and Argentine hemorrhagic fever (AHF). Some provinces also correspond to regions where lead NDVI PCs' modes are associated with high

Spatio-temporal variability of NDVI-precipitation over southernmost South America: possible linkages between climate signals and epidemics

Energy Technology Data Exchange (ETDEWEB)

Tourre, Y M [METEO-France, Meteopole, 42 Avenue Coriolis, 31057 Toulouse Cedex 1 (France); Jarlan, L [Centre d' Etudes Spatiales de la Biosphere (CESBIO), 18 avenue Edouard Belin, F-31401 Toulouse Cedex 4 (France); Lacaux, J-P [Universite Paul Sabatier (UPS), Observatoire Midi Pyrenees (OMP), 12 Avenue Edouard Belin, 31400 Toulouse (France); Rotela, C H [Instituto de Altos Estudios Espaciales ' Mario Gulich' , Comision Nacional de Actividades Espaciales (CONAE), Universidad Nacional de Cordoba (Argentina); Lafaye, M [CNES, DSP/ARP/AV, 18 Avenue Edouard Belin, F-31401 Toulouse Cedex 4 (France)

2008-10-15

Climate-environment variability affects the rates of incidence of vector-borne and zoonotic diseases and is possibly associated with epidemics outbreaks. Over southernmost South America the joint spatio-temporal evolution of climate-environment is analyzed for the 1982-2004 period. Detailed mapping of normalized difference vegetation index (NDVI) and rainfall variability are then compared to zones with preliminary epidemiological reports. A significant quasi-biennial signal (2.2- to 2.4-year periods, or QB) for joint NDVI-rainfall variability is revealed. From rotated EOFs, dominant NDVI patterns are partitioned according to their lead frequencies: (1) the 'QB group' (2.1-to 3-year periods) includes six modes over southern Brazil, Uruguay, northern-central Argentina (two modes), the southern Paraguay-northern Argentina border, and the Santa Cruz Province; (2) the QB1 (2.4- to 3-year periods) + quasi-quadrennial (QQ) mode over the Misiones Province; and (3) the QB2 (2.1- to 2.5-year periods) + QQ + inter-annual (IA) (3- to 7-year periods) two modes over south-eastern Argentina. Modes within the 'QB group' are positively correlated with global climate signals and SST. The Uruguayan mode is correlated with global ENSO (8-month lag) whilst the southern Entre-Rios/northern Buenos Aires provinces are correlated with central equatorial Pacific SSTs (3-month lag). The Santa Cruz (Patagonia) Province is most correlated with the Pacific South America (PSA) index and SST patterns (3-month lag) along the Antarctica circumpolar current. The spatial distribution of lead NDVI modes includes the Formosa, Misiones, Chaco and Buenos Aires provinces among others, known for being prone to vector-borne epidemics such as dengue fever, malaria, leishmaniasis (American cutaneous leishmaniasis or ACL), hantivirus, chagas and Argentine hemorrhagic fever (AHF). Some provinces also correspond to regions where lead NDVI PCs' modes are associated with high-frequency climate signals such as the

Spatio-temporal variability of NDVI-precipitation over southernmost South America: possible linkages between climate signals and epidemics

Science.gov (United States)

Tourre, Y. M.; Jarlan, L.; Lacaux, J.-P.; Rotela, C. H.; Lafaye, M.

2008-10-01

Climate-environment variability affects the rates of incidence of vector-borne and zoonotic diseases and is possibly associated with epidemics outbreaks. Over southernmost South America the joint spatio-temporal evolution of climate-environment is analyzed for the 1982-2004 period. Detailed mapping of normalized difference vegetation index (NDVI) and rainfall variability are then compared to zones with preliminary epidemiological reports. A significant quasi-biennial signal (2.2- to 2.4-year periods, or QB) for joint NDVI-rainfall variability is revealed. From rotated EOFs, dominant NDVI patterns are partitioned according to their lead frequencies: (1) the 'QB group' (2.1-to 3-year periods) includes six modes over southern Brazil, Uruguay, northern-central Argentina (two modes), the southern Paraguay-northern Argentina border, and the Santa Cruz Province; (2) the QB1 (2.4- to 3-year periods) + quasi-quadrennial (QQ) mode over the Misiones Province; and (3) the QB2 (2.1- to 2.5-year periods) + QQ + inter-annual (IA) (3- to 7-year periods) two modes over south-eastern Argentina. Modes within the 'QB group' are positively correlated with global climate signals and SST. The Uruguayan mode is correlated with global ENSO (8-month lag) whilst the southern Entre-Rios/northern Buenos Aires provinces are correlated with central equatorial Pacific SSTs (3-month lag). The Santa Cruz (Patagonia) Province is most correlated with the Pacific South America (PSA) index and SST patterns (3-month lag) along the Antarctica circumpolar current. The spatial distribution of lead NDVI modes includes the Formosa, Misiones, Chaco and Buenos Aires provinces among others, known for being prone to vector-borne epidemics such as dengue fever, malaria, leishmaniasis (American cutaneous leishmaniasis or ACL), hantivirus, chagas and Argentine hemorrhagic fever (AHF). Some provinces also correspond to regions where lead NDVI PCs' modes are associated with high-frequency climate signals such as the

Spatio-temporal variability of NDVI-precipitation over southernmost South America: possible linkages between climate signals and epidemics

International Nuclear Information System (INIS)

Tourre, Y M; Jarlan, L; Lacaux, J-P; Rotela, C H; Lafaye, M

2008-01-01

Climate-environment variability affects the rates of incidence of vector-borne and zoonotic diseases and is possibly associated with epidemics outbreaks. Over southernmost South America the joint spatio-temporal evolution of climate-environment is analyzed for the 1982-2004 period. Detailed mapping of normalized difference vegetation index (NDVI) and rainfall variability are then compared to zones with preliminary epidemiological reports. A significant quasi-biennial signal (2.2- to 2.4-year periods, or QB) for joint NDVI-rainfall variability is revealed. From rotated EOFs, dominant NDVI patterns are partitioned according to their lead frequencies: (1) the 'QB group' (2.1-to 3-year periods) includes six modes over southern Brazil, Uruguay, northern-central Argentina (two modes), the southern Paraguay-northern Argentina border, and the Santa Cruz Province; (2) the QB1 (2.4- to 3-year periods) + quasi-quadrennial (QQ) mode over the Misiones Province; and (3) the QB2 (2.1- to 2.5-year periods) + QQ + inter-annual (IA) (3- to 7-year periods) two modes over south-eastern Argentina. Modes within the 'QB group' are positively correlated with global climate signals and SST. The Uruguayan mode is correlated with global ENSO (8-month lag) whilst the southern Entre-Rios/northern Buenos Aires provinces are correlated with central equatorial Pacific SSTs (3-month lag). The Santa Cruz (Patagonia) Province is most correlated with the Pacific South America (PSA) index and SST patterns (3-month lag) along the Antarctica circumpolar current. The spatial distribution of lead NDVI modes includes the Formosa, Misiones, Chaco and Buenos Aires provinces among others, known for being prone to vector-borne epidemics such as dengue fever, malaria, leishmaniasis (American cutaneous leishmaniasis or ACL), hantivirus, chagas and Argentine hemorrhagic fever (AHF). Some provinces also correspond to regions where lead NDVI PCs' modes are associated with high-frequency climate signals such as the

Psychometric Properties and Norms of the German ABC-Community and PAS-ADD Checklist

Science.gov (United States)

Zeilinger, Elisabeth L.; Weber, Germain; Haveman, Meindert J.

2011-01-01

Aim: The aim of the present study was to standardize and generate psychometric evidence of the German language versions of two well-established English language mental health instruments: the "Aberrant Behavior Checklist-Community" (ABC-C) and the "Psychiatric Assessment Schedule for Adults with Developmental Disabilities" (PAS-ADD) Checklist. New…

Ciprofloxacin and probiotic Escherichia coli Nissle add-on treatment in active ulcerative colitis

DEFF Research Database (Denmark)

Petersen, Andreas Munk; Mirsepasi, Hengameh; Halkjær, Sofie Ingdam

2014-01-01

BACKGROUND AND AIM: Ulcerative colitis (UC) is a chronic inflammatory bowel disease. The probiotic bacterium Escherichia coli Nissle 1917 (EcN) has been used to maintain and induce clinical remission in UC. Our aim was to test the effect of Ciprofloxacin and/or orally administered EcN as add...

40 CFR 63.3555 - How do I determine the outlet THC emissions and add-on control device emission destruction or...

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 12 2010-07-01 2010-07-01 true How do I determine the outlet THC.../outlet Concentration Option § 63.3555 How do I determine the outlet THC emissions and add-on control... section to determine either the outlet THC emissions or add-on control device emission destruction or...

Transforming nanomedicine manufacturing toward Quality by Design and microfluidics

DEFF Research Database (Denmark)

Colombo, Stefano; Beck-Broichsitter, Moritz; Bøtker, Johan Peter

2018-01-01

-oriented manufacturing of pharmaceuticals has undergone an unprecedented change toward process and product development interaction. In this context, Quality by Design (QbD) aims to integrate product and process development resulting in an increased number of product applications to regulatory agencies and stronger...... proprietary defense strategies of process-based products. Although QbD can be applied to essentially any production approach, microfluidic production offers particular opportunities for QbD-based manufacturing of nanopharmaceuticals. Microfluidics provides unique design flexibility, process control...... and parameter predictability, and also offers ample opportunities for modular production setups, allowing process feedback for continuously operating production and process control. The present review aims at outlining emerging opportunities in the synergistic implementation of QbD strategies and microfluidic...

All-Optical Regenerative OTDM Add/Drop Multiplexing at 40 Gbit/s using Monolithic InP Mach-Zehnder Interferometer

DEFF Research Database (Denmark)

Buxens, Alvaro A.; Clausen, Anders; Poulsen, Henrik Nørskov

2000-01-01

We report a novel method for simultaneous add-drop multiplexing in OTDM systems which includes regenerative capabilities and perfect clearing of the drop channel time slot. The principle has been demonstrated at 40 Gb/s showing an excellent performance.......We report a novel method for simultaneous add-drop multiplexing in OTDM systems which includes regenerative capabilities and perfect clearing of the drop channel time slot. The principle has been demonstrated at 40 Gb/s showing an excellent performance....

ADD1/SREBP1c activates the PGC1-alpha promoter in brown adipocytes

DEFF Research Database (Denmark)

Hao, Qin; Hansen, Jacob B; Petersen, Rasmus K

2010-01-01

Cold adaptation elicits a paradoxical simultaneous induction of fatty acid synthesis and beta-oxidation in brown adipose tissue. We show here that cold exposure coordinately induced liver X receptor alpha (LXRalpha), adipocyte determination and differentiation-dependent factor 1 (ADD1)/sterol...

Contribution of two ζ-carotene desaturases to the poly-cis desaturation pathway in the cyanobacterium Nostoc PCC 7120.

Science.gov (United States)

Breitenbach, Jürgen; Bruns, Marius; Sandmann, Gerhard

2013-07-01

The presence of two completely unrelated ζ-carotene desaturases CrtQa and CrtQb in some Nostoc strains is unique. CrtQb is the ζ-carotene desaturase, which was acquired by almost all cyanobacteria. The additional CrtQa can be regarded as an evolutionary relict of the CrtI desaturase present in non-photosynthetic bacteria. By reconstruction of the carotene desaturation pathway, we showed that both enzymes from Nostoc PCC 7120 were active. However, they differed in their preferred utilization of ζ-carotene Z isomers. CrtQa converted ζ-carotene isomers that were poorly metabolized by CrtQb. In this respect, CrtQa complemented the reactions of CrtQb, which is an advantage avoiding dead ends in the poly-cis desaturation pathway. In addition to ζ-carotene desaturation, CrtQa still possesses the Z to E isomerase function of the ancestral desaturase CrtI. Biochemical characterization showed that CrtQb is an enzyme with one molecule of tightly bound FAD and acts as a dehydrogenase transferring hydrogen to oxidized plastoquinone.

Does Gonadotropin Releasing Hormone Agonists plus add-back therapy bring an aurora to orthodontic treatment?

Directory of Open Access Journals (Sweden)

Jiang Lingyong

2012-01-01

Full Text Available Introduction: Obviously, long therapy time of orthodontic treatment and a number of its adverse effects, such as pain, root resorption, enamel demineralization, periodontal disease, are the main reasons of complaints from patients. It is the first thing for an orthodontist to shorten the period of treatment and decrease the complications of orthodontic treatment as much as possible. The Hypothesis: We hypothesis Gonadotropin Releasing Hormone Agonists (GnRHa and add-back therapy can create the "therapeutic window", namely, the appropriate estrogen level and assuage the adverse effects of estrogen deficiency which should be avoided as much as possible. Evaluation of the Hypothesis: It is generally acknowledged that estrogen has direct regulating role in bone metabolism by acting on osteoblasts and osteoclasts. Estrogen deficiency can increase the rate of orthodontic tooth movement and also bring about some adverse effects. The appropriate estrogen level, which we call the "therapeutic window" in orthodontic treatment, can speed up the orthodontic tooth movement and eliminate the adverse effects as far as possible. GnRHa can be the maker of estrogen deficiency; meanwhile, add-back therapy can remove the adverse effects by estrogen deficiency. So, we believe that GnRHa plus add-back therapy could be a new adjuvant method of orthodontic treatment and be good for orthodontists and patients.

Complement mRNA in the mammalian brain: responses to Alzheimer's disease and experimental brain lesioning.

Science.gov (United States)

Johnson, S A; Lampert-Etchells, M; Pasinetti, G M; Rozovsky, I; Finch, C E

1992-01-01

This study describes evidence in the adult human and rat brain for mRNAs that encode two complement (C) proteins, C1qB and C4. C proteins are important effectors of humoral immunity and inflammation in peripheral tissues but have not been considered as normally present in brain. Previous immunocytochemical studies showed that C proteins are associated with plaques, tangles, and dystrophic neurites in Alzheimer's disease (AD), but their source is unknown. Combined immunocytochemistry and in situ hybridization techniques show C4 mRNA in pyramidal neurons and C1qB mRNA in microglia. Primary rat neuron cultures also show C1qB mRNA. In the cortex from AD brains, there were two- to threefold increases of C1qB mRNA and C4 mRNA, and increased C1qB mRNA prevalence was in part associated with microglia. As a model for AD, we examined entorhinal cortex perforant path transection in the rat brain, which caused rapid increases of C1qB mRNA in the ipsilateral, but not contralateral, hippocampus and entorhinal cortex. The role of brain-derived acute and chronic C induction during AD and experimental lesions can now be considered in relation to functions of C proteins that pertain to cell degeneration and/or cell preservation and synaptic plasticity.

Just add water: reproducible singly dispersed silver nanoparticle suspensions on-demand

International Nuclear Information System (INIS)

MacCuspie, Robert I.; Allen, Andrew J.; Martin, Matthew N.; Hackley, Vincent A.

2013-01-01

Silver nanoparticles (AgNPs) are of interest due to their antimicrobial attributes, which are derived from their inherent redox instability and subsequent release of silver ions. At the same time, this instability is a substantial challenge for achieving stable long-term storage for on-demand use of AgNPs. In this study, we describe and validate a “just add water” approach for achieving suspensions of principally singly dispersed AgNPs. By lyophilizing (freeze drying) the formulated AgNPs into a solid powder, or cake, water is removed thereby eliminating solution-based chemical changes. Storing under inert gas further reduces surface reactions such as oxidation. An example of how to optimize a lyophilization formulation is presented, as well as example formulations for three AgNP core sizes. This “just add water” approach enables ease of use for the researcher desiring on-demand singly dispersed AgNP suspensions from a single master batch. Implementation of this methodology will enable studies to be performed over long periods of time and across different laboratories using particles that are identical chemically and physically and available on-demand. In addition, the approach of freeze drying and on-demand reconstitution by adding water has enabled the development of AgNP reference materials with the required shelf-life stability, one of the principal objectives of this research

Regional identity can add value to agricultural products

Directory of Open Access Journals (Sweden)

Bradley C. Christensen

2015-04-01

Full Text Available Regional identity creation is being recognized for its economic benefits and as a strategic resource for producer communities. A regional identity is not a brand; it is built through a complicated process of developing cohesion and sharing in the industry community and communicating outside the industry community to opinion-makers and consumers. The California fine wine industry has built successful regional identities and leveraged them to add value to their wines. As regional identities in the wine industry have strengthened, so has the industry, and a symbiotic relationship with other local value-added industries, such as tourism and hospitality, has emerged. Other agricultural producers can learn from the identity creation experiences in the wine industry. With the many challenges faced by California agriculture, identity formation may offer producers new ideas for adding value to their products and finding larger markets.

MetaEasy: A Meta-Analysis Add-In for Microsoft Excel

Directory of Open Access Journals (Sweden)

Evangelos Kontopantelis

2009-04-01

Full Text Available Meta-analysis is a statistical methodology that combines or integrates the results ofseveral independent clinical trials considered by the analyst to be `combinable' (Huque1988. However, completeness and user-friendliness are uncommon both in specialisedmeta-analysis software packages and in mainstream statistical packages that have to relyon user-written commands. We implemented the meta-analysis methodology in an Mi-crosoft Excel add-in which is freely available and incorporates more meta-analysis models(including the iterative maximum likelihood and prole likelihood than are usually avail-able, while paying particular attention to the user-friendliness of the package.

Hera-FFX: a Firefox add-on for Semi-automatic Web Accessibility Evaluation

OpenAIRE

Fuertes Castro, José Luis; González, Ricardo; Gutiérrez, Emmanuelle; Martínez Normand, Loïc

2009-01-01

Website accessibility evaluation is a complex task requiring a combination of human expertise and software support. There are several online and offline tools to support the manual web accessibility evaluation process. However, they all have some weaknesses because none of them includes all the desired features. In this paper we present Hera-FFX, an add-on for the Firefox web browser that supports semi-automatic web accessibility evaluation.

PLOT3D Export Tool for Tecplot

Science.gov (United States)

Alter, Stephen

2010-01-01

The PLOT3D export tool for Tecplot solves the problem of modified data being impossible to output for use by another computational science solver. The PLOT3D Exporter add-on enables the use of the most commonly available visualization tools to engineers for output of a standard format. The exportation of PLOT3D data from Tecplot has far reaching effects because it allows for grid and solution manipulation within a graphical user interface (GUI) that is easily customized with macro language-based and user-developed GUIs. The add-on also enables the use of Tecplot as an interpolation tool for solution conversion between different grids of different types. This one add-on enhances the functionality of Tecplot so significantly, it offers the ability to incorporate Tecplot into a general suite of tools for computational science applications as a 3D graphics engine for visualization of all data. Within the PLOT3D Export Add-on are several functions that enhance the operations and effectiveness of the add-on. Unlike Tecplot output functions, the PLOT3D Export Add-on enables the use of the zone selection dialog in Tecplot to choose which zones are to be written by offering three distinct options - output of active, inactive, or all zones (grid blocks). As the user modifies the zones to output with the zone selection dialog, the zones to be written are similarly updated. This enables the use of Tecplot to create multiple configurations of a geometry being analyzed. For example, if an aircraft is loaded with multiple deflections of flaps, by activating and deactivating different zones for a specific flap setting, new specific configurations of that aircraft can be easily generated by only writing out specific zones. Thus, if ten flap settings are loaded into Tecplot, the PLOT3D Export software can output ten different configurations, one for each flap setting.

[The add-on effect of omalizumab on patients with uncontrolled bronchial asthma].

Science.gov (United States)

Minami, Yoshinori; Endo, Satoshi; Okumur, Shunsuke; Sasaki, Takaaki; Yamamoto, Yasushi; Ogasa, Toshiyuki; Osanai, Shinobu; Ohsaki, Yoshinobu

2011-11-01

A high-dose administration of inhaled corticosteroid is effective in the majority of patients with bronchial asthma, but is often difficult to attain sufficient control in certain subsets of patients. Omalizumab has recently emerged as a promising drug for bronchial asthma. To assess its add-on effect we administered omalizumab to patients with uncontrolled atopic asthma for more than 16 weeks and gave them questionnaires. The study population comprised 9 patients with frequent asthmatic symptoms despite the administration of high-dose inhaled corticosteroid and other disease controllers. We scored disease control using the Asthma Health Questionnaire-33-Japan and the Asthma Control Test, and evaluated the frequencies of short-acting beta2-agonist use for rescue and drip infusion of theophyllines and/or systemic steroids in a retrospective fashion. Asthmatic scores were significantly improved after 16 weeks of omalizumab therapy. The frequencies of reliever use and drip infusion were also decreased. These trends were present even in patients in whom no aeroallergen-specific IgE antibodies were detected. No statistically significant side effects were observed. Our study confirmed the add-on effect of omalizumab based on evaluation by simple questionnaires. Further studies are needed to clarify whether omalizumab therapy is suitable for patients without specific IgE antibodies.

Polymorphism of the H-FABP, MC4R and ADD1 genes in the ...

African Journals Online (AJOL)

4 Receptor (MC4R) and the Adipocyte Determination and Differentiation factor-1 (ADD1) play an important role in meat quality in pigs. The Meishan is one of the most prolific pig breeds in the world, but it is in danger, in China, of being replaced ...

What a signature adds to the consent process.

LENUS (Irish Health Repository)

Neary, Peter

2012-02-03

BACKGROUND: "Consent is a process by which a patient is informed and becomes a participant in decisions regarding their medical management." It is argued, however, that providing a signature to a form adds little to the quality of this process. METHODS: Views regarding the consent ritual of nonselected patients undergoing endoscopy (cystoscopy or sigmoidoscopy) were prospectively studied together with those of the attending staff. Patient volunteers were randomly assigned to one of two groups and given verbal explanation before the procedure, either alone (group A) or with a request to sign a form in addition (group B). A standardized questionnaire regarding preferences then was applied. RESULTS: A total of 37 patients (22 men) were studied along with seven staff members. Most surveyed felt that signing a consent form helped to empower the patient (group A, 84%; group B, 83%; staff, 100%). Although the patients mainly believed that it functioned primarily to protect the hospital and doctor (group A, 89%; group B, 67%), only one patient (3% of total) felt that such a formality undermined the patient-doctor relationship. Most staff members favored signing a form (86%). The majority of patients either favored it (group A, 47%; group B, 78%) or expressed no strong preference (group A, 32%; group B, 11%). Interestingly, more women than men preferred signing (73 vs. 55%; p = 0.25), perhaps because more women believed that it functioned to preserve autonomy (93 vs. 77% of men). Age was no particular determinant of perspective. CONCLUSION: Although it may be viewed as primarily serving to protect the doctor and hospital, the formal process of signing written consent forms appeals to patients and staff.

TEST DESIGN FOR ENVIRONMENTAL TECHNOLOGY VERIFICATION (ETV) OF ADD-ON NOX CONTROL UTILIZING OZONE INJECTION

Science.gov (United States)

The paper discusses the test design for environmental technology verification (ETV) of add-0n nitrogen oxides (NOx) control utilizing ozone injection. (NOTE: ETV is an EPA-established program to enhance domestic and international market acceptance of new or improved commercially...

Proton conduction within the reaction centers of Rhodobacter capsulatus: the electrostatic role of the protein.

Science.gov (United States)

Maróti, P; Hanson, D K; Baciou, L; Schiffer, M; Sebban, P

1994-06-07

Light-induced charge separation in the photosynthetic reaction center results in delivery of two electrons and two protons to the terminal quinone acceptor QB. In this paper, we have used flash-induced absorbance spectroscopy to study three strains that share identical amino acid sequences in the QB binding site, all of which lack the protonatable amino acids Glu-L212 and Asp-L213. These strains are the photosynthetically incompetent site-specific mutant Glu-L212/Asp-L213-->Ala-L212/Ala-L213 and two different photocompetent derivatives that carry both alanine substitutions and an intergenic suppressor mutation located far from QB (class 3 strain, Ala-Ala + Arg-M231-->Leu; class 4 strain, Ala-Ala + Asn-M43-->Asp). At pH 8 in the double mutant, we observe a concomitant decrease of nearly 4 orders of magnitude in the rate constants of second electron and proton transfer to QB compared to the wild type. Surprisingly, these rates are increased to about the same extent in both types of suppressor strains but remain > 2 orders of magnitude smaller than those of the wild type. In the double mutant, at pH 8, the loss of Asp-L213 and Glu-L212 leads to a substantial stabilization (> or = 60 meV) of the semiquinone energy level. Both types of compensatory mutations partially restore, to nearly the same level, the original free energy difference for electron transfer from primary quinone QA to QB. The pH dependence of the electron and proton transfer processes in the double-mutant and the suppressor strains suggests that when reaction centers of the double mutant are shifted to lower pH (1.5-2 units), they function like those of the suppressor strains at physiological pH. Our data suggest that the main effect of the compensatory mutations is to partially restore the negative electrostatic environment of QB and to increase an apparent "functional" pK of the system for efficient proton transfer to the active site. This emphasizes the role of the protein in tuning the

40 CFR 63.3174 - What are the requirements for a capture system or add-on control device which is not taken into...

Science.gov (United States)

2010-07-01

... control device which is not taken into account when demonstrating compliance with the applicable emission limitations? You may have capture systems or add-on control devices which you choose not to take into account... system or add-on control device which is not taken into account when demonstrating compliance with the...

The reliability of in-home measures of height and weight in large cohort studies: Evidence from Add Health

Directory of Open Access Journals (Sweden)

Jon Hussey

2015-05-01

Full Text Available Background: With the emergence of obesity as a global health issue, an increasing number of major demographic surveys are collecting measured anthropometric data. Yet little is known about the characteristics and reliability of these data. Objective: We evaluate the accuracy and reliability of anthropometric data collected in the home during Wave IV of the National Longitudinal Study of Adolescent to Adult Health (Add Health, compare our estimates to national standard, clinic-based estimates from the National Health and Nutrition Examination Survey (NHANES and, using both sources, provide a detailed anthropometric description of young adults in the United States. Methods: The reliability of Add Health in-home anthropometric measures was estimated from repeat examinations of a random subsample of study participants. A digit preference analysis evaluated the quality of anthropometric data recorded by field interviewers. The adjusted odds of obesity and central obesity in Add Health vs. NHANES were estimated with logistic regression. Results: Short-term reliabilities of in-home measures of height, weight, waist and arm circumference - as well as derived body mass index (BMI, kg/m2 - were excellent. Prevalence of obesity (37Š vs. 29Š and central obesity (47Š vs. 38Š was higher in Add Health than in NHANES, while socio-demographic patterns of obesity and central obesity were comparable in the two studies. Conclusions: Properly trained non-medical field interviewers can collect reliable anthropometric data in a nationwide, home visit study. This national cohort of young adults in the United States faces a high risk of early-onset chronic disease and premature mortality.

Efficient androst-1,4-diene-3,17-dione production by co-expressing 3-ketosteroid-Δ1 -dehydrogenase and catalase in Bacillus subtilis.

Science.gov (United States)

Shao, M; Sha, Z; Zhang, X; Rao, Z; Xu, M; Yang, T; Xu, Z; Yang, S

2017-01-01

3-ketosteroid-Δ 1 -dehydrogenase (KSDD), a flavin adenine dinucleotide (FAD)-dependent enzyme involved in sterol metabolism, specifically catalyses the conversion of androst-4-ene-3,17-dione (AD) to androst-1,4-diene-3,17-dione (ADD). However, the low KSDD activity and the toxic effects of hydrogen peroxide (H 2 O 2 ) generated during the biotransformation of AD to ADD with FAD regeneration hinder its application on AD conversion. The aim of this work was to improve KSDD activity and eliminate the toxic effects of the generated H 2 O 2 to enhance ADD production. The ksdd gene obtained from Mycobacterium neoaurum JC-12 was codon-optimized to increase its expression level in Bacillus subtilis, and the KSDD activity reached 12·3 U mg -1 , which was sevenfold of that of codon-unoptimized gene. To improve AD conversion, catalase was co-expressed with KSDD in B. subtilis 168/pMA5-ksdd opt -katA to eliminate the toxic effects of H 2 O 2 generated during AD conversion. Finally, under optimized bioconversion conditions, fed-batch strategy was carried out and the ADD yield improved to 8·76 g l -1 . This work demonstrates the potential to improve enzyme activity by codon-optimization and eliminate the toxic effects of H 2 O 2 by co-expressing catalase. This study showed the highest ADD productivity ever reported and provides a promising strain for efficient ADD production in the pharmaceutical industry. © 2016 The Society for Applied Microbiology.

Digital Tomosynthesis System Geometry Analysis Using Convolution-Based Blur-and-Add (BAA) Model.

Science.gov (United States)

Wu, Meng; Yoon, Sungwon; Solomon, Edward G; Star-Lack, Josh; Pelc, Norbert; Fahrig, Rebecca

2016-01-01

Digital tomosynthesis is a three-dimensional imaging technique with a lower radiation dose than computed tomography (CT). Due to the missing data in tomosynthesis systems, out-of-plane structures in the depth direction cannot be completely removed by the reconstruction algorithms. In this work, we analyzed the impulse responses of common tomosynthesis systems on a plane-to-plane basis and proposed a fast and accurate convolution-based blur-and-add (BAA) model to simulate the backprojected images. In addition, the analysis formalism describing the impulse response of out-of-plane structures can be generalized to both rotating and parallel gantries. We implemented a ray tracing forward projection and backprojection (ray-based model) algorithm and the convolution-based BAA model to simulate the shift-and-add (backproject) tomosynthesis reconstructions. The convolution-based BAA model with proper geometry distortion correction provides reasonably accurate estimates of the tomosynthesis reconstruction. A numerical comparison indicates that the simulated images using the two models differ by less than 6% in terms of the root-mean-squared error. This convolution-based BAA model can be used in efficient system geometry analysis, reconstruction algorithm design, out-of-plane artifacts suppression, and CT-tomosynthesis registration.

Production Of The ADD Type Kaluza-Klein Excitations At Future e+e-, ep And pp Colliders

International Nuclear Information System (INIS)

Billur, A. A.; Ciftci, A. K.; Ciftci, R.; Inan, S. C.; Sultansoy, S.

2007-01-01

Possible production of ADD type Kaluza-Klein excitations are investigated at future high energy e+e-, ep and pp colliders. Discovery limits and signatures of such excitations are discussed at above colliders comparatively

Symbolic BDD and ADD Algorithms for Energy Games

Directory of Open Access Journals (Sweden)

Shahar Maoz

2016-11-01

Full Text Available Energy games, which model quantitative consumption of a limited resource, e.g., time or energy, play a central role in quantitative models for reactive systems. Reactive synthesis constructs a controller which satisfies a given specification, if one exists. For energy games a synthesized controller ensures to satisfy not only the safety constraints of the specification but also the quantitative constraints expressed in the energy game. A symbolic algorithm for energy games, recently presented by Chatterjee et al., is symbolic in its representation of quantitative values but concrete in the representation of game states and transitions. In this paper we present an algorithm that is symbolic both in the quantitative values and in the underlying game representation. We have implemented our algorithm using two different symbolic representations for reactive games, Binary Decision Diagrams (BDD and Algebraic Decision Diagrams (ADD. We investigate the commonalities and differences of the two implementations and compare their running times on specifications of energy games.

Ritanserin as add-on medication to neuroleptic therapy for patients with chronic or subchronic schizophrenia

NARCIS (Netherlands)

Den Boer, JA; Vahlne, JO; Post, P; Heck, AH; Daubenton, F; Olbrich, R

The effect of ritanserin, a potent 5HT(2A/2C) receptor antagonist, used as an add-on medication to neuroleptic treatmentin patients with schizophrenia, was compared with that of placebo, in an international, double-blind, parallel-group study. Previously established neuroleptic therapy was

76 FR 65935 - Brucellosis in Swine; Add Texas to List of Validated Brucellosis-Free States

Science.gov (United States)

2011-10-25

... DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service 9 CFR Part 78 [Docket No. APHIS-2011-0005] Brucellosis in Swine; Add Texas to List of Validated Brucellosis- Free States AGENCY... or birth of weak offspring, reduced milk production, and infertility. There is no economically...

Add-on treatment of benzoate for schizophrenia: a randomized, double-blind, placebo-controlled trial of D-amino acid oxidase inhibitor.

Science.gov (United States)

Lane, Hsien-Yuan; Lin, Ching-Hua; Green, Michael F; Hellemann, Gerhard; Huang, Chih-Chia; Chen, Po-Wei; Tun, Rene; Chang, Yue-Cung; Tsai, Guochuan E

2013-12-01

In addition to dopaminergic hyperactivity, hypofunction of the N-methyl-d-aspartate receptor (NMDAR) has an important role in the pathophysiology of schizophrenia. Enhancing NMDAR-mediated neurotransmission is considered a novel treatment approach. To date, several trials on adjuvant NMDA-enhancing agents have revealed beneficial, but limited, efficacy for positive and negative symptoms and cognition. Another method to enhance NMDA function is to raise the levels of d-amino acids by blocking their metabolism. Sodium benzoate is a d-amino acid oxidase inhibitor. To examine the clinical and cognitive efficacy and safety of add-on treatment of sodium benzoate for schizophrenia. A randomized, double-blind, placebo-controlled trial in 2 major medical centers in Taiwan composed of 52 patients with chronic schizophrenia who had been stabilized with antipsychotic medications for 3 months or longer. Six weeks of add-on treatment of 1 g/d of sodium benzoate or placebo. The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS) total score. Clinical efficacy and adverse effects were assessed biweekly. Cognitive functions were measured before and after the add-on treatment. Benzoate produced a 21% improvement in PANSS total score and large effect sizes (range, 1.16-1.69) in the PANSS total and subscales, Scales for the Assessment of Negative Symptoms-20 items, Global Assessment of Function, Quality of Life Scale and Clinical Global Impression and improvement in the neurocognition subtests as recommended by the National Institute of Mental Health's Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative, including the domains of processing speed and visual learning. Benzoate was well tolerated without significant adverse effects. Benzoate adjunctive therapy significantly improved a variety of symptom domains and neurocognition in patients with chronic schizophrenia. The preliminary results show promise for d-amino acid oxidase

Pleasure and pedagogy: the consumption of DVD add-ons among Irish teenagers

OpenAIRE

Brereton, Pat; O'Connor, Barbara

2007-01-01

This article addresses the issue of young people and media use in the digital age, more specifically the interconnection between new media pleasures and pedagogy as they relate to the consumption of DVD add-ons. Arguing against the view of new media as having predominantly detrimental effects on young people, the authors claim that new media can enable young people to develop media literacy skills and are of the view that media literacy strategies must be based on an understanding and legitim...

Phantom examination for reduction of radiation dose using new needle screen storage phosphor radiography and add beam filter in digital thoracic radiography on adolescents and larger children

International Nuclear Information System (INIS)

Heyne, J.P.; Mentzel, H.J.; Neumann, R.; Lopatta, E.; Zimmermann, U.; Kaiser, W.A.

2008-01-01

Purpose: how much can the radiation dose be reduced in thoracic radiography on adolescents and larger children by using needle screen storage phosphor (NIP) radiography and add beam filtration? Materials and methods: a chest phantom with typical anatomical structures, pathological findings, added catheters, and simulated nodules, tumors, and calcifications was X-rayed digitally (DX-S, Agfa Healthcare) in posterior-anterior (p.a.) orientation with and without add beam filter. While keeping the voltage constant, the tube current time product was reduced gradually. In addition to LgM, the surface entrance dose (ED) and the dose area product (DAP) were measured by the Dosimax sensor and Kerma X-plus (both Wellhoefer). Five investigators evaluated the images for characteristics and critical features, pathological findings, and catheter recognizability. Results: the ED of the digital chest radiogram p.a. with 115 kV and 0.71 mAs was 27 μGy, the DAP 3.6 μGy x m 2 , the LgM value 1.56. This initial radiogram was able to be evaluated very well and conforms to the quality guidelines. The dose-reduced chest radiograms with the add beam filter Al 1.0 mm/Cu 0.1 mm were evaluated as sufficiently reduced to a dose of 63% of the initial dose, with the add beam filter Al 1.0 mm/Cu 0.2 mm reduced to 50% (0.52 mAs, DAP 1.82 μGy x m 2 , LgM 1.35). P.a. radiograms were able to be X-rayed on 115 kV with 0.52 mAs. (orig.)

A subsurface add-on for standard atomic force microscopes

Energy Technology Data Exchange (ETDEWEB)

Verbiest, G. J., E-mail: Verbiest@physik.rwth-aachen.de [JARA-FIT and II. Institute of Physics, RWTH Aachen University, 52074 Aachen (Germany); Zalm, D. J. van der; Oosterkamp, T. H.; Rost, M. J., E-mail: Rost@physics.leidenuniv.nl [Kamerlingh Onnes Laboratory, Leiden University, P.O. Box 9504, 2300 RA Leiden (Netherlands)

2015-03-15

The application of ultrasound in an Atomic Force Microscope (AFM) gives access to subsurface information. However, no commercially AFM exists that is equipped with this technique. The main problems are the electronic crosstalk in the AFM setup and the insufficiently strong excitation of the cantilever at ultrasonic (MHz) frequencies. In this paper, we describe the development of an add-on that provides a solution to these problems by using a special piezo element with a lowest resonance frequency of 2.5 MHz and by separating the electronic connection for this high frequency piezo element from all other connections. In this sense, we support researches with the possibility to perform subsurface measurements with their existing AFMs and hopefully pave also the way for the development of a commercial AFM that is capable of imaging subsurface features with nanometer resolution.

Dinitraminic acid (HDN) isomerization and self-decomposition revisited

International Nuclear Information System (INIS)

Rahm, Martin; Brinck, Tore

2008-01-01

Density functional theory (DFT) and the ab initio based CBS-QB3 method have been used to study possible decomposition pathways of dinitraminic acid HN(NO 2 ) 2 (HDN) in gas-phase. The proton transfer isomer of HDN, O 2 NNN(O)OH, and its conformers can be formed and converted into each other through intra- and intermolecular proton transfer. The latter has been shown to proceed substantially faster via double proton transfer. The main mechanism for HDN decomposition is found to be initiated by a dissociation reaction, splitting of nitrogen dioxide from either HDN or the HDN isomer. This reaction has an activation enthalpy of 36.5 kcal/mol at the CBS-QB3 level, which is in good agreement with experimental estimates of the decomposition barrier

Integrated Application of Quality-by-Design Principles to Drug Product Development: A Case Study of Brivanib Alaninate Film-Coated Tablets.

Science.gov (United States)

Badawy, Sherif I F; Narang, Ajit S; LaMarche, Keirnan R; Subramanian, Ganeshkumar A; Varia, Sailesh A; Lin, Judy; Stevens, Tim; Shah, Pankaj A

2016-01-01

Modern drug product development is expected to follow quality-by-design (QbD) paradigm. At the same time, although there are several issue-specific examples in the literature that demonstrate the application of QbD principles, a holistic demonstration of the application of QbD principles to drug product development and control strategy, is lacking. This article provides an integrated case study on the systematic application of QbD to product development and demonstrates the implementation of QbD concepts in the different aspects of product and process design for brivanib alaninate film-coated tablets. Using a risk-based approach, the strategy for development entailed identification of product critical quality attributes (CQAs), assessment of risks to the CQAs, and performing experiments to understand and mitigate identified risks. Quality risk assessments and design of experiments were performed to understand the quality of the input raw materials required for a robust formulation and the impact of manufacturing process parameters on CQAs. In addition to the material property and process parameter controls, the proposed control strategy includes use of process analytical technology and conventional analytical tests to control in-process material attributes and ensure quality of the final product. Copyright © 2016. Published by Elsevier Inc.

Adult Dyslexia and Attention Deficit Disorder in Finland--Project DyAdd: WAIS-III Cognitive Profiles

Science.gov (United States)

Laasonen, Marja; Leppamaki, Sami; Tani, Pekka; Hokkanen, Laura

2009-01-01

The project Adult Dyslexia and Attention Deficit Disorder in Finland (Project DyAdd) compares adults (n = 119, 18-55 years) with dyslexia, attention-deficit/hyperactivity disorder (ADHD), dyslexia together with ADHD (comorbid), and healthy controls with neuropsychological, psychophysical, and biological methods. The focus of this article is on the…

Appropriate statistical methods are required to assess diagnostic tests for replacement, add-on, and triage

NARCIS (Netherlands)

Hayen, Andrew; Macaskill, Petra; Irwig, Les; Bossuyt, Patrick

2010-01-01

To explain which measures of accuracy and which statistical methods should be used in studies to assess the value of a new binary test as a replacement test, an add-on test, or a triage test. Selection and explanation of statistical methods, illustrated with examples. Statistical methods for

Vocabulario enla lengua Castellana, la del Ynga y Xebera (British Library, Ms. Add. 25,323)

NARCIS (Netherlands)

Alexander-Bakkerus, A.

2013-01-01

The codex Vocabulario enla Lengua Castellana, la del Inga y Xebera (British Library, shelf mark Ms. Add. 25,323), does not only contain a Spanish-Quechua-Xebero vocabulary, but also a rather elaborate description of certain Xebero sounds. Although the author of the manuscript is unknown, we may

[Research advances in secondary development of Chinese patent medicines based on quality by design concept].

Science.gov (United States)

Gong, Xing-Chu; Chen, Teng; Qu, Hai-Bin

2017-03-01

Quality by design (QbD) concept is an advanced pharmaceutical quality control concept. The application of QbD concept in the research and development of pharmaceutical processes of traditional Chinese medicines (TCM) mainly contains five parts, including the definition of critical processes and their evaluation criteria, the determination of critical process parameters and critical material attributes, the establishment of quantitative models, the development of design space, as well as the application and continuous improvement of control strategy. In this work, recent research advances in QbD concept implementation methods in the secondary development of Chinese patent medicines were reviewed, and five promising fields of the implementation of QbD concept were pointed out, including the research and development of TCM new drugs and Chinese medicine granules for formulation, modeling of pharmaceutical processes, development of control strategy based on industrial big data, strengthening the research of process amplification rules, and the development of new pharmaceutical equipment.. Copyright© by the Chinese Pharmaceutical Association.

40 CFR Table 4 to Subpart Kkkk of... - Operating Limits If Using the Emission Rate With Add-on Controls Option or the Control Efficiency...

Science.gov (United States)

2010-07-01

... Rate With Add-on Controls Option or the Control Efficiency/Outlet Concentration Compliance Option 4... Add-on Controls Option or the Control Efficiency/Outlet Concentration Compliance Option If you are... volumetric flow rate at a location upstream of the control device, or duct static pressure at a location...

Granisetron as an add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: randomized double-blind placebo-controlled study.

Science.gov (United States)

Khodaie-Ardakani, Mohammad-Reza; Seddighi, Sahar; Modabbernia, Amirhossein; Rezaei, Farzin; Salehi, Bahman; Ashrafi, Mandana; Shams-Alizadeh, Narges; Mohammad-Karimi, Maryam; Esfandiari, Gholam-Reza; Hajiaghaee, Reza; Akhondzadeh, Shahin

2013-04-01

Some 5-HT3 antagonists such as ondansetron have shown beneficial effects on negative symptoms of patients with schizophrenia. We aimed to evaluate the efficacy of granisetron (another 5-HT3 antagonist) add-on therapy in the treatment of negative symptoms of patients with stable schizophrenia. In a randomized, double-blind, and placebo-controlled study, forty stable patients with schizophrenia (DSM-IV-TR), were randomized to either granisetron (1 mg twice daily) or placebo (twice daily) in addition to risperidone up to 6 mg/day for eight weeks. The patients were assessed using positive and negative syndrome scale (PANSS) and extrapyramidal symptom rating scale (ESRS) at baseline, week 4 and 8. Hamilton depression rating scale (HDRS) was used to assess depression at baseline and week 8. Thirty-eight patients completed the trial. Granisetron group showed a significantly greater improvement on negative subscale than the placebo group at endpoint [t(38) = 6.046, mean difference (±95% CI) = 3.2(1.8-3.7), P granisetron groups did not differ in their reduction of positive and general psychopathology symptoms scores. HDRS scores and its changes did not differ between the two groups. The ESRS score at week 4 was significantly lower in the granisetron than the placebo group while the two groups showed similar ESRS score at week 8. Frequency of other side effects was similar between the two groups. In summary, granisetron add-on can safely and effectively reduce the primary negative symptoms of patients with schizophrenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

High-Pressure Limit Rate Rules for α-H Isomerization of Hydroperoxyalkylperoxy Radicals

KAUST Repository

Mohamed, Samah Y; Davis, Alexander Cory; Al Rashidi, Mariam J; Sarathy, Mani

2018-01-01

group. In this work, a combination of high level composite methods - CBS-QB3, G3 and G4 - is used to determine the high-pressure-limit rate parameters for the title reaction. Rate rules for H-migration reactions proceeding through 5-, 6-, 7- and 8

The study of business opportunities and value add of NFC applications in security

OpenAIRE

Niemelä, Harri

2011-01-01

Niemelä, Harri 2011. The study of business opportunities and value add of NFC applications in security access control solutions. Master´s Thesis. Kemi-Tornio University of Applied Sciences. Business and Culture. Pages 59. Appendices 2. Since wireless technologies and electrical identification is already our everyday life, it is naturally to utilize latest technologies and in this case Near Field Communication technology to security access control purposes what we meet in our life at wo...

Approach to the unfolding and folding dynamics of add A-riboswitch upon adenine dissociation using a coarse-grained elastic network model

Energy Technology Data Exchange (ETDEWEB)

Li, Chunhua [College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124 (China); Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 45108 (United States); Lv, Dashuai; Zhang, Lei; Yang, Feng; Wang, Cunxin [College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124 (China); Su, Jiguo, E-mail: jiguosu@ysu.edu.cn, E-mail: zhng@umich.edu [College of Science, Yanshan University, Qinhuangdao 066004 (China); Zhang, Yang, E-mail: jiguosu@ysu.edu.cn, E-mail: zhng@umich.edu [Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 45108 (United States)

2016-07-07

Riboswitches are noncoding mRNA segments that can regulate the gene expression via altering their structures in response to specific metabolite binding. We proposed a coarse-grained Gaussian network model (GNM) to examine the unfolding and folding dynamics of adenosine deaminase (add) A-riboswitch upon the adenine dissociation, in which the RNA is modeled by a nucleotide chain with interaction networks formed by connecting adjoining atomic contacts. It was shown that the adenine binding is critical to the folding of the add A-riboswitch while the removal of the ligand can result in drastic increase of the thermodynamic fluctuations especially in the junction regions between helix domains. Under the assumption that the native contacts with the highest thermodynamic fluctuations break first, the iterative GNM simulations showed that the unfolding process of the adenine-free add A-riboswitch starts with the denature of the terminal helix stem, followed by the loops and junctions involving ligand binding pocket, and then the central helix domains. Despite the simplified coarse-grained modeling, the unfolding dynamics and pathways are shown in close agreement with the results from atomic-level MD simulations and the NMR and single-molecule force spectroscopy experiments. Overall, the study demonstrates a new avenue to investigate the binding and folding dynamics of add A-riboswitch molecule which can be readily extended for other RNA molecules.

Measurement of the Economic Growth and Add-on of the R.M. Solow Adjusted Model

Directory of Open Access Journals (Sweden)

Ion Gh. Rosca

2007-08-01

Full Text Available Besides the models of M. Keynes, R.F. Harrod, E. Domar, D. Romer, Ramsey-Cass-Koopmans model etc., the R.M. Solow model is part of the category which characterizes the economic growth.The paper aim is the economic growth measurement and add-on of the R.M. Solow adjusted model.

The influence of participation in target-shooting sport for children with inattentive, hyperactive and impulsive symptoms - A controlled study of best practice.

Science.gov (United States)

Månsson, Annegrete Gohr; Elmose, Mette; Dalsgaard, Søren; Roessler, Kirsten K

2017-03-28

Practising target-shooting sport requires focused attention and motoric steadiness. A previous non-controlled pilot study suggests that children with impairing symptoms of attention-deficit/hyperactivity disorder (ADHD) benefit from participating in target-shooting sport in local shooting associations, as rated by parents and teachers. This study aims at examining if, and to which extent, target-shooting sport reduces parent- and teacher-reported severity of inattentiveness, hyperactivity, and impulsivity in children with attention difficulties, and if, and to which extend, target-shooting sport improves the children's wellbeing and quality of life. A mixed method approach is applied. A non-blinded, waiting list controlled study is combined with a case study, consisting of interviews and observations. The intervention consists of children practising target-shooting sport, by attending a local shooting association, once a week for six months, during regular school hours. Data from questionnaires (ADHD-RS, SDQ, Kidscreen-27), as well as a computerized continued performance test (Qb test), measure the children's activity and attention. The study includes 50 children in an intervention group and 50 children in a waiting list control group. The Qb test collects data from at least 20 children from the intervention group and at least 20 children from the waiting list control group. Data from the questionnaires and Qb-test is collected at baseline, and six months post intervention. In addition, a case study is carried out, consisting of interviews of at least five children from the intervention group, their parents, teachers and shooting instructors. Observations are carried out, when children are in school and while they are attending the local shooting association. The case study adds to an in-depth understanding of children's participation in target-shooting sports. At present, little is known about the effects and influence of practising target-shooting sport for

42 CFR 83.19 - How can the Secretary cancel or modify a final decision to add a class of employees to the Cohort?

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false How can the Secretary cancel or modify a final... to the Cohort § 83.19 How can the Secretary cancel or modify a final decision to add a class of employees to the Cohort? (a) The Secretary can cancel a final decision to add a class to the Cohort, or can...

The food-borne pathogen Campylobacter jejuni depends on the AddAB DNA repair system to defend against bile in the intestinal environment.

Science.gov (United States)

Gourley, Christopher R; Negretti, Nicholas M; Konkel, Michael E

2017-10-31

Accurate repair of DNA damage is crucial to ensure genome stability and cell survival of all organisms. Bile functions as a defensive barrier against intestinal colonization by pathogenic microbes. Campylobacter jejuni, a leading bacterial cause of foodborne illness, possess strategies to mitigate the toxic components of bile. We recently found that growth of C. jejuni in medium with deoxycholate, a component of bile, caused DNA damage consistent with the exposure to reactive oxygen species. We hypothesized that C. jejuni must repair DNA damage caused by reactive oxygen species to restore chromosomal integrity. Our efforts focused on determining the importance of the putative AddAB DNA repair proteins. A C. jejuni addAB mutant demonstrated enhanced sensitivity to deoxycholate and was impaired in DNA double strand break repair. Complementation of the addAB mutant restored resistance to deoxycholate, as well as function of the DNA double strand break repair system. The importance of these findings translated to the natural host, where the AddAB system was found to be required for efficient C. jejuni colonization of the chicken intestine. This research provides new insight into the molecular mechanism utilized by C. jejuni, and possibly other intestinal pathogens, to survive in the presence of bile.

Quality By Design: Concept To Applications.

Science.gov (United States)

Swain, Suryakanta; Padhy, Rabinarayan; Jena, Bikash Ranjan; Babu, Sitty Manohar

2018-03-08

Quality by Design is associated to the modern, systematic, scientific and novel approach which is concerned with pre-distinct objectives that not only focus on product, process understanding but also leads to process control. It predominantly signifies the design and product improvement and the manufacturing process in order to fulfill the predefined manufactured goods or final products quality characteristics. It is quite essential to identify desire and required product performance report such as Target Product Profile, typical Quality Target Product Profile (QTPP) and Critical Quality attributes (CQA). This review highlighted about the concepts of QbD design space, for critical material attributes (CMAs) as well as the critical process parameters that can totally affect the CQAs within which the process shall be unaffected and consistently manufacture the required product. Risk assessment tools and design of experiments are its prime components. This paper outlines the basic knowledge of QbD, the key elements; steps as well as various tools for QbD implementation in pharmaceutics field are presented briefly. In addition to this, quite a lot of applications of QbD in numerous pharmaceutical related unit operations are discussed and summarized. This article provides a complete data as well as the road map for universal implementation and application of QbD for pharmaceutical products. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Numerical Study on Self-Cleaning Canister Filter With Add-On Filter Cap

Directory of Open Access Journals (Sweden)

Mohammed Akmal Nizam

2017-01-01

Full Text Available Filtration in a turbo machinery system such as a gas turbine will ensure that the air entering the inlet is free from contaminants that could bring damage to the main system. Self-cleaning filter systems for gas turbines are designed for continuously efficient flow filtration. A good filter would be able to maintain its effectiveness over a longer time period, prolonging the duration between filter replacements and providing lower pressure drop over its operating lifetime. With this goal in mind, the current study is focused on the difference in pressure loss of the benchmark Salutary Avenue Self-cleaning filter in comparison to a new design with an add-on filter cap. Geometry for the add-on filter cap will be based from Salutary Avenue Manufacturing Sdn.Bhd. SOLIDWORKS software was used to model the geometry of the filter, while simulation analysis on the flow through the filter was done using Computational Fluid Dynamic (CFD software. The simulations are based on a low velocity condition, in which the parameter for the inlet velocity are set at 0.032 m/s, 0.063 m/s, 0.094 m/s and 0.126 m/s respectively. From the simulation data obtained for the inlet velocities considered, the pressure drop reduction of the modified filter compared to the benchmark was found to be between 7.59% and 30.18%. All in all, the modification of the filter cap produced a lower pressure drop in comparison with the benchmark filter; an improvement of 27.02% for the total pressure drop was obtained.

Kinetics of the high-temperature combustion reactions of dibutylether using composite computational methods

KAUST Repository

Rachidi, Mariam El; Davis, Alexander C.; Sarathy, Mani

2015-01-01

. The energetics of H-abstraction by OH radicals is also studied. All rates are determined computationally using the CBS-QB3 and G4 composite methods in conjunction with conventional transition state theory. The B3LYP/6-311++G(2df,2pd) method is used to optimize

Joint-Base Contracting: A Comparative Analysis of Joint-Base Contracting Activities Between Services

Science.gov (United States)

2011-11-09

ã= do^ar^qb=p`elli=lc=_rpfkbpp=C=mr_if`=mlif`v= = - 2 - k^s^i=mlpqdo^ar^qb=p`elli= Fiat purchase automotive supplies cooperatively while Renault and...Monica, CA: RAND. Midler, C., Neffa, P., & Monnet, J. (2002). Globalizing the firm through co- operative projects: The case of Renault . International

Does Supplementation with Omega-3 PUFAs Add to the Prevention of Cardiovascular Disease?

Science.gov (United States)

Rizos, Evangelos C; Elisaf, Moses S

2017-06-01

Omega-3 fatty acids are increasingly used for the protection of cardiovascular disease. The main but not the sole mechanism of action is the reduction of triglyceride levels. In this review, we summarize the effect of omega-3 supplements on all-cause and cardiovascular mortality, myocardial infarction, and stroke from the relevant randomized controlled trials. Twenty-one randomized controlled trials assessed omega-3 supplementation on mortality and cardiovascular-related outcomes. From these studies, as well as from the relevant meta-analyses, we found that omega-3 supplements do not exert a consistent benefit for cardiovascular protection. There is uncertainty of a clear profit from omega-3 supplementation in cardiovascular disease.

Psychoacoustical evaluation of the pitch-synchronous overlap-and-add speech-waveform manipulation technique using single-format stimuli

NARCIS (Netherlands)

Kortekaas, R.W.L.; Kohlrausch, A.G.

1997-01-01

This article presents two experiments dealing with a psychoacoustical evaluation of the pitch synchronous overlap-and-add (PSOLA) technique. This technique has been developed for modification of duration and fundamental frequency of speech and is based on simple waveform manipulations. Both

Alternative inactivated poliovirus vaccines adjuvanted with Quillaja brasiliensis or Quil-a saponins are equally effective in inducing specific immune responses.

Directory of Open Access Journals (Sweden)

Fernanda de Costa

Full Text Available Inactivated polio vaccines (IPV have an important role at the final stages of poliomyelitis eradication programs, reducing the risks associated with the use of attenuated polio vaccine (OPV. An affordable option to enhance vaccine immunogenicity and reduce costs of IPV may be the use of an effective and renewable adjuvant. In the present study, the adjuvant activity of aqueous extract (AE and saponin fraction QB-90 from Quillaja brasiliensis using poliovirus antigen as model were analyzed and compared to a preparation adjuvanted with Quil-A, a well-known saponin-based commercial adjuvant. Experimental vaccines were prepared with viral antigen plus saline (control, Quil-A (50 µg, AE (400 µg or QB-90 (50 µg. Sera from inoculated mice were collected at days 0, 28, 42 and 56 post-inoculation of the first dose of vaccine. Serum levels of specific IgG, IgG1 and IgG2a were significantly enhanced by AE, QB-90 and Quil-A compared to control group on day 56. The magnitude of enhancement was statistically equivalent for QB-90 and Quil-A. The cellular response was evaluated through DTH and analysis of IFN-γ and IL-2 mRNA levels using in vitro reestimulated splenocytes. Results indicated that AE and QB-90 were capable of stimulating the generation of Th1 cells against the administered antigen to the same extent as Quil-A. Mucosal immune response was enhanced by the vaccine adjuvanted with QB-90 as demonstrated by increases of specific IgA titers in bile, feces and vaginal washings, yielding comparable or higher titers than Quil-A. The results obtained indicate that saponins from Q. brasiliensis are potent adjuvants of specific cellular and humoral immune responses and represent a viable option to Quil-A.

Inclusion of Whole Flour from Latin-American Crops into Bread Formulations as Substitute of Wheat Delays Glucose Release and Uptake.

Science.gov (United States)

Laparra, José Moisés; Haros, Monika

2018-03-01

Bakery formulations limiting glucose availability for uptake without compromising product quality are required. Herein, bread formulations containing whole flour from Amaranthus hypochondriacus (AB), Chenopodium quinoa (QB), Salvia hispanica L (ChB) or wheat (WWB) were compared to white bread (WB) for glycaemic index (GI) in fasted animals. The hepatic expression (mRNA) of PPAR-γ receptor as key regulator in substrate fractionation towards energy expenditure was monitored. GIs were associated to fluxes of glucose release (F Gluc ) and metabolic response (MTT assay) of HepG2 cells. ChB (19.7%) and AB (13.5%) decreased GI to a higher extent than QB (2.7%), but all increased expression of PPARγ in relation to WB. F Gluc (AB> > ChB, WWB, WB > QB) showed a reciprocal relationship with the area under curve (AUC) in vivo, and decreased MTT conversion values (WB > WWB, ChB, AB, QB) by HepG2 cells. Thus, inclusion of latin-american crops (LAcs) reducing GI, without compromising bread quality, could help preventing metabolic diseases.

Simvastatin as add-on therapy to interferon β-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial

DEFF Research Database (Denmark)

Sorensen, Per Soelberg; Lycke, Jan; Erälinna, Juha-Pekka

2011-01-01

Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective. We aimed to establish whether add-on of simvastatin, a statin with anti-inflammatory properties, improves this efficacy.......Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective. We aimed to establish whether add-on of simvastatin, a statin with anti-inflammatory properties, improves this efficacy....

Effects of Mg doping in the quantum barriers on the efficiency droop of GaN based light emitting diodes

International Nuclear Information System (INIS)

Liu Yang; Yang Yongchun

2016-01-01

The effects of Mg doping in the quantum barriers (QBs) on the efficiency droop of GaN based light emitting diodes (LEDs) were investigated through a duel wavelength method. Barrier Mg doping would lead to the enhanced hole transportation and reduced polarization field in the quantum wells (QWs), both may reduce the efficiency droop. However, heavy Mg doping in the QBs would strongly deteriorate the crystal quality of the QWs grown after the doped QB. When increasing the injection current, the carriers would escape from the QWs between n-GaN and the doped QB and recombine non-radiatively in the QWs grown after the doped QB, leading to a serious efficiency droop. (paper)

Associations between Dopamine and Serotonin Genes and Job Satisfaction: Preliminary Evidence from the Add Health Study

Science.gov (United States)

Song, Zhaoli; Li, Wendong; Arvey, Richard D.

2011-01-01

Previous behavioral genetic studies have found that job satisfaction is partially heritable. We went a step further to examine particular genetic markers that may be associated with job satisfaction. Using an oversample from the National Adolescent Longitudinal Study (Add Health Study), we found 2 genetic markers, dopamine receptor gene DRD4 VNTR…

Investigation on the absolute and relative photoionization cross sections of 3 potential propargylic fuels.

Science.gov (United States)

Winfough, Matthew; Meloni, Giovanni

2017-12-01

Absolute photoionization cross sections for 2 potential propargylic fuels (propargylamine and dipropargyl ether) along with the partial ionization cross sections for their dissociative fragments are measured and presented for the first time via synchrotron photoionization mass spectrometry. The experimental setup consists of a multiplexed orthogonal time-of-flight mass spectrometer and is located at the Advanced Light Source facility of the Lawrence Berkeley National Laboratory in Berkeley, California. Data for a third propargylic compound (propargyl alcohol) were taken; however, because of its low signal, due to its weakly bound cation, only the dissociative ionization fragment from the H-loss channel is observed and presented. Suggested pathways leading to formation of dissociative photoionization fragments along with CBS-QB3 calculated adiabatic ionization energies and appearance energies for the dissociative fragments are also presented. Copyright © 2017 John Wiley & Sons, Ltd.

On (dynamic) range minimum queries in external memory

DEFF Research Database (Denmark)

Arge, L.; Fischer, Johannes; Sanders, Peter

2013-01-01

We study the one-dimensional range minimum query (RMQ) problem in the external memory model. We provide the first space-optimal solution to the batched static version of the problem. On an instance with N elements and Q queries, our solution takes Θ(sort(N + Q)) = Θ( N+QB log M /B N+QB ) I...

Combining Two Large MRI Data Sets (AddNeuroMed and ADNI) Using Multivariate Data Analysis to Distinguish between Patients with Alzheimer's Disease and Healthy Controls

DEFF Research Database (Denmark)

Westman, Eric; Simmons, Andrew; Muehlboeck, J.-Sebastian

2010-01-01

Background: The European Union AddNeuroMed project and the US-based Alzheimer Disease Neuroimaging Initiative (ADNI) are two large multi-centre initiatives designed to analyse and validate biomarkers for AD. This study aims to compare and combine magnetic resonance imaging (MRI) data from the two...... study cohorts using an automated image analysis pipeline and multivariate data analysis. Methods: A total of 664 subjects were included in this study (AddNeuroMed: 126 AD, 115 CTL, ADNI: 194 AD, 229 CTL) Data acquisition for the AddNeuroMed project was set up to be compatible with the ADNI study...... used are robust and that large data sets can be combined if MRI imaging protocols are carefully aligned....

HANSF 1.3 user's manual

International Nuclear Information System (INIS)

PLYS, M.G.

1999-01-01

The HANSF analysis tool is an integrated model considering phenomena inside a multi-canister overpack (MCO) spent nuclear fuel container such as fuel oxidation, convective and radiative heat transfer, and the potential for fission product release. It may be used for all phases of spent fuel disposition including cold vacuum drying, transportation, and storage. This manual reflects HANSF version 1.3, a revised version of version 1.2a. HANSF 1.3 was written to add new models for axial nodalization, add new features for ease of usage, and correct errors. HANSF 1.3 is intended for use on personal computers such as IBM-compatible machines with Intel processors running under a DOS-type operating system. HANSF 1.3 is known to compile under Lahey TI and Digital Visual FORTRAN, Version 6.0, but this does not preclude operation in other environments

Antidiabetic Effects of Add-On Gynostemma pentaphyllum Extract Therapy with Sulfonylureas in Type 2 Diabetic Patients

Directory of Open Access Journals (Sweden)

V. T. T. Huyen

2012-01-01

Full Text Available Aims. To investigate the antidiabetic effect of the traditional Vietnamese herb Gynostemma pentaphyllum (GP together with sulfonylurea (SU in 25 drug-naïve type 2 diabetic patients. Methods. After 4-week treatment with gliclazide (SU, 30 mg daily, all patients were randomly assigned into 2 groups to add on GP extract or placebo extract, 6 g daily, during eight weeks. Results. After 4-week SU treatment, fasting plasma glucose (FPG and HbA1C decreased significantly (P<0.001. FPG was further reduced after add-on therapy with 2.9 ± 1.7 and 0.9 ± 0.6 mmol/L in the GP and placebo groups, respectively (P<0.001. Therapy with GP extract also reduced 30- and 120-minute oral glucose tolerance test postload values. HbA1C levels decreased approximately 2% units in the GP group compared to 0.7% unit in the placebo group (P<0.001. Conclusion. GP extract in addition to SU offers an alternative to addition of other oral medication to treat type 2 diabetic patients.

Identification of a mutation in ADD1/SREBP-1 in the spontaneously hypertensive rat

Czech Academy of Sciences Publication Activity Database

Pravenec, Michal; Jansa, Petr; Kostka, Vlastimil; Zídek, Václav; Křen, Vladimír; Forejt, Jiří; Kurtz, T. W.

2001-01-01

Roč. 12, č. 4 (2001), s. 295-298 ISSN 0938-8990 R&D Projects: GA ČR(CZ) GA305/00/1646; GA MŠk(CZ) LN00A079; GA ČR(CZ) GV204/98/K015 Grant - others:HHMI(US) 55000331 Institutional research plan: CEZ:AV0Z5011922 Keywords : mutations in genes * ADD1/SREBP-1c * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.318, year: 2001

A high resolution 16 k multi-channel analyzer PC add-on card

International Nuclear Information System (INIS)

Kulkarni, C.P.; Paulson, Molly; Vaidya, P.P.

2001-01-01

This paper describes the system details of a 16 K channel resolution Multi-Channel Analyzer (MCA) developed at Electronics Division, BARC, which is used in high resolution nuclear spectroscopy systems for pulse height analysis. The high resolution data acquisition PC add-on card is architectured using a state of the art digital circuit design technology which makes use of a Field Programmable Gate Array (FPGA), and some of the most modern and advanced analog counterparts like low power, high speed and high precision comparators, Op-amps, ADCs and DACs etc. The 16 K MCA card gives an economic, compact, and low power alternative for nuclear pulse spectroscopy use. (author)

Risk-based Process Development of Biosimilars as Part of the Quality by Design Paradigm.

Science.gov (United States)

Zalai, Dénes; Dietzsch, Christian; Herwig, Christoph

2013-01-01

In the last few years, several quality by design (QbD) studies demonstrated the benefit of systematic approaches for biopharmaceutical development. However, only very few studies identified biosimilars as a special case of product development. The targeted quality profile of biosimilars is strictly defined by the originator's product characteristic. Moreover, the major source of prior knowledge is the experience with the originator product itself. Processing this information in biosimilar development has a major effect on risk management and process development strategies. The main objective of this contribution is to demonstrate how risk management can facilitate the implementation of QbD in early-stage product development with special emphasis on fitting the reported approaches to biosimilars. Risk assessments were highlighted as important tools to integrate prior knowledge in biosimilar development. The risk assessment process as suggested by the International Conference on Harmonization (ICH Q9) was reviewed and three elements were identified to play a key role in targeted risk assessment approaches: proper understanding of target linkage, risk assessment tool compliance, and criticality threshold value. Adjusting these steps to biosimilar applications helped to address some unique challenges of these products such as a strictly defined quality profile or a lack of process knowledge. This contribution demonstrates the need for tailored risk management approaches for the risk-based development of biosimilars and provides novel tools for the integration of additional knowledge available for these products. The pharmaceutical industry is facing challenges such as profit loss and price competition. Companies are forced to rationalize business models and to cut costs in development as well as manufacturing. These trends recently hinder the implementation of any concepts that do not offer certain financial benefit or promise a long return of investment. Quality by

Add-on conservation benefits of marine territorial user rights fishery policies in central Chile.

Science.gov (United States)

Gelcich, Stefan; Godoy, Natalio; Prado, Luis; Castilla, Juan Carlos

2008-01-01

To combine the rational use of marine benthic resources and economic development of small-scale fishers, Chile passed legislation in 1991 establishing a comanagement policy that grants exclusive territorial user rights for fisheries (TURFs) to artisanal fisher organizations in well-defined inshore coastal areas, known as Management and Exploitation Areas for Benthic Resources (MEABRs). In general the policy has been proclaimed a management and economic success because benthic resource abundances have increased inside MEABRs in comparison with open-access areas. However, there is a lack of studies assessing the impact of this management policy on nontargeted subtidal species and community assemblages and the policy's implications for biodiversity and conservation. This study starts to fill this gap and links the allocation of TURFs for benthic resources with add-on conservation benefits for species that are not directly linked with the fishery policy. Comparative subtidal surveys inside vs. outside MEABRs were used to assess the effects of three MEABRs on managed targeted benthic species, biodiversity (species richness), and community assemblages in central Chile. Surveys focused exclusively on subtidal kelp forest habitats dominated by Lessonia trabeculata, spanning 4-12 m in depth and with similar levels of habitat complexity. The study comprised: (1) quantification of kelp forest complexity, (2) understory survey of sessile species, (3) quantification of conspicuous benthic macroinvertebrates, including those under management, and (4) quantification of reef-fish species inside the kelp habitat. Results showed population enhancement of target-managed invertebrates inside MEABRs. Moreover, reef-fish species were significantly more diverse and abundant inside MEABRs, and community assemblages of nontarget benthic invertebrates and reef fish were significantly different inside vs. outside MEABRs. The comanagement of inshore benthic resources in Chile, through MEABRs

Characterization of RNS multiply-add units for power efficient DSP

DEFF Research Database (Denmark)

Cardarilli, Gian Carlo; Nannarelli, Alberto; Petricca, Massimo

2015-01-01

) for a fused multiply-add unit by taking into account four metrics: area, delay, power consumption, and switching activity. The results of the DSE are verified against the TCS and RNS implementation of parallel FIR filters of different characteristics. In both the DSE and the filter implementation, we consider......In the past decades, the Residue Number System (RNS) has been adopted in DSP as an alternative to the traditional two's complement number system (TCS) because of the savings in area, higher speed and reduced power dissipation. In this work, we perform a comprehensive Design Space Exploration (DSE...... two design corners: maximum speed and minimum area. The experimental results demonstrate that for high data rates and high order filters, the RNS implementation is more power efficient than the TCS because of the reduced switching activity and the larger amount of low-power cells placed in the unit....

How to Reach and Teach Children with ADD/ADHD: Practical Techniques, Strategies, and Interventions. Third Edition

Science.gov (United States)

Rief, Sandra F.

2016-01-01

The third edition of "How to Reach and Teach Children and Teens with ADD/ADHD" has been completely revised to offer the most updated and comprehensive guidance to everyone engaged in the positive education of children and teens who have been diagnosed with ADHD or show signs and symptoms of the disorder. This valuable resource contains…

In Building a Script for an Emotion, Do Preschoolers Add Its Cause before Its Behavior Consequence?

Science.gov (United States)

Widen, Sherri C.; Russell, James A.

2011-01-01

An emotion concept is a script in which an emotion event is an ordered sequence of subevents from situational cause through bodily changes to behavioral consequence. As children build a script for each emotion, in what order do they add each subevent? Preschoolers (N = 108, three to five years), were asked to name the protagonist's emotion in…

Effect of heart failure reversal treatment as add-on therapy in patients with chronic heart failure: A randomized, open-label study.

Science.gov (United States)

Sane, Rohit; Aklujkar, Abhijeet; Patil, Atul; Mandole, Rahul

The present study was designed to evaluate effect of heart failure reversal therapy (HFRT) using herbal procedure (panchakarma) and allied therapies, as add-on to standard CHF treatment (SCT) in chronic heart failure (CHF) patients. This open-label, randomized study conducted in CHF patients (aged: 25-65 years, ejection fraction: 30-65%), had 3-phases: 1-week screening, 6-week treatment (randomized [1:1] to HFRT+SCT or SCT-alone) and follow-up (12-week). Twice weekly HFRT (60-75min) consisting of snehana (external oleation), swedana (passive heat therapy), hrudaydhara (concoction dripping treatment) and basti (enema) was administered. Primary endpoints included evaluation of change in metabolic equivalents of task (MET) and peak oxygen uptake (VO 2peak ) from baseline, at end of 6-week treatment and follow-up at week-18 (non-parametric rank ANCOVA analysis). Safety and quality of life (QoL) was assessed. Seventy CHF patients (n=35, each treatment-arm; mean [SD] age: 53.0 [8.6], 80% men) were enrolled in the study. All patients completed treatment phase. Add-on HFRT caused a significant increase in METs (least square mean difference [LSMD], 6-week: 1.536, p=0.0002; 18-week: -1.254, p=0.0089) and VO 2peak (LSMD, 6-week: -5.52, p=0.0002; 18-week: -4.517, p=0.0089) as compared with SCT-alone. Results were suggestive of improved functional capacity in patients with HFRT (QoL; Mean [SD] HFRT+SCT vs. SCT-alone; 6-week: -0.44 [0.34] vs. -0.06 [0.25], p<0.0001 and 18-week: -0.53 [0.35] vs. -0.29 [0.26], p=0.0013). Seven treatment-emergent adverse events (mild severity) were reported in HFRT-arm. Findings of this study highlight therapeutic efficacy of add-on HFRT vs. SCT-alone in CHF patients. The non-invasive HFRT showed no safety concerns. Copyright © 2016. Published by Elsevier B.V.

Effects of vildagliptin as add-on treatment in patients with type 2 diabetes mellitus: insights from long-term clinical studies in Japan.

Science.gov (United States)

Odawara, Masato; Sagara, Rieko

2015-01-01

Vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is wildly used to treat type 2 diabetes mellitus (T2DM) with mono- or combination-therapy. We review two previously published open-label studies to extract insights on the long-term efficacy and safety of vildagliptin. Two studies were conducted in Japan to assess the efficacy and safety of vildagliptin as an add-on to other oral antidiabetes drugs (OADs) for 52 weeks. These studies were performed under the similar protocol in Japanese patients with T2DM who were inadequately controlled with OAD monotherapy [excluding other dipeptidyl peptidase-4 (DPP-4) inhibitors]. Addition of vildagliptin (50 mg twice daily) to other OAD monotherapy [sulfonylurea (SU), metformin, thiazolidinedione, alpha-glucosidase inhibitor and glinide] reduced glycated hemoglobin (HbA1c) levels by -0.64 %,-0.75 %,-0.92 %,-0.94 % and - 0.64 %, respectively, over 52 weeks of treatment. Overall, the incidence of hypoglycemia was low and was slightly higher in the add-on to SU treatment group compared with the other groups. The incidences of adverse events were comparable among the treatment groups, and vildagliptin was well-tolerated as add-on therapy to other OADs. The evidence from the two studies indicates that vildagliptin as an add-on therapy to other OADs is a clinically reasonable option for Japanese patients with T2DM who respond inadequately to other OAD monotherapy.

Helping Students with Disabilities Transition to College: 21 Tips for Students with LD and/or ADD/ADHD

Science.gov (United States)

Connor, David J.

2012-01-01

Making the transition from high school to college poses challenges for most students. Moving from a secure, regulated world of secondary education into an unfamiliar environment requiring greater independence can be a destabilizing experience. For students with learning disabilities (LD) and/or Attention Deficit Disorder (ADD), managing this…

Marriage and Health in the Transition to Adulthood: Evidence for African Americans in the Add Health Study

Science.gov (United States)

Harris, Kathleen Mullan; Lee, Hedwig; DeLeone, Felicia Yang

2010-01-01

This article explores the relationships among early marriage (before age 26 years), cohabitation, and health for African Americans and Whites during the transition to adulthood using the National Longitudinal Study of Adolescent Health (Add Health). The study examines three categories of health outcomes relevant to young adulthood: physical…

78 FR 17624 - Wireline Competition Bureau Adds New Discussion Topic To Connect America Cost Model Virtual Workshop

Science.gov (United States)

2013-03-22

... Competition Bureau Adds New Discussion Topic To Connect America Cost Model Virtual Workshop AGENCY: Federal... a new virtual workshop discussion topic, entitled ``Rate of Return for Connect America Cost Model,'' to seek public input on what cost of money should be utilized in the forward-looking cost model that...

78 FR 23192 - Wireline Competition Bureau Adds New Discussion Topic to Connect America Cost Model Virtual Workshop

Science.gov (United States)

2013-04-18

... Competition Bureau Adds New Discussion Topic to Connect America Cost Model Virtual Workshop AGENCY: Federal... be filed by posting comments at http://www.fcc.gov/blog/wcb-cost-model-virtual-workshop-2012 . [ssquf....gov/blog/wcb-cost-model-virtual-workshop-2012 . 1. On Tuesday, October 9, 2012, the Wireline...

Application of quality by design approach to optimize process and formulation parameters of rizatriptan loaded chitosan nanoparticles

Directory of Open Access Journals (Sweden)

Ajinath Eknath Shirsat

2015-01-01

Full Text Available The purpose of present study was to optimize rizatriptan (RZT chitosan (CS nanoparticles using ionic gelation method by application of quality by design (QbD approach. Based on risk assessment, effect of three variables, that is CS %, tripolyphosphate % and stirring speed were studied on critical quality attributes (CQAs; particle size and entrapment efficiency. Central composite design (CCD was implemented for design of experimentation with 20 runs. RZT CS nanoparticles were characterized for particle size, polydispersity index, entrapment efficiency, in-vitro release study, differential scanning calorimetric, X-ray diffraction, scanning electron microscopy (SEM. Based on QbD approach, design space (DS was optimized with a combination of selected variables with entrapment efficiency > 50% w/w and a particle size between 400 and 600 nm. Validation of model was performed with 3 representative formulations from DS for which standard error of − 0.70-3.29 was observed between experimental and predicted values. In-vitro drug release followed initial burst release 20.26 ± 2.34% in 3-4 h with sustained drug release of 98.43 ± 2.45% in 60 h. Lower magnitude of standard error for CQAs confirms the validation of selected CCD model for optimization of RZT CS nanoparticles. In-vitro drug release followed dual mechanism via, diffusion and polymer erosion. RZT CS nanoparticles were prepared successfully using QbD approach with the understanding of the high risk process and formulation parameters involved and optimized DS with a multifactorial combination of critical parameters to obtain predetermined RZT loaded CS nanoparticle specifications.

Acupuncture and related therapies used as add-on or alternative to prokinetics for functional dyspepsia: overview of systematic reviews and network meta-analysis.

Science.gov (United States)

Ho, Robin S T; Chung, Vincent C H; Wong, Charlene H L; Wu, Justin C Y; Wong, Samuel Y S; Wu, Irene X Y

2017-09-04

Prokinetics for functional dyspepsia (FD) have relatively higher number needed to treat values. Acupuncture and related therapies could be used as add-on or alternative. An overview of systematic reviews (SRs) and network meta-analyses (NMA) were performed to evaluate the comparative effectiveness of different acupuncture and related therapies. We conducted a comprehensive literature search for SRs of randomized controlled trials (RCTs) in eight international and Chinese databases. Data from eligible RCTs were extracted for random effect pairwise meta-analyses. NMA was used to explore the most effective treatment among acupuncture and related therapies used alone or as add-on to prokinetics, compared to prokinetics alone. From five SRs, 22 RCTs assessing various acupuncture and related therapies were included. No serious adverse events were reported. Two pairwise meta-analyses showed manual acupuncture has marginally stronger effect in alleviating global FD symptoms, compared to domperidone or itopride. Results from NMA showed combination of manual acupuncture and clebopride has the highest probability in alleviating patient reported global FD symptom. Combination of manual acupuncture and clebopride has the highest probability of being the most effective treatment for FD symptoms. Patients who are contraindicated for prokinetics may use manual acupuncture or moxibustion as alternative. Future confirmatory comparative effectiveness trials should compare clebopride add-on manual acupuncture with domperidone add-on manual acupuncture and moxibustion.

High-Power Collective Charging of a Solid-State Quantum Battery

Science.gov (United States)

Ferraro, Dario; Campisi, Michele; Andolina, Gian Marcello; Pellegrini, Vittorio; Polini, Marco

2018-03-01

Quantum information theorems state that it is possible to exploit collective quantum resources to greatly enhance the charging power of quantum batteries (QBs) made of many identical elementary units. We here present and solve a model of a QB that can be engineered in solid-state architectures. It consists of N two-level systems coupled to a single photonic mode in a cavity. We contrast this collective model ("Dicke QB"), whereby entanglement is genuinely created by the common photonic mode, to the one in which each two-level system is coupled to its own separate cavity mode ("Rabi QB"). By employing exact diagonalization, we demonstrate the emergence of a quantum advantage in the charging power of Dicke QBs, which scales like √{N } for N ≫1 .

Computational study of the combustion and atmospheric decomposition of 2-methylfuran

KAUST Repository

Davis, Alexander C.; Sarathy, Mani

2013-01-01

methods, G4 and CBS-QB3, to determine the bond dissociation energies for the C-H bond in 2MF and the reaction enthalpies and barrier heights of several of the known possible initiation reaction pathways. This study also investigates the possible subsequent

Rapid response to methylphenidate as an add-on therapy to mirtazapine in the treatment of major depressive disorder in terminally ill cancer patients: a four-week, randomized, double-blinded, placebo-controlled study.

Science.gov (United States)

Ng, Chong Guan; Boks, Marco P M; Roes, Kit C B; Zainal, Nor Zuraida; Sulaiman, Ahmad Hatim; Tan, Seng Beng; de Wit, Niek J

2014-04-01

This is a 4 week, randomized, double-blind, placebo-controlled study to examine the effects of methylphenidate as add-on therapy to mirtazapine compared to placebo for treatment of depression in terminally ill cancer patients. It involved 88 terminally ill cancer patients from University of Malaya Medical Centre, Kuala Lumpur, Malaysia. They were randomized and treated with either methylphenidate or placebo as add on to mirtazapine. The change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 3 was analyzed by linear regression. Changes of MADRS and Clinical Global Impression-Severity Scale (CGI-S) over 28 days were analyzed using mixed model repeated measures (MMRM). Secondary analysis of MADRS response rates, defined as 50% or more reduction from baseline score. A significantly larger reduction of Montgomery-Åsberg Depression Rating Scale (MADRS) score in the methylphenidate group was observed from day 3 (B=4.14; 95% CI=1.83-6.45). Response rate (defined as 50% or more reduction from baseline MADRS score) in the methylphenidate treated group was superior from day 14. Improvement in Clinical Global Impression-Severity Scale (CGI-S) was greater in the methylphenidate treated group from day 3 until day 28. The drop-out rates were 52.3% in the methylphenidate group and 59.1% in the placebo group (relative risk=0.86, 95%CI=0.54-1.37) due to cancer progression. Nervous system adverse events were more common in methylphenidate treated subjects (20.5% vs 9.1%, p=0.13). In conclusions, methylphenidate as add on therapy to mirtazapine demonstrated an earlier antidepressant response in terminally ill cancer patients, although at an increased risk of the nervous system side effects. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Quality by design in the chiral separation strategy for the determination of enantiomeric impurities: development of a capillary electrophoresis method based on dual cyclodextrin systems for the analysis of levosulpiride.

Science.gov (United States)

Orlandini, S; Pasquini, B; Del Bubba, M; Pinzauti, S; Furlanetto, S

2015-02-06

Quality by design (QbD) concepts, in accordance with International Conference on Harmonisation Pharmaceutical Development guideline Q8(R2), represent an innovative strategy for the development of analytical methods. In this paper QbD principles have been comprehensively applied in the set-up of a capillary electrophoresis method aimed to quantify enantiomeric impurities. The test compound was the chiral drug substance levosulpiride (S-SUL) and the developed method was intended to be used for routine analysis of the pharmaceutical product. The target of analytical QbD approach is to establish a design space (DS) of critical process parameters (CPPs) where the critical quality attributes (CQAs) of the method have been assured to fulfil the desired requirements with a selected probability. QbD can improve the understanding of the enantioseparation process, including both the electrophoretic behavior of enantiomers and their separation, therefore enabling its control. The CQAs were represented by enantioresolution and analysis time. The scouting phase made it possible to select a separation system made by sulfated-β-cyclodextrin and a neutral cyclodextrin, operating in reverse polarity mode. The type of neutral cyclodextrin was included among other CPPs, both instrumental and related to background electrolyte composition, which were evaluated in a screening phase by an asymmetric screening matrix. Response surface methodology was carried out by a Doehlert design and allowed the contour plots to be drawn, highlighting significant interactions between some of the CPPs. DS was defined by applying Monte-Carlo simulations, and corresponded to the following intervals: sulfated-β-cyclodextrin concentration, 9-12 mM; methyl-β-cyclodextrin concentration, 29-38 mM; Britton-Robinson buffer pH, 3.24-3.50; voltage, 12-14 kV. Robustness of the method was examined by a Plackett-Burman matrix and the obtained results, together with system repeatability data, led to define a method

Difluorophosphoryl nitrene F2P(O)N: matrix isolation and unexpected rearrangement to F2PNO.

Science.gov (United States)

Zeng, Xiaoqing; Beckers, Helmut; Willner, Helge; Neuhaus, Patrik; Grote, Dirk; Sander, Wolfram

2009-12-14

Triplet difluorophosphoryl nitrene F(2)P(O)N (X(3)A'') was generated on ArF excimer laser irradiation (lambda=193 nm) of F(2)P(O)N(3) in solid argon matrix at 16 K, and characterized by its matrix IR, UV/Vis, and EPR spectra, in combination with DFT and CBS-QB3 calculations. On visible light irradiation (lambda>420 nm) at 16 K F(2)P(O)N reacts with molecular nitrogen and some of the azide is regenerated. UV irradiation (lambda=255 nm) of F(2)P(O)N (X(3)A'') induced a Curtius-type rearrangement, but instead of a 1,3-fluorine shift, nitrogen migration to give F(2)PON is proposed to be the first step of the photoisomerization of F(2)P(O)N into F(2)PNO (difluoronitrosophosphine). Formation of novel F(2)PNO was confirmed with (15)N- and (18)O-enriched isotopomers by IR spectroscopy and DFT calculations. Theoretical calculations predict a rather long P-N bond of 1.922 A [B3LYP/6-311+G(3df)] and low bond-dissociation energy of 76.3 kJ mol(-1) (CBS-QB3) for F(2)PNO.

Trainees May Add Value to Patient Care by Decreasing Addendum Utilization in Radiology Reports.

Science.gov (United States)

Balthazar, Patricia; Konstantopoulos, Christina; Wick, Carson A; DeSimone, Ariadne K; Tridandapani, Srini; Simoneaux, Stephen; Applegate, Kimberly E

2017-11-01

The purpose of this study was to evaluate the impact of trainee involvement and other factors on addendum rates in radiology reports. This retrospective study was performed in a tertiary care pediatric hospital. From the institutional radiology data repository, we extracted all radiology reports from January 1 to June 30, 2016, as well as trainee (resident or fellow) involvement, imaging modality, patient setting (emergency, inpatient, or outpatient), order status (routine vs immediate), time of interpretation (regular work hours vs off-hours), radiologist's years of experience, and sex. We grouped imaging modalities as advanced (CT, MRI, and PET) or nonadvanced (any modality that was not CT, MRI, or PET) and radiologist experience level as ≤ 20 years or > 20 years. Our outcome measure was the rate of addenda in radiology reports. Statistical analysis was performed using multivariate logistic regression. From 129,033 reports finalized during the study period, 418 (0.3%) had addenda. Reports generated without trainees were 12 times more likely than reports with trainee involvement to have addenda (odds ratio [OR] = 12.2, p use (OR = 4.7, p use than those in an inpatient setting (OR = 1.5, p = 0.04; and OR = 1.3, p = 0.04, respectively). Routine orders had a slightly higher likelihood of addendum use compared with immediate orders (OR = 1.3, p = 0.01). We found no difference in addendum use by radiologist's sex, radiologist's years of experience, emergency versus outpatient setting, or time of interpretation. Trainees may add value to patient care by decreasing addendum rates in radiology reports.

Interaction and dynamics of add-atoms with 2-dimensional structures

CERN Multimedia

The interaction and dynamics of add-atoms with graphene, graphene-derivate structures and, later, MoSi$_2$, two-dimensional – single and few – atomic layers will be studied with the Perturbed Angular Correlation – PAC – technique. Graphene is also envisaged as new platform for growing semiconductor nanostructure devices, such as quantum dots and as a particularly powerful catalyst. Understanding nucleation of nanostructures and clusters on graphene and related phases in wet conditions as they are used in chemical methods in research and industry require complementary studies. These systems will therefore be studied systematically using radioactive probe atoms attaching via a transfer media (e.g., water in catalysis process) or being deposited with soft-landing techniques under vacuum and UHV conditions, as put in place at the ASPIC setup at ISOLDE. The hyperfine fields obtained under different environments are expected to reveal basic information on the rich atomic and physical mechanisms associated w...

The COMT Val158Met Polymorphism Is Associated With Response to Add-on Dextromethorphan Treatment in Bipolar Disorder.

Science.gov (United States)

Lee, Sheng-Yu; Chen, Shiou-Lan; Wang, Tzu-Yun; Chang, Yun-Hsuan; Chen, Po See; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Liang-Jen; Lee, I Hui; Chen, Kao Ching; Yang, Yen Kuang; Lu, Ru-Band

2017-02-01

We previously conducted a randomized, double-blind, controlled, 12-week study evaluating the effect of add-on dextromethorphan (DM), a noncompetitive N-methyl-D-aspartate receptor antagonist, on patients with bipolar disorder (BD) treated using valproate (VPA), which showed negative clinical differences. The genetic variation between each individual may be responsible for interindividual differences. The catechol-O-methyltransferase (COMT) gene has been a candidate gene for BD. In the current study, we investigated whether the COMT Val158Met polymorphism predicts treatment response to VPA + add-on DM and to VPA + placebo. Patients with BD (n = 309) undergoing regular VPA treatments were randomly assigned to groups given either add-on DM (30 mg/d) (n = 102), DM (60 mg/d) (n = 101), or placebo (n = 106) for 12 weeks. The Hamilton Depression Rating Scale and Young Mania Rating Scale were used to evaluate clinical response during weeks 0, 1, 2, 4, 8, and 12. The genotypes of the COMT Val158Met polymorphism were determined using polymerase chain reaction plus restriction fragment length polymorphism analysis. To adjust for within-subject dependence over repeated assessments, multiple linear regression with generalized estimating equation methods was used. When stratified by the COMT Val158Met genotypes, significantly greater decreases in Hamilton Depression Rating Scale scores were found in the VPA + DM (30 mg/d) group in patients with the Val/Met genotype (P = 0.008). We conclude that the COMT Val158Met polymorphism may influence responses to DM (30 mg/d) by decreasing depressive symptoms in BD patients.

78 FR 38265 - Wireline Competition Bureau Adds Two New Discussion Topics to Connect America Cost Model Virtual...

Science.gov (United States)

2013-06-26

... Competition Bureau Adds Two New Discussion Topics to Connect America Cost Model Virtual Workshop AGENCY... comments in this proceeding to be filed by posting comments at http://www.fcc.gov/blog/wcb-cost-model... via the Internet at http://www.fcc.gov/blog/wcb-cost-model-virtual-workshop-2012 . 1. On Tuesday...

All-Optical Regenerative OTDM Add-Drop Multiplexing at 40 Gb/s using Monolithic InP Mach-Zehnder Interferometer

DEFF Research Database (Denmark)

Fischer, St.; Dülk, M.; Gamper, E.

2000-01-01

We present a novel method for all-optical add-drop multiplexing having regenerative capability for 40-Gb/s optical time-division multiplexed (OTDM) data using a semiconductor optical amplifier (SOA) based, monolithic Mach-Zehnder interferometer (MZI). Simultaneous dropping of one 10-Gb/s channel ...

A practical method for three-dimensional reconstruction of joints using a C-arm system and shift-and-add algorithm

International Nuclear Information System (INIS)

Li Senhu; Jiang Huabei

2005-01-01

Currently, radiography with C-arm systems is playing a major role in the assessment of arthritis. However, the radiographic two-dimensional projection images of joints often interfere with physicians' efforts to better understand and measure the structure changes of joints due to the overlap of bone structures at different depths. An accurate, low-cost, and practical three-dimensional (3D) reconstruction approach of joints will be beneficial in diagnosing arthritis. Toward this end, a novel method is developed in this paper based on a C-arm system. The idea is to apply the shift-and-add algorithm (commonly used in digital tomosynthesis) on the segmented projection images at multiple angles, which results in accurate reconstruction of the 3D structures of joints. The method provides a new solution to precisely distinguish objects from blurring background. The proposed method has been tested and evaluated on simulated cylinders, a chicken bone phantom with known structure, and an in vivo human index finger. The results are demonstrated and discussed

HANSF 1.3 user's manual; TOPICAL

International Nuclear Information System (INIS)

PLYS, M.G.

1999-01-01

The HANSF analysis tool is an integrated model considering phenomena inside a multi-canister overpack (MCO) spent nuclear fuel container such as fuel oxidation, convective and radiative heat transfer, and the potential for fission product release. It may be used for all phases of spent fuel disposition including cold vacuum drying, transportation, and storage. This manual reflects HANSF version 1.3, a revised version of version 1.2a. HANSF 1.3 was written to add new models for axial nodalization, add new features for ease of usage, and correct errors. HANSF 1.3 is intended for use on personal computers such as IBM-compatible machines with Intel processors running under a DOS-type operating system. HANSF 1.3 is known to compile under Lahey TI and Digital Visual FORTRAN, Version 6.0, but this does not preclude operation in other environments

Lacosamide as add-on treatment of focal symptomatic epilepsy in a patient with alcoholic liver cirrhosis

Directory of Open Access Journals (Sweden)

A. Romigi

2014-01-01

Full Text Available The occurrence of epileptic seizures in the presence of hepatic disease is not uncommon in clinical practice. Selecting an appropriate AED for patients affected by liver failure who have new-onset epileptic seizures can be challenging. We describe a 64-year-old man affected by liver cirrhosis. The patient developed partial epilepsy with secondary generalization because of an intracerebral hemorrhage in the left parieto-occipital regions. After the neurosurgery procedure, seizures reappeared and were initially managed with levetiracetam. After one month, the patient experienced clusters of seizures while on stable treatment with levetiracetam. Pregabalin as add-on was not tolerated; therefore, he received a low dose of phenobarbital as add-on treatment. The patient developed hepatic encephalopathy. Phenobarbital was immediately stopped, and oral lacosamide was added. A rapid recovery of encephalopathy with a 6-month seizure freedom was obtained. The patient died 6 months later because of progressive impairment of liver function. Lacosamide may represent an alternative to other AEDs in patients with liver failure; however, further prospective evaluation of its efficacy and safety in this clinical setting is needed.

Cost-effectiveness of add-on treatments to metformin in a Swedish setting: liraglutide vs sulphonylurea or sitagplitin.

Science.gov (United States)

Steen Carlsson, Katarina; Persson, Ulf

2014-09-01

To evaluate long-run cost-effectiveness in a Swedish setting for liraglutide compared with sulphonylureas (glimepiride) or sitagliptin, all as add-on to metformin for patients with type 2 diabetes insufficiently controlled with metformin in monotherapy. The IHE Cohort Model of Type 2 Diabetes was used to evaluate clinical and economic outcomes from a societal perspective. Model input data were obtained from two clinical trials, the Swedish National Diabetes Register and the literature. Cost data reflected year 2013 price level. The robustness of results was checked with one-way-sensitivity analysis and probability sensitivity analysis. The cost per QALY gained for liraglutide (1.2 mg) compared to SU (glimepiride 4 mg), both as add-on to metformin, ranged from SEK 226,000 to SEK 255,000 in analyzed patient cohorts. The cost per QALY for liraglutide (1.2 mg) vs sitagliptin (100 mg) as second-line treatment was lower, ranging from SEK 149,000 to SEK 161,000. Costs of preventive treatment were driving costs, but there was also a cost offset from reduced costs of complications of ∼ 20%. Notable cost differences were found for nephropathy, stroke, and heart failure. The predicted life expectancy with liraglutide increased the cost of net consumption for liraglutide. The analysis was an ex-ante analysis using model input data from clinical trials which may not reflect effectiveness in real-world clinical practice in broader patient populations. This limitation was explored in the sensitivity analysis. The lack of specific data on loss of production due to diabetes complications implied that these costs may be under-estimated. Treatment strategies with liraglutide 1.2 mg improved the expected quality-of-life and increased costs when compared to SU and to sitagliptin for second-line add-on treatments. The cost per QALY for liraglutide was in the range considered medium by Swedish authorities.

N-Acetylcysteine in the Treatment of Pediatric Trichotillomania: A Randomized, Double-Blind, Placebo-Controlled Add-On Trial

Science.gov (United States)

Bloch, Michael H.; Panza, Kaitlyn E.; Grant, Jon E.; Pittenger, Christopher; Leckman, James F.

2013-01-01

Objective: To examine the efficacy of N-acetylcysteine (NAC) for the treatment of pediatric trichotillomania (TTM) in a double-blind, placebo-controlled, add-on study. Method: A total of 39 children and adolescents aged 8 to 17 years with pediatric trichotillomania were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary…

Lixisenatide as add-on therapy to basal insulin

Directory of Open Access Journals (Sweden)

Brown DX

2013-12-01

Full Text Available Dominique Xavier Brown, Emma Louise Butler, Marc Evans Diabetes Department, University Hospital Llandough, Cardiff, UK Abstract: Many patients with type 2 diabetes mellitus do not achieve target glycosylated hemoglobin A1c levels despite optimally titrated basal insulin and satisfactory fasting plasma glucose levels. Current evidence suggests that HbA1c levels are dictated by both basal glucose and postprandial glucose levels. This has led to a consensus that postprandial glucose excursions contribute to poor glycemic control in these patients. Lixisenatide is a once-daily, prandial glucagon-like peptide 1 (GLP-1 receptor agonist with a four-fold affinity for the GLP-1 receptor compared with native GLP-1. Importantly, lixisenatide causes a significant delay in gastric emptying time, an important determinant of the once-daily dosing regimen. An exendin-4 mimetic with six lysine residues removed at the C-terminal, lixisenatide has pronounced postprandial glucose-lowering effects, making it a novel incretin agent for use in combination with optimally titrated basal insulin. Lixisenatide exerts profound effects on postprandial glucose through established mechanisms of glucose-dependent insulin secretion and glucagon suppression in combination with delayed gastric emptying. This review discusses the likely place that lixisenatide will occupy in clinical practice, given its profound effects on postprandial glucose and potential to reduce glycemic variability. Keywords: lixisenatide, add-on therapy, insulin, GLP-1 receptor agonist, postprandial glucose, pharmacodynamics

Theophylline as an add-on to thrombolytic therapy in acute ischaemic stroke (TEA-Stroke)

DEFF Research Database (Denmark)

Modrau, Boris; Hjort, Niels; Østergaard, Leif

2016-01-01

the collateral supply in acute ischaemic brain tissue and thus facilitate reperfusion despite proximal vessel occlusion. The primary study objective is to evaluate whether theophylline is safe and efficient in acute ischaemic stroke patients as an add-on to thrombolytic therapy.MethodsThe TEA-Stroke Trial...... models, clinical case series and randomized clinical trials are controversial. A Cochrane analysis from 2004 concluded that there was not enough evidence to assess whether theophylline is safe and improves outcomes in patients with acute ischaemic stroke. The TEA-Stroke Trial will clarify whether...

Development of 8K-MCA Add-on based on FPGA technique with a control of VB6 software application under windows environment

International Nuclear Information System (INIS)

Dang Lanh; Nguyen Nhi Dien; Nguyen Xuan Hai; Nguyen Bach Viet; Pham Ngoc Son; Huynh Minh; Vuong Huu Tan; Pham Dinh Khang; Phan Nam Anh

2003-01-01

The multichannel analyzer is the heart of most experimental measurements. Today, it becomes popular and convenient. It can play a role of getting, processing data and easily interfacing to PC. Some standard-alone multichannel analysis systems can be replaced by Add-on MCA card. Especially, MCA card is necessary for application in nuclear physics research. The main aim of this sub-project is to focus on a design and construction of an 8K-MCA Add-on served for studying nuclear structure, for development of Gamma spectroscopy system, and for a production of low-cost electronics instruments as well. Some experimental results were obtained through the aforementioned card combining with other needed functional analog units. A multichannel data processing (MCD) circuit for nuclear spectroscopy application was developed using a field programmable gate arrays (FPGA) as the central processing element. In addition to the first role, A 13-bit analog-to-digital converter (8k ADC) circuit for nuclear spectroscopy application was also developed using a successive approximation ADC with a control of FPGA technology. The FPGA operates a program that builds the distributed functions of data collected by the ADC and then corrects the ADC differential non-linearity (DNL) via the sliding scale method. The acquisition routine runs in 3.7μ s. the conversion time is approximated 2.2μ s, and the integral non-linearity ≤ 0.14%. (author)

MolPrint3D: Enhanced 3D Printing of Ball-and-Stick Molecular Models

Science.gov (United States)

Paukstelis, Paul J.

2018-01-01

The increased availability of noncommercial 3D printers has provided instructors and students improved access to printing technology. However, printing complex ball-and-stick molecular structures faces distinct challenges, including the need for support structures that increase with molecular complexity. MolPrint3D is a software add-on for the…

Structural studies of cyclic ureas: 3. Enthalpy of formation of barbital

International Nuclear Information System (INIS)

Ribeiro da Silva, Maria das Dores M.C.; Ribeiro da Silva, Manuel A.V.; Freitas, Vera L.S.; Roux, Maria Victoria; Jimenez, Pilar; Temprado, Manuel; Davalos, Juan Z.; Cabildo, Pilar; Claramunt, Rosa M.; Elguero, Jose

2009-01-01

A thermochemical and thermophysical study has been carried out for crystalline barbital [5,5'-diethylbarbituric acid]. The thermochemical study was made by static bomb combustion calorimetry, from which the standard (p 0 =0.1MPa) molar enthalpy of formation of the crystalline barbital, at T = 298.15 K, was derived as -(753.0 ± 1.8) kJ . mol -1 . The thermophysical study was made by differential scanning calorimetry over the temperature interval (265 to 470) K. A solid-solid phase transition was found at T = 413.3 K. The vapour pressures of the crystalline barbital were measured at several temperatures between T = (355 and 377) K, by the Knudsen mass-loss effusion technique, from which the standard molar enthalpy of sublimation, at T = 298.15 K was derived as (117.3 ± 0.6) kJ . mol -1 . The combination of the experimental results yielded the standard molar enthalpy of formation of barbital in the gaseous phase, at T = 298.15 K, as -(635.8 ± 1.9) kJ . mol -1 . This value is compared and discussed with our theoretical calculations by several methods (Gaussian-n theories G2 and G3, complete basis set CBS-QB3, density functional B3P86 and B3LYP) by means of atomization and isodesmic reaction schemes.

The Add-On Effect of Solifenacin for Patients with Remaining Overactive Bladder after Treatment with Tamsulosin for Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Obstruction

Directory of Open Access Journals (Sweden)

Naoya Masumori

2010-01-01

Full Text Available Objectives. To investigate the add-on effect of solifenacin for Japanese men with remaining overactive bladder (OAB symptoms after tamsulosin monotherapy for lower urinary tract symptoms (LUTS suggestive of benign prostatic obstruction (BPO in real-life clinical practice. Methods. Patients aged ≥ 50 having remaining OAB symptoms (≥ 3 of OAB symptom score (OABSS with ≥2 of urgency score after at least 4 weeks treatment by 0.2 mg of tamsulosin for BPO/LUTS received 2.5 or 5.0 mg of solifenacin for 12 weeks. The International Prostate Symptom Score (IPSS, QOL index and OABSS, maximum flow rate (Qmax and postvoid residual urine volume (PVR were determined. Results. A total of 48 patients (mean age 72.5 years completed the study. There were significant improvement in IPSS (15.1 to 11.2 and QOL index (4.2 to 3.0 by add-on of solifenacin. Although the IPSS storage symptom score was significantly improved, there were no changes observed in the IPSS voiding symptom score. The OABSS showed significant improvement (8.0 to 4.8. No changes were observed in Qmax and PVR. Conclusions. Under the supervision of an experienced urologist, the additional administration of solifenacin to patients with BPO/LUTS treated with tamsulosin, is effective in controlling remaining OAB symptoms.

US adolescents' friendship networks and health risk behaviors: a systematic review of studies using social network analysis and Add Health data.

Science.gov (United States)

Jeon, Kwon Chan; Goodson, Patricia

2015-01-01

Background. Documented trends in health-related risk behaviors among US adolescents have remained high over time. Studies indicate relationships among mutual friends are a major influence on adolescents' risky behaviors. Social Network Analysis (SNA) can help understand friendship ties affecting individual adolescents' engagement in these behaviors. Moreover, a systematic literature review can synthesize findings from a range of studies using SNA, as well as assess these studies' methodological quality. Review findings also can help health educators and promoters develop more effective programs. Objective. This review systematically examined studies of the influence of friendship networks on adolescents' risk behaviors, which utilized SNA and the Add Health data (a nationally representative sample). Methods. We employed the Matrix Method to synthesize and evaluate 15 published studies that met our inclusion and exclusion criteria, retrieved from the Add Health website and 3 major databases (Medline, Eric, and PsycINFO). Moreover, we assigned each study a methodological quality score (MQS). Results. In all studies, friendship networks among adolescents promoted their risky behaviors, including drinking alcohol, smoking, sexual intercourse, and marijuana use. The average MQS was 4.6, an indicator of methodological rigor (scale: 1-9). Conclusion. Better understanding of risky behaviors influenced by friends can be useful for health educators and promoters, as programs targeting friendships might be more effective. Additionally, the overall MQ of these reviewed studies was good, as average scores fell above the scale's mid-point.

US adolescents’ friendship networks and health risk behaviors: a systematic review of studies using social network analysis and Add Health data

Directory of Open Access Journals (Sweden)

Kwon Chan Jeon

2015-06-01

Full Text Available Background. Documented trends in health-related risk behaviors among US adolescents have remained high over time. Studies indicate relationships among mutual friends are a major influence on adolescents’ risky behaviors. Social Network Analysis (SNA can help understand friendship ties affecting individual adolescents’ engagement in these behaviors. Moreover, a systematic literature review can synthesize findings from a range of studies using SNA, as well as assess these studies’ methodological quality. Review findings also can help health educators and promoters develop more effective programs.Objective. This review systematically examined studies of the influence of friendship networks on adolescents’ risk behaviors, which utilized SNA and the Add Health data (a nationally representative sample.Methods. We employed the Matrix Method to synthesize and evaluate 15 published studies that met our inclusion and exclusion criteria, retrieved from the Add Health website and 3 major databases (Medline, Eric, and PsycINFO. Moreover, we assigned each study a methodological quality score (MQS.Results. In all studies, friendship networks among adolescents promoted their risky behaviors, including drinking alcohol, smoking, sexual intercourse, and marijuana use. The average MQS was 4.6, an indicator of methodological rigor (scale: 1–9.Conclusion. Better understanding of risky behaviors influenced by friends can be useful for health educators and promoters, as programs targeting friendships might be more effective. Additionally, the overall MQ of these reviewed studies was good, as average scores fell above the scale’s mid-point.

15 CFR 19.5 - How will Commerce entities add interest, penalty charges, and administrative costs to a Commerce...

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false How will Commerce entities add interest, penalty charges, and administrative costs to a Commerce debt? 19.5 Section 19.5 Commerce and Foreign Trade Office of the Secretary of Commerce COMMERCE DEBT COLLECTION Procedures To Collect Commerce...

Meeting the food, energy, and water demands of nine billion people: Will climate change add a new dimension?

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Climate change will add a new stress to our ability to produce food and supply water and energy for the expanding population. There is an emerging gap between the current production trends in food commodities around the world and the projected needs to meet the demands for the world population. This...

Does Size Really Matter? How Quality Should be Analyzed for the Acquisition Workforce

Science.gov (United States)

2012-12-20

Five Factor Model ( FFM ) of personality. Five traits, also known as = = ^Åèìáëáíáçå=oÉëÉ~êÅÜ=mêçÖê~ã= do^ar^qb=p`elli=lc=_rpfkbpp=C=mr_if`=mlif`v...13 - k^s^i=mlpqdo^ar^qb=p`elli= the Big 5, comprise the FFM : emotional stability, extraversion, openness to experience, agreeableness, and

The loss of NH2O from the N-hydroxyacetamide radical cation CH3C(O)NHOH+

Science.gov (United States)

Jobst, Karl J.; Burgers, Peter C.; Ruttink, Paul J. A.; Terlouw, Johan K.

2006-08-01

A previous study [Ch. Lifshitz, P.J.A. Ruttink, G. Schaftenaar, J.K. Terlouw, Rapid Commun. Mass Spectrom. 1 (1987) 61] shows that metastable N-hydroxyacetamide ions CH3C(O)NHOH+ (HA-1) do not dissociate into CH3CO+ + NHOH by direct bond cleavage but rather yield CH3CO+ + NH2OE The tandem mass spectrometry based experiments of the present study on the isotopologue CH3C(O)NDOD+ reveal that the majority of the metastable ions lose the NH2O radical as NHDO rather than ND2O. A mechanistic analysis using the CBS-QB3 model chemistry shows that the molecular ions HA-1 rearrange into hydrogen-bridged radical cations [OCC(H2)H...N(H)OH]+ whose acetyl cation component then catalyses the transformation NHOH --> NH2O prior to dissociation. The high barrier for the unassisted 1,2-H shift in the free radical, 43 kcal mol-1, is reduced to a mere 7 kcal mol-1 for the catalysed transformation which can be viewed as a quid-pro-quo reaction involving two proton transfers.

HANSF 1.3 user's manual

Energy Technology Data Exchange (ETDEWEB)

PLYS, M.G.

1999-05-21

The HANSF analysis tool is an integrated model considering phenomena inside a multi-canister overpack (MCO) spent nuclear fuel container such as fuel oxidation, convective and radiative heat transfer, and the potential for fission product release. It may be used for all phases of spent fuel disposition including cold vacuum drying, transportation, and storage. This manual reflects HANSF version 1.3, a revised version of version 1.2a. HANSF 1.3 was written to add new models for axial nodalization, add new features for ease of usage, and correct errors. HANSF 1.3 is intended for use on personal computers such as IBM-compatible machines with Intel processors running under a DOS-type operating system. HANSF 1.3 is known to compile under Lahey TI and Digital Visual FORTRAN, Version 6.0, but this does not preclude operation in other environments.

Cost-effectiveness of exenatide twice daily vs insulin glargine as add-on therapy to oral antidiabetic agents in patients with type 2 diabetes in China.

Science.gov (United States)

Gu, Shuyan; Wang, Xiaoyong; Qiao, Qing; Gao, Weiguo; Wang, Jian; Dong, Hengjin

2017-12-01

To estimate the long-term cost-effectiveness of exenatide twice daily vs insulin glargine once daily as add-on therapy to oral antidiabetic agents (OADs) for Chinese patients with type 2 diabetes (T2DM). The Cardiff Diabetes Model was used to simulate disease progression and estimate the long-term effects of exenatide twice daily vs insulin glargine once daily. Patient profiles and treatment effects required for the model were obtained from literature reviews (English and Chinese databases) and from a meta-analysis of 8 randomized controlled trials comparing exenatide twice daily with insulin glargine once daily add-on to OADs for T2DM in China. Medical expenditure data were collected from 639 patients with T2DM (aged ≥18 years) with and without complications incurred between January 1, 2014 and December 31, 2015 from claims databases in Shandong, China. Costs (2014 Chinese Yuan [¥]) and benefits were estimated, from the payers' perspective, over 40 years at a discount rate of 3%. A series of sensitivity analyses were performed. Patients on exenatide twice daily + OAD had a lower predicted incidence of most cardiovascular and hypoglycaemic events and lower total costs compared with those on insulin glargine once daily + OAD. A greater number of quality-adjusted life years (QALYs; 1.94) at a cost saving of ¥117 706 gained was associated with exenatide twice daily vs insulin glargine once daily. (i.e. cost saving of ¥60 764/QALY) per patient. In Chinese patients with T2DM inadequately controlled by OADs, exenatide twice daily is a cost-effective add-on therapy alternative to insulin glargine once daily, and may address the problem of an excess of medical needs resulting from weight gain and hypoglycaemia in T2DM treatment. © 2017 John Wiley & Sons Ltd.

Do "premium" joint implants add value?: analysis of high cost joint implants in a community registry.

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Gioe, Terence J; Sharma, Amit; Tatman, Penny; Mehle, Susan

2011-01-01

Numerous joint implant options of varying cost are available to the surgeon, but it is unclear whether more costly implants add value in terms of function or longevity. We evaluated registry survival of higher-cost "premium" knee and hip components compared to lower-priced standard components. Premium TKA components were defined as mobile-bearing designs, high-flexion designs, oxidized-zirconium designs, those including moderately crosslinked polyethylene inserts, or some combination. Premium THAs included ceramic-on-ceramic, metal-on-metal, and ceramic-on-highly crosslinked polyethylene designs. We compared 3462 standard TKAs to 2806 premium TKAs and 868 standard THAs to 1311 premium THAs using standard statistical methods. The cost of the premium implants was on average approximately $1000 higher than the standard implants. There was no difference in the cumulative revision rate at 7-8 years between premium and standard TKAs or THAs. In this time frame, premium implants did not demonstrate better survival than standard implants. Revision indications for TKA did not differ, and infection and instability remained contributors. Longer followup is necessary to demonstrate whether premium implants add value in younger patient groups. Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Improving risk assessment of color additives in medical device polymers.

Science.gov (United States)

Chandrasekar, Vaishnavi; Janes, Dustin W; Forrey, Christopher; Saylor, David M; Bajaj, Akhil; Duncan, Timothy V; Zheng, Jiwen; Riaz Ahmed, Kausar B; Casey, Brendan J

2018-01-01

Many polymeric medical device materials contain color additives which could lead to adverse health effects. The potential health risk of color additives may be assessed by comparing the amount of color additive released over time to levels deemed to be safe based on available toxicity data. We propose a conservative model for exposure that requires only the diffusion coefficient of the additive in the polymer matrix, D, to be specified. The model is applied here using a model polymer (poly(ether-block-amide), PEBAX 2533) and color additive (quinizarin blue) system. Sorption experiments performed in an aqueous dispersion of quinizarin blue (QB) into neat PEBAX yielded a diffusivity D = 4.8 × 10 -10 cm 2  s -1 , and solubility S = 0.32 wt %. On the basis of these measurements, we validated the model by comparing predictions to the leaching profile of QB from a PEBAX matrix into physiologically representative media. Toxicity data are not available to estimate a safe level of exposure to QB, as a result, we used a Threshold of Toxicological Concern (TTC) value for QB of 90 µg/adult/day. Because only 30% of the QB is released in the first day of leaching for our film thickness and calculated D, we demonstrate that a device may contain significantly more color additive than the TTC value without giving rise to a toxicological concern. The findings suggest that an initial screening-level risk assessment of color additives and other potentially toxic compounds found in device polymers can be improved. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 310-319, 2018. © 2017 Wiley Periodicals, Inc.

Towards the implementation of quality by design to the production of therapeutic monoclonal antibodies with desired glycosylation patterns.

Science.gov (United States)

del Val, Ioscani Jimenez; Kontoravdi, Cleo; Nagy, Judit M

2010-01-01

Quality by design (QbD) is a scheme for the development, manufacture, and approval of pharmaceutical products. The end goal of QbD is to ensure product quality by building it into the manufacturing process. The main regulatory bodies are encouraging its implementation to the manufacture of all new pharmaceuticals including biological products. Monoclonal antibodies (mAbs) are currently the leading products of the biopharmaceutical industry. It has been widely reported that glycosylation directly influences the therapeutic mechanisms by which mAbs function in vivo. In addition, glycosylation has been identified as one of the main sources of monoclonal antibody heterogeneity, and thus, a critical parameter to follow during mAb manufacture. This article reviews the research on glycosylation of mAbs over the past 2 decades under the QbD scope. The categories presented under this scope are: (a) definition of the desired clinical effects of mAbs, (b) definition of the glycosylation-associated critical quality attributes (glycCQAs) of mAbs, (c) assessment of process parameters that pose a risk for mAb glycCQAs, and (d) methods for accurately quantifying glycCQAs of mAbs. The information available in all four areas leads us to conclude that implementation of QbD to the manufacture of mAbs with specific glycosylation patterns will be a reality in the near future. We also foresee that the implementation of QbD will lead to the development of more robust and efficient manufacturing processes and to a new generation of mAbs with increased clinical efficacy. Copyright © 2010 American Institute of Chemical Engineers (AIChE).

Acute effects of volume-oriented incentive spirometry on chest wall volumes in patients after a stroke.

Science.gov (United States)

Lima, Illia Ndf; Fregonezi, Guilherme Af; Melo, Rodrigo; Cabral, Elis Ea; Aliverti, Andrea; Campos, Tânia F; Ferreira, Gardênia Mh

2014-07-01

The aim of the present study was to assess how volume-oriented incentive spirometry applied to patients after a stroke modifies the total and compartmental chest wall volume variations, including both the right and left hemithoraces, compared with controls. Twenty poststroke patients and 20 age-matched healthy subjects were studied by optoelectronic plethysmography during spontaneous quiet breathing (QB), during incentive spirometry, and during the recovery period after incentive spirometry. Incentive spirometry was associated with an increased chest wall volume measured at the pulmonary rib cage, abdominal rib cage and abdominal compartment (P = .001) and under 3 conditions (P spirometry, and postincentive spirometry, respectively. Under all 3 conditions, the contribution of the abdominal compartment to VT was greater in the stroke subjects (54.1, 43.2, and 48.9%) than in the control subjects (43.7, 40.8, and 46.1%, P = .039). In the vast majority of subjects (13/20 and 18/20 during QB and incentive spirometry, respectively), abdominal expansion precedes rib cage expansion during inspiration. Greater asymmetry between the right and left hemithoracic expansions occurred in stroke subjects compared with control subjects, but it decreased during QB (62.5%, P = .002), during incentive spirometry (19.7%), and postincentive spirometry (67.6%, P = .14). Incentive spirometry promotes increased expansion in all compartments of the chest wall and reduces asymmetric expansion between the right and left parts of the pulmonary rib cage; therefore, it should be considered as a tool for rehabilitation. Copyright © 2014 by Daedalus Enterprises.

Role of Knowledge Management in Development and Lifecycle Management of Biopharmaceuticals.

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Rathore, Anurag S; Garcia-Aponte, Oscar Fabián; Golabgir, Aydin; Vallejo-Diaz, Bibiana Margarita; Herwig, Christoph

2017-02-01

Knowledge Management (KM) is a key enabler for achieving quality in a lifecycle approach for production of biopharmaceuticals. Due to the important role that it plays towards successful implementation of Quality by Design (QbD), an analysis of KM solutions is needed. This work provides a comprehensive review of the interface between KM and QbD-driven biopharmaceutical production systems as perceived by academic as well as industrial viewpoints. A comprehensive set of 356 publications addressing the applications of KM tools to QbD-related tasks were screened and a query to gather industrial inputs from 17 major biopharmaceutical organizations was performed. Three KM tool classes were identified as having high relevance for biopharmaceutical production systems and have been further explored: knowledge indicators, ontologies, and process modeling. A proposed categorization of 16 distinct KM tool classes allowed for the identification of holistic technologies supporting QbD. In addition, the classification allowed for addressing the disparity between industrial and academic expectations regarding the application of KM methodologies. This is a first of a kind attempt and thus we think that this paper would be of considerable interest to those in academia and industry that are engaged in accelerating development and commercialization of biopharmaceuticals.

Cost-effectiveness analysis of exenatide twice daily (BID) vs insulin glargine once daily (QD) as add-on therapy in Chinese patients with Type 2 diabetes mellitus inadequately controlled by oral therapies.

Science.gov (United States)

Deng, Jing; Gu, Shuyan; Shao, Hui; Dong, Hengjin; Zou, Dajin; Shi, Lizheng

2015-01-01

To estimate cost-effectiveness of exenatide twice daily (BID) vs insulin glargine once daily (QD) as add-on therapy in Chinese type 2 diabetes patients not well controlled by oral anti-diabetic (OAD) agents. The Cardiff model was populated with data synthesized from three head-to-head randomized clinical trials of up to 30 weeks in China comparing exenatide BID vs insulin glargine as add-on therapies to oral therapies in the Chinese population. The Cardiff model generated outputs including macrovascular and microvascular complications, diabetes-specific mortality, costs, and quality-adjusted life years (QALYs). Cost and QALYs were estimated with a time horizon of 40 years at a discount rate of 3% from a societal perspective. Compared with insulin glargine plus OAD treatments, patients on exenatide BID plus OAD gained 1.88 QALYs, at an incremental cost saving of Chinese Renminbi (RMB) 114,593 (i.e., cost saving of RMB 61078/QALY). The cost-effectiveness results were robust to various sensitivity analyses including probabilistic sensitivity analysis. The variables with the most impact on incremental cost-effectiveness ratio included HbA1c level at baseline, health utilities decrement, and BMI at baseline. Compared with insulin glargine QD, exenatide BID as add-on therapy to OAD is a cost-effective treatment in Chinese patients inadequately controlled by OAD treatments.

40 CFR Table 1 to Subpart IIIi of... - Operating Limits for Capture Systems and Add-On Control Devices

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Operating Limits for Capture Systems... 63—Operating Limits for Capture Systems and Add-On Control Devices If you are required to comply with operating limits by § 63.3093, you must comply with the applicable operating limits in the following table...

Porting and using PanGIA for Cytoscape 3: challenges and solutions [v1; ref status: indexed, http://f1000r.es/3r3

Directory of Open Access Journals (Sweden)

David Welker

2014-07-01

Full Text Available Much of the biologically significant functionality in Cytoscape is contained within third-party add-ons, called plugins in Cytoscape 2 and apps in Cytoscape 3. In the transition from Cytoscape 2 to Cystoscape 3, some of the underlying assumptions upon which plugins relied changed, requiring a significant porting effort for plugins to work as Cytoscape 3 apps. PanGIA is a Cytoscape add-on (http://apps.cytoscape.org/apps/pangia designed to analyze and visualize genetic interaction data in light of physical interaction data. In order to convert the PanGIA plugin to an app, various challenges, including those related to a transformed data model, concurrency, and randomization had to be overcome. In the process, the ability to control randomization was added to the GUI, a feature which was not only integral to the porting process, but which also ensures more easily reproducible scientific analysis for PanGIA users. Most authors of Cytoscape 2 plugins will face similar challenges porting their software to work with Cytoscape 3, and this paper gives details of how the PanGIA port addressed them.

Management implications for the perioperative surgical home related to inpatient case cancellations and add-on case scheduling on the day of surgery.

Science.gov (United States)

Epstein, Richard H; Dexter, Franklin

2015-07-01

cancellations on the scheduled day of surgery were considered, the cancellation rate was 14.0% ± 0.3% of scheduled inpatient minutes and 11.8% ± 0.2% of scheduled inpatient cases. There were 0.59 ± 0.02 OR schedule decisions per hour per 10 ORs between 6:00 AM and 3:59 PM (P data suggest that efforts of the Perioperative Surgical Home related to inpatient cancellations should focus on management decision-making to mitigate the disruptions to the planned OR schedule caused by inpatient case cancellations and add-on cases, more so than on efforts to reduce inpatient cancellation rates.

Mozart K.448 acts as a potential add-on therapy in children with refractory epilepsy.

Science.gov (United States)

Lin, Lung-Chang; Lee, Wei-Te; Wang, Chien-Hua; Chen, Hsiu-Lin; Wu, Hui-Chuan; Tsai, Chin-Lin; Wei, Ruey-Chang; Mok, Hin-Kiu; Weng, Chia-Fen; Lee, Mei-Wen; Yang, Rei-Cheng

2011-03-01

Mozart's Sonata for two pianos in D major, K.448 (Mozart K.448), has been shown to improve mental function, leading to what is known as the Mozart effect. Our previous work revealed that epileptiform discharges in children with epilepsy decreased during and immediately after listening to Mozart K.448. In this study, we evaluated the long-term effects of Mozart K.448 on children with refractory epilepsy. Eleven children with refractory epilepsy were enrolled. All of the patients were diagnosed as having had refractory epilepsy for more than 1 year (range =1 year to 6 years 4 months, mean =3 years 11 months) and had been receiving at least two antiepileptic drugs (AED). During the study period, they listened to Mozart K.448 once a day before bedtime for 6 months. Seizure frequencies were recorded 6 months before they started listening to this music and monthly during the study period. All of the patients remained on the same AEDs during the 6-month study period. Frequencies of seizures were compared before and after listening to Mozart K.448. Eight of eleven patients were seizure free (N=2) or had very good responses (N=6) after 6 months of listening to Mozart K.448. The remaining three (27.3%) showed minimal or no effect (effectiveness Mozart K.448 should be further studied as a potential add-on therapy in the treatment of children with refractory epilepsy. Copyright © 2011 Elsevier Inc. All rights reserved.

Mainstream web standards now support science data too

Science.gov (United States)

Richard, S. M.; Cox, S. J. D.; Janowicz, K.; Fox, P. A.

2017-12-01

The science community has developed many models and ontologies for representation of scientific data and knowledge. In some cases these have been built as part of coordinated frameworks. For example, the biomedical communities OBO Foundry federates applications covering various aspects of life sciences, which are united through reference to a common foundational ontology (BFO). The SWEET ontology, originally developed at NASA and now governed through ESIP, is a single large unified ontology for earth and environmental sciences. On a smaller scale, GeoSciML provides a UML and corresponding XML representation of geological mapping and observation data. Some of the key concepts related to scientific data and observations have recently been incorporated into domain-neutral mainstream ontologies developed by the World Wide Web consortium through their Spatial Data on the Web working group (SDWWG). OWL-Time has been enhanced to support temporal reference systems needed for science, and has been deployed in a linked data representation of the International Chronostratigraphic Chart. The Semantic Sensor Network ontology has been extended to cover samples and sampling, including relationships between samples. Gridded data and time-series is supported by applications of the statistical data-cube ontology (QB) for earth observations (the EO-QB profile) and spatio-temporal data (QB4ST). These standard ontologies and encodings can be used directly for science data, or can provide a bridge to specialized domain ontologies. There are a number of advantages in alignment with the W3C standards. The W3C vocabularies use discipline-neutral language and thus support cross-disciplinary applications directly without complex mappings. The W3C vocabularies are already aligned with the core ontologies that are the building blocks of the semantic web. The W3C vocabularies are each tightly scoped thus encouraging good practices in the combination of complementary small ontologies. The W3C

The Politics, Development and Problems of Small Irrigation Dams in Malawi: Experiences from Mzuzu ADD

Directory of Open Access Journals (Sweden)

Bryson Gwiyani Nkhoma

2011-10-01

Full Text Available The paper examines the progress made regarding the development of small irrigation dams in Malawi with the view of establishing their significance in improving rural livelihoods in the country. The paper adopts a political economy theory and a qualitative research approach. Evidence from Mzuzu Agricultural Development Division (ADD, where small reservoirs acquire specific relevance, shows that despite the efforts made, the development of small dams is making little progress. The paper highlights that problems of top-down planning, high investment costs, negligence of national and local interests, over-dependency on donors, and conflicts over the use of dams – which made large-scale dams unpopular in the 1990s – continue to affect the development of small irrigation dams in Malawi. The paper argues that small irrigation dams should not be simplistically seen as a panacea to the problems of large-scale irrigation dams. Like any other projects, small dams are historically and socially constructed through interests of different actors in the local settings, and can only succeed if actors, especially those from formal institutions, develop adaptive learning towards apparent conflicting relations that develop among them in the process of implementation. In the case of Mzuzu ADD, it was the failure of the government to develop this adaptive learning to the contestations and conflicts among these actors that undermined successful implementation of small irrigation dams. The paper recommends the need to consider local circumstances, politics, interests, rights and institutions when investing in small irrigation dams.

Comparison of vildagliptin as an add-on therapy and sulfonylurea dose-increasing therapy in patients with inadequately controlled type 2 diabetes using metformin and sulfonylurea (VISUAL study): A randomized trial.

Science.gov (United States)

Hong, A Ram; Lee, Jeun; Ku, Eu Jeong; Hwangbo, Yul; Kim, Kyoung Min; Moon, Jae Hoon; Choi, Sung Hee; Jang, Hak Chul; Lim, Soo

2015-07-01

The aim of present study is to compare the efficacy and safety of adding vildagliptin with sulfonylurea dose-increasing as an active comparator in patients who had inadequately controlled type 2 diabetes mellitus (T2DM) using metformin plus sulfonylurea in real clinical practice. Patients using metformin plus sulfonylurea were assigned to either vildagliptin add-on (50 mg twice a day, n=172) or sulfonylurea dose-increasing by 50% (n=172) treatment groups. The primary endpoint was a change in HbA(1c) after 24 weeks. The secondary endpoints were patients achieving HbA(1c)≤7.0% (53 mmol/mol) and changes in the fasting plasma glucose (FPG), 2-h postprandial glucose (2pp), lipid profiles, and urine albumin-to-creatinine ratio. Body weight and hypoglycemia were also investigated. The mean HbA(1c) at baseline was 8.6% (70 mmol/mol) in both groups. At week 24, the adjusted mean HbA(1c) levels decreased by -1.19% (-13.09 mmol/mol) with vildagliptin add-on and -0.46% (-5.06 mmol/mol) with sulfonylurea (Pvildagliptin add-on patients achieved HbA(1c)≤7.0% (53 mmol/mol) than did sulfonylurea patients (40.1% vs. 7.9%; Pvildagliptin add-on than with sulfonylurea (Pvildagliptin add-on group exhibited no clinically relevant weight gain and had a lower incidence of hypoglycemia compared with the sulfonylurea group. Vildagliptin add-on therapy might be a suitable option for patients with T2DM that is controlled inadequately by metformin and sulfonylurea, based on its greater glucose control and better safety profile (ClinicalTrial.gov: NCT01099137). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Atom-radical reaction dynamics of O(3P)+C3H5→C3H4+OH: Nascent rovibrational state distributions of product OH

Science.gov (United States)

Park, Jong-Ho; Lee, Hohjai; Kwon, Han-Cheol; Kim, Hee-Kyung; Choi, Young-Sang; Choi, Jong-Ho

2002-08-01

The reaction dynamics of ground-state atomic oxygen [O(3P)] with allyl radicals (C3H5) has been investigated by applying a combination of crossed beams and laser induced fluorescence techniques. The reactants O(3P) and C3H5 were produced by the photodissociation of NO2 and the supersonic flash pyrolysis of precursor allyl iodide, respectively. A new exothermic channel of O(3P)+C3H5→C3H4+OH was observed and the nascent internal state distributions of the product OH (X 2Π:υ″=0,1) showed substantial bimodal internal excitations of the low- and high-N″ components without Λ-doublet and spin-orbit propensities in the ground and first excited vibrational states. With the aid of the CBS-QB3 level of ab initio theory and Rice-Ramsperger-Kassel-Marcus calculations, it is predicted that on the lowest doublet potential energy surface the major reaction channel of O(3P) with C3H5 is the formation of acrolein (CH2CHCHO)+H, which is consistent with the previous bulk kinetic experiments performed by Gutman et al. [J. Phys. Chem. 94, 3652 (1990)]. The counterpart C3H4 of the probed OH product in the title reaction is calculated to be allene after taking into account the factors of reaction enthalpy, barrier height and the number of intermediates involved along the reaction pathway. On the basis of population analyses and comparison with prior calculations, the statistical picture is not suitable to describe the reactive atom-radical scattering processes, and the dynamics of the title reaction is believed to proceed through two competing dynamical pathways. The major low N″-components with significant vibrational excitation may be described by the direct abstraction process, while the minor but extraordinarily hot rotational distribution of high N″-components implies that some fraction of reactants is sampled to proceed through the indirect short-lived addition-complex forming process.

Formulation and Optimization of Multiparticulate Drug Delivery System Approach for High Drug Loading.

Science.gov (United States)

Shah, Neha; Mehta, Tejal; Gohel, Mukesh

2017-08-01

The aim of the present work was to develop and optimize multiparticulate formulation viz. pellets of naproxen by employing QbD and risk assessment approach. Mixture design with extreme vertices was applied to the formulation with high loading of drug (about 90%) and extrusion-spheronization as a process for manufacturing pellets. Independent variables chosen were level of microcrystalline cellulose (MCC)-X 1 , polyvinylpyrrolidone K-90 (PVP K-90)-X 2 , croscarmellose sodium (CCS)-X 3 , and polacrilin potassium (PP)-X 4 . Dependent variables considered were disintegration time (DT)-Y 1 , sphericity-Y 2 , and percent drug release-Y 3 . The formulation was optimized based on the batches generated by MiniTab 17 software. The batch with maximum composite desirability (0.98) proved to be optimum. From the evaluation of design batches, it was observed that, even in low variation, the excipients affect the pelletization property of the blend and also the final drug release. In conclusion, pellets with high drug loading can be effectively manufactured and optimized systematically using QbD approach.

Adaptation of the quality by design concept in early pharmaceutical development of an intranasal nanosized formulation.

Science.gov (United States)

Pallagi, Edina; Ambrus, Rita; Szabó-Révész, Piroska; Csóka, Ildikó

2015-08-01

Regulatory science based pharmaceutical development and product manufacturing is highly recommended by the authorities nowadays. The aim of this study was to adapt regulatory science even in the nano-pharmaceutical early development. Authors applied the quality by design (QbD) concept in the early development phase of nano-systems, where the illustration material was meloxicam. The meloxicam nanoparticles produced by co-grinding method for nasal administration were studied according to the QbD policy and the QbD based risk assessment (RA) was performed. The steps were implemented according to the relevant regulatory guidelines (quality target product profile (QTPP) determination, selection of critical quality attributes (CQAs) and critical process parameters (CPPs)) and a special software (Lean QbD Software(®)) was used for the RA, which represents a novelty in this field. The RA was able to predict and identify theoretically the factors (e.g. sample composition, production method parameters, etc.) which have the highest impact on the desired meloxicam-product quality. The results of the practical research justified the theoretical prediction. This method can improve pharmaceutical nano-developments by achieving shorter development time, lower cost, saving human resource efforts and more effective target-orientation. It makes possible focusing the resources on the selected parameters and area during the practical product development. Copyright © 2015 Elsevier B.V. All rights reserved.

Analysis of silicon on insulator (SOI) optical microring add-drop filter based on waveguide intersections

Science.gov (United States)

Kaźmierczak, Andrzej; Bogaerts, Wim; Van Thourhout, Dries; Drouard, Emmanuel; Rojo-Romeo, Pedro; Giannone, Domenico; Gaffiot, Frederic

2008-04-01

We present a compact passive optical add-drop filter which incorporates two microring resonators and a waveguide intersection in silicon-on-insulator (SOI) technology. Such a filter is a key element for designing simple layouts of highly integrated complex optical networks-on-chip. The filter occupies an area smaller than 10μm×10μm and exhibits relatively high quality factors (up to 4000) and efficient signal dropping capabilities. In the present work, the influence of filter parameters such as the microring-resonators radii and the coupling section shape are analyzed theoretically and experimentally

SCEW: a Microsoft Excel add-in for easy creation of survival curves.

Science.gov (United States)

Khan, Haseeb Ahmad

2006-07-01

Survival curves are frequently used for reporting survival or mortality outcomes of experimental pharmacological/toxicological studies and of clinical trials. Microsoft Excel is a simple and widely used tool for creation of numerous types of graphic presentations however it is difficult to create step-wise survival curves in Excel. Considering the familiarity of clinicians and biomedical scientists with Excel, an algorithm survival curves in Excel worksheet (SCEW) has been developed for easy creation of survival curves directly in Excel worksheets. The algorithm has been integrated in the form of Excel add-in for easy installation and usage. The program is based on modification of frequency data for binary break-up using the spreadsheet formula functions whereas a macro subroutine automates the creation of survival curves. The advantages of this program are simple data input, minimal procedural steps and the creation of survival curves in the familiar confines of Excel.

Caloric beverages consumed freely at meal-time add calories to an ad libitum meal.

Science.gov (United States)

Panahi, Shirin; El Khoury, Dalia; Luhovyy, Bohdan L; Goff, H Douglas; Anderson, G Harvey

2013-06-01

The objective was to compare the effects of ad libitum consumption of commonly consumed meal-time beverages on energy and fluid intakes and post-meal average subjective appetite and blood glucose in healthy adults. In a randomized controlled design, 29 males and females consumed to satiation an ad libitum pizza meal with one of five beverages in unlimited amount including water (0 kcal), 1% milk (44 kcal/100 ml), regular cola (44 kcal/100 ml), orange juice (44 kcal/100 ml) and diet cola (0 kcal). Food and fluid intakes were measured at the meal. Average subjective appetite and blood glucose were measured before and for 2h after the meal. Although energy intake from pizza was similar among all beverage treatments, the amount of fluid consumed (g) varied among the beverages with intake of orange juice higher than regular and diet cola, but not different from water or milk. Meal-time ingestion of caloric beverages, milk, orange juice and regular cola, led to higher total meal-time energy intakes compared to either water or diet cola. Post-meal blood glucose area under the curve (AUC) was lower after milk than after meals with water, orange juice and regular cola and post-meal average subjective appetite AUC was lower after milk than after meals with water. Meal intakes of nutrients including protein, calcium, phosphorus, zinc, vitamins B12, A and D were higher at the meal with milk compared to the other beverages. Thus, caloric beverages consumed ad libitum during a meal add to total meal-time energy intake, but 1% milk favors a lower post-meal blood glucose and average subjective appetite score and adds to nutrient intake. Copyright © 2013 Elsevier Ltd. All rights reserved.

Exploring the dynamics of hydrogen atom release from the radical-radical reaction of O(3P) with C3H5

International Nuclear Information System (INIS)

Joo, Sun-Kyu; Kwon, Lee-Kyoung; Lee, Hohjai; Choi, Jong-Ho

2004-01-01

The gas-phase radical-radical reaction dynamics of O( 3 P)+C 3 H 5 →H( 2 S)+C 3 H 4 O was studied at an average collision energy of 6.4 kcal/mol in a crossed beam configuration. The ground-state atomic oxygen [O( 3 P)] and allyl radicals (C 3 H 5 ) were generated by the photolysis of NO 2 and the supersonic flash pyrolysis of allyl iodide, respectively. Nascent hydrogen atom products were probed by the vacuum-ultraviolet-laser induced fluorescence spectroscopy in the Lyman-α region centered at 121.6 nm. With the aid of the CBS-QB3 level of ab initio theory, it has been found that the barrierless addition of O( 3 P) to C 3 H 5 forms the energy-rich addition complexes on the lowest doublet potential energy surface, which are predicted to undergo a subsequent direct decomposition step leading to the reaction products H+C 3 H 4 O. The major counterpart C 3 H 4 O of the probed hydrogen atom is calculated to be acrolein after taking into account the factors of barrier height, reaction enthalpy, and the number of intermediates involved along the reaction pathway. The nascent H-atom Doppler profile analysis shows that the average center-of-mass translational energy of the H+C 3 H 4 O products and the fraction of the total available energy released as the translational energy were determined to be 3.83 kcal/mol and 0.054, respectively. On the basis of comparison with statistical calculations, the reaction proceeds through the formation of short-lived addition complexes rather than statistical, long-lived intermediates, and the polyatomic acrolein product is significantly internally excited at the moment of the decomposition

Exploring the dynamics of hydrogen atom release from the radical-radical reaction of O(3P) with C3H5

Science.gov (United States)

Joo, Sun-Kyu; Kwon, Lee-Kyoung; Lee, Hohjai; Choi, Jong-Ho

2004-05-01

The gas-phase radical-radical reaction dynamics of O(3P)+C3H5→H(2S)+C3H4O was studied at an average collision energy of 6.4 kcal/mol in a crossed beam configuration. The ground-state atomic oxygen [O(3P)] and allyl radicals (C3H5) were generated by the photolysis of NO2 and the supersonic flash pyrolysis of allyl iodide, respectively. Nascent hydrogen atom products were probed by the vacuum-ultraviolet-laser induced fluorescence spectroscopy in the Lyman-α region centered at 121.6 nm. With the aid of the CBS-QB3 level of ab initio theory, it has been found that the barrierless addition of O(3P) to C3H5 forms the energy-rich addition complexes on the lowest doublet potential energy surface, which are predicted to undergo a subsequent direct decomposition step leading to the reaction products H+C3H4O. The major counterpart C3H4O of the probed hydrogen atom is calculated to be acrolein after taking into account the factors of barrier height, reaction enthalpy, and the number of intermediates involved along the reaction pathway. The nascent H-atom Doppler profile analysis shows that the average center-of-mass translational energy of the H+C3H4O products and the fraction of the total available energy released as the translational energy were determined to be 3.83 kcal/mol and 0.054, respectively. On the basis of comparison with statistical calculations, the reaction proceeds through the formation of short-lived addition complexes rather than statistical, long-lived intermediates, and the polyatomic acrolein product is significantly internally excited at the moment of the decomposition.

Retention, dosing, tolerability and patient reported seizure outcome of Zonisamide as only add-on treatment under real-life conditions in adult patients with partial onset seizures: Results of the observational study ZOOM.

Science.gov (United States)

Hamer, Hajo; Baulac, Michel; McMurray, Rob; Kockelmann, Edgar

2016-01-01

Zonisamide is licensed for adjunctive therapy for partial-onset seizures with or without secondary generalisation in patients 6 years and older and as monotherapy for the treatment of partial seizures in adult patients with newly diagnosed epilepsy, and shows a favourable pharmacokinetic profile with low interaction potential with other drugs. The aim of the present study was to gather real-life data on retention and modalities of zonisamide use when administered as only add-on treatment to a current AED monotherapy in adult patients with partial-onset seizures. This multicenter observational study was performed in 4 European countries and comprised three visits: baseline, and after 3 and 6 months. Data on patients' retention, reported efficacy, tolerability and safety, and quality of life was collected. Of 100 included patients, 93 could be evaluated. After 6 months, the retention rate of zonisamide add-on therapy was 82.8%. At this time, a reduction of seizure frequency of at least 50% was observed in 79.7% of patients, with 43.6% reporting seizure freedom over the last 3 months of the study period. Adverse events were reported by 19.4% of patients, with fatigue, agitation, dizziness, and headache being most frequent. Approximately 25% of patients were older than 60 years, many of whom suffered from late-onset epilepsy. Compared to younger patients, these patients showed considerable differences with regard to their antiepileptic drug regimen at baseline, and slightly higher responder and retention rates at 6 months. Despite limitations due to the non-interventional open-label design and the low sample size, the results show that zonisamide as only add-on therapy is well retained, indicating effectiveness in the majority of patients under real-life conditions. Copyright © 2015. Published by Elsevier Ltd.

Nothing Changes, Really: Why Women Who Break Through the Glass Ceiling End Up Reinforcing It.

Science.gov (United States)

Faniko, Klea; Ellemers, Naomi; Derks, Belle; Lorenzi-Cioldi, Fabio

2017-05-01

Two correlational studies conducted in Switzerland ( N = 222) and Albania ( N = 156) explained the opposition of female managers to gender quotas by examining the origins and consequences of the "Queen Bee (QB)-phenomenon," whereby women who have been successful in male-dominated organizations do not support the advancement of junior women. Results disconfirm previous accounts of the QB-phenomenon as indicating competitiveness among women. Instead, the tendency of women managers to consider themselves as different from other women, and their opposition to gender quotas, emerged when junior women were addressed but not when they considered their direct competitors, other women managers. Personal sacrifices women managers reported having made for career success predicted self-distancing from junior women and opposition to gender quotas targeting these women. We provide a more nuanced picture of what the QB-response is really about, explaining why women managers oppose quotas for junior women, while supporting quotas for women in the same rank.

Extension of quality-by-design concept to the early development phase of pharmaceutical R&D processes.

Science.gov (United States)

Csóka, Ildikó; Pallagi, Edina; Paál, Tamás L

2018-03-27

Here, we propose the extension of the quality-by-design (QbD) concept to also fit the early development phases of pharmaceuticals by adding elements that are currently widely applied, but not yet included in the QbD model in a structured way. These are the introduction of a 'zero' preformulation phase (i.e., selection of drug substance, possible dosage forms and administration routes based on the evaluated therapeutic need); building in stakeholders' (industry, patient, and regulatory) requirements into the quality target product profile (QTTP); and the use of modern quality management tools during the composition and process design phase [collecting critical quality attributes (CQAs) and selection of CPPs) for (still laboratory-scale) design space (DS) development. Moreover, during industrial scale-up, CQAs (as well as critical process parameters; CPPs) can be changed; however, we recommend that the existing QbD elements are reconsidered and updated after this phase. Copyright © 2018 Elsevier Ltd. All rights reserved.

Rapid process development of chromatographic process using direct analysis in real time mass spectrometry as a process analytical technology tool.

Science.gov (United States)

Yan, Binjun; Chen, Teng; Xu, Zhilin; Qu, Haibin

2014-06-01

The concept of quality by design (QbD) is widely applied in the process development of pharmaceuticals. However, the additional cost and time have caused some resistance about QbD implementation. To show a possible solution, this work proposed a rapid process development method, which used direct analysis in real time mass spectrometry (DART-MS) as a process analytical technology (PAT) tool for studying the chromatographic process of Ginkgo biloba L., as an example. The breakthrough curves were fast determined by DART-MS at-line. A high correlation coefficient of 0.9520 was found between the concentrations of ginkgolide A determined by DART-MS and HPLC. Based on the PAT tool, the impacts of process parameters on the adsorption capacity were discovered rapidly, which showed a decreased adsorption capacity with the increase of the flow rate. This work has shown the feasibility and advantages of integrating PAT into QbD implementation for rapid process development. Copyright © 2014 Elsevier B.V. All rights reserved.

Nothing Changes, Really: Why Women Who Break Through the Glass Ceiling End Up Reinforcing It

Science.gov (United States)

Faniko, Klea; Ellemers, Naomi; Derks, Belle; Lorenzi-Cioldi, Fabio

2017-01-01

Two correlational studies conducted in Switzerland (N = 222) and Albania (N = 156) explained the opposition of female managers to gender quotas by examining the origins and consequences of the “Queen Bee (QB)-phenomenon,” whereby women who have been successful in male-dominated organizations do not support the advancement of junior women. Results disconfirm previous accounts of the QB-phenomenon as indicating competitiveness among women. Instead, the tendency of women managers to consider themselves as different from other women, and their opposition to gender quotas, emerged when junior women were addressed but not when they considered their direct competitors, other women managers. Personal sacrifices women managers reported having made for career success predicted self-distancing from junior women and opposition to gender quotas targeting these women. We provide a more nuanced picture of what the QB-response is really about, explaining why women managers oppose quotas for junior women, while supporting quotas for women in the same rank. PMID:28903635

Efficacy and Safety of Lamotrigine as Add-On Treatment to Lithium in Bipolar Depression : A Multicenter, Double-Blind, Placebo-Controlled Trial

NARCIS (Netherlands)

van der Loos, Marc L. M.; Mulder, Paul G. H.; Hartong, Erwin G. Th. M.; Blom, Marc B. J.; Vergouwen, Anton C.; de Keyzer, Herman J. U. E. M.; Notten, Peter J. H.; Luteijn, Marijke L.; Timmermans, Manuela A.; Nolen, Willem A.

Objective: Lamotrigine is one of the pharmacologic options for the treatment of bipolar depression but has only been studied as monotherapy. This study compared the acute effects of lamotrigine and placebo as add-on therapy to ongoing treatment with lithium in patients with bipolar depression.

Does aquaculture add resilience to the global food system?

Science.gov (United States)

Troell, Max; Naylor, Rosamond L; Metian, Marc; Beveridge, Malcolm; Tyedmers, Peter H; Folke, Carl; Arrow, Kenneth J; Barrett, Scott; Crépin, Anne-Sophie; Ehrlich, Paul R; Gren, Asa; Kautsky, Nils; Levin, Simon A; Nyborg, Karine; Österblom, Henrik; Polasky, Stephen; Scheffer, Marten; Walker, Brian H; Xepapadeas, Tasos; de Zeeuw, Aart

2014-09-16

Aquaculture is the fastest growing food sector and continues to expand alongside terrestrial crop and livestock production. Using portfolio theory as a conceptual framework, we explore how current interconnections between the aquaculture, crop, livestock, and fisheries sectors act as an impediment to, or an opportunity for, enhanced resilience in the global food system given increased resource scarcity and climate change. Aquaculture can potentially enhance resilience through improved resource use efficiencies and increased diversification of farmed species, locales of production, and feeding strategies. However, aquaculture's reliance on terrestrial crops and wild fish for feeds, its dependence on freshwater and land for culture sites, and its broad array of environmental impacts diminishes its ability to add resilience. Feeds for livestock and farmed fish that are fed rely largely on the same crops, although the fraction destined for aquaculture is presently small (∼4%). As demand for high-value fed aquaculture products grows, competition for these crops will also rise, as will the demand for wild fish as feed inputs. Many of these crops and forage fish are also consumed directly by humans and provide essential nutrition for low-income households. Their rising use in aquafeeds has the potential to increase price levels and volatility, worsening food insecurity among the most vulnerable populations. Although the diversification of global food production systems that includes aquaculture offers promise for enhanced resilience, such promise will not be realized if government policies fail to provide adequate incentives for resource efficiency, equity, and environmental protection.

Continuous glucose monitoring adds information beyond HbA1c in well-controlled diabetes patients with early cardiovascular autonomic neuropathy

DEFF Research Database (Denmark)

Fleischer, Jesper; Laugesen, Esben; Cichosz, Simon Lebech

2017-01-01

AIMS: Hyperglycemia as evaluated by HbA1c is a risk factor for the development of cardiovascular autonomic neuropathy (CAN). The aim of the present study was to investigate whether continuous glucose monitoring (CGM) may add information beyond HbA1c in patients with type 2 diabetes and CAN. METHO...

Psychometric evaluation of a Dutch version of the Mini PAS-ADD for assessing psychiatric disorders in adults with different levels of intellectual disability.

Science.gov (United States)

Janssen, R; Maes, B

2013-08-01

People with intellectual disabilities (ID) have an increased vulnerability to develop psychiatric problems. Moreover, the early recognition and the accurate diagnosis of psychiatric disorders in the population of persons with ID are challenging. A Dutch version of the Mini PAS-ADD, which is a screening instrument for identification of mental health problems in people with ID, was evaluated in terms of internal consistency, interinformant reliability, item grouping and criterion validity based on a large-scale random sample (n = 377) and a clinical sample (n = 99) of adults with ID. The Dutch version of the Mini PAS-ADD showed moderate internal consistency, and moderate concordance among informants. Both aspects of the reliability were comparable for different levels of ID. A factor analysis largely confirmed the scale structure. Concurrent validity with the Reiss Screen for Maladaptive Behavior was high for the Depression, Psychosis and Autism scale. The outcome of the criterion-validity analysis indicated high specificity. The sensitivity for specific psychiatric disorders by the corresponding scales was moderate, but the general sensitivity for the presence of psychopathology on the basis of any of the scales was satisfying. The present research reconfirmed the use of the Mini PAS-ADD as a primary screening device for the identification of mental health problems among people with ID. © 2012 The Authors. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID.

Angiotensin-Converting Enzyme (ACE) I/D and Alpha-Adducin (ADD1) G460W Gene Polymorphisms in Turkish Patients with Severe Chronic Tinnitus.

Science.gov (United States)

Yuce, Salim; Sancakdar, Enver; Bağcı, Gokhan; Koc, Sema; Kurtulgan, Hande Kucuk; Bağcı, Binnur; Doğan, Mansur; Uysal, İsmail Onder

2016-04-01

Tinnitus is described as a disturbing sound sensation in the absence of external stimulation. We aimed to investigate whether there is any relationship between severe chronic tinnitus and angiotensin-converting enzyme (ACE) I/D and α-adducin (ADD1) G460W gene polymorphisms. The patient group and control group consisted of 89 and 104 individuals, respectively. The evaluation of tinnitus was performed using the Strukturiertes Tinnitus-Interview (STI). The Tinnitus Handicap Inventory (THI) was used to evaluate the tinnitus severity. Polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques were used for genotyping. With regard to the ACE I/D polymorphism, there was no significant difference in genotype and allele frequencies between the patient group and control group. However, a statistically significant difference was found in genotype (pgene polymorphism. Combined genotype analysis showed that the ACE II /ADD1 GW genotype was statistically significantly higher in the patient group than in the control group (X2: 7.15, p=0.007). The odds ratio value of the GW genotype was 2.5 (95% CI=1.4-4.7) (pgene polymorphism and susceptibility to severe chronic tinnitus. It was found that the GW genotype increased the disease risk by 2.5-fold compared with other genotypes. This indicates that ADD1 G460W polymorphism could be an important factor in the pathophysiology of tinnitus.

Add-on deep transcranial magnetic stimulation (dTMS) in patients with dysthymic disorder comorbid with alcohol use disorder: a comparison with standard treatment.

Science.gov (United States)

Girardi, Paolo; Rapinesi, Chiara; Chiarotti, Flavia; Kotzalidis, Georgios D; Piacentino, Daria; Serata, Daniele; Del Casale, Antonio; Scatena, Paola; Mascioli, Flavia; Raccah, Ruggero N; Brugnoli, Roberto; Digiacomantonio, Vittorio; Ferri, Vittoria Rachele; Ferracuti, Stefano; Zangen, Abraham; Angeletti, Gloria

2015-01-01

Dorsolateral prefrontal cortex (DLPFC) is dysfunctional in mood and substance use disorders. We predicted higher efficacy for add-on bilateral prefrontal high-frequency deep transcranial magnetic stimulation (dTMS), compared with standard drug treatment (SDT) in patients with dysthymic disorder (DD)/alcohol use disorder (AUD) comorbidity. We carried-out a 6-month open-label study involving 20 abstinent patients with DSM-IV-TR AUD comorbid with previously developed DD. Ten patients received SDT for AUD with add-on bilateral dTMS (dTMS-AO) over the DLPFC, while another 10 received SDT alone. We rated alcohol craving with the Obsessive Compulsive Drinking Scale (OCDS), depression with the Hamilton Depression Rating Scale (HDRS), clinical status with the Clinical Global Impressions scale (CGI), and global functioning with the Global Assessment of Functioning (GAF). At the end of the 20-session dTMS period (or an equivalent period in the SDT group), craving scores and depressive symptoms in the dTMS-AO group dropped significantly more than in the SDT group (P < 0.001 and P < 0.02, respectively). High frequency bilateral DLPFC dTMS with left preference was well tolerated and found to be effective as add-on in AUD. The potential of dTMS for reducing craving in substance use disorder patients deserves to be further investigated.

Proton conduction within the reaction centers of Rhodobacter capsulatus: the electrostatic role of the protein.

OpenAIRE

Maróti, P; Hanson, D K; Baciou, L; Schiffer, M; Sebban, P

1994-01-01

Light-induced charge separation in the photosynthetic reaction center results in delivery of two electrons and two protons to the terminal quinone acceptor QB. In this paper, we have used flash-induced absorbance spectroscopy to study three strains that share identical amino acid sequences in the QB binding site, all of which lack the protonatable amino acids Glu-L212 and Asp-L213. These strains are the photosynthetically incompetent site-specific mutant Glu-L212/Asp-L213-->Ala-L212/Ala-L213 ...

Usage of OpenStack Virtual Machine and MATLAB HPC Add-on leads to faster turnaround

KAUST Repository

Van Waveren, Matthijs

2017-03-16

We need to run hundreds of MATLAB® simulations while changing the parameters between each simulation. These simulations need to be run sequentially, and the parameters are defined manually from one simulation to the next. This makes this type of workload unsuitable for a shared cluster. For this reason we are using a cluster running in an OpenStack® Virtual Machine and are using the MATLAB HPC Add-on for submitting jobs to the cluster. As a result we are now able to have a turnaround time for the simulations of the order of a few hours, instead of the 24 hours needed on a local workstation.

Just add a pinch of salt!--current directions for the use of salt in recipes in Australian magazines.

Science.gov (United States)

Webster, Jacqui; Dunford, Elizabeth; Barzi, Federica; Neal, Bruce

2010-02-01

Australians currently consume too much salt causing adverse consequences for health. The media play an important role in the provision of nutrition advice to consumers. Previous research shows that many foods advertized in consumer magazines are high in salt, but little research has examined magazine recipes in this context. The aim of this project was to summarize directions for salt use in recipes in leading Australian magazines. In August 2007 and 2008, the top 10 magazines by circulation that included at least five recipes, were examined. Standardized information was collected about directions for salt use in recipes. Three hundred and thirty recipes were identified in 2007 and 417 in 2008. About 68% of recipes included high-salt ingredients, 37% instructed to season with salt, 10% instructed to add a specific quantity of salt and 15% recommended selection of low-salt ingredients. There was substantial variability in directions for salt use in recipes between magazines, but no clear differences between 2007 and 2008. Many recipes advised to add salt in direct contradiction to national dietary guidelines. There is clear potential for editorial guidelines on salt use in recipes to play a role in advancing public health efforts in Australia and other such nations.

Circadian rest-activity rhythms during benzodiazepine tapering covered by melatonin versus placebo add-on

DEFF Research Database (Denmark)

Baandrup, Lone; Fasmer, Ole Bernt; Glenthøj, Birte Yding

2016-01-01

is associated with changes in circadian rhythm parameters. METHOD: Data were derived from a randomized, double-blinded clinical trial with 24 weeks follow-up. Participants were randomized to add-on treatment with prolonged-release melatonin (2 mg) or matching placebo, and usual benzodiazepine dosage...... significantly increased the interdaily stability and at a trend level decreased the intradaily variability compared with placebo. Benzodiazepine dose reduction was not associated with these circadian rhythm parameters. Activity counts were generally higher after benzodiazepine dose reduction compared with pre......BACKGROUND: Patients with severe mental illness often suffer from disruptions in circadian rest-activity cycles, which might partly be attributed to ongoing psychopharmacological medication. Benzodiazepines are frequently prescribed for prolonged periods despite recommendations of only short...

Phacomatosis pigmento-pigmentaria: should we add a new type of phacomatosis? Fact and controversies.

Science.gov (United States)

Wolf, Ronni; Wolf, Danny; Ruocco, Vincenzo; Baroni, Adone; Ruocco, Eleonora

2013-01-01

There are currently five types of recognized phacomatosis pigmentovascularis plus one more, phacomatosis pigmentokeratotica, making six types altogether. Should we stop here and consider the classification as being complete? Or, do we leave room to add more types or, alternatively, lump the ones we have together and shorten the list? We present our reasons for adding one or two new types of phacomatoses to the current classification, in full recognition that it is already complicated and somewhat cumbersome. We consider that the benefits of doing so outweigh any additional strain on the already complicated classification. We expect that this might not sit well with some of our colleagues, but we are prepared to do battle. Copyright © 2013 Elsevier Inc. All rights reserved.

Real-life efficacy and safety of vildagliptin compared with sulfonylureas as add-on to metformin in patients with type 2 diabetes mellitus in Germany.

Science.gov (United States)

Göke, R; Gruenberger, J B; Bader, G; Dworak, M

2014-05-01

Metformin is an established first-line treatment for type 2 diabetes mellitus (T2DM) patients, but intensification of oral anti-diabetes therapy is usually required over time. A large observational study of 45,868 T2DM patients in 27 countries (EDGE) was conducted to compare the effectiveness and safety of vildagliptin as add-on therapy to another oral anti-diabetes drug (OAD) vs other dual OAD combinations. This report presents results from a post-hoc analysis of patients in Germany who received vildagliptin or a sulfonylurea (SU) in combination with metformin. Patients inadequately controlled with monotherapy became eligible only after the add-on treatment was finalized. Patients included were assigned to receive either vildagliptin or another OAD (SUs, thiazolidinediones, glinides, α-glucosidase inhibitors, or metformin; DPP-4 inhibitors or glucagon-like peptide-1 [GLP-1] mimetics/analogs were excluded). The primary end-point was the proportion of patients achieving a reduction in HbA1c >0.3% without peripheral edema, hypoglycemia, discontinuation due to gastrointestinal event, or weight gain ≥5%. Of 8887 patients enrolled in Germany, 6439 received vildagliptin and 971 received SUs as add-on to metformin. The primary end-point was reached in 34.9% and 29.6% of patients in the vildagliptin and SU groups, respectively, with an unadjusted odds ratio of 1.27 (95% CI = 1.09, 1.47; p = 0.001). HbA1c decreased in both cohorts from baseline (-0.7% with vildagliptin vs -0.5% with SUs), with a mean between-group difference of -0.2% (95% CI = -0.22, -0.09). The number of hypoglycemic events was 4-fold higher in the SU group than in the vildagliptin group (vildagliptin = 0.11%; SU = 0.41%). In a real-life setting, vildagliptin was associated with a numerically greater reduction in HbA1c, less hypoglycemia, and more patients reaching target HbA1c without hypoglycemia or weight gain compared with SUs. Open-label design and under reporting of adverse

Crouzon syndrome associated with acanthosis nigricans: prenatal 2D and 3D ultrasound findings and postnatal 3D CT findings

DEFF Research Database (Denmark)

Nørgaard, P.; Hagen, CP; Hove, H.

2012-01-01

Crouzon syndrome with acanthosis nigricans (CAN) is a very rare condition with an approximate prevalence of 1 per 1 million newborns. We add the first report on prenatal 2D and 3D ultrasound findings in CAN. In addition we present the postnatal 3D CT findings. The diagnosis was confirmed...

Twelve-week, prospective, open-label, randomized trial on the effects of an anticholinergic agent or antidiuretic agent as add-on therapy to an alpha-blocker for lower urinary tract symptoms

Directory of Open Access Journals (Sweden)

Shin YS

2014-07-01

Full Text Available Yu Seob Shin,1 Li Tao Zhang,1 Chen Zhao,2 Young Gon Kim,1 Jong Kwan Park1 1Department of Urology, Chonbuk National University Medical School, and Institute for Medical Sciences, Chonbuk National University and Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University Hospital, Jeonju, South Korea; 2Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, and Shanghai Institute of Andrology, Shanghai, People’s Republic of China Purpose: The effects of an anticholinergic or antidiuretic agent as add-on therapy to an ­alpha-blocker for lower urinary tract symptoms (LUTS according to a voiding diary in 3 days are unknown. We prospectively investigated the efficacy of an anticholinergic or antidiuretic agent as add-on therapy for nocturia in men previously treated with an alpha-blocker for LUTS.Subjects and methods: Patients were randomly subdivided into two groups. All patients had a 4-week washout. Group A had alpha-blocker for 4 weeks, then an alpha-blocker plus an anticholinergic agent for 4 weeks, and, finally, 4 weeks of an alpha-blocker plus an antidiuretic agent. Group B had an alpha-blocker for 4 weeks, then an alpha-blocker plus an antidiuretic agent for 4 weeks, and, finally, 4 weeks of an alpha-blocker plus an anticholinergic agent. In both groups, patients were subdivided into nocturnal polyuria, decreased nocturnal bladder capacity (NBC, or nocturia by both causes subgroups. A 3-day voiding diary, total International Prostate Symptom Score (IPSS, IPSS sub-scores, Overactive Bladder Symptom Score, uroflowmetry, and post-void residual urine volume, were assessed at baseline, and at 4, 8, and 12 weeks.Results: A total of 405 patients completed the study. During treatment, the changes from baseline in total IPSS and IPSS sub-scores were significantly decreased at 4 weeks and were maintained for 12 weeks. In the nocturnal polyuria subgroup of Groups A and B

ATOM - an OMERO add-on for automated import of image data

Directory of Open Access Journals (Sweden)

Lipp Peter

2011-10-01

Full Text Available Abstract Background Modern microscope platforms are able to generate multiple gigabytes of image data in a single experimental session. In a routine research laboratory workflow, these data are initially stored on the local acquisition computer from which files need to be transferred to the experimenter's (remote image repository (e.g., DVDs, portable hard discs or server-based storage because of limited local data storage. Although manual solutions for this migration, such as OMERO - a client-server software for visualising and managing large amounts of image data - exist, this import process may be a time-consuming and tedious task. Findings We have developed ATOM, a Java-based and thus platform-independent add-on for OMERO enabling automated transfer of image data from a wide variety of acquisition software packages into OMERO. ATOM provides a graphical user interface and allows pre-organisation of experimental data for the transfer. Conclusions ATOM is a convenient extension of the OMERO software system. An automated interface to OMERO will be a useful tool for scientists working with file formats supported by the Bio-Formats file format library, a platform-independent library for reading the most common file formats of microscope images.

Enhanced Production of Androst-1,4-Diene-3,17-Dione by Mycobacterium neoaurum JC-12 Using Three-Stage Fermentation Strategy

Science.gov (United States)

Shao, Minglong; Zhang, Xian; Rao, Zhiming; Xu, Meijuan; Yang, Taowei; Li, Hui; Xu, Zhenghong

2015-01-01

To improve the androst-1,4-diene-3,17-dione (ADD) production from phytosterol by Mycobacterium neoaurum JC-12, fructose was firstly found favorable as the initial carbon source to increase the biomass and eliminate the lag phase of M. neoaurum JC-12 in the phytosterol transformation process. Based on this phenomenon, two-stage fermentation by using fructose as the initial carbon source and feeding glucose to maintain strain metabolism was designed. By applying this strategy, the fermentation duration was decreased from 168 h to 120 h with the ADD productivity increased from 0.071 g/(L·h) to 0.108 g/(L·h). Further, three-stage fermentation by adding phytosterol to improve ADD production at the end of the two-stage fermentation was carried out and the final ADD production reached 18.6 g/L, which is the highest reported ADD production using phytosterol as substrate. Thus, this strategy provides a possible way in enhancing the ADD production in pharmaceutical industry. PMID:26352898

Enhanced Production of Androst-1,4-Diene-3,17-Dione by Mycobacterium neoaurum JC-12 Using Three-Stage Fermentation Strategy.

Directory of Open Access Journals (Sweden)

Minglong Shao

Full Text Available To improve the androst-1,4-diene-3,17-dione (ADD production from phytosterol by Mycobacterium neoaurum JC-12, fructose was firstly found favorable as the initial carbon source to increase the biomass and eliminate the lag phase of M. neoaurum JC-12 in the phytosterol transformation process. Based on this phenomenon, two-stage fermentation by using fructose as the initial carbon source and feeding glucose to maintain strain metabolism was designed. By applying this strategy, the fermentation duration was decreased from 168 h to 120 h with the ADD productivity increased from 0.071 g/(L·h to 0.108 g/(L·h. Further, three-stage fermentation by adding phytosterol to improve ADD production at the end of the two-stage fermentation was carried out and the final ADD production reached 18.6 g/L, which is the highest reported ADD production using phytosterol as substrate. Thus, this strategy provides a possible way in enhancing the ADD production in pharmaceutical industry.

Does aquaculture add resilience to the global food system?

Science.gov (United States)

Troell, Max; Naylor, Rosamond L.; Metian, Marc; Beveridge, Malcolm; Tyedmers, Peter H.; Folke, Carl; Arrow, Kenneth J.; Barrett, Scott; Crépin, Anne-Sophie; Ehrlich, Paul R.; Gren, Åsa; Kautsky, Nils; Levin, Simon A.; Nyborg, Karine; Österblom, Henrik; Polasky, Stephen; Scheffer, Marten; Walker, Brian H.; Xepapadeas, Tasos; de Zeeuw, Aart

2014-01-01

Aquaculture is the fastest growing food sector and continues to expand alongside terrestrial crop and livestock production. Using portfolio theory as a conceptual framework, we explore how current interconnections between the aquaculture, crop, livestock, and fisheries sectors act as an impediment to, or an opportunity for, enhanced resilience in the global food system given increased resource scarcity and climate change. Aquaculture can potentially enhance resilience through improved resource use efficiencies and increased diversification of farmed species, locales of production, and feeding strategies. However, aquaculture’s reliance on terrestrial crops and wild fish for feeds, its dependence on freshwater and land for culture sites, and its broad array of environmental impacts diminishes its ability to add resilience. Feeds for livestock and farmed fish that are fed rely largely on the same crops, although the fraction destined for aquaculture is presently small (∼4%). As demand for high-value fed aquaculture products grows, competition for these crops will also rise, as will the demand for wild fish as feed inputs. Many of these crops and forage fish are also consumed directly by humans and provide essential nutrition for low-income households. Their rising use in aquafeeds has the potential to increase price levels and volatility, worsening food insecurity among the most vulnerable populations. Although the diversification of global food production systems that includes aquaculture offers promise for enhanced resilience, such promise will not be realized if government policies fail to provide adequate incentives for resource efficiency, equity, and environmental protection. PMID:25136111

Globes from global data: Charting international research networks with the GRASS GIS r.out.polycones add-on module.

Science.gov (United States)

Löwe, Peter

2015-04-01

Many Free and Open Source Software (FOSS) tools have been created for the various application fields within geoscience. While FOSS allows re-implementation of functionalities in new environments by access to the original codebase, the easiest approach to build new software solutions for new problems is the combination or merging of existing software tools. Such mash-ups are implemented by embedding and encapsulating FOSS tools within each another, effectively focusing the use of the embedded software to the specific role it needs to perform in the given scenario, while ignoring all its other capabilities. GRASS GIS is a powerful and established FOSS GIS for raster, vector and volume data processing while the Generic Mapping Tools (GMT) are a suite of powerful Open Source mapping tools, which exceed the mapping capabilities of GRASS GIS. This poster reports on the new GRASS GIS add-on module r.out.polycones. It enables users to utilize non-continuous projections for map production within the GRASS production environment. This is implemented on the software level by encapsulating a subset of GMT mapping capabilities into a GRASS GIS (Version 6.x) add-on module. The module was developed at the German National Library of Science and Technology (TIB) to provide custom global maps of scientific collaboration networks, such as the DataCite consortium, the registration agency for Digital Object Identifiers (DOI) for research data. The GRASS GIS add-on module can be used for global mapping of raster data into a variety of non continuous sinosoidal projections, allowing the creation of printable biangles (gores) to be used for globe making. Due to the well structured modular nature of GRASS modules, technical follow-up work will focus on API-level Python-based integration in GRASS 7 [1]. Based on this, GMT based mapping capabilities in GRASS will be extended beyond non-continuous sinosoidal maps and advanced from raster-layers to content GRASS display monitors. References

7 CFR 1770.3 - Index of records.

Science.gov (United States)

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Index of records. 1770.3 Section 1770.3 Agriculture... Index of records. (a) Each borrower shall maintain a master index of records. The master index shall... maintained. The master index shall be subject to review by RUS and RUS shall reserve the right to add records...

Synthesis of highly integrated optical network based on microdisk-resonator add-drop filters in silicon-on-insulator technology

Science.gov (United States)

Kaźmierczak, Andrzej; Dortu, Fabian; Giannone, Domenico; Bogaerts, Wim; Drouard, Emmanuel; Rojo-Romeo, Pedro; Gaffiot, Frederic

2009-10-01

We analyze a highly compact optical add-drop filter topology based on a pair of microdisk resonators and a bus waveguide intersection. The filter is further assessed on an integrated optical 4×4 network for optical on-chip communication. The proposed network structure, as compact as 50×50 μm, is fabricated in a CMOS-compatible process on a silicon-on-insulator (SOI) substrate. Finally, the experimental results demonstrate the proper operation of the fabricated devices.

Pubertal Stress and Nutrition and their Association with Sexual Orientation and Height in the Add Health Data.

Science.gov (United States)

Skorska, Malvina N; Bogaert, Anthony F

2017-01-01

A number of studies have indicated that gay men tend to be shorter, on average, than heterosexual men. Less evidence exists that lesbian women are taller, on average, than heterosexual women. The most popular explanation of the association between sexual orientation and height involves prenatal factors, such that, for example, gay men may have been exposed to lower than typical androgens during fetal development, which impacts their height and sexual orientation as adults. An alternative explanation involves stress, given that stress has been associated with sexual minority identification and with lower height. Another alternative explanation involves nutrition, although its relationship is less clear with sexual minority identification. Using the Add Health data, which is a large, nationally representative and longitudinal sample of American adolescents (n = 14,786), we tested a mediation model, such that sexual orientation → pubertal stress/nutrition → height. Within men, we found that gay men (n = 126) were shorter, on average, than heterosexual men (n = 6412). None of the 24 pubertal stress-related and 15 pubertal nutrition-related variables assessed in the Add Health data mediated the relationship between sexual orientation and height in men. Within women, lesbians (n = 75) did not differ significantly in stature compared to heterosexual women (n = 6267). Thus, prenatal mechanisms (e.g., hormones, maternal immune response) are likely better candidates for explaining the height difference between gay men and heterosexual men.

ALDH2 polymorphism, associated with attenuating negative symptoms in patients with schizophrenia treated with add-on dextromethorphan.

Science.gov (United States)

Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chen, Po-See; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Liang-Jen; Lee, I-Hui; Wang, Tzu-Yun; Chen, Kao-Chin; Yang, Yen-Kuang; Hong, Jau-Shyong; Lu, Ru-Band

2015-10-01

Increasing the evidence of inflammation's contribution to schizophrenia; using anti-inflammatory or neurotrophic therapeutic agents to see whether they improve schizophrenia treatment. Dextromethorphan (DM), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, might protect monoamine neurons. Whether treating schizophrenia with risperidone plus add-on DM is more effective than risperidone (RISP) alone, and the association between the ALDH2 polymorphism and treatment response were investigated. A double-blind study in which patients with schizophrenia were randomly assigned to the RISP + DM (60 mg/day; n = 74) or the RISP + Placebo (n = 75) group. The Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) scores were used to evaluate clinical response during weeks 0, 1, 2, 4, 6, 8, and 11. The genotypes of the ALDH2 polymorphism were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. A generalized estimating equation was used to analyze the effects of ALDH2 polymorphism on the clinical performance of DM. PANSS and SANS scores were significantly lower in both groups after 11 weeks of treatment. SANS total scores were significantly lower in the RISP + DM group in patients with the ALDH2*2*2 genotype. RISP plus add-on DM treatment reduced negative schizophrenia symptoms in patients with the ALDH2 polymorphism. Copyright © 2015 Elsevier Ltd. All rights reserved.

Addiction surplus: the add-on margin that makes addictive consumptions difficult to contain.

Science.gov (United States)

Adams, Peter J; Livingstone, Charles

2015-01-01

Addictive consumptions generate financial surpluses over-and-above non-addictive consumptions because of the excessive consumption of addicted consumers. This add-on margin or 'addiction surplus' provides a powerful incentive for beneficiaries to protect their income by ensuring addicted consumers keep consuming. Not only that, addiction surplus provides the financial base that enables producers to sponsor activities which aim to prevent public health initiatives from reducing consumption. This paper examines the potency of addiction surplus to engage industry, governments and communities in an on-going reliance on addiction surplus. It then explores how neo-liberal constructions of a rational consumer disguise the ethical and exploitative dynamics of addiction surplus by examining ways in which addictive consumptions fail to conform to notions of autonomy and rationality. Four measures are identified to contain the distorting effects of addiction surplus. Copyright © 2014 Elsevier B.V. All rights reserved.

3D motion graphics for 2D artists conquering the 3rd dimension

CERN Document Server

Byrne, Bill

2011-01-01

Add 3D to your mograph skillset! For the experienced 2D artist, this lavishly illustrated, 4 color book presents the essentials to building and compositing 3D elements into your 2D world of film and broadcast. Concepts and techniques are presented in concise, step-by-step tutorials, hundreds of which are featured throughout. Featured applications include Photoshop, Illustrator, After Effects, and Cinema 4D. Lessons include exploring the expanded 3D functionality of the Adobe Creative Suite applications (After Effects, Photoshop, and Illustrator) through a series of practical tutorials. More

Safety and tolerability of once-daily tiotropium Respimat(®) as add-on to at least inhaled corticosteroids in adult patients with symptomatic asthma

DEFF Research Database (Denmark)

Dahl, Ronald; Engel, Michael; Dusser, Daniel

2016-01-01

BACKGROUND: Tiotropium, a long-acting anticholinergic bronchodilator, has demonstrated efficacy and safety as add-on therapy to inhaled corticosteroids (ICS), with or without other maintenance therapies, in patients with symptomatic asthma. OBJECTIVE: To evaluate safety and tolerability of tiotro...

Calling all LEGO lovers! Add a mini control room to your collection

CERN Multimedia

Katarina Anthony

2015-01-01

The mini LHC Lego project launched in March (see here) now has almost 6,000 supporters - well on its way to the 10,000 votes needed for it to (hopefully!) hit store shelves. This week, the project added a new feature to its line: a mini control centre! The new LEGO Control centre, featuring operators "Kerstin" and "Marco".   The mini LHC project is the brainchild of ATLAS PhD student Nathan Readioff, who designed Lego replicas of the LHC and the ALICE, ATLAS, CMS and LHCb experiments on a micro scale. Each detector model is small enough to fit in the palm of your hand but crammed with detailed internal systems revealed by cutaway walls. Every major detector component is represented by a Lego piece. Now, Nathan has created a control centre to complement the mini LHC project. This would be an add-on feature for Lego’s consideration, should they decide to develop the accelerator into a box set. “The control centre is ...

Wireless Rover Meets 3D Design and Product Development

Science.gov (United States)

Deal, Walter F., III; Hsiung, Steve C.

2016-01-01

Today there are a number of 3D printing technologies that are low cost and within the budgets of middle and high school programs. Educational technology companies offer a variety of 3D printing technologies and parallel curriculum materials to enable technology and engineering teachers to easily add 3D learning activities to their programs.…

On Measuring the Sixth Basic Personality Dimension: A Comparison Between HEXACO Honesty-Humility and Big Six Honesty-Propriety.

Science.gov (United States)

Thielmann, Isabel; Hilbig, Benjamin E; Zettler, Ingo; Moshagen, Morten

2017-12-01

Recent developments in personality research led to the proposition of two alternative six-factor trait models, the HEXACO model and the Big Six model. However, given the lack of direct comparisons, it is unclear whether the HEXACO and Big Six factors are distinct or essentially equivalent, that is, whether corresponding inventories measure similar or distinct personality traits. Using Structural Equation Modeling (Study 1), we found substantial differences between the traits as measured via the HEXACO-60 and the 30-item Questionnaire Big Six (30QB6), particularly for Honesty-Humility and Honesty-Propriety (both model's critical difference to the Big Five approach). This distinction was further supported by Study 2, showing differential capabilities of the HEXACO-60 and the 30QB6 to account for several criteria representing the theoretical core of Honesty-Humility and/or Honesty-Propriety. Specifically, unlike the indicator of Honesty-Humility, the indicator of Honesty-Propriety showed low predictive power for some conceptually relevant criteria, suggesting a limited validity of the 30QB6.

1.25 Gbit/s bidirectional link in an access network employing a reconfigurable optical add/drop multiplexer and a reflective semiconductor optical amplifier

NARCIS (Netherlands)

Urban, P.J.; de Laat, M.M.; Klein, E.J.; Koonen, A.M.J.; Khoe, G.D.; de Waardt, H.; Marciniak, M.; Jaworski, M.; Zdabiwicz, M.

2008-01-01

In this paper, we demonstrate symmetrical bidirectional transmission of 1.25 Gbit/s wavelength channels in an access network link employing centralized light generation, colourless optical network unit (ONU) and a reconfigurable optical add/drop multiplexer (ROADM). The architecture of ONU is based

Marketing strategies to add economic value, reactions on corporate social responsibility advertising in print media: an Indian company case

OpenAIRE

Karunamoorthy, S; Selvarasu, A.; Filipe, J.

2013-01-01

Corporate social responsibility advertising (CSR Advertising) results from commercial advertising, having social dimensions. This concept works as a marketing tool of cause-related marketing (CR Marketing). In this study, the case of IOCL (an Indian oil company) is presented to show how the company creates innovative advertising ideas, serves the society, contributes to save environmental natural resources and allows to add economic value. In addition to the usual ways of commercial advertisi...

Randomized, controlled trial of rasagiline as an add-on to dopamine agonists in Parkinson's disease.

Science.gov (United States)

Hauser, Robert A; Silver, Dee; Choudhry, Azhar; Eyal, Eli; Isaacson, Stuart

2014-07-01

Dopamine agonists (DA) are often used as first-line monotherapy for the symptomatic control of Parkinson's disease (PD). However, DA monotherapy typically becomes inadequate within a few years, at which time the DA dosage must be increased or other antiparkinsonian medications added. Adding a monoamine oxidase-B (MAO-B) inhibitor to DA monotherapy might improve symptomatic control while maintaining good safety and tolerability. We conducted an 18-week, randomized, double-blind, placebo-controlled trial of rasagiline 1 mg/d as an add-on to DA therapy (ropinirole ≥ 6 mg/d or pramipexole ≥ 1.0 mg/d) in early PD patients whose conditions were not adequately controlled on their current treatment regimen. The primary efficacy variable was the change in total Unified Parkinson Disease Rating Scale (UPDRS) score (sum of parts I, II, and III) from baseline to week 18, comparing rasagiline and placebo groups. The modified intent-to-treat (ITT) population included 321 subjects whose mean ± SD age was 62.6 ± 9.7, and duration of PD was 2.1 ± 2.1 years. Results demonstrated a significantly greater improvement in total UPDRS scores from baseline to week 18 in the rasagiline group compared with the placebo group (least squares [LS] mean difference ± SE, -2.4 ± 0.95; 95% confidence interval [CI], -4.3, -0.5; P = 0.012). Mean improvement (LS mean ± SE) was -3.6 ± 0.68 in the rasagiline group and -1.2 ± 0.68 in the placebo group. Rasagiline was well tolerated, and the most common adverse events (AEs; rasagiline vs. placebo) were dizziness (7.4% vs. 6.1%), somnolence (6.8% vs. 6.7%), and headache (6.2% vs. 4.3%). Rasagiline 1 mg/d provided statistically significant improvement when added to dopamine agonist therapy and was well tolerated. © 2014 International Parkinson and Movement Disorder Society.

Full-length genome sequences of five hepatitis C virus isolates representing subtypes 3g, 3h, 3i and 3k, and a unique genotype 3 variant.

Science.gov (United States)

Lu, Ling; Li, Chunhua; Yuan, Jie; Lu, Teng; Okamoto, Hiroaki; Murphy, Donald G

2013-03-01

We characterized the full-length genomes of five distinct hepatitis C virus (HCV)-3 isolates. These represent the first complete genomes for subtypes 3g and 3h, the second such genomes for 3k and 3i, and of one novel variant presently not assigned to a subtype. Each genome was determined from 18-25 overlapping fragments. They had lengths of 9579-9660 nt and each contained a single ORF encoding 3020-3025 aa. They were isolated from five patients residing in Canada; four were of Asian origin and one was of Somali origin. Phylogenetic analysis using 64 partial NS5B sequences differentiated 10 assigned subtypes, 3a-3i and 3k, and two additional lineages within genotype 3. From the data of this study, HCV-3 full-length sequences are now available for six of the assigned subtypes and one unassigned. Our findings should add insights to HCV evolutionary studies and clinical applications.

SwathProfiler and NProfiler: Two new ArcGIS Add-ins for the automatic extraction of swath and normalized river profiles

Science.gov (United States)

Pérez-Peña, J. V.; Al-Awabdeh, M.; Azañón, J. M.; Galve, J. P.; Booth-Rea, G.; Notti, D.

2017-07-01

The present-day great availability of high-resolution Digital Elevation Models has improved tectonic geomorphology analyses in their methodological aspects and geological meaning. Analyses based on topographic profiles are valuable to explore the short and long-term landscape response to tectonic activity and climate changes. Swath and river longitudinal profiles are two of the most used analysis to explore the long and short-term landscape responses. Most of these morphometric analyses are conducted in GIS software, which have become standard tools for analyzing drainage network metrics. In this work we present two ArcGIS Add-Ins to automatically delineate swath and normalized river profiles. Both tools are programmed in Visual Basic . NET and use ArcObjects library-architecture to access directly to vector and raster data. The SwathProfiler Add-In allows analyzing the topography within a swath or band by representing maximum-minimum-mean elevations, first and third quartile, local relief and hypsometry. We have defined a new transverse hypsometric integral index (THi) that analyzes hypsometry along the swath and offer valuable information in these kind of graphics. The NProfiler Add-In allows representing longitudinal normalized river profiles and their related morphometric indexes as normalized concavity (CT), maximum concavity (Cmax) and length of maximum concavity (Lmax). Both tools facilitate the spatial analysis of topography and drainage networks directly in a GIS environment as ArcMap and provide graphical outputs. To illustrate how these tools work, we analyzed two study areas, the Sierra Alhamilla mountain range (Betic Cordillera, SE Spain) and the Eastern margin of the Dead Sea (Jordan). The first study area has been recently studied from a morphotectonic perspective and these new tools can show an added value to the previous studies. The second study area has not been analyzed by quantitative tectonic geomorphology and the results suggest a landscape

Cost-consequence analysis of sitagliptin versus sulfonylureas as add-on therapy for the treatment of diabetic patients in Italy

Directory of Open Access Journals (Sweden)

Lorenzoni V

2017-11-01

Full Text Available Valentina Lorenzoni,1 Fabio Baccetti,2 Stefano Genovese,3 Enrico Torre,4 Giuseppe Turchetti1 1Institute of Management, Scuola Superiore Sant’Anna, Pisa, Italy; 2SD Diabetology, ASL Toscana Nordovest, Massa Carrara, Italy; 3Cardiovascular and Metabolic Department, IRCCS Multimedica Sesto San Giovanni, Milan, Italy; 4SSD Endocrinologia, Diabetologia e Malattie metaboliche, ASL 3 Genovese, Genoa, Italy Objective: Diabetes mellitus is a chronic disease related to a significant impact in both epidemiologic and economic terms. In Italy, around 3.6 million people are affected by diabetes and this number is expected to increase significantly in the next few years. As recommended by current national and international guidelines, metformin (Met is prescribed as first-line pharmacological treatment, and many pharmacological alternatives are available for patients uncontrolled with Met monotherapy. Despite the availability of many innovative oral antidiabetic drugs (OADs, such as dipeptidyl peptidase 4 inhibitors (DPP4-i and its first-in-class sitagliptin (SITA, which entered the Italian market in the last 10 years, their usage is consistently lower than traditional drugs such as sulfonylureas (SUs. In fact, due to higher acquisition costs, the prescription of innovative OADs in Italy is restricted to specialist, resulting in a prominent usage of traditional OAD that can be prescribed also by general practitioners (GPs. A cost consequence analysis (CCA was performed in order to compare SITA with SU, as second-line therapy in add-on to Met, in terms of costs and related clinical events over 36 months.Methods: A CCA was conducted on a hypothetical cohort of 100,000 type 2 diabetes mellitus (T2DM patients uncontrolled with Met monotherapy, from both the Italian National Health Service (INHS and societal perspective. Therefore, both direct (drugs, self-monitoring, hypoglycemia, major cardiovascular events [MACEs], and switch to insulin and indirect costs

Una riconsiderazione sul ripostiglio di S'Adde 'e S'Ulumu-Usini

Directory of Open Access Journals (Sweden)

Salvatore Merella

2012-12-01

Full Text Available In this poster the author presents the results of a study on several pieces of ashlar masonry were recently discovered in a locale called S'Iscia 'e Su Puttu, indicating the likely presence of sacred place belonging to the Nuragic - Bronze and Early Iron Age - phase. It is located very close to the site of S'Adde 'e S'Ulumu, where an important hoard of bronze objects was found, once considered to belong to a single individual for the absence of any clear archaeological context. This hoard acquires a new dimension thanks to the new data presented here: it could have reasonably been part of a set of ritual activities carried out in a sacred area formed of buildings and spaces between them, a common pattern in Sardinian communities during the Early Iron phase. This poster was presented at the Workshop Materiali e contesti dell'Età del Ferro sarda (Materials and contexts in the Sardinian Iron Age, organised by the University of Glasgow and the Comune di San Vero Milis on the 25th of May 2012, and supported for by the Royal Society of Edinburgh, the Comune di San Vero Milis, the University of Glasgow and the Carnegie Trust of the Universities of Scotland.

Stereotaxic percutaneous core biopsy versus surgical biopsy of nonpalpable breast lesions using a standard mammographic table with an add-on device

International Nuclear Information System (INIS)

Levin, M.F.; Papoff, W.J.; Doan, L.; Eliasziw, M.

2001-01-01

To determine the accuracy of using a regular mammographic table with an add-on device for biopsy of nonpalpable breast lesions in women in a community hospital setting. During a 3-year period, 70 consenting women (39-80 years of age) with a nonpalpable mammographically suspicious lesion on routine screening mammography underwent 14-gauge automated percutaneous core biopsies, immediate needle localization and lumpectomy. The needle and surgical biopsy results were independently classified into 1 of 5 categories: cancer, fibroadenomal fibrocystic change, normal or other. The procedure was well tolerated, and all core specimens yielded adequate tissue for pathologic evaluation. There were 3 episodes of vasovagal reaction. There was complete agreement in histologic findings in 64 cases (91%), including 22 of 24 cancers (92%). The overall agreement for categorizing lesions was 91% (k 0.88), and there was 97% agreement (k = 0.94) for the classification of cancer versus benign lesion. The results are similar to those of studies performed with dedicated prone equipment. Stereotaxic core biopsies can be done safely and accurately in a community hospital setting with relatively inexpensive nondedicated mammographic equipment. (author)

Stereotaxic percutaneous core biopsy versus surgical biopsy of nonpalpable breast lesions using a standard mammographic table with an add-on device

Energy Technology Data Exchange (ETDEWEB)

Levin, M.F.; Papoff, W.J.; Doan, L.; Eliasziw, M. [St. Thomas-Elgin General Hospital, St. Thomas, Ontario (Canada)

2001-02-01

To determine the accuracy of using a regular mammographic table with an add-on device for biopsy of nonpalpable breast lesions in women in a community hospital setting. During a 3-year period, 70 consenting women (39-80 years of age) with a nonpalpable mammographically suspicious lesion on routine screening mammography underwent 14-gauge automated percutaneous core biopsies, immediate needle localization and lumpectomy. The needle and surgical biopsy results were independently classified into 1 of 5 categories: cancer, fibroadenomal fibrocystic change, normal or other. The procedure was well tolerated, and all core specimens yielded adequate tissue for pathologic evaluation. There were 3 episodes of vasovagal reaction. There was complete agreement in histologic findings in 64 cases (91%), including 22 of 24 cancers (92%). The overall agreement for categorizing lesions was 91% (k 0.88), and there was 97% agreement (k = 0.94) for the classification of cancer versus benign lesion. The results are similar to those of studies performed with dedicated prone equipment. Stereotaxic core biopsies can be done safely and accurately in a community hospital setting with relatively inexpensive nondedicated mammographic equipment. (author)

Design of experiments (DoE) in pharmaceutical development.

Science.gov (United States)

N Politis, Stavros; Colombo, Paolo; Colombo, Gaia; M Rekkas, Dimitrios

2017-06-01

At the beginning of the twentieth century, Sir Ronald Fisher introduced the concept of applying statistical analysis during the planning stages of research rather than at the end of experimentation. When statistical thinking is applied from the design phase, it enables to build quality into the product, by adopting Deming's profound knowledge approach, comprising system thinking, variation understanding, theory of knowledge, and psychology. The pharmaceutical industry was late in adopting these paradigms, compared to other sectors. It heavily focused on blockbuster drugs, while formulation development was mainly performed by One Factor At a Time (OFAT) studies, rather than implementing Quality by Design (QbD) and modern engineering-based manufacturing methodologies. Among various mathematical modeling approaches, Design of Experiments (DoE) is extensively used for the implementation of QbD in both research and industrial settings. In QbD, product and process understanding is the key enabler of assuring quality in the final product. Knowledge is achieved by establishing models correlating the inputs with the outputs of the process. The mathematical relationships of the Critical Process Parameters (CPPs) and Material Attributes (CMAs) with the Critical Quality Attributes (CQAs) define the design space. Consequently, process understanding is well assured and rationally leads to a final product meeting the Quality Target Product Profile (QTPP). This review illustrates the principles of quality theory through the work of major contributors, the evolution of the QbD approach and the statistical toolset for its implementation. As such, DoE is presented in detail since it represents the first choice for rational pharmaceutical development.

Quasi-bivariate variational mode decomposition as a tool of scale analysis in wall-bounded turbulence

Science.gov (United States)

Wang, Wenkang; Pan, Chong; Wang, Jinjun

2018-01-01

The identification and separation of multi-scale coherent structures is a critical task for the study of scale interaction in wall-bounded turbulence. Here, we propose a quasi-bivariate variational mode decomposition (QB-VMD) method to extract structures with various scales from instantaneous two-dimensional (2D) velocity field which has only one primary dimension. This method is developed from the one-dimensional VMD algorithm proposed by Dragomiretskiy and Zosso (IEEE Trans Signal Process 62:531-544, 2014) to cope with a quasi-2D scenario. It poses the feature of length-scale bandwidth constraint along the decomposed dimension, together with the central frequency re-balancing along the non-decomposed dimension. The feasibility of this method is tested on both a synthetic flow field and a turbulent boundary layer at moderate Reynolds number (Re_{τ } = 3458) measured by 2D particle image velocimetry (PIV). Some other popular scale separation tools, including pseudo-bi-dimensional empirical mode decomposition (PB-EMD), bi-dimensional EMD (B-EMD) and proper orthogonal decomposition (POD), are also tested for comparison. Among all these methods, QB-VMD shows advantages in both scale characterization and energy recovery. More importantly, the mode mixing problem, which degrades the performance of EMD-based methods, is avoided or minimized in QB-VMD. Finally, QB-VMD analysis of the wall-parallel plane in the log layer (at y/δ = 0.12) of the studied turbulent boundary layer shows the coexistence of large- or very large-scale motions (LSMs or VLSMs) and inner-scaled structures, which can be fully decomposed in both physical and spectral domains.

Electrostatic dominoes: long distance propagation of mutational effects in photosynthetic reaction centers of Rhodobacter capsulatus.

Science.gov (United States)

Sebban, P; Maróti, P; Schiffer, M; Hanson, D K

1995-07-04

Two point mutants from the purple bacterium Rhodobacter capsulatus, both modified in the M protein of the photosynthetic reaction center, have been studied by flash-induced absorbance spectroscopy. These strains carry either the M231Arg --> Leu or M43ASN --> Asp mutations, which are located 9 and 15 A, respectively, from the terminal electron acceptor QB. In the wild-type Rb. sphaeroides structure, M231Arg is involved in a conserved salt bridge with H125Glu and H232Glu and M43Asn is located among several polar residues that form or surround the QB binding site. These substitutions were originally uncovered in phenotypic revertants isolated from the photosynthetically incompetent L212Glu-L213Asp --> Ala-Ala site-specific double mutant. As second-site suppressor mutations, they have been shown to restore the proton transfer function that is interrupted in the L212Ala-L213Ala double mutant. The electrostatic effects that are induced in reaction centers by the M231Arg --> Leu and M43Asn --> Asp substitutions are roughly the same in either the double-mutant or wild-type backgrounds. In a reaction center that is otherwise wild type in sequence, they decrease the free energy gap between the QA- and QB- states by 24 +/- 5 and 45 +/- 5 meV, respectively. The pH dependences of K2, the QA-QB QAQB- equilibrium constant, are altered in reaction centers that carry either of these substitutions, revealing differences in the pKas of titratable groups compared to the wild type.(ABSTRACT TRUNCATED AT 250 WORDS)

Transforming nanomedicine manufacturing toward Quality by Design and microfluidics.

Science.gov (United States)

Colombo, Stefano; Beck-Broichsitter, Moritz; Bøtker, Johan Peter; Malmsten, Martin; Rantanen, Jukka; Bohr, Adam

2018-04-05

Nanopharmaceuticals aim at translating the unique features of nano-scale materials into therapeutic products and consequently their development relies critically on the progression in manufacturing technology to allow scalable processes complying with process economy and quality assurance. The relatively high failure rate in translational nanopharmaceutical research and development, with respect to new products on the market, is at least partly due to immature bottom-up manufacturing development and resulting sub-optimal control of quality attributes in nanopharmaceuticals. Recently, quality-oriented manufacturing of pharmaceuticals has undergone an unprecedented change toward process and product development interaction. In this context, Quality by Design (QbD) aims to integrate product and process development resulting in an increased number of product applications to regulatory agencies and stronger proprietary defense strategies of process-based products. Although QbD can be applied to essentially any production approach, microfluidic production offers particular opportunities for QbD-based manufacturing of nanopharmaceuticals. Microfluidics provides unique design flexibility, process control and parameter predictability, and also offers ample opportunities for modular production setups, allowing process feedback for continuously operating production and process control. The present review aims at outlining emerging opportunities in the synergistic implementation of QbD strategies and microfluidic production in contemporary development and manufacturing of nanopharmaceuticals. In doing so, aspects of design and development, but also technology management, are reviewed, as is the strategic role of these tools for aligning nanopharmaceutical innovation, development, and advanced industrialization in the broader pharmaceutical field. Copyright © 2018 Elsevier B.V. All rights reserved.

Flexible add-on solution for MR image-guided interventions in a closed-bore scanner environment.

Science.gov (United States)

Busse, Harald; Garnov, Nikita; Thörmer, Gregor; Zajonz, Dirk; Gründer, Wilfried; Kahn, Thomas; Moche, Michael

2010-09-01

MRI is of great clinical utility for the guidance of various diagnostic and therapeutic procedures. In a standard closed-bore scanner, the simplest approach is to manipulate the instrument outside the bore and move the patient into the bore for reference and control imaging only. Without navigational assistance, however, such an approach can be difficult, inaccurate, and time consuming. Therefore, an add-on navigation solution is described that addresses these limitations. Patient registration is established by an automatic, robust, and fast (<30 sec) localization of table-mounted MR reference markers and the instrument is tracked optically. Good hand-eye coordination is provided by following the virtual instrument on MR images that are reconstructed in real time from the reference data. Needle displacements of 2.2 +/- 0.6 mm and 3.9 +/- 2.4 mm were determined in a phantom (P < 0.05), depending on whether the reference markers were placed at smaller (98-139 mm) or larger (147-188 mm) distances from the isocenter. Clinical functionality of the navigation concept is demonstrated by a double oblique, subscapular hook-wire insertion in a patient with a body mass index of 30.1 kg/m(2). Ease of use, compactness, and flexibility of this technique suggest that it can be used for many other procedures in different body regions. More patient cases are needed to evaluate clinical performance and workflow. 2010 Wiley-Liss, Inc.

A Design of Experiments Approach to Readiness Risk Analysis for Performance-Based Logistics

Science.gov (United States)

2006-09-30

a set of best practice recommendations. Apgar and Keane (2004) describe the strategic goals of PBL and assert that the principle of specifying...Åèìáëáíáçå=oÉëÉ~êÅÜ=mêçÖê~ã= do^ar^qb=p`elli=lc=_rpfkbpp=C=mr_if`=mlif`v= = - 20- k^s^i=mlpqdo^ar^qb=p`elli= List of References Apgar IV, M...Contract Writing, Phase II. June 2004. NPS-CM-04-002 Burger, Major Kenneth A., Captain Brian . Marine Corps Contingency Contracting MCI. Revised Manual

Dicty_cDB: Contig-U05302-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available F275295 |AF275295.1 Eretmocerus queenslandensis clone 262Q c... 38 0.26 2 AF27529...4 |AF275294.1 Eretmocerus queenslandensis clone 171Q c... 38 0.26 2 AF275293 |AF275293.1 Eretmocerus queensland...ensis clone 168Qb ... 38 0.26 2 AF275292 |AF275292.1 Eretmocerus queenslandensis clone 168Qa ... 38 0.26 ...2 AF275291 |AF275291.1 Eretmocerus queenslandensis clone 165Qb ... 38 0.26 2 AF275290 |AF275290.1 Eretmocerus queensland...ensis clone 165Qa ... 38 0.26 2 AF275289 |AF275289.1 Eretmocerus queensland

3D cine phase-contrast MRI at 3T in intracranial aneurysms compared with patient-specific computational fluid dynamics

NARCIS (Netherlands)

van Ooij, P.; Schneiders, J. J.; Marquering, H. A.; Majoie, C. B.; van Bavel, E.; Nederveen, A. J.

2013-01-01

CFD has been proved valuable for simulating blood flow in intracranial aneurysms, which may add to better rupture risk assessment. However, CFD has drawbacks such as the sensitivity to assumptions needed for the model, which may hinder its clinical implementation. 3D PC-MR imaging is a technique

How to Add Value to your Business with CEA: A Practical Approach

Directory of Open Access Journals (Sweden)

Daniel Cardenas

2010-04-01

Full Text Available Companies are always trying to differentiate themselves from the rest of the pack by applying different strategies such as improving customer service, increasing the efficiency of their operations, or reducing their costs. Most of the time, however, these goals are competing against each other for scarce resources, and managers often need to decide to concentrate on one. A small company can effectively and simultaneously accomplish these goals for a fraction of the cost by implementing communications-enabled business processes or solutions, which are a set of technology components that add real-time networking functionality to applications. One particular implementation of this framework is the one provided by Coral CEA. Coral CEA is a business ecosystem anchored around CEA functionalities that are offered as building blocks, out-of-the-box components that link the capabilities and intelligence of networks platforms with the power of current applications to provide a new set of features and functionalities. In this article, we show how a small company called Rezact, located in the ski resort town of Mont-Tremblant, Quebec, successfully implemented CEA capabilities within its own operations using Coral CEA services.

Psychometric Evaluation of a Dutch Version of the Mini PAS-ADD for Assessing Psychiatric Disorders in Adults with Different Levels of Intellectual Disability

Science.gov (United States)

Janssen, R.; Maes, B.

2013-01-01

Background: People with intellectual disabilities (ID) have an increased vulnerability to develop psychiatric problems. Moreover, the early recognition and the accurate diagnosis of psychiatric disorders in the population of persons with ID are challenging. Method: A Dutch version of the Mini PAS-ADD, which is a screening instrument for…

Cost-effectiveness of omalizumab add-on to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting.

Science.gov (United States)

Suzuki, Cibele; Lopes da Silva, Nilceia; Kumar, Praveen; Pathak, Purnima; Ong, Siew Hwa

2017-08-01

Omalizumab add-on to standard-of-care therapy has proven to be efficacious in severe asthma patients for whom exacerbations cannot be controlled otherwise. Moreover, evidence from different healthcare settings suggests reduced healthcare resource utilization with omalizumab. Based on these findings, this study aimed to assess the cost-effectiveness of the addition of omalizumab to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting. A previously published Markov model was adapted using Brazil-specific unit costs to compare the costs and outcomes of the addition of omalizumab to standard-of-care therapy vs standard-of-care therapy alone. Model inputs were largely based on the eXpeRience study. Costs and health outcomes were calculated for lifetime-years and were annually discounted at 5%. Both one-way and probabilistic sensitivity analyses were performed. An additional cost of R$280,400 for 5.20 additional quality-adjusted life-years was estimated with the addition of omalizumab to standard-of-care therapy, resulting in an incremental cost-effectiveness ratio of R$53,890. One-way sensitivity analysis indicated that discount rates, standard-of-care therapy exacerbation rates, and exacerbation-related mortality rates had the largest impact on incremental cost-effectiveness ratios. Assumptions of lifetime treatment adherence and rate of future exacerbations, independent of previous events, might affect the findings. The lack of Brazilian patients in the eXpeRience study may affect the findings, although sample size and baseline characteristics suggest that the modeled population closely resembles Brazilian severe allergic asthma patients. Results indicate that omalizumab as an add-on therapy is more cost-effective than standard-of-care therapy alone for Brazilian patients with uncontrolled severe allergic asthma, based on the World Health Organization's cost-effectiveness threshold of up to 3-times the gross

Developing a quality by design approach to model tablet dissolution testing: an industrial case study.

Science.gov (United States)

Yekpe, Ketsia; Abatzoglou, Nicolas; Bataille, Bernard; Gosselin, Ryan; Sharkawi, Tahmer; Simard, Jean-Sébastien; Cournoyer, Antoine

2017-11-02

This study applied the concept of Quality by Design (QbD) to tablet dissolution. Its goal was to propose a quality control strategy to model dissolution testing of solid oral dose products according to International Conference on Harmonization guidelines. The methodology involved the following three steps: (1) a risk analysis to identify the material- and process-related parameters impacting the critical quality attributes of dissolution testing, (2) an experimental design to evaluate the influence of design factors (attributes and parameters selected by risk analysis) on dissolution testing, and (3) an investigation of the relationship between design factors and dissolution profiles. Results show that (a) in the case studied, the two parameters impacting dissolution kinetics are active pharmaceutical ingredient particle size distributions and tablet hardness and (b) these two parameters could be monitored with PAT tools to predict dissolution profiles. Moreover, based on the results obtained, modeling dissolution is possible. The practicality and effectiveness of the QbD approach were demonstrated through this industrial case study. Implementing such an approach systematically in industrial pharmaceutical production would reduce the need for tablet dissolution testing.

Studies with lucid dreaming as add-on therapy to Gestalt therapy.

Science.gov (United States)

Holzinger, B; Klösch, G; Saletu, B

2015-06-01

The aim of the present exploratory clinical study was to evaluate LD as an add-on therapy for treating nightmares. Thirty-two subjects having nightmares (ICD-10: F51.5) at least twice a week participated. Subjects were randomly assigned to group: A) Gestalt therapy group (= GTG), or B) Gestalt and lucid dreaming group therapy (= LDG). Each group lasted ten weeks. Participants kept a sleep/dream diary over the treatment. Examinations with respect to nightmare frequency and sleep quality (Pittsburgh Sleep Quality Index) were carried out at the beginning, after five and ten weeks and at a follow-up three months later. Concerning nightmare frequency, a significant reduction was found in both groups after the ten-week-study and at the follow-up (Wilcoxon test: P ≤ 0.05). Significant reduction in dream recall frequency could only be observed in the GTG (Wilcoxon test: P ≤ 0.05). For subjects having succeeded in learning lucid dreaming, reduction was sooner and higher. Sleep quality improved for both groups at the follow-up (P ≤ 0.05, Wilcoxon test). Only the LDG showed significant improvement at the end of therapy (P ≤ 0.05). Lucid dreaming, in combination with Gestalt therapy, is a potent technique to reduce nightmare frequency and improve the subjective quality of sleep. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Application of quality by design principles to the development and technology transfer of a major process improvement for the manufacture of a recombinant protein.

Science.gov (United States)

Looby, Mairead; Ibarra, Neysi; Pierce, James J; Buckley, Kevin; O'Donovan, Eimear; Heenan, Mary; Moran, Enda; Farid, Suzanne S; Baganz, Frank

2011-01-01

This study describes the application of quality by design (QbD) principles to the development and implementation of a major manufacturing process improvement for a commercially distributed therapeutic protein produced in Chinese hamster ovary cell culture. The intent of this article is to focus on QbD concepts, and provide guidance and understanding on how the various components combine together to deliver a robust process in keeping with the principles of QbD. A fed-batch production culture and a virus inactivation step are described as representative examples of upstream and downstream unit operations that were characterized. A systematic approach incorporating QbD principles was applied to both unit operations, involving risk assessment of potential process failure points, small-scale model qualification, design and execution of experiments, definition of operating parameter ranges and process validation acceptance criteria followed by manufacturing-scale implementation and process validation. Statistical experimental designs were applied to the execution of process characterization studies evaluating the impact of operating parameters on product quality attributes and process performance parameters. Data from process characterization experiments were used to define the proven acceptable range and classification of operating parameters for each unit operation. Analysis of variance and Monte Carlo simulation methods were used to assess the appropriateness of process design spaces. Successful implementation and validation of the process in the manufacturing facility and the subsequent manufacture of hundreds of batches of this therapeutic protein verifies the approaches taken as a suitable model for the development, scale-up and operation of any biopharmaceutical manufacturing process. Copyright © 2011 American Institute of Chemical Engineers (AIChE).

Characterization of an add-on multileaf collimator for electron beam therapy

Energy Technology Data Exchange (ETDEWEB)

Gauer, T; Sokoll, J; Cremers, F; Schmidt, R [Department of Radiotherapy and Radio-Oncology, University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Harmansa, R [3D Line, Schwarzenbruck (Germany); Luzzara, M [3D Line, Milan (Italy)], E-mail: t.gauer@uke.uni-hamburg.de

2008-02-21

An add-on multileaf collimator for electrons (eMLC) has been developed that provides computer-controlled beam collimation and isocentric dose delivery. The design parameters result from the design study by Gauer et al (2006 Phys. Med. Biol. 51 5987-6003) and were configured such that a compact and light-weight eMLC with motorized leaves can be industrially manufactured and stably mounted on a conventional linear accelerator. In the present study, the efficiency of an initial computer-controlled prototype was examined according to the design goals and the performance of energy- and intensity-modulated treatment techniques. This study concentrates on the attachment and gantry stability as well as the dosimetric characteristics of central-axis and off-axis dose, field size dependence, collimator scatter, field abutment, radiation leakage and the setting of the accelerator jaws. To provide isocentric irradiation, the eMLC can be placed either 16 or 28 cm above the isocentre through interchangeable holders. The mechanical implementation of this feature results in a maximum field displacement of less than 0.6 mm at 90{sup 0} and 270{sup 0} gantry angles. Compared to a 10 x 10 cm applicator at 6-14 MeV, the beam penumbra of the eMLC at a 16 cm collimator-to-isocentre distance is 0.8-0.4 cm greater and the depth-dose curves show a larger build-up effect. Due to the loss in energy dependence of the therapeutic range and the much lower dose output at small beam sizes, a minimum beam size of 3 x 3 cm is necessary to avoid suboptimal dose delivery. Dose output and beam symmetry are not affected by collimator scatter when the central axis is blocked. As a consequence of the broader beam penumbra, uniform dose distributions were measured in the junction region of adjacent beams at perpendicular and oblique beam incidence. However, adjacent beams with a high difference in a beam energy of 6 to 14 MeV generate cold and hot spots of approximately 15% in the abutting region. In

Characterization of an add-on multileaf collimator for electron beam therapy

International Nuclear Information System (INIS)

Gauer, T; Sokoll, J; Cremers, F; Schmidt, R; Harmansa, R; Luzzara, M

2008-01-01

An add-on multileaf collimator for electrons (eMLC) has been developed that provides computer-controlled beam collimation and isocentric dose delivery. The design parameters result from the design study by Gauer et al (2006 Phys. Med. Biol. 51 5987-6003) and were configured such that a compact and light-weight eMLC with motorized leaves can be industrially manufactured and stably mounted on a conventional linear accelerator. In the present study, the efficiency of an initial computer-controlled prototype was examined according to the design goals and the performance of energy- and intensity-modulated treatment techniques. This study concentrates on the attachment and gantry stability as well as the dosimetric characteristics of central-axis and off-axis dose, field size dependence, collimator scatter, field abutment, radiation leakage and the setting of the accelerator jaws. To provide isocentric irradiation, the eMLC can be placed either 16 or 28 cm above the isocentre through interchangeable holders. The mechanical implementation of this feature results in a maximum field displacement of less than 0.6 mm at 90 0 and 270 0 gantry angles. Compared to a 10 x 10 cm applicator at 6-14 MeV, the beam penumbra of the eMLC at a 16 cm collimator-to-isocentre distance is 0.8-0.4 cm greater and the depth-dose curves show a larger build-up effect. Due to the loss in energy dependence of the therapeutic range and the much lower dose output at small beam sizes, a minimum beam size of 3 x 3 cm is necessary to avoid suboptimal dose delivery. Dose output and beam symmetry are not affected by collimator scatter when the central axis is blocked. As a consequence of the broader beam penumbra, uniform dose distributions were measured in the junction region of adjacent beams at perpendicular and oblique beam incidence. However, adjacent beams with a high difference in a beam energy of 6 to 14 MeV generate cold and hot spots of approximately 15% in the abutting region. In order to

Implementation of quality by design toward processing of food products.

Science.gov (United States)

Rathore, Anurag S; Kapoor, Gautam

2017-05-28

Quality by design (QbD) is a systematic approach that begins with predefined objectives and emphasizes product and process understanding and process control. It is an approach based on principles of sound science and quality risk management. As the food processing industry continues to embrace the idea of in-line, online, and/or at-line sensors and real-time characterization for process monitoring and control, the existing gaps with regard to our ability to monitor multiple parameters/variables associated with the manufacturing process will be alleviated over time. Investments made for development of tools and approaches that facilitate high-throughput analytical and process development, process analytical technology, design of experiments, risk analysis, knowledge management, and enhancement of process/product understanding would pave way for operational and economic benefits later in the commercialization process and across other product pipelines. This article aims to achieve two major objectives. First, to review the progress that has been made in the recent years on the topic of QbD implementation in processing of food products and second, present a case study that illustrates benefits of such QbD implementation.

Effects of pitavastatin add-on therapy on chronic kidney disease with albuminuria and dyslipidemia.

Science.gov (United States)

Ohsawa, Masato; Tamura, Kouichi; Wakui, Hiromichi; Kanaoka, Tomohiko; Azushima, Kengo; Uneda, Kazushi; Haku, Sona; Kobayashi, Ryu; Ohki, Kohji; Haruhara, Kotaro; Kinguchi, Sho; Toya, Yoshiyuki; Umemura, Satoshi

2015-12-09

In non-dialysis chronic kidney disease (CKD) patients with dyslipidemia, statin therapy is recommended to prevent cardiovascular complications. Dyslipidemia has been also shown to be an independent risk factor for the progression of CKD. However, it is still unclear whether statin therapy exerts an inhibitory effect on renal deterioration in CKD patients with dyslipidemia. The purpose of the present study was to examine possible therapeutic effects of statin add-on therapy on renal function as well as parameters of lipid and glucose metabolism, arterial stiffness and oxidative stress, in comparison to diet therapy, in CKD patients with dyslipidemia. This study was a randomized, open-label, and parallel-group trial consisted of a 12-months treatment period in non-dialysis CKD patients with alubuminuria and dyslipidemia. Twenty eight patients were randomly assigned either to receive diet counseling alone (diet therapy group) or diet counseling plus pitavastatin (diet-plus-statin therapy group), to achieve the LDL-cholesterol (LDL-C) target of dyslipidemia.

Air pollution, deprivation and health: Understanding relationships to add value to local air quality management policy and practice in Wales, UK

OpenAIRE

Brunt, H.; Barnes, J.; Jones, S.; Longhurst, J.; Scally, G.; Hayes, E. T.

2017-01-01

Background \\ud Air pollution exposure reduces life expectancy. Air pollution, deprivation and poor-health status combinations can create increased and disproportionate disease burdens. Problems and solutions are rarely considered in a broad public health context, but doing so can add value to air quality management efforts by reducing air pollution risks, impacts and inequalities.\\ud \\ud Methods \\ud An ecological study assessed small-area associations between air pollution (nitrogen dioxide a...

An exploratory study on the potential value add of social networking to the Entrepreneurial process

Directory of Open Access Journals (Sweden)

Alex Antonites

2011-12-01

Full Text Available It is widely established in scientific literature that entrepreneurship directly contributes to both employment generation and economic growth. Entrepreneurship is said to be subject to a very specific process which includes opportunity recognition, resource allocation, innovation and networking. Networking specifically, is an essential part of the entrepreneurial process as it is employed to assist entrepreneurs to capitalise on opportunities, allocate resources, find ways to innovate and contest ambiguity. With the advent of Web 2.0 and online social networking platforms the way in which people exchange information and network has changed significantly and has spawned a new social culture on a global level. The purpose of this study is to examine the value that online social networking adds to the entrepreneurial process, specifically focussing on the South African landscape. Keywords and phrases: Entrepreneurship; Networking; Social capital; Social networking; Social media

Remote Sensing and Mapping of Tamarisk along the Colorado River, USA: A Comparative Use of Summer-Acquired Hyperion, Thematic Mapper and QuickBird Data

Directory of Open Access Journals (Sweden)

Jerry A. Griffith

2009-07-01

Full Text Available Tamarisk (Tamarix spp., saltcedar is a well-known invasive phreatophyte introduced from Asia to North America in the 1800s. This report compares the efficacy of Landsat 5 Thematic Mapper (TM5, QuickBird (QB and EO-1 Hyperion data in discriminating tamarisk populations near De Beque, Colorado, USA. As a result of highly correlated reflectance among the spectral bands provided by each sensor, relatively standard image analysis methods were employed. Multispectral data at high spatial resolution (QB, 2.5 m Ground Spatial Distance or GSD proved more effective in tamarisk delineation than either multispectral (TM5 or hyperspectral (Hyperion data at moderate spatial resolution (30 m GSD.

Having Older Siblings Is Associated with Lower Rates of Depression, ADD/ADHD, Anxiety and Behavior Problems Among Children with ASD.

Science.gov (United States)

Montes, Guillermo

2018-05-01

Objective Within the social determinants of mental health framework, this article investigated whether children with ASD who have older siblings are less likely to experience depression, anxiety, behavior problems or have ADD/ADHD after controlling for standard social determinants of mental health such as household income, parental education and adverse childhood experiences (ACEs). Methods Using the National Survey of Children's Health 2011-2012, children with ASD spectrum disorders (n = 1624) were categorized into three groups: only child, oldest child and has older siblings. Design corrected cross-tabulations, univariate and multivariate logistic regressions were estimated. Results The three groups of children with ASD were comparable in demographic characteristics (except age), ACEs, and parent-reported ASD severity. Children with ASD who had older siblings were significantly less likely to experience depression, anxiety or behavior problems. They were also less likely to have been diagnosed with ADD or ADHD. Adjusted odds ratios ranged from 0.12 to 0.53 indicating robust associations. Conclusions for Practice Children with ASD who have older siblings were less likely to have comorbid mental health disorders than other children with ASD. Conversely, oldest and only children with ASD were at increased risk for these disorders. Further research is needed to understand how this protection is conferred on children with ASD, and whether it can be adapted into interventions for only and oldest children with ASD.

Cortical atrophy rates in Alzheimer's patients and subjects with mild cognitive impairment from the AddNeuroMed data collection

DEFF Research Database (Denmark)

Eskildsen, Simon Fristed; Westman, Eric; Gwadry-Sridhar, Femida

2010-01-01

Background: The AddNeuroMed project is a multi-centre European project which aims to identify biomarkers in Alzheimer's disease (AD). In this study we measured the rate of cortical atrophy in AD patients, subjects with mild cognitive impairment (MCI), and healthy controls (HC) using MRI. Methods...... quality control for both the acquisition and image processing were included in the study. Cortical thickness was measured using FACE (fast accurate cortex extraction) and averaged within main lobes using a stereotaxic atlas. Atrophy rates were calculated as percent decrease in cortical thickness and rate...

Homozygous mutation in the NPHP3 gene causing foetal nephronophthisis

DEFF Research Database (Denmark)

Abdullah, Uzma; Farooq, Muhammad; Fatima, Ambrin

2017-01-01

We present a case of a foetal sonographic finding of hyper-echogenic kidneys, which led to a strategic series of genetic tests and identified a homozygous mutation (c.424C > T, p. R142*) in the NPHP3 gene. Our study provides a rare presentation of NPHP3-related ciliopathy and adds to the mutation...

Cost-consequence analysis of sitagliptin versus sulfonylureas as add-on therapy for the treatment of diabetic patients in Italy.

Science.gov (United States)

Lorenzoni, Valentina; Baccetti, Fabio; Genovese, Stefano; Torre, Enrico; Turchetti, Giuseppe

2017-01-01

Diabetes mellitus is a chronic disease related to a significant impact in both epidemiologic and economic terms. In Italy, around 3.6 million people are affected by diabetes and this number is expected to increase significantly in the next few years. As recommended by current national and international guidelines, metformin (Met) is prescribed as first-line pharmacological treatment, and many pharmacological alternatives are available for patients uncontrolled with Met monotherapy. Despite the availability of many innovative oral antidiabetic drugs (OADs), such as dipeptidyl peptidase 4 inhibitors (DPP4-i) and its first-in-class sitagliptin (SITA), which entered the Italian market in the last 10 years, their usage is consistently lower than traditional drugs such as sulfonylureas (SUs). In fact, due to higher acquisition costs, the prescription of innovative OADs in Italy is restricted to specialist, resulting in a prominent usage of traditional OAD that can be prescribed also by general practitioners (GPs). A cost consequence analysis (CCA) was performed in order to compare SITA with SU, as second-line therapy in add-on to Met, in terms of costs and related clinical events over 36 months. A CCA was conducted on a hypothetical cohort of 100,000 type 2 diabetes mellitus (T2DM) patients uncontrolled with Met monotherapy, from both the Italian National Health Service (INHS) and societal perspective. Therefore, both direct (drugs, self-monitoring, hypoglycemia, major cardiovascular events [MACEs], and switch to insulin) and indirect costs (expressed in terms of productivity losses) were evaluated. Clinical and economic data were collected through Italian national tariffs, literature, and experts' opinions. Three expert clinicians finally validated data inputs. To assess robustness of base case results, a one-way sensitivity analysis (OWSA) and a conservative scenario analysis - excluding MACEs - were carried out. In the base case analysis, the higher drug costs related

Technology management-An effective tool to add competitiveness to the business

Energy Technology Data Exchange (ETDEWEB)

Layrisse, I.; Izquierdo, A. [Intevep, S.A., Caracas (Venezuela)

1996-08-01

Petreleos de Venezuela (PDVSA) and its affiliated companies, aware of the importance of the technology to sustain the viability of a successful corporation in global markets with increasing competition and stringent economies, are devoting important efforts in technology as an effective tool to add competitiveness to its core businesses. These efforts are based in the conception of the technology as a structural aspect of the corporation integrated to each one of its businesses. In this sense technology is considered in an integrated way together with markets, operations, infrastructure, resources, etc., across the value chain of the company, from the conception of its vision and mission to the formulation and execution of its operating plans. In this presentation, the conceptual and methodological aspects employed by PDVSA in the establishment of its technology strategy integrated to its business plan, and subsequent project portfolio definition, are summarized. The experience acquired through this corporative exercise conducted by PDVSA confirms that technology and its management are highly linked to the culture of the companies and of the countries where they operate. The technology management best practices are very helpful in establishing processes and specific methodologies; however, the consideration of other aspects such as leadership, management style, shared values, etc., need to be taken into account with the same emphasis, in order to accomplish the changes needed to create a technology culture fitted to a given setting and ideology.

3-D Image Encryption Based on Rubik's Cube and RC6 Algorithm

Science.gov (United States)

Helmy, Mai; El-Rabaie, El-Sayed M.; Eldokany, Ibrahim M.; El-Samie, Fathi E. Abd

2017-12-01

A novel encryption algorithm based on the 3-D Rubik's cube is proposed in this paper to achieve 3D encryption of a group of images. This proposed encryption algorithm begins with RC6 as a first step for encrypting multiple images, separately. After that, the obtained encrypted images are further encrypted with the 3-D Rubik's cube. The RC6 encrypted images are used as the faces of the Rubik's cube. From the concepts of image encryption, the RC6 algorithm adds a degree of diffusion, while the Rubik's cube algorithm adds a degree of permutation. The simulation results demonstrate that the proposed encryption algorithm is efficient, and it exhibits strong robustness and security. The encrypted images are further transmitted over wireless Orthogonal Frequency Division Multiplexing (OFDM) system and decrypted at the receiver side. Evaluation of the quality of the decrypted images at the receiver side reveals good results.

Associations between dopamine and serotonin genes and job satisfaction: preliminary evidence from the Add Health Study.

Science.gov (United States)

Song, Zhaoli; Li, Wendong; Arvey, Richard D

2011-11-01

Previous behavioral genetic studies have found that job satisfaction is partially heritable. We went a step further to examine particular genetic markers that may be associated with job satisfaction. Using an oversample from the National Adolescent Longitudinal Study (Add Health Study), we found 2 genetic markers, dopamine receptor gene DRD4 VNTR and serotonin transporter gene 5-HTTLPR, to be weakly but significantly associated with job satisfaction. Furthermore, we found study participants' level of pay to mediate the DRD4 and job satisfaction relationship. However, we found no evidence that self-esteem mediated the relationships between these 2 genes and job satisfaction. The study represents an initial effort to introduce a molecular genetics approach to the fields of organizational psychology and organizational behavior. (c) 2011 APA, all rights reserved.

Long-term efficacy and safety of vildagliptin add-on therapy in type 2 diabetes mellitus with insulin treatment.

Science.gov (United States)

Kanazawa, Ippei; Tanaka, Ken-Ichiro; Notsu, Masakazu; Tanaka, Sayuri; Kiyohara, Nobuaki; Koike, Sayo; Yamane, Yuko; Tada, Yuko; Sasaki, Motofumi; Yamauchi, Mika; Sugimoto, Toshitsugu

2017-01-01

The use of dipeptidyl peptidase (DPP)-4 inhibitors in patients with type 2 diabetes treated with insulin may be beneficial. However, the long-term efficacy and safety of vildagliptin add-on therapy in these patients remains unclear. A total of 73 patients with type 2 diabetes treated with insulin were randomly assigned to receive either add-on therapy of vildagliptin (n=37) or conventional therapy without DPP-4 inhibitors (n=36) for glucose control. Hemoglobin A1c (HbA1c) levels, dose and number of insulin injections, number of hypoglycemia episodes, and liver and renal function were monitored for 2years. The baseline characteristics of subjects, including age, dose of insulin injections, or HbA1c levels, did not differ between the two groups. In the vildagliptin group, HbA1c levels significantly decreased and the significance of HbA1c reduction was maintained for 24months (from 8.0±1.2% to 7.4±1.0%, pinsulin injections significantly reduced (-5.6units, p1, and -0.9 times, p1). However, these parameters were unchanged in the control group. The number of patients who experienced three or more episodes of hypoglycemia per year was significantly lower in the vildagliptin group (n=4) than in the control group (n=11) (odds ratio, 0.28; 95% confidence interval, 0.08-0.97; pinsulin treatment for 24months was well tolerated and led to sustained reductions in HbA1c, the dose and number of insulin injections, and the risk of hypoglycemia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Interference Canceller Based on Cycle-and-Add Property for Single User Detection in DS-CDMA

Science.gov (United States)

Hettiarachchi, Ranga; Yokoyama, Mitsuo; Uehara, Hideyuki; Ohira, Takashi

In this paper, performance of a novel interference cancellation technique for the single user detection in a direct-sequence code-division multiple access (DS-CDMA) system has been investigated. This new algorithm is based on the Cycle-and-Add property of PN (Pseudorandom Noise) sequences and can be applied for both synchronous and asynchronous systems. The proposed strategy provides a simple method that can delete interference signals one by one in spite of the power levels of interferences. Therefore, it is possible to overcome the near-far problem (NFP) in a successive manner without using transmit power control (TPC) techniques. The validity of the proposed procedure is corroborated by computer simulations in additive white Gaussian noise (AWGN) and frequency-nonselective fading channels. Performance results indicate that the proposed receiver outperforms the conventional receiver and, in many cases, it does so with a considerable gain.

A Comparison of Modeled and Observed Ocean Mixed Layer Behavior in a Sea Breeze Influenced Coastal Region

Science.gov (United States)

1993-12-21

Latent(Lower Solid), Net Infrared (Dashed), and Net viii Heat Loss (Upper Solid - the Other 3 Surmmed) are Plotted, with Positive Values :ndicating...gained from solar insolation, Qs, and the heat lost from the surface due to latent, Qe, sensible, Qh, and net infrared radiation, Qb is positive...five empirically derived dimensionless constants in the model. With the introduction of two new unknowns, <E> and < ww2 >, the prediction of the upper

The integration of the neurosciences, child public health, and education practice: hemisphere-specific remediation strategies as a discipline partnered rehabilitation tool in ADD/ADHD

Directory of Open Access Journals (Sweden)

Gerry eLeisman

2013-07-01

Full Text Available ADHD is the most common and most studied neurodevelopmental problem. Recent statistics from the CDC state that 11% approximately 1 out of every 9 children in the US and 1 in 5 high school boys are diagnosed with ADHD. Lacking from treatment is an interdisciplinary knowledge-based strategy to intervention with child public health concerns addressed the educational system. This study is based on previous findings that ADHD children possess underactivity between sub-cortical and cortical regions. An imbalance of activity or arousal in one area can result in functional disconnections similar to that seen in split-brain patients. As ADD/ADHD children exhibit deficient performance on tests measuring perceptual laterality, evidence of weak laterality or failure to develop laterality has been found across various modalities (auditory, visual, tactile resulting in abnormal cerebral organization and associated dysfunctional specialization needed for lateralized processing of language and non-language function. This pilot study examines groups of ADD/ADHD and control elementary school children all of whom were administered all the subtests of the Wechsler Individual Achievement Tests, the Brown Parent Questionnaire, and given objective performance measures on tests of motor and sensory coordinative abilities. Results measured after a 12-week remediation program aimed at increasing the activity of the hypothesized underactive right hemisphere function, yielded significant improvement of greater than two years in grade level in all domains except in mathematical reasoning. The treated group also displayed a significant improvement in behavior with a reduction in Brown scale behavioral scores. Non-treated control participants did not exhibit significant differences during the same 12-week period in academic measurements, but did so when compared to the treated group. Results are discussed in the context of the concept of functional disconnectivity in ADD

Translation of Berlin Questionnaire to Portuguese language and its application in OSA identification in a sleep disordered breathing clinic

Directory of Open Access Journals (Sweden)

A.P. Vaz

2011-03-01

Full Text Available Background: Berlin Questionnaire (BQ, an English language screening tool for obstructive sleep apnea (OSA in primary care, has been applied in tertiary settings, with variable results. Aims: Development of BQ Portuguese version and evaluation of its utility in a sleep disordered breathing clinic (SDBC. Material and methods: BQ was translated using back translation methodology and prospectively applied, previously to cardiorespiratory sleep study, to 95 consecutive subjects, referred to a SDBC, with OSA suspicion. OSA risk assessment was based on responses in 10 items, organized in 3 categories: snoring and witnessed apneas (category 1, daytime sleepiness (category 2, high blood pressure (HBP/obesity (category 3. Results: In the studied sample, 67.4% were males, with a mean age of 51 ± 13 years. Categories 1, 2 and 3 were positive in 91.6, 24.2 and 66.3%, respectively. BQ identified 68.4% of the patients as being in the high risk group for OSA and the remaining 31.6% in the low risk. BQ sensitivity and specificity were 72.1 and 50%, respectively, for an apnea-hipopnea index (AHI > 5, 82.6 and 44.8% for AHI > 15, 88.4 and 39.1% for AHI > 30. Being in the high risk group for OSA did not infl uence significantly the probability of having the disease (positive likelihood ratio [LR] between 1.44-1.49. Only the items related to snoring loudness, witnessed apneas and HBP/obesity presented a statistically positive association with AHI, with the model constituted by their association presenting a greater discrimination capability, especially for an AHI > 5 (sensitivity 65.2%, specificity 80%, positive LR 3.26. Conclusions: The BQ is not an appropriate screening tool for OSA in a SDBC, although snoring loudness, witnessed apneas, HBP/obesity have demonstrated being significant questionnaire elements in this population. Resumo: Introdução: O Questionário de Berlim (QB, originalmente desenvolvido em língua inglesa como um instrumento de

Sample-based engine noise synthesis using an enhanced pitch-synchronous overlap-and-add method.

Science.gov (United States)

Jagla, Jan; Maillard, Julien; Martin, Nadine

2012-11-01

An algorithm for the real time synthesis of internal combustion engine noise is presented. Through the analysis of a recorded engine noise signal of continuously varying engine speed, a dataset of sound samples is extracted allowing the real time synthesis of the noise induced by arbitrary evolutions of engine speed. The sound samples are extracted from a recording spanning the entire engine speed range. Each sample is delimitated such as to contain the sound emitted during one cycle of the engine plus the necessary overlap to ensure smooth transitions during the synthesis. The proposed approach, an extension of the PSOLA method introduced for speech processing, takes advantage of the specific periodicity of engine noise signals to locate the extraction instants of the sound samples. During the synthesis stage, the sound samples corresponding to the target engine speed evolution are concatenated with an overlap and add algorithm. It is shown that this method produces high quality audio restitution with a low computational load. It is therefore well suited for real time applications.

Green synthesis of silver nanoparticles using tannins

Science.gov (United States)

Raja, Pandian Bothi; Rahim, Afidah Abdul; Qureshi, Ahmad Kaleem; Awang, Khalijah

2014-09-01

Colloidal silver nanoparticles were prepared by rapid green synthesis using different tannin sources as reducing agent viz. chestnut (CN), mangrove (MG) and quebracho (QB). The aqueous silver ions when exposed to CN, MG and QB tannins were reduced which resulted in formation of silver nanoparticles. The resultant silver nanoparticles were characterized using UV-Visible, X-ray diffraction (XRD), scanning electron microscopy (SEM/EDX), and transmission electron microscopy (TEM) techniques. Furthermore, the possible mechanism of nanoparticles synthesis was also derived using FT-IR analysis. Spectroscopy analysis revealed that the synthesized nanoparticles were within 30 to 75 nm in size, while XRD results showed that nanoparticles formed were crystalline with face centered cubic geometry.

A single competency-based education and training and competency-based career framework for the Australian health workforce: discussing the potential value add

Science.gov (United States)

Brownie, Sharon Mary; Thomas, Janelle

2014-01-01

This brief discusses the policy implications of a research study commissioned by Health Workforce Australia (HWA) within its health workforce innovation and reform work program. The project explored conceptually complex and operationally problematic concepts related to developing a whole-of-workforce competency-based education and training and competency-based career framework for the Australian health workforce and culminated with the production of three reports published by HWA. The project raised important queries as to whether such a concept is desirable, feasible or implementable – in short what is the potential value add and is it achievable? In setting the scene for discussion, the foundation of the project’s genesis and focus of the study are highlighted. A summary of key definitions related to competency-based education and training frameworks and competency-based career frameworks are provided to further readers’ commonality of understanding. The nature of the problem to be solved is explored and the potential value-add for the Australian health workforce and its key constituents proposed. The paper concludes by discussing relevance and feasibility issues within Australia’s current and changing healthcare context along with the essential steps and implementation realities that would need to be considered and actioned if whole-of-workforce frameworks were to be developed and implemented. PMID:25279384

Patriot Script 1.0.13 User Guide for PEM 1.3.2

Energy Technology Data Exchange (ETDEWEB)

Cleland, Timothy James [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Kubicek, Deborah Ann [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Stroud, Phillip David [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Cuellar-Hengartner, Leticia [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mathis, Mark [Descartes Labs, Inc., Los Alamos, NM (United States)

2015-11-02

This document provides an updated user guide for Patriot Script Version 1.0.13, for release with PEM 1.3.1 (LAUR-1422817) that adds description and instructions for the new excursion capability (see section 4.5.1).

Ozone therapy as add-on treatment in fibromyalgia management by rectal insufflation: an open-label pilot study.

Science.gov (United States)

Hidalgo-Tallón, Javier; Menéndez-Cepero, Silvia; Vilchez, Juan S; Rodríguez-López, Carmen M; Calandre, Elena P

2013-03-01

The objectives of this study were to evaluate the effectiveness and tolerability of ozone therapy by rectal insufflation as add-on therapy in fibromyalgia management. Patients with fibromyalgia received 24 sessions of ozone therapy during a 12-week period. At each session, the administered dose of ozone was 8 mg (200 mL of gas, at a concentration of 40 μg/mL). Ozone sessions were given 5 days a week during the first 2 weeks, twice a week from weeks 3-6, and weekly from weeks 7-12. Fibromyalgia Impact Questionnaire (FIQ) was the main outcome measure, and was administered at baseline and at weeks 4, 8, and 12. Secondary outcome measures, administered at baseline and at endpoint, were the Pittsburgh Sleep Quality Index, the Beck Depression Inventory, the State and Trait Anxiety Inventory, and the SF-12, the abbreviated form of the Short Form Health Survey. Emergent adverse reactions to treatment were recorded. FIQ total scores decreased significantly during the study period, with the decrease being observed in the first 4 weeks of the study. Significant improvement was also seen both in depression scores and in the Physical Summary Score of the SF-12. Transient meteorism after ozone therapy sessions was the most frequently reported side-effect. At the dose and number of sessions used in this study, ozone therapy by rectal insufflation seems to be beneficial for physical symptoms and depression of fibromyalgia.

Implementation of an advanced hybrid MPC-PID control system using PAT tools into a direct compaction continuous pharmaceutical tablet manufacturing pilot plant.

Science.gov (United States)

Singh, Ravendra; Sahay, Abhishek; Karry, Krizia M; Muzzio, Fernando; Ierapetritou, Marianthi; Ramachandran, Rohit

2014-10-01

It is desirable for a pharmaceutical final dosage form to be manufactured through a quality by design (QbD)-based approach rather than a quality by testing (QbT) approach. An automatic feedback control system coupled with PAT tools that is part of the QbD paradigm shift, has the potential to ensure that the pre-defined end product quality attributes are met in a time and cost efficient manner. In this work, an advanced hybrid MPC-PID control architecture coupled with real time inline/online monitoring tools and principal components analysis (PCA) based additional supervisory control layer has been proposed for a continuous direct compaction tablet manufacturing process. The advantages of both MPC and PID have been utilized in a hybrid scheme. The control hardware and software integration and implementation of the control system has been demonstrated using feeders and blending unit operation of a continuous tablet manufacturing pilot plant and an NIR based PAT tool. The advanced hybrid MPC-PID control scheme leads to enhanced control loop performance of the critical quality attributes in comparison to a regulatory (e.g. PID) control scheme indicating its potential to improve pharmaceutical product quality. Copyright © 2014 Elsevier B.V. All rights reserved.

Modeling in the quality by design environment: Regulatory requirements and recommendations for design space and control strategy appointment.

Science.gov (United States)

Djuris, Jelena; Djuric, Zorica

2017-11-30

Mathematical models can be used as an integral part of the quality by design (QbD) concept throughout the product lifecycle for variety of purposes, including appointment of the design space and control strategy, continual improvement and risk assessment. Examples of different mathematical modeling techniques (mechanistic, empirical and hybrid) in the pharmaceutical development and process monitoring or control are provided in the presented review. In the QbD context, mathematical models are predominantly used to support design space and/or control strategies. Considering their impact to the final product quality, models can be divided into the following categories: high, medium and low impact models. Although there are regulatory guidelines on the topic of modeling applications, review of QbD-based submission containing modeling elements revealed concerns regarding the scale-dependency of design spaces and verification of models predictions at commercial scale of manufacturing, especially regarding real-time release (RTR) models. Authors provide critical overview on the good modeling practices and introduce concepts of multiple-unit, adaptive and dynamic design space, multivariate specifications and methods for process uncertainty analysis. RTR specification with mathematical model and different approaches to multivariate statistical process control supporting process analytical technologies are also presented. Copyright © 2017 Elsevier B.V. All rights reserved.

A new roadmap for biopharmaceutical drug product development: Integrating development, validation, and quality by design.

Science.gov (United States)

Martin-Moe, Sheryl; Lim, Fredric J; Wong, Rita L; Sreedhara, Alavattam; Sundaram, Jagannathan; Sane, Samir U

2011-08-01

Quality by design (QbD) is a science- and risk-based approach to drug product development. Although pharmaceutical companies have historically used many of the same principles during development, this knowledge was not always formally captured or proactively submitted to regulators. In recent years, the US Food and Drug Administration has also recognized the need for more controls in the drug manufacturing processes, especially for biological therapeutics, and it has recently launched an initiative for Pharmaceutical Quality for the 21st Century to modernize pharmaceutical manufacturing and improve product quality. In the biopharmaceutical world, the QbD efforts have been mainly focused on active pharmaceutical ingredient processes with little emphasis on drug product development. We present a systematic approach to biopharmaceutical drug product development using a monoclonal antibody as an example. The approach presented herein leverages scientific understanding of products and processes, risk assessments, and rational experimental design to deliver processes that are consistent with QbD philosophy without excessive incremental effort. Data generated using these approaches will not only strengthen data packages to support specifications and manufacturing ranges but hopefully simplify implementation of postapproval changes. We anticipate that this approach will positively impact cost for companies, regulatory agencies, and patients, alike. Copyright © 2011 Wiley-Liss, Inc.

Prostate cancer volume adds significantly to prostate-specific antigen in the prediction of early biochemical failure after external beam radiation therapy

International Nuclear Information System (INIS)

D'Amico, Anthony V.; Propert, Kathleen J.

1996-01-01

Purpose: A new clinical pretreatment quantity that closely approximates the true prostate cancer volume is defined. Methods and Materials: The cancer-specific prostate-specific antigen (PSA), PSA density, prostate cancer volume (V Ca ), and the volume fraction of the gland involved with carcinoma (V Ca fx) were calculated for 227 prostate cancer patients managed definitively with external beam radiation therapy. 1. PSA density PSA/ultrasound prostate gland volume 2. Cancer-specific PSA = PSA - [PSA from benign epithelial tissue] 3. V Ca = Cancer-specific PSA/[PSA in serum per cm 3 of cancer] 4. V Ca fx = V Ca /ultrasound prostate gland volume A Cox multiple regression analysis was used to test whether any of these-clinical pretreatment parameters added significantly to PSA in predicting early postradiation PSA failure. Results: The prostate cancer volume (p = 0.039) and the volume fraction of the gland involved by carcinoma (p = 0.035) significantly added to the PSA in predicting postradiation PSA failure. Conversely, the PSA density and the cancer-specific PSA did not add significantly (p > 0.05) to PSA in predicting postradiation PSA failure. The 20-month actuarial PSA failure-free rates for patients with calculated tumor volumes of ≤0.5 cm 3 , 0.5-4.0 cm 3 , and >4.0 cm 3 were 92, 80, and 47%, respectively (p = 0.00004). Conclusion: The volume of prostate cancer (V Ca ) and the resulting volume fraction of cancer both added significantly to PSA in their ability to predict for early postradiation PSA failure. These new parameters may be used to select patients in prospective randomized trials that examine the efficacy of combining radiation and androgen ablative therapy in patients with clinically localized disease, who are at high risk for early postradiation PSA failure

Conducting Automated Test Assembly Using the Premium Solver Platform Version 7.0 with Microsoft Excel and the Large-Scale LP/QP Solver Engine Add-In

Science.gov (United States)

Cor, Ken; Alves, Cecilia; Gierl, Mark J.

2008-01-01

This review describes and evaluates a software add-in created by Frontline Systems, Inc., that can be used with Microsoft Excel 2007 to solve large, complex test assembly problems. The combination of Microsoft Excel 2007 with the Frontline Systems Premium Solver Platform is significant because Microsoft Excel is the most commonly used spreadsheet…

Effect of Exercise Intervention on Flow-Mediated Dilation in Overweight and Obese Adults: Meta-Analysis

Directory of Open Access Journals (Sweden)

Younsun Son

2017-01-01

Full Text Available The objective of this meta-analysis is to summarize the effect of exercise intervention on flow-mediated dilatation (FMD in overweight and obese adults. We searched four electronic databases (PubMed/Medline, Scopus, and CINAHL through June 2016 for relevant studies pertaining to the effectiveness of exercise intervention on FMD. Seventeen of the 91 studies identified met the inclusion criteria. Comprehensive Meta-Analysis software (version 3 was used to compute the standardized mean difference effect size (ES and 95% CI using a random effects model. We calculated 34 ESs. We found that exercise intervention had medium and positive effects on FMD, with an overall ES of 0.522 (95% CI = 0.257, 0.786. Heterogeneity of ESs was observed (Qb=239, p≤0.001, I2 = 86.19, and the effect was moderated by comorbidity (Qb = 6.39, df = 1, p=0.011. A large ES for the combination exercise, low intensity exercise, and comorbidity subgroups (ES = 0.82~1.24 was found. We conclude that while exercise intervention significantly improves FMD in overweight and obese adults, the effect may depend on the different characteristics of exercise intervention and on participants’ demographics.

Long-term efficacy and safety of sodium-glucose cotransporter-2 inhibitors as add-on to metformin treatment in the management of type 2 diabetes mellitus

Science.gov (United States)

Li, Jian; Gong, Yanping; Li, Chunlin; Lu, Yanhui; Liu, Yu; Shao, Yinghong

2017-01-01

Abstract Background: Drug intensification is often required for patients with type 2 diabetes mellitus on stable metformin therapy. Among the potential candidates for a combination therapy, sodium-glucose transporter-2 (SGLT2) inhibitors have shown promising outcomes. This meta-analysis was performed to compare the efficacy and safety of SGLT2 inhibitors with non-SGLT2 combinations as add-on treatment to metformin. Methods: Literature search was carried out in multiple electronic databases for the acquisition of relevant randomized controlled trials (RCTs) by following a priori eligibility criteria. After the assessment of quality of the included RCTs, meta-analyses of mean differences or odds ratios (OR) were performed to achieve overall effect sizes of the changes from baseline in selected efficacy and safety endpoints reported in the individual studies. Between-studies heterogeneity was estimated with between-studies statistical heterogeneity (I2) index. Results: Six RCTs fulfilled the eligibility criteria. SGLT2 inhibitors as add-on to metformin treatment reduced % HbA1c significantly more than non-SGLT2 combinations after 52 weeks (P = .002) as well as after 104 weeks (P SGLT2 inhibitors also reduced fasting plasma glucose levels, body weight, systolic, and diastolic blood pressures after 52 weeks and 104 weeks significantly (P SGLT2 combinations. Incidence of hypoglycemia was significantly lower (P = .02) but incidence of suspected or confirmed genital tract infections was significantly higher (P SGLT2 inhibitors treated in comparison with non-SGLT2 combinations. Conclusion: As add-on to metformin treatment, SGLT2 inhibitors are found significantly more efficacious than non-SGLT2 inhibitor combinations in the management of type 2 diabetes mellitus, although, SGLT2 inhibitor therapy is associated with significantly higher incidence of suspected or confirmed genital tract infections. PMID:28682870

Reactions of dialkyl hydrogen phosphites with 2,3-diphenylindone

International Nuclear Information System (INIS)

Arbuzov, B.A.; Fuzhenkova, A.V.; Banderova, N.A.

1987-01-01

Dialkyl hydrogen phosphites are found to add to 2,3-diphenylindone at the carbonyl group with the formation of dialkyl 1-hydroxy-2,3-diphenylinden-1-yl phosphonates, which, under conditions of basic catalysis, are rearranged into diakyl 2,3-diphenylinden-1-yl phosphates, presumably as a result of phosphonate-phosphate rearrangement. Data derived by IR and NMR spectroscopy are included on the electronic and molecular structure of the resulting isomers. Electron density and spin-spin coupling constants are also determined

Acupuncture and related therapies used as add-on or alternative to prokinetics for functional dyspepsia: overview of systematic reviews and network meta-analysis

OpenAIRE

Ho, Robin S. T.; Chung, Vincent C. H.; Wong, Charlene H. L.; Wu, Justin C. Y.; Wong, Samuel Y. S.; Wu, Irene X. Y.

2017-01-01

Prokinetics for functional dyspepsia (FD) have relatively higher number needed to treat values. Acupuncture and related therapies could be used as add-on or alternative. An overview of systematic reviews (SRs) and network meta-analyses (NMA) were performed to evaluate the comparative effectiveness of different acupuncture and related therapies. We conducted a comprehensive literature search for SRs of randomized controlled trials (RCTs) in eight international and Chinese databases. Data from ...

Psychometric evaluation of a Dutch version of the Mini PAS-ADD for assessing psychiatric disorders in adults with different levels of intellectual disability

OpenAIRE

Janssen, Rianne; Maes, Bea

2013-01-01

Background People with intellectual disabilities (ID) have an increased vulnerability to develop psychiatric problems. Moreover, the early recognition and the accurate diagnosis of psychiatric disorders in the population of persons with ID are challenging. Method A Dutch version of the Mini PAS-ADD, which is a screening instrument for identification of mental health problems in people with ID, was evaluated in terms of internal consistency, interinformant reliability, item grouping and ...

Inactivation and Augmentation of the Primary 3-Ketosteroid-Δ1- Dehydrogenase in Mycobacterium neoaurum NwIB-01: Biotransformation of Soybean Phytosterols to 4-Androstene- 3,17-Dione or 1,4-Androstadiene-3,17-Dione▿ †

Science.gov (United States)

Wei, Wei; Wang, Feng-qing; Fan, Shu-yue; Wei, Dong-zhi

2010-01-01

3-Ketosteroid-Δ1-dehydrogenase, KsdDM, was identified by targeted gene disruption and augmentation from Mycobacterium neoaurum NwIB-01, a newly isolated strain. The difficulty of separating 4-androstene-3,17-dione (AD) from 1,4-androstadiene-3,17-dione (ADD) is a key bottleneck to the microbial transformation of phytosterols in industry. This problem was tackled via genetic manipulation of the KsdD-encoding gene. Mutants in which KsdDM was inactivated or augmented proved to be good AD(D)-producing strains. PMID:20453136

Non-severe Hypoglycemia Risk Difference between Sulfonylurea and Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2-I) as an Add-On to Metformin in Randomized Controlled Trials.

Science.gov (United States)

Farahani, Pendar

2017-05-23

Non-severe hypoglycemia reduces well-being, lowers quality of life, reduces productivity and increases treatment costs. The non-severe hypoglycemia rate, attributable to sulfonylurea (SU) utilization compared with newer classes such as SGLT2-I, could be of clinical significance. To explore the non-severe hypoglycemia risk difference (RD) for SU use compared with SGLT2-I in randomized controlled trials (RCTs) as an add on to metformin. A search was conducted for RCTs of SGLT2-I. PubMed database were utilized for this search. The search was limited to RCTs reported in English language for canagliflozin, dapagliflozin, and empagliflozin. SU dose comparison was utilized to convert the dose of SUs to glimepiride equivalent doses. Totally, 118 RCTs were reviewed; 6 articles had an arm for a SU as add on to metformin. Six articles belong to 3 RCTs, which reported results for 52 weeks and 104 weeks. Average non-severe hypoglycemia rate for SU arm was 30% (5.5%) [Mean (SD)] for 52 weeks and 35.6% (6.1%) for 104 weeks. RD for non-severe hypoglycemia events for SU compared to SGLT2-I was 26.7% (4.9%) for 52 weeks (p-value less than 0.001) and 30.6% (5.5%) for 104 weeks (p-value less than 0.001). There was a significant correlation between dose of SU and hypoglycemia rate (Pearson correlation 0.995; R-square 99%). This study illustrated that a large proportion of patients who had exposure to SU in RCTs of SGLT2-I experienced non-severe hypoglycemia compared to SGLT2-I. There was a close relation between SU dose and increased probability of non-severe hypoglycemia events. © 2017 Journal of Population Therapeutics and Clinical Pharmacology. All rights reserved.

Equilibrium expert: an add-in to Microsoft Excel for multiple binding equilibrium simulations and parameter estimations.

Science.gov (United States)

Raguin, Olivier; Gruaz-Guyon, Anne; Barbet, Jacques

2002-11-01

An add-in to Microsoft Excel was developed to simulate multiple binding equilibriums. A partition function, readily written even when the equilibrium is complex, describes the experimental system. It involves the concentrations of the different free molecular species and of the different complexes present in the experiment. As a result, the software is not restricted to a series of predefined experimental setups but can handle a large variety of problems involving up to nine independent molecular species. Binding parameters are estimated by nonlinear least-square fitting of experimental measurements as supplied by the user. The fitting process allows user-defined weighting of the experimental data. The flexibility of the software and the way it may be used to describe common experimental situations and to deal with usual problems such as tracer reactivity or nonspecific binding is demonstrated by a few examples. The software is available free of charge upon request.

Does secretin stimulation add to magnetic resonance cholangiopancreatography in characterising pancreatic cystic lesions as side-branch intraductal papillary mucinous neoplasm?

International Nuclear Information System (INIS)

Purysko, Andrei S.; Gandhi, Namita S.; Veniero, Joseph C.; Walsh, R.M.; Obuchowski, Nancy A.

2014-01-01

To assess the value of secretin during magnetic resonance cholangiopancreatography (MRCP) in demonstrating communication between cystic lesions and the pancreatic duct to help determine the diagnosis of side-branch intraductal papillary mucinous neoplasm (SB-IPMN). This is an IRB-approved, HIPAA-compliant retrospective study of 29 SB-IPMN patients and 13 non-IPMN subjects (control) who underwent secretin-enhanced MRCP (s-MRCP). Two readers blinded to the final diagnosis reviewed three randomised image sets: (1) pre-secretin HASTE, (2) dynamic s-MRCP and (3) post-secretin HASTE. Logistic regression, generalised linear models and ROC analyses were used to compare pre- and post-secretin results. There was no significant difference in median scores for the pre-secretin [reader 1: 1; reader 2: 2 (range -2 to 2)] and post-secretin HASTE [reader 1: 1; reader 2: 1 (range -2 to 2)] in the SB-IPMN group (P = 0.14), while the scores were lower for s-MRCP [reader 1: 0.5 (range -2 to 2); reader 2: 0 (range -1 to 2); P = 0.016]. There was no significant difference in mean maximum diameter of SB-IPMN on pre- and post-secretin HASTE, and s-MRCP (P > 0.05). Secretin stimulation did not add to MRCP in characterising pancreatic cystic lesions as SB-IPMN. (orig.)

A New and Versatile Adjustable Rigidity Actuator with Add-on Locking Mechanism (ARES-XL

Directory of Open Access Journals (Sweden)

Manuel Cestari

2018-01-01

Full Text Available Adjustable compliant actuators are being designed and implemented in robotic devices because of their ability to minimize large forces due to impacts, to safely interact with the user, and to store and release energy in passive elastic elements. Conceived as a new force-controlled compliant actuator, an adjustable rigidity with embedded sensor and locking mechanism actuator (ARES-XL is presented in this paper. This compliant system is intended to be implemented in a gait exoskeleton for children with neuro muscular diseases (NMDs to exploit the intrinsic dynamics during locomotion. This paper describes the mechanics and initial evaluation of the ARES-XL, a novel variable impedance actuator (VIA that allows the implementation of an add-on locking mechanism to this system, and in combination with its zero stiffness capability and large deflection range, provides this novel joint with improved properties when compared to previous prototypes developed by the authors and other state-of-the-art (SoA devices. The evaluation of the system proves how this design exceeds the main capabilities of a previous prototype as well as providing versatile actuation that could lead to its implementation in multiple joints.

Reduced expression of IL-12 p35 by SJL/J macrophages responding to Theiler's virus infection is associated with constitutive activation of IRF-3

International Nuclear Information System (INIS)

Dahlberg, Angela; Auble, Mark R.; Petro, Thomas M.

2006-01-01

Macrophages responding to viral infections may contribute to autoimmune demyelinating diseases (ADD). Macrophages from ADD-susceptible SJL/J mice responding to Theiler's Virus (TMEV) infection, the TLR7 agonist loxoribine, or the TLR4 agonist-LPS expressed less IL-12 p35 but more IL-12/23 p40 and IFN-β than macrophages from ADD-resistant B10.S mice. While expression of IRF-1 and -7 was similar between B10.S and SJL/J TMEV-infected macrophages, SJL/J but not B10.S macrophages exhibited constitutively active IRF-3. In contrast to overexpressed IRF-1, IRF-5, and IRF-7, which stimulated p35 promoter reporter activity, overexpressed IRF-3 repressed p35 promoter activity in response to TMEV infection, loxoribine, IFN-γ/LPS, but not IFN-γ alone. IRF-3 lessened but did not eliminate IRF-1-stimulated p35 promoter activity. Repression by IRF-3 required bp -172 to -122 of the p35 promoter. The data suggest that pre-activated IRF-3 is a major factor in the differences in IL-12 production between B10.S and SJL/J macrophages responding to TMEV

Influence of temperature on nucleus degradation of 4-androstene-3, 17-dione in phytosterol biotransformation by Mycobacterium sp.

Science.gov (United States)

Xu, X W; Gao, X Q; Feng, J X; Wang, X D; Wei, D Z

2015-07-01

One of the steroid intermediates, 4-androstene-3, 17-dione (AD), in the biotransformation of phytosterols is valuable for the production of steroid medicaments. However, its degradation during the conversion process is one of the main obstacles to obtain high yields. In this study, the effect of temperature on nucleus degradation during microbial biotransformation of phytosterol was investigated. The results indicated that microbial degradation of phytosterol followed the AD-ADD-'9-OH-ADD' pathway, and that two important reactions involved in nucleus degradation, conversions of AD to ADD and ADD to 9-OH-ADD, were inhibited at 37°C. With a change in the culture temperature from 30 to 37°C, nucleus degradation was reduced from 39·9% to 17·6%, due to inhibition of the putative KstD and Ksh. These results suggested a simple way to decrease the nucleus degradation in phytosterol biotransformation and a new perspective on the possibilities of modifying the metabolism of strains used in industrial applications. Nucleus degradation of products is one of the main problems encountered during phytosterol biotransformation. To solve this problem, the effect of temperature on nucleus degradation was investigated in the industrial production of steroid intermediates. The results are also helpful to the genetic modification of sterol-producing strains. © 2015 The Society for Applied Microbiology.

Efficacy and safety of dipeptidyl peptidase-4 inhibitors as an add-on to insulin treatment in patients with Type 2 diabetes

DEFF Research Database (Denmark)

Frandsen, Christian S.; Madsbad, S

2014-01-01

diabetes. METHODS: We searched the MEDLINE and PubMed databases to identify all randomized controlled clinical trials evaluating dipeptidyl peptidase-4 inhibitors as an add-on to insulin in patients with Type 2 diabetes, which were selected for review. The abstracts and posters of the recent annual...... and placebo treatment. CONCLUSION: Adding a dipeptidyl peptidase-4 inhibitor treatment to insulin has a moderate effect on HbA1c , a weight-neutral effect and a good safety profile. The risk of hypoglycaemia is not increased despite a significant improvement in HbA1c ....

Comparison of conventional inserts and an add-on electron MLC for chest wall irradiation of left-sided breast cancer

International Nuclear Information System (INIS)

Vatanen, Tero; Lahtinen, Tapani; Traneus, Erik

2009-01-01

Background. Collimation of irregularly shaped clinical electron beams is currently based on electron inserts made of low melting point alloys. The present investigation compares a conventional electron applicator with insert and add-on eMLC-based dose distributions in the postoperative chest wall irradiation of left-sided breast cancer. Material and methods. Voxel Monte Carlo++ (VMC++) calculated dose distributions related to electron fields were compared with 10 left-sided breast cancer patients after radical mastectomy. The prescription dose was 50 Gy at a build-up maximum. The same dose was prescribed for the ipsilateral axillary, parasternal and supraclavicular lymph nodes that were treated with photons and calculated with a pencil beam algorithm. The insert beams were shaped with 1.5 cm thick Wood's metal electron inserts in an electron applicator of a Varian 2100 C/D linac. Doses for the eMLC-shaped beams were calculated for an eMLC prototype with 2 cm thick and 5 mm wide steel leaves. The same collimator-to-surface distance (CSD) of 5.8 cm was used for both collimators. Results. The mean PTV dose was slightly higher for the eMLC plans (50.7 vs 49.5 Gy, p<0.001, respectively). The maximum doses assessed by D5% for the eMLC and insert were 60.9 and 59.1 Gy (p<0.001). The difference was due to the slightly higher doses near the field edges for the eMLC. The left lung V20 volumes were 34.5% and 34.0% (p<0.001). There was only a marginal difference in heart doses. Discussion: Despite a slight increase of maximum dose in PTV the add-on electron MLC for chest wall irradiation results in practically no differences in dose distributions compared with the present insert-based collimation

Internet-based attentional bias modification training as add-on to regular treatment in alcohol and cannabis dependent outpatients: a study protocol of a randomized control trial.

Science.gov (United States)

Heitmann, Janika; van Hemel-Ruiter, Madelon E; Vermeulen, Karin M; Ostafin, Brian D; MacLeod, Colin; Wiers, Reinout W; DeFuentes-Merillas, Laura; Fledderus, Martine; Markus, Wiebren; de Jong, Peter J

2017-05-23

The automatic tendency to attend to and focus on substance-related cues in the environment (attentional bias), has been found to contribute to the persistence of addiction. Attentional bias modification (ABM) interventions might, therefore, contribute to treatment outcome and the reduction of relapse rates. Based on some promising research findings, we designed a study to test the clinical relevance of ABM as an add-on component of regular intervention for alcohol and cannabis patients. The current protocol describes a study which will investigate the effectiveness and cost-effectiveness of a newly developed home-delivered, multi-session, internet-based ABM (iABM) intervention as an add-on to treatment as usual (TAU). TAU consists of cognitive behavioural therapy-based treatment according to the Dutch guidelines for the treatment of addiction. Participants (N = 213) will be outpatients from specialized addiction care institutions diagnosed with alcohol or cannabis dependency who will be randomly assigned to one of three conditions: TAU + iABM; TAU + placebo condition; TAU-only. Primary outcome measures are substance use, craving, and rates of relapse. Changes in attentional bias will be measured to investigate whether changes in primary outcome measures can be attributed to the modification of attentional bias. Indices of cost-effectiveness and secondary physical and psychological complaints (depression, anxiety, and stress) are assessed as secondary outcome measures. This randomized control trial will be the first to investigate whether a home-delivered, multi-session iABM intervention is (cost-) effective in reducing relapse rates in alcohol and cannabis dependency as an add-on to TAU, compared with an active and a waiting list control group. If proven effective, this ABM intervention could be easily implemented as a home-delivered component of current TAU. Netherlands Trial Register, NTR5497 , registered on 18th September 2015.

Treatment of traumatised refugees with basic body awareness therapy versus mixed physical activity as add-on treatment

DEFF Research Database (Denmark)

Nordbrandt, Maja Sticker; Carlsson, Jessica; Lindberg, Laura Glahder

2015-01-01

. In clinical studies, physical activity has shown a positive effect on psychiatric illnesses such as depression and anxiety and for patients with chronic pain. However, scientific knowledge about physical activity as part of the treatment for traumatised refugees is very limited and no guidelines exist......-based Cognitive Behavioural Therapy. The first group only receives treatment as usual while the second and the third groups receive either Basic-Body Awareness Therapy or mixed physical activity as add-on treatments. Each physical activity is provided for an individual 1-hour consultation per week...... as well as quality of life, functional capacity, coping with pain, body awareness and physical fitness. DISCUSSION: This study will examine the effect of physical activity for traumatised refugees. This has not yet been done in a randomised controlled setting on such a large scale before. Hereby the study...

A novel reflux inhibitor lesogaberan (AZD3355) as add-on treatment in patients with GORD with persistent reflux symptoms despite proton pump inhibitor therapy: a randomised placebo-controlled trial

NARCIS (Netherlands)

Boeckxstaens, Guy E.; Beaumont, Hanneke; Hatlebakk, Jan G.; Silberg, Debra G.; Björck, Karin; Karlsson, Maria; Denison, Hans

2011-01-01

o evaluate the efficacy and tolerability of add-on treatment with lesogaberan (AZD3355), a novel reflux inhibitor, in patients with persistent gastro-oesophageal reflux disease (GORD) symptoms despite proton pump inhibitor (PPI) therapy. double-blind, placebo-controlled, randomised, parallel-group,

Phenobarbital or potassium bromide as an add-on antiepileptic drug for the management of canine idiopathic epilepsy refractory to imepitoin.

Science.gov (United States)

Royaux, E; Van Ham, L; Broeckx, B J G; Van Soens, I; Gielen, I; Deforce, D; Bhatti, S F M

2017-02-01

Imepitoin has recently been approved in Europe for the management of dogs with idiopathic epilepsy. Currently, there is no evidence-based information available on the efficacy of antiepileptic drugs used as additions to the therapeutic regimen in dogs with idiopathic epilepsy that are not well controlled with imepitoin. The goal of this study was to evaluate the efficacy of phenobarbital or potassium bromide (KBr) as add-on antiepileptic drugs for controlling dogs refractory to a maximum dose of imepitoin (30 mg/kg twice daily). The study was performed as a prospective, randomised, controlled clinical trial. The efficacy of phenobarbital and KBr was evaluated by comparing monthly seizure frequency (MSF), monthly seizure day frequency (MSDF), the presence of cluster seizures during a retrospective 2-month period with a prospective follow-up of 6 months, and the overall responder rate. Twenty-seven dogs were included in the study, 14 dogs in the phenobarbital group and 13 dogs in the KBr group. Both median MSF and MSDF decreased in the phenobarbital group (both P = 0.001) and in the KBr group (P = 0.004 and P = 0.003, respectively). Overall, the number of dogs with cluster seizures decreased (P = 0.0005). The responder rate was 79% vs. 69% in the phenobarbital and KBr groups, respectively. We conclude that phenobarbital or KBr add-on treatment decreases median MSF and MSDF in epileptic dogs refractory to a maximum dose of imepitoin. Combination therapy was generally well tolerated and resulted in an improvement in seizure management in the majority of the dogs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Substance Abuse among High-Risk Sexual Offenders: Do Measures of Lifetime History of Substance Abuse Add to the Prediction of Recidivism over Actuarial Risk Assessment Instruments?

Science.gov (United States)

Looman, Jan; Abracen, Jeffrey

2011-01-01

There has been relatively little research on the degree to which measures of lifetime history of substance abuse add to the prediction of risk based on actuarial measures alone among sexual offenders. This issue is of relevance in that a history of substance abuse is related to relapse to substance using behavior. Furthermore, substance use has…

Redox potential tuning through differential quinone binding in the photosynthetic reaction center of Rhodobacter sphaeroides.

Science.gov (United States)

Vermaas, Josh V; Taguchi, Alexander T; Dikanov, Sergei A; Wraight, Colin A; Tajkhorshid, Emad

2015-03-31

Ubiquinone forms an integral part of the electron transport chain in cellular respiration and photosynthesis across a vast number of organisms. Prior experimental results have shown that the photosynthetic reaction center (RC) from Rhodobacter sphaeroides is only fully functional with a limited set of methoxy-bearing quinones, suggesting that specific interactions with this substituent are required to drive electron transport and the formation of quinol. The nature of these interactions has yet to be determined. Through parameterization of a CHARMM-compatible quinone force field and subsequent molecular dynamics simulations of the quinone-bound RC, we have investigated and characterized the interactions of the protein with the quinones in the Q(A) and Q(B) sites using both equilibrium simulation and thermodynamic integration. In particular, we identify a specific interaction between the 2-methoxy group of ubiquinone in the Q(B) site and the amide nitrogen of GlyL225 that we implicate in locking the orientation of the 2-methoxy group, thereby tuning the redox potential difference between the quinones occupying the Q(A) and Q(B) sites. Disruption of this interaction leads to weaker binding in a ubiquinone analogue that lacks a 2-methoxy group, a finding supported by reverse electron transfer electron paramagnetic resonance experiments of the Q(A)⁻Q(B)⁻ biradical and competitive binding assays.

Evaluating the Properties of Poly(lactic-co-glycolic acid) Nanoparticle Formulations Encapsulating a Hydrophobic Drug by Using the Quality by Design Approach.

Science.gov (United States)

Kozaki, Masato; Kobayashi, Shin-Ichiro; Goda, Yukihiro; Okuda, Haruhiro; Sakai-Kato, Kumiko

2017-01-01

We applied the Quality by Design (QbD) approach to the development of poly(lactic-co-glycolic acid) (PLGA) nanoparticle formulations encapsulating triamcinolone acetonide, and the critical process parameters (CPPs) were identified to clarify the correlations between critical quality attributes and CPPs. Quality risk management was performed by using an Ishikawa diagram and experiments with a fractional factorial design (ANOVA). The CPPs for particle size were PLGA concentration and rotation speed, and the CPP for relative drug loading efficiency was the poor solvent to good solvent volume ratio. By assessing the mutually related factors in the form of ratios, many factors could be efficiently considered in the risk assessment. We found a two-factor interaction between rotation speed and rate of addition of good solvent by using a fractional factorial design with resolution V. The system was then extended by using a central composite design, and the results obtained were visualized by using the response surface method to construct a design space. Our research represents a case study of the application of the QbD approach to pharmaceutical development, including formulation screening, by taking actual production factors into consideration. Our findings support the feasibility of using a similar approach to nanoparticle formulations under development. We could establish an efficient method of analyzing the CPPs of PLGA nanoparticles by using a QbD approach.

Narrative self-consciousness in Virgil’s Aeneid 3

Directory of Open Access Journals (Sweden)

Helen Gasti

2010-11-01

Full Text Available In this paper I intend to examine some instances of narrative and poetic self-consciousness in Aeneid 3 as manifested in the rich textures and inter/intratextualities of its beginning and end. First I discuss the devices used to mark the beginning of the narrative in Book 3 (sailing imagery – key motifs of proems – temporal punctuation and then I propose a systematic analysis of the end which is clearly articulated and adds to the sense of completion and closure. In this interpretive framework I suggest a new reading of digressum (3.715, fata renarrabat and cursusque docebat (3.717.

How social learning adds up to a culture: from birdsong to human public opinion.

Science.gov (United States)

Tchernichovski, Ofer; Feher, Olga; Fimiarz, Daniel; Conley, Dalton

2017-01-01

Distributed social learning may occur at many temporal and spatial scales, but it rarely adds up to a stable culture. Cultures vary in stability and diversity (polymorphism), ranging from chaotic or drifting cultures, through cumulative polymorphic cultures, to stable monolithic cultures with high conformity levels. What features can sustain polymorphism, preventing cultures from collapsing into either chaotic or highly conforming states? We investigate this question by integrating studies across two quite separate disciplines: the emergence of song cultures in birds, and the spread of public opinion and social conventions in humans. In songbirds, the learning process has been studied in great detail, while in human studies the structure of social networks has been experimentally manipulated on large scales. In both cases, the manner in which communication signals are compressed and filtered - either during learning or while traveling through the social network - can affect culture polymorphism and stability. We suggest a simple mechanism of a shifting balance between converging and diverging social forces to explain these effects. Understanding social forces that shape cultural evolution might be useful for designing agile communication systems, which are stable and polymorphic enough to promote gradual changes in institutional behavior. © 2017. Published by The Company of Biologists Ltd.

PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel.

Science.gov (United States)

Zhang, Yong; Huo, Meirong; Zhou, Jianping; Xie, Shaofei

2010-09-01

This study presents PKSolver, a freely available menu-driven add-in program for Microsoft Excel written in Visual Basic for Applications (VBA), for solving basic problems in pharmacokinetic (PK) and pharmacodynamic (PD) data analysis. The program provides a range of modules for PK and PD analysis including noncompartmental analysis (NCA), compartmental analysis (CA), and pharmacodynamic modeling. Two special built-in modules, multiple absorption sites (MAS) and enterohepatic circulation (EHC), were developed for fitting the double-peak concentration-time profile based on the classical one-compartment model. In addition, twenty frequently used pharmacokinetic functions were encoded as a macro and can be directly accessed in an Excel spreadsheet. To evaluate the program, a detailed comparison of modeling PK data using PKSolver and professional PK/PD software package WinNonlin and Scientist was performed. The results showed that the parameters estimated with PKSolver were satisfactory. In conclusion, the PKSolver simplified the PK and PD data analysis process and its output could be generated in Microsoft Word in the form of an integrated report. The program provides pharmacokinetic researchers with a fast and easy-to-use tool for routine and basic PK and PD data analysis with a more user-friendly interface. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Add-on clinical effects of selective antagonist of 5HT6 receptors AVN-211 (CD-008-0173) in patients with schizophrenia stabilized on antipsychotic treatment: pilot study.

Science.gov (United States)

Morozova, Margarita A; Lepilkina, Taisiya A; Rupchev, Georgy E; Beniashvily, Allan G; Burminskiy, Denis S; Potanin, Sergey S; Bondarenko, Evgeny V; Kazey, Vasily I; Lavrovsky, Yan; Ivachtchenko, Alexandre V

2014-08-01

The serotoninergic system as a target for add-on treatment seems to be a promising approach in patients with schizophrenia. To clarify if selective 5HT-6 antagonist AVN-211 (CD-008-0173) adds clinical and cognitive effects to stable antipsychotic treatment. A randomized, double-blind, placebo-controlled, add-on, 4r-week trial in 47 schizophrenia patients (21 patients receiving study drug and 26 receiving placebo) who were stabilized on antipsychotic medication was performed. Seventeen patients from the study drug group and 25 patients from the placebo group completed the trial. Treatment effects were measured using clinical rating scales and attention tests. With no differences at baseline, there was a significant difference between the groups in Positive and Negative Syndrome Scale (PANSS) positive subscale score (p = 0.058) in favor of patients in the treatment group at the endpoint. The PANSS positive subscore (p = 0.0068) and Clinical Global Impression-Severity (CGI-S) (p = 0.048) score significantly changed only in the treatment group. Only in the placebo group were significant changes in Calgary Depression Rating Scale (CDRS) total score registered. The indices of attention tests at endpoint did not show differences between the groups, with the exception of the scope of change in the results of the subtest VIII of the Wechsler Adult Intelligence Scale (WAIS), which showed difference between the groups (p = 0.02) and was significantly larger in the treatment group. Only inside the study drug group, significant changes in selectivity and continuous attention were observed regarding total correct responses (p = 0.0038) and reaction time (p = 0.058) in the Continuous Attention Task (CAT) test. Selective 5HT6 antagonist AVN-211 (CD-008-0173) added antipsychotic and some procognitive (attention) effects to antipsychotic medication.

Anisotropic 3D texture synthesis with application to volume rendering

DEFF Research Database (Denmark)

Laursen, Lasse Farnung; Ersbøll, Bjarne Kjær; Bærentzen, Jakob Andreas

2011-01-01

images using a 12.1 megapixel camera. Next, we extend the volume rendering pipeline by creating a transfer function which yields not only color and opacity from the input intensity, but also texture coordinates for our synthesized 3D texture. Thus, we add texture to the volume rendered images....... This method is applied to a high quality visualization of a pig carcass, where samples of meat, bone, and fat have been used to produce the anisotropic 3D textures....

Main Quality Attributes of Monoclonal Antibodies and Effect of Cell Culture Components

Science.gov (United States)

Torkashvand, Fatemeh; Vaziri, Behrouz

2017-05-01

The culture media optimization is an inevitable part of upstream process development in therapeutic monoclonal antibodies (mAbs) production. The quality by design (QbD) approach defines the assured quality of the final product through the development stage. An important step in QbD is determination of the main quality attributes. During the media optimization, some of the main quality attributes such as glycosylation pattern, charge variants, aggregates, and low-molecular-weight species, could be significantly altered. Here, we provide an overview of how cell culture medium components affects the main quality attributes of the mAbs. Knowing the relationship between the culture media components and the main quality attributes could be successfully utilized for a rational optimization of mammalian cell culture media for industrial mAbs production.

Short-Term Prognosis of Mechanically Ventilated Patients With Guillain–Barré Syndrome Is Worsened by Corticosteroids as an Add-On Therapy

Science.gov (United States)

Wu, Xiujuan; Zhang, Bing; Li, Chunrong; Shen, Donghui; Liu, Kangding; Zhu, Jie; Zhang, Hong-Liang

2015-01-01

Abstract Intravenous immunoglobulin (IVIg) has been proven most effective in treating Guillain–Barré syndrome (GBS). Corticosteroids as an add-on therapy have been prescribed in severe GBS cases. However, the efficacy of intravenous corticosteroids combined with IVIg in dealing with severe GBS remains unclear. We explored the therapeutic effects of different therapeutic regimens on the short-term prognosis of GBS patients, especially the severe cases. We retrospectively analyzed the clinical data of 527 adult patients with GBS who were prescribed to different treatments from 2003 to 2014. The therapeutic effect of a treatment was evaluated by the improvement of Hughes Functional Grading Scale (HFGS) and Medical Research Council (MRC) sum score. With comparable incidence of infectious complications (P > 0.05), more mechanically ventilated patients were found improvement after IVIg treatment than combination IVIg with intravenous corticosteroids (MRC: 97% vs. 72.4%, P bedridden patients without mechanical ventilation, incidence of infectious complications (P > 0.05) and ratio of patients who were improved after IVIg were insignificantly different from the combination therapy (MRC: 89.6% vs. 86.5%; HFGS: 69.6% vs. 61.5%; both P > 0.05), even if the intravenous corticosteroids were initiated within 7 days after onset (P > 0.05). In addition, supportive treatment was sufficient for patients who were able to walk with help (HFGS = 3) and mildly affected (HFGS  3), while corticosteroids are detrimental for short-term prognosis in mechanically ventilated patients when used in combination with IVIg. Further prospective and randomized studies are warranted to validate this finding. PMID:26512609

Short-Term Prognosis of Mechanically Ventilated Patients With Guillain-Barré Syndrome Is Worsened by Corticosteroids as an Add-On Therapy.

Science.gov (United States)

Wu, Xiujuan; Zhang, Bing; Li, Chunrong; Shen, Donghui; Liu, Kangding; Zhu, Jie; Zhang, Hong-Liang

2015-10-01

Intravenous immunoglobulin (IVIg) has been proven most effective in treating Guillain-Barré syndrome (GBS). Corticosteroids as an add-on therapy have been prescribed in severe GBS cases. However, the efficacy of intravenous corticosteroids combined with IVIg in dealing with severe GBS remains unclear. We explored the therapeutic effects of different therapeutic regimens on the short-term prognosis of GBS patients, especially the severe cases.We retrospectively analyzed the clinical data of 527 adult patients with GBS who were prescribed to different treatments from 2003 to 2014. The therapeutic effect of a treatment was evaluated by the improvement of Hughes Functional Grading Scale (HFGS) and Medical Research Council (MRC) sum score.With comparable incidence of infectious complications (P > 0.05), more mechanically ventilated patients were found improvement after IVIg treatment than combination IVIg with intravenous corticosteroids (MRC: 97% vs. 72.4%, P bedridden patients without mechanical ventilation, incidence of infectious complications (P > 0.05) and ratio of patients who were improved after IVIg were insignificantly different from the combination therapy (MRC: 89.6% vs. 86.5%; HFGS: 69.6% vs. 61.5%; both P > 0.05), even if the intravenous corticosteroids were initiated within 7 days after onset (P > 0.05). In addition, supportive treatment was sufficient for patients who were able to walk with help (HFGS = 3) and mildly affected (HFGS  3), while corticosteroids are detrimental for short-term prognosis in mechanically ventilated patients when used in combination with IVIg. Further prospective and randomized studies are warranted to validate this finding.

Scintillation characteristics of LiPO3:Ce3+ glass scintillators

International Nuclear Information System (INIS)

Shin, S. W.; Hwang, J. H.

2003-01-01

LiPO 3 :Ce 3+ glass scintillators doped with 0.5, 0.75, 1.0, 1.25 and 1.5wt% cerium as an activator were fabricated. For the best transparency of the LiPO 3 glasses, optimum heating conditions were investigated. Optimum heating temperature and time is 950 .deg. C and 90 min with 1wt% sugar add as reductant. The lattice structure of LiPO 3 :Ce 3+ glass scintillator was monoclinic, its lattice constants(a 0 , b 0 , c 0 ) being 16,490λ, 5.427λ and 13.120λ. Photo-refraction index of LiPO 3 :Ce 3 + measured by SE(Spectroscopic ellipsometry) was 1.45 ∼ 1.5 and its bandgap energy was 2.342 eV. The absorption spectral range of LiPO 3 :Ce 3+ measured by UV-VIS spectrophotometry was 350∼ 375nm and the spectral ranges of photoluminescence(PL) were 400∼450nm and 750∼900nm, its maximum PL intensity appeared at 417nm and 791nm. LiPO 3 :Ce 3 + glass scintillator doped with 0.75wt% cerium showed the best PL intensity. The PL intensity increased until cerium content reaches 0.75wt% above which ir decreased

Structures, internal rotor potentials, and thermochemical properties for a series of nitrocarbonyls, nitroolefins, corresponding nitrites, and their carbon centered radicals.

Science.gov (United States)

Snitsiriwat, Suarwee; Asatryan, Rubik; Bozzelli, Joseph W

2011-12-01

Structures, enthalpy (Δ(f)H°(298)), entropy (S°(T)), and heat capacity (C(p)(T)) are determined for a series of nitrocarbonyls, nitroolefins, corresponding nitrites, and their carbon centered radicals using the density functional B3LYP and composite CBS-QB3 calculations. Enthalpies of formation (Δ(f)H°(298)) are determined at the B3LYP/6-31G(d,p), B3LYP/6-31+G(2d,2p), and composite CBS-QB3 levels using several work reactions for each species. Entropy (S) and heat capacity (C(p)(T)) values from vibration, translational, and external rotational contributions are calculated using the rigid-rotor-harmonic-oscillator approximation based on the vibration frequencies and structures obtained from the density functional studies. Contribution to Δ(f)H(T), S, and C(p)(T) from the analysis on the internal rotors is included. Recommended values for enthalpies of formation of the most stable conformers of nitroacetone cc(═o)cno2, acetonitrite cc(═o)ono, nitroacetate cc(═o)no2, and acetyl nitrite cc(═o)ono are -51.6 kcal mol(-1), -51.3 kcal mol(-1), -45.4 kcal mol(-1), and -58.2 kcal mol(-1), respectively. The calculated Δ(f)H°(298) for nitroethylene c═cno2 is 7.6 kcal mol(-1) and for vinyl nitrite c═cono is 7.2 kcal mol(-1). We also found an unusual phenomena: an intramolecular transfer reaction (isomerization) with a low barrier (3.6 kcal mol(-1)) in the acetyl nitrite. The NO of the nitrite (R-ONO) in CH(3)C(═O')ONO moves to the C═O' oxygen in a motion of a stretching frequency and then a shift to the carbonyl oxygen (marked as O' for illustration purposes). © 2011 American Chemical Society

Modulation of in vitro rumen biohydrogenation by Cistus ladanifer tannins compared with other tannin sources.

Science.gov (United States)

Costa, Mónica; Alves, Susana P; Cabo, Ângelo; Guerreiro, Olinda; Stilwell, George; Dentinho, Maria T; Bessa, Rui Jb

2017-01-01

Tannins are polyphenolic compounds able to modify the ruminal biohydrogenation (BH) of unsaturated fatty acids, but their activity may vary among different tannin sources. The effect of rockrose (Cistus ladanifer) on BH has never been compared with other more common tannin sources. Tannin extracts (100 g kg -1 substrate dry matter) from chestnut (CH), quebracho (QB), grape seed (GS) and rockrose (CL) were incubated in vitro for 6 h with ruminal fluid using as substrate a feed containing 60 g kg -1 of sunflower oil. A control treatment with no added tannins was also included. Compared with the control, GS and CL, but not CH and QB, increased (P 0.05) were observed for the disappearance of c9-18:1 and c9,c12,c15-18:3. The production of 18:0 was not different (P > 0.05) among treatments, although its proportion in the total BH products was lower (P < 0.05) for GS than for the other treatments. Condensed tannins from GS and, to a lesser extent, from CL stimulate the first steps of BH, without a clear inhibition of 18:0 production. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

A quality by design study applied to an industrial pharmaceutical fluid bed granulation.

Science.gov (United States)

Lourenço, Vera; Lochmann, Dirk; Reich, Gabriele; Menezes, José C; Herdling, Thorsten; Schewitz, Jens

2012-06-01

The pharmaceutical industry is encouraged within Quality by Design (QbD) to apply science-based manufacturing principles to assure quality not only of new but also of existing processes. This paper presents how QbD principles can be applied to an existing industrial pharmaceutical fluid bed granulation (FBG) process. A three-step approach is presented as follows: (1) implementation of Process Analytical Technology (PAT) monitoring tools at the industrial scale process, combined with multivariate data analysis (MVDA) of process and PAT data to increase the process knowledge; (2) execution of scaled-down designed experiments at a pilot scale, with adequate PAT monitoring tools, to investigate the process response to intended changes in Critical Process Parameters (CPPs); and finally (3) the definition of a process Design Space (DS) linking CPPs to Critical to Quality Attributes (CQAs), within which product quality is ensured by design, and after scale-up enabling its use at the industrial process scale. The proposed approach was developed for an existing industrial process. Through enhanced process knowledge established a significant reduction in product CQAs, variability already within quality specifications ranges was achieved by a better choice of CPPs values. The results of such step-wise development and implementation are described. Copyright © 2012 Elsevier B.V. All rights reserved.

Optimization of the Critical Parameters of the Spherical Agglomeration Crystallization Method by the Application of the Quality by Design Approach

Directory of Open Access Journals (Sweden)

Orsolya Gyulai

2018-04-01

Full Text Available This research work presents the use of the Quality by Design (QbD concept for optimization of the spherical agglomeration crystallization method in the case of the active agent, ambroxol hydrochloride (AMB HCl. AMB HCl spherical crystals were formulated by the spherical agglomeration method, which was applied as an antisolvent technique. Spherical crystals have good flowing properties, which makes the direct compression tableting method applicable. This means that the amount of additives used can be reduced and smaller tablets can be formed. For the risk assessment, LeanQbD Software was used. According to its results, four independent variables (mixing type and time, dT (temperature difference between solvent and antisolvent, and composition (solvent/antisolvent volume ratio and three dependent variables (mean particle size, aspect ratio, and roundness were selected. Based on these, a 2–3 mixed-level factorial design was constructed, crystallization was accomplished, and the results were evaluated using Statistica for Windows 13 program. Product assay was performed and it was revealed that improvements in the mean particle size (from ~13 to ~200 µm, roundness (from ~2.4 to ~1.5, aspect ratio (from ~1.7 to ~1.4, and flow properties were observed while polymorphic transitions were avoided.

Computer Optimization of Biodegradable Nanoparticles Fabricated by Dispersion Polymerization

Directory of Open Access Journals (Sweden)

Emmanuel O. Akala

2015-12-01

Full Text Available Quality by design (QbD in the pharmaceutical industry involves designing and developing drug formulations and manufacturing processes which ensure predefined drug product specifications. QbD helps to understand how process and formulation variables affect product characteristics and subsequent optimization of these variables vis-à-vis final specifications. Statistical design of experiments (DoE identifies important parameters in a pharmaceutical dosage form design followed by optimizing the parameters with respect to certain specifications. DoE establishes in mathematical form the relationships between critical process parameters together with critical material attributes and critical quality attributes. We focused on the fabrication of biodegradable nanoparticles by dispersion polymerization. Aided by a statistical software, d-optimal mixture design was used to vary the components (crosslinker, initiator, stabilizer, and macromonomers to obtain twenty nanoparticle formulations (PLLA-based nanoparticles and thirty formulations (poly-ɛ-caprolactone-based nanoparticles. Scheffe polynomial models were generated to predict particle size (nm, zeta potential, and yield (% as functions of the composition of the formulations. Simultaneous optimizations were carried out on the response variables. Solutions were returned from simultaneous optimization of the response variables for component combinations to (1 minimize nanoparticle size; (2 maximize the surface negative zeta potential; and (3 maximize percent yield to make the nanoparticle fabrication an economic proposition.

Optimization of the Critical Parameters of the Spherical Agglomeration Crystallization Method by the Application of the Quality by Design Approach.

Science.gov (United States)

Gyulai, Orsolya; Kovács, Anita; Sovány, Tamás; Csóka, Ildikó; Aigner, Zoltán

2018-04-20

This research work presents the use of the Quality by Design (QbD) concept for optimization of the spherical agglomeration crystallization method in the case of the active agent, ambroxol hydrochloride (AMB HCl). AMB HCl spherical crystals were formulated by the spherical agglomeration method, which was applied as an antisolvent technique. Spherical crystals have good flowing properties, which makes the direct compression tableting method applicable. This means that the amount of additives used can be reduced and smaller tablets can be formed. For the risk assessment, LeanQbD Software was used. According to its results, four independent variables (mixing type and time, dT (temperature difference between solvent and antisolvent), and composition (solvent/antisolvent volume ratio)) and three dependent variables (mean particle size, aspect ratio, and roundness) were selected. Based on these, a 2⁻3 mixed-level factorial design was constructed, crystallization was accomplished, and the results were evaluated using Statistica for Windows 13 program. Product assay was performed and it was revealed that improvements in the mean particle size (from ~13 to ~200 µm), roundness (from ~2.4 to ~1.5), aspect ratio (from ~1.7 to ~1.4), and flow properties were observed while polymorphic transitions were avoided.

Application of Absorption Modeling in Rational Design of Drug Product Under Quality-by-Design Paradigm.

Science.gov (United States)

Kesisoglou, Filippos; Mitra, Amitava

2015-09-01

Physiologically based absorption models can be an important tool in understanding product performance and hence implementation of Quality by Design (QbD) in drug product development. In this report, we show several case studies to demonstrate the potential application of absorption modeling in rational design of drug product under the QbD paradigm. The examples include application of absorption modeling—(1) prior to first-in-human studies to guide development of a formulation with minimal sensitivity to higher gastric pH and hence reduced interaction when co-administered with PPIs and/or H2RAs, (2) design of a controlled release formulation with optimal release rate to meet trough plasma concentrations and enable QD dosing, (3) understanding the impact of API particle size distribution on tablet bioavailability and guide formulation design in late-stage development, (4) assess impact of API phase change on product performance to guide specification setting, and (5) investigate the effect of dissolution rate changes on formulation bioperformance and enable appropriate specification setting. These case studies are meant to highlight the utility of physiologically based absorption modeling in gaining a thorough understanding of the product performance and the critical factors impacting performance to drive design of a robust drug product that would deliver the optimal benefit to the patients.

Predictors of life satisfaction among Asian American adolescents- analysis of add health data.

Science.gov (United States)

Huang, Jui-Yen; Wang, Kuan-Yuan; Ringel-Kulka, Tamar

2015-01-01

Life satisfaction correlates with adolescent risk taking behavior and their outcomes in adulthood. Despite the fast rise in numbers of Asian adolescents in the U.S., the predictors of their life satisfaction are not well understood. This study examined the relationship between several demographic and contextual factors and global life satisfaction among this population. Data were derived from the National Longitudinal Study of Adolescent Health (Add Health), a nationally representative probability sample of US adolescents. Bivariate and multivariable logistic regression was conducted to evaluate hypothesized predictors of global life satisfaction of Asian American adolescents. All analyses were conducted using STATA version 11. After exclusion of cases with missing values, 1021 Asian American adolescents were studied. Self- rated health, self-esteem, perceived neighborhood quality, parental support and peer support were significantly and positively related to better global life satisfaction. However, after controlling for other factors, only self-esteem (adjusted odds ratio [aOR]: 4.76; 95% confidence interval [CI]: 2.86-8.33) and perceived peer support (aOR: 2.76; 95% CI: 1.33-5.76) significantly predicted higher life satisfaction. Peer support and adolescents' self-concept are strongly correlated with Asian American adolescents' subjective well-being. To promote the wellness of this population, culturally sensitive strategies in developing peer relationship and healthy self-concept may be effective. More studies are needed for subgroup comparison of various ethnicities among Asian American adolescents.

Final Technical Report: Thermoelectric-Enhanced Cookstove Add-on (TECA) for Clean Biomass Cookstoves

Energy Technology Data Exchange (ETDEWEB)

Stokes, David [RTI International, Research Triangle Park, NC (United States)

2015-09-29

This program seeks to demonstrate a solution to enhance existing biomass cookstove performance through the use of RTI’s Thermoelectric Enhanced Cookstove Add-on (TECA) device. The self-powered TECA device captures a portion of heat from the stove and converts it to electricity through a thermoelectric (TE) device to power a blower. Colorado State University and Envirofit International are partners to support the air injection design and commercialization to enhance combustion in the stove and reduce emissions. Relevance: By demonstrating a proof of concept of the approach with the Envirofit M-5000 stove and TECA device, we hope to apply this technology to existing stoves that are already in use and reduce emissions for stoves that have already found user acceptance to provide a true health benefit. Challenges: The technical challenges include achieving Tier 4 emissions from a biomass stove and for such a stove to operate reliably in the harsh field environment. Additional challenges include the fact that it is difficult to develop a cost effective solution and insure adoption and proper use in the field. Outcomes: In this program we have demonstrated PM emissions at 82 mg/MJd, a 70% reduction as compared to baseline stove operation. We have also developed a stove optimization approach that reduces the number of costly experiments. We have evaluated component-level reliability and will be testing the stove prototype in the field for performance and reliability.

A heuristic model linking yoga philosophy and self-reflection to examine underlying mechanisms of add-on yoga treatment in schizophrenia.

Science.gov (United States)

Rao, Naren; Menon, Sangeetha

2016-06-01

Preliminary evidence suggests efficacy of yoga as add-on treatment for schizophrenia, but the underlying mechanism by which yoga improves the symptoms of schizophrenia is not completely understood. Yoga improves self-reflection in healthy individuals, and self-reflection abnormalities are typically seen in schizophrenia. However, whether yoga treatment improves impairments in self-reflection typically seen in patients with schizophrenia is not examined. This paper discusses the potential mechanism of yoga in the treatment of schizophrenia and proposes a testable hypothesis for further empirical studies. It is proposed that self-reflection abnormalities in schizophrenia improve with yoga and the neurobiological changes associated with this can be examined using empirical behavioural measures and neuroimaging measures such as magnetic resonance imaging.

Metabolic and other effects of pioglitazone as an add-on therapy to metformin in the treatment of polycystic ovary syndrome (PCOS).

Science.gov (United States)

Valsamakis, Georgios; Lois, Kostas; Kumar, Sudhesh; Mastorakos, George

2013-01-01

Insulin resistance is a key pathogenic defect of the clustered metabolic disturbances seen in polycystic ovary syndrome (PCOS). Metformin is an insulin sensitizer acting in the liver and the peripheral tissues that ameliorates the metabolic and reproductive defects in PCOS. In addition, pioglitazone is an insulin sensitizer used in diabetes mellitus type 2 (T2DM), improving insulin resistance (IR) in adipose tissue and muscles. In T2DM, these drugs are also used as a combined treatment due to their "add-on effect" on insulin resistance. Although the beneficial role of troglitazone (a member of the thiazolidinediones (TZDs) family) in PCOS has been shown in the past, currently only pioglitazone is available in the market. A few small randomized controlled trials have directly compared the effectiveness of pioglitazone in women with PCOS, while there are a limited number of small studies that support the beneficial metabolic add-on effect of pioglitazone on metformin-treated PCOS women as compared to metformin or pioglitazone monotherapy. These findings suggest a potentially promising role for combined pioglitazone/metformin treatment in the management of PCOS in metformin-resistant patients. In view of recent concerns regarding pioglitazone usage and its associated health risk, we aim to compare the pros and cons of each drug regarding their metabolic and other hormonal effects in women with PCOS and to explore the possible beneficial effect of combined therapy in certain cases, taking into consideration the teratogenic effect of pioglitazone. Finally, we discuss the need for a randomized controlled trial that will evaluate the metabolic and other hormonal effects of combined metformin/pioglitazone treatment in PCOS with selective treatment targets.

Evaluation of the Single-precision Floatingpoint Vector Add Kernel Using the Intel FPGA SDK for OpenCL

Energy Technology Data Exchange (ETDEWEB)

Jin, Zheming [Argonne National Lab. (ANL), Argonne, IL (United States); Yoshii, Kazutomo [Argonne National Lab. (ANL), Argonne, IL (United States); Finkel, Hal [Argonne National Lab. (ANL), Argonne, IL (United States); Cappello, Franck [Argonne National Lab. (ANL), Argonne, IL (United States)

2017-04-20

Open Computing Language (OpenCL) is a high-level language that enables software programmers to explore Field Programmable Gate Arrays (FPGAs) for application acceleration. The Intel FPGA software development kit (SDK) for OpenCL allows a user to specify applications at a high level and explore the performance of low-level hardware acceleration. In this report, we present the FPGA performance and power consumption results of the single-precision floating-point vector add OpenCL kernel using the Intel FPGA SDK for OpenCL on the Nallatech 385A FPGA board. The board features an Arria 10 FPGA. We evaluate the FPGA implementations using the compute unit duplication and kernel vectorization optimization techniques. On the Nallatech 385A FPGA board, the maximum compute kernel bandwidth we achieve is 25.8 GB/s, approximately 76% of the peak memory bandwidth. The power consumption of the FPGA device when running the kernels ranges from 29W to 42W.

User information document for WinGridder Version 3.0

International Nuclear Information System (INIS)

Pan, Lehua; Pan, Lehua

2007-01-01

WINGRIDDER V3.0 is a Windows-based software for designing and generating numerical grids for numerical simulators that are based on the 'integral finite difference' or the 'control volume' numerical scheme (e.g., TOUGH2, Pruess et al., 1996). The user can design and generate grid that properly represents the stratigraphic features, inclined faults, and repository. WINGRIDDER V3.0 is an upgrade from WINGRIDDER V2.0. This revision includes testable requirements as listed in the Requirements Document (RD), 10024-RD-3.0-00, Section 2. With new features, WINGRIDDER V3.0 adds the ability to generate a multiple-interactive-continuum (MINC) grid

Extraction/spectrophotometric determination of molybdenum(VI) with 4,6-di-t-butyl-3-methoxycatechol and Malachite Green

Energy Technology Data Exchange (ETDEWEB)

Oshima, Mitsuko; Nishizaki, Youko; Motomizu, Shoji

1988-10-01

Mo(VI) forms an chelate anion with 4,6-di-t-butyl-3-methoxycatechol (DBMC) and the ion asscoiate between the chelate anion and Malachite Green (MG) is extracted into toluene in the pH range from 1.8 to 3.5. DBMC was synthesized according to our previous work. The standard procedure was as follows: transfer a sample solution /Mo (VI) < 4.8 /mu/g/ into a 25 ml test tube with stopper, and add 0.5 ml each of 5 x 10/sup -2/ M sulfuric acid and 1.0 x 10/sup -3/ M MG solution. If necessary, add masking agent solution (ascorbic acid and tartaric acid). After adding water to make up to 10 ml, add 5 ml of 1.5 x 10/sup -2/ M DBMC toluene solution, then shake for 30 min. Measure the absorbance of the organic phase at 635 nm. Apparent molar absorptivity was 8.0 x 10/sup 4/ l mol/sup -1/ cm/sup -1/ and the absorbance of the reagent blank was 0.01. The relative standard deviation of 10 measurements of 1.92 ..mu..g of Mo(VI) was 0.52 %. The present method was applied to steel samples with satisfactory results. The effect of W(VI) coexisting at concentrations over 1 x 10/sup -6/ M was corrected by the equations using apparent molar absorptivities of Mo(VI) and W(VI) obtained with or without the masking agent (2.5 x 10/sup -3/ M tartaric acid).

Penetration resistance and ballistic-impact behavior of Ti/TiAl3 metal/intermetallic laminated composites (MILCs: A computational investigation

Directory of Open Access Journals (Sweden)

Jennifer S. Snipes

2016-06-01

Full Text Available A comprehensive computational engineering analysis is carried out in order to assess suitability of the Ti/TiAl3 metal/intermetallic laminated composites (MILCs for use in both structural and add-on armor applications. This class of composite materials consists of alternating sub-millimeter thick layers of Ti (the ductile and tough constituent and TiAl3 (the stiff and hard constituent. In recent years, this class of materials has been investigated for potential use in light-armor applications as a replacement for the traditional metallic or polymer-matrix composite materials. Within the computational analysis, an account is given to differing functional requirements for candidate materials when used in structural and add-on ballistic armor. The analysis employed is of a transient, nonlinear-dynamics, finite-element character, and the problem investigated involves normal impact (i.e. under zero obliquity angle of a Ti/TiAl3 MILC target plate, over a range of incident velocities, by a fragment simulating projectile (FSP. This type of analysis can provide more direct information regarding the ballistic limit of the subject armor material, as well as help with the identification of the nature and the efficacy of various FSP material-deformation/erosion and kinetic-energy absorption/dissipation phenomena and processes. The results obtained clearly revealed that Ti/TiAl3 MILCs are more suitable for use in add-on ballistic, than in structural armor applications.

Computational study of the hydrolysis of carbonyl sulphide: Thermodynamics and kinetic constants estimation using ab initio calculations

International Nuclear Information System (INIS)

Vidal-Vidal, Á.; Pérez-Rodríguez, M.; Piñeiro, M.M.

2017-01-01

Highlights: • OCS hydrolysis equilibrium constants were calculated using QM composite methods. • CBS-QB3 was found to be the most adequate method for OCS thermodynamic calculations. • Calculated hydrolysis yields decrease when temperature increases. • The isotopic effect is less significant than temperature or initial concentration dependences. - Abstract: Carbonyl sulphide is the predominant sulphur compound in the atmosphere, contributing to the formation of aerosol particles affecting global climate. Human activity has significantly increased its total amount since the beginning of the Industrial Revolution due to its presence in petroleum and coal, reason why it is necessary to understand and control its emissions. On the other hand, carbonyl sulphide is an undesired substance for catalysis in important industrial processes. Hydrolysis is the most promising among the different strategies to reduce its presence, giving as products carbon dioxide and hydrogen sulphide. In the present work, the mechanism of reaction of carbonyl sulphide hydrolysis process in gas phase was studied from 400 K to 1500 K, equilibrium constants were obtained and reaction yields were estimated, by means of composite quantum-computational methods. Good agreement with literature experimental results confirms the suitability of the chosen methods, specially CBS-QB3, in supporting the reaction mechanism, giving accurate equilibrium constant values, and obtaining realistic yields. The effect of isotopic substitution in OCS was also studied, from 300 K to 1500 K, being much less significant than temperature dependence.

Adducin family proteins possess different nuclear export potentials.

Science.gov (United States)

Liu, Chia-Mei; Hsu, Wen-Hsin; Lin, Wan-Yi; Chen, Hong-Chen

2017-05-10

The adducin (ADD) family proteins, namely ADD1, ADD2, and ADD3, are actin-binding proteins that play important roles in the stabilization of membrane cytoskeleton and cell-cell junctions. All the ADD proteins contain a highly conserved bipartite nuclear localization signal (NLS) at the carboxyl termini, but only ADD1 can localize to the nucleus. The reason for this discrepancy is not clear. To avoid the potential effect of cell-cell junctions on the distribution of ADD proteins, HA epitope-tagged ADD proteins and mutants were transiently expressed in NIH3T3 fibroblasts and their distribution in the cytoplasm and nucleus was examined by immunofluorescence staining. Several nuclear proteins were identified to interact with ADD1 by mass spectrometry, which were further verified by co-immunoprecipitation. In this study, we found that ADD1 was detectable both in the cytoplasm and nucleus, whereas ADD2 and ADD3 were detected only in the cytoplasm. However, ADD2 and ADD3 were partially (~40%) sequestered in the nucleus by leptomycin B, a CRM1/exportin1 inhibitor. Upon the removal of leptomycin B, ADD2 and ADD3 re-distributed to the cytoplasm. These results indicate that ADD2 and ADD3 possess functional NLS and are quickly transported to the cytoplasm upon entering the nucleus. Indeed, we found that ADD2 and ADD3 possess much higher potential to counteract the activity of the NLS derived from Simian virus 40 large T-antigen than ADD1. All the ADD proteins appear to contain multiple nuclear export signals mainly in their head and neck domains. However, except for the leucine-rich motif ( 377 FEALMRMLDWLGYRT 391 ) in the neck domain of ADD1, no other classic nuclear export signal was identified in the ADD proteins. In addition, the nuclear retention of ADD1 facilitates its interaction with RNA polymerase II and zinc-finger protein 331. Our results suggest that ADD2 and ADD3 possess functional NLS and shuttle between the cytoplasm and nucleus. The discrepancy in the

Effects of add on PTH(1-84) substitution therapy in hypoparathyroidism: results from a double-blind randomised controlled study

DEFF Research Database (Denmark)

Sikjær, Tanja Tvistholm; Rejnmark, Lars; Mosekilde, Leif

-phosphate levels within the physiological range. Compared with placebo, participants randomised to PTH (1-84) reduced their daily dose of calcium supplements by 68 % (pvitamin D dose by 53% (pneed of calcium supplements...... and 7 were not in need of active vitamin D. With the actual add on therapy there were no change in renal calcium excretion in response to treatment. Compared with placebo, bone mineral density (BMD) decreased significantly at the hip (-1.59 ± 0.57%), lumbar spine (-1.76 ± 1.03%) and whole body (-1...... bone packets. In conclusion, PTH substitution therapy is capable of maintaining normal p-calcium levels with a significantly reduced need for calcium supplements and active vitamin D. In contrast to the effect of PTH(1-84) treatment in patients with osteoporosis, causing an increase in BMD...

IP3 Receptor-Dependent Cytoplasmic Ca2+ Signals Are Tightly Controlled by Cavβ3

Directory of Open Access Journals (Sweden)

Anouar Belkacemi

2018-01-01

Full Text Available Voltage-gated calcium channels (Cavs are major Ca2+ entry pathways in excitable cells. Their β subunits facilitate membrane trafficking of the channel’s ion-conducting α1 pore and modulate its gating properties. We report that one β subunit, β3, reduces Ca2+ release following stimulation of phospholipase C-coupled receptors and inositol 1,4,5-trisphosphate (IP3 formation. This effect requires the SH3-HOOK domain of Cavβ3, includes physical β3/IP3 receptor interaction, and prevails when agonist-induced IP3 formation is bypassed by photolysis of caged IP3. In agreement with β3 acting as a brake on Ca2+ release, fibroblast migration is enhanced in vitro, and in vivo, closure of skin wounds is accelerated in the absence of β3. To mediate specific physiological responses and to prevent Ca2+ toxicity, cytoplasmic Ca2+ signals must be tightly controlled. The described function of β3, unrelated to its function as a Cav subunit, adds to this tight control.

Cyanobacterial flv4-2 Operon-Encoded Proteins Optimize Light Harvesting and Charge Separation in Photosystem II.

Science.gov (United States)

Chukhutsina, Volha; Bersanini, Luca; Aro, Eva-Mari; van Amerongen, Herbert

2015-05-01

Photosystem II (PSII) complexes drive the water-splitting reaction necessary to transform sunlight into chemical energy. However, too much light can damage and disrupt PSII. In cyanobacteria, the flv4-2 operon encodes three proteins (Flv2, Flv4, and Sll0218), which safeguard PSII activity under air-level CO2 and in high light conditions. However, the exact mechanism of action of these proteins has not been clarified yet. We demonstrate that the PSII electron transfer properties are influenced by the flv4-2 operon-encoded proteins. Accelerated secondary charge separation kinetics was observed upon expression/overexpression of the flv4-2 operon. This is likely induced by docking of the Flv2/Flv4 heterodimer in the vicinity of the QB pocket of PSII, which, in turn, increases the QB redox potential and consequently stabilizes forward electron transfer. The alternative electron transfer route constituted by Flv2/Flv4 sequesters electrons from QB(-) guaranteeing the dissipation of excess excitation energy in PSII under stressful conditions. In addition, we demonstrate that in the absence of the flv4-2 operon-encoded proteins, about 20% of the phycobilisome antenna becomes detached from the reaction centers, thus decreasing light harvesting. Phycobilisome detachment is a consequence of a decreased relative content of PSII dimers, a feature observed in the absence of the Sll0218 protein. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

Enhancement of Hole Confinement by Monolayer Insertion in Asymmetric Quantum-Barrier UVB Light Emitting Diodes

KAUST Repository

Janjua, Bilal; Alyamani, Ahmed Y.; El-Desouki, M. M.; Ng, Tien Khee; Ooi, Boon S.

2014-01-01

We study the enhanced hole confinement by having a large bandgap AlGaN monolayer insertion (MLI) between the quantum well (QW) and the quantum barrier (QB). The numerical analysis examines the energy band alignment diagrams, using a self

Efeitos da quercetina na lesão pulmonar induzida por bleomicina: um estudo preliminar Effects of quercetin on bleomycin-induced lung injury: a preliminary study

Directory of Open Access Journals (Sweden)

José Antônio Baddini Martinez

2008-07-01

Full Text Available OBJETIVO: Investigar os efeitos da quercetina em um modelo de inflamação pulmonar e fibrose induzidas por bleomicina. MÉTODOS: Setenta e nove hamsters machos adultos foram randomizados para aplicação de injeções pelas vias intratraqueal (IT e intraperitoneal (IP em quatro configurações: veículo IP/salina IT (grupo VS, n = 16; salina IT/quercetina IP (grupo QS, n = 16; bleomicina IT/veículo IP (grupo VB, n = 27; e bleomicina IT/quercetina IP (grupo QB, n = 20. A quercetina e a bleomicina foram aplicadas em doses de 30 mg/kg/dia e 10 U/kg, respectivamente.A quercetina foi iniciada/suspensa 3 dias antes/14 dias depois das injeções IT. RESULTADOS: A taxa de mortalidade do grupo VB foi significantemente superior à dos demais grupos (44% vs. VS: 0%; QS: 0%; QB: 15%. O grupo VB exibiu níveis pulmonares de substâncias reativas ao ácido tiobarbitúrico (× 10-2 nmol/mg significativamente maiores (6,6 ± 1,3 vs. VS: 5,5 ± 0,8; QS: 2,5 ± 0,6; e QB: 5,8 ± 0,6.Os grupos VB/QB mostraram níveis pulmonares de glutationa reduzida (× 10-2 nmol/mg significativamente menores que os dos grupos VS/QS (28,9 ± 13,8/28,6 ± 14,8 vs. 43,9 ± 16,0/51,1 ± 20,3 e níveis de hidroxiprolina (mg/g significativamente maiores (201,6 ± 37,3/177,6 ± 20,3 vs. 109,6 ± 26,1/117,5 ± 32,0. CONCLUSÕES: Em um modelo animal de lesão pulmonar, a quercetina exibiu efeitos antiinflamatórios que são relacionados, pelo menos em parte, a suas propriedades antioxidantes.OBJECTIVE: The aim of this study was to identify the best experimental model in which to observe the pulmonary alterations characterizing hepatopulmonary syndrome (HPS. METHODS: Male Wistar rats, with mean weight of 250 g, were used in four experimental models: inhaled carbon tetrachloride; intraperitoneal carbon tetrachloride; partial portal vein ligation; and bile duct ligation (BDL. The animals in all groups were divided into control and experimental subgroups. The following variables were

Add-on high frequency deep transcranial magnetic stimulation (dTMS) to bilateral prefrontal cortex in depressive episodes of patients with major depressive disorder, bipolar disorder I, and major depressive with alcohol use disorders.

Science.gov (United States)

Rapinesi, Chiara; Kotzalidis, Georgios D; Ferracuti, Stefano; Girardi, Nicoletta; Zangen, Abraham; Sani, Gabriele; Raccah, Ruggero N; Girardi, Paolo; Pompili, Maurizio; Del Casale, Antonio

2018-04-03

Dorsolateral prefrontal cortex (DLPFC) is critically involved in mood and alcohol use disorders. We aimed to investigate the safety of intervention with add-on bilateral prefrontal high-frequency deep transcranial magnetic stimulation (dTMS) and between-group differences in treatment response in patients with different types of depressive episodes, including major depressive episodes in the course of major depressive disorder (MDD), bipolar disorder, type I (BD-I), and MDD with alcohol use disorder (MDAUD). We conducted a 6-month open-label study, involving 82 patients with DSM-5 Depressive Episode. Of these, 41 had diagnosis of MDD, 20 BD-I, and 21 MDAUD. All patients received standard drug treatment and add-on dTMS over the bilateral DLPFC with left prevalence for four weeks, with five sessions in each week. We rated mood state with the Hamilton Depression Rating Scale (HDRS) at baseline, one-month, and six-month follow-up visits. Mean total HDRS scores dropped from 22.8 (SD = 5.9) at baseline to 10.4 (SD = 3.6) at 1 month, to 10.0 (SD = 4.5) at 6 months, while response/remission were 70.73% (N = 58) and 19.51% (N = 16) at 1 month and 76.83% (N = 63) and 32.93% (27) at 6 months, respectively, with no between-group differences. No patient experienced any side effects. High-frequency DLPFC dTMS was well tolerated and did not significantly differ on improvement of depression in MDD, BD-I, and MDAUD. Copyright © 2018 Elsevier B.V. All rights reserved.

An Algorithm for Fast Computation of 3D Zernike Moments for Volumetric Images

OpenAIRE

Hosny, Khalid M.; Hafez, Mohamed A.

2012-01-01

An algorithm was proposed for very fast and low-complexity computation of three-dimensional Zernike moments. The 3D Zernike moments were expressed in terms of exact 3D geometric moments where the later are computed exactly through the mathematical integration of the monomial terms over the digital image/object voxels. A new symmetry-based method was proposed to compute 3D Zernike moments with 87% reduction in the computational complexity. A fast 1D cascade algorithm was also employed to add m...

A hybrid WDM/OCDMA ring with a dynamic add/drop function based on Fourier code for local area networks.

Science.gov (United States)

Choi, Yong-Kyu; Hosoya, Kenta; Lee, Chung Ghiu; Hanawa, Masanori; Park, Chang-Soo

2011-03-28

We propose and experimentally demonstrate a hybrid WDM/OCDMA ring with a dynamic add/drop function based on Fourier code for local area networks. Dynamic function is implemented by mechanically tuning the Fourier encoder/decoder for optical code division multiple access (OCDMA) encoding/decoding. Wavelength division multiplexing (WDM) is utilized for node assignment and 4-chip Fourier code recovers the matched signal from the codes. For an optical source well adapted to WDM channels and its short optical pulse generation, reflective semiconductor optical amplifiers (RSOAs) are used with a fiber Bragg grating (FBG) and gain-switched. To demonstrate we experimentally investigated a two-node hybrid WDM/OCDMA ring with a 4-chip Fourier encoder/decoder fabricated by cascading four FBGs with the bit error rate (BER) of <10(-9) for the node span of 10.64 km at 1.25 Gb/s.

Computerized cognitive training in children and adolescents with attention deficit/hyperactivity disorder as add-on treatment to stimulants: feasibility study and protocol description.

Science.gov (United States)

Rosa, Virginia de Oliveira; Schmitz, Marcelo; Moreira-Maia, Carlos Roberto; Wagner, Flavia; Londero, Igor; Bassotto, Caroline de Fraga; Moritz, Guilherme; de Souza, Caroline Dos Santos; Rohde, Luis Augusto Paim

2017-01-01

Cognitive training has received increasing attention as a non-pharmacological approach for the treatment of attention deficit/hyperactivity disorder (ADHD) in children and adolescents. Few studies have assessed cognitive training as add-on treatment to medication in randomized placebo controlled trials. The purpose of this preliminary study was to explore the feasibility of implementing a computerized cognitive training program for ADHD in our environment, describe its main characteristics and potential efficacy in a small pilot study. Six ADHD patients aged 10-12-years old receiving stimulants and presenting residual symptoms were enrolled in a randomized clinical trial to either a standard cognitive training program or a controlled placebo condition for 12 weeks. The primary outcome was core ADHD symptoms measured using the Swanson, Nolan and Pelham Questionnaire (SNAP-IV scale). We faced higher resistance than expected to patient enrollment due to logistic issues to attend face-to-face sessions in the hospital and to fill the requirement of medication status and absence of some comorbidities. Both groups showed decrease in parent reported ADHD symptoms without statistical difference between them. In addition, improvements on neuropsychological tests were observed in both groups - mainly on trained tasks. This protocol revealed the need for new strategies to better assess the effectiveness of cognitive training such as the need to implement the intervention in a school environment to have an assessment with more external validity. Given the small sample size of this pilot study, definitive conclusions on the effects of cognitive training as add-on treatment to stimulants would be premature.

Efficacy and safety comparison of add-on therapy with liraglutide, saxagliptin and vildagliptin, all in combination with current conventional oral hypoglycemic agents therapy in poorly controlled Chinese type 2 diabetes.

Science.gov (United States)

Li, C-J; Yu, Q; Yu, P; Zhang, Q-M; Ding, M; Liu, X-J; Yu, D-M

2014-09-01

To compare the efficacy and safety of adding liraglutide, saxagliptin and vildagliptin to current therapy in Chinese type 2 diabetes subjects with poor glycemic control.A 24-week, randomized, open-label, parallel clinical trial was performed. A total 178 patients completed the trial who had been randomly assigned to add-on once daily liraglutide (1.2 mg/day injected subcutaneously), to saxagliptin (5 mg once daily) or to vildagliptin (50 mg twice daily). Glycosylated hemoglobin (HbA1c) values, fasting and postprandial blood glucose (FBG and P2BG), body weight, body mass index (BMI), episodes of hypoglycemia and adverse events were evaluated.Over the 24-week treatment period, greater lowering of mean of HbA1c was achieved with 1.2 mg liraglutide (-1.50%, 95% CI [-1.67, -1.34]) than with saxagliptin (-1.23%, 95% CI [-1.36, -1.11]) and vildagliptin (-1.25%, 95% CI [-1.37, -1.13]). There was no significant between-group difference of percentages of subjects who reached a target HbA1cvildagliptin. The mean reduction of FBG value from baseline was 2.23 mmol/L with liraglutide, much greater than 1.83 mmol/L with saxagliptin (p=0.013), but similar to 2.03 mmol/L with -vildaglitpin group. As to the P2BG value, greater reductions was found with liraglutide (-4.80 mmol/L) than -3.56 mmol/L with saxagliptin (p=0.000) and -3.57 mmol/L with vildagliptin (p=0.000). Moreover, greater mean reductions of body weight and BMI with liraglutide (-6.0 kg and -2.1 kg/m(2)) were achieved than with saxagliptin and vildagliptin (both pvildagliptin group. The incidence of hypoglycemia was recorded low and similar in each treatment group. Nausea was more common with liraglutide (27%) than with saxagliptin (3.2%) and vildagliptin (5.2%), but no significant between-group difference was reported in other AEs.Adding liraglutide demonstrated superiority to saxagliptin and vildagliptin for reductions of HbA1c and weight loss in Chinese subjects with T2DM who had inadequate glycemic

Low- vs high- frequency Repetitive Transcranial Magnetic Stimulation as an add-on treatment for refractory depression

Directory of Open Access Journals (Sweden)

julien eeche

2012-03-01

Full Text Available Objectives: Repetitive transcranial magnetic stimulation (rTMS seems to be effective as an antidepressant treatment, however, some confusion remain about the best parameters to apply and the efficacy of its association with pharmacological antidepressant treatments.Method: In a single blind randomized study14 patients with unipolar resistant depression to one antidepressant treatment were enrolled to received, in combination with venlafaxine (150 mg, either 20 sessions of 10Hz rTMS (2 000 pulses per session applied over le left dorsolateral prefrontal cortex (DLPFC or 20 sessions of 1 Hz rTMS (120 stimulations per sessions applied over the right DLPFC. Results: A similar antidepressant effect was observed in both groups with a comparable antidepressant delay of action (2 weeks and a comparable number of patients in remission after 4 weeks of daily rTMS sessions (66 vs 50 %.Conclusion: Low- and high- frequency rTMS seem to be effective as an add-on treatment to venlafaxine in pharmacological refractory major depression. Due to its short duration and its safety, low frequency rTMS may be a useful alternative treatment for patients with refractory depression.

Inflammation in Patients with Schizophrenia: the Therapeutic Benefits of Risperidone Plus Add-On Dextromethorphan

Science.gov (United States)

Chen, Shiou-Lan; Lee, Sheng-Yu; Chang, Yun-Hsuan; Chen, Shih-Heng; Chu, Chun-Hsieh; Tzeng, Nian-Sheng; Lee, I-Hui; Chen, Po-See; Yeh, Tzung Lieh; Huang, San-Yuan; Yang, Yen-Kuang; Lu, Ru-Band; Hong, Jau-Shyong

2013-01-01

Objectives Increasing evidence suggests that inflammation contributes to the etiology and progression of schizophrenia. Molecules that initiate inflammation, such as virus- and toxin-induced cytokines, are implicated in neuronal degeneration and schizophrenia-like behavior. Using therapeutic agents with anti-inflammatory or neurotrophic effects may be beneficial for treating schizophrenia. Methods One hundred healthy controls and 95 Han Chinese patients with schizophrenia were tested in this double-blind study. Their PANSS scores, plasma interleukin (IL)-1β, TNF-α and brain-derived neurotrophic factor (BDNF) levels were measured before and after pharmacological treatment. Results Pretreatment, plasma levels of IL-1β and TNF-α were significantly higher in patients with schizophrenia than in controls, but plasma BDNF levels were significantly lower. Patients were treated with the atypical antipsychotic risperidone (Risp) only or with Risp+add-on dextromethorphan (DM). PANSS scores and plasma IL-1β levels significantly decreased, but plasma TNF-α and BDNF levels significantly increased after 11 weeks of Risp treatment. Patients in the Risp+DM group showed a greater and earlier reduction of symptoms than did those in the Risp-only group. Moreover, Risp+DM treatment attenuated Risp-induced plasma increases in TNF-α. Conclusion Patients with schizophrenia had a high level of peripheral inflammation and a low level of peripheral BDNF. Long-term Risp treatment attenuated inflammation and potentiated the neurotrophic function but also produced a certain degree of toxicity. Risp+DM was more beneficial and less toxic than Risp-only treatment. PMID:22730040

Should we add visual acuity ratios to referral criteria for potential cerebral visual impairment?

Science.gov (United States)

van der Zee, Ymie J; Stiers, Peter; Evenhuis, Heleen M

To determine whether the assessment of visual acuity ratios might improve the referral of children with (sub)normal visual acuity but at risk of cerebral visual impairment. In an exploratory study, we assessed visual acuity, crowding ratio and the ratios between grating acuity (Teller Acuity Cards-II) and optotype acuity (Cambridge Crowding Cards) in 60 typically developing school children (mean age 5y8m±1y1m), 21 children with ocular abnormalities only (5y7m±1y9m) and 26 children with (suspected) brain damage (5y7m±1y11m). Sensitivities and specificities were calculated for targets and controls from the perspective of different groups of diagnosticians: youth health care professionals (target: children with any visual abnormalities), ophthalmologists and low vision experts (target: children at risk of cerebral visual impairment). For youth health care professionals subnormal visual acuity had the best sensitivity (76%) and specificity (70%). For ophthalmologists and low vision experts the crowding ratio had the best sensitivity (67%) and specificity (79 and 86%). Youth health care professionals best continue applying subnormal visual acuity for screening, whereas ophthalmologists and low vision experts best add the crowding ratio to their routine diagnostics, to distinguish children at risk of visual impairment in the context of brain damage from children with ocular pathology only. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

3D Laser Imprint Using a Smoother Ray-Traced Power Deposition Method

Science.gov (United States)

Schmitt, Andrew J.

2017-10-01

Imprinting of laser nonuniformities in directly-driven icf targets is a challenging problem to accurately simulate with large radiation-hydro codes. One of the most challenging aspects is the proper construction of the complex and rapidly changing laser interference structure driving the imprint using the reduced laser propagation models (usually ray-tracing) found in these codes. We have upgraded the modelling capability in our massively-parallel fastrad3d code by adding a more realistic EM-wave interference structure. This interference model adds an axial laser speckle to the previous transverse-only laser structure, and can be impressed on our improved smoothed 3D raytrace package. This latter package, which connects rays to form bundles and performs power deposition calculations on the bundles, is intended to decrease ray-trace noise (which can mask or add to imprint) while using fewer rays. We apply this improved model to 3D simulations of recent imprint experiments performed on the Omega-EP laser and the Nike laser that examined the reduction of imprinting due to very thin high-Z target coatings. We report on the conditions in which this new model makes a significant impact on the development of laser imprint. Supported by US DoE/NNSA.

3-D Topo Surface Visualization of Acid-Base Species Distributions: Corner Buttes, Corner Pits, Curving Ridge Crests, and Dilution Plains

Science.gov (United States)

Smith, Garon C.; Hossain, Md Mainul

2017-01-01

Species TOPOS is a free software package for generating three-dimensional (3-D) topographic surfaces ("topos") for acid-base equilibrium studies. This upgrade adds 3-D species distribution topos to earlier surfaces that showed pH and buffer capacity behavior during titration and dilution procedures. It constructs topos by plotting…

Quinone reduction via secondary B-branch electron transfer in mutant bacterial reaction centers.

Science.gov (United States)

Laible, Philip D; Kirmaier, Christine; Udawatte, Chandani S M; Hofman, Samuel J; Holten, Dewey; Hanson, Deborah K

2003-02-18

Symmetry-related branches of electron-transfer cofactors-initiating with a primary electron donor (P) and terminating in quinone acceptors (Q)-are common features of photosynthetic reaction centers (RC). Experimental observations show activity of only one of them-the A branch-in wild-type bacterial RCs. In a mutant RC, we now demonstrate that electron transfer can occur along the entire, normally inactive B-branch pathway to reduce the terminal acceptor Q(B) on the time scale of nanoseconds. The transmembrane charge-separated state P(+)Q(B)(-) is created in this manner in a Rhodobacter capsulatus RC containing the F(L181)Y-Y(M208)F-L(M212)H-W(M250)V mutations (YFHV). The W(M250)V mutation quantitatively blocks binding of Q(A), thereby eliminating Q(B) reduction via the normal A-branch pathway. Full occupancy of the Q(B) site by the native UQ(10) is ensured (without the necessity of reconstitution by exogenous quinone) by purification of RCs with the mild detergent, Deriphat 160-C. The lifetime of P(+)Q(B)(-) in the YFHV mutant RC is >6 s (at pH 8.0, 298 K). This charge-separated state is not formed upon addition of competitive inhibitors of Q(B) binding (terbutryn or stigmatellin). Furthermore, this lifetime is much longer than the value of approximately 1-1.5 s found when P(+)Q(B)(-) is produced in the wild-type RC by A-side activity alone. Collectively, these results demonstrate that P(+)Q(B)(-) is formed solely by activity of the B-branch carriers in the YFHV RC. In comparison, P(+)Q(B)(-) can form by either the A or B branches in the YFH RC, as indicated by the biexponential lifetimes of approximately 1 and approximately 6-10 s. These findings suggest that P(+)Q(B)(-) states formed via the two branches are distinct and that P(+)Q(B)(-) formed by the B side does not decay via the normal (indirect) pathway that utilizes the A-side cofactors when present. These differences may report on structural and energetic factors that further distinguish the functional

Multivariate PAT solutions for biopharmaceutical cultivation: current progress and limitations

NARCIS (Netherlands)

Mercier, S.M.; Diepenbroek, B.; Wijffels, R.H.; Streefland, M.

2014-01-01

Increasingly elaborate and voluminous datasets are generated by the (bio)pharmaceutical industry and are a major challenge for application of PAT and QbD principles. Multivariate data analysis (MVDA) is required to delineate relevant process information from large multi-factorial and multi-collinear

Quality by design approach for optimizing the formulation and physical properties of extemporaneously prepared orodispersible films

NARCIS (Netherlands)

Visser, J. Caroline; Dohmen, Willem M. C.; Hinrichs, Wouter L. J.; Breitkreutz, Joerg; Frijlink, Henderik W.; Woerdenbag, Herman J.

2015-01-01

The quality by design (QbD) approach was applied for optimizing the formulation of extemporaneously prepared orodispersible films (ODFs) using Design-Expert Software. The starting formulation was based on earlier experiments and contained the film forming agents hypromellose and carbomer 974P and

Quasi-bound states, resonance tunnelling, and tunnelling times ...

Indian Academy of Sciences (India)

analysis of bound states below the threshold energy E = 0 and continuum above the threshold .... p are time reversal states of each other. Similarly, the ... are occurring at above-barrier energies and we do not treat them as QB states. They can ...

Petro-Canada's project to add petroleum product storage tanks to the Municipality of Montreal-East

International Nuclear Information System (INIS)

Lefebvre, G.; Joly, R.; Guay, T.

2006-01-01

This paper explored the environmental impacts associated with Petro-Canada's project to add petroleum product storage tanks to its refinery in the east-end of Montreal. The project plan is based on a 6 year horizon from 2006-2012. The additional reservoirs would store new products destined for the petrochemical industry and for consumers, thus improving the flexibility and reliability of the refinery. The products would include low sulfur diesel and ethanol gasoline. The project does not involve any increase in refining capacity, and is estimated to cost $15 million. The main issues associated with this project are ambient air quality, the protection of groundwater and soil, as well as the security of areas inhabited by neighbouring areas in risk of a major accident. Emissions of organic compounds, including benzene, are considered minimal considering the use of sealed floating roofs. Geomembranes will be installed under the storage tanks to ensure the protection of groundwater and soil. Any consequences to the population of neighbouring areas resulting from accidents inside the industrial park will be limited since the reservoirs will be located more than 1 km away from a populated area. Quebec's Ministry of Sustainable Development, Environment and Parks recommended that this project be approved as long as the terms and measures of environmental regulations are respected, and that an emergency plan is submitted before the operation of the first reservoir. 1 tab

Influence of partial replacement of sodium chloride by potassium chloride in Minas fresh cheese of sheep’s milk

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Dalana Cecília Hanauer

2017-08-01

Full Text Available The sheep’s milk has high contents of fat, protein and minerals in relation to the cow’s milk and is suitable for the production of cheeses, as the Minas fresh. The production of this cheese includes the salting, by offering important functions for this product. The salting is performed by adding sodium chloride (NaCl, however in excess this salt may be harmful to consumer health. Then, it was evaluated the development of tree formulations of Minas fresh cheese sheep’s milk (100% NaCl – QA; 75% NaCl and 25% potassium chloride (KCl – QB; 50% NaCl and 50% KCl – QC and they were evaluated by physical-chemical, microbiological and sensorial analyzes. A partial replacement of NaCl by KCl did not influence the moisture, protein and ash contents, pH and water activity of the cheeses. Furthermore, a 50% substitution of NaCl by KCl enabled to obtain a cheese with reduced sodium content in relation to the standard with 100% NaCl. The sensorial analysis showed that the substitution of 50% (QC and 25% (QB of NaCl by KCl did not show significant for the overall acceptance index, however, the use of KCl was perceived by the evaluators, since the formulations QB and QC differed significantly from the standard (QA. However, in the multiple comparison test there was no significant difference between the samples. Thus, the results indicated that a partial replacement of NaCl by KCl can be performed at Minas fresh cheese from sheep’smilk.

Quality by design for herbal drugs: a feedforward control strategy and an approach to define the acceptable ranges of critical quality attributes.

Science.gov (United States)

Yan, Binjun; Li, Yao; Guo, Zhengtai; Qu, Haibin

2014-01-01

The concept of quality by design (QbD) has been widely accepted and applied in the pharmaceutical manufacturing industry. There are still two key issues to be addressed in the implementation of QbD for herbal drugs. The first issue is the quality variation of herbal raw materials and the second issue is the difficulty in defining the acceptable ranges of critical quality attributes (CQAs). To propose a feedforward control strategy and a method for defining the acceptable ranges of CQAs for the two issues. In the case study of the ethanol precipitation process of Danshen (Radix Salvia miltiorrhiza) injection, regression models linking input material attributes and process parameters to CQAs were built first and an optimisation model for calculating the best process parameters according to the input materials was established. Then, the feasible material space was defined and the acceptable ranges of CQAs for the previous process were determined. In the case study, satisfactory regression models were built with cross-validated regression coefficients (Q(2) ) all above 91 %. The feedforward control strategy was applied successfully to compensate the quality variation of the input materials, which was able to control the CQAs in the 90-110 % ranges of the desired values. In addition, the feasible material space for the ethanol precipitation process was built successfully, which showed the acceptable ranges of the CQAs for the concentration process. The proposed methodology can help to promote the implementation of QbD for herbal drugs. Copyright © 2013 John Wiley & Sons, Ltd.

VZLUSAT-1: Nanosatellite with miniature lobster eye X-ray telescope and qualification of the radiation shielding composite for space application

Science.gov (United States)

Urban, Martin; Nentvich, Ondrej; Stehlikova, Veronika; Baca, Tomas; Daniel, Vladimir; Hudec, Rene

2017-11-01

In the upcoming generation of small satellites there is a great potential for testing new sensors, processes and technologies for space and also for the creation of large in situ sensor networks. It plays a significant role in the more detailed examination, modelling and evaluation of the orbital environment. Scientific payloads based on the CubeSat technology are also feasible and the miniature X-ray telescope described in this paper may serve as an example. One of these small satellites from CubeSat family is a Czech CubeSat VZLUSAT-1, which is going to be launched during QB50 mission in 2017. This satellite has dimensions of 100 mm × 100 mm × 230 mm. The VZLUSAT-1 has three main payloads. The tested Radiation Hardened Composites Housing (RHCH) has ambitions to be used as a structural and shielding material to protect electronic devices in space or for constructions of future manned and unmanned spacecraft as well as Moon or Martian habitats. The novel miniaturized X-ray telescope with a Lobster Eye (LE) optics represents an example of CubeSat's scientific payload. The telescope has a wide field of view and such systems may be essential in detecting the X-ray sources of various physical origin. VZLUSAT-1 also carries the FIPEX payload which measures the molecular and atomic oxygen density among part of the satellite group in QB50 mission. The VZLUSAT-1 is one of the constellation in the QB50 mission that create a measuring network around the Earth and provide multipoint, in-situ measurements of the atmosphere.

Implementation of Quality by Design for Formulation of Rebamipide Gastro-retentive Tablet.

Science.gov (United States)

Ha, Jung-Myung; Seo, Jeong-Woong; Kim, Su-Hyeon; Kim, Ju-Young; Park, Chun-Woong; Rhee, Yun-Seok; Park, Eun-Seok

2017-11-01

The purpose of the present study was to develop a rebamipide (RBM) gastro-retentive (GR) tablet by implementing quality by design (QbD). RBM GR tablets were prepared using a sublimation method. Quality target product profile (QTPP) and critical quality attributes (CQAs) of the RBM GR tablets were defined according to the preliminary studies. Factors affecting the CQAs were prioritized using failure mode and effects analysis (FMEA). Design space and optimum formulation were established through a mixture design. The validity of the design space was confirmed using runs within the area. The QTPP of the RBM GR tablets was the orally administered GR tablet containing 300 mg of RBM taken once daily. Based on the QTPP, dissolution rate, tablet friability, and floating property were chosen as CQAs. According to the risk assessment, the amount of sustained-release agent, sublimating material, and diluent showed high-risk priority number (RPN) values above 40. Based on the RPN, these factors were further investigated using mixture design methodology. Design space of formulations was depicted as an overlaid contour plot and the optimum formulation to satisfy the desired responses was obtained by determining the expected value of each response. The similarity factor (f2) of the release profile between predicted response and experimental response was 89.463, suggesting that two release profiles are similar. The validity of the design space was also confirmed. Consequently, we were able to develop the RBM GR tablets by implementing the QbD concept. These results provide useful information for development of tablet formulations using the QbD.

Electrostatics of the photosynthetic bacterial reaction center. Protonation of Glu L 212 and Asp L 213 - A new method of calculation.

Science.gov (United States)

Ptushenko, Vasily V; Cherepanov, Dmitry A; Krishtalik, Lev I

2015-12-01

Continuum electrostatic calculation of the transfer energies of anions from water into aprotic solvents gives the figures erroneous by order of magnitude. This is due to the hydrogen bond disruption that suggests the necessity to reconsider the traditional approach of the purely electrostatic calculation of the transfer energy from water into protein. In this paper, the method combining the experimental estimates of the transfer energies from water into aprotic solvent and the electrostatic calculation of the transfer energies from aprotic solvent into protein is proposed. Hydrogen bonds between aprotic solvent and solute are taken into account by introducing an imaginary aprotic medium incapable to form hydrogen bonds with the solute. Besides, a new treatment of the heterogeneous intraprotein dielectric permittivity based on the microscopic protein structure and electrometric measurements is elaborated. The method accounts semi-quantitatively for the electrostatic effect of diverse charged amino acid substitutions in the donor and acceptor parts of the photosynthetic bacterial reaction center from Rhodobacter sphaeroides. Analysis of the volatile secondary acceptor site QB revealed that in the conformation with a minimal distance between quinone QB and Glu L 212 the proton uptake upon the reduction of QB is prompted by Glu L 212 in alkaline and by Asp L 213 in slightly acidic regions. This agrees with the pH dependences of protonation degrees and the proton uptake. The method of pK calculation was applied successfully also for dissociation of Asp 26 in bacterial thioredoxin. Copyright © 2015 Elsevier B.V. All rights reserved.

Application of Quality by Design Approach to Bioanalysis: Development of a Method for Elvitegravir Quantification in Human Plasma.

Science.gov (United States)

Baldelli, Sara; Marrubini, Giorgio; Cattaneo, Dario; Clementi, Emilio; Cerea, Matteo

2017-10-01

The application of Quality by Design (QbD) principles in clinical laboratories can help to develop an analytical method through a systematic approach, providing a significant advance over the traditional heuristic and empirical methodology. In this work, we applied for the first time the QbD concept in the development of a method for drug quantification in human plasma using elvitegravir as the test molecule. The goal of the study was to develop a fast and inexpensive quantification method, with precision and accuracy as requested by the European Medicines Agency guidelines on bioanalytical method validation. The method was divided into operative units, and for each unit critical variables affecting the results were identified. A risk analysis was performed to select critical process parameters that should be introduced in the design of experiments (DoEs). Different DoEs were used depending on the phase of advancement of the study. Protein precipitation and high-performance liquid chromatography-tandem mass spectrometry were selected as the techniques to be investigated. For every operative unit (sample preparation, chromatographic conditions, and detector settings), a model based on factors affecting the responses was developed and optimized. The obtained method was validated and clinically applied with success. To the best of our knowledge, this is the first investigation thoroughly addressing the application of QbD to the analysis of a drug in a biological matrix applied in a clinical laboratory. The extensive optimization process generated a robust method compliant with its intended use. The performance of the method is continuously monitored using control charts.

Shallow trapping vs. deep polarons in a hybrid lead halide perovskite, CH3NH3PbI3.

Science.gov (United States)

Kang, Byungkyun; Biswas, Koushik

2017-10-18

There has been considerable speculation over the nature of charge carriers in organic-inorganic hybrid perovskites, i.e., whether they are free and band-like, or they are prone to self-trapping via short range deformation potentials. Unusually long minority-carrier diffusion lengths and moderate-to-low mobilities, together with relatively few deep defects add to their intrigue. Here we implement density functional methods to investigate the room-temperature, tetragonal phase of CH 3 NH 3 PbI 3 . We compare charge localization behavior at shallow levels and associated lattice relaxation versus those at deep polaronic states. The shallow level originates from screened Coulomb interaction between the perturbed host and an excited electron or hole. The host lattice has a tendency towards forming these shallow traps where the electron or hole is localized not too far from the band edge. In contrast, there is a considerable potential barrier that must be overcome in order to initiate polaronic hole trapping. The formation of a hole polaron (I 2 - center) involves strong lattice relaxation, including large off-center displacement of the organic cation, CH 3 NH 3 + . This type of deep polaron is energetically unfavorable, and active shallow traps are expected to shape the carrier dynamics in this material.

Computerized cognitive training in children and adolescents with attention deficit/hyperactivity disorder as add-on treatment to stimulants: feasibility study and protocol description

Directory of Open Access Journals (Sweden)

Virginia de Oliveira Rosa

Full Text Available Abstract Background Cognitive training has received increasing attention as a non-pharmacological approach for the treatment of attention deficit/hyperactivity disorder (ADHD in children and adolescents. Few studies have assessed cognitive training as add-on treatment to medication in randomized placebo controlled trials. The purpose of this preliminary study was to explore the feasibility of implementing a computerized cognitive training program for ADHD in our environment, describe its main characteristics and potential efficacy in a small pilot study. Methods Six ADHD patients aged 10-12-years old receiving stimulants and presenting residual symptoms were enrolled in a randomized clinical trial to either a standard cognitive training program or a controlled placebo condition for 12 weeks. The primary outcome was core ADHD symptoms measured using the Swanson, Nolan and Pelham Questionnaire (SNAP-IV scale. Results We faced higher resistance than expected to patient enrollment due to logistic issues to attend face-to-face sessions in the hospital and to fill the requirement of medication status and absence of some comorbidities. Both groups showed decrease in parent reported ADHD symptoms without statistical difference between them. In addition, improvements on neuropsychological tests were observed in both groups – mainly on trained tasks. Conclusions This protocol revealed the need for new strategies to better assess the effectiveness of cognitive training such as the need to implement the intervention in a school environment to have an assessment with more external validity. Given the small sample size of this pilot study, definitive conclusions on the effects of cognitive training as add-on treatment to stimulants would be premature.

Development of a NIR-based blend uniformity method for a drug product containing multiple structurally similar actives by using the quality by design principles.

Science.gov (United States)

Lin, Yiqing; Li, Weiyong; Xu, Jin; Boulas, Pierre

2015-07-05

The aim of this study is to develop an at-line near infrared (NIR) method for the rapid and simultaneous determination of four structurally similar active pharmaceutical ingredients (APIs) in powder blends intended for the manufacturing of tablets. Two of the four APIs in the formula are present in relatively small amounts, one at 0.95% and the other at 0.57%. Such small amounts in addition to the similarity in structures add significant complexity to the blend uniformity analysis. The NIR method is developed using spectra from six laboratory-created calibration samples augmented by a small set of spectra from a large-scale blending sample. Applying the quality by design (QbD) principles, the calibration design included concentration variations of the four APIs and a main excipient, microcrystalline cellulose. A bench-top FT-NIR instrument was used to acquire the spectra. The obtained NIR spectra were analyzed by applying principal component analysis (PCA) before calibration model development. Score patterns from the PCA were analyzed to reveal relationship between latent variables and concentration variations of the APIs. In calibration model development, both PLS-1 and PLS-2 models were created and evaluated for their effectiveness in predicting API concentrations in the blending samples. The final NIR method shows satisfactory specificity and accuracy. Copyright © 2015 Elsevier B.V. All rights reserved.

Use of a Microsoft Excel based add-in program to calculate plasma sinistrin clearance by a two-compartment model analysis in dogs.

Science.gov (United States)

Steinbach, Sarah M L; Sturgess, Christopher P; Dunning, Mark D; Neiger, Reto

2015-06-01

Assessment of renal function by means of plasma clearance of a suitable marker has become standard procedure for estimation of glomerular filtration rate (GFR). Sinistrin, a polyfructan solely cleared by the kidney, is often used for this purpose. Pharmacokinetic modeling using adequate software is necessary to calculate disappearance rate and half-life of sinistrin. The purpose of this study was to describe the use of a Microsoft excel based add-in program to calculate plasma sinistrin clearance, as well as additional pharmacokinetic parameters such as transfer rates (k), half-life (t1/2) and volume of distribution (Vss) for sinistrin in dogs with varying degrees of renal function. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of Ravi river water quality

International Nuclear Information System (INIS)

Ahmed, K.; Ali, W.

2000-01-01

Investigation from 1989 to 1998 on river Ravi pollution was carried out to study the effects of wastewater discharges on its water quality in relation to its various water use. The sources of pollution entering the river between Syphon (20 Km upstream) and Balloki Head works (75 Km downstream) includes Upper Chenab Canal (U.C.) which bring industrial effluents through Deg municipal swage from the city of Lahore. Investigation revealed that the flow in the river are highly variable with time during the year U.C. canal with a capacity of 220 m/sup 3//S at the tail and Qadiarabad (Q.B.) Link canal with a capacity of 410 m3/S are mainly responsible for higher flows during dry season. A desecrating trend has been observed in the D.O. Levels indicating increasing pollution. Over times D.O values are above 4 mg/l indicating recovery due to dilution biodegradation and aeration. An increasing trend has been observed in Biochemical Oxygen Demand (BOD), suspended solids, total dissolved solids and indicator organisms. Even with the discharges of pollutions from U.C. canal, Hudiara Nullah and city sewage, BOD at Balloki was unexpectedly low. It was investigated that because of pollution free Q.B. link canal which joins the river just before Balloki Head works makes the water diluted, which accounted for low BOD. Water of river Ravi meet the chemical water quality requirement for irrigation. However the water quality does not meet the coliform and faecal coliform criteria for most water use. (orig../A.B.)

Engineering of budesonide-loaded lipid-polymer hybrid nanoparticles using a quality-by-design approach

DEFF Research Database (Denmark)

Leng, Donglei; Thanki, Kaushik; Fattal, Elias

2018-01-01

-by-design (QbD) approach was adopted to identify the optimal formulation parameters. The quality target product profile (QTPP) of the LPNs was identified based on risk assessment. Two critical formulation parameters (CFPs) were identified, including the theoretical budesonide loading and the theoretical DOTAP...

Behavioral symptoms of eating disorders in Native Americans: results from the ADD Health Survey Wave III.

Science.gov (United States)

Striegel-Moore, Ruth H; Rosselli, Francine; Holtzman, Niki; Dierker, Lisa; Becker, Anne E; Swaney, Gyda

2011-09-01

To examine prevalence and correlates (gender, Body Mass Index) of disordered eating in American Indian/Native American (AI/NA) and white young adults. We examined data from the 10,334 participants (mean age 21.93 years, SD = 1.8) of the National Longitudinal Study of Adolescent Health (ADD Health) Wave III for gender differences among AI/NA participants (236 women, 253 men) and ethnic group differences on measures of eating pathology. Among AI/NA groups, women were significantly more likely than men to report loss of control and embarrassment due to overeating. In gender-stratified analyses, a significantly higher prevalence of AI/NA women reported disordered eating behaviors compared with white women; there were no between group differences in prevalence for breakfast skipping or having been diagnosed with an eating disorder. Among men, disordered eating behaviors were uncommon and no comparison was statistically significant. Our study offers a first glimpse into the problem of eating pathology among AI/NA individuals. Gender differences among AI/NA participants are similar to results reported in white samples. That AI/NA women were as likely as white women to have been diagnosed with an eating disorder is striking in light of well documented under-utilization of mental health care among AI/NA individuals. Copyright © 2010 Wiley Periodicals, Inc.

Positional cloning of "Lisch-Like", a candidate modifier of susceptibility to type 2 diabetes in mice.

Directory of Open Access Journals (Sweden)

Marija Dokmanovic-Chouinard

2008-07-01

Full Text Available In 404 Lep(ob/ob F2 progeny of a C57BL/6J (B6 x DBA/2J (DBA intercross, we mapped a DBA-related quantitative trait locus (QTL to distal Chr1 at 169.6 Mb, centered about D1Mit110, for diabetes-related phenotypes that included blood glucose, HbA1c, and pancreatic islet histology. The interval was refined to 1.8 Mb in a series of B6.DBA congenic/subcongenic lines also segregating for Lep(ob. The phenotypes of B6.DBA congenic mice include reduced beta-cell replication rates accompanied by reduced beta-cell mass, reduced insulin/glucose ratio in blood, reduced glucose tolerance, and persistent mild hypoinsulinemic hyperglycemia. Nucleotide sequence and expression analysis of 14 genes in this interval identified a predicted gene that we have designated "Lisch-like" (Ll as the most likely candidate. The gene spans 62.7 kb on Chr1qH2.3, encoding a 10-exon, 646-amino acid polypeptide, homologous to Lsr on Chr7qB1 and to Ildr1 on Chr16qB3. The largest isoform of Ll is predicted to be a transmembrane molecule with an immunoglobulin-like extracellular domain and a serine/threonine-rich intracellular domain that contains a 14-3-3 binding domain. Morpholino knockdown of the zebrafish paralog of Ll resulted in a generalized delay in endodermal development in the gut region and dispersion of insulin-positive cells. Mice segregating for an ENU-induced null allele of Ll have phenotypes comparable to the B.D congenic lines. The human ortholog, C1orf32, is in the middle of a 30-Mb region of Chr1q23-25 that has been repeatedly associated with type 2 diabetes.

Add-On Effect of Probucol in Atherosclerotic, Cholesterol-Fed Rabbits Treated with Atorvastatin

Science.gov (United States)

Keyamura, Yuka; Nagano, Chifumi; Kohashi, Masayuki; Niimi, Manabu; Nozako, Masanori; Koyama, Takashi; Yasufuku, Reiko; Imaizumi, Ayako; Itabe, Hiroyuki; Yoshikawa, Tomohiro

2014-01-01

Objective Lowering the blood concentration of low-density lipoprotein (LDL) cholesterol is the primary strategy employed in treating atherosclerotic disorders; however, most commonly prescribed statins prevent cardiovascular events in just 30% to 40% of treated patients. Therefore, additional treatment is required for patients in whom statins have been ineffective. In this study of atherosclerosis in rabbits, we examined the effect of probucol, a lipid-lowering drug with potent antioxidative effects, added to treatment with atorvastatin. Methods and Results Atherosclerosis was induced by feeding rabbits chow containing 0.5% cholesterol for 8 weeks. Probucol 0.1%, atorvastatin 0.001%, and atorvastatin 0.003% were administered solely or in combination for 6 weeks, beginning 2 weeks after the start of atherosclerosis induction. Atorvastatin decreased the plasma concentration of non-high-density lipoprotein cholesterol (non-HDLC) dose-dependently; atorvastatin 0.003% decreased the plasma concentration of non-HDLC by 25% and the area of atherosclerotic lesions by 21%. Probucol decreased the plasma concentration of non-HDLC to the same extent as atorvastatin (i.e., by 22%) and the area of atherosclerotic lesions by 41%. Probucol with 0.003% atorvastatin decreased the plasma concentration of non-HDLC by 38% and the area of atherosclerotic lesions by 61%. Co-administration of probucol with atorvastatin did not affect the antioxidative effects of probucol, which were not evident on treatment with atorvastatin alone, such as prevention of in vitro LDL-oxidation, increase in paraoxonase-1 activity of HDL, and decreases in plasma and plaque levels of oxidized-LDL in vivo. Conclusions Probucol has significant add-on anti-atherosclerotic effects when combined with atorvastatin treatment; suggesting that this combination might be beneficial for treatment of atherosclerosis. PMID:24810608

Immunostaining of skin biopsy adds no diagnostic value in MGUS-associated peripheral neuropathy.

Science.gov (United States)

Al-Zuhairy, Ali; Schrøder, Henrik Daa; Plesner, Torben; Abildgaard, Niels; Sindrup, Søren H

2015-02-15

For several decades an association between MGUS, IgM-MGUS in particular, and peripheral neuropathy has been suspected. Several histopathology studies have shown binding of IgM to myelin and a secondary widening of myelin lamellae in cutaneous nerves and in the sural nerve of patients with IgM-MGUS, or Waldenström's Macroglobulinaemia (WM), and peripheral neuropathy. In this retrospective study we investigated the value of skin biopsy examination in the diagnosis of MGUS- and WM-associated peripheral neuropathy. A total of 117 patients, who were examined for an M-component in serum with associated nerve symptoms, had a skin biopsy taken and examined for immunoglobulin deposition in cutaneous nerves. Thirty-five patients were diagnosed with MGUS or WM and peripheral neuropathy with no other cause of neuropathy. Nineteen patients had MGUS but no peripheral neuropathy. Of the 35 patients with MGUS or WM and peripheral neuropathy, four had immunoglobulin deposition in the skin biopsy, all of whom had an IgM gammopathy. In the control group of 19 without peripheral neuropathy, three had immunoglobulin deposition in the skin biopsy, all of whom had IgM-MGUS. In both groups, there was a trend towards higher IgM blood levels in patients with immunoglobulin deposition. Half of the patients with IgM gammopathy in the neuropathy group had anti-MAG reactivity, whereas only one in the control group had weak anti-MAG reactivity. Our study indicates that examination of skin biopsies for immunoglobulin deposition does not add significant diagnostic value in the evaluation of neuropathies suspected to be caused by MGUS or WM. IgM immunoglobulin deposition in skin biopsy might merely be an epiphenomenon secondary to high IgM blood levels. Copyright © 2014 Elsevier B.V. All rights reserved.

EFFECTS OF CO2 AND O3 ON CARBON FLUX FOR PONDEROSA PINE PLANT/LITTER/SOIL SYSTEM

Science.gov (United States)

Carbon dioxide (CO2), a main contributor to global climate change, also adds carbon to forests. In contrast, tropospheric ozone (O3) can reduce carbon uptake and increase carbon loss by forests. Thus, the net balance of carbon uptake and loss for forests can be affected by concu...

Expert and Generalist Local Knowledge about Land-cover Change on South Africa's Wild Coast: Can Local Ecological Knowledge Add Value to Science?

Directory of Open Access Journals (Sweden)

Nigel Chalmers

2007-06-01

Full Text Available Local ecological knowledge (LEK can shed light on ecosystem change, especially in under-researched areas such as South Africa's Wild Coast. However, for ecosystem planning purposes, it is necessary to assess the accuracy and validity of LEK, and determine where such knowledge is situated in a community, and how evenly it is spread. Furthermore, it is relevant to ask: does LEK add value to science, and how do science and local knowledge complement one another? We assessed change in woodland and forest cover in the Nqabara Administrative Area on South Africa's Wild Coast between 1974 and 2001. The inhabitants of Nqabara are "traditional" Xhosa-speaking people who are highly dependent on natural resources for their livelihoods. More recently, however, infrastructural development has influenced traditional lifestyles at Nqabara, although poverty remains high and formal education levels low. We assessed LEK about changes in woodland and forest cover over the past 30 years by interviewing 11 local "experts," who were recognized as such by the Nqabara community, and 40 senior members of randomly selected households in each village. We also analyzed land-cover change, using orthorectified aerial photos taken in 1974 and 2001. Forest and woodland cover had increased by 49% between 1974 and 2001. The 11 "experts" had a nuanced understanding of these changes and their causes. Their understanding was not only remarkably consistent with that of scientists, but it added considerable value to scientific understanding of the ultimate causes of land-cover change in the area. The experts listed combinations of several causal factors, operating at different spatial and temporal scales. The 40 randomly selected respondents also knew that forest and woodland cover had increased, but their understanding of the causes, and the role of fire in particular, was somewhat simplistic. They could identify only three causal factors and generally listed single factors rather

The Systems Biology Markup Language (SBML Level 3 Package: Layout, Version 1 Core

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Gauges Ralph

2015-06-01

Full Text Available Many software tools provide facilities for depicting reaction network diagrams in a visual form. Two aspects of such a visual diagram can be distinguished: the layout (i.e.: the positioning and connections of the elements in the diagram, and the graphical form of the elements (for example, the glyphs used for symbols, the properties of the lines connecting them, and so on. For software tools that also read and write models in SBML (Systems Biology Markup Language format, a common need is to store the network diagram together with the SBML representation of the model. This in turn raises the question of how to encode the layout and the rendering of these diagrams. The SBML Level 3 Version 1 Core specification does not provide a mechanism for explicitly encoding diagrams, but it does provide a mechanism for SBML packages to extend the Core specification and add additional syntactical constructs. The Layout package for SBML Level 3 adds the necessary features to SBML so that diagram layouts can be encoded in SBML files, and a companion package called SBML Rendering specifies how the graphical rendering of elements can be encoded.

Current status of surface water pollution in Punjab

International Nuclear Information System (INIS)

Bashir, M.T.; Ghauri, Moin-ud-Din

2001-01-01

Eleven years investigations (1988-99) on river Ravi revealed that U.C. canal with a capacity of 220 m/sup 3//s at the tail and Q.B. Link canal with capacity of 410 m/sup 3//s are mainly responsible for higher flows during dry season. A decreasing trend has been observed in the DO levels indicating increasing pollution. An increasing trend has been observed in BOD, SS, TDS and Indicators. Even with the discharge of pollution from U.C. canal, Hudiara Nullah and Lahore city BOD at Balkoi was unexpectedly low. Problems confronting environment engineers regarding surface water pollution control has been highlighted and their solutions has been recommended. (author)

Characterization of iminothiosulfine-type ions [HNCS 2] rad +/ rad - and their neutral counterparts by mass spectrometry and computational chemistry

Science.gov (United States)

Vivekananda, S.; Raghunath, P.; Bhanuprakash, K.; Srinivas, R.; Trikoupis, Moschoula A.; Terlouw, Johan K.

2000-12-01

Electron ionization of rhodanine yields iminothiosulfine ions H- N C- S- Srad + , 1brad + , which readily communicate with the higher energy cyclic isomer H- N CS2rad + , 1arad + . CBS-QB3 and G AUSSIAN-2 model chemistries predict that one electron reduction reverses the stability order but that the (singlet) neutrals remain connected via a negligible energy barrier. Neutralization-reionization (NR) experiments demonstrate that singlet 1a and its heterocumulene isomer 1b are stable species in the gas-phase. However, the co-generated triplet species readily dissociate into 3S2rad + + HNC. Confirmatory experimental evidence comes from charge reversal (CR) and NR experiments on the cyclic anion H- N CS2rad - , 1arad - .

Nothing Changes, Really: Why Women Who Break Through the Glass Ceiling End Up Reinforcing It

NARCIS (Netherlands)

Faniko, Klea; Ellemers, Naomi; Derks, Belle; Lorenzi-Cioldi, Fabio

Two correlational studies conducted in Switzerland (N = 222) and Albania (N = 156) explained the opposition of female managers to gender quotas by examining the origins and consequences of the “Queen Bee (QB)-phenomenon,” whereby women who have been successful in male-dominated organizations do not

75 FR 59745 - In the Matter of: Certain Components for Installation of Marine Autopilots With GPS or IMU...

Science.gov (United States)

2010-09-28

..., Southampton Road. Portsmouth Hampshire, PO6 4QB, United Kingdom. Raymarine Inc., 21 Manchester Street... violations of section 337 based upon the importation into the United States, the sale for importation, and the sale within the United States after importation of certain installation of marine autopilots with...

Genetic variation within and between three Vietnamese pine ...

African Journals Online (AJOL)

Pinus merkusii is an important species in Vietnam with many economic and biological contributions. The information on diversity within and between populations of a species is necessary for plantation programs, breeding and conservation strategies. Genetic diversity of three Vietnamese populations (NA, QB and QN) was ...

HERBICIDAS INIBIDORES DO FOTOSSISTEMA II – PARTE II / PHOTOSYSTEM II INHIBITOR HERBICIDES - PART

Directory of Open Access Journals (Sweden)

ILCA P. DE F. E SILVA

2013-11-01

Full Text Available Os herbicidas inibidores do fotossistema II (PSII ligam-se ao sítio da QB localizado na proteína D1 o qual se localiza na membrana dos tilacóides dos cloroplastos, causando, o bloqueia do transporte de elétrons da QA para QB, tendo como consequência, a peroxidação dos lipídios. Os principais fatores que afetam a evolução da resistência de plantas daninhas aos herbicidas têm sido agrupados em: genéticos, bioecológicos e agronômicos. A resistência de plantas daninhas a herbicidas é definida como a habilidade de uma planta sobreviver e reproduzir, após exposição a uma dose de herbicida normalmente letal para um biótipo normal da planta. A seletividade de um herbicida está relacionada à capacidade de eliminar plantas daninhas sem interferir na qualidade da planta de interesse econômico.

Effective diffusion volume flow rates (Qe) for urea, creatinine, and inorganic phosphorous (Qeu, Qecr, QeiP) during hemodialysis.

Science.gov (United States)

Gotch, Frank A; Panlilio, Froilan; Sergeyeva, Olga; Rosales, Laura; Folden, Tom; Kaysen, George; Levin, Nathan

2003-01-01

In vivo solute clearances can be estimated from dialyzer blood (Qb) and dialysate (Qd) flow rates and a solute- and dialyzer-specific overall permeability membrane area product (KoA). However, these calculations require knowledge of the flow rate of the effective solute distribution volume in the flowing bloodstream (Qe) in order to calculate in vivo clearances and KoAs. We have determined Qe for urea, creatinine, and inorganic phosphorus from changes in concentrations across the blood compartment and mass balance between the blood and dialysate streams. We made four serial measurements over one dialysis in 23 patients and found that Qeu equals the total blood water flow rate, Qecr equals the plasma water flow rate plus 61% of red cell water flow rate, and QeiP is limited to the plasma water flow rate. Equations are derived to calculate Qe for each of these solutes from Qb and hematocrit and in vivo KoAs for each solute were calculated.

Twelve-Week Treatment With Liraglutide as Add-on to Insulin in Normal-Weight Patients With Poorly Controlled Type 1 Diabetes

DEFF Research Database (Denmark)

Frandsen, Christian S; Dejgaard, Thomas F; Holst, Jens J

2015-01-01

OBJECTIVE: This study investigated the efficacy and safety of once-daily liraglutide 1.2 mg versus placebo as add-on to insulin treatment in normal-weight patients with poorly controlled type 1 diabetes. RESEARCH DESIGN AND METHODS: In a randomized (1:1), double-blind, placebo-controlled design, 40...... patients with type 1 diabetes (HbA1c ≥8% [64 mmol/mol]) received once-daily liraglutide 1.2 mg or placebo for 12 weeks. Continuous glucose monitoring was performed before and at the end of treatment. The primary end point was change in HbA1c. Secondary end points included change in insulin dose, weight...... was more frequently associated with gastrointestinal adverse effects. The incidence of hypoglycemia did not differ between groups. CONCLUSIONS: Liraglutide significantly reduces body weight and insulin requirements but has no additional effect on HbA1c in normal-weight patients with type 1 diabetes...

Implementation of IGMP v3 and its application to IPTV carrying network

Science.gov (United States)

Zhou, Min; Dong, Ximing

2008-11-01

IGMP is a host-router signaling protocol, and it is used to manage the membership of Internet Protocol multicast groups for IPv4. IGMPv3 adds "source filtering" function required to support SSM. Firstly, this paper analyses the improvements and implementation of IGMPv3. Secondly, it points out the problems when applying IGMPv3 to IPTV carrying network. Then it presents the solutions by improving IGMPv3 protocol to reduce channel zapping time which is one of the important metrics affecting the QoE in IPTV service. Method to realize the end user authentication, authorization and accounting in the IP multicast security and authentication area by extending the IGMPv3 protocol is described at last.

Composites of 3D-Printed Polymers and Textile Fabrics*

Science.gov (United States)

Martens, Yasmin; Ehrmann, Andrea

2017-08-01

3D printing belongs to the rapidly emerging technologies of our time. Due to its recent drawback - the technology is relatively slow compared with other primary shaping methods, such as injection molding -, 3D printing is often not used for creating complete large components but to add specific features to existing larger objects. One of the possibilities to create such composites with an additional value consists in combining 3D printed polymers with textile fabrics. Several attempts have been made to enhance the adhesion between both materials, a task which is still challenging for diverse material combinations. Our paper reports about new experiments combining 3D printed embossed designs, snap fasteners and zip fasteners with different textile base materials, showing the possibilities and technical limits of these novel composites.

Efficacy and Safety of Vildagliptin as an Add-on to Insulin with or without Metformin in Japanese Patients with Type 2 Diabetes Mellitus: A 12-week, Double-Blind, Randomized Study.

Science.gov (United States)

Hirose, Takahisa; Suzuki, Manabu; Tsumiyama, Isao

2015-12-01

To assess the efficacy and safety of vildagliptin as add-on therapy in Japanese patients with type 2 diabetes mellitus (T2DM), inadequately controlled on stable long-acting, intermediate-acting, or pre-mixed insulin, with or without concomitant metformin. In this 12-week placebo-controlled study, patients were randomized to receive either vildagliptin 50 mg twice daily (bid) or placebo treatment in a 1:1 ratio. The primary endpoint was change in glycated hemoglobin A1c (HbA1c) from baseline to 12-week endpoint. Secondary endpoints included proportion of patients achieving pre-defined HbA1c targets of ≤6.5%, vildagliptin, n = 76; placebo, n = 75). Patient demographics and clinical characteristics were comparable between the groups at baseline. Addition of vildagliptin resulted in statistically significant reductions in HbA1c after 12 weeks (-1.01 ± 0.06%), with a between-treatment difference of -0.91 ± 0.09% (p vildagliptin group (-1.2 ± 0.2 mmol/L), with a between-treatment difference of -1.2 ± 0.3 mmol/L which was significant (p vildagliptin treatment for all pre-defined responder rate categories. The overall incidence of AEs was comparable between groups (vildagliptin, 46.2% vs. placebo, 43.6%). The overall incidence of hypoglycemic events was low and all events were self-treatable without using drug therapy. No severe hypoglycemic events were reported. Treatment with vildagliptin 50 mg bid as add-on to insulin with or without metformin resulted in statistically significant reductions in HbA1c in Japanese patients with T2DM. Overall, vildagliptin was well tolerated with a safety profile similar to that of placebo in this patient population. ClinicalTrials.gov Identifier, NCT02002221 FUNDING: Novartis Pharma K.K.

The Sloan Digital Sky Survey Stripe 82 Imaging Data: Depth-Optimized Co-adds Over 300 deg$^2$ in Five Filters

Energy Technology Data Exchange (ETDEWEB)

Jiang, Linhua; Fan, Xiaohui; Bian, Fuyan; McGreer, Ian D.; Strauss, Michael A.; Annis, James; Buck, Zoë; Green, Richard; Hodge, Jacqueline A.; Myers, Adam D.; Rafiee, Alireza; Richards, Gordon

2014-06-25

We present and release co-added images of the Sloan Digital Sky Survey (SDSS) Stripe 82. Stripe 82 covers an area of ~300 deg(2) on the celestial equator, and has been repeatedly scanned 70-90 times in the ugriz bands by the SDSS imaging survey. By making use of all available data in the SDSS archive, our co-added images are optimized for depth. Input single-epoch frames were properly processed and weighted based on seeing, sky transparency, and background noise before co-addition. The resultant products are co-added science images and their associated weight images that record relative weights at individual pixels. The depths of the co-adds, measured as the 5σ detection limits of the aperture (3.''2 diameter) magnitudes for point sources, are roughly 23.9, 25.1, 24.6, 24.1, and 22.8 AB magnitudes in the five bands, respectively. They are 1.9-2.2 mag deeper than the best SDSS single-epoch data. The co-added images have good image quality, with an average point-spread function FWHM of ~1'' in the r, i, and z bands. We also release object catalogs that were made with SExtractor. These co-added products have many potential uses for studies of galaxies, quasars, and Galactic structure. We further present and release near-IR J-band images that cover ~90 deg(2) of Stripe 82. These images were obtained using the NEWFIRM camera on the NOAO 4 m Mayall telescope, and have a depth of about 20.0-20.5 Vega magnitudes (also 5σ detection limits for point sources).

77 FR 13513 - Modernizing the Regulation of Clinical Trials and Approaches to Good Clinical Practice; Public...

Science.gov (United States)

2012-03-07

...., monitoring and training), quality assurance (e.g., auditing), and any other processes directed at ensuring... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I [Docket No...) principles and Quality by Design (QbD) as models that, with adaptations, could contribute to improved data...

LSD Dimensions: Use and Reuse of Linked Statistical Data

NARCIS (Netherlands)

Meroño-Peñuela, Albert

2014-01-01

RDF Data Cube (QB) has boosted the publication of Linked Statistical Data (LSD) on the Web, making them linkable to other related datasets and concepts following the Linked Data paradigm. In this demo we present LSD Dimensions, a web based application that monitors the usage of dimensions and codes

Safety and effectiveness of tacrolimus add-on therapy for rheumatoid arthritis patients without an adequate response to biological disease-modifying anti-rheumatic drugs (DMARDs): Post-marketing surveillance in Japan.

Science.gov (United States)

Takeuchi, Tsutomu; Ishida, Kota; Shiraki, Katsuhisa; Yoshiyasu, Takashi

2018-01-01

Post-marketing surveillance (PMS) was conducted to assess the safety and effectiveness of tacrolimus (TAC) add-on therapy for patients with rheumatoid arthritis (RA) and an inadequate response to biological disease-modifying anti-rheumatic drugs (DMARDs). Patients with RA from 180 medical sites across Japan were registered centrally with an electronic investigation system. The observational period was 24 weeks from the first day of TAC administration concomitantly with biological DMARDs. Safety and effectiveness populations included 624 and 566 patients, respectively. Patients were predominantly female (81.1%), with a mean age of 61.9 years. Overall, 125 adverse drug reactions (ADRs) occurred in 94 patients (15.1%), and 15 serious ADRs occurred in 11 patients (1.8%). These incidences were lower compared with previously reported incidences after TAC treatment in PMS, and all of the observed ADRs were already known. A statistically significant improvement was observed in the primary effectiveness variable of Simplified Disease Activity Index after TAC treatment; 62.7% of patients achieved remission or low disease activity at week 24. TAC is well tolerated and effective when used as an add-on to biological DMARDs in Japanese patients with RA who do not achieve an adequate response to biological DMARDs in a real-world clinical setting.

Athermal silicon optical add-drop multiplexers based on thermo-optic coefficient tuning of sol-gel material.

Science.gov (United States)

Namnabat, Soha; Kim, Kyung-Jo; Jones, Adam; Himmelhuber, Roland; DeRose, Christopher T; Trotter, Douglas C; Starbuck, Andrew L; Pomerene, Andrew; Lentine, Anthony L; Norwood, Robert A

2017-09-04

Silicon photonics has gained interest for its potential to provide higher efficiency, bandwidth and reduced power consumption compared to electrical interconnects in datacenters and high performance computing environments. However, it is well known that silicon photonic devices suffer from temperature fluctuations due to silicon's high thermo-optic coefficient and therefore, temperature control in many applications is required. Here we present an athermal optical add-drop multiplexer fabricated from ring resonators. We used a sol-gel inorganic-organic hybrid material as an alternative to previously used materials such as polymers and titanium dioxide. In this work we studied the thermal curing parameters of the sol-gel and their effect on thermal wavelength shift of the rings. With this method, we were able to demonstrate a thermal shift down to -6.8 pm/°C for transverse electric (TE) polarization in ring resonators with waveguide widths of 325 nm when the sol-gel was cured at 130°C for 10.5 hours. We also achieved thermal shifts below 1 pm/°C for transverse magnetic (TM) polarization in the C band under different curing conditions. Curing time compared to curing temperature shows to be the most important factor to control sol-gel's thermo-optic value in order to obtain an athermal device in a wide temperature range.

The structure of omega3 food emulsions

DEFF Research Database (Denmark)

Jensen, Louise Helene Søgaard; Loussert, C.; Horn, Anna Frisenfeldt

Fish oil is rich in polyunsaturated omega-3 fatty acids (omega-3 PUFAs) which are generally recognized as being beneficial to the health [1]. The addition of fish oil to food products is attractive to both the consumers and the food industry. Indeed, these components will improve nutritional value...... and add product value. Omega-3 PUFAs are rich in double bonds in their fatty acid chains and this attribute renders them highly susceptible to lipid oxidation. Omega-3 PUFAs can be added to food products as neat oil or as a delivery system such as oil-in-water emulsions. In this last configuration...... and the prooxidants. But this protective aspect is a really complex process and it is dependent on the food matrix to which the oil is added [2]. Oxidation is presumed to be initiated at the emulsifier layer, i.e. the interface layer between the oil and water where the oil is most likely to come into contact...

Does the Order of Item Difficulty of the Addenbrooke's Cognitive Examination Add Anything to Subdomain Scores in the Clinical Assessment of Dementia?

Science.gov (United States)

McGrory, Sarah; Starr, John M; Shenkin, Susan D; Austin, Elizabeth J; Hodges, John R

2015-01-01

The Addenbrooke's Cognitive Examination (ACE) is used to measure cognition across a range of domains in dementia. Identifying the order in which cognitive decline occurs across items, and whether this varies between dementia aetiologies could add more information to subdomain scores. ACE-Revised data from 350 patients were split into three groups: Alzheimer's type (n = 131), predominantly frontal (n = 119) and other frontotemporal lobe degenerative disorders (n = 100). Results of factor analysis and Mokken scaling analysis were compared. Principal component analysis revealed one factor for each group. Confirmatory factor analysis found that the one-factor model fit two samples poorly. Mokken analyses revealed different item ordering in terms of difficulty for each group. The different patterns for each diagnostic group could aid in the separation of these different types of dementia.

Risk management and statistical multivariate analysis approach for design and optimization of satranidazole nanoparticles.

Science.gov (United States)

Dhat, Shalaka; Pund, Swati; Kokare, Chandrakant; Sharma, Pankaj; Shrivastava, Birendra

2017-01-01

Rapidly evolving technical and regulatory landscapes of the pharmaceutical product development necessitates risk management with application of multivariate analysis using Process Analytical Technology (PAT) and Quality by Design (QbD). Poorly soluble, high dose drug, Satranidazole was optimally nanoprecipitated (SAT-NP) employing principles of Formulation by Design (FbD). The potential risk factors influencing the critical quality attributes (CQA) of SAT-NP were identified using Ishikawa diagram. Plackett-Burman screening design was adopted to screen the eight critical formulation and process parameters influencing the mean particle size, zeta potential and dissolution efficiency at 30min in pH7.4 dissolution medium. Pareto charts (individual and cumulative) revealed three most critical factors influencing CQA of SAT-NP viz. aqueous stabilizer (Polyvinyl alcohol), release modifier (Eudragit® S 100) and volume of aqueous phase. The levels of these three critical formulation attributes were optimized by FbD within established design space to minimize mean particle size, poly dispersity index, and maximize encapsulation efficiency of SAT-NP. Lenth's and Bayesian analysis along with mathematical modeling of results allowed identification and quantification of critical formulation attributes significantly active on the selected CQAs. The optimized SAT-NP exhibited mean particle size; 216nm, polydispersity index; 0.250, zeta potential; -3.75mV and encapsulation efficiency; 78.3%. The product was lyophilized using mannitol to form readily redispersible powder. X-ray diffraction analysis confirmed the conversion of crystalline SAT to amorphous form. In vitro release of SAT-NP in gradually pH changing media showed 95%) in pH7.4 in next 3h, indicative of burst release after a lag time. This investigation demonstrated effective application of risk management and QbD tools in developing site-specific release SAT-NP by nanoprecipitation. Copyright © 2016 Elsevier B.V. All

"Effect of pranayama and meditation as an add-on therapy in rehabilitation of patients with Guillain-Barré syndrome--a randomized control pilot study".

Science.gov (United States)

Sendhilkumar, Ragupathy; Gupta, Anupam; Nagarathna, Raghuram; Taly, Arun B

2013-01-01

To study the add-on effects of pranayama and meditation in rehabilitation of patients with Guillain-Barré syndrome (GBS). This randomized control pilot study was conducted in neurological rehabilitation unit of university tertiary research hospital. Twenty-two GBS patients, who consented for the study and satisfied selection criteria, were randomly assigned to yoga and control groups. Ten patients in each group completed the study. The yoga group received 15 sessions in total over a period of 3 weeks (1 h/session), one session per day on 5 days per week that consisted of relaxation, Pranayama (breathing practices) and Guided meditation in addition to conventional rehabilitation therapeutics. The control group received usual rehabilitation care. All the patients were assessed using Pittsburgh Sleep Quality Index, Numeric pain rating scale, Hospital anxiety and Depression scale and Barthel index score. Mann-Whitney U test and Wilcoxon's signed rank test were used for statistical analysis. Quality of sleep improved significantly with reduction of PSQI score in the yoga group (p = 0.04). There was reduction of pain scores, anxiety and depression in both the groups without statistical significance between groups (pain p > 0.05, anxiety p > 0.05 and depression p > 0.05). Overall functional status improved in both groups without significant difference (p > 0.05). Significant improvement was observed in quality of sleep with yogic relaxation, pranayama, and meditation in GBS patients.