Protocol investigating the clinical utility of an objective measure of attention, impulsivity and activity (QbTest) for optimising medication management in children and young people with ADHD 'QbTest Utility for Optimising Treatment in ADHD' (QUOTA): a feasibility randomised controlled trial.

PubMed

Hall, Charlotte L; James, Marilyn; Brown, Sue; Martin, Jennifer L; Brown, Nikki; Selby, Kim; Clarke, Julie; Vijayan, Hena; Guo, Boliang; Sayal, Kapil; Hollis, Chris; Groom, Madeleine J

2018-02-15

Attention-deficit hyperactivity disorder (ADHD) is characterised by symptoms of inattention, hyperactivity and impulsivity. To improve outcomes, the National Institute for Health and Care Excellence ADHD guidelines recommend regular monitoring of symptoms when children commence medication. However, research suggests that routine monitoring rarely happens, and clinicians often rely on subjective information such as reports from parents and teachers to ascertain improvement. These sources can be unreliable and difficult to obtain. The addition of an objective test of attention and activity (QbTest) may improve the objectivity, reliability and speed of clinical decision-making and so reduce the time to identify the optimal medication dose. This study aims to assess the feasibility and acceptability of a QbTest medication management protocol delivered in routine healthcare services for children with ADHD. This multisite feasibility randomised controlled trial (RCT) will recruit 60 young people (aged 6-17 years old), diagnosed with ADHD, and starting stimulant medication who are seen by Child and Adolescent Mental Health Services or Community Paediatric services. Participants will be randomised into one of two arms. In the experimental arm (QbTest protocol), the participant will complete a QbTest at baseline (prior to medication initiation), and two follow-up QbTests on medication (2-4 weeks and 8-10 weeks later). In the control arm, participants will receive treatment as usual, with at least two follow-up consultations. Measures of parent-, teacher- and clinician-rated symptoms and global functioning will be completed at each time point. Health economic measures will be completed. Clinicians will record treatment decision-making. Acceptability and feasibility of the protocol will be assessed alongside outcome measure completion rates. Qualitative interviews will be conducted. The findings will be used to inform the development of a fully powered RCT. The results will

B-side charge separation in bacterial photosynthetic reaction centers: nanosecond time scale electron transfer from HB- to QB.

PubMed

Kirmaier, Christine; Laible, Philip D; Hanson, Deborah K; Holten, Dewey

2003-02-25

We report time-resolved optical measurements of the primary electron transfer reactions in Rhodobacter capsulatus reaction centers (RCs) having four mutations: Phe(L181) --> Tyr, Tyr(M208) --> Phe, Leu(M212) --> His, and Trp(M250) --> Val (denoted YFHV). Following direct excitation of the bacteriochlorophyll dimer (P) to its lowest excited singlet state P, electron transfer to the B-side bacteriopheophytin (H(B)) gives P(+)H(B)(-) in approximately 30% yield. When the secondary quinone (Q(B)) site is fully occupied, P(+)H(B)(-) decays with a time constant estimated to be in the range of 1.5-3 ns. In the presence of excess terbutryn, a competitive inhibitor of Q(B) binding, the observed lifetime of P(+)H(B)(-) is noticeably longer and is estimated to be in the range of 4-8 ns. On the basis of these values, the rate constant for P(+)H(B)(-) --> P(+)Q(B)(-) electron transfer is calculated to be between approximately (2 ns)(-)(1) and approximately (12 ns)(-)(1), making it at least an order of magnitude smaller than the rate constant of approximately (200 ps)(-)(1) for electron transfer between the corresponding A-side cofactors (P(+)H(A)(-) --> P(+)Q(A)(-)). Structural and energetic factors associated with electron transfer to Q(B) compared to Q(A) are discussed. Comparison of the P(+)H(B)(-) lifetimes in the presence and absence of terbutryn indicates that the ultimate (i.e., quantum) yield of P(+)Q(B)(-) formation relative to P is 10-25% in the YFHV RC.

Endothelial markers in malignant vascular tumours of the liver: superiority of QB-END/10 over von Willebrand factor and Ulex europaeus agglutinin 1.

PubMed

Anthony, P P; Ramani, P

1991-01-01

A new monoclonal antibody, QB-END/10, raised against the CD34 antigen in human endothelial cell membranes and haemopoietic progenitor cells, was studied for its usefulness as a marker of neoplastic vascular cells in 21 angiosarcomas and seven malignant haemangioendotheliomas of the liver. QB-END/10 was both more sensitive and more specific than Von Willebrand factor (VWF) and Ulex europaeus 1 agglutinin (UEA-1) in labelling endothelial cells and it did not cross react with epithelia as UEA-1 often does. Staining was uniformly strong and clear in all histological variants of these two tumours. QB-END/10 should prove particularly useful in the differential diagnosis of malignant vascular tumours of the liver.

Endothelial markers in malignant vascular tumours of the liver: superiority of QB-END/10 over von Willebrand factor and Ulex europaeus agglutinin 1.

PubMed Central

Anthony, P P; Ramani, P

1991-01-01

A new monoclonal antibody, QB-END/10, raised against the CD34 antigen in human endothelial cell membranes and haemopoietic progenitor cells, was studied for its usefulness as a marker of neoplastic vascular cells in 21 angiosarcomas and seven malignant haemangioendotheliomas of the liver. QB-END/10 was both more sensitive and more specific than Von Willebrand factor (VWF) and Ulex europaeus 1 agglutinin (UEA-1) in labelling endothelial cells and it did not cross react with epithelia as UEA-1 often does. Staining was uniformly strong and clear in all histological variants of these two tumours. QB-END/10 should prove particularly useful in the differential diagnosis of malignant vascular tumours of the liver. Images PMID:1705261

Analysis of PNGase F-resistant N-glycopeptides using SugarQb for Proteome Discoverer 2.1 reveals cryptic substrate specificities.

PubMed

Stadlmann, Johannes; Hoi, David M; Taubenschmid, Jasmin; Mechtler, Karl; Penninger, Josef M

2018-05-18

SugarQb (www.imba.oeaw.ac.at/sugarqb) is a freely available collection of computational tools for the automated identification of intact glycopeptides from high-resolution HCD MS/MS data-sets in the Proteome Discoverer environment. We report the migration of SugarQb to the latest and free version of Proteome Discoverer 2.1, and apply it to the analysis of PNGase F-resistant N-glycopeptides from mouse embryonic stem cells. The analysis of intact glycopeptides highlights unexpected technical limitations to PNGase F-dependent glycoproteomic workflows at the proteome level, and warrants a critical re-interpretation of seminal data-sets in the context of N-glycosylation-site prediction. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Exploring the energy landscape for Q(A)(-) to Q(B) electron transfer in bacterial photosynthetic reaction centers: effect of substrate position and tail length on the conformational gating step.

PubMed

Xu, Qiang; Baciou, Laura; Sebban, Pierre; Gunner, M R

2002-08-06

The ability to initiate reactions with a flash of light and to monitor reactions over a wide temperature range allows detailed analysis of reaction mechanisms in photosynthetic reaction centers (RCs) of purple bacteria. In this protein, the electron transfer from the reduced primary quinone (Q(A)(-)) to the secondary quinone (Q(B)) is rate-limited by conformational changes rather than electron tunneling. Q(B) movement from a distal to a proximal site has been proposed to be the rate-limiting change. The importance of quinone motion was examined by shortening the Q(B) tail from 50 to 5 carbons. No change in rate was found from 100 to 300 K. The temperature dependence of the rate was also measured in three L209 proline mutants. Under conditions where Q(B) is in the distal site in wild-type RCs, it is trapped in the proximal site in the Tyr L209 mutant [Kuglstatter, A., et al. (2001) Biochemistry 40, 4253-4260]. The electron transfer slows at low temperature for all three mutants as it does in wild-type protein, indicating that conformational changes still limit the reaction rate. Thus, Q(B) movement is unlikely to be the sole, rate-limiting conformational gating step. The temperature dependence of the reaction in the L209 mutants differs somewhat from wild-type RCs. Entropy-enthalpy compensation reduces the difference in rates and free energy changes at room temperature.

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

PubMed

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.

PubMed

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).

PubMed

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.

PubMed

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.

Application of quality by design (QbD) to formulation and processing of naproxen pellets by extrusion-spheronization.

PubMed

Wang, Junlin; Kan, Shuling; Chen, Tong; Liu, Jianping

2015-03-01

The aim of this research was to apply quality by design (QbD) to the development of naproxen loaded core pellets which can be used as the potential core for colon-specific pellets. In the early stages of this study, prior knowledge and preliminary studies were systematically incorporated into the risk assessment using failure mode and effect analysis (FMEA) and fishbone diagram. Then Plackett-Burman design was used to screen eight potential high risk factors (spheronization speed, spheronization time, extrusion speed, drying method, CCMC-Na concentration, lactose concentration, water concentration and Tween 80 concentration) obtained from the above risk assessment. It was discovered that out of the eight potential high risk factors only three factors (spheronization speed, extrusion speed and CCMC-Na concentration) had significant effects on the quality of the pellets. This allowed the use of Box-Behnken design (BBD) to fully elucidate the relationship between the variables and critical quality attribute (CQA). Finally, the final control space was established within which the quality of the pellets can meet the requirement of colon-specific drug delivery system. This study demonstrated that naproxen loaded core pellets were successfully designed using QbD principle.

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.

PubMed

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.

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

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

Plummer, J.; Immel, D.; Bobbitt, J.

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 ontomore » the visual image of the location being surveyed.« less

QbD-oriented development and validation of a bioanalytical method for nevirapine with enhanced liquid-liquid extraction and chromatographic separation.

PubMed

Beg, Sarwar; Chaudhary, Vandna; Sharma, Gajanand; Garg, Babita; Panda, Sagar Suman; Singh, Bhupinder

2016-06-01

The present studies describe the systematic quality by design (QbD)-oriented development and validation of a simple, rapid, sensitive and cost-effective reversed-phase HPLC bioanalytical method for nevirapine in rat plasma. Chromatographic separation was carried out on a C18 column using isocratic 68:9:23% v/v elution of methanol, acetonitrile and water (pH 3, adjusted by orthophosphoric acid) at a flow rate of 1.0 mL/min using UV detection at 230 nm. A Box-Behnken design was applied for chromatographic method optimization taking mobile phase ratio, pH and flow rate as the critical method parameters (CMPs) from screening studies. Peak area, retention time, theoretical plates and peak tailing were measured as the critical analytical attributes (CAAs). Further, the bioanalytical liquid-liquid extraction process was optimized using an optimal design by selecting extraction time, centrifugation speed and temperature as the CMPs for percentage recovery of nevirapine as the CAA. The search for an optimum chromatographic solution was conducted through numerical desirability function. Validation studies performed as per the US Food and Drug Administration requirements revealed results within the acceptance limit. In a nutshell, the studies successfully demonstrate the utility of analytical QbD approach for the rational development of a bioanalytical method with enhanced chromatographic separation and recovery of nevirapine in rat plasma. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

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

PubMed

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).

PubMed

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.

Strategic funding priorities in the pharmaceutical sciences allied to Quality by Design (QbD) and Process Analytical Technology (PAT).

PubMed

Aksu, Buket; De Beer, Thomas; Folestad, Staffan; Ketolainen, Jarkko; Lindén, Hans; Lopes, Joao Almeida; de Matas, Marcel; Oostra, Wim; Rantanen, Jukka; Weimer, Marco

2012-09-29

Substantial changes in Pharmaceutical R&D strategy are required to address existing issues of low productivity, imminent patent expirations and pressures on pricing. Moves towards personalized healthcare and increasing diversity in the nature of portfolios including the rise of biopharmaceuticals however have the potential to provide considerable challenges to the establishment of cost effective and robust supply chains. To guarantee product quality and surety of supply for essential medicines it is necessary that manufacturing science keeps pace with advances in pharmaceutical R&D. In this position paper, the EUFEPS QbD and PAT Sciences network make recommendations that European industry, academia and health agencies focus attention on delivering step changes in science and technology in a number of key themes. These subject areas, all underpinned by the sciences allied to QbD and PAT, include product design and development for personalized healthcare, continuous-processing in pharmaceutical product manufacture, quantitative quality risk assessment for pharmaceutical development including life cycle management and the downstream processing of biopharmaceutical products. Plans are being established to gain commitment for inclusion of these themes into future funding priorities for the Innovative Medicines Initiative (IMI). Copyright © 2012 Elsevier B.V. All rights reserved.

[Research on whole blending end-point evaluation method of Angong Niuhuang Wan based on QbD concept].

PubMed

Liu, Xiao-Na; Zheng, Qiu-Sheng; Che, Xiao-Qing; Wu, Zhi-Sheng; Qiao, Yan-Jiang

2017-03-01

The blending end-point determination of Angong Niuhuang Wan (AGNH) is a key technology problem. The control strategy based on quality by design (QbD) concept proposes a whole blending end-point determination method, and provides a methodology for blending the Chinese materia medica containing mineral substances. Based on QbD concept, the laser induced breakdown spectroscopy (LIBS) was used to assess the cinnabar, realgar and pearl powder blending of AGNH in a pilot-scale experiment, especially the whole blending end-point in this study. The blending variability of three mineral medicines including cinnabar, realgar and pearl powder, was measured by moving window relative standard deviation (MWRSD) based on LIBS. The time profiles of realgar and pearl powder did not produce consistent results completely, but all of them reached even blending at the last blending stage, so that the whole proposal blending end point was determined. LIBS is a promising Process Analytical Technology (PAT) for process control. Unlike other elemental determination technologies such ICP-OES, LIBS does not need an elaborate digestion procedure, which is a promising and rapid technique to understand the blending process of Chinese materia medica (CMM) containing cinnabar, realgar and other mineral traditional Chinese medicine. This study proposed a novel method for the research of large varieties of traditional Chinese medicines.. Copyright© by the Chinese Pharmaceutical Association.

Quality by design (QbD) based development and validation of an HPLC method for amiodarone hydrochloride and its impurities in the drug substance.

PubMed

Karmarkar, S; Yang, X; Garber, R; Szajkovics, A; Koberda, M

2014-11-01

The USP monograph describes an HPLC method for seven impurities in the amiodarone drug substance using a L1 column, 4.6mm×150mm, 5μm packing (PF listed ODS2 GL-Science, Inertsil column) at 30°C with detection at 240nm. The standard contains 0.01mg/mL of amiodarone, and USP specified impurities D and E with a resolution requirement of NLT 3.5 between peaks D and E. Impurities in a 5mg/mL sample are quantitated against the standard. Impurity A peak elutes just before peak D. We observed two problems with the method; the column lot-to-lot variability resulted in unresolved A, D, and E peaks, and peak D in the sample preparation eluted much later than that in the standard solution. Therefore, optimization experiments were conducted on the USP method following the QbD approach with Fusion AE™ software (S-Matrix Corporation). The resulting optimized conditions were within the allowable changes per USP 〈621〉. Lot-to-lot variability was negligible with the Atlantis T3 (Waters Corporation) L1 column. Peak D retention time remained constant from standard to sample. The optimized method was validated in terms of accuracy, precision, linearity, range, LOQ/LOD, specificity, robustness, equivalency to the USP method, and solution stability. The QbD based development helped in generating a design space and operating space with knowledge of all method performance characteristics and limitations and successful method robustness within the operating space. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

PubMed

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.

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

Code of Federal Regulations, 2010 CFR

2010-10-01

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

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

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Test specimen requirements and definition of ranges (modifies QW 202, QW 210, QW 451, and QB 202). 57.04-1 Section 57.04-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING WELDING AND BRAZING Procedure Qualification Range § 57.04...

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

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Test specimen requirements and definition of ranges (modifies QW 202, QW 210, QW 451, and QB 202). 57.04-1 Section 57.04-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING WELDING AND BRAZING Procedure Qualification Range § 57.04...

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

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Test specimen requirements and definition of ranges (modifies QW 202, QW 210, QW 451, and QB 202). 57.04-1 Section 57.04-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING WELDING AND BRAZING Procedure Qualification Range § 57.04...

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

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Test specimen requirements and definition of ranges (modifies QW 202, QW 210, QW 451, and QB 202). 57.04-1 Section 57.04-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING WELDING AND BRAZING Procedure Qualification Range § 57.04...

A quality by design (QbD) study on enoxaparin sodium loaded polymeric microspheres for colon-specific delivery.

PubMed

Hales, Dana; Vlase, Laurian; Porav, Sebastian Alin; Bodoki, Andreea; Barbu-Tudoran, Lucian; Achim, Marcela; Tomuță, Ioan

2017-03-30

The aim of this study was to apply quality by design (QbD) for pharmaceutical development of enoxaparin sodium microspheres for colon-specific delivery. The Process Parameters (CPPs) and Critical Quality Attributes (CQAs) were identified. A central composite experimental design was used in order to develop the design space of microspheres for colon-specific delivery that have the desired Quality Target Product Profile (QTPP). The CPPs studied were Eudragit® FS-30D/Eudragit® RS-PO ratio, poly(vinyl alcohol) (PVA) concentration and sodium chloride (NaCl) concentration. The encapsulation efficiency increased with NaCl concentration increase, the percentages of enoxaparin sodium reaching 94% for some formulations. Increasing the ratio Eudragit® FS-30D/Eudragit® RS-PO ensured a relatively complete release of enoxaparin sodium in the environment simulating the colonic pH. Based on these results, the optimum conditions were decided and the optimum formulation was prepared. The results obtained for the latter in terms of in vitro enoxaparin sodium release were good, the microparticles releasing only 9.42% enoxaparin sodium in acidic environment and 15.16% in the medium which simulated duodenal pH, but allowing the release of up to 89.24% in the medium which simulated colonic pH. The in vitro release profile of enoxaparin sodium was close to the ideal one, therefore the system was successfully designed using QbD approach. Copyright © 2017 Elsevier B.V. All rights reserved.

ADD and Physicians.

ERIC Educational Resources Information Center

Hewick, Walter; And Others

In the United States today Attention Deficit Disorder (ADD) is recognized by professionals as a distinct disorder, a neurobiological disability marked by inattentiveness, impulsivity, and hyperactivity. About 2-10% of school-age children suffer from ADD, making it an issue of rising concern to families and school leaders. It is necessary that…

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

PubMed

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.

PubMed

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.

PubMed

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

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

PubMed

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.

PubMed

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

Embedding objects during 3D printing to add new functionalities

PubMed Central

2016-01-01

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. These

Impact of add-on laboratory testing at an academic medical center: a five year retrospective study.

PubMed

Nelson, Louis S; Davis, Scott R; Humble, Robert M; Kulhavy, Jeff; Aman, Dean R; Krasowski, Matthew D

2015-01-01

Clinical laboratories frequently receive orders to perform additional tests on existing specimens ('add-ons'). Previous studies have examined add-on ordering patterns over short periods of time. The objective of this study was to analyze add-on ordering patterns over an extended time period. We also analyzed the impact of a robotic specimen archival/retrieval system on add-on testing procedure and manual effort. In this retrospective study at an academic medical center, electronic health records from were searched to obtain all add-on orders that were placed in the time period of May 2, 2009 to December 31, 2014. During the time period of retrospective study, 880,359 add-on tests were ordered on 96,244 different patients. Add-on testing comprised 3.3 % of total test volumes. There were 443,411 unique ordering instances, leading to an average of 1.99 add-on tests per instance. Some patients had multiple episodes of add-on test orders at different points in time, leading to an average of 9.15 add-on tests per patient. The majority of add-on orders were for chemistry tests (78.8 % of total add-ons) with the next most frequent being hematology and coagulation tests (11.2 % of total add-ons). Inpatient orders accounted for 66.8 % of total add-on orders, while the emergency department and outpatient clinics had 14.8 % and 18.4 % of total add-on orders, respectively. The majority of add-ons were placed within 8 hours (87.3 %) and nearly all by 24 hours (96.8 %). Nearly 100 % of add-on orders within the emergency department were placed within 8 hours. The introduction of a robotic specimen archival/retrieval unit saved an average of 2.75 minutes of laboratory staff manual time per unique add-on order. This translates to 24.1 hours/day less manual effort in dealing with add-on orders. Our study reflects the previous literature in showing that add-on orders significantly impact the workload of the clinical laboratory. The majority of add-on orders are clinical chemistry

Early Implementation of QbD in Biopharmaceutical Development: A Practical Example

PubMed Central

Zurdo, Jesús; Arnell, Andreas; Obrezanova, Olga; Smith, Noel; Gómez de la Cuesta, Ramón; Gallagher, Thomas R. A.; Michael, Rebecca; Stallwood, Yvette; Ekblad, Caroline; Abrahmsén, Lars; Höidén-Guthenberg, Ingmarie

2015-01-01

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. PMID:26075248

Firefox add-ons for medical reference.

PubMed

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).

PubMed

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

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

PubMed

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.

Top 5 Ways to Help Students with ADD/ADHD

ERIC Educational Resources Information Center

Johnson, Kathy

2011-01-01

This article suggests five ways to help students with ADD/ADHD. These are: (1) Integrate the primitive reflexes; (2) Diet; (3) Visual attention; (4) Help for auditory attention; and (5) Cognitive training.

2017 National Household Travel Survey - California Add-On |

Science.gov Websites

Transportation Secure Data Center | NREL 7 National Household Travel Survey - California Add-On 2017 National Household Travel Survey - California Add-On The California add-on survey supplements the 2017 National Household Travel Survey (NHTS) with additional household samples and detailed travel

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

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

Iwase, Shigeki; Xiang, Bin; Ghosh, Sharmistha

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,more » 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.« less

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

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

S Iwase; B Xiang; S Ghosh

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,more » 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.« less

Lacosamide add-on therapy for partial epilepsy.

PubMed

Weston, Jennifer; Shukralla, Arif; McKay, Andrew J; Marson, Anthony G

2015-06-16

Around half of people with epilepsy will not achieve seizure freedom on their first antiepileptic drug; many will require add-on treatment with another drug. Sometimes multiple treatment combinations are tried to achieve maximum seizure control, although around a third of people do not achieve complete seizure control. Lacosamide is an antiepileptic drug that has been licensed as an add-on treatment for partial epilepsy. To evaluate the efficacy and tolerability of lacosamide when used as an add-on treatment for patients with drug-resistant partial epilepsy. We searched the Cochrane Epilepsy Group's Specialized Register (21 May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL , The Cochrane Library Issue 4, April 2015), MEDLINE (Ovid, 1946 to 21 May 2015), Scopus (1823 to 13 November 2014), ClinicalTrials.gov (21 May 2015) and the WHO International Clinical Trials Registry Platform (ICTRP, 21 May 2015). We imposed no language restrictions. We contacted UCB (sponsors of lacosamide) and experts in the field. Randomised controlled trials of add-on lacosamide in people with drug-resistant partial epilepsy. Two review authors independently assessed trials for inclusion and extracted the relevant data. We assessed the following outcomes: (1) 50% or greater reduction in seizure frequency; (2) seizure freedom; (3) treatment withdrawal for any reason; and (4) adverse events. Primary analyses were intention-to-treat. Summary risk ratios were estimated for each outcome. We included three trials in our review (1311 participants), which were classified as having low risk of bias. All trials were placebo-controlled and assessed doses ranging from 200 mg to 600 mg per day. Trial duration ranged from 24 to 26 weeks. All trials used adequate methods of randomisation and were double-blind. Overall the quality of the evidence was rated as moderate to high. The overall risk ratio for a 50% or greater reduction in seizure frequency for all doses of lacosamide compared

User's manual for Axisymmetric Diffuser Duct (ADD) code. Volume 1: General ADD code description

NASA Technical Reports Server (NTRS)

Anderson, O. L.; Hankins, G. B., Jr.; Edwards, D. E.

1982-01-01

This User's Manual contains a complete description of the computer codes known as the AXISYMMETRIC DIFFUSER DUCT code or ADD code. It includes a list of references which describe the formulation of the ADD code and comparisons of calculation with experimental flows. The input/output and general use of the code is described in the first volume. The second volume contains a detailed description of the code including the global structure of the code, list of FORTRAN variables, and descriptions of the subroutines. The third volume contains a detailed description of the CODUCT code which generates coordinate systems for arbitrary axisymmetric ducts.

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

PubMed

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.

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

PubMed Central

Chakrabarti, B.; Lastras-Montaño, M. A.; Adam, G.; Prezioso, M.; Hoskins, B.; Cheng, K.-T.; Strukov, D. B.

2017-01-01

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. PMID:28195239

Safety and tolerability of dapagliflozin, saxagliptin and metformin in combination: Post-hoc analysis of concomitant add-on versus sequential add-on to metformin and of triple versus dual therapy with metformin.

PubMed

Del Prato, Stefano; Rosenstock, Julio; Garcia-Sanchez, Ricardo; Iqbal, Nayyar; Hansen, Lars; Johnsson, Eva; Chen, Hungta; Mathieu, Chantal

2018-06-01

The safety of triple oral therapy with dapagliflozin plus saxagliptin plus metformin versus dual therapy with dapagliflozin or saxagliptin plus metformin was compared in a post-hoc analysis of 3 randomized trials of sequential or concomitant add-on of dapagliflozin and saxagliptin to metformin. In the concomitant add-on trial, patients with type 2 diabetes on stable metformin received dapagliflozin 10 mg/d plus saxagliptin 5 mg/d. In sequential add-on trials, patients on metformin plus either saxagliptin 5 mg/d or dapagliflozin 10 mg/d received dapagliflozin 10 mg/d or saxagliptin 5 mg/d, respectively, as add-on therapy. After 24 weeks, incidences of adverse events and serious adverse events were similar between triple and dual therapy and between concomitant and sequential add-on regimens. Urinary tract infections were more common with sequential than with concomitant add-on therapy; genital infections were reported only with sequential add-on of dapagliflozin to saxagliptin plus metformin. Hypoglycaemia incidence was <2.0% across all analysis groups. In conclusion, the safety and tolerability of triple therapy with dapagliflozin, saxagliptin and metformin, as either concomitant or sequential add-on, were similar to dual therapy with either agent added to metformin. © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

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.

PubMed

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 (P<0.0001) and faster BP recovery (P=0.0003). The TT genotype of rs3775067 was associated with slower SBP recovery (P=0.004). For the GNB3 gene, the C allele of SNP rs4963516 was associated with faster diastolic BP recovery (P=0.002) and smaller overall AUC (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.

Inviting Calm Within: ADD, Neurology, and Mindfulness

ERIC Educational Resources Information Center

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…

One-year efficacy and safety of saxagliptin add-on in patients receiving dapagliflozin and metformin.

PubMed

Matthaei, S; Aggarwal, N; Garcia-Hernandez, P; Iqbal, N; Chen, H; Johnsson, E; Chin, A; Hansen, L

2016-11-01

Greater reductions in glycated haemoglobin (HbA1c) with saxagliptin, a dipeptidyl peptidase-4 inhibitor, versus placebo add-on in patients with type 2 diabetes who had inadequate glycaemic control with dapagliflozin 10 mg/d plus metformin were demonstrated after 24 weeks of treatment. Results over 52 weeks of treatment were assessed in this analysis. Patients (mean baseline HbA1c 7.9%) receiving open-label dapagliflozin 10 mg/d plus metformin were randomized to double-blind saxagliptin 5 mg/d or placebo add-on. The adjusted mean change from baseline to week 52 in HbA1c was greater with saxagliptin than with placebo add-on -0.38% vs 0.05%; difference -0.42% (95% confidence interval -0.64, -0.20)]. More patients achieved the HbA1c target of <7% with saxagliptin than with placebo add-on (29% vs 13%), and fewer patients were rescued or discontinued the study for lack of glycaemic control with saxagliptin than with placebo add-on (19% vs 28%). Reductions from baseline in body weight (≤1.5 kg) occurred in both groups. Similar proportions of patients reported ≥1 adverse event with saxagliptin (58.2%) and placebo add-on (58.0%); no new safety signals were detected. Hypoglycaemia was infrequent in both treatment groups (≤2.5%), with no major episodes. The rate of urinary tract infections was similar in the saxagliptin and placebo add-on groups (7.8% vs 7.4%). The incidence of genital infections was 3.3% with saxagliptin versus 6.2% with placebo add-on. Triple therapy with saxagliptin add-on to dapagliflozin plus metformin for 52 weeks resulted in sustained improvements in glycaemic control without an increase in body weight or increased risk of hypoglycaemia. © 2016 John Wiley & Sons Ltd.

Losigamone add-on therapy for partial epilepsy.

PubMed

Xiao, Yousheng; Luo, Man; Wang, Jin; Luo, Hongye

2012-06-13

taking placebo (RR 2.16; 95% CI 1.28 to 3.67). For the safety outcomes, results indicated the proportion of patients who experienced adverse events in the losigamone group was higher than the placebo group (RR 1.34; 95% CI 1.00 to 1.80), dizziness was the only adverse event significantly in relation to losigamone (RR 3.82; 99% CI 1.69 to 8.64). The proportion of patients achieving seizure freedom was not reported in either trial report. A subgroup analysis according to different doses of losigamone showed that a higher dose of losigamone (1500 mg/d) is associated with a greater reduction in seizure frequency than lower doses, but is also associated with more dropouts due to adverse events. The results of this review showed losigamone can reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with partial epilepsy. However, trials included were of short-term duration and uncertain quality. Future well-designed randomized, double-blind, placebo-controlled trials with a longer-term duration are needed.

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

PubMed

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.

PubMed

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.

Stiripentol add-on therapy for focal refractory epilepsy.

PubMed

Brigo, Francesco; Igwe, Stanley C; Bragazzi, Nicola Luigi

2018-05-10

intervals were very wide and showed the possibility of substantial increases and small reductions in risks of neurological (RR 2.65, 95% CI 0.88 to 8.01, low-quality evidence) or gastrointestinal adverse effects (RR 11.56, 95% CI 0.71 to 189.36, low-quality evidence). Researchers noted no clear reduction in the risk of study withdrawal (RR 0.66, 95% CI 0.30 to 1.47, low-quality evidence), which was high in both groups (35.0% in add-on placebo and 53.3% in stiripentol group, low-quality evidence). The external validity of this study was limited because only responders to stiripentol (i.e. patients experiencing a ≥ 50% decrease in seizure frequency compared with baseline) were included in the randomised, add-on, placebo-controlled, double-blind phase. Furthermore, carry-over and withdrawal effects probably influenced outcomes related to seizure frequency. Very limited information derived from the only included study shows that adverse effects considered as a whole seemed to occur significantly more often with add-on stiripentol than with add-on placebo. Since the last version of this review was published, we have found no new studies. Hence, we have made no changes to the conclusions of this update as presented in the initial review. We can draw no conclusions to support the use of stiripentol as add-on treatment for focal refractory epilepsy. Additional large, randomised, well-conducted trials are needed.

Losigamone add-on therapy for partial epilepsy.

PubMed

Xiao, Yousheng; Luo, Man; Wang, Jin; Luo, Hongye

2015-12-10

greater reduction in seizure frequency (RR 1.76; 95% CI 1.14 to 2.72), but associated with a significant increase of treatment withdrawal when compared with those taking placebo (RR 2.16; 95% CI 1.28 to 3.67). For the safety outcomes, results indicated the proportion of patients who experienced adverse events in the losigamone group was higher than the placebo group (RR 1.34; 95% CI 1.00 to 1.80), dizziness was the only adverse event significantly reported in relation to losigamone (RR 3.82; 99% CI 1.69 to 8.64). The proportion of patients achieving seizure freedom was not reported in either trial report. A subgroup analysis according to different doses of losigamone showed that a higher dose of losigamone (1500 mg/day) was associated with a greater reduction in seizure frequency than lower doses, but was also associated with more dropouts due to adverse events. The results of this review showed losigamone did reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with partial epilepsy. However, trials included were of short-term duration and uncertain quality. Future well-designed randomized, double-blind, placebo-controlled trials with a longer-term duration are needed. No new studies have been found since the last version of this review.

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.

PubMed

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

Alternative Fuels Data Center: Seattle Rideshare Fleet Adds EVs, Enjoys

Science.gov Websites

Fuels Data Center: Seattle Rideshare Fleet Adds EVs, Enjoys Success on Facebook Tweet about Alternative Fuels Data Center: Seattle Rideshare Fleet Adds EVs, Enjoys Success on Twitter Bookmark Alternative Fuels Data Center: Seattle Rideshare Fleet Adds EVs, Enjoys Success on Google Bookmark Alternative Fuels

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

Zhou, Kun; Ikeda, Masao, E-mail: mikeda2013@sinano.ac.cn, E-mail: jpliu2010@sinano.ac.cn; Liu, Jianping, E-mail: mikeda2013@sinano.ac.cn, E-mail: jpliu2010@sinano.ac.cn

The efficiency droop of InGaN/GaN(InGaN) multiple quantum well (MQW) light emitting diodes (LEDs) with thin quantum barriers (QB) is studied. With thin GaN QB (3 nm–6 nm thickness), the efficiency droop is not improved, which indicates that hole transport cannot be significantly enhanced by the thin GaN QBs. On the contrary, the efficiency droop was remarkably reduced by using a InGaN staircase QB (InGaN SC-QB) MQWs structure where InGaN SC-QBs lower the transport energy barrier of holes. The efficiency droop ratio was as low as 3.3% up to 200 A/cm{sup 2} for the InGaN SC-QB LED. By using monitoring QW with longer wavelengthmore » we observe a much uniform carrier distribution in the InGaN SC-QB LEDs, which reveals the mechanism of improvement in the efficiency droop.« less

Efficacy and safety of add on low-dose mirtazapine in depression.

PubMed

Matreja, Prithpal S; Badyal, Dinesh K; Deswal, Randhir S; Sharma, Arvind

2012-03-01

Although antidepressant medications are effective, they have a delayed onset of effect. Mirtazapine, an atypical antidepressant is an important option for add-on therapy in major depression. There is insufficient data on mirtazapine in Indian population; hence this study was designed to study the add-on effect of low-dose mirtazapine with selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD) in Indian population. In an open, randomized study, 60 patients were divided into two groups. In Group A (n=30) patients received conventional SSRIs for 6 weeks. In Group B (n=30) patients received conventional SSRIs with low-dose mirtazapine for 6 weeks. Patients were evaluated at baseline and then at 1, 2, 3, 4, 5, and 6 weeks. There was significant improvement in Hamilton Depression Rating Scale (HDRS), Montgomery and Asberg depression rating scale (MADRS) scores (P<0.05) in both groups. Mirtazapine in low dose as add on therapy showed improvement in scores, had earlier onset of action, and more number of responders and remitters as compared to conventional treatment (P<0.05). No serious adverse event was reported in either of the groups. Low-dose mirtazapine as add-on therapy has shown better efficacy, earlier onset of action and more number of responders and remitters as compared to conventional treatment in MDD in Indian patients.

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

PubMed

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.

Losigamone add-on therapy for focal epilepsy.

PubMed

Xiao, Yousheng; Luo, Man; Wang, Jin; Luo, Hongye

2018-01-22

.72), but associated with a significant increase of treatment withdrawal when compared with those taking placebo (RR 2.16, 95% CI 1.28 to 3.67). For the safety outcomes, results indicated that the proportion of participants who experienced adverse events in the losigamone group was higher than in the placebo group (RR 1.34, 95% CI 1.00 to 1.80), dizziness was the only adverse event significantly reported in relation to losigamone (RR 3.82, 99% CI 1.69 to 8.64). The proportion of participants achieving seizure freedom was not reported in either trial report. A subgroup analysis according to different doses of losigamone showed that a higher dose of losigamone (1500 mg/day) was associated with a greater reduction in seizure frequency than lower doses, but was also associated with more dropouts due to adverse events. The results of this review showed that losigamone did reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with focal epilepsy. However, the included trials were of short-term duration and uncertain quality. Future well-designed randomized, double-blind, placebo-controlled trials with a longer-term duration are needed. No new studies have been found since the last version of this review. We judged the overall quality of the evidence for the outcomes assessed as moderate.

Hydrogen bond network around the semiquinone of the secondary quinone acceptor Q(B) in bacterial photosynthetic reaction centers.

PubMed

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

2015-05-07

By utilizing a combined pulsed EPR and DFT approach, the high-resolution structure of the QB site semiquinone (SQB) was determined. The development of such a technique is crucial toward an understanding of protein-bound semiquinones on the structural level, as (i) membrane protein crystallography typically results in low resolution structures, and (ii) obtaining protein crystals in the semiquinone form is rarely feasible. The SQB hydrogen bond network was investigated with Q- (∼34 GHz) and X-band (∼9.7 GHz) pulsed EPR spectroscopy on fully deuterated reactions centers from Rhodobacter sphaeroides. Simulations in the SQB g-tensor reference frame provided the principal values and directions of the H-bond proton hyperfine tensors. Three protons were detected, one with an anisotropic tensor component, T = 4.6 MHz, assigned to the histidine NδH of His-L190, and two others with similar anisotropic constants T = 3.2 and 3.0 MHz assigned to the peptide NpH of Gly-L225 and Ile-L224, respectively. Despite the strong similarity in the peptide couplings, all hyperfine tensors were resolved in the Q-band ENDOR spectra. The Euler angles describing the series of rotations that bring the hyperfine tensors into the SQB g-tensor reference frame were obtained by least-squares fitting of the spectral simulations to the ENDOR data. These Euler angles show the locations of the hydrogen bonded protons with respect to the semiquinone. Our geometry optimized model of SQB used in previous DFT work is in strong agreement with the angular constraints from the spectral simulations, providing the foundation for future joint pulsed EPR and DFT semiquinone structural determinations in other proteins.

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

PubMed Central

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

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

PubMed

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

Lamotrigine add-on for drug-resistant partial epilepsy.

PubMed

Ramaratnam, S; Marson, A G; Baker, G A

2001-01-01

Epilepsy is a common neurological disorder, affecting almost 0.5 to 1% of the population. Nearly 30% of patients with epilepsy are refractory to currently available drugs. Lamotrigine is one of the newer antiepileptic drugs and is the topic of this review. To examine the effects of lamotrigine on seizures, side effects, cognition and quality of life, when used as an add-on treatment for patients with drug-resistant partial epilepsy. We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2001), MEDLINE (January 1966 to April 2001) and reference lists of articles. We also contacted the manufacturers of lamotrigine (Glaxo-Wellcome). Randomized placebo controlled trials, of patients with drug-resistant partial epilepsy of any age, in which an adequate method of concealment of randomization was used. The studies may be double, single or unblinded. For crossover studies, the first treatment period was treated as a parallel trial. Two reviewers independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), side effects, effects on cognition, and quality of life. We found three parallel add-on studies and eight cross-over studies, which included 1243 patients (199 children and 1044 adults). The overall Peto's Odds Ratio (OR) and 95% confidence intervals (CIs) across all studies for 50% or greater reduction in seizure frequency was 2.71 (1.87, 3.91) indicating that lamotrigine is significantly more effective than placebo in reducing seizure frequency. The overall OR (95%CI) for treatment withdrawal (for any reason) is 1.12 (0.78, 1.61). The 99% CIs for ataxia, dizziness, nausea, and diplopia do not include unity, indicating that they are significantly associated with lamotrigine. The limited data available precludes any conclusions about effects on cognition

Lamotrigine add-on for drug-resistant partial epilepsy.

PubMed

Ramaratnam, S; Marson, A G; Baker, G A

2000-01-01

Epilepsy is a common neurological disorder, affecting almost 0.5 to 1% of the population. Nearly 30% of patients with epilepsy are refractory to currently available drugs. Lamotrigine is one of the newer antiepileptic drugs and is the topic of this review. To examine the effects of lamotrigine on seizures, side effects, cognition and quality of life, when used as an add-on treatment for patients with drug-resistant partial epilepsy. We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled Trials Register (Cochrane Library Issue 1, 2000), MEDLINE (January 1966 to December 1999) and reference lists of articles. We also contacted the manufacturers of lamotrigine (Glaxo-Wellcome). Randomized placebo controlled trials, of patients with drug-resistant partial epilepsy of any age, in which an adequate method of concealment of randomization was used. The studies may be double, single or unblinded. For crossover studies, the first treatment period was treated as a parallel trial. Two reviewers independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), side effects, effects on cognition, and quality of life. We found three parallel add-on studies and eight cross-over studies, which included 1243 patients (199 children and 1044 adults). The overall Peto's Odds Ratio (OR) and 95% confidence intervals (CIs) across all studies for 50% or greater reduction in seizure frequency was 2.71 (1.87, 3.91) indicating that lamotrigine is significantly more effective than placebo in reducing seizure frequency. The overall OR (95%CI) for treatment withdrawal (for any reason) is 1.12 (0.78, 1. 61). The 99% CIs for ataxia, dizziness, nausea, and diplopia do not include unity, indicating that they are significantly associated with lamotrigine. The limited data available preclude any conclusions about effects on

Add-on unidirectional elastic metamaterial plate cloak

PubMed Central

Lee, Min Kyung; Kim, Yoon Young

2016-01-01

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. PMID:26860896

Add-on unidirectional elastic metamaterial plate cloak

NASA Astrophysics Data System (ADS)

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.

Nintedanib with Add-on Pirfenidone in Idiopathic Pulmonary Fibrosis. Results of the INJOURNEY Trial.

PubMed

Vancheri, Carlo; Kreuter, Michael; Richeldi, Luca; Ryerson, Christopher J; Valeyre, Dominique; Grutters, Jan C; Wiebe, Sabrina; Stansen, Wibke; Quaresma, Manuel; Stowasser, Susanne; Wuyts, Wim A

2018-02-01

Nintedanib and pirfenidone slow the progression of idiopathic pulmonary fibrosis (IPF), but the disease continues to progress. More data are needed on the safety and efficacy of combination therapy with nintedanib and add-on pirfenidone. To investigate safety, tolerability, and pharmacokinetic and exploratory efficacy endpoints in patients treated with nintedanib and add-on pirfenidone versus nintedanib alone. Patients with IPF and FVC greater than or equal to 50% predicted at screening who completed a 4- to 5-week run-in with nintedanib 150 mg twice daily without dose reduction or treatment interruption were randomized to receive nintedanib 150 mg twice daily with add-on pirfenidone (titrated to 801 mg three times daily) or nintedanib 150 mg twice daily alone in an open-label manner for 12 weeks. The primary endpoint was the percentage of patients with on-treatment gastrointestinal adverse events from baseline to Week 12. Analyses were descriptive and exploratory. On-treatment gastrointestinal adverse events were reported in 37 of 53 patients (69.8%) treated with nintedanib with add-on pirfenidone and 27 of 51 patients (52.9%) treated with nintedanib alone. Predose plasma trough concentrations of nintedanib were similar when it was administered alone or with add-on pirfenidone. Mean (SE) changes from baseline in FVC at Week 12 were -13.3 (17.4) ml and -40.9 (31.4) ml in patients treated with nintedanib with add-on pirfenidone (n = 48) and nintedanib alone (n = 44), respectively. Nintedanib with add-on pirfenidone had a manageable safety and tolerability profile in patients with IPF, in line with the adverse event profiles of each drug. These data support further research into combination regimens in the treatment of IPF. Clinical trial registered with www.clinicaltrials.gov (NCT02579603).

Significant treatment effect of add-on ketamine anesthesia in electroconvulsive therapy in depressive patients: A meta-analysis.

PubMed

Li, Dian-Jeng; Wang, Fu-Chiang; Chu, Che-Sheng; Chen, Tien-Yu; Tang, Chia-Hung; Yang, Wei-Cheng; Chow, Philip Chik-Keung; Wu, Ching-Kuan; Tseng, Ping-Tao; Lin, Pao-Yen

2017-01-01

Add-on ketamine anesthesia in electroconvulsive therapy (ECT) has been studied in depressive patients in several clinical trials with inconclusive findings. Two most recent meta-analyses reported insignificant findings with regards to the treatment effect of add-on ketamine anesthesia in ECT in depressive patients. The aim of this study is to update the current evidence and investigate the role of add-on ketamine anesthesia in ECT in depressive patients via a systematic review and meta-analysis. We performed a thorough literature search of the PubMed and ScienceDirect databases, and extracted all relevant clinical variables to compare the antidepressive outcomes between add-on ketamine anesthesia and other anesthetics in ECT. Total 16 articles with 346 patients receiving add-on ketamine anesthesia in ECT and 329 controls were recruited. We found that the antidepressive treatment effect of add-on ketamine anesthesia in ECT in depressive patients was significantly higher than that of other anesthetics (p<0.001). This significance persisted in both short-term (1-2 weeks) and moderate-term (3-4 weeks) treatment courses (all p<0.05). However, the side effect profiles and recovery time profiles were significantly worse in add-on ketamine anesthesia group than in control group. Our meta-analysis highlights the significantly higher antidepressive treatment effect of add-on ketamine in depressive patients receiving ECT compared to other anesthetics. However, clinicians need to take undesirable side effects into consideration when using add-on ketamine anesthesia in ECT in depressive patients. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Discovering Focus: Helping Students with ADD (Attention Deficit Disorder)

ERIC Educational Resources Information Center

Valkenburg, Jim

2012-01-01

Attention Deficit Disorder (ADD) is a neurological disorder which effects learning and that has a confusing set of diagnostic symptoms and an even more confusing set of remedies ranging from medication to meditation to nothing at all. Current neurological research suggests, however, that there are strategies that the individual with ADD can use to…

Alternative Fuels Data Center: Ozinga Adds 14 Natural Gas Concrete Mixers

Science.gov Websites

to Its Fleet Ozinga Adds 14 Natural Gas Concrete Mixers to Its Fleet to someone by E-mail Share Alternative Fuels Data Center: Ozinga Adds 14 Natural Gas Concrete Mixers to Its Fleet on Facebook Tweet about Alternative Fuels Data Center: Ozinga Adds 14 Natural Gas Concrete Mixers to Its Fleet on Twitter Bookmark

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

PubMed

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.

PubMed

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.

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

PubMed Central

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

2017-01-01

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. PMID:28923934

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

PubMed

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].

PubMed

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.

Distribution and progression of add power among people in need of near correction.

PubMed

Han, Xiaotong; Lee, Pei Ying; Liu, Chi; He, Mingguang

2018-04-16

This study helps to better understand the need and trend in presbyopic add power in the aging society. Distribution and progression of presbyopic add power in East Asian population is largely unknown. Prospective cohort study. About 303 participants from a population-based study of residents aged 35 years and older in Guangzhou, China. Visual acuity (VA) test and non-cycloplegic automated refraction were performed at baseline in 2008 and the 6-year follow-up per standardized protocol. Participants with presenting near VA ≤ 20/40 underwent distance subjective refraction and add power measurement by increasing plus lens at a standard distance of 40 cm at each visit. Add power at baseline and follow-ups. Mean (standard deviation) age of the study participants was 57.6 (11.1) years and 50.2% were female. The mean add power at baseline was 1.43, 1.73, 2.03 and 2.20 diopters (D) for individuals in the age groups of 35-44, 45-54, 55-64 and 65+ years, respectively. Participants with older age and lower educational level had significantly higher add power requirements (P < 0.001). The overall 6-year increase in add power was 0.15D (95% CI: 0.06 to 0.25), and was smaller in myopic subjects (P = 0.03). Baseline age and add power, but not changes in biometric factors, were associated with longitudinal change in add power (P < 0.001). Distribution and progression of add power in Chinese was different from that previously suggested by Caucasian studies. More studies are needed to establish up-to-date age-related add power prescription norms for population of different ethnicities. © 2018 Royal Australian and New Zealand College of Ophthalmologists.

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

NASA Astrophysics Data System (ADS)

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.

Early add-on lacosamide in a real-life setting: results of the REALLY study.

PubMed

Villanueva, Vicente; Garcés, Mercedes; López-Gomáriz, Elena; Serratosa, José María; González-Giráldez, Beatriz; Parra, Jaime; Rodríguez-Uranga, Juan; Toledo, Manuel; López González, Francisco Javier; Bermejo, Pedro; Giner, Pau; Castillo, Ascensión; Molins, Albert; Campos, Dulce; Mauri, José Ángel; Muñoz, Rosario; Bonet, Macarena; Serrano-Castro, Pedro; del Villar, Ana; Saiz-Díaz, Rosa Ana

2015-02-01

Many patients with epilepsy are treated with antiepileptic drug (AED) polytherapy. Several factors influence the choice of early add-on therapy, and deciding on the most appropriate drug can be difficult. This study aimed to assess the efficacy and tolerability of lacosamide as early add-on therapy in patients with partial-onset seizures. REALLY (REtrospective study of lAcosamide as earLy add-on aLong one Year) was a multicenter, retrospective, 1-year, real-life study. Patients included were aged older than 16 years, had partial-onset seizures, and were treated with lacosamide as add-on therapy after one or two prior AEDs. Data were collected retrospectively from clinical records. The primary study objective was to assess the efficacy of lacosamide over 12 months (seizure-free and responder rates), and the secondary objective was to assess the tolerability of lacosamide at 3, 6, and 12 months [adverse events (AEs) and discontinuation]. One hundred and ninety-nine patients were enrolled in the study; 89 patients (44.7 %) had tried one AED and 110 patients (55.3 %) had tried two AEDs before lacosamide. At 12 months, the proportion of patients who were seizure free was 44.9 %, and 76 % of patients were responders. The seizure-free rate at 12 months for patients who had previously received one or two AEDs was 58 and 34.3 %, and the responder rate at 12 months was 83.0 and 70.4 %, respectively. The AE rate was 21.5 % at 3 months, 27.1 % at 6 months, and 31.2 % at 12 months, with 7.0 % of patients discontinuing treatment because of an AE. The most common AE reported was dizziness (11.6 %). Cryptogenic epilepsy, a higher number of prior AEDs, and the use of a sodium channel blocker at onset were associated with a worse outcome. The number of concomitant AEDs decreased over 1 year (Z = 5.89; p < 0.001). Twenty-two patients were converted to lacosamide monotherapy with at least one evaluation ≥6 months from the beginning of monotherapy conversion

Social Capital: Does It Add to the Health Inequalities Debate?

ERIC Educational Resources Information Center

Chappell, Neena L.; Funk, Laura M.

2010-01-01

This paper empirically examines the relationship between advantage, social capital and health status to assess (a) whether social capital adds explanatory power to what we already know about the relationship between advantage and health and (b) whether social capital adds anything beyond its component parts, namely social participation and trust.…

Polymorphisms in the GNB3 and ADD1 genes and blood pressure in a Chinese population.

PubMed

Chen, Shufeng; Wang, Hongwei; Lu, Xiangfeng; Liu, De-Pei; Chen, Jing; Jaquish, Cashell E; Rao, Dabeeru C; Hixson, James E; Kelly, Tanika N; Hou, Liping; Wang, Laiyuan; Huang, Jianfeng; Chen, Chung-Shiuan; Rice, Treva K; Whelton, Paul K; He, Jiang; Gu, Dongfeng

2010-08-01

A large proportion of the phenotypic variation in blood pressure (BP) appears to be inherited as a polygenic trait. This study examined the association between 12 single nucleotide polymorphisms (SNPs) in the guanine nucleotide binding protein beta polypeptide 3 (GNB3) and adducin 1 alpha (ADD1) genes and systolic (SBP), diastolic (DBP), and mean arterial (MAP) BP. A total of 3,142 individuals from 636 families were recruited from rural north China, and 2,746 met the eligibility criteria for analysis. BP measurements were obtained using a random-zero sphygmomanometer. Genetic variants were determined using SNPlex assays on an automated DNA Sequencer. A mixed linear model was used to estimate the association between each SNP and BP level. After Bonferroni correction, marker rs4963516 of the GNB3 gene remained significantly associated with DBP (corrected P values = 0.006, 0.007 and 0.002 for co-dominant, additive, and recessive models, respectively) and MAP (corrected P values = 0.02, 0.049, and 0.005, respectively). Compared to carriers of the major A allele, CC homozygotes had higher mean DBP (75.81 +/- 0.62 vs. 73.46 +/- 0.25 mmHg, P = 0.0002) and MAP (91.87 +/- 0.68 vs. 89.42 +/- 0.28 mmHg, P = 0.0004) after adjusting for covariates of age, gender, BMI, study site, and room temperature during BP measurement. In summary, these data support a role for the GNB3 gene in BP regulation in the Chinese population. Future studies aimed at replicating these novel findings are warranted.

Impact of Modafinil Add-on with Atypical Anti-psychotics on Excessive Daytime Drowsiness

PubMed Central

Prasuna, P Lakshmi; Sudhakar, TP

2015-01-01

Background: Atypical antipsychotic drugs are known to cause many side effects which include daytime drowsiness. So many add on drugs are tried to reduce the same. Materials and Methods: 72 patients who were on atypical antipsychotic drugs were randomly assigned to either Modafinil or placebo and were followed for a period of 12 weeks. Daytime drowsiness, was taken at baseline, week 3, and at week 12 by using VAS, EDD scales. Results: The results were analyzed and showed that the Modafinil add on therapy significantly reduced the daytime Drowsiness. Conclusions: Modafinil could be a potential candidate in selected group of patients to decrease some of the unwanted adverse events like daytime drowsiness produced by atypical antipsychotics. PMID:26702168

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

PubMed

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.

The Source for ADD/ADHD: Attention Deficit Disorder and Attention Deficit/Hyperactivity Disorder.

ERIC Educational Resources Information Center

Richard, Gail J.; Russell, Joy L.

This book is intended for professionals who are responsible for designing and implementing educational programs for children with attention deficit disorders and attention deficit/hyperactivity disorder (ADD/ADHD). Chapters address: (1) myths and realities about ADD/ADHD; (2) definitions, disorders associated with ADD/ADHD, and federal educational…

Efficacy and safety of lacosamide as first add-on or later adjunctive treatment for uncontrolled partial-onset seizures: A multicentre open-label trial.

PubMed

Zadeh, Wendy Waldman; Escartin, Antonio; Byrnes, William; Tennigkeit, Frank; Borghs, Simon; Li, Ting; Dedeken, Peter; De Backer, Marc

2015-09-01

To evaluate the efficacy and safety of lacosamide administered as either first add-on or later add-on antiepileptic drug (AED) therapy for patients with uncontrolled partial-onset seizures (POS). In this open-label, multicentre trial, patients with POS initiated oral lacosamide (titrated to 400 mg/day) either as add-on to first AED monotherapy, or as later add-on to 1-3 concomitant AEDs after ≥ 2 previous AEDs. The primary efficacy variable was the proportion of patients achieving seizure freedom for the first 12 weeks of the 24-week Maintenance Phase. 456 patients received ≥ 1 dose of lacosamide (96 as first add-on, 360 as later add-on). In the first add-on cohort, 27/72 (37.5%) patients completed 12 weeks treatment and remained seizure-free; 18/68 (26.5%) remained seizure-free after 24 weeks. 64/91 (70.3%) patients achieved ≥ 50% reduction in seizure frequency during maintenance treatment. This was accompanied by a mean 7.1 ± 16.00 point improvement from Baseline in the Quality of Life Inventory in Epilepsy (QOLIE-31-P) total score for 24-week completers, with improvement reported in all subscales. Most common treatment-emergent adverse events (TEAEs) were dizziness (31.3%) and headache (13.5%). In the later add-on cohort, 39/261 (14.9%) and 29/249 (11.6%) patients remained seizure-free after completing 12 and 24 weeks' treatment, respectively. 178/353 (50.4%) patients achieved ≥ 50% reduction in seizure frequency during maintenance treatment. Mean change in QOLIE-31-P total score was 4.8 ± 14.74 points among 24-week completers. Common TEAEs were dizziness (33.6%), somnolence (15.0%) and headache (11.4%). Lacosamide initiated as first add-on treatment was efficacious and well tolerated in patients with uncontrolled POS. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Neural Biomarkers for Dyslexia, ADHD, and ADD in the Auditory Cortex of Children.

PubMed

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

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, magnetencephalography 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 allowed for 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.

Neural Biomarkers for Dyslexia, ADHD, and ADD in the Auditory Cortex of Children

PubMed Central

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

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, magnetencephalography 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 allowed for 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. PMID:27471442

The dubious assessment of gay, lesbian, and bisexual adolescents of add health.

PubMed

Savin-Williams, Ritch C; Joyner, Kara

2014-04-01

In this essay, we argue that researchers who base their investigations of nonheterosexuality derived from reports of romantic attractions of adolescent participants from Wave 1 of Add Health must account for their disappearance in future waves of data collection. The high prevalence of Wave 1 youth with either both-sex or same-sex romantic attractions was initially striking and unexpected. Subsequent data from Add Health indicated that this prevalence sharply declined over time such that over 70 % of these Wave 1 adolescents identified as exclusively heterosexual as Wave 4 young adults. Three explanations are proposed to account for the high prevalence rate and the temporal inconsistency: (1) gay adolescents going into the closet during their young adult years; (2) confusion regarding the use and meaning of romantic attraction as a proxy for sexual orientation; and (3) the existence of mischievous adolescents who played a "jokester" role by reporting same-sex attraction when none was present. Relying on Add Health data, we dismissed the first explanation as highly unlikely and found support for the other two. Importantly, these "dubious" gay, lesbian, and bisexual adolescents may have led researchers to erroneously conclude from the data that sexual-minority youth are more problematic than heterosexual youth in terms of physical, mental, and social health.

QbD-Oriented Development and Characterization of Effervescent Floating-Bioadhesive Tablets of Cefuroxime Axetil.

PubMed

Bansal, Sanjay; Beg, Sarwar; Garg, Babita; Asthana, Abhay; Asthana, Gyati S; Singh, Bhupinder

2016-10-01

The objective of the present studies was systematic development of floating-bioadhesive gastroretentive tablets of cefuroxime axetil employing rational blend of hydrophilic polymers for attaining controlled release drug delivery. As per the QbD-based approach, the patient-centric target product profile and quality attributes of tablet were earmarked, and preliminary studies were conducted for screening the suitability of type of polymers, polymer ratio, granulation technique, and granulation time for formulation of tablets. A face-centered cubic design (FCCD) was employed for optimization of the critical material attributes, i.e., concentration of release controlling polymers, PEO 303 and HPMC K100 LV CR, and evaluating in vitro buoyancy, drug release, and ex vivo mucoadhesion strength. The optimized formulation was embarked upon through numerical optimization, which yield excellent floatation characteristic with drug release control (i.e., T 60% > 6 h) and bioadhesion strength. Drug-excipient compatibility studies through FTIR and P-XRD revealed the absence of any interaction between the drug and polymers. In vivo evaluation of the gastroretentive characteristics through X-ray imaging and in vivo pharmacokinetic studies in rabbits revealed significant extension in the rate of drug absorption (i.e., T max, K a, and MRT) from the optimized tablet formulation as compared to the marketed formulation. Successful establishment of various levels of in vitro/in vivo correlations (IVIVC) substantiated high degree of prognostic ability of in vitro dissolution conditions in predicting the in vivo performance. In a nutshell, the studies demonstrate successful development of the once-a-day gastroretentive formulations of cefuroxime axetil with controlled drug release profile and improved compliance.

Channel add-drop filter based on dual photonic crystal cavities in push-pull mode.

PubMed

Poulton, Christopher V; Zeng, Xiaoge; Wade, Mark T; Popović, Miloš A

2015-09-15

We demonstrate an add-drop filter based on a dual photonic crystal nanobeam cavity system that emulates the operation of a traveling wave resonator, and, thus, provides separation of the through and drop port transmission from the input port. The device is on a 3×3  mm chip fabricated in an advanced microelectronics silicon-on-insulator complementary metal-oxide semiconductor (SOI CMOS) process (IBM 45 nm SOI) without any foundry process modifications. The filter shows 1 dB of insertion loss in the drop port with a 3 dB bandwidth of 64 GHz, and 16 dB extinction in the through port. To the best of our knowledge, this is the first implementation of a port-separating, add-drop filter based on standing wave cavities coupled to conventional waveguides, and demonstrates a performance that suggests potential for photonic crystal devices within optical immersion lithography-based advanced CMOS electronics-photonics integration.

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

NASA Astrophysics Data System (ADS)

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.

Cognitive Control and Attentional Selection in Adolescents with ADHD versus ADD

ERIC Educational Resources Information Center

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-10

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ENVIRONMENTAL TECHNOLOGY VERIFICATION: ADD-ON NOX CONTROLS

EPA Science Inventory

The paper discusses the environmental technology verification (ETV) of add-on nitrogen oxide (NOx) controls. Research Triangle Institute (RTI) is EPA's cooperating partner for the Air Pollution Control Technology (APCT) Program, one of a dozen ETV pilot programs. Verification of ...

Real-world data on eslicarbazepine acetate as add-on to antiepileptic monotherapy.

PubMed

Holtkamp, M; McMurray, R; Bagul, M; Sousa, R; Kockelmann, E

2016-07-01

To assess retention, tolerability, and safety, efficacy and effects on quality of life (QoL) of eslicarbazepine acetate (ESL) add-on treatment over 6 months in a real-world adult population with partial-onset seizures. This non-interventional, multicenter, prospective study was performed in eight European countries. Adult patients (n = 247) for whom the physician had decided to initiate ESL as add-on to an existing antiepileptic drug (AED) monotherapy were invited to participate. The study comprised three visits: baseline, and after 3 and 6 months. Data on ESL retention, efficacy, tolerability, safety, and QoL were collected. After 6 months, the retention rate of ESL was 82.2%, and 81.8% of patients reported a reduction of seizure frequency of at least 50%; 39.2% of patients reported seizure freedom at this time. The mean QOLIE-10 score improved from 2.9 (SD ± 0.8) at baseline to 2.1 (SD ± 0.8) after 6 months. 109 adverse events (AEs) were reported in 57 patients (26.0%); the majority were rated as related to ESL by the investigator and led to a discontinuation of ESL in 25 patients (11.4%). Eight patients (3.7%) suffered at least one serious AE. The most frequently reported AEs were dizziness, headache, convulsion, and fatigue. This study shows that ESL was well tolerated and efficacious as add-on therapy to one baseline AED. The use of ESL in patients less refractory than those included in previous clinical trials led to higher responder and seizure freedom rates. No new safety issues were observed. © 2016 Esai Europe Ltd. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.

Producers add 3 cts/gal

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

Vames, S.

Methanol list prices will continue to rise in March with a nominated price increase of 3 cts/gal (CW, Feb. 26, p. 39). The increases will bring Methanex`s posting price to 70 cts/gal, while most other producers will be at 67 cts/gal. Several producers, including Methanex and Hoechst, expanded capacity last month, but the methanol market remains strong and there are no indications that prices will soften soon. There are hints, however, that the rate of increase of methanol prices may slow. Tightness in the market seems to be easing as producers in eastern Europe increase capacity. The psychology of tightnessmore » was stoked by reports of spot and regional shortages and resulted in buying panics and price increases in fourth-quarter 1996.« less

Prevalence of Aggression and Defiance in Children with ADD/ADHD Tendencies

ERIC Educational Resources Information Center

Hill, Janella

2011-01-01

Attention Deficit Disorder (ADD) and Attention Deficit Hyperactivity Disorder (ADHD) appear to have become more prevalent in the past few years. Many children who display ADD/ADHD tendencies also display behaviors which cause problems in a classroom setting. Considering the fact that these behaviors could be displayed by the student population as…

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

Federal Register 2010, 2011, 2012, 2013, 2014

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... Disability Employment Policy (ODEP) announces the availability of approximately $1.65 million to be awarded...

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

NASA Astrophysics Data System (ADS)

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.

The effect of bifocal add on accommodative lag in myopic children with high accommodative lag.

PubMed

Berntsen, David A; Mutti, Donald O; Zadnik, Karla

2010-12-01

To determine the effect of a bifocal add and manifest correction on accommodative lag in myopic children with high accommodative lag, who have been reported to have the greatest reduction in myopia progression with progressive addition lenses (PALs). Monocular accommodative lag to a 4-D Badal stimulus was measured on two occasions 6 months apart in 83 children (mean ± SD age, 9.9 ± 1.3 years) with high lag randomized to wearing single-vision lenses (SVLs) or PALs. Accommodative lag was measured with the following corrections: habitual, manifest, manifest with +2.00-D add, and habitual with +2.00-D add (6-month visit only). At baseline, accommodative lag was higher (1.72 ± 0.37 D; mean ± SD) when measured with manifest correction than with habitual correction (1.51 ± 0.50; P < 0.05). This higher lag with manifest correction correlated with a larger amount of habitual undercorrection at baseline (r = -0.29, P = 0.009). A +2.00-D add over the manifest correction reduced lag by 0.45 ± 0.34 D at baseline and 0.33 ± 0.38 D at the 6-month visit. Lag results at 6 months were not different between PAL and SVL wearers (P = 0.92). A +2.00-D bifocal add did not eliminate accommodative lag and reduced lag by less than 25% of the bifocal power, indicating that children mainly responded to a bifocal by decreasing accommodation. If myopic progression is substantial, measuring lag with full correction can overestimate the hyperopic retinal blur that a child most recently experienced. (ClinicalTrials.gov number, NCT00335049.).

The Effect of Bifocal Add on Accommodative Lag in Myopic Children with High Accommodative Lag

PubMed Central

Mutti, Donald O.; Zadnik, Karla

2010-01-01

Purpose. To determine the effect of a bifocal add and manifest correction on accommodative lag in myopic children with high accommodative lag, who have been reported to have the greatest reduction in myopia progression with progressive addition lenses (PALs). Methods. Monocular accommodative lag to a 4-D Badal stimulus was measured on two occasions 6 months apart in 83 children (mean ± SD age, 9.9 ± 1.3 years) with high lag randomized to wearing single-vision lenses (SVLs) or PALs. Accommodative lag was measured with the following corrections: habitual, manifest, manifest with +2.00-D add, and habitual with +2.00-D add (6-month visit only). Results. At baseline, accommodative lag was higher (1.72 ± 0.37 D; mean ± SD) when measured with manifest correction than with habitual correction (1.51 ± 0.50; P < 0.05). This higher lag with manifest correction correlated with a larger amount of habitual undercorrection at baseline (r = −0.29, P = 0.009). A +2.00-D add over the manifest correction reduced lag by 0.45 ± 0.34 D at baseline and 0.33 ± 0.38 D at the 6-month visit. Lag results at 6 months were not different between PAL and SVL wearers (P = 0.92). Conclusions. A +2.00-D bifocal add did not eliminate accommodative lag and reduced lag by less than 25% of the bifocal power, indicating that children mainly responded to a bifocal by decreasing accommodation. If myopic progression is substantial, measuring lag with full correction can overestimate the hyperopic retinal blur that a child most recently experienced. (ClinicalTrials.gov number, NCT00335049.) PMID:20688729

Mode-routed fiber-optic add-drop filter

NASA Technical Reports Server (NTRS)

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.

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

PubMed

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.

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

PubMed Central

2010-01-01

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. PMID:20181245

Effect of formaldehyde/bleach reprocessing on in vivo performances of high-efficiency cellulose and high-flux polysulfone dialyzers.

PubMed

Murthy, B V; Sundaram, S; Jaber, B L; Perrella, C; Meyer, K B; Pereira, B J

1998-03-01

Among the several disadvantages of reprocessed dialyzers is the concern that reuse could decrease the clearance of uremic toxins, leading to a decrease in the delivered dose of dialysis. To examine this possibility in the clinical setting, the clearances of small molecular weight solutes (urea and creatinine) and middle molecular weight substances (beta 2 microglobulin) were compared during dialysis with "high-efficiency" cellulose (T220L) and "high-flux" polysulfone (F80B) dialyzers reprocessed with formaldehyde and bleach. In a crossover study, six chronic hemodialysis patients were alternately assigned to undergo 21 dialysis treatments with a single T220L dialyzer or F80B dialyzer. Each patient was studied during first use (0 reuse), 2nd reuse (3rd use), and 5th, 10th, 15th, and 20th reuse of each dialyzer. Urea, creatinine, and beta 2 microglobulin clearances were measured at blood flow rates of 300 ml/min (Qb 300) and 400 ml/min (Qb 400). Total albumin loss into the dialysate was measured during each treatment. Urea or creatinine clearance of new T220L dialyzers was not significantly different from that of new F80B dialyzers at either Qb. Urea clearance of F80B dialyzers at Qb 300 decreased from 241 +/- 2 ml/min for new dialyzers to 221 +/- 5 ml/min after 20 reuses (P < 0.001), and Qb 400 from 280 +/- 4 ml/min for new dialyzers to 253 +/- 7 ml/min after 20 reuses (P = 0.001). Similarly, with reuse, creatinine clearance of F80B dialyzers also decreased at Qb 300 (P = 0.07) and Qb 400 (P = 0.03). In contrast, urea or creatinine clearance of T220L dialyzers did not decrease with reuse at either Qb. Urea clearance of T220L dialyzers was significantly higher than that of F80B at Qb 300 at the 5th, 10th, 15th, and 20th reuse (P < 0.001, = 0.005, = 0.004, and = 0.006, respectively), and Qb 400 at the 2nd, 5th, 10th, 15th, and 20th reuse (P = 0.04, 0.008, 0.03, 0.02, and 0.008, respectively). Beta 2 microglobulin clearance of T220L dialyzers was < 5.0 ml/min across

radEq Add-On Module for CFD Solver Loci-CHEM

NASA Technical Reports Server (NTRS)

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.

Effect and Potential Mechanism of Electroacupuncture Add-On Treatment in Patients with Parkinson's Disease

PubMed Central

Wang, Fang; Sun, Li; Zhang, Xiao-zhe; Jia, Jun; Liu, Zhuo; Huang, Xi-yan; Yu, Shu-yang; Zuo, Li-jun; Cao, Chen-jie; Wang, Xiao-min; Zhang, Wei

2015-01-01

Objectives. To explore effectiveness and mechanisms of electroacupuncture (EA) add-on treatment in Parkinson's disease (PD) patients. Methods. Fifty PD patients were randomly assigned to drug plus EA (D + EA) group and drug alone (D) group. Subjects in D + EA group received stimulation in points of bilateral fengfu, fengchi, hegu, and central dazhui. Participants were evaluated by scales for motor and nonmotor symptoms. Levels of neuroinflammatory factors and neurotransmitters in serum were detected. Results. EA add-on treatment remarkably reduced scores of Unified Parkinson's Disease Rating Scale (UPDRS) III and its subitems of tremor, rigidity, and bradykinesia and conspicuously decreased UPDRS III scores in patients with bradykinesia-rigidity and mixed types and mild severity. Depression and sleep disturbances were eased, which were reflected by decreased scores of Hamilton Depression Rating Scale, Pittsburgh Sleep Quality Index, and elevated noradrenaline level. Effects of EA add-on treatment on motor symptoms and sleep disturbances were superior to drug alone treatment, markedly improving life quality of PD patients. EA add-on treatment decreased nitric oxide level in serum. Conclusions. EA add-on treatment is effective on most motor symptoms and some nonmotor symptoms and is particularly efficacious in PD patients at early stage. Antineuroinflammation may be a mechanism of EA add-on treatment. PMID:26351515

High temperature superconductivity in distinct phases of amorphous B-doped Q-carbon

NASA Astrophysics Data System (ADS)

Narayan, Jagdish; Bhaumik, Anagh; Sachan, Ritesh

2018-04-01

Distinct phases of B-doped Q-carbon are formed when B-doped and undoped diamond tetrahedra are packed randomly after nanosecond laser melting and quenching of carbon. By changing the ratio of doped to undoped tetrahedra, distinct phases of B-doped Q-carbon with concentration varying from 5.0% to 50.0% can be created. We have synthesized three distinct phases of amorphous B-doped Q-carbon, which exhibit high-temperature superconductivity following the Bardeen-Cooper-Schrieffer mechanism. The first phase (QB1) has a B-concentration ˜17 at. % (Tc = 37 K), the second phase (QB2) has a B-concentration ˜27 at. % (Tc = 55 K), and the third phase (QB3) has a B-concentration ˜45 at. % (Tc expected over 100 K). From geometrical modeling, we derive that QB1 consists of randomly packed tetrahedra, where one out of every three tetrahedra contains a B atom in the center which is sp3 bonded to four carbon atoms with a concentration of 16.6 at. %. QB2 consists of randomly packed tetrahedra, where one out of every two tetrahedra contains a B atom in the center which is sp3 bonded to four carbon atoms with a concentration of 25 at. %. QB3 consists of randomly packed tetrahedra, where every tetrahedron contains a B atom in the center which is sp3 bonded to four carbon atoms with a concentration of 50 at. %. We present detailed high-resolution TEM results on structural characterization, and EELS and Raman spectroscopy results on the bonding characteristics of B and C atoms. From these studies, we conclude that the high electronic density of states near the Fermi energy level coupled with moderate electron-phonon coupling result in high-temperature superconductivity in B-doped Q-carbon.

Characterization of galactic bars from 3.6 μm S4G imaging

NASA Astrophysics Data System (ADS)

Díaz-García, S.; Salo, H.; Laurikainen, E.; Herrera-Endoqui, M.

2016-03-01

Context. Stellar bars play an essential role in the secular evolution of disk galaxies because they are responsible for the redistribution of matter and angular momentum. Dynamical models predict that bars become stronger and longer in time, while their rotation speed slows down. Aims: We use the Spitzer Survey of Stellar Structure in Galaxies (S4G) 3.6 μm imaging to study the properties (length and strength) and fraction of bars at z = 0 over a wide range of galaxy masses (M∗ ≈ 108-1011 M⊙) and Hubble types (-3 ≤ T ≤ 10). Methods: We calculated gravitational forces from the 3.6 μm images for galaxies with a disk inclination lower than 65°. We used the maximum of the tangential-to-radial force ratio in the bar region (Qb) as a measure of the bar-induced perturbation strength for a sample of ~600 barred galaxies. We also used the maximum of the normalized m = 2 Fourier density amplitude (A2max) to characterize the bar. Bar sizes were estimated I) visually; II) from ellipse fitting; III) from the radii of the strongest torque; and iv) from the radii of the largest m = 2 Fourier amplitude in the bar region. By combining our force calculations with the H I kinematics from the literature, we estimated the ratio of the halo-to-stellar mass (Mh/M∗) within the optical disk and by further using the universal rotation curve models, we obtained a first-order model of the rotation curve decomposition of 1128 disk galaxies. Results: We probe possible sources of uncertainty in our Qb measurements: the assumed scale height and its radial variation, the influence of the spiral arms torques, the effect of non-stellar emission in the bar region, and the dilution of the bar forces by the dark matter halo (our models imply that only ~10% of the disks in our sample are maximal). We find that for early- and intermediate-type disks (-3 ≤ T< 5), the relatively modest influence of the dark matter halo leads to a systematic reduction of the mean Qb by about 10-15%, which is

Add Control: plant virtualization for control solutions in WWTP.

PubMed

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.

Experimental re-evaluation of flunarizine as add-on antiepileptic therapy.

PubMed

Thakur, Anamika; Sahai, A K; Thakur, J S

2011-04-01

Experimental studies have found several calcium channel blockers with anticonvulsant property. Flunarizine is one of the most potent calcium channel blockers, which has shown anticonvulsant effect against pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced seizures. However, further experimental and clinical trials have shown varied results. We conducted a PTZ model experimental study to re-evaluate the potential of flunarizine for add-on therapy in the management of refractory epilepsy. Experiments were conducted in PTZ model involving Swiss strain mice. Doses producing seizures in 50% and 99% mice, i.e. CD(50) and CD(99) values of PTZ were obtained from the dose-response study. Animals received graded, single dose of sodium valproate (100-300 mg/kg), lamotrigine (3-12 mg/kg) and flunarizine (5-20 mg/kg), and then each group of mice was injected with CD(99) dose of PTZ (65mg/kg i.p.). Another group of mice received single ED(50) dose (dose producing seizure protection in 50% mice) of sodium valproate and flunarizine separately in left and right side of abdomen. Results were analysed by Kruskal-Wallis ANOVA on Ranks test. As compared to control, sodium valproate at 250 mg/kg and 300 mg/kg produced statistical significant seizure protection. At none of the pre-treatment dose levels of lamotrigine, the seizure score with PTZ differed significantly from that observed in the vehicle-treated group. Pre-treatment with flunarizine demonstrated dose-dependent decrease in the seizure score to PTZ administration. As compared to control group, flunarizine at 20 mg/kg produced statistical significant seizure protection. As combined use of sodium valproate and flunarizine has shown significant seizure protection in PTZ model, flunarizine has a potential for add-on therapy in refractory cases of partial seizures. It is therefore, we conclude that further experimental studies and multicenter clinical trials involving large sample size are needed to establish

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

PubMed

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.

Alternative Deployment Duration - Reserve Component (ADD-RC)

DTIC Science & Technology

2003-02-01

Other Personnel Equipment & S 8,375.00 1.50 12,562.50 2.00 16,750.00 Medical Support/Health Services 158.50...VAARNG) CPT Zana , 29th Infantry Division (VAARNG) ADD-RC A-1 CAA-R-01-67 (THIS PAGE INTENTIONALLY... Medical , Signal) as well as on availability of qualified instructors - Current training requirements being fulfilled through an additional cycle of

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

PubMed

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.

Memantine add-on to antipsychotic treatment for residual negative and cognitive symptoms of schizophrenia: a meta-analysis.

PubMed

Kishi, Taro; Matsuda, Yuki; Iwata, Nakao

2017-07-01

We examined whether memantine add-on to antipsychotic treatment is beneficial in schizophrenia treatment. This systematic review and meta-analysis aimed to achieve stronger evidence on the efficacy and safety of memantine add-on for treating schizophrenia. We analyzed double-blind, randomized, placebo-controlled trials of memantine add-on treatment in schizophrenia patients receiving antipsychotics. The primary outcomes were amelioration of negative symptoms and all-cause discontinuation. Dichotomous outcomes are presented as risk ratios (RRs), and continuous outcomes are presented as mean differences (MDs) or standardized mean differences (SMDs). Eight studies (n = 448) were included. Although memantine add-on treatment was superior to placebo for ameliorating negative symptoms (SMD = -0.96, p = 0.006, I 2  = 88%; N = 7, n = 367) in the Positive and Negative Syndrome Scale general subscale (MD = -1.62, p = 0.002, I 2  = 0%; N = 4, n = 151) and Mini-Mental Status Examination score (MD = -3.07, p < 0.0001, I 2  = 21%; N = 3, n = 83), there were no statistically significant differences in the amelioration of overall (SMD = -0.75, p = 0.06, I 2  = 86%; N = 5, n = 271), positive (SMD = -0.46, p = 0.07, I 2  = 80%; N = 7, n = 367), and depressive symptoms (SMD = -0.127, p = 0.326, I 2  = 0%; N = 4, n = 201); all-cause discontinuation (RR = 1.34, p = 0.31, I 2  = 0%; N = 8, n = 448); and individual adverse events (fatigue, dizziness, headache, nausea, constipation) between the groups. For negative symptoms, the significant heterogeneity disappeared when risperidone studies alone were considered (I 2  = 0%). However, memantine add-on treatment remained superior to placebo (SMD = -1.29, p = 0.00001). Meta-regression analysis showed that patient age was associated with memantine-associated amelioration of negative symptoms (slope = 0.171, p = 0.0206). Memantine add-on treatment may be

Sensitivity analysis of add-on price estimate for select silicon wafering technologies

NASA Technical Reports Server (NTRS)

Mokashi, A. R.

1982-01-01

The cost of producing wafers from silicon ingots is a major component of the add-on price of silicon sheet. Economic analyses of the add-on price estimates and their sensitivity internal-diameter (ID) sawing, multiblade slurry (MBS) sawing and fixed-abrasive slicing technique (FAST) are presented. Interim price estimation guidelines (IPEG) are used for estimating a process add-on price. Sensitivity analysis of price is performed with respect to cost parameters such as equipment, space, direct labor, materials (blade life) and utilities, and the production parameters such as slicing rate, slices per centimeter and process yield, using a computer program specifically developed to do sensitivity analysis with IPEG. The results aid in identifying the important cost parameters and assist in deciding the direction of technology development efforts.

Rivastigmine as an effective add-on to standard treatment of veterans with chronic posttraumatic stress disorder: a case series.

PubMed

Fayyazi Bordbar, Mohammad Reza; Talaei, Ali

2013-10-01

After 23 years of the end of the Iran-Iraq war, the country is left with many patients with chronic posttraumatic stress disorder (PTSD) who need close psychiatric services and are in need for recurrent hospitalization. So far, there are no reports of the rivastigmine use in PTSD patients. We report dramatic reduction of symptoms in 3 veterans with chronic PTSD, after rivastigmine augmentation. This report describes the efficacy of rivastigmine as an add-on to standard treatment of 3 Iranian male veterans with chronic PTSD (aged 52, 46, and 45 years) with severe active symptoms in all 3 dimensions of the disorder. Although they had gone through many approved drug treatments (selective serotonin reuptake inhibitors, tricyclic antidepressants, mood stabilizers, antipsychotics, benzodiazepines, β-blockers, and so on), from the beginning of the disorder, their recovery remained poor (PTSD Checklist-Military Version [PCL-M] scores were 67, 71, and 73 before rivastigmine add-on). Rivastigmine was added to the ongoing therapeutic regimens of the patients for 6 months.Evaluating their condition with PCL-M after 1 and 6 months of treatment showed a significant improvement in patients with PTSD (PCL-M scores were 37, 40, and 47 and dropped to 30, 27, and 31, respectively). Hyperarousal symptoms of PTSD in patients are noted to be the most improved. The rivastigmine add-on experience did not report any adverse effects. The present study showed that rivastigmine is an effective and safe add-on to treatment of patients with chronic PTSD. This effect could be due to improved cognitive status or cholinergic-adrenergic balance adjustment in patients.

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

PubMed

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.

The pumping oxygenator: design criteria and first in vitro results.

PubMed

Fiore, G B; Costantino, M L; Fumero, R; Montevecchi, F M

2000-10-01

A new project is presented, the pumping oxygenator, functionally integrating pulsatile pumping and blood oxygenation in a single device. Solid, semipermeable silicone membranes allow gas exchange and simultaneously transfer energy from pressurized gas to blood thanks to their distensibility and to inlet and outlet 1-way valves. Two small-sized (1 m2 exchange surface area) prototypes were designed, constructed, hydraulically characterized, and subjected to gas transfer evaluation tests. Blood flow rates (Q(b)) up to 1,250 ml/min were obtained with 30 mm Hg static preload and 130 mm Hg afterload with 0.7 m upstream and 2.1 m downstream 3/8 inch pipes. Physiological oxygen transfer (VO2 = 5 ml/dl, ml of transferred O2/dl of treated blood) was delivered at Q(b) < 900 ml/min, about 4 ml/dl at Q(b) = 1,250 ml/min. VO2 also was significantly increased by increasing percent systolic time. CO2 transfer decreased regularly with increasing Q(b) from VCO2 = 4.8 ml/dl at Q(b) = 400 ml/min to VCO 2 = 2.1 ml/dl at Q(b) = 1,250 ml/min. The results confirm the possibility of integrating oxygenation and pulsatile pumping. The pumping oxygenator represents a promising project deserving further improvements.

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

Code of Federal Regulations, 2010 CFR

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

ERIC Educational Resources Information Center

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…

Sensory feedback add-on for upper-limb prostheses.

PubMed

Fallahian, Nader; Saeedi, Hassan; Mokhtarinia, Hamidreza; Tabatabai Ghomshe, Farhad

2017-06-01

Sensory feedback systems have been of great interest in upper-limb prosthetics. Despite tremendous research, there are no commercial modality-matched feedback systems. This article aims to introduce the first detachable and feedback add-on option that can be attached to in-use prostheses. A sensory feedback system was tested on a below-elbow myoelectric prosthesis. The aim was to have the amputee grasp fragile objects without crushing while other accidental feedback sources were blocked. A total of 8 successful trials (out of 10) showed that sensory feedback system decreased the amputee's visual dependency by improving awareness of his prosthesis. Sensory feedback system can be used either as post-fabrication (prosthetic add-on option) or para-fabrication (incorporated into prosthetic design). The use of these direct feedback systems can be explored with a current prosthesis before ordering new high-tech prosthesis. Clinical relevance This technical note introduces the first attach/detach-able sensory feedback system that can simply be added to in-use (myo)electric prosthesis, with no obligation to change prosthesis design or components.

Energetics of the O-H bond and of intramolecular hydrogen bonding in HOC6H4C(O)Y (Y = H, CH3, CH2CH=CH2, C[triple bond]CH, CH2F, NH2, NHCH3, NO2, OH, OCH3, OCN, CN, F, Cl, SH, and SCH3) compounds.

PubMed

Bernardes, Carlos E S; Minas da Piedade, Manuel E

2008-10-09

The energetics of the phenolic O-H bond in a series of 2- and 4-HOC 6H 4C(O)Y (Y = H, CH3, CH 2CH=CH2, C[triple bond]CH, CH2F, NH2, NHCH 3, NO2, OH, OCH3, OCN, CN, F, Cl, SH, and SCH3) compounds and of the intramolecular O...H hydrogen bond in 2-HOC 6H 4C(O)Y, was investigated by using a combination of experimental and theoretical methods. The standard molar enthalpies of formation of 2-hydroxybenzaldehyde (2HBA), 4-hydroxybenzaldehyde (4HBA), 2'-hydroxyacetophenone (2HAP), 2-hydroxybenzamide (2HBM), and 4-hydroxybenzamide (4HBM), at 298.15 K, were determined by micro- or macrocombustion calorimetry. The corresponding enthalpies of vaporization or sublimation were also measured by Calvet drop-calorimetry and Knudsen effusion measurements. The combination of the obtained experimental data led to Delta f H m (o)(2HBA, g) = -238.3 +/- 2.5 kJ.mol (-1), DeltafHm(o)(4HBA, g) = -220.3 +/- 2.0 kJ.mol(-1), Delta f H m (o)(2HAP, g) = -291.8 +/- 2.1 kJ.mol(-1), DeltafHm(o)(2HBM, g) = -304.8 +/- 1.5 kJ.mol (-1), and DeltafHm(o) (4HBM, g) = -278.4 +/- 2.4 kJ.mol (-1). These values, were used to assess the predictions of the B3LYP/6-31G(d,p), B3LYP/6-311+G(d,p), B3LYP/aug-cc-pVDZ, B3P86/6-31G(d,p), B3P86/6-311+G(d,p), B3P86/aug-cc-pVDZ, and CBS-QB3 methods, for the enthalpies of a series of isodesmic gas phase reactions. In general, the CBS-QB3 method was able to reproduce the experimental enthalpies of reaction within their uncertainties. The B3LYP/6-311+G(d,p) method, with a slightly poorer accuracy than the CBS-QB3 approach, achieved the best performance of the tested DFT models. It was further used to analyze the trends of the intramolecular O...H hydrogen bond in 2-HOC 6H 4C(O)Y evaluated by the ortho-para method and to compare the energetics of the phenolic O-H bond in 2- and 4-HOC 6H 4C(O)Y compounds. It was concluded that the O-H bond "strength" is systematically larger for 2-hydroxybenzoyl than for the corresponding 4-hydroxybenzoyl isomers mainly due to the presence of

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

PubMed

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.

Enhancing Teaching using MATLAB Add-Ins for Excel

ERIC Educational Resources Information Center

Hamilton, Paul V.

2004-01-01

In this paper I will illustrate how to extend the capabilities of Microsoft Excel spreadsheets with add-ins created by MATLAB. Excel provides a broad array of fundamental tools but often comes up short when more sophisticated scenarios are involved. To overcome this short-coming of Excel while retaining its ease of use, I will describe how…

Randomized, Double-Blind Trial of Triple Therapy With Saxagliptin Add-on to Dapagliflozin Plus Metformin in Patients With Type 2 Diabetes.

PubMed

Matthaei, Stephan; Catrinoiu, Doina; Celiński, Aleksander; Ekholm, Ella; Cook, William; Hirshberg, Boaz; Chen, Hungta; Iqbal, Nayyar; Hansen, Lars

2015-11-01

The objective of this study was to assess the efficacy and safety of triple therapy with saxagliptin add-on versus placebo add-on to dapagliflozin plus metformin in adults with type 2 diabetes. Patients on stable metformin (≥1,500 mg/day) for ≥8 weeks with glycated hemoglobin (HbA1c) 8.0-11.5% (64-102 mmol/mol) at screening received open-label dapagliflozin (10 mg/day) plus metformin immediate release (IR) for 16 weeks. Patients with inadequate glycemic control (HbA1c 7-10.5% [53-91 mmol/mol]) were then randomized to receive placebo (n = 153) or saxagliptin 5 mg/day (n = 162) in addition to background dapagliflozin plus metformin IR. The primary efficacy end point was change in HbA1c from baseline to week 24. There was a significantly greater reduction in HbA1c at 24 weeks with saxagliptin add-on (-0.51% [-5.6 mmol/mol]) versus placebo (-0.16% [-1.7 mmol/mol]) add-on to dapagliflozin plus metformin (difference, -0.35% [95% CI -0.52% to -0.18%] and -3.8 [-5.7 to -2.0 mmol/mol], respectively; P < 0.0001). Reductions in fasting plasma glucose and 2-h postprandial glucose were similar between treatment arms. A larger proportion of patients achieved HbA1c <7% (53 mmol/mol) with saxagliptin add-on (35.3%) versus placebo add-on (23.1%) to dapagliflozin plus metformin. Adverse events were similar between treatment groups. Episodes of hypoglycemia were infrequent in both treatment arms, and there were no episodes of major hypoglycemia. Triple therapy with the addition of saxagliptin to dapagliflozin plus metformin was well tolerated and produced significant improvements in HbA1c in patients with type 2 diabetes inadequately controlled with dapagliflozin plus metformin. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Single-faced GRAYQB™: a radiation mapping device

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

Mayer, J.; Farfan, E.; Immel, D.

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 inmore » 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

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

PubMed

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.

Optical add/drop filter for wavelength division multiplexed systems

DOEpatents

Deri, Robert J.; Strand, Oliver T.; Garrett, Henry E.

2002-01-01

An optical add/drop filter for wavelength division multiplexed systems and construction methods are disclosed. The add/drop filter includes a first ferrule having a first pre-formed opening for receiving a first optical fiber; an interference filter oriented to pass a first set of wavelengths along the first optical fiber and reflect a second set of wavelengths; and, a second ferrule having a second pre-formed opening for receiving the second optical fiber, and the reflected second set of wavelengths. A method for constructing the optical add/drop filter consists of the steps of forming a first set of openings in a first ferrule; inserting a first set of optical fibers into the first set of openings; forming a first set of guide pin openings in the first ferrule; dividing the first ferrule into a first ferrule portion and a second ferrule portion; forming an interference filter on the first ferrule portion; inserting guide pins through the first set of guide pin openings in the first ferrule portion and second ferrule portion to passively align the first set of optical fibers; removing material such that light reflected from the interference filter from the first set of optical fibers is accessible; forming a second set of openings in a second ferrule; inserting a second set of optical fibers into the second set of openings; and positioning the second ferrule with respect to the first ferrule such that the second set of optical fibers receive the light reflected from the interference filter.

Molecular cytogenetic characterisation of a mosaic add(12)(p13.3) with an inv dup(3)(q26.31 --> qter) detected in an autistic boy.

PubMed

Carreira, Isabel M; Melo, Joana B; Rodrigues, Carlos; Backx, Liesbeth; Vermeesch, Joris; Weise, Anja; Kosyakova, Nadezda; Oliveira, Guiomar; Matoso, Eunice

2009-08-04

Inverted duplications (inv dup) of a terminal chromosome region are a particular subset of rearrangements that often results in partial tetrasomy or partial trisomy when accompanied by a deleted chromosome. Associated mosaicism could be the consequence of a post-zygotic event or could result from the correction of a trisomic conception. Tetrasomies of distal segments of the chromosome 3q are rare genetic events and their phenotypic manifestations are diverse. To our knowledge, there are only 12 cases reported with partial 3q tetrasomy. Generally, individuals with this genomic imbalance present mild to severe developmental delay, facial dysmorphisms and skin pigmentary disorders. We present the results of the molecular cytogenetic characterization of an unbalanced mosaic karyotype consisting of mos 46,XY,add(12)(p13.3) [56]/46,XY [44] in a previously described 11 years old autistic boy, re-evaluated at adult age. The employment of fluorescence in situ hybridization (FISH) and multicolor banding (MCB) techniques identified the extra material on 12p to be derived from chromosome 3, defining the additional material on 12p as an inv dup(3)(qter --> q26.3::q26.3 --> qter). Subsequently, array-based comparative genomic hybridization (aCGH) confirmed the breakpoint at 3q26.31, defining the extra material with a length of 24.92 Mb to be between 174.37 and 199.29 Mb. This is the thirteenth reported case of inversion-duplication 3q, being the first one described as an inv dup translocated onto a non-homologous chromosome. The mosaic terminal inv dup(3q) observed could be the result of two proposed alternative mechanisms. The most striking feature of this case is the autistic behavior of the proband, a characteristic not shared by any other patient with tetrasomy for 3q26.31 --> 3qter. The present work further illustrates the advantages of the use of an integrative cytogenetic strategy, composed both by conventional and molecular techniques, on providing powerful information

Philanthropies Add Weight to "i3" Effort

ERIC Educational Resources Information Center

Robelen, Erik W.; McNeil, Michele

2010-01-01

The author reports on a new effort by 12 major education philanthropies that aims to dovetail with the Education Department's "i3" agenda, raising complex issues. The decision by a dozen major education grantmakers to team up on an initiative designed to dovetail with the federal "Investing in Innovation" grant competition is being seen by…

Photothermally tunable silicon-microring-based optical add-drop filter through integrated light absorber.

PubMed

Chen, Xi; Shi, Yuechun; Lou, Fei; Chen, Yiting; Yan, Min; Wosinski, Lech; Qiu, Min

2014-10-20

An optically pumped thermo-optic (TO) silicon ring add-drop filter with fast thermal response is experimentally demonstrated. We propose that metal-insulator-metal (MIM) light absorber can be integrated into silicon TO devices, acting as a localized heat source which can be activated remotely by a pump beam. The MIM absorber design introduces less thermal capacity to the device, compared to conventional electrically-driven approaches. Experimentally, the absorber-integrated add-drop filter shows an optical response time of 13.7 μs following the 10%-90% rule (equivalent to a exponential time constant of 5 μs) and a wavelength shift over pump power of 60 pm/mW. The photothermally tunable add-drop filter may provide new perspectives for all-optical routing and switching in integrated Si photonic circuits.

47 CFR 73.9006 - Add-in covered demodulator products.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Section 73.9006 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES... passed to an output (e.g., where a demodulator add-in card in a personal computer passes such content to an associated software application installed in the same computer), it shall pass such content: (1...

Unsteady jet in designing innovative drug delivery system

NASA Astrophysics Data System (ADS)

Wang, Cong; Mazur, Paul; Cosse, Julia; Rider, Stephanie; Gharib, Morteza

2014-11-01

Micro-needle injections, a promising pain-free drug delivery method, is constrained by its limited penetration depth. This deficiency can be overcome by implementing fast unsteady jet that can penetrate sub-dermally. The development of a faster liquid jet would increase the penetration depth and delivery volume of micro-needles. In this preliminary work, the nonlinear transient behavior of an elastic tube balloon in providing fast discharge is analyzed. A physical model that combines the Mooney Rivlin Material model and Young-Lapalce's Law was developed and used to investigate the fast discharging dynamic phenomenon. A proof of concept prototype was constructed to demonstrate the feasibility of a simple thumb-sized delivery system to generate liquid jet with desired speed in the range of 5-10 m/s. This work is supported by ZCUBE Corporation.

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

Code of Federal Regulations, 2010 CFR

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...

Empagliflozin as add-on to metformin in people with Type 2 diabetes.

PubMed

Merker, L; Häring, H-U; Christiansen, A V; Roux, F; Salsali, A; Kim, G; Meinicke, T; Woerle, H J; Broedl, U C

2015-12-01

To investigate the long-term efficacy and safety of empagliflozin as add-on to metformin in people with Type 2 diabetes. Of 637 participants treated with empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily for 24 weeks, 463 (72.7%) were treated in a double-blind extension trial for ≥ 52 weeks. Prespecified exploratory endpoints included changes from baseline in HbA1c , weight and blood pressure at week 76. Compared with placebo, adjusted mean changes from baseline in HbA1c (overall baseline mean ± sd 63 ± 9 mmol/mol [7.9 ± 0.9%]) were -7 mmol/mol [(-0.6%) 95% CI -8, -5 mmol/mol (-0.8, -0.5%); P < 0.001] and -8 mmol/mol [(-0.7%) 95% CI -10, -6 mmol/mol (-0.9, -0.6%); P < 0.001], for empagliflozin 10 mg and 25 mg, respectively. Compared with placebo, adjusted mean changes from baseline in weight were -1.9 kg (95% CI -2.5, -1.3; P < 0.001) and -2.2 kg (95% CI -2.8, -1.6; P < 0.001) for empagliflozin 10 mg and 25 mg, respectively. Empagliflozin led to sustained reductions in systolic blood pressure vs. placebo. Adverse events were reported in 77.7, 80.2 and 72.0% of participants on placebo, empagliflozin 10 mg and empagliflozin 25 mg, respectively. Confirmed hypoglycaemic adverse events (glucose ≤ 3.9 mmol/l and/or event requiring assistance) were reported in 3.4, 4.1 and 4.2% of participants in these groups, respectively. In people with Type 2 diabetes, empagliflozin 10 mg and 25 mg given as add-on to metformin for 76 weeks were well tolerated and led to sustained reductions in HbA1c , weight and systolic blood pressure. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

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

PubMed

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.

Do petroleum-based protective coatings add fuel value to slash

Treesearch

James L. Murphy; Charles W. Philpot

1965-01-01

Asphalts and wax emulsions have been recommended as protective coatings to help obtain clean, safe burns in slash disposal work. Fuel value determinations in the laboratory indicate that such coatings add little to the fuel value of slash.

The Impact of a Pay-for-Performance Program on Central Line-Associated Blood Stream Infections in Pennsylvania.

PubMed

Bastian, Nathaniel D; Kang, Hyojung; Nembhard, Harriet B; Bloschichak, Andrew; Griffin, Paul M

2016-01-01

Healthcare associated infections have significantly contributed to the rising cost of hospital care in the United States. The implementation of pay-for-performance (P4P) programs has been one approach to improve quality at a reduced cost. We quantify the impact of Highmark's Quality Blue (QB) hospital P4P program on central line-associated blood stream infections (CLABSI) in Pennsylvania. The impact of years of participation in QB on CLABSI is also evaluated. Data from 149 Pennsylvania hospitals on CLABSI from 2008-2013 are used. Negative binomial regression and fixed effects panel regression are performed. Hospitals participating in QB have 0.727 times the CLABSI as those hospitals that do not participate. Hospitals participating for four or more years have on average 3.13 fewer CLABSI per year compared to those participating for less than four years. Highmark's P4P program has shown improved outcomes with regards to CLABSI, but further research is needed to determine if QB is cost effective.

24 CFR 990.190 - Other formula expenses (add-ons).

Code of Federal Regulations, 2010 CFR

2010-04-01

... operating subsidy is determined to be zero based on the formula is still eligible to receive operating... formula expenses (add-ons). In addition to calculating operating subsidy based on the PEL and UEL, a PHA's... receive an amount for PILOT in accordance with section 6(d) of the 1937 Act, based on its cooperation...

24 CFR 990.190 - Other formula expenses (add-ons).

Code of Federal Regulations, 2011 CFR

2011-04-01

... operating subsidy is determined to be zero based on the formula is still eligible to receive operating... formula expenses (add-ons). In addition to calculating operating subsidy based on the PEL and UEL, a PHA's... receive an amount for PILOT in accordance with section 6(d) of the 1937 Act, based on its cooperation...

Global analysis of double-strand break processing reveals in vivo properties of the helicase-nuclease complex AddAB

PubMed Central

Badrinarayanan, Anjana; Cisse, Ibrahim I.

2017-01-01

In bacteria, double-strand break (DSB) repair via homologous recombination is thought to be initiated through the bi-directional degradation and resection of DNA ends by a helicase-nuclease complex such as AddAB. The activity of AddAB has been well-studied in vitro, with translocation speeds between 400–2000 bp/s on linear DNA suggesting that a large section of DNA around a break site is processed for repair. However, the translocation rate and activity of AddAB in vivo is not known, and how AddAB is regulated to prevent excessive DNA degradation around a break site is unclear. To examine the functions and mechanistic regulation of AddAB inside bacterial cells, we developed a next-generation sequencing-based approach to assay DNA processing after a site-specific DSB was introduced on the chromosome of Caulobacter crescentus. Using this assay we determined the in vivo rates of DSB processing by AddAB and found that putative chi sites attenuate processing in a RecA-dependent manner. This RecA-mediated regulation of AddAB prevents the excessive loss of DNA around a break site, limiting the effects of DSB processing on transcription. In sum, our results, taken together with prior studies, support a mechanism for regulating AddAB that couples two key events of DSB repair–the attenuation of DNA-end processing and the initiation of homology search by RecA–thereby helping to ensure that genomic integrity is maintained during DSB repair. PMID:28489851

Add-on levetiracetam in children and adolescents with refractory epilepsy: results of an open-label multi-centre study.

PubMed

Callenbach, Petra M C; Arts, Willem Frans M; ten Houten, Robert; Augustijn, Paul; Gunning, W Boudewijn; Peeters, Els A J; Weber, Alma M; Stroink, Hans; Geerts, Yvette; Geerts, Ada T; Brouwer, Oebele F

2008-07-01

To study the efficacy and tolerability of add-on levetiracetam in children and adolescents with refractory epilepsy. In this prospective multi-centre, open-label, add-on study, 33 children aged 4-16 years (median 8.5 years) with epilepsy refractory to at least two antiepileptic drugs were treated with levetiracetam in addition to their present treatment regimen with a follow-up of 26 weeks. The starting dose of 10 mg/kg/day was increased with 2-week steps of 10 mg/kg/day, if necessary, up to a maximum dose of 60 mg/kg/day. Retention rate was 69.7% after 26 weeks on a median levetiracetam dosage of 22 mg/kg/day. Four children dropped-out because levetiracetam was ineffective, four because seizure frequency increased and/or seizures became more severe, and two because they developed aggressive behaviour. Compared to their baseline seizure frequency, 13 children (39.4%) had a >50% seizure reduction 12 weeks after initiation of levetiracetam, and 17 children (51.5%) at 26 weeks. At 26 weeks, nine children (27.3%) had been seizure-free for at least the last 4 weeks, terminal remission ranged from 0 to 187 days (mean 46 days). Levetiracetam was effective in both partial and primary generalized seizures, but had most effect in partial seizures. Most reported side effects were hyperactivity (48.5%), somnolence (36.4%), irritability (33.3%) and aggressive behaviour (27.3%). Severity of most side effects was mild. Five children had a serious adverse event, which all concerned hospital admissions that were not related to levetiracetam use. Levetiracetam proved to be an effective and well-tolerated add-on treatment in this group of children with refractory epilepsy.

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

PubMed

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.

Power Parenting for Children with ADD/ADHD: A Practical Parent's Guide for Managing Difficult Behaviors.

ERIC Educational Resources Information Center

Flick, Grad L.

The first step in dealing with an attention deficit disorder (ADD/ADHD) child's difficult behavior is to understand its origins. This book presents behavior management techniques to help parents care for their ADD child while ensuring that the child continues to develop positive, healthy self-esteem. The guide shows how to: (1) ensure an accurate…

Novel tunable dynamic tweezers using dark-bright soliton collision control in an optical add/drop filter.

PubMed

Teeka, Chat; Jalil, Muhammad Arif; Yupapin, Preecha P; Ali, Jalil

2010-12-01

We propose a novel system of the dynamic optical tweezers generated by a dark soliton in the fiber optic loop. A dark soliton known as an optical tweezer is amplified and tuned within the microring resonator system. The required tunable tweezers with different widths and powers can be controlled. The analysis of dark-bright soliton conversion using a dark soliton pulse propagating within a microring resonator system is analyzed. The dynamic behaviors of soliton conversion in add/drop filter is also analyzed. The control dark soliton is input into the system via the add port of the add/drop filter. The dynamic behavior of the dark-bright soliton conversion is observed. The required stable signal is obtained via a drop and throughput ports of the add/drop filter with some suitable parameters. In application, the trapped light/atom and transportation can be realized by using the proposed system.

Quillaja brasiliensis saponins are less toxic than Quil A and have similar properties when used as an adjuvant for a viral antigen preparation.

PubMed

Silveira, F; Cibulski, S P; Varela, A P; Marqués, J M; Chabalgoity, A; de Costa, F; Yendo, A C A; Gosmann, G; Roehe, P M; Fernández, C; Ferreira, F

2011-11-15

In this study, a preparation of saponins (QB-90U) extracted from leaves of Quillaja brasiliensis collected in Uruguay was evaluated as a vaccine adjuvant by comparison with alum and the well known saponin-based adjuvant, Quil A. The haemolytic activity and cellular toxicity of the saponin preparations were also evaluated. QB-90U was only slightly haemolytic and showed a low cytotoxicity when compared to Quil A. The adjuvant properties of QB-90U were assayed by sub-cutaneous immunization of mice with a preparation of inactivated bovine herpesvirus 5 (BoHV-5) either with no adjuvant or adjuvanted with QB-90U, Quil A or alum. Serum levels of anti-BoHV-5 IgG, IgG1, IgG2a, IgG2b and also IgG3 were significantly increased by QB-90U and were of the same order as those elicited by Quil A. Furthermore, high titres of neutralizing antibodies were found to be present in the serum of immunized animals from both groups. The cellular response induced by QB-90U did also reproduce the one elicited by Quil A. In fact, a robust DTH response was observed in mice immunized with both saponin preparations; as well as increased splenocytes levels of Th1-type cytokines, namely IFN-γ and IL-2. Taken together, the above results confirm and extend our previous observation regarding the similarity of the responses elicited by Quil A and the saponin preparation from Q. brasiliensis (Fleck et al., 2006) and indicate that QB-90U is worth of further studies as a safe and potent vaccine adjuvant. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed

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.

PubMed

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®.

Acute symptoms during and between hemodialysis: the relative role of speed, duration, and biocompatibility of dialysis.

PubMed

Skroeder, N R; Jacobson, S H; Lins, L E; Kjellstrand, C M

1994-12-01

The relationship between hemodialysis (HD) symptoms and dialyzer membrane composition and area, blood-flow, treatment duration, urea removal, ultrafiltration volume, leukocyte activation, and complement generation (C3a) was studied in 20 patients undergoing 234 HD treatments by 12 different modes in random order using Cuprophan, hemophane, or polyamide membranes with small or large membrane areas with high Qb (400 ml/min) and short duration (2 h) or low Qb (200 ml/min) and long duration (4 h). Fewer symptoms occurred during the 2-h HD at high Qb than during the 4-h HD with low Qb (19% vs. 32%, p = 0.0351). No differences were observed between different dialyzer membranes or areas. More intradialytic symptoms occurred when urea elimination was high than it was low (p = 0.0044). Leukocyte activation (leukocyte drop) after 15 min of dialysis and complement generation did not influence symptom incidence. Blood pressure changes were mainly influenced by ultrafiltration volume (p < 0.001). Symptoms between dialyses were determined by urea removal and ultrafiltration. Membrane, area, or Qb were of no importance. Thus, duration of dialysis, urea removal, and demand for ultrafiltration, but not membrane composition, area, or biocompatability, are important for the development of HD-related symptoms.

Serum cardiac troponin T and effective blood flow in stable extracorporeal dialysis patients.

PubMed

Grzegorzewska, Alicja E; Cieszyński, Krzysztof; Niepolski, Leszek; Kaczmarek, Andrzej; Sowińska, Anna

2016-03-01

We examined the association between extracorporeal dialysis (ED)-related effective blood flow (eQB) and serum cardiac troponin T (cTnT) as a possible indicator of silent myocardial damage in stable ED patients. In a cross-sectional study, cTnT was determined in 247 ED patients dialyzed using stable eQB and dialysate flow (QD). In a prospective study, 91 patients were switched from low-flux (LF) to high-flux (HF) hemodialysis (HD), and subsequently, the eQB increased, and the QD decreased; 65 patients continued LF-HD with stable eQB and QD. Clinical/laboratory evaluations were performed at 0, 15, 36, and 53 weeks from the start of the study. In the cross-sectional study, the main cTnT predictors were dialysis vintage, age, eQB, phosphorus, and C-reactive protein. Patients with cTnT levels in the highest quartile were excluded from the analysis, and subjects dialyzed with eQB ≤316 ml/min exhibited lower cTnT levels compared with patients dialyzed with higher eQB (P = 0.002). The all-cause and cardiac mortality rates of 154 patients, without changes in ED modality for up to 42 months, were associated with the initial cTnT concentrations but not with the initial eQB. In the prospective study, higher values for eQB and cTnT were observed during HF-HD at weeks 36 (P = 0.045) and 53 (P = 0.01) of the present study. The initial cTnT, ∆eQB, and ∆albumin influenced the ∆cTnT. The all-cause and cardiac mortality rates were not different between LF and HF groups at 21 months after the prospective study was completed. In stable ED patients, higher eQB rates and QB/QD values might contribute to silent myocardial injury, particularly in patients with lower cTnT levels, but do not affect the outcome of ED patients.

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.

PubMed

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.

PubMed

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.

PubMed

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.

Meeting Learning Challenges: Working with the Child Who Has ADD

ERIC Educational Resources Information Center

Greenspan, Stanley I.

2006-01-01

The terms ADD (Attention Deficit Disorder) and ADHD (Attention Deficit Hyperactivity Disorder) are applied to several symptoms, including: difficulty in paying attention, distractibility, having a hard time following through on things, and sometimes over-activity and impulsivity. There are many different reasons why children have these symptoms.…

Molecular cytogenetic characterisation of a mosaic add(12)(p13.3) with an inv dup(3)(q26.31 → qter) detected in an autistic boy

PubMed Central

Carreira, Isabel M; Melo, Joana B; Rodrigues, Carlos; Backx, Liesbeth; Vermeesch, Joris; Weise, Anja; Kosyakova, Nadezda; Oliveira, Guiomar; Matoso, Eunice

2009-01-01

Background Inverted duplications (inv dup) of a terminal chromosome region are a particular subset of rearrangements that often results in partial tetrasomy or partial trisomy when accompanied by a deleted chromosome. Associated mosaicism could be the consequence of a post-zygotic event or could result from the correction of a trisomic conception. Tetrasomies of distal segments of the chromosome 3q are rare genetic events and their phenotypic manifestations are diverse. To our knowledge, there are only 12 cases reported with partial 3q tetrasomy. Generally, individuals with this genomic imbalance present mild to severe developmental delay, facial dysmorphisms and skin pigmentary disorders. Results We present the results of the molecular cytogenetic characterization of an unbalanced mosaic karyotype consisting of mos 46,XY,add(12)(p13.3) [56]/46,XY [44] in a previously described 11 years old autistic boy, re-evaluated at adult age. The employment of fluorescence in situ hybridization (FISH) and multicolor banding (MCB) techniques identified the extra material on 12p to be derived from chromosome 3, defining the additional material on 12p as an inv dup(3)(qter → q26.3::q26.3 → qter). Subsequently, array-based comparative genomic hybridization (aCGH) confirmed the breakpoint at 3q26.31, defining the extra material with a length of 24.92 Mb to be between 174.37 and 199.29 Mb. Conclusion This is the thirteenth reported case of inversion-duplication 3q, being the first one described as an inv dup translocated onto a non-homologous chromosome. The mosaic terminal inv dup(3q) observed could be the result of two proposed alternative mechanisms. The most striking feature of this case is the autistic behavior of the proband, a characteristic not shared by any other patient with tetrasomy for 3q26.31 → 3qter. The present work further illustrates the advantages of the use of an integrative cytogenetic strategy, composed both by conventional and molecular techniques, on

Humor adds the creative touch to CQI teams.

PubMed

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 product development: A quality by design approach

PubMed Central

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.

PubMed

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.

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

PubMed

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.

Does fibrinogen add to prediction of cardiovascular disease? Results from the Scottish Heart Health Extended Cohort Study.

PubMed

Woodward, Mark; Tunstall-Pedoe, Hugh; Rumley, Ann; Lowe, Gordon D O

2009-08-01

Plasma fibrinogen is an established risk factor for cardiovascular disease (CVD), but it has not been established whether it adds predictive value to risk scores. In the Scottish Heart Health Extended Cohort Study, we measured plasma fibrinogen in 13 060 men and women, aged 30-74 years, initially free of CVD. After follow-up for a median of 19.2 years, 2626 subjects had at least one CVD event. After adjusting for classical CVD risk factors and socio-economic status, the hazard ratios (95% confidence interval) for a one unit (g/l) increase in plasma fibrinogen were 1.09 (1.02, 1.16) for men and 1.10 (1.02, 1.19) for women. Although fibrinogen added significantly to the discrimination of the Framingham risk score for women, it failed to do so for men. Fibrinogen did not add significantly to the ASSIGN risk score. Fibrinogen added between 1.3% and 3.2% to the classification of CVD status by the existing risk scores. We conclude that the added value of fibrinogen to two currently used risk scores is low; hence population screening with fibrinogen for this purpose is unlikely to be clinically useful or cost-effective.

NASA Adds Leap Second to Master Clock

NASA Image and Video Library

2017-12-08

On Dec. 31, 2016, official clocks around the world will add a leap second just before midnight Coordinated Universal Time — which corresponds to 6:59:59 p.m. EST. NASA missions will also have to make the switch, including the Solar Dynamics Observatory, or SDO, which watches the sun 24/7. Clocks do this to keep in sync with Earth's rotation, which gradually slows down over time. When the dinosaurs roamed Earth, for example, our globe took only 23 hours to make a complete rotation. In space, millisecond accuracy is crucial to understanding how satellites orbit. "SDO moves about 1.9 miles every second," said Dean Pesnell, the project scientist for SDO at NASA's Goddard Space Flight Center in Greenbelt, Maryland. "So does every other object in orbit near SDO. We all have to use the same time to make sure our collision avoidance programs are accurate. So we all add a leap second to the end of 2016, delaying 2017 by one second." The leap second is also key to making sure that SDO is in sync with the Coordinated Universal Time, or UTC, used to label each of its images. SDO has a clock that counts the number of seconds since the beginning of the mission. To convert that count to UTC requires knowing just how many leap seconds have been added to Earth-bound clocks since the mission started. When the spacecraft wants to provide a time in UTC, it calls a software module that takes into consideration both the mission's second count and the number of leap seconds — and then returns a time in UTC.

Randomized, Double-Blind, Phase 3 Trial of Triple Therapy With Dapagliflozin Add-on to Saxagliptin Plus Metformin in Type 2 Diabetes.

PubMed

Mathieu, Chantal; Ranetti, Aurelian Emil; Li, Danshi; Ekholm, Ella; Cook, William; Hirshberg, Boaz; Chen, Hungta; Hansen, Lars; Iqbal, Nayyar

2015-11-01

To compare the efficacy and safety of treatment with dapagliflozin versus that with placebo add-on to saxagliptin plus metformin in patients whose type 2 diabetes is inadequately controlled with saxagliptin plus metformin treatment. Patients receiving treatment with stable metformin (stratum A) (screening HbA1c level 8.0-11.5% [64-102 mmol/mol]) or stable metformin and a dipeptidyl peptidase-4 (DPP-4) inhibitor (stratum B) (HbA1c 7.5-10.5% [58-91 mmol/mol]) for ≥8 weeks received open-label saxagliptin 5 mg/day and metformin for 16 weeks (stratum A) or 8 weeks (stratum B) (saxagliptin replaced any DPP-4 inhibitor). Patients with inadequate glycemic control (HbA1c 7-10.5% [53-91 mmol/mol]) were randomized to receive placebo or dapagliflozin 10 mg/day plus saxagliptin and metformin. The primary end point was the change in HbA1c from baseline to week 24. Secondary end points included fasting plasma glucose (FPG) level, 2-h postprandial glucose (PPG) level, body weight, and proportion of patients achieving an HbA1c level of <7% (53 mmol/mol). Treatment with dapagliflozin add-on to saxagliptin plus metformin resulted in a greater mean HbA1c reduction than placebo (-0.82 vs. -0.10% [-9 vs. -1.1 mmol/mol], P < 0.0001). Significantly greater reductions in FPG level, 2-h PPG level, and body weight were observed, and more patients achieved an HbA1c level of <7% (53 mmol/mol) with treatment with dapagliflozin versus placebo. Adverse events were similar across treatment groups, with a low overall risk of hypoglycemia (∼1%). Genital infections developed in more patients with dapagliflozin treatment (5%) than with placebo (0.6%). Triple therapy with dapagliflozin add-on to saxagliptin plus metformin improves glycemic control and is well tolerated in patients whose type 2 diabetes is inadequately controlled with saxagliptin plus metformin therapy. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is

Tour of the World’s Largest 3D Printed Polymer Structure on Display at IBS 2016

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

Green, Johney

ORNL’s Johney Green guides a Periscope tour of the 3D printed house and vehicle demonstration called AMIE (Additive Manufacturing Integrated Energy) during the International Builders’ Show 2016 in Las Vegas. See the world’s largest 3D printed polymer structure – made with carbon fiber reinforced ABS plastic, insulated with next-generation vacuum insulation panels, and outfitted with a micro-kitchen by GE Appliances – that was designed to be powered by a 3D printed utility vehicle using bidirectional wireless power technology. Learn more about AMIE at https://www.youtube.com/watch?v=RCkQB... and http://www.ornl.gov/amie.

40 CFR 63.4965 - How do I determine the add-on control device emission destruction or removal efficiency?

Code of Federal Regulations, 2010 CFR

2010-07-01

... an alternative to Method 3B, the manual method for measuring the oxygen, carbon dioxide, and carbon..., Instruments and Apparatus]” (incorporated by reference, see § 63.14). (4) Use Method 4 of appendix A to 40 CFR... total gaseous organic mass emissions as carbon at the inlet and outlet of the add-on control device...

40 CFR 63.3545 - How do I determine the add-on control device emission destruction or removal efficiency?

Code of Federal Regulations, 2010 CFR

2010-07-01

... an alternative to Method 3B the manual method for measuring the oxygen, carbon dioxide, and carbon..., Instruments and Apparatus]” (incorporated by reference, see § 63.14). (4) Use Method 4 of appendix A to 40 CFR... total gaseous organic mass emissions as carbon at the inlet and outlet of the add-on control device...

Project DyAdd: Visual Attention in Adult Dyslexia and ADHD

ERIC Educational Resources Information Center

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

Code of Federal Regulations, 2013 CFR

2013-07-01

... system and add-on control device operating limits during the performance test? 63.4167 Section 63.4167... Emission Rate 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...

Chance of reimbursement for ADD-ON therapies in Poland and in the world - review of the reimbursement recommendations

PubMed

Borowiack, Ewa; Marzec, Magdalena; Nowotarska, Anna; Jarosz, Joanna; Orkisz, Agata; Prząda-Machno, Patrycja

2018-01-01

Oncology drugs combined with standard therapies (so-called add-on therapies, e.g. bevacizumab, palbociclib) often receive negative recommendations regarding the legitimacy of public financing, issued by government agencies responsible for their assessment, i.e. health technology assessment agencies. The aim of the study was to estimate the scale of the problem related to the reimbursement of add-on therapies used in the treatment of breast and genitourinary cancers in Poland and in the world. A multimodal approach was used to select add-on therapies. The reimbursement routes were analysed in 8 reference countries (Poland, Canada, England, Wales, France, Scotland, Australia, New Zealand). Based on a systematic search, data for breast and urogenital cancers were included. A total of 68 reimbursement documents for add-on therapies were identified. The analysis showed that in Poland, 20% of innovative schemes including add-on therapies should be reimbursed, while in the world the percentage of positive recommendations reaches 56%. It was observed that globally (including data for Poland) the chance for a favorable reimbursement recommendation for add-on therapies is 53%, with 29% being positive recommendations with limitations. In Poland, the majority of negative recommendations concern genitourinary cancers in comparison to breast cancer (83% vs 75%). Poland is at the head of the countries in terms of the number of negative reimbursement recommendations. Bearing in mind the world’s need of modifying the criteria for the evaluation of oncological therapies in the context of the possibility of their reimbursement, one should expect a change in the approach to the assessment of the legitimacy of financing innovative add-on therapies in Poland.

Steep Gravel Bedload Rating Curves Obtained From Bedload Traps Shift Effective Discharge to Flows Much Higher Than "Bankfull"

NASA Astrophysics Data System (ADS)

Bunte, K.; Swingle, K. W.; Abt, S. R.; Cenderelli, D.

2012-12-01

Effective discharge (Qeff) is defined as the flow at which the product of flow frequency and bedload transport rates obtains its maximum. Qeff is often reported to correspond with bankfull flow (Qbf), where Qeff approximates the 1.5 year recurrence interval flow (Q1.5). Because it transports the majority of all bedload, Qeff is considered a design flow for stream restoration and flow management. This study investigates the relationship between Qeff and Q1.5 for gravel bedload in high elevation Rocky Mountain streams. Both the flow frequency distribution (FQ = a × Qbin-b) where Qbin is the flow class, and the bedload transport rating curve (QB = c × Qd) can be described by power functions. The product FQ × QB = (a × c × Q(-b + d)) is positive if d + -b >0, and negative if d + -b <0. FQ × QB can only attain a maximum (=Qeff) if either FQ or QB exhibit an inflection point. In snowmelt regimes, low flows prevail for much of the year, while high flows are limited to a few days, and extreme floods are rare. In log-log plotting scale, this distribution causes the longterm flow frequency function FQ to steepen in the vicinity of Q1.5. If the bedload rating curve exponent is small, e.g., = 3 as is typical of Helley-Smith bedload samples, d + -b shifts from >0 to <0, causing FQ × QB to peak, and Qeff to be around Q1.5. For measurements thought to be more representative of actual gravel transport obtained using bedload traps and similar devices, large rating curve exponents d of 6 - 16 are typical. In this case, d + -b remains >0, and FQ × QB reaches its maximum near the largest flow on record (Qeff,BT = Qmax). Expression of FQ by negative exponential functions FQ = k × e(Qbin×-m) smooths the product function FQ × QB that displays its maximum as a gentle hump rather than a sharp peak, but without drastically altering Qeff. However, a smooth function FQ × QB allows Qeff to react to small changes in rating curve exponents d. As d increases from <1 to >10, Qeff

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

Code of Federal Regulations, 2011 CFR

2011-07-01

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

Code of Federal Regulations, 2010 CFR

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

Code of Federal Regulations, 2013 CFR

2013-07-01

... 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... Emission Rate with Add-on Controls Option § 63.4966 How do I establish the emission capture system and add...

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... 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...

Code of Federal Regulations, 2010 CFR

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... 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...

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

Code of Federal Regulations, 2010 CFR

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...

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

Code of Federal Regulations, 2010 CFR

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... 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...

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

DTIC Science & Technology

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

Reprogramming of leukemic cell metabolism through the naphthoquinonic compound Quambalarine B

PubMed Central

Vališ, Karel; Grobárová, Valéria; Hernychová, Lucie; Bugáňová, Martina; Kavan, Daniel; Kalous, Martin; Černý, Jiří; Stodůlková, Eva; Kuzma, Marek; Flieger, Miroslav; Černý, Jan; Novák, Petr

2017-01-01

Abnormalities in cancer metabolism represent potential targets for cancer therapy. We have recently identified a natural compound Quambalarine B (QB), which inhibits proliferation of several leukemic cell lines followed by cell death. We have predicted ubiquinone binding sites of mitochondrial respiratory complexes as potential molecular targets of QB in leukemia cells. Hence, we tracked the effect of QB on leukemia metabolism by applying several omics and biochemical techniques. We have confirmed the inhibition of respiratory complexes by QB and found an increase in the intracellular AMP levels together with respiratory substrates. Inhibition of mitochondrial respiration by QB triggered reprogramming of leukemic cell metabolism involving disproportions in glycolytic flux, inhibition of proteins O-glycosylation, stimulation of glycine synthesis pathway, and pyruvate kinase activity, followed by an increase in pyruvate and a decrease in lactate levels. Inhibition of mitochondrial complex I by QB suppressed folate metabolism as determined by a decrease in formate production. We have also observed an increase in cellular levels of several amino acids except for aspartate, indicating the dependence of Jurkat (T-ALL) cells on aspartate synthesis. These results indicate blockade of mitochondrial complex I and II activity by QB and reduction in aspartate and folate metabolism as therapeutic targets in T-ALL cells. Anti-cancer activity of QB was also confirmed during in vivo studies, suggesting the therapeutic potential of this natural compound. PMID:29262552

The use of a supplemental sulcus fixated IOL (HumanOptics Add-On IOL) to correct pseudophakic refractive errors.

PubMed

Basarir, Berna; Kaya, Vedat; Altan, Cigdem; Karakus, Sezen; Pinarci, Eylem Y; Demirok, Ahmet

2012-01-01

To evaluate the safety and efficacy of piggybacking with the HumanOptics Add-On intraocular lens (IOL) to correct pseudophakic refractive errors. Ten eyes of 10 patients with pseudophakic refractive errors were included in this study. All patients were targeted for a range of refraction -0.50 to +0.50 D. Uncorrected and corrected distance visual acuities (UDVA and CDVA, respectively), endothelial cell count (ECC), anterior chamber depth (ACD), the distance between intraocular lenses, and contrast sensitivity measurements under mesopic, scotopic, and scotopic with glare conditions were evaluated preoperatively and postoperatively. The mean age of the patients was 54±27 years (range 4-78). Mean follow-up time was 10.5±1.36 months (range 6-15 months). Mean diopters of implanted Add-On IOLs were -1.4±6.9 (range -12 to +9 D). Mean preoperative and postoperative UDVA was 0.133±0.12 and 0.73±0.27, respectively (p=0.0001); mean preoperative and postoperative CDVA were 0.77±0.26 and 0.79±0.27, respectively (p=0.066). Mean preoperative and postoperative ACD were 3.87±0.91 mm vs 3.58±1.05 mm, respectively (p=0.343); mean inter-IOL distance was 0.53±0.08 mm. Mean preoperative and postoperative ECC were 2455±302 and 2426±294, respectively (p=0.55). All patients were within the targeted refractive range of -0.50 D to +0.50 D. No complications were observed during the operations or postoperative follow-up period. Piggybacking with the Add-On IOL is a safe, efficient, and reliable technique to correct pseudophakic refractive errors.

Evaluation of ADD392124 for the Delayed Treatment of Nerve Agent-Induced Status Epilepticus Seizures

DTIC Science & Technology

2011-09-01

Induced Status Epilepticus Seizures John H. McDonough Kerry E. Van Shura Megan E. Lyman Claire G. Eisner Amelia Mazza Robert K. Kan Tsung...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Evaluation of ADD392124 for the delayed treatment of nerve agent-induced status epilepticus seizures 5b... status epilepticus seizures. We evaluated the ability of ADD392124 to control seizures induced by the nerve agent soman. Rats were exposed to a

Digging Postholes Adds Depth and Authenticity to a Shallow Curriculum

ERIC Educational Resources Information Center

Virtue, David C.; Buchanan, Anne; Vogler, Kenneth E.

2012-01-01

In the current era of high-stakes testing and accountability, many social studies teachers struggle to find creative ways to add depth and authenticity to a broad, shallow curriculum. Teachers can use the time after tests are administered for students to reflect back on the social studies curriculum and select topics they want to study more deeply…

Project DyAdd: Implicit Learning in Adult Dyslexia and ADHD

ERIC Educational Resources Information Center

Laasonen, Marja; Väre, Jenni; Oksanen-Hennah, Henna; Leppämäki, Sami; Tani, Pekka; Harno, Hanna; Hokkanen, Laura; Pothos, Emmanuel; Cleeremans, Axel

2014-01-01

In this study of the project DyAdd, implicit learning was investigated through two paradigms in adults (18-55 years) with dyslexia (n?=?36) or with attention deficit/hyperactivity disorder (ADHD, n?=?22) and in controls (n?=?35). In the serial reaction time (SRT) task, there were no group differences in learning. However, those with ADHD exhibited…

Spin-lattice relaxation of coupled metal-radical spin-dimers in proteins: application to Fe(2+)-cofactor (Q(A)(-.), Q(B)(-.), phi(-.)) dimers in reaction centers from photosynthetic bacteria.

PubMed Central

Calvo, Rafael; Isaacson, Roger A; Abresch, Edward C; Okamura, Melvin Y; Feher, George

2002-01-01

The spin-lattice relaxation times (T(1)) for the reduced quinone acceptors Q(A)(-.) and Q(B)(-.), and the intermediate pheophytin acceptor phi(-.), were measured in native photosynthetic reaction centers (RC) containing a high spin Fe(2+) (S = 2) and in RCs in which Fe(2+) was replaced by diamagnetic Zn(2+). From these data, the contribution of the Fe(2+) to the spin-lattice relaxation of the cofactors was determined. To relate the spin-lattice relaxation rate to the spin-spin interaction between the Fe(2+) and the cofactors, we developed a spin-dimer model that takes into account the zero field splitting and the rhombicity of the Fe(2+) ion. The relaxation mechanism of the spin-dimer involves a two-phonon process that couples the fast relaxing Fe(2+) spin to the cofactor spin. The process is analogous to the one proposed by R. Orbach (Proc. R. Soc. A. (Lond.). 264:458-484) for rare earth ions. The spin-spin interactions are, in general, composed of exchange and dipolar contributions. For the spin dimers studied in this work the exchange interaction, J(o), is predominant. The values of J(o) for Q(A)(-.)Fe(2+), Q(B)(-.)Fe(2+), and phi(-.)Fe(2+) were determined to be (in kelvin) -0.58, -0.92, and -1.3 x 10(-3), respectively. The |J(o)| of the various cofactors (obtained in this work and those of others) could be fitted with the relation exp(-beta(J)d), where d is the distance between cofactor spins and beta(J) had a value of (0.66-0.86) A(-1). The relation between J(o) and the matrix element |V(ij)|(2) involved in electron transfer rates is discussed. PMID:12414679

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.

PubMed

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.

A novel photonic crystal ring resonator configuration for add/drop filtering

NASA Astrophysics Data System (ADS)

Zhang, Juan; Liu, Hao; Ding, Yipeng; Wang, Yang

2018-07-01

A novel compact photonic crystal ring resonator (PCRR) configuration is proposed to realize high-efficiency waveguided add-drop filtering. Its wavelength selection and dropping-direction exchange functions are demonstrated numerically. The working mechanism of this nested dual-loop resonant cavity structure is analyzed in detail.

Effects of postmeal exercise on postprandial glucose excursions in people with type 2 diabetes treated with add-on hypoglycemic agents.

PubMed

Erickson, Melissa L; Little, Jonathan P; Gay, Jennifer L; McCully, Kevin K; Jenkins, Nathan T

2017-04-01

Type 2 diabetes treatment primarily focuses on reducing hyperglycemia, including postprandial glucose excursions. Hypoglycemic agents are used clinically to lower fasting and postprandial glucose. Metformin is the first-line therapy; however, if metformin is inadequate then 'add-on' hypoglycemic agents are implemented. Postmeal exercise has been shown to lower postprandial glucose. The aim of this study was to assess if postmeal exercise provides additional glucose-lowering benefit, beyond medication alone, in those on add-on hypoglycemic agents. Postprandial glucose excursions in eight participants with type 2 diabetes (Age: 60±10.7, HbA 1C : 7.9±2.3) being treated with add-on hypoglycemic agents were assessed during both drug-treated sedentary and drug-treated postmeal exercise conditions. Continuous glucose monitoring was used to assess peak and area under the glucose curve (AUC) during exercise, as well as peak within a 2-h time window, 2-h total and 2-h incremental AUC after a standardized breakfast meal. Postmeal exercise consisted of 3×10-min intervals of treadmill walking at 50% maximal oxygen uptake. Glucose peak (drug only: 13.8±3.7, drug/exercise: 9.9±2.7mmol/L; p=0.02) and AUC (drug only: 500±136, drug/exercise: 357±89mmol/L×40min; p=0.03) were reduced during postmeal exercise. Breakfast 2-h incremental AUC was also reduced (drug only: 585±291, drug/exercise: 330±294; p=0.047). Post-breakfast exercise lowered glucose during the exercise bout, although this effect was not sustained on later meals. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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.

Lopez-Alegria adds patch to bulkhead in Node 1 / Unity module

NASA Image and Video Library

2007-04-17

ISS014-E-19541 (17 April 2007) --- Astronaut Michael E. Lopez-Alegria, Expedition 14 commander and NASA space station science officer, adds the Expedition 14 patch to the Unity node's growing collection of insignias representing crews who have lived and worked on the International Space Station.

Add/drop filters based on SiC technology for optical interconnects

NASA Astrophysics Data System (ADS)

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

2014-03-01

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.

Influence of the effective lens position, as predicted by axial length and keratometry, on the near add power of multifocal intraocular lenses.

PubMed

Savini, Giacomo; Hoffer, Kenneth J; Lombardo, Marco; Serrao, Sebastiano; Schiano-Lomoriello, Domenico; Ducoli, Pietro

2016-01-01

To calculate the near focal distance of different multifocal intraocular lenses (IOLs) as a function of the 2 parameters that are measured before cataract surgery; that is, axial length (AL) and refractive corneal power (keratometry [K]). GB Bietti Foundation IRCCS, Rome, Italy. Noninterventional theoretical study. The IOL power for emmetropia was first calculated in an eye model with the AL ranging from 20 to 30 mm and K from 38 to 48 diopters (D). Then, the predicted myopic refraction for any given IOL add power (from +1.5 to +4.0 D) was calculated, and from this value the near focal distance was obtained. Calculations were also performed for the average eye (K = 43.81 D; AL = 23.65 mm). The near focal distance increased with increasing values of K and AL for each near power add. The near focal distance ranged between 53 cm and 72 cm (21 inches and 28 inches) for a multifocal IOL with +2.50 D, between 44 cm and 60 cm (17 inches and 24 inches) for a multifocal IOL with +3.00 D add, and between 33 cm and 44 cm (13 inches and 18 inches) for a multifocal IOL with +4.00 D add. In the average eye, the near focal distance ranges between 36 cm (near add power = 4.00 D) and 99 cm (near add power = 1.5 D). Longer eyes with steeper corneas showed the longest near focal distance and could experience more difficulties in focusing near objects after surgery. The opposite was true for short hyperopic eyes. Dr. Hoffer receives licensing fees for the commercial use of the registered trademark Hoffer from all biometry manufacturers using the Hoffer Q formula to ensure that it is programmed correctly and book royalties from Slack, Inc., for the textbook IOL Power. None of the authors has a financial or proprietary interest in any material or method mentioned. Copyright © 2016 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

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

PubMed

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.

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

PubMed Central

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

2017-01-01

Abstract 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. PMID:29049185

Efficacy and Safety of Saxagliptin as Add-On Therapy in Type 2 Diabetes

PubMed Central

Neumiller, Joshua J.

2014-01-01

In Brief Combination therapy for type 2 diabetes using agents with complementary mechanisms of action may improve glycemic control to a greater extent than monotherapy and allow the use of lower doses of antihyperglycemic medications. Dipeptidyl peptidase-4 inhibitors, including saxagliptin, are recommended as add-on therapy to metformin and as part of two- or three-drug combinations in patients not meeting individualized glycemic goals with metformin alone or as part of a dual-therapy regimen. This article reviews the efficacy and safety of saxagliptin as an add-on therapy to metformin, glyburide, a thiazolidinedione, or insulin (with or without metformin) and as a component of triple therapy with metformin and a sulfonylurea. PMID:25646943

How to Add Philosophy Dimensions in Your Basic International Business Course

ERIC Educational Resources Information Center

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…

A third-order silicon racetrack add-drop filter with a moderate feature size

NASA Astrophysics Data System (ADS)

Wang, Ying; Zhou, Xin; Chen, Qian; Shao, Yue; Chen, Xiangning; Huang, Qingzhong; Jiang, Wei

2018-01-01

In this work, we design and fabricate a highly compact third-order racetrack add-drop filter consisting of silicon waveguides with modified widths on a silicon-on-insulator (SOI) wafer. Compared to the previous approach that requires an exceedingly narrow coupling gap less than 100nm, we propose a new approach that enlarges the minimum feature size of the whole device to be 300 nm to reduce the process requirement. The three-dimensional finite-difference time-domain (3D-FDTD) method is used for simulation. Experiment results show good agreement with simulation results in property. In the experiment, the filter shows a nearly box-like channel dropping response, which has a large flat 3-dB bandwidth ({3 nm), relatively large FSR ({13.3 nm) and out-of-band rejection larger than 14 dB at the drop port with a footprint of 0.0006 mm2 . The device is small and simple enough to have a wide range of applications in large scale on-chip photonic integration circuits.

Sturckow adds STS-128 crew patch to wall in Node 1 Unity

NASA Image and Video Library

2009-09-07

S128-E-007940 (7 Sept. 2009) --- NASA astronaut Rick Sturckow, STS-128 commander, adds his crew’s patch to the growing collection, in the Unity node, of insignias representing crews who have worked on the International Space Station.

Sturckow adds STS-128 crew patch to wall in Node 1 Unity

NASA Image and Video Library

2009-09-07

S128-E-007939 (7 Sept. 2009) --- NASA astronaut Rick Sturckow, STS-128 commander, adds his crew’s patch to the growing collection, in the Unity node, of insignias representing crews who have worked on the International Space Station.

Cilostazol as an add-on therapy for patients with Alzheimer's disease in Taiwan: a case control study.

PubMed

Tai, Shu-Yu; Chen, Chun-Hung; Chien, Chen-Yu; Yang, Yuan-Han

2017-02-23

Combination therapy using acetylcholinesterase inhibitors (AChEIs) and cilostazol is of unknown efficacy for patients with Alzheimer's disease (AD). We explored the therapeutic responses by using a case-control study, which was conducted in Taiwan. We enrolled 30 participants with stable AD who were receiving cilostazol (50 mg) twice per day as an add-on therapy combined with AChEIs, and 30 participants as controls who were not receiving cilostazol as an add-on therapy. The therapeutic responses were measured using neuropsychological assessments and analyzed in relation to cilostazol use, apolipoprotein E genotype, and demographic characteristics. Mini-mental state examination (MMSE) and clinical dementia rating sum of boxes (CDR-SB) were administered at the outset of the study and 12 months later. Multiple logistic regression analysis was used to estimate the association between the therapeutic response and cilostazol use. For the therapeutic indicator of cognition, Cilostazol use (adjusted odds ratio (aOR) = 0.17, 95% confidence interval (CI) = 0.03-0.80), initial CDR-SB score (aOR = 2.06, 95% CI = 1.31-3.72), and initial MMSE score (aOR = 1.41, 95% CI = 1.11-1.90), but not age, sex, education, or ApoE ε4 status, were significantly associated with poor therapeutic outcomes. For the therapeutic indicator of global status, no significant association was observed between the covariates and poor therapeutic outcomes. Cilostazol may reduce the decline of cognitive function in stable AD patients when applied as an add-on therapy.

76 FR 37114 - Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort AGENCY: National Institute for Occupational Safety and Health... determination concerning a petition to add a class of employees from the Linde Ceramics Plant in Tonawanda, New...

77 FR 76490 - Determination Concerning a Petition to Add a Class of Employees to the Special Exposure Cohort

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Determination Concerning a Petition to Add a Class of Employees to the Special Exposure Cohort AGENCY: National Institute for Occupational Safety and Health...). ACTION: Notice. SUMMARY: HHS gives notice of a determination concerning a petition to add a class of...

76 FR 37114 - Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort AGENCY: National Institute for Occupational Safety and Health... determination concerning a petition to add a class of employees from the Dow Chemical Company in Madison...

77 FR 9251 - Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort AGENCY: National Institute for Occupational Safety and Health...). ACTION: Notice. SUMMARY: HHS gives notice of a determination concerning a petition to add a class of...

78 FR 98 - Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort AGENCY: National Institute for Occupational Safety and Health...). ACTION: Notice. SUMMARY: HHS gives notice of a determination concerning a petition to add a class of...

76 FR 37115 - Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort AGENCY: National Institute for Occupational Safety and Health... determination concerning a petition to add a class of employees from the Bliss & Laughlin Steel Company located...

76 FR 37115 - Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort AGENCY: National Institute for Occupational Safety and Health... determination concerning a petition to add a class of employees from the Wah Chang facility in Albany, Oregon...

78 FR 64501 - Determination Concerning a Petition to Add a Class of Employees to the Special Exposure Cohort

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Determination Concerning a Petition to Add a Class of Employees to the Special Exposure Cohort AGENCY: National Institute for Occupational Safety and Health...). ACTION: Notice. SUMMARY: HHS gives notice of a determination concerning a petition to add a class of...

77 FR 58383 - Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort AGENCY: National Institute for Occupational Safety and Health...). ACTION: Notice. SUMMARY: HHS gives notice of a determination concerning a petition to add a class of...

78 FR 64502 - Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort AGENCY: National Institute for Occupational Safety and Health...). ACTION: Notice. SUMMARY: HHS gives notice of a determination concerning a petition to add a class of...

76 FR 37115 - Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort AGENCY: National Institute for Occupational Safety and Health... determination concerning a petition to add a class of employees from the Chapman Valve Manufacturing Company (i...

Antileukotriene Agents Versus Long-Acting Beta-Agonists in Older Adults with Persistent Asthma: A Comparison of Add-On Therapies.

PubMed

Altawalbeh, Shoroq M; Thorpe, Carolyn T; Zgibor, Janice C; Kane-Gill, Sandra; Kang, Yihuang; Thorpe, Joshua M

2016-08-01

To compare the effectiveness and cardiovascular safety of long-acting beta-agonists (LABAs) with those of leukotriene receptor antagonists (LTRAs) as add-on treatments in older adults with asthma already taking inhaled corticosteroids (ICSs). Retrospective cohort study. Medicare fee-for-service (FFS) claims (2009-10) for a 10% random sample of beneficiaries continuously enrolled in Parts A, B, and D in 2009. Medicare beneficiaries aged 66 and older continuously enrolled in FFS Medicare with Part D coverage with a diagnosis of asthma before 2009 treated exclusively with ICSs plus LABAs or ICSs plus LTRAs (N = 14,702). The augmented inverse propensity-weighted estimator was used to compare the effect of LABA add-on therapy with that of LTRA add-on therapy on asthma exacerbations requiring inpatient, emergency, or outpatient care and on cardiovascular (CV) events, adjusting for demographic characteristics, comorbidities, and county-level healthcare-access variables. The primary analysis showed that LTRA add-on treatment was associated with greater odds of asthma-related hospitalizations or emergency department visits (odds ratio (OR) = 1.4, P < .001), as well as outpatient exacerbations requiring oral corticosteroids or antibiotics (OR = 1.41, P < .001) than LABA treatment. LTRA add-on therapy was also less effective in controlling acute symptoms, as indicated by greater use of short-acting beta agonists (rate ratio = 1.58, P < .001). LTRA add-on treatment was associated with lower odds of experiencing a CV event than LABA treatment (OR = 0.86, P = .006). This study provides new evidence specific to older adults to help healthcare providers weigh the risks and benefits of these add-on treatments. Further subgroup analysis is needed to personalize asthma treatments in this high-risk population. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Effects of saxagliptin add-on therapy to insulin on blood glycemic fluctuations in patients with type 2 diabetes

PubMed Central

Li, Feng-fei; Jiang, Lan-lan; Yan, Reng-na; Zhu, Hong-hong; Zhou, Pei-hua; Zhang, Dan-feng; Su, Xiao-fei; Wu, Jin-dan; Ye, Lei; Ma, Jian-hua

2016-01-01

Abstract Background: To investigate whether saxagliptin add-on therapy to continuous subcutaneous insulin infusion (CSII) further improve blood glycemic control than CSII therapy in patients with newly diagnosed type 2 diabetes (T2D). Methods: This was a single-center, randomized, control, open-labeled trial. Newly diagnosed T2D patients were recruited between February 2014 and December 2015. Subjects were divided into saxagliptin add-on therapy to CSII group (n = 31) and CSII therapy group (n = 38). The treatment was maintained for 4 weeks. Oral glucose tolerance test was performed at baseline. Serum samples were obtained before and 30 and 120 minutes after oral administration for glucose, insulin, and C-peptide determination. Continuous glucose monitoring (CGM) was performed before and endpoint. Results: A total of 69 subjects were admitted. After 4-week therapy, CGM data showed that patients with saxagliptin add-on therapy exhibited further improvement of mean amplitude glycemic excursion (MAGE), the incremental area under curve of plasma glucose >7.8 and 10 mmol/L compared with that of control group. In addition, the hourly mean blood glucose concentrations, especially between 0000 and 0600 in patient with saxagliptin add-on therapy, were significantly lower compared with that of the control patients. Furthermore, patients in saxagliptin add-on group needed lower insulin dose to maintain euglycemic control. In addition, severe hypoglycemic episode was not observed from any group. Conclusion: Saxagliptin add-on therapy to insulin had the ability of further improve blood glycemic controlling, with lower insulin dose required by patients with T2D to maintain euglycemic controlling. PMID:27787387

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

PubMed

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.

Stereovision Imaging in Smart Mobile Phone Using Add on Prisms

NASA Astrophysics Data System (ADS)

Bar-Magen Numhauser, Jonathan; Zalevsky, Zeev

2014-03-01

In this work we present the use of a prism-based add on component installed on top of a smart phone to achieve stereovision capabilities using iPhone mobile operating system. Through these components and the combination of the appropriate application programming interface and mathematical algorithms the obtained results will permit the analysis of possible enhancements for new uses to such system, in a variety of areas including medicine and communications.

Modulation of quasi-biennial ozone oscillations in the equatorial stratosphere by the solar cycle

NASA Astrophysics Data System (ADS)

Bezverkhnii, Viacheslav; Gruzdev, Aleksandr

Analysis of variation in ozone concentration, temperature, and zonal wind velocity in the equatorial stratosphere at the quasi-biennial (QB) and quasi-decadal (QD) time scales and their relation to the QB and 11-year variations in solar activity is made with the help of wavelet, cross-wavelet and cross-spectral techniques using SBUV/SBUV 2 (ozone), NMC, ERA-40, ERA-Interim (wind and temperature), and radiosonde (wind) data. Sunspot number and 10.7 cm solar radio flux data are used as indices of solar activity. The QD mode with the mean period of 128 months and the QB mode with 28-29 month period are derived from variations in ozone concentration , ozone meridional gradient, temperature and wind velocity. Local maxima of amplitudes of the QD variation in the ozone meridional gradient occur in 4-5 and 20-30 hPa layers. The amplitude of the QB mode of the ozone meridional gradient in 30-50 hPa layer is modulated by the solar cycle in such a way that the amplitude maximum corresponds approximately to the solar cycle maximum. Similar modulation is not found in the QB mode of ozone concentration. While the QD variations in ozone and zonal wind velocity are weak compared to the QB oscillation, the amplitudes of the QD and QB modes of temperature oscillations in the lower and middle stratosphere are close to each other. The modulation of the QB oscillations in the ozone meridional gradient in the lower stratosphere by the 11-year solar cycle is an additional evidence of solar activity influence on the stratosphere, which extends results by Soukharev and Hood (2001), Bezverkhnii and Gruzdev (2007), and Gruzdev and Bezverkhnii (2010). References: 1. Bezverkhnii, V.A., and A.N. Gruzdev. Relation between quasi-decadal and quasi-biennial oscillations of solar activity and the equatorial stratospheric wind. Doklady Earth Sciences, 2007, Vol. 415A, No 6, pp. 970-974. 2. Gruzdev, A.N., and V.A. Bezverkhnii. Possible ozone influence on the quasi-biennial oscillation in the

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

PubMed

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.

PubMed

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.

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

PubMed Central

2014-01-01

Background 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). Results 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. Conclusion 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. PMID:24401194

42 CFR § 510.320 - Treatment of incentive programs or add-on payments under existing Medicare payment systems.

Code of Federal Regulations, 2010 CFR

2017-10-01

... INFRASTRUCTURE AND MODEL PROGRAMS COMPREHENSIVE CARE FOR JOINT REPLACEMENT MODEL Pricing and Payment § 510.320 Treatment of incentive programs or add-on payments under existing Medicare payment systems. The CJR model... 42 Public Health 5 2017-10-01 2017-10-01 false Treatment of incentive programs or add-on payments...

42 CFR § 510.320 - Treatment of incentive programs or add-on payments under existing Medicare payment systems.

Code of Federal Regulations, 2010 CFR

2016-10-01

... INFRASTRUCTURE AND MODEL PROGRAMS COMPREHENSIVE CARE FOR JOINT REPLACEMENT MODEL Pricing and Payment § 510.320 Treatment of incentive programs or add-on payments under existing Medicare payment systems. The CJR model... 42 Public Health 5 2016-10-01 2016-10-01 false Treatment of incentive programs or add-on payments...

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

Code of Federal Regulations, 2010 CFR

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...

Novel all-optical logic gate using an add/drop filter and intensity switch.

PubMed

Threepak, T; Mitatha, S; Yupapin, P P

2011-12-01

A novel design of all-optical logic device is proposed. An all-optical logic device system composes of an optical intensity switch and add/drop filter. The intensity switch is formed to switch signal by using the relationship between refraction angle and signal intensity. In operation, two input signals are coupled into one with some coupling loss and attenuation, in which the combination of add/drop with intensity switch produces the optical logic gate. The advantage is that the proposed device can operate the high speed logic function. Moreover, it uses low power consumption. Furthermore, by using the extremely small component, this design can be put into a single chip. Finally, we have successfully produced the all-optical logic gate that can generate the accurate AND and NOT operation results.

The incremental validity of a computerised assessment added to clinical rating scales to differentiate adult ADHD from autism spectrum disorder.

PubMed

Groom, Madeleine J; Young, Zoe; Hall, Charlotte L; Gillott, Alinda; Hollis, Chris

2016-09-30

There is a clinical need for objective evidence-based measures that are sensitive and specific to ADHD when compared with other neurodevelopmental disorders. This study evaluated the incremental validity of adding an objective measure of activity and computerised cognitive assessment to clinical rating scales to differentiate adult ADHD from Autism spectrum disorders (ASD). Adults with ADHD (n=33) or ASD (n=25) performed the QbTest, comprising a Continuous Performance Test with motion-tracker to record physical activity. QbTest parameters measuring inattention, impulsivity and hyperactivity were combined to provide a summary score ('QbTotal'). Binary stepwise logistic regression measured the probability of assignment to the ADHD or ASD group based on scores on the Conners Adult ADHD Rating Scale-subscale E (CAARS-E) and Autism Quotient (AQ10) in the first step and then QbTotal added in the second step. The model fit was significant at step 1 (CAARS-E, AQ10) with good group classification accuracy. These predictors were retained and QbTotal was added, resulting in a significant improvement in model fit and group classification accuracy. All predictors were significant. ROC curves indicated superior specificity of QbTotal. The findings present preliminary evidence that adding QbTest to clinical rating scales may improve the differentiation of ADHD and ASD in adults. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

42 CFR § 512.320 - Treatment of incentive programs or add-on payments under existing Medicare payment systems.

Code of Federal Regulations, 2010 CFR

2017-10-01

... INFRASTRUCTURE AND MODEL PROGRAMS EPISODE PAYMENT MODEL Pricing and Payment § 512.320 Treatment of incentive... under such models are independent of, and do not affect, any incentive programs or add-on payments under... 42 Public Health 5 2017-10-01 2017-10-01 false Treatment of incentive programs or add-on payments...

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

ERIC Educational Resources Information Center

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…

Medicalization, ambivalence and social control: mothers' descriptions of educators and ADD/ADHD.

PubMed

Malacrida, Claudia

2004-01-01

Conrad notes that non-medical personnel often accomplish the routine, everyday work of medicalization. This is particularly so in the case of Attention Deficit (Hyperactivity) Disorder, where teachers, special educators and school psychologists identify, assess and administer medication to 'problematic' children. Drawing on data from interviews with Canadian and British mothers of ADD/ADHD children, this article explores mothers' perceptions of educators' roles in medicalizing children who are different, comparing medicalization in two divergent sites. In Canada, where ADD/ADHD is a highly medicalized phenomenon, and teachers have few alternative forms of social control available to them in classrooms, it appears that educators are prepared to identify problem children and press for medical treatment with remarkable vigor. In Britain, where medicalization remains incomplete, and where teachers and special educators have more stringent alternative forms of social control available to them, educators were often described as gatekeepers who will refuse the label or to administer medication.

Effects of add-on treatment with sitagliptin on narrowing the range of glucose fluctuations in Japanese type 2 diabetes patients receiving insulin therapy.

PubMed

Mori, Yutaka; Taniguchi, Yukiko; Miyazaki, Shigeru; Yokoyama, Junichi; Utsunomiya, Kazunori

2013-03-01

In an earlier continuous glucose monitoring (CGM)-based study, we reported that sitagliptin not only reduced 24-h mean glucose levels but also suppressed postprandial glucose increases, thus reducing the range of glycemic fluctuations in type 2 diabetes patients. In this study, we investigated whether sitagliptin might provide similar benefits in type 2 diabetes patients receiving insulin therapy by using CGM. The study included a total of 13 type 2 diabetes patients in whom stable glycemic control had been achieved after admission for glycemic control. Insulin regimens used included long-acting insulin preparations once daily in four patients and biphasic insulin preparations twice daily in nine, with the daily insulin dose being 19.0±12.7 U. During the CGM-based study, the patients were given insulin therapy alone on Days 1 and 2 and were given sitagliptin 50 mg/day as add-on treatment on Days 3-6, with their daily insulin doses maintained. The add-on treatment with sitagliptin led to significant decreases in 24-h mean glucose levels and SDs of 288 glucose levels measured by CGM for 24 h, as well as in the indices for magnitude of glucose variability and proportion of time in hyperglycemia, compared with insulin therapy alone (P<0.01), whereas there was no significant change seen in regard to the proportion of time in hypoglycemia with or without add-on treatment with sitagliptin. This CGM-based study clearly demonstrated that insulin therapy alone, whether with long-acting or biphasic insulin preparations, does not provide adequate glycemic control in type 2 diabetes patients. In contrast, add-on sitagliptin was shown to narrow the range of 24-h glucose fluctuations in these patients, suggesting that add-on treatment with sitagliptin is effective for postprandial glucose control in type 2 diabetes patients receiving insulin therapy.

Charting a Course for Change: Acquisition Theory and Practice for a Transforming Defense

DTIC Science & Technology

2004-09-30

for public release; distribution unlimited 13. SUPPLEMENTARY NOTES 14 . ABSTRACT 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION...a = ^Åèìáëáíáçå=oÉëÉ~êÅÜ= do^ar^qb=p`elli=lc=_rpfkbpp=C=mr_if`=mlif`v= = = - 5 - k^s^i=mlpqdo^ar^qb=p`elli= block one, a block two, a block three...3) the changing nature of warfare and its associated technology; 4) new acquisition practices; 5 ) globalization’s impact (including inter-national

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

PubMed

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 < 0.05). Interestingly, Cox regression analysis indicated that patients under detemir or glargine treatment had a higher probability of CKD progression as compared with the pioglitazone group, with hazard ratios of 2.63 (95% CI 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.

Tour of the World’s Largest 3D Printed Polymer Structure on Display at IBS 2016

ScienceCinema

Green, Johney

2018-01-16

ORNL’s Johney Green guides a Periscope tour of the 3D printed house and vehicle demonstration called AMIE (Additive Manufacturing Integrated Energy) during the International Builders’ Show 2016 in Las Vegas. See the world’s largest 3D printed polymer structure – made with carbon fiber reinforced ABS plastic, insulated with next-generation vacuum insulation panels, and outfitted with a micro-kitchen by GE Appliances – that was designed to be powered by a 3D printed utility vehicle using bidirectional wireless power technology. Learn more about AMIE at https://www.youtube.com/watch?v=RCkQB... and http://www.ornl.gov/amie.

40 CFR 63.3167 - How do I establish the add-on control device operating limits during the performance test?

Code of Federal Regulations, 2010 CFR

2010-07-01

... device operating limits during the performance test? 63.3167 Section 63.3167 Protection of Environment... Limitations § 63.3167 How do I establish the add-on control device operating limits during the performance.... (a) Thermal oxidizers. If your add-on control device is a thermal oxidizer, establish the operating...

A common reference-based indirect comparison meta-analysis of eslicarbazepine versus lacosamide as add on treatments for focal epilepsy.

PubMed

Brigo, Francesco; Trinka, Eugen; Bragazzi, Nicola Luigi; Nardone, Raffaele; Milan, Alberto; Grillo, Elisabetta

2016-11-01

Eslicarbazepine acetate (ESL) and lacosamide (LCM) have recently emerged as add-on treatments in patients with focal epilepsy experiencing seizures despite adequate monotherapy. Both drugs enhance slow inactivation of voltage-gated sodium channels. To date no randomized controlled trial (RCT) has directly compared ESL with LCM as add-on treatments for focal epilepsy. Our aim was to indirectly compare the efficacy of ESL and LCM used as add-on treatments in patients with focal epilepsy using common reference-based indirect comparison meta-analysis. We systematically searched RCTs in which ESL or LCM has been used as add-on treatment in patients with focal epilepsy and compared with placebo. Following outcomes were considered: ≥50% reduction in seizure frequency; seizure freedom; treatment withdrawal for any reason; ≥25% increase in seizure frequency. Random-effects Mantel-Haenszel meta-analyses were performed to obtain odds ratios (ORs) for the efficacy of ESL or LCM versus placebo. Adjusted indirect comparisons were then made between ESL and LCM using the obtained results, and comparing the minimum and the highest effective recommended daily dose of each drug. Eight studies were included. Indirect comparisons adjusted for dose-effect showed no difference between ESL and LCM for responder rate, seizure freedom, and withdrawal rates. We could not assess increase in seizure frequency due to lack of data. Indirect comparisons failed to find a significant difference in efficacy between add-on ESL and LCM in patients with focal epilepsy. Direct head-to-head clinical trials comparing ESL with LCM as add-on antiepileptic treatment are required to confirm these results. Copyright © 2016 Elsevier B.V. All rights reserved.

An automated exploration of the isomerization and dissociation pathways of (E)-1,2-dichloroethene cations and anions

NASA Astrophysics Data System (ADS)

Kishimoto, Naoki; Nishi, Yuito

2017-04-01

Isomerization and dissociation pathways after the photoionization or electron attachment of (E)-1,2-dichloroethene were calculated with an automated exploration method utilizing a scaled hypersphere search of the anharmonic downward distortion following algorithm at the UB3LYP/6-311G(2d,d,p) level of theory. The potential energies of transition states and dissociation channels were calculated by a composite method ((RO)CBS-QB3) and compared with the breakdown diagrams and electron attachment spectra observed in previous spectroscopic studies. The results of single point calculations with several DFT and post-SCF methods are compared using the root mean square deviations from the (RO)CBS-QB3 energies for six states of anionic dichloroethene.

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

ERIC Educational Resources Information Center

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…

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

Code of Federal Regulations, 2010 CFR

2010-07-01

... charges and administrative costs will the Presidio Trust add to a debt? 1011.5 Section 1011.5 Parks, Forests, and Public Property PRESIDIO TRUST DEBT COLLECTION Procedures To Collect Presidio Trust Debts § 1011.5 What interest, penalty charges and administrative costs will the Presidio Trust add to a debt...

Aerodynamic drag reduction tests on a full-scale tractor-trailer combination with several add-on devices

NASA Technical Reports Server (NTRS)

Montoya, L. C.; Steers, L. L.

1974-01-01

Aerodynamic drag tests were performed on a conventional cab-over-engine tractor with a 45-foot trailer and five commercially available or potentially available add-on devices using the coast-down method. The tests ranged in velocity from approximately 30 miles per hour to 65 miles per hour and included some flow visualization. A smooth, level runway at Edwards Air Force Base was used for the tests, and deceleration measurements were taken with both accelerometers and stopwatches. An evaluation of the drag reduction results obtained with each of the five add-on devices is presented.

Using patient lists to add value to integrated data repositories.

PubMed

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.

Lopez-Alegria adds patch to collection in Node 1 / Unity module

NASA Image and Video Library

2007-04-17

ISS014-E-19545 (17 April 2007) --- Astronauts Michael E. Lopez-Alegria (right), Expedition 14 commander and NASA space station science officer; Sunita L. Williams, flight engineer; and cosmonaut Mikhail Tyurin (left), flight engineer representing Russia's Federal Space Agency, add the Expedition 14 patch to the Unity node's growing collection of insignias representing crews who have lived and worked on the International Space Station.

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... Limits if Using Add-On Control Devices and Capture System If you are required to comply with operating... 40 Protection of Environment 12 2011-07-01 2009-07-01 true Operating Limits if Using Add-On Control Devices and Capture System 1 Table 1 to Subpart JJJJ of Part 63 Protection of Environment...

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... Using Add-on Control Devices and Capture System If you are required to comply with operating limits by... 40 Protection of Environment 12 2011-07-01 2009-07-01 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 Ssss of... - Operating Limits if Using Add-on Control Devices and Capture System

Code of Federal Regulations, 2010 CFR

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

Code of Federal Regulations, 2010 CFR

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...

Add+VantageMR® Assessments: A Case Study of Teacher and Student Gains

ERIC Educational Resources Information Center

Briand, Cathy

2013-01-01

This case study analyzes the effect of the Add+VantageMRRTM (AVMR) program on a teacher's pedagogy and on her students' progress in mathematics. AVMR, a professional development program in early mathematics, trains teachers to assess their students' progress and apply those insights to their teaching pedagogy. The AVMR assessment uses a…

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... to Subpart OOOO of Part 63—Operating Limits if Using Add-On Control Devices and Capture System If you... 40 Protection of Environment 13 2014-07-01 2014-07-01 false Operating Limits if Using Add-On Control Devices and Capture System 2 Table 2 to Subpart OOOO 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

Code of Federal Regulations, 2014 CFR

2014-07-01

...—Operating Limits if Using Add-On Control Devices and Capture System If you are required to comply with... 40 Protection of Environment 13 2014-07-01 2014-07-01 false Operating Limits if Using Add-On Control Devices and Capture System 1 Table 1 to Subpart JJJJ of Part 63 Protection of Environment...

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

Code of Federal Regulations, 2014 CFR

2014-07-01

...—Operating Limits if Using Add-on Control Devices and Capture System If you are required to comply with... 40 Protection of Environment 13 2014-07-01 2014-07-01 false 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

Code of Federal Regulations, 2012 CFR

2012-07-01

...—Operating Limits if Using Add-On Control Devices and Capture System If you are required to comply with... 40 Protection of Environment 13 2012-07-01 2012-07-01 false Operating Limits if Using Add-On Control Devices and Capture System 1 Table 1 to Subpart JJJJ of Part 63 Protection of Environment...

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

Code of Federal Regulations, 2013 CFR

2013-07-01

... to Subpart OOOO of Part 63—Operating Limits if Using Add-On Control Devices and Capture System If you... 40 Protection of Environment 13 2013-07-01 2012-07-01 true Operating Limits if Using Add-On Control Devices and Capture System 2 Table 2 to Subpart OOOO of Part 63 Protection of Environment...

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

Code of Federal Regulations, 2013 CFR

2013-07-01

...—Operating Limits if Using Add-on Control Devices and Capture System If you are required to comply with... 40 Protection of Environment 13 2013-07-01 2012-07-01 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 2 to Subpart Oooo of... - Operating Limits if Using Add-On Control Devices and Capture System

Code of Federal Regulations, 2012 CFR

2012-07-01

... to Subpart OOOO of Part 63—Operating Limits if Using Add-On Control Devices and Capture System If you... 40 Protection of Environment 13 2012-07-01 2012-07-01 false Operating Limits if Using Add-On Control Devices and Capture System 2 Table 2 to Subpart OOOO of Part 63 Protection of Environment...

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

Code of Federal Regulations, 2010 CFR

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...

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

Code of Federal Regulations, 2012 CFR

2012-07-01

...—Operating Limits if Using Add-on Control Devices and Capture System If you are required to comply with... 40 Protection of Environment 13 2012-07-01 2012-07-01 false 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 2 to Subpart Oooo of... - Operating Limits if Using Add-On Control Devices and Capture System

Code of Federal Regulations, 2011 CFR

2011-07-01

... OOOO of Part 63—Operating Limits if Using Add-On Control Devices and Capture System If you are required... 40 Protection of Environment 12 2011-07-01 2009-07-01 true Operating Limits if Using Add-On Control Devices and Capture System 2 Table 2 to Subpart OOOO of Part 63 Protection of Environment...

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

Code of Federal Regulations, 2013 CFR

2013-07-01

...—Operating Limits if Using Add-On Control Devices and Capture System If you are required to comply with... 40 Protection of Environment 13 2013-07-01 2012-07-01 true Operating Limits if Using Add-On Control Devices and Capture System 1 Table 1 to Subpart JJJJ of Part 63 Protection of Environment...

Efficacy and Safety of Dapagliflozin or Dapagliflozin Plus Saxagliptin Versus Glimepiride as Add-on to Metformin in Patients With Type 2 Diabetes.

PubMed

Müller-Wieland, Dirk; Kellerer, Monika; Cypryk, Katarzyna; Skripova, Dasa; Rohwedder, Katja; Johnsson, Eva; Garcia-Sanchez, Ricardo; Kurlyandskaya, Raisa; David Sjöström, C; Jacob, Stephan; Seufert, Jochen; Dronamraju, Nalina; Csomós, Katalin

2018-06-27

To compare efficacy and safety of dapagliflozin ± saxagliptin with glimepiride as add-on to metformin in patients with type 2 diabetes. This 52-week, multicenter, double-blind, active-controlled study (NCT02471404) randomized (1:1:1) patients (n=939; HbA 1C 7.5-10.5%) on metformin monotherapy (≥1500 mg/day) to add-on dapagliflozin 10 mg, dapagliflozin 10 mg plus saxagliptin 5 mg, or glimepiride 1-6 mg (titrated). The primary efficacy end point was change in HbA 1C from baseline to week 52. Baseline mean age, diabetes duration and HbA 1C were 58.4 years, 7.0 years and 8.3%, respectively. Adjusted mean HbA 1C change from baseline was -1.20% with dapagliflozin plus saxagliptin and -0.82% with dapagliflozin, vs. -0.99% with glimepiride (mean dose at week 52: 4.6 mg). Changes in body weight (-3.2 kg and -3.5 k vs +1.8 kg) and systolic blood pressure (SBP; -6.4 mmHg and -5.6 mmHg vs -1.6 mmHg) were significantly greater with dapagliflozin plus saxagliptin and dapagliflozin vs glimepiride; FPG decreased significantly with dapagliflozin plus saxagliptin vs glimepiride (-2.1 mmol/L vs -1.5 mmol/L) and was similar for dapagliflozin (-1.6 mmol/L) vs glimepiride. Confirmed hypoglycemia incidence was lower with dapagliflozin regimens than with glimepiride (0 and 1 vs 13 patients) and fewer patients required rescue. Genital infections were more frequent with dapagliflozin; other AE profiles were similar. Dapagliflozin, saxagliptin and metformin improved glycemic control compared with glimepiride plus metformin; add-on of dapagliflozin alone showed similar efficacy to glimepiride. Both dapagliflozin regimens decreased body weight and SBP, with lower hypoglycemia incidence compared with glimepiride. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... capture system and add-on control device operating limits during the performance test? 63.3556 Section 63... system and add-on control device operating limits during the performance test? During the performance... of key parameters of the valve operating system (e.g., solenoid valve operation, air pressure...

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

Code of Federal Regulations, 2012 CFR

2012-07-01

... capture system and add-on control device operating limits during the performance test? 63.3556 Section 63... system and add-on control device operating limits during the performance test? During the performance... of key parameters of the valve operating system (e.g., solenoid valve operation, air pressure...

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... capture system and add-on control device operating limits during the performance test? 63.4966 Section 63... system and add-on control device operating limits during the performance test? During the performance... outlet gas temperature is the maximum operating limit for your condenser. (e) Emission capture system...

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

Code of Federal Regulations, 2012 CFR

2012-07-01

... capture system and add-on control device operating limits during the performance test? 63.4966 Section 63... system and add-on control device operating limits during the performance test? During the performance... outlet gas temperature is the maximum operating limit for your condenser. (e) Emission capture system...

Vinogradov adds a patch to the Node 1/Unity collection during Expedition 13

NASA Image and Video Library

2006-09-04

ISS013-E-75813 (4 Sept. 2006) --- Cosmonaut Pavel V. Vinogradov, Expedition 13 commander representing Russia's Federal Space Agency, adds the Expedition 13 patch to the Unity node's growing collection of insignias representing crews who have lived and worked on the International Space Station.

Estimation of streamflow, base flow, and nitrate-nitrogen loads in Iowa using multiple linear regression models

USGS Publications Warehouse

Schilling, K.E.; Wolter, C.F.

2005-01-01

Nineteen variables, including precipitation, soils and geology, land use, and basin morphologic characteristics, were evaluated to develop Iowa regression models to predict total streamflow (Q), base flow (Qb), storm flow (Qs) and base flow percentage (%Qb) in gauged and ungauged watersheds in the state. Discharge records from a set of 33 watersheds across the state for the 1980 to 2000 period were separated into Qb and Qs. Multiple linear regression found that 75.5 percent of long term average Q was explained by rainfall, sand content, and row crop percentage variables, whereas 88.5 percent of Qb was explained by these three variables plus permeability and floodplain area variables. Qs was explained by average rainfall and %Qb was a function of row crop percentage, permeability, and basin slope variables. Regional regression models developed for long term average Q and Qb were adapted to annual rainfall and showed good correlation between measured and predicted values. Combining the regression model for Q with an estimate of mean annual nitrate concentration, a map of potential nitrate loads in the state was produced. Results from this study have important implications for understanding geomorphic and land use controls on streamflow and base flow in Iowa watersheds and similar agriculture dominated watersheds in the glaciated Midwest. (JAWRA) (Copyright ?? 2005).

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

Code of Federal Regulations, 2013 CFR

2013-07-01

... system and add-on control device operating limits during the performance test? 63.4767 Section 63.4767... system and add-on control device operating limits during the performance test? During the performance... operating limits required by § 63.4692 according to this section, unless you have received approval for...

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

Code of Federal Regulations, 2010 CFR

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...

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... 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...

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

Code of Federal Regulations, 2013 CFR

2013-07-01

... system and add-on control device operating limits during the performance test? 63.3967 Section 63.3967... emission 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...

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

Code of Federal Regulations, 2012 CFR

2012-07-01

... capture system and add-on control device operating limits during the performance test? 63.4167 Section 63... capture system and add-on control device operating limits during the performance test? During the... the operating limits required by § 63.4092 according to this section unless you have received approval...

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... capture system and add-on control device operating limits during the performance test? 63.4567 Section 63... emission capture system and add-on control device operating limits during the performance test? During the... the operating limits required by § 63.4492 according to this section, unless you have received...

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... capture system and add-on control device operating limits during the performance test? 63.4167 Section 63... capture system and add-on control device operating limits during the performance test? During the... the operating limits required by § 63.4092 according to this section unless you have received approval...

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... capture system and add-on control device operating limits during the performance test? 63.4767 Section 63... capture system and add-on control device operating limits during the performance test? During the... the operating limits required by § 63.4692 according to this section, unless you have received...

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

Code of Federal Regulations, 2012 CFR

2012-07-01

... capture system and add-on control device operating limits during the performance test? 63.4767 Section 63... capture system and add-on control device operating limits during the performance test? During the... the operating limits required by § 63.4692 according to this section, unless you have received...

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

Code of Federal Regulations, 2012 CFR

2012-07-01

... capture system and add-on control device operating limits during the performance test? 63.4567 Section 63... emission capture system and add-on control device operating limits during the performance test? During the... the operating limits required by § 63.4492 according to this section, unless you have received...

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

Code of Federal Regulations, 2013 CFR

2013-07-01

... system and add-on control device operating limits during the performance test? 63.4567 Section 63.4567... capture system and add-on control device operating limits during the performance test? During the... the operating limits required by § 63.4492 according to this section, unless you have received...

Adjunctive antiepileptic drugs in adult epilepsy: how the first add-on could be the last.

PubMed

Cretin, Benjamin; Hirsch, Edouard

2010-05-01

In adult epilepsies, incomplete seizure control under monotherapy affects approximately 20-25% of patients with idiopathic generalized epilepsies (IGE) and approximately 20-40% of patients with epilepsies with focal seizures (FE). The choice of an adjunctive therapy is therefore a common event. Efficacy studies of add-on anti-epileptic drugs for adult epilepsies--approved since the early 1990s until 2008--were reviewed. An exception was made for valproate. Efficacy studies give important clues for add-on drug choice but--beyond this--we encourage physicians to consider other parameters, especially co-morbidity(ies) and special situation(s). According to clinical and pharmacological data, an original, practical approach is proposed, by which decisions are based on three main criteria, which aim to optimize patients' seizure control and quality of life. The need for drugs that act not only on 'ictogenesis' but also on 'epileptogenesis' is also discussed briefly. Given the increasing disposal of anti-epileptic drugs, the choice of an add-on therapy appears to be partly based on subjective criteria (physician opinions and preferences). In fact, the selection criteria can be clarified as: treatment decisions rely not only on seizure type, efficacy and tolerability profiles but also on patient-related factors.

Higher efficacy of pegylated interferon-α2b add-on therapy in hepatitis B envelope antigen-positive chronic hepatitis B patients on tenofovir monotherapy.

PubMed

Jindal, Ankur; Vyas, Ashish Kumar; Kumar, Devesh; Kumar, Guresh; Sharma, Manoj Kumar; Sarin, Shiv Kumar

2018-05-01

Monotherapy with pegylated interferon-α (Peg-IFNα) or the nucleos(t)ide analogs (NA) currently approved for treating chronic hepatitis B (CHB) has limited efficacy. Studies on the combination of Peg-IFNα/NA have shown conflicting results. We investigated whether sequentially adding on Peg-IFNα to tenofovir enhances serological response rates. Treatment-naïve, hepatitis B envelope antigen (HBeAg)-positive CHB patients with moderately elevated alanine aminotransferase (ALT; 48-200 IU/mL) were started on tenofovir (300 mg/day) and enrolled at week 12 in a 1:1 ratio to either receive Peg-IFNα2b add-on (1.5 μg/kg/week) from week 12 to 36 (n = 53) or continue tenofovir monotherapy (n = 53). Both treatment arms received tenofovir consolidation therapy until week 72. The primary end-point was HBeAg loss at week 72. At week 72, the rate of HBeAg loss was higher in the Peg-IFNα2b add-on group (35.8%) compared to the tenofovir monotherapy group (17%) (P = 0.028; odds ratio, 2.73, 95% confidence interval, 1.09-6.79), and considerably higher in patients with a baseline hepatitis B virus (HBV)-DNA level >6 log IU/mL (32.6% vs 11.4%; P = 0.021). Rates of HBV-DNA loss (77.4% vs 71.7%; P = 0.51), ALT normalization (62.3% vs 52.8%; P = 0.32), and sustained virologic response (20.8% vs 11.3%; P = 0.18) at week 72 were comparable between the two groups. Significantly more patients in the add-on group had >3 log HBV-DNA reduction at week 36 (92.5% vs 66%; P = 0.001). Four patients treated with Peg-IFNα2b add-on achieved hepatitis B surface antigen (HBsAg) loss compared with one patient receiving tenofovir monotherapy. Decline of HBV-DNA of >2 log at week 4 led to higher HBeAg loss at week 72, independent of treatment arm. No patient had treatment-related adverse effects requiring treatment discontinuation. Twenty-four weeks of Peg-IFNα2b as an add-on sequential regimen to tenofovir is safe and resulted in greater loss of HBeAg and HBs

[Toric add-on intraocular lenses for correction of high astigmatism after pseudophakic keratoplasty].

PubMed

Hassenstein, A; Niemeck, F; Giannakakis, K; Klemm, M

2017-06-01

Perforating keratoplasty shows good morphological results with a clear cornea; however, a limiting factor is often the resulting astigmatism, which cannot be corrected with either glasses or contact lenses (CL) in up to 20% of the patients. We retrospectively investigated 15 patients after pseudophakic perforating keratoplasty, who received implantation of toric add-on intraocular lenses (IOL) to correct astigmatism. The mean preoperative astigmatism of 6.5 diopter (dpt) could be reduced to a mean postoperative value of 1.0 dpt. The mean visual acuity could be improved from a preoperative value of sc <0.05 (cc 0.6) to a postoperative value of sc 0.4 (cc 0.63). There were no complications except for one case of a lens extension tear. Based on our good experiences we now provide toric add-on IOL to all patients with pseudophakic perforating keratoplasty when this cannot be corrected or only insufficiently corrected by conservative methods.

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

Code of Federal Regulations, 2010 CFR

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...

Code of Federal Regulations, 2010 CFR

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...

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

Code of Federal Regulations, 2012 CFR

2012-07-01

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

Code of Federal Regulations, 2013 CFR

2013-07-01

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

Code of Federal Regulations, 2014 CFR

2014-07-01

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... capture system and add-on control device operating limits during the performance test? 63.3967 Section 63... establish the emission capture system and add-on control device operating limits during the performance test... must establish the operating limits required by § 63.3892 according to this section, unless you have...

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... 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...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 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...

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

Code of Federal Regulations, 2012 CFR

2012-07-01

... capture system and add-on control device operating limits during the performance test? 63.3967 Section 63... establish the emission capture system and add-on control device operating limits during the performance test... must establish the operating limits required by § 63.3892 according to this section, unless you have...

Lacosamide in refractory mixed pediatric epilepsy: a prospective add-on study.

PubMed

Rastogi, Reena Gogia; Ng, Yu-Tze

2012-04-01

Lacosamide is a new antiepileptic drug that is currently approved by the US Food and Drug Administration (FDA) for adults 17 years or older for partial-onset seizures. The authors reviewed 21 pediatric patients (<17 years) with various seizure types who were started on oral lacosamide as part of a prospective add-on study as adjunctive therapy for refractory epilepsy. Five patients were excluded due to less than 3 months of meaningful follow-up. Maintenance dosages used ranged from 2.4 to 19.4 mg/kg/d. Eight of 16 (50%) patients had greater than 50% reduction in seizure frequency with adjunctive lacosamide therapy. Eight (50%) patients had generalized epilepsy including 4 with Lennox-Gastaut syndrome. Lacosamide was effective therapy for most seizure types but was particularly effective for partial-onset seizures. Lacosamide was effective in treating 5 of 8 (62.5%) localization-related epilepsies but only 2 of 8 (25%) generalized epilepsies, both Lennox-Gastaut syndrome patients with greater than 90% seizure reduction. None of these very refractory patients remained seizure free.

Increased Water Storage in the Qaidam Basin, the North Tibet Plateau from GRACE Gravity Data

PubMed Central

Jiao, Jiu Jimmy; Zhang, Xiaotao; Liu, Yi; Kuang, Xingxing

2015-01-01

Groundwater plays a key role in maintaining the ecology and environment in the hyperarid Qaidam Basin (QB). Indirect evidence and data from sparse observation wells suggest that groundwater in the QB is increasing but there has been no regional assessment of the groundwater conditions in the entire basin because of its remoteness and the severity of the arid environment. Here we report changes in the spatial and temporal distribution of terrestrial water storage (TWS) in the northern Tibetan Plateau (NTP) using Gravity Recovery and Climate Experiment (GRACE) data. Our study confirms long-term (2003–2012) TWS increases in the NTP. Between 2003 and 2012 the TWS increased by 88.4 and 20.6 km3 in the NTP and the QB, respectively, which is 225% and 52% of the capacity of the Three Gorges Reservoir, respectively. Soil and water changes from the Global Land Data Assimilation System (GLDAS) were also used to identify groundwater storage in the TWS and to demonstrate a long-term increase in groundwater storage in the QB. We demonstrate that increases in groundwater, not lake water, are dominant in the QB, as observed by groundwater levels. Our study suggests that the TWS increase was likely caused by a regional increase in precipitation and a decrease in evaporation. Degradation of the permafrost increases the thickness of the active layers providing increased storage for infiltrated precipitation and snow and ice melt water, which may also contribute to the increased TWS. The huge increase of water storage in the NTP will have profound effects, not only on local ecology and environment, but also on global water storage and sea level changes. PMID:26506230

Increased Water Storage in the Qaidam Basin, the North Tibet Plateau from GRACE Gravity Data.

PubMed

Jiao, Jiu Jimmy; Zhang, Xiaotao; Liu, Yi; Kuang, Xingxing

2015-01-01

Groundwater plays a key role in maintaining the ecology and environment in the hyperarid Qaidam Basin (QB). Indirect evidence and data from sparse observation wells suggest that groundwater in the QB is increasing but there has been no regional assessment of the groundwater conditions in the entire basin because of its remoteness and the severity of the arid environment. Here we report changes in the spatial and temporal distribution of terrestrial water storage (TWS) in the northern Tibetan Plateau (NTP) using Gravity Recovery and Climate Experiment (GRACE) data. Our study confirms long-term (2003-2012) TWS increases in the NTP. Between 2003 and 2012 the TWS increased by 88.4 and 20.6 km3 in the NTP and the QB, respectively, which is 225% and 52% of the capacity of the Three Gorges Reservoir, respectively. Soil and water changes from the Global Land Data Assimilation System (GLDAS) were also used to identify groundwater storage in the TWS and to demonstrate a long-term increase in groundwater storage in the QB. We demonstrate that increases in groundwater, not lake water, are dominant in the QB, as observed by groundwater levels. Our study suggests that the TWS increase was likely caused by a regional increase in precipitation and a decrease in evaporation. Degradation of the permafrost increases the thickness of the active layers providing increased storage for infiltrated precipitation and snow and ice melt water, which may also contribute to the increased TWS. The huge increase of water storage in the NTP will have profound effects, not only on local ecology and environment, but also on global water storage and sea level changes.

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

NASA Astrophysics Data System (ADS)

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

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

ERIC Educational Resources Information Center

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…

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

Code of Federal Regulations, 2010 CFR

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...

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 12 2011-07-01 2009-07-01 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...

Coupling analysis of high Q resonators in add-drop configuration through cavity ringdown spectroscopy

NASA Astrophysics Data System (ADS)

Frigenti, G.; Arjmand, M.; Barucci, A.; Baldini, F.; Berneschi, S.; Farnesi, D.; Gianfreda, M.; Pelli, S.; Soria, S.; Aray, A.; Dumeige, Y.; Féron, P.; Nunzi Conti, G.

2018-06-01

An original method able to fully characterize high-Q resonators in an add-drop configuration has been implemented. The method is based on the study of two cavity ringdown (CRD) signals, which are produced at the transmission and drop ports by wavelength sweeping a resonance in a time interval comparable with the photon cavity lifetime. All the resonator parameters can be assessed with a single set of simultaneous measurements. We first developed a model describing the two CRD output signals and a fitting program able to deduce the key parameters from the measured profiles. We successfully validated the model with an experiment based on a fiber ring resonator of known characteristics. Finally, we characterized a high-Q, home-made, MgF2 whispering gallery mode disk resonator in the add-drop configuration, assessing its intrinsic and coupling parameters.

Effect of AlInGaN barrier layers with various TMGa flows on optoelectronic characteristics of near UV light-emitting diodes grown by atmospheric pressure metalorganic vapor phase epitaxy

NASA Astrophysics Data System (ADS)

Fu, Yi-Keng; Lu, Yu-Hsuan; Jiang, Ren-Hao; Chen, Bo-Chun; Fang, Yen-Hsiang; Xuan, Rong; Su, Yan-Kuin; Lin, Chia-Feng; Chen, Jebb-Fang

2011-08-01

Near ultraviolet light-emitting diodes (LEDs) with quaternary AlInGaN quantum barriers (QBs) are grown by atmospheric pressure metalorganic vapor phase epitaxy. The indium mole fraction of AlInGaN QB could be enhanced as we increased the TMG flow rate. Both the wavelength shift in EL spectra and forward voltage at 20 mA current injection were reduced by using AlInGaN QB. Under 100 mA current injection, the LED output power with Al 0.089In 0.035Ga 0.876N QB can be enhanced by 15.9%, compared to LED with GaN QB. It should be attributed to a reduction of lattice mismatch induced polarization mismatch in the active layer.

Effectiveness of vildagliptin versus other oral antidiabetes drugs as add-on to sulphonylurea monotherapy: Post hoc analysis from the EDGE study.

PubMed

Prasanna Kumar, K M; Phadke, U; Brath, H; Gawai, A; Paldánius, P M; Mathieu, C

2016-12-01

In this post hoc analysis of the EDGE study, we assessed the effectiveness and safety of vildagliptin versus other oral antidiabetes drugs (OADs) as add-on to first-line sulphonylurea (SU) therapy in patients who did not receive metformin in a real-life setting. The primary endpoint was odds of achieving an HbA1c reduction of >0.3% without tolerability issues. Secondary endpoint was odds of achieving HbA1c <7.0% without hypoglycaemia or weight gain. Changes in HbA1c, body weight; and safety were also assessed. 2936 patients received vildagliptin and 820 received comparator OADs (any α-GI, TZD, glinide) as add-on to first-line SU therapy. Overall, the mean age, disease duration, HbA1c, and BMI at baseline were 57.1 years, 6.3 years, 8.5%, and 27.7kg/m 2 , respectively. The odds ratios for achieving primary and secondary endpoints were 1.6 (95% CI: 1.36, 1.86; p<0.0001) and 1.8 (1.45, 2.21; p<0.0001), respectively, in favour of vildagliptin. The between-treatment differences (vildagliptin vs. comparator OAD) for the mean change in HbA1c and body weight were -0.2±0.04% (p<0.0001) and -0.8±0.16kg (p<0.0001), respectively. Overall, the incidence of adverse events was low (vildagliptin, 7% vs. comparator, 8.2%) in both groups. Similar results were observed in a subset of patients enrolled from India and patients who received TZDs as a comparator OAD. Under real-life settings, vildagliptin as add-on to SU monotherapy showed better glycaemic response without tolerability issues compared with other OADs. Copyright © 2016 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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.

Quillaja brasiliensis saponins induce robust humoral and cellular responses in a bovine viral diarrhea virus vaccine in mice.

PubMed

Cibulski, Samuel Paulo; Silveira, Fernando; Mourglia-Ettlin, Gustavo; Teixeira, Thais Fumaco; dos Santos, Helton Fernandes; Yendo, Anna Carolina; de Costa, Fernanda; Fett-Neto, Arthur Germano; Gosmann, Grace; Roehe, Paulo Michel

2016-04-01

A saponin fraction extracted from Quillaja brasiliensis leaves (QB-90) and a semi-purified aqueous extract (AE) were evaluated as adjuvants in a bovine viral diarrhea virus (BVDV) vaccine in mice. Animals were immunized on days 0 and 14 with antigen plus either QB-90 or AE or an oil-adjuvanted vaccine. Two-weeks after boosting, antibodies were measured by ELISA; cellular immunity was evaluated by DTH, lymphoproliferation, cytokine release and single cell IFN-γ production. Serum anti-BVDV IgG, IgG1 and IgG2b were significantly increased in QB-90- and AE-adjuvanted vaccines. A robust DTH response, increased splenocyte proliferation, Th1-type cytokines and enhanced production of IFN-γ by CD4(+) and CD8(+) T lymphocytes were detected in mice that received QB-90-adjuvanted vaccine. The AE-adjuvanted preparation stimulated humoral responses but not cellular immune responses. These findings reveal that QB-90 is capable of stimulating both cellular and humoral immune responses when used as adjuvant. Copyright © 2016 Elsevier Ltd. All rights reserved.

Saxagliptin versus glipizide as add-on therapy to metformin: assessment of hypoglycemia.

PubMed

Mintz, Matthew L; Minervini, Gianmaria

2014-05-01

To compare characteristics of hypoglycemic episodes in patients with type 2 diabetes receiving saxagliptin or glipizide add-on therapy to metformin. This was a post hoc analysis of an international, randomized, parallel-group, double-blind, active-controlled, phase 3 trial. The 52-week trial and 52-week extension were conducted from December 2007 to August 2010. Patients aged ≥18 years with glycated hemoglobin (HbA1c) >6.5% to 10.0% receiving stable metformin doses (≥1500 mg/d) were randomized 1:1 to add-on therapy with saxagliptin 5 mg/d or glipizide 5 to 20 mg/d (titrated to optimal effect or highest tolerable dose during the initial 18 weeks). Hypoglycemic episodes were recorded in patient diaries. Confirmed hypoglycemic events were defined as fingerstick glucose ≤50 mg/dL (≤2.8 mmol/L) with associated symptoms. Of 858 patients randomized, 428 received saxagliptin + metformin, and 430 received glipizide + metformin. Saxagliptin was noninferior to glipizide in lowering HbA1c. Hypoglycemia with saxagliptin + metformin and glipizide + metformin was reported by 15 (24 events) and 165 (896 events) patients, respectively, through week 104. The mean (SD) number of hypoglycemic events per patient reporting hypoglycemia was lower with saxagliptin + metformin versus glipizide + metformin through weeks 52 (1.5 [SD 0.88] vs 4.8 [SD 4.9], respectively) and 104 (1.6 [SD 0.99] vs 5.4 [SD 5.8]). Most patients receiving glipizide + metformin with hypoglycemia had multiple events (124/165 patients [75%]). Confirmed hypoglycemia, major events, and severe events occurred only with glipizide + metformin. Time to first hypoglycemic event was shorter with glipizide versus saxagliptin. Limitations of this analysis include its post hoc nature, a high rate of study discontinuation, and exclusion of patients with serious comorbidities and complications. Saxagliptin + metformin was associated with fewer patients reporting hypoglycemia

Better Acquisition Management through Alternative Dispute Resolution (ADR) and Other Best Practices for Preventing and Resolving Bid Protests

DTIC Science & Technology

2012-01-24

ESLS ) made cost = = ^Åèìáëáíáçå=oÉëÉ~êÅÜ=mêçÖê~ã= do^ar^qb=p`elli=lc=_rpfkbpp=C=mr_if`=mlif`v - 66 - k^s^i=mlpqdo^ar^qb=p`elli= and availability...Mobility Command (AMC). Regarding cost, the ESLS found that the KC-135 fleet would incur “significant cost increases” between 2001 and 2040, but “no...the ESLS publication, the Air Force planned to wait until 2013 to begin KC-135 replacement. (Gupta, Belasco, Else, & O’Rourke, 2003, pp. 2– 3

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

PubMed

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.

Scientific Data Analysis Toolkit: A Versatile Add-in to Microsoft Excel for Windows

ERIC Educational Resources Information Center

Halpern, Arthur M.; Frye, Stephen L.; Marzzacco, Charles J.

2018-01-01

Scientific Data Analysis Toolkit (SDAT) is a rigorous, versatile, and user-friendly data analysis add-in application for Microsoft Excel for Windows (PC). SDAT uses the familiar Excel environment to carry out most of the analytical tasks used in data analysis. It has been designed for student use in manipulating and analyzing data encountered in…

Nonvisualization of the ovaries on pelvic ultrasound: does MRI add anything?

PubMed

Lisanti, Christopher J; Wood, Jonathan R; Schwope, Ryan B

2014-02-01

The purpose of our study is to assess the utility of pelvic magnetic resonance imaging (MRI) in the event that either one or both ovaries are not visualized by pelvic ultrasound. This HIPAA-compliant retrospective study was approved by our local institutional review board and informed consent waived. 1926 pelvic MRI examinations between March 2007 and December 2011 were reviewed and included if a combined transabdominal and endovaginal pelvic ultrasound had been performed in the preceding 6 months with at least one ovary nonvisualized. Ovaries not visualized on pelvic ultrasound were assumed to be normal and compared with the pelvic MRI findings. MRI findings were categorized as concordant or discordant. Discordant findings were divided into malignant, non-malignant physiologic or non-malignant non-physiologic. The modified Wald, the "rule of thirds", and the binomial distribution probability tests were performed. 255 pelvic ultrasounds met inclusion criteria with 364 ovaries not visualized. 0 malignancies were detected on MRI. 6.9% (25/364) of nonvisualized ovaries had non-malignant discordant findings on MRI: 5.2% (19/364) physiologic, 1.6% (6/364) non-physiologic. Physiologic findings included: 16 functional cysts and 3 hemorrhagic cysts. Non-physiologic findings included: 3 cysts in post-menopausal women, 1 hydrosalpinx, and 2 broad ligament fibroids. The theoretical risk of detecting an ovarian carcinoma on pelvic MRI when an ovary is not visualized on ultrasound ranges from 0 to 1.3%. If an ovary is not visualized on pelvic ultrasound, it can be assumed to be without carcinoma and MRI rarely adds additional information.

PLOT3D Export Tool for Tecplot

NASA Technical Reports Server (NTRS)

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.

Ex vivo T-cell-depleted allogeneic stem cell transplantation for hematologic malignancies: The search for an optimum transplant T-cell dose and T-cell add-back strategy.

PubMed

Anandi, Prathima; Tian, Xin; Ito, Sawa; Muranski, Pawel; Chokshi, Puja D; Watters, Noelle; Chawla, Upneet; Hensel, Nancy; Stroncek, David F; Battiwalla, Minoo; Barrett, A John

2017-06-01

T-cell depletion (TCD) of allogeneic stem cell transplants (SCT) can reduce graft-versus-host disease but may negatively affect transplant outcome by delaying immune recovery. To optimize TCD in HLA-matched siblings with hematologic malignancies, we explored varying the transplant CD3+ T-cell dose between 2 and 50 × 10 4 /kg (corresponding to 3-4 log depletion) and studied the impact of 0-6 × 10 7 /kg CD3+ donor lymphocyte infusion (DLI) "add-back" on immune recovery post-SCT. Two hundred seventeen consecutive patients (age range, 10-75 years) with hematologic malignancy (excluding chronic leukemias) underwent ex vivo TCD SCT from HLA-identical sibling donors from 1994-2015. Ninety-four patients had standard-risk disease (first remission acute leukemia [AL] and early stage myelodysplastic syndromes [MDS]) and 123 had high-risk disease (AL beyond first complete remission, advanced MDS or refractory B-cell malignancy). Median follow-up was 8.5 years. At 20 years post-SCT, overall survival (OS) was 40%, nonrelapse mortality (NRM) was 27% and relapse incidence was 39%. Factors affecting outcome in multivariate analysis were transplantation era, with OS increasing from 38% in the period 1994-2000 to 58% in 2011-2015, disease risk (hazard ratio [HR], 1.68 for high risk) and increasing age (HR, 1.19 per decade). Neither the T-cell dose or the add back of T cells in the first 100 days had any effect on OS, NRM and relapse. Outcomes for TCD SCT have greatly improved. However, our data do not support the need to precisely manipulate transplant CD3+ T-cell dose provided at least 3-log depletion is achieved or the use of T-cell add-back. Future improvements for TCD SCT await better strategies to prevent relapse, especially in high-risk recipients. Published by Elsevier Inc.

Pregabalin as mono- or add-on therapy for patients with refractory chronic neuropathic pain: a post-marketing prescription-event monitoring study.

PubMed

Lampl, Christian; Schweiger, Christine; Haider, Bernhard; Lechner, Anita

2010-08-01

This observational study examined the outcome of two different therapeutic strategies in the treatment of chronic neuropathic pain by including pregabalin (PGB) as mono- or add-on therapy in one of two treatment options. Patients with a pain score of > or =4, refractory to usual care for neuropathic pain for at least 6 months, were allocated consecutively to one of two treatment strategies according to the decision of the physician: complete switch to a flexible-dosage, monotherapeutic or add-on therapy with pregabalin (PGB group), or change established doses and combinations of pre-existing mono- or combination therapy without pregabalin (non-PGB group). After 4 weeks (primary endpoint) a significant improvement in pain reduction was documented in both intention-to treat (ITT) analysis (PGB group, n = 85: mean pain score reduction of 3.53, SD 2.03, p < 0.001; non-PGB group, n = 102; mean pain score reduction of 2.83, SD 2.23, p < 0.001) and per-protocol (PP) analysis (PGB group, n = 79: mean pain score reduction 3.53 vs. 2.83, p < 0.05; non-PGB group, n = 81; 3.5 vs. 2.9, p < 0.05) compared to baseline. Comparison of the results observed in the two groups shows that patients in the PGB group achieved significantly greater pain reduction. These results demonstrate that PGB administered twice daily is superior to treatment regimes without PGB in reducing pain and pain-related interference in quality of life.

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

PubMed

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 < .001). Compared with healthy control subjects, the tidal volume (VT) of the subjects with stroke was 24.7, 18.0, and 14.7% lower during QB, incentive 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.

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

EPA Science Inventory

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.

PubMed

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...

Code of Federal Regulations, 2010 CFR

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...

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

PubMed

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.

A low-complexity add-on score for protein remote homology search with COMER.

PubMed

Margelevicius, Mindaugas

2018-06-15

Protein sequence alignment forms the basis for comparative modeling, the most reliable approach to protein structure prediction, among many other applications. Alignment between sequence families, or profile-profile alignment, represents one of the most, if not the most, sensitive means for homology detection but still necessitates improvement. We aim at improving the quality of profile-profile alignments and the sensitivity induced by them by refining profile-profile substitution scores. We have developed a new score that represents an additional component of profile-profile substitution scores. A comprehensive evaluation shows that the new add-on score statistically significantly improves both the sensitivity and the alignment quality of the COMER method. We discuss why the score leads to the improvement and its almost optimal computational complexity that makes it easily implementable in any profile-profile alignment method. An implementation of the add-on score in the open-source COMER software and data are available at https://sourceforge.net/projects/comer. The COMER software is also available on Github at https://github.com/minmarg/comer and as a Docker image (minmar/comer). Supplementary data are available at Bioinformatics online.

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

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false What adjustment factors does OPM add to the price indexes? 591.227 Section 591.227 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS ALLOWANCES AND DIFFERENTIALS Cost-of-Living Allowance and Post Differential-Nonforeign Areas Cost-Of-Living Allowances §...

Once-Daily Liraglutide Versus Lixisenatide as Add-on to Metformin in Type 2 Diabetes: A 26-Week Randomized Controlled Clinical Trial.

PubMed

Nauck, Michael; Rizzo, Manfredi; Johnson, Andrew; Bosch-Traberg, Heidrun; Madsen, Jesper; Cariou, Bertrand

2016-09-01

To compare the efficacy and safety of liraglutide versus lixisenatide as add-on to metformin in patients with type 2 diabetes not achieving adequate glycemic control on metformin alone. In this 26-week, randomized, parallel-group, open-label trial, 404 patients were randomized 1:1 to liraglutide 1.8 mg or lixisenatide 20 µg as add-on to metformin. Liraglutide was administered once daily at any time of the day. Lixisenatide was administered once daily within 1 h prior to the morning or evening meal. At week 26, liraglutide reduced HbA1c (primary end point) more than lixisenatide (estimated treatment difference -0.62% [95% CI -0.8; -0.4]; P < 0.0001), with more patients reaching HbA1c <7% (53 mmol/mol) and ≤6.5% (48 mmol/mol) versus lixisenatide (74.2% and 54.6% for liraglutide vs. 45.5% and 26.2% for lixisenatide; P < 0.0001 for both). Liraglutide reduced fasting plasma glucose more than lixisenatide (estimated treatment difference -1.15 mmol/L [95% CI -1.5; -0.8]; P < 0.0001). Liraglutide provided greater reduction in mean 9-point self-measured plasma glucose (P < 0.0001). However, postprandial glucose increments were smaller with lixisenatide for the meal directly after injection compared with liraglutide (P < 0.05), with no differences between treatments across all meals. Both drugs promoted similar body weight decrease (-4.3 kg for liraglutide, -3.7 kg for lixisenatide; P = 0.23). The most common adverse events in both groups were gastrointestinal disorders. Greater increases in pulse, lipase, and amylase were observed with liraglutide. Hypoglycemic episodes were rare and similar between the two treatments. At the dose levels studied, liraglutide was more effective than lixisenatide as add-on to metformin in improving glycemic control. Body weight reductions were similar. Both treatments were well tolerated, with low risk of hypoglycemia and similar gastrointestinal adverse event profiles. © 2016 by the American Diabetes Association.

Polar and singular value decomposition of 3×3 magic squares

NASA Astrophysics Data System (ADS)

Trenkler, Götz; Schmidt, Karsten; Trenkler, Dietrich

2013-07-01

In this note, we find polar as well as singular value decompositions of a 3×3 magic square, i.e. a 3×3 matrix M with real elements where each row, column and diagonal adds up to the magic sum s of the magic square.

Quality cell therapy manufacturing by design.

PubMed

Lipsitz, Yonatan Y; Timmins, Nicholas E; Zandstra, Peter W

2016-04-01

Transplantation of live cells as therapeutic agents is poised to offer new treatment options for a wide range of acute and chronic diseases. However, the biological complexity of cells has hampered the translation of laboratory-scale experiments into industrial processes for reliable, cost-effective manufacturing of cell-based therapies. We argue here that a solution to this challenge is to design cell manufacturing processes according to quality-by-design (QbD) principles. QbD integrates scientific knowledge and risk analysis into manufacturing process development and is already being adopted by the biopharmaceutical industry. Many opportunities to incorporate QbD into cell therapy manufacturing exist, although further technology development is required for full implementation. Linking measurable molecular and cellular characteristics of a cell population to final product quality through QbD is a crucial step in realizing the potential for cell therapies to transform healthcare.

Implementation of palliative care as a mandatory cross-disciplinary subject (QB13) at the Medical Faculty of the Heinrich-Heine-University Düsseldorf, Germany

PubMed Central

Schulz, Christian; Wenzel-Meyburg, Ursula; Karger, André; Scherg, Alexandra; in der Schmitten, Jürgen; Trapp, Thorsten; Paling, Andreas; Bakus, Simone; Schatte, Gesa; Rudolf, Eva; Decking, Ulrich; Ritz-Timme, Stephanie; Grünewald, Matthias; Schmitz, Andrea

2015-01-01

Background: By means of the revision of the Medical Licensure Act for Physicians (ÄAppO) in 2009, undergraduate palliative care education (UPCE) was incorporated as a mandatory cross sectional examination subject (QB13) in medical education in Germany. Its implementation still constitutes a major challenge for German medical faculties. There is a discrepancy between limited university resources and limited patient availabilities and high numbers of medical students. Apart from teaching theoretical knowledge and skills, palliative care education is faced with the particular challenge of imparting a professional and adequate attitude towards incurably ill and dying patients and their relatives. Project description: Against this background, an evidence-based longitudinal UPCE curriculum was systematically developed following Kern’s Cycle [1] and partly implemented and evaluated by the students participating in the pilot project. Innovative teaching methods (virtual standardised/simulated patient contacts, e-learning courses, interdisciplinary and interprofessional collaborative teaching, and group sessions for reflective self-development) aim at teaching palliative care-related core competencies within the clinical context and on an interdisciplinary and interprofessional basis. Results: After almost five years of development and evaluation, the UPCE curriculum comprises 60 teaching units and is being fully implemented and taught for the first time in the winter semester 2014/15. The previous pilot phases were successfully concluded. To date, the pilot phases (n=26), the subproject “E-learning in palliative care” (n=518) and the blended-learning elective course “Communication with dying patients” (n=12) have been successfully evaluated. Conclusion: All conducted development steps and all developed programmes are available for other palliative care educators (Open Access). The integrated teaching formats and methods (video, e-learning module

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

PubMed

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

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

PubMed

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

ERIC Educational Resources Information Center

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…

Effects of saxagliptin add-on therapy to insulin on blood glycemic fluctuations in patients with type 2 diabetes: A randomized, control, open-labeled trial.

PubMed

Li, Feng-Fei; Jiang, Lan-Lan; Yan, Reng-Na; Zhu, Hong-Hong; Zhou, Pei-Hua; Zhang, Dan-Feng; Su, Xiao-Fei; Wu, Jin-Dan; Ye, Lei; Ma, Jian-Hua

2016-10-01

To investigate whether saxagliptin add-on therapy to continuous subcutaneous insulin infusion (CSII) further improve blood glycemic control than CSII therapy in patients with newly diagnosed type 2 diabetes (T2D). This was a single-center, randomized, control, open-labeled trial. Newly diagnosed T2D patients were recruited between February 2014 and December 2015. Subjects were divided into saxagliptin add-on therapy to CSII group (n = 31) and CSII therapy group (n = 38). The treatment was maintained for 4 weeks. Oral glucose tolerance test was performed at baseline. Serum samples were obtained before and 30 and 120 minutes after oral administration for glucose, insulin, and C-peptide determination. Continuous glucose monitoring (CGM) was performed before and endpoint. A total of 69 subjects were admitted. After 4-week therapy, CGM data showed that patients with saxagliptin add-on therapy exhibited further improvement of mean amplitude glycemic excursion (MAGE), the incremental area under curve of plasma glucose >7.8 and 10 mmol/L compared with that of control group. In addition, the hourly mean blood glucose concentrations, especially between 0000 and 0600 in patient with saxagliptin add-on therapy, were significantly lower compared with that of the control patients. Furthermore, patients in saxagliptin add-on group needed lower insulin dose to maintain euglycemic control. In addition, severe hypoglycemic episode was not observed from any group. Saxagliptin add-on therapy to insulin had the ability of further improve blood glycemic controlling, with lower insulin dose required by patients with T2D to maintain euglycemic controlling.

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

PubMed

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.

CosmoCalc: An Excel add-in for cosmogenic nuclide calculations

NASA Astrophysics Data System (ADS)

Vermeesch, Pieter

2007-08-01

As dating methods using Terrestrial Cosmogenic Nuclides (TCN) become more popular, the need arises for a general-purpose and easy-to-use data reduction software. The CosmoCalc Excel add-in calculates TCN production rate scaling factors (using Lal, Stone, Dunai, and Desilets methods); topographic, snow, and self-shielding factors; and exposure ages, erosion rates, and burial ages and visualizes the results on banana-style plots. It uses an internally consistent TCN production equation that is based on the quadruple exponential approach of Granger and Smith (2000). CosmoCalc was designed to be as user-friendly as possible. Although the user interface is extremely simple, the program is also very flexible, and nearly all default parameter values can be changed. To facilitate the comparison of different scaling factors, a set of converter tools is provided, allowing the user to easily convert cut-off rigidities to magnetic inclinations, elevations to atmospheric depths, and so forth. Because it is important to use a consistent set of scaling factors for the sample measurements and the production rate calibration sites, CosmoCalc defines the production rates implicitly, as a function of the original TCN concentrations of the calibration site. The program is best suited for 10Be, 26Al, 3He, and 21Ne calculations, although basic functionality for 36Cl and 14C is also provided. CosmoCalc can be downloaded along with a set of test data from http://cosmocalc.googlepages.com.

Theoretical study of the thermodynamics and kinetics of hydrogen abstractions from hydrocarbons.

PubMed

Vandeputte, Aäron G; Sabbe, Maarten K; Reyniers, Marie-Françoise; Van Speybroeck, Veronique; Waroquier, Michel; Marin, Guy B

2007-11-22

Thermochemical and kinetic data were calculated at four cost-effective levels of theory for a set consisting of five hydrogen abstraction reactions between hydrocarbons for which experimental data are available. The selection of a reliable, yet cost-effective method to study this type of reactions for a broad range of applications was done on the basis of comparison with experimental data or with results obtained from computationally demanding high level of theory calculations. For this benchmark study two composite methods (CBS-QB3 and G3B3) and two density functional theory (DFT) methods, MPW1PW91/6-311G(2d,d,p) and BMK/6-311G(2d,d,p), were selected. All four methods succeeded well in describing the thermochemical properties of the five studied hydrogen abstraction reactions. High-level Weizmann-1 (W1) calculations indicated that CBS-QB3 succeeds in predicting the most accurate reaction barrier for the hydrogen abstraction of methane by methyl but tends to underestimate the reaction barriers for reactions where spin contamination is observed in the transition state. Experimental rate coefficients were most accurately predicted with CBS-QB3. Therefore, CBS-QB3 was selected to investigate the influence of both the 1D hindered internal rotor treatment about the forming bond (1D-HR) and tunneling on the rate coefficients for a set of 21 hydrogen abstraction reactions. Three zero curvature tunneling (ZCT) methods were evaluated (Wigner, Skodje & Truhlar, Eckart). As the computationally more demanding centrifugal dominant small curvature semiclassical (CD-SCS) tunneling method did not yield significantly better agreement with experiment compared to the ZCT methods, CD-SCS tunneling contributions were only assessed for the hydrogen abstractions by methyl from methane and ethane. The best agreement with experimental rate coefficients was found when Eckart tunneling and 1D-HR corrections were applied. A mean deviation of a factor 6 on the rate coefficients is found for

Add Java extensions to your wiki: Java applets can bring dynamic functionality to your wiki pages

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

Scarberry, Randall E.

Virtually everyone familiar with today’s world wide web has encountered the free online encyclopedia Wikipedia many times. What you may not know is that Wikipedia is driven by an excellent open-source product called MediaWiki which is available to anyone for free. This has led to a proliferation of wiki sites devoted to just about any topic one can imagine. Users of a wiki can add content -- all that is required of them is that they type in their additions into their web browsers using the simple markup language called wikitext. Even better, the developers of wikitext made it extensible.more » With a little server-side development of your own, you can add your own custom syntax. Users aware of your extensions can then utilize them on their wiki pages with a few simple keystrokes. These extensions can be custom decorations, formatting, web applications, and even instances of the venerable old Java applet. One example of a Java applet extension is the Jmol extension (REF), used to embed a 3-D molecular viewer. This article will walk you through the deployment of a fairly elaborate applet via a MediaWiki extension. By no means exhaustive -- an entire book would be required for that -- it will demonstrate how to give the applet resize handles using using a little Javascript and CSS coding and some popular Javascript libraries. It even describes how a user may customize the extension somewhat using a wiki template. Finally, it explains a rudimentary persistence mechanism which allows applets to save data directly to the wiki pages on which they reside.« less

The Integration of the Neurosciences, Child Public Health, and Education Practice: Hemisphere-Specific Remediation Strategies as a Discipline Partnered Rehabilitation Tool in ADD/ADHD.

PubMed

Leisman, Gerry; Mualem, Raed; Machado, Calixto

2013-01-01

ADD/ADHD is the most common and most studied neurodevelopmental problem. Recent statistics from the U.S. Center for Disease Control state that 11% or approximately one out of every nine children in the US and one in five high school boys are diagnosed with ADD/ADHD. This number is thought to be increasing at around 15-20% per year. The US National Institute of Mental Health's Multi-modal Treatment Study has shown that medication has no long-term benefit for those with ADHD. To effectively address ADD/ADHD from within the framework of child public health, an interdisciplinary strategy is necessary that is based on a neuroeducational model that can be readily implemented on a large-scale within the educational system. This study is based on previous findings that ADD/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. Since ADD/ADHD children exhibit deficient performance on tests developed to measure perceptual laterality, evidence of weak laterality or failure to develop laterality has been found across various modalities (auditory, visual, tactile). This has reportedly resulted in abnormal cerebral organization and ineffective cortical specialization necessary for the development 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 of 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 2 years in grade level in all domains except in mathematical reasoning. The treated group also

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

NASA Astrophysics Data System (ADS)

Li, Chunhua; Lv, Dashuai; Zhang, Lei; Yang, Feng; Wang, Cunxin; Su, Jiguo; Zhang, Yang

2016-07-01

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.

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

PubMed

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?

Code of Federal Regulations, 2010 CFR

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...

FAQs Related to Response to Petition to Add Oil And Gas Extraction Sector to the TRI Program

EPA Pesticide Factsheets

Questions and answers related to EPA's response to a petition by the Environmental Integrity Project and 16 other organizations to add the Oil and Gas Extraction sector to the scope of industries subject to TRI reporting requirements.

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

PubMed

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.

Psychometric properties and norms of the German ABC-Community and PAS-ADD Checklist.

PubMed

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

2011-01-01

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 methods in this field were introduced: a simulation method for testing the factor structure and an exploration of long-term stability over two years. The checklists were both administered to a representative sample of 270 individuals with intellectual disability (ID) and, two years later in a second data collection, to 128 participants of the original sample. Principal component analysis and parallel analysis were performed. Reliability measures, long-term stability, subscale intercorrelations, as well as standardized norms were generated. Prevalence of mental health problems was examined. Psychometric properties were mostly excellent, with long-term stability showing moderate to strong effects. The original factor structure of the ABC-C was replicated. PAS-ADD Checklist produced a similar, but still different structure compared with findings from the English language area. The overall prevalence rate of mental health problems in the sample was about 20%. Considering the good results on the measured psychometric properties, the two checklists are recommended for the early detection of mental health problems in persons with ID. Copyright © 2011 Elsevier Ltd. All rights reserved.

Quality By Design: Concept To Applications.

PubMed

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.

Baclofen add-on to citalopram in treatment of posttraumatic stress disorder.

PubMed

Manteghi, Ali Akhoundpour; Hebrani, Paria; Mortezania, Mohammad; Haghighi, Mehri Baghban; Javanbakht, Arash

2014-04-01

Posttraumatic stress disorder (PTSD) is a chronic disabling illness, resulting from exposure to extreme traumatic event. Although different pharmacologic agents are suggested for treatment of PTSD, none have been completely effective in eliminating symptoms. The purpose of this study was to assess the use of baclofen as an add-on to citalopram in treatment of PTSD. In this double-blind clinical trial, 40 Iranian combat veterans with PTSD were randomly assigned to 2 groups. The first group received a combination treatment of 20 to 60 mg/d citalopram and 40 mg/d baclofen, and the second group received 20 to 60 mg/d citalopram plus placebo. Symptom severity was assessed by Clinician-Administered PTSD Scale at the beginning of the study and after 2, 4, 6, and 8 weeks. Global Assessment of Functioning and Hamilton Rating Scale for Anxiety and Depression were also used at the same periods. Data were analyzed with independent t test and paired t test using SPSS software version 13 (IBM, Armonk, NY). Twenty-three male patients (baclofen group, 13 patients; placebo group, 10 patients) completed the study. Dropout from the treatment was not caused by adverse effects of the new medications in any of the subjects. Baclofen group showed significantly larger improvement in Clinician-Administered PTSD Scale total (P = 0.040), hyperarousal (P = 0.020), and avoidance (0.020) scores, Global Assessment of Functioning score (0.001), depression (P = 0.000), and anxiety (P = 0.000) after 8 weeks of treatment. No intergroup difference was found in improvement of reexperience symptoms (P = 0.740). Baclofen showed to be an effective add-on to selective serotonin reuptake inhibitors in treatment of PTSD for better symptom recovery and functional improvement.

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

PubMed

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 (p<0.01) and allele frequencies (p=0.021) of the ADD1 G460W gene 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) (p<0.01). Our results demonstrate an association between ADD1 G460W gene 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.

Characteristics of Learning Disabled, Emotionally Disturbed, ADHD/ADD, and Nonexceptional Children: A Behavioral Assessment Measurement Approach.

ERIC Educational Resources Information Center

Palomares, Ronald S.; And Others

This paper presents data comparing normal, learning-disabled (LD), emotionally disturbed (ED), and attention deficit/hyperactivity disorder (ADHD) or attention deficit disorder (ADD) children, from a total of 1,303 children used to standardize the Texas Features of Emotional Disturbance (Tx-FED), an assessment system involving parent and teacher…

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

PubMed

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.

Thermochemistry of C7H16 to C10H22 alkane isomers: primary, secondary, and tertiary C-H bond dissociation energies and effects of branching.

PubMed

Hudzik, Jason M; Bozzelli, Joseph W; Simmie, John M

2014-10-09

Standard enthalpies of formation (ΔH°f 298) of methyl, ethyl, primary and secondary propyl, and n-butyl radicals are evaluated and used in work reactions to determine internal consistency. They are then used to calculate the enthalpy of formation for the tert-butyl radical. Other thermochemical properties including standard entropies (S°(T)), heat capacities (Cp(T)), and carbon-hydrogen bond dissociation energies (C-H BDEs) are reported for n-pentane, n-heptane, 2-methylhexane, 2,3-dimethylpentane, and several branched higher carbon number alkanes and their radicals. ΔH°f 298 and C-H BDEs are calculated using isodesmic work reactions at the B3LYP (6-31G(d,p) and 6-311G(2d,2p) basis sets), CBS-QB3, CBS-APNO, and G3MP2B3 levels of theory. Structures, moments of inertia, vibrational frequencies, and internal rotor potentials are calculated at the B3LYP/6-31G(d,p) level for contributions to entropy and heat capacities. Enthalpy calculations for these hydrocarbon radical species are shown to have consistency with the CBS-QB3 and CBS-APNO methods using all work reactions. Our recommended ideal gas phase ΔH°f 298 values are from the average of all CBS-QB3, CBS-APNO, and for G3MP2B3, only where the reference and target radical are identical types, and are compared with literature values. Calculated values show agreement between the composite calculation methods and the different work reactions. Secondary and tertiary C-H bonds in the more highly branched alkanes are shown to have bond energies that are several kcal mol(-1) lower than the BDEs in corresponding smaller molecules often used as reference species. Entropies and heat capacities are calculated and compared to literature values (when available) when all internal rotors are considered.

Additional low-dose antimuscarinics can improve overactive bladder symptoms in patients with suboptimal response to beta 3 agonist monotherapy

PubMed Central

Shin, Jung Hyun; Kim, Aram

2017-01-01

Purpose We aimed to assess the patient-reported outcome (PRO) and efficacy of add-on low-dose antimuscarinic therapy in over-active bladder (OAB) patients with suboptimal response to 4-week treatment with beta 3 agonist monotherapy (mirabegron, 50 mg). Materials and Methods We enrolled OAB patients with 4-week mirabegron (50 mg) treatment if the patients' symptoms improved, but not to a satisfactory extent (patient perception of bladder condition [PPBC] ≥4). Enrolled patients had 8-week low-dose antimuscarinics add-on therapy (propiverine HCl, 10 mg). Patients recorded 3-day voiding diary at screening, enrollment (after 4 weeks of mirabegron monotherapy) and after 8 weeks of add-on therapy. We assessed the change of PRO (PPBC) as a primary end point and the efficacy of add-on therapy (change of frequency, urgency, urinary urgency incontinence [UUI] based on voiding diary) as a secondary end point. Results Thirty patients (mean age, 62.3±12.8 years; mean symptom duration, 16.0±12.3 months) were finally enrolled in the study. The mean PPBC value was 4.3±0.4 after mirabegron monotherapy, and decreased to 3.2±1.0 after 8-week add-on therapy. The mean urinary frequency decreased from 10.1±3.1 to 8.8±3, the mean number of urgency episodes decreased from 3.6±1.6 to 1.8±1.2 and the number of urgency incontinence episodes decreased from 0.7±1.0 to 0.2±0.5 after add-on therapy. No patients had event of acute urinary retention and three patients complained of mild dry mouth after add-on therapy. Conclusions Add-on therapy of low-dose antimuscarinics exhibits good efficacy and safety in patients with suboptimal response after 4-week of mirabegron (50 mg) monotherapy. PMID:28681036

Additional low-dose antimuscarinics can improve overactive bladder symptoms in patients with suboptimal response to beta 3 agonist monotherapy.

PubMed

Shin, Jung Hyun; Kim, Aram; Choo, Myung-Soo

2017-07-01

We aimed to assess the patient-reported outcome (PRO) and efficacy of add-on low-dose antimuscarinic therapy in over-active bladder (OAB) patients with suboptimal response to 4-week treatment with beta 3 agonist monotherapy (mirabegron, 50 mg). We enrolled OAB patients with 4-week mirabegron (50 mg) treatment if the patients' symptoms improved, but not to a satisfactory extent (patient perception of bladder condition [PPBC] ≥4). Enrolled patients had 8-week low-dose antimuscarinics add-on therapy (propiverine HCl, 10 mg). Patients recorded 3-day voiding diary at screening, enrollment (after 4 weeks of mirabegron monotherapy) and after 8 weeks of add-on therapy. We assessed the change of PRO (PPBC) as a primary end point and the efficacy of add-on therapy (change of frequency, urgency, urinary urgency incontinence [UUI] based on voiding diary) as a secondary end point. Thirty patients (mean age, 62.3±12.8 years; mean symptom duration, 16.0±12.3 months) were finally enrolled in the study. The mean PPBC value was 4.3±0.4 after mirabegron monotherapy, and decreased to 3.2±1.0 after 8-week add-on therapy. The mean urinary frequency decreased from 10.1±3.1 to 8.8±3, the mean number of urgency episodes decreased from 3.6±1.6 to 1.8±1.2 and the number of urgency incontinence episodes decreased from 0.7±1.0 to 0.2±0.5 after add-on therapy. No patients had event of acute urinary retention and three patients complained of mild dry mouth after add-on therapy. Add-on therapy of low-dose antimuscarinics exhibits good efficacy and safety in patients with suboptimal response after 4-week of mirabegron (50 mg) monotherapy.

Effect of ezetimibe add-on therapy over 52 weeks extension analysis of prospective randomized trial (RESEARCH study) in type 2 diabetes subjects.

PubMed

Sakamoto, Kentaro; Kawamura, Mitsunobu; Watanabe, Takayuki; Ashidate, Keiko; Kohro, Takahide; Tanaka, Akira; Mori, Yasumichi; Tagami, Motoki; Hirano, Tsutomu; Yamazaki, Tsutomu; Shiba, Teruo

2017-06-24

Lowering cholesterol levels decreases the risk of atherosclerotic diseases. Effective ways to stably reduce LDL-C level are warranted in type 2 diabetic patients, a high-risk population for CVD, with various anti-diabetic therapeutic background. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles. We evaluated long-term ezetimibe add-on therapy in T2DM patients with hypercholesterolemia. In a randomized, multicenter, open-label, prospective study, a total of 109 T2DM patients not attaining LDL-C target value despite first-line dose statin (10 mg of atorvastatin or 1 mg of pitavastatin) therapy in Japan were recruited. We investigated the difference in cholesterol lowering effect between ezetimibe (10 mg) add-on statin (EAT) group and double-dose statin (DST) group. Changes of parameters related to atherosclerotic event risks were assessed. The reduction of LDL-C was larger in the EAT group (28.3%) than in the DST group (9.2%) at 52 weeks as well as the primary endpoint of 12 weeks. EAT achieved significant lower levels of TC and apo B, respectively. Both treatments attained significant reduction in sd-LDL-C or hsCRP on this long-term basis. Notably, sd-LDL-C in EAT reduced as low as 36.1 ± 14.9 mg/dl to reach near the threshold (35.0 mg/dl) for atherosclerosis with significantly higher achievement rate (55.6%) than DST treatment. Simultaneously, hsCRP reduction by EAT attained as low value as 0.52 ± 0.43 mg/l. In the present 52-week long-term period, ezetimibe add-on therapy showed a robust advantage in lowering LDL-C and in attaining target LDL-C values compared with the doubling of statin dose. Moreover, it's meaningful that sd-LDL, powerfully atherogenic lipoprotein, exhibited prominent decrease consistently prominently by ezetimibe add-on therapy. DM patients with hypercholesterolemia are at high risk for CAD, and adding ezetimibe onto usual-dose statin treatment in Japan has been

Characterization of C1q in Teleosts

PubMed Central

Hu, Yu-Lan; Pan, Xin-Min; Xiang, Li-Xin; Shao, Jian-Zhong

2010-01-01

C1qs are key components of the classical complement pathway. They have been well documented in human and mammals, but little is known about their molecular and functional characteristics in fish. In the present study, full-length cDNAs of c1qA, c1qB, and c1qC from zebrafish (Danio rerio) were cloned, revealing the conservation of their chromosomal synteny and organization between zebrafish and other species. For functional analysis, the globular heads of C1qA (ghA), C1qB (ghB), and C1qC (ghC) were expressed in Escherichia coli as soluble proteins. Hemolytic inhibitory assays showed that hemolytic activity in carp serum can be inhibited significantly by anti-C1qA, -C1qB, and -C1qC of zebrafish, respectively, indicating that C1qA, C1qB, and C1qC are involved in the classical pathway and are conserved functionally from fish to human. Zebrafish C1qs also could specifically bind to heat-aggregated zebrafish IgM, human IgG, and IgM. The involvement of globular head modules in the C1q-dependent classical pathway demonstrates the structural and functional conservation of these molecules in the classical pathway and their IgM or IgG binding sites during evolution. Phylogenetic analysis revealed that c1qA, c1qB, and c1qC may be formed by duplications of a single copy of c1qB and that the C1q family is, evolutionarily, closely related to the Emu family. This study improves current understanding of the evolutionary history of the C1q family and C1q-mediated immunity. PMID:20615881

Alternative Inactivated Poliovirus Vaccines Adjuvanted with Quillaja brasiliensis or Quil-A Saponins Are Equally Effective in Inducing Specific Immune Responses

PubMed Central

de Costa, Fernanda; Yendo, Anna Carolina A.; Cibulski, Samuel P.; Fleck, Juliane D.; Roehe, Paulo M.; Spilki, Fernando R.; Gosmann, Grace; Fett-Neto, Arthur G.

2014-01-01

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. PMID:25148077

Improvement of a stability-indicating method by Quality-by-Design versus Quality-by-Testing: a case of a learning process.

PubMed

Hubert, C; Lebrun, P; Houari, S; Ziemons, E; Rozet, E; Hubert, Ph

2014-01-01

The understanding of the method is a major concern when developing a stability-indicating method and even more so when dealing with impurity assays from complex matrices. In the presented case study, a Quality-by-Design approach was applied in order to optimize a routinely used method. An analytical issue occurring at the last stage of a long-term stability study involving unexpected impurities perturbing the monitoring of characterized impurities needed to be resolved. A compliant Quality-by-Design (QbD) methodology based on a Design of Experiments (DoE) approach was evaluated within the framework of a Liquid Chromatography (LC) method. This approach allows the investigation of Critical Process Parameters (CPPs), which have an impact on Critical Quality Attributes (CQAs) and, consequently, on LC selectivity. Using polynomial regression response modeling as well as Monte Carlo simulations for error propagation, Design Space (DS) was computed in order to determine robust working conditions for the developed stability-indicating method. This QbD compliant development was conducted in two phases allowing the use of the Design Space knowledge acquired during the first phase to define the experimental domain of the second phase, which constitutes a learning process. The selected working condition was then fully validated using accuracy profiles based on statistical tolerance intervals in order to evaluate the reliability of the results generated by this LC/ESI-MS stability-indicating method. A comparison was made between the traditional Quality-by-Testing (QbT) approach and the QbD strategy, highlighting the benefit of this QbD strategy in the case of an unexpected impurities issue. On this basis, the advantages of a systematic use of the QbD methodology were discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-22

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 54 [WC Docket No. 10-90; DA 13-311] Wireline... Communications Commission. ACTION: Proposed rule. SUMMARY: In this document, the Wireline Competition Bureau adds... . Follow the instructions for submitting comments. [ssquf] Federal Communications Commission's Web Site...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-18

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 54 [WC Docket No. 10-90; DA 13-704] Wireline... Communications Commission. ACTION: Proposed rule. SUMMARY: In this document, the Wireline Competition Bureau adds...://www.regulations.gov . Follow the instructions for submitting comments. [ssquf] Federal Communications...

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

PubMed

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 < 0.001]. The same effect was observed for total score [t(38) = 4.168, mean difference (95% CI) = 3.2(1.6-4.7), P < 0.001]. However the placebo and 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.

Efficacy and Safety of Vildagliptin as an Add-On Therapy in Inadequately Controlled Type 2 Diabetes Patients Treated With Basal Insulin.

PubMed

Saito, Daisuke; Kanazawa, Akio; Shigihara, Nayumi; Sato, Fumihiko; Uchida, Toyoyoshi; Sato, Junko; Goto, Hiromasa; Miyatsuka, Takeshi; Ikeda, Fuki; Ogihara, Takeshi; Ohmura, Chie; Watada, Hirotaka

2017-03-01

The aim of this study was to investigate the efficacy and safety of vildagliptin as an add-on therapy for patients with type 2 diabetes mellitus inadequately controlled with basal insulin. Twenty-four patients treated with basal insulin and oral anti-diabetes drugs were randomly allocated into two groups: the control group (did not receive any add-on drugs) and vildagliptin group (received vildagliptin 100 mg/day for 6 months). The primary outcome was changes in hemoglobin A1c (HbA1c) from baseline to end of study. Treatment with vildagliptin significantly reduced HbA1c from 8.1±0.7% at baseline to 7.1±0.7% (P < 0.01), while there was no significant change of HbA1c in the control group. Vildagliptin group showed significant reduction of HbA1c compared with control group (-1.0±0.3% vs. 0.2±0.8%, P < 0.01). In addition, vildagliptin group showed a significant increase in 1,5-anhydroglucitol compared with the control group (4.5 ± 3.4 vs. 0.5 ± 4.1 μg/mL, P < 0.05). Mild hypoglycemia was reported in one patient of the vildagliptin group and two patients of the control group. Vildagliptin improved glycemic control without increasing hypoglycemia in Japanese type 2 diabetes inadequately controlled with basal insulin treatment and other oral anti-diabetes drugs. This study was registered with UMIN (University Hospital Medical Information Network ID#000010849).

Preliminary, open-label, pilot study of add-on oral Δ9-tetrahydrocannabinol in chronic post-traumatic stress disorder.

PubMed

Roitman, Pablo; Mechoulam, Raphael; Cooper-Kazaz, Rena; Shalev, Arieh

2014-08-01

Many patients with post-traumatic stress disorder (PTSD) achieve but partial remission with current treatments. Patients with unremitted PTSD show high rates of substance abuse. Marijuana is often used as compassion add-on therapy for treatment-resistant PTSD. This open-label study evaluates the tolerance and safety of orally absorbable Δ(9)-tetrahydrocannabinol (THC) for chronic PTSD. Ten outpatients with chronic PTSD, on stable medication, received 5 mg of Δ(9)-THC twice a day as add-on treatment. There were mild adverse effects in three patients, none of which led to treatment discontinuation. The intervention caused a statistically significant improvement in global symptom severity, sleep quality, frequency of nightmares, and PTSD hyperarousal symptoms. Orally absorbable Δ(9)-THC was safe and well tolerated by patients with chronic PTSD.

Meeting report: applied biopharmaceutics and quality by design for dissolution/release specification setting: product quality for patient benefit.

PubMed

Selen, Arzu; Cruañes, Maria T; Müllertz, Anette; Dickinson, Paul A; Cook, Jack A; Polli, James E; Kesisoglou, Filippos; Crison, John; Johnson, Kevin C; Muirhead, Gordon T; Schofield, Timothy; Tsong, Yi

2010-09-01

A biopharmaceutics and Quality by Design (QbD) conference was held on June 10-12, 2009 in Rockville, Maryland, USA to provide a forum and identify approaches for enhancing product quality for patient benefit. Presentations concerned the current biopharmaceutical toolbox (i.e., in vitro, in silico, pre-clinical, in vivo, and statistical approaches), as well as case studies, and reflections on new paradigms. Plenary and breakout session discussions evaluated the current state and envisioned a future state that more effectively integrates QbD and biopharmaceutics. Breakout groups discussed the following four topics: Integrating Biopharmaceutical Assessment into the QbD Paradigm, Predictive Statistical Tools, Predictive Mechanistic Tools, and Predictive Analytical Tools. Nine priority areas, further described in this report, were identified for advancing integration of biopharmaceutics and support a more fundamentally based, integrated approach to setting product dissolution/release acceptance criteria. Collaboration among a broad range of disciplines and fostering a knowledge sharing environment that places the patient's needs as the focus of drug development, consistent with science- and risk-based spirit of QbD, were identified as key components of the path forward.

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

PubMed

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.

Aprepitant as an add-on therapy in children receiving highly emetogenic chemotherapy: a randomized, double-blind, placebo-controlled trial.

PubMed

Bakhshi, Sameer; Batra, Atul; Biswas, Bivas; Dhawan, Deepa; Paul, Reeja; Sreenivas, Vishnubhatla

2015-11-01

Aprepitant, a neurokinin-1 receptor antagonist, in combination with 5 HT-3 antagonist and dexamethasone is recommended in adults receiving moderately and highly emetogenic chemotherapy to reduce chemotherapy-induced vomiting (CIV). Data for use of aprepitant in children is limited and hence aprepitant is not recommended by Pediatric Oncology Group of Ontario guidelines for prevention of CIV in children <12 years. A randomized, double-blind, placebo-controlled trial was conducted at a single center in chemotherapy naïve children (5-18 years) receiving highly emetogenic chemotherapy. All patients received intravenous ondansetron (0.15 mg/kg) and dexamethasone (0.15 mg/kg) prior to chemotherapy followed by oral ondansetron and dexamethasone. Patients randomly assigned to aprepitant arm received oral aprepitant (15-40 kg = days 1-3, 80 mg; 41-65 kg = day 1, 125 mg and days 2-3, 80 mg) 1 h before chemotherapy. Control group received placebo as add-on therapy. Primary outcome measure was the incidence of acute moderate to severe vomiting, which was defined as more than two vomiting episodes within 24 h after the administration of the first chemotherapy dose until 24 h after the last chemotherapy dose in the block. Complete response (CR) was defined as absence of vomiting and retching during the specified phase. Of the 96 randomized patients, three were excluded from analysis; 93 patients were analyzed (50 in aprepitant arm and 43 in placebo arm). Acute moderate and severe vomiting was reported in 72 % patients receiving placebo and 38 % patients receiving aprepitant (p = 0.001). Complete response rates during acute phase were significantly higher in aprepitant arm (48 vs. 12 %, p < 0.001). No major adverse effects were reported by patients/guardians. This double-blind, randomized, placebo-controlled trial shows that aprepitant significantly decreases the incidence of CIV during acute phase when used as an add-on drug with ondansetron and dexamethasone in children

[Application of improved regional citrate anticoagulation in continuous hemofiltration in children].

PubMed

Bai, K; Liu, C J; Fu, Y Q; Xu, F

2017-05-04

Objective: To investigate the application of regional citrate anticoagulation with calcium hemofiltration basic solution in continuous hemofiltration in children. Method: The clinical data of 18 patients with citrate anticoagulation in continuous hemofiltration in children, excluding the hepatic failure and septic shock cases, were analyzed retrospectively, from September 2015 to August 2016 in Intensive Care Unit of the Children's Hospital of Chongqing Medical University.The commercial calcium hemofiltration basic solution was used as displacement liquid . The blood gas analysis, electrolyte, four coagulation tests during the treatment and the corresponding relations of quantity of blood flow(QB), quantity of citrate flow(QCi), quantity of sodium bicarbonate flow(QSB), quantity of calcium flow(QCa), quantity of filtered solution flow (Qf) were monitored. Meanwhile, the blood gas analysis, electrolyte, four coagulation tests, useful life of filter, bleeding and clotting events internal and external before, during and after the treatments were monitored, too. And the common complications of citrate anticoagulation, such as hypocalcaemia, metabolic alkalosis, citrate accumulation and hypernatremia were observed. Result: Continuous hemofiltration was applied in 18 patients for 734.5 hours, and the average useful life of filter was (25±11)h.There was no obvious clotting event. There were 168 groups of datum of the blood gas analysis, electrolyte, four coagulation tests during the treatment and the relationships of QB, QCi, QSB, QCa, Qf had been collected. The relationships of the initial parameter settings of QB, QCi, QSB, QCa and Qf were concluded as QCi=1.8×QB, QCa=0.12×QB, QSB=0.01×Qf . There were 150 times(89.3%)of extracorporeal ionized calcium(iCa(E)(2+)) and 162 times(96.4%) of intracorporal ionized calcium(iCa(I)(2+)) reached the anticoagulation target. Although all the comparisons of Na(+) ((136.2±4.1) vs .(138.2±2.4) vs .(138.5±3.9)mmol/L), iCa(2+) ((1

A large indel mutation of the bovine ADD1/SREBP1c gene and its effects on growth traits in some native cattle breeds from China.

PubMed

Huang, Yong-Zhen; Zhang, En-Ping; Wang, Jing; Huai, Yong-Tao; Ma, Liang; Chen, Fu-Ying; Lan, Xian-Yong; Lei, Chu-Zhao; Fang, Xing-Tang; Wang, Ju-Qiang; Chen, Hong

2011-03-01

Adipocyte determination and differentiation-dependent factor 1/sterol regulatory element-binding protein-1c (ADD1/SREBP1c) is a major determinant of tissue differential lipogenic capacity in mammalian and avian species. The objectives of the present study were to focus on insertion-deletion polymorphism (indel) in the bovine ADD1/SREBP1c gene, and analyzing its effect on growth traits in a sample of 1035 cattle belonging to four Chinese cattle breeds. PCR-SSCP, DNA sequencing and agarose electrophoresis methods were used. The 778 bp PCR products of ADD1/SREBP1c gene exhibited three genotypes and two alleles were revealed: W and D. Frequencies of the W allele varied from 0.8651 to 1.000. The associations of the 84 bp indel mutation of ADD1/SREBP1c gene with growth traits of 265 Nanyang cows were analyzed. The animals with genotype WD had significantly higher birth weight, body weight, average daily gain than those with genotype WW at birth, 6-, 12-, 18-, and 24-month old (P < 0.05 or P < 0.01). These results suggest that the indel mutation of bovine ADD1/SREBP1c gene may influence the growth traits in cattle.

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

ERIC Educational Resources Information Center

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.

PubMed

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.

Early add-on treatment vs alternative monotherapy in patients with partial epilepsy.

PubMed

Semah, Franck; Thomas, Pierre; Coulbaut, Safia; Derambure, Philippe

2014-06-01

The aim of this study was to evaluate the impact of two different therapeutic strategies in patients with partial seizures who were intractable to the first prescribed antiepileptic drug (AED); alternative monotherapy vs early add-on treatment. We conducted an open, cluster-randomised, prospective, controlled trial in patients with persistent partial seizures, despite treatment with one AED, who were never administered any other AEDs. Neurologists were randomised to two strategies: in group A, an alternative monotherapy with a second AED was employed; in group B, add-on treatment with a second AED was employed. The primary outcome was the percentage of seizure-free patients during a two-month period after six months of treatment. The secondary outcomes were: (i) the percentage of patients achieving a 50% reduction in the number of seizures at six months; (ii) the quality of life based on the Quality Of Life In Epilepsy scale; and (iii) tolerability. A total of 143 neurologists were included and randomised, and 264 patients were evaluated. At six months, the primary outcome was 51% in group A and 45% in group B (p=0.34). The percentage of patients achieving a 50% reduction in the number of seizures at six months was 76% in group A and 84% in group B (p=0.53). The quality of life and the tolerability did not significantly differ between the two groups. Alternative monotherapy or early treatment initiation with another AED drug resulted in similar efficacy, and the side effects associated with monotherapy and combined therapies were similar, which suggests that individual susceptibility is more important than the number and burden of AEDs used.

The role of melting alpine glaciers in mercury export and transport: An intensive sampling campaign in the Qugaqie Basin, inland Tibetan Plateau.

PubMed

Sun, Xuejun; Wang, Kang; Kang, Shichang; Guo, Junming; Zhang, Guoshuai; Huang, Jie; Cong, Zhiyuan; Sun, Shiwei; Zhang, Qianggong

2017-01-01

Glaciers, particularly alpine glaciers, have been receding globally at an accelerated rate in recent decades. The glacial melt-induced release of pollutants (e.g., mercury) and its potential impact on the atmosphere and glacier-fed ecosystems has drawn increasing concerns. During 15th-20th August, 2011, an intensive sampling campaign was conducted in Qugaqie Basin (QB), a typical high mountain glacierized catchment in the inland Tibetan Plateau, to investigate the export and transport of mercury from glacier to runoff. The total mercury (THg) level in Zhadang (ZD) glacier ranged from <1 to 20.8 ng L -1 , and was slightly higher than levels measured in glacier melt water and the glacier-fed river. Particulate Hg (PHg) was the predominant form of Hg in all sampled environmental matrices. Mercury concentration in Qugaqie River (QR) was characterized by a clear diurnal variation which is linked to glacier melt. The estimated annual Hg exports by ZD glacier, the upper river basin and the entire QB were 8.76, 7.3 and 157.85 g, respectively, with respective yields of 4.61, 0.99 and 2.74 μg m -2  yr -1 . Unique landforms and significant gradients from the glacier terminus to QB estuary might promote weathering and erosion, thereby controlling the transport of total suspended particulates (TSP) and PHg. In comparison with other glacier-fed rivers, QB has a small Hg export yet remarkably high Hg yield, underlining the significant impact of melting alpine glaciers on regional Hg biogeochemical cycles. Such impacts are expected to be enhanced in high altitude regions under the changing climate. Copyright © 2016 Elsevier Ltd. All rights reserved.

The role of melting alpine glaciers in mercury export and transport: an intensive sampling campaign in the Qugaqie Basin, inland Tibetan Plateau

NASA Astrophysics Data System (ADS)

Sun, X.; Zhang, Q.

2016-12-01

Glaciers, particularly alpine glaciers, have been receding globally at an accelerated rate in recent decades. The glacial melt-induced release of pollutants (e.g., mercury) and its potential impact on the atmosphere and glacier-fed ecosystems has drawn increasing concerns. During 15th to 20th August, 2011, an intensive sampling campaign was conducted in Qugaqie Basin (QB), a typical high mountain glacierized catchment in the inland Tibetan Plateau, to investigate the export and transport of mercury from glacier to runoff. The total mercury (THg) level in Zhadang (ZD) glacier ranged from < 1 to 20.8 ng L-1, and was slightly higher than levels measured in glacier melt water and the glacier-fed river. Particulate Hg (PHg) was the predominant form of Hg in all sampled environmental matrices. Mercury concentration in Qugaqie River (QR) was characterized by a clear diurnal variation which is linked to glacier melt. The estimated annual Hg exports by ZD glacier, the upper river basin and the entire QB were 8.76, 7.3 and 157.85 g, respectively, with respective yields of 4.61, 0.99 and 2.74 μg m-2 yr-1. Unique landforms and significant gradients from the glacier terminus to QB estuary might promote weathering and erosion, thereby controlling the transport of total suspended particulates (TSP) and PHg. In comparison with other glacier-fed rivers, QB has a small Hg export yet remarkably high Hg yield, underlining the significant impact of melting alpine glaciers on regional Hg biogeochemical cycles. Such impacts are expected to be enhanced in high altitude regions under the changing climate.

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

PubMed

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

Comparison of the clinical outcomes between antiviral-naïve patients treated with entecavir and lamivudine-resistant patients receiving adefovir add-on lamivudine combination treatment

PubMed Central

Kim, Hong Joo; Park, Soo Kyung; Yang, Hyo Joon; Jung, Yoon Suk; Park, Jung Ho; Park, Dong Il; Cho, Yong Kyun; Sohn, Chong Il; Jeon, Woo Kyu; Kim, Byung Ik; Choi, Kyu Yong

2016-01-01

Background/Aims To analyze the effects of preexisting lamivudine (LAM) resistance and applying antiviral treatment (adefovir [ADV] add-on LAM combination treatment) on long-term treatment outcomes, and comparing the clinical outcomes of antiviral-naïve chronic hepatitis B patients receiving entecavir (ETV) monotherapy. Methods This study enrolled 73 antiviral-naïve patients who received 0.5-mg ETV as an initial therapy and 54 patients who received ADV add-on LAM combination treatment as a rescue therapy from July 2006 to July 2010. Results During 24-month treatments, the decreases in serum log10HBV-DNA values (copies/mL) were significantly greater in the antiviral-naïve patients treated with ETV than the patients receiving ADV add-on LAM combination treatment. The biochemical response rates for alanine aminotransferase normalization at 6 months (ETV) and 12 months (ADV add-on LAM) were 90.4% (66/73) and 77.8% (42/54), respectively (P=0.048). A Kaplan-Meier analysis indicated that the rates of serologic response, viral breakthrough, and emergence of genotypic resistance did not differ significantly between the two patient groups. There were also no significant intergroup differences in the rates of disease progression (PD) and new development of hepatocellular carcinoma (HCC). Conclusion The long-term clinical outcomes of antiviral-naïve patients treated with ETV and LAM-resistant patients receiving ADV add-on LAM combination treatment were comparable in terms of the emergence of HCC and disease progression. PMID:27729626

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

PubMed

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

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

ERIC Educational Resources Information Center

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…

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

ERIC Educational Resources Information Center

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…

Dipeptidyl peptidase-4 inhibitors or sodium glucose co-transporter-2 inhibitors as an add-on to insulin therapy: A comparative review

PubMed Central

Singh, Awadhesh Kumar; Singh, Ritu

2016-01-01

The gradual decline in β-cell function is inevitable in type 2 diabetes mellitus and therefore, substantial proportions of patients require insulin subsequently, in order to achieve optimal glucose control. While weight gain, hypoglycemia, and fluid retention especially during dose intensification is a known limitation to insulin therapy, these adverse effects also reduce patient satisfaction and treatment adherence. It is also possible that the benefits of intensive control achieved by insulin therapy, perhaps get nullified by the weight gain and hypoglycemia. In addition, improvement in plasma glucose or glycated hemoglobin (HbA1c) itself is associated with weight gain. Notably, studies have already suggested that reduction in body weight by ~3–5%, may allow a significantly better glycemic control. Thus, a class of drugs, which can reduce HbA1c effectively, yet are weight neutral or preferably reduce body weight, could be the most sought out strategy as an add-on therapy to insulin. While sulfonylureas (SUs) are associated with weight gain and hypoglycemia, pioglitazone increases body weight and fluid retention. Moreover, SUs are not recommended once premix or prandial insulin is commenced. The addition of newer agents, such as glucagon-like peptide-1 receptor agonist to insulin certainly appears to be an effective tool in reducing both HbA1c and body weight as is evident across the studies; however, this approach incurs an additional injection as well as cost. Dipeptidyl peptidase-4 inhibitors (DPP-4I) and sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are other exciting options, as an add-on to insulin therapy primarily because these are oral drugs and do not possess any intrinsic potential of hypoglycemia. Furthermore, these are either weight neutral or induce significant weight loss. This review article aims to comparatively analyze the safety and efficacy of DPP-4I and SGLT-2I, as an add-on therapy to insulin. PMID:26904466

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

PubMed

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.

PubMed

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

ERIC Educational Resources Information Center

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

ERIC Educational Resources Information Center

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…

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

PubMed

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

NASA Astrophysics Data System (ADS)

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 .

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.

PubMed

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.

PubMed

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.

PubMed

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.

How PET/MR Can Add Value For Children With Cancer.

PubMed

Daldrup-Link, Heike

2017-03-01

To review how PET/MR technology could add value for pediatric cancer patients. Since many primary tumors in children are evaluated with MRI and metastases are detected with PET/CT, integrated PET/MR can be a time-efficient and convenient solution for pediatric cancer staging. 18 F-FDG PET/MR can assess primary tumors and the whole body in one imaging session, avoid repetitive anesthesia and reduce radiation exposure compared to 18 F-FDG PET/CT. This article lists 10 action points, which might improve the clinical value of PET/MR for children with cancer. However, even if PET/MR proves valuable, it cannot enter mainstream applications if it is not accessible to the majority of pediatric cancer patients. Therefore, innovations are needed to make PET/MR scanners affordable and increase patient throughput. PET/MR offers opportunities for more efficient, accurate and safe diagnoses of pediatric cancer patients. The impact on patient management and outcomes has to be substantiated by large-scale prospective clinical trials.

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

PubMed

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.

Add-On Memantine Treatment for Bipolar II Disorder Comorbid with Alcohol Dependence: A 12-Week Follow-Up Study.

PubMed

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

2018-06-01

Bipolar disorder (BD), especially BD-II, is frequently comorbid with alcohol dependence. Because BD-II and alcohol dependence are neurodegenerative disorders, agents with anti-inflammatory and neurotrophic effects might provide effective therapy. We investigated whether add-on memantine to regular valproic acid treatment ameliorated clinical symptoms, reduced alcohol use, and cytokine levels, and increased plasma brain-derived neurotrophic factor (BDNF) in BD-II patients with comorbid alcohol dependence. In a single-arm 12-week clinical trial, BD-II patients with comorbid alcohol dependence (n = 45) undergoing regular valproic acid treatments were given add-on memantine (5 mg/d). Symptom severity, alcohol use, cytokine (plasma tumor necrosis factor-α and C-reactive protein [CRP], transforming growth factor-β1 [TGF-β1], interleukin-8 [IL-8], IL-10), and plasma BDNF levels were regularly assessed. Mean within-group decreases in Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) scores, alcohol use, CRP, BDNF, and IL-8 levels were significantly different from baseline after 12 weeks of treatment. We found no significant correlation between alcohol use levels and changes in HDRS or YMRS scores. The correlation between reduced alcohol use and reduced TGF-β1 level was significant (B = 0.003, p = 0.019). BD-II comorbid with alcohol dependence might benefit from add-on memantine treatment, which significantly reduced clinical severity, alcohol use, and plasma cytokine levels, and increased BDNF levels. Copyright © 2018 by the Research Society on Alcoholism.

76 FR 65763 - Self-Regulatory Organizations; ICE Clear Credit LLC; Order Approving Proposed Rule Change To Add...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-24

... Organizations; ICE Clear Credit LLC; Order Approving Proposed Rule Change To Add Rules Related to the Clearing of Emerging Markets Sovereigns October 18, 2011. I. Introduction On August 30, 2011, ICE Clear Credit... Contracts by ICE Trust), 26D- 315 (Terms of the Cleared SES Contract), 26D-316 (Relevant Physical Settlement...

A tutorial for developing a topical cream formulation based on the Quality by Design approach.

PubMed

Simões, Ana; Veiga, Francisco; Vitorino, Carla; Figueiras, Ana

2018-06-20

The pharmaceutical industry has entered in a new era, as there is a growing interest in increasing the quality standards of dosage forms, through the implementation of more structured development and manufacturing approaches. For many decades, the manufacturing of drug products was controlled by a regulatory framework to guarantee the quality of the final product through a fixed process and exhaustive testing. Limitations related to the Quality by Test (QbT) system have been widely acknowledged. The emergence of Quality by Design (QbD) as a systematic and risk-based approach introduced a new quality concept based on a good understanding of how raw materials and process parameters influence the final quality profile. Although the QbD system has been recognized as a revolutionary approach to product development and manufacturing, its full implementation in the pharmaceutical field is still limited. This is particularly evident in the case of semisolid complex formulation development. The present review aims at establishing a practical QbD framework to describe all stages comprised in the pharmaceutical development of a conventional cream in a comprehensible manner. Copyright © 2018. Published by Elsevier Inc.

Quality of life, mood and seizure control in patients with brain tumor related epilepsy treated with lacosamide as add-on therapy: A prospective explorative study with a historical control group.

PubMed

Maschio, Marta; Zarabla, Alessia; Maialetti, Andrea; Fabi, Alessandra; Vidiri, Antonello; Villani, Veronica; Giannarelli, Diana

2017-08-01

Brain tumor-related epilepsy (BTRE) is often drug resistant and patients can be forced to take polytherapy that can adversely affect their quality of life (QoL). Lacosamide (LCM) is a new antiepileptic drug (AED) used as adjunctive therapy in patients with partial seizures with or without secondary generalization, with a favorable pharmacokinetic profile that seems to be effective and well tolerated. Therefore it represents a possible therapeutic choice for patients with BTRE. We propose a prospective study with a historical control group to evaluate the effect of LCM as add-on therapy on seizure control and quality of life in patients with BTRE. This study has been designed to test the superiority of Lacosamide over Levetiracetam as an add-on. We compared a prospective cohort of 25 patients treated with Lacosamide with a historical control group (n=19) treated with Levetiracetam as an add-on. We recruited 25 adult patients (M 18, F 7; mean age 41.9) affected by BTRE with uncontrolled partial-onset seizures treated with AED polytherapy. We added LCM as an add-on. Patients were evaluated at baseline, after 3months and at 6months. This population has been compared with a historical control group of 19 BTRE adult patients (M 13, F 6; median age 48.0, range: 28-70) with uncontrolled partial-onset seizures treated with LEV as add-on. The patients underwent QoL, mood and adverse events tests (Adverse Event Profile-AEP) and evaluation of seizure frequency. Twelve patients had high grade gliomas, and thirteen had low grade gliomas. During follow-up, thirteen patients underwent chemotherapy, three radiotherapy and five patients had disease progression. Nine patients had simple partial seizures, eight had complex partial seizures, and eight had secondary generalized seizures. Fifteen patients were in monotherapy and ten in polytherapy with AEDs. LCM was added up to reach the maximum dosage of 400mg/die (mean final dose 300mg/die). Four patients dropped out due to poor

Sociodemographic and diagnostic characteristics of prescribing a second-line lipid-lowering medication: ezetimibe used as initial medication, switch from statins, or add-on medication.

PubMed

Wallach-Kildemoes, Helle; Hansen, Ebba Holme

2015-10-01

Ezetimibe is used as a second-line lipid-lowering medication (LLM) if statin therapy is not tolerated or cholesterol targets are not reached by statins alone. We aimed to investigate the impact of sociodemographic factors on ezetimibe initiation as (a) incident LLM therapy, (b) add-on therapy, and (c) switch from statins. All individuals aged 30+ who had filled at least one prescription for either statins (N = 581.074) or ezetimibe (N = 7.932) in 2011 were followed in the nationwide Danish registries to explore LLM prescribing patterns from 1 January 2011 to end 2012. Using logistic regression analyses, the odds ratio (OR) with 95% confidence intervals (CIs) was calculated for (a) incident ezetimibe use among LLM initiators (N = 77,472), (b) ezetimibe switching by discontinuing statin users (N = 37,509), and (c) ezetimibe as add-on by non-discontinuing statin users (N = 442,672). Women had higher odds for initiating ezetimibe than men (switch OR = 1.55; 95% CI = 1.32-1.82). While prior use of newer high-potency statins was the strongest predictor (add-on (5.56; 4.95-6.24), income was the strongest socioeconomic predictor for incident LLM use (1.33; 1.14-1.56) and switching (1.64; 1.27-2.13). Both income and education were predictors for add-on therapy, with the educational effect mediated by prior use of high-potency statins. Odds for ezetimibe prescribing were highest in myocardial infarction patients. While higher income is a predictor for switching to ezetimibe, both higher education and income are weak predictors for using ezetimibe as add-on therapy. Women and individuals with myocardial infarction are more likely to be prescribed ezetimibe than others, despite lack of evidence of ezetimibe lowering the risk of cardiovascular events.

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

ERIC Educational Resources Information Center

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…

78 FR 12409 - Self-Regulatory Organizations; ICE Clear Credit LLC; Order Approving Proposed Rule Change To Add...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-22

... Organizations; ICE Clear Credit LLC; Order Approving Proposed Rule Change To Add Rules Related to the Clearing of iTraxx Europe Index CDS February 15, 2013. I. Introduction On December 6, 2012, ICE Clear Credit... (Acceptance of iTraxx Europe Untranched Contracts by ICE Clear Credit), 26F-315 (Terms of the Cleared iTraxx...

The Effects of Gonadotropin-Releasing Hormone Agonist Combined with Add-Back Therapy on Quality of Life for Adolescents with Endometriosis: A Randomized Controlled Trial.

PubMed

Sadler Gallagher, Jenny; Feldman, Henry A; Stokes, Natalie A; Laufer, Marc R; Hornstein, Mark D; Gordon, Catherine M; DiVasta, Amy D

2017-04-01

Use of gonadotropin-releasing hormone agonists (GnRHa) to treat endometriosis can cause mood and vasomotor side effects. "Add-back therapy," the combination of low-dose hormones, limits side effects but research is limited to adults. We sought to characterize quality of life (QOL) before treatment and to compare an add-back regimen of norethindrone acetate (NA) with conjugated estrogens (CEE) to NA alone for preventing side effects of GnRHa therapy in female adolescents with endometriosis. Twelve-month double-blind, placebo-controlled trial. Pediatric Gynecology clinic in Boston, Massachusetts. Fifty female adolescents (aged 15-22 years) with surgically confirmed endometriosis initiating treatment with GnRHa. Subjects were randomized to: NA (5 mg/d) with CEE (0.625 mg/d) or NA (5 mg/d) with placebo. All subjects received leuprolide acetate depot every 3 months. The Short Form-36 v2 Health Survey, Beck Depression Inventory II, and Menopause Rating Scale were completed at repeated intervals. At baseline, subjects reported impaired physical health-related QOL compared with national norms (all P < .0001). Over 12 months, these Short Form-36 v2 scores improved (all P < .05). Subjects receiving NA with CEE showed greater improvements in the pain, vitality, and physical health subscales (P between groups < .05) than those receiving NA alone, as well as better physical functioning (P < .05). There were no changes in depression or menopause-like symptoms in either group. Female adolescents with endometriosis initiating GnRHa therapy have impaired QOL. Treatment with GnRHa combined with add-back therapy led to improved QOL, with no worsening of mood or menopausal side effects. NA with CEE was superior to NA alone for improving physical health-related QOL. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

The Psychiatric Assessment Schedule for Adult with Developmental Disability (PAS-ADD) Checklist: Reliability and Validity of French Version

ERIC Educational Resources Information Center

Gerber, F.; Carminati, G. Galli

2013-01-01

Background: The lack of psychometric measures of psychopathology especially in intellectual disabilities (ID) population was addressed by creation of the Psychiatric Assessment Schedule for Adult with Developmental Disability (PAS-ADD-10) in Moss et?al. This schedule is a structured interview designed for professionals in psychopathology. The…

77 FR 76490 - Determination Concerning a Petition to Add a Class of Employees to the Special Exposure Cohort

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Determination Concerning a Petition to Add a Class of... (NIOSH), Centers for Disease Control and Prevention, Department of Health and Human Services (HHS... employees from the Mound Plant in Miamisburg, Ohio, to the Special Exposure Cohort (SEC) under the Energy...

40 CFR 63.3966 - How do I determine the add-on control device emission destruction or removal efficiency?

Code of Federal Regulations, 2010 CFR

2010-07-01

... device emission destruction or removal efficiency? 63.3966 Section 63.3966 Protection of Environment... or removal efficiency? You must use the procedures and test methods in this section to determine the add-on control device emission destruction or removal efficiency as part of the performance test...

40 CFR 63.3966 - How do I determine the add-on control device emission destruction or removal efficiency?

Code of Federal Regulations, 2011 CFR

2011-07-01

... device emission destruction or removal efficiency? 63.3966 Section 63.3966 Protection of Environment... or removal efficiency? You must use the procedures and test methods in this section to determine the add-on control device emission destruction or removal efficiency as part of the performance test...

Tip Design of Hemodialysis Catheters Influences Thrombotic Events and Replacement Rate.

PubMed

Petridis, C; Nitschke, M; Lehne, W; Smith, E; Goltz, J P; Lehnert, H; Meier, M

2017-02-01

Central venous tunnelled hemodialysis catheters (CVTC) are used for initial vascular access in patients with renal failure. Tip design of the CVTC may play an important role in catheter function and complication rates, influencing adequate hemodialysis treatment of these patients. This prospective, observational cohort study compared the function and complication rates of two CVTCs in patients with end stage renal disease (ESRD) within a follow-up period of 24 months. The study included patients with ESRD who received either a CVTC with a split tip (ST) or a shotgun tip (SG). All patients underwent dialysis within 24 h of intervention. Blood flow was documented initially (Qb 0 ) and was followed up after 6 (Qb 6 ), 12 (Qb 12 ), and 24 (Qb 24 ) months. Analysis of blood flow and complication rates within the follow-up period was performed by questionnaires. In total, 185 patients were included, of whom 93 received a ST CVTC and 92 a SG CVTC. Baseline parameters did not differ significantly between groups. CVTC blood flow was not significantly different between the two devices. Thrombolytic therapy with Alteplase was used significantly more often in the ST group (29%) than in the SG group (16%) (p < 0.05). The CVTC replacement rate was significantly higher in the ST group (19.3%) compared with the SG group (8.7%) (p < 0.05). The tip design of CVTC (split or shotgun) appears to be irrelevant for long-term blood flow during dialysis treatment. However, patients may benefit from SG catheters over ST catheters where replacement rates and thrombolytic treatment are concerned. Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Gaseous Structures in Barred Galaxies: Effects of the Bar Strength

NASA Astrophysics Data System (ADS)

Kim, Woong-Tae; Seo, Woo-Young; Kim, Yonghwi

2012-10-01

Using hydrodynamic simulations, we investigate the physical properties of gaseous substructures in barred galaxies and their relationships with the bar strength. The gaseous medium is assumed to be isothermal and unmagnetized. The bar potential is modeled as a Ferrers prolate with index n. To explore situations with differing bar strength, we vary the bar mass f bar relative to the spheroidal component as well as its aspect ratio { R}. We derive expressions as functions of f bar and { R} for the bar strength Qb and the radius r(Qb ) where the maximum bar torque occurs. When applied to observations, these expressions suggest that bars in real galaxies are most likely to have f bar ~ 0.25-0.50 and n <~ 1. Dust lanes approximately follow one of the x 1-orbits and tend to be straighter under a stronger and more elongated bar, but are insensitive to the presence of self-gravity. A nuclear ring of a conventional x 2 type forms only when the bar is not so massive or elongated. The radius of an x 2-type ring is generally smaller than the inner Lindblad resonance, decreases systematically with increasing Qb , and is slightly larger when self-gravity is included. This is evidence that the ring position is not determined by the resonance, but instead by the amount of angular momentum loss at dust-lane shocks. Nuclear spirals exist only when the ring is of the x 2 type and is sufficiently large in size. Unlike the other features, nuclear spirals are transient in that they start out being tightly wound and weak, and then, due to the nonlinear effect, unwind and become stronger until they turn into shocks, with an unwinding rate that is higher for larger Qb . The mass inflow rate to the galaxy center is found to be less than 0.01 M ⊙ yr-1 for models with Qb <~ 0.2, while becoming larger than 0.1 M ⊙ yr-1 when Qb >~ 0.2 and self-gravity is included.

When do drilling alliances add value? The alliance value model

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

Brett, J.F.; Craig, V.B.; Wadsworth, D.B.

1996-12-31

A recent GRI report details three previously unstudied aspects of alliances: specific measurable factors that improve alliance success, how a successful alliance should be structured, and when an alliance makes economic sense. The most innovative tool to emerge from the report, the Alliance Value Model, addresses the third aspect. The theory behind the Alliance Value Model is that the long-term viability of any drilling relationship hinges on its ability to create real value and achieve stability. Based upon the report`s findings, the most effective way to form such an alliance is through a detailed description and integration of the technicalmore » processes involved. This new type of process-driven alliance is characterized by a value chain which links together a common set of technical processes, mutually defined bottomline goals, and shared benefits. Building a process-driven alliance requires time and people and therefore has an associated cost. The real value generated by an alliance must exceed this start-up cost. The Alliance Value Model computes the net present value (NPV) of the cash flows for four different operating arrangements: (1) Business As Usual (conventional competitive bidding process), (2) Process-Driven Alliance (linking technical processes to accelerate production and reduce expenses), (3) Incentivized Process-Driven Alliance (linked technical processes with performance incentives to promote stability), and (4) No Drill Case (primarily used to gauge the market value of services). These arrangements test different degrees of process integration between an operator and its suppliers. They can also help determine if the alliance can add enough value to exceed startup costs and if the relationship will be stable. Each partner can test the impact of the relational structure on its own profitability. When an alliance is warranted, all participants can benefit from real value generated in a stable relationship.« less

78 FR 18351 - Determination Concerning a Petition To Add a Class of Employees to the Special Exposure Cohort

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Determination Concerning a Petition To Add a Class of... (NIOSH), Centers for Disease Control and Prevention, Department of Health and Human Services (HHS... monitored (urine or fecal), who worked at the Plutonium Finishing Plant in the 200 Area at the Hanford site...

40 CFR 63.9323 - How do I determine the add-on control device emission destruction or removal efficiency?

Code of Federal Regulations, 2011 CFR

2011-07-01

... device emission destruction or removal efficiency? 63.9323 Section 63.9323 Protection of Environment... determine the add-on control device emission destruction or removal efficiency? You must use the procedures... removal efficiency as part of the performance test required by § 63.9310. You must conduct three test runs...

40 CFR 63.9323 - How do I determine the add-on control device emission destruction or removal efficiency?

Code of Federal Regulations, 2010 CFR

2010-07-01

... device emission destruction or removal efficiency? 63.9323 Section 63.9323 Protection of Environment... determine the add-on control device emission destruction or removal efficiency? You must use the procedures... removal efficiency as part of the performance test required by § 63.9310. You must conduct three test runs...

40 CFR 63.4166 - How do I determine the add-on control device emission destruction or removal efficiency?

Code of Federal Regulations, 2011 CFR

2011-07-01

... device emission destruction or removal efficiency? 63.4166 Section 63.4166 Protection of Environment....4166 How do I determine the add-on control device emission destruction or removal efficiency? (a) For... device organic emissions destruction or removal efficiency, using Equation 2 of this section. ER23JY02...

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... device emission destruction or removal efficiency? 63.4566 Section 63.4566 Protection of Environment... efficiency? You must use the procedures and test methods in this section to determine the add-on control device emission destruction or removal efficiency as part of the performance test required by § 63.4560...

40 CFR 63.4965 - How do I determine the add-on control device emission destruction or removal efficiency?

Code of Federal Regulations, 2011 CFR

2011-07-01

... device emission destruction or removal efficiency? 63.4965 Section 63.4965 Protection of Environment....4965 How do I determine the add-on control device emission destruction or removal efficiency? You must... destruction or removal efficiency as part of the performance test required by § 63.4960. You must conduct...

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

Code of Federal Regulations, 2010 CFR

2010-07-01

... device emission destruction or removal efficiency? 63.4566 Section 63.4566 Protection of Environment... efficiency? You must use the procedures and test methods in this section to determine the add-on control device emission destruction or removal efficiency as part of the performance test required by § 63.4560...

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

ERIC Educational Resources Information Center

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…

SBML Level 3 package: Groups, Version 1 Release 1

PubMed Central

Hucka, Michael; Smith, Lucian P.

2017-01-01

Summary Biological models often contain components that have relationships with each other, or that modelers want to treat as belonging to groups with common characteristics or shared metadata. The SBML Level 3 Version 1 Core specification does not provide an explicit mechanism for expressing such relationships, but it does provide a mechanism for SBML packages to extend the Core specification and add additional syntactical constructs. The SBML Groups package for SBML Level 3 adds the necessary features to SBML to allow grouping of model components to be expressed. Such groups do not affect the mathematical interpretation of a model, but they do provide a way to add information that can be useful for modelers and software tools. The SBML Groups package enables a modeler to include definitions of groups and nested groups, each of which may be annotated to convey why that group was created, and what it represents. PMID:28187406

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

PubMed Central

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. PMID:26157622

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

Code of Federal Regulations, 2014 CFR

2014-01-01

... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 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...

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

Code of Federal Regulations, 2010 CFR

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...

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

Code of Federal Regulations, 2013 CFR

2013-01-01

... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 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...

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

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 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...

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

Code of Federal Regulations, 2012 CFR

2012-01-01

... 15 Commerce and Foreign Trade 1 2012-01-01 2012-01-01 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...

40 CFR 63.3166 - How do I determine the add-on control device emission destruction or removal efficiency?

Code of Federal Regulations, 2011 CFR

2011-07-01

... device emission destruction or removal efficiency? 63.3166 Section 63.3166 Protection of Environment... Limitations § 63.3166 How do I determine the add-on control device emission destruction or removal efficiency... emission destruction or removal efficiency as part of the performance test required by § 63.3160. You must...

40 CFR 63.3166 - How do I determine the add-on control device emission destruction or removal efficiency?

Code of Federal Regulations, 2010 CFR

2010-07-01

... device emission destruction or removal efficiency? 63.3166 Section 63.3166 Protection of Environment... Limitations § 63.3166 How do I determine the add-on control device emission destruction or removal efficiency... emission destruction or removal efficiency as part of the performance test required by § 63.3160. You must...

40 CFR 63.4766 - How do I determine the add-on control device emission destruction or removal efficiency?

Code of Federal Regulations, 2011 CFR

2011-07-01

... device emission destruction or removal efficiency? 63.4766 Section 63.4766 Protection of Environment... Option § 63.4766 How do I determine the add-on control device emission destruction or removal efficiency... emission destruction or removal efficiency as part of the performance test required by § 63.4760. You must...

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

USDA-ARS?s Scientific Manuscript database

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

DTIC Science & Technology

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

Linagliptin as add-on to empagliflozin and metformin in patients with type 2 diabetes: Two 24-week randomized, double-blind, double-dummy, parallel-group trials.

PubMed

Tinahones, Francisco J; Gallwitz, Baptist; Nordaby, Matias; Götz, Sophia; Maldonado-Lutomirsky, Mario; Woerle, Hans J; Broedl, Uli C

2017-02-01

To evaluate the efficacy and safety of linagliptin vs placebo as add-on to empagliflozin and metformin in patients with type 2 diabetes. Patients with inadequate glycaemic control despite stable-dose metformin received open-label empagliflozin 10 mg (study 1) or 25 mg (study 2) as add-on therapy for 16 weeks. Subsequently, those with HbA1c ≥7.0 and ≤10.5% (>53 and ≤91 mmol/mol) (N = 482) were randomized to 24 weeks' double-blind, double-dummy treatment with linagliptin 5 mg or placebo in study 1, or to linagliptin 5 mg or placebo in study 2; all patients continued treatment with metformin and empagliflozin 10 mg (study 1) or metformin and empagliflozin 25 mg (study 2). The primary endpoint was change from baseline (defined as the last value before first intake of randomized, double-blind treatment) in HbA1c at week 24. At week 24, HbA1c (mean baseline 7.82-8.04 [62-64 mmol/mol]) was significantly reduced with linagliptin vs placebo; adjusted mean (SE) differences in change from baseline in HbA1c with linagliptin vs placebo were -.32% (.10) (-3.59 [1.08] mmol/mol) ( P = .001) for patients on empagliflozin 10 mg and metformin, and -0.47% (0.10) (-5.15 [1.04] mmol/mol) ( P < 0.001) for patients on empagliflozin 25 mg and metformin. Adverse events were reported in more patients receiving placebo than in those receiving linagliptin: 55.5% vs 48.4% in study 1 and 58.9% vs 52.7% in study 2. Linagliptin as add-on to empagliflozin and metformin for 24 weeks improved glycaemic control vs placebo, and was well tolerated. © 2016 John Wiley & Sons Ltd.

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.

PubMed

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.

PubMed

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.

Steering air bubbles with an add-on vacuum layer for biopolymer membrane biofabrication in PDMS microfluidics.

PubMed

Pham, Phu; Vo, Thanh; Luo, Xiaolong

2017-01-17

Membrane functionality is crucial in microfluidics for realizing operations such as filtration, separation, concentration, signaling among cells and gradient generation. Currently, common methods often sandwich commercially available membranes in multi-layer devices, or use photopolymerization or temperature-induced gelation to fabricate membrane structures in one-layer devices. Biofabrication offers an alternative to forming membrane structures with biomimetic materials and mechanisms in mild conditions. We have recently developed a biofabrication strategy to form parallel biopolymer membranes in gas-permeable polydimethylsiloxane (PDMS) microfluidic devices, which used positive pressure to dissipate air bubbles through PDMS to initiate membrane formation but required careful pressure balancing between two flows. Here, we report a technical innovation by simply placing as needed an add-on PDMS vacuum layer on PDMS microfluidic devices to dissipate air bubbles and guide the biofabrication of biopolymer membranes. Vacuuming through PDMS was simply achieved by either withdrawing a syringe or releasing a squeezed nasal aspirator. Upon vacuuming, air bubbles dissipated within minutes, membranes were effortlessly formed, and the add-on vacuum layer can be removed. Subsequent membrane growth could be robustly controlled with the flows and pH of solutions. This new process is user-friendly and has achieved a 100% success rate in more than 200 trials in membrane biofabrication.

Experimental Investigation of the Influence of a Reverse Delta Type Add-on Device on the Flap-tip Vortex of a Wing

NASA Astrophysics Data System (ADS)

Altaf, A.; Thong, T. B.; Omar, A. A.; Asrar, W.

2017-03-01

Particle Image Velocimetry was used in a low speed wind tunnel to investigate the effect of interactions of vortices produced by an outboard flap-tip of a half wing (NACA 23012 in landing configuration) and a slender reverse delta type add-on device, placed in the proximity of the outboard flap-tip, on the upper surface of the half wing. This work investigates the characteristics of the vortex interactions generated downstream in planes perpendicular to the free stream direction at a chord-based Reynolds number of Rec=2.74×105 . It was found that the add-on device significantly reduces the tangential velocity magnitude and enlarges the vortex core of the resultant vortex by up to 36.1% and 36.8%, respectively.

Rotigotine transdermal system as add-on to oral dopamine agonist in advanced Parkinson's disease: an open-label study.

PubMed

Kim, Jong-Min; Chung, Sun Ju; Kim, Jae Woo; Jeon, Beom Seok; Singh, Pritibha; Thierfelder, Stephan; Ikeda, Junji; Bauer, Lars

2015-02-28

Achieving optimal symptom control with minimal side effects is a major goal in clinical practice. Dual-agent dopamine receptor agonist (DA) therapy in Parkinson's disease (PD) may represent a promising approach to treatment, as the combination of different pharmacokinetic/pharmacological profiles may result in a lesser need for high dosages and, accordingly, may be well tolerated. The objective of the current study was to investigate safety and efficacy of rotigotine transdermal system as add-on to oral DA in patients with advanced PD inadequately controlled with levodopa and low-dose oral DA. PD0015 was an open-label, multinational study in patients with advanced-PD and sleep disturbance or early-morning motor impairment. Patients were titrated to optimal dose rotigotine (≤8 mg/24 h) over 1-4 weeks and maintained for 4-7 weeks (8-week treatment). Dosage of levodopa and oral DA (pramipexole ≤1.5 mg/day, ropinirole ≤6.0 mg/day) was stable. Primary variable was Clinical Global Impressions (CGI) item 4: side effects, assessing safety. Other variables included adverse events (AEs), Patient Global Impressions of Change (PGIC), Unified Parkinson's Disease Rating Scale (UPDRS) II and III, Parkinson's Disease Sleep Scale (PDSS-2), Pittsburgh Sleep Quality Index (PSQI), and "off" time. Of 90 patients who received rotigotine, 79 (88%) completed the study; 5 (6%) withdrew due to AEs. Most (83/89; 93%) had a CGI-4 score <3 indicating that rotigotine add-on therapy did not interfere with functioning; 6 (7%) experienced drug-related AEs that interfered with functioning (score ≥3). AEs occurring in ≥5% were application site pruritus (13%), dizziness (10%), orthostatic hypotension (10%), nausea (8%), dyskinesia (8%), and nasopharyngitis (6%). Numerical improvements in motor function (UPDRS III), activities of daily living (UPDRS II), sleep disturbances (PDSS-2, PSQI), and reduction in "off" time were observed. The majority (71/88; 81%) improved on PGIC. Addition of

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

PubMed

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).

Improving risk assessment of color additives in medical device polymers.

PubMed

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.

Adjuncts in the IVF laboratory: where is the evidence for 'add-on' interventions?

PubMed

Harper, Joyce; Jackson, Emily; Sermon, Karen; Aitken, Robert John; Harbottle, Stephen; Mocanu, Edgar; Hardarson, Thorir; Mathur, Raj; Viville, Stephane; Vail, Andy; Lundin, Kersti

2017-03-01

Globally, IVF patients are routinely offered and charged for a selection of adjunct treatments and tests or 'add-ons' that they are told may improve their chance of a live birth, despite there being no clinical evidence supporting the efficacy of the add-on. Any new IVF technology claiming to improve live birth rates (LBR) should, in most cases, first be tested in an appropriate animal model, then in clinical trials, to ensure safety, and finally in a randomized controlled trial (RCT) to provide high-quality evidence that the procedure is safe and effective. Only then should the technique be considered as 'routine' and only when applied to the similar patient population as those studied in the RCT. Even then, further pediatric and long-term follow-up studies will need to be undertaken to examine the long-term safety of the procedure. Alarmingly, there are currently numerous examples where adjunct treatments are used in the absence of evidence-based medicine and often at an additional fee. In some cases, when RCTs have shown the technique to be ineffective, it is eventually withdrawn from the clinic. In this paper, we discuss some of the adjunct treatments currently being offered globally in IVF laboratories, including embryo glue and adherence compounds, sperm DNA fragmentation, time-lapse imaging, preimplantation genetic screening, mitochondria DNA load measurement and assisted hatching. We examine the evidence for their safety and efficacy in increasing LBRs. We conclude that robust studies are needed to confirm the safety and efficacy of any adjunct treatment or test before they are offered routinely to IVF patients. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Probing the kinetic energy-release dynamics of H-atom products from the gas-phase reaction of O(3P) with vinyl radical C2H3.

PubMed

Jang, Su-Chan; Choi, Jong-Ho

2014-11-21

The gas-phase radical-radical reaction dynamics of ground-state atomic oxygen O((3)P) with vinyl radicals C2H3 has been studied by combining the results of vacuum-ultraviolet laser-induced fluorescence spectroscopy in a crossed beam configuration with ab initio calculations. The two radical reactants O((3)P) and C2H3 were produced by photolysis of NO2 and supersonic flash pyrolysis of C2H3I, respectively. Doppler profile analysis of the kinetic energy release of the nascent H-atom products from the title reaction O((3)P) + C2H3→ H((2)S) + CH2CO (ketene) revealed that the average translational energy of the products and the average fraction of the total available energy were 7.03 ± 0.30 kcal mol(-1) and 7.2%. The empirical data combined with CBS-QB3 level ab initio theory and statistical calculations demonstrated that the title oxygen-hydrogen exchange reaction is a major reaction channel, through an addition-elimination mechanism involving the formation of a short-lived, dynamical complex on the doublet potential energy surface. On the basis of systematic comparison with several exchange reactions of hydrocarbon radicals, the observed kinetic energy release can be explained in terms of the weak impulse at the moment of decomposition in the loose transition state with a product-like geometry and a small reverse barrier along the exit channel.

Sensitivity analysis of the add-on price estimate for the silicon web growth process

NASA Technical Reports Server (NTRS)

Mokashi, A. R.

1981-01-01

The web growth process, a silicon-sheet technology option, developed for the flat plate solar array (FSA) project, was examined. Base case data for the technical and cost parameters for the technical and commercial readiness phase of the FSA project are projected. The process add on price, using the base case data for cost parameters such as equipment, space, direct labor, materials and utilities, and the production parameters such as growth rate and run length, using a computer program developed specifically to do the sensitivity analysis with improved price estimation are analyzed. Silicon price, sheet thickness and cell efficiency are also discussed.

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

PubMed

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.

Safinamide: an add-on treatment for managing Parkinson's disease.

PubMed

Müller, Thomas

2018-01-01

Heterogeneous expression of neurotransmitter deficits results from onset and progression of Parkinson's disease. Intervals, characterized by reappearance of motor and associated certain nonmotor symptoms, determine the end of good tolerability and efficacy of oral levodopa therapy. These "OFF" states result from levodopa pharmacokinetics and disease progression-related deterioration of the central buffering capacity for fluctuations of dopamine levels. This review discusses safinamide as an add-on therapeutic agent in orally levodopa-treated patients with "OFF" phenomena. Safinamide provided beneficial effects on "OFF" symptoms in pivotal trials with doses of 50 or 100 mg once daily. Safinamide reversibly inhibits mono-amine oxidase B and declines abnormal glutamate release by modulation of potassium- and sodium ion channels. An ideal candidate for combination with safinamide is opicapone. This inhibitor of peripheral catechol-O-methyltransferase supports continuous brain delivery of levodopa and, thus, the continuous dopaminergic stimulation concept. Both compounds with their once-daily application and good tolerability may complement each other by reduction of necessary oral levodopa intakes and "OFF" times. Thus, a promising, future option will be combination of safinamide and opicapone in one formulation. It will reduce adherence issues and may complement levodopa treatment. It will probably cause less nausea and edema than a dopamine agonist/levodopa regimen.

'Add women & stir'--the biomedical approach to cardiac research!

PubMed

O'Donnell, Sharon; Condell, Sarah; Begley, Cecily M

2004-07-01

In conditions shared by women and men, the biomedical model of disease assumes that illness-symptoms and outcomes are biologically and socially 'neutral'. Consequently, up until a decade ago, white middle-aged men were the model subjects in most funded cardiac trials, with the assumption that whatever the findings, the results would also hold true for women. This 'add women and stir' approach has resulted in imbalances in cardiac care and an image of coronary artery disease, which portrays a middle-aged male as its victim. Moreover, cardiac health care has been designed with the male anatomy and male experience of illness in mind, and health promotional measures have been targeted towards men. Women have received these health promotional messages to protect the hearts of men, and have been less likely to modify their own lifestyles in a cardio-protective manner. However, the biological and social differences that exist between women and men, must surely invalidate such biased biomedical assertions, and signify a need to delve beyond the realm of biomedical reductionism for greater insights and understanding. This review examines how scientific reductionism has failed to explore the impact of coronary artery disease on the lives of women and how the gendered image of this disease has privileged the normative frame.

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.

PubMed

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.

Long-term efficacy and safety of vildagliptin add-on therapy in type 2 diabetes mellitus with insulin treatment.

PubMed

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%, p<0.05, at the end of observational period). In addition, the dose and number of insulin injections significantly reduced (-5.6units, p<0.01, and -0.9 times, p<0.001). 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; p<0.05). Vildagliptin as an add-on to insulin 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.

Analytical procedure validation and the quality by design paradigm.

PubMed

Rozet, Eric; Lebrun, Pierre; Michiels, Jean-François; Sondag, Perceval; Scherder, Tara; Boulanger, Bruno

2015-01-01

Since the adoption of the ICH Q8 document concerning the development of pharmaceutical processes following a quality by design (QbD) approach, there have been many discussions on the opportunity for analytical procedure developments to follow a similar approach. While development and optimization of analytical procedure following QbD principles have been largely discussed and described, the place of analytical procedure validation in this framework has not been clarified. This article aims at showing that analytical procedure validation is fully integrated into the QbD paradigm and is an essential step in developing analytical procedures that are effectively fit for purpose. Adequate statistical methodologies have also their role to play: such as design of experiments, statistical modeling, and probabilistic statements. The outcome of analytical procedure validation is also an analytical procedure design space, and from it, control strategy can be set.

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

Code of Federal Regulations, 2010 CFR

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...

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 12 2011-07-01 2009-07-01 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...

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

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 13 2013-07-01 2012-07-01 true Operating Limits for Capture Systems... Subpart IIII of Part 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...

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

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 13 2012-07-01 2012-07-01 false Operating Limits for Capture Systems... Subpart IIII of Part 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...

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 13 2014-07-01 2014-07-01 false Operating Limits for Capture Systems... Subpart IIII of Part 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...

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

PubMed

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 < 0.001). Advanced imaging studies were more likely than nonadvanced studies to be associated with addendum use (OR = 4.7, p < 0.001). Reports generated for patients in emergency or outpatient settings had a slightly higher likelihood of addendum 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.

The incommensurately modulated(1 - x)Ta 2O 5· xWO 3, 0 ≤ x ≤ 0.267 solid solution

NASA Astrophysics Data System (ADS)

Schmid, Siegbert; Withers, Ray L.; Thompson, John G.

1992-08-01

The phase(1 - x)Ta 2O 5 · WO 3, 0 ≤ x ≤ 0.267 has been studied by X-ray powder diffraction and transmission electron microscopy. It was previously described as an infinite series of anion-deficient, α-UO 3-type "line phases," with compositions resulting from intergrowths of different blocks made up by small numbers of α-UO 3-type cells. More correctly(1 - x)Ta 2O 5· xWO 3, 0 ≤ x ≤ 0.267 is described as an incommensurately modulated structure with a linearly composition-dependent primary modulation wave-vector qprim. = qb*. The underlying orthorhombically distorted α-UO 3-type parent structure has space group symmetry Cmmm ( a ≈ 6.20-6.14, b ≈ 3.66, c ≈ 3.89-3.85Å). Characteristic extinction conditions imply a superspace group symmetry of P : Cmmmm : s, -1,1. The four previously reported crystal structures in the solid solution field are examined by means of apparent valence calculations. Crystal chemical reasons are proposed for the width of the composition range,0 ≤ x ≤ 0.267, observed for the title phase.

A multinational, observational study to investigate the efficacy, safety and tolerability of acarbose as add-on or monotherapy in a range of patients: the Gluco VIP study.

PubMed

Zhang, Weiwei; Kim, Dongjun; Philip, Elizabeth; Miyan, Zahid; Barykina, Irina; Schmidt, Birgit; Stein, Herbert

2013-04-01

The burden of type 2 diabetes mellitus is growing rapidly, particularly in the Asia-Pacific region. The aim of this international, large-scale, observational study was to investigate the efficacy and tolerability of the antidiabetic agent acarbose as add-on or monotherapy in a range of patients with type 2 diabetes, including those with cardiovascular morbidities. The majority of practices were included from high-burden regions (predominantly those in the Asia-Pacific region). This was an observational study conducted in 15 countries/regions. Adults with pre-treated or untreated type 2 diabetes prescribed acarbose as add-on or monotherapy were eligible. Two-hour postprandial blood glucose (2-h PPG), glycosylated haemoglobin (HbA1c) and fasting blood glucose (FBG) were measured over a 3-month observation period. A total of 15,034 patients were valid for the efficacy analysis and 15,661 for the safety analysis (mean age was 57.6 years and 92.6 % of patients were Asian). Mean (SD) 2-h PPG decreased by -71.9 (62.3) mg/dL, to 170.2 (46.5) mg/dL at final visit (after 12.8 [4.1] weeks). Mean HbA1c decreased by -1.1 % (1.3) to 7.2 % (1.1) and mean FBG decreased by -33.0 (43.3) mg/dL to 124.8 (30.5) mg/dL. Acarbose was effective regardless of the presence of cardiovascular co-morbidities or diabetic complications. The efficacy of acarbose was rated 'very good' or 'good' in 85.5 % of patients, and tolerability as 'very good' or 'good' in 84.9 % of patients. Drug-related adverse events, mainly gastrointestinal, were reported in 490/15,661 patients (3.13 %). The results of this observational study support the notion that acarbose is effective, safe and well tolerated in a large cohort of Asian patients with type 2 diabetes.

42 CFR 82.16 - How will NIOSH add to monitoring data to remedy limitations of individual monitoring and missed...

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false How will NIOSH add to monitoring data to remedy limitations of individual monitoring and missed dose? 82.16 Section 82.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES...

42 CFR 82.16 - How will NIOSH add to monitoring data to remedy limitations of individual monitoring and missed...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false How will NIOSH add to monitoring data to remedy limitations of individual monitoring and missed dose? 82.16 Section 82.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES...

42 CFR 82.16 - How will NIOSH add to monitoring data to remedy limitations of individual monitoring and missed...

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false How will NIOSH add to monitoring data to remedy limitations of individual monitoring and missed dose? 82.16 Section 82.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES...

42 CFR 82.16 - How will NIOSH add to monitoring data to remedy limitations of individual monitoring and missed...

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false How will NIOSH add to monitoring data to remedy limitations of individual monitoring and missed dose? 82.16 Section 82.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES...

42 CFR 82.16 - How will NIOSH add to monitoring data to remedy limitations of individual monitoring and missed...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false How will NIOSH add to monitoring data to remedy limitations of individual monitoring and missed dose? 82.16 Section 82.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES...

Application of shift-and-add algorithms for imaging objects within biological media

NASA Astrophysics Data System (ADS)

Aizert, Avishai; Moshe, Tomer; Abookasis, David

2017-01-01

The Shift-and-Add (SAA) technique is a simple mathematical operation developed to reconstruct, at high spatial resolution, atmospherically degraded solar images obtained from stellar speckle interferometry systems. This method shifts and assembles individual degraded short-exposure images into a single average image with significantly improved contrast and detail. Since the inhomogeneous refractive indices of biological tissue causes light scattering similar to that induced by optical turbulence in the atmospheric layers, we assume that SAA methods can be successfully implemented to reconstruct the image of an object within a scattering biological medium. To test this hypothesis, five SAA algorithms were evaluated for reconstructing images acquired from multiple viewpoints. After successfully retrieving the hidden object's shape, quantitative image quality metrics were derived, enabling comparison of imaging error across a spectrum of layer thicknesses, demonstrating the relative efficacy of each SAA algorithm for biological imaging.

Interference Effects of Radiation Emitted from Nuclear Excitons

NASA Astrophysics Data System (ADS)

Potzel, W.; van Bürck, U.; Schindelmann, P.; Hagn, H.; Smirnov, G. V.; Popov, S. L.; Gerdau, E.; Shvyd'Ko, Yu. V.; Jäschke, J.; Rüter, H. D.; Chumakov, A. I.; Rüffer, R.

2003-12-01

Interference effects in nuclear forward scattering of synchrotron radiation (NFSSR) from two spatially separated stainless-steel foils A and B mounted downstream behind each other have been investigated. Target A can be sinusoidally vibrated by high-frequency (MHz) ultrasound (US), target B is moved at a constant Doppler velocity which is large compared to the natural width of the nuclear transition. Due to this large Doppler shift radiative coupling between both targets is disrupted and the nuclear excitons in A and B develop independently in space and time after the SR pulse. As a consequence, the emission from the whole system (A&B) is dominated by the interference of the emissions from A and B. The application of US to target A is a powerful method to change the relative phasing of the emissions and thus to investigate interference effects originating from the two nuclear excitons in detail. Four distinct cases were studied: (a) If target A is kept stationary and only B is moved at large constant velocity v, the interference pattern exhibits a Quantum Beat (QB) whose period is determined by v. (b) If, in addition, target A is sinusoidally vibrated in a piston-like motion by US and the initial US phase Φ0 is locked to the SR pulse, the QB is frequency modulated by the US. The variation of the QB frequency increases with the US modulation index m. (c) In the case that Φ0 is not synchronized to the SR pulse (phase averaging over Φ0) drastic changes of the amplitude and phase reversals of the QB pattern occur in the time regions around odd multiples of half of the US period. (d) If Φ0 is not synchronized to the SR pulse and the US motion is no longer pistonlike, the NFSSR intensity has to be averaged over both Φ0 and m (amplitude) of the US motion. Surprisingly the QB interference pattern does not vanish completely but a short QB signal remains at times of the full US period even at high values of m. All NFSSR patterns investigated are interpreted and

triADD: The Risk for Alcohol Abuse, Depression, and Diabetes Multimorbidity in the American Indian and Alaska Native Population

ERIC Educational Resources Information Center

Tann, Sheila S.; Yabiku, Scott T.; Okamoto, Scott K.; Yanow, Jessica

2007-01-01

This study examined the risk for alcoholism, diabetes, and depression (triADD) in American Indian/Alaska Native (AI/AN) populations in the U.S. Using the Behavioral Risk Factor Surveillance System, a series of descriptive statistics and regression models were used to examine the interrelationships among these disorders in AI/AN populations.…

Effects of pitavastatin add-on therapy on chronic kidney disease with albuminuria and dyslipidemia.

PubMed

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 <100 mg/dl. The statin treatment by pitavastatin was well tolerated in all of the patients without any significant adverse events and the average dose of pitavastatin was 1.0 ± 0.0 mg daily after treatment. After the 12-months treatment period, LDL-C was significantly lower in the diet-plus-statin therapy group compared with the diet therapy group (diet vs diet-plus-statin: LDL-C, 126 ± 5 vs 83 ± 4 mg/dL, P < 0.001). On the other hand, the diet-plus-statin therapy did not significantly reduce albuminuria or delay the decline in eGFR compared with the diet therapy, and there was no relationship between the change in LDL-C and the change in eGFR or albuminuria. However, diet therapy as well as diet-plus-statin therapy exerted similar lowering effects on the pentosidine levels (diet therapy group, baseline vs 12 months: 40 ± 4 vs 24 ± 3 ng/mL, P = 0.001; diet-plus-statin therapy, 46 ± 7 vs 34�

Does waist circumference uncorrelated with BMI add valuable information?

PubMed

Ngueta, Gerard; Laouan-Sidi, Elhadji A; Lucas, Michel

2014-09-01

Estimation of relative contribution of Body Mass Index (BMI) and waist circumference (WC) on health outcomes requires a regression model that includes both obesity metrics. But, multicollinearity could yield biased estimates. To address the multicollinearity issue between BMI and WC, we used the residual model approach. The standard WC (Y-axis) was regressed on the BMI (X-axis) to obtain residual WC. Data from two adult population surveys (Nunavik Inuit and James Bay Cree) were analysed to evaluate relative effect of BMI and WC on four cardiometabolic risk factors: insulin, triglycerides, systolic blood pressure and high-density lipoprotein levels. In multivariate models, standard WC and BMI were significantly associated with cardiometabolic outcomes. Residual WC was not linked with any outcomes. The BMI effect was weakened by including standard WC in the model, but its effect remained unchanged if residual WC was considered. The strong correlation between standard WC and BMI does not allow assessment of their relative contributions to health in the same model without a risk of making erroneous estimations. By contrast with BMI, fat distribution (residual WC) does not add valuable information to a model that already contains overall adiposity (BMI) in Inuit and Cree. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Mainstream web standards now support science data too

NASA Astrophysics Data System (ADS)

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

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

Code of Federal Regulations, 2013 CFR

2013-07-01

... system and add-on control device operating limits during the performance test? 63.3546 Section 63.3546... of key parameters of the valve operating system (e.g., solenoid valve operation, air pressure... minimum operating limit for that specific capture device or system of multiple capture devices. The...

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... capture system and add-on control device operating limits during the performance test? 63.3546 Section 63... of key parameters of the valve operating system (e.g., solenoid valve operation, air pressure... minimum operating limit for that specific capture device or system of multiple capture devices. The...

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

Code of Federal Regulations, 2012 CFR

2012-07-01

... capture system and add-on control device operating limits during the performance test? 63.3546 Section 63... of key parameters of the valve operating system (e.g., solenoid valve operation, air pressure... minimum operating limit for that specific capture device or system of multiple capture devices. The...

76 FR 4399 - Joint Industry Plan; Order Approving Amendment To Add the BATS Y-Exchange, Inc. as Participant to...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-25

...; Order Approving Amendment To Add the BATS Y- Exchange, Inc. as Participant to National Market System... September 9, 2010, the BATS Y-Exchange, Inc. (``BYX'' or ``Exchange'') submitted to the Securities and... their monthly reports available to the public under Rule 11Ac1-5 under the Act (n/ k/a Rule 605 of...

Confirmation of Down syndrome critical region by FISH analysis in a patient with add(21)(p11)

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

Matsumoto, Naomichi; Niikawa, Norio; Mikawa, Makoto

1995-12-04

We have studied a patient with clinical Down syndrome (DS) who has a mosaic 46, XX/46, XX, 21p+ karyotype. The patient was born at 39 weeks of gestation with a birth weight of 3,025 g to healthy parents. At age 2 months, she was diagnosed clinically to have DS; she had flat facies, upslanted palpebral fissures, epicanthal folds, telecanthus, flat nasal bridge, abnormal dentition, malformed ears, short neck, short fingers, clinodactyly with single flexion crease of the fifth fingers, hyperextension of joints, pes planus, distal axial triradii, and bilateral tibial arch patterns. Chromosome analysis showed mosaicism consisting of a normalmore » 46,XX cell line and a line with a 21p+ chromosome, the final karyotype being mos46,XX[57]/46,XX,add(21)(p11)[43]. Although the origin of an additional segment on chromosome 21 was not identified with conventional banding analyses, it was suspected to represent partial trisomy 21 on the basis of clinical manifestations. 6 refs., 2 figs.« less

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.

PubMed

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 (P<0.001). Significantly more vildagliptin add-on patients achieved HbA(1c)≤7.0% (53 mmol/mol) than did sulfonylurea patients (40.1% vs. 7.9%; P<0.001). Greater reductions in FPG and 2pp were observed with vildagliptin add-on than with sulfonylurea (P<0.001). The vildagliptin 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.

7 CFR 1770.3 - Index of records.

Code of Federal Regulations, 2010 CFR

2010-01-01

... (CONTINUED) ACCOUNTING REQUIREMENTS FOR RUS TELECOMMUNICATIONS BORROWERS Preservation of Records § 1770.3... maintained. The master index shall be subject to review by RUS and RUS shall reserve the right to add records...

Health and labour force participation of older people in Europe: what do objective health indicators add to the analysis?

PubMed

Kalwij, Adriaan; Vermeulen, Frederic

2008-05-01

This paper studies labour force participation of older individuals in 11 European countries. The data are drawn from the new Survey of Health, Ageing and Retirement in Europe (SHARE). We examine the value added of objective health indicators in relation to potentially endogenous self-reported health. We approach the endogeneity of self-reported health as an omitted variables problem. In line with the literature on the reliability of self-reported health ambiguous results are obtained. In some countries self-reported health does a fairly good job and controlling for objective health indicators does not add much to the analysis. In other countries, however, the results show that objective health indicators add significantly to the analysis and that self-reported health is endogenous due to omitted objective health indicators. These latter results illustrate the multi-dimensional nature of health and the need to control for objective health indicators when analysing the relation between health status and labour force participation. This makes an instrumental variables approach to deal with the endogeneity of self-reported health less appropriate.

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

PubMed

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.

Effects of breathing maneuver and sitting posture on muscle activity in inspiratory accessory muscles in patients with chronic obstructive pulmonary disease

PubMed Central

2012-01-01

Background To determine the influence of breathing maneuver and sitting posture on tidal volume (TV), respiratory rate (RR), and muscle activity of the inspiratory accessory muscles in patients with chronic obstructive pulmonary disease (COPD). Methods Twelve men with COPD participated in the study. Inductive respiratory plethysmography and surface electromyography were used to simultaneously measure TV, RR, and muscle activity of the inspiratory accessory muscles [the scalenus (SM), sternocleidomastoid (SCM), and pectoralis major (PM) muscles] during quiet natural breathing (QB) and pursed-lips breathing (PLB) in three sitting postures: neutral position (NP), with armm support (WAS), and with arm and head support (WAHS). Results Two-way repeated-measures analysis of variance was employed. In a comparison of breathing patterns, PLB significantly increased TV and decreased RR compared to QB. Muscle activity in the SM and SCM increased significantly in PLB compared to QB. In a comparison of sitting postures, the muscle activity of the SM, SCM, and PM increased in the forward-leaning position. Conclusions The results suggest that in COPD, PLB induced a favorable breathing pattern (increased TV and reduced RR) compared to QB. Additionally, WAS and WAHS positions increased muscle activity of the inspiratory accessory muscles during inspiration versus NP. Differential involvement of accessory respiratory muscles can be readily studied in COPD patients, allowing monitoring of respiratory load during pulmonary rehabilitation. PMID:22958459

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

PubMed

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

NASA Astrophysics Data System (ADS)

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.

PubMed

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.

Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations

PubMed Central

Borgohain, Rupam; Szasz, J; Stanzione, P; Meshram, C; Bhatt, M; Chirilineau, D; Stocchi, F; Lucini, V; Giuliani, R; Forrest, E; Rice, P; Anand, R

2014-01-01

Levodopa is effective for the motor symptoms of Parkinson's disease (PD), but is associated with motor fluctuations and dyskinesia. Many patients require add-on therapy to improve motor fluctuations without exacerbating dyskinesia. The objective of this Phase III, multicenter, double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy and safety of safinamide, an α-aminoamide with dopaminergic and nondopaminergic mechanisms, as add-on to l-dopa in the treatment of patients with PD and motor fluctuations. Patients were randomized to oral safinamide 100 mg/day (n = 224), 50 mg/day (n = 223), or placebo (n = 222) for 24 weeks. The primary endpoint was total on time with no or nontroublesome dyskinesia (assessed using the Hauser patient diaries). Secondary endpoints included off time, Unified Parkinson's Disease Rating Scale (UPDRS) Part III (motor) scores, and Clinical Global Impression-Change (CGI-C). At week 24, mean ± SD increases in total on time with no or nontroublesome dyskinesia were 1.36 ± 2.625 hours for safinamide 100 mg/day, 1.37 ± 2.745 hours for safinamide 50 mg/day, and 0.97 ± 2.375 hours for placebo. Least squares means differences in both safinamide groups were significantly higher versus placebo. Improvements in off time, UPDRS Part III, and CGI-C were significantly greater in both safinamide groups versus placebo. There were no significant between-group differences for incidences of treatment-emergent adverse events (TEAEs) or TEAEs leading to discontinuation. The addition of safinamide 50 mg/day or 100 mg/day to l-dopa in patients with PD and motor fluctuations significantly increased total on time with no or nontroublesome dyskinesia, decreased off time, and improved parkinsonism, indicating that safinamide improves motor symptoms and parkinsonism without worsening dyskinesia. PMID:24323641

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

Code of Federal Regulations, 2013 CFR

2013-07-01

... 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... Control Efficiency/outlet Concentration Option § 63.3556 How do I establish the emission capture system...

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.

PubMed

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.

Evaluation of the efficiency of a new hollow fiber plasmapheresis filter.

PubMed

Orlandini, G C; Margaria, R

1983-07-01

Plasma separation for plasma exchange or plasma treatment has, until now, been obtained prevalently by centrifugal separators. Recently, filters capable of continuously separating the plasma have been proposed. We have evaluated, both in vivo and ex vivo, the efficiency of a plasma separating filter (BT 900, Dideco, Mirandola, Italy) incorporating polypropylene hollow fibers with a pore size of 0.55 micron (PS 510 W, Membrana, Wuppertal, Germany) and an effective surface of 0.23 m2, using two hemodialysis blood pumps. Ex vivo, (bovine blood) at a blood flow (QB) of 100 ml/min, 47 +/- 2.8 ml/min of plasma were obtained in the first hour and 34 +/- 3.1 ml/min in the second hour. The Sieving coefficient was 100 for albumin and IgG, 98.4 for IgA and 92.3 for IgM. Neither hemolysis nor platelet contamination were observed. In vivo, 35 treatment were performer on 19 patients affected with mixed essential cryoglobulinemia, autoimmune glomerulonephritis, Wegener disease, thrombotic thrombocytopenic microangiopathy and rheumatoid arthritis. There were no clinical complications and the treatment was always well tolerated. A mean of 2064 +/- 400 ml of plasma was obtained in 103.7 +/- 29 minutes. The plasma flow was correlated (p less than 0.001) with the blood flow (13.4 ml/min at QB = 30 ml/min; 29 ml/min at QB = 100 ml/min). In some cases, immune complexes were found in the plasma removed by the filter (conglutinin method), confirming the membrane permeability to these high weight molecules. The use of hollow fibers to separate formed elements of blood from plasma has a brief history (1, 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer's disease: a 6-month, randomized, placebo-controlled, multicenter trial.

PubMed

Wade, Alan G; Farmer, Mildred; Harari, Gil; Fund, Naama; Laudon, Moshe; Nir, Tali; Frydman-Marom, Anat; Zisapel, Nava

2014-01-01

A link between poor sleep quality and Alzheimer's disease (AD) has recently been suggested. Since endogenous melatonin levels are already reduced at preclinical AD stages, it is important to ask whether replenishing the missing hormone would be beneficial in AD and whether any such effects would be related to the presence of sleep disorder in patients. The effects of add-on prolonged-release melatonin (PRM) (2 mg) to standard therapy on cognitive functioning and sleep were investigated in 80 patients (men [50.7%], women [49.3%], average age 75.3 years [range, 52-85 years]) diagnosed with mild to moderate AD, with and without insomnia comorbidity, and receiving standard therapy (acetylcholinesterase inhibitors with or without memantine). In this randomized, double-blind, parallel-group study, patients were treated for 2 weeks with placebo and then randomized (1:1) to receive 2 mg of PRM or placebo nightly for 24 weeks, followed by 2 weeks placebo. The AD Assessment Scale-Cognition (ADAS-Cog), Instrumental Activities of Daily Living (IADL), Mini-Mental State Examination (MMSE), sleep, as assessed by the Pittsburgh Sleep Quality Index (PSQI) and a daily sleep diary, and safety parameters were measured. Patients treated with PRM (24 weeks) had significantly better cognitive performance than those treated with placebo, as measured by the IADL (P=0.004) and MMSE (P=0.044). Mean ADAS-Cog did not differ between the groups. Sleep efficiency, as measured by the PSQI, component 4, was also better with PRM (P=0.017). In the comorbid insomnia (PSQI ≥6) subgroup, PRM treatment resulted in significant and clinically meaningful effects versus the placebo, in mean IADL (P=0.032), MMSE score (+1.5 versus -3 points) (P=0.0177), and sleep efficiency (P=0.04). Median ADAS-Cog values (-3.5 versus +3 points) (P=0.045) were significantly better with PRM. Differences were more significant at longer treatment duration. PRM was well tolerated, with an adverse event profile similar to that

Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial.

PubMed

Chupp, Geoffrey L; Bradford, Eric S; Albers, Frank C; Bratton, Daniel J; Wang-Jairaj, Jie; Nelsen, Linda M; Trevor, Jennifer L; Magnan, Antoine; Ten Brinke, Anneke

2017-05-01

Mepolizumab, an anti-interleukin-5 monoclonal antibody approved as add-on therapy to standard of care for patients with severe eosinophilic asthma, has been shown in previous studies to reduce exacerbations and dependency on oral corticosteroids compared with placebo. We aimed to further assess mepolizumab in patients with severe eosinophilic asthma by examining its effect on health-related quality of life (HRQOL). We did a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial (MUSCA) in 146 hospitals or research centres in 19 countries worldwide. Eligible participants were patients aged 12 years or older with severe eosinophilic asthma and a history of at least two exacerbations requiring treatment in the previous 12 months before screening despite regular use of high-dose inhaled corticosteroids plus other controller medicines. Exclusion criteria included current smokers or former smokers with a history of at least ten pack-years. We randomly assigned participants (1:1) by country to receive a subcutaneous injection of either mepolizumab 100 mg or placebo, plus standard of care, every 4 weeks for 24 weeks (the final dose was given at week 20). We did the randomisation using an interactive voice response system and a centralised, computer-generated, permuted-block design of block size six. The two treatments were identical in appearance and administered in a masked manner; patients, investigators, other site staff and the entire study team including those assessing outcomes data were also masked to group assignment. The primary endpoint was the mean change from baseline in the St George's Respiratory Questionnaire (SGRQ) total score at week 24 in the modified intention-to-treat (modified ITT) population (analysed according to their randomly assigned treatment). Safety was assessed in all patients who received at least one dose of trial medication (analysed according to the actual treatment received). This trial is registered

Impact of sex on composition and quality of fresh loins, bellies, and fresh and processed hams

USDA-ARS?s Scientific Manuscript database

The objective was to characterize the effect of sex and selection focus on primal quality. Pigs (N=7,672) from a lean growth selection [n=1,468 barrows (LB); n=2,151 gilts (LG)] or superior meat quality selection [n=1,895 barrows (QB); n=2,158 gilts (QG)] focus were slaughtered in 3 marketing groups...

Buckley ANGB, Aurora, Colorado. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F

DTIC Science & Technology

1981-02-18

OSURATIKM) 23036 bUCALEY ANG8 Qb-7.37 SYATIALL WATHER ’. 2100-2300 6LASO Nouni IINYS15) 1.3 446 ?-to 11.16 17-1 21 .3V 3.33 34.46 41.0 4.33t 1116 WOW N . 19...bulb 3398619 561 6 0ol 2,63? 930 ,. 1 1 t,% 193720m~nK( �.44.9 810 3 I I z ~ -- - -. - - I I A U GSAFETAC PSYCHROMETRIC SUMMARY AIR WATHER

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

PubMed

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.

PubMed

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.

PubMed

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.

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

PubMed Central

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

16 CFR § 1130.3 - General requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... in the event of a product recall or safety alert. § 1130.3, Nt. Effective Date Note: At 77 FR 9524, Feb. 17, 2012, § 1130.3 was amended by removing “§ 1130.9” and add in its place “§ 1130.8”, effective...

21 CFR 556.220 - 3,5-Dinitrobenzamide.

Code of Federal Regulations, 2010 CFR

2010-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... equivalent, to remove arylamines; for example, 3-amino-5-nitrobenzamide. The 3,5-DNBA fraction is reduced.... Hydrochloric acid, 4N. Add two volumes of water to one volume of HCl. M. Diatomaceous earth—Hyflo Super Cel...

Does aquaculture add resilience to the global food system?

PubMed

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.

Safinamide: an add-on treatment for managing Parkinson’s disease

PubMed Central

Müller, Thomas

2018-01-01

Heterogeneous expression of neurotransmitter deficits results from onset and progression of Parkinson’s disease. Intervals, characterized by reappearance of motor and associated certain nonmotor symptoms, determine the end of good tolerability and efficacy of oral levodopa therapy. These “OFF” states result from levodopa pharmacokinetics and disease progression-related deterioration of the central buffering capacity for fluctuations of dopamine levels. This review discusses safinamide as an add-on therapeutic agent in orally levodopa-treated patients with “OFF” phenomena. Safinamide provided beneficial effects on “OFF” symptoms in pivotal trials with doses of 50 or 100 mg once daily. Safinamide reversibly inhibits mono-amine oxidase B and declines abnormal glutamate release by modulation of potassium- and sodium ion channels. An ideal candidate for combination with safinamide is opicapone. This inhibitor of peripheral catechol-O-methyltransferase supports continuous brain delivery of levodopa and, thus, the continuous dopaminergic stimulation concept. Both compounds with their once-daily application and good tolerability may complement each other by reduction of necessary oral levodopa intakes and “OFF” times. Thus, a promising, future option will be combination of safinamide and opicapone in one formulation. It will reduce adherence issues and may complement levodopa treatment. It will probably cause less nausea and edema than a dopamine agonist/levodopa regimen. PMID:29670409

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

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 13 2013-07-01 2012-07-01 true How do I determine the outlet THC... Control Efficiency/outlet Concentration Option § 63.3555 How do I determine the outlet THC emissions and... methods in this section to determine either the outlet THC emissions or add-on control device emission...

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 13 2014-07-01 2014-07-01 false How do I determine the outlet THC... Control Efficiency/outlet Concentration Option § 63.3555 How do I determine the outlet THC emissions and... methods in this section to determine either the outlet THC emissions or add-on control device emission...

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

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 13 2012-07-01 2012-07-01 false How do I determine the outlet THC... Control Efficiency/outlet Concentration Option § 63.3555 How do I determine the outlet THC emissions and... methods in this section to determine either the outlet THC emissions or add-on control device emission...