Structure-Based and Random Mutagenesis Approaches Increase the Organophosphate-Degrading Activity of a Phosphotriesterase Homologue from Deinococcus radiodurans

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

Hawwa, Renda; Larsen, Sonia D.; Ratia, Kiira

2010-11-09

An enzyme from the amidohydrolase family from Deinococcus radiodurans (Dr-OPH) with homology to phosphotriesterase has been shown to exhibit activity against both organophosphate (OP) and lactone compounds. We have characterized the physical properties of Dr-OPH and have found it to be a highly thermostable enzyme, remaining active after 3 h of incubation at 60 C and withstanding incubation at temperatures up to 70 C. In addition, it can withstand concentrations of at least 200 mg/mL. These properties make Dr-OPH a promising candidate for development in commercial applications. However, compared to the most widely studied OP-degrading enzyme, that from Pseudomonas diminuta,more » Dr-OPH has low hydrolytic activity against certain OP substrates. Therefore, we sought to improve the OP-degrading activity of Dr-OPH, specifically toward the pesticides ethyl and methyl paraoxon, using structure-based and random approaches. Site-directed mutagenesis, random mutagenesis, and site-saturation mutagenesis were utilized to increase the OP-degrading activity of Dr-OPH. Out of a screen of more than 30,000 potential mutants, a total of 26 mutant enzymes were purified and characterized kinetically. Crystal structures of w.t. Dr-OPH, of Dr-OPH in complex with a product analog, and of 7 mutant enzymes were determined to resolutions between 1.7 and 2.4 {angstrom}. Information from these structures directed the design and production of 4 additional mutants for analysis. In total, our mutagenesis efforts improved the catalytic activity of Dr-OPH toward ethyl and methyl paraoxon by 126- and 322-fold and raised the specificity for these two substrates by 557- and 183-fold, respectively. Our work highlights the importance of an iterative approach to mutagenesis, proving that large rate enhancements are achieved when mutations are made in already active mutants. In addition, the relationship between the kinetic parameters and the introduced mutations has allowed us to hypothesize on those factors most important for maintaining the structure and function of the enzyme.« less

The role of nonbonded interactions in the conformational dynamics of organophosphorous hydrolase adsorbed onto functionalized mesoporous silica surfaces.

PubMed

Gomes, Diego E B; Lins, Roberto D; Pascutti, Pedro G; Lei, Chenghong; Soares, Thereza A

2010-01-14

The enzyme organophosphorous hydrolase (OPH) catalyzes the hydrolysis of a wide variety of organophosphorous compounds with high catalytic efficiency and broad substrate specificity. The immobilization of OPH in functionalized mesoporous silica (FMS) surfaces increases significantly its catalytic specific activity, as compared to the enzyme in solution, with important applications for the detection and decontamination of insecticides and chemical warfare agents. Experimental measurements of immobilization efficiency as a function of the charge and coverage percentage of different functional groups have been interpreted as electrostatic forces being the predominant interactions underlying the adsorption of OPH onto FMS surfaces. Explicit solvent molecular dynamics simulations have been performed for OPH in bulk solution and adsorbed onto two distinct interaction potential models of the FMS functional groups to investigate the relative contributions of nonbonded interactions to the conformational dynamics and adsorption of the protein. Our results support the conclusion that electrostatic interactions are responsible for the binding of OPH to the FMS surface. However, these results also show that van der Waals forces are detrimental for interfacial adhesion. In addition, it is found that OPH adsorption onto the FMS models favors a protein conformation whose active site is fully accessible to the substrate, in contrast to the unconfined protein.

MID-INFRARED SPECTROSCOPIC OBSERVATIONS OF THE DUST-FORMING CLASSICAL NOVA V2676 OPH

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

Kawakita, Hideyo; Arai, Akira; Shinnaka, Yoshiharu

2017-02-01

The dust-forming nova V2676 Oph is unique in that it was the first nova to provide evidence of C{sub 2} and CN molecules during its near-maximum phase and evidence of CO molecules during its early decline phase. Observations of this nova have revealed the slow evolution of its lightcurves and have also shown low isotopic ratios of carbon ({sup 12}C/{sup 13}C) and nitrogen ({sup 14}N/{sup 15}N) in its envelope. These behaviors indicate that the white dwarf (WD) star hosting V2676 Oph is a CO-rich WD rather than an ONe-rich WD (typically larger in mass than the former). We performed mid-infraredmore » spectroscopic and photometric observations of V2676 Oph in 2013 and 2014 (respectively 452 and 782 days after its discovery). No significant [Ne ii] emission at 12.8 μ m was detected at either epoch. These provided evidence for a CO-rich WD star hosting V2676 Oph. Both carbon-rich and oxygen-rich grains were detected in addition to an unidentified infrared feature at 11.4 μ m originating from polycyclic aromatic hydrocarbon molecules or hydrogenated amorphous carbon grains in the envelope of V2676 Oph.« less

X-RAY OBSERVATIONS OF BOW SHOCKS AROUND RUNAWAY O STARS. THE CASE OF ζ OPH AND BD+43°3654

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

Toalá, J. A.; Guerrero, M. A.; Oskinova, L. M.

2016-04-20

Non-thermal radiation has been predicted within bow shocks around runaway stars by recent theoretical works. We present X-ray observations toward the runaway stars ζ Oph by Chandra and Suzaku and of BD+43°3654 by XMM-Newton to search for the presence of non-thermal X-ray emission. We found no evidence of non-thermal emission spatially coincident with the bow shocks; nonetheless, diffuse emission was detected in the vicinity of ζ Oph. After a careful analysis of its spectral characteristics, we conclude that this emission has a thermal nature with a plasma temperature of T ≈ 2 × 10{sup 6} K. The cometary shape ofmore » this emission seems to be in line with recent predictions of radiation-hydrodynamic models of runaway stars. The case of BD+43°3654 is puzzling, as non-thermal emission has been reported in a previous work for this source.« less

Efficient Degradation of Malathion in the Presence of Detergents Using an Engineered Organophosphorus Hydrolase Highly Expressed by Pichia pastoris without Methanol Induction.

PubMed

Bai, Yun-Peng; Luo, Xiao-Jing; Zhao, Yu-Lian; Li, Chun-Xiu; Xu, Dian-Sheng; Xu, Jian-He

2017-10-18

The biodegradation of pesticides by organophosphorus hydrolases (OPHs) requires an efficient enzyme production technology in industry. Herein, a Pichia pastoris strain was constructed for the extracellular expression of PoOPH M9 , an engineered malathion-degrading enzyme. After optimization, the maximum titer and yield of fermentation reached 50.8 kU/L and 4.1 g protein /L after 3 days, with the highest space-time yield (STY) reported so far, 640 U L -1 h -1 . PoOPH M9 displayed its high activity and stability in the presence of 0.1% (w/w) plant-derived detergent. Only 0.04 mg/mL enzyme could completely remove 0.15 mM malathion in aqueous solution within 20 min. Furthermore, 12 μmol malathion on apples and cucumbers surfaces was completely removed by 0.05 mg/mL PoOPH M9 in tap water after 35 min washing. The efficient production of the highly active PoOPH M9 has cleared a major barrier to biodegradation of pesticide residues in food industry.

The anti-caspase inhibitor Q-VD-OPH prevents AIDS disease progression in SIV-infected rhesus macaques.

PubMed

Laforge, Mireille; Silvestre, Ricardo; Rodrigues, Vasco; Garibal, Julie; Campillo-Gimenez, Laure; Mouhamad, Shahul; Monceaux, Valérie; Cumont, Marie-Christine; Rabezanahary, Henintsoa; Pruvost, Alain; Cordeiro-da-Silva, Anabela; Hurtrel, Bruno; Silvestri, Guido; Senik, Anna; Estaquier, Jérôme

2018-04-02

Apoptosis has been proposed as a key mechanism responsible for CD4+ T cell depletion and immune dysfunction during HIV infection. We demonstrated that Q-VD-OPH, a caspase inhibitor, inhibits spontaneous and activation-induced death of T cells from SIV-infected rhesus macaques (RMs). When administered during the acute phase of infection, Q-VD-OPH was associated with (a) reduced levels of T cell death, (b) preservation of CD4+/CD8+ T cell ratio in lymphoid organs and in the gut, (c) maintenance of memory CD4+ T cells, and (d) increased specific CD4+ T cell response associated with the expression of cytotoxic molecules. Although therapy was limited to the acute phase of infection, Q-VD-OPH-treated RMs showed lower levels of both viral load and cell-associated SIV DNA as compared with control SIV-infected RMs throughout the chronic phase of infection, and prevented the development of AIDS. Overall, our data demonstrate that Q-VD-OPH injection in SIV-infected RMs may represent an adjunctive therapeutic agent to control HIV infection and delaying disease progression to AIDS.

Effect of the phenoxy groups on PDIB and its derivatives

NASA Astrophysics Data System (ADS)

Song, Peng; Guan, Baijie; Zhou, Qiao; Zhao, Meiyu; Huang, Jindou; Ma, Fengcai

2016-10-01

The anisotropic hole and electron mobilities in N,N‧-3,4,9,10-perylenediimide-1,7-phenoxy (PDIB-2OPh) and N,Nʹ-3,4,9,10-perylenediimide (PDIB) were theoretically predicted using the Marcus-Hush theory. The substituent effect of phenoxy on their mobility rates, absorption spectra, electron affinities, and ionization potentials was explored. By comparing the simulated hole mobility in PDIB and PDIB-2OPh, it is found that the phenoxy rings act as spacers between adjacent stacking columns in the phenoxy-substituted derivatives. The increasement of the number of benzene oxygen groups leads to the absorption spectra red-shift of these molecular systems. This coincides with their change tendency of the adiabatic ionization potentials, vertical ionization potentials. However, the calculated adiabatic electron affinities and vertical electron affinities of N,N‧-butyl-3,4,9,10-perylenediimide-1,6,7,12-phenoxy (PDIB-4OPh) are larger than those of PDIB;OPh. The steric effect in PDIB-4OPh is expected to cause space reversal and thus to changes in the properties of the molecule.

Effect of the phenoxy groups on PDIB and its derivatives

PubMed Central

Song, Peng; Guan, Baijie; Zhou, Qiao; Zhao, Meiyu; Huang, Jindou; Ma, Fengcai

2016-01-01

The anisotropic hole and electron mobilities in N,N′-3,4,9,10-perylenediimide-1,7-phenoxy (PDIB-2OPh) and N,Nʹ-3,4,9,10-perylenediimide (PDIB) were theoretically predicted using the Marcus–Hush theory. The substituent effect of phenoxy on their mobility rates, absorption spectra, electron affinities, and ionization potentials was explored. By comparing the simulated hole mobility in PDIB and PDIB-2OPh, it is found that the phenoxy rings act as spacers between adjacent stacking columns in the phenoxy-substituted derivatives. The increasement of the number of benzene oxygen groups leads to the absorption spectra red-shift of these molecular systems. This coincides with their change tendency of the adiabatic ionization potentials, vertical ionization potentials. However, the calculated adiabatic electron affinities and vertical electron affinities of N,N′-butyl-3,4,9,10-perylenediimide-1,6,7,12-phenoxy (PDIB-4OPh) are larger than those of PDIB;OPh. The steric effect in PDIB-4OPh is expected to cause space reversal and thus to changes in the properties of the molecule. PMID:27759050

Rotation in USco and rho Oph with K2

NASA Astrophysics Data System (ADS)

Rebull, Luisa; Stauffer, John; K2 Clusters Team

2018-01-01

K2 observed Upper Scorpius and rho Oph as part of their Campaign 2 in 2014. At ~8 and ~1 Myr respectively, the stars in Upper Sco and rho Oph exhibit greater diversity of light curve shapes than are found in older clusters observed with K2 such as Pleiades or Praesepe. Nonetheless, we are able to derive rotation periods for 85% (971/1136) of the USco members and 80% (71/88) of the rho Oph members. About 25% of the periodic stars have evidence for multiple periods. These light curves sample smaller amplitudes to lower masses and with a far better cadence, than has even been probed before. We can compare USco with similar stars in Praesepe (~700 Myr) and the Pleiades (~125 Myr), all with K2 light curves.

Insights in Public Health: Training Today's Students to Meet Tomorrow's Challenges: Undergraduate Public Health at the University of Hawai'i at Manoa.

PubMed

Nelson-Hurwitz, Denise C; Arakaki, Lee-Ann; Uemoto, Maya

2017-03-01

The University of Hawai'i at Manoa (UHM) has long provided public health graduate education. The University's Office of Public Health Studies (OPHS) has recently started to offer a Bachelor of Arts in Public Health (BA PH) degree in response to the growing need for professionals in the health field. The purpose of this paper is to describe how UHM operates the BA PH and how the program complements OPHS's mission and goals. First, we describe the overall scope of the BA PH within OPHS and within UHM. Then we provide examples of how the BA PH program and past undergraduate student projects align with OPHS's four main goals: (1) education, (2) research, (3) service, and (4) program development.

Direct observation of the discrete energy spectrum of two lanthanide-based single-chain magnets by far-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Haas, Sabrina; Heintze, Eric; Zapf, Sina; Gorshunov, Boris; Dressel, Martin; Bogani, Lapo

2014-05-01

The far-infrared optical transmission has been studied for two lanthanide-based single-chain magnets DyPhOPh and TbPhOPh in the frequency range between 3 and 80 cm-1. The spectra were acquired at temperatures between 2 and 80 K and magnetic fields up to 6 T. Based on their magnetic field dependence in DyPhOPh two of the observed absorption lines are identified as transitions inside the crystal field split Dy3+ ground multiplet 6H15/2, coupled to the neighboring spins. In TbPhOPh one transition was observed inside the crystal-field-split Tb3+ ground multiplet 7F6. The results allow a spectroscopic investigation of the role of single-ion anisotropy and exchange in Glauber dynamics.

The Cytoplasmic and Periplasmic Expression Levels and Folding of Organophosphorus Hydrolase Enzyme in Escherichia coli

PubMed Central

Latifi, Ali Mohammad; Khajeh, Khosro; Farnoosh, Gholamreza; Hassanpour, Kazem; Khodi, Samaneh

2015-01-01

Background: Organophosphorus hydrolase (OPH) is a type of organophosphate-degrading enzyme which is widely used in the bioremediation process. Objectives: In this study, the periplasmic and cytoplasmic productions and the activity of recombinant OPH in Escherichia coli were investigated and compared using two pET systems (pET21a and pET26b). Materials and Methods: The sequence encoding the opd gene was synthesized and expressed in the form of inclusion body using pET21a-opd and in the periplasmic space in pET26b-opd. Results: Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed a band of about 37 kDa with a maximum expression level at 30°C from pET21a-opd.However, the obtained results of the periplasmic space extraction of OPH (pET26b-opd) showed a very weak band, while the cytoplasmic expression of OPH (pET21a-opd) produced a strong protein band. Conclusions: The activities studied by the production of PNP were determined by following the increase at 410 nm. The maximum PNP was produced at 30°C with an optical density of 10.62 in the presence of cytoplasmic expression of OPH (pET21a-opd). Consequently, our results suggest cytoplasmic expression system as an appropriate candidate with a high amount of OPH in spite of inclusion body formation, which needs an additional refolding step. PMID:26870308

The Biological Activities of Sesterterpenoid-Type Ophiobolins.

PubMed

Tian, Wei; Deng, Zixin; Hong, Kui

2017-07-18

Ophiobolins (Ophs) are a group of tricarbocyclic sesterterpenoids whose structures contain a tricyclic 5-8-5 carbotricyclic skeleton. Thus far, 49 natural Ophs have been reported and assigned into A-W subgroups in order of discovery. While these sesterterpenoids were first characterized as highly effective phytotoxins, later investigations demonstrated that they display a broad spectrum of biological and pharmacological characteristics such as phytotoxic, antimicrobial, nematocidal, cytotoxic, anti-influenza and inflammation-promoting activities. These bioactive molecules are promising drug candidates due to the developments of their anti-proliferative activities against a vast number of cancer cell lines, multidrug resistance (MDR) cells and cancer stem cells (CSCs). Despite numerous studies on the biological functions of Ophs, their pharmacological mechanism still requires further research. This review summarizes the chemical structures, sources, and biological activities of the oph family and discusses its mechanisms and structure-activity relationship to lay the foundation for the future developments and applications of these promising molecules.

Interfacial enhancement of polypropylene composites modified with sorbitol derivatives and siloxane-silsesquioxane resin

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

Dobrzyńska-Mizera, Monika, E-mail: monika.dobrzynska-mizera@doctorate.put.poznan.pl; Sterzyński, Tomasz; Dutkiewicz, Michał

Composites based on polypropylene (iPP) modified with a sorbitol derivative (NX8000) and siloxane-silsesquioxane resin (SiOPh) containing maleated polypropylene (MAPP) as compatibilizer were prepared by melt extrusion. Calorimetric investigations were carried out using differential scanning calorimetry (DSC), whereas the morphological and mechanical properties were investigated by scanning electron microscopy (SEM) and static tensile tests. DSC measurements revealed no influence of SiOPh and a slight effect of MAPP addition on the crystallization kinetics of polypropylene. Additionally, the introduction of MAPP into the iPP+NX8000+SiOPh composites increased plastic properties of the samples. All the above was attributed to the compatibilizing effect of MAPP whichmore » improved interfacial adhesion between iPP, NX8000 and SiOPh. This phenomenon was also confirmed by the SEM images illustrating more homogenous distribution of the filler in the compatibilized samples.« less

Interfacial enhancement of polypropylene composites modified with sorbitol derivatives and siloxane-silsesquioxane resin

NASA Astrophysics Data System (ADS)

Dobrzyńska-Mizera, Monika; Dutkiewicz, Michał; Sterzyński, Tomasz; Di Lorenzo, Maria Laura

2015-12-01

Composites based on polypropylene (iPP) modified with a sorbitol derivative (NX8000) and siloxane-silsesquioxane resin (SiOPh) containing maleated polypropylene (MAPP) as compatibilizer were prepared by melt extrusion. Calorimetric investigations were carried out using differential scanning calorimetry (DSC), whereas the morphological and mechanical properties were investigated by scanning electron microscopy (SEM) and static tensile tests. DSC measurements revealed no influence of SiOPh and a slight effect of MAPP addition on the crystallization kinetics of polypropylene. Additionally, the introduction of MAPP into the iPP+NX8000+SiOPh composites increased plastic properties of the samples. All the above was attributed to the compatibilizing effect of MAPP which improved interfacial adhesion between iPP, NX8000 and SiOPh. This phenomenon was also confirmed by the SEM images illustrating more homogenous distribution of the filler in the compatibilized samples.

Monitoring of V380 Oph requested in support of HST observations

NASA Astrophysics Data System (ADS)

Waagen, Elizabeth O.

2012-08-01

On behalf of a large Hubble Space Telescope consortium of which they are members, Dr. Joseph Patterson (Columbia University, Center for Backyard Astrophysics) and Dr. Arne Henden (AAVSO) requested observations from the amateur astronomer community in support of upcoming HST observations of the novalike VY Scl-type cataclysmic variable V380 Oph. The HST observations will likely take place in September but nightly visual observations are needed beginning immediately and continuing through at least October 2012. The astronomers plan to observe V380 Oph while it is in its current low state. Observations beginning now are needed to determine the behavior of this system at minimum and to ensure that the system is not in its high state at the time of the HST observations. V380 Oph is very faint in its low state: magnitude 17 to 19 and perhaps even fainter. Nightly snapshot observations, not time series, are requested, as is whatever technique - adding frames, lengthening exposur! es, etc. - necessary to measure the magnitude. It is not known whether V380 Oph is relatively inactive at minimum or has flares of one to two magnitudes; it is this behavior that is essential to learn in order to safely execute the HST observations. Finder charts with sequence may be created using the AAVSO Variable Star Plotter (http://www.aavso.org/vsp). Observations should be submitted to the AAVSO International Database. See full Alert Notice for more details. NOTE: This campaign was subsequently cancelled when it was learned V830 Oph was not truly in its low state. See AAVSO Alert Notice 468 for details.

No Expanding Fireball: Resolving the Recurrent Nova RS Ophiuchi with Infrared Interferometry

NASA Astrophysics Data System (ADS)

Monnier, J. D.; Barry, R. K.; Traub, W. A.; Lane, B. F.; Akeson, R. L.; Ragland, S.; Schuller, P. A.; Le Coroller, H.; Berger, J.-P.; Millan-Gabet, R.; Pedretti, E.; Schloerb, F. P.; Koresko, C.; Carleton, N. P.; Lacasse, M. G.; Kern, P.; Malbet, F.; Perraut, K.; Kuchner, M. J.; Muterspaugh, M. W.

2006-08-01

Following the recent outburst of the recurrent nova RS Oph on 2006 February 12, we measured its near-infrared size using the IOTA, Keck, and PTI Interferometers at multiple epochs. The characteristic size of ~3 mas hardly changed over the first 60 days of the outburst, ruling out currently popular models whereby the near-infrared emission arises from hot gas in the expanding shock. The emission was also found to be significantly asymmetric, evidenced by nonzero closure phases detected by IOTA. The physical interpretation of these data depends strongly on the adopted distance to RS Oph. Our data can be interpreted as the first direct detection of the underlying RS Oph binary, lending support to the recent ``reborn red giant'' models of Hachisu & Kato. However, this result hinges on an RS Oph distance of <~540 pc, in strong disagreement with the widely adopted distance of ~1.6 kpc. At the farther distance, our observations imply instead the existence of a nonexpanding, dense, and ionized circumbinary gaseous disk or reservoir responsible for the bulk of the near-infrared emission. Longer baseline infrared interferometry is uniquely suited to distinguish between these models and to ultimately determine the distance, binary orbit, and component masses for RS Oph, one of the closest known (candidate) Type 1a supernova progenitor systems.

Economic Evaluation of Global Endometrial Ablation Versus Inpatient and Outpatient Hysterectomy for Treatment of Abnormal Uterine Bleeding: US Commercial and Medicaid Payer Perspectives.

PubMed

Miller, Jeffrey D; Bonafede, Machaon M; Cai, Qian; Pohlman, Scott K; Troeger, Kathleen A; Cholkeri-Singh, Aarathi

2018-03-01

Every year, abnormal uterine bleeding (AUB) exacts a heavy toll on women's health and leads to high costs for the US health care system. The literature shows that endometrial ablation results in fewer complications, shorter recovery and lower costs than more commonly performed hysterectomy procedures. The objective of this study was to model clinical-economic outcomes, budget impact, and cost-effectiveness of global endometrial ablation (GEA) versus outpatient hysterectomy (OPH) and inpatient hysterectomy (IPH) procedures. A decision tree, state-transition (semi-Markov) economic model was developed to simulate 3 hypothetical cohorts of women who received surgical treatment for AUB (GEA, OPH, and IPH) over 1, 2, and 3 years to evaluate clinical and economic outcomes for GEA vs. OPH and GEA vs. IPH. Two versions of the model were created to reflect both commercial health care payer and US Medicaid perspectives, and analyses were conducted for both payer types. Total health care costs in the first year after GEA were substantially lower compared with those for IPH and OPH. Budget impact analysis results showed that increasing GEA utilization yields total annual cost savings of about $906,000 for a million-member commercial health plan and about $152,000 in cost savings for a typical-sized state Medicaid plan with 1.4 million members. Cost-effectiveness analysis results for both perspectives showed GEA as economically dominant (conferring greater benefit at lower cost) over both OPH and IPH in the 1-year commercial scenario. This study demonstrates that, for some patients, GEA may prove to be a safe, uterus-sparing, cost-effective alternative to OPH and IPH for the surgical treatment of AUB.

A simultaneous spectroscopic and photometric study of two eclipsing binaries: V566 Oph and V972 Her

NASA Astrophysics Data System (ADS)

Selam, S. O.; Esmer, E. M.; Şenavcı, H. V.; Bahar, E.; Yörükoğlu, O.; Yılmaz, M.; Baştürk, Ö.

2018-02-01

In this study, we have performed simultaneous solutions of light and radial velocity curves of two eclipsing binary systems, V566 Oph and V972 Her. We observed both systems spectroscopically with a very recently installed spectrograph on the 40 cm telescope, T40, located in Ankara University Kreiken Observatory (AUKR), for the first time. We made use of the photometric data from the Hipparcos satellite for V972 Her, while we obtained the photometric observations of V566 Oph by using the 35 cm telescope, T35, located also in our observatory campus. We derived the absolute parameters for both systems and discussed their evolutionary states. In addition to the simultaneous analysis, we have also analyzed the change in mid-eclipse times for V566 Oph, and found cyclic variations, for which we have discussed light-time effect and magnetic activity as their potential origin, superimposed on a secular change due to a mass transfer between the components of the binary.

RS Ophiuchi: The Gift that Keeps on Giving

NASA Astrophysics Data System (ADS)

Starrfield, S.

2008-12-01

RS Oph experienced its sixth recorded outburst in 2006 and was observed in virtually every wavelength region from hard X-rays to the radio. Each observation, especially those with instruments that have come online since its last outburst in 1985, provided new and exciting information about the explosion. As a result, some of us organized a second workshop on the RS Oph outburst and it was held in June 2007 at Keele University. I gave the lead off talk in which I presented a number of questions to be discussed during the workshop, a brief summary of what had been discovered in previous outbursts concentrating on the ultraviolet studies with IUE, and a few observations of the 2006 outburst concentrating on the results from Swift and HST.

Spectrophotometric observations of symbiotic stars and related objects

NASA Technical Reports Server (NTRS)

Blair, W. P.; Feibelman, W. A.; Michalitsianos, A. G.; Stencel, R. E.

1983-01-01

Calibrated optical spectrophotometric observations of 16 symbiotic and symbiotic-like objects are presented. The objects observed include Z And, T CrB, CH Cyg, CI Cyg, V1016 Cyg, V1329 Cyg, AG Dra, YY Her, RS Oph, XX Oph, AG Peg, AX Per, CL Sco, HM Sge, AS 289, and M1-2. Integrated emission-line intensities are tabulated for comparison with ultraviolet and infrared data, as well as with previous optical studies. The reddening to each of the objects is derived by assuming that Balmer lines are emitted in their case B recombination ratios. However, the values so derived are often systematically higher than reddening estimates from the ultraviolet 2200 A feature. Comparisons with the available data from other wavelength ranges are noted.

BIOSENSOR FOR DIRECT DETERMINATION OF ORGANOPHOSPHATE NERVE AGENTS. 1. POTENTIOMETRIC ENZYME ELECTRODE. (R823663)

EPA Science Inventory

A potentiometric enzyme electrode for the direct measurement of organophosphate (OP)
nerve agents was developed. The basic element of this enzyme electrode was a pH electrode
modified with an immobilized organophosphorus hydrolase (OPH) layer formed by cross-linking
OPH ...

9 CFR 391.4 - Laboratory services rate.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Laboratory services rate. 391.4 Section 391.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... dividing the Office of Public Health Science (OPHS) previous fiscal year's regular direct pay by OPHS...

9 CFR 391.4 - Laboratory services rate.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Laboratory services rate. 391.4 Section 391.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... dividing the Office of Public Health Science (OPHS) previous fiscal year's regular direct pay by OPHS...

9 CFR 391.4 - Laboratory services rate.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Laboratory services rate. 391.4 Section 391.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... dividing the Office of Public Health Science (OPHS) previous fiscal year's regular direct pay by OPHS...

The peculiar fast-rotating star 51 Ophiuchi probed by VEGA/CHARA

NASA Astrophysics Data System (ADS)

Jamialahmadi, N.; Berio, P.; Meilland, A.; Perraut, K.; Mourard, D.; Lopez, B.; Stee, P.; Nardetto, N.; Pichon, B.; Clausse, J. M.; Spang, A.; McAlister, H.; ten Brummelaar, T.; Sturmann, J.; Sturmann, L.; Turner, N.; Farrington, C.; Vargas, N.; Scott, N.

2015-07-01

Context. Stellar rotation is a key in our understanding of both mass-loss and evolution of intermediate and massive stars. It can lead to anisotropic mass-loss in the form of radiative wind or an excretion disk. Aims: We wished to spatially resolve the photosphere and gaseous environment of 51 Oph, a peculiar star with a very high vsini of 267 km s-1 and an evolutionary status that remains unsettled. It has been classified by different authors as a Herbig, a β Pic, or a classical Be star. Methods: We used the VEGA visible beam combiner installed on the CHARA array that reaches a submilliarcsecond resolution. Observation were centered on the Hα emission line. Results: We derived, for the first time, the extension and flattening of 51 Oph photosphere. We found a major axis of θeq = 8.08 ± 0.70 R⊙ and a minor axis of θpol = 5.66 ± 0.23 R⊙. This high photosphere distortion shows that the star is rotating close to its critical velocity. Finally, using spectro-interferometric measurements in the Hα line, we constrained the circumstellar environment geometry and kinematics and showed that the emission is produced in a 5.2 ± 2 R⋆ disk in Keplerian rotation. Conclusions: From the visible point of view, 51 Oph presents all the features of a classical Be star: near critical-rotation and double-peaked Hα line in emission produced in a gaseous disk in Keplerian rotation. However, this does not explain the presence of dust as seen in the mid-infrared and millimeter spectra, and the evolutionary status of 51 Oph remains unsettled.

Chemistry of a newly detected circumbinary disk in Ophiuchus

NASA Astrophysics Data System (ADS)

Artur de la Villarmois, Elizabeth; Kristensen, Lars E.; Jørgensen, Jes K.; Bergin, Edwin A.; Brinch, Christian; Frimann, Søren; Harsono, Daniel; Sakai, Nami; Yamamoto, Satoshi

2018-06-01

Context. Astronomers recently started discovering exoplanets around binary systems. Therefore, understanding the formation and evolution of circumbinary disks and their environment is crucial for a complete scenario of planet formation. Aims: The purpose of this paper is to present the detection of a circumbinary disk around the system Oph-IRS67 and analyse its chemical and physical structure. Methods: We present high-angular-resolution (0.''4, 60 AU) observations of C17O, H13CO+, C34S, SO2, C2H and c-C3H2 molecular transitions with the Atacama Large Millimeter/submillimeter Array (ALMA) at wavelengths of 0.8 mm. The spectrally and spatially resolved maps reveal the kinematics of the circumbinary disk as well as its chemistry. Molecular abundances are estimated using the non-local thermodynamic equilibrium (LTE) radiative-transfer tool RADEX. Results: The continuum emission agrees with the position of Oph-IRS67 A and B, and reveals the presence of a circumbinary disk around the two sources. The circumbinary disk has a diameter of 620 AU and is well traced by C17O and H13CO+ emission. Two further molecular species, C2H and c-C3H2, trace a higher-density region which is spatially offset from the sources ( 430 AU). Finally, SO2 shows compact and broad emission around only one of the sources, Oph-IRS67 B. The molecular transitions which trace the circumbinary disk are consistent with a Keplerian profile on smaller disk scales (≲200 AU) and an infalling profile for larger envelope scales (≳200 AU). The Keplerian fit leads to an enclosed mass of 2.2 M⊙. Inferred CO abundances with respect to H2 are comparable to the canonical ISM value of 2.7 × 10-4, reflecting that freeze-out of CO in the disk midplane is not significant. Conclusions: Molecular emission and kinematic studies prove the existence and first detection of the circumbinary disk associated with the system Oph-IRS67. The high-density region shows a different chemistry than the disk, being enriched in carbon chain molecules. The lack of methanol emission agrees with the scenario where the extended disk dominates the mass budget in the innermost regions of the protostellar envelope, generating a flat density profile where less material is exposed to high temperatures, and thus, complex organic molecules would be associated with lower column densities. Finally, Oph-IRS67 is a promising candidate for proper motion studies and the detection of both circumstellar disks with higher-angular-resolution observations.

Be Star Monitoring Using a Small Aperture Telescope and Fiber-fed Spectrograph

NASA Astrophysics Data System (ADS)

Austin, S. J.

2003-12-01

Initial results are reported from a Be star monitoring project developed for undergraduate student research involvement at a small undergraduate university using a small aperture telescope and a custom-built fiber-fed spectrograph. Beginning in 2003 June, 0.8 Angstrom/pixel resolution spectra of the H-alpha line for over forty Be stars (Omi Aqr, 4 Aql, V923 Aql, V1294 Aql, Nu 2 Boo, 24 CVn, Gamma Cas, 4 CrB, Beta Cyg, 11 Cyg, 28 Cyg, 55 Cyg, 59 Cyg, 66 Cyg, V2136 Cyg, 1 Del, CX Dra, Omi Her, Sigma Her, 4 Her, 11 Her, 88 Her, 48 Lib, Chi Oph, Zeta Oph, 51 Oph, 66 Oph, Eta PsA, V4024 Sgr, 64 Ser, Delta Sco, QR Vul, 12 Vul, 20 Vul, 25 Vul, HD142184, HD165174, HD169033, HD170235, HD174179, HD181615, HD184279, HD195554, HD201733) have been obtained. H-alpha line profile velocities and evolution are shown. Funding has been provided by the UCA University Research Council and the Arkansas Space Grant Consortium.

ESTABLISHING {alpha} Oph AS A PROTOTYPE ROTATOR: IMPROVED ASTROMETRIC ORBIT

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

Hinkley, Sasha; Hillenbrand, Lynne; Crepp, Justin R.

2011-01-10

The nearby star {alpha} Oph (Ras Alhague) is a rapidly rotating A5IV star spinning at {approx} 89% of its breakup velocity. This system has been imaged extensively by interferometric techniques, giving a precise geometric model of the star's oblateness and the resulting temperature variation on the stellar surface. Fortuitously, {alpha} Oph has a previously known stellar companion, and characterization of the orbit provides an independent, dynamically based check of both the host star and the companion mass. Such measurements are crucial to constrain models of such rapidly rotating stars. In this study, we combine eight years of adaptive optics imagingmore » data from the Palomar, AEOS, and CFHT telescopes to derive an improved, astrometric characterization of the companion orbit. We also use photometry from these observations to derive a model-based estimate of the companion mass. A fit was performed on the photocenter motion of this system to extract a component mass ratio. We find masses of 2.40{sup +0.23}{sub -0.37} M{sub sun} and 0.85{sup +0.06}{sub -0.04} M{sub sun} for {alpha} Oph A and {alpha} Oph B, respectively. Previous orbital studies of this system found a mass too high for this system, inconsistent with stellar evolutionary calculations. Our measurements of the host star mass are more consistent with these evolutionary calculations, but with slightly higher uncertainties. In addition to the dynamically derived masses, we use IJHK photometry to derive a model-based mass for {alpha} Oph B, of 0.77 {+-} 0.05 M{sub sun} marginally consistent with the dynamical masses derived from our orbit. Our model fits predict a periastron passage on 2012 April 19, with the two components having a 50 mas separation from 2012 March to May. A modest amount of interferometric and radial velocity data during this period could provide a mass determination of this star at the few percent level.« less

Hyperprolactinemia in Children with Subclinical Hypothyroidism.

PubMed

Sharma, Neera; Dutta, Deep; Sharma, Lokesh Kumar

2017-12-15

Prevalence of hyperprolactinemia in children with subclinical hypothyroidism (ScH) is not known. This study aimed to determine the occurrence and predictors of hyperprolactinemia in euthyroid children and in children with ScH and overt primary hypothyroidism (OPH). Serum prolactin levels were estimated in consecutive children <18 years of age undergoing thyroid function evaluation and diagnosed to have normal thyroid function, ScH, or OPH. Children with pituitary adenomas, secondary hypothyroidism, multiple pituitary hormone deficiency, comorbid states, and drug-induced hyperprolactinemia were excluded. From the initially screened 791 children, hormonal data from 602 children who fulfilled all criteria were analyzed. Seventy-one (11.79%) of these had ScH, and 33 (5.48%) had OPH. Occurrence of hyperprolactinemia was highest in the OPH group (51.51%), followed by ScH (30.98%) and euthyroid children (4.41%) (p<0.001). Median (25 th -75 th percentiles) levels for prolactin in euthyroid, ScH, and OPH children were 13.3 (9.4-17.95), 19.15 (15.97-30.12), and 28.86 (17.05-51.9) ng/mL, respectively (p<0.001). In children, prolactin levels were comparable in males and females. An age-related increase in serum prolactin was noted in euthyroid children, which was statistically significant in post-pubertal (16-18 years) children. Area under the curve for thyroid stimulating hormone (TSH) in predicting hyperprolactinemia in children was 0.758 (95% confidence interval: 0.673-0.829; p<0.001). TSH ≥4.00 mIU/L had a sensitivity of 69.4% and specificity of 77.6% in detecting hyperprolactinemia. Hyperprolactinemia is common in children with ScH and OPH. TSH ≥4.00 mIU/L has a good sensitivity and specificity in predicting hyperprolactinemia in children. More studies are needed to establish if hyperprolactinemia should be an indication for treating ScH in children.

Monitoring of V2487 Oph requested

NASA Astrophysics Data System (ADS)

Waagen, Elizabeth O.

2016-10-01

Dr. Ashley Pagnotta (Louisiana State University) has requested AAVSO assistance in monitoring the recurrent nova V2487 Oph in order to catch and observe its next outburst. Pagnotta writes: "V2487 Oph is a recurrent nova that was first seen to erupt in 1998. During a search of the Harvard College Observatory plate archives for previous eruptions, we found one that was recorded in 1900. Based on the speed and magnitude of the eruption, and the coverage of the archival plates and other detection sources, we calculated how often V2487 Oph would have to erupt for us to have actually detected one random outburst on the plates, which is about once every 18-20 years (for more, Pagnotta et al. 2009AJ....138.1230P). As we are now 18 years from the previous (1998) eruption, we request regular AAVSO observations to help us detect the next eruption of V2487 Oph. Because V2487 Oph is a very fast nova, we are requesting a high cadence [when the outburst occurs. Previous outbursts have been as bright as V=9.5.]...Once the eruption has been confirmed (likely by other AAVSO observers, thanks to the flexibility of your observing programs), we will notify collaborators and invoke ToO observations to observe the eruption as comprehensively as possible." Observers are requested to make nightly observations in V or Clear. If V2487 Oph is brighter than V=17.5, please report the observation(s) to the AAVSO immediately and switch to multi-color (UBVRI or Sloan equivalents; Clear if other filters are not available) and high (fast) cadence time-series - exposures of a few minutes, with a S/N of at least 40-50. Continue at high cadence until the decline is underway. Time-series observations during the decline are not absolutely essential, but they would be useful to continue to look for flares and the late time dips that were seen in U Sco around days 41-61. Nightly observations as before should be continued until the star has faded to V=17.5, and then for two weeks m! ore. Finder charts with sequence may be created using the AAVS! O Variab le Star Plotter (https://www.aavso.org/vsp). Observations should be submitted to the AAVSO International Database. See full Alert Notice for more details.

Ophiobolin A, a sesterpenoid fungal phytotoxin, displays different mechanisms of cell death in mammalian cells depending upon the cancer cell origin.

PubMed

Morrison, Rachel; Lodge, Tiffany; Evidente, Antonio; Kiss, Robert; Townley, Helen

2017-03-01

Herein we have undertaken a systematic analysis of the effects of the fungal derivative ophiobolin A (OphA) on eight cancer cell lines from different tissue types. The LD50 for each cell line was determined and the change in cell size determined. Flow cytometric analysis and western blotting were used to assess the cell death markers for early apoptosis, late apoptosis and necrosis, and the involvement of the caspase signalling pathway. Alterations in calcium levels and reactive oxygen species were assessed due to their integral involvement in intracellular signalling. Subsequently, the endoplasmic reticulum (ER) and mitochondrial responses were investigated more closely. The extent of ER swelling, and the upregulation of proteins involved in the unfolded protein responses (UPR) were seen to vary according to cell line. The mitochondria were also shown to behave differently in response to the OphA in the different cell lines in terms of the change in membrane potential, the total area of mitochondria in the cell and the number of mitochondrial bifurcations. The data obtained in the present study indicate that the cancer cell lines tested are unable to successfully activate the ER stress/UPR responses, and that the mitochondria appear to be a central player in OphA-induced cancer cell death.

Early X- and HE γ-ray emission from the symbiotic recurrent novae V745 Sco & RS Oph.

NASA Astrophysics Data System (ADS)

Delgado, L.; Hernanz, M.

2017-10-01

RS Oph was the first nova for which evidence of particle acceleration during its 2006 outburst was found. In recent years, several nova explosions - eight classical and two symbiotic recurrent novae - have been detected by Fermi/LAT at E>100 MeV. In most cases, this emission has been observed early after the explosion, around the optical maximum, and for a short period of time. The high-energy γ-ray emission is a consequence of π^{0} decay and/or Inverse Compton, which are related to particle (p and e^{-}) acceleration in the strong shock between the nova ejecta and the circumstellar matter. Our aim is to understand the acceleration process through the analysis of contemporaneous X-ray emission, and in particular, through the evolution of the shock wave. A deep analysis of early X-ray observations of the symbiotic recurrent novae V745 Sco (2014) by Swift/XRT, Chandra/HETG and NuStar, and RS Oph (2006) by XMM-Newton/EPIC and RGS, Swift/XRT and BAT and RXTE/PCA is presented taking into account the contemporaneous information from the IR and radio observations. This provides for the first time a global view of the early evolution of a nova remnant and its relationship with particle acceleration.

Potential of agroindustrial waste from olive oil industry for fuel ethanol production.

PubMed

Georgieva, Tania I; Ahring, Birgitte K

2007-12-01

Olive pulp (OP) is a highly polluting semi-solid residue generated from the two-stage extraction processing of olives and is a major environmental issue in Southern Europe, where 80% of the world olive oil is produced. At present, OP is either discarded to the environment or combusted with low calorific value. In this work, utilization of OP as a potential substrate for production of bioethanol was studied. Enzymatic hydrolysis and subsequent glucose fermentation by baker's yeast were evaluated for OP from 10% to 30% dry matter (i.e., undiluted). Enzymatic hydrolysis resulted in an increase in glucose concentration by 75%, giving final glucose yields near 70%. Fermentation of undiluted OP hydrolysate (OPH) resulted in the maximum ethanol produced (11.2 g/L) with productivity of 2.1 g/L/h. Ethanol yields were similar for all tested OPH concentrations and were in the range of 0.49-0.51 g/g. Results showed that yeast could effectively ferment OPH even without nutrient addition, revealing the tolerance of yeast to OP toxicity. Because of low xylan (12.4%) and glucan (16%) content in OP, this specific type of OP is not a suitable material for producing only ethanol and thus, bioethanol production should be integrated with production of other value-added products.

Determination of Organophosphate Pesticides at a Carbon Nanotube/Organophosphorus Hydrolase Electrochemical Biosensor

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

Deo, R P.; Wang, Joseph; Block, I

2005-02-08

An amperometric biosensor for organophosphorus (OP) pesticides based on a carbon-nanotube (CNT) modified transducer and an organophosphorus hydrolase (OPH) biocatalyst is described. A bilayer approach with the OPH layer atop of the CNT film was used for preparing the CNT/OPH biosensor. The CNT layer leads to a greatly improved anodic detection of the enzymatically-generated p-nitrophenol product, including higher sensitivity and stability. The sensor performance was optimized with respect to the surface modification and operating conditions. Under the optimal conditions the biosensor was used to measure as low as 0.15 {micro}M paraoxon and 0.8 {micro}M methyl parathion with sensitivities of 25more » and 6 nA/{micro}M, respectively.« less

Phytodegradation of organophosphorus compounds by transgenic plants expressing a bacterial organophosphorus hydrolase.

PubMed

Wang, Xiaoxue; Wu, Ningfeng; Guo, Jun; Chu, Xiaoyu; Tian, Jian; Yao, Bin; Fan, Yunliu

2008-01-18

Organophosphorus (OP) compounds are widely used as pesticides in agriculture but cause broad-area environmental pollution. In this work, we have expressed a bacterial organophosphorus hydrolase (OPH) gene in tobacco plants. An assay of enzyme activity showed that transgenic plants could secrete OPH into the growth medium. The transgenic plants were resistant to methyl parathion (Mep), an OP pesticide, as evidenced by a toxicity test showing that the transgenic plants produced greater shoot and root biomass than did the wild-type plants. Furthermore, at 0.02% (v/v) Mep, the transgenic plants degraded more than 99% of Mep after 14 days of growth. Our work indicates that transgenic plants expressing an OPH gene may provide a new strategy for decontaminating OP pollutants.

Comparing federal and state healthcare provider performance in villages targeted by the conditional cash transfer programme of Mexico.

PubMed

Bustamante, Arturo Vargas

2011-10-01

This study investigates household out-of-pocket healthcare expenditures (OPH) and preventive care utilization (PHU) to compare federal and state healthcare provider performance in villages targeted by conditional cash transfer (CCT) programmes in poor rural areas of Mexico. Lower OPH and higher PHU are indicative of better performance in the study setting. Log-linear and probit regression models were used to compare outcomes in households from treatment and control villages reached by federal and state healthcare providers. In treatment villages, eligible households receive cash grants from the CCT programme. In control villages, eligible households do not receive cash grants from the CCT programme at the time of the survey. Families who live in treatment villages reported lower OPH (-52.5% for federal and -46.2% for state clinics) and higher PHU (21% for federal and 20% for state clinics) regardless of clinic setting. As the reduction in OPH is higher in areas reached by the federal clinics, it implies better performance from this healthcare delivery system. Additionally, federal clinic outcomes were also more homogeneous because OPH are not significantly different between treatment and control villages. Alternative measures such as drug and physician expenditures, diabetes and hypertension tests and nutritional-supplement receipt confirmed these findings. Mexico has two healthcare delivery systems that cater to identical rural populations. The better-funded and more centralized federal system is more effective at providing health care in poor rural villages of Mexico regardless of CCT participation. State clinics in villages targeted by the CCT programme, however, perform significantly better. © 2011 Blackwell Publishing Ltd.

Optical and Near-infrared Study of Nova V2676 Oph 2012

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

Raj, A.; Das, R. K.; Walter, F. M., E-mail: ashish.raj@iiap.res.in

2017-02-01

We present optical spectrophotometric and near-infrared (NIR) photometric observations of the nova V2676 Oph covering the period from 2012 March 29 through 2015 May 8. The optical spectra and photometry of the nova have been taken from SMARTS and Asiago; the NIR photometry was obtained from SMARTS and Mt. Abu. The spectra were dominated by strong H i lines from the Balmer series, Fe ii, N i, and [O i] lines in the initial days, typical of an Fe ii type nova. The measured FWHM for the H β and H α lines was 800–1200 km s{sup −1}. There wasmore » pronounced dust formation starting 90 days after the outburst. The J − K color was the largest among recent dust-forming novae.« less

Ophiobolin A, a sesterpenoid fungal phytotoxin, displays different mechanisms of cell death in mammalian cells depending upon the cancer cell origin

PubMed Central

Morrison, Rachel; Lodge, Tiffany; Evidente, Antonio; Kiss, Robert; Townley, Helen

2017-01-01

Herein we have undertaken a systematic analysis of the effects of the fungal derivative ophiobolin A (OphA) on eight cancer cell lines from different tissue types. The LD50 for each cell line was determined and the change in cell size determined. Flow cytometric analysis and western blotting were used to assess the cell death markers for early apoptosis, late apoptosis and necrosis, and the involvement of the caspase signalling pathway. Alterations in calcium levels and reactive oxygen species were assessed due to their integral involvement in intracellular signalling. Subsequently, the endoplasmic reticulum (ER) and mitochondrial responses were investigated more closely. The extent of ER swelling, and the upregulation of proteins involved in the unfolded protein responses (UPR) were seen to vary according to cell line. The mitochondria were also shown to behave differently in response to the OphA in the different cell lines in terms of the change in membrane potential, the total area of mitochondria in the cell and the number of mitochondrial bifurcations. The data obtained in the present study indicate that the cancer cell lines tested are unable to successfully activate the ER stress/UPR responses, and that the mitochondria appear to be a central player in OphA-induced cancer cell death. PMID:28112374

Computational study of An-X bonding (An = Th, U; X = p-block-based ligands) in pyrrolic macrocycle-supported complexes from the quantum theory of atoms in molecules and bond energy decomposition analysis.

PubMed

O'Brien, Kieran T P; Kaltsoyannis, Nikolas

2017-01-17

A systematic computational study of organoactinide complexes of the form [LAnX] n+ has been carried out using density functional theory, the quantum theory of atoms in molecules (QTAIM) and Ziegler-Rauk energy decomposition analysis (EDA) methods. The systems studied feature L = trans-calix[2]benzene[2]pyrrolide, An = Th(iv), Th(iii), U(iii) and X = BH 4 , BO 2 C 2 H 4 , Me, N(SiH 3 ) 2 , OPh, CH 3 , NH 2 , OH, F, SiH 3 , PH 2 , SH, Cl, CH 2 Ph, NHPh, OPh, SiH 2 Ph, PHPh 2 , SPh, CPh 3 , NPh 2 , OPh, SiPh 3 PPh 2 , SPh. The PBE0 hybrid functional proved most suitable for geometry optimisations based on comparisons with available experimental data. An-X bond critical point electron densities, energy densities and An-X delocalisation indices, calculated with the PBE functional at the PBE0 geometries, are correlated with An-X bond energies, enthalpies and with the terms in the EDA. Good correlations are found between energies and QTAIM metrics, particularly for the orbital interaction term, provided the X ligand is part of an isoelectronic series and the number of open shell electrons is low (i.e. for the present Th(iv) and Th(iii) systems).

XMM-Newton Proposal 03039101

NASA Astrophysics Data System (ADS)

Hernanz, Margarita

2004-10-01

Two recent galactic novae, V2487 Oph 1998 and V4633 Sgr 1998, have been detec- ted in both soft and hard X-rays with XMM. V2487 Oph showed an iron fluores- cent line only 2.7 yrs after its explosion, a clear signature of the very fast recovery of accretion, and V4633 Sgr displayed hard X-ray emission not clearly attributable to shocked ejecta or accretion. Longer observations are needed to do accurate timing and high resolution spectroscopy, essential to determine the main properties of the underlying cataclysmic variable in V2487 Oph (first nova seen in X-rays prior and after exploding) and to disentangle the origin of the hard X-rays from V4633 Sgr, through an analysis of the chemical compo- sition of the emitting thermal plasma, solar if accretion, non solar if ejecta.

Hydrolysis of VX and related compounds by organophosphorus hydrolase. Final report, Februray-December 1993

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

Kolakowski, J.E.; DeFrank, J.J.; Lai, K.

1995-11-01

Organophosphorus Hydrolase (OPH) is a fully characterized and cloned enzyme, derived from Pseudomonas diminuta, consisting of 365 amino acids with a total molecular weight of 38,0(X). The enzyme has a leader sequence of 29 amino acids which has been removed in the construction used in this study. OPH was evaluated for its effectiveness in catalyzing the S-(2-diisopwpylaminoethyl) methylphosphonothioate (VX) and its analogs.

Soft X-ray observation of the Rho Ophiuchus dark cloud region

NASA Technical Reports Server (NTRS)

Apparao, K. M. V.; Hayakawa, S.; Hearn, D. R.

1979-01-01

Soft X-rays (0.1-0.8 keV) from the region including the Rho Oph dark cloud were observed with the SAS-3 low-energy X-ray telescope. No X-ray absorption by the cloud was observed. This indicates that the diffuse component of soft X-rays in this region is mostly from the foreground of the Rho Oph cloud which is located at a distance of 160-200 pc.

HD 93521, zeta Ophiuchi, and the effects of rapid rotation on the atmospheres and winds of 09.5 V stars

NASA Technical Reports Server (NTRS)

Massa, Derck

1995-01-01

Both low- and high-resolution IUE spectra of the rapidly rotating 09.5 V stars HD 93521 and zeta Oph are used to develop a coherent picture of the effects of rapid rotation on the atmospheres and winds of late, main-sequence O stars. The observational consequences are by far the strongest on HD 93521, most likely because it is being viewed nearly equator-on. In particular, it is shown that HD 93521 (1) a much smaller UV optical flux ratio than expected, (2) UV photospheric lines indicative of a BO supergiant, (3) an abnormally strong N v wind doublet, and (4) wind profiles suggesting that its wind has latitudinally dependent properties. Because HD 93521 has a larger observed v sin i than zeta Oph and yet its H-alpha emission is no stronger than in zeta Oph, it is speculated that zeta Oph actually rotates as fast or faster than HD 93521, but has a smaller sin i. Because zeta Oph is significantly reddened, nothing can be determined about its intrinsic UV energy distribution. However, it is shown that its UV photospheric lines are a bit peculiar and that its C IV and N V wind doublets are abnormally strong and have unusual profiles. The C IV profile agrees with models of a rotationally distorted wind similar to the one in HD 93521, except viewed at an angle i approximately 60 deg-80 deg. The spectral peculiarities of both stars are attributed to the combined effects of gravity darkening of their atmospheres and rotational distortion of their winds. The differences between their spectra are interpreted as the result of being viewed at different inclination angles. Because of the gravity darkening, atmospheric analyses of either star based on single temperature and surface gravity model atmospheres are probably unreliable. Finally, I describe how different effects conspire to make the spectroscopic signatures of gravity darkening so pronounced at 09.5 V.

Influence of the redox active ligand on the reactivity and electronic structure of a series of Fe(TIM) complexes.

PubMed

Hess, Corinna R; Weyhermüller, Thomas; Bill, Eckhard; Wieghardt, Karl

2010-06-21

The redox properties of Fe and Zn complexes coordinated by an alpha-diimine based N(4)-macrocyclic ligand (TIM) have been examined using spectroscopic methods and density functional theory (DFT) computational analysis. DFT results on the redox series of [Zn(TIM*)](n) and [Fe(TIM*)](n) molecules indicate the preferential reduction of the alpha-diimine ligand moiety. In addition to the previously reported [Fe(TIM*)](2) dimer, we have now synthesized and characterized a further series of monomeric and dimeric complexes coordinated by the TIM ligand. This includes the five-coordinate monomeric [Fe(TIM*)I], the neutral and cationic forms of a monomeric phosphite adduct, [Fe(TIM*)(P(OPh)(3))] and [Fe(TIM*)(P(OPh)(3))](PF(6)), as well as a binuclear hydroxy-bridged complex, [{Fe(TIM*)}(2)(mu-OH)](PF(6)). Experimental and computational data for these synthetic compounds denote the presence of ferrous and ferric species, suggesting that the alpha-diimine based macrocycles do not readily support the formation of formally low-valent (M(0) or M(I)) metal complexes as previously speculated. Magnetochemical, Mossbauer, electron paramagnetic resonance (EPR), and electronic spectral data have been employed to experimentally determine the oxidation state of the central metal ion and of the macrocyclic ligand (TIM*) in each compound. The series of compounds is described as follows: [Fe(II)(TIM(0))(CH(3)CN(2))](2+), S(Fe) = S(T) = 0; [Fe(2.5)(TIM(2.5-))](2), S(T) = 1; [{Fe(III)(TIM(2-))}(2)(mu-OH)](+), S(Fe) = 3/2, S(T) = 0; [Fe(III)(TIM(2-))I], S(Fe) = 3/2, S(T) = 1/2; [Fe(II)(TIM(2-))(P(OPh(3)))], S(Fe) = S(T) = 0; and [Fe(II)(TIM(1-))(P(OPh(3)))](1+)/[Fe(I)(TIM(0))(P(OPh(3)))](1+), S(T) = 1/2. The results have been corroborated by DFT calculations.

Velocity Curve Analysis of Spectroscopic Binary Stars AI Phe, GM Dra, HD 93917 and V502 Oph by Nonlinear Regression

NASA Astrophysics Data System (ADS)

Karami, K.; Mohebi, R.

2007-08-01

We introduce a new method to derive the orbital parameters of spectroscopic binary stars by nonlinear least squares of (o-c). Using the measured radial velocity data of the four double lined spectroscopic binary systems, AI Phe, GM Dra, HD 93917 and V502 Oph, we derived both the orbital and combined spectroscopic elements of these systems. Our numerical results are in good agreement with the those obtained using the method of Lehmann-Filhé.

Highly Selective Coupling of Alkenes and Aldehydes Catalyzed by NHC–Ni–P(OPh)3: Synergy Between a Strong σ-Donor and a Strong π-Acceptor**

PubMed Central

Ho, Chun-Yu; Jamison, Timothy F.

2011-01-01

Both a strong electron donor (IPr) and a strong electron acceptor (P(OPh)3) are necessary for a highly selective, nickel-catalyzed coupling reaction between alkenes, aldehydes, and silyltriflates. Without the phosphite, catalysis is not observed and several side reactions are observed. The phosphite appears to suppress the formation of these byproducts and rescue the catalytic cycle by accelerating reductive elimination from an (IPr–Ni–H)(OTf) complex. PMID:17154217

The Fast Rotating Star 51 Oph Probed by VEGA/CHARA

NASA Astrophysics Data System (ADS)

Jamialahmadi, N.; Berio, P.; Meilland, A.; Perraut, K.; Mourard, D.; Lopez, B.; Stee, P.; Nardetto, N.; Pichon, B.; Clausse, J. M.; Spang, A.; McAlister, H.; ten Brummelaar, T.

2015-12-01

Stellar rotation is a key in our understanding of both mass-loss and evolution of intermediate and massive stars. It can lead to anisotropic mass-loss in the form of radiative wind or an excretion disk. We used the VEGA visible beam combiner installed on the CHARA array that reaches a sub milliarcsecond resolution. We derived, for the first time, the extension and flattening of 51 Oph photosphere. We found an elongated ratio of 1.45 ± 0.12.

Nova Oph 2017 (TCP J17394608-2457555) detected at millimeter wavelengths

NASA Astrophysics Data System (ADS)

Kaminski, T.; Gehrz, R.

2017-06-01

Millimeter-wave continuum emission was detected in Nova Oph 2017 (ATel #10366, #10367) with the Submillimeter Array in Hawaii. The object was observed on July 20, 2017 in four spectral ranges: 224.3-232.3, 240.6-248.6, 336-344, and 352-360 GHz. The combined continuum flux in the two lower ranges (i.e., at a wavelength of 1.3 mm) is of 4.8 mJy, well above the noise with an rms of 0.6 mJy per beam.

Establishing Alpha Oph as a Prototype Rotator: Improved Astrometric Orbit

DTIC Science & Technology

2011-01-10

astrometric characterization of the companion orbit. We also use photometry from these observations to derive a model-based estimate of the companion mass. A...uncertainties. In addition to the dynamically derived masses, we use IJHK photometry to derive a model-based mass for α Oph B, of 0.77 ± 0.05 M...man 1966; Gatewood 2005) with a 8.62 yr period, well estab- lished over several decades of monitoring and first resolved by McCarthy (1983). But a

Non-verbal communication of the residents living in homes for the older people in Slovenia.

PubMed

Zaletel, Marija; Kovacev, Asja Nina; Sustersic, Olga; Kragelj, Lijana Zaletel

2010-09-01

Aging of the population is a growing problem in all developed societies. The older people need more health and social services, and their life quality in there is getting more and more important. The study aimed at determining the characteristics of non-verbal communication of the older people living in old people's homes (OPH). The sample consisted of 267 residents of the OPH, aged 65-96 years, and 267 caregivers from randomly selected twenty-seven OPH. Three types of non-verbal communication were observed and analysed using univariate and multivariate statistical methods. In face expressions and head movements about 75% older people looked at the eyes of their caregivers, and about 60% were looking around, while laughing or pressing the lips together was rarely noticed. The differences between genders were not statistically significant while statistically significant differences among different age groups was observed in dropping the eyes (p = 0.004) and smiling (0.008). In hand gestures and trunk movements, majority of older people most often moved forwards and clenched fingers, while most rarely they stroked and caressed their caregivers. The differences between genders were statistically significant in leaning on the table (p = 0.001), and changing the position on the chair (0.013). Statistically significant differences among age groups were registered in leaning forwards (p = 0.006) and pointing to the others (p = 0.036). In different modes of speaking and paralinguistic signs almost 75% older people spoke normally, about 70% kept silent, while they rarely quarrelled. The differences between genders were not statistically significant while statistically significant differences among age groups was observed in persuasive speaking (p = 0.007). The present study showed that older people in OPH in Slovenia communicated significantly less frequently with hand gestures and trunk movements than with face expressions and head movements or different modes of speaking and paralinguistic signs. The caregivers should be aware of this and pay a lot of attention to these two groups of non-verbal expressions. Their importance should be constantly emphasized during the educational process of all kinds of health-care professionals as well.

Forming isolated brown dwarfs by turbulent fragmentation

NASA Astrophysics Data System (ADS)

Lomax, O.; Whitworth, A. P.; Hubber, D. A.

2016-05-01

We use Smoothed Particle Hydrodynamics to explore the circumstances under which an isolated very low mass pre-stellar core can be formed by colliding turbulent flows and collapse to form a brown dwarf. Our simulations suggest that the flows need not be very fast, but do need to be very strongly convergent, I.e. the gas must flow in at comparable speeds from all sides, which seems rather unlikely. We therefore revisit the object Oph-B11, which André et al. have identified as a pre-stellar core with mass between ˜0.020 M⊙ and ˜0.030 M⊙. We re-analyse the observations using a Markov-chain Monte Carlo method that allows us (I) to include the uncertainties on the distance, temperature and dust mass opacity, and (II) to consider different Bayesian prior distributions of the mass. We estimate that the posterior probability that Oph-B11 has a mass below the hydrogen-burning limit at ˜0.075 M⊙, is between 0.66 and 0.86 . We conclude that, if Oph-B11 is destined to collapse, it probably will form a brown dwarf. However, the flows required to trigger this appear to be so contrived that it is difficult to envisage this being the only way, or even a major way, of forming isolated brown dwarfs. Moreover, Oph-B11 could easily be a transient, bouncing, prolate core, seen end-on; there could, indeed should, be many such objects masquerading as very low mass pre-stellar cores.

Optimization of the Use of His₆-OPH-Based Enzymatic Biocatalysts for the Destruction of Chlorpyrifos in Soil.

PubMed

Senko, Olga; Maslova, Olga; Efremenko, Elena

2017-11-23

Applying enzymatic biocatalysts based on hexahistidine-containing organophosphorus hydrolase (His₆-OPH) is suggested for the decomposition of chlorpyrifos, which is actively used in agriculture in many countries. The application conditions were optimized and the following techniques was suggested to ensure the highest efficiency of the enzyme: first, the soil is alkalinized with hydrated calcitic lime Ca(OH)₂, then the enzyme is introduced into the soil at a concentration of 1000 U/kg soil. Non-equilibrium low temperature plasma (NELTP)-modified zeolite is used for immobilization of the relatively inexpensive polyelectrolyte complexes containing the enzyme His₆-OPH and a polyanionic polymer: poly-l-glutamic acid (PLE 50 ) or poly-l-aspartic acid (PLD 50 ). The soil's humidity is then increased up to 60-80%, the top layer (10-30 cm) of soil is thoroughly stirred, and then exposed for 48-72 h. The suggested approach ensures 100% destruction of the pesticide within 72 h in soils containing as much as 100 mg/kg of chlorpyrifos. It was concluded that using this type of His₆-OPH-based enzyme chemical can be the best approach for soils with relatively low humus concentrations, such as sandy and loam-sandy chestnut soils, as well as types of soil with increased alkalinity (pH 8.0-8.4). Such soils are often encountered in desert, desert-steppe, foothills, and subtropical regions where chlorpyrifos is actively used.

Optimization of the Use of His6-OPH-Based Enzymatic Biocatalysts for the Destruction of Chlorpyrifos in Soil

PubMed Central

Senko, Olga; Efremenko, Elena

2017-01-01

Applying enzymatic biocatalysts based on hexahistidine-containing organophosphorus hydrolase (His6-OPH) is suggested for the decomposition of chlorpyrifos, which is actively used in agriculture in many countries. The application conditions were optimized and the following techniques was suggested to ensure the highest efficiency of the enzyme: first, the soil is alkalinized with hydrated calcitic lime Ca(OH)2, then the enzyme is introduced into the soil at a concentration of 1000 U/kg soil. Non-equilibrium low temperature plasma (NELTP)-modified zeolite is used for immobilization of the relatively inexpensive polyelectrolyte complexes containing the enzyme His6-OPH and a polyanionic polymer: poly-l-glutamic acid (PLE50) or poly-l-aspartic acid (PLD50). The soil’s humidity is then increased up to 60–80%, the top layer (10–30 cm) of soil is thoroughly stirred, and then exposed for 48–72 h. The suggested approach ensures 100% destruction of the pesticide within 72 h in soils containing as much as 100 mg/kg of chlorpyrifos. It was concluded that using this type of His6-OPH-based enzyme chemical can be the best approach for soils with relatively low humus concentrations, such as sandy and loam-sandy chestnut soils, as well as types of soil with increased alkalinity (pH 8.0–8.4). Such soils are often encountered in desert, desert-steppe, foothills, and subtropical regions where chlorpyrifos is actively used. PMID:29168784

Rotationally excited HD toward Zeta Ophiuchi

NASA Technical Reports Server (NTRS)

Wright, E. L.; Morton, D. C.

1979-01-01

Copernicus satellite measurements of HD in J-double prime = 1 and J-double prime = 0 toward Zeta Oph are reported. The ratio of the number densities of HD in the J = 0 and J = 1 states is determined to be 0.15 + or - 0.02 at the 1-sigma level. A value of approximately 24 x 10 to the -17th erg/cu cm per A at 1000 A is obtained for the UV energy density at the Zeta Oph cloud, and the mechanisms for excitation of HD are examined. A tight upper limit is derived for the abundance of HCl, which has been predicted to be present due to the interaction of ionized chlorine with neutral hydrogen. A calculation is performed which indicates that the cloud is 28 pc from the star. It is shown that the two-component cloud model of Black and Dalgarno (1977) with densities of 500 and 2500 H nuclei per cu cm for the outer regions and core, respectively, is in excellent agreement with the observations.

A family of rare-earth-based single chain magnets: playing with anisotropy.

PubMed

Bernot, Kevin; Bogani, Lapo; Caneschi, Andrea; Gatteschi, Dante; Sessoli, Roberta

2006-06-21

The first family of rare-earth-based single chain magnets is presented. Compounds of general formula [M(hfac)3(NITPhOPh)], where M = Eu, Gd, Tb, Dy, Ho, Er, or Yb, and PhOPh is the nitronyl-nitroxide radical (2,4'-benzoxo-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide), have been structurally characterized and found to be isostructural. The characterization of both static and dynamic magnetic properties of the whole family is reported. Dy, Tb, and Ho compounds display slow relaxation of the magnetization, and ac susceptibility shows a thermally activated regime with energy barriers of 69, 45, and 34 K for Dy, Tb, and Ho compounds, respectively, while only a frequency-dependent susceptibility is observed for Er below 2.0 K. In Gd and Yb derivatives, antiferromagnetic interactions dominate. The pre-exponential factors differ by about 4 orders of magnitude. Finite size effects, due to naturally occurring defects, affect the static and dynamic properties of the compounds differently.

Enzyme system comprising an enzyme bonded in a porous matrix

DOEpatents

Ackerman, Eric [Richland, WA; Liu, Jun [West Richland, WA

2010-12-07

A protein system is described in which a protein is bound within a matrix material that has pores that are sized to achieve excellent properties such as: activity, protein density, and stability. In a preferred embodiment, the pore sizes range from 50 to 400 .ANG.. One protein that has demonstrated surprisingly good results in this system is OPH. This protein is known to degrade organophosphorus compounds such as are found in chemical weapons and pesticides. Novel methods of forming the protein system and methods of making OPH are also described.

Synthesis of Ruthenium Carbonyl Complexes with Phosphine or Substituted Cp Ligands, and Their Activity in the Catalytic Deoxygenation of 1,2-Propanediol

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

Ghosh, Prasenjit; Fagan, Paul J.; Marshall, William J.

2009-07-20

A ruthenium hydride with a bulky substituted Cp ligand, (CpiPr4)Ru(CO)2H (CpiPr4 = C5(i-C3H7)4H) was prepared from the reaction of Ru3(CO)12 with 1,2,3,4-tetraisopropylcyclopentadiene. The molecular structure of (CpiPr4)Ru(CO)2H was determined by x-ray crystallography. The ruthenium hydride complex (C5Bz5)Ru(CO)2H (Bz = CH2Ph) was similarly prepared. The Ru-Ru bonded dimer, [(1,2,3-trimethylindenyl)Ru(CO)2]2, was produced from the reaction of 1,2,3-trimethylindene with Ru3(CO)12, and protonation of this dimer with HOTf gives {[(1,2,3-trimethylindenyl)Ru(CO)2]2(μ H)}+OTf –. A series of ruthenium hydride complexes CpRu(CO)(L)H [L = P(OPh)3, PCy3, PMe3, P(p C6H4F)3] were prepared by reaction of Cp(CO)2RuH with added L. Protonation of (CpiPr4)Ru(CO)2H, Cp*Ru(CO)2H or CpRu(CO)[P(OPh)3]H by HOTf 80more » °C led to equilibria with the cationic dihydrogen complexes, but H2 was released at higher temperatures. Protonation of CpRu[P(OPh)3]2H with HOTf gave an observable dihydrogen complex, {CpRu[P(OPh)3]2(η2 H2)}+OTf – that was converted at -20 °C to the dihydride complex {CpRu[P(OPh)3]2(H)2}+OTf –. These Ru complexes serve as catalyst precursors for the catalytic deoxygenation of 1,2-propanediol to give n-propanol. The catalytic reactions were carried out in sulfolane solvent with added HOTf under H2 (750 psi) at 110 °C. This work was supported by the U.S. Department of Energy's (DOE) Office of Basic Energy Sciences, Chemical Sciences program. Pacific Northwest National Laboratory is operated by Battelle for DOE.« less

Detection of magnetic field in the B2 star ρ Ophiuchi A with ESO FORS2

NASA Astrophysics Data System (ADS)

Pillitteri, I.; Fossati, L.; Castro Rodriguez, N.; Oskinova, L.; Wolk, S. J.

2018-02-01

Circumstantial evidence suggests that magnetism and enhanced X-ray emission are likely correlated in early B-type stars: similar fractions of them ( 10%) are strong and hard X-ray sources and possess strong magnetic fields. It is also known that some B-type stars have spots on their surface. Yet up to now no X-ray activity associated with spots on early-type stars was detected. In this Letter we report the detection of a magnetic field on the B2V star ρ Oph A. Previously, we assessed that the X-ray activity of this star is associated with a surface spot, herewith we establish its magnetic origin. We analyze spectra of ρ Oph A obtained with the FORS2 spectrograph at ESO Very Large Telescope (VLT) at two epochs, and detect a longitudinal component of the magnetic field of the order of 500 G in one of the datasets. The detection of the magnetic field only at one epoch can be explained by stellar rotation which is also invoked to explain observed periodic X-ray activity. From archival HARPS ESO VLT high resolution spectra we derived the fundamental stellar parameters of ρ Oph A and further constrained its age. We conclude that ρ Oph A provides strong evidence for the presence of active X-ray emitting regions on young magnetized early type stars. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere under ESO programmes 099.D-0067(A) and 078.C-0403(A).

Mesoporous silica as the enzyme carrier for organophosphate detection and/or detoxification

NASA Astrophysics Data System (ADS)

Frančič, Nina; Nedeljko, Polonca; Lobnik, Aleksandra

2013-05-01

In the past decade, interest in mesoporous materials has developed dramatically since they can be useful in a number of applications, including adsorption and sensor technology. Mesoporous materials are a class of nanostrustures with well-defined mesoscale (2-50 nm) pores, surface areas up to 1000 m2/g and large pore volumes (~1.0 mL/g). In general, ordered mesoporous materials are formed from solution by co-assembly and cross-linking of network-forming inorganic species (typically oxides) in the presence of structure-directing agents (SDAs) [1]. The SDAs are typically surfactants or blockcopolymers that self-organize into mesoscale (2-50 nm) structures, according to the solution composition and processing conditions used [2]. Owing to their structural properties and regular morphology, mesoporous silicas (MPS) are promising materials for applications in the immobilization processes or as supports for bulky bio-molecules, such as enzymes. We report on the synthesis of mesoporous silica (MPS) particles and their potential use for immobilization of the enzyme hexahistidine tagged OPH (His6-OPH). Particle characterization points out a strong influence of the synthesis parameters (addition of ethyl acetate). BET results show a high specific surface area (300-450 m2/g) and an appropriate pore size distribution ranging from 10 to 40 nm. Immobilization of the enzyme His6-OPH, with the size of 72 kDa and isoelectric point (pI) of 8.5, was carried out in MPS particles of spherical morphology. Preliminary results indicate significant potential in use of encapsulated enzyme His6-OPH for the purpose of bio-sensing or in the detoxification processes of organophosphates.

Identification of an opd (organophosphate degradation) gene in an Agrobacterium isolate.

PubMed

Horne, Irene; Sutherland, Tara D; Harcourt, Rebecca L; Russell, Robyn J; Oakeshott, John G

2002-07-01

We isolated a bacterial strain, Agrobacterium radiobacter P230, which can hydrolyze a wide range of organophosphate (OP) insecticides. A gene encoding a protein involved in OP hydrolysis was cloned from A. radiobacter P230 and sequenced. This gene (called opdA) had sequence similarity to opd, a gene previously shown to encode an OP-hydrolyzing enzyme in Flavobacterium sp. strain ATCC 27551 and Brevundimonas diminuta MG. Insertional mutation of the opdA gene produced a strain lacking the ability to hydrolyze OPs, suggesting that this is the only gene encoding an OP-hydrolyzing enzyme in A. radiobacter P230. The OPH and OpdA proteins, encoded by opd and opdA, respectively, were overexpressed and purified as maltose-binding proteins, and the maltose-binding protein moiety was cleaved and removed. Neither protein was able to hydrolyze the aliphatic OP malathion. The kinetics of the two proteins for diethyl OPs were comparable. For dimethyl OPs, OpdA had a higher k(cat) than OPH. It was also capable of hydrolyzing the dimethyl OPs phosmet and fenthion, which were not hydrolyzed at detectable levels by OPH.

Catabolism of 4-alkylphenols by Acinetobacter sp. OP5: genetic organization of the oph gene cluster and characterization of alkylcatechol 2, 3-dioxygenase.

PubMed

Tuan, Nguyen Ngoc; Lin, Yi-Wen; Huang, Shir-Ly

2013-03-01

In this study, a specific PCR primer set was successfully designed for alkylcatechol 2, 3-dioxygenase genes and applied to detect the presence of this biomarker in 4-t-octylphenol-degrading Acinetobacter sp. strain OP5. A gene cluster (ophRBA1A2A3A4A5A6CEH) encoding multicomponent phenol hydroxylase and alkylcatechol 2, 3-dioxygenase was then cloned from this strain and showed the highest homology to those involved in the published medium-chain alkylphenol gene clusters. The pure enzyme of recombinant cell harboring ophB showed meta-cleavage activities for 4-methylcatechol (1,435%), 4-ethylcatechol (982%), catechol (100%), 4-t-butylcatechol (16.6%), and 4-t-octylcatechol (3.2%). The results suggest that the developed molecular technique is useful and easy in detection of medium/long-chain alkylphenol degradation gene cluster. In addition, it also provides a better understanding of the distribution of biodegradative genes and pathway for estrogenic-active long-chain alkylphenols in bacteria. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Full Virial Analysis of the Prestellar Cores in the Ophiuchus Molecular Cloud

NASA Astrophysics Data System (ADS)

Pattle, Kate; Ward-Thompson, Derek

We use SCUBA-2, HARP C18O J= 3 -> 2, Herschel and IRAM N2H+ J= 1 -> 0 observations of the Ophiuchus molecular cloud to identify and characterise the properties of the starless cores in the region. The SCUBA-2, HARP and Herschel data were taken as part of the JCMT and Herschel Gould Belt Surveys. We determine masses and temperatures and perform a full virial analysis on our cores, and find that our cores are all either bound or virialised, with gravitational energy and external pressure energy on average of similar importance in confining the cores. There is wide variation from region to region, with cores in the region influenced by B stars (Oph A) being substantially gravitationally bound, and cores in the most quiescent region (Oph C) being pressure-confined. We observe dissipation of turbulence in all our cores, and find that this dissipation is more effective in regions which do not contain outflow-driving protostars. Full details of this analysis are presented by Pattle et al. (2015).

Catalytic degradation of organophosphorous nerve agent simulants by polymer beads@graphene oxide with organophosphorus hydrolase-like activity based on rational design of functional bimetallic nuclear ligand.

PubMed

Ma, Xuejuan; Zhang, Lin; Xia, Mengfan; Zhang, Xiaohong; Zhang, Yaodong

2018-05-15

The degradation of organophosphorous nerve agents is of primary concern due to the severe toxicity of these agents. Based on the active center of organophosphorus hydrolase (OPH), a bimetallic nuclear ligand, (5-vinyl-1,3-phenylene)bis(di(1H-imidazol-2-yl) methanol) (VPIM), was designed and synthesized, which contains four imidazole groups to mimic the four histidines at OPH active center. By grafting VPIM on graphene oxide (GO) surface via polymerization, the VPIM-polymer beads@GO was produced. The obtained OPH mimics has an impressive activity in dephosphorylation reactions (turnover frequency (TOF) towards paraoxon: 2.3 s -1 ). The synergistic catalytic effect of the bimetallic Zn 2+ nuclear center and carboxyl groups on surface of GO possibly contributes to the high hydrolysis on organophosphate substrate. Thus, a biomimetic catalyst for efficient degradation of some organophosphorous nerve agent simulants, such as paraoxon and chlorpyrifos, was prepared by constructing catalytic active sites. The proposed mechanism and general synthetic strategy open new avenues for the engineering of functional GOs for biomimetic catalysts. Copyright © 2018 Elsevier B.V. All rights reserved.

Synthesis of Ruthenium Carbonyl Complexes with Phosphine or Substituted Cp Ligands, and Their Activity in the Catalytic Deoxygenation of 1,2-Propanediol

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

Bullock, R.M.; Ghosh, P.; Fagan, P.J.

2009-07-20

A ruthenium hydride with a bulky tetra-substituted Cp ligand, (Cp{sup iPr{sub 4}})Ru(CO){sub 2}H (Cp{sup iPr{sub 4}} = C{sub 5}(i-C{sub 3}H{sub 7}){sub 4}H) was prepared from the reaction of Ru{sub 3}(CO){sub 12} with 1,2,3,4-tetraisopropylcyclopentadiene. The molecular structure of (Cp{sup iPr{sub 4}})Ru(CO){sub 2}H was determined by X-ray crystallography. The ruthenium hydride complex (C{sub 5}Bz{sub 5})Ru(CO){sub 2}H (Bz = CH{sub 2}Ph) was similarly prepared. The Ru-Ru bonded dimer, [(1,2,3-trimethylindenyl)Ru(CO){sub 2}]{sub 2}, was produced from the reaction of 1,2,3-trimethylindene with Ru{sub 3}(CO){sub 12}, and protonation of this dimer with HOTf gives {l_brace}[(1,2,3-trimethylindenyl)Ru(CO){sub 2}]{sub 2}-({mu}-H){r_brace}{sup +}OTf{sup -}. A series of ruthenium hydride complexes CpRu(CO)(L)H [Lmore » = P(OPh){sub 3}, PCy{sub 3}, PMe{sub 3}, P(p-C{sub 6}H{sub 4}F){sub 3}] were prepared by reaction of Cp(CO){sub 2}RuH with added L. Protonation of (Cp{sup iPr{sub 4}})Ru(CO){sub 2}H, Cp*Ru(CO){sub 2}H, or CpRu(CO)[P-(OPh){sub 3}]H by HOTf at -80 C led to equilibria with the cationic dihydrogen complexes, but H{sub 2} was released at higher temperatures. Protonation of CpRu[P(OPh){sub 3}]{sub 2}H with HOTf gave an observable dihydrogen complex, {l_brace}CpRu[P-(OPh){sub 3}]{sub 2}({eta}{sup 2}-H{sub 2}){r_brace}+OTf{sup -} that was converted at -20 C to the dihydride complex {l_brace}CpRu[P(OPh){sub 3}]{sub 2}(H){sub 2}{r_brace}{sup +}OTf{sup -}. These Ru complexes serve as catalyst precursors for the catalytic deoxygenation of 1,2-propanediol to give n-propanol. The catalytic reactions were carried out in sulfolane solvent with added HOTf under H{sub 2} (750 psi) at 110 C.« less

Agenda: EDRN FDA Education Workshop — EDRN Public Portal

Cancer.gov

The purpose of this workshop was to open dialogue between FDA staff that provide oversight for review of in vitro diagnostic applications and EDRN scientists currently performing clinical validation studies on cancer biomarkers. Issues related to FDA review of diagnostic tests were presented by FDA personnel. Representatives from EDRN provided details on supporting data of their validation studies and the resources developed within EDRN to facilitate such research for FDA compliance. The agenda provided here provides links to the presentations by each speaker.

Binary supersoft X-ray sources and the supernova Ia progenitor problem

NASA Astrophysics Data System (ADS)

Nelson, Thomas John

In this thesis I present a study of several binary supersoft X-ray sources in order to assess their properties and to determine whether they may be supernova Ia (SN Ia) progenitors. The first chapter is an introduction to the problem and the sources of interest. In the second and third chapters I present an X-ray spectroscopic study of the recurrent nova RS Ophiuchi (RS Oph) during and after its 2006 outburst, carried out with Chandra and XMM-Newton. I discuss the physical origins of the X-ray emission at each stage of the outburst and place the first direct constraints on the mass of the white dwarf, which is very close to the Chandrasekhar limit. I also show that the surface composition of the white dwarf during the supersoft phase is consistent with nuclear processed material, indicating that RS Oph retains mass after each outburst and is likely growing in mass with time, and is therefore a potential SN Ia progenitor. I discuss the lack of accretion signatures in the quiescent emission from RS Oph, which are at odds with the high frequency of nova outbursts, and explore the possibility that an alternative accretion model may account for the quiescent X-ray properties in the system. Finally, in the fourth chapter, I examine the supersoft X-ray source (SSS) population in the nearby galaxy M31 at X-ray, ultraviolet (UV) and optical wavelengths. I explore the long-term behavior of these objects, and find that a much smaller fraction are persistent or recurrent X-ray sources than in the Magellanic Clouds. I carry out a search for counterparts of the SSS using the Galactic Evolution Explorer (GALEX) satellite and the WIYN 3.5m telescope, and find that the majority of sources do not have any UV counterparts. For those that do, I find that the UV sources have properties consistent with young, massive stars in M31. I find indications that some SSS may be in high mass binaries. If these sources are nuclear burning white dwarfs, then they may be the progenitors of the SNe Ia that appear to be associated with recent star formation.

Optimizing Referral Management: A Multiple Service Health System Perspective Anyone Can Use

DTIC Science & Technology

2011-01-26

RET  LOS  OFFICER 5 0 1 0 1 0 0 7 2‐8701 USA ACTIVE DUTY ENLISTED 0 6 0 0 1 0 0 7 3‐2589 USAF ACTIVE DUTY 7 0 0 0 0 0 0 7 Grand Total 20 13 13 8 2 0 0...NBIRO ORTHO All.IRCiY PUlM VASCULAR DIRM URO OPH HEMOC BAMC-IlOFR External Consults Timeline by Appointed MTF by Top 10 Spedalty by Volume Avg First...Review • Avg Booking W Avg from Bod< to Appt Dab! • Avg Resulting DRlHO CARDIO WOMBf"S VASCULAR NBJRO PULM HLlH WHMC-Rm:R URO CARDIO PULM OPH

Mid-infrared multi-wavelength imaging of Ophiuchus IRS 48 transitional disk†

NASA Astrophysics Data System (ADS)

Honda, Mitsuhiko; Okada, Kazushi; Miyata, Takashi; Mulders, Gijs D.; Swearingen, Jeremy R.; Kamizuka, Takashi; Ohsawa, Ryou; Fujiyoshi, Takuya; Fujiwara, Hideaki; Uchiyama, Mizuho; Yamashita, Takuya; Onaka, Takashi

2018-04-01

Transitional disks around the Herbig Ae/Be stars are fascinating targets in the contexts of disk evolution and planet formation. Oph IRS 48 is one of such Herbig Ae stars, which shows an inner dust cavity and azimuthally lopsided large dust distribution. We present new images of Oph IRS 48 at eight mid-infrared (MIR) wavelengths from 8.59 to 24.6 μm taken with COMICS mounted on the 8.2 m Subaru Telescope. The N-band (7 to 13 μm) images show that the flux distribution is centrally peaked with a slight spatial extent, while the Q-band (17 to 25 μm) images show asymmetric double peaks (east and west). Using 18.8- and 24.6 μm images, we derived the dust temperature at both east and west peaks to be 135 ± 22 K. Thus, the asymmetry may not be attributed to a difference in the temperature. Comparing our results with previous modeling works, we conclude that the inner disk is aligned to the outer disk. A shadow cast by the optically thick inner disk has a great influence on the morphology of MIR thermal emission from the outer disk.

Mid-infrared multi-wavelength imaging of Ophiuchus IRS 48 transitional disk†

NASA Astrophysics Data System (ADS)

Honda, Mitsuhiko; Okada, Kazushi; Miyata, Takashi; Mulders, Gijs D.; Swearingen, Jeremy R.; Kamizuka, Takashi; Ohsawa, Ryou; Fujiyoshi, Takuya; Fujiwara, Hideaki; Uchiyama, Mizuho; Yamashita, Takuya; Onaka, Takashi

2018-06-01

Transitional disks around the Herbig Ae/Be stars are fascinating targets in the contexts of disk evolution and planet formation. Oph IRS 48 is one of such Herbig Ae stars, which shows an inner dust cavity and azimuthally lopsided large dust distribution. We present new images of Oph IRS 48 at eight mid-infrared (MIR) wavelengths from 8.59 to 24.6 μm taken with COMICS mounted on the 8.2 m Subaru Telescope. The N-band (7 to 13 μm) images show that the flux distribution is centrally peaked with a slight spatial extent, while the Q-band (17 to 25 μm) images show asymmetric double peaks (east and west). Using 18.8- and 24.6 μm images, we derived the dust temperature at both east and west peaks to be 135 ± 22 K. Thus, the asymmetry may not be attributed to a difference in the temperature. Comparing our results with previous modeling works, we conclude that the inner disk is aligned to the outer disk. A shadow cast by the optically thick inner disk has a great influence on the morphology of MIR thermal emission from the outer disk.

A New Orbit for the Eclipsing Binary V577 Oph

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

Jeffery, Elizabeth J.; Barnes, Thomas G. III; Montemayor, Thomas J.

Pulsating stars in eclipsing binary systems are unique objects for providing constraints on stellar models. To fully leverage the information available from the binary system, full orbital radial velocity curves must be obtained. We report 23 radial velocities for components of the eclipsing binary V577 Oph, whose primary star is a δ Sct variable. The velocities cover a nearly complete orbit and a time base of 20 years. We computed orbital elements for the binary and compared them to the ephemeris computed by Creevey et al. The comparison shows marginally different results. In particular, a change in the systemic velocitymore » by −2 km s{sup −1} is suggested by our results. We compare this systemic velocity difference to that expected due to reflex motion of the binary in response to the third body in the system. The systemic velocity difference is consistent with reflex motion, given our mass determination for the eclipsing binary and the orbital parameters determined by Volkov and Volkova for the three-body orbit. We see no evidence for the third body in our spectra, but we do see strong interstellar Na D lines that are consistent in strength with the direction and expected distance of V577 Oph.« less

Metabolic engineering of Pseudomonas putida for the utilization of parathion as a carbon and energy source.

PubMed

Walker, Andy W; Keasling, Jay D

2002-06-30

Pseudomonas putida KT2442 was engineered to use the organophosphate pesticide parathion, a compound similar to other organophosphate pesticides and chemical warfare agents, as a source of carbon and energy. The initial step in the engineered degradation pathway was parathion hydrolysis by organophosphate hydrolase (OPH) to p-nitrophenol (PNP) and diethyl thiophosphate, compounds that cannot be metabolized by P. putida KT2442. The gene encoding the native OPH (opd), with and without the secretory leader sequence, was cloned into broad-host-range plasmids under the control of tac and taclac promoters. Expression of opd from the tac promoter resulted in high OPH activity, whereas expression from the taclac promoter resulted in low activity. A plasmid-harboring operons encoding enzymes for p-nitrophenol transformation to beta-ketoadipate was transformed into P. putida allowing the organism to use 0.5 mM PNP as a carbon and energy source. Transformation of P. putida with the plasmids harboring opd and the PNP operons allowed the organism to utilize 0.8 mM parathion as a source of carbon and energy. Degradation studies showed that parathion formed a separate dense, non-aqueous phase liquid phase but was still bioavailable. Copyright 2002 Wiley Periodicals, Inc.

Intersstellar absorption lines between 2000 and 3000 A in nearby stars observed with BUSS. [Balloon Borne Ultraviolet Spectrophotometer

NASA Technical Reports Server (NTRS)

De Boer, K. S.; Lenhart, H.; Van Der Hucht, K. A.; Kamperman, T. M.; Kondo, Y.

1986-01-01

Spectra obtained between 2000 and 3000 A with the Balloon Borne Ultraviolet Spectrophotometer (BUSS) payload were examined for interstellar absorption lines. In bright stars, with spectral types between O9V and F5V, such lines were measured of Mg I, Mg II, Cr II, Mn II, Fe II and Zn II, with Cr II and Zn II data of especially high quality. Column densities were derived and interstellar abundances were determined for the above species. It was found that metal depletion increases with increasing E(B-V); Fe was most affected and Zn showed a small depletion for E(B-V) greater than 0.3 towards Sco-Oph. The metal column densities, derived for Alpha-And, Kappa-Dra, Alpha-Com, Alpha-Aql, and 29 Cyg were used to infer N(H I). It was shown that the ratio of Mg I to Na I is instrumental in determining the ionization structure along each line of sight. The spectra of Aql stars confirms the presence of large gas densities near Alpha-Oph. Moreover, data indicated that the Rho-Oph N(H I) value needs to be altered to 35 x 10 to the 20th/sq cm, based on observed ion ratios and analysis of the Copernicus L-alpha profile.

The Massive CO White Dwarf in the Symbiotic Recurrent Nova RS Ophiuchi

NASA Astrophysics Data System (ADS)

Mikołajewska, Joanna; Shara, Michael M.

2017-10-01

If accreting white dwarfs (WDs) in binary systems are to produce type Ia supernovae (SNe Ia), they must grow to nearly the Chandrasekhar mass and ignite carbon burning. Proving conclusively that a WD has grown substantially since its birth is a challenging task. Slow accretion of hydrogen inevitably leads to the erosion, rather than the growth of WDs. Rapid hydrogen accretion does lead to growth of a helium layer, due to both decreased degeneracy and the inhibition of mixing of the accreted hydrogen with the underlying WD. However, until recently, simulations of helium-accreting WDs all claimed to show the explosive ejection of a helium envelope once it exceeded ˜ {10}-1 {M}⊙ . Because CO WDs cannot be born with masses in excess of ˜ 1.1 {M}⊙ , any such object in excess of ˜ 1.2 {M}⊙ must have grown substantially. We demonstrate that the WD in the symbiotic nova RS Oph is in the mass range 1.2-1.4 M ⊙. We compare UV spectra of RS Oph with those of novae with ONe WDs and with novae erupting on CO WDs. The RS Oph WD is clearly made of CO, demonstrating that it has grown substantially since birth. It is a prime candidate to eventually produce an SN Ia.

Hemodynamic alterations after stent implantation in 15 cases of intracranial aneurysm.

PubMed

Wang, Chao; Tian, Zhongbin; Liu, Jian; Jing, Linkai; Paliwal, Nikhil; Wang, Shengzhang; Zhang, Ying; Xiang, Jianping; Siddiqui, Adnan H; Meng, Hui; Yang, Xinjian

2016-04-01

Stent-assisted coiling technology has been widely used in the treatment of intracranial aneurysms. In the current study, we investigated the intra-aneurysmal hemodynamic alterations after stent implantation and their association with the aneurysm location. We first retrospectively studied 15 aneurysm cases [8 internal carotid artery-ophthalmic artery (ICA-OphA) aneurysms and 7 posterior communicating artery (PcoA) aneurysms] treated with Enterprise stents and coils. Then, based on the patient-specific geometries before and after stenting, we built virtual stenting computational fluid dynamics (CFD) simulation models. Before and after the stent deployment, the average wall shear stress (WSS) on the aneurysmal sac at systolic peak changed from 7.04 Pa (4.14 Pa, 15.77 Pa) to 6.04 Pa (3.86 Pa, 11.13 Pa), P = 0.001; the spatially averaged flow velocity in the perpendicular plane of the aneurysm dropped from 0.5 m/s (0.28 m/s, 0.7 m/s) to 0.33 m/s (0.25 m/s, 0.49 m/s), P = 0.001, respectively. Post stent implantation, the WSS in ICA-OphA aneurysms and PcoA aneurysms decreased by 14.4 % (P = 0.012) and 16.6 % (P = 0.018), respectively, and the flow velocity also reduced by 10.3 % (P = 0.029) and 10.5 % (P = 0.013), respectively. Changes in the WSS, flow velocity, and pressure were not significantly different between ICA-OphA and PcoA aneurysms (P > 0.05). Stent implantation did not significantly change the peak systolic pressure in either aneurysm type. After the stent implantation, both the intra-aneurysmal flow velocity and WSS decreased independently of aneurysm type (ICA-OphA and PcoA). Little change was observed in peak systolic pressure.

Microsurgical clipping of ophthalmic artery aneurysms: surgical results and visual outcomes with 208 aneurysms.

PubMed

Kamide, Tomoya; Tabani, Halima; Safaee, Michael M; Burkhardt, Jan-Karl; Lawton, Michael T

2018-01-26

OBJECTIVE While most paraclinoid aneurysms can be clipped with excellent results, new postoperative visual deficits are a concern. New technology, including flow diverters, has increased the popularity of endovascular therapy. However, endovascular treatment of paraclinoid aneurysms is not without procedural risks, is associated with higher rates of incomplete aneurysm occlusion and recurrence, and may not address optic nerve compression symptoms that surgical debulking can. The increasing endovascular management of paraclinoid aneurysms should be justified by comparisons to surgical benchmarks. The authors, therefore, undertook this study to define patient, visual, and aneurysm outcomes in the most common type of paraclinoid aneurysm: ophthalmic artery (OphA) aneurysms. METHODS Results from microsurgical clipping of 208 OphA aneurysms in 198 patients were retrospectively reviewed. Patient demographics, aneurysm morphology (size, calcification, etc.), clinical characteristics, and patient outcomes were recorded and analyzed. RESULTS Despite 20% of these aneurysms being large or giant in size, complete aneurysm occlusion was accomplished in 91% of 208 cases, with OphA patency preserved in 99.5%. The aneurysm recurrence rate was 3.1% and the retreatment rate was 0%. Good outcomes (modified Rankin Scale score 0-2) were observed in 96.2% of patients overall and in all 156 patients with unruptured aneurysms. New visual field defects (hemianopsia or quadrantanopsia) were observed in 8 patients (3.8%), decreased visual acuity in 5 (2.4%), and monocular blindness in 9 (4.3%). Vision improved in 9 (52.9%) of the 17 patients with preoperative visual deficits. CONCLUSIONS The most important risk associated with clipping OphA aneurysms is a new visual deficit. Meticulous microsurgical technique is necessary during anterior clinoidectomy, aneurysm dissection, and clip application to optimize visual outcomes, and aggressive medical management postoperatively might potentially decrease the incidence of delayed visual deficits. As the results of endovascular therapy and specifically flow diverters become known, they warrant comparison with these surgical benchmarks to determine best practices.

Site-selective chemical modification of chymotrypsin using peptidyl derivatives bearing optically active diphenyl 1-amino-2-phenylethylphosphonate: Stereochemical effect of the diphenyl phosphonate moiety.

PubMed

Ono, Shin; Nakai, Takahiko; Kuroda, Hirofumi; Miyatake, Ryuta; Horino, Yoshikazu; Abe, Hitoshi; Umezaki, Masahito; Oyama, Hiroshi

2016-11-04

Diphenyl (α-aminoalkyl)phosphonates act as mechanism-based inhibitors against serine proteases by forming a covalent bond with the hydroxy group of the active center Ser residue. Because the covalent bond was found to be broken and replaced by 2-pyridinaldoxime methiodide (2PAM), we employed a peptidyl derivative bearing diphenyl 1-amino-2-phenylethylphosphonate moiety (Phe(p) (OPh)2 ) to target the active site of chymotrypsin and to selectively anchor to Lys175 in the vicinity of the active site. Previously, it was reported that the configuration of the α-carbon of phosphorus in diphenyl (α-aminoalkyl)phosphonates affects the inactivation reaction of serine proteases, i.e., the (R)-enantiomeric diphenyl phosphonate is comparable to l-amino acids and it effectively reacts with serine proteases, whereas the (S)-enantiomeric form does not. In this study, we evaluated the stereochemical effect of the phosphonate moiety on the selective chemical modification. Epimeric dipeptidyl derivatives, Ala-(R or S)-Phe(p) (OPh)2 , were prepared by separation with RP-HPLC. A tripeptidyl (R)-epimer (Ala-Ala-(R)-Phe(p) (OPh)2 ) exhibited a more potent inactivation ability against chymotrypsin than the (S)-epimer. The enzyme inactivated by the (R)-epimer was more effectively reactivated with 2PAM than the enzyme inactivated by the (S)-epimer. Finally, N-succinimidyl (NHS) active ester derivatives, NHS-Suc-Ala-Ala- (R or S)-Phe(p) (OPh)2 , were prepared, and we evaluated their action when modifying Lys175 in chymotrypsin. We demonstrated that the epimeric NHS derivative that possessed the diphenyl phosphonate moiety with the (R)-configuration effectively modified Lys175 in chymotrypsin, whereas that with the (S)-configuration did not. These results demonstrate the utility of peptidyl derivatives that bear an optically active diphenyl phosphonate moiety as affinity labeling probes in protein bioconjugation. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 521-530, 2016. © 2015 Wiley Periodicals, Inc.

Sensitive survey for 13CO, CN, H2CO, and SO in the disks of T Tauri and Herbig Ae stars. II. Stars in ρ Ophiuchi and upper Scorpius

NASA Astrophysics Data System (ADS)

Reboussin, L.; Guilloteau, S.; Simon, M.; Grosso, N.; Wakelam, V.; Di Folco, E.; Dutrey, A.; Piétu, V.

2015-06-01

Aims: We attempt to determine the molecular composition of disks around young low-mass stars in the ρ Oph region and to compare our results with a similar study performed in the Taurus-Auriga region. Methods: We used the IRAM 30 m telescope to perform a sensitive search for CN N = 2-1 in 29 T Tauri stars located in the ρ Oph and upper Scorpius regions. 13CO J = 2-1 is observed simultaneously to provide an indication of the level of confusion with the surrounding molecular cloud. The bandpass also contains two transitions of ortho-H2CO, one of SO, and the C17O J = 2-1 line, which provides complementary information on the nature of the emission. Results: Contamination by molecular cloud in 13CO and even C17O is ubiquitous. The CN detection rate appears to be lower than for the Taurus region, with only four sources being detected (three are attributable to disks). H2CO emission is found more frequently, but appears in general to be due to the surrounding cloud. The weaker emission than in Taurus may suggest that the average disk size in the ρ Oph region is smaller than in the Taurus cloud. Chemical modeling shows that the somewhat higher expected disk temperatures in ρ Oph play a direct role in decreasing the CN abundance. Warmer dust temperatures contribute to convert CN into less volatile forms. Conclusions: In such a young region, CN is no longer a simple, sensitive tracer of disks, and observations with other tracers and at high enough resolution with ALMA are required to probe the gas disk population. Based on observations carried out with the IRAM 30-m telescope. IRAM is supported by INSU/CNRS (France), MPG (Germany) and IGN (Spain).Appendix A is available in electronic form at http://www.aanda.org

Nova in Ophiuchus

NASA Astrophysics Data System (ADS)

Templeton, Matthew R.

2009-08-01

Nova Ophiuchi 2009 was discovered by Koichi Itagaki, Teppo-Cho, Yamagata, Japan, at unfiltered CCD magnitude 10.1 on August 16.515 UT, and confirmed by him on Aug. 16.526. After posting to the CBET Unconfirmed Observations page, the object was confirmed independently by several observers. The discovery and confirmatory information were intially reported in CBET 1910, CBET 1911, and AAVSO Special Notice #166. The nova, located in a very crowded field within the Milky Way, is reported by T. Kato (vsnet-alert 11399) to have a large B-V (+1.6), indicating it is highly reddened. N Oph 2009 has been assigned the identifiers VSX J173819.7-264413 and the AUID 000-BJP-605. Please submit observations to the AAVSO International Database using the name N OPH 2009.

Knowledge, attitudes, beliefs and practices of construction workers towards tetanus vaccine in Northern Italy.

PubMed

Riccò, Matteo; Cattani, Silvia; Veronesi, Licia; Colucci, Maria Eugenia

2016-12-07

Construction workers (CWs) are both more exposed to tetanus and at higher risk to be inadequately immunized. Our aim was to evaluate tetanus immunization status and knowledge/attitudes towards tetanus vaccination in CWs in Italy. In this field report, the immunization status of 554 unskilled CWs (i.e. labourers). Immunization status was assessed recalling immunization booklets/certificates. Attitudes and knowledge were collected through a standardized questionnaire. In 240/554 CWs, immunization status was inadequate/not documented: in 184 subjects (33.2%), the last vaccination shot was older than 10 years, whereas basal immunization was incomplete in 20 cases, more frequently in foreign-born people (FBP) than in Italian born (IBP) (OR=7.116). In 198 cases (35.7%), an Occupational Physician (OPh) performed last booster, usually with monovalent (T, n=173) vaccine. The main reason for inadequate immunization was having forgotten the periodic booster (148/554; 26.7%), whereas 42 subjects (7.6%) deliberately avoided tetanus vaccine because of personal/religious beliefs, more frequently in FBP than in IBP (OR=3.182). In summary, the prevalence of inadequate immunization status was relatively high (43.4%): the high prevalence of "forgotten boosters" enlightens the key role of OPh in recalling and promoting vaccination policies. Moreover, the inappropriate use of Td vaccine points out the opportunity for educational campaigns in OPh.

Phosphonium carbosilane dendrimers - interaction with a simple biological membrane model.

PubMed

Wrobel, Dominika; Kubikova, Radka; Müllerová, Monika; Strašák, Tomas; RůŽička, Květoslav; Fulem, Michal; Maly, Jan

2018-05-30

The influence of three generations of five different phosphonium carbosilane dendrimers and one ammonium carbosilane dendrimer as a reference (PMe3, PBu3, P(Et2)2(CH2)3OH, PPh3, P(MeOPh)3 and NMe3, peripheral functional groups) on dimyristoylphosphatidylcholine (DMPC) or a lipid mixture dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DMPC/DMPG) of liposomes was studied by fluorescence polarization measurements and differential scanning calorimetry. All types of dendrimers interacted with neutral as well as negatively charged liposomes, but the strength and observed influence were different. Concentration, type of peripheral functional group modification and dendrimer generation were the main factors influencing the interaction. Generally, weak interactions as well as destabilization of the lipid membranes at low concentrations, regardless of liposome type, were observed in the case of DmPMe3, DmNMe3, DmPBu3 and DmP(Et2)2(CH2)3OH. Dendrimers with PPh3 and P(MeOPh)3 peripheral functional groups interacted much more strongly and increased the rigidity of liposomes. Electrostatic interactions, the hydrophobicity of substituents and charge shielding on the peripheral phosphonium group are important factors in the interaction. We suggest that, among the other types of dendrimers, the dendrimer with the P(MeOPh)3 peripheral functional group is a highly promising candidate for the design of a drug delivery system due to its positive charge, efficient interaction with lipidic membranes and low cytotoxicity.

Synthesis of silyl iron hydride via Si-H activation and its dual catalytic application in the hydrosilylation of carbonyl compounds and dehydration of benzamides.

PubMed

Ren, Shishuai; Xie, Shangqing; Zheng, Tingting; Wang, Yangyang; Xu, Shilu; Xue, Benjing; Li, Xiaoyan; Sun, Hongjian; Fuhr, Olaf; Fenske, Dieter

2018-03-28

The hydrido silyl iron complex (o-Ph 2 PC 6 H 4 SiMe 2 )Fe(PMe 3 ) 3 H (2) was obtained via the activation of the Si-H bond of the bidentate silyl ligand o-Ph 2 P(C 6 H 4 )SiMe 2 H (1) by Fe(PMe 3 ) 4 . 2 showed good to excellent catalytic activity in both the reduction of aldehydes/ketones and the dehydration of benzamide. In addition, with complex 2 as a catalyst, α,β-unsaturated carbonyls could be selectively reduced to the corresponding α,β-unsaturated alcohols. The mechanisms of the formation of 2 and the catalytic dehydration process are proposed and partly experimentally verified.

Nova V2214 Ophiuchi 1988 - A magnetic nova inside the period gap

NASA Technical Reports Server (NTRS)

Baptista, R.; Jablonski, F. J.; Cieslinski, D.; Steiner, J. E.

1993-01-01

The discovery of a coherent photometric modulation in Nova Oph 1988 with period 0.117515 +/- 0.000002 d, which is associated with the orbital period of the underlying binary, is reported. On the basis of photometric observations, it is concluded that Nova V2214 Oph 1988 is a magnetic nova with an orbital period inside the period gap. The inclusion of this system in the statistics of novae suggests that there is no period gap for novae and that there is a clear correlation between the occurrence of novae with short orbital periods and the presence of magnetic white dwarfs. It is suggested that funneling of the accretion flow onto the magnetic poles favors the conditions for a thermonuclear runaway, increasing the frequency of eruptions for magnetic systems.

Evidence for mass loss at polar latitudes in the Be stars Omega Orionis and 66 Ophiuchi

NASA Technical Reports Server (NTRS)

Peters, G. J.

1982-01-01

IUE observations of the pole-on Be stars Omega Ori and 66 Oph have revealed the unexpected presence of high velocity (-250 to -850 km/sec), relatively narrow (about 1 A) absorption components to the resonance lines of C IV, Si IV, and Si III. The C IV features show structure indicative of multiple shells or clouds. If Omega Ori and 66 Oph are indeed viewed pole-on, then these observations suggest that substantial matter is being ejected from the polar regions of these stars. The nature of these unusual high velocity features, which were not observed in other pole-on Be stars considered in the program, and the column densities and mass loss rates implied by them are discussed in this Letter.

Interstellar abundances - Gas and dust

NASA Technical Reports Server (NTRS)

Field, G. B.

1974-01-01

Data on abundances of interstellar atoms, ions and molecules in front of zeta Oph are assembled and analyzed. The gas-phase abundances of at least 11 heavy elements are significantly lower, relative to hydrogen, than in the solar system. The abundance deficiencies of certain elements correlate with the temperatures derived theoretically for particle condensation in stellar atmospheres or nebulae, suggesting that these elements have condensed into dust grains near stars. There is evidence that other elements have accreted onto such grains after their arrival in interstellar space. The extinction spectrum of zeta Oph can be explained qualitatively and, to a degree, quantitatively by dust grains composed of silicates, graphite, silicon carbide, and iron, with mantles composed of complex molecules of H, C, N, and O. This composition is consistent with the observed gas-phase deficiencies.

Externally Heated Protostellar Cores in the Ophiuchus Star-Forming Region

NASA Technical Reports Server (NTRS)

Lindberg, Johan E.; Charnley, Steven B.; Jorgensen, Jes K.; Cordiner, Martin A.; Bjerkeli, Per

2017-01-01

We present APEX 218 GHz observations of molecular emission in a complete sample of embedded protostars in the Ophiuchus star-forming region. To study the physical properties of the cores, we calculate H2CO and c-C3H2 rotational temperatures, both of which are good tracers of the kinetic temperature of the molecular gas. We find that the H2CO temperatures range between 16K and 124K, with the highest H2CO temperatures toward the hot corino source IRAS 16293-2422 (69-124 K) and the sources in the rho Oph A cloud (23-49 K) located close to the luminous Herbig Be star S1, which externally irradiates the rho Oph A cores. On the other hand, the c-C3H2 rotational temperature is consistently low (7-17 K) in all sources. Our results indicate that the c-C3H2 emission is primarily tracing more shielded parts of the envelope whereas the H2CO emission (at the angular scale of the APEX beam; 3600 au in Ophiuchus) mainly traces the outer irradiated envelopes, apart from in IRAS?16293-2422, where the hot corino emission dominates. In some sources, a secondary velocity component is also seen, possibly tracing the molecular outflow.

Adherence of Pharmaceutical Advertisements in Medical Journals to FDA Guidelines and Content for Safe Prescribing

PubMed Central

Korenstein, Deborah; Keyhani, Salomeh; Mendelson, Ali; Ross, Joseph S.

2011-01-01

Background Physician-directed pharmaceutical advertising is regulated in the United States by the Food and Drug Administration (FDA); adherence to current FDA guidelines is unknown. Our objective was to determine adherence rates of physician-directed print advertisements in biomedical journals to FDA guidelines and describe content important for safe prescribing. Methods and Findings Cross-sectional analysis of November 2008 pharmaceutical advertisements within top U.S.-based biomedical journals publishing original research. We excluded advertisements for devices, over the counter medications, and disease awareness. We utilized FDA guideline items identifying unique forms of advertisement bias to categorize advertisements as adherent to FDA guidelines, possibly non-adherent to at least 1 item, or non-adherent to at least 1 item. We also evaluated advertisement content important for safe prescribing, including benefit quantification, risk information and verifiable references. All advertisements were evaluated by 2 or more investigators, with differences resolved by discussion. Twelve journals met inclusion criteria. Nine contained pharmaceutical advertisements, including 192 advertisements for 82 unique products; median 2 per product (range 1–14). Six “teaser” advertisements presented only drug names, leaving 83 full unique advertisements. Fifteen advertisements (18.1%) adhered to all FDA guidelines, 41 (49.4%) were non-adherent with at least one form of FDA-described bias, and 27 (32.5%) were possibly non-adherent due to incomplete information. Content important for safe prescribing was often incomplete; 57.8% of advertisements did not quantify serious risks, 48.2% lacked verifiable references and 28.9% failed to present adequate efficacy quantification. Study limitations included its focus on advertisements from a single month, the subjectivity of FDA guidelines themselves, and the necessary subjectivity of determinations of adherence. Conclusions Few physician-directed print pharmaceutical advertisements adhere to all FDA guidelines; over half fail to quantify serious risks. The FDA could better protect public health by creating new more objective advertisement guidelines requiring transparent presentation of basic safety and efficacy information. PMID:21858076

Adherence of pharmaceutical advertisements in medical journals to FDA guidelines and content for safe prescribing.

PubMed

Korenstein, Deborah; Keyhani, Salomeh; Mendelson, Ali; Ross, Joseph S

2011-01-01

Physician-directed pharmaceutical advertising is regulated in the United States by the Food and Drug Administration (FDA); adherence to current FDA guidelines is unknown. Our objective was to determine adherence rates of physician-directed print advertisements in biomedical journals to FDA guidelines and describe content important for safe prescribing. Cross-sectional analysis of November 2008 pharmaceutical advertisements within top U.S.-based biomedical journals publishing original research. We excluded advertisements for devices, over the counter medications, and disease awareness. We utilized FDA guideline items identifying unique forms of advertisement bias to categorize advertisements as adherent to FDA guidelines, possibly non-adherent to at least 1 item, or non-adherent to at least 1 item. We also evaluated advertisement content important for safe prescribing, including benefit quantification, risk information and verifiable references. All advertisements were evaluated by 2 or more investigators, with differences resolved by discussion. Twelve journals met inclusion criteria. Nine contained pharmaceutical advertisements, including 192 advertisements for 82 unique products; median 2 per product (range 1-14). Six "teaser" advertisements presented only drug names, leaving 83 full unique advertisements. Fifteen advertisements (18.1%) adhered to all FDA guidelines, 41 (49.4%) were non-adherent with at least one form of FDA-described bias, and 27 (32.5%) were possibly non-adherent due to incomplete information. Content important for safe prescribing was often incomplete; 57.8% of advertisements did not quantify serious risks, 48.2% lacked verifiable references and 28.9% failed to present adequate efficacy quantification. Study limitations included its focus on advertisements from a single month, the subjectivity of FDA guidelines themselves, and the necessary subjectivity of determinations of adherence. Few physician-directed print pharmaceutical advertisements adhere to all FDA guidelines; over half fail to quantify serious risks. The FDA could better protect public health by creating new more objective advertisement guidelines requiring transparent presentation of basic safety and efficacy information.

Photometric evolution of seven recent novae and the double-component characterizing the light curve of those emitting in gamma rays

NASA Astrophysics Data System (ADS)

Munari, U.; Hambsch, F.-J.; Frigo, A.

2017-08-01

The BVI light curves of seven recent novae (I.e. V1534 Sco, V1535 Sco, V2949 Oph, V3661 Oph, MASTER OT J010603.18-744715.8, TCP J1734475-240942 and ASASSN-16ma) have been extensively mapped with daily robotic observations from Atacama (Chile): five belong to the Galactic bulge, one to the Small Magellanic Cloud and another is a Galactic disc object. The two programme novae detected in γ-rays by Fermi-LAT (I.e. TCP J1734475-240942 and ASASSN-16ma) are bulge objects with unevolved companions. They distinguish themselves by showing a double-component optical light curve. The first component to develop is the fireball from freely expanding, ballistic-launched ejecta, with a time of passage through maximum that is strongly dependent on wavelength (˜1 d delay between the B and I bands). The second component, emerging simultaneously with the nova detection in γ-rays, evolves at a slower pace, its optical brightness being proportional to the γ-ray flux, and its passage through maximum not dependent on wavelength. The fact that γ-rays are detected at a flux level that differs by four times from novae at the distance of the bulge seems to suggest that γ-ray emission is not a widespread property of normal novae. We discuss the advantages offered by high-quality photometric observations collected with only one telescope (as opposed to data provided by a number of different instruments). We also observe the effects of the wavelength dependence of fireball expansion, the recombination in the flashed wind of a giant companion, the subtle presence of hiccups and plateaus, and the super-soft X-ray emission and its switch-off. Four programme novae (V2949 Oph, V3661 Oph, TCP J18102829-2729590 and ASASSN-16ma) have normal dwarf companions: V1534 Sco contains an M3 III giant, V1535 Sco a K-type giant and MASTER OT J010603.18-744715.8 a subgiant. We also comment briefly on the maximum absolute magnitude relation with decline time (MMRD).

ROSAT X-ray sources embedded in the rho Ophiuchi cloud core

NASA Astrophysics Data System (ADS)

Casanova, Sophie; Montmerle, Thierry; Feigelson, Eric D.; Andre, Philippe

1995-02-01

We present a deep ROSAT Position Sensitive Proportional Counter (PSPC) image of the central region of the rho Oph star-forming region. The selected area, about 35 x 35 arcmins in size, is rich with dense molecular cores and young stellar objects (YSOs). Fifty-five reliable X-ray sources are detected (and up to 50 more candidates may be present) above approximately 1 keV,, doubling the number of Einstein sources in this area. These sources are cross-identified with an updated list of 88 YSOs associated with the rho Oph cloud core. A third of the reliable X-ray sources do not have optical counterparts on photographic plates. Most can be cross-identified wth Class II and Class III infrared (IR) sources, which are embedded T Tauri stars, but three reliable X-ray sources and up to seven candidate sources are tentatively identified with Class I protostars. Eighteen reliable, and up to 20 candidate, X-ray sources are probably new cloud members. The overall detection rate of the bona fide cloud population is very high (73% for the Class II and Class III objects). The spatial distribution of the X-ray sources closely follows that of the moleclar gas. The visual extinctions Av estimated from near-IR data) of the ROSAT sources can be as high as 50 or more, confirming that most are embedded in the cloud core and are presumably very young. Using bolometric luminosities Lbol estimated from J-magnitudes a tight correlation between Lx and Lbol is found, similar to that seen for older T Tauri stars in the Cha I cloud: Lx approximately 10-4 Lbol. A general relation Lxproportional to LbolLj seems to apply to all T Tauri-like YSOs. The near equality of the extintion in the IR J band and in the keV X-ray rage implies that this relation is valid for the detected fluxes as well as for the dereddened fluxes. The X-ray luminosity function of the embedded sourced in rho Oph spans a range of Lx approximately 1028.5 to approximately equal to or greater than 1031.5 ergs/s and is statistically indistinguishable from that of X-ray-detected visile T Tauri stars. We estimate a total X-ray luminosity Lx, Oph approximately equal to or greater than 6 x 10 32 ergs/s from approximately equal to 200 X-ray sources in the cloud core, down to Lbol approximately 0.1 solar luminosity or Mstar approximately 0.3 solar mass. We discuss several consequences of in situ irradiation of molecular clouds by X-rays from embedded YSOs. These X-rays must partially ionize the inner regions of circumstellar disk coronae, possibly playing an important role in coupling magnetic ionize the fields and wind or bipolar outflows. Photon-stimulated deportion of large molecules by YSO X-rays may be partly responsible for the bright 12 micrometer halos seen in some molecular clouds.

Deciphering the role and nature of phosphate species at the surface of stainless steel immersed in phosphoric acid solutions

NASA Astrophysics Data System (ADS)

Liascukiene, I.; Ben Salah, M.; Sabot, R.; Refait, Ph.; Dhouibi, L.; Méthivier, C.; Landoulsi, J.; Jeannin, M.

2018-03-01

We investigate the evolution of the surface of a highly alloyed stainless steel (Sanicro 28) upon immersion in aqueous phosphoric acid solutions. For this purpose, both short- (few hours) and long-term immersion (several days) were carried out. A detailed analysis of XPS spectra allowed a distinction to be made between oxygen originating from the organic adlayer (adventitious contamination), the passive oxide layer, and adsorbed phosphate species. By estimating the fraction of oxygen due to phosphate species (Oph), it was shown that the Oph/P molar concentration ratio was ranging from about 2 to 3. This suggests the presence of a polyphosphate layer at the stainless steel surface, as also supported by Raman analysis, which influence the electrochemical behavior of SS in the acidic media.

Local spin dynamics at low temperature in the slowly relaxing molecular chain [Dy(hfac)3{NIT(C6H4OPh)}]: A μ+ spin relaxation study

NASA Astrophysics Data System (ADS)

Arosio, Paolo; Corti, Maurizio; Mariani, Manuel; Orsini, Francesco; Bogani, Lapo; Caneschi, Andrea; Lago, Jorge; Lascialfari, Alessandro

2015-05-01

The spin dynamics of the molecular magnetic chain [Dy(hfac)3{NIT(C6H4OPh)}] were investigated by means of the Muon Spin Relaxation (μ+SR) technique. This system consists of a magnetic lattice of alternating Dy(III) ions and radical spins, and exhibits single-chain-magnet behavior. The magnetic properties of [Dy(hfac)3{NIT(C6H4OPh)}] have been studied by measuring the magnetization vs. temperature at different applied magnetic fields (H = 5, 3500, and 16500 Oe) and by performing μ+SR experiments vs. temperature in zero field and in a longitudinal applied magnetic field H = 3500 Oe. The muon asymmetry P(t) was fitted by the sum of three components, two stretched-exponential decays with fast and intermediate relaxation times, and a third slow exponential decay. The temperature dependence of the spin dynamics has been determined by analyzing the muon longitudinal relaxation rate λinterm(T), associated with the intermediate relaxing component. The experimental λinterm(T) data were fitted with a corrected phenomenological Bloembergen-Purcell-Pound law by using a distribution of thermally activated correlation times, which average to τ = τ0 exp(Δ/kBT), corresponding to a distribution of energy barriers Δ. The correlation times can be associated with the spin freezing that occurs when the system condenses in the ground state.

Interstellar detection of the intersystem line Si II lambda 2335 toward zeta Ophiuchi

NASA Technical Reports Server (NTRS)

Cardelli, Jason A.; Sofia, Ulysses J.; Savage, Blair D.; Keenan, Francis P.; Dufton, Philip L.

1994-01-01

We report on the detection of the weak intersystem transistion of Si II lambda 2335 A in the sight line toward zeta Oph using the Ech-B mode (3.5 km/s resolution) of the Goddard High Resolution Spectrograph. The high-quality spectrum is characterized by an empirically measured signal-to-noise of 450, in excellent agreement with that expected from photon-statistics. The measured equivalent width of the Si II line is W(sub lambda) = 0.48 +/- 0.12 mA. Using the new experimental f-value of Calamai, Smith, and Bergeson, we find a Si II column density of 2.34 (+/- 0.58) x 10(exp 15) atoms/sq cm and (Si/H)(sub zeta Oph) = 1.78 (+/- 0.44) x 10(exp -6) for the principal absorbing component(s) at v(sub sun) approx. = -15 km/s. Analysis of the Si II lambda 1808 absorption over the same velocity range using the new experimental f-value of Bergeson & Lawler yields a column density (corrected for saturation) that is consistent within the weak line errors and confirms the relative accuracies of these new f-values. Furthermore, these results indicate that accurate abundances can now be derived for Si II, particularly from the weak Si II lambda 2335 A since it is free of saturation effects. For the zeta Oph v(sub sun) approx. = -15 km/s component(s), we find that greater than 95% of the available cosmic abundance (i.e. the 1989 meteoritic abundances of Anders & Grevesse) of Mg, Fe, and Si is 'missing' from the gas phase and is presumably locked up in the dust. These elements are present in the dust grains in ratios of Fe/Si approximately equals 0.9 and Mg/Si approximately equals 1.1, consistent with the ratio of their cosmic abundances. These ratios are in sharp contrast to more diffuse clouds like those seen toward the high-latitude halo star HD 93521 where in the dust Fe/Si approximately equals 1.8 and Mg/Si approximately equals 2.1.

The JCMT Gould Belt Survey: first results from the SCUBA-2 observations of the Ophiuchus molecular cloud and a virial analysis of its prestellar core population

NASA Astrophysics Data System (ADS)

Pattle, K.; Ward-Thompson, D.; Kirk, J. M.; White, G. J.; Drabek-Maunder, E.; Buckle, J.; Beaulieu, S. F.; Berry, D. S.; Broekhoven-Fiene, H.; Currie, M. J.; Fich, M.; Hatchell, J.; Kirk, H.; Jenness, T.; Johnstone, D.; Mottram, J. C.; Nutter, D.; Pineda, J. E.; Quinn, C.; Salji, C.; Tisi, S.; Walker-Smith, S.; di Francesco, J.; Hogerheijde, M. R.; André, Ph.; Bastien, P.; Bresnahan, D.; Butner, H.; Chen, M.; Chrysostomou, A.; Coude, S.; Davis, C. J.; Duarte-Cabral, A.; Fiege, J.; Friberg, P.; Friesen, R.; Fuller, G. A.; Graves, S.; Greaves, J.; Gregson, J.; Griffin, M. J.; Holland, W.; Joncas, G.; Knee, L. B. G.; Könyves, V.; Mairs, S.; Marsh, K.; Matthews, B. C.; Moriarty-Schieven, G.; Rawlings, J.; Richer, J.; Robertson, D.; Rosolowsky, E.; Rumble, D.; Sadavoy, S.; Spinoglio, L.; Thomas, H.; Tothill, N.; Viti, S.; Wouterloot, J.; Yates, J.; Zhu, M.

2015-06-01

In this paper, we present the first observations of the Ophiuchus molecular cloud performed as part of the James Clerk Maxwell Telescope (JCMT) Gould Belt Survey (GBS) with the SCUBA-2 instrument. We demonstrate methods for combining these data with previous HARP CO, Herschel, and IRAM N2H+ observations in order to accurately quantify the properties of the SCUBA-2 sources in Ophiuchus. We produce a catalogue of all of the sources found by SCUBA-2. We separate these into protostars and starless cores. We list all of the starless cores and perform a full virial analysis, including external pressure. This is the first time that external pressure has been included in this level of detail. We find that the majority of our cores are either bound or virialized. Gravitational energy and external pressure are on average of a similar order of magnitude, but with some variation from region to region. We find that cores in the Oph A region are gravitationally bound prestellar cores, while cores in the Oph C and E regions are pressure-confined. We determine that N2H+ is a good tracer of the bound material of prestellar cores, although we find some evidence for N2H+ freeze-out at the very highest core densities. We find that non-thermal linewidths decrease substantially between the gas traced by C18O and that traced by N2H+, indicating the dissipation of turbulence at higher densities. We find that the critical Bonnor-Ebert stability criterion is not a good indicator of the boundedness of our cores. We detect the pre-brown dwarf candidate Oph B-11 and find a flux density and mass consistent with previous work. We discuss regional variations in the nature of the cores and find further support for our previous hypothesis of a global evolutionary gradient across the cloud from south-west to north-east, indicating sequential star formation across the region.

Implementing the Biopharmaceutics Classification System in Drug Development: Reconciling Similarities, Differences, and Shared Challenges in the EMA and US-FDA-Recommended Approaches.

PubMed

Cardot, J-M; Garcia Arieta, A; Paixao, P; Tasevska, I; Davit, B

2016-07-01

The US-FDA recently posted a draft guideline for industry recommending procedures necessary to obtain a biowaiver for immediate-release oral dosage forms based on the Biopharmaceutics Classification System (BCS). This review compares the present FDA BCS biowaiver approach, with the existing European Medicines Agency (EMA) approach, with an emphasis on similarities, difficulties, and shared challenges. Some specifics of the current EMA BCS guideline are compared with those in the recently published draft US-FDA BCS guideline. In particular, similarities and differences in the EMA versus US-FDA approaches to establishing drug solubility, permeability, dissolution, and formulation suitability for BCS biowaiver are critically reviewed. Several case studies are presented to illustrate the (i) challenges of applying for BCS biowaivers for global registration in the face of differences in the EMA and US-FDA BCS biowaiver criteria, as well as (ii) challenges inherent in applying for BCS class I or III designation and common to both jurisdictions.

A review of the FDA draft guidance document for software validation: guidance for industry.

PubMed

Keatley, K L

1999-01-01

A Draft Guidance Document (Version 1.1) was issued by the United States Food and Drug Administration (FDA) to address the software validation requirement of the Quality System Regulation, 21 CFR Part 820, effective June 1, 1997. The guidance document outlines validation considerations that the FDA regards as applicable to both medical device software and software used to "design, develop or manufacture" medical devices. The Draft Guidance is available at the FDA web site http:@www.fda.gov/cdrh/comps/swareval++ +.html. Presented here is a review of the main features of the FDA document for Quality System Regulation (QSR), and some guidance for its implementation in industry.

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

Jacob, Reed B.; Ding, Feng; Ye, Dongmei

Organophosphates are widely used for peaceful (agriculture) and military purposes (chemical warfare agents). The extraordinary toxicity of organophosphates and the risk of deployment, make it critical to develop means for their rapid and efficient deactivation. Organophosphate hydrolase (OPH) already plays an important role in organophosphate remediation, but is insufficient for therapeutic or prophylactic purposes primarily due to low substrate affinity. Current efforts focus on directly modifying the active site to differentiate substrate specificity and increase catalytic activity. Here, we present a novel strategy for enhancing the general catalytic efficiency of OPH through computational redesign of the residues that are allostericallymore » coupled to the active site and validated our design by mutagenesis. Specifically, we identify five such hot-spot residues for allosteric regulation and assay these mutants for hydrolysis activity against paraoxon, a chemical-weapons simulant. A high percentage of the predicted mutants exhibit enhanced activity over wild-type (k cat =16.63 s -1), such as T199I/T54I (899.5 s -1) and C227V/T199I/T54I (848 s -1), while the Km remains relatively unchanged in our high-throughput cell-free expression system. Further computational studies of protein dynamics reveal four distinct distal regions coupled to the active site that display significant changes in conformation dynamics upon these identified mutations. These results validate a computational design method that is both efficient and easily adapted as a general procedure for enzymatic enhancement.« less

EXTERNALLY HEATED PROTOSTELLAR CORES IN THE OPHIUCHUS STAR-FORMING REGION

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

Lindberg, Johan E.; Charnley, Steven B.; Cordiner, Martin A.

We present APEX 218 GHz observations of molecular emission in a complete sample of embedded protostars in the Ophiuchus star-forming region. To study the physical properties of the cores, we calculate H{sub 2}CO and c -C{sub 3}H{sub 2} rotational temperatures, both of which are good tracers of the kinetic temperature of the molecular gas. We find that the H{sub 2}CO temperatures range between 16 K and 124 K, with the highest H{sub 2}CO temperatures toward the hot corino source IRAS 16293-2422 (69–124 K) and the sources in the ρ Oph A cloud (23–49 K) located close to the luminous Herbigmore » Be star S1, which externally irradiates the ρ Oph A cores. On the other hand, the c -C{sub 3}H{sub 2} rotational temperature is consistently low (7–17 K) in all sources. Our results indicate that the c -C{sub 3}H{sub 2} emission is primarily tracing more shielded parts of the envelope whereas the H{sub 2}CO emission (at the angular scale of the APEX beam; 3600 au in Ophiuchus) mainly traces the outer irradiated envelopes, apart from in IRAS 16293-2422, where the hot corino emission dominates. In some sources, a secondary velocity component is also seen, possibly tracing the molecular outflow.« less

MIR imaging of the transitional disk source Oph IRS48

NASA Astrophysics Data System (ADS)

Honda, Mitsuhiko

2015-06-01

We propose to make 25 mum mid-infrared imaging of the transitional disk around the young star Oph IRS 48 to derive the temperature of the emitting dust in this disk. Recently, ALMA observation revealed the apparent difference of the infrared (18.7 mum) and radio (440 mum) dust continuum of this system and implied that the large mm-sized grains are trapped and accumulated to the local pressure maximum, which may eventually form planetesimals/planets. However, there can be other explanations to such apparent difference in the different wavelengths. To verify such interpretation, new 25 mum imaging can provide some clues, since it is the wavelength between the previous 18.7 mum and the 440 mum observations. Furthermore, multi-wavelength study of the disk is a natural step towards detailed understanding of disk structure, and new 25 mum image can be complemental to forthecoming ALMA and NIR polarimetric data.

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

Sanner, Robert D.; Cherepy, Nerine J.; Young, Jr., Victor G.

In this study, we describe the synthesis and crystal structures of four iridium compounds containing the 2-(4,6-difluorophenyl)pyridyl ligand. Cleavage of dichloro-bridged iridium(III) dimers with phosphorus ligands leads to (46dfppy)2Ir(L)(Cl) where L = PPh 3 or P(OPh) 3. Treatment of the chloro compounds with cyanide forms the cyano complexes (46dfppy) 2Ir(L)(CN). All complexes exhibit a trans effect in their molecular structures due to the phosphorus ligands, with the phosphite having a greater effect than the phosphine. With L = PPh 3, blue photoluminescence with CIE coordinates (x = 0.16, y = 0.24), quantum yield of 0.66 ± 0.15 and 4.5 ±more » 0.5 μs decay time is measured. For L = P(OPh) 3, blue photoluminescence with CIE coordinates (x = 0.16, y = 0.21), quantum yield of 0.65 ± 0.15 and 2.9 ± 0.3 μs decay time is measured.« less

V2676 Oph: Estimating Physical Parameters of a Moderately Fast Nova

NASA Astrophysics Data System (ADS)

Raj, A.; Pavana, M.; Kamath, U. S.; Anupama, G. C.; Walter, F. M.

2018-03-01

Using our previously reported observations, we derive some physical parameters of the moderately fast nova V2676 Oph 2012 #1. The best-fit Cloudy model of the nebular spectrum obtained on 2015 May 8 shows a hot white dwarf source with TBB≍1.0×105 K having a luminosity of 1.0×1038 erg/s. Our abundance analysis shows that the ejecta are significantly enhanced relative to solar, He/H=2.14, O/H=2.37, S/H=6.62 and Ar/H=3.25. The ejecta mass is estimated to be 1.42×10-5 M⊙. The nova showed a pronounced dust formation phase after 90 d from discovery. The J-H and H-K colors were very large as compared to other molecule- and dust-forming novae in recent years. The dust temperature and mass at two epochs have been estimated from spectral energy distribution fits to infrared photometry.

MIR imaging of the transitional disk source Oph IRS48

NASA Astrophysics Data System (ADS)

Honda, Mitsuhiko

2014-01-01

We propose to make 25 micron mid-infrared imaging of the transitional disk around the young star Oph IRS 48 to derive the temperature of the emitting dust in this disk. Recently, ALMA observation revealed the apparent difference of the infrared (18.7 micron) and radio (440 micron) dust continuum of this system and implied that the large mm-sized grains are trapped and accumulated to the local pressure maximum, which may eventually form planetesimals/planets. However, there can be other explanations to such apparent difference in the different wavelengths. To verify such interpretation, new 25 micron imaging can provide some clues, since it is the wavelength between previous 18.7 micron and 440 micron observations. Furthermore, multi-wavelength study of the disk is a natural step towards detailed understanding of disk structure, and new 25 micron image can be complemental to forthecoming ALMA and NIR polarimetric data.

Structural insights into enzymatic degradation of oxidized polyvinyl alcohol.

PubMed

Yang, Yu; Ko, Tzu-Ping; Liu, Long; Li, Jianghua; Huang, Chun-Hsiang; Chan, Hsiu-Chien; Ren, Feifei; Jia, Dongxu; Wang, Andrew H-J; Guo, Rey-Ting; Chen, Jian; Du, Guocheng

2014-09-05

The ever-increasing production and use of polyvinyl alcohol (PVA) threaten our environment. Yet PVA can be assimilated by microbes in two steps: oxidation and cleavage. Here we report novel α/β-hydrolase structures of oxidized PVA hydrolase (OPH) from two known PVA-degrading organisms, Sphingopyxis sp. 113P3 and Pseudomonas sp. VM15C, including complexes with substrate analogues, acetylacetone and caprylate. The active site is covered by a lid-like β-ribbon. Unlike other esterase and amidase, OPH is unique in cleaving the CC bond of β-diketone, although it has a catalytic triad similar to that of most α/β-hydrolases. Analysis of the crystal structures suggests a double-oxyanion-hole mechanism, previously only found in thiolase cleaving β-ketoacyl-CoA. Three mutations in the lid region showed enhanced activity, with potential in industrial applications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Investigation of the interfacial reaction between metal and fluorine-contained polyimides

NASA Astrophysics Data System (ADS)

Yang, Ching-Yu; Chen, J. S.; Hsu, S. L. C.

2005-07-01

In this work, thin metal films (Cr and Ta) were deposited on fluorine-contained polyimides, 6FDA-BisAAF, and 6FDA-PPD. The chemical states of the metal/polyimide samples were characterized by using x-ray photoelectron spectroscopy (XPS). XPS analysis reveals that metal-C, C-O, and metal-O bondings are present in metallized 6FDA-BisAAF and 6FDA-PPD. C-F bonds are observed in bare 6FDA-BisAAF and 6FDA-PPD however, they are not seen in the metallized samples. Disappearance of the C-F bonding is attributed to the disruption of CF3 side groups from the main chains of 6FDA-BisAAF and 6FDA-PPD when the chains are exposed to the plasma during the metal deposition. Nevertheless, the disruption of CF3 side groups also creates sites for the formation of metal-C or C-O bondings, which provide a positive adhesion strength at the metal/polyimide interface, as revealed by the tape test.

75 FR 47820 - Generic Drug User Fee; Public Meeting; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0381... fee program. The number of human generic drug applications awaiting FDA action and the median review... needed for presentations, FDA reserves the right to terminate the meeting early. If you need special...

America, you are digging your grave with your spoon--should the FDA tell you that on food labels?

PubMed

Card, Melissa M

2013-01-01

R.J. Reynolds Tobacco Co. v. Food & Drug Admin. discussed whether the FDA's promulgation of graphic images violated tobacco companies' First Amendment rights. While the tobacco companies contested the graphic images, the tobacco companies did not contest the promulgation of nine textual statements about the adverse effects of cigarettes. This uncontested mandate opens a door for the FDA to further expand its regulatory scheme. If the FDA can mandate textual statements about the adverse effects of cigarettes, can the FDA mandate textual statements about the adverse effects of sugar to combat the obesity crisis? This Article presents three textual statements about the adverse effects of sugar, to define the line between acceptable and unacceptable forms of compelled commercial speech under Central Hudson. Establishing this line ensures that the commercial speech doctrine does not deny the FDA from its authority to provide consumers with accurate information. While three textual statements are presented, this Article advocates that one of the textual statements is likely to serve as the best solution to the obesity crisis. The chosen textual statement serves as an effective solution because it presents meaningful information to the consumers enabling consumers to make healthful decisions about their food and encourages manufacturers to modify their products.

Mononuclear Sulfido-Tungsten(V) Complexes: Completing the Tp*MEXY (M = Mo, W; E = O, S) Series.

PubMed

Sproules, Stephen; Eagle, Aston A; George, Graham N; White, Jonathan M; Young, Charles G

2017-05-01

Orange Tp*WSCl 2 has been synthesized from the reactions of Tp*WOCl 2 with boron sulfide in refluxing toluene or Tp*WS 2 Cl with PPh 3 in dichloromethane at room temperature. Mononuclear sulfido-tungsten(V) complexes, Tp*WSXY {X = Y = Cl, OPh, SPh, SePh; X = Cl, Y = OPh; XY = toluene-3,4-dithiolate (tdt), quinoxaline-2,3-dithiolate (qdt); and Tp* = hydrotris(3,5-dimethylpyrazol-1-yl)borate} were prepared by metathesis of Tp*WSCl 2 with the respective alkali metal salt of X - /XY 2- , or [NHEt 3 ] 2 (qdt). The complexes were characterized by microanalysis, mass spectrometry, electrochemistry, and infrared (IR), electron paramagnetic resonance (EPR) and electronic absorption spectroscopies. The molecular structures of Tp*WS(OPh) 2 , Tp*WS(SePh) 2 , and Tp*WS(tdt) have been determined by X-ray crystallography. The six-coordinate, distorted-octahedral W centers are coordinated by terminal sulfido (W≡S = 2.128(2) - 2.161(1) Å), terdentate facial Tp*, and monodentate/bidentate O/S/Se-donor ligands. The sulfido-W(V) complexes are characterized by lower energy electronic transitions, smaller g iso , and larger A iso ( 183 W) values, and more positive reduction potentials compared with their oxo-W(V) counterparts. This series has been probed by sulfur K-edge X-ray absorption spectroscopy (XAS), the spectra being assigned by comparison to Tp*WOXY (X = Y = SPh; XY = tdt, qdt) and time-dependent density functional theoretical (TD-DFT) calculations. This study provides insight into the electronic nature and chemistry of the catalytically and biologically important sulfido-W unit.

Better Strength, Better Balance! Partnering to deliver a fall prevention program for older adults.

PubMed

Taing, Darcie; McKay, Kelly

2017-09-14

Falls incur significant health and economic costs, particularly among older adults. Physical activity has been found to be the single most important fall prevention behaviour an older adult can do. This manuscript describes Ottawa Public Health's (OPH) experience implementing the Better Strength, Better Balance! (BSBB) program, a fall prevention exercise program for older adults, through an innovative partnership with the local Recreation, Cultural & Facility Services (RCFS) Department. BSBB aims to reach 1300 community-dwelling adults (aged 65 years and older) per year through approximately 86-130 exercise programs. Designed as a universal program, BSBB addresses participation barriers such as transportation, cost and location. BSBB was enabled with funding from the Champlain Local Health Integration Network, and coincided with the implementation of an Older Adult Plan for the City of Ottawa. BSBB is a beginner-level, fall prevention exercise and education program that takes place twice a week, over 12 weeks. Certified RCFS instructors delivered the exercise components of the program and OPH staff incorporated fall prevention messaging and conducted the evaluation. The formative evaluation indicated that participants experienced improved strength and balance, decreased fear of falling and the intent to adopt new fall prevention behaviours following the program. The partnership between OPH and RCFS allowed both partners to leverage their unique and mutual strengths to continually improve the program. Improving access to strength and balance programming is an important public health strategy to reduce falls. The recreation sector is an ideal partner to help public health in this pursuit.

Biomimetic Inspired Core-Canopy Quantum Dots: Ions Trapped in Voids Induce Kinetic Fluorescence Switching.

PubMed

Saha, Arpita; Oleshkevich, Elena; Vinas, Clara; Teixidor, Francesc

2017-12-01

Closely packed hollow spheres connected through pillars to a CdSe quantum dot (QD) core produce channels through which ions navigate. This particular structure is well represented by [CdSe@CarbOPH(O)]@Cl/[N(Caprylyl) 3 Me 1 ] indicating that in the channels between the canopy made by the carboranyl spheres (carboranylphosphinate, CarbOPH(O)) and the CdSe core exist chloride anions. Due to the close packing, the spheres produce openings. These are converted into gates because [N(Caprylyl) 3 Me 1 ] acts as a plug. The [CdSe@CarbOPH(O)]@Cl/assembly is negatively charged because the Cd positive charges are outnumbered by the negative charges due to the Se, the phosphinic acid and, very importantly, the trapped chloride anions, and this negative load is compensated by the cationic surfactant. Here, it is shown that this synergism produces an unprecedented phenomenon, namely, kinetic fluorescence switching. It is observed that the material shines brightly then loses its brightness and, upon the application of kinetic energy, shines back to the maximum power. This process continues for an extended period of time, up to half a year, at least. This new type of architecture in QDs is named as core-canopy QDs. In this case, this study demonstrates one property, the kinetic fluorescence switching, as a consequence of the trapping of Cl - in the QDs channels, but other properties can be envisaged with the judicious choice of the anions or even the pillar connecting the hollow sphere with the ground. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Local spin dynamics at low temperature in the slowly relaxing molecular chain [Dy(hfac)3(NIT(C6H4OPh))]: A μ{sup +} spin relaxation study

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

Arosio, Paolo, E-mail: paolo.arosio@guest.unimi.it; Orsini, Francesco; Corti, Maurizio

2015-05-07

The spin dynamics of the molecular magnetic chain [Dy(hfac){sub 3}(NIT(C{sub 6}H{sub 4}OPh))] were investigated by means of the Muon Spin Relaxation (μ{sup +}SR) technique. This system consists of a magnetic lattice of alternating Dy(III) ions and radical spins, and exhibits single-chain-magnet behavior. The magnetic properties of [Dy(hfac){sub 3}(NIT(C{sub 6}H{sub 4}OPh))] have been studied by measuring the magnetization vs. temperature at different applied magnetic fields (H = 5, 3500, and 16500 Oe) and by performing μ{sup +}SR experiments vs. temperature in zero field and in a longitudinal applied magnetic field H = 3500 Oe. The muon asymmetry P(t) was fitted by the sum of three components, twomore » stretched-exponential decays with fast and intermediate relaxation times, and a third slow exponential decay. The temperature dependence of the spin dynamics has been determined by analyzing the muon longitudinal relaxation rate λ{sub interm}(T), associated with the intermediate relaxing component. The experimental λ{sub interm}(T) data were fitted with a corrected phenomenological Bloembergen-Purcell-Pound law by using a distribution of thermally activated correlation times, which average to τ = τ{sub 0} exp(Δ/k{sub B}T), corresponding to a distribution of energy barriers Δ. The correlation times can be associated with the spin freezing that occurs when the system condenses in the ground state.« less

MICROCHIP ENZYMATIC ASSAY OF ORGANOPHOSPHATE NERVE AGENTS. (R830900)

EPA Science Inventory

An on-chip enzymatic assay for screening organophosphate (OP) nerve agents, based on a pre-column reaction of organophosphorus hydrolase (OPH), electrophoretic separation of the phosphonic acid products, and their contactless-conductivity detection, is described. Factors affec...

Aberrant regeneration of the third cranial nerve.

PubMed

Shrestha, U D; Adhikari, S

2012-01-01

Aberrant regeneration of the third cranial nerve is most commonly due to its damage by trauma. A ten-month old child presented with the history of a fall from a four-storey building. She developed traumatic third nerve palsy and eventually the clinical features of aberrant regeneration of the third cranial nerve. The adduction of the eye improved over time. She was advised for patching for the strabismic amblyopia as well. Traumatic third nerve palsy may result in aberrant regeneration of the third cranial nerve. In younger patients, motility of the eye in different gazes may improve over time. © NEPjOPH.

OpenVigil FDA - Inspection of U.S. American Adverse Drug Events Pharmacovigilance Data and Novel Clinical Applications.

PubMed

Böhm, Ruwen; von Hehn, Leocadie; Herdegen, Thomas; Klein, Hans-Joachim; Bruhn, Oliver; Petri, Holger; Höcker, Jan

2016-01-01

Pharmacovigilance contributes to health care. However, direct access to the underlying data for academic institutions and individual physicians or pharmacists is intricate, and easily employable analysis modes for everyday clinical situations are missing. This underlines the need for a tool to bring pharmacovigilance to the clinics. To address these issues, we have developed OpenVigil FDA, a novel web-based pharmacovigilance analysis tool which uses the openFDA online interface of the Food and Drug Administration (FDA) to access U.S. American and international pharmacovigilance data from the Adverse Event Reporting System (AERS). OpenVigil FDA provides disproportionality analyses to (i) identify the drug most likely evoking a new adverse event, (ii) compare two drugs concerning their safety profile, (iii) check arbitrary combinations of two drugs for unknown drug-drug interactions and (iv) enhance the relevance of results by identifying confounding factors and eliminating them using background correction. We present examples for these applications and discuss the promises and limits of pharmacovigilance, openFDA and OpenVigil FDA. OpenVigil FDA is the first public available tool to apply pharmacovigilance findings directly to real-life clinical problems. OpenVigil FDA does not require special licenses or statistical programs.

THERMALLY TRIGGERED PURIFICATION AND IMMOBILIZATION OF ELASTIN-OPH FUSION. (R829606)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

REMOTE BIOSENSOR FOR IN SITU MONITORING OF ORGANOPHOSPHATE NERVE AGENTS. (R823663)

EPA Science Inventory

A remote electrochemical biosensor for field monitoring of organophosphate nerve agents is described. The new sensor relies on the coupling of the effective biocatalytic action of organophosphorus hydrolase (OPH) with a submersible amperometric probe design. This combination resu...

ORGANOPHOSPHORUS HYDROLASE-BASED AMPEROMETRIC SENSOR: MODULATION OF SENSITIVITY AND SUBSTRATE SELECTIVITY

EPA Science Inventory

The detection of organophosphate (OP) insecticides with nitrophenyl substituents is reported using an enzyme electrode composed of Organophosphorus Hydrolase (OPH) and albumin co-immobilized to a nylon net and attached to a carbon paste electrode. The mechanism for this biosen...

ORGANOPHOSPHORUS HYDROLASE-BASED ASSAY FOR ORGANOPHOSPHATE PESTICIDES

EPA Science Inventory

We report a rapid and versatile Organophosphorus hydrolase (OPH)-based method for measurement of organophosphates. This assay is based on a substrate-dependent change in pH at the local vicinity of the enzyme. The pH change is monitored using fluorescein isothiocyanate (FITC), ...

Searching Cyclical Period Variations in Cataclysmic Variable Stars

NASA Astrophysics Data System (ADS)

Borges, B. W.; Baptista, R.

2006-08-01

Cataclymic variables (CVs) are semi-detached binary systems in which a main sequence late-type star (the secondary) fills its Roche lobe and transfers matter to a white dwarf (the primary) through the inner Lagragian point L[1]. Evolutive models of CVs predicts that the orbital periods P[orb] of these systems would decrease on time scales of 10^8-10^9 years due to angular momentum losses either by magnetic braking via the secondary star's wind (P [orb] > 3 hr) or by emission of gravitational radiation (P[orb] < 3 hr). These models try to explain the observed gap of systems with P[orb] in the range of ~ 2 to 3 hr as the consequence of a sharp reduction of magnetic field open lines when the secondary star become fully convective (at P[orb] ~ 3 hr). However, up to now no well-studied CVs shows evidence of period decrease. Instead, most well-observed eclipsing CVs show cyclical period changes probably associated to solar-type (quasi-periodic and/or multiperiodic) magnetic activity cycles in the secondary star. The fast spinning secondaries of CVs, covering a range of masses and rotation periods, are an important laboratory to understanding magnetic activities cycles in late type stars. In the present work, we report some results of the search of cyclical period in four Cvs: V4140 Sgr, V2051 Oph, UU Aqr and IP Peg. Both V4140 Sgr and V2051 Oph show modulation periods of 22 yr and 7 yr respectively. A discussion of the distinct magnetic activity properties of short and long orbital period (P[orb] < 3 hr and P[orb] > 3 hr, respectively) systems in the framework of the CV evolution scenarios is presented.

Accommodative spasm with bilateral vision loss due to untreated intermittent exotropia in an adult.

PubMed

Shanker, V; Ganesh, S; Sethi, S

2012-01-01

Intermittent exotropia (IXT) is an exodeviation intermittently controlled by fusional mechanisms. Patients with IXT may present with asthenopic symptoms, blurred vision, headaches, diplopia or visual confusion and reading difficulties; especially after prolonged periods of near work. To report the presentation and management of a young adult with intractable accommodative spasm secondary to long standing intermittent exotropia. The patient was found to have bilateral accommodative spasm with high pseudomyopia and severe impairment of vision. There was a tendency for recurrence with discontinuation of cycloplegics. A total relief of symptoms was noticed after strabismus surgery was undertaken for the exotropia. A detailed orthoptic evaluation with emphasis on recognizing accommodative spasm as an unusual presentation of IXT, could aid in appropriate diagnosis and treatment of such cases. © NEPjOPH.

Extended Envelopes around Galactic Cepheids. III. Y Ophiuchi and α Persei from Near-Infrared Interferometry with CHARA/FLUOR

NASA Astrophysics Data System (ADS)

Mérand, Antoine; Aufdenberg, Jason P.; Kervella, Pierre; Foresto, Vincent Coudé du; ten Brummelaar, Theo A.; McAlister, Harold A.; Sturmann, Laszlo; Sturmann, Judit; Turner, Nils H.

2007-08-01

Unbiased angular diameter measurements are required for accurate distances to Cepheids using the interferometric Baade-Wesselink method (IBWM). The precision of this technique is currently limited by interferometric measurements at the 1.5% level. At this level, the center-to-limb darkening (CLD) and the presence of circumstellar envelopes (CSE) seem to be the two main sources of bias. The observations we performed aim at improving our knowledge of the interferometric visibility profile of Cepheids. In particular, we assess the systematic presence of CSE around Cepheids in order determine accurate distances with the IBWM free from CSE biased angular diameters. We observed a Cepheid (Y Oph) for which the pulsation is well resolved and a nonpulsating yellow supergiant (α Per) using long-baseline near-infrared interferometry. We interpreted these data using a simple CSE model we previously developed. We found that our observations of α Per do not provide evidence for a CSE. The measured CLD is explained by an hydrostatic photospheric model. Our observations of Y Oph, when compared to smaller baseline measurements, suggest that it is surrounded by a CSE with characteristics similar to CSEs found previously around other Cepheids. We have determined the distance to Y Oph to be d=491+/-18 pc. Additional evidence points toward the conclusion that most Cepheids are surrounded by faint CSEs, detected by near-infrared interferometry: after observing four Cepheids, all show evidence for a CSE. Our CSE nondetection around a nonpulsating supergiant in the instability strip, α Per, provides confidence in the detection technique and suggests a pulsation driven mass-loss mechanism for the Cepheids.

Identify and Translate Learnings from On-Going Assay ...

EPA Pesticide Factsheets

Presentation for FDA-CFSAN ILSI workshop on State of the Science on Alternatives to Animal Testing and Integration of Testing Strategies for Food Safety Assessments Presentation for FDA-CFSAN ILSI workshop on State of the Science on Alternatives to Animal Testing and Integration of Testing Strategies for Food Safety Assessments

20170228 - Identify and Translate Learnings from On-Going ...

EPA Pesticide Factsheets

Presentation for FDA-CFSAN ILSI workshop on State of the Science on Alternatives to Animal Testing and Integration of Testing Strategies for Food Safety Assessments Presentation for FDA-CFSAN ILSI workshop on State of the Science on Alternatives to Animal Testing and Integration of Testing Strategies for Food Safety Assessments

Frequency Diverse Array Receiver Architectures

DTIC Science & Technology

2015-06-29

completely associated with FDA, the Hybrid MIMO phased array (HMPAR) concept presented in [18] developed the basic beam patern synthesis theory for an...20], that analyzed beam paterns of chirp waveforms with slightly 6 different starting frequencies. In [21] and [11] they investigated using FDA for...forward-looking radar GMTI benefits. This research showed the ability of the range-dependent energy distribution characteristics of the FDA beam patern

Blue light emission from cyclometallated iridium (III) cyano complexes: Syntheses, crystal structures, and photophysical properties

DOE PAGES

Sanner, Robert D.; Cherepy, Nerine J.; Young, Jr., Victor G.

2015-11-02

In this study, we describe the synthesis and crystal structures of four iridium compounds containing the 2-(4,6-difluorophenyl)pyridyl ligand. Cleavage of dichloro-bridged iridium(III) dimers with phosphorus ligands leads to (46dfppy)2Ir(L)(Cl) where L = PPh 3 or P(OPh) 3. Treatment of the chloro compounds with cyanide forms the cyano complexes (46dfppy) 2Ir(L)(CN). All complexes exhibit a trans effect in their molecular structures due to the phosphorus ligands, with the phosphite having a greater effect than the phosphine. With L = PPh 3, blue photoluminescence with CIE coordinates (x = 0.16, y = 0.24), quantum yield of 0.66 ± 0.15 and 4.5 ±more » 0.5 μs decay time is measured. For L = P(OPh) 3, blue photoluminescence with CIE coordinates (x = 0.16, y = 0.21), quantum yield of 0.65 ± 0.15 and 2.9 ± 0.3 μs decay time is measured.« less

An interstellar cloud density from Copernicus observations of CO in the spectrum of Zeta Ophiuchi

NASA Technical Reports Server (NTRS)

Smith, A. M.; Stecher, T. P.; Krishna Swamy, K. S.

1978-01-01

Interstellar CO absorption bands in Copernicus spectra of Zeta Oph have been studied. Absorption profiles, computed under the assumption that excitation is due to collisions with H2 molecules and interaction with the 3-K background radiation field, were fitted to the reduced data of nine bands. When a gas kinetic temperature of 56 K is assumed, the best-fit condition implies a hydrogen-nucleus density of 120 per cu cm, a CO column density of 1.2 by 10 to the 15th power per sq cm, and a radial-velocity dispersion of 0.9 km/s. The relevance of these results to existing ideas concerning the Zeta Oph interstellar clouds is discussed. It is suggested that the strongest interstellar component is not circumstellar in origin but is instead part of a supernova remnant. Simple calculations are made to establish the plausibility of the supernova-remnant identification. This suggestion is also supported by Heiles's (1976) 21-cm pictures.

Structurally Resolved Abundances and Depletions in the Rho OPH Cloud

NASA Astrophysics Data System (ADS)

Seab, C.

1995-07-01

The mechanism that determines the pattern of depletion ofelements in the interstellar medium has been a problem for along time. It is clear that some of the most refractoryelements such as Si, Fe, and Mg, are heavily depleted onto theinterstellar grains. On the other hand, some elements such asS and Zn are normally either undepleted or very lightlydepleted. The difference between the two cases is notunderstood. We propose to address this question with adetailed study of the depletion patterns in the Rho Ophiuchicloud. This study is strongly based on a combination of thecapabilities of two modern instruments: the GHRS for high-resolution UV data, and the Ultra High Resolution Facility(UHRF) of the AAT. This instrument has been used to obtain NaI line profiles in the Rho Oph cloud with a resolution ofR=1,000,000. The combination of these two types of data willbe used to resolve the velocity structure of the elementdepletions in the cloud.

76 FR 24495 - Reprocessing of Reusable Medical Devices; Public Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-02

... workshop will be held in the Great Room at the FDA White Oak Conference Center, Bldg. 31, Rm. 1503, 10903... requests to make oral presentations, as well as presentation materials, must be sent to the contact person... sterilization process, potentially resulting in HAIs or other adverse patient outcomes. FDA receives reports of...

Read Across Approaches: Chemical Structure and Bioactivity ...

EPA Pesticide Factsheets

Presentation for FDA-CFSAN and ILSI workshop on Workshop on State of the Science on Alternatives to Animal Testing and Integration of Testing Strategies for Food Safety Assessments Presentation for FDA-CFSAN and ILSI workshop on Workshop: State of the Science on Alternatives to Animal Testing and Integration of Testing Strategies for Food Safety Assessments

State of the Art in the Cramer Classification Scheme and ...

EPA Pesticide Factsheets

Slide presentation at the SOT FDA Colloquium on State of the Art in the Cramer Classification Scheme and Threshold of Toxicological Concern in College Park, MD. Slide presentation at the SOT FDA Colloquium on State of the Art in the Cramer Classification Scheme and Threshold of Toxicological Concern in College Park, MD.

Alternative methods to determine headwater benefits

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

Bao, Y.S.; Perlack, R.D.; Sale, M.J.

1997-11-10

In 1992, the Federal Energy Regulatory Commission (FERC) began using a Flow Duration Analysis (FDA) methodology to assess headwater benefits in river basins where use of the Headwater Benefits Energy Gains (HWBEG) model may not result in significant improvements in modeling accuracy. The purpose of this study is to validate the accuracy and appropriateness of the FDA method for determining energy gains in less complex basins. This report presents the results of Oak Ridge National Laboratory`s (ORNL`s) validation of the FDA method. The validation is based on a comparison of energy gains using the FDA method with energy gains calculatedmore » using the MWBEG model. Comparisons of energy gains are made on a daily and monthly basis for a complex river basin (the Alabama River Basin) and a basin that is considered relatively simple hydrologically (the Stanislaus River Basin). In addition to validating the FDA method, ORNL was asked to suggest refinements and improvements to the FDA method. Refinements and improvements to the FDA method were carried out using the James River Basin as a test case.« less

IOTA: recent science and technology

NASA Astrophysics Data System (ADS)

Schloerb, F. Peter; Berger, J.-P.; Carleton, N. P.; Hagenauer, P.; Kern, P. Y.; Labeye, P. R.; Lacasse, M. G.; Malbet, F.; Millan-Gabet, R.; Monnier, J. D.; Pearlman, M. R.; Pedretti, E.; Rousselet-Perraut, K.; Ragland, S. D.; Schuller, P. A.; Traub, W. A.; Wallace, G.

2006-06-01

We present a brief review of recent scientific and technical advances at the Infrared Optical Telescope Array (IOTA). IOTA is a long-baseline interferometer located atop Mount Hopkins, Arizona. Recent work has emphasized the use of the three-telescope interferometer completed in 2002. We report on results obtained on a range of scientific targets, including AGB stars, Herbig AeBe Stars, binary stars, and the recent outburst of the recurrent nova RS Oph. We report the completion of a new spectrometer which allows visibility measurements at several high spectral resolution channels simultaneously. Finally, it is our sad duty to report that IOTA will be closed this year.

77 FR 43086 - Agency Information Collection Request; 60-Day Public Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-23

...; Sterilization of Persons in Federally Assisted Family Planning Projects--OMB No. 0937- 0166--Extension--OPHS..., subpart B (``Sterilization of Persons in Federally Assisted Family Planning Projects''). The consent form solicits information to assure voluntary and informed consent to persons undergoing sterilization in...

BIODEGRADATION OF ORGANOPHOSPHORUS PESTICIDES BY SURFACE-EXPRESSED ORGANOPHOSPHORUS HYDROLASE. (R823663)

EPA Science Inventory

Organophosphorus hydrolase (OPH) was displayed and anchored onto the surface of
Escherichia coli using an Lpp-OmpA fusion system. Production of the fusion proteins in membrane
fractions was verified by immunoblotting with OmpA antisera. inclusion of the organophosphorus
...

Association of the FDA Amendment Act with trial registration, publication, and outcome reporting.

PubMed

Phillips, Adam T; Desai, Nihar R; Krumholz, Harlan M; Zou, Constance X; Miller, Jennifer E; Ross, Joseph S

2017-07-18

Selective clinical trial publication and outcome reporting has the potential to bias the medical literature. The 2007 Food and Drug Administration (FDA) Amendment Act (FDAAA) mandated clinical trial registration and outcome reporting on ClinicalTrials.gov, a publicly accessible trial registry. Using publicly available data from ClinicalTrials.gov, FDA documents, and PubMed, we determined registration, publication, and reporting of findings for all efficacy trials supporting FDA approval of new drugs for cardiovascular disease and diabetes between 2005 and 2014, before and after the FDAAA. For published trials, we compared the published interpretation of the findings (positive, equivocal, or negative) with the FDA reviewer's interpretation. Between 2005 and 2014, the FDA approved 30 drugs for 32 indications of cardiovascular disease (n = 17) and diabetes (n = 15) on the basis of 183 trials (median per indication 5.7 (IQR, 3-8)). Compared with pre FDAAA, post-FDAAA studies were more likely to be registered (78 of 78 (100%) vs 73 of 105 (70%); p < 0.001), to be published (76 of 78 (97%) vs 93 of 105 (89%); p = 0.03), and to present findings concordant with the FDA reviewer's interpretation (74 of 76 (97%) vs 78 of 93 (84%); p = 0.004). Pre FDAAA, the FDA reviewer interpreted 80 (76%) trials as positive and 91 (98%) were published as positive. Post FDAAA, the FDA reviewer interpreted 71 (91%) trials as positive and 71 (93%) were published as positive. FDAAA was associated with increased registration, publication, and FDA-concordant outcome reporting for trials supporting FDA approval of new drugs for cardiovascular disease and diabetes.

AMPEROMETRIC THICK-FILM STRIP ELECTRODES FOR MONITORING ORGANOPHOSPHATE NERVE AGENTS BASED ON IMMOBILIZED ORGANOPHOSPHORUS HYDROLASE. (R823663)

EPA Science Inventory

An amperometric biosensor based on the immobilization of organophosphorus hydrolase
(OPH) onto screen-printed carbon electrodes is shown useful for the rapid, sensitive, and low-cost
detection of organophosphate (OP) nerve agents. The sensor relies upon the sensitive and ra...

Development of Enzyme-Containing Functional Nanoparticles

DTIC Science & Technology

2012-08-01

thoroughly studied in the presence of a 50:1 mass ratio of a stabilizer, trehalose (as shown in Figure 5). After lyophilization the enzymes were assayed...studies of OPH encapsulated nanoparticles will begin in the upcoming weeks. Initial data shows that the stabilizer, trehalose , used at a 50:1 mass

75 FR 3696 - Announcement of the Fifth Dietary Guidelines Advisory Committee Meeting and Solicitation of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-22

... HUMAN SERVICES Announcement of the Fifth Dietary Guidelines Advisory Committee Meeting and Solicitation... Services (FNCS) and Research, Education and Economics (REE); and U.S. Department of Health and Human Services (HHS), Office of Public Health and Science (OPHS). ACTION: Notice. SUMMARY: The Department of...

Outbreak of invasive listeriosis associated with the consumption of hog head cheese, Louisiana, 2010

USDA-ARS?s Scientific Manuscript database

A cluster of eight cases of laboratory-confirmed invasive listeriosis was reported to the Louisiana Office of Public Health (OPH) between February and June of 2010. All eight clinical isolates were Listeria monocytogenes, serotype 1/2a and had indistinguishable pulsed-field gel electrophoresis (PFGE...

Public voices in pharmaceutical deliberations: negotiating "clinical benefit" in the FDA's Avastin Hearing.

PubMed

Teston, Christa B; Graham, S Scott; Baldwinson, Raquel; Li, Andria; Swift, Jessamyn

2014-06-01

This article offers a hybrid rhetorical-qualitative discourse analysis of the FDA's 2011 Avastin Hearing, which considered the revocation of the breast cancer indication for the popular cancer drug Avastin. We explore the multiplicity of stakeholders, the questions that motivated deliberations, and the kinds of evidence presented during the hearing. Pairing our findings with contemporary scholarship in rhetorical stasis theory, Mol's (2002) construct of multiple ontologies, and Callon, Lascoumes, and Barthe's (2011) "hybrid forums," we demonstrate that the FDA's deliberative procedures elides various sources of evidence and the potential multiplicity of definitions for "clinical benefit." Our findings suggest that while the FDA invited multiple stakeholders to offer testimony, there are ways that the FDA might have more meaningfully incorporated public voices in the deliberative process. We conclude with suggestions for how a true hybrid forum might be deployed.

The history and contemporary challenges of the US Food and Drug Administration.

PubMed

Borchers, Andrea T; Hagie, Frank; Keen, Carl L; Gershwin, M Eric

2007-01-01

The year 2006 marks the 100th anniversary of the regulatory agency now known as the US Food and Drug Administration (FDA), the first consumer protection agency of the federal government and arguably the most influential regulatory agency in the world. The FDA thus plays an integral role in the use of pharmaceuticals, not only in the United States but worldwide. The goal of this review was to present an overview of the FDA and place its current role in the perspectives of history and contemporary needs. Relevant materials for this review were identified through a search of the English-language literature indexed on MEDLINE (through 2006) using the main search terms United States Food and Drug Administration, FDA, history of the FDA, drug approvals, drug legislation, and FDA legislation. Results from the initial searches were then explored further. The statute that created the bureau which later became the FDA established this agency to prohibit interstate commerce of adulterated foods, drinks, and drugs. The Food, Drug, and Cosmetic Act that replaced it in 1938, and subsequent food and drug laws and amendments, expanded the FDA's responsibilities to cosmetics, medical devices, biological products, and radiation-emitting products. These amendments have also established the FDA as a mainly preventive regulatory agency that relies chiefly on pre-market control. As such, the FDA has played an important role in shaping the modern pharmaceutical industry by making the scientific approach and the clinical trial process the standard for establishing safety and efficacy and by making rigorous scientific analysis the predominant component of the process for pharmaceutical regulation. As shown in this review, the evolution of the FDA can be described as a series of "crisis-legislation-adaptation" cycles: a public health crisis promoted the passage of congressional legislation, which was then followed by implementation of the law by the FDA. However, the crises the FDA faces currently are likely to be overcome only under strong and permanent leadership willing to redefine the role and procedures of the FDA with an open mind.

Evidentiary Support in Public Comments to the FDA's Center for Tobacco Products.

PubMed

Hemmerich, Natalie; Klein, Elizabeth G; Berman, Micah

2017-08-01

Electronic Nicotine Delivery Systems (ENDS) were introduced into the US market in 2007, and until recently these devices were unregulated at the federal level. In 2014, the US Food and Drug Administration (FDA) published a Notice of Proposed Rulemaking asserting its intention to regulate ENDS and requesting public comments on numerous related issues, including potential limits on the sale of flavored ENDS. This article analyzes key comments submitted to the FDA on the issue of flavor regulation in ENDS and examines the weight and credibility of the evidence presented by both supporters and opponents of regulation. It also describes the final deeming rule, published in May 2016, and the FDA's response to the evidence submitted. This is the first study to examine public comments submitted to the FDA's Center for Tobacco Products, and it concludes that opponents of regulation were more likely to rely on sources that were not peer reviewed and that were affected by conflicts of interest. In light of these findings, the FDA and the research community should develop processes to carefully and critically analyze public comments submitted to the FDA on issues of tobacco regulation. Copyright © 2017 by Duke University Press.

[Effects of Drugs Given During Pregnancy and Lactation on the Unborn Child and Neonate.

ERIC Educational Resources Information Center

Kelsey, Frances O.

This symposium presentation outlines the activity of the Food and Drug Administration (FDA) in regulating the use during pregnancy and lactation of drugs which affect the fetus and neonate. When presented with an unexpected adverse effect of a drug or of a class of drugs, the FDA can take several steps. These steps include ordering total removal…

Radial Velocity Studies of Close Binary Stars. XI.

NASA Astrophysics Data System (ADS)

Pribulla, Theodor; Rucinski, Slavek M.; Lu, Wenxian; Mochnacki, Stefan W.; Conidis, George; Blake, R. M.; DeBond, Heide; Thomson, J. R.; Pych, Wojtek; Ogłoza, Waldemar; Siwak, Michal

2006-08-01

Radial-velocity measurements and sine-curve fits to orbital radial velocity variations are presented for 10 close binary systems: DU Boo, ET Boo, TX Cnc, V1073 Cyg, HL Dra, AK Her, VW LMi, V566 Oph, TV UMi, and AG Vir. With this contribution, the David Dunlap Observatory program has reached the point of 100 published radial velocity orbits. The radial velocities have been determined using an improved fitting technique that uses rotational profiles to approximate individual peaks in broadening functions. Three systems, ET Boo, VW LMi, and TV UMi, are found to be quadruple, while AG Vir appears to be a spectroscopic triple. ET Boo, a member of a close visual binary with Pvis=113 yr, was previously known to be a multiple system, but we show that the second component is actually a close, noneclipsing binary. The new observations have enabled us to determine the spectroscopic orbits of the companion, noneclipsing pairs in ET Boo and VW LMi. A particularly interesting case is VW LMi, for which the period of the mutual revolution of the two spectroscopic binaries is only 355 days. While most of the studied eclipsing pairs are contact binaries, ET Boo is composed of two double-lined detached binaries, and HL Dra is a single-lined detached or semidetached system. Five systems of this group have been observed spectroscopically before: TX Cnc, V1073 Cyg, AK Her (as a single-lined binary), V566 Oph, and AG Vir, but our new data are of much higher quality than in the previous studies. Based on data obtained at the David Dunlap Observatory, University of Toronto, Canada.

A Continuum of Accretion Burst Behavior in Young Stars Observed by K2

NASA Astrophysics Data System (ADS)

Cody, Ann Marie; Hillenbrand, Lynne A.; David, Trevor J.; Carpenter, John M.; Everett, Mark E.; Howell, Steve B.

2017-02-01

We present 29 likely members of the young ρ Oph or Upper Sco regions of recent star formation that exhibit “accretion burst” type light curves in K2 time series photometry. The bursters were identified by visual examination of their ˜80-day light curves, though all satisfy the M< -0.25 flux asymmetry criterion for burst behavior defined by Cody et al. The burst sources represent ≈9% of cluster members with strong infrared excess indicative of circumstellar material. Higher amplitude burster behavior is correlated with larger inner disk infrared excesses, as inferred from WISE W1-W2 color. The burst sources are also outliers in their large Hα emission equivalent widths. No distinction between bursters and non-bursters is seen in stellar properties such as multiplicity or spectral type. The frequency of bursters is similar between the younger, more compact ρ Oph region, and the older, more dispersed Upper Sco region. The bursts exhibit a range of shapes, amplitudes (˜10%-700%), durations (˜1-10 days), repeat timescales (˜3-80 days), and duty cycles (˜10%-100%). Our results provide important input to models of magnetospheric accretion, in particular, by elucidating the properties of accretion-related variability in the low state between major longer duration events such as EX Lup and FU Ori type accretion outbursts. We demonstrate the broad continuum of accretion burst behavior in young stars—extending the phenomenon to lower amplitudes and shorter timescales than traditionally considered in the theory of pre-main sequence accretion history.

Problems caused by regulatory delays and lack of regulation

NASA Astrophysics Data System (ADS)

Reamer, Lynne A.

1994-12-01

An FDA perspective on some of the problems encountered during the device review process is described. Emphasis is placed on the need for communication and teamwork among all parties to make the system work. Manufacturers are encouraged to `Do it right the first time.' Pertinent questions are asked of the manufacturers and proposed solutions are presented. Day to day reality at FDA is described and document workload is revealed. Lack of regulation, or more appropriately, when less regulation is appropriate is discussed. FDA has distributed to manufacturers a new draft guidance document to help in the decisionmaking process and when to submit a 510(k) when modifications are made to a device. This and other mechanisms are in place at the FDA to streamline the review process. Manufacturers are cautioned about their decisions and to seek advice from qualified persons. FDA emphasizes that help is available and that when in doubt, call.

Human factors and the FDA's goals: improved medical device design.

PubMed

Burlington, D B

1996-01-01

The Food and Drug Administration's new human factors design requirements for medical devices were previewed by the director of the FDA's Center for Devices and Radiological Health (CDRH) at AAMI/FDA's Human Factors in Medical Devices Conference held in September 1995. Director Bruce Burlington, MD, said the FDA plans to take a closer look at how new medical devices are designed to ensure proper attention has been paid to human error prevention. As a medical practitioner who has witnessed use-related deaths and injuries, Burlington stressed the importance of the medical community's reporting use errors as they occur and manufacturers' creating easy-to-use labeling and packaging. He also called for simplicity and quality of design in medical products, and asked for a consolidated effort of all professionals involved in human factors issues to help implement and further the FDA's new human factors program. An edited version of his presentation appears here.

75 FR 57954 - Agency Information Collection Request; 30-Day Public Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-23

...: Uniform Data Set (UDS)--Reinstatement with Change--OMB No. 0990-0275-Office of Public Health Science (OPHS... approval on a revised collection, Uniform Data Set (OMB No. 0990- 0275), the tool used by the Office Minority Health (OMH) to collect program management and performance data for all OMH-funded projects...

Photometric Analysis of Overcontact Binaries AK Her, HI Dra, V1128 Tau, and V2612 Oph

NASA Astrophysics Data System (ADS)

Çalışkan, Ş.; Latković, O.; Djurašević, G.; Özavcı, İ.; Baştürk, Ö.; Cséki, A.; Şenavcı, H. V.; Kılıçoğlu, T.; Yılmaz, M.; Selam, S. O.

2014-12-01

We analyze new, high quality multicolor light curves of four overcontact binaries: AK Her, HI Dra, V1128 Tau, and V2612 Oph, and determine their orbital and physical parameters using the modeling program of G. Djurasevic and recently published results of radial velocity studies. The achieved precision in absolute masses is between 10% and 20%, and the precision in absolute radii is between 5% and 10%. All four systems are W UMa-type binaries with bright or dark spots indicative of mass and energy transfer or surface activity. We estimate the distances and the ages of the systems using the luminosities computed through our analysis, and perform an O - C study for V1128 Tau, which reveals a complex period variation that can be interpreted in terms of mass loss/exchange and either the presence of the third body, or the magnetic activity on one of the components. We conclude that further observations of these systems are needed to deepen our understanding of their nature and variability.

Far-infrared observations of young clusters embedded in the R Coronae Australis and Rho Ophiuchi dark clouds

NASA Technical Reports Server (NTRS)

Wilking, B. A.; Harvey, P. M.; Joy, M.; Hyland, A. R.; Jones, T. J.

1985-01-01

Multicolor far-infrared maps in two nearby dark clouds, R Coronae Australis and Rho Ophiuchi, have been made in order to investigate the individual contribution of low-mass stars to the energetics and dynamics of the surrounding gas and dust. Emission from cool dust associated with five low-mass stars has been detected in CrA and four in Rho Oph; their far-infrared luminosities range from 2 solar luminosities to 40 solar luminosities. When an estimate of the bolometric luminosity was possible, it was found that typically more than 50 percent of the star's energy was radiated longward of 20 microns. Meaningful limits to the far-infrared luminosities of an additional 11 association members in CrA and two in Rho Oph were also obtained. The dust optical depth surrounding the star R CrA appears to be asymmetric and may control the dynamics of the surrounding molecular gas. The implications of these results for the cloud energetics and star formation efficiency in these two clouds are discussed.

THE NEW DETECTIONS OF {sup 7}Li/{sup 6}Li ISOTOPIC RATIO IN THE INTERSTELLAR MEDIA

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

Kawanomoto, S.; Kajino, T.; Aoki, W.

We have determined the isotopic abundance ratio of {sup 7}Li/{sup 6}Li in the interstellar media (ISMs) along lines of sight to HD169454 and HD250290 using the High-Dispersion Spectrograph on the Subaru Telescope. We also observed {zeta} Oph for comparison with previous data. The observed abundance ratios were {sup 7}Li/{sup 6}Li = 8.1{sup +3.6} {sub -1.8} and 6.3{sup +3.0} {sub -1.7} for HD169454 and HD250290, respectively. These values are in reasonable agreement with those observed previously in the solar neighborhood ISMs within {+-}2{sigma} error bars and are also consistent with our measurement of {sup 7}Li/{sup 6}Li = 7.1{sup +2.9} {sub -1.6}more » for a cloud along the line of sight to {zeta} Oph. This is good evidence for homogeneous mixing and instantaneous recycling of the gas component in the Galactic disk. We also discuss several source compositions of {sup 7}Li, Galactic cosmic-ray interactions, stellar nucleosynthesis, and big bang nucleosynthesis.« less

ζ Oph and the weak-wind problem

NASA Astrophysics Data System (ADS)

Gvaramadze, V. V.; Langer, N.; Mackey, J.

2012-11-01

Mass-loss rate, ?, is one of the key parameters affecting evolution and observational manifestations of massive stars and their impact on the ambient medium. Despite its importance, there is a factor of ˜100 discrepancy between empirical and theoretical ? of late-type O dwarfs, the so-called weak-wind problem. In this Letter, we propose a simple novel method to constrain ? of runaway massive stars through observation of their bow shocks and Strömgren spheres, which might be of decisive importance for resolving the weak-wind problem. Using this method, we found that ? of the well-known runaway O9.5 V star ζ Oph is more than an order of magnitude higher than that derived from ultraviolet (UV) line fitting and is by a factor of 6-7 lower than those based on the theoretical recipe by Vink et al. and the Hα line. The discrepancy between ? derived by our method and that based on UV lines would be even more severe if the stellar wind is clumpy. At the same time, our estimate of ? agrees with that predicted by the moving reversing layer theory by Lucy.

Apsidal motion in eccentric eclipsing binaries: TV Ceti and V451 Ophiuchi

NASA Astrophysics Data System (ADS)

Wolf, M.; Diethelm, R.; Hornoch, K.

2001-07-01

Several new times of minimum light recorded with photoelectric means have been gathered for two bright eccentric eclipsing binaries TV Cet (P = 9fd1 , e = 0.055) and V451 Oph (P = 2fd2 , e = 0.013). Analysis of all available eclipse timings of TV Ceti has revealed a small motion of the line of apsides of dot ω = 0.000 30 +/- 0.000 08 deg cycle-1, corresponding to an apsidal period of U = 30 000 +/- 8 000 years. The contribution from the general relativity effects is dominant (dot ωrel/dot ω ~ 80 % ). In this system, the third body on an eccentric orbit with a period of 28.5 years is also predicted. The more precise values for the apsidal motion elements were computed for V451 Oph, where apsidal motion with a period of 170 +/- 5 years was confirmed. The corresponding internal structure constants log k2 were derived. Some of the observations reported in this paper were obtained at the South Africa Astronomical Observatory, Sutherland, South Africa.

Photometric analysis of overcontact binaries AK Her, HI Dra, V1128 Tau, and V2612 Oph

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

Çalışkan, Ş.; Özavcı, İ.; Baştürk, Ö.

2014-12-01

We analyze new, high quality multicolor light curves of four overcontact binaries: AK Her, HI Dra, V1128 Tau, and V2612 Oph, and determine their orbital and physical parameters using the modeling program of G. Djurasevic and recently published results of radial velocity studies. The achieved precision in absolute masses is between 10% and 20%, and the precision in absolute radii is between 5% and 10%. All four systems are W UMa-type binaries with bright or dark spots indicative of mass and energy transfer or surface activity. We estimate the distances and the ages of the systems using the luminosities computedmore » through our analysis, and perform an O – C study for V1128 Tau, which reveals a complex period variation that can be interpreted in terms of mass loss/exchange and either the presence of the third body, or the magnetic activity on one of the components. We conclude that further observations of these systems are needed to deepen our understanding of their nature and variability.« less

Far-infrared observations of young clusters embedded in the R Coronae Austrinae and RHO Ophiuchi dark clouds

NASA Technical Reports Server (NTRS)

Wilking, B. A.; Harvey, P. M.; Joy, M.; Hyland, A. R.; Jones, T. J.

1985-01-01

Multicolor far infrared maps in two nearby dark clouds, R Coronae Austrinae and rho Ophiuchi, were made in order to investigate the individual contribution of low mass stars to the energetics and dynamics of the surrounding gas and dust. Emission from cool dust associated with five low mass stars in Cr A and four in rho Oph was detected; their far infrared luminosities range from 2 far infrared luminosities L. up to 40 far infrared luminosities. When an estimate of the bolometric luminosity was possible, it was found that typically more than 50% of the star's energy was radiated longward of 20 micrometers. meaningful limits to the far infrared luminosities of an additional eleven association members in Cr A and two in rho Oph were also obtained. The dust optical depth surrounding the star R Cr A appears to be asymmetric and may control the dynamics of the surrounding molecular gas. The implications of the results for the cloud energetics and star formation efficiency in these two clouds are discussed.

Evaluation of efficacy of heartworm preventive products at the FDA.

PubMed

Hampshire, Victoria A

2005-10-24

The Center for Veterinary Medicine, U.S. Food and Drug Administration (FDA/CVM) has authority under the United States Code 21 under Section 514.80 to monitor for adverse experiences of approved animal products. Although veterinarians voluntarily report suspect drug-related events to manufacturers, firms that market FDA-approved animal products must report serious events to the FDA within 15 working days of the veterinarian or pet-owner's call to them. Under the present regulations, canine heartworm preventatives are approved for 100% efficacy after testing in laboratory and field conditions. The report of lack of efficacy against heartworm larvae is a serious adverse drug event because the resulting condition or the treatment of the condition is life threatening. Information on lack of effect that are deemed possibly, probably, or definitely drug-related available for review under generic product on the FDA/CVM website Surveillance of these reports indicates there are some failures for virtually all heartworm prevention product categories. Most failures have been reported in heartworm-endemic states. At this time, it is unclear whether these are representative of the rare occurrences of failure that have been in existence for a long time, but not reported regularly or promptly, or whether there is a true increase in complaints of ineffectiveness and real variability between products. This paper discusses methods, personnel, and procedures in place in the Division of Surveillance that will aid the FDA to better assess heartworm preventive treatment failures. It discusses scoring paradigms presently utilized by FDA/CVM to assess severity of complaints of lack of efficacy against heartworms, and welcomes audience input as to how to improve existing processes. Results suggest that more comprehensive reporting will provide FDA/CVM more accurate surveillance information regarding efficacy problems. Such practices will permit FDA/CVM to better interpret both incidence and severity of in-effect and possible patterns of emerging resistance and to convey this in any necessary updated labeling. It also indicates that as part of that process, practitioners should return to a more conservative testing schedule.

Paramagnetic oxotungsten(V) complexes containing the hydrotris(3,5-dimethylpyrazol-1-yl)borate ligand.

PubMed

Sproules, Stephen; Eagle, Aston A; Taylor, Michelle K; Gable, Robert W; White, Jonathan M; Young, Charles G

2011-05-16

Sky-blue Tp*WOCl(2) has been synthesized from the high-yielding reaction of Tp*WO(2)Cl with boron trichloride in refluxing toluene. Dark-red Tp*WOI(2) was prepared via thermal decarbonylation followed by aerial oxidation of Tp*WI(CO)(3) in acetonitrile. From these precursors, an extensive series of mononuclear tungstenyl complexes, Tp*WOXY [X = Cl(-), Y = OPh(-), SPh(-); X = Y = OPh(-), 2-(n-propyl)phenolate (PP(-)), SPh(-), SePh(-); XY = toluene-3,4-dithiolate (tdt(2-)), quinoxaline-2,3-dithiolate (qdt(2-)), benzene-1,2-diselenolate (bds(2-)); Tp* = hydrotris(3,5-dimethylpyrazol-1-yl)borate], was prepared by metathesis with the respective alkali-metal salt of X(-)/XY(2-) or (NHEt(3))(2)(qdt). The complexes were characterized by microanalysis, mass spectrometry, electrochemistry, IR, electron paramagnetic resonance (EPR), and electronic absorption spectroscopies, and X-ray crystallography (for X = Y = OPh(-), PP(-), SPh(-); XY = bds(2-)). The six-coordinate, distorted-octahedral tungsten centers are coordinated by terminal oxo [W≡O = 1.689(6)-1.704(3) Å], tridentate Tp*, and monodentate or bidentate O/S/Se-donor ligands. Spin Hamiltonian parameters derived from the simulation of fluid-solution X-band EPR spectra revealed that the soft-donor S/Se ligand complexes had larger g values and smaller (183)W hyperfine coupling constants than the less covalent hard-donor O/Cl species. The former showed low-energy ligand-to-metal charge-transfer bands in the near-IR region of their electronic absorption spectra. These oxotungsten(V) complexes display lower reduction potentials than their molybdenum counterparts, underscoring the preference of tungsten for higher oxidation states. Furthermore, the protonation of the pyrazine nitrogen atoms of the qdt(2-) ligand has been examined by spectroelectrochemistry; the product of the one-electron reduction of [Tp*WO(qdtH)](+) revealed usually intense low-energy bands.

Absolute dimensions of eclipsing binaries. XXVI.. Setting a new standard: Masses, radii, and abundances for the F-type systems AD Bootis VZ Hydrae, and WZ Ophiuchi

NASA Astrophysics Data System (ADS)

Clausen, J. V.; Torres, G.; Bruntt, H.; Andersen, J.; Nordström, B.; Stefanik, R. P.; Latham, D. W.; Southworth, J.

2008-09-01

Context: Accurate mass, radius, and abundance determinations from binaries provide important information on stellar evolution, fundamental to central fields in modern astrophysics and cosmology. Aims: We aim to determine absolute dimensions and abundances for the three F-type main-sequence detached eclipsing binaries AD Boo, VZ Hya, and WZ Oph and to perform a detailed comparison with results from recent stellar evolutionary models. Methods: uvby light curves and uvbyβ standard photometry were obtained with the Strömgren Automatic Telescope at ESO, La Silla, radial velocity observations at CfA facilities, and supplementary high-resolution spectra with ESO's FEROS spectrograph. State-of-the-art methods were applied for the analyses: the EBOP and Wilson-Devinney binary models, two-dimensional cross-correlation and disentangling, and the VWA abundance analysis tool. Results: Masses and radii that are precise to 0.5-0.7% and 0.4-0.9%, respectively, have been established for the components, which span the ranges of 1.1 to 1.4 M⊙ and 1.1 to 1.6 R⊙. The [Fe/H] abundances are from -0.27 to +0.10, with uncertainties between 0.07 and 0.15 dex. We find indications of a slight α-element overabundance of [α/Fe] ˜ + 0.1 for WZ Oph. The secondary component of AD Boo and both components of WZ Oph appear to be slightly active. Yale-Yonsai and Victoria-Regina evolutionary models fit the components of AD Boo and VZ Hya almost equally well, assuming coeval formation, at ages of about 1.75/1.50 Gyr (AD Boo) and 1.25/1.00 Gyr (VZ Hya). BaSTI models, however, predict somewhat different ages for the primary and secondary components. For WZ Oph, the models from all three grids are significantly hotter than observed. A low He content, decreased envelope convection coupled with surface activity, and/or higher interstellar absorption would remove the discrepancy, but its cause has not been definitively identified. Conclusions: We have demonstrated the power of testing and comparing recent stellar evolutionary models using eclipsing binaries, provided their abundances are known. The strongest limitations and challenges are set by T_eff and interstellar absorption determinations, and by their effects on and correlation with abundance results. Based on observations carried out at the Strömgren Automatic Telescope (SAT) and the 1.5 m and 2.2 m telescopes at ESO, La Silla, Chile (62.L-0284, 63.H-0080, 71.D-0554); the 1.5 m Wyeth reflector at the Oak Ridge Observatory, Harvard, Massachusetts, USA; the 1.5-m Tillinghast reflector and the Multiple Mirror Telescope at the F. L. Whipple Observatory, Mt. Hopkins, Arizona.

77 FR 26768 - Food and Drug Administration/International Society for Pharmaceutical Engineering Cosponsorship...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-07

... year, FDA speakers provide updates on current efforts affecting the development of global regulatory strategies, while industry professionals from some of today's leading pharmaceutical companies present case... hear directly from FDA experts and representatives of global regulatory authorities on best practices...

Intracellular esterase activity in living cells may distinguish between metastatic and tumor-free lymph nodes.

PubMed

Afrimzon, Elena; Deutsch, Assaf; Shafran, Yana; Zurgil, Naomi; Sandbank, Judith; Pappo, Itzhak; Deutsch, Mordechai

2008-01-01

One of the major clinical problems in breast cancer detection is the relatively high incidence of occult lymph node metastases undetectable by standard procedures. Since the ascertainment of breast cancer stage determines the following treatment, such a "hypo-diagnosis" leads to inadequate therapy, and hence is detrimental for the outcome and survival of the patients. The purpose of our study was to investigate functional metabolic characteristics of living cells derived from metastatic and tumor-free lymph nodes of breast cancer (BC) patients. Our methodology is based on the ability of living cells to hydrolyze fluorescein diacetate (FDA) by intracellular esterases and on the association of FDA hydrolysis rates with a specific cell status, both in physiological and pathological conditions. The present study demonstrates a significant difference in the ability to utilize FDA by lymph node cells derived from metastatic and tumor-free lymph nodes in general average, as well as in the metastatic and tumor-free lymph nodes of individual patients. Cells from metastatic lymph nodes had a higher capacity for FDA hydrolysis, and increased this activity after additional activation by autologous tumor tissue (tt). The association between increased FDA hydrolysis rate and activated T lymphocytes and antigen-presenting cells (APC) was shown. The results of the present study may contribute to predicting the risk of involvement of seemingly "tumor-free" axillary lymph nodes in occult metastatic processes, and to reducing false-negative results of axillary examination.

The educational potential of direct-to-consumer prescription drug advertising.

PubMed

Kaphingst, Kimberly A; DeJong, William

2004-01-01

Food and Drug Administration (FDA) regulations for direct-to-consumer (DTC) prescription drug advertising allow broadcast advertisements with incomplete risk information if the ads refer consumers to physicians, pharmacists, and supplemental information sources. New research reveals several problems with both television advertisements and supplemental text materials that might compromise their ability to meet the FDA's requirement for "fair balance" in the presentation of risks and benefits. In response, we make several recommendations to improve the educational quality of DTC advertising, which can be implemented through either voluntary agreements or revised FDA regulations.

76 FR 43847 - Poison Prevention Packaging Requirements; Exemption of Powder Formulations of Colesevelam...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-22

... FDA-regulated drug, biologic, medical device, dietary supplement, or cosmetic. (See http://www.fda.gov... powders generally present a low risk because they are more difficult to ingest, particularly in large quantities. Generally, with the exception of caustics, the primary exposure risk associated with powders is...

Ophiuchus

NASA Astrophysics Data System (ADS)

Murdin, P.

2000-11-01

(the Serpent-bearer; abbrev. Oph, gen. Ophiuchi; area 948 sq. deg.) An equatorial constellation which lies between Hercules and Scorpius, and culminates at midnight in mid-June. The ecliptic cuts across the southern part of Ophiuchus, but the constellation is not included among the constellations of the zodiac. Ophiuchus is usually said to represent Asclepius, the Greek god of medicine, and is sh...

75 FR 57955 - Agency Information Collection Request; 30-Day Public Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-23

... approval on a revised collection, Uniform Data Set (OMB No. 0990- 0275), the tool used by the Office... notice directly to the OS OMB Desk Officer; faxed to OMB at 202-395-5806. Proposed Project: Uniform Data Set (UDS)--Reinstatement with Change--OMB No. 0990-0275-Office of Public Health Science (OPHS...

Ensuring the safe and effective FDA regulation of fecal microbiota transplantation

PubMed Central

Sachs, Rachel E.; Edelstein, Carolyn A.

2015-01-01

Scientists, policymakers, and medical professionals alike have become increasingly worried about the rise of antibiotic resistance, and the growing number of infections due to bacteria like Clostridium difficile, which cause a significant number of deaths and are imposing increasing costs on our health care system. However, in the last few years, fecal microbiota transplantation (FMT), the transplantation of stool from a healthy donor into the bowel of a patient, has emerged as a startlingly effective means to treat recurrent C. difficile infections. At present, the FDA is proposing to regulate FMT as a biologic drug. However, this proposed classification is both underregulatory and overregulatory. The FDA's primary goal is to ensure that patients have access to safe, effective treatments—and as such they should regulate some aspects of FMT more stringently than they propose to, and others less so. This essay will examine the nature of the regulatory challenges the FDA will face in deciding to regulate FMT as a biologic drug, and will then evaluate available policy alternatives for the FDA to pursue, ultimately concluding that the FDA ought to consider adopting a hybrid regulatory model as it has done in the case of cord blood. PMID:27774199

FDA has the legal authority to adopt a threshold of toxicological concern (TTC) for substances in food at trace levels.

PubMed

Hahn, Martin J

2010-01-01

It now is possible to detect many substances in the parts per trillion and further advances will allow for even lower levels of detection. Many of these substances may always have been present in the food supply, but escaped detection. Others may have been introduced through environmental contamination, changes in food processing, sourcing of ingredients from different manufacturers or countries, and a myriad of other reasons. The adulteration and various safety provisions of the Federal Food, Drug, and Cosmetic Act (FDCA), principles of statutory construction, and case law, provide FDA with the legal authority to adopt the threshold concept. FDA and the courts have long recognized it is possible to establish safe levels of poisonous or deleterious substances found in foods. FDA routinely conducts such an analysis under the general adulteration provisions of the FDCA and has identified safe levels for numerous environmental contaminants found in food. The courts have recognized that through its exercise of enforcement discretion, FDA has the legal authority to establish non-binding defect action levels for contaminants. FDA similarly could implement the Threshold of Toxicological Concern (TTC) through its exercise of enforcement discretion.

Biologics as countermeasures for acute radiation syndrome: where are we now?

PubMed

Singh, Vijay K; Romaine, Patricia L P; Newman, Victoria L

2015-04-01

Despite significant scientific advances toward the development of a safe, nontoxic and effective radiation countermeasure for acute radiation syndrome (ARS) over the past six decades, no drug has been approved by the US FDA. Several biologics are currently under development as radiation countermeasures for ARS, of which three have received FDA Investigational New Drug (IND) status for clinical investigation. Presently, two of these agents, entolimod (CBLB502) and HemaMax (recombinant human IL-12) are progressing with large animal studies and clinical trials. Neupogen (G-CSF, filgrastim) has recently been recommended for approval by an FDA Advisory Committee. Filgrastim, GM-CSF (Leukine, sargramostim), and PEGylated G-CSF (Neulasta) have high potential and well-documented therapeutic effects in countering myelosuppression and may receive full licensing approval by the FDA in the future. The former two biologics are available in the US Strategic National Stockpile (SNS) for use in the event of nuclear or radiological emergency. The Emergency Use Authorization (EAU) application for entolimod may be filed soon with the FDA. Biologics are attractive agents that are progressing along the path for FDA approval, to fill the unmet need for ARS countermeasures.

Regulation of prescription drug promotion: direct-to-consumer advertising.

PubMed

Baylor-Henry, M; Drezin, N A

1998-01-01

The US Food and Drug Administration (FDA) is responsible for regulating the information on prescription drugs disseminated by sponsors to health care providers and consumers to ensure that it is truthful and not misleading, and that it presents a fair balance of benefit and risk information. Thus the public health is both protected and promoted by the dissemination of honest, accurate information about regulated products. This paper discusses the regulatory requirements for promotional materials for prescription drugs and the standards used by the FDA to evaluate these materials. It also discusses the agency's views on direct-to-consumer advertising, the enforcement actions that are available to the FDA, the process used by the FDA to determine what action should be taken and when, and what remedies are available.

Anatomy of a recall.

PubMed

Dzanis, David A

2008-08-01

Pet foods on the market that are contaminated or otherwise present a health risk to humans or animals may be subject to a recall under US Food and Drug Administration (FDA) regulations. Legally, all recalls are "voluntary," but there is little incentive for companies to refuse a request by FDA to conduct a recall. While the firm does the bulk of the work, FDA oversees all aspects of a recall to help ensure that violative product is swiftly removed from the market. A recent new federal law will require FDA to improve its abilities to detect outbreaks of pet food-borne illness, respond to a contamination incident, and communicate with industry and the public on the matter of recalls. Veterinarians play a key role in detecting and reporting pet food-borne illness.

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

Pan, Zhichen; Li, Di; Qian, Lei

We present 2.5-square-degree C{sub 2}H N = 1–0 and N{sub 2}H{sup +} J = 1–0 maps of the ρ Ophiuchi molecular cloud complex. These are the first large-scale maps of the ρ Ophiuchi molecular cloud complex with these two tracers. The C{sub 2}H emission is spatially more extended than the N{sub 2}H{sup +} emission. One faint N{sub 2}H{sup +} clump, Oph-M, and one C{sub 2}H ring, Oph-RingSW, are identified for the first time. The observed C{sub 2}H-to-N{sub 2}H{sup +} abundance ratio ([C{sub 2}H]/[N{sub 2}H{sup +}]) varies between 5 and 110. We modeled the C{sub 2}H and N{sub 2}H{sup +} abundancesmore » with 1D chemical models, which show a clear decline of [C{sub 2}H]/[N{sub 2}H{sup +}] with chemical age. Such an evolutionary trend is little affected by temperatures when they are below 40 K. At high density ( n {sub H} > 10{sup 5} cm{sup −3}), however, the time it takes for the abundance ratio to drop at least one order of magnitude becomes less than the dynamical time (e.g., turbulence crossing time of ∼10{sup 5} yr). The observed [C{sub 2}H]/[N{sub 2}H{sup +}] difference between L1688 and L1689 can be explained by L1688 having chemically younger gas in relatively less dense regions. The observed [C{sub 2}H]/[N{sub 2}H{sup +}] values are the results of time evolution, accelerated at higher densities. For the relatively low density regions in L1688 where only C{sub 2}H emission was detected, the gas should be chemically younger.« less

Enhanced caspase activity contributes to aortic wall remodeling and early aneurysm development in a murine model of Marfan syndrome.

PubMed

Emrich, Fabian C; Okamura, Homare; Dalal, Alex R; Penov, Kiril; Merk, Denis R; Raaz, Uwe; Hennigs, Jan K; Chin, Jocelyn T; Miller, Miquell O; Pedroza, Albert J; Craig, Juliana K; Koyano, Tiffany K; Blankenberg, Francis G; Connolly, Andrew J; Mohr, Friedrich W; Alvira, Cristina M; Rabinovitch, Marlene; Fischbein, Michael P

2015-01-01

Rupture and dissection of aortic root aneurysms remain the leading causes of death in patients with the Marfan syndrome, a hereditary connective tissue disorder that affects 1 in 5000 individuals worldwide. In the present study, we use a Marfan mouse model (Fbn1(C1039G/+)) to investigate the biological importance of apoptosis during aneurysm development in Marfan syndrome. Using in vivo single-photon emission computed tomographic-imaging and ex vivo autoradiography for Tc99m-annexin, we discovered increased apoptosis in the Fbn1(C1039G/+) ascending aorta during early aneurysm development peaking at 4 weeks. Immunofluorescence colocalization studies identified smooth muscle cells (SMCs) as the apoptotic cell population. As biological proof of concept that early aortic wall apoptosis plays a role in aneurysm development in Marfan syndrome, Fbn1(C1039G/+) mice were treated daily from 2 to 6 weeks with either (1) a pan-caspase inhibitor, Q-VD-OPh (20 mg/kg), or (2) vehicle control intraperitoneally. Q-VD-OPh treatment led to a significant reduction in aneurysm size and decreased extracellular matrix degradation in the aortic wall compared with control mice. In vitro studies using Fbn1(C1039G/+) ascending SMCs showed that apoptotic SMCs have increased elastolytic potential compared with viable cells, mostly because of caspase activity. Moreover, in vitro (1) cell membrane isolation, (2) immunofluorescence staining, and (3) scanning electron microscopy studies illustrate that caspases are expressed on the exterior cell surface of apoptotic SMCs. Caspase inhibition attenuates aneurysm development in an Fbn1(C1039G/+) Marfan mouse model. Mechanistically, during apoptosis, caspases are expressed on the cell surface of SMCs and likely contribute to elastin degradation and aneurysm development in Marfan syndrome. © 2014 American Heart Association, Inc.

77 FR 55845 - Anti-Infective Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-11

... and Drug Administration (FDA). The meeting will be open to the public. Name of Committee: Anti... indication of treatment of inhalational anthrax. FDA intends to make background material available to the... of the general nature of the evidence or arguments they wish to present, the names and addresses of...

Direct-to-Consumer Broadcast Advertisements for Pharmaceuticals: Off-Label Promotion and Adherence to FDA Guidelines.

PubMed

Klara, Kristina; Kim, Jeanie; Ross, Joseph S

2018-05-01

Direct-to-consumer (DTC) advertisements for prescription drugs in the United States are regulated by the Food and Drug Administration (FDA). Off-label promotion, or the advertisement of a drug for an indication not approved by the FDA, is prohibited. Our objective was to examine the presence of off-label promotion in broadcast DTC ads and to assess their adherence to FDA guidelines mandating fair balance in presentation of risks and benefits and prohibiting misleading advertisement claims. All English-language broadcast DTC ads for prescription drugs that aired in the United States from January 2015 to July 2016 were obtained from AdPharm, an online collection of healthcare advertisements. Ad length was measured and adherence to FDA guidelines was assessed for several categories: key regulatory items, indicators of false or misleading ads, and indicators of fair balance in presentation of risks and benefits. Our sample included 97 unique DTC ads, representing 60 unique drugs and 67 unique drug-indication combinations. No ads described drug risks quantitatively, whereas drug efficacy was presented quantitatively in 25 (26%) ads. Thirteen (13%) ads, all for diabetes medications, suggested off-label uses for weight loss and blood pressure reduction. The most commonly advertised drugs were indicated for the treatment of inflammatory conditions (n = 12; 18%), diabetes or diabetic neuropathy (n = 11; 16%), bowel or bladder dysfunction (n = 6; 9%), and infections or allergic reaction (n = 6; 9%). More than three-quarters (n = 51; 76%) advertised drugs to treat chronic conditions. Few broadcast DTC ads were fully compliant with FDA guidelines. The overall quality of information provided in ads was low, and suggestions of off-label promotion were common for diabetes medications. The impact of current DTC ads and off-label marketing on patient and prescriber decisions merits further scrutiny.

Training the Research Integrity Officers (RIO): The Federally Funded "RIO Boot Camps" Backward Design to Train for the Future

ERIC Educational Resources Information Center

Wright, David E.; Schneider, Paige P.

2010-01-01

Research institutions receiving U. S. Public Health Service (PHS) funding must assure the Office of Research Integrity (ORI/OPHS/DHHS) that policies and procedures are in place conforming to 42 CFR 93 to investigate allegations of Misconduct in Research, defined as fabrication or falsification of research data, or plagiarism. An institutional…

Stellar model chromospheres. VIII - 70 Ophiuchi A /K0 V/ and Epsilon Eridani /K2 V/

NASA Technical Reports Server (NTRS)

Kelch, W. L.

1978-01-01

Model atmospheres for the late-type active-chromosphere dwarf stars 70 Oph A and Epsilon Eri are computed from high-resolution Ca II K line profiles as well as Mg II h and k line fluxes. A method is used which determines a plane-parallel homogeneous hydrostatic-equilibrium model of the upper photosphere and chromosphere which differs from theoretical models by lacking the constraint of radiative equilibrium (RE). The determinations of surface gravities, metallicities, and effective temperatures are discussed, and the computational methods, model atoms, atomic data, and observations are described. Temperature distributions for the two stars are plotted and compared with RE models for the adopted effective temperatures and gravities. The previously investigated T min/T eff vs. T eff relation is extended to Epsilon Eri and 70 Oph A, observed and computed Ca II K and Mg II h and k integrated emission fluxes are compared, and full tabulations are given for the proposed models. It is suggested that if less than half the observed Mg II flux for the two stars is lost in noise, the difference between an active-chromosphere star and a quiet-chromosphere star lies in the lower-chromospheric temperature gradient.

Interactions of stars and interstellar matter in Scorpio Centaurus

NASA Technical Reports Server (NTRS)

De Geus, E. J.

1992-01-01

The interaction of the stars in the Scorpio-Centaurus OB association with the ambient interstellar medium is investigated. Large H I loops in the fourth galactic quadrant are parts of expanding shells surrounding the subgroups of the association. The energy output of the original stellar population of the subgroups is calculated. Comparison with the kinetic energy of the shells shows that the energy output of the stars in the subgroups is sufficient to form the shells. The masses of the shells are consistent with those of giant molecular clouds GMCs, suggesting that the shells consist of swept-up, original GMC material. The influence of the expanding shell around the young Upper-Scorpius subgroup on the morphology of the Ophiuchus molecular clouds is investigated. The interaction of the shell with the Ophiuchus clouds accounts for the presence of a slow shock and for the shape of the elongated dark clouds connected to the Rho Oph dense cloud. The close passage of the trajectory of the runaway star Zeta Oph by the center of the Upper-Scorpius shell, combined with the time scale of formation of the shell, strongly suggests that the star has originated in the Upper-Scorpius subgroup.

THEORETICAL p-MODE OSCILLATION FREQUENCIES FOR THE RAPIDLY ROTATING {delta} SCUTI STAR {alpha} OPHIUCHI

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

Deupree, Robert G., E-mail: bdeupree@ap.smu.ca

2011-11-20

A rotating, two-dimensional stellar model is evolved to match the approximate conditions of {alpha} Oph. Both axisymmetric and nonaxisymmetric oscillation frequencies are computed for two-dimensional rotating models which approximate the properties of {alpha} Oph. These computed frequencies are compared to the observed frequencies. Oscillation calculations are made assuming the eigenfunction can be fitted with six Legendre polynomials, but comparison calculations with eight Legendre polynomials show the frequencies agree to within about 0.26% on average. The surface horizontal shape of the eigenfunctions for the two sets of assumed number of Legendre polynomials agrees less well, but all calculations show significant departuresmore » from that of a single Legendre polynomial. It is still possible to determine the large separation, although the small separation is more complicated to estimate. With the addition of the nonaxisymmetric modes with |m| {<=} 4, the frequency space becomes sufficiently dense that it is difficult to comment on the adequacy of the fit of the computed to the observed frequencies. While the nonaxisymmetric frequency mode splitting is no longer uniform, the frequency difference between the frequencies for positive and negative values of the same m remains 2m times the rotation rate.« less

The new Be-type star HD 147196 in the Rho Ophiuchi dark cloud region

NASA Technical Reports Server (NTRS)

The, P. S.; Perez, M. R.; De Winter, D.; Van Den Ancker, M. E.

1993-01-01

The newly discovered hot-emission line star, HD 147196 in the Rho Oph dark cloud region was observed spectroscopically and photometrically and high and low resolution IUE spectra were obtained. The finding of Irvine (1990) that this relatively bright star show its H-alpha-line in emission is confirmed. Previous H-alpha-surveys of the Rho Oph star-forming region did not detect HD 147196 as an H-alpha-emission star, meaning that it must recently be very active and has perhaps transformed itself from a B-type star at shell phase to a Be-phase. The Mg II h + k resonance lines are in absorption and they appear to be interstellar in nature, which means that either the abundance of Mg in the extended atmosphere of the star is low or that the shell is not extended enough to produce emission lines of Mg II. Photometric observations of this B8 V type star do not show any variations during at least the years covered by our monitoring or any excess of NIR radiation in its spectral energy distribution up to the M-passband at 4.8 microns.

FDA regulation of adult stem cell therapies as used in sports medicine.

PubMed

Chirba, Mary Ann; Sweetapple, Berkley; Hannon, Charles P; Anderson, John A

2015-02-01

In sports medicine, adult stem cells are the subject of great interest. Several uses of stem cells are under investigation including cartilage repair, meniscal regeneration, anterior cruciate ligament reconstruction, and tendinopathy. Extensive clinical and basic science research is warranted as stem cell therapies become increasingly common in clinical practice. In the United States, the Food and Drug Administration (FDA) is responsible for regulating the use of stem cells through its "Human Cells, Tissues, and Cellular and Tissue-Based Products" regulations. This report provides a brief overview of FDA regulation of adult stem cells. Several common clinical case scenarios are then presented that highlight how stem cells are currently being used in sports medicine and how current FDA regulations are likely to affect the physicians who use them. In the process, it explains how a variety of factors in sourcing and handling these cells, particularly the extent of cell manipulation, will affect what a physician can and cannot do without first obtaining the FDA's express approval. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Interstellar gas phase abundance of carbon, oxygen, nitrogen, copper, gallium, germanium, and krypton toward Zeta Ophiuchi

NASA Technical Reports Server (NTRS)

Cardelli, Jason A.; Savage, Blair D.; Ebbets, Dennis C.

1991-01-01

An analysis of weak (less than 10 mA) UV interstellar absorption line data obtained for the line of sight to the O9.5 IV star Zeta Oph is presented. Measurements of weak semiforbidden lines of N I, O I, Cu II, and a new UV detection of Na I are reported along with a small upper limit for C II. Interstellar detections of Ga II, Ge II, and Kr I are also presented. Ga, Ge, and Kr represent the heaviest elements detected in the ISM. A comparison of the derived column densities to cosmic abundances shows Ga to be depleted by about -1.2 dex while Ge is overabundant by +0.2 dex. Assuming Kr to be undepleted, a logarithmic cosmic abundance of Kr/H = 2.95 is obtained on the scale where H = 12.00.

Overcoming obstacles to repurposing for neurodegenerative disease

PubMed Central

Shineman, Diana W; Alam, John; Anderson, Margaret; Black, Sandra E; Carman, Aaron J; Cummings, Jeffrey L; Dacks, Penny A; Dudley, Joel T; Frail, Donald E; Green, Allan; Lane, Rachel F; Lappin, Debra; Simuni, Tanya; Stefanacci, Richard G; Sherer, Todd; Fillit, Howard M

2014-01-01

Repurposing Food and Drug Administration (FDA)-approved drugs for a new indication may offer an accelerated pathway for new treatments to patients but is also fraught with significant commercial, regulatory, and reimbursement challenges. The Alzheimer’s Drug Discovery Foundation (ADDF) and the Michael J. Fox Foundation for Parkinson’s Research (MJFF) convened an advisory panel in October 2013 to understand stakeholder perspectives related to repurposing FDA-approved drugs for neurodegenerative diseases. Here, we present opportunities on how philanthropy, industry, and government can begin to address these challenges, promote policy changes, and develop targeted funding strategies to accelerate the potential of FDA-approved repurposed drugs. PMID:25356422

New 3-D coordination polymers based on semi-rigid V-shape tetracarboxylates

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

Huang, Jing-Jing; Xu, Wei; Wang, Yan-Ning

Under the hydrothermal conditions, the reactions of transition-metal salts, tetracarboxylic acids and N,N′-donor ligands yielded three new coordination polymers as [Cu{sub 4}(fph){sub 2}(bpe){sub 3}(H{sub 2}O){sub 2}]·2H{sub 2}O (fph=4,4′-(hexafluoroisopropylidene)diphthalate, bpe=1,2-bis(pyridyl)ethylene) 1, [Co{sub 2}(fph)(bpa){sub 2}(H{sub 2}O){sub 2}]·3H{sub 2}O (bpa=1,2-bis(pyridyl)ethylane) 2, and [Ni(H{sub 2}O)(H{sub 2}oph)(bpa)] (oph=4,4′-oxydiphthalate) 3. X-ray single-crystal diffraction analysis revealed that the title three compounds all possess the three-dimensional (3-D) network structures. For compound 1, the fph molecules first link the Cu{sup 2+} ions into a two-dimensional (2-D) wave-like layer with a (4,4) topology. The bpe molecules act as the second linkers, extending the 2-D layers into a 3-D network. Formore » compound 2, the fph molecules still serve as the first connectors, linking the Co{sup 2+} ions into a one-dimensional (1-D) tube-like chain. Then the bpa molecules propagate the chains into a 3-D (4,4,4)-connected network. In the formation of the 3-D network of compound 3, the oph molecule does not play a role. The bpa molecules as well as the water molecules act as a mixed bridge. Only a kind of 4-connected metal node is observed in compound 3. The magnetic properties of compounds 1–3 were investigated and all exhibit the predominant antiferromegnetic magnetic behaviors. - Graphical abstract: Structures of three semi-rigid V-shape tetracarboxylate-based coordination polymers were reported, and their magnetic properties were investigated. - Highlights: • Structures of three tetracarboxylate-based coordination polymers were reported. • Role of organic bases in metal–tetracarboxylate compounds was discussed. • Characters of V-shape and semi-rigidity for tetracarboxylate play a key role in crystal growth. • Their magnetic properties were investigated.« less

US FDA perspective on regulatory issues affecting circulatory assist devices.

PubMed

Sapirstein, Wolf; Chen, Eric; Swain, Julie; Zuckerman, Bram

2006-11-01

There has been a rapid development in mechanical circulatory support systems in the decade since the US FDA first approved a mechanical device to provide the circulatory support lacking from a failing heart. Devices are presently approved for marketing by the FDA to replace a failing ventricle, the Ventricular Assist Device or the entire heart, Total Artificial Heart. Contemporaneous with, and permitted by, improvement in technology and design, devices have evolved from units located extracorporeally to paracorporeal systems and totally implanted devices. Clinical studies have demonstrated a parallel improvement in the homeostatic adequacy of the circulatory support provided. Thus, while the circulatory support was initially tolerated for short periods to permit recovery of cardiac function, this technology eventually provided effective circulatory support for increasing periods that permitted the FDA to approve devices for bridging patients in end-stage cardiac failure awaiting transplant and eventually a device for destination therapy where patients in end-stage heart failure are not cardiac transplant candidates. The approved devices have relied on displacement pumps that mimic the pulsatility of the physiological system. Accelerated development of more compact devices that rely on alternative pump mechanisms have challenged both the FDA and device manufacturers to assure that the regulatory requirements for safety and effectiveness are met for use of mechanical circulatory support systems in expanded target populations. An FDA regulatory perspective is reviewed of what can be a potentially critical healthcare issue.

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

Samec, R. G.; Melton, R. A.; Figg, E. R.

GSC 3355 0394 has an EB-type light curve, which is dominated by hot and cool spot activities. It displays night-to-night variations in light-curve shapes. The period study yields six new times of minimum light and the first precision ephemeris, HJD T{sub min}I = 2, 454, 408.9547 {+-} 0.0017 + 0.4621603 {+-} 0.0000008d*E. VR{sub c}I{sub c} standard magnitudes are presented. BVRI Wilson synthetic light-curve solutions are calculated for both a Mode 4 (V1010 Oph-type, semidetached, more massive component filling its Roche lobe) configuration and a Mode 3, contact configuration (fill-out 100% or critical contact). The critical contact is the lowest residualmore » solution. Four major spot regions are needed to model this binary, at least one is evidently a stream spot.« less

An IRAS/ISSA Survey of Bow Shocks Around Runaway Stars

NASA Technical Reports Server (NTRS)

Buren, David Van

1995-01-01

We searched for bow shock-like objects like those known around Oph and a Cam near the positions of 183 runaway stars. Based primarily on the presence and morphology of excess 60 micron emission we identify 56 new candidate bow shocks, for which we determine photometric and morphological parameters. Previously only a dozen or so were known. Well resolved structures are present around 25 stars. A comparison of the distribution of symmetry axes of the infrared nebulae with that of their proper motion vectors indicates that these two directions are very significantly aligned. The observed alignment strongly suggests that the structures we see arise from the interaction of stellar winds with the interstellar medium, justifying the identification of these far-infrared objects as stellar wind bow shocks.

76 FR 20588 - FDA Food Safety Modernization Act: Focus on Preventive Controls for Facilities; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-13

.... FDA-2011-N-0251] FDA Food Safety Modernization Act: Focus on Preventive Controls for Facilities... comment. SUMMARY: The Food and Drug Administration (FDA) is announcing a public meeting entitled ``FDA... controls for facilities provisions of the recently enacted FDA Food Safety Modernization Act (FSMA). FDA is...

Drugs@FDA: FDA Approved Drug Products

MedlinePlus

... Cosmetics Tobacco Products Home Drug Databases Drugs@FDA Drugs@FDA: FDA Approved Drug Products Share Tweet Linkedin Pin it More sharing ... Download Drugs@FDA Express for free Search by Drug Name, Active Ingredient, or Application Number Enter at ...

Avelumab Impresses in Merkel Cell Carcinoma.

PubMed

2017-06-01

The PD-L1 inhibitor avelumab-approved by the FDA in March for the treatment of Merkel cell carcinoma-demonstrated a high number of durable responses in an international, open-label, prospective phase II study. The results of the study, which supported the FDA's decision, were presented in April at the American Association for Cancer Research (AACR) Annual Meeting 2017. ©2017 American Association for Cancer Research.

FDA regulation of labeling and promotional claims in therapeutic color vision devices: a tutorial.

PubMed

Drum, Bruce

2004-01-01

The Food and Drug Administration (FDA) is responsible for determining whether medical device manufacturers have provided reasonable assurance, based on valid scientific evidence, that new devices are safe and effective for their intended use before they are introduced into the U.S. market. Most existing color vision devices pose so little risk that their manufacturers are not required to submit a premarket notification [510(k)] to FDA prior to market. However, even low-risk devices may not be acceptable if they are marketed on the basis of misleading or excessive claims. Although most color vision devices are diagnostic, two types that are therapeutic rather than diagnostic are colored lenses intended to improve deficient color vision and colored lenses intended to improve reading performance. Both of these devices have presented special regulatory challenges to FDA because the intended uses and effectiveness claims initially proposed by the manufacturers were not supported by valid scientific evidence. In each instance, however, FDA worked with the manufacturer to restrict labeling and promotional claims in ways that were consistent with the available device performance data and that allowed for the legal marketing of the device.

The Use of Published Clinical Study Reports to Support U.S. Food and Drug Administration Approval of Imaging Agents.

PubMed

Rieves, Dwaine; Jacobs, Paula

2016-12-01

Pharmaceutical companies typically perform prospective, multicenter phase 3 clinical studies to support approval of a new imaging agent by the U.S. Food and Drug Administration (FDA). In uncommon situations, the FDA has approved imaging agents based solely, or in large part, on the clinical study experience described in published reports, including reports of exploratory (i.e., phase 1 or 2) studies performed at a single clinical site. We performed a survey of published reports to assess the potential of the reported information to support FDA approval of a commonly cited investigational imaging agent. Our survey revealed critical data limitations in most publications, all of which reported exploratory clinical studies. Here we summarize the precedent for FDA approval of imaging agents using effectiveness data from publications, FDA guidance, and our experience in reviewing publications. We also present a key-data checklist for investigators to consider in the design, conduct, and reporting of exploratory clinical studies for publication. We encourage editors and peer reviewers to consider requiring these key data when reviewing these reports for publication. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Excimer laser photorefractive keratectomy for myopia: preliminary results at one year

NASA Astrophysics Data System (ADS)

Thompson, Keith P.; Waring, George O., III; Steinert, Roger; Durrie, Daniel S.; Gordon, Michael; Brint, Stephen F.

1992-08-01

Excimer laser photorefractive keratectomy (PRK) is presently under investigation for the correction of myopia. Two companies in the United States, Summit Technology (Waltham, Mass.) and VisX, Inc. (Sunnyvale, Calif.) have developed excimer laser delivery systems and are participating in an FDA study to determine the safety and efficacy of PRK. This is a preliminary report on the refractive and visual results of 51 of 100 eyes treated between October 10, 1990 and March 7, 1991 by the Summit Technology UV200LA excimer laser under the FDA Phase IIB FDA protocol one year after surgery. More detailed information on eight patients treated at Emory University Eye Center (Emory Subgroup) is also reported.

Leveraging prior quantitative knowledge in guiding pediatric drug development: a case study.

PubMed

Jadhav, Pravin R; Zhang, Jialu; Gobburu, Jogarao V S

2009-01-01

The manuscript presents the FDA's focus on leveraging prior knowledge in designing informative pediatric trial through this case study. In developing written request for Drug X, an anti-hypertensive for immediate blood pressure (BP) control, the sponsor and FDA conducted clinical trial simulations (CTS) to design trial with proper sample size and support the choice of dose range. The objective was to effectively use prior knowledge from adult patients for drug X, pediatric data from Corlopam (approved for a similar indication) trial and general experience in developing anti-hypertensive agents. Different scenarios governing the exposure response relationship in the pediatric population were simulated to perturb model assumptions. The choice of scenarios was based on the past observation that pediatric population is less responsive and sensitive compared with adults. The conceptual framework presented here should serve as an example on how the industry and FDA scientists can collaborate in designing the pediatric exclusivity trial. Using CTS, inter-disciplinary scientists with the sponsor and FDA can objectively discuss the choice of dose range, sample size, endpoints and other design elements. These efforts are believed to yield plausible trial design, qrational dosing recommendations and useful labeling information in pediatrics. Published in 2009 by John Wiley & Sons, Ltd.

New FDA draft guidance on immunogenicity.

PubMed

Parenky, Ashwin; Myler, Heather; Amaravadi, Lakshmi; Bechtold-Peters, Karoline; Rosenberg, Amy; Kirshner, Susan; Quarmby, Valerie

2014-05-01

A "Late Breaking" session was held on May 20 at the 2013 American Association of Pharmaceutical Scientists-National Biotech Conference (AAPS-NBC) to discuss the US Food and Drug Administration's (FDA) 2013 draft guidance on Immunogenicity Assessment for Therapeutic Protein Products. The session was initiated by a presentation from the FDA which highlighted several key aspects of the 2013 draft guidance pertaining to immunogenicity risk, the potential impact on patient safety and product efficacy, and risk mitigation. This was followed by an open discussion on the draft guidance which enabled delegates from biopharmaceutical companies to engage the FDA on topics that had emerged from their review of the draft guidance. The multidisciplinary audience fostered an environment that was conducive to scientific discussion on a broad range of topics such as clinical impact, immune mitigation strategies, immune prediction and the role of formulation, excipients, aggregates, and degradation products in immunogenicity. This meeting report highlights several key aspects of the 2013 draft guidance together with related dialog from the session.

Gas and dust in the star-forming region ρ Oph A. II. The gas in the PDR and in the dense cores

NASA Astrophysics Data System (ADS)

Larsson, B.; Liseau, R.

2017-12-01

Context. The evolution of interstellar clouds of gas and dust establishes the prerequisites for star formation. The pathway to the formation of stars can be studied in regions that have formed stars, but which at the same time also display the earliest phases of stellar evolution, i.e. pre-collapse/collapsing cores (Class -1), protostars (Class 0), and young stellar objects (Class I, II, III). Aims: We investigate to what degree local physical and chemical conditions are related to the evolutionary status of various objects in star-forming media. Methods: ρ Oph A displays the entire sequence of low-mass star formation in a small volume of space. Using spectrophotometric line maps of H2, H2O, NH3, N2H+, O2, O I, CO, and CS, we examine the distribution of the atomic and molecular gas in this dense molecular core. The physical parameters of these species are derived, as are their relative abundances in ρ Oph A. Using radiative transfer models, we examine the infall status of the cold dense cores from their resolved line profiles of the ground state lines of H2O and NH3, where for the latter no contamination from the VLA 1623 outflow is observed and line overlap of the hyperfine components is explicitly taken into account. Results: The stratified structure of this photon dominated region (PDR), seen edge-on, is clearly displayed. Polycyclic aromatic hydrocarbons (PAHs) and O I are seen throughout the region around the exciting star S 1. At the interface to the molecular core 0.05 pc away, atomic hydrogen is rapidly converted into H2, whereas O I protrudes further into the molecular core. This provides oxygen atoms for the gas-phase formation of O2 in the core SM 1, where X(O2) 5 × 10-8. There, the ratio of the O2 to H2O abundance [X(H2O) 5 × 10-9] is significantly higher than unity. Away from the core, O2 experiences a dramatic decrease due to increasing H2O formation. Outside the molecular core ρ Oph A, on the far side as seen from S 1, the intense radiation from the 0.5 pc distant early B-type star HD 147889 destroys the molecules. Conclusions: Towards the dark core SM 1, the observed abundance ratio X(O2)/X(H2O) > 1, which suggests that this object is extremely young, which would explain why O2 is such an elusive molecule outside the solar system. Based on observations with Herschel which is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.The data cubes of Figs. 3-10, 12, and A.1 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/608/A133

Patient-Focused Drug Development: A New Direction for Collaboration.

PubMed

Perfetto, Eleanor M; Burke, Laurie; Oehrlein, Elisabeth M; Epstein, Robert S

2015-01-01

Patient-Focused Drug Development (PFDD) is a new initiative from the Food and Drug Administration (FDA) intended to bring patient perspectives into an earlier stage of product development. The goal is that patients will be able to provide context for benefit-risk assessments and input to review divisions, and also aid in the development of new assessment tools, study endpoints, and risk communications. This paper provides a summary on what is known to date about FDA's PFDD initiative and describes implications for patients, researchers, payers, and the biopharmaceutical industry. It also provides a roadmap for stakeholders to consider in defining their role in and in shaping PFDD's direction, and for expanding PFDD principles to conditions beyond the current 20 under FDA consideration. A search was conducted of the peer-reviewed and gray literature using PubMed and Google. This included laws, FDA guidance documents, the peer-reviewed literature, and FDA presentations for content relevant to the search term "patient-focused drug development." Currently, FDA activities within PFDD are limited to gaining patient insights through 20 disease-specific meetings. However, many stakeholders see the initiative much more generally as representing a broad shift toward patient centeredness in biopharmaceutical product development. Depending upon the trajectory taken and whether or not all PFDD aims are eventually addressed, the initiative has the potential to change product development in fundamental ways. Further research should explore how patient input on disease manifestation and treatment options is best ascertained from patients and documented before initiating and during drug development.

78 FR 19715 - Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1153] Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish Pilot Projects and...: The Food and Drug Administration (FDA) is extending the comment period for the notice entitled...

77 FR 14404 - Guidance for the Public, Food and Drug Administration (FDA) Advisory Committee Members, and FDA...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2002-D-0094; (formerly Docket No. 02D-0049)] Guidance for the Public, Food and Drug Administration (FDA) Advisory... Food and Drug Administration (FDA) is announcing the availability of a guidance for the public, FDA...

78 FR 950 - Medical Devices; Availability of Safety and Effectiveness Summaries for Premarket Approval...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-07

..., FDA- 2012-M-0965, FDA-2012-M-0968, FDA-2012-M-1011, and FDA-2012-M-1013] Medical Devices; Availability...\\ February 16, 2011. Adjustable Gastric Banding System. P100049, FDA-2012-M-0893....... Torax Medical, Inc.... Trabecular Micro- Bypass Stent and Inserter. P110007, FDA-2012-M-0734....... Abbott Medical Healon[supreg...

75 FR 76992 - Guidance for the Public, FDA Advisory Committee Members, and FDA Staff: The Open Public Hearing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2005-D-0072] (formerly Docket No. 2005D-0042) Guidance for the Public, FDA Advisory Committee Members, and FDA Staff: The Open Public Hearing at FDA Advisory Committee Meetings; Availability AGENCY: Food and Drug...

78 FR 14309 - Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1153] Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish Pilot Projects and... information. SUMMARY: In September 2011, the Food and Drug Administration (FDA or the Agency) asked the...

Perceptions of the Food and Drug Administration as a Tobacco Regulator

PubMed Central

Jarman, Kristen L.; Ranney, Leah M.; Baker, Hannah M.; Vallejos, Quirina M.; Goldstein, Adam O.

2017-01-01

Objectives The U. S. Food and Drug Administration (FDA) now has regulatory authority over all tobacco products. Little is known about public awareness and perceptions of FDA in their new role as a tobacco regulator. This research utilizes focus groups to examine perceptions of FDA as a tobacco regulator so that FDA can better communicate with the public about this role. Methods We conducted 6 focus groups in 2014 among a diverse sample of smokers and non-smokers. Participants were asked if they had heard of FDA, what they knew about FDA, if they associated FDA with tobacco, and their thoughts about this FDA role. Results A total of 41 individuals participated. Although nearly all participants had heard of FDA, most were not aware of FDA’s regulatory authority over tobacco products, did not associate the role of FDA with tobacco, and some drew comparisons between FDA’s work in tobacco and their work regulating food and drugs. Conclusion Data suggest that although public awareness of FDA regulatory authority over tobacco is low, with proper public education, the public may find FDA to be a trustworthy source of tobacco regulation. PMID:29051917

Fine mapping of the rice Bph1 gene, which confers resistance to the brown planthopper (Nilaparvata lugens stal), and development of STS markers for marker-assisted selection.

PubMed

Cha, Young-Soon; Ji, Hyeonso; Yun, Doh-Won; Ahn, Byoung-Ohg; Lee, Myung Chul; Suh, Seok-Cheol; Lee, Chun Seok; Ahn, Eok Keun; Jeon, Yong-Hee; Jin, Il-Doo; Sohn, Jae-Keun; Koh, Hee-Jong; Eun, Moo-Young

2008-08-31

The brown planthopper (BPH) is a major insect pest in rice, and damages these plants by sucking phloem-sap and transmitting viral diseases. Many BPH resistance genes have been identified in indica varieties and wild rice accessions, but none has yet been cloned. In the present study we report fine mapping of the region containing the Bph1 locus, which enabled us to perform marker-aided selection (MAS). We used 273 F8 recombinant inbred lines (RILs) derived from a cross between Cheongcheongbyeo, an indica type variety harboring Bph1 from Mudgo, and Hwayeongbyeo, a BPH susceptible japonica variety. By random amplification of polymorphic DNA (RAPD) analysis using 656 random 10-mer primers, three RAPD markers (OPH09, OPA10 and OPA15) linked to Bph1 were identified and converted to SCAR (sequence characterized amplified region) markers. These markers were found to be contained in two BAC clones derived from chromosome 12: OPH09 on OSJNBa0011B18, and both OPA10 and OPA15 on OSJNBa0040E10. By sequence analysis of ten additional BAC clones evenly distributed between OSJNBa0011B18 and OSJNBa0040E10, we developed 15 STS markers. Of these, pBPH4 and pBPH14 flanked Bph1 at distances of 0.2 cM and 0.8 cM, respectively. The STS markers pBPH9, pBPH19, pBPH20, and pBPH21 co-segregated with Bph1. These markers were shown to be very useful for marker-assisted selection (MAS) in breeding populations of 32 F6 RILs from a cross between Andabyeo and IR71190, and 32 F5 RILs from a cross between Andabyeo and Suwon452.

Looking at the bright side of the rho Ophiuchi dark cloud. Far infrared spectrophotometric observations of the rho Oph cloud with the ISO

NASA Astrophysics Data System (ADS)

Liseau, R.; White, G. J.; Larsson, B.; Sidher, S.; Olofsson, G.; Kaas, A.; Nordh, L.; Caux, E.; Lorenzetti, D.; Molinari, S.; Nisini, B.; Sibille, F.

1999-04-01

We present far infrared (45-195 mu m) spectrophotometric observations with the Iso-Lws of the active star forming rho Oph main cloud (L 1688). The [C ii] 158 mu m and [O i] 63 mu m lines were detected at each of the 33 positions observed, whereas the [O i] 145 mu m line was clearly seen toward twelve. The principal observational result is that the [C ii] 158 mu m line fluxes exhibit a clear correlation with projected distance from the dominant stellar source in the field (HD 147889). We interpret this in terms of Pdr-type emission from the surface layers of the rho Ophc. The observed [C ii] 158 mu m/[O i] 63 mu m flux ratios are larger than unity everywhere. A comparison of the [C ii] 158 mu m line emission and the Fir dust continuum fluxes yields estimates of the efficiency at which the gas in the cloud converts stellar to [C ii] 158 mu m photons (chi_ {_C II},>_{ ~ },0.5%). We first develop an empirical model, which provides us with a three dimensional view of the far and bright side of the dark rho Ophc, showing that the cloud surface towards the putative energy source is concave. This model also yields quantitative estimates of the incident flux of ultraviolet radiation (G_0 ~ , \\powten{1} - \\powten{2}) and of the degree of clumpiness/texture of the cloud surface (filling of the 80({') '} beam ~ ,0.2). Subsequently, we use theoretical models of Pdr s to derive the particle density, n(H), and the temperature structures, for T_gas and T_dust, in the surface layers of the rho Ophc. T_gas is relatively low, ~ ,60 K, but higher than T_dust ( ~ ,30 K), and densities are generally found within the interval (1-3) \\powten{4} cm(-3) . These Pdr models are moderately successful in explaining the Lws observations. They correctly predict the [O i] 63 mu m and [C ii] 158 mu m line intensities and the observed absence of any molecular line emission. The models do fail, however, to reproduce the observed small [O i] 63 mu m/[O i] 145 mu m ratios. We examine several possible explanations, but are unable to uniquely identify (or to disentangle) the cause(s) of this discrepancy. From pressure equilibrium arguments we infer that the total mass of the rho Oph main cloud (2 pc(2) ) is ~ ,2 500 Msun, which implies that the star formation efficiency to date is <_{ ~ },4%, significantly lower than previous estimates. Based on observations with ISO, an ESA project with instruments funded by ESA Member States (especially the PI countries: France, Germany, the Netherlands and the United Kingdom) and with the participation of ISAS and NASA.

Fair Balance and Adequate Provision in Direct-to-Consumer Prescription Drug Online Banner Advertisements: A Content Analysis.

PubMed

Adams, Crystal

2016-02-18

The current direct-to-consumer advertising (DTCA) guidelines were developed with print, television, and radio media in mind, and there are no specific guidelines for online banner advertisements. This study evaluates how well Internet banner ads comply with existing Food and Drug Administration (FDA) guidelines for DTCA in other media. A content analysis was performed of 68 banner advertisements. A coding sheet was developed based on (1) FDA guidance documents for consumer-directed prescription drug advertisements and (2) previous DTCA content analyses. Specifically, the presence of a brief summary detailing the drug's risks and side effects or of a "major statement" identifying the drug's major risks, and the number and type of provisions made available to consumers for comprehensive information about the drug were coded. In addition, the criterion of "fair balance," the FDA's requirement that prescription drug ads balance information relating to the drug's risks with information relating to its benefits, was measured by numbering the benefit and risk facts identified in the ads and by examining the presentation of risk and benefit information. Every ad in the sample included a brief summary of risk information and at least one form of adequate provision as required by the FDA for broadcast ads that do not give audiences a brief summary of a drug's risks. No ads included a major statement. There were approximately 7.18 risk facts for every benefit fact. Most of the risks (98.85%, 1292/1307) were presented in the scroll portion of the ad, whereas most of the benefits (66.5%, 121/182) were presented in the main part of the ad. Out of 1307 risk facts, 1292 were qualitative and 15 were quantitative. Out of 182 benefit facts, 181 were qualitative and 1 was quantitative. The majority of ads showed neutral images during the disclosure of benefit and risk facts. Only 9% (6/68) of the ads displayed positive images and none displayed negative images when presenting risks facts. When benefit facts were being presented, 7% (5/68) showed only positive images. No ads showed negative images when the benefit facts were being presented. In the face of ambiguous regulatory guidelines for online banner promotion, drug companies appear to make an attempt to adapt to regulatory guidelines designed for traditional media. However, banner ads use various techniques of presentation to present the advertised drug in the best possible light. The FDA should formalize requirements that drug companies provide a brief summary and include multiple forms of adequate provision in banner ads.

On the Absence of Non-thermal X-Ray Emission around Runaway O Stars

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

Toalá, J. A.; Oskinova, L. M.; Ignace, R.

Theoretical models predict that the compressed interstellar medium around runaway O stars can produce high-energy non-thermal diffuse emission, in particular, non-thermal X-ray and γ -ray emission. So far, detection of non-thermal X-ray emission was claimed for only one runaway star, AE Aur. We present a search for non-thermal diffuse X-ray emission from bow shocks using archived XMM-Newton observations for a clean sample of six well-determined runaway O stars. We find that none of these objects present diffuse X-ray emission associated with their bow shocks, similarly to previous X-ray studies toward ζ Oph and BD+43°3654. We carefully investigated multi-wavelength observations ofmore » AE Aur and could not confirm previous findings of non-thermal X-rays. We conclude that so far there is no clear evidence of non-thermal extended emission in bow shocks around runaway O stars.« less

Labeling of trans fatty acid content in food, regulations and limits-the FDA view.

PubMed

Moss, Julie

2006-05-01

With the scientific evidence associating trans fatty acid (TFA) intake with an increased risk of coronary heart disease (CHD), the U.S. Food and Drug Administration (FDA) issued a final rule that requires the declaration of the amount of TFA present in foods, including dietary supplements, on the nutrition label by January 1, 2006. The addition of TFA to the nutrition label will lead to the prevention of 600 to 1200 cases of CHD and 240-480 deaths each year saving Dollars 900 million to Dollars 1.8 billion per year in medical costs, lost productivity, and pain and suffering. For the purpose of nutrition labeling, TFA are defined as the sum of all unsaturated fatty acids that contain one or more isolated (i.e. non-conjugated) double bonds in a trans configuration. There are many issues that FDA has yet to resolve: (1) defining nutrient content claims for "free" and "reduced" levels of trans fat, (2) placing limits on the amount of TFA in conjunction with saturated fat limits for nutrient content claims, health claims, and disclosure and disqualifying levels, (3) a daily value, and (4) a possible footnote or disclosure statement to enhance consumer understanding of cholesterol raising lipids. FDA issued an Advanced Notice of Proposed Rulemaking (ANPR) requesting comments on the unresolved issues. FDA will also be conducting consumer research to determine consumer understanding of various TFA labeling possibilities. Comments to the ANPR, results of consumer research and current science will be used by FDA to resolve these issues and to determine future rulemaking for TFA labeling.

Enrollment and Monitoring of Women in Post-Approval Studies for Medical Devices Mandated by the Food and Drug Administration

PubMed Central

Herz, Naomi; Loyo-Berrios, Nilsa; Tarver, Michelle

2014-01-01

Abstract Background: Disease presentation, prevalence, and treatment effects vary by sex, thus it is important to ensure adequate participation of both sexes in medical device post-approval studies (PAS). Methods: The goals of this study were to determine the participation rate of women in PAS mandated by the Food and Drug Administration (FDA) and if participation varied by clinical area. The study also evaluated the frequency in which enrollment by sex is reported by applicant reports and FDA reviews, as well as the frequency in which final study reports analyze whether outcomes differ by sex. Results: Of 89 studies with enrollment completed, data on sex of participants were available in 93% of submitted reports, while data on enrollment by sex was evaluated and noted in 43% of FDA review memos. Study participation varied by clinical area, with female participation ranging from 32% in cardiovascular PAS to 90% in PAS for reconstructive devices. Of 53 completed studies, data on enrollment by sex was provided in 49 of the final reports. Of these 14% included a multivariate analysis that included sex as a covariate and 4% included a subgroup analysis for female participants. Conclusions: Data on sex was not routinely assessed in FDA reviews. Based on these findings, FDA implemented new procedures to ensure participation by sex is evaluated in PAS reviews. FDA will continue working with applicants to develop PAS that enroll and retain proportions of women consistent with the sex-specific prevalence for the disease or condition the device is used to treat. PMID:24405314

Phytochemical characteristic and uterotonic effect of aqueous extract of Ficus deltoidea leaves in rats uterus.

PubMed

Amiera, Z Umi Romaizatul; Nihayah, M; Wahida, I Farah; Rajab, N F

2014-09-01

Ficus deltoidea is traditionally consumed by Malay woman to augment labour and hastening parturition. This study was to investigate the phytochemical present and uterotonic activity of F. deltoidea var. Deltoidea (FDD) and F. deltoidea var. Angustifolia (FDA) leaves aqueous extract. FDD and FDA were qualitatively analysed. In uterine contraction activity, adult female Sprague Dawley rats were pretreated with 0.2 mg kg(-1) diethylstilbestrol 24 h to induce oestrus phase. The rats then killed and uterine horns were taken out, cut into two centimetres length and put into organ bath that connected to Powerlab instrument. The uterus separately tested with cumulative concentrations of FDD (10-1280 μg mL(-1)), FDA (10-1280 μg mL(-1)), oxytocin (0.02-0.64 μg mL(-1)) and combination of oxytocin (0.08 μg mL(-1)) with FDD and FDA (10-1280 μg mL(-1)). FDD showed presence of flavonoid, saponin and tannin meanwhile FDA consist of flavonoid, tannin and terpenoid. Result showed FDD, FDA and oxytocin induced a dose-related increase in force of contraction of isolated rat uterus. The maximum uterine contraction (Emax) produced by FDD, FDA and oxytocin were at the concentration 640 μg mL(-1) (EC50, 5.903 ± 0.529 μg mL), 20 μg mL(-1) (EC50, 290.5 ± 0.158 μg mL(-1)) and 0.4 μg mL(-1) (EC50, 0.060 ± 0.011 μg mL(-1)) respectively. Combination effects of oxytocin with FDD and FDA produced Emax at the concentration 80 μg mL(-1) (EC50, 270.3 ± 0.643 μg mL(-1)) and 1280 μg mL(-1) (EC50, 26.83 ± 0.727 μg mL(-1)), respectively. Study indicated F. deltoidea possess contractile effect on uterine contraction. This plant has great potential to develop as natural uterotonic agent in inducing labour and treatment for post-partum haemorrhage.

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

FDA Kids' Home Page

MedlinePlus

... and Drug Administration A to Z Index Follow FDA En Español Search FDA Submit search Popular Content Home Food Drugs Medical ... 日本語 | فارسی | English FDA Accessibility Careers FDA Basics FOIA No FEAR Act ...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

78 FR 18233 - Medical Devices; Technical Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

... the right column: Section Remove Add 814.20 http://www.fda.gov/ http://www.fda.gov/ cdrh/devadvice.../ PremarketApproval PMA/default.htm. 822.7 http://www.fda.gov/ http://www.fda.gov/ cdrh/ombudsman/ AboutFDA/ dispute.html. CentersOffices/ OfficeofMedicalPr oductsandTobacco/ CDRH/ CDRHOmbudsman/ default.htm. 822.15...

Oscillator strengths for ionized iron and manganese

NASA Technical Reports Server (NTRS)

De Boer, K. S.; Pottasch, S. R.; Morton, D. C.; York, D. G.

1974-01-01

The observed strengths of interstellar absorption lines of Fe II and Mn II in the spectra of alpha Vir, beta Cen, pi Sco, and zeta Oph along with laboratory f values of some of these lines between 2343 and 2606 A have been used to determine curves of growth for these ions and the f-values of ten lines of Fe II and three lines of Mn II between 1055 and 1261 A. The Fe and Mn abundances are derived.

Prophylaxis against Organophosphorous Nerve Agents - State of the Art (profylaxe tegen organofosfaat zenuwgassen - stand van zaken)

DTIC Science & Technology

2005-12-01

consists of those that catalytically hydrolyze (in some cases stereoselectively) OP’s into non-toxic alkyl methyl phosphonic acids. These enzymes are so...8217fluorosphatase’, nowadays known as OPH, capable of hydrolyzing organophosphates. For therapy and/or profylaxis, a hydrolytic enzyme could be...HuPON hydrolyzes OP insecticides and nerve gases and a relationship was found between the amount of enzyme in different species and the toxic response

Development of the Electrochemical Biosensor for Organophosphate Chemicals Using CNT/Ionic Liquid Bucky Gel Electrode

DTIC Science & Technology

2010-04-01

www.elsevier .com/locate /e lecomDevelopment of the electrochemical biosensor for organophosphate chemicals using CNT/ ionic liquid bucky gel electrode Bong...hydrolase Ionic liquid CNT Electrochemical property1388-2481/$ - see front matter 2009 Elsevier B.V. A doi:10.1016/j.elecom.2009.01.006 * Corresponding...kaist.ac.kr (S.Y. Lee), whhOrganophosphorus hydrolase (OPH) immobilized on CNT/ ionic liquid (IL) electrodes were prepared by using three different intrinsic

Optophononics with Coupled Quantum Dots

DTIC Science & Technology

2014-02-18

polarons’ applicability as an amplifier of the visibility of weakest tunnel coupling channels. This observation via destructive interference proves the...exhibit weak electric field dependence . The |iXnS states exhibit much larger electric field dependence owing to the greater spatial separation of the...gate voltage, Dph¼pr0t2 is the phonon-assisted tunnelling broadening, r0 is the phonon density of states, qFano ¼ niXt=ðnDphÞ is the Fano factor; oph,0

Optical evolution of Nova Ophiuchi 2007 = V2615 Oph

NASA Astrophysics Data System (ADS)

Munari, U.; Henden, A.; Valentini, M.; Siviero, A.; Dallaporta, S.; Ochner, P.; Tomasoni, S.

2008-06-01

The moderately fast Nova Oph 2007 reached maximum brightness on 2007 March 28 at V= 8.52, B-V=+1.12, V-RC=+0.76, V-IC=+1.59 and RC-IC=+0.83, after fast initial rise and a pre-maximum halt lasting a week. Decline times were tV2= 26.5, tB2= 30, tV3= 48.5 and tB3= 56.5 d. The distance to the nova is d= 3.7 ± 0.2 kpc, the height above the Galactic plane is z= 215 pc, the reddening is E(B-V) = 0.90 and the absolute magnitude at maximum is MmaxV=-7.2 and MmaxB=-7.0. The spectrum four days before maximum resembled a F6 supergiant, in an agreement with broad-band colours. It later developed into that of a standard `Fe ii'-class nova. Nine days past maximum, the expansion velocity estimated from the width of Hα emission component was ˜730 km s-1, and the displacement from it of the principal and diffuse-enhanced absorption systems was ˜650 and 1380 km s-1, respectively. Dust probably formed and disappeared during the period from 82 to 100 d past maximum, causing (at peak dust concentration) an extinction of ΔB= 1.8 mag and an extra ΔE(B-V) = 0.44 reddening.

Consumer advertising of psychiatric medications biases the public against nonpharmacological treatment.

PubMed

Lacasse, Jeffrey R

2005-01-01

In the United States, antidepressant medications are heavily promoted through direct-to-consumer advertising, which is regulated by the Food and Drug Administration (FDA). Advertisements for selective serotonin reuptake inhibitors frequently contain information inconsistent with the scientific evidence on the treatment of depression with antidepressants. The information presented serves to promote the use of antidepressants by biasing the public against nonpharmacological treatment of depression. While the FDA enforces regulations requiring fair and balanced presentation when comparing one medication to another, there appears to be no action taken against pharmaceutical companies that distort scientific evidence in order to disparage nonmedical approaches to depression.

21 CFR 1.280 - How must you submit prior notice?

Code of Federal Regulations, 2010 CFR

2010-04-01

... to FDA. You must submit all prior notice information in the English language, except that an... Commercial System (ABI/ACS); or (2) The FDA PNSI at http://www.access.fda.gov. You must submit prior notice through the FDA Prior Notice System Interface (FDA PNSI) for articles of food imported or offered for...

78 FR 65329 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... Safety Testing of Sunlamp Products'' Form FDA 3632 ``Guide for Preparing Product Reports on Lasers and Products Containing Lasers'' Form FDA 3633''General Variance Request'' Form FDA 3634 ``Television Products Annual Report'' Form FDA 3635 ``Laser Light Show Notification'' Form FDA 3636 ``Guide for Preparing...

78 FR 35279 - Agency Information Collection Activities; Proposed Collection; Comment Request; Electronic Products

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-12

... Lasers and Products Containing Lasers'' FDA Form 3633 ``General Variance Request'' FDA Form 3634 ``Television Products Annual Report'' FDA Form 3635 ``Laser Light Show Notification'' FDA Form 3636 ``Guide for Preparing Annual Reports on Radiation Safety Testing of Laser and Laser Light Show Products'' FDA Form 3637...

75 FR 26964 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-13

... of Sunlamps and Sunlamp Products'' FDA Form 3632 ``Guide for Preparing Product Reports on Lasers and Products Containing Lasers'' FDA Form 3633 ``General Variance Request'' FDA Form 3634 ``Television Products Annual Report'' FDA Form 3635 ``Laser Light Show Notification'' FDA Form 3636 ``Guide for Preparing...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2012 CFR

2012-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2013 CFR

2013-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 2 2014-10-01 2014-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2010 CFR

2010-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 2 2013-10-01 2013-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2011 CFR

2011-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2014 CFR

2014-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 2 2011-10-01 2011-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 2 2012-10-01 2012-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

76 FR 30175 - Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-1999-D-0792] (Formerly FDA-1999-D-0792) Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial.... SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a draft guidance...

21 CFR 830.100 - FDA accreditation of an issuing agency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA accreditation of an issuing agency. 830.100... (CONTINUED) MEDICAL DEVICES UNIQUE DEVICE IDENTIFICATION FDA Accreditation of an Issuing Agency § 830.100 FDA... issuing agency. (b) Accreditation criteria. FDA may accredit an organization as an issuing agency, if the...

Extending FDA guidance to include consumer medication information (CMI) delivery on mobile devices.

PubMed

Sage, Adam; Blalock, Susan J; Carpenter, Delesha

This paper describes the current state of consumer-focused mobile health application use and the current U.S. Food and Drug Administration (FDA) guidance on the distribution of consumer medication information (CMI), and discusses recommendations and considerations for the FDA to expand CMI guidance to include CMI in mobile applications. Smartphone-based health interventions have been linked to increased medication adherence and improved health outcomes. Trends in smartphone ownership present opportunities to more effectively communicate and disseminate medication information; however, current FDA guidance for CMI does not outline how to effectively communicate CMI on a mobile platform, particularly in regards to user-centered design and information sourcing. As evidence supporting the potential effectiveness of mobile communication in health care continues to increase, CMI developers, regulating entities, and researchers should take note. Although mobile-based CMI offers an innovative mechanism to deliver medication information, caution should be exercised. Specifically, considerations for developing mobile CMI include consumers' digital literacy, user experience (e.g., usability), and the quality and accuracy of new widely used sources of information (e.g., crowd-sourced reviews and ratings). Recommended changes to FDA guidance for CMI include altering the language about scientific accuracy to address more novel methods of information gathering (e.g., anecdotal experiences and Google Consumer Surveys) and including guidance for usability testing of mobile health applications. Copyright © 2016 Elsevier Inc. All rights reserved.

Determination of radionuclides in foods from Minsk, Belarus, from Chernobyl to the present

NASA Astrophysics Data System (ADS)

Baratta, E. J.

2003-01-01

The U.S. Food and Drug Administration (FDA) are responsible for the wholesomeness of the food supply in the United States (US). The FDA has been monitoring the food supply in the United States for radioactivity since 1961, because of the Fallout generated by above the ground testing in the early 60’s. This Radionuclide in Foods Program is maintained to allow the FDA to respond to any nuclear emergency that may affect the food supply. The Three Mile Island incident in 1979 was one of these. In 1986 the Chernobyl incident occurred. As a result, the FDA began extensive monitoring of imported foods, especially those from Europe. One of its sister agencies has personnel in the areas effected by the latter incident and requested that the FDA analyze selected food samples from these places. Since that time, they have requested on a periodic basis, selected food samples be analysed. One such city was Minsk in Belarus. This paper will discuss the radionuclides of interest such as iodine-131, cesium-134/137, strontium-90, ruthenium-106 and other short-lived ones. It will discuss the types of foods sampled and the methodology used in determining the concentrations found in these items. The results will be compared to the permissible levels allowed in the US. In addition it will show the lower limits of detection for each of the radionuclides of interest.

Laboratory Testing of Donors and Stool Samples for Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection

PubMed Central

Neish, Emma M.; Miller, Nancy S.; Dhere, Tanvi; Burd, Eileen M.; Carpentieri, Cynthia; Sitchenko, Kaitlin L.

2017-01-01

ABSTRACT Fecal microbiota transplantation is an efficacious and inexpensive therapy for recurrent Clostridium difficile infection, yet its safety is thought to depend on appropriate fecal donor screening. FDA guidance for regulation of this procedure is in flux, but screening and manufacture of fecal material from asymptomatic donors present many challenges to clinical laboratories. This minireview summarizes FDA regulatory changes, principles of donor selection, and recommended laboratory screening practices for fecal microbiota transplantation. PMID:28077694

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

77 FR 52036 - Privacy Act of 1974; Report of a New System of Records; FDA Records Related to Research...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0253] Privacy Act of 1974; Report of a New System of Records; FDA Records Related to Research Misconduct... Drug Administration's (FDA's) regulations for the protection of privacy, FDA is publishing notice of a...

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

21 CFR 830.220 - Termination of FDA service as an issuing agency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Termination of FDA service as an issuing agency... SERVICES (CONTINUED) MEDICAL DEVICES UNIQUE DEVICE IDENTIFICATION FDA as an Issuing Agency § 830.220 Termination of FDA service as an issuing agency. (a) FDA may end our services as an issuing agency if we...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

FDA Warns About Stem Cell Therapies

MedlinePlus

... For Consumers Consumer Updates FDA Warns About Stem Cell Therapies Share Tweet Linkedin Pin it More sharing ... the boxed section below for more advice. Stem Cell Uses and FDA Regulation The FDA has the ...

Why (not) go east? Comparison of findings from FDA Investigational New Drug study site inspections performed in Central and Eastern Europe with results from the USA, Western Europe, and other parts of the world.

PubMed

Caldron, Paul H; Gavrilova, Svetlana I; Kropf, Siegfried

2012-01-01

Since the mid-1990s, investigational sites in the countries of Central and Eastern Europe (CEE) have been increasingly utilized by pharmaceutical companies because of their high productivity in terms of patient enrolment into clinical trials. Based on the FDA's publicly accessible Clinical Investigator Inspection List, we present an analysis of findings and outcome classifications from FDA inspections during Investigational New Drug (IND) studies and compare the results for the CEE region to those from Western European countries and the USA. Data from all 5531 FDA clinical trials inspections that occurred between 1994 (when the FDA first performed inspections in CEE) and the end of 2010 were entered into the database for comparative analysis. Of these, 4865 routine data audit (DA) inspections were analyzed: 401 from clinical trials performed in Western Europe, 230 in CEE, 3858 in the USA, and 376 in other countries. The average number of deficiencies per inspection ranged between 0.99 for CEE and 1.97 in Western Europe. No deficiencies were noted during 16.6%, 39.0%, and 21.5% of the inspections in Western Europe, CEE and USA, respectively. The percentages of inspections after which no follow-up action was indicated were 36.9% for Western Europe, 55.7% for CEE, and 44.3% for US sites. CEE was also the region with the lowest percentage of inspections that required official or voluntary action. On the basis of FDA inspection data, the high productivity of CEE sites appears to be accompanied by regulatory compliance as well as by data quality standards that are not inferior to those in Western regions.

Smokers' attitudes and support for e-cigarette policies and regulation in the USA.

PubMed

Wackowski, Olivia A; Delnevo, Cristine D

2015-11-01

In April 2014, the Food and Drug Administration (FDA) proposed a rule to extend its tobacco regulatory authority to e-cigarettes, which have been unregulated and growing in use since their 2006-2007 US introduction. The FDA will issue a final rule based on comments and data received from researchers, tobacco companies and the public. We aimed to present data about current smokers' awareness of and attitudes towards potential e-cigarette regulation and various policies in the USA. We conducted a cross-sectional online e-cigarette focused survey of 519 adult current smokers in April 2014, before the FDA's proposed rule was announced. Participants were recruited from a private research panel (GFK's Knowledge Networks) designed to be representative of the US population. The majority of respondents (62.5%) did not know that e-cigarettes are unregulated by the FDA but agreed that e-cigarettes should be regulated by the FDA for safety and quality (83.5%), carry warning labels about their potential risks (86.6%) and have the same legal age of sale as other tobacco (87.7%). Support was similarly high among current e-cigarette users. Support was substantial though lower overall for policies to restrict e-cigarette indoor use (41.2%), flavouring (44.3%) and advertising (55.5%), and was negatively associated with current e-cigarette use. Support for many e-cigarette regulatory policies is strong among smokers, including for policies that the FDA has recently proposed and potential future regulations. States considering indoor e-cigarette restrictions should know that a substantial number of current smokers support such regulations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Review of Usnic Acid and Usnea Barbata Toxicity

PubMed Central

Guo, Lei; Shi, Qiang; Fang, Jia-Long; Mei, Nan; Ali, A. Afshan; Lewis, Sherry M.; Leakey, Julian E.A.; Frankos, Vasilios H.

2017-01-01

Usnic acid is a prominent secondary lichen metabolite that has been used for various purposes worldwide. Crude extracts of usnic acid or pure usnic acid have been marketed in the United States as dietary supplements to aid in weight loss. The US Food and Drug Administration (FDA) received 21 reports of liver toxicity related to the ingestion of dietary supplements that contain usnic acid. This prompted the FDA to issue a warning about one such supplement, LipoKinetix, in 2001 (http://www.cfsan.fda.gov/~dms/ds-lipo.html). Subsequently, usnic acid and Usnea barbata lichen were nominated by the National Toxicology Program (NTP) for toxicity evaluations. At present, a toxicological evaluation of usnic acid is being conducted by the NTP. This review focuses on the recent findings of usnic acid-induced toxicities and their underlying mechanisms of action. PMID:19034791

Fabrication of 6FDA-durene membrane incorporated with zeolite T and aminosilane grafted zeolite T for CO2/CH4 separation

NASA Astrophysics Data System (ADS)

Jusoh, Norwahyu; Fong Yeong, Yin; Keong Lau, Kok; Shariff, Azmi Mohd

2017-08-01

In the present work, zeolite T and aminosilane grafted zeolite T are embedded into 6FDA-durene polyimide phase for the fabrication of mixed matrix membranes (MMMs). FESEM images demonstrated that the improvement of interfacial adhesion between zeolite and polymer phases in MMM loaded with aminosilane grafted zeolite T was not significant as compared to zeolite T/6FDA-durene MMM. From the gas permeation test, CO2/CH4 selectivity up to 26.4 was achieved using MMM containing aminosilane grafted zeolite T, while MMM loaded with ungrafted zeolite T showed CO2/CH4 selectivity of 19.1. In addition, MMM incorporated with aminosilane grafted zeolite T particles successfully lies on Robeson upper bound 2008, which makes it an attractive candidate for CO2/CH4 separation.

77 FR 16973 - Direct-to-Consumer Prescription Drug Advertisements; Presentation of the Major Statement in...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-23

...The Food and Drug Administration (FDA) is reopening the comment period on specific data related to a proposed rule published in the Federal Register of March 29,, to establish standards that would be considered in determining whether the major statement in direct-to- consumer (DTC) television and radio advertisements relating to the side effects and contraindications of an advertised prescription drug intended for use by humans is presented in a clear, conspicuous, and neutral manner. In the Federal Register of January 27, 2012, FDA announced that it had added a document to the docket for the proposed rulemaking concerning a study entitled ``Experimental Evaluation of the Impact of Distraction on Consumer Understanding of Risk and Benefit Information in Direct-to-Consumer Prescription Drug Television Advertisements'' (Distraction Study) and the public was given until February 27, 2012, to comment on this study as it relates to the proposed standards. FDA is reopening the comment period for the rulemaking proceeding in response to a request for more time to submit comments to the Agency.

Environmental Impact Analysis Process. Environmental Assessment for Defense Satellite Communications System III With Integrated Apogee Boost System

DTIC Science & Technology

1995-07-01

spectabilis Royal fern C FDA n/o Remirea maritima Beach star E FDA, FNAI o Scaevola plumeria Scaevola T FDA o Tillandsia simulata Wildpine; air plant...unnamed) T FDA n/o Tillandsia utriculata Giant wildpine; giant air plant C FDA o 1 E = Endangered; T = Threatened; T(S/A) = Threatened due to

21 CFR 1.393 - What information must FDA include in the detention order?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false What information must FDA include in the detention... Consumption How Does Fda Order A Detention? § 1.393 What information must FDA include in the detention order? (a) FDA must issue the detention order in writing, in the form of a detention notice, signed and...

21 CFR 1.393 - What information must FDA include in the detention order?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false What information must FDA include in the detention... Consumption How Does Fda Order A Detention? § 1.393 What information must FDA include in the detention order? (a) FDA must issue the detention order in writing, in the form of a detention notice, signed and...

45 CFR 73a.735-201 - Control activity employees formerly associated with organizations subject to FDA regulation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... with organizations subject to FDA regulation. 73a.735-201 Section 73a.735-201 Public Welfare Department... with organizations subject to FDA regulation. (a) For a period of 1 year after FDA appointment, or... employed in a regulated organization within 1 year before FDA employment shall not participate in any...

21 CFR 1.383 - What expedited procedures apply when FDA initiates a seizure action against a detained perishable...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false What expedited procedures apply when FDA initiates... procedures apply when FDA initiates a seizure action against a detained perishable food? If FDA initiates a... under this subpart, FDA will send the seizure recommendation to the Department of Justice (DOJ) within 4...

21 CFR 1.393 - What information must FDA include in the detention order?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false What information must FDA include in the detention... Consumption How Does Fda Order A Detention? § 1.393 What information must FDA include in the detention order? (a) FDA must issue the detention order in writing, in the form of a detention notice, signed and...

21 CFR 830.210 - Eligibility for use of FDA as an issuing agency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Eligibility for use of FDA as an issuing agency... SERVICES (CONTINUED) MEDICAL DEVICES UNIQUE DEVICE IDENTIFICATION FDA as an Issuing Agency § 830.210 Eligibility for use of FDA as an issuing agency. When FDA acts as an issuing agency, any labeler will be...

21 CFR 1.383 - What expedited procedures apply when FDA initiates a seizure action against a detained perishable...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false What expedited procedures apply when FDA initiates... procedures apply when FDA initiates a seizure action against a detained perishable food? If FDA initiates a... under this subpart, FDA will send the seizure recommendation to the Department of Justice (DOJ) within 4...

21 CFR 1.383 - What expedited procedures apply when FDA initiates a seizure action against a detained perishable...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false What expedited procedures apply when FDA initiates... procedures apply when FDA initiates a seizure action against a detained perishable food? If FDA initiates a... under this subpart, FDA will send the seizure recommendation to the Department of Justice (DOJ) within 4...

21 CFR 1.383 - What expedited procedures apply when FDA initiates a seizure action against a detained perishable...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false What expedited procedures apply when FDA initiates... procedures apply when FDA initiates a seizure action against a detained perishable food? If FDA initiates a... under this subpart, FDA will send the seizure recommendation to the Department of Justice (DOJ) within 4...

45 CFR 73a.735-201 - Control activity employees formerly associated with organizations subject to FDA regulation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... with organizations subject to FDA regulation. 73a.735-201 Section 73a.735-201 Public Welfare DEPARTMENT... with organizations subject to FDA regulation. (a) For a period of 1 year after FDA appointment, or... employed in a regulated organization within 1 year before FDA employment shall not participate in any...

21 CFR 1.383 - What expedited procedures apply when FDA initiates a seizure action against a detained perishable...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false What expedited procedures apply when FDA initiates... procedures apply when FDA initiates a seizure action against a detained perishable food? If FDA initiates a... under this subpart, FDA will send the seizure recommendation to the Department of Justice (DOJ) within 4...

21 CFR 1.393 - What information must FDA include in the detention order?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false What information must FDA include in the detention... Consumption How Does Fda Order A Detention? § 1.393 What information must FDA include in the detention order? (a) FDA must issue the detention order in writing, in the form of a detention notice, signed and...

45 CFR 73a.735-201 - Control activity employees formerly associated with organizations subject to FDA regulation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... with organizations subject to FDA regulation. 73a.735-201 Section 73a.735-201 Public Welfare DEPARTMENT... with organizations subject to FDA regulation. (a) For a period of 1 year after FDA appointment, or... employed in a regulated organization within 1 year before FDA employment shall not participate in any...

45 CFR 73a.735-201 - Control activity employees formerly associated with organizations subject to FDA regulation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... with organizations subject to FDA regulation. 73a.735-201 Section 73a.735-201 Public Welfare DEPARTMENT... with organizations subject to FDA regulation. (a) For a period of 1 year after FDA appointment, or... employed in a regulated organization within 1 year before FDA employment shall not participate in any...

45 CFR 73a.735-201 - Control activity employees formerly associated with organizations subject to FDA regulation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... with organizations subject to FDA regulation. 73a.735-201 Section 73a.735-201 Public Welfare DEPARTMENT... with organizations subject to FDA regulation. (a) For a period of 1 year after FDA appointment, or... employed in a regulated organization within 1 year before FDA employment shall not participate in any...

21 CFR 1.393 - What information must FDA include in the detention order?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false What information must FDA include in the detention... Consumption How Does Fda Order A Detention? § 1.393 What information must FDA include in the detention order? (a) FDA must issue the detention order in writing, in the form of a detention notice, signed and...

Imaging the cool stars in the interacting binaries AE Aqr, BV Cen and V426 Oph

NASA Astrophysics Data System (ADS)

Watson, C. A.; Steeghs, D.; Dhillon, V. S.; Shahbaz, T.

2007-10-01

It is well known that magnetic activity in late-type stars increases with increasing rotation rate. Using inversion techniques akin to medical imaging, the rotationally broadened profiles from such stars can be used to reconstruct `Doppler images' of the distribution of cool, dark starspots on their stellar surfaces. Interacting binaries, however, contain some of the most rapidly rotating late-type stars known and thus provide important tests of stellar dynamo models. Furthermore, magnetic activity is thought to play a key role in their evolution, behaviour and accretion dynamics. Despite this, we know comparatively little about the magnetic activity and its influence on such binaries. In this review we summarise the concepts behind indirect imaging of these systems, and present movies of the starspot distributions on the cool stars in some interacting binaries. We conclude with a look at the future opportunities that such studies may provide.

Follow-up Observations of SDSS and CRTS Candidate Cataclysmic Variables II

NASA Astrophysics Data System (ADS)

Szkody, Paula; Everett, Mark E.; Dai, Zhibin; Serna-Grey, Donald

2018-01-01

Spectra of 38 candidate or known cataclysmic variables are presented. Most are candidate dwarf novae or systems containing possible highly magnetic white dwarfs, while a few (KR Aur, LS Peg, V380 Oph, and V694 Mon) are previously known objects caught in unusual states. Individual spectra are used to confirm a dwarf nova nature or other classification while radial velocities of 15 systems provide orbital periods and velocity amplitudes that aid in determining the nature of the objects. Our results substantiate a polar nature for four objects, find an eclipsing SW Sex star below the period gap, another as a likely intermediate polar, as well as two dwarf novae with periods in the middle of the gap. Based on observations obtained with the Apache Point Observatory (APO) 3.5 m telescope, which is owned and operated by the Astrophysical Research Consortium (ARC).

First detection of nonflare microwave emissions from the coronae of single late-type dwarf stars

NASA Technical Reports Server (NTRS)

Gary, D. E.; Linsky, J. L.

1981-01-01

Results are presented of a search for nonflare microwave radiation from the coronae of nearby late-type dwarf stars comparable to the sun: single stars without evidence for either a large wind or circumstellar envelope. The observing program consisted of flux measurements of six stars over a 24-h period with the VLA in the C configuration at a wavelength of 6 cm with 50 MHz bandwidth. Positive detections at 6 cm were made for Chi 1 Ori (0.6 mJy) and the flare star UV Cet (1.55 mJy), and upper limits were obtained for the stars Pi 1 UMa, Xi Boo A, 70 Oph A and Epsilon Eri. It is suggested that Chi 1 Ori, and possibly UV Cet, represent the first detected members of a new class of radio sources which are driven by gyroresonance emission, i.e. cyclotron emission from nonrelativistic Maxwellian electrons.

Non-Ionizing Radiation Used in Microwave Ovens

MedlinePlus

... Human Services (HHS), U.S. Food and Drug Administration (FDA) FDA's Center for Devices and Radiological Health (CDRH) sets ... public health. These standards can be viewed on FDA's Code of Federal Regulations on Microwave Ovens . FDA ...

Physical properties of gas disks around shell stars with and without dust

NASA Technical Reports Server (NTRS)

Grady, Carol A.

1992-01-01

Analysis of archival IRAS and IUE data has resulted in: (1) identification of 8 new A star proto-planetary candidates; (2) detection of a mass outflow event around Beta Pic (subsequently confirmed by the 1991 July HST observation); and (3) confirmation of the suggestion by Waters et al. (1988) that 51 Oph is a protoplanetary system similar to beta Pic with the detection of high density, high velocity, collisionally ionized accreting gas in the line of sight toward this star.

Optical Spectroscopy of Nova Ophiuchi 2015 (PNV J17291350-1846120)

NASA Astrophysics Data System (ADS)

Danilet, A. B.; Holoien, T. W.-S.; Wagner, R. M.; Woodward, C. E.; Starrfield, S.; Wilber, A.; Walter, F.; Shore, S.

2015-04-01

Following the discovery by Y. Sakurai (Ibaraki-ken, Japan) on 2015 Mar. 29.766 UT of a new stellar object of magnitude 12.2 in Ophiuchus (S. Nakano, CBET 4086) and its subsequent confirmation as a likely He/N classical nova (K Ayani, CBET 4086), we obtained a spectrum (range: 398-685 nm; resolution 0.3 nm) of Nova Oph 2015 on 2015 April 1.459 UT with the 2.4 m Hiltner telescope (+OSMOS) of the MDM Observatory on Kitt Peak.

OpenFDA: an innovative platform providing access to a wealth of FDA's publicly available data.

PubMed

Kass-Hout, Taha A; Xu, Zhiheng; Mohebbi, Matthew; Nelsen, Hans; Baker, Adam; Levine, Jonathan; Johanson, Elaine; Bright, Roselie A

2016-05-01

The objective of openFDA is to facilitate access and use of big important Food and Drug Administration public datasets by developers, researchers, and the public through harmonization of data across disparate FDA datasets provided via application programming interfaces (APIs). Using cutting-edge technologies deployed on FDA's new public cloud computing infrastructure, openFDA provides open data for easier, faster (over 300 requests per second per process), and better access to FDA datasets; open source code and documentation shared on GitHub for open community contributions of examples, apps and ideas; and infrastructure that can be adopted for other public health big data challenges. Since its launch on June 2, 2014, openFDA has developed four APIs for drug and device adverse events, recall information for all FDA-regulated products, and drug labeling. There have been more than 20 million API calls (more than half from outside the United States), 6000 registered users, 20,000 connected Internet Protocol addresses, and dozens of new software (mobile or web) apps developed. A case study demonstrates a use of openFDA data to understand an apparent association of a drug with an adverse event. With easier and faster access to these datasets, consumers worldwide can learn more about FDA-regulated products. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved.

21 CFR 1.391 - Who approves a detention order?

Code of Federal Regulations, 2013 CFR

2013-04-01

... Fda Order A Detention? § 1.391 Who approves a detention order? An authorized FDA representative, i.e., the FDA District Director in whose district the article of food involved is located or an FDA official...

FDA Issues Final Guidance Clarifying FDA and EPA Jurisdiction over Mosquito-Related Products

EPA Pesticide Factsheets

FDA finalized guidance to provide information on FDA and EPA jurisdiction over the regulation of mosquito-related products intended to function as pesticides, including those products intended to function as pesticides

21 CFR 1.391 - Who approves a detention order?

Code of Federal Regulations, 2011 CFR

2011-04-01

... Fda Order A Detention? § 1.391 Who approves a detention order? An authorized FDA representative, i.e., the FDA District Director in whose district the article of food involved is located or an FDA official...

21 CFR 1.391 - Who approves a detention order?

Code of Federal Regulations, 2010 CFR

2010-04-01

... Fda Order A Detention? § 1.391 Who approves a detention order? An authorized FDA representative, i.e., the FDA District Director in whose district the article of food involved is located or an FDA official...

21 CFR 1.391 - Who approves a detention order?

Code of Federal Regulations, 2012 CFR

2012-04-01

... Fda Order A Detention? § 1.391 Who approves a detention order? An authorized FDA representative, i.e., the FDA District Director in whose district the article of food involved is located or an FDA official...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

The Food and Drug Administration advisory committees and panels: how they are applied to the drug regulatory process.

PubMed

Ciociola, Arthur A; Karlstadt, Robyn G; Pambianco, Daniel J; Woods, Karen L; Ehrenpreis, Eli D

2014-10-01

Food and Drug Administration (FDA) advisory panels and committees play a critical role in advising the FDA on the safety and efficacy of medical devices and drugs marketed in the US. Advisory panel recommendations are used by the FDA to make decisions regarding medical products. Currently, the FDA utilizes over 50 advisory panels that serve the three major FDA centers, including the Centers for Biologics, Drugs and Device Products. Members of an advisory panel typically include academicians, clinicians, consumers, patients, and industry representatives. The FDA establishes the schedules for advisory panel meetings on an annual basis and a panel usually meets several times a year for two consecutive days in Washington, DC. Typically, the advisory panel discusses issues highlighted by the FDA and is then asked to vote a response to the questions posed in advance by the FDA. Advisory panel recommendations have a strong influence on FDA's decision to approve a product, as evidenced by the 214 Advisory Panels FDA convened between January 2008 to November 2012, during which advisory panel members voted to approve the product (or use of the product) ∼74% of the time, with FDA ultimately approving the medical product (or use of the product) ∼79% of the time. The ACG membership are encouraged to consider serving the public's interest by participating in an FDA advisory panel utilizing their expertise for the evaluation of a new drug or medical device, and providing advice about whether the product should be sold in the US.

Patient Experience Data in US Food and Drug Administration (FDA) Regulatory Decision Making:: A Policy Process Perspective.

PubMed

Kuehn, Carrie M

2018-01-01

The influence of patient advocates on FDA regulatory decision making has increased. Despite enhanced engagement with FDA, there remain challenges to achieving the regulatory goals of patients within FDA's regulatory framework. Gaps exist between patient advocates' knowledge of the agency's processes and FDA's need for rigorous, clinically meaningful patient experience data. This study examined the policy process in which patient experience data are collected by patient advocates and provided to FDA for regulatory decision making. Semistructured, narrative interviews were conducted with 14 professionals working in patient advocacy or at FDA. The purpose was to examine, in depth, participants' perceptions and experiences regarding this new regulatory process. Interviews were coded and examined for themes. The use of patient experience data by FDA is an evolving regulatory process. Participants identified a number of barriers and contributors to regulatory success. Well-organized and sophisticated patient advocacy groups with access to scientific and policy expertise are more likely to find success meeting FDA's patient experience data requirements. A conceptual model of this regulatory process was developed. Use of patient experience data by FDA has the potential to positively influence the regulation of medical products in the United States. Success within this new regulatory process will depend on clear guidance from FDA regarding the collection, analysis, and use of patient experience data. Patient advocacy groups must enhance internal capacity and expertise while engaging in substantive collaborations with FDA and other stakeholders in order to meaningfully contribute to the regulatory review of new therapeutics.

Fluorescein Diacetate Microplate Assay in Cell Viability Detection.

PubMed

Chen, Xi; Yang, Xiu-Ying; Fang, Lian-Hua; DU, Guan-Hua

2016-12-20

Objective To investigate the application of the fluorescein diacetate (FDA) microplate assay in cell viability detection. Methods Cells were seeded in a 96-well culture plate until detection. After incubated with FDA,the plate was detected by fluorescence microplate analyzer. The effects of FDA incubation duration,concentration,and other factors on the assay's accuracy and stability were assessed. We also compared the results of FDA with methyl thiazolyl(MTT) in terms of cell numbers and H 2 O 2 injury. Results Within 0-30 minutes,the fluorescence-cell number coefficient of FDA assay increased with duration and reached 0.99 in 27-30 minutes. The optimum concentration of final FDA in this study was 10-30 μg/ml. On cell viability detection,the result of FDA method was equivalent to MTT method. As to H 2 O 2 injury assay,the sensitivity of FDA method was superior to MTT on the higher concentration H 2 O 2 treatment due to a relative shorter duration for detection. Conclusion As a stable and reliable method,FDA is feasible for cell variability detection under varied conditions.

76 FR 1180 - FDA Transparency Initiative: Improving Transparency to Regulated Industry

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-07

...] FDA Transparency Initiative: Improving Transparency to Regulated Industry AGENCY: Food and Drug... the Transparency Initiative, the Food and Drug Administration (FDA) is announcing the availability of a report entitled ``FDA Transparency Initiative: Improving Transparency to Regulated Industry.'' The...

77 FR 70955 - FDA Actions Related to Nicotine Replacement Therapies and Smoking-Cessation Products; Report to...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-28

.... FDA-2012-N-1148] FDA Actions Related to Nicotine Replacement Therapies and Smoking-Cessation Products... comments. SUMMARY: The Food and Drug Administration (FDA) is announcing a 1-day public hearing to obtain...

Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval

DTIC Science & Technology

2016-10-01

consensus meeting, with input from investigators in the Prostate Cancer Clinical Trials Consortium, FDA Office of Oncology Drug Products, FDA Study...Cancer Clinical Trials Consortium, FDA Office of Oncology Drug Products, FDA Study Endpoint and Label Development Team, and FDA Division of...Abstract. American Society of Clinical Oncology . Chicago IL, June 1-5, 2013. INVENTIONS, PATENTS AND LICENSES None 11 REPORTABLE OUTCOMES

High-risk medical devices, children and the FDA: regulatory challenges facing pediatric mechanical circulatory support devices.

PubMed

Almond, Christopher S D; Chen, Eric A; Berman, Michael R; Less, Joanne R; Baldwin, J Timothy; Linde-Feucht, Sarah R; Hoke, Tracey R; Pearson, Gail D; Jenkins, Kathy; Duncan, Brian W; Zuckerman, Bram D

2007-01-01

Pediatric mechanical circulatory support is a critical unmet need in the United States. Infant- and child-sized ventricular assist devices are currently being developed largely through federal contracts and grants through the National Heart, Lung, and Blood Institute (NHLBI). Human testing and marketing of high-risk devices for children raises epidemiologic and regulatory issues that will need to be addressed. Leaders from the US Food and Drug Administration (FDA), NHLBI, academic pediatric community, and industry convened in January 2006 for the first FDA Workshop on the Regulatory Process for Pediatric Mechanical Circulatory Support Devices. The purpose was to provide the pediatric community with an overview of the federal regulatory process for high-risk medical devices and to review the challenges specific to the development and regulation of pediatric mechanical circulatory support devices. Pediatric mechanical circulatory support present significant epidemiologic, logistic, and financial challenges to industry, federal regulators, and the pediatric community. Early interactions with the FDA, shared appreciation of challenges, and careful planning will be critical to avoid unnecessary delays in making potentially life-saving devices available for children. Collaborative efforts to address these challenges are warranted.

FDA-approved drugs that are spermatotoxic in animals and the utility of animal testing for human risk prediction.

PubMed

Rayburn, Elizabeth R; Gao, Liang; Ding, Jiayi; Ding, Hongxia; Shao, Jun; Li, Haibo

2018-02-01

This study reviews FDA-approved drugs that negatively impact spermatozoa in animals, as well as how these findings reflect on observations in human male gametes. The FDA drug warning labels included in the DailyMed database and the peer-reviewed literature in the PubMed database were searched for information to identify single-ingredient, FDA-approved prescription drugs with spermatotoxic effects. A total of 235 unique, single-ingredient, FDA-approved drugs reported to be spermatotoxic in animals were identified in the drug labels. Forty-nine of these had documented negative effects on humans in either the drug label or literature, while 31 had no effect or a positive impact on human sperm. For the other 155 drugs that were spermatotoxic in animals, no human data was available. The current animal models are not very effective for predicting human spermatotoxicity, and there is limited information available about the impact of many drugs on human spermatozoa. New approaches should be designed that more accurately reflect the findings in men, including more studies on human sperm in vitro and studies using other systems (ex vivo tissue culture, xenograft models, in silico studies, etc.). In addition, the present data is often incomplete or reported in a manner that prevents interpretation of their clinical relevance. Changes should be made to the requirements for pre-clinical testing, drug surveillance, and the warning labels of drugs to ensure that the potential risks to human fertility are clearly indicated.

TU-AB-204-00: CDRH/FDA Regulatory Processes and Device Science Activities

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

NONE

The responsibilities of the Food and Drug Administration (FDA) have increased since the inception of the Food and Drugs Act in 1906. Medical devices first came under comprehensive regulation with the passage of the 1938 Food, Drug, and Cosmetic Act. In 1971 FDA also took on the responsibility for consumer protection against unnecessary exposure to radiation-emitting devices for home and occupational use. However it was not until 1976, under the Medical Device Regulation Act, that the FDA was responsible for the safety and effectiveness of medical devices. This session will be presented by the Division of Radiological Health (DRH) andmore » the Division of Imaging, Diagnostics, and Software Reliability (DIDSR) from the Center for Devices and Radiological Health (CDRH) at the FDA. The symposium will discuss on how we protect and promote public health with a focus on medical physics applications organized into four areas: pre-market device review, post-market surveillance, device compliance, current regulatory research efforts and partnerships with other organizations. The pre-market session will summarize the pathways FDA uses to regulate the investigational use and commercialization of diagnostic imaging and radiation therapy medical devices in the US, highlighting resources available to assist investigators and manufacturers. The post-market session will explain the post-market surveillance and compliance activities FDA performs to monitor the safety and effectiveness of devices on the market. The third session will describe research efforts that support the regulatory mission of the Agency. An overview of our regulatory research portfolio to advance our understanding of medical physics and imaging technologies and approaches to their evaluation will be discussed. Lastly, mechanisms that FDA uses to seek public input and promote collaborations with professional, government, and international organizations, such as AAPM, International Electrotechnical Commission (IEC), Image Gently, and the Quantitative Imaging Biomarkers Alliance (QIBA) among others, to fulfill FDA’s mission will be discussed. Learning Objectives: Understand FDA’s pre-market and post-market review processes for medical devices Understand FDA’s current regulatory research activities in the areas of medical physics and imaging products Understand how being involved with AAPM and other organizations can also help to promote innovative, safe and effective medical devices J. Delfino, nothing to disclose.« less

Performance of Cleared Blood Glucose Monitors.

PubMed

Klonoff, David C; Prahalad, Priya

2015-07-01

Cleared blood glucose monitor (BGM) systems do not always perform as accurately for users as they did to become cleared. We performed a literature review of recent publications between 2010 and 2014 that present data about the frequency of inaccurate performance using ISO 15197 2003 and ISO 15197 2013 as target standards. We performed an additional literature review of publications that present data about the clinical and economic risks of inaccurate BGMs for making treatment decisions or calibrating continuous glucose monitors (CGMs). We found 11 publications describing performance of 98 unique BGM systems. 53 of these 98 (54%) systems met ISO 15197 2003 and 31 of the 98 (32%) tested systems met ISO 15197 2013 analytical accuracy standards in all studies in which they were evaluated. Of the tested systems, 33 were identified by us as FDA-cleared. Among these FDA-cleared BGM systems, 24 out of 32 (75%) met ISO 15197 2003 and 15 out of 31 (48.3%) met ISO 15197 2013 in all studies in which they were evaluated. Among the non-FDA-cleared BGM systems, 29 of 65 (45%) met ISO 15197 2003 and 15 out of 65 (23%) met ISO 15197 2013 in all studies in which they were evaluated. It is more likely that an FDA-cleared BGM system, compared to a non-FDA-cleared BGM system, will perform according to ISO 15197 2003 (χ(2) = 6.2, df = 3, P = 0.04) and ISO 15197 2013 (χ(2) = 11.4, df = 3, P = 0.003). We identified 7 articles about clinical risks and 3 articles about economic risks of inaccurate BGMs. We conclude that a significant proportion of cleared BGMs do not perform at the level for which they were cleared or according to international standards of accuracy. Such poor performance leads to adverse clinical and economic consequences. © 2015 Diabetes Technology Society.

Occurrence and methods of control of chemical contaminants in foods.

PubMed

Jelinek, C

1981-06-01

Contamination of food by chemicals can result from their use on agricultural commodities; accidents or misuse during food handling and processing; nucler weapon testing and operation of nuclear power plants; and disposal of industrial chemicals or by-products with subsequent dispersal into the environment. The Food and Drug Administration (FDA), as the Federal agency mainly responsible for evaluating the hazards of chemical contaminants and enforcing any established tolerance levels for them in foods, has been monitoring pesticides, industrial chemicals, metals, and radionuclides in foods in its nationwide programs for many years. In addition, FDA searches for potential contaminants among the approximately 50,000 industrial chemicals manufactured in the United States and coordinates its efforts with those of other Federal and state agencies in these investigations. The overall results of the FDA surveillance and compliance programs for chemical contaminants in foods, as well as specific examples illustrating the wide range of incidents and types of occurrences, are presented.

Food and Drug Administration criteria for the diagnosis of drug-induced valvular heart disease in patients previously exposed to benfluorex: a prospective multicentre study.

PubMed

Maréchaux, Sylvestre; Rusinaru, Dan; Jobic, Yannick; Ederhy, Stéphane; Donal, Erwan; Réant, Patricia; Arnalsteen, Elise; Boulanger, Jacques; Garban, Thierry; Ennezat, Pierre-Vladimir; Jeu, Antoine; Szymanski, Catherine; Tribouilloy, Christophe

2015-02-01

The Food and Drug Administration (FDA) criteria for diagnosis of drug-induced valvular heart disease (DIVHD) are only based on the observation of aortic regurgitation ≥ mild and/or mitral regurgitation ≥ moderate. We sought to evaluate the diagnostic value of FDA criteria in a cohort of control patients and in a cohort of patients exposed to a drug (benfluorex) known to induce VHD. This prospective, multicentre study included 376 diabetic control patients not exposed to valvulopathic drugs and 1000 subjects previously exposed to benfluorex. Diagnosis of mitral or aortic DIVHD was based on a combined functional and morphological echocardiographic analysis of cardiac valves. Patients were classified according to the FDA criteria [mitral or aortic-FDA(+) and mitral or aortic-FDA(-)]. Among the 376 control patients, 2 were wrongly classified as mitral-FDA(+) and 17 as aortic-FDA(+) (0.53 and 4.5% of false positives, respectively). Of those exposed to benfluorex, 48 of 58 with a diagnosis of mitral DIVHD (83%) were classified as mitral-FDA(-), and 901 of the 910 patients (99%) without a diagnosis of the mitral DIVHD group were classified as mitral-FDA(-). All 40 patients with a diagnosis of aortic DIVHD were classified as aortic-FDA(+), and 105 of the 910 patients without a diagnosis of aortic DIVHD (12%) were classified aortic-FDA(+). Older age and lower BMI were independent predictors of disagreement between FDA criteria and the diagnosis of DIVHD in patients exposed to benfluorex (both P ≤ 0.001). FDA criteria solely based on the Doppler detection of cardiac valve regurgitation underestimate for the mitral valve and overestimate for the aortic valve the frequency of DIVHD. Therefore, the diagnosis of DIVHD must be based on a combined echocardiographic and Doppler morphological and functional analysis of cardiac valves. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Seeking approval: Present and future therapies for pemphigus vulgaris

PubMed Central

Mao, Xuming; Payne, Aimee S

2014-01-01

Pemphigus vulgaris is an autoimmune blistering disease of the skin and mucous membranes. Despite the potentially fatal prognosis, there are currently no FDA-approved treatments specifically for pemphigus. In 2006, the FDA designated orphan drug status to mycophenolate mofetil for the treatment of pemphigus vulgaris indicating both federal and commercial interest in developing therapies for this devastating disease. This review focuses on pemphigus therapies that are currently in preclinical or clinical trials, as well as potential novel therapies based on recent advances in the understanding of the pathophysiology of this disease. PMID:18465660

Seeking approval: present and future therapies for pemphigus vulgaris.

PubMed

Mao, Xuming; Payne, Aimee S

2008-05-01

Pemphigus vulgaris is an autoimmune blistering disease of the skin and mucous membranes. Despite the potentially fatal prognosis, there are currently no FDA-approved treatments specifically for pemphigus. In 2006, the FDA designated orphan drug status to mycophenolate mofetil for the treatment of pemphigus vulgaris, indicating both federal and commercial interest in developing therapies for this devastating disease. This review focuses on pemphigus therapies that are currently in preclinical or clinical trials, as well as potential novel therapies based on recent advances in the understanding of the pathophysiology of this disease.

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

Reflections on the US FDA's Warning on Direct-to-Consumer Genetic Testing.

PubMed

Yim, Seon-Hee; Chung, Yeun-Jun

2014-12-01

In November 2013, the US Food and Drug Administration (FDA) sent a warning letter to 23andMe, Inc. and ordered the company to discontinue marketing of the 23andMe Personal Genome Service (PGS) until it receives FDA marketing authorization for the device. The FDA considers the PGS as an unclassified medical device, which requires premarket approval or de novo classification. Opponents of the FDA's action expressed their concerns, saying that the FDA is overcautious and paternalistic, which violates consumers' rights and might stifle the consumer genomics field itself, and insisted that the agency should not restrict direct-to-consumer (DTC) genomic testing without empirical evidence of harm. Proponents support the agency's action as protection of consumers from potentially invalid and almost useless information. This action was also significant, since it reflected the FDA's attitude towards medical application of next-generation sequencing techniques. In this review, we followed up on the FDA-23andMe incident and evaluated the problems and prospects for DTC genetic testing.

Policy at play: The implementation of Healthy Eating and Active Living Guidelines in municipal child care settings.

PubMed

McKay, Kelly; Nigro, Sherry

2017-03-01

In 2012, Ottawa Public Health (OPH) partnered with the City of Ottawa Municipal Child Care (MCC) Services to develop Healthy Eating and Active Living (HEAL) Guidelines. The Guidelines aim to promote consistent standards of practice in child care settings related to healthy environments and food, physical activity, physical literacy, decreased sedentary behaviours, and positive role modeling by staff. The Guidelines targeted 498 children aged 18 months to 5 years, attending MCC centres. Resources and training were provided to 10 supervisors, 63 child care educators and 9 cooks. Components of the Guidelines were piloted in 5 MCC sites prior to being launched in 10 MCC sites across Ottawa, Ontario. Two project Advisory Groups supported the development of the Guidelines. Staff training, resources, recipes and menus were provided. An evaluation was conducted and has informed the Guidelines' subsequent community implementation. In 2015, accompanying web-based resources and e-modules were developed. The evaluation demonstrated environmental and programming changes. Parent satisfaction was high and preliminary findings showed no real changes in food costs. Following implementation, the cooks reported high compliance to the 6-week menu plans provided, and the number of sites offering 120 minutes or more of daily physical activity increased. Through novel intersectoral partnerships, OPH was able to implement and evaluate HEAL Guidelines in tandem. The interdisciplinary project Advisory Groups, training of cooks, and engagement of the Ontario Coaches Association were all innovative elements of this project and may influence future public health activity in this area.

HPLC and HPLC/MS/MS Studies on Stress, Accelerated and Intermediate Degradation Tests of Antivirally Active Tricyclic Analog of Acyclovir.

PubMed

Lesniewska, Monika A; Dereziński, Paweł; Klupczyńska, Agnieszka; Kokot, Zenon J; Ostrowski, Tomasz; Zeidler, Joanna; Muszalska, Izabela

2015-01-01

The degradation behavior of a tricyclic analog of acyclovir [6-(4-MeOPh)-TACV] was determined in accordance with International Conference on Harmonization guidelines for good clinical practice under different stress conditions (neutral hydrolysis, strong acid/base degradation, oxidative decomposition, photodegradation, and thermal degradation). Accelerated [40±2°C/75%±5% relative humidity (RH)] and intermediate (30±2°C/65%±5% RH) stability tests were also performed. For observation of the degradation of the tested compound the RP-HPLC was used, whereas for the analysis of its degradation products HPLC/MS/MS was used. Degradation of the tested substance allowed its classification as unstable in neutral environment, acidic/alkaline medium, and in the presence of oxidizing agent. The tested compound was also light sensitive and was classified as photolabile both in solution and in the solid phase. However, the observed photodegradation in the solid phase was at a much lower level than in the case of photodegradation in solution. The study showed that both air temperature and RH had no significant effect on the stability of the tested substance during storage for 1 month at 100°C (dry heat) as well as during accelerated and intermediate tests. Based on the HPLC/MS/MS analysis, it can be concluded that acyclovir was formed as a degradation product of 6-(4-MeOPh)-TACV.

Balancing the stability and the catalytic specificities of OP hydrolases with enhanced V-agent activities.

PubMed

Reeves, T E; Wales, M E; Grimsley, J K; Li, P; Cerasoli, D M; Wild, J R

2008-06-01

Rational site-directed mutagenesis and biophysical analyses have been used to explore the thermodynamic stability and catalytic capabilities of organophosphorus hydrolase (OPH) and its genetically modified variants. There are clear trade-offs in the stability of modifications that enhance catalytic activities. For example, the H254R/H257L variant has higher turnover numbers for the chemical warfare agents VX (144 versus 14 s(-1) for the native enzyme (wild type) and VR (Russian VX, 465 versus 12 s(-1) for wild type). These increases are accompanied by a loss in stability in which the total Gibb's free energy for unfolding is 19.6 kcal/mol, which is 5.7 kcal/mol less than that of the wild-type enzyme. X-ray crystallographic studies support biophysical data that suggest amino acid residues near the active site contribute to the chemical and thermal stability through hydrophobic and cation-pi interactions. The cation-pi interactions appear to contribute an additional 7 kcal/mol to the overall global stability of the enzyme. Using rational design, it has been possible to make amino acid changes in this region that restored the stability, yet maintained effective V-agent activities, with turnover numbers of 68 and 36 s(-1) for VX and VR, respectively. This study describes the first rationally designed, stability/activity balance for an OPH enzyme with a legitimate V-agent activity, and its crystal structure.

Electronic structure description of the cis-MoOS unit in models for molybdenum hydroxylases.

PubMed

Doonan, Christian J; Rubie, Nick D; Peariso, Katrina; Harris, Hugh H; Knottenbelt, Sushilla Z; George, Graham N; Young, Charles G; Kirk, Martin L

2008-01-09

The molybdenum hydroxylases catalyze the oxidation of numerous aromatic heterocycles and simple organics and, unlike other hydroxylases, utilize water as the source of oxygen incorporated into the product. The electronic structures of the cis-MoOS units in CoCp2[TpiPrMoVOS(OPh)] and TpiPrMoVIOS(OPh) (TpiPr = hydrotris(3-isopropylpyrazol-1-yl)borate), new models for molybdenum hydroxylases, have been studied in detail using S K-edge X-ray absorption spectroscopy, vibrational spectroscopy, and detailed bonding calculations. The results show a highly delocalized Mo=S pi* LUMO redox orbital that is formally Mo(dxy) with approximately 35% sulfido ligand character. Vibrational spectroscopy has been used to quantitate Mo-Ssulfido bond order changes in the cis-MoOS units as a function of redox state. Results support a redox active molecular orbital that has a profound influence on MoOS bonding through changes to the relative electro/nucleophilicity of the terminal sulfido ligand accompanying oxidation state changes. The bonding description for these model cis-MoOS systems supports enzyme mechanisms that are under orbital control and dominantly influenced by the unique electronic structure of the cis-MoOS site. The electronic structure of the oxidized enzyme site is postulated to play a role in polarizing a substrate carbon center for nucleophilic attack by metal activated water and acting as an electron sink in the two-electron oxidation of substrates.

Current FDA directives for promoting public health

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

Hayes, A.H. Jr.

1982-03-01

The current directions of the FDA are outlined. The underlying philosophy of the FDA under the Reagan Administration is that both the private sector and the government must address the responsibilities to which they are best suited for the health-care system to work more efficiently. To facilitate this, FDA is conducting comprehensive reviews of FDA regulations and the drug-evaluation process. There are many dimensions to promoting public health, and the FDA alone cannot assure an adequate supply of safe and effective drugs. Innovative science and technology are needed to develop new drugs, followed by maximum potentiation (maximum good and leastmore » harm) after FDA approval. Hospital pharmacists have a role in maximizing the potential benefits of drugs through pharmacy and therapeutics committees. The current status of the pilot program for patient package inserts is described. The response at a recent hearing on the program indicates that the responsibility to protect the public health is shared by the government, health professions, industry, and the public. The FDA's campaign on sodium is based on that shared responsibility. By improving communication and building upon their common objections, both pharmacy and the FDA can do their jobs successfully.« less

76 FR 38184 - Agency Information Collection Activities; Proposed Collection; Comment Request; FDA Recall...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0439] Agency Information Collection Activities; Proposed Collection; Comment Request; FDA Recall Regulations AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA...

TU-AB-204-04: Partnerships

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

Ochs, R.

The responsibilities of the Food and Drug Administration (FDA) have increased since the inception of the Food and Drugs Act in 1906. Medical devices first came under comprehensive regulation with the passage of the 1938 Food, Drug, and Cosmetic Act. In 1971 FDA also took on the responsibility for consumer protection against unnecessary exposure to radiation-emitting devices for home and occupational use. However it was not until 1976, under the Medical Device Regulation Act, that the FDA was responsible for the safety and effectiveness of medical devices. This session will be presented by the Division of Radiological Health (DRH) andmore » the Division of Imaging, Diagnostics, and Software Reliability (DIDSR) from the Center for Devices and Radiological Health (CDRH) at the FDA. The symposium will discuss on how we protect and promote public health with a focus on medical physics applications organized into four areas: pre-market device review, post-market surveillance, device compliance, current regulatory research efforts and partnerships with other organizations. The pre-market session will summarize the pathways FDA uses to regulate the investigational use and commercialization of diagnostic imaging and radiation therapy medical devices in the US, highlighting resources available to assist investigators and manufacturers. The post-market session will explain the post-market surveillance and compliance activities FDA performs to monitor the safety and effectiveness of devices on the market. The third session will describe research efforts that support the regulatory mission of the Agency. An overview of our regulatory research portfolio to advance our understanding of medical physics and imaging technologies and approaches to their evaluation will be discussed. Lastly, mechanisms that FDA uses to seek public input and promote collaborations with professional, government, and international organizations, such as AAPM, International Electrotechnical Commission (IEC), Image Gently, and the Quantitative Imaging Biomarkers Alliance (QIBA) among others, to fulfill FDA’s mission will be discussed. Learning Objectives: Understand FDA’s pre-market and post-market review processes for medical devices Understand FDA’s current regulatory research activities in the areas of medical physics and imaging products Understand how being involved with AAPM and other organizations can also help to promote innovative, safe and effective medical devices J. Delfino, nothing to disclose.« less

Did FDA Decisionmaking Affect Anti-Psychotic Drug Prescribing in Children?: A Time-Trend Analysis.

PubMed

Wang, Bo; Franklin, Jessica M; Eddings, Wesley; Landon, Joan; Kesselheim, Aaron S

2016-01-01

Following Food and Drug Administration (FDA) approval, many drugs are prescribed for non-FDA-approved ("off-label") uses. If substantial evidence supports the efficacy and safety of off-label indications, manufacturers can pursue formal FDA approval through supplemental new drug applications (sNDAs). We evaluated the effect of FDA determinations on pediatric sNDAs for antipsychotic drugs on prescribing of these products in children. Retrospective, segmented time-series analysis using new prescription claims during 2003-2012 for three atypical antipsychotics (olanzapine, quetiapine, ziprasidone). FDA approved the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but did not approve the sNDA for pediatric use of ziprasidone. During the months before FDA approval of its pediatric sNDA, new prescriptions of olanzapine decreased for both children and adults. After FDA approval, the increase in prescribing trends was similar for both age groups (P = 0.47 for schizophrenia and bipolar disorder; P = 0.37 for other indications). Comparable decreases in use of quetiapine were observed between pediatrics and adults following FDA approval of its pediatric sNDA (P = 0.88; P = 0.63). Prescribing of ziprasidone decreased similarly for pediatric and adult patients after FDA non-approval of its pediatric sNDA (P = 0.61; P = 0.79). The FDA's sNDA determinations relating to use of antipsychotics in children did not result in changes in use that favored the approved sNDAs and disfavored the unapproved sNDA. Improved communication may help translate the agency's expert judgments to clinical practice.

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

76 FR 61709 - Agency Information Collection Activities; Proposed Collection; Comment Request; FDA Form 3728...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0708] Agency Information Collection Activities; Proposed Collection; Comment Request; FDA Form 3728, Animal...: The Food and Drug Administration (FDA) is announcing an opportunity for public comment on the proposed...

21 CFR 830.120 - Responsibilities of an FDA-accredited issuing agency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Responsibilities of an FDA-accredited issuing... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES UNIQUE DEVICE IDENTIFICATION FDA Accreditation of an Issuing Agency § 830.120 Responsibilities of an FDA-accredited issuing agency. To maintain its accreditation, an...

21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2011 CFR

2011-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... resubmit to FDA adverse drug experience reports forwarded to the applicant by FDA; however, applicants must submit all followup information on such reports to FDA. Any person subject to the reporting requirements...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

21 CFR 314.108 - New drug product exclusivity.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and... investigation means that before or during the investigation, the applicant was named in Form FDA-1571 filed with FDA as the sponsor of the investigational new drug application under which the investigation was...

77 FR 51949 - Privacy Act, Exempt Record System

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-28

.... FDA-2011-N-0252] Office of the Secretary 45 CFR Part 5b Privacy Act, Exempt Record System AGENCY... Drug Administration (FDA) of the Department of Health and Human Services (HHS) will be implementing a new system of records, 09-10-0020, ``FDA Records Related to Research Misconduct Proceedings, HHS/FDA...

21 CFR 314.96 - Amendments to an unapproved abbreviated application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Abbreviated... applicant on the same drug product formulation, unless the information has previously been submitted to FDA... and FDA determines that there may be bioequivalence issues or concerns with the product, FDA may...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

Internet Database Review: The FDA BBS.

ERIC Educational Resources Information Center

Tomaiuolo, Nicholas G.

1993-01-01

Describes the electronic bulletin board system (BBS) of the Food and Drug Administration (FDA) that is accessible through the Internet. Highlights include how to gain access; the menu-driven software; other electronic sources of FDA information; and adding value. Examples of the FDA BBS menu and the help screen are included. (LRW)

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

77 FR 14401 - Draft Guidance on Drug Safety Information-FDA's Communication to the Public; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2005-D-0339] Draft Guidance on Drug Safety Information--FDA's Communication to the Public; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2013 CFR

2013-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... resubmit to FDA adverse drug experience reports forwarded to the applicant by FDA; however, applicants must submit all followup information on such reports to FDA. Any person subject to the reporting requirements...

21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2012 CFR

2012-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... resubmit to FDA adverse drug experience reports forwarded to the applicant by FDA; however, applicants must submit all followup information on such reports to FDA. Any person subject to the reporting requirements...

78 FR 36194 - Draft Guidance for Industry and FDA Staff: Investigational New Drug Applications for Minimally...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-D-0490] Draft Guidance for Industry and FDA Staff: Investigational New Drug Applications for Minimally... Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the...

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

21 CFR 314.96 - Amendments to an unapproved abbreviated application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Abbreviated... applicant on the same drug product formulation, unless the information has previously been submitted to FDA... and FDA determines that there may be bioequivalence issues or concerns with the product, FDA may...

Quantum chemistry of the minimal CdSe clusters

NASA Astrophysics Data System (ADS)

Yang, Ping; Tretiak, Sergei; Masunov, Artëm E.; Ivanov, Sergei

2008-08-01

Colloidal quantum dots are semiconductor nanocrystals (NCs) which have stimulated a great deal of research and have attracted technical interest in recent years due to their chemical stability and the tunability of photophysical properties. While internal structure of large quantum dots is similar to bulk, their surface structure and passivating role of capping ligands (surfactants) are not fully understood to date. We apply ab initio wavefunction methods, density functional theory, and semiempirical approaches to study the passivation effects of substituted phosphine and amine ligands on the minimal cluster Cd2Se2, which is also used to benchmark different computational methods versus high level ab initio techniques. Full geometry optimization of Cd2Se2 at different theory levels and ligand coverage is used to understand the affinities of various ligands and the impact of ligands on cluster structure. Most possible bonding patterns between ligands and surface Cd/Se atoms are considered, including a ligand coordinated to Se atoms. The degree of passivation of Cd and Se atoms (one or two ligands attached to one atom) is also studied. The results suggest that B3LYP/LANL2DZ level of theory is appropriate for the system modeling, whereas frequently used semiempirical methods (such as AM1 and PM3) produce unphysical results. The use of hydrogen atom for modeling of the cluster passivating ligands is found to yield unphysical results as well. Hence, the surface termination of II-VI semiconductor NCs with hydrogen atoms often used in computational models should probably be avoided. Basis set superposition error, zero-point energy, and thermal corrections, as well as solvent effects simulated with polarized continuum model are found to produce minor variations on the ligand binding energies. The effects of Cd-Se complex structure on both the electronic band gap (highest occupied molecular orbital-lowest unoccupied molecular orbital energy difference) and ligand binding energies are systematically examined. The role played by positive charges on ligand binding is also explored. The calculated binding energies for various ligands L are found to decrease in the order OPMe3>OPH3>NH2Me>=NH3>=NMe3>PMe3>PH3 for neutral clusters and OPMe3>OPH3>PMe3>=NMe3>=NH2Me>=NH3>PH3 and OPMe3>OPH3>NH2Me>=NMe3>=PMe3>=NH3>PH3 for single and double ligations of positively charged Cd2Se22+ cluster, respectively.

The debate on FDA reform: a view from the U.S. Senate. Food and Drug Administration.

PubMed

Baker, R

1995-09-01

The recently released concept paper on Food and Drug Administration (FDA) reform from Republican Senator, Nancy Kassebaum, is reviewed. Senator Kassebaum chairs the Senate Committee on Labor and Human Resources that will influence the Senate's action on FDA reform. The paper outlines the Senator's priorities for Congressional legislation on FDA reform in the following areas: the FDA mission and its accountability; creation of a Performance Review Panel and Industry Advisory Council; approval and access of products for seriously ill patients; the FDA's responsibility for good manufacturing practices; establishment of an Ombudsman Office for resolving disputes; dissemination of information on unapproved uses of approved products; and approval standards for new drugs.

Use of data mining at the Food and Drug Administration.

PubMed

Duggirala, Hesha J; Tonning, Joseph M; Smith, Ella; Bright, Roselie A; Baker, John D; Ball, Robert; Bell, Carlos; Bright-Ponte, Susan J; Botsis, Taxiarchis; Bouri, Khaled; Boyer, Marc; Burkhart, Keith; Condrey, G Steven; Chen, James J; Chirtel, Stuart; Filice, Ross W; Francis, Henry; Jiang, Hongying; Levine, Jonathan; Martin, David; Oladipo, Taiye; O'Neill, Rene; Palmer, Lee Anne M; Paredes, Antonio; Rochester, George; Sholtes, Deborah; Szarfman, Ana; Wong, Hui-Lee; Xu, Zhiheng; Kass-Hout, Taha

2016-03-01

This article summarizes past and current data mining activities at the United States Food and Drug Administration (FDA). We address data miners in all sectors, anyone interested in the safety of products regulated by the FDA (predominantly medical products, food, veterinary products and nutrition, and tobacco products), and those interested in FDA activities. Topics include routine and developmental data mining activities, short descriptions of mined FDA data, advantages and challenges of data mining at the FDA, and future directions of data mining at the FDA. Published by Oxford University Press on behalf of the American Medical Informatics Association 2015. This work is written by US Government employees and is in the public domain in the US.

The Drug Facts Box: Improving the communication of prescription drug information.

PubMed

Schwartz, Lisa M; Woloshin, Steven

2013-08-20

Communication about prescription drugs ought to be a paragon of public science communication. Unfortunately, it is not. Consumers see $4 billion of direct-to-consumer advertising annually, which typically fails to present data about how well drugs work. The professional label--the Food and Drug Administration's (FDA) mechanism to get physicians information needed for appropriate prescribing--may also fail to present benefit data. FDA labeling guidance, in fact, suggests that industry omit benefit data for new drugs in an existing class and for drugs approved on the basis of unfamiliar outcomes (such as depression rating scales). The medical literature is also problematic: there is selective reporting of favorable trials, favorable outcomes within trials, and "spinning" unfavorable results to maximize benefit and minimize harm. In contrast, publicly available FDA reviews always include the phase 3 trial data on benefit and harm, which are the basis of drug approval. However, these reviews are practically inaccessible: lengthy, poorly organized, and weakly summarized. To improve accessibility, we developed the Drug Facts Box: a one-page summary of benefit and harm data for each indication of a drug. A series of studies--including national randomized trials--demonstrates that most consumers understand the Drug Facts Box and that it improves decision-making. Despite calls from their own Risk Communication Advisory Committee and Congress (in the Affordable Care Act) to consider implementing boxes, the FDA announced it needs at least 3-5 y more to make a decision. Given its potential public health impact, physicians and the public should not have to wait that long for better drug information.

The Drug Facts Box: Improving the communication of prescription drug information

PubMed Central

Schwartz, Lisa M.; Woloshin, Steven

2013-01-01

Communication about prescription drugs ought to be a paragon of public science communication. Unfortunately, it is not. Consumers see $4 billion of direct-to-consumer advertising annually, which typically fails to present data about how well drugs work. The professional label—the Food and Drug Administration's (FDA) mechanism to get physicians information needed for appropriate prescribing—may also fail to present benefit data. FDA labeling guidance, in fact, suggests that industry omit benefit data for new drugs in an existing class and for drugs approved on the basis of unfamiliar outcomes (such as depression rating scales). The medical literature is also problematic: there is selective reporting of favorable trials, favorable outcomes within trials, and “spinning” unfavorable results to maximize benefit and minimize harm. In contrast, publicly available FDA reviews always include the phase 3 trial data on benefit and harm, which are the basis of drug approval. However, these reviews are practically inaccessible: lengthy, poorly organized, and weakly summarized. To improve accessibility, we developed the Drug Facts Box: a one-page summary of benefit and harm data for each indication of a drug. A series of studies—including national randomized trials—demonstrates that most consumers understand the Drug Facts Box and that it improves decision-making. Despite calls from their own Risk Communication Advisory Committee and Congress (in the Affordable Care Act) to consider implementing boxes, the FDA announced it needs at least 3–5 y more to make a decision. Given its potential public health impact, physicians and the public should not have to wait that long for better drug information. PMID:23942130

Foreword: Follow-on Biologics: Implementation Challenges and Opportunities.

PubMed

Paradise, Jordan

2011-01-01

This Book of the Seton Hall Law Review presents the contributions to Follow-On Biologics: Implementation Challenges and Opportunities, a one-day roundtable event hosted by Seton Hall University School of Law in the fall of 2010. The roundtable fostered an international dialogue regarding the future of follow-on biologics in the United States resulting from the Patient Protection and Affordable Care Act of March 2010. THE BIOLOGIC PRICE COMPETITION AND INNOVATION ACT OF 2010. The March 23, 2010, enactment of the Patient Protection and Affordable Care Act (PPACA) and the companion Health Care and Education Affordability Reconciliation Act of 2010 ushered in landmark reform of the American health care system. Along with sweeping overhauls of the health care system generally, PPACA also provides a new regulatory challenge for the Food and Drug Administration (FDA). A subtitle within PPACA, the Biologics Price Competition and Innovation Act (BPCIA), bestows upon FDA broad authority to implement an abbreviated approval route to market for biological products (also known as biologics) that are "biosimilar" to an existing marketed product. The brief introduction will provide a basic comparison of biologics and conventional pharmaceutical drugs that will prove central to the FDA's development of this follow-on biologic pathway as well as specifically examine the content and scope of the BPCIA provisions and identify future challenges for the FDA. It will conclude by highlighting details of presentations during the roundtable held at the Seton Hall University School of Law and introduce the two resulting articles contained with this Book of the Seton Hall Law Review.

Evaluation of Radiation Doses Due to Consumption of Contaminated Food Items and Calculation of Food Class-Specific Derived Intervention Levels

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

Heinzelman, K M; Mansfield, W G

This document evaluates the expected radiation dose due to the consumption of several specific food classes (dairy, meat, produce, etc.) contaminated with specific radionuclides, and relates concentration levels in food to the detection abilities of typical aboratory analysis/measurement methods. The attached charts present the limiting organ dose as a function of the radionuclide concentration in a particular food class, and allow the user to compare these concentrations and doses to typical analytical detection apabilities. The expected radiation dose depends on several factors: the age of the individual; the radionuclide present in the food; the concentration of the radionuclide in themore » food; and the amount of food consumed. Food consumption rates for individuals of various ges were taken from the 1998 United States Food and Drug Administration (FDA) document, Accidental Radioactive Contamination of HUman Food and Animal Feeds: Recommendations for State and Local Agencies. In that document, the FDA defines the erived Intervention Level (DIL), which is the concentration of a particular radionuclide in food that if consumed could result in an individual receiving a radiation dose exceeding the Protection Action Guide (PAG) thresholds for intervention. This document also resents odified, food class specific DIL, which is calculated using a somewhat modified version of the FDA's procedure. This document begins with an overview of the FDA's DIL calculation, followed by a description of the food class specific DIL calculations, and finally charts of the radiation dose per radioactivity concentration for several food class/radionuclide combinations.« less

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 314.125 - Refusal to approve an application.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given in...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

76 FR 31615 - Draft Guidance for Industry and FDA Staff: Commercially Distributed In Vitro Diagnostic Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0305] Draft Guidance for Industry and FDA Staff: Commercially Distributed In Vitro Diagnostic Products Labeled...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

21 CFR 60.10 - FDA assistance on eligibility.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false FDA assistance on eligibility. 60.10 Section 60.10... TERM RESTORATION Eligibility Assistance § 60.10 FDA assistance on eligibility. (a) Upon written request from the U.S. Patent and Trademark Office, FDA will assist the U.S. Patent and Trademark Office in...

21 CFR 60.10 - FDA assistance on eligibility.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false FDA assistance on eligibility. 60.10 Section 60.10... TERM RESTORATION Eligibility Assistance § 60.10 FDA assistance on eligibility. (a) Upon written request from the U.S. Patent and Trademark Office, FDA will assist the U.S. Patent and Trademark Office in...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

77 FR 11553 - Draft Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0080... Food and Drug Administration (FDA) is announcing the availability of a draft guidance entitled ``FDA... that address nearly all aspects of the FDA approval and surveillance processes, including application...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 314.125 - Refusal to approve an application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given in...

21 CFR 830.110 - Application for accreditation as an issuing agency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES UNIQUE DEVICE IDENTIFICATION FDA Accreditation of an Issuing Agency.... (1) An applicant seeking initial FDA accreditation as an issuing agency shall notify FDA of its desire to be accredited by sending a notification by email to [email protected]fda.hhs.gov, or by correspondence to...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

29 CFR 1987.108 - Role of Federal agencies.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) PROCEDURES FOR HANDLING RETALIATION COMPLAINTS UNDER SECTION 402 OF THE FDA FOOD SAFETY...) The FDA, if interested in a proceeding, may participate as amicus curiae at any time in the proceeding, at the FDA's discretion. At the request of the FDA, copies of all documents in a case must be sent to...

21 CFR 314.125 - Refusal to approve an application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given in...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

76 FR 32367 - Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-1999-D-0742 (formerly Docket No. 1999D-4396)] Draft Guidance for Clinical Investigators, Industry, and FDA Staff...: Notice; correction. SUMMARY: The Food and Drug Administration (FDA) is correcting a notice that appeared...

78 FR 29141 - Center for Devices and Radiological Health Appeals Processes; Guidance for Industry and FDA Staff...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0893] Center for Devices and Radiological Health Appeals Processes; Guidance for Industry and FDA Staff... Administration (FDA) is announcing the availability of the guidance entitled ``Center for Devices and...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

21 CFR 801.57 - Discontinuation of legacy FDA identification numbers assigned to devices.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Discontinuation of legacy FDA identification... Device Identification § 801.57 Discontinuation of legacy FDA identification numbers assigned to devices... been assigned an FDA labeler code to facilitate use of NHRIC or NDC numbers may continue to use that...

78 FR 19492 - Draft Guidance for Industry on Formal Meetings Between FDA and Biosimilar Biological Product...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-0286] Draft Guidance for Industry on Formal Meetings Between FDA and Biosimilar Biological Product Sponsors or... Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled...

21 CFR 60.10 - FDA assistance on eligibility.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false FDA assistance on eligibility. 60.10 Section 60.10... TERM RESTORATION Eligibility Assistance § 60.10 FDA assistance on eligibility. (a) Upon written request from the U.S. Patent and Trademark Office, FDA will assist the U.S. Patent and Trademark Office in...

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

21 CFR 314.125 - Refusal to approve an application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given in...

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

75 FR 11893 - Food and Drug Administration Transparency Task Force; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-12

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0247... Administration, HHS. ACTION: Notice; request for comments. SUMMARY: The Food and Drug Administration (FDA) is soliciting comments from interested persons on ways in which FDA can increase transparency between FDA and...

77 FR 71803 - Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0080... and Drug Administration (FDA) is announcing the availability of a guidance entitled ``FDA Oversight of... nearly all aspects of the FDA approval and surveillance processes, including application submission...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 314.125 - Refusal to approve an application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given in...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 60.10 - FDA assistance on eligibility.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false FDA assistance on eligibility. 60.10 Section 60.10... TERM RESTORATION Eligibility Assistance § 60.10 FDA assistance on eligibility. (a) Upon written request from the U.S. Patent and Trademark Office, FDA will assist the U.S. Patent and Trademark Office in...

76 FR 41506 - Draft Guidance for Industry and FDA Staff on In Vitro Companion Diagnostic Devices; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0215] Draft Guidance for Industry and FDA Staff on In Vitro Companion Diagnostic Devices; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

76 FR 56205 - Request for Notification From Industry Organizations Interested in Participating in the Selection...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-12

... Products Scientific Advisory Committee, notify FDA in writing. FDA is also requesting nominations for... letters stating interest in participating in the selection process to FDA by October 12, 2011 (see... candidates should be sent to FDA by October 12, 2011. ADDRESSES: All letters of interest and nominations...

Regulating (for the benefit of) future persons: a different perspective on the FDA's jurisdiction to regulate human reproductive cloning.

PubMed

Javitt, Gail H; Hudson, Kathy

2003-01-01

The Food and Drug Administration (FDA) has taken the position that human reproductive cloning falls within its regulatory jurisdiction. This position has been subject to criticism on both procedural and substantive grounds. Some have contended that the FDA has failed to follow administrative law principles in asserting its jurisdiction, while others claim the FDA is ill suited to the task of addressing the ethical and social implications of human cloning. This Article argues, that, notwithstanding these criticisms, the FDA could plausibly assert jurisdiction over human cloning as a form of human gene therapy, an area in which the FDA is already regarded as having primary regulatory authority. Such an assertion would require that the FDA's jurisdiction extend to products affecting future persons, i.e., those not yet born. This Article demonstrates, for the first time, that such jurisdiction was implicit in the enactment of the 1962 Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act and that the FDA has historically relied on such authority in promulgating regulations for drugs and devices.

EBOLA and FDA: reviewing the response to the 2014 outbreak, to find lessons for the future

PubMed Central

Largent, Emily A.

2016-01-01

Abstract In 2014, West Africa confronted the most severe outbreak of Ebola virus disease (EVD) in history. At the onset of the outbreak—as now—there were no therapies approved by the U.S. Food and Drug Administration (FDA) for prevention of, post-exposure prophylaxis against, or treatment of EVD. As a result, the outbreak spurred interest in developing novel treatments, sparked calls to use experimental interventions in the field, and highlighted challenges to the standard approach to FDA approval of new drugs. Although the outbreak was geographically centered in West Africa, it showcased FDA's global role in drug development, approval, and access. FDA's response to EVD highlights the panoply of agency powers and demonstrates the flexibility of FDA's regulatory framework. This paper evaluates the strengths and weaknesses of FDA's response and makes policy recommendations regarding how FDA should respond to new and re-emerging public health threats. In particular, it argues that greater emphasis should be placed on drug development in interoutbreak periods and on assuring access to approved products. The current pandemic of Zika virus infection is but one example of an emerging health threat that will require FDA involvement in order to achieve a successful response. PMID:28852537

A Critical Review of Methods to Evaluate the Impact of FDA Regulatory Actions

PubMed Central

Briesacher, Becky A.; Soumerai, Stephen B.; Zhang, Fang; Toh, Sengwee; Andrade, Susan E.; Wagner, Joann L.; Shoaibi, Azadeh; Gurwitz, Jerry H.

2013-01-01

Purpose To conduct a synthesis of the literature on methods to evaluate the impacts of FDA regulatory actions, and identify best practices for future evaluations. Methods We searched MEDLINE for manuscripts published between January 1948 and August 2011 that included terms related to FDA, regulatory actions, and empirical evaluation; the review additionally included FDA-identified literature. We used a modified Delphi method to identify preferred methodologies. We included studies with explicit methods to address threats to validity, and identified designs and analytic methods with strong internal validity that have been applied to other policy evaluations. Results We included 18 studies out of 243 abstracts and papers screened. Overall, analytic rigor in prior evaluations of FDA regulatory actions varied considerably; less than a quarter of studies (22%) included control groups. Only 56% assessed changes in the use of substitute products/services, and 11% examined patient health outcomes. Among studies meeting minimal criteria of rigor, 50% found no impact or weak/modest impacts of FDA actions and 33% detected unintended consequences. Among those studies finding significant intended effects of FDA actions, all cited the importance of intensive communication efforts. There are preferred methods with strong internal validity that have yet to be applied to evaluations of FDA regulatory actions. Conclusions Rigorous evaluations of the impact of FDA regulatory actions have been limited and infrequent. Several methods with strong internal validity are available to improve trustworthiness of future evaluations of FDA policies. PMID:23847020

A comparison of new drugs approved by the FDA, the EMA, and Swissmedic: an assessment of the international harmonization of drugs.

PubMed

Zeukeng, Minette-Joëlle; Seoane-Vazquez, Enrique; Bonnabry, Pascal

2018-06-01

This study compared the characteristics of new human drugs approved by the Food and Drug Administration (FDA), the European Medicine Agency (EMA), and Swissmedic (SMC) in the period 2007 to 2016. The list of new drugs and therapeutic biologics approved by the FDA, the EMA, and SMC in the period 2007 to 2016 was collected from websites of those agencies. The study included regulatory information, approval date, and indication for each drug. Descriptive statistical t tests and x 2 -tests were performed for the analysis. From 2007 to 2016, 134 new drugs were approved by all three regulatory agencies. Overall, 66.4% of the drugs were first approved by the FDA, 30.6% by the EMA, and 3.0% by SMC. The difference in approval dates between SMC and the EMA, SMC and the FDA, and the FDA and the EMA were statistically significant. The indications approved by the FDA, the EMA, and SMC for the same drugs were similar in content for 23.1% drugs and different in 76.9% of the drugs. Significant differences in indications existed between the FDA and SMC and the FDA and the EMA, but not between the EMA and SMC. There were differences in the characteristics of new drugs approved by the EMA, the FDA, and SMC in the period 2007-2016. Overall, two thirds of the new drugs were first approved by the FDA. Differences in indications were found in three out of four new drugs approved by the three regulatory agencies. Despite international drug regulation harmonization efforts, significant differences in the characteristics of new drugs approved by different agencies persist.

Spin in RCTs of anxiety medication with a positive primary outcome: a comparison of concerns expressed by the US FDA and in the published literature.

PubMed

Beijers, Lian; Jeronimus, Bertus F; Turner, Erick H; de Jonge, Peter; Roest, Annelieke M

2017-03-29

This study aimed to determine the presence of spin in papers on positive randomised clinical trials (RCTs) of antidepressant medication for anxiety disorders by comparing concerns expressed in the Food and Drug Administration (FDA) reviews with those expressed in the published paper. For every positive anxiety medication trial with a matching publication (n=41), two independent reviewers identified the concerns raised in the US FDA reviews and those in the published literature. Spin was identified when concerns or limitations were expressed by the FDA (about the efficacy of the study drug) but not in the corresponding published paper. Concerns mentioned in the papers but not by the FDA were scored as 'non-FDA' concerns. Only six out of 35 (17%) of the FDA concerns pertaining to drug efficacy were reported in the papers. Two papers mentioned a concern that fit the FDA categories, but was not mentioned in the corresponding FDA review. Eighty-seven non-FDA concerns were counted, which often reflected general concerns or concerns related to the study design. Results indicate the presence of substantial spin in the clinical trial literature on drugs for anxiety disorders. In papers describing RCTs on anxiety medication, the concerns raised by the authors differed from those raised by the FDA. Published papers mentioned a large number of generic concerns about RCTs, such as a lack of long-term research and limited generalisability, while they mentioned few concerns about drug efficacy. These results warrant the promotion of independent statistical review, reporting of patient-level data, more study of spin, and an increased expectation that authors report FDA concerns. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Enhancing the incorporation of the patient's voice in drug development and evaluation.

PubMed

Chalasani, Meghana; Vaidya, Pujita; Mullin, Theresa

2018-01-01

People living with a condition are uniquely positioned to inform the understanding of the therapeutic context for drug development and evaluation. In 2012, the U.S. Food and Drug Administration (FDA) established the Patient-Focused Drug Development (PFDD) initiative to more systematically obtain the patient perspective on specific diseases and their currently available treatments. PFDD meetings are unique among FDA public meetings, with a format designed to engage patients and elicit their perspectives on two topic areas: (1) the most significant symptoms of their condition and the impact of the condition on daily life; and, (2) their current approaches to treatment. FDA has conducted 24 disease-specific PFDD meetings to date. The lessons learned from PFDD meetings range from experiences common across rare diseases to more disease specific experiences that matter most to patients. FDA recognizes that FDA-led PFDD meetings alone cannot address the gaps in information on the patient perspective. Patient-focused drug development is an ongoing effort and FDA looks forward to the next steps in advancing the science and the utilization of patient input throughout drug development and evaluation. The U.S. Food and Drug Administration (FDA) has multiple mechanisms for its regulators and staff to interact with patients -- but none quite like its novel Patient-Focused Drug Development (PFDD) initiative. FDA established the PFDD initiative to more systematically obtain the patient perspective on specific diseases and their currently available treatments. Since the initiative's inception in 2012, FDA has held 24 PFDD meetings, covering a range of disease areas and hearing directly from thousands of patients and caregivers. FDA's PFDD meetings have also provided key stakeholders, including patient advocates, researchers, drug developers, healthcare providers, and other government officials, an opportunity to hear the patient's voice. The lessons learned include but are not limited to specific experiences that matter most to patients, patient perspectives on meaningful treatment benefits and how patients want to be engaged in the drug development process. FDA recognizes that FDA-led PFDD meetings alone cannot address the gaps in information on the patient perspective. Further enhancing the incorporation of the patient's voice in drug development and evaluation continues to be a priority for FDA.

Characteristics of Clinical Studies Conducted Over the Total Product Life Cycle of High-Risk Therapeutic Medical Devices Receiving FDA Premarket Approval in 2010 and 2011.

PubMed

Rathi, Vinay K; Krumholz, Harlan M; Masoudi, Frederick A; Ross, Joseph S

2015-08-11

The US Food and Drug Administration (FDA) approves high-risk medical devices, those that support or sustain human life or present potential unreasonable risk to patients, via the Premarket Approval (PMA) pathway. The generation of clinical evidence to understand device safety and effectiveness is shifting from predominantly premarket to continual study throughout the total product life cycle. To characterize the clinical evidence generated for high-risk therapeutic devices over the total product life cycle. All clinical studies of high-risk therapeutic devices receiving initial market approval via the PMA pathway in 2010 and 2011 identified through ClinicalTrials.gov and publicly available FDA documents as of October 2014. Studies were characterized by type (pivotal, studies that served as the basis of FDA approval; FDA-required postapproval studies [PAS]; or manufacturer/investigator-initiated); premarket or postmarket; status (completed, ongoing, or terminated/unknown); and design features, including enrollment, comparator, and longest duration of primary effectiveness end point follow-up. In 2010 and 2011, 28 high-risk therapeutic devices received initial marketing approval via the PMA pathway. We identified 286 clinical studies of these devices: 82 (28.7%) premarket and 204 (71.3%) postmarket, among which there were 52 (18.2%) nonpivotal premarket studies, 30 (10.5%) pivotal premarket studies, 33 (11.5%) FDA-required PAS, and 171 (59.8%) manufacturer/investigator-initiated postmarket studies. Six of 33 (18.2%) PAS and 20 of 171 (11.7%) manufacturer/investigator-initiated postmarket studies were reported as completed. No postmarket studies were identified for 5 (17.9%) devices; 3 or fewer were identified for 13 (46.4%) devices overall. Median enrollment was 65 patients (interquartile range [IQR], 25-111), 241 patients (IQR, 147-415), 222 patients (IQR, 119-640), and 250 patients (IQR, 60-800) for nonpivotal premarket, pivotal, FDA-required PAS, and manufacturer/investigator-initiated postmarket studies, respectively. Approximately half of all studies used no comparator (pivotal: 13/30 [43.3%]; completed postmarket: 16/26 [61.5%]; ongoing postmarket: 70/153 [45.8%]). Median duration of primary effectiveness end point follow-up was 3.0 months (IQR, 3.0-12.0), 9.0 months (IQR, 0.3-12.0), and 12.0 months (IQR, 7.0-24.0) for pivotal, completed postmarket, and ongoing postmarket studies, respectively. Among high-risk therapeutic devices approved via the FDA PMA pathway, total product life cycle evidence generation varied in both the number and quality of premarket and postmarket studies, with approximately 13% of initiated postmarket studies completed between 3 and 5 years after FDA approval.

The FDA's Experience with Emerging Genomics Technologies-Past, Present, and Future.

PubMed

Xu, Joshua; Thakkar, Shraddha; Gong, Binsheng; Tong, Weida

2016-07-01

The rapid advancement of emerging genomics technologies and their application for assessing safety and efficacy of FDA-regulated products require a high standard of reliability and robustness supporting regulatory decision-making in the FDA. To facilitate the regulatory application, the FDA implemented a novel data submission program, Voluntary Genomics Data Submission (VGDS), and also to engage the stakeholders. As part of the endeavor, for the past 10 years, the FDA has led an international consortium of regulatory agencies, academia, pharmaceutical companies, and genomics platform providers, which was named MicroArray Quality Control Consortium (MAQC), to address issues such as reproducibility, precision, specificity/sensitivity, and data interpretation. Three projects have been completed so far assessing these genomics technologies: gene expression microarrays, whole genome genotyping arrays, and whole transcriptome sequencing (i.e., RNA-seq). The resultant studies provide the basic parameters for fit-for-purpose application of these new data streams in regulatory environments, and the solutions have been made available to the public through peer-reviewed publications. The latest MAQC project is also called the SEquencing Quality Control (SEQC) project focused on next-generation sequencing. Using reference samples with built-in controls, SEQC studies have demonstrated that relative gene expression can be measured accurately and reliably across laboratories and RNA-seq platforms. Besides prediction performance comparable to microarrays in clinical settings and safety assessments, RNA-seq is shown to have better sensitivity for low expression and reveal novel transcriptomic features. Future effort of MAQC will be focused on quality control of whole genome sequencing and targeted sequencing.

Compounding pharmacy conundrum: "we cannot live without them but we cannot live with them" according to the present paradigm.

PubMed

Guharoy, Roy; Noviasky, John; Haydar, Ziad; Fakih, Mohamad G; Hartman, Christian

2013-04-01

Compounding pharmacies serve a critical role in modern health care to meet special patient care needs. Although the US Food and Drug Administration (FDA) has clearly delineated jurisdiction over drug companies and products manufactured under Good Manufacturing Practice (GMP) regulations to ensure quality, potency, and purity, compounding pharmacies are regulated by the State Boards and are not registered by the FDA. In recent years, some compounding pharmacies acted like a manufacturer, preparing large amounts of injectable drugs with interstate activities. Multiple outbreaks have been linked to compounding pharmacies, including a recent outbreak of fungal meningitis related to contaminated methylprednisolone, exposing > 14,000 patients in multiple states. This tragedy underscores the urgency of addressing safety related to compounding pharmacies. There is a call for action at the federal and state levels to set minimum production standards, impose new labeling conditions on compounded drugs, and require large-scale compounders be regulated by the FDA. "Industrial" compounding must come under FDA oversight, require those pharmacies to meet GMP standards, and ensure quality and safe products for patient use. Moreover, compliance with the Institute for Safe Medication Practices 2011 recommendations that any type of sterile compounding must be in compliance with the United States Pharmacopoeia chapter 797 guidelines will reduce the risk of patient harm from microbial contamination. Finally, other critical factors that require close attention include addressing injectable products compounded in hospitals and other outpatient health-care centers. The FDA and State Boards of Pharmacy must be adequately funded to exercise the oversight effectively.

Optimal Protective Hypothermia in Arrested Mammalian Hearts

PubMed Central

Villet, Outi M.; Ge, Ming; Sekhar, Laigam N.; Corson, Marshall A.; Tylee, Tracy S.; Fan, Lu-Ping; Yao, Lin; Zhu, Chun; Olson, Aaron K.; Buroker, Norman E.; Xu, Cheng-Su; Anderson, David L.; Soh, Yong-Kian; Wang, Elise; Chen, Shi-Han; Portman, Michael A.

2015-01-01

Many therapeutic hypothermia recommendations have been reported, but the information supporting them is sparse, and reveals a need for the data of target therapeutic hypothermia (TTH) from well-controlled experiments. The core temperature ≤35°C is considered as hypothermia, and 29°C is a cooling injury threshold in pig heart in vivo. Thus, an optimal protective hypothermia (OPH) should be in the range 29–35°C. This study was conducted with a pig cardiopulmonary bypass preparation to decrease the core temperature to 29–35°C range at 20 minutes before and 60 minutes during heart arrest. The left ventricular (LV) developed pressure, maximum of the first derivative of LV (dP/dtmax), cardiac power, heart rate, cardiac output, and myocardial velocity (Vmax) were recorded continuously via an LV pressure catheter and an aortic flow probe. At 20 minutes of off-pump during reperfusion after 60 minutes arrest, 17 hypothermic hearts showed that the recovery of Vmax and dP/dtmax established sigmoid curves that consisted of two plateaus: a good recovery plateau at 29–30.5°C, the function recovered to baseline level (BL) (Vmax=118.4%±3.9% of BL, LV dP/dtmax=120.7%±3.1% of BL, n=6); another poor recovery plateau at 34–35°C (Vmax=60.2%±2.8% of BL, LV dP/dtmax=28.0%±5.9% of BL, p<0.05, n=6; ), which are similar to the four normothermia arrest (37°C) hearts (Vmax=55.9%±4.8% of BL, LV dP/dtmax=24.5%±2.1% of BL, n=4). The 32–32.5°C arrest hearts showed moderate recovery (n=5). A point of inflection (around 30.5–31°C) existed at the edge of a good recovery plateau followed by a steep slope. The point presented an OPH that should be the TTH. The results are concordant with data in the mammalian hearts, suggesting that the TTH should be initiated to cool core temperature at 31°C. PMID:25514569

Periodic and Aperiodic Variability in the Molecular Cloud ρ Ophiuchus

NASA Astrophysics Data System (ADS)

Parks, J. Robert; Plavchan, Peter; White, Russel J.; Gee, Alan H.

2014-03-01

Presented are the results of a near-IR photometric survey of 1678 stars in the direction of the ρ Ophiuchus (ρ Oph) star forming region using data from the 2MASS Calibration Database. For each target in this sample, up to 1584 individual J-, H-, and Ks -band photometric measurements with a cadence of ~1 day are obtained over three observing seasons spanning ~2.5 yr it is the most intensive survey of stars in this region to date. This survey identifies 101 variable stars with ΔKs -band amplitudes from 0.044 to 2.31 mag and Δ(J - Ks ) color amplitudes ranging from 0.053 to 1.47 mag. Of the 72 young ρ Oph star cluster members included in this survey, 79% are variable; in addition, 22 variable stars are identified as candidate members. Based on the temporal behavior of the Ks time-series, the variability is distinguished as either periodic, long time-scale or irregular. This temporal behavior coupled with the behavior of stellar colors is used to assign a dominant variability mechanism. A new period-searching algorithm finds periodic signals in 32 variable stars with periods between 0.49 to 92 days. The chief mechanism driving the periodic variability for 18 stars is rotational modulation of cool starspots while 3 periodically vary due to accretion-induced hot spots. The time-series for six variable stars contains discrete periodic "eclipse-like" features with periods ranging from 3 to 8 days. These features may be asymmetries in the circumstellar disk, potentially sustained or driven by a proto-planet at or near the co-rotation radius. Aperiodic, long time-scale variations in stellar flux are identified in the time-series for 31 variable stars with time-scales ranging from 64 to 790 days. The chief mechanism driving long time-scale variability is variable extinction or mass accretion rates. The majority of the variable stars (40) exhibit sporadic, aperiodic variability over no discernable time-scale. No chief variability mechanism could be identified for these variable stars.

A Resolved and Asymmetric Ring of PAHs within the Young Circumstellar Disk of IRS 48

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

Schworer, Guillaume; Lacour, Sylvestre; Du Foresto, Vincent Coudé

2017-06-20

For one decade, the spectral type and age of the ρ Oph object IRS-48 were subject to debate and mystery. Modeling its disk with mid-infrared to millimeter observations led to various explanations to account for the complex intricacy of dust holes and gas-depleted regions. We present multi-epoch high-angular-resolution interferometric near-infrared data of spatially resolved emissions in the first 15 au of IRS-48, known to have very strong polycyclic aromatic hydrocarbon (PAH) emissions within this dust-depleted region. We make use of new Sparse-Aperture-Masking data to instruct a revised radiative-transfer model, where spectral energy distribution fluxes and interferometry are jointly fitted. Neutralmore » and ionized PAH, very small grains (VSG), and classical silicates are incorporated into the model; new stellar parameters and extinction laws are explored. A bright (42 L {sub ⊙}) and hence large (2.5 R {sub ⊙}) central star with A {sub v} = 12.5 mag and R {sub v} = 6.5 requires less near-infrared excess: the inner-most disk at ≈1 au is incompatible with the interferometric data. The revised stellar parameters place this system on a 4 Myr evolutionary track, four times younger than the previous estimations, which is in better agreement with the surrounding ρ Oph region and disk-lifetime observations. The disk-structure solution converges to a classical-grain outer disk from 55 au combined with an unsettled and fully resolved VSG and PAH ring, between 11 and 26 au. We find two overluminosities in the PAH ring at color-temperatures consistent with the radiative transfer simulations; one follows a Keplerian circular orbit at 14 au. We show a depletion of a factor of ≈5 of classical dust grains up to 0.3 mm compared to very small particles: the IRS-48 disk is nearly void of dust grains in the first 55 au. A 3.5 M {sub Jup} planet on a 40 au orbit can qualitatively explain the new disk structure.« less

Chemistry in Magnetohydrodynamic Shock Waves in Diffuse Molecular Clouds

NASA Astrophysics Data System (ADS)

Peimbert, Antonio

1998-09-01

Absorption observations of the CH+ molecule with column densities of up to 1014 cm-2 in diffuse molecular clouds in many lines of sight are reviewed, and compared to the reddening and to abundances and velocity shifts of molecules like CH. Special attention is placed on the observations of the line of sight towards ς Ophiuchi where high quality observations of many chemical species are available. The problem of the required CH+ is described, and many formation mechanisms from the literature are reviewed, finding that none of them is particularly apt at describing the observations towards ς-Oph. Two fluid J-type shock models are studied as an alternative. The necessary conditions for their formation are discussed, and it is shown how they are expected to be present widely in the interstellar medium. Plane parallel numerical integrations, for the particular case in which the magnetic field is perpendicular to the shock velocity, are employed to study the region of phase-space of initial conditions that will produce 2 fluid shocks. A chemical network is developed and formation of key molecules like CH+, CH and OH, along with the excited roto-vibrational levels of H2, are studied under the shock dynamics. These models are then compared to the observations of the different lines of sight, showing they are capable of reproducing the features of the observations towards most of those clouds. An attempt to model the line of sight towards ς-Oph is done, finding that a shock with a shock speed vs = 9.0km/s going through a cloud with a density of nH = 14cm-3 with a magnetic field of B = 4.7μG does a reasonable job at satisfying most of the observations with the exception of the highest rotational excited states of molecular hydrogen for which observations are available. There is a small family of solutions capable of explaining the observed results which make specific predictions for the velocity profiles of the H2 lines of various excited levels. New observations with the Interstellar Medium Absorption Profile Spectrograph (IMAPS) camera would be useful in confirming or rejecting these models.

Application of a new non-linear least squares velocity curve analysis technique for spectroscopic binary stars

NASA Astrophysics Data System (ADS)

Karami, K.; Mohebi, R.; Soltanzadeh, M. M.

2008-11-01

Using measured radial velocity data of nine double lined spectroscopic binary systems NSV 223, AB And, V2082 Cyg, HS Her, V918 Her, BV Dra, BW Dra, V2357 Oph, and YZ Cas, we find corresponding orbital and spectroscopic elements via the method introduced by Karami and Mohebi (Chin. J. Astron. Astrophys. 7:558, 2007a) and Karami and Teimoorinia (Astrophys. Space Sci. 311:435, 2007). Our numerical results are in good agreement with those obtained by others using more traditional methods.

Phosphazenes with Olefinic Side Groups: Proton Abstraction Reactions of Fluoroalkoxy Derivatives.

DTIC Science & Technology

1982-06-24

OPh) (OC(Li)=CF2) 13 and [NP(OC(Li)CF2)2]3 1 respectively. These species are stable in solution at -78*C, but react with electrophiles such as 2...an -OCH2CF3 side group to generate an -OC(M)-CF2 unit. Subsequent treatment with an electrophile was designed to yield an -OC(R)-CF2 side group...resonances for the fluorine atoms in 2 and 5 appeared as multiplets due to the slight differences in chemical shift between the cis and trans

Hydrosilylation of aldehydes and ketones catalyzed by hydrido iron complexes bearing imine ligands.

PubMed

Zuo, Zhenyu; Sun, Hongjian; Wang, Lin; Li, Xiaoyan

2014-08-14

Two new hydrido iron complexes (2 and 4) were synthesized by the reactions of (4-methoxyphenyl)phenylketimine ((4-MeOPh)PhC=NH) with Fe(PMe3)4 or FeMe2(PMe3)4. The molecular structures of complexes 2 and 4 were confirmed by X-ray single crystal diffraction. Using hydrido iron complexes (1-4) as catalysts, the hydrosilylations of aldehydes and ketones were investigated. The four complexes were effective catalysts for this reduction reaction. Complex 1 among them is the best catalyst.

75 FR 29561 - Memorandum of Understanding Between the Food and Drug Administration and Drugs.Com

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0004] [FDA 225-09-0012] Memorandum of Understanding Between the Food and Drug Administration and Drugs.Com... Administration (FDA) is providing notice of a memorandum of understanding (MOU) between FDA and Drugs.Com. The...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false The Food and Drug Administration's (FDA's... (CONTINUED) FOOD ADDITIVES Premarket Notifications § 170.105 The Food and Drug Administration's (FDA's... data or other information available to FDA, including data not submitted by the manufacturer or...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

21 CFR 314.160 - Approval of an application or abbreviated application for which approval was previously refused...

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... of an applicant, FDA may, on the basis of new data, approve an application or abbreviated application which it had previously refused, suspended, or withdrawn approval. FDA will publish a notice in the...

21 CFR 314.160 - Approval of an application or abbreviated application for which approval was previously refused...

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... of an applicant, FDA may, on the basis of new data, approve an application or abbreviated application which it had previously refused, suspended, or withdrawn approval. FDA will publish a notice in the...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 314.160 - Approval of an application or abbreviated application for which approval was previously refused...

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... of an applicant, FDA may, on the basis of new data, approve an application or abbreviated application which it had previously refused, suspended, or withdrawn approval. FDA will publish a notice in the...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

21 CFR 314.160 - Approval of an application or abbreviated application for which approval was previously refused...

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... of an applicant, FDA may, on the basis of new data, approve an application or abbreviated application which it had previously refused, suspended, or withdrawn approval. FDA will publish a notice in the...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 314.162 - Removal of a drug product from the list.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

77 FR 55845 - Science Board to the Food and Drug Administration: Request for Nominations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001... Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is requesting nominations to serve on the Science Board to FDA (Science Board). FDA seeks to include the views of women and men...

21 CFR 314.162 - Removal of a drug product from the list.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

76 FR 62073 - Guidance for Industry on Implementation of the Fee Provisions of the FDA Food Safety...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0721] Guidance for Industry on Implementation of the Fee Provisions of the FDA Food Safety Modernization Act... Administration (FDA) is announcing the availability of a guidance for industry entitled ``Implementation of the...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 314.160 - Approval of an application or abbreviated application for which approval was previously refused...

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... of an applicant, FDA may, on the basis of new data, approve an application or abbreviated application which it had previously refused, suspended, or withdrawn approval. FDA will publish a notice in the...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

21 CFR 314.162 - Removal of a drug product from the list.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 314.162 - Removal of a drug product from the list.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

21 CFR 314.162 - Removal of a drug product from the list.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

78 FR 5463 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-25

... currently assessing any additional data requirements. In this regard, FDA published an Advance Notice of... report. Here, e-form FDA 3744a and reporting via the Electronic Submission Gateway are provided by FDA... January 17, 2012 (77 FR 2302), FDA published a 60-day notice requesting public comment on the proposed...

Drugs and Alcohol in Civil Aviation Accident Pilot Fatalities from 2004-2008

DTIC Science & Technology

2011-09-01

Quinine 16 0.9 19 1.1 37 2.3 42 3.1 FDA 򒾅 Salicylatesβ 96 5.2 114 6.8 41 2.6 11 0.8 FDA 򒾅 Simethicone 0 0.0 0 0.0 0 0.0 1 0.1 FDA 1996... Simethicone 0 0.0 0 0.0 0 0.0 1 0.1 FDA 1996 Triprolidine 0 0.0 0 0.0 2 0.1 2 0.1 FDA 򒾅 β – Screening Cutoff Increased in 2002 μ - Public Law

Removal of Review and Reclassification Procedures for Biological Products Licensed Prior to July 1, 1972. Final rule.

PubMed

2016-02-12

The Food and Drug Administration (FDA, the Agency, or we) is removing two regulations that prescribe procedures for FDA's review and classification of biological products licensed before July 1, 1972. FDA is taking this action because the two regulations are obsolete and no longer necessary in light of other statutory and regulatory authorities established since 1972, which allow FDA to evaluate and monitor the safety and effectiveness of all biological products. In addition, other statutory and regulatory authorities authorize FDA to revoke a license for biological products because they are not safe and effective, or are misbranded. FDA is taking this action as part of its retrospective review of its regulations to promote improvement and innovation.

Medical countermeasures for unwanted CBRN exposures: part II radiological and nuclear threats with review of recent countermeasure patents

PubMed Central

Singh, Vijay K.; Romaine, Patricia L.P.; Newman, Victoria L.; Seed, Thomas M.

2016-01-01

ABSTRACT Introduction: The global threat of a chemical, biological, radiological, or nuclear (CBRN) disaster is an important priority for all government agencies involved in domestic security and public health preparedness. Radiological/nuclear (RN) attacks or accidents have become a larger focus of the United States Food and Drug administration (US FDA) over time because of their increased likeliness. Clinical signs and symptoms of a developing acute radiation syndrome (ARS) are grouped into three sub-syndromes named for the dominant organ system affected, namely the hematopoietic (H-ARS), gastrointestinal (GI-ARS), and neurovascular systems. The availability of safe and effective countermeasures against radiological/nuclear threats currently represents a significant unmet medical need. Areas covered: This article reviews the development of RN threat medical countermeasures and highlights those specific countermeasures that have been recently patented and approved following the FDA Animal Rule. Patents for such agents from 2015 have been presented. Expert opinion: Two granulocyte colony-stimulating factor (G-CSF)-based radiation countermeasures (Neupogen® (Amgen, Thousand Oaks, CA) and Neulasta® (Amgen, Thousand Oaks, CA)) have recently been approved by the FDA for treatment of H-ARS and both these agents are radiomitigators, used after radiation exposure. To date, there are no FDA-approved radioprotectors for ARS. PMID:27610458

Advertising for AIDS drugs: it's everywhere lately, but is it helpful?

PubMed

Mirken, B

1998-07-01

The recent proliferation of direct to consumer (DTC) advertisements for prescription drugs, including HIV/AIDS drugs, can present a confusing and unrealistic picture of treatment options and outcomes; however, supporters claim that it stimulates awareness of treatment options and encourages dialogue between doctors and patients. The Food and Drug Administration (FDA), which regulates DTC advertising, requires that manufacturers disclose a complete description of benefits and adverse effects, similar to the information on the product's label. This balance of information applies to the written portion of the ad, but not to the visual message, which is arguably the most powerful part of the advertisement. Many of the visuals in the AIDS drugs advertisements misconstrue the effect of the virus on the patients. However, the FDA has not yet developed restrictions to more accurately control the visual component of advertisements, in order to depict the downside of disease. Additionally, manufacturers whose advertisements match the wording on their labels have an easier time getting acceptance from the FDA, but use more technical language than the typical lay person can understand. Reliance on the FDA- approved label description, restricts the drug companies from promoting off-label uses of their products, and also does not allow for the constantly changing information of a drug's effectiveness.

Fault detection and accommodation testing on an F100 engine in an F-15 airplane. [digital engine control system

NASA Technical Reports Server (NTRS)

Myers, L. P.; Baer-Riedhart, J. L.; Maxwell, M. D.

1985-01-01

The fault detection and accommodation (FDA) methods that can be used for digital engine control systems are presently subjected to a flight test program in the case of the F-15 fighter's F100 engine electronic controls, inducing selected faults and then evaluating the resulting digital engine control responses. In general, flight test results were found to compare well with both ground tests and predictions. It is noted that the inducement of dual-pressure failures was not feasible, since FDA logic was not designed to accommodate them.

OpenFDA: an innovative platform providing access to a wealth of FDA’s publicly available data

PubMed Central

Kass-Hout, Taha A; Mohebbi, Matthew; Nelsen, Hans; Baker, Adam; Levine, Jonathan; Johanson, Elaine; Bright, Roselie A

2016-01-01

Objective The objective of openFDA is to facilitate access and use of big important Food and Drug Administration public datasets by developers, researchers, and the public through harmonization of data across disparate FDA datasets provided via application programming interfaces (APIs). Materials and Methods Using cutting-edge technologies deployed on FDA’s new public cloud computing infrastructure, openFDA provides open data for easier, faster (over 300 requests per second per process), and better access to FDA datasets; open source code and documentation shared on GitHub for open community contributions of examples, apps and ideas; and infrastructure that can be adopted for other public health big data challenges. Results Since its launch on June 2, 2014, openFDA has developed four APIs for drug and device adverse events, recall information for all FDA-regulated products, and drug labeling. There have been more than 20 million API calls (more than half from outside the United States), 6000 registered users, 20,000 connected Internet Protocol addresses, and dozens of new software (mobile or web) apps developed. A case study demonstrates a use of openFDA data to understand an apparent association of a drug with an adverse event. Conclusion With easier and faster access to these datasets, consumers worldwide can learn more about FDA-regulated products. PMID:26644398

78 FR 65334 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... information, including certain labeling information, to FDA for approval to market a product in interstate... and in a form that FDA can process, review, and archive. This requirement is in addition to the....12(b) in table 1 of this document. In July 1997, FDA revised Form FDA 356h ``Application to Market a...

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2012 CFR

2012-04-01

... virus, Type 1 (e.g., FDA licensed screening test for anti-HIV-1); (2) Human immunodeficiency virus, Type 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2014 CFR

2014-04-01

... virus, Type 1 (e.g., FDA licensed screening test for anti-HIV-1); (2) Human immunodeficiency virus, Type 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... virus, Type 1 (e.g., FDA licensed screening test for anti-HIV-1); (2) Human immunodeficiency virus, Type 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2013 CFR

2013-04-01

... virus, Type 1 (e.g., FDA licensed screening test for anti-HIV-1); (2) Human immunodeficiency virus, Type 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

21 CFR 1.392 - Who receives a copy of the detention order?

Code of Federal Regulations, 2013 CFR

2013-04-01

... Fda Order A Detention? § 1.392 Who receives a copy of the detention order? (a) FDA must issue the... place where the article is detained, FDA must provide a copy of the detention order to the owner of the article of food if the owner's identity can be determined readily. (b) If FDA issues a detention order for...

21 CFR 1.392 - Who receives a copy of the detention order?

Code of Federal Regulations, 2012 CFR

2012-04-01

... Fda Order A Detention? § 1.392 Who receives a copy of the detention order? (a) FDA must issue the... place where the article is detained, FDA must provide a copy of the detention order to the owner of the article of food if the owner's identity can be determined readily. (b) If FDA issues a detention order for...

21 CFR 111.610 - What records must be made available to FDA?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false What records must be made available to FDA? 111... records must be made available to FDA? (a) You must have all records required under this part, or copies of such records, readily available during the retention period for inspection and copying by FDA when...

21 CFR 14.171 - Utilization of an advisory committee on the initiative of FDA.

Code of Federal Regulations, 2014 CFR

2014-04-01

... initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any... monitoring of the matter and consultation with FDA on behalf of the committee. The member or consultant may...

21 CFR 314.72 - Change in ownership of an application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.72... required to be kept under § 314.81, or a request for a copy of the application from FDA's files. FDA will provide a copy of the application to the new owner under the fee schedule in § 20.45 of FDA's public...