10 CFR 71.123 - Test control.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Test control. 71.123 Section 71.123 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PACKAGING AND TRANSPORTATION OF RADIOACTIVE MATERIAL Quality Assurance § 71.123 Test control. The licensee, certificate holder, and applicant for a CoC shall establish a test...

10 CFR 72.162 - Test control.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Test control. 72.162 Section 72.162 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR THE INDEPENDENT STORAGE OF SPENT NUCLEAR FUEL... Test control. The licensee, applicant for a license, certificate holder, and applicant for a CoC shall...

10 CFR 72.162 - Test control.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Test control. 72.162 Section 72.162 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR THE INDEPENDENT STORAGE OF SPENT NUCLEAR FUEL... Test control. The licensee, applicant for a license, certificate holder, and applicant for a CoC shall...

10 CFR 71.125 - Control of measuring and test equipment.

Code of Federal Regulations, 2010 CFR

2010-01-01

... MATERIAL Quality Assurance § 71.125 Control of measuring and test equipment. The licensee, certificate holder, and applicant for a CoC shall establish measures to assure that tools, gauges, instruments, and other measuring and testing devices used in activities affecting quality are properly controlled...

10 CFR 72.232 - Inspection and tests.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Inspection and tests. 72.232 Section 72.232 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR THE INDEPENDENT STORAGE OF SPENT NUCLEAR FUEL... Storage Casks § 72.232 Inspection and tests. (a) The certificate holder and applicant for a CoC shall...

10 CFR 72.162 - Test control.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Test control. 72.162 Section 72.162 Energy NUCLEAR... Test control. The licensee, applicant for a license, certificate holder, and applicant for a CoC shall establish a test program to ensure that all testing, required to demonstrate that the structures, systems...

10 CFR 71.123 - Test control.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Test control. 71.123 Section 71.123 Energy NUCLEAR....123 Test control. The licensee, certificate holder, and applicant for a CoC shall establish a test... satisfactorily in service is identified and performed in accordance with written test procedures that incorporate...

10 CFR 71.107 - Package design control.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Package design control. 71.107 Section 71.107 Energy... Assurance § 71.107 Package design control. (a) The licensee, certificate holder, and applicant for a CoC... identification and control of design interfaces and for coordination among participating design organizations...

10 CFR 71.107 - Package design control.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Package design control. 71.107 Section 71.107 Energy... Assurance § 71.107 Package design control. (a) The licensee, certificate holder, and applicant for a CoC... identification and control of design interfaces and for coordination among participating design organizations...

10 CFR 72.146 - Design control.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Design control. 72.146 Section 72.146 Energy NUCLEAR... Design control. (a) The licensee, applicant for a license, certificate holder, and applicant for a CoC... shall establish measures for the identification and control of design interfaces and for coordination...

10 CFR 72.146 - Design control.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Design control. 72.146 Section 72.146 Energy NUCLEAR... Design control. (a) The licensee, applicant for a license, certificate holder, and applicant for a CoC... shall establish measures for the identification and control of design interfaces and for coordination...

10 CFR 71.107 - Package design control.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Package design control. 71.107 Section 71.107 Energy... Assurance § 71.107 Package design control. (a) The licensee, certificate holder, and applicant for a CoC... identification and control of design interfaces and for coordination among participating design organizations...

10 CFR 72.146 - Design control.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Design control. 72.146 Section 72.146 Energy NUCLEAR... Design control. (a) The licensee, applicant for a license, certificate holder, and applicant for a CoC... shall establish measures for the identification and control of design interfaces and for coordination...

10 CFR 71.107 - Package design control.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Package design control. 71.107 Section 71.107 Energy... Assurance § 71.107 Package design control. (a) The licensee, certificate holder, and applicant for a CoC... identification and control of design interfaces and for coordination among participating design organizations...

10 CFR 71.107 - Package design control.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Package design control. 71.107 Section 71.107 Energy... Assurance § 71.107 Package design control. (a) The licensee, certificate holder, and applicant for a CoC... identification and control of design interfaces and for coordination among participating design organizations...

10 CFR 72.146 - Design control.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Design control. 72.146 Section 72.146 Energy NUCLEAR... Design control. (a) The licensee, applicant for a license, certificate holder, and applicant for a CoC... shall establish measures for the identification and control of design interfaces and for coordination...

10 CFR 72.146 - Design control.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Design control. 72.146 Section 72.146 Energy NUCLEAR... Design control. (a) The licensee, applicant for a license, certificate holder, and applicant for a CoC... shall establish measures for the identification and control of design interfaces and for coordination...

10 CFR 72.152 - Document control.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Document control. 72.152 Section 72.152 Energy NUCLEAR... Document control. The licensee, applicant for a license, certificate holder, and applicant for a CoC shall establish measures to control the issuance of documents such as instructions, procedures, and drawings...

10 CFR 72.152 - Document control.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Document control. 72.152 Section 72.152 Energy NUCLEAR... Document control. The licensee, applicant for a license, certificate holder, and applicant for a CoC shall establish measures to control the issuance of documents such as instructions, procedures, and drawings...

10 CFR 72.152 - Document control.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Document control. 72.152 Section 72.152 Energy NUCLEAR... Document control. The licensee, applicant for a license, certificate holder, and applicant for a CoC shall establish measures to control the issuance of documents such as instructions, procedures, and drawings...

10 CFR 72.172 - Corrective action.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Corrective action. 72.172 Section 72.172 Energy NUCLEAR... Corrective action. The licensee, applicant for a license, certificate holder, and applicant for a CoC shall... that the cause of the condition is determined and corrective action is taken to preclude repetition...

10 CFR 72.172 - Corrective action.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Corrective action. 72.172 Section 72.172 Energy NUCLEAR... Corrective action. The licensee, applicant for a license, certificate holder, and applicant for a CoC shall... that the cause of the condition is determined and corrective action is taken to preclude repetition...

Budget of coral-derived organic carbon in a fringing coral reef of the Gulf of Aqaba, Red Sea

NASA Astrophysics Data System (ADS)

Naumann, Malik S.; Richter, Claudio; Mott, Claudius; el-Zibdah, Mohammad; Manasrah, Riyad; Wild, Christian

2012-12-01

The continuous release of organic C-rich material by reef-building corals can contribute substantially to biogeochemical processes and concomitant rapid nutrient recycling in coral reef ecosystems. However, our current understanding of these processes is limited to platform reefs exhibiting a high degree of ecosystem closure compared to the globally most common fringing reef type. This study carried out in the northern Gulf of Aqaba (Red Sea) presents the first quantitative budget for coral-derived organic carbon (COC) in a fringing reef and highlights the importance of local hydrodynamics. Diel reef-wide COC release amounted to 1.1 ± 0.2 kmol total organic carbon (TOC) representing 1-3% of gross benthic primary production. Most COC (73%) was released as particulate organic C (POC), the bulk of which (34-63%) rapidly settled as mucus string aggregates accounting for approximately 28% of total POC sedimentation. Sedimentation of mucus strings, but also dilution of suspended and dissolved COC in reef waters retained 82% of diel COC release in the fringing reef, providing a potentially important organic source for a COC-based food web. Pelagic COC degradation represented 0.1-1.6% of pelagic microbial respiration recycling 32% of diel retained COC. Benthic COC degradation contributed substantially (29-47%) to reef-wide microbial respiration in reef sands, including 20-38% by mucus string POC, and consumed approximately 52% of all retained COC. These findings point out the importance of COC as a C carrier for different reef types. COC may further represent a source of organic carbon for faunal communities colonising reef framework cavities complementing the efficient retention and recycling of COC within fringing reef environments.

48 CFR 419.602-3 - Resolving differences between the agency and the Small Business Administration.

Code of Federal Regulations, 2010 CFR

2010-10-01

... between the agency and the Small Business Administration. 419.602-3 Section 419.602-3 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Certificates of... Small Business Administration. The HCA is authorized to appeal the issuance of a COC to SBA Headquarters...

48 CFR 19.602-3 - Resolving differences between the agency and the Small Business Administration.

Code of Federal Regulations, 2011 CFR

2011-10-01

... between the agency and the Small Business Administration. 19.602-3 Section 19.602-3 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Certificates... and the Small Business Administration. (a) COCs valued between $100,000 and $25,000,000. (1) When...

48 CFR 419.602-3 - Resolving differences between the agency and the Small Business Administration.

Code of Federal Regulations, 2011 CFR

2011-10-01

... between the agency and the Small Business Administration. 419.602-3 Section 419.602-3 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Certificates of... Small Business Administration. The HCA is authorized to appeal the issuance of a COC to SBA Headquarters...

10 CFR 72.248 - Safety analysis report updating.

Code of Federal Regulations, 2014 CFR

2014-01-01

... appropriate, the last update to the FSAR under this section. The update shall include the effects 1 of: 1... for a spent fuel storage cask design shall update periodically, as provided in paragraph (b) of this... the issued Certificate of Compliance (CoC). (b) Each update shall contain all the changes necessary to...

10 CFR 72.248 - Safety analysis report updating.

Code of Federal Regulations, 2013 CFR

2013-01-01

... appropriate, the last update to the FSAR under this section. The update shall include the effects 1 of: 1... for a spent fuel storage cask design shall update periodically, as provided in paragraph (b) of this... the issued Certificate of Compliance (CoC). (b) Each update shall contain all the changes necessary to...

10 CFR 72.248 - Safety analysis report updating.

Code of Federal Regulations, 2012 CFR

2012-01-01

... appropriate, the last update to the FSAR under this section. The update shall include the effects 1 of: 1... for a spent fuel storage cask design shall update periodically, as provided in paragraph (b) of this... the issued Certificate of Compliance (CoC). (b) Each update shall contain all the changes necessary to...

10 CFR 72.248 - Safety analysis report updating.

Code of Federal Regulations, 2011 CFR

2011-01-01

... appropriate, the last update to the FSAR under this section. The update shall include the effects 1 of: 1... for a spent fuel storage cask design shall update periodically, as provided in paragraph (b) of this... the issued Certificate of Compliance (CoC). (b) Each update shall contain all the changes necessary to...

48 CFR 419.602-3 - Resolving differences between the agency and the Small Business Administration.

Code of Federal Regulations, 2012 CFR

2012-10-01

... between the agency and the Small Business Administration. 419.602-3 Section 419.602-3 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Certificates of... Small Business Administration. The HCA is authorized to appeal the issuance of a COC to SBA Headquarters...

Toxic cocaine- and convulsant-induced modification of forced swimming behaviors and their interaction with ethanol: comparison with immobilization stress

PubMed Central

Hayase, Tamaki; Yamamoto, Yoshiko; Yamamoto, Keiichi

2002-01-01

Background Swimming behaviors in the forced swimming test have been reported to be depressed by stressors. Since toxic convulsion-inducing drugs related to dopamine [cocaine (COC)], benzodiazepine [methyl 6,7-dimethoxy-4-ethyl-β-carboline-carboxylate (DMCM)], γ-aminobutyric acid (GABA) [bicuculline (BIC)], and glutamate [N-methyl-D-aspartate (NMDA)] receptors can function as stressors, the present study compared their effects on the forced swimming behaviors with the effects of immobilization stress (IM) in rats. Their interactions with ethanol (EtOH), the most frequently coabused drug with COC which also induces convulsions as withdrawal symptoms but interferes with the convulsions caused by other drugs, were also investigated. Results Similar to the IM (10 min) group, depressed swimming behaviors (attenuated time until immobility and activity counts) were observed in the BIC (5 mg/kg IP) and DMCM (10 mg/kg IP) groups at the 5 h time point, after which no toxic behavioral symptoms were observed. However, they were normalized to the control levels at the 12 h point, with or without EtOH (1.5 g/kg IP). In the COC (60 mg/kg IP) and NMDA (200 mg/kg IP) groups, the depression occurred late (12 h point), and was normalized by the EtOH cotreatment. At the 5 h point, the COC treatment enhanced the swimming behaviors above the control level. Conclusions Although the physiological stress (IM), BIC, and DMCM also depressed the swimming behaviors, a delayed occurrence and EtOH-induced recovery of depressed swimming were observed only in the COC and NMDA groups. This might be correlated with the previously-reported delayed responses of DA and NMDA neurons rather than direct effects of the drugs, which could be suppressed by EtOH. Furthermore, the characteristic psychostimulant effects of COC seemed to be correlated with an early enhancement of swimming behaviors. PMID:12425723

RECERTIFICATION OF THE MODEL 9977 RADIOACTIVE MATERIAL PACKAGING

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

Abramczyk, G.; Bellamy, S.; Loftin, B.

2013-06-05

The Model 9977 Packaging was initially issued a Certificate of Compliance (CoC) by the Department of Energy’s Office of Environmental Management (DOE-EM) for the transportation of radioactive material (RAM) in the Fall of 2007. This first CoC was for a single radioactive material and two packing configurations. In the five years since that time, seven Addendums have been written to the Safety Analysis Report for Packaging (SARP) and five Letter Amendments have been written that have authorized either new RAM contents or packing configurations, or both. This paper will discuss the process of updating the 9977 SARP to include allmore » the contents and configurations, including the addition of a new content, and its submittal for recertification.« less

Extrapolation of radiation thermometry scales for determining the transition temperature of metal-carbon points. Experiments with the Co-C

NASA Astrophysics Data System (ADS)

Battuello, M.; Girard, F.; Florio, M.

2009-02-01

Four independent radiation temperature scales approximating the ITS-90 at 900 nm, 950 nm and 1.6 µm have been realized from the indium point (429.7485 K) to the copper point (1357.77 K) which were used to derive by extrapolation the transition temperature T90(Co-C) of the cobalt-carbon eutectic fixed point. An INRIM cell was investigated and an average value T90(Co-C) = 1597.20 K was found with the four values lying within 0.25 K. Alternatively, thermodynamic approximated scales were realized by assigning to the fixed points the best presently available thermodynamic values and deriving T(Co-C). An average value of 1597.27 K was found (four values lying within 0.25 K). The standard uncertainties associated with T90(Co-C) and T(Co-C) were 0.16 K and 0.17 K, respectively. INRIM determinations are compatible with recent thermodynamic determinations on three different cells (values lying between 1597.11 K and 1597.25 K) and with the result of a comparison on the same cell by an absolute radiation thermometer and an irradiance measurement with filter radiometers which give values of 1597.11 K and 1597.43 K, respectively (Anhalt et al 2006 Metrologia 43 S78-83). The INRIM approach allows the determination of both ITS-90 and thermodynamic temperature of a fixed point in a simple way and can provide valuable support to absolute radiometric methods in defining the transition temperature of new high-temperature fixed points.

Co-C and Pd-C Eutectic Fixed Points for Radiation Thermometry and Thermocouple Thermometry

NASA Astrophysics Data System (ADS)

Wang, L.

2017-12-01

Two Co-C and Pd-C eutectic fixed point cells for both radiation thermometry and thermocouple thermometry were constructed at NMC. This paper describes details of the cell design, materials used, and fabrication of the cells. The melting curves of the Co-C and Pd-C cells were measured with a reference radiation thermometer realized in both a single-zone furnace and a three-zone furnace in order to investigate furnace effect. The transition temperatures in terms of ITS-90 were determined to be 1324.18 {°}C and 1491.61 {°}C with the corresponding combined standard uncertainty of 0.44 {°}C and 0.31 {°}C for Co-C and Pd-C, respectively, taking into account of the differences of two different types of furnaces used. The determined ITS-90 temperatures are also compared with that of INRIM cells obtained using the same reference radiation thermometer and the same furnaces with the same settings during a previous bilateral comparison exercise (Battuello et al. in Int J Thermophys 35:535-546, 2014). The agreements are within k=1 uncertainty for Co-C cell and k = 2 uncertainty for Pd-C cell. Shapes of the plateaus of NMC cells and INRIM cells are compared too and furnace effects are analyzed as well. The melting curves of the Co-C and Pd-C cells realized in the single-zone furnace are also measured by a Pt/Pd thermocouple, and the preliminary results are presented as well.

Co-C and Pd-C Fixed Points for the Evaluation of Facilities and Scales Realization at INRIM and NMC

NASA Astrophysics Data System (ADS)

Battuello, M.; Wang, L.; Girard, F.; Ang, S. H.

2014-04-01

Two hybrid cells for realizing the Co-C and Pd-C fixed points and constructed at Istituto Nazionale di Ricerca Metrologica (INRIM) were used for an evaluation of facilities and procedures adopted by INRIM and National Metrology Institute of Singapore (NMC) for the realization of the solid-liquid phase transitions of high-temperature fixed points and for determining their transition temperatures. Four different furnaces were used for the investigations, i.e., two single-zone furnaces, one of them of the direct-heating type, and two identical three-zone furnaces. The transition temperatures were measured at both institutes by adopting different procedures for realizing the radiation scales, i.e., at INRIM a scheme based on the extrapolation of fixed-point interpolated scales and an International Temperature Scale of 1990 (ITS-90) approach at NMC. The point of inflection (POI) of the melting curves was determined and assumed as a practical representation of the melting temperature. Different methods for deriving the POI were used, and differences as large as some hundredths of a kelvin were found with the different approaches. The POIs of the different melting curves were analyzed with respect to the different possible operative conditions with the aim of deriving reproducibility figures to improve the estimated uncertainty. As regard to the institutes inter-comparison, differences of 0.13 K and 0.29 K were found between INRIM and NMC determinations at the Co-C and Pd-C points, respectively. Such differences are compatible with the combined standard uncertainties of the comparison, which are estimated to be 0.33 K and 0.36 K at the Co-C and Pd-C points, respectively.

Laser-Induced Melting of Co-C Eutectic Cells as a New Research Tool

NASA Astrophysics Data System (ADS)

van der Ham, E.; Ballico, M.; Jahan, F.

2015-08-01

A new laser-based technique to examine heat transfer and energetics of phase transitions in metal-carbon fixed points and potentially to improve the quality of phase transitions in furnaces with poor uniformity is reported. Being reproducible below 0.1 K, metal-carbon fixed points are increasingly used as reference standards for the calibration of thermocouples and radiation thermometers. At NMIA, the Co-C eutectic point is used for the calibration of thermocouples, with the fixed point traceable to the International Temperature Scale (ITS-90) using radiation thermometry. For thermocouple use, these cells are deep inside a high-uniformity furnace, easily obtaining excellent melting plateaus. However, when used with radiation thermometers, the essential large viewing cone to the crucible restricts the furnace depth and introduces large heat losses from the front furnace zone, affecting the quality of the phase transition. Short laser bursts have been used to illuminate the cavity of a conventional Co-C fixed-point cell during various points in its melting phase transition. The laser is employed to partially melt the metal at the rear of the crucible providing a liquid-solid interface close to the region being observed by the reference pyrometer. As the laser power is known, a quantitative estimate of can be made for the Co-C latent heat of fusion. Using a single laser pulse during a furnace-induced melt, a plateau up to 8 min is observed before the crucible resumes a characteristic conventional melt curve. Although this plateau is satisfyingly flat, well within 100 mK, it is observed that the plateau is laser energy dependent and elevates from the conventional melt "inflection-point" value.

78 FR 8050 - Spent Fuel Cask Certificate of Compliance Format and Content

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-05

... Rule for CoC Format and Content The petitioner states that amending 10 CFR part 72, subpart L, to... conforming changes be made to 10 CFR 72.13. The petitioner argues that ``[n]ew or amended NRC staff positions... 72, subpart L, be amended to remove the requirement that the empty weight be marked on storage casks...

Safety evaluation for packaging for the transport of K Basin sludge samples in the PAS-1 cask

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

SMITH, R.J.

1998-11-17

This safety evaluation for packaging authorizes the shipment of up to two 4-L sludge samples to and from the 325 Lab or 222-S Lab for characterization. The safety of this shipment is based on the current U.S. Department of Energy Certification of Compliance (CoC) for the PAS-1 cask, USA/9184/B(U) (DOE).

Influence of the Cavity Length on the Behavior of Hybrid Fixed-Point Cells Constructed at INRIM

NASA Astrophysics Data System (ADS)

Battuello, M.; Girard, F.; Florio, M.

2015-03-01

Hybrid cells with double carbon/carbon sheets are used at the Istituto Nazionale di Ricerca Metrologica (INRIM) for the realization of both pure metal fixed points and high-temperature metal-carbon eutectic points. Cells for the Cu and Co-C fixed points have been prepared to be used in the high-temperature fixed-point project of the Comité Consultatif de Thermométrie. The results of the evaluation processes were not completely satisfactory for the INRIM cells because of their low transition temperatures with respect to the best cells, and of a rather large melting range for the Co-C cell. A new design of the cells was devised, and considerable improvements were achieved with respect to the transition temperature, and the plateau shape and duration. As for the Cu point, the duration of the freezing plateaux increased by more than 50 % and the freezing temperature increased by 18 mK. As for the Co-C point, the melting temperature, expressed in terms of the point of inflection of the melting curve, increased by about 70 mK. The melting range of the plateaux, expressed as a difference was reduced from about 180 mK to about 130 mK, with melting times increased by about 50 %, as a consequence of an improvement of flatness and run-off of the plateaux.

Traceable Co-C eutectic points for thermocouple calibration

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

Jahan, F.; Ballico, M. J.

2013-09-11

National Measurement Institute of Australia (NMIA) has developed a miniature crucible design suitable for measurement by both thermocouples and radiation thermometry, and has established an ensemble of five Co-C eutectic-point cells based on this design. The cells in this ensemble have been individually calibrated using both ITS-90 radiation thermometry and thermocouples calibrated on the ITS-90 by the NMIA mini-coil methodology. The assigned ITS-90 temperatures obtained using these different techniques are both repeatable and consistent, despite the use of different furnaces and measurement conditions. The results demonstrate that, if individually calibrated, such cells can be practically used as part of amore » national traceability scheme for thermocouple calibration, providing a useful intermediate calibration point between Cu and Pd.« less

[Effect of combined oral contraceptives on the hypophyseo-thyroid and hypophyseo-adrenal systems in women with various anatomy of the thyroid gland].

PubMed

Zigizmund, V A; Sadykova, M Sh; Samoĭlova, O N; Moiseeva, O M

1988-11-01

Potential therapeutic effects of combined oral contraceptives (COC) rigevidon and ovidon (estrogen:gestagen ratio of 1:5) were studied in 97 women aged 19-35 years. With respect to the anatomical state of the thyroid, the patients were divided into two groups: group 1 included 42 women with normal thyroid function and group 2 included 55 women with euthyroid hyperplasia of the thyroid gland of stage I-II (the anatomical state of the thyroid gland was ranked according to the five-point Swiss scale adopted by WHO in 1975). All patients had a history of pregnancy, normal delivery, or abortion. The state of the pituitary-thyroid system was estimated by absorption of iodine isotopes in the thyroid tissue, and by the blood levels of thyrotropic hormone, thyroxine-binding globulin, thyroxine, and triiodothyronine. Activity of the pituitary- adrenal system was estimated by the blood levels of adrenocorticotropic hormone (ACTH) and cortisol. Blood samples were withdrawn 9 and 10 hours prior to the onset of COC administration, and after 24 and 48 weeks of COC use. The changes in the functional state of the pituitary- thyroid system in groups 1 and 2 were identical throughout the entire period of COC administration. Progressive increase in the levels of thyroxine and triiodothyronine was associated with inhibition of the thyrotropic function of the pituitary seen as decrease in thyrotropin levels. COC administration caused decrease in size of hyperplastic tyroid gland. Prior to COC administration, women in group 2 showed significant elevation of ACTH levels and marked decrease in ACTH levels and increase in cortisol levels in both groups. Normalization of the size of thyroid gland indicated that COC be used therapeutically in patients with thyroid hyperplasia.

Source-water susceptibility assessment in Texas—Approach and methodology

USGS Publications Warehouse

Ulery, Randy L.; Meyer, John E.; Andren, Robert W.; Newson, Jeremy K.

2011-01-01

Public water systems provide potable water for the public's use. The Safe Drinking Water Act amendments of 1996 required States to prepare a source-water susceptibility assessment (SWSA) for each public water system (PWS). States were required to determine the source of water for each PWS, the origin of any contaminant of concern (COC) monitored or to be monitored, and the susceptibility of the public water system to COC exposure, to protect public water supplies from contamination. In Texas, the Texas Commission on Environmental Quality (TCEQ) was responsible for preparing SWSAs for the more than 6,000 public water systems, representing more than 18,000 surface-water intakes or groundwater wells. The U.S. Geological Survey (USGS) worked in cooperation with TCEQ to develop the Source Water Assessment Program (SWAP) approach and methodology. Texas' SWAP meets all requirements of the Safe Drinking Water Act and ultimately provides the TCEQ with a comprehensive tool for protection of public water systems from contamination by up to 247 individual COCs. TCEQ staff identified both the list of contaminants to be assessed and contaminant threshold values (THR) to be applied. COCs were chosen because they were regulated contaminants, were expected to become regulated contaminants in the near future, or were unregulated but thought to represent long-term health concerns. THRs were based on maximum contaminant levels from U.S. Environmental Protection Agency (EPA)'s National Primary Drinking Water Regulations. For reporting purposes, COCs were grouped into seven contaminant groups: inorganic compounds, volatile organic compounds, synthetic organic compounds, radiochemicals, disinfection byproducts, microbial organisms, and physical properties. Expanding on the TCEQ's definition of susceptibility, subject-matter expert working groups formulated the SWSA approach based on assumptions that natural processes and human activities contribute COCs in quantities that vary in space and time; that increased levels of COC-producing activities within a source area may increase susceptibility to COC exposure; and that natural and manmade conditions within the source area may increase, decrease, or have no observable effect on susceptibility to COC exposure. Incorporating these assumptions, eight SWSA components were defined: identification, delineation, intrinsic susceptibility, point- and nonpoint-source susceptibility, contaminant occurrence, area-of-primary influence, and summary components. Spatial datasets were prepared to represent approximately 170 attributes or indicators used in the assessment process. These primarily were static datasets (approximately 46 gigabytes (GB) in size). Selected datasets such as PWS surface-water-intake or groundwater-well locations and potential source of contamination (PSOC) locations were updated weekly. Completed assessments were archived, and that database is approximately 10 GB in size. SWSA components currently (2011) are implemented in the Source Water Assessment Program-Decision Support System (SWAP-DSS) computer software, specifically developed to produce SWSAs. On execution of the software, the components work to identify the source of water for the well or intake, assess intrinsic susceptibility of the water- supply source, assess susceptibility to contamination with COCs from point and nonpoint sources, identify any previous detections of COCs from existing water-quality databases, and summarize the results. Each water-supply source's susceptibility is assessed, source results are weighted by source capacity (when a PWS has multiple sources), and results are combined into a single SWSA for the PWS.'SWSA reports are generated using the software; during 2003, more than 6,000 reports were provided to PWS operators and the public. The ability to produce detailed or summary reports for individual sources, and detailed or summary reports for a PWS, by COC or COC group was a unique capability of SWAP-DSS. In 2004, the TCEQ began a rotating schedule for SWSA wherein one-third of PWSs statewide would be assessed annually, or sooner if protection-program activities deemed it necessary, and that schedule has continued to the present. Cooperative efforts by the TCEQ and the USGS for SWAP software maintenance and enhancements ended in 2011 with the TCEQ assuming responsibility for all tasks.

77 FR 67678 - Content Specifications and Shielding Evaluations for Type B Transportation Packages

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-13

...The U.S. Nuclear Regulatory Commission (NRC or the Commission) is issuing for public comment Draft Regulatory Issue Summary (RIS) 2012-XX, ``Content Specifications and Shielding Evaluations for Type B Transportation Packages.'' This RIS clarifies the NRC's use of staff guidance in NUREG-1609, ``Standard Review Plan for Transport Packages for Radioactive Material,'' for the review of content specifications and shielding evaluations included in the Certificates of Compliance (CoC) and safety analysis reports (SARs) for Type B transportation packages.

Successful implementation of property cleanup under the Ohio and the Texas voluntary programs

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

Roffman, A.

1999-07-01

Cleanups of two properties, one located in Ohio and the other in Texas were successfully implemented. The facilities were printing plants that manufactured printed material and forms for commercial and industrial use. Primary products and chemicals involved in the manufacturing of the forms included ink, petroleum products and cleaning solvents. The Ohio property underwent a successful cleanup under the Ohio EPA Voluntary Action Program (VAP). It met the Ohio EPA residential land use cleanup standards for soil and shallow groundwater. A No Further Action letter has been submitted to the state and it resulted in the issuance of a Covenantmore » Not to Sue. The Texas facility underwent a successful cleanup under the Texas Natural Resource Conservation Commission (TNRCC) Voluntary Cleanup Program (VCP). It resulted in the issuance of a Certificate of Completion (COC) for residential land use for soil, and a conditional COC for industrial land use for the shallow groundwater.« less

Effect of heat stress on the survival and development of in vitro cultured bovine preantral follicles and on in vitro maturation of cumulus-oocyte complex.

PubMed

Paes, V M; Vieira, L A; Correia, H H V; Sa, N A R; Moura, A A A; Sales, A D; Rodrigues, A P R; Magalhães-Padilha, D M; Santos, F W; Apgar, G A; Campello, C C; Camargo, L S A; Figueiredo, J R

2016-09-01

The deleterious effect of heat stress (HS) on competence of oocytes from antral follicles is well recognized, but there is a lack of data regarding its impact on the viability and growth of preantral follicles. In this study, we used in vitro preantral follicle cultures to investigate the effects of HS on the following parameters: survival and development of primordial follicles after in vitro culture of ovarian fragments (experiment I); growth and antrum formation of isolated advanced secondary follicles (experiment II); and maturation rates after in vitro maturation (IVM) of cumulus-oocyte complexes (COCs) from antral follicles (>2-6 mm) grown in vivo (experiment III). Furthermore, the following end points were evaluated in all experiments: follicle/oocyte survival, reactive oxygen species (ROS), estradiol (E2) and progesterone (P4) production, as well as mRNA expression for select genes related to stress (HSP70) and apoptosis (MCL1 and BAX). In all experiments, HS consisted of exposing the structures (ovarian fragments, isolated preantral follicles and COCs) to 41 °C for 12 hours and then to 38.5 °C until the end of the culture (7 days for experiments I and II and 24 hours for experiment III). The temperature for the control group was held at 38.5 °C for the entire culture period. Heat stress increased (P < 0.05) the percentage of developing follicles (intermediate, primary, and secondary follicles) at 12 hours and increased levels of ROS at all evaluated time points (12, 24 hours, and D7), when compared to the control (experiment I). Heat stress did not affect (P > 0.05) any identified end points when preantral follicles were cultured in their isolated form (experiment II). However, in experiment III, HS decreased (P < 0.05) both the rates of metaphase II after 24 hours and E2 production at 12 hours of IVM. Moreover, HS increased (P < 0.0001) levels of P4 after IVM and ROS production at every evaluated time point, compared with the control (12 and 24 hours). In conclusion, HS caused: (1) early activation of primordial follicles; (2) an increase in ROS production by early preantral follicles enclosed in ovarian tissue and by COCs; (3) a short-term reduction of E2 production by COCs; and (4) an increase in P4 secretion from COCs. However, HS did not affect in vitro culture of advanced isolated secondary follicles. Experimental evidence indicates that preantral follicles are less sensitive to HS than COC. Copyright © 2016 Elsevier Inc. All rights reserved.

Modeling Natural Attenuation of an Industrial Facility in Houston

NASA Astrophysics Data System (ADS)

Sun, D.

2016-12-01

Groundwater monitoring is currently ongoing at a commercial/industrial facility located in Deer Park, Texas (the site). The subject site is an approximate 10 acre commercial/industrial facility that began operation in the late-1970s. Operations have historically consisted of vehicle maintenance services, administrative, and equipment storage. Assessment and groundwater monitoring activities have been conducted at the site to evaluate the magnitude and extent of groundwater affected with chlorinated volatile organic compounds (VOCs). Groundwater data has been collected at this site since the mid-2000s on a quarterly basis. Presently, VOC constituents tetrachloroethene (PCE), trichloroethene (TCE), cis-1,2-dichloroethene (DCE), 1,1-dichloroethene (1,1-DCE), and vinyl chloride (VC) are the only chemicals of concern (COCs) detected at concentrations exceeding the TCEQ Actions Levels established by the state of Texas. The goal is that one day the site will receive a certificate of completion from the state, which states that all non-responsible parties are released from all liability to the state for cleanup. The remediation technology that is currently being used at this site is Monitoring Natural Attenuation (MNA). A significant question is whether MNA is efficiently removing COCs in groundwater and how long will this process take to achieve the remediation goals. The objective of this study is to provide an estimate of concentrations of COCs in groundwater at the site using the Biochlor model. The Biochlor model will help answer the question as to whether or not natural attenuation is occurring at the site efficiently. Results show that Monitored Natural Attenuation may not be the optimal remediation technology to use at this site. Other remedial technologies are needed to clean up chemical in the site. Groundwater monitoring is currently ongoing at a commercial/industrial facility located in Deer Park, Texas (the site). The subject site is an approximate 10 acre commercial/industrial facility that began operation in the late-1970s. Operations have historically consisted of vehicle maintenance services, administrative, and equipment storage. Assessment and groundwater monitoring activities have been conducted at the site to evaluate the magnitude and extent of groundwater affected with chlorinated volatile organic compounds (VOCs). Groundwater data has been collected at this site since the mid-2000s on a quarterly basis. Presently, VOC constituents tetrachloroethene (PCE), trichloroethene (TCE), cis-1,2-dichloroethene (DCE), 1,1-dichloroethene (1,1-DCE), and vinyl chloride (VC) are the only chemicals of concern (COCs) detected at concentrations exceeding the TCEQ Actions Levels established by the state of Texas. The goal is that one day the site will receive a certificate of completion from the state, which states that all non-responsible parties are released from all liability to the state for cleanup. The remediation technology that is currently being used at this site is Monitoring Natural Attenuation (MNA). A significant question is whether MNA is efficiently removing COCs in groundwater and how long will this process take to achieve the remediation goals. The objective of this study is to provide an estimate of concentrations of COCs in groundwater at the site using the Biochlor model. The Biochlor model will help answer the question as to whether or not natural attenuation is occurring at the site efficiently. Results show that Monitored Natural Attenuation may not be the optimal remediation technology to use at this site. Other remedial technologies are needed to clean up chemical in the site.

Sedimentary sources of old high molecular weight dissolved organic carbon from the ocean margin benthic nepheloid layer

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

Guo, L. Santschi, P.H.

2000-02-01

Average {sup 14}C ages of dissolved organic carbon (DOC) in the ocean are 3--6,000 years, and are influenced by old DOC from continental margins. However, sources of DOC from terrestrial, autochthonous, and sedimentary organic carbon seem to be too young to be responsible for the old DOC observed in the ocean. Since colloidal organic carbon (COC, i.e., high molecular weight DOC), which is chemically very similar to that of bulk DOC, can be effectively isolated from seawater using cross-flow ultrafiltration, it can hold clues to sources and pathways of DOC turnover in the ocean. Radiocarbon measurements on COC in themore » water column and benthic nepheloid layer (BNL) from two continental margin areas (the Middle Atlantic Bight and the Gulf of Mexico) and controlled laboratory experiments were carried out to study sources of old DOC in the ocean margin areas. Vertical distributions of suspended particulate matter (SPM), particulate organic carbon (POC), nitrogen (PON), and DOC in the water column and bottom waters near the sediment-water interface all demonstrate a well developed benthic nepheloid layer in both ocean margin areas. COC from the BNL was much older than COC from the overlying water column. These results, together with strong concentration gradients of SPM, POC, PON, and DOC, suggest a sedimentary source for organic carbon species and possibly for old COC as well in BNL waters. This is confirmed by the results from controlled laboratory experiments. The heterogeneity of {Delta}{sup 14}C signatures in bulk SOC thus points to a preferential release of old organic components from sediment resuspension, which can be the transport mechanism of the old benthic COC observed in ocean margin areas. Old COC from continental margin nepheloid layers may thus be a potential source of old DOC to the deep ocean.« less

78 FR 26090 - Content Specifications and Shielding Evaluations for Type B Transportation Packages

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-03

...The U.S. Nuclear Regulatory Commission (NRC) is issuing Regulatory Issue Summary (RIS) 2013-04, ``Content Specifications and Shielding Evaluations for Type B Transportation Packages.'' This RIS clarifies the NRC's use of staff guidance in NUREG-1609, ``Standard Review Plan for Transport Packages for Radioactive Material,'' for the review of content specifications and shielding evaluations included in the Certificates of Compliance (CoC) and safety analysis reports (SARs) for Type B transportation packages. The RIS does not impose any additional regulatory requirements on NRC licensees.

Investigations on Two Co-C Fixed-Point Cells Prepared at INRIM and LNE-Cnam

NASA Astrophysics Data System (ADS)

Battuello, M.; Florio, M.; Sadli, M.; Bourson, F.

2011-08-01

INRIM and LNE-Cnam agreed to undertake a collaboration aimed to verify, through the use of metal-carbon eutectic fixed-point cells, methods and facilities used for defining the transition temperature of eutectic fixed points and manufacturing procedures of cells. To this purpose and as a first step of the cooperation, a Co-C cell manufactured at LNE-Cnam was measured at INRIM and compared with a local cell. The two cells were of different designs: the INRIM cell of 10 cm3 inner volume and the LNE-Cnam one of 3.9 cm3. The external dimensions of the two cells were noticeably different, namely, 40 mm in length and 24 mm in diameter for the LNE-Cnam cell 3Co4 and 110 mm in length and 42 mm in diameter for the INRIM cell. Consequently, the investigation of the effect of temperature distributions in the heating furnace was undertaken by implementing the cells inside single-zone and three-zone furnaces. The transition temperature of the cell was determined at the two institutes making use of different techniques: at INRIM radiation scales at 900 nm, 950 nm, and 1.6 μm were realized from In to Cu and then used to define T 90(Co-C) by extrapolation. At LNE-Cnam, a radiance comparator based on a grating monochromator was used for the extrapolation from the Cu fixed point. This paper presents a comparative description of the cells and the manufacturing methods and the results in terms of equivalence between the two cells and melting temperatures determined at INRIM and LNE-Cnam.

Determination of hydroxy metabolites of cocaine from hair samples and comparison with street cocaine samples.

PubMed

Franz, Thomas; Scheufler, Frank; Stein, Klaus; Uhl, Michael; Dame, Torsten; Schwarz, Gerlinde; Sachs, Hans; Skopp, Gisela; Musshoff, Frank

2018-07-01

Drugs which are commonly smoked or sniffed (e.g. cocaine), can contaminate hair through smoke or dust; therefore testing for metabolites, especially hydroxy metabolites, is highly recommended. The presence of hydroxy metabolites in street-cocaine (COC) has been discussed. To check if detection of hydroxy metabolites definitely proves ingestion, the presence of these metabolites in street COC samples has to be checked. It is expected that the more hydrophilic hydroxy metabolites of COC are incorporated into the hair-matrix to a lesser extent. For this study 576 COC positive hair samples (≥0.1ng COC/mg hair) were analysed by LC-MS/MS for benzoylecgonine (BE), norcocaine (NC), cocaethylene (CE), ortho-, meta- and para-hydroxy COC (o-, m-, p-OH-COC), meta- and para-hydroxy BE (m-, p-OH-BE), and meta- and para-hydroxy NC (m-, p-OH-NC). The results were compared with the respective metabolite/COC concentration ratios in 146 street COC samples, confiscated by the Bavarian police. Peak areas were used to estimate BE/COC, NC/COC, CE/COC and hydroxy metabolites/COC. Similar metabolic ratios were found for o-OH-COC in 88% of the samples, but for p-OH-COC and m-OH-COC only in 5.1% and 6.8%, respectively. Notably, p- and m-OH-BE as well as p- and m-OH-NC could not be identified from seized samples. We propose that area ratios exceeding the ratios of street COC more than twice or identification of OH-BE and OH-NC enable to differentiate COC consumption from contamination. Using these criteria, consumption of the drug could be proven in 92% of COC positive samples. As detection of meta- and para-hydroxy metabolites using the above mentioned criteria is a reliable tool to distinguish between ingestion and external contamination, it is recommended to implement their measurement into daily routine work. Copyright © 2018 Elsevier B.V. All rights reserved.

Beef donor cows with high number of retrieved COC produce more in vitro embryos compared with cows with low number of COC after repeated ovum pick-up sessions.

PubMed

Monteiro, F M; Batista, E O S; Vieira, L M; Bayeux, B M; Accorsi, M; Campanholi, S P; Dias, E A R; Souza, A H; Baruselli, P S

2017-03-01

The aim of the present study was to evaluate whether repeated ovum pick-up (OPU) procedures may affect the efficiency of OPU programs for in vitro embryo production (IVEP) in Bos indicus (Nelore) donors. In addition, the repeatability (r) efficiency of IVEP was also assessed. Data available were from 432 OPU-IVEP sessions that were performed at random stages of the estrous cycle in 36 cycling, nonlactating Nelore donors. Semen from three Nelore bulls was used for the IVF. Donors were submitted to 12 consecutive OPU procedures, with an interval of approximately 30 days between sessions. Data were analyzed as repeated measures using the GLIMMIX procedure of SAS 9.3. Cows yielding ≥15 COCs were defined as "high" COCs and cows with less than 15 COCs were defined as "low" COCs donors. The number of COCs retrieved decreased over time in donors classified with high COCs and remained fairly steady in cows with low COCs at the beginning of the program (P session*COC retrieved groups  = 0.02). Moreover, the number of COCs retrieved (P < 0.0001), and number of blastocysts produced per OPU (P = 0.001) was greater for the high COCs donors compared with the low COCs category, and these results were consistent across OPU sessions. Interestingly, there was no effect of COCs category on the rate of blastocyst development (P = 0.83). In addition, number of blastocysts produced were not affected by repeated OPU (P = 0.37) and interactions between time and COC category (P = 0.72). Similarly, blastocyst rate was not affected by repeated OPU (P = 0.21) and interactions between time and COC category (P = 0.58). Despite of COC category of the donor cows, repeatability was high for the number of COCs retrieved (r = 0.81), number of blastocysts produced per OPU (r = 0.79), and blastocyst rate (0.69). In conclusion, overall numbers of COCs decreased over time in donors classified as having high COCs. However, cumulative amounts of produced blastocysts were greater in donors with high COCs. More importantly, high repeatability was observed in terms of IVEP efficiency. Therefore, IVEP programs can be significantly improved with more aggressive selection toward donors with greater numbers of COCs. Copyright © 2016 Elsevier Inc. All rights reserved.

The Fate of Bacterial Cocaine Esterase (CocE): An In Vivo Study of CocE-Mediated Cocaine Hydrolysis, CocE Pharmacokinetics, and CocE EliminationS⃞

PubMed Central

Brim, Remy L.; Noon, Kathleen R.; Collins, Gregory T.; Stein, Aron; Nichols, Joseph; Narasimhan, Diwa; Ko, Mei-Chuan; Woods, James H.

2012-01-01

Cocaine abuse and toxicity remain widespread problems in the United States. Currently cocaine toxicity is treated only symptomatically, because there is no Food and Drug Administration-approved pharmacotherapy for this indication. To address the unmet need, a stabilized mutant of bacterial cocaine esterase [T172R/G173Q-CocE (DM-CocE)], which hydrolyzes cocaine into inactive metabolites and has low immunogenic potential, has been developed and previously tested in animal models of cocaine toxicity. Here, we document the rapid cocaine hydrolysis by low doses of DM-CocE in vitro and in vivo, as well as the pharmacokinetics and distribution of the DM-CocE protein in rats. DM-CocE at 50.5 μg/kg effectively eliminated 4 mg/kg cocaine within 2 min in both male and female rats as measured by mass spectrometry. We expanded on these findings by using a pharmacologically relevant dose of DM-CocE (0.32 mg/kg) in rats and monkeys to hydrolyze convulsant doses of cocaine. DM-CocE reduced cocaine to below detection limits rapidly after injection; however, elimination of DM-CocE resulted in peripheral cocaine redistribution by 30 to 60 min. Elimination of DM-CocE was quantified by using [35S] labeling of the enzyme and was found to have a half-life of 2.1 h in rats. Minor urinary output of DM-CocE was also observed. Immunohistochemistry, Western blotting, and radiography all were used to elucidate the mechanism of DM-CocE elimination, rapid proteolysis, and recycling of amino acids into all tissues. This rapid elimination of DM-CocE is a desirable property of a therapeutic for cocaine toxicity and should reduce the likelihood of immunogenic or adverse reactions as DM-CocE moves toward clinical use. PMID:21990608

A combined oral contraceptive containing 3-mg drospirenone/ 20-microg ethinyl estradiol in the treatment of acne vulgaris: a randomized, double-blind, placebo-controlled study evaluating lesion counts and participant self-assessment.

PubMed

Lucky, Anne W; Koltun, William; Thiboutot, Diane; Niknian, Minoo; Sampson-Landers, Carole; Korner, Paul; Marr, Joachim

2008-08-01

This study compared the efficacy of a low-dose combined oral contraceptive (COC) containing 3-mg drospirenone and 20-microg ethinyl estradiol (3-mg DRSP/20-microg EE) administered in a 24-day active pill/4-day inert pill (24/4) regimen and placebo in women with moderate acne vulgaris during 6 treatment cycles. A total of 534 participants were randomized and dispensed study medication (n = 266 [3-mg DRSP/20-microg EE 24/4 regimen COC group]; n = 268 [placebo group]). Women of reproductive age were eligible for inclusion in the study. Treatment with the 3-mg DRSP/20-microg EE 24/4 regimen COC was associated with a greater reduction from baseline to end point in individual lesion counts (papules, pustules, open and closed comedones) compared with placebo. The mean nodule count remained essentially constant throughout the study and was low in both treatment groups. There was a significantly higher probability that a participant had an improved assessment on the investigator's overall improvement rating scale (odds ratio [OR], 4.02; 95% CI [confidence interval], 2.29-7.31; P < .0001) and participant's overall self-assessment rating scale (OR, 2.82; 95% CI, 1.60-5.13; P = .0005) in the 3-mg DRSP/20-microg EE 24/4 regimen COC group than in the placebo group. The COC 3-mg DRSP/20-microg EE 24/4 regimen is a suitable option for women with moderate acne vulgaris who require contraception.

Combined oral contraceptives plus spironolactone compared with metformin in women with polycystic ovary syndrome: a one-year randomized clinical trial.

PubMed

Alpañés, Macarena; Álvarez-Blasco, Francisco; Fernández-Durán, Elena; Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F

2017-11-01

We aimed to compare a combined oral contraceptive (COC) plus the antiandrogen spironolactone with the insulin sensitizer metformin in women with polycystic ovary syndrome (PCOS). We conducted a randomized, parallel, open-label, clinical trial comparing COC (30 μg of ethinylestradiol and 150 μg of desogestrel) plus spironolactone (100 mg/day) with metformin (850 mg b.i.d.) for one year in women with PCOS (EudraCT2008-004531-38). The composite primary outcome included efficacy (amelioration of hirsutism, androgen excess and menstrual dysfunction) and cardiometabolic safety (changes in the frequencies of disorders of glucose tolerance, dyslipidemia and hypertension). A complete anthropometric, biochemical, hormonal and metabolic evaluation was conducted every three months and data were submitted to intention-to-treat analyses. Twenty-four patients were assigned to COC plus spironolactone and 22 patients to metformin. Compared with metformin, COC plus spironolactone caused larger decreases in hirsutism score (mean difference 4.6 points, 95% CI: 2.6-6.7), total testosterone (1.1 nmol/L, 0.4-1.7), free testosterone (25 pmol/L, 12-39), androstenedione (5.5 nmol/L, 1.8-9.2) and dehydroepiandrosterone sulfate (2.7 μmol/L, 1.4-4.0). Menstrual dysfunction was less frequent with COC plus spironolactone (OR: 0.06, 95% CI: 0.02-0.23). No differences were found in frequencies of abnormal glucose tolerance (OR: 1.7, 95% CI: 0.7-4.4), dyslipidemia (OR: 0.6, 95% CI: 0.2-1.8) or hypertension (OR: 0.3, 95% CI: 0.5-2.0). No major adverse events occurred and biochemical markers were similarly safe with both treatments. COC plus spironolactone was more effective than metformin for symptoms of PCOS showing similar safety and overall neutral effects on cardiometabolic risk factors. © 2017 European Society of Endocrinology.

Label free quantitative proteomics analysis on the cisplatin resistance in ovarian cancer cells.

PubMed

Wang, F; Zhu, Y; Fang, S; Li, S; Liu, S

2017-05-20

Quantitative proteomics has been made great progress in recent years. Label free quantitative proteomics analysis based on the mass spectrometry is widely used. Using this technique, we determined the differentially expressed proteins in the cisplatin-sensitive ovarian cancer cells COC1 and cisplatin-resistant cells COC1/DDP before and after the application of cisplatin. Using the GO analysis, we classified those proteins into different subgroups bases on their cellular component, biological process, and molecular function. We also used KEGG pathway analysis to determine the key signal pathways that those proteins were involved in. There are 710 differential proteins between COC1 and COC1/DDP cells, 783 between COC1 and COC1/DDP cells treated with cisplatin, 917 between the COC1/DDP cells and COC1/DDP cells treated with LaCl3, 775 between COC1/DDP cells treated with cisplatin and COC1/DDP cells treated with cisplatin and LaCl3. Among the same 411 differentially expressed proteins in cisplatin-sensitive COC1 cells and cisplain-resistant COC1/DDP cells before and after cisplatin treatment, 14% of them were localized on the cell membrane. According to the KEGG results, differentially expressed proteins were classified into 21 groups. The most abundant proteins were involved in spliceosome. This study lays a foundation for deciphering the mechanism for drug resistance in ovarian tumor.

Use of Oral Contraceptives for Management of Acne Vulgaris: Practical Considerations in Real World Practice.

PubMed

Harper, Julie C

2016-04-01

Acne vulgaris may be effectively treated with combination oral contraceptive pills (COCs) in women. COCs may be useful in any woman with acne in the absence of known contraindications. When prescribing a COC to a woman who also desires contraception, the risks of the COC are compared with the risks associated with pregnancy. When prescribing a COC to a woman who does not desire contraception, the risks of the COC must be weighed against the risks associated with acne. COCs may take 3 cycles of use to show an effect in acne lesion count reductions. Copyright © 2016 Elsevier Inc. All rights reserved.

Adverse mood effects of combined oral contraceptives in relation to personality traits.

PubMed

Borgström, Anna; Odlind, Viveca; Ekselius, Lisa; Sundström-Poromaa, Inger

2008-12-01

Mood symptoms, such as depressed mood, anxiety and increased irritability, remain one of the major reasons for discontinuation of combined oral contraceptive (COC) pills. The aim of this study was to compare personality traits in women with ongoing or previous use of COCs and different experiences from these compounds with respect to adverse mood symptoms. Thirty women currently on COCs with no reports of adverse mood symptoms, 28 women currently on COCs and experiencing mood-related side effects, 27 women who had discontinued COC use for reasons other than adverse mood symptoms and 33 women who had discontinued COC use due to adverse mood effects were included. All participants were asked to fill out the Swedish universities Scales of Personality (SSP) to assess different personality traits. The women who were experiencing mood-related side effects on their current COC use exhibited higher scores on the somatic anxiety and stress susceptibility traits as compared to the women who did not experience any mood-related side effects from their current COCs. Women who had discontinued COC treatment because of adverse mood effects had higher scores of detachment and mistrust compared to women who had discontinued COC for reasons unrelated to mood effects. Higher scores on specific personality traits such as somatic anxiety and stress susceptibility are found in women with ongoing experience of adverse mood symptoms from COC. Higher scores of mistrust and detachment are more common among women who have discontinued COC treatment due to adverse mood effects.

Endogenous Thrombin Potential Changes during the First Cycle of Oral Contraceptive Use

PubMed Central

Westhoff, Carolyn L.; Pike, Malcolm C.; Cremers, Serge; Eisenberger, Andrew; Thomassen, Stella; Rosing, Jan

2017-01-01

Objectives Venous thromboembolism (VTE) risk increases within months of combination oral contraceptive (COC) initiation. Because elevated endogenous thrombin potential (ETP) has been found in several studies to be a VTE risk factor, we evaluated the extent of ETP changes during the initial cycle of an ethinyl estradiol (EE) and levonorgestrel (LNG) COC. We also assessed the relationship between ETP changes and systemic EE and LNG concentrations. Study Design Participants provided multiple blood samples during a first 21-day cycle of a 30 µg EE/150 µg LNG COC and after a further 7 days without an active COC. Thrombin generation measured with and without addition of activated protein C (APC) yielded ETP+APC and ETP−APC and the normalized APC sensitivity ratio (nAPCsr). EE and LNG pharmacokinetic analyses were conducted over 24 hours after the first COC tablet and again at steady state. Results Thrombin generation was determined in 16 of the 17 women who completed the study. Mean ETP−APC increased steadily to 21% above baseline at 24 hours after the 6th COC tablet (COC624; p < 0.001) and to 28% above baseline at steady state (COC21; p < 0.001). Mean ETP+APC increased considerably more – by 54% at COC624 and by 79% at steady state. Mean nAPCsr increased by 28% at COC624 and by 41% at steady state. Higher concentrations of EE or LNG were not correlated with greater increases in ETP. Conclusions ETP increases during the first COC cycle were substantial. Implications The early increases in ETP may provide biological support for the rapid increase in VTE risk during initial COC use. The lack of association between this clotting system perturbation and the systemic EE concentration is surprising and deserves further study. PMID:28088496

Effects of Acute Oral Naltrexone on the Subjective and Physiological Effects of Oral D-Amphetamine and Smoked Cocaine in Cocaine Abusers

PubMed Central

Comer, Sandra D; Mogali, Shanthi; Saccone, Phillip A; Askalsky, Paula; Martinez, Diana; Walker, Ellen A; Jones, Jermaine D; Vosburg, Suzanne K; Cooper, Ziva D; Roux, Perrine; Sullivan, Maria A; Manubay, Jeanne M; Rubin, Eric; Pines, Abigail; Berkower, Emily L; Haney, Margaret; Foltin, Richard W

2013-01-01

Despite the prevalent worldwide abuse of stimulants, such as amphetamines and cocaine, no medications are currently approved for treating this serious public health problem. Both preclinical and clinical studies suggest that the opioid antagonist naltrexone (NTX) is effective in reducing the abuse liability of amphetamine, raising the question of whether similar positive findings would be obtained for cocaine. The purpose of this study was to evaluate the ability of oral NTX to alter the cardiovascular and subjective effects of D-amphetamine (D-AMPH) and cocaine (COC). Non-treatment-seeking COC users (N=12) completed this 3-week inpatient, randomized, crossover study. Participants received 0, 12.5, or 50 mg oral NTX 60 min before active or placebo stimulant administration during 10 separate laboratory sessions. Oral AMPH (0, 10, and 20 mg; or all placebo) was administered in ascending order within a laboratory session using a 60-min interdose interval. Smoked COC (0, 12.5, 25, and 50 mg; or all placebo) was administered in ascending order within a laboratory session using a 14-min interdose interval. Active COC and AMPH produced dose-related increases in cardiovascular function that were of comparable magnitude. In contrast, COC, but not AMPH, produced dose-related increases in several subjective measures of positive drug effect (eg, high, liking, and willingness to pay for the drug). NTX did not alter the cardiovascular effects of AMPH or COC. NTX also did not alter positive subjective ratings after COC administration, but it did significantly reduce ratings of craving for COC and tobacco during COC sessions. These results show that (1) oral AMPH produces minimal abuse-related subjective responses in COC smokers, and (2) NTX reduces craving for COC and tobacco during COC sessions. Future studies should continue to evaluate NTX as a potential anti-craving medication for COC dependence. PMID:23736314

A Mouse Model of Transplacental Cocaine Exposure: Clinical Implications for Exposed Infants and Childrena.

PubMed

Kosofsky, Barry E; Wilkins, Aaron S

1998-06-01

To characterize the effects of cocaine on developing brain we have developed a mouse model of gestational cocaine exposure. We studied pregnant dams injected twice daily with cocaine HCl at 40, 20, or 10 mg/kg/day sc from embryonic days (E)8 to E17 (COC 40, COC20, and COC10, respectively), vehicle-injected dams allowed access to food ad libitum (SAL) or pair-fed with the COC 40 dams (SPF 40), animals pretreated with the short-acting α-adrenergic antagonist phentolamine prior to each cocaine injection (P COC 40), and animals administered phentolamine prior to saline (PHENT). COC 40, P COC 40, and SPF 40 dams demonstrated the lowest percentage weight gain during gestation. The surrogate-fostered offspring of COC 40, P COC 40, and SPF 40 dams demonstrated transient brain and body growth retardation on postnatal days (P)1 and P9 when compared to pups born to SAL dams. We conducted behavioral tests which allowed us to dissociate the indirect effect of cocaine-induced malnutrition from a direct effect of prenatal cocaine administration in altering postnatal behavior. Pups from all groups were tested for first-order Pavlovian conditioning on P9 or P12 or for the ability to ignore redundant information in a blocking paradigm on P50. Unlike the SPF 40, PHENT, and SAL controls, COC 40 and P COC 40 mice were unable to acquire an aversion to an odor previously paired with shock on P9, a learning deficit that resolved by P12. However, on P50, COC 40 mice and, to a lesser extent, P COC 40 and SPF 40 mice demonstrated a persistent behavioral deficit in our blocking paradigm, which may reflect alterations in selective attention. We discuss how these findings in our rodent model have developmental implications for human infants exposed to cocaine in utero.

A mouse model of transplacental cocaine exposure. Clinical implications for exposed infants and children.

PubMed

Kosofsky, B E; Wilkins, A S

1998-06-21

To characterize the effects of cocaine on developing brain we have developed a mouse model of gestational cocaine exposure. We studied pregnant dams injected twice daily with cocaine HCl at 40, 20, or 10 mg/kg/day sc from embryonic days (E)8 to E17 (COC 40, COC20, and COC10, respectively), vehicle-injected dams allowed access to food ad libitum (SAL) or pair-fed with the COC 40 dams (SPF 40), animals pretreated with the short-acting alpha-adrenergic antagonist phentolamine prior to each cocaine injection (P COC 40), and animals administered phentolamine prior to saline (PHENT). COC 40, P COC 40, and SPF 40 dams demonstrated the lowest percentage weight gain during gestation. The surrogate-fostered offspring of COC 40, P COC 40, and SPF 40 dams demonstrated transient brain and body growth retardation on postnatal days (P)1 and P9 when compared to pups born to SAL dams. We conducted behavioral tests which allowed us to dissociate the indirect effect of cocaine-induced malnutrition from a direct effect of prenatal cocaine administration in altering postnatal behavior. Pups from all groups were tested for first-order Pavlovian conditioning on P9 or P12 or for the ability to ignore redundant information in a blocking paradigm on P50. Unlike the SPF 40, PHENT, and SAL controls, COC 40 and P COC 40 mice were unable to acquire an aversion to an odor previously paired with shock on P9, a learning deficit that resolved by P12. However, on P50, COC 40 mice and, to a lesser extent, P COC 40 and SPF 40 mice demonstrated a persistent behavioral deficit in our blocking paradigm, which may reflect alterations in selective attention. We discuss how these findings in our rodent model have developmental implications for human infants exposed to cocaine in utero.

Oral contraceptive use changes brain activity and mood in women with previous negative affect on the pill--a double-blinded, placebo-controlled randomized trial of a levonorgestrel-containing combined oral contraceptive.

PubMed

Gingnell, Malin; Engman, Jonas; Frick, Andreas; Moby, Lena; Wikström, Johan; Fredrikson, Mats; Sundström-Poromaa, Inger

2013-07-01

Most women on combined oral contraceptives (COC) report high levels of satisfaction, but 4-10% complain of adverse mood effects. The aim of this randomized, double-blinded, placebo-controlled trial was to investigate if COC use would induce more pronounced mood symptoms than placebo in women with previous history of COC-induced adverse mood. A second aim was to determine if COC use is associated with changes in brain reactivity in regions previously associated with emotion processing. Thirty-four women with previous experience of mood deterioration during COC use were randomized to one treatment cycle with a levonorgestrel-containing COC or placebo. An emotional face matching task (vs. geometrical shapes) was administered during functional magnetic resonance imaging (fMRI) prior to and during the COC treatment cycle. Throughout the trial, women recorded daily symptom ratings on the Cyclicity Diagnoser (CD) scale. During the last week of the treatment cycle COC users had higher scores of depressed mood, mood swings, and fatigue than placebo users. COC users also had lower emotion-induced reactivity in the left insula, left middle frontal gyrus, and bilateral inferior frontal gyri as compared to placebo users. In comparison with their pretreatment cycle, the COC group had decreased emotion-induced reactivity in the bilateral inferior frontal gyri, whereas placebo users had decreased reactivity in the right amygdala. COC use in women who previously had experienced emotional side effects resulted in mood deterioration, and COC use was also accompanied by changes in emotional brain reactivity. These findings are of relevance for the understanding of how combined oral contraceptives may influence mood. Placebo-controlled fMRI studies in COC sensitive women could be of relevance for future testing of adverse mood effects in new oral contraceptives. Copyright © 2012 Elsevier Ltd. All rights reserved.

Tacky COC: a solvent bonding technique for fabrication of microfluidic systems

NASA Astrophysics Data System (ADS)

Keller, Nico; Nargang, Tobias M.; Helmer, Dorothea; Rapp, Bastian E.

2016-03-01

The academic community knows cyclic olefin copolymer (COC) as a well suited material for microfluidic applications because COC has numerous interesting properties such as high transmittance, good chemical resistance and good biocompatibility. Here we present a fast and cost-effective method for bonding of two COC substrates: exposure to appropriate solvents gives a tacky COC surface which when brought in contact with untreated COC forms a strong and optical clear bond. The bonding process is carried out at room temperature and takes less than three minutes which makes it significantly faster than currently described methods: This method does not require special lab equipment such as hot plates or hydraulic presses. The mild conditions of the bond process also allow for such "tacky COC" lids to be used for sealing of microfluidic chips containing immobilized protein patterns which is of high interest for immunodiagnostic testing inside microfluidic chips.

Free energy profiles of cocaine esterase-cocaine binding process by molecular dynamics and potential of mean force simulations.

PubMed

Zhang, Yuxin; Huang, Xiaoqin; Han, Keli; Zheng, Fang; Zhan, Chang-Guo

2016-11-25

The combined molecular dynamics (MD) and potential of mean force (PMF) simulations have been performed to determine the free energy profile of the CocE)-(+)-cocaine binding process in comparison with that of the corresponding CocE-(-)-cocaine binding process. According to the MD simulations, the equilibrium CocE-(+)-cocaine binding mode is similar to the CocE-(-)-cocaine binding mode. However, based on the simulated free energy profiles, a significant free energy barrier (∼5 kcal/mol) exists in the CocE-(+)-cocaine binding process whereas no obvious free energy barrier exists in the CocE-(-)-cocaine binding process, although the free energy barrier of ∼5 kcal/mol is not high enough to really slow down the CocE-(+)-cocaine binding process. In addition, the obtained free energy profiles also demonstrate that (+)-cocaine and (-)-cocaine have very close binding free energies with CocE, with a negligible difference (∼0.2 kcal/mol), which is qualitatively consistent with the nearly same experimental K M values of the CocE enzyme for (+)-cocaine and (-)-cocaine. The consistency between the computational results and available experimental data suggests that the mechanistic insights obtained from this study are reasonable. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Understanding the Collaborative Planning Process in Homeless Services: Networking, Advocacy, and Local Government Support May Reduce Service Gaps.

PubMed

Jarpe, Meghan; Mosley, Jennifer E; Smith, Bikki Tran

2018-06-07

The Continuum of Care (CoC) process-a nationwide system of regional collaborative planning networks addressing homelessness-is the chief administrative method utilized by the US Department of Housing and Urban Development to prevent and reduce homelessness in the United States. The objective of this study is to provide a benchmark comprehensive picture of the structure and practices of CoC networks, as well as information about which of those factors are associated with lower service gaps, a key goal of the initiative. A national survey of the complete population of CoCs in the United States was conducted in 2014 (n = 312, 75% response rate). This survey is the first to gather information on all available CoC networks. Ordinary least squares (OLS) regression was used to determine the relationship between internal networking, advocacy frequency, government investment, and degree of service gaps for CoCs of different sizes. United States. Lead contacts for CoCs (n = 312) that responded to the 2014 survey. Severity of regional service gaps for people who are homeless. Descriptive statistics show that CoCs vary considerably in regard to size, leadership, membership, and other organizational characteristics. Several independent variables were associated with reduced regional service gaps: networking for small CoCs (β = -.39, P < .05) and local government support for midsized CoCs (β = -.10, P < .05). For large CoCs, local government support was again significantly associated with lower service gaps, but there was also a significant interaction effect between advocacy and networking (β = .04, P < .05). To reduce service gaps and better serve the homeless, CoCs should consider taking steps to improve networking, particularly when advocacy is out of reach, and cultivate local government investment and support.

Overexpression of hyaluronan synthase 2 and gonadotropin receptors in cumulus cells of goats subjected to one-shot eCG/FSH hormonal treatment for ovarian stimulation.

PubMed

Santos, Juliana D R; Batista, Ribrio I T P; Magalhães, Livia C; Paula, Alexandre R; Souza, Samara S; Salamone, Daniel F; Bhat, Maajid H; Teixeira, Dárcio I A; Freitas, Vicente J F; Melo, Luciana M

2016-07-01

Hormonal ovarian stimulation may affect transcripts in somatic cells of cumulus-oocyte complexes (COCs) and affect the resulting oocyte quality. Here, in parallel with morphological classification and in vitro maturation (IVM) rate analysis, we investigated the expression of hyaluronan synthase 2 (HAS2), gonadotropic receptors (FSHR and LHR) and connexin 43 (GJA1) in cumulus cells (CCs) from goat COCs after multi-dose FSH (MD) or one-shot FSH/eCG (OS) treatments, using bovine COCs as control groups. The MD treatment produced more large follicles, and the resulting COCs had a better morphology and IVM rate than were obtained with OS. The OS treatment produced COCs with increased HAS2, FSHR, LHR and GJA1 expression. This gene expression pattern was also observed in the CCs of COCs that showed poor morphological characteristics. On the other hand, the mRNA levels were more similar between groups after IVM; FSHR and LHR were the main genes that showed decreased expression. Some events that occurred in bovine CCs during IVM, such as cell expansion, increased HAS2 expression and decreased GJA1 expression, were less evident or did not occur in goat COCs. In conclusion, increasing HAS2, FSHR, LHR and GJA1 expression in goat COCs does not confer greater meiotic competence to oocytes. Instead, it may result from poor regulation of gene expression in CCs by lower quality oocytes. Finally, cumulus expansion, together with HAS2 upregulation and GJA1 downregulation, seems to be more important for bovine COCs than for goat COCs. Additional studies are needed to investigate the importance of other HAS isoforms and connexins in goat COCs. Copyright © 2016 Elsevier B.V. All rights reserved.

Repeated Administration of a Mutant Cocaine Esterase: Effects on Plasma Cocaine Levels, Cocaine-Induced Cardiovascular Activity, and Immune Responses in Rhesus Monkeys

PubMed Central

Collins, Gregory T.; Brim, Remy L.; Noon, Kathleen R.; Narasimhan, Diwahar; Lukacs, Nicholas W.; Sunahara, Roger K.; Woods, James H.

2012-01-01

Previous studies have demonstrated the capacity of a long-acting mutant form of a naturally occurring bacterial double mutant cocaine esterase (DM CocE) to antagonize the reinforcing, discriminative, convulsant, and lethal effects of cocaine in rodents and reverse the increases in mean arterial pressure (MAP) and heart rate (HR) produced by cocaine in rhesus monkeys. This study was aimed at characterizing the immunologic responses to repeated dosing with DM CocE and determining whether the development of anti-CocE antibodies altered the capacity of DM CocE to reduce plasma cocaine levels and ameliorate the cardiovascular effects of cocaine in rhesus monkeys. Under control conditions, intravenous administration of cocaine (3 mg/kg) resulted in a rapid increase in the plasma concentration of cocaine (n = 2) and long-lasting increases in MAP and HR (n = 3). Administration of DM CocE (0.32 mg/kg i.v.) 10 min after cocaine resulted in a rapid hydrolysis of cocaine with plasma levels below detection limits within 5 to 8 min. Elevations in MAP and HR were significantly reduced within 25 and 50 min of DM CocE administration, respectively. Although slight (10-fold) increases in anti-CocE antibodies were observed after the fourth administration of DM CocE, these antibodies did not alter the capacity of DM CocE to reduce plasma cocaine levels or ameliorate cocaine's cardiovascular effects. Anti-CocE titers were transient and generally dissipated within 8 weeks. Together, these results suggest that highly efficient cocaine esterases, such as DM CocE, may provide a novel and effective therapeutic for the treatment of acute cocaine intoxication in humans. PMID:22518021

Norcocaine in human hair as a biomarker of heavy cocaine use in a high risk population.

PubMed

Poon, S; Gareri, J; Walasek, P; Koren, G

2014-08-01

In hair analysis, cocaine (COC) and its metabolites have been studied relatively extensively with a consistent focus of distinguishing active drug use and excluding external contamination. Although quantitative cut-offs using major metabolite, benzolecgonine (BE), in hair have been proposed to distinguish likely active use from passive exposure, exogenously formed BE may result in false positive tests. Hence, the presence of less commonly detected COC metabolite, norcocaine (NCOC), may be useful in increasing certainty of illicit COC use and evaluating likelihood of environmental contamination. The objective of the present study was to observe the pattern of NCOC detection in a clinical population of suspected users and evaluate the possible role of NCOC in distinguishing systemic exposure from external contamination to COC and assessing intensity of cocaine use. Hair samples collected between January 2011 and May 2013 from the Motherisk Laboratory were analyzed by GC-MS for the presence of COC, BE, and NCOC. NCOC positivity rates (%) for various COC concentration ranges as well as sensitivity, specificity, positive predictive value, and negative predictive values of NCOC as a biomarker of different COC use profiles was calculated. The rate of NCOC positivity (%) within COC concentration ranges (ng/mg) 0.13-0.4 (above LOD, below LOQ), 0.4-3, 3-6, 6-10, 10-14, >14 were 0.26, 4.15, 29.63, 55.85, 80.37, and 94.02, respectively; p<0.0001 for all positivity comparisons between ranges. These results were used to determine a COC cut-off concentration for differing levels of COC use. The presence of NCOC above the LOD of 0.13 ng/mg predicted COC concentrations exceeding 14.00 ng/mg, with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 94.0%, 87.9%, 41.5%, and 99.4%, respectively. The presence NCOC above the LOD of 0.13 ng/mg predicted COC concentrations exceeding the 75th percentile, with sensitivity, specificity, PPV, and NPV of 76.6%, 94.7%, 74.7%, and 95.2%, respectively. Despite an inability to definitively rule out external contamination, the presence of NCOC in hair is strongly associated with elevated COC levels and performs as a highly specific surrogate marker for frequent/intensive cocaine use and highly sensitive marker for intensive/daily use of cocaine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Characterization of activated cyclic olefin copolymer: effects of ethylene/norbornene content on the physiochemical properties.

PubMed

O'Neil, Colleen E; Taylor, Scott; Ratnayake, Kumuditha; Pullagurla, Swathi; Singh, Varshni; Soper, Steven A

2016-11-28

The ethylene/norbornene content within cyclic olefin copolymer (COC) is well known to affect the chemical and physical properties of the copolymer, such as the glass transition temperature (T g ) and transparency. However, no work has been reported evaluating the effects of the ethylene/norbornene content on the surface properties of COC following UV/O 3 or O 2 plasma activation. Activation with either O 2 plasma or UV/O 3 is often used to assist in thermal assembly of fluidic devices, increasing the wettability of the surfaces, or generating functional scaffolds for the attachment of biological elements. Thus, we investigated differences in the physiochemical surface properties of various ethylene/norbornene compositions of COC following activation using analytical techniques such as water contact angle (WCA), ATR-FTIR, XPS, TOF-SIMS, UV-VIS, AFM and a colorimetric assay utilizing Toluidine Blue O (TBO). Results showed that increased norbornene content led to the generation of more oxygen containing functionalities such as alcohols, ketones, aldehydes and carboxyl groups when activated with either UV/O 3 or O 2 plasma. Specifically, COC with ∼60% norbornene content showed a significantly higher -COOH functional group density when compared to COC with a 50% norbornene content and COC with a 35% norbornene content following UV/O 3 or O 2 plasma activation. Furthermore, COC with large norbornene contents showed a smaller average RMS roughness (0.65 nm) when compared to COC containing low norbornene contents (0.95 nm) following activation making this substrate especially suited for nanofluidic applications, which require smooth surfaces to minimize effects arising from dielectrophoretic trapping or non-specific adsorption. Although all COC substrates showed >90% transparency at wavelengths >475 nm, COC possessing high norbornene contents showed significantly less transparency at wavelengths below 475 nm following activation, making optical detection in this region difficult. Our data showed distinct physiochemical differences in activated COC that was dependent upon the ethylene/norbornene content of the thermoplastic and thus, careful selection of the particular COC grade must be considered for micro- and nanofluidics.

Real-world experience of women using extended-cycle vs monthly-cycle combined oral contraception in the United States: the National Health and Wellness Survey.

PubMed

Nappi, Rossella E; Lete, Iñaki; Lee, Lulu K; Flores, Natalia M; Micheletti, Marie-Christine; Tang, Boxiong

2018-01-18

The real-world experience of women receiving extended-cycle combined oral contraception (COC) versus monthly-cycle COC has not been reported. Data were from the United States 2013 National Health and Wellness Survey. Eligible women (18-50 years old, premenopausal, without hysterectomy) currently using extended-cycle COC (3 months between periods) were compared with women using monthly-cycle COC. Treatment satisfaction (1 "extremely dissatisfied" to 7 "extremely satisfied"), adherence (8-item Morisky Medication Adherence Scale © ), menstrual cycle-related symptoms, health-related quality of life (HRQOL) and health state utilities (Medical Outcomes Short Form Survey-36v2®), depression (9-item Patient Health Questionnaire), sleep difficulties, Work Productivity and Activity Impairment-General Health, and healthcare resource use were assessed using one-way analyses of variance, chi-square tests, and generalized linear models (adjusted for covariates). Participants included 260 (6.7%) women using extended-cycle and 3616 (93.3%) using monthly-cycle COC. Women using extended-cycle COC reported significantly higher treatment satisfaction (P = 0.001) and adherence (P = 0.04) and reduced heavy menstrual bleeding (P = 0.029). A non-significant tendency toward reduced menstrual pain (39.5% versus 47.3%) and menstrual cycle-related symptoms (40.0% versus 48.7%) was found in women using extended-cycle versus monthly-cycle COC. Significantly more women using extended-cycle COC reported health-related diagnoses, indicating preferential prescription for extended-cycle COC among women reporting more health problems. Consistent with this poorer health, more women using extended-cycle COC reported fatigue, headache, and activity impairment (P values < 0.05). There were no other significant differences between groups. This real-world observational study supports extended-cycle COC as a valuable treatment option with high satisfaction, high adherence, and reduced heavy menstrual bleeding.

Effects of a long-acting mutant bacterial cocaine esterase on acute cocaine toxicity in rats

PubMed Central

Collins, Gregory T.; Zaks, Matthew E.; Cunningham, Alyssa R.; St. Clair, Carley; Nichols, Joseph; Narasimhan, Diwahar; Ko, Mei-Chuan; Sunahara, Roger K.; Woods, James H.

2011-01-01

Background A longer acting, double mutant bacterial cocaine esterase (CocE T172R/G173Q; DM CocE) has been shown to protect mice from cocaine-induced lethality, inhibit the reinforcing effects of cocaine in rats, and reverse cocaine’s cardiovascular effects in rhesus monkeys. The current studies evaluated the effectiveness of DM CocE to protect against, and reverse cocaine’s cardiovascular, convulsant, and lethal effects in male and female rats. Methods Pretreatment studies were used to determine the effectiveness and in vivo duration of action for DM CocE to protect rats against the occurrence of cardiovascular changes, convulsion and lethality associated with acute cocaine toxicity. Posttreatment studies were used to evaluate the capacity of DM CocE to rescue rats from the cardiovascular and lethal effects of large doses of cocaine. In addition, male and female rats were studied to determine if there were any potential effects of sex on the capacity of DM CocE to protect against, or reverse acute cocaine toxicity in rats. Results Pretreatment with DM CocE dose-dependently protected rats against cocaine-induced cardiovascular changes, convulsion and lethality, with higher doses active for up to 4 hrs, and shifting cocaine-induced lethality at least 10-fold to the right. In addition to dose-dependently recovering rats from an otherwise lethal dose of cocaine, post-treatment with DM CocE also reversed the cardiovascular effects of cocaine. There were no sex-related differences in the effectiveness of DM CocE to protect against, or reverse acute cocaine toxicity. Conclusions Together, these results support the development of DM CocE for the treatment of acute cocaine toxicity. PMID:21481548

Anti-inflammatory and antithrombotic effects of nicotine exposure in oral contraceptive-induced insulin resistance are glucocorticoid-independent.

PubMed

Olatunji, Lawrence Aderemi; Michael, Olugbenga Samuel; Adeyanju, Oluwaseun Aremu; Areola, Emmanuel Damilare; Soladoye, Ayodele Olufemi

2017-06-01

Reports showed that estrogen-progestin oral contraceptive (COC) or tobacco smoking causes increased risk of cardiovascular diseases (CVD) in premenopausal women. Studies also suggest that nicotine, a major tobacco alkaloid, may worsen or improve atherothrombotic CVD. Altered hemorheology, prothrombotic and pro-inflammatory biomarkers, have been implicated in the development of atherothrombotic CVD events. However, the effect of non-smoking nicotine exposure on these biomarkers during COC treatment is not yet established. We therefore sought to determine the effects of nicotine exposure during COC treatment on these biomarkers, and also tested the hypothesis that the nicotine effects would be glucocorticoid-dependent. Female Sprague-Dawley rats aged 10 weeks were given (po) vehicle, low-dose nicotine (0.1mg/kg) or high-dose nicotine (1.0mg/kg) with or without COC steroids (5.0μg/kg ethinylestradiol and 25.0μg/kg levonorgestrel) daily for 6 weeks. COC treatment or nicotine exposure led to increased insulin resistance (IR), hemorheological (blood viscosity, hematocrit and plasma viscosity), prothrombotic (plasminogen activator inhibitor-1), pro-inflammatory (uric acid, C-reactive protein, neutrophil/lymphocyte and platelet/lymphocyte ratios) biomarkers and corticosterone. However, these effects except that on corticosterone were abrogated by nicotine exposure during COC treatment. Our study indicates that nicotine- or COC-induced IR may be mediated via inflammatory/thrombotic pathway. The results imply that nicotine exposure could impact negatively on atherothrombotic biomarkers in COC non-users, whereas the impact in COC users could be positive. The results also suggest that the anti-inflammatory, antithrombotic and blood viscosity-lowering effects of nicotine exposure during COC use is circulating glucocorticoid-independent. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Stromal-derived factor 1 directly promotes genes expressed within the ovulatory cascade in feline cumulus oocyte complexes.

PubMed

Rojo, Julieta L; Linari, Martina; Young, Kelly A; Peluffo, Marina C

2018-05-01

We hypothesized that the chemokine SDF1/CXCR4 system was present in feline cumulus-oocyte complexes (COCs) and that COCs cultured with SDF1 would directly upregulate gene expression in the ovulatory cascade. Ovaries (n = 50) were obtained from adult domestic cats during the breeding season and COCs were recovered from antral follicles. Because IVM media triggers cumulus-oocyte expansion, culture conditions needed to be optimized to study periovulatory genes. After optimization, the effects of 25 ng/ml SDF1 and the CXCR4 inhibitor were examined in a COC culture for 3, 12, and 24 h. MEM-hepes with 1% of charcoal stripped-FBS was the optimized culture medium, assessed by the expansion of COCs at 24 h in the gonadotropin (GNT) group but not in the media with serum alone. The mRNA expression of HAS2, TNFAIP6, PTX3, and AREG peaked at 3 h in GNT group as compared to all other groups (p < 0.05). COCs cultured with SDF1 showed increased HAS2 and TNFAIP6 mRNA expression at 3 h compared to negative controls and to the CXCR4 inhibitor group. CXCR4 and SDF1 immunostaining was present in both cumulus cells and the oocyte. These results demonstrate that GNT stimulation upregulates key periovulatory genes and expansion in feline COCs from antral follicles, and support the use of this culture system to examine molecular processes within the COC. In addition, SDF1 directly promotes key periovulatory genes in feline COCs, suggesting that the SDF1-CXCR4 pathway may extend its function beyond a chemoattractant, and may play a direct role within the COC.

User satisfaction with the combined oral contraceptive drospirenone 3 mg/ethinylestradiol 20 microg (Yasminelle) in clinical practice: a multi-country, questionnaire-based study.

PubMed

Short, Mary

2009-01-01

To assess women's perception of a combined oral contraceptive (COC) containing drospirenone 3 mg/ethinylestradiol (EE) 20 microg administered in the conventional 21/7 regimen (drospirenone 3 mg/EE 20 microg 21/7 regimen [Yasminelle]) in clinical practice. This questionnaire-based study was performed in 12 European countries and included women who had been taking the drospirenone 3 mg/EE 20 microg 21/7 regimen COC for > or =3 months. Of 16 461 completed questionnaires, 12 277 were from women who had been using the drospirenone 3 mg/EE 20 microg 21/7 regimen COC for > or =3 months - 34% of women were new users of COCs and 65% had switched from alternative contraceptive brands. The mean age of these respondents was approximately 27 years. Seventy percent of women who indicated that they had skin problems before taking the drospirenone 3 mg/EE 20 microg 21/7 regimen COC responded that their skin had improved with treatment (3030/4305). Sixty-nine percent of women who had switched to the drospirenone 3 mg/EE 20 microg 21/7 regimen COC because of weight problems with their previous method of contraception responded that they had experienced weight loss (1205/1745). Approximately 95% of respondents said they were satisfied with the drospirenone 3 mg/EE 20 microg 21/7 regimen COC. Moreover, 83% of respondents said they would recommend this COC to a friend. There were high levels of perceived satisfaction with the drospirenone 3 mg/EE 20 microg 21/7 regimen COC. The reported effects on weight loss (due to decreased water retention) and skin problems are consistent with the antimineralocorticoid and antiandrogenic benefits of drospirenone-containing COCs.

40 CFR 86.1105-87 - Emission standards for which nonconformance penalties are available.

Code of Federal Regulations, 2014 CFR

2014-07-01

... engine oxides of nitrogen standard of 5.0 grams per brake horsepower-hour. (i) For petroleum-fueled light... § 86.1113-87(a): (1) COC50: $830. (2) COC90: $946. (3) MC50: $1,167 per gram per brake horsepower-hour...-87(a): (1) COC50: $905. (2) COC90: $1,453. (3) MC50: $1,417 per gram per brake horsepower-hour. (4) F...

Transplacental cocaine exposure. 2: Effects of cocaine dose and gestational timing.

PubMed

Wilkins, A S; Jones, K; Kosofsky, B E

1998-01-01

We have utilized a mouse model of transplacental cocaine exposure to investigate the effects of cocaine dose and gestational timing in altering brain and body growth and postnatal behavior in exposed offspring. Pregnant dams were injected with cocaine HCl at 40 mg/kg/day (COC 40) or 20 mg/kg/day (COC 20), or 10 mg/kg/day (COC 10) SC from embryonic day (E) 8 to E17, or cocaine HCl at 40 mg/kg/day SC from E8 to E13 (COC Early) or from E13 to E17 (COC Late) divided in two daily doses. COC 40 and COC Late dams, as well as dams in nutritionally paired control groups (injected with saline vehicle and pair-fed with the COC dams: SPF 40, SPF 20, SPF 10), demonstrated less weight gain than SAL controls (injected with saline vehicle and allowed access to food ad lib). The surrogate fostered offspring of COC 40 and SPF 40 dams demonstrated brain and body growth retardation [on postnatal day (P) 1 and P9] when compared to pups born to SAL dams. Offspring of COC Late, SPF 20, and SPF 10 dams demonstrated brain and body growth retardation on P1 when compared to pups born to SAL dams. Pups from all groups were tested for first-order Pavlovian conditioning on P9, or for the ability to ignore redundant information in a blocking paradigm on P50. Only COC 40 mice (i.e., offspring born to COC 40 dams) were unable to acquire an aversion to an odor previously paired with shock on P9. When compared with SAL controls, COC 40 mice (and to a less significant extent SPF 40 mice) demonstrated a persistent behavioral deficit in the blocking paradigm on P50, which may reflect alterations in selective attention. Correlation analyses indicated that the dose and gestational timing of transplacental cocaine exposure, and varying degrees of malnutrition, had effects on blocking performance, with greater prenatal cocaine exposure and increased prenatal malnutrition resulting in more significant behavioral impairments. A path regression analysis demonstrated independent and significant effects of prenatal cocaine as well as prenatal malnutrition in contributing to impaired performance in the blocking paradigm. As suggested by the clinical literature, our preclinical data support a model whereby the dose and duration of prenatal cocaine exposure have direct effects on offspring brain and body growth and on behavioral performance.

Extended regimen combined oral contraception: A review of evolving concepts and acceptance by women and clinicians.

PubMed

Nappi, Rossella E; Kaunitz, Andrew M; Bitzer, Johannes

2016-01-01

The clinical utility of extended regimen combined oral contraceptives (COCs) is increasingly being recognised. Our objective was to understand the attitudes of women and clinicians about the use of these regimens. We present the rationale for extended regimen COCs from a historical perspective, and trace their evolution and growing popularity in light of their clinical benefits. We conclude by offering potential strategies for counselling women about extended regimen COC options. We conducted a MEDLINE search to identify and summarise studies of extended regimen COCs, focusing on attitudes of women and clinicians regarding efficacy, safety/tolerability and fewer scheduled bleeding episodes and other potential benefits. The body of contemporary literature on extended regimen COCs suggests that their contraceptive efficacy is comparable to that of conventional 28-day (i.e., 21/7) regimens. For women seeking contraception that allows infrequent scheduled bleeding episodes, particularly those who suffer from hormone withdrawal symptoms and cyclical symptoms (e.g., headache, mood changes, dysmenorrhoea, heavy menstrual bleeding), extended regimen COCs are an effective and safe option. Although satisfaction with extended regimen COCs in clinical trials is high, misperceptions about continuous hormone use may still limit the widespread acceptance of this approach. Despite the widespread acceptance among clinicians of extended regimen COCs as an effective and safe contraceptive option, these regimens are underused, likely due to a lack of awareness about their availability and utility among women. Improved patient education and counselling regarding the safety and benefits of extended regimen COCs may help women make more informed contraceptive choices.

Extended regimen combined oral contraception: A review of evolving concepts and acceptance by women and clinicians

PubMed Central

Nappi, Rossella E.; Kaunitz, Andrew M.; Bitzer, Johannes

2016-01-01

ABSTRACT Objectives: The clinical utility of extended regimen combined oral contraceptives (COCs) is increasingly being recognised. Our objective was to understand the attitudes of women and clinicians about the use of these regimens. We present the rationale for extended regimen COCs from a historical perspective, and trace their evolution and growing popularity in light of their clinical benefits. We conclude by offering potential strategies for counselling women about extended regimen COC options. Methods: We conducted a MEDLINE search to identify and summarise studies of extended regimen COCs, focusing on attitudes of women and clinicians regarding efficacy, safety/tolerability and fewer scheduled bleeding episodes and other potential benefits. Results: The body of contemporary literature on extended regimen COCs suggests that their contraceptive efficacy is comparable to that of conventional 28-day (i.e., 21/7) regimens. For women seeking contraception that allows infrequent scheduled bleeding episodes, particularly those who suffer from hormone withdrawal symptoms and cyclical symptoms (e.g., headache, mood changes, dysmenorrhoea, heavy menstrual bleeding), extended regimen COCs are an effective and safe option. Although satisfaction with extended regimen COCs in clinical trials is high, misperceptions about continuous hormone use may still limit the widespread acceptance of this approach. Conclusions: Despite the widespread acceptance among clinicians of extended regimen COCs as an effective and safe contraceptive option, these regimens are underused, likely due to a lack of awareness about their availability and utility among women. Improved patient education and counselling regarding the safety and benefits of extended regimen COCs may help women make more informed contraceptive choices. PMID:26572318

Discovery of syn-/anti-cocaine-N-oxide diastereomers in unwashed postmortem hair via LC-MS-MS.

PubMed

Marsh, Christine M; Crawley, Lindsey R; Himes, Sarah K; Aranda, Roman; Miller, Mark L

2014-01-01

The discovery of two cocaine-N-oxide (CNO) diastereomers, syn- and anti-CNO, is reported for the first time. Prior to this study, only one structural form of CNO was known to exist and has not been analyzed in hair before. CNO is a metabolite of cocaine (COC) and may be considered as an additional biomarker of COC use, along with other known COC metabolites. The analysis of COC in hair for forensic applications is under scrutiny due to the possibility of external contamination. A qualitative liquid chromatography-tandem mass spectrometry method was developed, validated and applied to unwashed postmortem hair samples from drug users. The limit of detection in hair was 8 pg/mg (using 10 mg of unwashed hair) for each CNO diastereomer. The presence of both syn- and anti-forms of CNO was verified in vivo using hair samples collected from known COC-using individuals. Due to the low levels of CNO, it will not always be detectable in COC user hair. In the hair samples analyzed, syn-CNO was detected in more samples than anti-CNO. The stereoselective N-oxidation of COC which favors syn-CNO could have a diagnostic value for COC ingestion determination in hair analysis. Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Crataegus oxycantha extract attenuates apoptotic incidence in myocardial ischemia-reperfusion injury by regulating Akt and HIF-1 signaling pathways.

PubMed

Jayachandran, Kesavan S; Khan, Mahmood; Selvendiran, Karuppaiyah; Devaraj, S Niranjali; Kuppusamy, Periannan

2010-11-01

The objective of the present study was to evaluate the efficacy and mechanism of Crataegus oxycantha (COC) extract in preventing ischemia-reperfusion (IR) injury in an in vivo rat model of acute myocardial infarction induced by a 30-minute regional ischemia followed by 72 hours of reperfusion. The COC extract [100 mg/(kg body weight)] was administered 12 hours after the surgical procedure and then at 24-hour intervals for 3 days. Animals treated with COC extract showed a significant decrease in creatine kinase activity and infarct size. At the molecular level, COC administration resulted in a significant attenuation of PTEN (phosphatase and tensin homolog deleted on chromosome 10) and upregulation of phospho-Akt and c-Raf levels in the heart. As a consequence, cleaved caspase-9 and cleaved caspase-7 levels were significantly downregulated, indicating negative regulation of apoptosis by COC extract. In part with the hypoxia-inducible factor (HIF) signaling pathway, COC extract administration significantly upregulated the prolyl hydroxylase-2 level. In contrast, other proapoptotic proteins such as nuclear factor-κB, cytochrome c, apoptosis-inducing factor, and cleaved poly(adenosine diphosphate-ribose) polymerase levels were significantly downregulated in the COC-treated group when compared with the untreated control group. The results suggested that COC extract attenuated apoptotic incidence in the experimental myocardial ischemia-reperfusion model by regulating Akt and HIF-1 signaling pathways.

Drug development costs when financial risk is measured using the Fama-French three-factor model.

PubMed

Vernon, John A; Golec, Joseph H; Dimasi, Joseph A

2010-08-01

In a widely cited article, DiMasi, Hansen, and Grabowski (2003) estimate the average pre-tax cost of bringing a new molecular entity to market. Their base case estimate, excluding post-marketing studies, was $802 million (in $US 2000). Strikingly, almost half of this cost (or $399 million) is the cost of capital (COC) used to fund clinical development expenses to the point of FDA marketing approval. The authors used an 11% real COC computed using the capital asset pricing model (CAPM). But the CAPM is a single factor risk model, and multi-factor risk models are the current state of the art in finance. Using the Fama-French three factor model we find that the cost of drug development to be higher than the earlier estimate. Copyright (c) 2009 John Wiley & Sons, Ltd.

Continuity of care with physicians and risk of subsequent hospitalization and end-stage renal disease in newly diagnosed type 2 diabetes mellitus patients.

PubMed

Chang, Po-Ya; Chien, Li-Nien; Bai, Chyi-Huey; Lin, Yuh-Feng; Chiou, Hung-Yi

2018-01-01

Effective management for type 2 diabetes mellitus (DM) can slow the progression of kidney outcomes and reduce hospital admissions. Better continuity of care (COC) was found to improve patients' adherence and self-management. This study examined the associations between COC, hospitalization, and end-stage renal disease (ESRD) in DM patients. In the cohort study, data from 1996 to 2012 were retrieved from the Longitudinal Health Insurance Database, using inverse probability weighted analysis. A total of 26,063 patients with newly diagnosed type 2 DM who had been treated with antihyperglycemic agents were included. COC is to assess the extent to which a DM patient visited the same physician during the study period. This study categorized COC into 3 groups - low, intermediate, and high, - according to the distribution of scores in our sample. The number of ESRD patients in the high, intermediate, and low COC groups were 92 (22.33%), 130 (31.55%), and 190 (46.12%), respectively, and the mean follow-up periods for the 3 groups were 7.13, 7.12, and 7.27 years, respectively. After using inverse probability weighting, the intermediate and low COC groups were significantly associated with an increased risk of ESRD compared with the high COC group (adjusted hazard ratio (aHR) 1.36 [95% CI, 1.03-1.80] and aHR 1.76 [95% CI, 1.35-2.30], respectively). The intermediate and low COC groups were also significantly associated with the subsequent hospitalization compared with the high COC group (aHR 1.15 [95% CI, 0.99-1.33] and aHR 1.72 [95% CI, 1.50-1.97], respectively). COC is related to ESRD onset and subsequent hospitalization among patients with DM. This study suggested that when DM patients keep visiting the same physician for managing their diseases, the progression of renal disease can be prevented.

A Thermally Stable Form of Bacterial Cocaine Esterase: A Potential Therapeutic Agent for Treatment of Cocaine Abuse

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

Brim, Remy L.; Nance, Mark R.; Youngstrom, Daniel W.

Rhodococcal cocaine esterase (CocE) is an attractive potential treatment for both cocaine overdose and cocaine addiction. CocE directly degrades cocaine into inactive products, whereas traditional small-molecule approaches require blockade of the inhibitory action of cocaine on a diverse array of monoamine transporters and ion channels. The usefulness of wild-type (wt) cocaine esterase is hampered by its inactivation at 37 C. Herein, we characterize the most thermostable form of this enzyme to date, CocE-L169K/G173Q. In vitro kinetic analyses reveal that CocE-L169K/G173Q displays a half-life of 2.9 days at 37 C, which represents a 340-fold improvement over wt and is 15-fold greatermore » than previously reported mutants. Crystallographic analyses of CocE-L169K/G173Q, determined at 1.6-{angstrom} resolution, suggest that stabilization involves enhanced domain-domain interactions involving van der Waals interactions and hydrogen bonding. In vivo rodent studies reveal that intravenous pretreatment with CocE-L169K/G173Q in mice provides protection from cocaine-induced lethality for longer time periods before cocaine administration than wt CocE. Furthermore, intravenous administration (pretreatment) of CocE-L169K/G173Q prevents self-administration of cocaine in a time-dependent manner. Termination of the in vivo effects of CoCE seems to be dependent on, but not proportional to, its clearance from plasma as its half-life is approximately 2.3 h and similar to that of wt CocE (2.2 h). Taken together these data suggest that CocE-L169K/G173Q possesses many of the properties of a biological therapeutic for treating cocaine abuse but requires additional development to improve its serum half-life.« less

Epigenetic mechanisms associated with addiction-related behavioural effects of nicotine and/or cocaine: implication of the endocannabinoid system.

PubMed

Hayase, Tamaki

2017-10-01

The addictive use of nicotine (NC) and cocaine (COC) continues to be a major public health problem, and their combined use has been reported, particularly during adolescence. In neural plasticity, commonly induced by NC and COC, as well as behavioural plasticity related to the use of these two drugs, the involvement of epigenetic mechanisms, in which the reversible regulation of gene expression occurs independently of the DNA sequence, has recently been reported. Furthermore, on the basis of intense interactions with the target neurotransmitter systems, the endocannabinoid (ECB) system has been considered pivotal for eliciting the effects of NC or COC. The combined use of marijuana with NC and/or COC has also been reported. This article presents the addiction-related behavioural effects of NC and/or COC, based on the common behavioural/neural plasticity and combined use of NC/COC, and reviews the interacting role of the ECB system. The epigenetic processes inseparable from the effects of NC and/or COC (i.e. DNA methylation, histone modifications and alterations in microRNAs) and the putative therapeutic involvement of the ECB system at the epigenetic level are also discussed.

The bioequivalence of the contraceptive steroids ethinylestradiol and drospirenone is not affected by co-administration of dehydroepiandrosterone.

PubMed

Zimmerman, Yvette; Wouters, Wout; Coelingh Bennink, Herjan J T

2013-06-01

To study the effect of co-administration of 50 mg dehydroepiandrosterone (DHEA) on the bioequivalence of ethinylestradiol (EE) and drospirenone (DRSP) in women who were using a combined oral contraceptive (COC) containing 30 μg EE and 3 mg DRSP, and to estimate whether the addition of DHEA to this COC affects the serum levels and the bioequivalence of the synthetic contraceptive steroids. This was a randomised, double-blind, two-period crossover study. Participants received two EE/DRSP COC treatment cycles in random order, one with and one without daily 50 mg DHEA , separated by a 28-day wash-out cycle during which the subjects used an EE/levonorgestrel (LNG) COC without DHEA. Serum levels of EE and DRSP were measured according to a sampling scheme allowing pharmacokinetic evaluations. Addition of DHEA to an EE/DRSP COC had no effect on serum levels of EE and DRSP. The COC regimens with and without DHEA were bioequivalent. Oestradiol levels were equally suppressed during pill intake, whether with placebo or DHEA. Adding DHEA to a COC containing EE and DRSP does not affect the pharmacokinetic properties of EE and DRSP. Therefore, it will most likely not affect its contraceptive efficacy.

Efficacy, acceptability and tolerability of the combined contraceptive ring, NuvaRing, compared with an oral contraceptive containing 30 microg of ethinyl estradiol and 3 mg of drospirenone.

PubMed

Ahrendt, Hans-Joachim; Nisand, Israel; Bastianelli, Carlo; Gómez, Maria Angeles; Gemzell-Danielsson, Kristina; Urdl, Wolfgang; Karskov, Birgit; Oeyen, Luc; Bitzer, Johannes; Page, Geert; Milsom, Ian

2006-12-01

This randomized multicenter, open-label, trial compared efficacy, acceptability, tolerability and compliance of NuvaRing with a combined oral contraceptive (COC), containing 30 microg of ethinyl estradiol (EE) and 3 mg of drospirenone. In this 13-cycle study, 983 women were randomized and treated (intent-to-treat population) with NuvaRing or COC. One in-treatment pregnancy occurred with NuvaRing (Pearl Index=0.25) (95% confidence interval [CI]: 0.006, 1.363) and four with the COC (Pearl Index=0.99) (95% CI: 0.269, 2.530). For both groups, compliance (89.2% NuvaRing, 85.5% COC) and satisfaction (84% NuvaRing; 87% COC) were high; the vast majority of women found NuvaRing easy to insert (96%) and remove (97%). Tolerability was similar; the most frequent adverse events with NuvaRing were related to ring use, whereas estrogen-related events were more common with the COC. NuvaRing has comparable efficacy and tolerability to a COC containing 30 microg of EE and 3 mg drospirenone. User acceptability of both methods was high.

Use of simulated patients to evaluate combined oral contraceptive dispensing practices of community pharmacists.

PubMed

Obreli-Neto, Paulo Roque; Pereira, Leonardo Régis Leira; Guidoni, Camilo Molino; de Oliveira Baldoni, André; Marusic, Srecko; de Lyra-Júnior, Divaldo Pereira; de Almeida, Kelsen Luis; Pazete, Ana Claudia Montolezi; do Nascimento, Janaina Dutra; Kos, Mitja; Girotto, Edmarlon; Cuman, Roberto Kenji Nakamura

2013-01-01

Combined oral contraceptive (COC) use is the most commonly used reversible method of birth control. The incorrect use of COCs is frequent and one of the most common causes of unintended pregnancies. Community pharmacists (CPs) are in a strategic position to improve COC use because they are the last health professional to interact with patients before drug use. To evaluate the COC dispensing practices of CPs in a developing country. A cross-sectional study was conducted in community pharmacies of Assis and Ourinhos microregions, Brazil, between June 1, 2012, and October 30, 2012. Four simulated patients (SPs) (with counseled audio recording) visited community pharmacies with a prescription for Ciclo 21(®) (a COC containing ethinyl estradiol 30 mcg + levonorgestrel 15 mcg). The audio recording of every SP visit was listened to independently by 3 researchers to evaluate the COC dispensing practice. The percentage of CPs who performed a screening for safe use of COCs (i.e., taking of patients' medical and family history, and measuring of blood pressure) and provided counseling, as well as the quality of the screening and counseling, were evaluated. Of the 185 CPs contacted, 41 (22.2%) agreed to participate in the study and finished the study protocol. Only 3 CPs asked the SP a question (1 question asked by each professional), and all of the questions were closed-ended, viz., "do you smoke?" (n = 2) and "what is your age?" (n = 1). None of the CPs measured the patient's blood pressure. Six CPs provided counseling when dispensing COCs (drug dosing, 5 CPs; possible adverse effects, 2 CPs), and one CP provided counseling regarding both aspects. The CPs evaluated did not dispense COC appropriately and could influence in the occurrence of negatives therapeutic outcomes such as adverse effects and treatment failure.

Analysis of extensively washed hair from cocaine users and drug chemists to establish new reporting criteria.

PubMed

Morris-Kukoski, Cynthia L; Montgomery, Madeline A; Hammer, Rena L

2014-01-01

Samples from a self-proclaimed cocaine (COC) user, from 19 drug users (postmortem) and from 27 drug chemists were extensively washed and analyzed for COC, benzoylecgonine, norcocaine (NC), cocaethylene (CE) and aryl hydroxycocaines by liquid chromatography-tandem mass spectrometry. Published wash criteria and cutoffs were applied to the results. Additionally, the data were used to formulate new reporting criteria and interpretation guidelines for forensic casework. Applying the wash and reporting criteria, hair that was externally contaminated with COC was distinguished from hair collected from individuals known to have consumed COC. In addition, CE, NC and hydroxycocaine metabolites were only present in COC users' hair and not in drug chemists' hair. When properly applied, the use of an extended wash, along with the reporting criteria defined here, will exclude false-positive results from environmental contact with COC. Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Wavelength division multiplexing of chaotic secure and fiber-optic communications.

PubMed

Zhang, Jian-Zhong; Wang, An-Bang; Wang, Juan-Fen; Wang, Yun-Cai

2009-04-13

Wavelength division multiplexing (WDM) transmission of chaotic optical communication (COC) and conventional fiber-optic communication (CFOC) is numerically confirmed and analyzed. For an 80-km-long two-channel communication system, a 1-Gb/s secure message in COC channel and 10-Gb/s digital signal in CFOC channel are simultaneously achieved with 100 GHz channel spacing. Our numerical simulations demonstrate that the COC and CFOC can realize no-crosstalk transmission of 80 km when the peak power of CFOC channel is less than 8dBm. We also find that the crosstalk between COC and CFOC does not depend on channel spacing when the channel spacing exceeds 100GHz. Moreover, the crosstalk does not limit channel number by comparing the synchronization performance of COC in four- and six-channel WDM systems.

Blood clots in the cumulus-oocyte complex predict poor oocyte quality and post-fertilization development.

PubMed

Ebner, T; Moser, M; Shebl, O; Sommergruber, M; Yaman, C; Tews, G

2008-06-01

Assessment of oocyte maturity and quality (morphological appearance) at the time of retrieval is difficult as the egg is obscured by a large cumulus mass that hinders adequate scoring. Since no data are available on the possible relationship between the cumulus-oocyte complex (COC) and oocyte morphology, this prospective intracytoplasmic sperm injection study was set up in 87 consecutive patients. COC were grouped according to expansion of both corona radiata and cumulus matrix. Special emphasis was placed on recording morphological anomalies of COC (inclusion of blood clots and amorphous clumps). For all mature ovae, quality was assessed and preimplantation development followed up to blastocyst stage if fertilized. The risk of not harvesting an oocyte was higher in COC with blood clots compared with normal cumulus matrices (P = 0.004). COC expansion did not allow for prediction of either nuclear status or quality of the egg. The presence of blood clots within the cumulus matrix was associated with reduced oocyte quality (dense central granulation), fertilization rate and blastocyst formation, compared with unaffected COC (P < 0.05). It may be postulated that COC showing blood inclusions derive from poor quality follicles, which has a detrimental effect on oocyte quality and further cleavage to blastocyst stage. Consequently, mechanical removal of blood clots cannot rescue the corresponding embryo.

The not-so-bitter pill: Effects of combined oral contraceptives on peripheral physiological indicators of emotional reactivity.

PubMed

Armbruster, Diana; Kirschbaum, Clemens; Strobel, Alexander

2017-08-01

Combined oral contraceptives (COC) are used by millions of women worldwide. Although findings are not entirely consistent, COC have been found to impact on brain function and, thus, to modulate affective processes. Here, we investigated electro-physiological responses to emotional stimuli in free cycling women in both the early follicular and late luteal phase as well as in COC users. Skin conductance response (SCR), startle reflex, corrugator and zygomaticus activity were assessed. COC users showed reduced overall startle magnitude and SCR amplitude, but heightened overall zygomaticus activity, although effect sizes were small. Thus, COC users displayed reduced physiological reactions indicating negative affect and enhanced physiological responses signifying positive affect. In free cycling women, endogenous 17β-estradiol levels were associated with fear potentiated startle in both cycle phases as well as with SCR and zygomaticus activity during the follicular phase. Testosterone was associated with corrugator and zygomaticus activity during the luteal phase, while progesterone levels correlated with corrugator activity in the follicular phase. To the contrary, in COC users, endogenous hormones were not associated with electro-physiological measures. The results further underscore the importance of considering COC use in psychophysiological studies on emotional processing. Copyright © 2017 Elsevier Inc. All rights reserved.

Continuum of care in maternal, newborn and child health in Pakistan: analysis of trends and determinants from 2006 to 2012.

PubMed

Iqbal, Sarosh; Maqsood, Sidra; Zakar, Rubeena; Zakar, Muhammad Zakria; Fischer, Florian

2017-03-09

Pakistan, being a developing country, presents the dismal picture of maternal and neonatal mortality and morbidity. The majority of maternal and neonatal deaths could be avoided if Continuum of Care (CoC) is provided in a structured pathway from pregnancy to birth and to the first week of life of the newborn child. This study aimed to analyse the trends of CoC at all three levels (antenatal care, skilled delivery and postpartum care) and to identify various factors affecting the continuation in receiving CoC in Pakistan during 2006 to 2012. Secondary data analysis was performed on nationally representative data from the last two iterations of Pakistan Demographic and Health Survey (PDHS), conducted during 2006/07 to 2012/13. The analysis is limited to women of the reproductive age group (15-49 years) who gave birth during the last five years preceding both surveys. This leads to a sample size of 5,724 and 7,461 respondents from PDHS 2006/07 and 2012/13 respectively. The association between CoC and several factors, including individual attributes (reproductive status), family influences, community context, as well as cultural and social values was assessed in bivariate analyses in a first step. Furthermore, odds ratios and adjusted odds ratios with 95% confidence intervals using a binary and multivariable logistic regression were calculated. Our research presents the trends of a composite measure of CoC including antenatal care, delivery assistance and postpartum care. The largest gap in CoC was observed at antenatal care followed by delivery and postnatal care within 48 h after delivery. Results show that CoC completion rate has increased from 15% to 27% amongst women in Pakistan over time from 2006 to 2012. Women with high age at first birth, having less number of children, with higher education, belonging to richest quintile, living in Sindh province and urban areas, having high autonomy and exposure to mass media were most likely to avail complete CoC. The findings show that women in Pakistan still lack the CoC. This calls for attention to develop and implement tailored interventions, focusing on the needs of women in Pakistan to provide CoC in an integrated manner, involving both public and private sectors by appropriately addressing the factors hindering CoC completion rates.

Innovative Water Management Technology to Reduce Environmental Impacts of Produced Water

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

Castle, James; Rodgers, John; Alley, Bethany

2013-05-15

Clemson University with Chevron as an industry partner developed and applied treatment technology using constructed wetland systems to decrease targeted constituents in simulated and actual produced waters to achieve reuse criteria and discharge limits. Pilot-scale and demonstration constructed wetland treatment system (CWTS) experiments led to design strategies for treating a variety of constituents of concern (COCs) in produced waters including divalent metals, metalloids, oil and grease, and ammonia. Targeted biogeochemical pathways for treatment of COCs in pilot-scale CWTS experiments included divalent metal sulfide precipitation through dissimilatory sulfate reduction, metal precipitation through oxidation, reduction of selenite to insoluble elemental selenium, aerobicmore » biodegradation of oil, nitrification of ammonia to nitrate, denitrification of nitrate to nitrogen gas, separation of oil using an oilwater separator, and sorption of ammonia to zeolite. Treatment performance results indicated that CWTSs can be designed and built to promote specific environmental and geochemical conditions in order for targeted biogeochemical pathways to operate. The demonstration system successfully achieved consistent removal extents even while inflow concentrations of COCs in the produced water differed by orders of magnitude. Design strategies used in the pilot-scale and demonstration CWTSs to promote specific conditions that can be applied to designing full-scale CWTSs include plant and soil selection, water-depth selection, addition of amendments, and hydraulic retention time (HRT). These strategies allow conditions within a CWTS to be modified to achieve ranges necessary for the preferred biogeochemical treatment pathways. In the case of renovating a produced water containing COCs that require different biogeochemical pathways for treatment, a CWTS can be designed with sequential cells that promote different conditions. For example, the pilot-scale CWTS for post-reverse osmosis produced water was designed to promote oxidizing conditions within the first wetland cell for nitrification of ammonia, and the subsequent three cells were designed to promote reducing conditions for denitrification of nitrate. By incorporating multiple wetland cells in a CWTS, the conditions within each cell can be modified for removal of specific COCs. In addition, a CWTS designed with multiple cells allows for convenient sample collection points so that biogeochemical conditions of individual cells can be monitored and performance evaluated. Removal rate coefficients determined from the pilot-scale CWTS experiments and confirmed by the demonstration system can be used to calculate HRTs required to treat COCs in full-scale CWTSs. The calculated HRTs can then be used to determine the surface area or ?footprint? of a full-size CWTS for a given inflow rate of produced water.« less

Innovative Water Management Technology to Reduce Environment Impacts of Produced Water

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

Castle, James W.; Rodgers, John H.; Alley, Bethany

2013-08-08

Clemson University with Chevron as an industry partner developed and applied treatment technology using constructed wetland systems to decrease targeted constituents in simulated and actual produced waters to achieve reuse criteria and discharge limits. Pilot-scale and demonstration constructed wetland treatment system (CWTS) experiments led to design strategies for treating a variety of constituents of concern (COCs) in produced waters including divalent metals, metalloids, oil and grease, and ammonia. Targeted biogeochemical pathways for treatment of COCs in pilot-scale CWTS experiments included divalent metal sulfide precipitation through dissimilatory sulfate reduction, metal precipitation through oxidation, reduction of selenite to insoluble elemental selenium, aerobicmore » biodegradation of oil, nitrification of ammonia to nitrate, denitrification of nitrate to nitrogen gas, separation of oil using an oilwater separator, and sorption of ammonia to zeolite. Treatment performance results indicated that CWTSs can be designed and built to promote specific environmental and geochemical conditions in order for targeted biogeochemical pathways to operate. The demonstration system successfully achieved consistent removal extents even while inflow concentrations of COCs in the produced water differed by orders of magnitude. Design strategies used in the pilot-scale and demonstration CWTSs to promote specific conditions that can be applied to designing full-scale CWTSs include plant and soil selection, water-depth selection, addition of amendments, and hydraulic retention time (HRT). These strategies allow conditions within a CWTS to be modified to achieve ranges necessary for the preferred biogeochemical treatment pathways. In the case of renovating a produced water containing COCs that require different biogeochemical pathways for treatment, a CWTS can be designed with sequential cells that promote different conditions. For example, the pilot-scale CWTS for post-reverse osmosis produced water was designed to promote oxidizing conditions within the first wetland cell for nitrification of ammonia, and the subsequent three cells were designed to promote reducing conditions for denitrification of nitrate. By incorporating multiple wetland cells in a CWTS, the conditions within each cell can be modified for removal of specific COCs. In addition, a CWTS designed with multiple cells allows for convenient sample collection points so that biogeochemical conditions of individual cells can be monitored and performance evaluated. Removal rate coefficients determined from the pilot-scale CWTS experiments and confirmed by the demonstration system can be used to calculate HRTs required to treat COCs in full-scale CWTSs. The calculated HRTs can then be used to determine the surface area or footprint of a full-size CWTS for a given inflow rate of produced water.« less

Innovative Water Management Technology to Reduce Environment Impacts of Produced Water

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

Castle, James; Rodgers, John; Alley, Bethany

2013-05-15

Clemson University with Chevron as an industry partner developed and applied treatment technology using constructed wetland systems to decrease targeted constituents in simulated and actual produced waters to achieve reuse criteria and discharge limits. Pilot-scale and demonstration constructed wetland treatment system (CWTS) experiments led to design strategies for treating a variety of constituents of concern (COCs) in produced waters including divalent metals, metalloids, oil and grease, and ammonia. Targeted biogeochemical pathways for treatment of COCs in pilot-scale CWTS experiments included divalent metal sulfide precipitation through dissimilatory sulfate reduction, metal precipitation through oxidation, reduction of selenite to insoluble elemental selenium, aerobicmore » biodegradation of oil, nitrification of ammonia to nitrate, denitrification of nitrate to nitrogen gas, separation of oil using an oilwater separator, and sorption of ammonia to zeolite. Treatment performance results indicated that CWTSs can be designed and built to promote specific environmental and geochemical conditions in order for targeted biogeochemical pathways to operate. The demonstration system successfully achieved consistent removal extents even while inflow concentrations of COCs in the produced water differed by orders of magnitude. Design strategies used in the pilot-scale and demonstration CWTSs to promote specific conditions that can be applied to designing full-scale CWTSs include plant and soil selection, water-depth selection, addition of amendments, and hydraulic retention time (HRT). These strategies allow conditions within a CWTS to be modified to achieve ranges necessary for the preferred biogeochemical treatment pathways. In the case of renovating a produced water containing COCs that require different biogeochemical pathways for treatment, a CWTS can be designed with sequential cells that promote different conditions. For example, the pilot-scale CWTS for post-reverse osmosis produced water was designed to promote oxidizing conditions within the first wetland cell for nitrification of ammonia, and the subsequent three cells were designed to promote reducing conditions for denitrification of nitrate. By incorporating multiple wetland cells in a CWTS, the conditions within each cell can be modified for removal of specific COCs. In addition, a CWTS designed with multiple cells allows for convenient sample collection points so that biogeochemical conditions of individual cells can be monitored and performance evaluated. Removal rate coefficients determined from the pilot-scale CWTS experiments and confirmed by the demonstration system can be used to calculate HRTs required to treat COCs in full-scale CWTSs. The calculated HRTs can then be used to determine the surface area or footprint of a full-size CWTS for a given inflow rate of produced water.« less

Cocaine action on peripheral, non-monoamine neural substrates as a trigger of electroencephalographic desynchronization and electromyographic activation following i.v. administration in freely moving rats.

PubMed

Smirnov, M S; Kiyatkin, E A

2010-01-20

Many important physiological, behavioral and subjective effects of i.v. cocaine (COC) are exceptionally rapid and transient, suggesting a possible involvement of peripheral neural substrates in their triggering. In the present study, we used high-speed electroencephalographic (EEG) and electromyographic (EMG) recordings (4-s resolution) in freely moving rats to characterize the central electrophysiological effects of i.v. COC at low doses within a self-administration range (0.25-1.0 mg/kg). We found that COC induces rapid, strong, and prolonged desynchronization of cortical EEG (decrease in alpha and increase in beta and gamma activity) and activation of the neck EMG that begin within 2-6 s following the start of a 10-s injection; immediate components of both effects were dose-independent. The rapid effects of COC were mimicked by i.v. COC methiodide (COC-MET), a derivative that cannot cross the blood-brain barrier. At equimolar doses (0.33-1.33 mg/kg), COC-MET had equally fast and strong effects on EEG and EMG total powers, decreasing alpha and increasing beta and gamma activities. Rapid EEG desynchronization and EMG activation was also induced by i.v. procaine, a structurally similar, short-acting local anesthetic with virtually no effects on monoamine uptake; at equipotential doses (1.25-5.0 mg/kg), these effects were weaker and shorter in duration than those of COC. Surprisingly, i.v. saline injection delivered during slow-wave sleep (but not during quiet wakefulness) also induced a transient EEG desynchronization but without changes in EMG and motor activity; these effects were significantly weaker and much shorter than those induced by all tested drugs. These data suggest that in awake animals, i.v. COC induces rapid cortical activation and a subsequent motor response via its action on peripheral non-monoamine neural elements, involving neural transmission via visceral sensory pathways. By providing a rapid neural signal and triggering neural activation, such an action might play a crucial role in the sensory effects of COC, thus contributing to the learning and development of drug-taking behavior.

Quantifying Mass Transfer Processes in Groundwater as a Function of Molecular Structure Variation for Multicomponent NAPL Sources

NASA Astrophysics Data System (ADS)

Abbott, J. B., III; Tick, G. R.; Greenberg, R. R.; Carroll, K. C.

2017-12-01

The remediation of nonaqueous liquid (NAPL) contamination sources in groundwater has been shown to be challenging and have limited success in the field. The presence of multicomponent NAPL sources further complicates the remediation due to variability of mass-transfer (dissolution) behavior as a result of compositional and molecular structure variations between the different compounds within the NAPL phase. This study investigates the effects of the contaminant of concern (COC) composition and the bulk-NAPL components molecular structure (i.e. carbon chain length, aliphatic and aromatic) on dissolution and aqueous phase concentrations in groundwater. The specific COCs tested include trichloroethene (TCE), toluene (TOL), and perfluorooctanoic acid (PFOA). Each COC was tested in a series of binary batch experiments using insoluble bulk NAPL including n-hexane (HEX), n-decane (DEC), and n-hexadecane (HEXDEC). These equilibrium batch tests were performed to understand how different carbon-chain-length (NAPL) systems affect resulting COC aqueous phase concentrations. The experiments were conducted with four different COC mole fractions mixed within the bulk-NAPL derivatives (0.1:0.9, 0.05:0.95, 0.01:0.99, 0.001:0.999). Raoult's Law was used to assess the relative ideality of the mass transfer processes for each binary equilibrium dissolution experiment. Preliminary results indicate that as mole fraction of the COC decreases (composition effects), greater deviance from dissolution ideality occurs. It was also shown that greater variation in molecular structure (i.e. greater carbon chain length of bulk-NAPL with COC and aromatic COC presence) exhibited greater dissolution nonideality via Raoult's Law analysis. For instance, TOL (aromatic structure) showed greater nonideality than TCE (aliphatic structure) in the presence of the different bulk-NAPL derivatives (i.e. of various aliphatic carbon chains lengths). The results suggest that the prediction of aqueous phase concentration, from complex multicomponent NAPL sources, is highly dependent upon both composition and molecular structure variations of COC-NAPL mixtures, and such impacts should be taken into account when designing and evaluating a remediation strategy and/or predicting COC concentrations from a source zone region.

78 FR 19520 - Notice of Competitive Coal Lease Sale COC-74813, CO

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-01

..., COC-74813] Notice of Competitive Coal Lease Sale COC-74813, CO AGENCY: Bureau of Land Management, Interior. ACTION: Notice of Competitive Coal Lease Sale. SUMMARY: Notice is hereby given that certain Federal coal reserves (Red Wash Tracts 1 and 2) in Moffat and Rio Blanco Counties, Colorado, will be...

76 FR 35909 - Notice of Proposed Reinstatement of Terminated Oil and Gas Lease COC64168

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-20

...] Notice of Proposed Reinstatement of Terminated Oil and Gas Lease COC64168 AGENCY: Bureau of Land Management, Interior. ACTION: Notice of Proposed Reinstatement of Terminated Oil and Gas Lease. SUMMARY... Management (BLM) received a petition for reinstatement of oil and gas lease COC64168 from SG Interests VII...

77 FR 9696 - Notice of Proposed Reinstatement of Terminated Oil and Gas Lease COC68134

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-17

...] Notice of Proposed Reinstatement of Terminated Oil and Gas Lease COC68134 AGENCY: Bureau of Land Management, Interior. ACTION: Notice of Proposed Reinstatement of Terminated Oil and Gas Lease. SUMMARY... Management (BLM) received a petition for reinstatement of oil and gas lease COC68134 from Western Operation...

CTEPP STANDARD OPERATING PROCEDURE FOR MAINTAINING AND RECORDING ELECTRONIC CHAIN-OF-CUSTODY (SOP-4.11)

EPA Science Inventory

The method for maintaining and recording electronic Chain-of-Custody (CoC) Records for CTEPP samples is summarized in this SOP. The CoC Records that will be logged electronically include the creation of a sample's identification code, bar code labels, and hard-copy CoC document...

Effect of saxagliptin on the pharmacokinetics of the active components of Ortho-Cyclen(®), a combined oral contraceptive containing ethinyl estradiol and norgestimate, in healthy women.

PubMed

Upreti, V V; Hsiang, C B; Li, L; Xu, X; LaCreta, F P; Boulton, D W

2012-12-01

Saxagliptin (Onglyza™) is a dipeptidyl peptidase-4 (DPP4) inhibitor for treating type 2 diabetes mellitus. This open-label, randomized, two-way crossover study in 20 healthy female subjects investigated the effect of saxagliptin on the pharmacokinetics (PK) of the active components of a combined oral contraceptive (COC). Subjects received either COC (Ortho-Cyclen(®)) once daily (QD) for 21 days, then 5 mg saxagliptin QD + COC QD for 21 days, or vice versa. Coadministration of saxagliptin and COC did not alter the steady-state PK of the primary active oestrogen (ethinyl estradiol) or progestin (norelgestromin) COC components. The area under the concentration-time curve (AUC) and peak plasma concentration (Cmax) of an active metabolite of norelgestromin (norgestrel) were increased by 13 and 17%, respectively, a magnitude that was not considered clinically meaningful. Coadministration of saxagliptin and COC in this study was generally well-tolerated. Saxagliptin can be co-prescribed with an oestrogen/progestin combination for women taking oral contraceptive. © 2012 Blackwell Publishing Ltd.

A Direct Aqueous Derivatization GSMS Method for Determining Benzoylecgonine Concentrations in Human Urine.

PubMed

Chericoni, Silvio; Stefanelli, Fabio; Da Valle, Ylenia; Giusiani, Mario

2015-09-01

A sensitive and reliable method for extraction and quantification of benzoylecgonine (BZE) and cocaine (COC) in urine is presented. Propyl-chloroformate was used as derivatizing agent, and it was directly added to the urine sample: the propyl derivative and COC were then recovered by liquid-liquid extraction procedure. Gas chromatography-mass spectrometry was used to detect the analytes in selected ion monitoring mode. The method proved to be precise for BZE and COC both in term of intraday and interday analysis, with a coefficient of variation (CV)<6%. Limits of detection (LOD) were 2.7 ng/mL for BZE and 1.4 ng/mL for COC. The calibration curve showed a linear relationship for BZE and COC (r2>0.999 and >0.997, respectively) within the range investigated. The method, applied to thirty authentic samples, showed to be very simple, fast, and reliable, so it can be easily applied in routine analysis for the quantification of BZE and COC in urine samples. © 2015 American Academy of Forensic Sciences.

Activation of cardiac renin-angiotensin system and plasminogen activator inhibitor-1 gene expressions in oral contraceptive-induced cardiometabolic disorder.

PubMed

Olatunji, Lawrence A; Usman, Taofeek O; Seok, Young-Mi; Kim, In-Kyeom

2017-02-01

Clinical studies have shown that combined oral contraceptive (COC) use is associated with cardiometabolic disturbances. Elevated renin-angiotensin system (RAS) and plasminogen activator inhibitor-1 (PAI-1) have also been implicated in the development of cardiometabolic events. To determine the effect of COC treatment on cardiac RAS and PAI-1 gene expressions, and whether the effect is circulating aldosterone or corticosterone dependent. Female rats were treated (p.o.) with olive oil (vehicle) or COC (1.0 µg ethinylestradiol and 10.0 µg norgestrel) daily for six weeks. COC treatment led to increases in blood pressure, HOMA-IR, Ace1 mRNA, Atr1 mRNA, Pai1 mRNA, cardiac PAI-1, plasma PAI-1, C-reactive protein, uric acid, insulin and corticosterone. COC treatment also led to dyslipidemia, decreased glucose tolerance and plasma 17β-estradiol. These results demonstrates that hypertension and insulin resistance induced by COC is associated with increased cardiac RAS and PAI-1 gene expression, which is likely to be through corticosterone-dependent but not aldosterone-dependent mechanism.

Use of Simulated Patients to Evaluate Combined Oral Contraceptive Dispensing Practices of Community Pharmacists

PubMed Central

Obreli-Neto, Paulo Roque; Pereira, Leonardo Régis Leira; Guidoni, Camilo Molino; Baldoni, André de Oliveira; Marusic, Srecko; de Lyra-Júnior, Divaldo Pereira; de Almeida, Kelsen Luis; Pazete, Ana Claudia Montolezi; do Nascimento, Janaina Dutra; Kos, Mitja; Girotto, Edmarlon; Cuman, Roberto Kenji Nakamura

2013-01-01

Background Combined oral contraceptive (COC) use is the most commonly used reversible method of birth control. The incorrect use of COCs is frequent and one of the most common causes of unintended pregnancies. Community pharmacists (CPs) are in a strategic position to improve COC use because they are the last health professional to interact with patients before drug use. Objective To evaluate the COC dispensing practices of CPs in a developing country. Method A cross-sectional study was conducted in community pharmacies of Assis and Ourinhos microregions, Brazil, between June 1, 2012, and October 30, 2012. Four simulated patients (SPs) (with counseled audio recording) visited community pharmacies with a prescription for Ciclo 21® (a COC containing ethinyl estradiol 30 mcg + levonorgestrel 15 mcg). The audio recording of every SP visit was listened to independently by 3 researchers to evaluate the COC dispensing practice. The percentage of CPs who performed a screening for safe use of COCs (i.e., taking of patients’ medical and family history, and measuring of blood pressure) and provided counseling, as well as the quality of the screening and counseling, were evaluated. Results Of the 185 CPs contacted, 41 (22.2%) agreed to participate in the study and finished the study protocol. Only 3 CPs asked the SP a question (1 question asked by each professional), and all of the questions were closed-ended, viz., “do you smoke?” (n = 2) and “what is your age?” (n = 1). None of the CPs measured the patient’s blood pressure. Six CPs provided counseling when dispensing COCs (drug dosing, 5 CPs; possible adverse effects, 2 CPs), and one CP provided counseling regarding both aspects. Conclusion The CPs evaluated did not dispense COC appropriately and could influence in the occurrence of negatives therapeutic outcomes such as adverse effects and treatment failure. PMID:24324584

Understanding the Role of Nitrogen in Plasma-Assisted Surface Modification of Magnetic Recording Media with and without Ultrathin Carbon Overcoats

PubMed Central

Dwivedi, Neeraj; Yeo, Reuben J.; Satyanarayana, Nalam; Kundu, Shreya; Tripathy, S.; Bhatia, C. S.

2015-01-01

A novel scheme of pre-surface modification of media using mixed argon-nitrogen plasma is proposed to improve the protection performance of 1.5 nm carbon overcoats (COC) on media produced by a facile pulsed DC sputtering technique. We observe stable and lower friction, higher wear resistance, higher oxidation resistance, and lower surface polarity for the media sample modified in 70%Ar + 30%N2 plasma and possessing 1.5 nm COC as compared to samples prepared using gaseous compositions of 100%Ar and 50%Ar + 50%N2 with 1.5 nm COC. Raman and X-ray photoelectron spectroscopy results suggest that the surface modification process does not affect the microstructure of the grown COC. Instead, the improved tribological, corrosion-resistant and oxidation-resistant characteristics after 70%Ar + 30%N2 plasma-assisted modification can be attributed to, firstly, the enrichment in surface and interfacial bonding, leading to interfacial strength, and secondly, more effective removal of ambient oxygen from the media surface, leading to stronger adhesion of the COC with media, reduction of media corrosion and oxidation, and surface polarity. Moreover, the tribological, corrosion and surface properties of mixed Ar + N2 plasma treated media with 1.5 nm COCs are found to be comparable or better than ~2.7 nm thick conventional COC in commercial media. PMID:25586898

76 FR 42725 - Notice of Proposed Reinstatement of Terminated Oil and Gas Lease COC64399

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-19

...] Notice of Proposed Reinstatement of Terminated Oil and Gas Lease COC64399 AGENCY: Bureau of Land Management, Interior. ACTION: Notice of proposed reinstatement of terminated oil and gas lease. SUMMARY... Management (BLM) received a petition for reinstatement of oil and gas lease COC64399 from Encana Oil and Gas...

Community of Communities: An Electronic Link to Integrating Cultural Diversity in Nursing Curriculum.

ERIC Educational Resources Information Center

Ryan, Marilyn; Ali, Nagia; Carlton, Kay Hodson

2002-01-01

The Community of Communities (COC) website contains information and case studies based on cultural assessment. Online nursing courses are linked to a cultural module in the COC. Evaluation results from 63 students showed that the COC increased awareness of the role of culture in health care and knowledge of international health practices.…

Sustained Release d-Amphetamine Reduces Cocaine but not ‘Speedball'-Seeking in Buprenorphine-Maintained Volunteers: A Test of Dual-Agonist Pharmacotherapy for Cocaine/Heroin Polydrug Abusers

PubMed Central

Greenwald, Mark K; Lundahl, Leslie H; Steinmiller, Caren L

2010-01-01

The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid/cocaine combination (‘speedball'-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8 mg/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8 mg/day maintenance and double-blind ascending SR-AMP weekly doses of 0, 30, and 60 mg/day, respectively. After 3 days (Saturday–Monday) stabilization at each SR-AMP weekly dose (0, 15, or 30 mg administered at 0700 and 1225 each day), on Tuesday–Friday mornings (0900–1200 hours), participants sampled four drug combinations in randomized, counterbalanced order under double-blind, double-dummy (intranasal cocaine and intramuscular hydromorphone) conditions: cocaine (COC 100 mg+saline); hydromorphone (COC 4 mg+HYD 24 mg); ‘speedball' (COC 100 mg+HYD 24 mg); and placebo (COC 4 mg+saline). Subjective and physiological effects of these drug combinations were measured. From 1230 to 1530 hours, participants could respond on a choice, 12-trial progressive ratio schedule to earn drug units (1/12th of total morning dose) or money units (US$2). SR-AMP significantly reduced COC, but not HYD or speedball, choices and breakpoints. SR-AMP also significantly reduced COC subjective (eg, abuse-related) effects and did not potentiate COC-induced cardiovascular responses. This study shows the ability of SR-AMP to attenuate COC self-administration, as well as its selectivity, in cocaine/heroin polydrug abusers. Further research is warranted to ascertain whether SR-AMP combined with BUP could be a useful dual-agonist pharmacotherapy. PMID:20881947

Modification of pharmacokinetic and abuse-related effects of cocaine by human-derived cocaine hydrolase in monkeys

PubMed Central

Schindler, Charles W.; Justinova, Zuzana; Lafleur, David; Woods, Doug; Roschke, Viktor; Hallak, Hussein; Sklair-Tavron, Liora; Redhi, Godfrey H.; Yasar, Sevil; Bergman, Jack; Goldberg, Steven R.

2011-01-01

Although substantial research effort has focused on developing pharmacological treatments for cocaine abuse, no effective medications have been developed. Recent studies show that enzymes that metabolize cocaine in the periphery, forestalling its entry into the brain, can prevent cocaine toxicity and its behavioral effects in rodents. Here we report on effects of one such enzyme (Albu-CocH) on the pharmacokinetic and behavioral effects of cocaine in squirrel monkeys. Albu-CocH was developed from successive mutations of human butyrylcholinesterase (BChE) and has 1000-fold greater catalytic activity against cocaine than naturally occurring BChE. Pharmacokinetic studies showed that Albu-CocH (5 mg/kg) had a half-life of 56.6 hours in squirrel monkeys. In these studies, plasma levels of cocaine following i.v. 1 mg/kg cocaine were reduced two hours after administration of Albu-CocH, whereas plasma levels of the cocaine metabolite ecgonine methyl ester were increased. These effects were still evident 72 hrs following Albu-CocH administration. In behavioral experiments in monkeys, pretreatment with 5 mg/kg Albu-CocH dramatically decreased self-administration of a reinforcing dose of i.v. cocaine (30 μg/kg/injection) for over 24 hours. Pretreatment with 5 mg/kg Albu-CocH also attenuated the reinstatement of extinguished cocaine self-administration by an i.v. priming injection of cocaine (0.1 or 0.3 mg/kg) and, in separate studies, attenuated the discriminative stimulus effects of cocaine. The ability of Albu-CocH to attenuate the abuse-related effects of cocaine in squirrel monkeys indicates that further investigation of BChE mutants as potential treatment for cocaine abuse and toxicity is warranted. PMID:22264200

The New Substance Abuse and Mental Health Services Administration Oral Fluid Cutoffs for Cocaine and Heroin-Related Analytes Applied to an Addiction Medicine Setting: Important, Unanticipated Findings with LC-MS/MS.

PubMed

Flood, James G; Khaliq, Tahira; Bishop, Kenneth A; Griggs, David A

2016-05-01

We implemented oral fluid (OF) as an alternative specimen type to urine for detection of cocaine (COC) and opiate abuse in outpatient addiction medicine clinics. We implemented a 2-μg/L limit of quantification OF LC-MS/MS assay and compiled and reviewed all findings from a 22-month collection period for COC, benzoylecgonine (BZE), codeine (COD), 6-acetylmorphine (MAM), and morphine (MOR). We also compared the results of our clinical samples at different OF cutoffs and analytes specified in the new 2015 SAMHSA OF guidelines. Of 3608 OF samples, COC and BZE were positive in 593 and 508, respectively. COC or BZE was positive in 662 samples. Importantly and unexpectedly, 154 samples were COC positive and BZE negative, with 125 having COC 2.0-7.9 μg/L. A simulation with the new guideline cutoffs confirmed 65% (430 of 662) of all COC- or BZE-positive data set samples. Similarly, the new guidelines confirmed 44% (263 of 603) of data set samples positive for MOR or COD. Simulation found that the new, lower MAM guideline cutoffs detected 89% of the 382 MAM-positive samples in the data set, 104 of which the new guidelines had identified as negative for MOR and COD. COC (not BZE) is the dominant low-concentration OF analyte in an addiction medicine setting. This information will aid OF test interpretation. It also illustrates the importance of the 2015 guideline's new immunoassay cross-reactivity requirements and the likely improvement in detection of heroin use stemming from the new, lower MAM cutoffs. © 2016 American Association for Clinical Chemistry.

Effect of the ethinylestradiol/levonorgestrel combined oral contraceptive on the activity of cytochrome P4503A in obese women

PubMed Central

Edelman, Alison; Munar, Myrna; Elman, Miriam R; Koop, Dennis; Cherala, Ganesh

2012-01-01

AIM(S) While it is known that CYP3A4/5 activity is decreased with combined oral contraceptive (COC) use and obesity suppresses CYP expression, the combined effects of obesity and COC use on CYP3A4/5 activity are unclear. Therefore, our aim was to examine the effect of COC usage on CYP3A4/5 activity in obese women. METHODS Thirty-four, obese (body mass index, BMI > 30 kg m−2) women of reproductive age (18–35 years old) were placed on a COC pill containing 20 µg ethinylestradiol/100 µg levonorgestrel for 21 days starting at the onset of menses. A midazolam pharmacokinetic study was conducted prior to initiation and after 21 days of COC treatment. Serial blood samples were collected and plasma concentrations of midazolam were measured using liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were estimated using a non-compartmental method. RESULTS Midazolam clearance, a surrogate measure of CYP3A4/5 activity, was significantly decreased upon COC use (63.3 l h−1vs. 53.9 l h−1, P < 0.05). A median decrease of 5.6 l h−1 (95% CI −4.1, 13.3 l h−1) was observed. However, the magnitude of change was similar to that reported in women with normal BMI. CONCLUSIONS Although we hypothesized that obesity might amplify the impact on CYP3A4/5 activity in COC users, we found that this was not the case. This finding is reassuring regarding potential additional drug−drug interactions in obese COC users as CYP3A4/5 is a major enzyme in the metabolism of many marketed drugs. PMID:22299599

Comparison of the risk of revision in cementless total hip arthroplasty with ceramic-on-ceramic and metal-on-polyethylene bearings

PubMed Central

Varnum, Claus; Pedersen, Alma B; Kjærsgaard-Andersen, Per; Overgaard, Søren

2015-01-01

Background and purpose Ceramic-on-ceramic (CoC) bearings were introduced in total hip arthroplasty (THA) to reduce problems related to polyethylene wear. We compared the 9-year revision risk for cementless CoC THA and for cementless metal-on-polyethylene (MoP) THA. Patients and methods In this prospective, population-based study from the Danish Hip Arthroplasty Registry, we identified all the primary cementless THAs that had been performed from 2002 through 2009 (n = 25,656). Of these, 1,773 THAs with CoC bearings and 9,323 THAs with MoP bearings were included in the study. To estimate the relative risk (RR) of revision, we used regression with the pseudo-value approach and treated death as a competing risk. Results 444 revisions were identified: 4.0% for CoC THA (71 of 1,773) and 4.0% for MoP THA (373 of 9,323). No statistically significant difference in the risk of revision for any reason was found for CoC and MoP bearings after 9 years of follow-up (adjusted RR = 1.3, 95% CI: 0.72–2.4). Revision rates due to component failure were 0.5% (n = 8) for CoC bearings and 0.1% (n = 6) for MoP bearings (p < 0.001). 6 patients with CoC bearings (0.34%) underwent revision due to ceramic fracture. Interpretation When compared to the “standard” MoP bearings, CoC THA had a 33% higher (though not statistically significantly higher) risk of revision for any reason at 9 years. PMID:25637339

Use of ethinylestradiol/drospirenone combination in patients with the polycystic ovary syndrome

PubMed Central

Mathur, Ruchi; Levin, Olga; Azziz, Ricardo

2008-01-01

Polycystic ovary syndrome (PCOS) is one of the most common endocrine/metabolic disorders found in women, affecting approximately 105 million women worldwide. It is characterized by ovulatory dysfunction, often presenting as oligomenorrhea or amenorrhea and either clinical or biochemical hyperandrogenism. Combined oral contraceptive (COC) therapy has long been a cornerstone of care for women with PCOS. COC therapy often provides clinical improvement in the areas of excessive hair growth, unpredictable menses, acne, and weight gain. One of the main issues in COC therapy is choosing the most appropriate progestin component to provide the greatest anti androgenic effects. Drospirenone, a relatively new progestin, has shown benefit in the PCOS population when used in conjunction with ethinyl estradiol. We now review the role of COCs in PCOS, focusing specifically on drospirenone. Controversy over metabolic effects of COCs in PCOS is also discussed. PMID:18728832

77 FR 76516 - Notice of Availability of the Record of Decision for the Federal Coal Lease Modifications COC...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-28

...] Notice of Availability of the Record of Decision for the Federal Coal Lease Modifications COC-1362 and... INFORMATION: The ROD covered by this Notice of Availability (NOA) is for modification Federal coal leases in..., to modify Mountain Coal Company's existing Federal coal lease COC-1362 by adding 921 acres and the...

Antiandrogenic and antimineralocorticoid health benefits of COC containing newer progestogens: dienogest and drospirenone.

PubMed

Regidor, Pedro-Antonio; Schindler, Adolf E

2017-10-10

Data have demonstrated that COCs, besides offering a satisfactory and safe contraception, offer a variety of non-contraceptive health benefits and therapeutic positive aspects. Many prescribes and users, however, do not realize these positive aspects especially the non-contraceptive health benefits. While the contraceptive use is the primary indication for COC use for most women, these users should be advised in regard of the non-contraceptive benefits when contraception is discussed and prescribed. Using COCs specifically for non-contraceptive indications is an off-label use in many clinical situations (only some exceptions as e.g. acne vulgaris in some countries are allowed clinical entities for the use of these drugs). Therefore, appropriate discussions with the patient regarding this fact should performed and documented by the prescribing physicians. Independent of the off-label situation, COCs containing the newer progestogens dienogest and drospirenone with their antiandrogenic and antimineralocorticoid health benefits play an important role in the management of many diseases and their use should therefore be considered by clinician's. This review will focus on the effects of these COCs on the endometrium, the skin, the fat tissue and the premenstrual syndrome.

Effect of combined oral contraceptive use on serum 25-hydroxy vitamin D levels and ultrasound parameters in patients with polycystic ovary syndrome.

PubMed

Namli Kalem, Müberra; Hizli, Deniz; Kamalak, Zeynep; Kösüs, Aydin; Kösüs, Nermin; Turhan, Nilgün; Kafali, Hasan

2016-01-01

To investigate if there is an effect of combined oral contraceptive (COC) use on serum 25-hydroxy vitamin D [25(OH)D] levels in patients with polycystic ovary syndrome (PCOS). PCOS was defined by the 2003 Rotterdam criteria. All patients with PCOS were treated with a COC containing 0.035 mg ethinylestradiol and 2 mg cyproterone acetate for 6 months. Serum 25(OH)D levels, HOMA-IR, ovarian volume and antral follicule count were measured before and after the treatment. The median 25(OH)D levels were 9.40 (range 4.40-24.50) μg/l and 7.00 (5.00-13.50) μg/l before and after COC use, respectively. Serum 25(OH)D levels decreased after the treatment; however, the difference was not statistically significant (p = 0.055). This study seems to be the first prospective trial revealing the effect of COC use on serum 25(OH)D levels in women with PCOS. Although the decrease in serum 25(OH)D levels in patients with PCOS with the use of COC alone, did not reach to statistically significance level after 6 months treatment with COC.

Antiandrogenic and antimineralocorticoid health benefits of COC containing newer progestogens: dienogest and drospirenone

PubMed Central

Regidor, Pedro-Antonio; Schindler, Adolf E.

2017-01-01

Data have demonstrated that COCs, besides offering a satisfactory and safe contraception, offer a variety of non-contraceptive health benefits and therapeutic positive aspects. Many prescribes and users, however, do not realize these positive aspects especially the non-contraceptive health benefits. While the contraceptive use is the primary indication for COC use for most women, these users should be advised in regard of the non-contraceptive benefits when contraception is discussed and prescribed. Using COCs specifically for non-contraceptive indications is an off-label use in many clinical situations (only some exceptions as e.g. acne vulgaris in some countries are allowed clinical entities for the use of these drugs). Therefore, appropriate discussions with the patient regarding this fact should performed and documented by the prescribing physicians. Independent of the off-label situation, COCs containing the newer progestogens dienogest and drospirenone with their antiandrogenic and antimineralocorticoid health benefits play an important role in the management of many diseases and their use should therefore be considered by clinician’s. This review will focus on the effects of these COCs on the endometrium, the skin, the fat tissue and the premenstrual syndrome. PMID:29137347

Metabolic and cardiovascular impact of oral contraceptives in polycystic ovary syndrome.

PubMed

Soares, G M; Vieira, C S; de Paula Martins, W; Dos Reis, R M; de Sá, M F S; Ferriani, R A

2009-01-01

Chronic anovulation, polycystic ovarian morphology and hyperandrogenism are the diagnostic criteria for polycystic ovary syndrome (PCOS). Metabolic disturbances are more common in PCOS women who are prone to develop metabolic syndrome and to present higher levels of some cardiovascular disease risk marker. Oral contraceptives are widely used in PCOS, but conflicting data have been reported regarding their impact on carbohydrate and lipid metabolism on PCOS women. This paper presents a critical evaluation of combined oral contraceptives (COCs) metabolic effect - carbohydrate metabolism and insulin sensitivity, lipid metabolism, haemostasis, body weight, arterial pressure and cardiovascular impact - on PCOS women. Because of the paucity of data on the impact of COCs on cardiovascular and metabolic parameters in PCOS patients, most of there commendations are based on studies involving ovulatory women. The use of low-dose COCs is preferable in PCOS, especially among patients with glucose intolerance, insulin resistance and uncomplicated diabetes mellitus. Although reported as a side effect of COCs, marked weight gain has not been confirmed among users. However, when arterial hypertension or elevated risk for thromboembolism is present, progestogen-only hormonal contraceptives should be used instead of COCs. Regarding dyslipidaemia, COCs reduce low-density lipoprotein and total cholesterol and elevate high-density lipoprotein and triglycerides, and therefore are not recommended for women with high triglycerides levels. The choice of a COC, which alleviates the PCOS-induced hyperandrogenism without significant negative impact on cardiovascular risk, is one of the greatest challenges faced by gynaecologists nowadays.

The Ability of Bacterial Cocaine Esterase to Hydrolyze Cocaine Metabolites and Their Simultaneous Quantification Using High-Performance Liquid Chromatography-Tandem Mass Spectrometry

PubMed Central

Brim, Remy L.; Noon, Kathleen R.; Collins, Gregory T.; Nichols, Joseph; Narasimhan, Diwahar; Sunahara, Roger K.

2011-01-01

Cocaine toxicity is a widespread problem in the United States, responsible for more than 500,000 emergency department visits a year. There is currently no U.S. Food and Drug Administration-approved pharmacotherapy to directly treat cocaine toxicity. To this end, we have developed a mutant bacterial cocaine esterase (DM-CocE), which has been previously shown to rapidly hydrolyze cocaine into inert metabolites, preventing and reversing toxicity with limited immunogenic potential. Herein we describe the ability of DM-CocE to hydrolyze the active cocaine metabolites norcocaine and cocaethylene and its inability to hydrolyze benzoylecgonine. DM-CocE hydrolyzes norcocaine and cocaethylene with 58 and 45% of its catalytic efficiency for cocaine in vitro as measured by a spectrophotometric assay. We have developed a mass spectrometry method to simultaneously detect cocaine, benzoylecgonine, norcocaine, and ecgonine methyl ester to quantify the effect of DM-CocE on normal cocaine metabolism in vivo. DM-CocE administered to rats 10 min after a convulsant dose of cocaine alters the normal metabolism of cocaine, rapidly decreasing circulating levels of cocaine and norcocaine while increasing ecgonine methyl ester formation. Benzoylecgonine was not hydrolyzed in vivo, but circulating concentrations were reduced, suggesting that DM-CocE may bind and sequester this metabolite. These findings suggest that DM-CocE may reduce cocaine toxicity by eliminating active and toxic metabolites along with the parent cocaine molecule. PMID:21885621

Cocaine action on peripheral, non-monoamine neural substrates as a trigger of EEG desynchronization and EMG activation following intravenous administration in freely moving rats

PubMed Central

Smirnov, Michael S.; Kiyatkin, Eugene A.

2009-01-01

Many important physiological, behavioral and subjective effects of intravenous (iv) cocaine (COC) are exceptionally rapid and transient, suggesting a possible involvement of peripheral neural substrates in their triggering. In the present study, we used high-speed EEG and EMG recordings (4-s resolution) in freely moving rats to characterize the central electrophysiological effects of iv COC at low doses within a self-administration range (0.25-1.0 mg/kg). We found that COC induces rapid, strong, and prolonged desynchronization of cortical EEG (decrease in alpha and increase in beta and gamma activity) and activation of the neck EMG that begin within 2-6 s following the start of a 10-s injection; immediate components of both effects were dose-independent. The rapid effects of COC were mimicked by iv COC methiodide, a derivative that cannot cross the blood-brain barrier. At equimolar doses (0.33-1.33 mg/kg), COC methiodide had equally fast and strong effects on EEG and EMG total powers, decreasing alpha and increasing beta and gamma activities. Rapid EEG desynchronization and EMG activation was also induced by iv procaine, a structurally similar, short-acting local anesthetic with virtually no effects on monoamine uptake; at equipotential doses (1.25-5.0 mg/kg), these effects were weaker and shorter in duration than those of COC. Surprisingly, iv saline injection delivered during slow-wave sleep (but not during quiet wakefulness) also induced a transient EEG desynchronization but without changes in EMG and motor activity; these effects were significantly weaker and much shorter than those induced by all tested drugs. These data suggest that in awake animals, iv COC induces rapid cortical activation and a subsequent motor response via its action on peripheral non-monoamine neural elements, involving neural transmission via visceral sensory pathways. By providing a rapid neural signal and triggering neural activation, such an action might play a crucial role in the sensory effects of COC, thus contributing to the learning and development of drug-taking behavior. PMID:19861149

Developmental competence of different quality bovine oocytes retrieved through ovum pick-up following in vitro maturation and fertilization.

PubMed

Saini, N; Singh, M K; Shah, S M; Singh, K P; Kaushik, R; Manik, R S; Singla, S K; Palta, P; Chauhan, M S

2015-12-01

In the present study, oocytes retrieved from cross bred Karan Fries cows by ovum pick-up technique were graded into Group 1 and Group 2, based on the morphological appearance of the individual cumulus-oocyte complexes (COCs). To analyze whether the developmental potential of the COCs bears a relation to morphological appearance, relative expression of a panel of genes associated with; (a) cumulus-oocyte interaction (Cx43, Cx37, GDF9 and BMP15), (b) fertilization (ZP2 and ZP3), (c) embryonic development (HSF1, ZAR1 and bFGF) and (d) apoptosis and survival (BAX, BID and BCL-XL, MCL-1, respectively) was studied at two stages: germinal vesicle (GV) stage and after in vitro maturation. The competence was further corroborated by evaluating the embryonic progression of the presumed zygotes obtained from fertilization of the graded COCs. The gene expression profile and development rate in pooled A and B grade (Group 1) COCs and pooled C and D grade (Group 2) COCs were determined and compared according to the original grades. The results of the study demonstrated that the morphologically characterized Group 2 COCs showed significantly (P<0.05) lower expression for most of the genes related to cumulus-oocyte interplay, fertilization and embryonic development, both at GV stage as well as after maturation. Group 1 COCs also showed greater expression of anti-apoptotic genes (BCL-XL and MCL1) both at GV stage and after maturation, while pro-apoptotic genes (BAX and BID) showed significantly (P<0.05) elevated expression in poor quality COCs at both the stages. The cleavage rate in Group 1 COCs was significantly higher than that of Group 2 (74.46±7.06 v. 31.57±5.32%). The development of the presumed zygotes in Group 2 oocytes proceeded up to 8- to 16-cell stages only, while in Group 1 it progressed up to morulae (35.38±7.11%) and blastocyst stages (9.70±3.15%), indicating their better developmental potential.

Anti-bacterial factors secreted from cumulus cells of ovulated COCs enhance sperm capacitation during in vitro fertilization.

PubMed

Shimada, Masayuki; Mihara, Toshihiro; Kawashima, Ikko; Okazaki, Tetsuji

2013-02-01

The aim of this study was to find immune-related genes expressed in cumulus cells of ovulated cumulus oocyte complexes (COCs) and to clear the functional roles during fertilization process. Ovulated COCs were collected from oviduct 16 hr after the hCG injections followed by eCG priming. The cumulus cells were used for RT-PCR or western blotting study. COCs were also used for in vitro fertilization study. Cramp, Trf, Lyz2, S100a8, and S100a9 were expressed in cumulus cells during ovulation process. The protein levels of CRAMP or transferrin were detected in ovulated COCs and then secreted into hyaluronan-rich matrix. The high dose of these factors reduced the proliferative activity of E. coli; however, the lower levels of them significantly increased the rate of fertilization in in vitro via the induction of sperm capacitation. Cumulus-secreted anti-bacterial factors act on sperm to induce sperm capacitation. © 2012 John Wiley & Sons A/S.

Surface functionalization of cyclic olefin copolymer with aryldiazonium salts: A covalent grafting method

NASA Astrophysics Data System (ADS)

Brisset, Florian; Vieillard, Julien; Berton, Benjamin; Morin-Grognet, Sandrine; Duclairoir-Poc, Cécile; Le Derf, Franck

2015-02-01

Covalent immobilization of biomolecules on the surface of cyclic olefin copolymer (COC) is still a tough challenge. We developed a robust method for COC surface grafting through reaction with aryldiazonium. Chemical diazonium reduction generated an aryl radical and the formation of a grafted film layer on the organic surface. We also demonstrated that the chemical reduction of diazonium salt was not sufficient to form a film on the COC surface. UV illumination had to be combined with chemical reduction to graft an aryl layer onto the COC surface. We optimized organic film deposition by using different chemical reducers, different reaction times and reagent proportions. We characterized surface modifications by fluorescence microscopy and contact angle measurements, infrared spectroscopy, X-ray photoemission spectroscopy and Raman spectroscopy, and assessed the topography of the aryl film by atomic force microscopy. This original strategy allowed us to evidence various organic functions to graft biomolecules onto COC surfaces with a fast and efficient technique.

Rationale for eliminating the hormone-free interval in modern oral contraceptives.

PubMed

London, Andrew; Jensen, Jeffrey T

2016-07-01

Although most low-dose combined oral contraceptives (COCs) include 7-day hormone-free intervals (HFIs), these COCs could incompletely suppress ovarian activity. To review the impact of HFIs on ovarian suppression and tolerability, and evaluate the utility of COCs without traditional 7-day HFIs. PubMed was searched for clinical studies published in English between January 1980 and April 2015 on the impact of HFIs and HFI modifications in COCs. Articles assessing contraceptive efficacy or tolerability as the primary focus were included. Abstracts of 319 articles were screened. Analysis of the 161 articles selected revealed that suppression of ovarian activity with low-dose COCs with 7-day HFIs is suboptimal. Loss of ovarian suppression during 7-day HFIs is commonly associated with follicular development, and most dominant follicles appear during this period. By contrast, increased ovarian suppression was noted in regimens that shortened or eliminated the HFI, or that substituted low-dose ethinyl estradiol for the HFI. Extended regimens with modified HFIs may provide greater ovarian suppression with the potential for increased contraceptive effectiveness. Additional research is needed to evaluate whether COC regimens that include 10μg ethinyl estradiol instead of an HFI may improve tolerability. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Ultrastructural changes of sheep cumulus-oocyte complexes following different methods of vitrification.

PubMed

Ebrahimi, Bita; Valojerdi, Mojtaba Rezazadeh; Eftekhari-Yazdi, Poopak; Baharvand, Hossein

2012-05-01

To determine the ultrastructural changes of sheep cumulus-oocyte complexes (COCs) following different methods of vitrification, good quality isolated COCs (GV stage) were randomly divided into the non-vitrified control, conventional straw, cryotop and solid surface vitrification groups. In both conventional and cryotop methods, vitrified COCs were respectively loaded by conventional straws and cryotops, and then plunged directly into liquid nitrogen (LN2); whereas in the solid surface group, vitrified COCs were first loaded by cryotops and then cooled before plunging into LN2. Post-warming survivability and ultrastructural changes of healthy COCs in the cryotop group especially in comparison with the conventional group revealed better viability rate and good preservation of the ooplasm organization. However in all vitrification groups except the cryotop group, mitochondria were clumped. Solely in the conventional straw group, the mitochondria showed different densities and were extremely distended. Moreover in the latter group, plenty of large irregular connected vesicles in the ooplasm were observed and in some parts their membrane ruptured. Also, in the conventional and solid surface vitrification groups, cumulus cells projections became retracted from the zona pellucida in some parts. In conclusion, the cryotop vitrification method as compared with other methods seems to have a good post-warming survivability and shows less deleterious effects on the ultrastructure of healthy vitrified-warmed sheep COCs.

Rapid determination of recent cocaine use with magnetic particles-based enzyme immunoassays in serum, saliva, and urine fluids.

PubMed

Vidal, Juan C; Bertolín, Juan R; Bonel, Laura; Asturias, Laura; Arcos-Martínez, M Julia; Castillo, Juan R

2016-06-05

Cocaine is one of the most worldwide used illicit drugs. We report a magnetic particles-based enzyme-linked immunoassay (mpEIA) method for the rapid and sensitive determination of cocaine (COC) in saliva, urine and serum samples. Under optimized conditions, the limits of detections were 0.09ngmL(-1) (urine), 0.15ngmL(-1) (saliva), and 0.06ngmL(-1) COC (human serum). Sensitivities were in the range EC50=0.6-2.5ngmL(-1) COC. The cross-reactivity with the principal metabolite benzoylecgonine (BZE) was only 1.6%. Recovering percentages of doped samples (0, 10, 50, and 100ngmL(-1) of COC) ranged from about 86-111%. Some advantages of the developed mpEIA over conventional ELISA kits are faster incubations, improved reproducibility, and consumption of lower amounts of antibody and enzyme conjugates due to the use of magnetic beads. The reported method was validated following the guidelines on bioanalytical methods of the European Medicines Agency (2011). Unmetabolized COC detection has a great interest in pharmacological, pharmacokinetics, and toxicokinetics studies, and can be used to detect a very recent COC use (1-6h). Copyright © 2016 Elsevier B.V. All rights reserved.

Hemostatic effects of a novel estradiol-based oral contraceptive: an open-label, randomized, crossover study of estradiol valerate/dienogest versus ethinylestradiol/levonorgestrel.

PubMed

Klipping, Christine; Duijkers, Ingrid; Parke, Susanne; Mellinger, Uwe; Serrani, Marco; Junge, Wolfgang

2011-01-01

A novel estradiol-based combined oral contraceptive (COC) is currently available in many countries worldwide, including Europe and the US. Based on previous studies, it is expected that this estradiol-based COC will have a reduced hepatic effect compared with COCs containing ethinylestradiol with regard to proteins controlling the hemostatic balance. The aim of this study was to compare the hemostatic effects of the estradiol valerate/dienogest COC with a monophasic low-estrogen dose COC containing ethinylestradiol/levonorgestrel. Healthy women aged 18-50 years were randomized to receive a COC containing estradiol valerate/dienogest (2 days estradiol valerate 3 mg, 5 days estradiol valerate 2 mg/dienogest 2 mg, 17 days estradiol valerate 2 mg/dienogest 3 mg, 2 days estradiol valerate 1 mg, 2 days placebo) or ethinylestradiol 0.03 mg/levonorgestrel 0.15 mg in a crossover study design. Women received each treatment for three cycles, with two washout cycles between treatments. The primary efficacy variables were the intra-individual absolute changes in prothrombin fragment 1 + 2 and D-dimer from baseline to cycle three. Data from 29 women were assessed. Intra-individual absolute changes in prothrombin fragment 1 + 2 and D-dimer from baseline to cycle three were less pronounced with estradiol valerate/dienogest than with ethinylestradiol/levonorgestrel. The novel COC containing estradiol valerate/dienogest had similar or less pronounced effects on hemostatic parameters than ethinylestradiol/levonorgestrel.

Methylphenidate and Cocaine Self-Administration Produce Distinct Dopamine Terminal Alterations

PubMed Central

Calipari, Erin S.; Ferris, Mark J.; Melchior, James R.; Bermejo, Kristel; Salahpour, Ali; Roberts, David C. S.; Jones, Sara R.

2012-01-01

Methylphenidate (MPH) is a commonly abused psychostimulant prescribed for the treatment of attention deficit hyperactivity disorder. MPH has a mechanism of action similar to cocaine (COC) and is commonly characterized as a dopamine transporter (DAT) blocker. While there has been extensive work aimed at understanding dopamine (DA) nerve terminal changes following COC self-administration, very little is known about the effects of MPH self-administration on the DA system. We used fast scan cyclic voltammetry in nucleus accumbens core slices from animals with a five-day self-administration history of 40 injections/day of either MPH (0.56 mg/kg) or COC (1.5 mg/kg) to explore alterations in baseline DA release and uptake kinetics as well as alterations in the interaction of each compound with the DAT. Although MPH and COC have similar behavioral effects, the consequences of self-administration on DA system parameters were found to be divergent. We show that COC self-administration reduced DAT levels and maximal rates of DA uptake, as well as reducing electrically stimulated release, suggesting decreased DA terminal function. In contrast, MPH self-administration increased DAT levels, DA uptake rates, and DA release, suggesting enhanced terminal function, which was supported by findings of increased metabolite/DA tissue content ratios. Tyrosine hydroxylase mRNA, protein and phosphorylation levels were also assessed in both groups. Additionally, COC self-administration reduced COC-induced DAT inhibition, while MPH self-administration increased MPH-induced DAT inhibition, suggesting opposite pharmacodynamic effects of these two drugs. These findings suggest that the factors governing DA system adaptations are more complicated than simple DA uptake blockade. PMID:22458761

Association of oral contraceptive and metformin did not improve insulin resistance in women with polycystic ovary syndrome.

PubMed

Iwata, Margareth Chiharu; Porquere, Livia; Sorpreso, Isabel C Espósito; Baracat, Edmund C; Soares Júnior, José Maria

2015-01-01

to compare clinical and laboratory parameters in women with polycystic ovary syndrome (PCOS) using metformin or combined oral contraceptive (COC) after 6 months. retrospective study analyzing records of patients with PCOS using the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society criteria. The groups were: I-COC (21 tablets, pause of 7 days; n=16); II-metformin (850 mg 12/12h, n=16); III-COC plus metformin (n=9). Body mass index (BMI), acne (% of improvement), modified Ferriman-Gallway index and menstrual cycle index (MCI), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), androstenedione (A) and homeostasis model assessment: insulin resistance (HOMA-IR) index were assessed Results: isolated use of COC compared to metformin was better regarding to acne, Ferriman index, MCI, LH, TT and A levels. On the other hand, metformin was better in the HOMA-IR index (4.44 and 1.67 respectively, p=0.0007). The association COC plus metformin, compared to metformin alone shows the maintenance of improvement of acne, Ferriman index, MCI, and testosterone levels. The HOMA-IR index remained lower in the metformin alone group (4.19 and 1.67, respectively; p=0,046). The comparison between COC plus metformin and COC alone, in turn, shows no difference in the improvement of acne, Ferriman index, MCI, LH, TT and A levels, indicating that the inclusion of metformin did not lead to additional benefits in these parameters. Still, the HOMA-IR index was similar in both groups (4.19 and 4.44 respectively; p=0.75), showing that the use of metformin associated with COC may not improve insulin resistance as much as it does if used alone. our data suggest that the combination of metformin and contraceptive does not improve insulin resistance as observed with metformin alone.

Modification of pharmacokinetic and abuse-related effects of cocaine by human-derived cocaine hydrolase in monkeys.

PubMed

Schindler, Charles W; Justinova, Zuzana; Lafleur, David; Woods, Doug; Roschke, Viktor; Hallak, Hussein; Sklair-Tavron, Liora; Redhi, Godfrey H; Yasar, Sevil; Bergman, Jack; Goldberg, Steven R

2013-01-01

Although substantial research effort has focused on developing pharmacological treatments for cocaine abuse, no effective medications have been developed. Recent studies show that enzymes that metabolize cocaine in the periphery, forestalling its entry into the brain, can prevent cocaine toxicity and its behavioral effects in rodents. Here we report on effects of one such enzyme (Albu-CocH) on the pharmacokinetic and behavioral effects of cocaine in squirrel monkeys. Albu-CocH was developed from successive mutations of human butyrylcholinesterase (BChE) and has 1000-fold greater catalytic activity against cocaine than naturally occurring BChE. Pharmacokinetic studies showed that Albu-CocH (5 mg/kg) had a half-life of 56.6 hours in squirrel monkeys. In these studies, plasma levels of cocaine following i.v. 1 mg/kg cocaine were reduced 2 hours after administration of Albu-CocH, whereas plasma levels of the cocaine metabolite ecgonine methyl ester were increased. These effects were still evident 72 hours following Albu-CocH administration. In behavioral experiments in monkeys, pre-treatment with 5 mg/kg Albu-CocH dramatically decreased self-administration of a reinforcing dose of i.v. cocaine (30 µg/kg/injection) for over 24 hours. Pre-treatment with 5 mg/kg Albu-CocH also attenuated the reinstatement of extinguished cocaine self-administration by an i.v. priming injection of cocaine (0.1 or 0.3 mg/kg) and, in separate studies, attenuated the discriminative-stimulus effects of cocaine. The ability of Albu-CocH to attenuate the abuse-related effects of cocaine in squirrel monkeys indicates that further investigation of BChE mutants as potential treatment for cocaine abuse and toxicity is warranted. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

Low-dose combined oral contraceptive use is associated with lower bone mineral content variation in adolescents over a 1-year period.

PubMed

Biason, Talita Poli; Goldberg, Tamara Beres Lederer; Kurokawa, Cilmery Suemi; Moretto, Maria Regina; Teixeira, Altamir Santos; Nunes, Hélio Rubens de Carvalho

2015-04-03

Low-dose combined oral contraceptives (COCs) can interfere with bone mass acquisition during adolescence. This study aimed to evaluate bone mineral density (BMD) and bone mineral content (BMC) in female adolescents taking a standard low-dose COC (ethinylestradiol 20 μg/desogestrel 150 μg) over a 1-year period and to compare their data with those of healthy adolescents from the same age group not taking COCs. This was a non-randomized parallel-control study with a 1-year follow-up. Sixty-seven adolescents aged from 12 to 19 years, divided into COC users (n = 41) taking 20 μg ethinylestradiol/150 μg desogestrel and COC non-user controls (n = 26), were evaluated by bone densitometry examinations at baseline and after 12 months. Comparisons between the groups at the study onset were performed using the Mann-Whitney test with the significance level fixed at 5% or p < 0.05. Comparisons between the groups at the study onset and after 12 months were based on variations in the median percentages for bone mass variables. The COC users presented with low bone mass acquisition in the lumbar spine, and had BMD and BMC median variations of 2.07% and +1.57%, respectively, between the measurements at baseline and 12 months. The control group had median variations of +12.16% and +16.84% for BMD and BMC, respectively, over the same period. The total body BMD and BMC showed similar evolutions during the study in both groups. Statistical significance (p < 0.05) was seen for the BMC percentage variation between COC users and non-users. Use of a low-dose COC (ethinylestradiol 20 μg/desogestrel 150 μg) was associated with lower bone mass acquisition in adolescents during the study period. Registry Number, RBR-5h9b3c.

Initial locomotor sensitivity to cocaine varies widely among inbred mouse strains.

PubMed

Wiltshire, T; Ervin, R B; Duan, H; Bogue, M A; Zamboni, W C; Cook, S; Chung, W; Zou, F; Tarantino, L M

2015-03-01

Initial sensitivity to psychostimulants can predict subsequent use and abuse in humans. Acute locomotor activation in response to psychostimulants is commonly used as an animal model of initial drug sensitivity and has been shown to have a substantial genetic component. Identifying the specific genetic differences that lead to phenotypic differences in initial drug sensitivity can advance our understanding of the processes that lead to addiction. Phenotyping inbred mouse strain panels are frequently used as a first step for studying the genetic architecture of complex traits. We assessed locomotor activation following a single, acute 20 mg/kg dose of cocaine (COC) in males from 45 inbred mouse strains and observed significant phenotypic variation across strains indicating a substantial genetic component. We also measured levels of COC, the active metabolite, norcocaine and the major inactive metabolite, benzoylecgonine, in plasma and brain in the same set of inbred strains. Pharmacokinetic (PK) and behavioral data were significantly correlated, but at a level that indicates that PK alone does not account for the behavioral differences observed across strains. Phenotypic data from this reference population of inbred strains can be utilized in studies aimed at examining the role of psychostimulant-induced locomotor activation on drug reward and reinforcement and to test theories about addiction processes. Moreover, these data serve as a starting point for identifying genes that alter sensitivity to the locomotor stimulatory effects of COC. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Rottlerin impairs the formation and maintenance of psychostimulant-supported memory.

PubMed

Liao, Tien You; Tzeng, Wen-Yu; Wu, Hsin-Hua; Cherng, Chianfang G; Wang, Ching-Yi; Hu, Sherry S-J; Yu, Lung

2016-04-01

Since brain proteins such as protein kinase C (PKC), brain-derived neurotrophic factor (BDNF), and mammalian target of rapamycin (mTOR) are involved in the establishment and maintenance of psychostimulant memory, we sought to determine if systemic treatment with rottlerin, a natural compound affecting all these proteins, may modulate stimulant-supported memory. Stimulant-induced conditioned place preference (CPP) was used in modeling stimulant-supported memory. Three cocaine (10 mg/kg; COC) or three methamphetamine (1 mg/kg; MA) conditioning trials reliably established the drug-induced CPP in male C57BL/6 mice. An intra-peritoneal rottlerin injection (5 mg/kg) at least 24 h prior to the first COC or first MA conditioning trial prevented the establishment of CPP. Following the establishment of the COC- or MA-induced CPP, saline conditioning trial was used to extinguish the CPP. Rottlerin (5 mg/kg, intra-peritoneal (i.p.)) administered 20 h prior to the first saline conditioning trial diminished subsequent drug- and stressor-primed reinstatement of the extinguished CPP. Rottlerin (5 mg/kg, i.p.) produced a fast-onset and long-lasting increase in hippocampal BDNF levels. However, treatment with a BDNF tropomyosin receptor kinase B (TrkB) receptor antagonist, K252a (5 μg/kg), did not affect rottlerin's suppressing effect on COC-induced CPP and treatment with 7,8-dihydroxyflavone (10 mg/kg x 6, 7,8-DHF), a selective TrkB agonist, prior to each conditioning trial did not affect COC-induced CPP. These results suggest that systemic rottlerin treatment may impair the formation of COC- and MA-supported memory. Importantly, such a treatment may advance our understanding of the underlying mechanism through which extinction training resulted in the "forgetting" of the COC- and MA-supported memory.

Combined oral contraceptive treatment for bleeding complaints with the etonogestrel contraceptive implant: a randomised controlled trial.

PubMed

Hou, Melody Y; McNicholas, Colleen; Creinin, Mitchell D

2016-10-01

Estimate symptom improvement rate of women with bleeding complaints using the etonogestrel contraceptive implant when started on continuous combined oral contraceptives (COC). We conducted a double-blinded randomised controlled trial of women reporting troublesome bleeding related to their etonogestrel contraceptive implant and desiring intervention. Participants received continuous COCs or placebo for four weeks to evaluate self-reported bleeding improvement at four weeks. Participants could continue study treatment or prescribed COCs for another eight weeks if desired. We planned to enroll 130 participants between two sites (80% power to detect a 20% effect size at a 0.05 significance level, with 10% loss to follow up). We closed the study after enrolling 26 participants due to recruitment futility. All women on COCs and 75% of placebo users reported bleeding improvement at four weeks (p = 0.09), with 92% and 42%, respectively, reporting significant improvement (p = 0.03). The median number of days until bleeding stopped for at least four days in COC and placebo users was 1 day (range 1-9) and 4.5 days (range 1-28), respectively (p = 0.63). Eight (75%) COC and five (42%) placebo users opted to continue study treatment (p = 0.41). Despite bleeding improvement, women who desired implant removal at enrollment were more likely to re-request removal than those who initially considered other interventions (3 of 5 [60%] vs 1 of 17 [6%], p = 0.03). Although women who have troublesome bleeding while using the contraceptive implant may experience improvement with no treatment over 4 weeks, women using COCs are more likely to report significant improvement. Clinicaltrials.gov registration number: NCT01963403.

The CORALIE study: improving patient education to help new users better understand their oral contraceptive.

PubMed

de Reilhac, Pia; Plu-Bureau, Geneviève; Serfaty, David; Letombe, Brigitte; Gondry, Jean; Christin-Maitre, Sophie

2016-10-01

Combined oral contraceptives (COCs) are the most widely used contraceptive method in Europe. Paradoxically, rates of unintended pregnancy and abortion are still remarkably high. A lack of knowledge about COCs is often reported to lead to poor adherence, suggesting an unmet need for adequate contraceptive counselling. Our objective was to investigate the impact on the knowledge level of users of a structured approach to deliver contraceptive information for a first COC prescription. The Oral Contraception Project to Optimise Patient Information (CORALIE) is a multicentre, prospective, randomised study conducted in France between March 2009 and January 2013. The intervention involved providing either an 'essential information' checklist or unstructured counselling to new COC users. The outcome measure was a questionnaire that assessed whether the information provided to the new user by the gynaecologist had been correctly understood. One hundred gynaecologists and an expert committee used the Delphi method to develop an 'essential information' checklist, after which 161 gynaecologists were randomised to two groups. Group I (n = 81) used the checklist with 324 new COC users and group II (n = 80) delivered unstructured information to 307 new COC users. The average score for understanding the information delivered during the visit was significantly higher in women in group I than in the women in group II, even after adjustment for age and previous history of pregnancy: 16.48/20 vs 14.27/20 (p < 0.0001). Delivering structured information for a first COC prescription is beneficial for understanding contraception. Our tool could ultimately contribute to increased adherence and should be investigated in a prospective study of long-term outcomes.

Escalation of cocaine self-administration in adulthood after social defeat of adolescent rats: Role of social experience and adaptive coping behavior

PubMed Central

Burke, Andrew R.; Miczek, Klaus A.

2015-01-01

Background The link between adolescent social stress and substance abuse is modeled in social defeat of adolescent male rats, at an age when social experiences are essential for neurobehavioral maturation. Objective We investigated the role of social experience and social defeat stress during adolescence on social behavior and cocaine self administration (CocSelfAd) in early adulthood. Methods We manipulated social experience by housing male rats in pairs (PH) or singly (SH) on postnatal day (P) 21. In addition, rats were subjected to social defeat from P35-44. Social behavior was measured during the first and last social defeat in PH and SH adolescents and PH adults. After assessing the behavioral response to novelty and cocaine (P57-61), intra-jugular catheters were implanted and CocSelfAd was analyzed. Results Residents were less aggressive toward PH adolescent intruders compared to PH adult intruders. Adults were submissive and defensive when attacked, whereas PH adolescents froze. In the course of repeated defeats, adolescent PH rats increased freezing, while SH rats decreased freezing. Longer attack-induced freezing after repeated defeats predicted escalated CocSelfAd in adulthood. PH controls acquired CocSelfAd more slowly than PH defeated and SH rats. Defeated PH rats increased CocSelfAd during progressive ratio schedules of reinforcement and during a 24-hour continuous access binge compared to PH controls and SH defeated rats. Conclusions Social defeat in adolescence of PH rats caused persistent increases in adult CocSelfAd. Adolescent PH rats coped with attacks adaptively by increasing freezing behavior after repeated social defeats, a measure that predicted CocSelfAd in adulthood. PMID:25943168

Fertility and combined oral contraceptives - unintended pregnancies and planned pregnancies following oral contraceptive use - results from the INAS-SCORE study.

PubMed

Barnett, Clare; Hagemann, Christine; Dinger, Jürgen; Do Minh, Thai; Heinemann, Klaas

2017-02-01

To estimate the real-use contraceptive effectiveness of the combined oral contraceptive containing dienogest and estradiol valerate (DNG/EV) and whether DNG/EV compared to other combined oral contraceptives (oCOC) has a negative effect on return to fertility. Transatlantic, prospective, non-interventional cohort study conducted in the USA and seven European countries with two main exposure groups and one exposure subgroup: new users of DNG/EV and other COC (oCOC), particularly levonorgestrel-containing COCs (LNG). In a planned secondary analysis, pregnancy outcomes were investigated including contraceptive effectiveness and pregnancy following contraceptive cessation. The influence of age, parity and OC-type were assessed. 50,203 COC users were followed for 105,761 woman-years (WY). There were 677 unintended pregnancies reported: 451 in the USA and 226 in Europe. The contraceptive failure rate in Europe was 0.5 events/100 WY (95% CI: 0.4-0.5) and in the USA 1.9 events/100 WY (95% CI: 1.7-2.1). Differences in compliance (1.3 pregnancies/100 WY) accounted for 90% of the geographical difference seen between Europe and the USA. DNG/EV showed lower contraceptive failure rates compared to the comparators; 0.9% DNG/EV, 2.1% oCOC and 2.8% LNG after 4 years. Overall, 1167 (2.3%) of women stopped contraceptive use with the intention of becoming pregnant with 89% conceiving within 2 years. No significant differences were seen between groups after adjusting for age. DNG/EV is associated with similar contraceptive effectiveness in typical-use settings when compared to oCOC and LNG. There was no difference observed between cohorts in fertility following OC use.

Developmental potential of murine germinal vesicle stage cumulus-oocyte complexes following exposure to dimethylsulphoxide or cryopreservation: loss of membrane integrity of cumulus cells after thawing.

PubMed

Ruppert-Lingham, C J; Paynter, S J; Godfrey, J; Fuller, B J; Shaw, R W

2003-02-01

Cumulus cells of the cumulus-oocyte complex (COC) are important in oocyte maturation. Thus, in preserving immature oocytes it is prudent to also preserve their associated cumulus cells. The survival and function of oocytes and their associated cumulus cells was assessed following cryopreservation or exposure to cryoprotectant without freezing. Immature COCs were collected from mice primed with pregnant mare's serum. COCs were either slow-cooled or exposed to 1.5 mol/l dimethylsulphoxide without freezing. Treated and fresh COCs were stained for membrane integrity or, after in-vitro maturation and IVF, were assessed for developmental capability. Development of cumulus-denuded fresh oocytes, as well as denuded and frozen-thawed oocytes co-cultured with fresh cumulus cells, was assessed. Slow-cooled oocytes had significantly reduced coverage by intact cumulus cells compared with fresh COCs. Cumulus cell association and developmental capability were not substantially affected by exposure to cryoprotectant without freezing. Denuded fresh oocytes and cryopreserved COCs had decreased developmental potential that was not overcome by co-culture with fresh cumulus cells. Loss of association between oocyte and cumulus cells was induced by cryopreservation, but not by treatment with cryoprotectant alone. The data indicate that direct physical contact between cumulus cells and the oocyte, throughout maturation, improves subsequent embryo development.

A primer on the hormone-free interval for combined oral contraceptives.

PubMed

Hauck, Brian A; Brown, Vivien

2015-01-01

The dosing, schedules, and other aspects of combined oral contraceptive (COC) design have evolved in recent years to address a variety of issues including short- and long-term safety, bleeding profiles, and contraceptive efficacy. In particular, several newer formulations have altered the length of the hormone-free interval (HFI), in order to minimize two key undesired effects that occur during this time: hormone-withdrawal-associated symptoms (HWaS) and follicular development. This primer reviews our current understanding of the key biological processes that occur during the HFI and how this understanding has led to changes in the dosing and schedule of newer COC formulations. In brief, HWaS are common, underappreciated, and a likely contributor to COC discontinuation; because of this, shortening the HFI and/or supplementing with estrogen during the progestin-free interval may provide relief from these symptoms and improve adherence. A short HFI (with or without estrogen supplementation) may also help maintain effective follicular suppression and contraceptive efficacy, even when the overall dose of estrogen throughout the cycle is low. Taken together, the available data about HWaS and follicular activity during the HFI support the rationale for recent COC designs that use a low estrogen dose and a short HFI. The availability of a variety of COC regimens gives physicians a range of choices when selecting the most appropriate COC for each woman's particular priorities and needs.

A comprehensive evaluation of the toxicology of cigarette ingredients: cocoa-derived ingredients.

PubMed

Coggins, Christopher R E; Fisher, Michael T; Smith, Donna C; Oldham, Michael J

2011-06-01

Cocoa-derived ingredients are used in cigarette tobacco. A battery of tests was used to compare toxicity of mainstream smoke from experimental cigarettes containing different added levels of cocoa-derived ingredients. Five cocoa-derived ingredients chocolate (CH), cocoa (COC), cocoa-grand prix black (CGPB), cocoa nibs tincture (CNT) and cocoa shells extract (CSE) were added individually to experimental cigarettes at three different levels. Smoke from each of the experimental cigarette types was evaluated using analytical chemistry; in vitro cytotoxicity and mutagenicity testing were performed for four of the five compounds. For CH, COC and CNT, 90-day smoke inhalation studies were performed with 6-week recovery periods. No consistent changes were found in the analytical chemistry results. Results of the cytotoxicity and mutagenicity were unaffected by any of the ingredients. Two of the three inhalation studies showed very few differences between the groups. The inhalation study with COC showed several increases in mean histopathology severity scores in groups exposed to different levels of COC, compared with the controls. These apparent effects of COC on histopathology lesion severity scores were only present in a single sex and none were dose-related, which is not consistent with a true increase in biological activity. Also there were effectively no differences in the patterns of recovery for any of the compounds. Even at high inclusion levels there was a lack of toxicological response in these COC derived ingredients.

Dealloyed Pt3Co nanoparticles with higher geometric strain for superior hydrogen evolution reaction

NASA Astrophysics Data System (ADS)

Saquib, Mohammad; Halder, Aditi

2018-06-01

In the present work, the effect of surface strain in the carbon supported Pt3Co dealloy catalyst towards hydrogen evolution reaction (HER) has been reported. Dealloying process is adopted to generate the geometric strain in Pt3Co/C alloy by preferential dissolution of non-noble metal (Co) from the alloy. The developed geometric strain has been estimated by different microstructural characterization techniques. Electrochemical studies showed that the highest current density for HER was obtained for Pt3Co/C dealloy catalyst and it was nearly 2 and 5 times higher than Pt3Co/C alloy and Pt/C respectively. Tafel slope for HER was improved from 49 (Pt/C) to 34 mV dec-1 (Pt3Co/C dealloy), indicating that the surface strain plays important role in the improvement of the catalytic activity of Pt3Co catalyst. The chronoamperometry data, LSV curves and ECSA values before and after chronoamperometry confirmed that Pt3Co/C dealloy catalyst was a stable as well as a durable electrocatalyst for HER.

Adverse mood symptoms with oral contraceptives.

PubMed

Poromaa, Inger Sundström; Segebladh, Birgitta

2012-04-01

In spite of combined oral contraceptives (COCs) having been available for more than 50 years, surprisingly little is known about the prevalence of truly COC-related adverse mood symptoms and about the underlying biological mechanisms of proposed changes in mood and affect. Precise estimates of COC-related adverse mood symptoms are not available due to the lack of placebo-controlled trials. In prospective trials the frequency of women who report deteriorated mood or deteriorated emotional well-being varies between 4 and 10%, but it can be assumed that the causal relation in these prevalence rates is overestimated. Adverse mood symptoms and somatic symptoms are most pronounced during the pill-free interval of the treatment cycles, but whether extended COC regimens would be more favorable in this respect is not known. COCs with anti-androgenic progestagens, such as drospirenone and desogestrel, appear more favorable in terms of mood symptoms than progestagens with a more androgenic profile. Available data suggest that lower doses of ethinylestradiol could be beneficial. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

Comparing the Effects of Combined Oral Contraceptives Containing Progestins With Low Androgenic and Antiandrogenic Activities on the Hypothalamic-Pituitary-Gonadal Axis in Patients With Polycystic Ovary Syndrome: Systematic Review and Meta-Analysis

PubMed Central

Amiri, Mina; Nahidi, Fatemeh; Kabir, Ali; Azizi, Fereidoun

2018-01-01

Background Different products of combined oral contraceptives (COCs) can improve clinical and biochemical findings in patients with polycystic ovary syndrome (PCOS) through suppression of the hypothalamic-pituitary-gonadal (HPG) axis. Objective This systematic review and meta-analysis aimed to compare the effects of COCs containing progestins with low androgenic and antiandrogenic activities on the HPG axis in patients with PCOS. Methods We searched PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science databases (1980-2017) to identify randomized controlled trials or nonrandomized studies investigating the effect of COCs containing progestins with low androgenic and antiandrogenic activities, including the products containing desogestrel, cyproterone acetate, and drospirenone, on the HPG axis in patients with PCOS. In this meta-analysis, fixed and random effect models were used. Outcomes of interest were weighted mean differences (WMD) of hormonal parameters, including the follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH-to-FSH ratio, estradiol, total testosterone, and sex hormone–binding globulin. Potential sources of heterogeneity were investigated using meta-regression and subgroup analyses. Subgroup analyses were performed based on the used progestin compound and treatment duration. We assessed quality of included studies and their risk of bias using Cochrane guidelines. Publication bias was assessed using Egger test and funnel plot. Results COC use was significantly associated with a decrease in gonadotropin levels, including FSH and LH. Use of products containing cyproterone acetate was associated with a decrease in FSH levels after 3 months (WMD=−0.48; 95% CI −0.81 to −0.15), 6 months (WMD=−2.33; 95% CI −3.48 to −1.18), and 12 months (WMD=−4.70; 95% CI −4.98 to −4.42) and a decrease in LH levels after 3 months (WMD=−3.57; 95% CI −5.14 to −1.99), 6 months (WMD=−5.68; 95% CI −9.57 to −1.80), and 12 months (WMD=−11.60; 95% CI −17.60 to −5.60). Use of COCs containing drospirenone for 6 months decreased FSH (WMD=−0.93; 95% CI −1.79 to −0.08) and LH (WMD=−4.59; 95% CI −7.53 to −1.66) levels. Data for products containing desogestrel were few, but this compound generally had no statistically significant influence on gonadotropin levels similar to that observed with COCs containing cyproterone acetate and drospirenone. Use of COCs was not associated with any significant change in LH-to-FSH ratio. COCs containing cyproterone acetate showed maximum effect on gonadotropin suppression. COCs containing cyproterone acetate significantly decreased estradiol concentrations, whereas those containing drospirenone exhibited no such effect. All COCs demonstrated improvement in androgenic profile and had the same effects on total testosterone and sex hormone–binding globulin concentrations. Progestin compound and treatment duration had no statistically significant effects on changing total testosterone and sex hormone–binding globulin levels. Conclusions COCs containing cyproterone acetate can effectively suppress gonadotropins, leading to a decrease in androgenic parameters. Although different products of COCs could significantly suppress the androgenic profile, it seems that products containing cyproterone acetate are more effective in suppressing gonadotropin and estradiol levels in patients with PCOS. PMID:29695378

Comparing the Effects of Combined Oral Contraceptives Containing Progestins With Low Androgenic and Antiandrogenic Activities on the Hypothalamic-Pituitary-Gonadal Axis in Patients With Polycystic Ovary Syndrome: Systematic Review and Meta-Analysis.

PubMed

Amiri, Mina; Ramezani Tehrani, Fahimeh; Nahidi, Fatemeh; Kabir, Ali; Azizi, Fereidoun

2018-04-25

Different products of combined oral contraceptives (COCs) can improve clinical and biochemical findings in patients with polycystic ovary syndrome (PCOS) through suppression of the hypothalamic-pituitary-gonadal (HPG) axis. This systematic review and meta-analysis aimed to compare the effects of COCs containing progestins with low androgenic and antiandrogenic activities on the HPG axis in patients with PCOS. We searched PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science databases (1980-2017) to identify randomized controlled trials or nonrandomized studies investigating the effect of COCs containing progestins with low androgenic and antiandrogenic activities, including the products containing desogestrel, cyproterone acetate, and drospirenone, on the HPG axis in patients with PCOS. In this meta-analysis, fixed and random effect models were used. Outcomes of interest were weighted mean differences (WMD) of hormonal parameters, including the follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH-to-FSH ratio, estradiol, total testosterone, and sex hormone-binding globulin. Potential sources of heterogeneity were investigated using meta-regression and subgroup analyses. Subgroup analyses were performed based on the used progestin compound and treatment duration. We assessed quality of included studies and their risk of bias using Cochrane guidelines. Publication bias was assessed using Egger test and funnel plot. COC use was significantly associated with a decrease in gonadotropin levels, including FSH and LH. Use of products containing cyproterone acetate was associated with a decrease in FSH levels after 3 months (WMD=-0.48; 95% CI -0.81 to -0.15), 6 months (WMD=-2.33; 95% CI -3.48 to -1.18), and 12 months (WMD=-4.70; 95% CI -4.98 to -4.42) and a decrease in LH levels after 3 months (WMD=-3.57; 95% CI -5.14 to -1.99), 6 months (WMD=-5.68; 95% CI -9.57 to -1.80), and 12 months (WMD=-11.60; 95% CI -17.60 to -5.60). Use of COCs containing drospirenone for 6 months decreased FSH (WMD=-0.93; 95% CI -1.79 to -0.08) and LH (WMD=-4.59; 95% CI -7.53 to -1.66) levels. Data for products containing desogestrel were few, but this compound generally had no statistically significant influence on gonadotropin levels similar to that observed with COCs containing cyproterone acetate and drospirenone. Use of COCs was not associated with any significant change in LH-to-FSH ratio. COCs containing cyproterone acetate showed maximum effect on gonadotropin suppression. COCs containing cyproterone acetate significantly decreased estradiol concentrations, whereas those containing drospirenone exhibited no such effect. All COCs demonstrated improvement in androgenic profile and had the same effects on total testosterone and sex hormone-binding globulin concentrations. Progestin compound and treatment duration had no statistically significant effects on changing total testosterone and sex hormone-binding globulin levels. COCs containing cyproterone acetate can effectively suppress gonadotropins, leading to a decrease in androgenic parameters. Although different products of COCs could significantly suppress the androgenic profile, it seems that products containing cyproterone acetate are more effective in suppressing gonadotropin and estradiol levels in patients with PCOS. ©Mina Amiri, Fahimeh Ramezani Tehrani, Fatemeh Nahidi, Ali Kabir, Fereidoun Azizi. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 25.04.2018.

Change to either a nonandrogenic or androgenic progestin-containing oral contraceptive preparation is associated with improved sexual function in women with oral contraceptive-associated sexual dysfunction.

PubMed

Davis, Susan R; Bitzer, Johannes; Giraldi, Annamaria; Palacios, Santiago; Parke, Susanne; Serrani, Marco; Mellinger, Uwe; Nappi, Rossella E

2013-12-01

It is a commonly held belief that combined oral contraceptive (COC) pills containing an androgenic progestin may be less likely to impair sexual function than COCs containing an anti-androgenic progestin. The study aims to compare the effects of a COC containing a progestin with an anti-androgenic profile (estradiol valerate [E2 V]/dienogest [DNG]) to that of one with an androgenic progestin (ethinyl estradiol [EE]/levonorgestrel [LNG]) on sexual function in women with COC-associated sexual dysfunction. In this multicenter, randomized, double-blind, noninferiority study, women with COC-associated female sexual dysfunction (FSD) were randomized to E2 V/DNG or EE/LNG for six cycles. The primary outcome was the change in the sum of Female Sexual Function Index (FSFI) desire and arousal component scores between baseline and cycle 6. Secondary outcome measures included changes to the FSFI domains, the Female Sexual Distress Scale (FSDS-R), Vaginal Health Assessment, the Atrophy Symptom Questionnaire, and the Psychological General Well Being Index over six treatment cycles. The main outcome is the change in the sum of FSFI desire and arousal component scores between baseline and cycle 6. Of 276 women screened, 213 received treatment and 191 completed the study. The mean increase in the sum of FSFI desire and arousal component scores was 5.90 (standard deviation [SD] 5.45) for E2 V/DNG and 5.79 (SD 6.17) for EE/LNG (change from baseline P < 0.0001, both groups). Both treatments showed equal efficacy and were associated with improvements in all domains of the FSFI, with no between-group differences. Both COCs reduced the distress associated with FSD, as indicated by reduced FSDS-R scores. In women with COC-associated FSD, switching to either E2 V/DNG or EE/LNG was associated with equivalent improvements in symptoms, challenging the perception that COCs containing anti-androgenic progestins have a detrimental effect on sexual function relative to those containing androgenic progestins. © 2013 International Society for Sexual Medicine.

The pharmacokinetics and pharmacodynamics of dehydroepiandrosterone during use of an ethinylestradiol- and drospirenone-containing oral contraceptive.

PubMed

Zimmerman, Yvette; Coelingh Bennink, Herjan J T; Wouters, Wout; Ebes, Frieda; Fauser, Bart C J M

2013-12-01

Combined oral contraceptives (COCs) reduce the levels of ovarian and adrenal androgens. Co-administration of dehydroepiandrosterone (DHEA) may normalise androgen levels during COC use. To investigate the effect of the addition of DHEA to a COC on the pharmacokinetics (PK) and pharmacodynamics (PD) of DHEA and its sulphate (DHEA-S), and on levels of total and free testosterone (T). In a prospective, randomised, double-blind, placebo-controlled, cross-over study involving 21 female volunteers, the PK and PD of DHEA and DHEA-S were investigated during the use of one cycle of a COC containing 30 μg ethinylestradiol (EE) and 3 mg drospirenone (DRSP) with and without daily co-administration of 50 mg DHEA. Treatment during one cycle with a COC containing EE and DRSP reduces the exposure to DHEA and DHEA-S by at least 20%. This loss of adrenal androgens can be fully compensated by daily oral co-administration of 50 mg DHEA. With DHEA co-administration total T levels rise significantly (1.44 nmol/L with DHEA vs. 0.82 nmol/L with placebo; p < 0.001). Free T levels decrease significantly with both DHEA and placebo treatment, but significantly less during co-administration of DHEA (6.34 pmol/L with DHEA vs. 3.96 pmol/L with placebo; p < 0.001). By adding DHEA to a COC the loss of adrenal and ovarian androgens can be restored.

Combined oral contraceptives and/or antiandrogens versus insulin sensitizers for polycystic ovary syndrome: a systematic review and meta-analysis.

PubMed

Luque-Ramírez, Manuel; Nattero-Chávez, Lía; Ortiz Flores, Andrés E; Escobar-Morreale, Héctor F

2017-12-27

Androgen excess is a key pathogenetic mechanism in polycystic ovary syndrome (PCOS), although hyperinsulinism also contributes to androgen secretion. Therapeutic approaches for adult patients not seeking fertility include combined oral contraceptives (COC), antiandrogens (AA) and/or insulin sensitizers, although these practices are supported by limited high-quality evidence. We aimed to assess the efficacy and safety of these common treatments for PCOS by conducting a meta-analysis of RCTs with the following review questions: Which is the more appropriate therapeutic approach for hyperandrogenic symptoms, hyperandrogenemia, and ovulatory dysfunction in adult women with PCOS not seeking fertility; What is the impact on classic cardiometabolic risk factors of the more common treatments used in those women; Does the combination of the antiandrogenic therapy plus metformin have any impact on efficacy or cardiometabolic profile? We searched PubMed and EMBASE for articles published up to 16 September 2017. After deleting duplicates, the abstracts of 1522 articles were analysed. We subsequently excluded 1446 articles leaving 76 studies for full-text assessment of eligibility. Of them, 43 articles were excluded. Hence, 33 studies and 1521 women were included in the quantitative synthesis and in the meta-analyses. Meta-analyses calculated mean differences (MD), standardized mean differences (SMD), odds ratio (OR) and 95% CIs. Heterogeneity and inconsistency across studies was assessed by χ2 test and Higgins's I2 statistics. Quality and risk of bias of individual studies were assessed according to the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0. We then used the approach recommended by the Grading of Recommendations, Assessments, Development, and Evaluation (GRADE) group to indicate the global quality of evidence for a selection of primary outcomes. Regarding efficacy, the MD in hirsutism score between COC and/or AA and metformin were not significant. The exclusion of one single study including most women with severe hirsutism yielded a significant effect in favour of COC and/or AA. When only those studies including an AA were compared with metformin, there were significant differences favouring antiandrogenic therapy. The combination of COC and/or AA with metformin was similar to COC and/or AA therapy alone in the whole group of patients. Post-intervention OR for the presence of regular menses favoured COC therapy. In terms of cardiometabolic impact, the MD in BMI were in favour of metformin. The negative effect of COC therapy on BMI was blunted by its combination with metformin. The MD in homoeostasis model assessment of insulin resistance (HOMA-IR) were also in favour of metformin therapy compared to COC and/or AA. The combination of COC and/or AA and metformin decreased MD in HOMA with respect to antiandrogenic therapy alone. There were no significant post-intervention SMD in circulating glucose levels between COC and/or AA and metformin. However, adding metformin to COC and/or AA yielded a beneficial effect on fasting glucose levels. Post-intervention OR for abnormal glucose tolerance showed no significant differences between COC and/or AA and metformin, although after excluding studies including an AA as a comparator (without COC) a significant effect in favour of metformin therapy was observed. There were no significant differences among therapies in lipid profile, blood pressure or prevalence of hypertension. The global quality of evidence was very low when addressing the impact of the treatments explored on prevalence of hypertension and lipid profiles, low in the case of hirsutism, BMI and blood pressure values, and high for endometrial protection and glucose tolerance. These data provide further scientific evidence for the choice of treatment of women with PCOS. COC and AA are more effective than metformin for hyperandrogenic symptoms and endometrial protection. Their combination with metformin adds a positive effect on BMI and glucose tolerance. CRD42016053457. © The Author(s) 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

[Acupuncture with Point Location-a mandatory examination for American NCCAOM certification of acupuncture and oriental medicine].

PubMed

Tian, Kaiyu; Rao, Hong; Lin, Yongqing; He, Yang; Zhao, Junqing; Chen, Qiang

2017-03-12

Acupuncture with Point Location is one of the mandatory examinations for the Diplomate of Oriental Medicine (Dipl.OM.) or Acupuncture (Dipl. Ac.) by American National Certification Commission for Acupuncture and Oriental Medicine (NCCAOM). In reference to NCCAOM Certification Handbook, Acupuncture with Point Location Expanded Content Outline , and Study Guide for Diplomates in Acupuncture Certification , the authors introduced the examination pattern and examination-related contents including such aspects as safety and professional responsibilities, treatment plan, and point location and discussed additionally the enlightening effects on acupuncture practice and examination in universities and international associations of Chinese medicine in our country.

Interactive effects of betaine and monensin in uninfected and Eimeria acervulina-infected chicks.

PubMed

Matthews, J O; Ward, T L; Southern, L L

1997-07-01

Three experiments (Exp.) were conducted to evaluate the interactive effects of dietary betaine (BET) and monensin (MON) in uninfected or Eimeria acervulina-infected chicks. The treatments were replicated with six (Exp. 1) or five (Exp. 2 and 3) pens of five chicks each. The experimental periods lasted 9 (Exp. 1 and 2) or 10 (Exp. 3) d each and the coccidiosis infections were established on Day 2 (Exp. 1 and 2) or Day 3 (Exp. 3) of the experiment. Average initial weight of the chicks was 101, 73, and 68 g in Exp. 1 to 3, respectively, and the initial age of the chicks was 5 (Exp. 1) or 4 (Exp. 2 and 3) d. A corn-soybean meal basal diet was used in each experiment. In Exp. 1, the effect of dietary BET (0, 0.1, or 0.5%) in uninfected or coccidiosis-infected (COC; 5 x 10(5) sporulated E. acervulina oocysts) chicks was investigated. In Exp. 2, the interactive effects of BET (0 or 0.1%) and MON (0 or 55 ppm) in uninfected or COC chicks were investigated in a 2 x 2 x 2 factorial arrangement of treatments. Experiment 3 was identical to Exp. 2, except the level of MON was 110 rather than 55 ppm. In Exp. 1, 2, and 3, COC reduced (P < 0.01) gain, feed intake (FI), feed efficiency (GF), and plasma carotenoid concentration (CAR) and increased (P < 0.01) lesion score (LS). In Exp. 1, gain and FI were decreased in uninfected chicks fed 0.1% BET but gain and FI were increased in COC chicks fed 0.1% BET (COC x BET quadratic, P < 0.01). Dietary BET linearly increased (P < 0.05) GF. In Exp. 2 and 3, MON increased (P < 0.01) gain, FI, GF, and CAR and decreased (P < 0.01) LS of COC chicks, but MON had no effect in uninfected chicks (COC x MON, P < 0.01). In Exp. 2, GF was increased more in chicks fed both MON and BET than in chicks fed MON (BET x MON, P < 0.06). In Exp. 3, BET increased GF of uninfected chicks fed MON and of COC chicks not fed MON (COC x BET x MON, P < 0.02). Betaine may have an effect on E. acervulina-infected chicks, but there is no conclusive evidence to indicate that the efficacy of MON is improved when fed in combination with BET.

Long term effect of Ovum Pick-up in buffalo species.

PubMed

Neglia, Gianluca; Gasparrini, Bianca; Vecchio, Domenico; Boccia, Lucia; Varricchio, Ettore; Di Palo, Rossella; Zicarelli, Luigi; Campanile, Giuseppe

2011-02-01

The aim of this study was to evaluate the effect of an Ovum Pick-up (OPU) treatment carried out for 9 months in buffalo (Bubalus bubalis) species. Eight pluriparous non-lactating buffalo cows underwent OPU for 9 months. Recovered cumulus enclosed oocytes (COCs) were classified and COCs suitable for in vitro embryo production (IVEP) were in vitro matured (IVM), fertilized (IVF) and cultured (IVC) to the blastocyst (Bl) stage. Animals were monitored for a total period of 270 days, but at the summer solstice, follicular turnover decreased and at the 68-day of the trial, we decided to increase the OPU sampling interval from 3-4 to 7 days. It was therefore possible to distinguish two phases: a first phase (18 sessions), during which OPU was carried out twice weekly and a second phase (16 sessions) during which OPU sessions were performed weekly. This reduction did not modify the percentage of good quality COCs, while the incidence of grade D COCs decreased (P<0.01). Furthermore, embryo production was higher in the second phase, either if embryos were calculated on the total recovered COCs (8.3% vs. 21.4%; P<0.01) and on grade A+B COCs (13.0% vs. 32.1%; P<0.01), that supposedly should have given similar blastocyst yield. During the total period of the trial it was possible to distinguish a first period of 6 months (34 sessions) characterized by blastocyst production (0.36 blastocyst/buffalo/session), followed by an unproductive period of 3 months (12 sessions), during which embryos were not produced. During the first 6 months a higher (P<0.01) number of follicles (5.06 vs. 3.71), small follicles (3.38 vs. 2.07), total COCs (2.58 vs. 1.56) and good quality (A+B) COCs (1.51 vs. 0.94) per subject/session were recorded compared to the last 3 months. No Blastocyst were produced during the second period, even if the percentage of grade A+B COCs was similar to that recorded during the first period. In conclusion, buffalo cows submitted to repeated OPU sampling for a 9-month period, showed a decline of follicle recruitment and oocyte collection after the first two months of samplings. After 6-month of samplings, in spite of the quality grade of the collected oocytes, we found a drop in their developmental competence. Copyright © 2011 Elsevier B.V. All rights reserved.

Cyclic guanosine monophosphate does not inhibit gonadotropin-induced activation of mitogen-activated protein kinase 3/1 in pig cumulus-oocyte complexes.

PubMed

Blaha, Milan; Nemcova, Lucie; Prochazka, Radek

2015-01-07

Recent results indicate a key role for cyclic guanosine monophosphate (cGMP) in the regulation of oocyte meiotic arrest in preovulatory mammalian follicles. The aim of our study was to determine whether the resumption of oocyte meiosis and expansion of cumulus cells in isolated pig cumulus-oocyte complexes (COCs) can be blocked by a high intracellular concentration of cGMP, and whether this effect is mediated by a cGMP-dependent inhibition of mitogen-activated protein kinase 3/1 (MAPK3/1). The COCs were isolated from ovaries of slaughtered gilts and cultured in vitro in M199 supplemented with 5% fetal calf serum. The expression levels of the C-type natriuretic peptide (CNP) precursor (NPPC) and its receptor (NPR2) mRNAs during the culture of COCs were determined by real-time RT-PCR. To control the intracellular concentration of cGMP in the COCs, the culture medium was further supplemented with CNP or various concentrations of synthetic cGMP analogues; the concentration of cGMP in COCs was then assessed by ELISA. The effect of the drugs on oocyte maturation was assessed after 24 and 44 h of culture by determining nuclear maturation. The expansion of cumulus cells was assessed by light microscopy and the expression of cumulus expansion-related genes by real-time RT-PCR. A possible effect of cGMP on FSH-induced activation of MAPK3/1 was assessed by immunoblotting the COC proteins with phospho-specific and total anti-Erk1/2 antibodies. The COCs expressed NPPC and NPR2, the key components of cGMP synthesis, and produced a large amount of cGMP upon stimulation with exogenous CNP, which lead to a significant (P < 0.05) delay in oocyte meiotic resumption. The COCs also responded to cGMP analogues by inhibiting the resumption of oocyte meiosis. The inhibitory effect of cGMP on meiotic resumption was reversed by stimulating the COCs with FSH. However, high concentration of intracellular cGMP was not able to suppress FSH-induced activation of MAPK3/1 in cumulus cells, cumulus expansion and expression of expansion-related genes (P > 0.05). The findings of this study indicate that high cGMP concentrations inhibit the maturation of pig oocytes in vitro but the inhibitory mechanism does not involve the suppression of MAPK3/1 activation in cumulus cells.

[Simultaneous determination of cocaine and its metabolite ecgonine methyl ester in human blood using microwave extraction-gas chromatography].

PubMed

Wang, Xiaobo; Ye, Nengsheng; Wang, Jifen; Gu, Xuexin

2010-07-01

A method was developed for the simultaneous determination of cocaine (COC) and its metabolite ecgonine methyl ester (EME) in human blood using gas chromatography-mass spectrometry (GC-MS) and gas chromatography-flame ionization detection (GC-FID). The blood sample was prepared by microwave extraction (MWE). The optimal parameters of MWE were as follows: 6 mL of chloroform-isopropanol (9: 1, v/v) mixture as extraction solvent, the pH value of the sample was adjusted at 10.0 with 0.05 mol/L Na2CO3-NaHCO3 buffer, the extraction was performed at 40 degrees C for 6 min. The COC and EME in the extract were qualified using GC-MS and quantitated using GC-FID. The average recoveries of COC and EME were from 79.91% to 99.85%, the relative standard deviations were less than 3.10%, and the limits of detection (LOD) were 60 and 40 mg/L, respectively. In the method COC and EME were detected without derivatization. The method is rapid, accurate and sensitive, and can be used for the simultaneous determination of COC and EME in blood samples.

Effects on cycle control and bodyweight of the combined contraceptive ring, NuvaRing, versus an oral contraceptive containing 30 microg ethinyl estradiol and 3 mg drospirenone.

PubMed

Milsom, I; Lete, I; Bjertnaes, A; Rokstad, K; Lindh, I; Gruber, C J; Birkhäuser, M H; Aubeny, E; Knudsen, T; Bastianelli, C

2006-09-01

The objective of this study was to compare cycle control, cycle-related characteristics and bodyweight effects of NuvaRing with those of a combined oral contraceptive (COC) containing 30 microg of ethinyl estradiol and 3 mg of drospirenone. A randomized, multicentre, open-label trial in which 983 women were treated (intent-to-treat population) with NuvaRing or the COC for 13 cycles. Breakthrough bleeding or spotting during cycles 2-13 was in general less frequent with NuvaRing than that with the COC (4.7-10.4%) and showed a statistically significant odds ratio of 0.61 (95% confidence interval: 0.46, 0.80) with longitudinal analysis. Intended bleeding was significantly better for all cycles with NuvaRing (55.2-68.5%) than that with the COC (35.6-56.6%) (P < 0.01). Changes from baseline in mean bodyweight and body composition parameters were relatively small for both groups with no notable between-group differences. NuvaRing was associated with better cycle control than the COC, and there was no clinically relevant difference between the two groups in bodyweight.

Pedophilia and the gay movement.

PubMed

Sandfort, T

A history of literature and views existing within the COC (Cultural and Recreational Center), the major Dutch organization of homosexual men and women, regarding pedophilia and its relationship to homosexuality are discussed, beginning with definite separation between the pedophile and homosexual identities and ending with an abolishment of oppression towards pedophilia, for which the COC is in part responsible. The article argues that the homosexual identify is by no means a "constant" but a fluid identity, based on societal views and conditions. By accepting pedophilia, the COC hopefully will broaden the idea of the gay identity.

Systematic review and meta-analysis of the association of combined oral contraceptives on the risk of venous thromboembolism: The role of the progestogen type and estrogen dose.

PubMed

Oedingen, Carina; Scholz, Stefan; Razum, Oliver

2018-05-01

Currently available combined oral contraceptives (COC) reportedly increase the risk of venous thromboembolism (VTE). We aimed to quantify this risk considering both progestogen type and estrogen dose. PubMed, Embase and LIVIVO were searched for relevant publications until April 2017. Case-control and cohort studies including healthy women taking COC and assessing incident VTE as outcome were selected. Adjusted relative risks (RR) with 95% confidence intervals (CI) derived from random effects model using a generic inverse-variance approach are reported. Overall, 1,359 references were identified and 17 studies were included in the meta-analysis. The pooled RR of VTE was associated with various COC, with the association depending on their respective estrogen dose and progestogen type. Compared to the reference, levonorgestrel with 30-40 μg ethinylestradiol, the overall risk of VTE was higher for all other COC. Preparations with desogestrel with 30-40 μg estrogen showed the highest relative risk (RR: 1.46; 95% CI: 1.33-1.59), while RRs for drospirenone (30-40 μg ethinylestradiol) and desogestrel (30-40/20 μg ethinylestradiol) were lower. COC containing gestodene and cyproterone with 30-40 μg estrogen showed the lowest risk (RR: 1.27; 95% CI: 1.15-1.41 and RR: 1.29; 95% CI: 1.12-1.49, respectively). Compared to levonorgestrel with 30-40 μg ethinylestradiol, all COC showed a significantly increased VTE risk. The association varied depending on the progestogen type and the dose of estrogen. Our results suggest that the prescription of COC with the lowest possible dose of ethinylestradiol may help to avoid VTE cases among young, healthy women. Copyright © 2018 Elsevier Ltd. All rights reserved.

Impact of delipidated estrous sheep serum supplementation on in vitro maturation, cryotolerance and endoplasmic reticulum stress gene expression of sheep oocytes

PubMed Central

dos Santos Neto, Pedro C.; Cuadro, Federico; Bosolasco, Diego; Mulet, Ana P.; Crispo, Martina

2018-01-01

High lipid content of oocytes and embryos in domestic animals is one of the well-known factors associated with poor cryosurvival. Herein, we wanted to determine whether the use of delipidated estrous sheep serum during in vitro maturation (IVM) of ovine oocytes reduces the cytoplasmic lipid droplets content and improves embryo development and cryotolerance after vitrification. Cumulus oocytes complexes (COCs) were matured in vitro for 24 h in medium supplemented with whole or delipidated estrous sheep serum prior to vitrification. Neutral lipid present in lipid droplets of COCs, cleavage rate, embryo development rate on Day 6 and Day 8, and hatching rate on Day 8, were compared among experimental groups. Endoplasmic reticulum stress genes were evaluated in in vitro matured COCs under different lipid conditions prior to vitrification. The lipid droplets’ content (mean fluorescence intensity) of oocytes cultured with IVM media supplemented with delipidated serum was lower than COCs matured with whole serum (7.6 ± 1.7 vs. 22.8 ± 5.0 arbitrary units, respectively; P< 0.05). Despite IVM treatment, oocytes subjected to vitrification showed impaired competence compared with the non-vitrified groups (P<0.05). No significant differences in embryo production were observed in non-vitrified COCs after maturation in delipidated or whole serum (33.4±4.9 vs 31.9 ±4.2). COCs matured in delipidated serum and subjected to vitrification showed increased expression of ATF4, ATF6, GRP78, and CHOP10 genes (ER stress markers). Collectively, our results demonstrate that although supplementation of IVM medium with delipidated estrous sheep serum reduces the presence of cytoplasmic lipid droplets in oocytes after maturation, oocyte cryotolerance is not improved. Notably, the expression of genes associated with the unfolded protein response (UPR) was increased in COCs, with fewer lipid droplets subjected to vitrification, suggesting that oocyte cryopreservation is associated with ER stress and activation of adaptive responses. PMID:29912910

The effect of combined oral contraceptives and age on dysmenorrhoea: an epidemiological study.

PubMed

Lindh, Ingela; Ellström, Agneta Andersson; Milsom, Ian

2012-03-01

Combined oral contraceptives (COCs) are widely advocated as treatment for primary dysmenorrhoea, but their efficacy has been questioned in a Cochrane review. The aim of this study was to evaluate COCs and the influence of age on the severity of dysmenorrhoea. Postal questionnaires regarding weight/height, contraception, pregnancy history and other reproductive health factors were sent to random samples of 19-year-old women born in 1962 (n = 656), 1972 (n = 780) and 1982 (n = 666) resident in the city of Gothenburg in 1981, 1991 and 2001. The responders were assessed again 5 years later at the age of 24 years. Current severity of dysmenorrhoea was measured on each occasion by a verbal multidimensional scoring system (VMS) and by a visual analogue scale (VAS). The severity of dysmenorrhoea was lower (P< 0.0001) in COC users compared with non-users. In a longitudinal analysis of the severity of dysmenorrhoea, COC use and increasing age, independently of each other, were associated with the severity of dysmenorrhoea (COC use, VMS score: a reduction of 0.3 units/VAS: a reduction of 9 mm, both P< 0.0001; increasing age, VMS score: a reduction of 0.1 units per 5 years, P< 0.0001/VAS: a reduction of 5 mm per 5 years, P< 0.0001). Childbirth also reduced the severity of dysmenorrhoea (VAS, P< 0.01 with a reduction of 7 mm). Women from the 82-cohort reported a greater severity of dysmenorrhoea compared with the 62 and 72 cohorts at both 19 and 24 years of age. In this longitudinal case-control study, COC use and increasing age, independent of each other, reduced the severity of dysmenorrhoea. COC use reduced the severity of dysmenorrhoea more than increasing age and childbirth. There was a trend over time regarding the severity of dysmenorrhoea where women from the 82-cohort reported a greater severity of dysmenorrhoea compared with the 62 and 72 cohorts.

Efficacy and safety of the contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive in Chinese women: a 1-year randomised trial.

PubMed

Fan, Guang Sheng; Ren, Mulan; Di, Wen; Su, Ping; Chang, Qin; Wu, Shuying; Qin, Yun; Korver, Tjeerd; Marintcheva-Petrova, Maya; Yacik, Carol; McCrary Sisk, Christine; Wang, Guoqin

2016-08-01

The aim of the study was to assess the efficacy and tolerability of the monthly vaginal ring (NuvaRing; 15 μg ethinylestradiol [EE] and 120 μg etonogestrel per day) compared with a monophasic (21/7) combined oral contraceptive (COC) containing 30 μg EE and 3 mg drospirenone in healthy Chinese women aged 18-40 years. This was a phase III, open-label, randomised multicentre trial conducted in China. Participants received NuvaRing or COC for 13 cycles (3 weeks of ring/pill treatment followed by a 1-week ring-free/pill-free period). Contraceptive efficacy was assessed by in-treatment pregnancies and expressed by the Pearl Index (PI; number of pregnancies/100 woman-years of use). Cycle control was assessed by unscheduled (breakthrough) and absence of scheduled (withdrawal) bleeding events. Safety and tolerability were assessed throughout the study. Participants were randomised either to the NuvaRing (n = 732) or to the COC (n = 214); 588 (82.4%) and 182 (78.4%) participants, respectively, completed the study. There were 10 in-treatment pregnancies in the NuvaRing group (PI 1.92; 95% confidence interval [CI] 0.92, 3.53) and five in the COC group (PI 3.12; 95% CI 1.01, 7.29). Breakthrough bleeding/spotting ranged from 18.6% (Cycle 1) to 4.2% (Cycle 11) for NuvaRing and from 21.6% (Cycle 1) to 7.9% (Cycle 11) for COC. Absence of withdrawal bleeding ranged from 8.6% (Cycle 1) to 3.0% (Cycle 11) for NuvaRing and from 14.6% (Cycle 1) to 6.4% (Cycle 5) for COC. For NuvaRing and COC, respectively, 26.6% and 25.0% of participants had treatment-related adverse events, and 7.0% and 9.1% discontinued the study as a result. Once-monthly NuvaRing is efficacious and safe for use in Chinese women.

Microwave Absorption Properties of Co@C Nanofiber Composite for Normal and Oblique Incidence

NASA Astrophysics Data System (ADS)

Zhang, Junming; Wang, Peng; Chen, Yuanwei; Wang, Guowu; Wang, Dian; Qiao, Liang; Wang, Tao; Li, Fashen

2018-05-01

Co@C nanofibers have been prepared by an electrospinning technique. Uniform morphology of the nanofibers and good dispersion of the magnetic cobalt nanoparticles in the carbon fiber frame were confirmed by field-emission scanning electron microscopy and high-resolution transmission electron microscopy. The electromagnetic parameters of a composite absorber composed of Co@C nanofibers/paraffin were measured from 2 GHz to 15 GHz. The electromagnetic wave absorption properties were simulated and investigated in the case of normal and oblique incidence. In the normal case, the absorber achieved absorption performance of - 40 dB at 7.1 GHz. When the angle of incidence was increased to 60°, the absorption effect with reflection loss (RL) exceeding - 10 dB could still be obtained. These results demonstrate that the reported Co@C nanofiber absorber exhibits excellent absorption performance over a wide range of angle of incidence.

Evaluation of Castor Oil Cake Starch and Recovered Glycerol and Development of “Green” Composites Based on Those with Plant Fibers

PubMed Central

Guimarães, José Luis; Trindade Cursino, Ana Cristina; Ketzer Saul, Cyro; Sierrakowski, Maria Rita; Ramos, Luiz Pereira; Satyanarayana, Kestur Gundappa

2016-01-01

Continuous efforts are being made in some countries for the recovery of crude glycerin (RG/CG) and castor oil cake (COC), the two byproducts of biodiesel production. These are expected to help, not only in addressing environmental safety, but also in adding value to those byproducts, which otherwise may go to waste. Finding ways to utilize those byproducts underlines the main objective of this study. This paper presents the evaluation of (i) COC, glycerin and banana and sugarcane fibers for moisture content; (ii) COC for structural and thermal properties; and (iii) CG for its chemical characteristics. The possibility of using COC and CG with the selected fibers as reinforcement in the development of bio-composites is attempted through thermo-molding. Results revealed enhanced mechanical properties for these composites. The obtained results are discussed in terms of the observed morphology. PMID:28787878

Fate and risk assessment of heavy metals in residue from co-liquefaction of Camellia oleifera cake and sewage sludge in supercritical ethanol.

PubMed

Chen, Hongmei; Zhai, Yunbo; Xu, Bibo; Xiang, Bobin; Zhu, Lu; Qiu, Lei; Liu, Xiaoting; Li, Caiting; Zeng, Guangming

2014-09-01

The fate and risk assessment of heavy metals (HMs) in solid residue from co-liquefaction of sewage sludge (SS) and Camellia oleifera cake (COC) in supercritical ethanol (SCE) were investigated. SCE effectively stabilized HMs in solid residues and a better stabilization was presented on Zn than Cd. Moreover, SCE significantly transformed Cd, Cu and Zn into F4, which reduced the risk to the environment. Furthermore, risk assessments of Igeo, Er(i), RI and RAC demonstrated that the addition of COC was beneficial to the contamination decrement of HMs since pollution levels of HMs all decreased after treatment, and the lowest pollution level was obtained with SC-350. Therefore, SS treated by SCE with the addition of COC could be a promising technology for disposal of SS, especially considering the safety of COC as regards HMs problem. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of a cocaine hydrolase engineered from human butyrylcholinesterase on metabolic profile of cocaine in rats.

PubMed

Chen, Xiabin; Zheng, Xirong; Zhou, Ziyuan; Zhan, Chang-Guo; Zheng, Fang

2016-11-25

Accelerating cocaine metabolism through enzymatic hydrolysis at cocaine benzoyl ester is recognized as a promising therapeutic approach for cocaine abuse treatment. Our more recently designed A199S/F227A/S287G/A328W/Y332G mutant of human BChE, denoted as cocaine hydrolase-3 (CocH3), has a considerably improved catalytic efficiency against cocaine and has been proven active in blocking cocaine-induced toxicity and physiological effects. In the present study, we have further characterized the effects of CocH3 on the detailed metabolic profile of cocaine in rats administrated intravenously (IV) with 5 mg/kg cocaine, demonstrating that IV administration of 0.15 mg/kg CocH3 dramatically changed the metabolic profile of cocaine. Without CocH3 administration, the dominant cocaine-metabolizing pathway in rats was cocaine methyl ester hydrolysis to benzoylecgonine (BZE). With the CocH3 administration, the dominant cocaine-metabolizing pathway in rats became cocaine benzoyl ester hydrolysis to ecgonine methyl ester (EME), and the other two metabolic pathways (i.e. cocaine methyl ester hydrolysis to BZE and cocaine oxidation to norcocaine) became insignificant. The CocH3-catalyzed cocaine benzoyl ester hydrolysis to EME was so efficient such that the measured maximum blood cocaine concentration (∼38 ng/ml) was significantly lower than the threshold blood cocaine concentration (∼72 ng/ml) required to produce any measurable physiological effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Oxidative stress as a damage mechanism in porcine cumulus-oocyte complexes exposed to malathion during in vitro maturation.

PubMed

Flores, Diana; Souza, Verónica; Betancourt, Miguel; Teteltitla, Mario; González-Márquez, Humberto; Casas, Eduardo; Bonilla, Edmundo; Ramírez-Noguera, Patricia; Gutiérrez-Ruíz, María Concepción; Ducolomb, Yvonne

2017-06-01

Malathion is one of the most commonly used insecticides. Recent findings have demonstrated that it induces oxidative stress in somatic cells, but there are not enough studies that have demonstrated this effect in germ cells. Malathion impairs porcine oocyte viability and maturation, but studies have not shown how oxidative stress damages maturation and which biochemical mechanisms are affected in this process in cumulus-oocyte complexes (COCs). The aims of the present study were to determine the amount of oxidative stress produced by malathion in porcine COCs matured in vitro, to define how biochemical mechanisms affect this process, and determine whether trolox can attenuate oxidative damage. Sublethal concentrations 0, 750, and 1000 µM were used to evaluate antioxidant enzyme expressions, reactive oxygen species (ROS production), protein oxidation, and lipid peroxidation, among other oxidation products. COCs viability and oocyte maturation decreased in a concentration-dependent manner. Malathion increased Cu, Zn superoxide dismutase (SOD1), glutathione-S-transferase (GST), and glucose 6 phosphate dehydrogenase (G6PD) protein level and decreased glutathione peroxidase (GSH-Px) and catalase (CAT) protein level. Species reactives of oxygen (ROS), protein oxidation and Thiobarbituric acid reactive substances (TBARS) levels increased in COCs exposed to the insecticide, but when COCs were pre-treated with the trolox (50 µM) 30 min before and during malathion exposure, these parameters decreased down to control levels. This study showed that malathion has a detrimental effect on COCs during in vitro maturation, inducing oxidative stress, while trolox attenuated malathion toxicity by decreasing oxidative damage. © 2017 Wiley Periodicals, Inc.

Simultaneous analyses of cocaine, cocaethylene, and their possible metabolic and pyrolytic products.

PubMed

Cardona, Patrick S; Chaturvedi, Arvind K; Soper, John W; Canfield, Dennis V

2006-02-10

A method was developed for simultaneously analyzing cocaine (COC), benzoylecgonine (BZE), norbenzoylecgonine (BNE), norcocaine (NCOC), ecgonine (ECG), ecgonine methyl ester (EME), m-hydroxybenzoylecgonine (HBZE), anhydroecgonine methyl ester (AEME), cocaethylene (CE), norcocaethylene (NCE), and ecgonine ethyl ester (EEE) in blood, urine, and muscle. Available deuterated analogs of these analytes were used as internal standards. Proteins from blood and muscle homogenate were precipitated with cold acetonitrile. After the removal of acetonitrile by evaporation, the supernatants and urine were subjected to solid-phase extraction. The eluted analytes were converted to their hydrochloride salts and derivatized with pentafluoropropionic anhydride and 2,2,3,3,3-pentafluoro-1-propanol. The derivatized products were analyzed by a gas chromatograph (GC)/mass spectrometer by selected ion monitoring. The limit of detection (LOD) for COC, BZE, NCOC, EME, CE, NCE, and EEE was 2ng/ml, while the LODs for BNE, ECG, HBZE, and AEME were 25, 640, 50, and 13 ng/ml, respectively. This method was successfully applied in analyzing 13 case samples from aviation accident pilot fatalities and motor vehicle operators. AEME concentrations found in the 13 samples were consistent with those produced solely by the GC inlet pyrolysis of COC controls in blood. Anhydroecgonine cannot be used as a marker for the abuse of COC by smoking because it is also pyrolytically produced from COC metabolites on the GC inlet. The developed method can be effectively adopted for analyzing COC and related compounds in urine, blood, and muscle by a single extraction with increased sensitivity through formation of hydrochloride salts and using a one-step derivatization.

Unrestricted access to methamphetamine or cocaine in the past is associated with increased current use

PubMed Central

Culbertson, C.; De La Garza, R.; Costello, M.; Newton, T. F.

2009-01-01

Laboratory animals allowed to self-administer stimulants for extended periods of time escalate drug intake compared to animals that self-administer under temporally limited conditions. To our knowledge, this phenomenon has not been systematically investigated in humans. We interviewed 106 (77 male, 29 female) methamphetamine (Meth) and 96 (81 male, 15 female) cocaine (Coc) users to determine if they had experienced discrete period(s) of unrestricted access to unlimited quantities of Meth or Coc in the past. Fifty-eight Meth users and 53 Coc users reported having a discrete period of unrestricted access in the past, but not in the present. Meth-using participants with a prior history of unrestricted access reported significantly more current Meth use, compared to Meth users with no prior history of unrestricted access. Specifically, these participants reported more days used in the past 30 d, more days of use per week, greater use per day and greater total use per week (p<0.05 for each). Coc-using participants with a prior history of unrestricted access also reported significantly more current Coc use, compared to Coc users with no prior history of unrestricted access. This was true across all measures of current use for these participants, including more days used in the past 30 d, more days of use per week, greater use per day, and higher total use per week (p<0.02 for each). Taken together, these results suggest that a history of unrestricted access to stimulants is associated with long-lasting increases in stimulant use. PMID:19220922

Ozone-Induced Responses in Croton floribundus Spreng. (Euphorbiaceae): Metabolic Cross-Talk between Volatile Organic Compounds and Calcium Oxalate Crystal Formation

PubMed Central

Cardoso-Gustavson, Poliana; Bolsoni, Vanessa Palermo; de Oliveira, Debora Pinheiro; Guaratini, Maria Tereza Gromboni; Aidar, Marcos Pereira Marinho; Marabesi, Mauro Alexandre; Alves, Edenise Segala; de Souza, Silvia Ribeiro

2014-01-01

Here, we proposed that volatile organic compounds (VOC), specifically methyl salicylate (MeSA), mediate the formation of calcium oxalate crystals (COC) in the defence against ozone (O3) oxidative damage. We performed experiments using Croton floribundus, a pioneer tree species that is tolerant to O3 and widely distributed in the Brazilian forest. This species constitutively produces COC. We exposed plants to a controlled fumigation experiment and assessed biochemical, physiological, and morphological parameters. O3 induced a significant increase in the concentrations of constitutive oxygenated compounds, MeSA and terpenoids as well as in COC number. Our analysis supported the hypothesis that ozone-induced VOC (mainly MeSA) regulate ROS formation in a way that promotes the opening of calcium channels and the subsequent formation of COC in a fast and stable manner to stop the consequences of the reactive oxygen species in the tissue, indeed immobilising the excess calcium (caused by acute exposition to O3) that can be dangerous to the plant. To test this hypothesis, we performed an independent experiment spraying MeSA over C. floribundus plants and observed an increase in the number of COC, indicating that this compound has a potential to directly induce their formation. Thus, the tolerance of C. floribundus to O3 oxidative stress could be a consequence of a higher capacity for the production of VOC and COC rather than the modulation of antioxidant balance. We also present some insights into constitutive morphological features that may be related to the tolerance that this species exhibits to O3. PMID:25165889

Differential expression and localization of glycosidic residues in in vitro- and in vivo-matured cumulus-oocyte complexes in equine and porcine species.

PubMed

Accogli, Gianluca; Douet, Cécile; Ambruosi, Barbara; Martino, Nicola Antonio; Uranio, Manuel Filioli; Deleuze, Stefan; Dell'Aquila, Maria Elena; Desantis, Salvatore; Goudet, Ghylène

2014-12-01

Glycoprotein oligosaccharides play major roles during reproduction, yet their function in gamete interactions is not fully elucidated. Identification and comparison of the glycan pattern in cumulus-oocyte complexes (COCs) from species with different efficiencies of in vitro spermatozoa penetration through the zona pellucida (ZP) could help clarify how oligosaccharides affect gamete interactions. We compared the expression and localization of 12 glycosidic residues in equine and porcine in vitro-matured (IVM) and preovulatory COCs by means of lectin histochemistry. The COCs glycan pattern differed between animals and COC source (IVM versus preovulatory). Among the 12 carbohydrate residues investigated, the IVM COCs from these two species shared: (a) sialo- and βN-acetylgalactosamine (GalNAc)-terminating glycans in the ZP; (b) sialylated and fucosylated glycans in cumulus cells; and (c) GalNAc and N-acetylglucosamine (GlcNAc) glycans in the ooplasm. Differences in the preovulatory COCs of the two species included: (a) sialoglycans and GlcNAc terminating glycans in the equine ZP versus terminal GalNAc and internal GlcNAc in the porcine ZP; (b) terminal galactosides in equine cumulus cells versus terminal GlcNAc and fucose in porcine cohorts; and (c) fucose in the mare ooplasm versus lactosamine and internal GlcNAc in porcine oocyte cytoplasm. Furthermore, equine and porcine cumulus cells and oocytes contributed differently to the synthesis of ZP glycoproteins. These results could be attributed to the different in vitro fertilization efficiencies between these two divergent, large-animal models. © 2014 Wiley Periodicals, Inc.

[Recertification and continuing education of NCCAOM Diplomates of Acupuncture and Oriental Medicine].

PubMed

Tian, Kaiyu; Tian, Yunyi; Li, Susu; Chen, Qiang; Yuan, Teng

2017-05-12

Diplomates certificated by National Certification Commission for Acupuncture and Oriental Medicine (NCCAOM) are needed to be recertified every four years. The certificate will be valid after 60 points of provided professional development activity (PDA). The different validity status of NCCAOM certificates, ways of participating continuing education and the requirements of PDA points including core competencies and professional enhancement (PE) are introduced in this paper.

Angles-centroids fitting calibration and the centroid algorithm applied to reverse Hartmann test

NASA Astrophysics Data System (ADS)

Zhao, Zhu; Hui, Mei; Xia, Zhengzheng; Dong, Liquan; Liu, Ming; Liu, Xiaohua; Kong, Lingqin; Zhao, Yuejin

2017-02-01

In this paper, we develop an angles-centroids fitting (ACF) system and the centroid algorithm to calibrate the reverse Hartmann test (RHT) with sufficient precision. The essence of ACF calibration is to establish the relationship between ray angles and detector coordinates. Centroids computation is used to find correspondences between the rays of datum marks and detector pixels. Here, the point spread function of RHT is classified as circle of confusion (CoC), and the fitting of a CoC spot with 2D Gaussian profile to identify the centroid forms the basis of the centroid algorithm. Theoretical and experimental results of centroids computation demonstrate that the Gaussian fitting method has a less centroid shift or the shift grows at a slower pace when the quality of the image is reduced. In ACF tests, the optical instrumental alignments reach an overall accuracy of 0.1 pixel with the application of laser spot centroids tracking program. Locating the crystal at different positions, the feasibility and accuracy of ACF calibration are further validated to 10-6-10-4 rad root-mean-square error of the calibrations differences.

Laboratory Information Management System Chain of Custody: Reliability and Security

PubMed Central

Tomlinson, J. J.; Elliott-Smith, W.; Radosta, T.

2006-01-01

A chain of custody (COC) is required in many laboratories that handle forensics, drugs of abuse, environmental, clinical, and DNA testing, as well as other laboratories that want to assure reliability of reported results. Maintaining a dependable COC can be laborious, but with the recent establishment of the criteria for electronic records and signatures by US regulatory agencies, laboratory information management systems (LIMSs) are now being developed to fully automate COCs. The extent of automation and of data reliability can vary, and FDA- and EPA-compliant electronic signatures and system security are rare. PMID:17671623

Performance of a pentafluorophenylpropyl stationary phase for the electrospray ionization high-performance liquid chromatography-mass spectrometry-mass spectrometry assay of cocaine and its metabolite ecgonine methyl ester in human urine.

PubMed

Needham, S R; Jeanville, P M; Brown, P R; Estape, E S

2000-10-01

A pentafluorophenylpropyl (PFPP) bonded silica column has been used for the high-performance liquid chromatography-electrospray ionization-mass spectrometry-mass spectrometry assay (HPLC-ESI-MS-MS) of cocaine (COC) and its metabolite, ecgonine methyl ester (EME) in human urine. COC and EME were used as model basic solutes to demonstrate that a PFPP phase yields excellent results for the assay and validation of drugs in biological fluids. The assay was linear over three orders of magnitude (1.0-1000 ng/ml) and precision and accuracy of the assay was 4 and 15%, respectively. The limit of detection (LOD) for COC and EME was 1.6 and 2.8 pg on column, respectively. In addition, only a simple 1:10 dilution of the urine was necessary for the sample preparation procedure thus saving time on a laborious extraction step. The major advantage of the PFPP phase was the enhancement of the ESI-MS signal by providing good retention and good peak shape of COC and EME with a mobile phase of 90% acetonitrile. The MS signal for COC was a factor of 12 times greater on the PFPP phase than on the C18 phase.

Solid-phase microfibers based on polyethylene glycol modified single-walled carbon nanotubes for the determination of chlorinated organic carriers in textiles.

PubMed

Zhang, Wei-Ya; Sun, Yin; Wang, Cheng-Ming; Wu, Cai-Ying

2011-09-01

Based on polyethylene glycol modified single-walled carbon nanotubes, a novel sol-gel fiber coating was prepared and applied to the headspace microextraction of chlorinated organic carriers (COCs) in textiles by gas chromatography-electron capture detection. The preparation of polyethylene glycol modified single-walled carbon nanotubes and the sol-gel fiber coating process was stated and confirmed by infrared spectra, Raman spectroscopy, and scanning electron microscopy. Several parameters affecting headspace microextraction, including extraction temperature, extraction time, salting-out effect, and desorption time, were optimized by detecting 11 COCs in simulative sweat samples. Compared with the commercial solid-phase microextraction fibers, the sol-gel polyethylene glycol modified single-walled carbon nanotubes fiber showed higher extraction efficiency, better thermal stability, and longer life span. The method detection limits for COCs were in the range from 0.02 to 7.5 ng L(-1) (S/N = 3). The linearity of the developed method varied from 0.001 to 50 μg L(-1) for all analytes, with coefficients of correlation greater than 0.974. The developed method was successfully applied to the analysis of trace COCs in textiles, the recoveries of the analytes indicated that the developed method was considerably useful for the determination of COCs in ecological textile samples.

Ultrathin Carbon with Interspersed Graphene/Fullerene-like Nanostructures: A Durable Protective Overcoat for High Density Magnetic Storage.

PubMed

Dwivedi, Neeraj; Satyanarayana, Nalam; Yeo, Reuben J; Xu, Hai; Ping Loh, Kian; Tripathy, Sudhiranjan; Bhatia, Charanjit S

2015-06-25

One of the key issues for future hard disk drive technology is to design and develop ultrathin (<2 nm) overcoats with excellent wear- and corrosion protection and high thermal stability. Forming carbon overcoats (COCs) having interspersed nanostructures by the filtered cathodic vacuum arc (FCVA) process can be an effective approach to achieve the desired target. In this work, by employing a novel bi-level surface modification approach using FCVA, the formation of a high sp(3) bonded ultrathin (~1.7 nm) amorphous carbon overcoat with interspersed graphene/fullerene-like nanostructures, grown on magnetic hard disk media, is reported. The in-depth spectroscopic and microscopic analyses by high resolution transmission electron microscopy, scanning tunneling microscopy, time-of-flight secondary ion mass spectrometry, and Raman spectroscopy support the observed findings. Despite a reduction of ~37% in COC thickness, the FCVA-processed thinner COC (~1.7 nm) shows promising functional performance in terms of lower coefficient of friction (~0.25), higher wear resistance, lower surface energy, excellent hydrophobicity and similar/better oxidation corrosion resistance than current commercial COCs of thickness ~2.7 nm. The surface and tribological properties of FCVA-deposited COC was further improved after deposition of lubricant layer.

Ultrathin Carbon with Interspersed Graphene/Fullerene-like Nanostructures: A Durable Protective Overcoat for High Density Magnetic Storage

NASA Astrophysics Data System (ADS)

Dwivedi, Neeraj; Satyanarayana, Nalam; Yeo, Reuben J.; Xu, Hai; Ping Loh, Kian; Tripathy, Sudhiranjan; Bhatia, Charanjit S.

2015-06-01

One of the key issues for future hard disk drive technology is to design and develop ultrathin (<2 nm) overcoats with excellent wear- and corrosion protection and high thermal stability. Forming carbon overcoats (COCs) having interspersed nanostructures by the filtered cathodic vacuum arc (FCVA) process can be an effective approach to achieve the desired target. In this work, by employing a novel bi-level surface modification approach using FCVA, the formation of a high sp3 bonded ultrathin (~1.7 nm) amorphous carbon overcoat with interspersed graphene/fullerene-like nanostructures, grown on magnetic hard disk media, is reported. The in-depth spectroscopic and microscopic analyses by high resolution transmission electron microscopy, scanning tunneling microscopy, time-of-flight secondary ion mass spectrometry, and Raman spectroscopy support the observed findings. Despite a reduction of ~37 % in COC thickness, the FCVA-processed thinner COC (~1.7 nm) shows promising functional performance in terms of lower coefficient of friction (~0.25), higher wear resistance, lower surface energy, excellent hydrophobicity and similar/better oxidation corrosion resistance than current commercial COCs of thickness ~2.7 nm. The surface and tribological properties of FCVA-deposited COC was further improved after deposition of lubricant layer.

Efficacy of Acupuncture versus Combined Oral Contraceptive Pill in Treatment of Moderate-to-Severe Dysmenorrhea: A Randomized Controlled Trial

PubMed Central

Sriprasert, Intira; Suerungruang, Suparerk; Athilarp, Porntip; Matanasarawoot, Anuchart

2015-01-01

This open-label randomized controlled trial was designed to compare the efficacy of acupuncture and combined oral contraceptive (COC) pill in treating moderate-to-severe primary dysmenorrhea. Fifty-two participants were randomly assigned to receive either acupuncture (n = 27) or COC (n = 25) for three menstrual cycles. Mefenamic acid was prescribed as a recue analgesic drug with both groups. The statistical approach used for efficacy and safety assessments was intention-to-treat analysis. By the end of the study, both treatments had resulted in significant improvement over baselines in all outcomes, that is, maximal dysmenorrhea pain scores, days suffering from dysmenorrhea, amount of rescue analgesic used, and quality of life assessed by SF-36 questionnaire. Over the three treatment cycles, COC caused greater reduction in maximal pain scores than acupuncture, while improvements in the remaining outcomes were comparable. Responders were defined as participants whose maximal dysmenorrhea pain scores decreased at least 33% below their baseline. Response rates following both interventions at the end of the study were not statistically different. Acupuncture commonly caused minimal local side effects but did not cause any hormone-related side effects as did COC. In conclusion, acupuncture is an alternative option for relieving dysmenorrhea, especially when COC is not a favorable choice. PMID:26346199

Ultrathin Carbon with Interspersed Graphene/Fullerene-like Nanostructures: A Durable Protective Overcoat for High Density Magnetic Storage

PubMed Central

Dwivedi, Neeraj; Satyanarayana, Nalam; Yeo, Reuben J.; Xu, Hai; Ping Loh, Kian; Tripathy, Sudhiranjan; Bhatia, Charanjit S.

2015-01-01

One of the key issues for future hard disk drive technology is to design and develop ultrathin (<2 nm) overcoats with excellent wear- and corrosion protection and high thermal stability. Forming carbon overcoats (COCs) having interspersed nanostructures by the filtered cathodic vacuum arc (FCVA) process can be an effective approach to achieve the desired target. In this work, by employing a novel bi-level surface modification approach using FCVA, the formation of a high sp3 bonded ultrathin (~1.7 nm) amorphous carbon overcoat with interspersed graphene/fullerene-like nanostructures, grown on magnetic hard disk media, is reported. The in-depth spectroscopic and microscopic analyses by high resolution transmission electron microscopy, scanning tunneling microscopy, time-of-flight secondary ion mass spectrometry, and Raman spectroscopy support the observed findings. Despite a reduction of ~37 % in COC thickness, the FCVA-processed thinner COC (~1.7 nm) shows promising functional performance in terms of lower coefficient of friction (~0.25), higher wear resistance, lower surface energy, excellent hydrophobicity and similar/better oxidation corrosion resistance than current commercial COCs of thickness ~2.7 nm. The surface and tribological properties of FCVA-deposited COC was further improved after deposition of lubricant layer. PMID:26109208

Comparison of Drospirenone- with Cyproterone Acetate-Containing Oral Contraceptives, Combined with Metformin and Lifestyle Modifications in Women with Polycystic Ovary Syndrome and Metabolic Disorders: A Prospective Randomized Control Trial.

PubMed

Wang, Qiu-Yi; Song, Yong; Huang, Wei; Xiao, Li; Wang, Qiu-Shi; Feng, Gui-Mei

2016-04-20

While combined oral contraceptives (COCs) are commonly used to treat polycystic ovary syndrome (PCOS), comparative data regarding metabolic effects of different progestogens on this patient population are missing. This study aimed to compare the different effects of drospirenone (DRP)-containing COCs with cyproterone acetate (CPA)-containing COCs, combined with metformin and lifestyle modifications in women with PCOS and metabolic disorders. Ninety-nine women with PCOS and a metabolic disorder between January 2011 and January 2013 were enrolled into this prospective randomized clinical trial. Participants were randomized into two groups such as DRP-containing COCs, and CPA-containing COCs. Participants took COCs cyclically for 6 months, combined with metformin administration (1.5 g/d) and lifestyle modifications (diet and exercise). Clinical measures and biochemical and hormone profiles were compared. Comparisons for continuous variables were evaluated with paired and unpaired Student's t-tests. The Wilcoxon signed rank test was used when the data were not normally distributed. Analysis of covariance was used to control for age, body mass index (BMI), and baseline data of each analyzed parameter when compared between the two groups. A total of 68 patients have completed the study. The combination regimen of COCs, metformin, and lifestyle modifications in these patients resulted in a significant decrease in BMI, acne, and hirsutism scores when compared to baseline levels in both groups (P < 0.05). Blood pressure (BP) was significantly different in the CPA group when compared to baseline (75.14 ± 6.77 mmHg vs. 80.70 ± 5.60 mmHg, P < 0.01), and after 6 months of treatment, only the change in systolic BP was significantly different between the two groups (4.00 [-6.00, 13.00] mmHg vs. -3.50 [-13.00, 9.00] mmHg, P = 0.009). Fasting glucose, fasting insulin, and homeostasis model assessment-insulin resistance decreased significantly in the DRP group (5.40 ± 0.41 mmol/L vs. 5.21 ± 0.32 mmol/L, P = 0.041; 13.90 [10.50, 18.40] μU/ml vs. 10.75 [8.60, 13.50] μU/ml, P = 0.020; 3.74 [2.85, 4.23] vs. 2.55 [1.92, 3.40], P = 0.008) but did not differ between the two groups. While individual lipid profiles increased in both groups, no statistically significant difference was observed. DRP-containing COCs combined with metformin and lifestyle modifications could better control BP and correct carbohydrate metabolism in women with PCOS and metabolic disorders compared with CPA-containing COCs. Chinese Clinical Trial Registry, ChiCTR-TRC-11001143; http://www.chictr.org.cn/showproj.aspx?proj=8395.

Skin patch and vaginal ring versus combined oral contraceptives for contraception.

PubMed

Lopez, Laureen M; Grimes, David A; Gallo, Maria F; Stockton, Laurie L; Schulz, Kenneth F

2013-04-30

The delivery of combination contraceptive steroids from a transdermal contraceptive patch or a contraceptive vaginal ring offers potential advantages over the traditional oral route. The transdermal patch and vaginal ring could require a lower dose due to increased bioavailability and improved user compliance. To compare the contraceptive effectiveness, cycle control, compliance (adherence), and safety of the contraceptive patch or the vaginal ring versus combination oral contraceptives (COCs). Through February 2013, we searched MEDLINE, POPLINE, CENTRAL, LILACS, ClinicalTrials.gov, and ICTRP for trials of the contraceptive patch or the vaginal ring. Earlier searches also included EMBASE. For the initial review, we contacted known researchers and manufacturers to identify other trials. We considered randomized controlled trials comparing a transdermal contraceptive patch or a contraceptive vaginal ring with a COC. Data were abstracted by two authors and entered into RevMan. For dichotomous variables, the Peto odds ratio (OR) with 95% confidence intervals (CI) was calculated. For continuous variables, the mean difference was computed. We also assessed the quality of evidence for this review. We found 18 trials that met our inclusion criteria. Of six patch studies, five examined the marketed patch containing norelgestromin plus ethinyl estradiol (EE); one studied a patch in development that contains levonorgestrel (LNG) plus EE. Of 12 vaginal ring trials, 11 examined the same marketing ring containing etonogestrel plus EE; one studied a ring being developed that contains nesterone plus EE.Contraceptive effectiveness was not significantly different for the patch or ring versus the comparison COC. Compliance data were limited. Patch users showed better compliance than COC users in three trials. For the norelgestromin plus EE patch, ORs were 2.05 (95% CI 1.83 to 2.29) and 2.76 (95% CI 2.35 to 3.24). In the levonorgestrel plus EE patch report, patch users were less likely to have missed days of therapy (OR 0.36; 95% CI 0.25 to 0.51). Of four vaginal ring trials, one found ring users had more noncompliance (OR 3.99; 95% CI 1.87 to 8.52), while another showed more compliance with the regimen (OR 1.67; 95% CI 1.04 to 2.68).More patch users discontinued early than COC users. ORs from two meta-analyses were 1.59 (95% CI 1.26 to 2.00) and 1.56 (95% CI 1.18 to 2.06) and another trial showed OR 2.57 (95% CI 0.99 to 6.64). Patch users also had more discontinuation due to adverse events than COC users. Users of the norelgestromin-containing patch reported more breast discomfort, dysmenorrhea, nausea, and vomiting. In the levonorgestrel-containing patch trial, patch users reported less vomiting, headaches, and fatigue.Of 11 ring trials with discontinuation data, two showed the ring group discontinued less than the COC group: OR 0.32 (95% CI 0.16 to 0.66) and OR 0.52 (95% CI 0.31 to 0.88). Ring users were less likely to discontinue due to adverse events in one study (OR 0.32; 95% CI 0.15 to 0.70). Compared to the COC users, ring users had more vaginitis and leukorrhea but less vaginal dryness. Ring users also reported less nausea, acne, irritability, depression, and emotional lability than COC users.For cycle control, only one trial study showed a significant difference. Women in the patch group were less likely to have breakthrough bleeding and spotting. Seven ring studies had bleeding data; four trials showed the ring group generally had better cycle control than the COC group. Effectiveness was not significantly different for the methods compared. Pregnancy data were available from half of the patch trials but two-thirds of ring trials. The patch could lead to more discontinuation than the COC. The patch group had better compliance than the COC group. Compliance data came from half of the patch studies and one-third of the ring trials. Patch users had more side effects than the COC group. Ring users generally had fewer adverse events than COC users but more vaginal irritation and discharge.The quality of the evidence for this review was considered low for the patch and moderate for the ring. The main reasons for downgrading were lack of information on the randomization sequence generation or allocation concealment, the outcome assessment methods, high losses to follow up, and exclusions after randomization.

SMART Fires: A COTS Approach to Tactical Fire Support Using a Smartphone

DTIC Science & Technology

2011-09-01

Battalion Landing Team C2 Command and Control C2PC Command and Control Personal Computer CAC Common Access Card COC Combat Operation Center COIN...functionality to way-points. It is currently available on the iTunes App Store for $5.99 (Tactical NAV, 2010). 11 MILS are a unit...download on both the iTunes App Store and the Android Marketplace. Apps for the Army (A4A) also created a repository for the applications submitted, along

United States Air Force 611th Air Support Group/Civil Engineering Squadron Elmendorf AFB, Alaska. Risk assessment Bullen Point Radar Installation, Alaska. Final report

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

Karmi, S.

1996-03-18

This document contains the baseline human health risk assessment and the ecological risk assessment (ERA) for the Bullen Point Distant Early Warning (DEW) Line radar installation. Five sites at the Bullen Point radar installation underwent remedial investigations (RIs) during the summer of 1993. The presence of chemical contamination in the soil, sediments, and surface water at the installation was evaluated and reported in the Bullen Point Remedial Investigation/Feasibility Study (RI/FS) (U.S. Air Force 1996). The analytical data reported in the RI/FS form the basis for the human health and ecological risk assessments. The primary chemicals of concern (COCs) at themore » five sites are diesel and gasoline from past spills and/or leaks.« less

Cognition and impulsivity in adults with attention deficit hyperactivity disorder with and without cocaine and/or crack dependence.

PubMed

Miguel, Carmen S; Martins, Paula A; Moleda, Nathalya; Klein, Margarete; Chaim-Avancini, Tiffany; Gobbo, Maria A; Alves, Tania M; Silva, Maria A; Louzã, Mario R

2016-03-01

Substance use disorder (SUD) is a common comorbidity in adults with attention deficit-hyperactivity disorder (ADHD). However,there have been few studies on cognitive profiles of these patients. Impulsivity is also commonly increased in both disorders. The central aim of this study was to compare cognition and impulsivity in subjects who had ADHD and cocaine dependence (ADHD+COC group) to those with ADHD only (ADHD-noSUD group). We hypothesized that the ADHD+COC group would show more marked cognitive dysfunction and greater impulsivity than their counterparts with ADHD only. A total of 70 adult patients diagnosed with ADHD according to (DSM-IV-TR) criteria were enrolled; 36 with ADHD+COC and 34 with ADHD-noSUD. All study participants were evaluated with a sociodemographic questionnaire; the Mini International Neuropsychiatric Interview; the Adult ADHD Self-Report Scale; the Addiction Severity Index; the Alcohol, Smoking and Substance Involvement Screening Test; the Barratt Impulsiveness Scale; and a comprehensive neurocognitive battery. Compared to individuals with ADHD-noSUD, ADHD+COC individuals had significantly lower mean IQ and higher motor impulsivity. On average, the ADHD+COC group also performed more poorly on tasks assessing verbal skills, vigilance, implicit learning during decision making, and ADHD-noSUD performed more poorly on selective attention, information processing, and visual search. Our results support the integrative theory of ADHD based on the cognitive and affective neuroscience model, and suggests that ADHD-noSUD patients have impairments in cognitive regulation, while ADHD+COC patients have impairments in both cognitive and affective regulation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Combined hormonal contraceptives: prescribing patterns, compliance, and benefits versus risks.

PubMed

Brynhildsen, Jan

2014-10-01

Combined hormonal contraceptives [combined oral contraceptives (COCs)] have been available for over 50 years and the impact of this invention may not be overestimated. Today over 100 million women are current users and in Western Europe and the United States approximately 80% of women of fertile ages can be considered as ever-users. Over the years several drawbacks have been identified and media alarms on risks are frequently presented, resulting in suboptimal compliance and low compliance and continuation rates. Poor compliance and discontinuation is a big problem and is not generally identified by prescribers. During ideal use COCs offer very good protection against unwanted pregnancies, however there is a big problem with compliance and continuation and thus the 'real-life' efficacy is much lower. Reasons for poor compliance include side effects and fear of side effects and it is crucial that the prescriber gives the individual woman thorough and balanced information on the benefits and risks. Most well known is the increased risk of venous thromboembolism, but also an elevated risk of arterial thrombosis and several types of cancer has been reported. The risk estimates are low but according to the large number of users a substantial number of extra cases will occur. However, use of COCs also offers several additional health benefits with significant impact on morbidity and quality of life. COC use is associated with a substantial decrease in the risk of ovarian cancer, endometrial cancer and colorectal cancer. Moreover, COCs are a major option of treatment for women suffering from heavy menstrual bleeding and dysmenorrhea as well as hirsutism and acne vulgaris. The net effect of the additional health effects of COC- use may very well be positive, i.e. a slight increase in life expectancy.

Monoaminergic Psychomotor Stimulants: Discriminative Stimulus Effects and Dopamine Efflux

PubMed Central

Desai, Rajeev I.; Paronis, Carol A.; Martin, Jared; Desai, Ramya

2010-01-01

The present studies were conducted to investigate the relationship between discriminative stimulus effects of indirectly acting monoaminergic psychostimulants and their ability to increase extracellular levels of dopamine (DA) in the nucleus accumbens (NAcb) shell. First, the behavioral effects of methamphetamine (MA), cocaine (COC), 1-[2-[bis(4-fluorophenyl-)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR 12909), d-amphetamine, and methylphenidate were established in rats trained to discriminate intraperitoneal injections of 0.3 mg/kg MA from saline. In other studies, in vivo microdialysis was used to determine the effects of MA, COC, and GBR 12909 on extracellular DA levels in the NAcb shell. Results show that all drugs produced dose-related and full substitution for the discriminative stimulus effects of 0.3 mg/kg MA. In microdialysis studies, cumulatively administered MA (0.3–3 mg/kg), COC (3–56 mg/kg), and GBR 12909 (3–30 mg/kg) produced dose-dependent increases in DA efflux in the NAcb shell to maxima of approximately 1200 to 1300% of control values. The increase in DA levels produced by MA and COC was rapid and short-lived, whereas the effect of GBR 12909 was slower and longer lasting. Dose-related increases in MA lever selection produced by MA, COC, and GBR 12909 corresponded with graded increases in DA levels in the NAcb shell. Doses of MA, COC, and GBR 12909 that produced full substitution increased DA levels to approximately 200 to 400% of control values. Finally, cumulatively administered MA produced comparable changes in DA levels in both naive and 0.3 mg/kg MA-trained rats. These latter results suggest that sensitization of DA release does not play a prominent role in the discriminative stimulus effects of psychomotor stimulants. PMID:20190012

Bleeding pattern and cycle control of a low-dose transdermal contraceptive patch compared with a combined oral contraceptive: a randomized study.

PubMed

Merz, M; Kroll, R; Lynen, R; Bangerter, K

2015-02-01

The aim of this study was to investigate the bleeding pattern and cycle control of a contraceptive patch containing 0.55 mg ethinyl estradiol (EE) and 2.1 mg gestodene (GSD) compared with a combined oral contraceptive (COC) containing 0.02 mg EE and 0.1 mg levonorgestrel (LNG). In this phase III, randomized, controlled, double-blind, double-dummy, multicenter trial, healthy women aged 18-45 years (smokers aged 18-35 years) received either the EE/GSD patch and a placebo tablet (n=171), or a placebo patch and the COC (n=175) for seven 28-day cycles. Bleeding control was assessed in two 90-day reference periods. Mean number of bleeding/spotting days was comparable across treatment groups in both reference periods (p>.05). Mean number of bleeding/spotting episodes was also comparable in reference period 1; however, there were fewer bleeding/spotting episodes for COC in reference period 2 (3.4 versus 3.1; p=.01). Mean length of bleeding/spotting episodes was comparable across treatment groups for both reference periods (p>.05). Withdrawal bleeding occurred consistently in both groups over the entire treatment period, but its absence was more common in the COC group in cycles 4 and 6 of reference period 2 (p<.01). Intracyclic bleeding was comparable between groups. Bleeding pattern and cycle control with the EE/GSD patch was comparable to an EE/LNG-containing COC. The findings suggest that bleeding patterns with the EE/GSD patch are similar to an EE/LNG-containing COC, except for absence of withdrawal bleeding, which was less common in patch users. The EE/GSD patch may constitute an additional contraceptive option for women. Copyright © 2015 Elsevier Inc. All rights reserved.

A combined oral contraceptive affects mucosal SHIV susceptibility factors in a pigtail macaque model

PubMed Central

Ostergaard, Sharon Dietz; Butler, Katherine; Ritter, Jana M.; Johnson, Ryan; Sanders, Jeanine; Powell, Nathaniel; Lathrop, George; Zaki, Sherif R.; McNicholl, Janet M.; Kersh, Ellen N.

2015-01-01

Background Injectable hormonal contraception may increase women’s risk of HIV acquisition, and can affect biological risk factors in animal models of HIV. We established, for the first time, a model to investigate whether combined oral contraceptives (COC) alter SHIV susceptibility in macaques. Methods Seven pigtail macaques were administered a monophasic levonorgestrel (LNG)/ethinyl estradiol (EE) COC at 33% or 66% of the human dose for 60 days. Menstrual cycling, vaginal epithelial thickness and other SHIV susceptibility factors were monitored for a mean of 18 weeks. Results Mean vaginal epithelial thicknesses was 290.8 μm at baseline and 186.2 μm during COC (p=0.0141, Mann Whitney test). Vaginal pH decreased from 8.5 during to 6.5 post- treatment (0.0176 two-tailed t-test). Measured microflora was unchanged. Conclusions COC caused thinning of the vaginal epithelium and vaginal pH changes, which may increase SHIV susceptibility. 0.033 mg LNG + 0.0066 mg EE appeared effective in suppressing ovulation. PMID:25536296

Exploring the 13CO/C18O abundance ratio towards Galactic young stellar objects and HII regions

NASA Astrophysics Data System (ADS)

Areal, M. B.; Paron, S.; Celis Peña, M.; Ortega, M. E.

2018-05-01

Aims: Determining molecular abundance ratios is important not only for the study of Galactic chemistry, but also because they are useful to estimate physical parameters in a large variety of interstellar medium environments. One of the most important molecules for tracing the molecular gas in the interstellar medium is CO, and the 13CO/C18O abundance ratio is usually used to estimate molecular masses and densities of regions with moderate to high densities. Nowadays isotope ratios are in general indirectly derived from elemental abundances ratios. We present the first 13CO/C18O abundance ratio study performed from CO isotope observations towards a large sample of Galactic sources of different natures at different locations. Methods: To study the 13CO/C18O abundance ratio, we used 12CO J = 3 - 2 data obtained from the CO High-Resolution Survey, 13CO and C18O J = 3 - 2 data from the 13CO/C18O (J = 3 - 2) Heterodyne Inner Milky Way Plane Survey, and some complementary data extracted from the James Clerk Maxwell Telescope database. We analyzed a sample of 198 sources composed of young stellar objects (YSOs), and HII and diffuse HII regions as catalogued in the Red MSX Source Survey in 27.°5 ≤ l ≤ 46.°5 and |b|0.°5. Results: Most of the analyzed sources are located in the galactocentric distance range 4.0-6.5 kpc. We found that YSOs have, on average, lower 13CO/C18O abundance ratios than HII and diffuse HII regions. Taking into account that the gas associated with YSOs should be less affected by the radiation than in the case of the others sources, selective far-UV photodissociation of C18O is confirmed. The 13CO/C18O abundance ratios obtained in this work are systematically lower than those predicted from the known elemental abundance relations. These results will be useful in future studies of molecular gas related to YSOs and HII regions based on the observation of these isotopes.

Making the continuum of care work for mothers and infants: Does gender equity matter? Findings from a quasi-experimental study in Bihar, India

PubMed Central

McDougal, Lotus; Atmavilas, Yamini; Hay, Katherine; Silverman, Jay G.; Tarigopula, Usha K.; Raj, Anita

2017-01-01

Background Improvements in continuum of care (CoC) utilization are needed to address inadequate reductions in neonatal and infant mortality in India and elsewhere. This study examines the effect of Ananya, a health system training and community outreach intervention, on reproductive, maternal and newborn health continuum of care (RMNH CoC) utilization in Bihar, India, and explores whether that effect is moderated by gender equity factors (child marriage, restricted mobility and low decision-making control). Methods A two-armed quasi-experimental design compared districts in Bihar that did/did not implement Ananya. Cross-sections of married women aged 15–49 with a 0–5 month old child were surveyed at baseline and two year follow-up (baseline n = 7191 and follow-up n = 6143; response rates 88.9% and 90.7%, respectively). Difference-in-difference analyses assessed program impact on RMNH CoC co-coverage, defined by 9 health services/behaviors for the index pregnancy (e.g., antenatal care, skin-to-skin care). Three-way interactions assessed gender equity as a moderator of Ananya’s impact. Findings Participants reported low RMNH CoC co-coverage at baseline (on average 3.2 and 3.0 of the 9 RMNH services/behaviors for Ananya and control groups, respectively). The Ananya group showed a significantly greater increase in RMNH CoC co-coverage (.41 services) compared with the control group over time (p<0.001), with the primary drivers being increases in clean cord care, skin-to-skin care and postpartum contraceptive use. Gender equity interaction analyses revealed diminished intervention effects on antenatal care, skilled birth attendance and exclusive breastfeeding for women married as minors. Conclusion Ananya improved RMNH CoC co-coverage among these recent mothers, largely through positive health behavior changes. Child marriage attenuated Ananya’s impact on utilization of key health services and behaviors. Supporting the health system with training and community outreach can be beneficial to RMNH CoC utilization; additional support is needed to adequately address the unique issues faced by women married as minors. PMID:28146586

Transplacental cocaine exposure. 1: A rodent model.

PubMed

Wilkins, A S; Genova, L M; Posten, W; Kosofsky, B E

1998-01-01

To characterize the transplacental effects of cocaine on the developing brain, we have developed a mouse model of gestational cocaine exposure. Pharmacokinetic analysis revealed that cocaine and its metabolites (BE, BNE, and NC) were found in fetal brain and plasma at 30 and 120 min following SC administration to embryonic day (E) 17 pregnant Swiss Webster mice. Pregnant dams injected twice daily with cocaine HCl at 20 mg/kg SC from gestational day E8 to E17 (COC) demonstrated less food intake and lower percentage weight gain than vehicle-injected dams allowed access to food ad lib (SAL). A nutritionally paired control group of dams injected with saline vehicle and pair-fed with the COC dams (SPF) demonstrated the lowest percentage weight gain of all three groups. The surrogate fostered offspring of COC and SPF dams demonstrated persistent growth retardation [on postnatal days (P) 1, P9, and P50] and transient brain growth retardation (on P1 and P9) when compared to pups born to SAL dams. We conducted behavioral tests that allowed us to dissociate the indirect effect of cocaine-induced malnutrition from a direct effect of prenatal cocaine administration in altering postnatal behavior. Pups from all three groups were tested for first-order Pavlovian conditioning on P9 or P12, or for the ability to ignore redundant information in a blocking paradigm on P50 or P100. Unlike the SPF and SAL controls, COC mice (i.e., mice born to COC dams) were unable to acquire an aversion to an odor previously paired with shock on P9. This learning deficit was transient because on P12, COC mice trained on the same conditioning task displayed an aversion to the odor that was indistinguishable from the SPF and SAL controls. P50 and P100 COC mice (and to a lesser extent, SPF mice) demonstrated a persistent behavioral deficit in the blocking paradigm, which may reflect alterations in selective attention. We discuss how these findings in our rodent model have developmental implications for human infants exposed to cocaine in utero.

Impact of exogenous organic carbon on the removal of chemicals of concern in the high rate nitrifying trickling filters.

PubMed

Mai, Lei; van den Akker, Ben; Du, Jun; Kookana, Rai S; Fallowfield, Howard

2016-06-01

The application of fixed bed high rate nitrifying trickling filters (NTFs) for the removal of track organic chemicals of concern (CoC) is less well known than their application to nutrient removal in water treatment. Particularly, the effect of exogenous organic carbon substrate (sucrose) loading on the performance of NTFs is not well understood. A laboratory-scale NTF system was operated in recirculation mode, with the objective of removing ammonia and CoC simultaneously. The efficiency of a high rate NTF for removal both of low concentration of ammonia (5 mg NH4-N L(-1)) and different concentrations of CoC in the presence of an exogenous organic carbon substrate (30 mg total organic carbon (TOC) L(-1)) was investigated. In the presence of exogenous organic carbon, the results demonstrated that the high rate NTF was able to successfully remove most of the CoCs investigated, with the removal ranging from 20.2% to 87.54%. High removal efficiencies were observed for acetaminophen (87.54%), bisphenol A (86.60%), trimethoprim (86.24%) and 17α-ethynylestradiol (80.60%). It was followed by the medium removal efficiency for N, N-diethyl-m-toluamide (61.31%) and atrazine (56.90%). In contrast, the removal of caffeine (28.43%) and benzotriazole (20.20%) was poorer in the presence of exogenous organic carbon. The removal efficiency for CoC was also compared with the results obtained in our previous study in the absence of exogenous organic carbon. The results showed that the addition of exogenous organic carbon was able to improve the removal of some of the CoC. Significant TOC percentage removals (45.68%-84.43%) and ammonia removal rate (mean value of 0.44 mg NH4-N L(-1) h(-1)) were also achieved in this study. The findings from this study provide valuable information for optimising the efficiency of high rate NTF for the removal of ammonia, CoC and TOC. Copyright © 2016 Elsevier Ltd. All rights reserved.

Making the continuum of care work for mothers and infants: Does gender equity matter? Findings from a quasi-experimental study in Bihar, India.

PubMed

McDougal, Lotus; Atmavilas, Yamini; Hay, Katherine; Silverman, Jay G; Tarigopula, Usha K; Raj, Anita

2017-01-01

Improvements in continuum of care (CoC) utilization are needed to address inadequate reductions in neonatal and infant mortality in India and elsewhere. This study examines the effect of Ananya, a health system training and community outreach intervention, on reproductive, maternal and newborn health continuum of care (RMNH CoC) utilization in Bihar, India, and explores whether that effect is moderated by gender equity factors (child marriage, restricted mobility and low decision-making control). A two-armed quasi-experimental design compared districts in Bihar that did/did not implement Ananya. Cross-sections of married women aged 15-49 with a 0-5 month old child were surveyed at baseline and two year follow-up (baseline n = 7191 and follow-up n = 6143; response rates 88.9% and 90.7%, respectively). Difference-in-difference analyses assessed program impact on RMNH CoC co-coverage, defined by 9 health services/behaviors for the index pregnancy (e.g., antenatal care, skin-to-skin care). Three-way interactions assessed gender equity as a moderator of Ananya's impact. Participants reported low RMNH CoC co-coverage at baseline (on average 3.2 and 3.0 of the 9 RMNH services/behaviors for Ananya and control groups, respectively). The Ananya group showed a significantly greater increase in RMNH CoC co-coverage (.41 services) compared with the control group over time (p<0.001), with the primary drivers being increases in clean cord care, skin-to-skin care and postpartum contraceptive use. Gender equity interaction analyses revealed diminished intervention effects on antenatal care, skilled birth attendance and exclusive breastfeeding for women married as minors. Ananya improved RMNH CoC co-coverage among these recent mothers, largely through positive health behavior changes. Child marriage attenuated Ananya's impact on utilization of key health services and behaviors. Supporting the health system with training and community outreach can be beneficial to RMNH CoC utilization; additional support is needed to adequately address the unique issues faced by women married as minors.

Improving in vitro maturation and pregnancy outcome in cattle using a novel oocyte shipping and maturation system not requiring a CO₂ gas phase.

PubMed

Barceló-Fimbres, M; Campos-Chillón, L F; Mtango, N R; Altermatt, J; Bonilla, L; Koppang, R; Verstegen, J P

2015-07-01

The present work evaluated the benefit of a novel shipping and maturation medium (SMM) not requiring a CO2 gas for maturation and subsequent embryonic development of slaughterhouse and ovum pickup (OPU) bovine cumulus-oocyte complexes (COCs). Four experiments were conducted. In experiment 1, COCs were maturated for 18 hours in SMM and then incubated for 6 hours in, or 24 hours in a conventional system (control). Experiment 2 compared maturation for 24 hours in SMM versus 24 hours in the control. Experiment 3 compared three different incubation temperatures (37 °C, 38 °C, and 38.5 °C) for COCs maturation in SMM. In experiment 4, COCs obtained from 166 OPU sessions (representing two dairy and two beef breeds) in two locations (Wisconsin and California) were matured in SMM or control and evaluated relative to embryo production and pregnancy rates. Frozen semen was used for all experiments. The results for experiment 1 showed that the blastocyst rate and total embryo production rate (TE, Day-7 morulae plus all blastocysts) were higher for SMM than those in the control. However, no differences were observed for cleavage rate or blastocyst stage. In experiment 2, the blastocyst rate and TE were higher for SMM than those in the control; however, there was no difference for cleavage rate, total cell number, blastocyst stage. In experiment 3, the cleavage rate was similar, but the blastocyst rate and TE were greater for 38.5 °C than those for 38.0 °C and 37.5 °C. For experiment 4, Wisconsin OPU-derived COCs had a greater cleavage rate, blastocyst rate, TE, and blastocyst stage for SMM versus control. There were no breed effects. For the California trial, OPU-derived COCs matured in SMM had similar cleavage and pregnancy rates at Day 35 but greater blastocyst rates and transferred embryos per session than the control, which resulted in 2.2 more pregnancies per OPU session. Holstein COCs had superior embryonic development but similar pregnancy compared with Jersey. We conclude that COCs matured in SMM had greater oocyte competence than the control. Also, maturation at 38.5 °C in SMM was optimal for embryonic development. In summary, SMM resulted in greater embryonic development, similar pregnancy rates, but higher pregnancies per OPU session than the conventional maturation system. Copyright © 2015 Elsevier Inc. All rights reserved.

Subunit Stabilization and Polyethylene Glycolation of Cocaine Esterase Improves In Vivo Residence Time

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

Narasimhan, Diwahar; Collins, Gregory T.; Nance, Mark R.

No small-molecule therapeutic is available to treat cocaine addiction, but enzyme-based therapy to accelerate cocaine hydrolysis in serum has gained momentum. Bacterial cocaine esterase (CocE) is the fastest known native enzyme that hydrolyzes cocaine. However, its lability at 37 C has limited its therapeutic potential. Cross-linking subunits through disulfide bridging is commonly used to stabilize multimeric enzymes. Herein we use structural methods to guide the introduction of two cysteine residues within dimer interface of CocE to facilitate intermolecular disulfide bond formation. The disulfide-crosslinked enzyme displays improved thermostability, particularly when combined with previously described mutations that enhance stability (T172R-G173Q). The newlymore » modified enzyme yielded an extremely stable form of CocE (CCRQ-CocE) that retained greater than 90% of its activity after 41 days at 37 C, representing an improvement of more than 4700-fold over the wild-type enzyme. CCRQ-CocE could also be modified by polyethylene glycol (PEG) polymers, which improved its in vivo residence time from 24 to 72 h, as measured by a cocaine lethality assay, by self-administration in rodents, and by measurement of inhibition of cocaine-induced cardiovascular effects in rhesus monkeys. PEG-CCRQ elicited negligible immune response in rodents. Subunit stabilization and PEGylation has thus produced a potential protein therapeutic with markedly higher stability both in vitro and in vivo.« less

Influence of co-culture with denuded oocytes during in vitro maturation on fertilization and developmental competence of cumulus-enclosed porcine oocytes in a defined system.

PubMed

Appeltant, Ruth; Somfai, Tamás; Kikuchi, Kazuhiro; Maes, Dominiek; Van Soom, Ann

2016-04-01

Co-culture of cumulus-oocyte complexes (COCs) with denuded oocytes (DOs) during in vitro maturation (IVM) was reported to improve the developmental competence of oocytes via oocyte-secreted factors in cattle. The aim of the present study was to investigate if addition of DOs during IVM can improve in vitro fertilization (IVF) and in vitro culture (IVC) results for oocytes in a defined in vitro production system in pigs. The maturation medium was porcine oocyte medium supplemented with gonadotropins, dbcAMP and β-mercaptoethanol. Cumulus-oocyte complexes were matured without DOs or with DOs in different ratios (9 COC, 9 COC+16 DO and 9 COC+36 DO). Consequently; oocytes were subjected to IVF as intact COCs or after denudation to examine if DO addition during IVM would affect cumulus or oocyte properties. After fertilization, penetration and normal fertilization rates of zygotes were not different between all tested groups irrespective of denudation before IVF. When zygotes were cultured for 6 days, no difference could be observed between all treatment groups in cleavage rate, blastocyst rate and cell number per blastocyst. In conclusion, irrespective of the ratio, co-culture with DOs during IVM did not improve fertilization parameters and embryo development of cumulus-enclosed porcine oocytes in a defined system. © 2015 Japanese Society of Animal Science.

Subunit Stabilization and Polyethylene Glycolation of Cocaine Esterase Improves In Vivo Residence TimeS⃞

PubMed Central

Narasimhan, Diwahar; Collins, Gregory T.; Nance, Mark R.; Nichols, Joseph; Edwald, Elin; Chan, Jimmy; Ko, Mei-Chuan; Woods, James H.; Tesmer, John J. G.

2011-01-01

No small-molecule therapeutic is available to treat cocaine addiction, but enzyme-based therapy to accelerate cocaine hydrolysis in serum has gained momentum. Bacterial cocaine esterase (CocE) is the fastest known native enzyme that hydrolyzes cocaine. However, its lability at 37°C has limited its therapeutic potential. Cross-linking subunits through disulfide bridging is commonly used to stabilize multimeric enzymes. Herein we use structural methods to guide the introduction of two cysteine residues within dimer interface of CocE to facilitate intermolecular disulfide bond formation. The disulfide-crosslinked enzyme displays improved thermostability, particularly when combined with previously described mutations that enhance stability (T172R-G173Q). The newly modified enzyme yielded an extremely stable form of CocE (CCRQ-CocE) that retained greater than 90% of its activity after 41 days at 37°C, representing an improvement of more than 4700-fold over the wild-type enzyme. CCRQ-CocE could also be modified by polyethylene glycol (PEG) polymers, which improved its in vivo residence time from 24 to 72 h, as measured by a cocaine lethality assay, by self-administration in rodents, and by measurement of inhibition of cocaine-induced cardiovascular effects in rhesus monkeys. PEG-CCRQ elicited negligible immune response in rodents. Subunit stabilization and PEGylation has thus produced a potential protein therapeutic with markedly higher stability both in vitro and in vivo. PMID:21890748

The influence of cumulus cells during in vitro fertilization of buffalo (Bubalus bubalis) denuded oocytes that have undergone vitrification.

PubMed

Attanasio, Laura; De Rosa, Anna; De Blasi, Marina; Neglia, Gianluca; Zicarelli, Luigi; Campanile, Giuseppe; Gasparrini, Bianca

2010-11-01

The aim of this work was to evaluate whether providing a support of cumulus cells during IVF of buffalo denuded oocytes submitted to vitrification-warming enhances their fertilizing ability. In vitro matured denuded oocytes were vitrified by Cryotop in 20% EG + 20% of DMSO and 0.5 M sucrose and warmed into decreasing concentrations of sucrose (1.25 M-0.3M). Oocytes that survived vitrification were fertilized: 1) in the absence of a somatic support (DOs); 2) in the presence of bovine cumulus cells in suspension (DOs+susp); 3) on a bovine cumulus monolayer (DOs+monol); and 4) with intact bovine COCs in a 1:1 ratio (DOs+COCs). In vitro matured oocytes were fertilized and cultured to the blastocyst stage as a control. An increased cleavage rate was obtained from DOs+COCs (60.9%) compared to DOs, DOs+susp (43.6 and 38.4, respectively; P < 0.01) and DOs+monol (47.5%; P < 0.05). Interestingly, cleavage rate of DOs+COCs was similar to that of fresh control oocytes (67.8%). However, development to blastocysts significantly decreased in all vitrification groups compared to the control (P < 0.01). In conclusion the co-culture with intact COCs during IVF completely restores fertilizing capability of buffalo denuded vitrified oocytes, without improving blastocyst development. Copyright © 2010 Elsevier Inc. All rights reserved.

Adenosylcobinamide methyl phosphate as a pseudocoenzyme for diol dehydrase.

PubMed

Ishida, A; Toraya, T

1993-02-16

Adenosylcobinamide methyl phosphate, a novel analog of adenosylcobalamin lacking the nucleotide loop moiety, was synthesized. It did not show detectable coenzymic activity but behaved as a strong competitive inhibitor against AdoCbl with relatively high affinity (Ki = 2.5 microM). When apoenzyme was incubated at 37 degrees C with this analog in the presence of substrate, the Co-C bond of the analog was almost completely and irreversibly cleaved within 10 min, forming an enzyme-bound Co(II)-containing species. The cleavage was not observed in the absence of substrate. The Co-C bond cleavage in the presence of substrate was not catalytic but stoichiometric, implying that the Co-C bond of the analog undergoes activation when the analog binds to the active site of the enzyme. 5'-Deoxyadenosine was the only product derived from the adenosyl group of the analog upon the Co-C bond cleavage. Apoenzyme did not undergo modification during this process. Therefore, it seems likely that adenosylcobinamide methyl phosphate acts as a pseudocoenzyme or a potent suicide coenzyme. Since adenosylcobinamide neither functions as coenzyme nor binds tightly to apoenzyme, it can be concluded that the phosphodiester moiety of the nucleotide loop of adenosylcobalamin is essential for tight binding to apoenzyme and therefore for subsequent activation of the Co-C bond and catalysis. It is also evident that the nucleotide loop is obligatory for the normal progress of catalytic cycle.

Comparison of Drospirenone- with Cyproterone Acetate-Containing Oral Contraceptives, Combined with Metformin and Lifestyle Modifications in Women with Polycystic Ovary Syndrome and Metabolic Disorders: A Prospective Randomized Control Trial

PubMed Central

Wang, Qiu-Yi; Song, Yong; Huang, Wei; Xiao, Li; Wang, Qiu-Shi; Feng, Gui-Mei

2016-01-01

Background: While combined oral contraceptives (COCs) are commonly used to treat polycystic ovary syndrome (PCOS), comparative data regarding metabolic effects of different progestogens on this patient population are missing. This study aimed to compare the different effects of drospirenone (DRP)-containing COCs with cyproterone acetate (CPA)-containing COCs, combined with metformin and lifestyle modifications in women with PCOS and metabolic disorders. Methods: Ninety-nine women with PCOS and a metabolic disorder between January 2011 and January 2013 were enrolled into this prospective randomized clinical trial. Participants were randomized into two groups such as DRP-containing COCs, and CPA-containing COCs. Participants took COCs cyclically for 6 months, combined with metformin administration (1.5 g/d) and lifestyle modifications (diet and exercise). Clinical measures and biochemical and hormone profiles were compared. Comparisons for continuous variables were evaluated with paired and unpaired Student's t-tests. The Wilcoxon signed rank test was used when the data were not normally distributed. Analysis of covariance was used to control for age, body mass index (BMI), and baseline data of each analyzed parameter when compared between the two groups. Results: A total of 68 patients have completed the study. The combination regimen of COCs, metformin, and lifestyle modifications in these patients resulted in a significant decrease in BMI, acne, and hirsutism scores when compared to baseline levels in both groups (P < 0.05). Blood pressure (BP) was significantly different in the CPA group when compared to baseline (75.14 ± 6.77 mmHg vs. 80.70 ± 5.60 mmHg, P < 0.01), and after 6 months of treatment, only the change in systolic BP was significantly different between the two groups (4.00 [–6.00, 13.00] mmHg vs. –3.50 [–13.00, 9.00] mmHg, P = 0.009). Fasting glucose, fasting insulin, and homeostasis model assessment-insulin resistance decreased significantly in the DRP group (5.40 ± 0.41 mmol/L vs. 5.21 ± 0.32 mmol/L, P = 0.041; 13.90 [10.50, 18.40] μU/ml vs. 10.75 [8.60, 13.50] μU/ml, P = 0.020; 3.74 [2.85, 4.23] vs. 2.55 [1.92, 3.40], P = 0.008) but did not differ between the two groups. While individual lipid profiles increased in both groups, no statistically significant difference was observed. Conclusions: DRP-containing COCs combined with metformin and lifestyle modifications could better control BP and correct carbohydrate metabolism in women with PCOS and metabolic disorders compared with CPA-containing COCs. Trial Registration: Chinese Clinical Trial Registry, ChiCTR-TRC-11001143; http://www.chictr.org.cn/showproj.aspx?proj=8395. PMID:27064030

78 FR 30342 - United States Enrichment Corporation, Paducah Gaseous Diffusion Plant

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-22

... Corporation, Paducah Gaseous Diffusion Plant AGENCY: Nuclear Regulatory Commission. ACTION: Notice of... Compliance (CoC) for the Paducah Gaseous Diffusion Plant (PGDP). The existing CoC (No. GDP-1) authorizes... compliance for PGDP on November 26, 1996, and assumed regulatory oversight for the plant on March 3, 1997...

33 CFR 150.110 - What are the notification requirements upon receipt of classification society certifications?

Code of Federal Regulations, 2010 CFR

2010-07-01

... requirements upon receipt of classification society certifications? 150.110 Section 150.110 Navigation and... society certifications? The licensee must notify the Captain of the Port, in writing, upon receipt of a classification society certification, interim class certificate, or single point mooring classification...

33 CFR 150.110 - What are the notification requirements upon receipt of classification society certifications?

Code of Federal Regulations, 2011 CFR

2011-07-01

... requirements upon receipt of classification society certifications? 150.110 Section 150.110 Navigation and... society certifications? The licensee must notify the Captain of the Port, in writing, upon receipt of a classification society certification, interim class certificate, or single point mooring classification...

Heparin and cAMP modulators interact during pre-in vitro maturation to affect mouse and human oocyte meiosis and developmental competence.

PubMed

Zeng, Hai-tao; Ren, Zi; Guzman, Luis; Wang, Xiaoqian; Sutton-McDowall, Melanie L; Ritter, Lesley J; De Vos, Michel; Smitz, Johan; Thompson, Jeremy G; Gilchrist, Robert B

2013-06-01

Does heparin ablate the advantageous effects of cyclic adenosine mono-phosphate (cAMP) modulators during pre-in vitro maturation (IVM) and have a deleterious effect in standard oocyte IVM? Heparin interrupts energy metabolism and meiotic progression and adversely affects subsequent development of oocytes under conditions of elevated cAMP levels in cumulus-oocyte complexes (COCs) after pre-IVM treatment with forskolin. In animal IVM studies, artificial regulation of meiotic resumption by cAMP-elevating agents improves subsequent oocyte developmental competence. Heparin has no effect on spontaneous, FSH- or epidermal growth factor (EGF)-stimulated meiotic maturation. An in vitro cross-sectional study was conducted using immature mouse and human COCs. Depending on individual experimental design, COCs were treated during pre-IVM with or without heparin, in the presence or absence of forskolin and/or 3-isobutyl-1-methylxanthine (IBMX), and then COC function was assessed by various means. Forty-two women with polycystic ovaries (PCOs) or polycystic ovarian syndrome (PCOS) donated COCs after oocyte retrieval in a non-hCG-triggered IVM cycle. COCs were collected in pre-IVM treatments and then cultured for 40 h and meiotic progression was assessed. COCs from 21- to 24-day-old female CBA F1 mice were collected 46 h after stimulation with equine chorionic gonadotrophin. Following treatments, COCs were checked for meiotic progression. Effects on mouse oocyte metabolism were measured by assessing oocyte mitochondrial membrane potential using JC-1 staining and oocyte ATP content. Post-IVM mouse oocyte developmental competence was assessed by in vitro fertilization and embryo production. Blastocyst quality was evaluated by differential staining of inner cell mass (ICM) and trophectoderm (TE) layers. In the absence of heparin in pre-IVM culture, the addition of cAMP modulators did not affect human oocyte MII competence after 40 h. In standard IVM, heparin supplementation in pre-IVM did not affect MII competence; however, when heparin was combined with cAMP modulators, MII competence was significantly reduced from 65 to 15% (P < 0.05). In mouse experiments, heparin alone in pre-IVM significantly delayed germinal vesicle breakdown (GVBD) so that fewer GVBDs were observed at 0 and 1 h of IVM (P < 0.05), but not by 2 or 3 h of IVM. Combined treatment with IBMX and forskolin in the pre-IVM medium produced a large delay in GVBD such that no COCs exhibited GVBD in the first 1 h of IVM, and the addition of heparin in pre-IVM further significantly delayed the progression of GVBD (P < 0.05), in a dose-dependent manner (P < 0.01). Combined IBMX and forskolin treatment of mouse COCs during pre-IVM significantly increased mitochondrial membrane potential and ATP production in the oocyte at the end of pre-IVM (P < 0.05), and significantly improved fertilization, embryo development and quality (P < 0.05). However, heparin abolished the IBMX + forskolin-stimulated increase in mitochondrial membrane potential and ATP production (P < 0.05), and adversely affected embryonic cleavage, development rates and embryo quality (P < 0.05). This latter adverse combinational effect was negated when mouse COCs were collected in heparin and IBMX for 15 min, washed and then cultured for 45 min in IBMX and forskolin without heparin. Experiments in mice found that heparin ablation of the advantageous effects of cAMP modulators during pre-IVM was associated with altered oocyte metabolism, but the mechanism by which heparin affects metabolism remains unclear. This study has revealed a novel and unexpected interaction between heparin and cAMP modulators in pre-IVM in immature mouse and human oocytes, and established a means to collect oocytes using heparin while modulating oocyte cAMP to improve developmental potential.

Do the Reasons for Ceramic-on-ceramic Revisions Differ From Other Bearings in Total Hip Arthroplasty?

PubMed

Migaud, Henri; Putman, Sophie; Kern, Grégory; Isida, Ronald; Girard, Julien; Ramdane, Nassima; Delaunay, Christian P; Hamadouche, Moussa

2016-10-01

Despite widespread use of ceramic-on-ceramic (CoC) in total hip arthroplasty (THA) during the past 10 years, little is known about why revisions are performed in hips with this bearing or the time elapsed before revision. The purposes of this study were: (1) Do the reasons for first revision differ between CoC bearings and other bearing couples? (2) Does the time to revision differ between CoC and other bearing couples? (3) Are there unique reasons for revisions of CoC bearings? All members of the Société Française de Chirurgie Orthopédique et Traumatologique (SoFCOT) who performed ≥ 30 revisions per year were invited to participate in this multicenter, prospective, observational study. Our data represent 12% of the revision procedures performed in France. A total of 2107 first revisions of THA (from January 2010 to December 2011) were done in 2107 patients (1201 females [57%] and 906 males [43%]; median age, 73 years; age range, 17-104 years) at the time of surgery after a median of 11 years (range, 0 day-42 years) after the primary THA. There were 238 of 2107 (11%) CoC, 148 of 2107 (7%) metal-on-metal (MoM), and 1721 of 2017 (82%) metal-on-polyethylene (MoP) bearings. The reasons for reoperation differed according to the bearing component: (1) for the MoP reference bearing (odds ratio [OR]; 95% confidence interval), cup loosening occurred in 698 of 1721 hips (41%), periprosthetic fracture in 220 of 1721 hips (13%), and osteolysis in 213 of 1721 hips (12%); (2) for CoC, cup loosening occurred in 41 of 238 hips (17%) (OR, 0.31 [0.22-0.43; p < 0.001), infection in 39 of 238 hips (16%) (OR, 1.63 [1.12-2.37]; p = 0.01), and dislocation in 23 of 238 hips (10%) (OR, 0.9 [0.57-1.42]; p = 0.9); (3) for MoM, cup loosening occurred in 28 of 148 hips (19%) (OR, 0.34 [0.22-0.52]; p < 0.001), adverse reaction to metallic debris in 26 of 148 hips (18%) (OR, 18.12 [9.84-33.4]; p < 0.001), and infection in 16 of 148 hips (11%) (OR, 1 [0.59-1.73]; p = 0.9). In comparison with MoP, osteolysis was rarely the reason for revision in CoC (four of 238 hips [2%]; OR, 0.12 [0.05-0.33]; p < 0.001), but this bearing was frequently revised because of iliopsoas irritation (18 of 238 hips [8%]; OR, 4.9 [2.7-9]; p < 0.001). The time elapsed before revision differed between bearings: median of 3 years (range, 3 days to 28 years) for CoC and 4 years (range, 14 days to 37 years) for MoM versus a median 13 years (range, 0 day to 42 years) for MoP (p < 0.001). Thirty-seven of the 238 revisions (16%) were directly related to ceramic use (ceramic breakage [n = 23], squeaking [n = 6], impingement [n = 7], incorrect ceramic insert insertion [n = 1]). No factors were identified that contributed to breakage of the 12 bulk ceramic components (eight heads, four inserts, four of 12 Delta ceramic). No factors were associated with squeaking, iliopsoas irritation, or impingement, but component orientation was not assessed. The reasons and time to first revision differed between CoC and other bearings. CoC THAs are revised earlier and are sensitive to mechanical problems such as impingement, squeaking, and ceramic rupture that did not disappear with introduction of Delta ceramics and large-diameter (≥ 36 mm) bearings. CoC was rarely revised for osteolysis, but a high rate of iliopsoas irritation requires further investigation. Level III, therapeutic study.

Outcomes of different bearings in total hip arthroplasty - implant survival, revision causes, and patient-reported outcome.

PubMed

Varnum, Claus

2017-03-01

Total hip arthroplasty (THA) is a common and successful treatment of patients suffering from severe osteoarthritis that significantly reduces pain and improves hip function and quality of life. Traditionally, the outcome of THA has been evaluated by orthopaedic surgeons and assessed in morbidity and mortality rates, and implant survival. As patients and surgeons may assess outcome after THA differently, patient-reported outcomes (PROMs) have gained much more interest and are today recognized as very important tools for evaluating the outcome and satisfaction after THA. One of the prognostic factors for the outcome of THA is the type of bearings. This PhD thesis focuses on the influence of different types of bearings on implant survival, revision causes, PROMs, and noises from THA. The aims of the thesis were: Study I: To examine the revision risk and to investigate the causes of revision of cementless ceramic-on-ceramic (CoC) THAs comparing them to those of "standard" metal-on-polyethylene (MoP) THAs. Study II: To compare the six-year revision risk for metal-on-metal (MoM) with that for MoP bearings in cementless stemmed THA, and further to study the revision risk for different designs of stemmed MoM THAs and the causes of revision. Study III: To examine the association between CoC, MoM, and MoP bearings and both generic and disease-specific PROMs, and furthermore to examine the incidence and types of noises from the three types of bearings and identify the effect of noises on PROM scores. In study I and III, we used data from the Danish Hip Arthroplasty Registry combined with data from the Civil Registration System and the Danish National Patient Registry. In study II, data from the Nordic Arthroplasty Register Association, containing data from hip arthroplasty registries in Denmark, Norway, Sweden, and Finland, was used. In study I, 11,096 patients operated from 2002 through 2009 with cementless THA were included. Of these, 16% had CoC THA and 84% had MoP THA. At 8.7-year follow-up, no difference in RR of revision for any cause was found for CoC compared to MoP THA. One cause of revision related only to CoC THA is ceramic fracture. Medical records were reviewed for patients who had revision surgery due to component failure, and six patients (0,34%) had been revised due to ceramic fracture. No other difference in prevalence of causes of revision was found when comparing CoC to MoP THA. Study II included 32,678 patients who were operated from 2002 through 2010 with cementless stemmed THA with either MoM bearings (11,567 patients, 35%) or MoP bearings (21,111 patients, 65%). At six-year follow-up, the RR of revision for any cause was significantly higher for MoM compared to MoP THA. When comparing different combinations of cup/stem with MoM to MoP bearings, there was an increased RR of revision for any cause for the ASR/Summit, ASR/Corail, and "other" combinations. There was a higher prevalence of revision due to aseptic loosening for MoM compared to MoP THA. In contrast, the prevalence of revision due to dislocation was lower for MoM THA. In study III, a set of questionnaires including HOOS, EQ-5D, UCLA activity score, and a questionnaire about noises from the THA was sendt to patients having THA with CoC, MoM, or MoP bearings. The response rate was 85% and among the 3,089 patients responding, 45% received CoC, 17% MoM, and 38% MoP THA. No differences in mean subscale scores were found for CoC and MoM compared to MoP THA, except for CoC THA that had a lower mean HOOS symptoms score than MoP THA. 27% of patients with CoC, 29% of patients with MoM, and 12% of patients with MoP bearings had experienced noises from the THA. For the three types of bearings, PROM scores from patients with noisy THA were significantly lower when compared to silent MoP THA, except for noisy CoC and MoM THA that had the same mean UCLA activity score as silent MoP THA.

United States Air Force 611th Air Support Group/Civil Engineering Squadron, Elmendorf AFB, Alaska Risk Assessment, Oliktok Point Radar Installation, Alaska. Final report

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

Karmi, S.

1996-04-15

This document contains the baseline human health risk assessment and the ecological risk assessment (ERA) for the Oliktok Point Distant Early Warning (DEW) Line radar installation. Eight sites at the Oliktok Point radar installation underwent remedial investigations (RIs) during the summer of 1993. The presence of chemical contamination in the soil, sediments, and surface water at the installation was evaluated and reported in the Oliktok Point Remedial Investigation/Feasibility Study (RI/FS) (U.S. Air Force 1996). The analytical data reported in the RI/FS form the basis for the human health and ecological risk assessments. The primary chemicals of concern (COCs) at themore » eight sites are diesel and gasoline from past spills and/or leaks, chlorinated solvents, metals, and polychlorinated biphenyls (PCBs).« less

Assessment of tungsten/rhenium thermocouples with metal-carbon eutectic fixed points up to 1500°C

NASA Astrophysics Data System (ADS)

Gotoh, M.

2013-09-01

Four Type A thermocouples and two Type C thermocouples were calibrated at the Au fixed point and Co-C and Pd-C eutectic fixed points. The thermocouples were exposed to 1330 °C for a total of 100 hours. The maximum drift due to the exposure was found to be 4.8 °C. The fixed-point calibration EMF of these thermocouples deviated by less than 0.86% from the temperature specified by the standards ASTM E230-2003 for Type C and GOSTR 8.585-2001 for Type A. The length of one of Type A thermocouples A52 is longer than the others by 150mm. Making use of this provision it was possible to place annealed part of A52 to the temperature gradient part of calibration arrangement every time. Therefore observed aging effect was as low as 0.5 °C compared to the other thermocouples.

Monitoring the delivery of cancer care: Commission on Cancer and National Cancer Data Base.

PubMed

Williams, Richelle T; Stewart, Andrew K; Winchester, David P

2012-07-01

The primary objective of the Commission on Cancer (CoC) is to ensure the delivery of comprehensive, high-quality care that improves survival while maintaining quality of life for patients with cancer. This article examines the initiatives of the CoC toward achieving this goal, utilizing data from the National Cancer Data Base (NCDB) to monitor treatment patterns and outcomes, to develop quality measures, and to benchmark hospital performance. The article also highlights how these initiatives align with the Institute of Medicine's recommendations for improving the quality of cancer care and briefly explores future projects of the CoC and NCDB. Copyright © 2012 Elsevier Inc. All rights reserved.

76 FR 38680 - Notice of Invitation-Coal Exploration License Application COC-74817

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-01

...] Notice of Invitation--Coal Exploration License Application COC- 74817 AGENCY: Bureau of Land Management... Mountain Energy, Inc. on a pro rata cost-sharing basis in a program for the exploration of coal deposits... is to gain additional geologic knowledge of the coal underlying the exploration area for the purpose...

CTEPP STANDARD OPERATING PROCEDURE FOR HANDLING SAMPLE AND DATA CUSTODY (SOP-2.26)

EPA Science Inventory

This SOP describes the method for handling sample custody. A standardized Chain-of-Custody (CoC) Record is used to document the sample/data custody. Each participant is assigned one CoC Record for the samples/data collected at their home and/or day care center.

77 FR 11155 - Notice of Proposed Reinstatement of Terminated Oil and Gas Lease COC73670

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-24

...: Under the provisions of 30 U.S.C. 188(d) and (e), and 43 CFR 3108.2-3(a) and (b)(1), the Bureau of Land... Act of 1920 (30 U.S.C. 188), and the BLM is proposing to reinstate lease COC73670 effective December 1...

77 FR 43112 - Notice of Proposed Reinstatement of Terminated Oil and Gas Lease COC73875

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-23

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Occurrence of illicit drugs in two wastewater treatment plants in the South of Italy.

PubMed

Cosenza, Alida; Maida, Carmelo Massimo; Piscionieri, Donatella; Fanara, Serena; Di Gaudio, Francesca; Viviani, Gaspare

2018-05-01

In this study the occurrence and the behavior of illicit drugs and their metabolites have been investigated for two wastewater treatment plants (WWTPs) (namely, WWTP-1 and WWTP-2) located in Sicily (island of Italy). Samples were analyzed for methamphetamine, cocaine (COC), 3,4-methylenedioxymethamphetamine (MDMA), methadone (METH), 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), 3,4-methylenedioxy amphetamine (MDA); 3,4-methylenedioxy ethylamphetamine (MDEA), 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) and Benzoylecgonine (BEG). The BEG, COC, MOR and THC-COOH were found at the highest concentration in both WWTPs. The Wastewater-based epidemiology calculation for BEG, COC, cannabinoids and THC-COOH was performed. On average, for both plants, population consumes 1.6 and 23.4 dose 1000 inh -1 day -1 of cocaine and cannabis, respectively. For WWTP-1 negative removals of illicit drugs were observed. For WWTP-2 the following average removal efficiencies were obtained: BEG (77.85%), COC (92.34%), CODEINE (64.75%), MOR (90.16%) and THC-COOH (68.64%). Copyright © 2018 Elsevier Ltd. All rights reserved.

Characterization of Bonding Between Poly(dimethylsiloxane) and Cyclic Olefin Coplymer Using Corona Discharge Induced Grafting Polymerization

PubMed Central

Liu, Ke; Gu, Pan; Hamaker, Kiri; Fan, Z. Hugh

2011-01-01

Thermoplastics have been increasingly used for fabricating microfluidic devices because of their low cost, mechanical/biocompatible attributes, and well-established manufacturing processes. However, there is sometimes a need to integrate such a device with components made from other materials such as polydimethylsiloxane (PDMS). Bonding thermoplastics with PDMS to produce hybrid devices is not straightforward. We have reported our method to modify the surface property of a cyclic olefin copolymer (COC) substrate by using corona discharge and grafting polymerization of 3-(trimethoxysilyl)propyl methacrylate; the modified surface enabled strong bonding of COC with PDMS. In this paper, we report our studies on the surface modification mechanism using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and contact angle measurement. Using this bonding method, we fabricated a three-layer (COC/PDMS/COC) hybrid device consisting of elastomer-based valve arrays. The microvalve operation was confirmed through the displacement of a dye solution in a fluidic channel when the elastomer membrane was pneumatically actuated. Valve-enabled microfluidic handling was demonstrated. PMID:21962541

Exposure to cadmium during in vitro maturation at environmental nanomolar levels impairs oocyte fertilization through oxidative damage: A large animal model study.

PubMed

Martino, N A; Marzano, G; Mangiacotti, M; Miedico, O; Sardanelli, A M; Gnoni, A; Lacalandra, G M; Chiaravalle, A E; Ciani, E; Bogliolo, L; Minervini, F; Pizzi, F; Dell'Aquila, M E

2017-04-01

Cadmium is a highly toxic heavy metal with negative effects on oocyte fertilization. The aim of this study was to analyse whether cadmium-induced impairment of fertilization is caused by mitochondria dysfunction and oxidative stress in the cumulus-oocyte complex (COC). Preliminarily, 19 trace element levels were measured in ovaries from juvenile and adult ewes and age-related cadmium ovarian bioaccumulation at nanomolar concentrations was found. COCs from juvenile and adult ewes, exposed during in vitro maturation to 1nM or 100nM CdCl 2 , and subjected to in vitro fertilization showed significantly lower fertilization rates in exposed COCs compared with controls. In vitro matured exposed and control COCs underwent confocal microscopy analysis of mitochondria activity and reactive oxygen species (ROS) levels and lipid peroxidation (LPO) assay at cumulus cell and oocyte level. In both age groups, cadmium at nanomolar concentrations induced cumulus-oocyte mitochondria over-activity and oxidative damage which were related to impaired oocyte fertilization. Copyright © 2017 Elsevier Inc. All rights reserved.

1D to 3D dimensional crossover in the superconducting transition of the quasi-one-dimensional carbide superconductor Sc3CoC4.

PubMed

He, Mingquan; Wong, Chi Ho; Shi, Dian; Tse, Pok Lam; Scheidt, Ernst-Wilhelm; Eickerling, Georg; Scherer, Wolfgang; Sheng, Ping; Lortz, Rolf

2015-02-25

The transition metal carbide superconductor Sc(3)CoC(4) may represent a new benchmark system of quasi-one-dimensional (quasi-1D) superconducting behavior. We investigate the superconducting transition of a high-quality single crystalline sample by electrical transport experiments. Our data show that the superconductor goes through a complex dimensional crossover below the onset T(c) of 4.5 K. First, a quasi-1D fluctuating superconducting state with finite resistance forms in the [CoC(4)](∞) ribbons which are embedded in a Sc matrix in this material. At lower temperature, the transversal Josephson or proximity coupling of neighboring ribbons establishes a 3D bulk superconducting state. This dimensional crossover is very similar to Tl(2)Mo(6)Se(6), which for a long time has been regarded as the most appropriate model system of a quasi-1D superconductor. Sc(3)CoC(4) appears to be even more in the 1D limit than Tl(2)Mo(6)Se(6).

PAT-1 safety analysis report addendum.

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

Weiner, Ruth F.; Schmale, David T.; Kalan, Robert J.

2010-09-01

The Plutonium Air Transportable Package, Model PAT-1, is certified under Title 10, Code of Federal Regulations Part 71 by the U.S. Nuclear Regulatory Commission (NRC) per Certificate of Compliance (CoC) USA/0361B(U)F-96 (currently Revision 9). The purpose of this SAR Addendum is to incorporate plutonium (Pu) metal as a new payload for the PAT-1 package. The Pu metal is packed in an inner container (designated the T-Ampoule) that replaces the PC-1 inner container. The documentation and results from analysis contained in this addendum demonstrate that the replacement of the PC-1 and associated packaging material with the T-Ampoule and associated packaging withmore » the addition of the plutonium metal content are not significant with respect to the design, operating characteristics, or safe performance of the containment system and prevention of criticality when the package is subjected to the tests specified in 10 CFR 71.71, 71.73 and 71.74.« less

International Space Station Payload Operations Integration

NASA Technical Reports Server (NTRS)

Fanske, Elizabeth Anne

2011-01-01

The Payload Operations Integrator (POINT) plays an integral part in the Certification of Flight Readiness process for the Mission Operations Laboratory and the Payload Operations Integration Function that supports International Space Station Payload operations. The POINTs operate in support of the POIF Payload Operations Manager to bring together and integrate the Certification of Flight Readiness inputs from various MOL teams through maintaining an open work tracking log. The POINTs create monthly metrics for current and future payloads that the Payload Operations Integration Function supports. With these tools, the POINTs assemble the Certification of Flight Readiness package before a given flight, stating that the Mission Operations Laboratory is prepared to support it. I have prepared metrics for Increment 29/30, maintained the Open Work Tracking Logs for Flights ULF6 (STS-134) and ULF7 (STS-135), and submitted the Mission Operations Laboratory Certification of Flight Readiness package for Flight 44P to the Mission Operations Directorate (MOD/OZ).

Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization.

PubMed

Jungheim, Emily S; Macones, George A; Odem, Randall R; Patterson, Bruce W; Lanzendorf, Susan E; Ratts, Valerie S; Moley, Kelle H

2011-05-01

To determine if follicular free fatty acid (FFA) levels are associated with cumulus oocyte complex (COC) morphology. Prospective cohort study. University in vitro fertilization (IVF) practice. A total of 102 women undergoing IVF. Measurement of FFAs in serum and ovarian follicular fluid. Total and specific follicular and serum FFA levels, correlations between follicular and serum FFAs, and associations between follicular FFA levels and markers of oocyte quality, including COC morphology. Predominant follicular fluid and serum FFAs were oleic, palmitic, linoleic, and stearic acids. Correlations between follicular and serum FFA concentrations were weak (r=0.252, 0.288, 0.236, 0.309, respectively for specific FFAs; r=0.212 for total FFAs). A receiver operating characteristic curve determined total follicular FFAs≥0.232 μmol/mL distinguished women with a lower versus higher percentage of COCs with favorable morphology. Women with elevated follicular FFAs (n=31) were more likely to have COCs with poor morphology than others (n=71; OR 3.3, 95% CI1.2-9.2). This relationship held after adjusting for potential confounders, including age, body mass index, endometriosis, and amount of gonadotropin administered (β=1.2; OR 3.4, 95% CI 1.1-10.4). Elevated follicular FFA levels are associated with poor COC morphology. Further work is needed to determine what factors influence follicular FFA levels and if these factors impact fertility. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Computational Design of a Thermostable Mutant of Cocaine Esterase via Molecular Dynamics Simulations

PubMed Central

Huang, Xiaoqin; Gao, Daquan; Zhan, Chang-Guo

2015-01-01

Cocaine esterase (CocE) has been known as the most efficient native enzyme for metabolizing the naturally occurring cocaine. A major obstacle to the clinical application of CocE is the thermoinstability of native CocE with a half-life of only ~11 min at physiological temperature (37°C). It is highly desirable to develop a thermostable mutant of CocE for therapeutic treatment of cocaine overdose and addiction. To establish a structure-thermostability relationship, we carried out molecular dynamics (MD) simulations at 400 K on wild-type CocE and previously known thermostable mutants, demonstrating that the thermostability of the active form of the enzyme correlates with the fluctuation (characterized as the RMSD and RMSF of atomic positions) of the catalytic residues (Y44, S117, Y118, H287, and D259) in the simulated enzyme. In light of the structure-thermostability correlation, further computational modeling including MD simulations at 400 K predicted that the active site structure of the L169K mutant should be more thermostable. The prediction has been confirmed by wet experimental tests showing that the active form of the L169K mutant had a half-life of 570 min at 37°C, which is significantly longer than those of the wild-type and previously known thermostable mutants. The encouraging outcome suggests that the high-temperature MD simulations and the structure-thermostability may be considered as a valuable tool for computational design of thermostable mutants of an enzyme. PMID:21373712

Cocaine dependence does not contribute substantially to white matter abnormalities in HIV infection.

PubMed

Cordero, Daniella M; Towe, Sheri L; Chen, Nan-Kuei; Robertson, Kevin R; Madden, David J; Huettel, Scott A; Meade, Christina S

2017-06-01

This study investigated the association of HIV infection and cocaine dependence with cerebral white matter integrity using diffusion tensor imaging (DTI). One hundred thirty-five participants stratified by HIV and cocaine status (26 HIV+/COC+, 37 HIV+/COC-, 37 HIV-/COC+, and 35 HIV-/COC-) completed a comprehensive substance abuse assessment, neuropsychological testing, and MRI with DTI. Among HIV+ participants, all were receiving HIV care and 46% had an AIDS diagnosis. All COC+ participants were current users and met criteria for cocaine use disorder. We used tract-based spatial statistics (TBSS) to assess the relation of HIV and cocaine to fractional anisotropy (FA) and mean diffusivity (MD). In whole-brain analyses, HIV+ participants had significantly reduced FA and increased MD compared to HIV- participants. The relation of HIV and FA was widespread throughout the brain, whereas the HIV-related MD effects were restricted to the corpus callosum and thalamus. There were no significant cocaine or HIV-by-cocaine effects. These DTI metrics correlated significantly with duration of HIV disease, nadir CD4+ cell count, and AIDS diagnosis, as well as some measures of neuropsychological functioning. These results suggest that HIV is related to white matter integrity throughout the brain, and that HIV-related effects are more pronounced with increasing duration of infection and greater immune compromise. We found no evidence for independent effects of cocaine dependence on white matter integrity, and cocaine dependence did not appear to exacerbate the effects of HIV.

Evaluation of the indoor air quality minimum ventilation rate procedure for use in California retail buildings.

PubMed

Dutton, S M; Mendell, M J; Chan, W R; Barrios, M; Sidheswaran, M A; Sullivan, D P; Eliseeva, E A; Fisk, W J

2015-02-01

This research assesses benefits of adding to California Title-24 ventilation rate (VR) standards a performance-based option, similar to the American Society of Heating, Refrigerating, and Air Conditioning Engineers 'Indoor Air Quality Procedure' (IAQP) for retail spaces. Ventilation rates and concentrations of contaminants of concern (CoC) were measured in 13 stores. Mass balance models were used to estimate 'IAQP-based' VRs that would maintain concentrations of all CoCs below health- or odor-based reference concentration limits. An intervention study in a 'big box' store assessed how the current VR, the Title 24-prescribed VR, and the IAQP-based VR (0.24, 0.69, and 1.51 air changes per hour) influenced measured IAQ and perceived of IAQ. Neither current VRs nor Title 24-prescribed VRs would maintain all CoCs below reference limits in 12 of 13 stores. In the big box store, the IAQP-based VR kept all CoCs below limits. More than 80% of subjects reported acceptable air quality at all three VRs. In 11 of 13 buildings, saving energy through lower VRs while maintaining acceptable IAQ would require source reduction or gas-phase air cleaning for CoCs. In only one of the 13 retail stores surveyed, application of the IAQP would have allowed reduced VRs without additional contaminant-reduction strategies. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

The effect of gonadal and adrenal steroid therapy on skeletal health in adolescents and young women with anorexia nervosa

PubMed Central

DiVasta, Amy D.; Feldman, Henry A.; Giancaterino, Courtney; Rosen, Clifford J.; LeBoff, Meryl S.; Gordon, Catherine M.

2012-01-01

Anorexia nervosa (AN) is characterized by subnormal estrogen and dehydroepiandrosterone (DHEA) levels. We sought to determine whether the combination of DHEA + estrogen/progestin is superior to placebo in preserving skeletal health over 18 months in AN. Females with AN, aged 13 to 27 years, were recruited for participation in this double-blind, placebo-controlled, randomized trial. Ninety-four subjects were randomized, of whom 80 completed baseline assessments and received either study drug (oral micronized DHEA 50 mg + 20 µg ethinyl estradiol/0.1 mg levonorgestrel combined oral contraceptive pill [COC] daily; n = 43) or placebo (n = 37). Serial measurements of areal bone mineral density (aBMD), bone turnover markers, and serum hormone concentrations were obtained. Sixty subjects completed the 18-month trial. Spinal and whole-body aBMD z scores were preserved in the DHEA + COC group, but decreased in the placebo group (comparing trends, P = .008 and P = .001, respectively). Bone turnover markers initially declined in subjects receiving DHEA + COC and then returned to baseline. No differences in body composition, adverse effects of therapy, or alterations in biochemical safety parameters were observed. Combined therapy with DHEA + COC appears to be safe and effective for preventing bone loss in young women with AN, whereas placebo led to decreases in aBMD. Dehydroepiandrosterone + COC may be safely used to preserve bone mass as efforts to reverse the nutritional, psychological, and other hormonal components of AN are implemented. PMID:22257645

Chronic exposure to cocaine binging predisposes to an accelerated course of dilated cardiomyopathy in conscious dogs following rapid ventricular pacing.

PubMed

Parikh, Pratik; Nikolaidis, Lazaros A; Stolarski, Carol; Shen, You-Tang; Shannon, Richard P

2005-12-01

Despite extensive study, the extent to which cocaine use predisposes to cardiac injury remains unknown. We hypothesized that chronic cocaine binging would increase susceptibility to a subsequent cardiac insult, even in the absence of demonstrable effects on baseline hemodynamics. We studied progression of dilated cardiomyopathy (DCM) induced by rapid ventricular pacing (240 beats per minute) in five conscious, chronically instrumented dogs, after exposure to repetitive cocaine binging (COC) in the form of four consecutive 1 mg/kg i.v. boluses daily for 8 days, to simulate human cocaine abuse. We compared the results with nine control dogs (CON) undergoing the exact pacing protocol, without prior cocaine exposure. Baseline hemodynamics were not significantly altered by chronic cocaine exposure. Following 2 weeks of pacing, COC dogs exhibited accelerated progression to DCM, depressed plasma nitric oxide levels (CON, 17 +/- 2 microM; COC, 10 +/- 2 microM, p < 0.05), and a significantly greater increase in plasma epinephrine (CON, 33 +/- 6 pg/ml; COC, 104 +/- 24 pg/ml). After only 2 weeks of pacing, COC dogs demonstrated progressive DCM of a magnitude comparable with end-stage pacing-induced DCM. Chronic cocaine binging increases susceptibility to a subsequent myocardial insult and accelerates progression of DCM in conscious dogs following rapid pacing. These data suggest that although chronic cocaine use alone may not affect myocardial function, it predisposes to greater susceptibility to a superimposed insult.

Cardioprotective properties of Crataegus oxycantha extract against ischemia-reperfusion injury.

PubMed

Swaminathan, J K; Khan, M; Mohan, I K; Selvendiran, K; Niranjali Devaraj, S; Rivera, B K; Kuppusamy, P

2010-08-01

The aim of the study was to investigate the cardioprotective effect and mechanism of Crataegus oxycantha (COC) extract, a well-known natural antioxidant-based cardiotonic, against ischemia/reperfusion (I/R) injury. Electron paramagnetic resonance studies showed that COC extract was capable of scavenging superoxide, hydroxyl, and peroxyl radicals, in vitro. The cardioprotective efficacy of the extract was studied in a crystalloid perfused heart model of I/R injury. Hearts were subjected to 30min of global ischemia followed by 45min of reperfusion. During reperfusion, COC extract was infused at a dose rate of 1mg/ml/min for 10min. Hearts treated with COC extract showed a significant recovery in cardiac contractile function, reduction in infarct size, and decrease in creatine kinase and lactate dehydrogenase activities. The expressions of xanthine oxidase and NADPH oxidase were significantly reduced in the treated group. A significant upregulation of the anti-apoptotic proteins Bcl-2 and Hsp70 with simultaneous downregulation of the pro-apoptotic proteins cytochrome c and cleaved caspase-3 was observed. The molecular signaling cascade including phospho-Akt (ser-473) and HIF-1alpha that lead to the activation or suppression of apoptotic pathway also showed a significant protective role in the treatment group. No significant change in phospho-p38 levels was observed. The results suggested that the COC extract may reduce the oxidative stress in the reperfused myocardium, and play a significant role in the inhibition of apoptotic pathways leading to cardioprotection. 2010 Elsevier GmbH. All rights reserved.

Cardioprotective properties of Crataegus oxycantha extract against ischemia-reperfusion injury

PubMed Central

Swaminathan, Jayachandran Kesavan; Khan, Mahmood; Mohan, Iyappu K; Selvendiran, Karuppaiyah; Devaraj, S. Niranjali; Rivera, Brian K.; Kuppusamy, Periannan

2010-01-01

The aim of the study was to investigate the cardioprotective effect and mechanism of Crataegus oxycantha (COC) extract, a well-known natural antioxidant-based cardiotonic, against ischemia/reperfusion (I/R) injury. Electron paramagnetic resonance studies showed that COC extract was capable of scavenging superoxide, hydroxyl, and peroxyl radicals, in vitro. The cardioprotective efficacy of the extract was studied in a crystalloid perfused heart model of I/R injury. Hearts were subjected to 30 min of global ischemia followed by 45 min of reperfusion. During reperfusion, COC extract was infused at a dose rate of 1 mg/ml/min for 10 min. Hearts treated with COC extract showed a significant recovery in cardiac contractile function, reduction in infarct size, and decrease in creatine kinase and lactate dehydrogenase activities. The expressions of xanthine oxidase and NADPH oxidase were significantly reduced in the treated group. A significant upregulation of the anti-apoptotic proteins Bcl-2 and Hsp70 with simultaneous downregulation of the pro-apoptotic proteins cytochrome c and cleaved caspase-3 was observed. The molecular signaling cascade including phospho-Akt (ser-473) and HIF-1α that lead to the activation or suppression of apoptotic pathway also showed a significant protective role in the treatment group. No significant change in phospho-p38 levels was observed. The results suggested that the COC extract may reduce the oxidative stress in the reperfused myocardium, and play a significant role in the inhibition of apoptotic pathways leading to cardioprotection. PMID:20171068

10-year follow-up of calcifying odontogenic cyst in the periapical region of vital maxillary central incisor.

PubMed

de Carvalhosa, Artur Aburad; de Araújo Estrela, Cyntia Rodrigues; Borges, Alvaro Henrique; Guedes, Orlando Aguirre; Estrela, Carlos

2014-10-01

Radiographic images may lead to misinterpretations of lesions of endodontic and nonendodontic origin. This report describes a case of a 10-year follow-up of a calcifying odontogenic cyst (COC) in the periapical region of a vital maxillary central incisor in a 9-year-old boy. The patient revealed a history of a swelling in the periapical area of tooth #9. The patient denied any dental trauma or history of pain. Clinical examination revealed no mobility, but there was discrete discomfort when horizontal pressure was applied. Pulp vitality was present in all maxillary anterior teeth. Radiographs revealed an oval radiolucent lesion in the periapical region of maxillary central incisor. The therapeutic option was enucleation of the periapical lesion and histologic examination of the specimen. Microscopic findings suggested the diagnosis of a COC. At a follow-up visit 10 years after surgery, panoramic and periapical radiographs showed new bone formation; the patient did not have any pain, and pulp vitality was maintained in all teeth in this area. A COC should be part of the differential diagnosis of other jaw lesions, such as apical periodontitis. The definitive diagnosis of a COC can only be made after microscopic evaluation of the specimen. The follow-up is a helpful reference because it confirms the survival of pulp tissue and no recurrence of the COC. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Opinion and experience of Brazilian women regarding menstrual bleeding and use of combined oral contraceptives.

PubMed

Makuch, Maria Y; Duarte-Osis, Maria J; de Pádua, Karla S; Petta, Carlos; Bahamondes, Luis

2012-04-01

To describe the opinion and experience of Brazilian women regarding menstruation and the use of combined oral contraceptives (COCs) to control monthly bleeding and induce amenorrhea. Women attending regional public healthcare clinics for non-gynecologic conditions, and female members of staff from university schools unrelated to the field of medicine completed a questionnaire. Of the 1111 women interviewed, 64.3% reported disliking menstruation. The desired frequency of bleeding was never (65.3%), less than monthly (18.2%), and every month or more often (16.5%). More than 60% of the women reported that they would use COCs to control menstrual bleeding, 82.0% would use COCs to reduce the amount of bleeding experienced, and 86.1% would use COCs to induce amenorrhea. When compared with women who disliked menstruation, those who reported that they liked to experience monthly bleeding had fewer years of schooling (OR1.98; 95% CI, 1.30-2.97), low socioeconomic status (OR 1.66; 95% CI, 1.12-2.46), fewer days of menstruation each month (OR 1.62; 95% CI, 1.11-2.36), and 1 or more child (OR 1.13; 95% CI, 1.01-1.26). Many of the women surveyed disliked monthly menstruation and were interested in the use of COCs to control menstrual bleeding and induce amenorrhea. Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Maintaining physiological testosterone levels by adding dehydroepiandrosterone to combined oral contraceptives: I. Endocrine effects.

PubMed

Coelingh Bennink, Herjan J T; Zimmerman, Yvette; Laan, Ellen; Termeer, Hanneke M M; Appels, Nicole; Albert, Adelin; Fauser, Bart C J M; Thijssen, Jos H H; van Lunsen, Rik H W

2017-11-01

To determine whether adding dehydroepiandrosterone to combined oral contraceptives (COCs) maintains physiological levels of free testosterone. A randomized, double-blind, placebo-controlled, two-way crossover study conducted in 81 healthy women (age range: 20-35 years; Body mass index (BMI) range: 18-35 kg/m 2 ) using oral contraceptives. Androgens, sex hormone-binding globulin (SHBG), estradiol (E2) and estrone (E1) were measured, and free testosterone and the free testosterone index were calculated. Subjects discontinued oral contraceptive use for at least one menstrual cycle before being randomized to receive five cycles of ethinyl estradiol (EE) combined with either levonorgestrel (EE/LNG group) or drospirenone (EE/DRSP group) together with either dehydroepiandrosterone (DHEA) (50 mg/day orally) or placebo. Subsequently, all subjects crossed over to the other treatment arm for an additional five cycles. Both COCs decreased the levels of all androgens measured. Significant decreases (p<.05) were found with EE/LNG and EE/DRSP for total testosterone (54.5% and 11.3%, respectively) and for free testosterone (66.8% and 75.6%, respectively). Adding DHEA to the COCs significantly increased all androgens compared to placebo. Moreover, including DHEA restored free testosterone levels to baseline values in both COC groups and total testosterone levels to baseline in the EE/LNG group and above baseline in the EE/DRSP group. SHBG concentrations were significantly higher with EE/DRSP compared to EE/LNG (p<.0001). The addition of DHEA did not affect the levels of SHBG. Taking COCs reduces total and free testosterone levels and increases SHBG concentrations. By coadministration with DHEA, physiological levels of total and free testosterone are restored while using EE/LNG. With EE/DRSP, only the free testosterone level is normalized by DHEA coadministration. A daily oral dose of 50-mg DHEA maintains physiological free and total testosterone levels in women who are using an EE/LNG-containing COC. Copyright © 2016 Pantarhei Bioscience. Published by Elsevier Inc. All rights reserved.

Do different types of bearings and noise from total hip arthroplasty influence hip-related pain, function, and quality of life postoperatively?

PubMed Central

Varnum, Claus; Pedersen, Alma B; Kjærsgaard-Andersen, Per; Overgaard, Søren

2016-01-01

Background and purpose — Patient-reported outcome (PRO) is recognized as an important tool for evaluating the outcome and satisfaction after total hip arthroplasty (THA). We wanted to compare patient-reported outcome measure (PROM) scores from patients with ceramic-on-ceramic (CoC) THAs and those with metal-on-metal (MoM) THAs to scores from patients with metal-on-polyethylene (MoP) THAs, and to determine the influence of THA-related noise on PROM scores. Patients and methods — We conducted a nationwide cross-sectional questionnaire survey in a cohort of patients identified from the Danish Hip Arthroplasty Registry. The PROMs included were: hip dysfunction and osteoarthritis and outcome score (HOOS), EQ-5D-3L, EQ VAS, UCLA activity score, and questions about noise from the THA. The response rate was 85% and the number of responders was 3,089. Of these, 45% had CoC THAs, 17% had MoM THAs, and 38% had MoP THAs, with a mean length of follow-up of 7, 5, and 7 years, respectively. Results — Compared to MoP THAs, the mean PROM scores for CoC and MoM THAs were similar, except that CoC THAs had a lower mean score for HOOS Symptoms than did MoP THA. 27% of patients with CoC THAs, 29% with MoM THAs, and 12% with MoP THAs reported noise from their hip. For the 3 types of bearings, PROM scores from patients with a noisy THA were statistically significantly worse than those from patients with a silent MoP THA. The exception was noisy CoC and MoM THAs, which had the same mean UCLA activity score as silent MoP THAs. Interpretation — A high proportion of patients reported noise from the THA, and these patients had worse PROM scores than patients with silent MoP THAs. PMID:27615443

Fatty acid composition of porcine cumulus oocyte complexes (COC) during maturation: effect of the lipid modulators trans-10, cis-12 conjugated linoleic acid (t10,c12 CLA) and forskolin.

PubMed

Prates, E G; Alves, S P; Marques, C C; Baptista, M C; Horta, A E M; Bessa, R J B; Pereira, R M

2013-05-01

The effect of maturation and of two lipid modulators supplementation along in vitro maturation (IVM) on fatty acid (FA) and dimethylacetal (DMA) composition of porcine cumulus oocyte complexes (COC) were studied. Abattoir-derived immature COC were analyzed for FA and DMA or submitted to IVM as follows: control group; t10,c12 CLA group, t10,c12 CLA supplementation for 44 h; Forskolin group, forskolin supplementation during the initial 2 h; t10,c12 CLA + forskolin group, t10,c12 CLA for 44 h and forskolin for just 2h. Each experimental group had five replicates. FA analysis of oocytes, cumulus cells (CC), follicular fluid, and culture media were performed by gas-liquid chromatography. Oocytes and their CC had different FA composition. Oocytes were richer in saturated FA (SFA) preferentially maintaining their FA profile during maturation. Mature CC had the highest polyunsaturated FA (PUFA) content. Five individual and total SFA, and monounsaturated FA (MUFA), notably oleic acid (c9-18:1), percentages were lower (P ≤ 0.023) in mature than in immature CC. t10,c12 CLA was accumulated by COC from t10,c12 CLA and t10,c12 CLA + forskolin groups, mostly in CC where MUFA and an eicosatrienoic isomer decreased (P ≤ 0.043). Nevertheless, PUFA or FA and DMA total content were not affected. Arachidonic acid was reduced in t10,c12 CLA + forskolin CC and hexadecanal-DMA-16:0 in t10,c12 CLA CC. Forskolin alone increased (P ≤ 0.043) c9-18:1 in oocytes. In conclusion, maturation process clearly changed porcine COC FA and DMA profiles, mostly of CC, also more susceptible to modifications induced by t10,c12 CLA. This possibility of manipulating COC lipid composition during IVM could be used to improve oocyte quality/cryopreservation efficiency.

Cocaine abuse versus cocaine dependence: cocaine self-administration and pharmacodynamic response in the human laboratory.

PubMed

Walsh, Sharon L; Donny, Eric C; Nuzzo, Paul A; Umbricht, Annie; Bigelow, George E

2010-01-01

Cocaine has high abuse liability but only a subset of individuals who experiment with it develop dependence. The DSM-IV (APA. Diagnostic and Statistical Manual of Mental Disorders DSM-IV-R. American Psychiatric Association, Washington, DC, 2000) provides criteria for diagnosing cocaine abuse and cocaine dependence as distinct disorders- the latter characterized by additional symptoms related to loss of control over drug use. In this study, two groups of cocaine users (n=8/group), matched on demographic factors and length of cocaine use history and meeting criteria for either cocaine abuse (CocAb) or cocaine dependence (CocDep), were compared on (1) measures related to impulsivity and sensation seeking, (2) response to experimenter-administered cocaine (0, 12.5, 25 and 50mg/70 kg, i.v.), and (3) cocaine self-administration using a Relapse Choice and a Progressive Ratio Procedure (0, 12.5 and 25mg/70 kg, i.v.). Groups did not differ on impulsivity or sensation seeking scores. After experimenter-administered cocaine, the CocAb group reported feeling more suspicious and observers rated them significantly higher on unpleasant effects (e.g., irritability, difficulty concentrating). In contrast, the CocDep group reported significantly greater desire for cocaine, which was sustained over the course of the study, and gave higher street value estimates for cocaine (p<0.05). While cocaine self-administration was dose-related and generally comparable across the two procedures, the CocDep users chose to take significantly more cocaine than the CocAb users. These data suggest that, while regular long-term users of cocaine with cocaine abuse or dependence diagnoses cannot be distinguished by trait measures related to impulsivity, they do exhibit significant differences with regard to cocaine-directed behavior and response to cocaine administration. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Investigation of the hemostatic effect of a transdermal patch containing 0.55 mg ethinyl estradiol and 2.1 mg gestodene compared with a monophasic oral contraceptive containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel: an open-label, randomized, crossover study.

PubMed

Junge, Wolfgang; Heger-Mahn, Doris; Trummer, Dietmar; Merz, Martin

2013-09-01

Transdermal delivery of contraceptives offers several advantages over combined oral contraceptives (COCs), including effective absorption and the provision of relatively constant serum concentrations. Ethinyl estradiol (EE) and the progestin gestodene are well-absorbed through the skin and, therefore, well-suited for use in a transdermal contraceptive patch. The objective of this study was to investigate the impact of a once-weekly transparent, transdermal patch delivering low doses of EE and gestodene equivalent to a COC containing 0.02 mg EE and 0.06 mg gestodene on hemostasis parameters compared with a monophasic COC containing 0.03 mg EE and 0.15 mg levonorgestrel. In this single-center, open-label, randomized, crossover study, 30 women (aged 18-35 years) received three cycles of each treatment, separated by a two-cycle washout period. The primary outcome measure was the absolute change from baseline in prothrombin fragments 1 + 2 and D-dimer. For both treatments, prothrombin fragments 1 + 2 remained stable during the first treatment period, and increased only slightly in the second period (mean absolute change 0.025 and 0.028 nmol/L in the novel Bayer patch and COC groups, respectively). Increases in D-dimer were observed in both periods (mean absolute change 107.0 ± 147.2 ng/L for the novel Bayer patch and 113.7 ± 159.0 ng/L for the COC). There were no statistically significant treatment differences in prothrombin 1 + 2 or D-dimer (p = 0.667 and p = 0.884, respectively) and no statistically significant treatment sequence or period effects. A COC containing 0.03 mg EE and 0.15 mg levonorgestrel and the novel Bayer patch have comparable influence on hemostatic endpoints. Both treatments were well-tolerated by subjects.

Continuum of Care in a Maternal, Newborn and Child Health Program in Ghana: Low Completion Rate and Multiple Obstacle Factors

PubMed Central

Yeji, Francis; Shibanuma, Akira; Oduro, Abraham; Debpuur, Cornelius; Kikuchi, Kimiyo; Owusu-Agei, Seth; Gyapong, Margaret; Okawa, Sumiyo; Ansah, Evelyn; Asare, Gloria Quansah; Nanishi, Keiko; Williams, John; Addei, Sheila; Tawiah, Charlotte; Yasuoka, Junko; Enuameh, Yeetey; Sakeah, Evelyn; Wontuo, Peter; Jimba, Masamine; Hodgson, Abraham

2015-01-01

Background Slow progress has been made in achieving the Millennium Development Goals 4 and 5 in Ghana. Ensuring continuum of care (at least four antenatal visits; skilled birth attendance; postnatal care within 48 hours, at two weeks, and six weeks) for mother and newborn is crucial in helping Ghana achieve these goals and beyond. This study examined the levels and factors associated with continuum of care (CoC) completion among Ghanaian women aged 15–49. Methods A retrospective cross-sectional survey was conducted among women who experienced live births between January 2011 and April 2013 in three regions of Ghana. In a two-stage random sampling method, 1,500 women with infants were selected and interviewed about maternal and newborn service usage in line with CoC. Multiple logistic regression models were used to assess factors associated with CoC completion. Results Only 8.0% had CoC completion; the greatest gap and contributor to the low CoC was detected between delivery and postnatal care within 48 hours postpartum. About 95% of women had a minimum of four antenatal visits and postnatal care at six weeks postpartum. A total of 75% had skilled assisted delivery and 25% received postnatal care within 48 hours. Factors associated with CoC completion at 95% CI were geographical location (OR = 0.35, CI 0.13–0.39), marital status (OR = 0.45; CI 0.22–0.95), education (OR = 2.71; CI 1.11–6.57), transportation (OR = 1.97; CI 1.07–3.62), and beliefs about childhood illnesses (OR = 0.34; CI0.21–0.61). Conclusion The continuum of care completion rate is low in the study site. Efforts should focus on increasing postnatal care within 48 hours and overcoming the known obstacles to increasing the continuum of care completion rate. PMID:26650388

[Enhanced prenatal HIV couple oriented counselling session and couple communication about HIV (ANRS 12127 Prenahtest Trial)].

PubMed

Plazy, M; Orne-Gliemann, J; Balestre, E; Miric, M; Darak, S; Butsashvili, M; Tchendjou, P; Dabis, F; Desgrées du Loû, A

2013-08-01

The Prenahtest study investigated the efficacy of a couple-oriented HIV counselling session (COC) in encouraging couple HIV counselling and testing, and improving intra-couple communication about sexual and reproductive health. We report here on the effect of COC on intra-couple communication about HIV. Within this 4-country trial (India, Georgia, Dominican Republic and Cameroon), 484 to 491 pregnant women per site were recruited and individually randomized to receive either the COC intervention, enhanced counselling with role playing, or standard post-test HIV counselling. Women were interviewed at recruitment, before HIV testing (T0), and 2 to 8 weeks after post-test HIV counselling (T1). Four dichotomous variables documented intra-couple communication about HIV at T1: 1) discussion about HIV, 2) discussion about condom use, 3) suggesting HIV testing and 4) suggesting couple HIV counselling to the partner. An intra-couple HIV communication index was created: low degree of communication ("yes" response to zero or one of the four variables), intermediate degree of communication ("yes" to two or three variables) or high degree of communication ("yes" to the four variables). To estimate the impact of COC on the intra-couple HIV communication index, multivariable logistic regressions were conducted. One thousand six hundred and seven women were included in the analysis of whom 54 (3.4%) were HIV-infected (49 in Cameroon). In the four countries, the counselling group was associated with intra-couple HIV communication (P≤0.03): women allocated to the COC group were significantly more likely to report high or intermediate degrees of intra-couple communication about HIV (versus low degree of communication) than women allocated to standard counselling. COC improved short-term communication about HIV within couples in different sociocultural contexts, a positive finding for a couple approach to HIV prevention. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

The fate of river organic carbon in coastal areas: A study in the Rhône River delta using multiple isotopic (δ13C, Δ14C) and organic tracers

NASA Astrophysics Data System (ADS)

Cathalot, C.; Rabouille, C.; Tisnérat-Laborde, N.; Toussaint, F.; Kerhervé, P.; Buscail, R.; Loftis, K.; Sun, M.-Y.; Tronczynski, J.; Azoury, S.; Lansard, B.; Treignier, C.; Pastor, L.; Tesi, T.

2013-10-01

A significant fraction of the global carbon flux to the ocean occurs in River-dominated Ocean Margins (RiOMar) although large uncertainties remain in the cycle of organic matter (OM) in these systems. In particular, the OM sources and residence time have not been well clarified. Surface (0-1 cm) and sub-surface (3-4 cm) sediments and water column particles (bottom and intermediate depth) from the Rhône River delta system were collected in June 2005 and in April 2007 for a multi-proxy study. Lignin phenols, black carbon (BC), proto-kerogen/BC mixture, polycyclic aromatic hydrocarbons (PAHs), carbon stable isotope (δ13COC), and radiocarbon measurements (Δ14COC) were carried out to characterize the source of sedimentary organic material and to address degradation and transport processes. The bulk OM in the prodelta sediment appears to have a predominantly modern terrigenous origin with a significant contribution of modern vascular C3 plant detritus (Δ14COC = 27.9‰, δ13COC = -27.4‰). In contrast, the adjacent continental shelf, below the river plume, seems to be dominated by aged OM (Δ14COC = -400‰, δ13COC = -24.2‰), and shows no evidence of dilution and/or replacement by freshly produced marine carbon. Our data suggest an important contribution of black carbon (50% of OC) in the continental shelf sediments. Selective degradation processes occur along the main dispersal sediment system, promoting the loss of a modern terrestrial OM but also proto-kerogen-like OM. In addition, we hypothesize that during the transport across the shelf, a long term resuspension/deposition loop induces efficient long term degradation processes able to rework such refractory-like material until the OC is protected by the mineral matrix of particles.

Structured triglycerides containing caprylic (8:0) and oleic (18:1) fatty acids reduce blood cholesterol concentrations and aortic cholesterol accumulation in hamsters.

PubMed

Wilson, Thomas A; Kritchevsky, David; Kotyla, Timothy; Nicolosi, Robert J

2006-03-01

The effects of structured triglycerides containing one long chain fatty acid (oleic acid, C18:1) and one short chain saturated fatty acid (caprylic acid, 8:0) on lipidemia, liver and aortic cholesterol, and fecal neutral sterol excretion were investigated in male Golden Syrian hamsters fed a hypercholesterolemic regimen consisting of 89.9% commercial ration to which was added 10% coconut oil and 0.1% cholesterol (w/w). After 2 weeks on the HCD diet, the hamsters were bled, following an overnight fast (16 h) and placed into one of three dietary treatments of eight animals each based on similar plasma cholesterol levels. The hamsters either continued on the HCD diet or were placed on diets in which the coconut oil was replaced by one of two structured triglycerides, namely, 1(3),2-dicaproyl-3(1)-oleoylglycerol (OCC) or 1,3-dicaproyl-2-oleoylglycerol (COC) at 10% by weight. Plasma total cholesterol (TC) in hamsters fed the OCC and COC compared to the HCD were reduced 40% and 49%, respectively (P<0.05). Similarly, hamsters fed the OCC and COC diets reduced their plasma nonHDL cholesterol levels by 47% and 57%, respectively (P<0.05), compared to hamsters fed the HCD after 2 weeks of dietary treatment. Although hamsters fed the OCC (-26%) and COC (-32%) had significantly lower plasma HDL levels compared to HCD, (P<0.05), the plasma nonHDL/HDL cholesterol ratio was significantly lower (P<0.05) compared to the HCD for the OCC-fed (-27%) and the COC-fed (-38%) hamsters, respectively. Compared to the HCD group, aortic esterified cholesterol was 20% and 53% lower for the OCC and COC groups, respectively, with the latter reaching statistical significance, P<0.05. In conclusion, the hamsters fed the structured triglyceride oils had lower blood cholesterol levels and lower aortic accumulation of cholesterol compared to the control fed hamsters.

75 FR 44983 - Notice of Invitation To Participate; Exploration for Coal in Colorado; License Application COC-74235

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-30

...] Notice of Invitation To Participate; Exploration for Coal in Colorado; License Application COC-74235... exploration of coal deposits owned by the United States of America in lands located in Delta County, Colorado...) of the Mineral Leasing Act of 1920, as amended by section 4 of the Federal Coal Leasing Amendments...

76 FR 53693 - Notice of Invitation To Participate; Coal Exploration License Application COC-74911, Colorado

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-29

...] Notice of Invitation To Participate; Coal Exploration License Application COC-74911, Colorado AGENCY..., as amended by the Federal Coal Leasing Amendments Act of 1976, and to Bureau of Land Management (BLM... cost-sharing basis, in a program for the exploration of coal deposits owned by the United States of...

48 CFR 19.602-3 - Resolving differences between the agency and the Small Business Administration.

Code of Federal Regulations, 2010 CFR

2010-10-01

... information, the SBA will make a final decision to either issue or deny the COC. (c) Reconsideration of a COC... complete exchange of information and in accordance with agency procedures. If agreement cannot be reached... and that an appeal decision may be requested by an authorized official. (3) If the contracting agency...

77 FR 43114 - Notice of Proposed Reinstatement of Terminated Oil and Gas Lease COC66025

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-23

... Management, Interior. ACTION: Notice. SUMMARY: Under the provisions of the Mineral Leasing Act of 1920, as... COC66025 from Robert P. Kirgan, for lands in Rio Blanco, Colorado. The petition was filed on time and was... CONTACT: Milada Krasilinec, BLM Land Law Examiner, Fluid Minerals Adjudication, at 303-239-3767. Persons...

77 FR 43112 - Notice of Proposed Reinstatement of Terminated Oil and Gas Lease COC66018

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-23

... Management, Interior. ACTION: Notice. SUMMARY: Under the provisions of the Mineral Leasing Act of 1920, as... COC66018 from Robert P. Kirgan, for lands in Rio Blanco, Colorado. The petition was filed on time and was... CONTACT: Milada Krasilinec, BLM Land Law Examiner, Fluid Minerals Adjudication, at 303-239-3767. Persons...

77 FR 43113 - Notice of Proposed Reinstatement of Terminated Oil and Gas Lease COC66020

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-23

... Management, Interior. ACTION: Notice. SUMMARY: Under the provisions of the Mineral Leasing Act of 1920, as... COC66020 from Robert P. Kirgan, for lands in Rio Blanco, Colorado. The petition was filed on time and was... CONTACT: Milada Krasilinec, BLM Land Law Examiner, Fluid Minerals Adjudication, at 303-239-3767. Persons...

75 FR 66786 - Notice of Invitation To Participate; Exploration for Coal in Colorado License Application COC-74447

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-29

...] Notice of Invitation To Participate; Exploration for Coal in Colorado License Application COC-74447... Routt Counties, Colorado. DATES: Any party electing to participate in this exploration program must send... notice will be published once a week for 2 consecutive weeks in the Craig Daily Press, Craig, Colorado...

21 CFR 1311.20 - Coordinators for CSOS digital certificate holders.

Code of Federal Regulations, 2011 CFR

2011-04-01

... digital certificates issued under that registrant's DEA registration. While the coordinator will be the main point of contact between one or more DEA registered locations and the CSOS Certification Authority... application that the DEA Certification Authority provides and submit the following: (1) Two copies of...

Cellular phone-based image acquisition and quantitative ratiometric method for detecting cocaine and benzoylecgonine for biological and forensic applications.

PubMed

Cadle, Brian A; Rasmus, Kristin C; Varela, Juan A; Leverich, Leah S; O'Neill, Casey E; Bachtell, Ryan K; Cooper, Donald C

2010-01-01

Here we describe the first report of using low-cost cellular or web-based digital cameras to image and quantify standardized rapid immunoassay strips as a new point-of-care diagnostic and forensics tool with health applications. Quantitative ratiometric pixel density analysis (QRPDA) is an automated method requiring end-users to utilize inexpensive (∼ $1 USD/each) immunotest strips, a commonly available web or mobile phone camera or scanner, and internet or cellular service. A model is described whereby a central computer server and freely available IMAGEJ image analysis software records and analyzes the incoming image data with time-stamp and geo-tag information and performs the QRPDA using custom JAVA based macros (http://www.neurocloud.org). To demonstrate QRPDA we developed a standardized method using rapid immunotest strips directed against cocaine and its major metabolite, benzoylecgonine. Images from standardized samples were acquired using several devices, including a mobile phone camera, web cam, and scanner. We performed image analysis of three brands of commercially available dye-conjugated anti-cocaine/benzoylecgonine (COC/BE) antibody test strips in response to three different series of cocaine concentrations ranging from 0.1 to 300 ng/ml and BE concentrations ranging from 0.003 to 0.1 ng/ml. This data was then used to create standard curves to allow quantification of COC/BE in biological samples. Across all devices, QRPDA quantification of COC and BE proved to be a sensitive, economical, and faster alternative to more costly methods, such as gas chromatography-mass spectrometry, tandem mass spectrometry, or high pressure liquid chromatography. The limit of detection was determined to be between 0.1 and 5 ng/ml. To simulate conditions in the field, QRPDA was found to be robust under a variety of image acquisition and testing conditions that varied temperature, lighting, resolution, magnification and concentrations of biological fluid in a sample. To determine the effectiveness of the QRPDA method for quantifying cocaine in biological samples, mice were injected with a sub-locomotor activating dose of cocaine (5 mg/kg; i.p.) and were found to have detectable levels of COC/BE in their urine (160.6 ng/ml) and blood plasma (8.1 ng/ml) after 15-30 minutes. By comparison rats self-administering cocaine in a 4 hour session obtained a final BE blood plasma level of 910 ng/ml with an average of 62.5 infusions. It is concluded that automated QRPDA is a low-cost, rapid and highly sensitive method for the detection of COC/BE with health, forensics, and bioinformatics application and the potential to be used with other rapid immunotest strips directed at several other targets. Thus, this report serves as a general reference and method describing the use of image analysis of lateral flow rapid test strips.

TOFA suppresses ovarian cancer cell growth in vitro and in vivo.

PubMed

Li, Shu; Qiu, Lihua; Wu, Buchu; Shen, Haoran; Zhu, Jing; Zhou, Liang; Gu, Liying; Di, Wen

2013-08-01

A characteristic feature of cancer cells is the activation of de novo fatty acid synthesis. Acetyl‑CoA carboxylase (ACC) is a key enzyme in fatty acid synthesis, accelerating the reaction that carboxylates cytosolic acetyl‑CoA to form malonyl‑CoA. ACC is highly expressed in several types of human cancer and is important in breast and prostate cancer cell growth. The aim of the present study was to investigate the effects of 5‑tetradecyloxy‑2‑furoic acid (TOFA), an allosteric inhibitor of ACC, on the proliferation and cell cycle progression of the ovarian cancer cell lines COC1 and COC1/DDP. TOFA was found to be cytotoxic to COC1 and COC1/DDP cells with a 50% inhibitory concentration (IC50) of ~26.1 and 11.6 µg/ml, respectively. TOFA inhibited the proliferation of the cancer cells examined in a time‑ and dose‑dependent manner, arrested the cells in the G0/G1 cell cycle phase and induced apoptosis. The expression of the cell cycle regulating proteins cyclin D1 and cyclin-dependent kinase (CDK) 4, as well as the expression of the apoptosis‑related proteins caspase‑3 and Bcl‑2, were detected by western blot analysis. Cyclin D1, CDK4 and Bcl‑2 protein expression was inhibited by TOFA, while caspase‑3 was cleaved and activated. To the best of our knowledge, the present study demonstrated for the first time that TOFA inhibits COC1/DDP cell growth in ovarian tumor mouse xenografts. By inhibiting ACC, TOFA may be a promising small molecule agent for ovarian cancer therapy.

Computational design of a thermostable mutant of cocaine esterase via molecular dynamics simulations.

PubMed

Huang, Xiaoqin; Gao, Daquan; Zhan, Chang-Guo

2011-06-07

Cocaine esterase (CocE) has been known as the most efficient native enzyme for metabolizing naturally occurring cocaine. A major obstacle to the clinical application of CocE is the thermoinstability of native CocE with a half-life of only ∼11 min at physiological temperature (37 °C). It is highly desirable to develop a thermostable mutant of CocE for therapeutic treatment of cocaine overdose and addiction. To establish a structure-thermostability relationship, we carried out molecular dynamics (MD) simulations at 400 K on wild-type CocE and previously known thermostable mutants, demonstrating that the thermostability of the active form of the enzyme correlates with the fluctuation (characterized as the root-mean square deviation and root-mean square fluctuation of atomic positions) of the catalytic residues (Y44, S117, Y118, H287, and D259) in the simulated enzyme. In light of the structure-thermostability correlation, further computational modelling including MD simulations at 400 K predicted that the active site structure of the L169K mutant should be more thermostable. The prediction has been confirmed by wet experimental tests showing that the active form of the L169K mutant had a half-life of 570 min at 37 °C, which is significantly longer than those of the wild-type and previously known thermostable mutants. The encouraging outcome suggests that the high-temperature MD simulations and the structure-thermostability relationship may be considered as a valuable tool for the computational design of thermostable mutants of an enzyme.

Treatment of moderate acne vulgaris using a combined oral contraceptive containing ethinylestradiol 20 μg plus drospirenone 3mg administered in a 24/4 regimen: a pooled analysis.

PubMed

Koltun, William; Maloney, J Michael; Marr, Joachim; Kunz, Michael

2011-04-01

To investigate the effects of an ethinylestradiol (EE) 20 μg/drospirenone (drsp) 3mg combined oral contraceptive (COC) administered in a 24/4 regimen (24 active tablets/4 inert tablets per cycle) for the treatment of moderate acne vulgaris, based on a pooled analysis of two identically designed US studies. Healthy females (n=893) aged 14-45 years with moderate facial acne were randomised to EE 20 μg/drsp 3mg COC (n=451) or placebo (n=442) for six cycles. Primary outcome measures were mean percent change in acne lesion counts and the investigators' assessment of acne from baseline to endpoint. There were significantly greater reductions in the mean percent change from baseline to endpoint in inflammatory, non-inflammatory and total lesion counts in the EE 20 μg/drsp 3mg 24/4 COC group compared with the placebo group (P<0.0001). The odds of women in the EE 20 μg/drsp 3mg 24/4 COC group having 'clear' or 'almost clear' skin as rated by the investigators at endpoint were around three-fold greater than in the placebo group (odds ratio 3.41; 95% CI: 2.15-5.43; P<0.0001). A low-dose COC containing EE 20 μg/drsp 3mg (24/4) more effectively reduced acne lesions than placebo and demonstrated greater improvement in the investigator global assessment of acne. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Video training and certification program improves reliability of postischemic neurologic deficit measurement in the rat.

PubMed

Taninishi, Hideki; Pearlstein, Molly; Sheng, Huaxin; Izutsu, Miwa; Chaparro, Rafael E; Goldstein, Larry B; Warner, David S

2016-12-01

Scoring systems are used to measure behavioral deficits in stroke research. Video-assisted training is used to standardize stroke-related neurologic deficit scoring in humans. We hypothesized that a video-assisted training and certification program can improve inter-rater reliability in assessing neurologic function after middle cerebral artery occlusion in rats. Three expert raters scored neurologic deficits in post-middle cerebral artery occlusion rats using three published systems having different complexity levels (3, 18, or 48 points). The system having the highest point estimate for the correlation between neurologic score and infarct size was selected to create a video-assisted training and certification program. Eight trainee raters completed the video-assisted training and certification program. Inter-rater agreement ( Κ: score) and agreement with expert consensus scores were measured before and after video-assisted training and certification program completion. The 48-point system correlated best with infarct size. Video-assisted training and certification improved agreement with expert consensus scores (pretraining = 65 ± 10, posttraining = 87 ± 14, 112 possible scores, P < 0.0001), median number of trainee raters with scores within ±2 points of the expert consensus score (pretraining = 4, posttraining = 6.5, P < 0.01), categories with Κ:  > 0.4 (pretraining = 4, posttraining = 9), and number of categories with an improvement in the Κ: score from pretraining to posttraining (n = 6). Video-assisted training and certification improved trainee inter-rater reliability and agreement with expert consensus behavioral scores in rats after middle cerebral artery occlusion. Video-assisted training and certification may be useful in multilaboratory preclinical studies. © The Author(s) 2015.

The contraceptive vaginal ring, NuvaRing(®), a decade after its introduction.

PubMed

Roumen, Frans J M E; Mishell, Daniel R

2012-12-01

To review the clinical experience with the contraceptive vaginal ring (CVR, NuvaRing(®)) since its introduction over ten years ago. The literature was searched on efficacy, cycle control, safety, user preference and satisfaction of the CVR in comparison with combined oral contraceptives (COCs) and the patch, with special attention to recent developments. The ring has the same working mechanism and contraindications as COCs. Serum levels of steroids are steadier, whereas oestrogenic exposure is lower. Contraceptive efficacy is similar, as are metabolic changes. Cycle control is better, and compliance and continuation rates are equal or higher. Oestrogen-related adverse symptoms appear to be fewer, but reports on the incidence of venous thrombosis are conflicting. Expulsion of the ring is reported by 4% to 20% of women. Local adverse events are the main reason for discontinuation. Acceptability is as high as with COCs and, after structured counselling, the ring is preferred by many women to the pill or the patch. Efficacy of the CVR, and the metabolic changes and adverse events it elicits, are generally comparable to those of COCs, yet oestrogenic exposure is lower and cycle control superior. After counselling, the ring is preferred to the pill by many women.

On-chip micropatterning of plastic (cylic olefin copolymer, COC) microfluidic channels for the fabrication of biomolecule microarrays using photografting methods.

PubMed

Pu, Qiaosheng; Oyesanya, Olufemi; Thompson, Bowlin; Liu, Shantang; Alvarez, Julio C

2007-01-30

This paper reports on the surface modification of plastic microfluidic channels to prepare different biomolecule micropatterns using ultraviolet (UV) photografting methods. The linkage chemistry is based upon UV photopolymerization of acryl monomers to generate thin films (0.01-6 microm) chemically linked to the organic backbone of the plastic surface. The commodity thermoplastic, cyclic olefin copolymer (COC) was selected to build microfluidic chips because of its significant UV transparency and easiness for microfabrication by molding techniques. Once the polyacrylic films were grafted on the COC surface using photomasks, micropatterns of proteins, DNA, and biotinlated conjugates were readily obtained by surface chemical reactions in one or two subsequent steps. The thickness of the photografted films can be tuned from several nanometers up to several micrometers, depending on the reaction conditions. The micropatterned films can be prepared inside the microfluidic channel (on-chip) or on open COC surfaces (off-chip) with densities of functional groups about 10(-7) mol/cm2. Characterization of these films was performed by attenuated-total-reflectance IR spectroscopy, fluorescence microscopy, profilometry, atomic force microscopy, and electrokinetic methods.

Characterization of bonding between poly(dimethylsiloxane) and cyclic olefin copolymer using corona discharge induced grafting polymerization.

PubMed

Liu, Ke; Gu, Pan; Hamaker, Kiri; Fan, Z Hugh

2012-01-01

Thermoplastics have been increasingly used for fabricating microfluidic devices because of their low cost, mechanical/biocompatible attributes, and well-established manufacturing processes. However, there is sometimes a need to integrate such a device with components made from other materials such as polydimethylsiloxane (PDMS). Bonding thermoplastics with PDMS to produce hybrid devices is not straightforward. We have reported our method to modify the surface property of a cyclic olefin copolymer (COC) substrate by using corona discharge and grafting polymerization of 3-(trimethoxysilyl)propyl methacrylate; the modified surface enabled strong bonding of COC with PDMS. In this paper, we report our studies on the surface modification mechanism using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and contact angle measurement. Using this bonding method, we fabricated a three-layer (COC/PDMS/COC) hybrid device consisting of elastomer-based valve arrays. The microvalve operation was confirmed through the displacement of a dye solution in a fluidic channel when the elastomer membrane was pneumatically actuated. Valve-enabled microfluidic handling was demonstrated. Copyright © 2011 Elsevier Inc. All rights reserved.

Persistent apical periodontitis associated with a calcifying odontogenic cyst.

PubMed

Estrela, C; Decurcio, D A; Silva, J A; Mendonça, E F; Estrela, C R A

2009-06-01

To report a case of calcifying odontogenic cyst (COC) that was suggestive of apical periodontitis adjacent to the roots of the maxillary incisor teeth. Tooth 21 presented with clinical and radiographic signs of secondary infection, a post within the root canal and substantial internal tooth destruction; it was scheduled for endodontic surgery. Teeth 12 and 22 were root filled following the placement of a calcium hydroxide intracanal dressing for 21 days. Three attempts at root canal disinfection in tooth 11 were unsuccessful, and a persistent purulent drainage precluded completion of root canal treatment. Surgical enucleation of the periapical lesion was undertaken and the tissues submitted for histopathological examination. A diagnosis of COC was established based on the microscopic analysis. COC is an unusual benign lesion that represents 2% of all odontogenic lesions. Depending on the stage of development, it can mimic a large lesion associated with apical periodontitis and should therefore be considered in the differential diagnosis. In the case of COC, the definitive diagnosis can only be made with histopathological analysis. Persistent apical periodontitis may be of nonendodontic origin. * Histological examination is essential to establish the cause of persistent apical periodontitis. * Calcifying odontogenic cyst can mimic apical periodontitis.

Differences in Reporting Pearl Indices in the United States and Europe: Focus on a 91-Day Extended-Regimen Combined Oral Contraceptive with Low-Dose Ethinyl Estradiol Supplementation

PubMed Central

Abascal, Paloma Lobo; Luzar-Stiffler, Vesna; Giljanovic, Silvana; Howard, Brandon; Weiss, Herman; Trussell, James

2017-01-01

Background Regulatory agencies in the United States (US) and Europe differ in requirements for defining pregnancies after the last dose of oral contraceptive, sometimes resulting in discrepant Pearl Indices (PIs) for the same product despite identical clinical data. This brief report highlights one such example, a 91-day extended-regimen combined oral contraceptive (COC). Methods The US- and European-based PI methodologies were compared for a 91-day extended-regimen COC consisting of 84 days of active levonorgestrel/EE 150 μg/30 μg tablets, followed by 7 days of EE 10 μg tablets in place of placebo. Conclusions At the times of approval of the 91-day extended-regimen COC in the US and Europe, the requirements for defining ‘on-treatment’ pregnancies differed (14-day vs. 2-day rule, respectively). This difference resulted in a higher PI in the US- vs. European-based calculation (1.34 and 0.76, respectively). The differences in the PI should not be interpreted as the extended-regimen COC being less effective in preventing pregnancy in the US compared with Europe. PMID:26115381

Differences in reporting Pearl Indices in the United States and Europe: Focus on a 91-day extended-regimen combined oral contraceptive with low-dose ethinyl estradiol supplementation.

PubMed

Lobo Abascal, Paloma; Luzar-Stiffler, Vesna; Giljanovic, Silvana; Howard, Brandon; Weiss, Herman; Trussell, James

2016-01-01

Regulatory agencies in the United States (US) and Europe differ in requirements for defining pregnancies after the last dose of oral contraceptive, sometimes resulting in discrepant Pearl Indices (PIs) for the same product despite identical clinical data. This brief report highlights one such example, a 91-day extended-regimen combined oral contraceptive (COC). The US- and European-based PI methodologies were compared for a 91-day extended-regimen COC consisting of 84 days of active levonorgestrel/EE 150 μg/30 μg tablets, followed by seven days of EE 10 μg tablets in place of placebo. At the times of approval of the 91-day extended-regimen COC in the US and Europe, the requirements for defining 'on-treatment' pregnancies differed (14-day vs. 2-day rule, respectively). This difference resulted in a higher PI in the US- vs. European-based calculation (1.34 and 0.76, respectively). The differences in the PI should not be interpreted as the extended-regimen COC being less effective in preventing pregnancy in the US compared with Europe.

A new oral contraceptive regimen for endometriosis management: preliminary experience with 24/4-day drospirenone/ethinylestradiol 3 mg/20 mcg.

PubMed

Mabrouk, Mohamed; Solfrini, Serena; Frascà, Clarissa; Del Forno, Simona; Montanari, Giulia; Ferrini, Giulia; Paradisi, Roberto; Seracchioli, Renato

2012-06-01

We report our preliminary experience with the use of a low-dose oral contraceptive containing Drospirenone/Ethinylestradiol 3 mg/20 mcg, both in cyclic and continuous regimen for endometriosis management. A total of 93 women were retrospectively included: 52 were treated by medical therapy (exclusive combined oral contraceptives (COC)-users), while 41 were submitted to surgery followed by postoperative therapy (postoperative COC-users). A clinical examination was performed at baseline and at 6-months follow-up. Presence and intensity of endometriosis-related symptoms were assessed by a visual analogue scale. Presence and dimension of endometriotic lesions were evaluated by transvaginal ultrasonography. Adverse effects and tolerability were analysed. In exclusive COC-users, significant reductions in dysmenorrhoea and dyspareunia scores and in endometrioma mean diameter were observed at follow-up. In postoperative COC-users, anatomical and symptom recurrence rates at follow-up were 4.9% and 17%, respectively. The most frequent adverse effects were spotting and headache. No difference between cyclic and continuous regimen in terms of symptom relief, lesion progression and tolerability was observed. From our preliminary experience, Drospirenone/Ethinylestradiol 3 mg/20 mcg seems to be promising in endometriosis management.

Is There a Cardiotoxicity Associated With Metallic Head Hip Prostheses? A Cohort Study in the French National Health Insurance Databases.

PubMed

Lassalle, Marion; Colas, Sandrine; Rudnichi, Annie; Zureik, Mahmoud; Dray-Spira, Rosemary

2018-07-01

There are four distinguishable types of THA devices in wide use, as defined by the femoral and acetabular bearing surfaces: metal-on-polyethylene (MoP), ceramic-on-polyethylene (CoP), metal-on-metal (MoM), and ceramic-on-ceramic (CoC). Metallic head THAs (MoP and MoM) can potentially induce cardiac toxicity because cobalt species, generated at the head-neck trunnion, and in the case of MoM devices, at the articular surface as well, can be absorbed systemically. However, studies have provided inconsistent results. The purpose of this study was to assess the risk of dilated cardiomyopathy (DCM) or heart failure (HF) associated with metallic head THAs using data from the French national health insurance databases. Between 2008 and 2011 in France, 399,968 patients ≥ 55 years had a first THA. A total of 127,481 were excluded after we applied the exclusion criteria regarding arthroplasty and 17,137 as a result of a history of DCM/HF, recorded in the French national health insurance reimbursement databases, between January 1, 2006, and the date of inclusion. The final cohort included 255,350 individuals (43% men; mean age 72 ± 9 years). Of them, 93,581 (37%) had been implanted with MoP, 58,095 (23%) with CoP, 11,298 (4%) with MoM, and 92,376 (36%) with CoC THAs. Patients were followed until December 2015. Patients with incident DCM/HF were identified by a new entitlement to the long-term disease scheme or a first hospitalization with a diagnosis of DCM or HF. MoP and CoP THAs are generally implanted in old patients, whereas MoM and CoC are mostly indicated in young, active male patients. Thus, to consider the specific indications of the bearing couples, analyses were separately performed in two distinct subcohorts, one comprising patients with MoP or CoP and one comprising patients with MoM or CoC THA. In each subcohort, the DCM/HF risk was compared between patients with metallic head versus nonmetallic head THAs (MoP versus CoP, MoM versus CoC). Hazard ratios (adjusted HRs) of incident DCM/HF were estimated using Cox models adjusted for baseline sex, age, THA characteristics (fixation technique with cement, use of a modular femoral neck), and comorbidities at baseline. Cox models were stratified by sex and age. The crude incidence of DCM/HF per 100 person-years was 2.4 in patients with MoP, 1.8 with CoP, 1.2 with MoM, and 1.1 with CoC THAs. Overall, metallic head THAs were associated with a slight increase in DCM/HF risk (MoP versus CoP: adjusted HR, 1.08; 95% confidence interval [CI], 1.05-1.12; p < 0.001; MoM versus CoC: adjusted HR, 1.11; 95% CI, 1.03-1.19; p = 0.007). In the MoM-CoC subcohort, the risk tended to be more pronounced with MoM versus CoC THAs in women (MoM versus CoC: adjusted HR, 1.20; 95% CI, 1.07-1.35; p = 0.002) and patients aged ≥ 75 years (MoM versus CoC: adjusted HR, 1.16; 95% CI, 1.04-1.29; p = 0.009). Metallic head THAs were associated with a slightly increased DCM/HF risk, especially with MoM in women and older patients. Some caveats should be mentioned: severity of DCM or HF was not available and residual confounding cannot be ruled out despite considering many covariates. Our findings suggest that cardiac function should be regularly monitored in patients with metallic head THAs. Further investigations should be planned on large international cohorts. Level III, therapeutic study.

[Analysis of several key problems of good agricultural practice (GAP) of Chinese materia medica].

PubMed

Yang, Guang; Guo, Lan-Ping; Zhou, Xiu-Teng; Huang, Lu-Qi

2016-04-01

This paper reviewed the historical background of the GAP, analyzed the development experience of five Ps (GMP, GLP, GSP, GCP, GAP), analyzed the GAP based on economic theories, and pointed out that the core problem of GAP is ignoring economic laws. Once the GAP, is a process of certification, but neither the GAP announcement could be transformed into signal transmission quality in the product market, nor consumers could recognize the difference between GAP and non-GAP herbs in the terminal market, so manufacturers lack motivation for GAP certification. In this paper, we pointed out, that the GAP certification system should be redesigned under the guidance of economics, third party certification body, supervised by drug administration organization, to certificate GAP as high quality standards, to improve signal transduction mechanism of GAP certification, and to integrate GAP with the market. Copyright© by the Chinese Pharmaceutical Association.

Comparison of rates of and charges from pregnancy complications in users of extended and cyclic combined oral contraceptive (COC) regimens: a brief report.

PubMed

Howard, Brandon; Trussell, James; Grubb, ElizaBeth; Lage, Maureen J

2014-05-01

To evaluate pregnancy complication rates and related charges in users of 84/7, 21/7 and 24/4 combined oral contraceptives (COCs). Data were obtained from the i3 InVision Data Mart™ retrospective claims database. Subjects were aged 15-40 years, first prescribed a COC between 1/1/2006 and 4/1/2011 and continuously insured for ≥1 year. 84/7 users were matched 1:1 to 21/7 and 24/4 users. Pregnancy-related complication rates and associated charges were significantly lower with 84/7 vs. 21/7 and 24/4 regimens. Preliminary data suggest 84/7 regimens may be associated with fewer pregnancy complications and lower related charges. Copyright © 2014 Elsevier Inc. All rights reserved.

Taking the Easy Way Out: How the GED Testing Program Induces Students to Drop Out.

PubMed

Heckman, James J; Humphries, John Eric; Lafontaine, Paul A; Rodríguez, Pedro L

2012-07-01

The option to obtain a General Education Development (GED) certificate changes the incentives facing high school students. This paper evaluates the effect of three different GED policy innovations on high school graduation rates. A six point decrease in the GED pass rate due to an increase in passing standards produced a 1.3 point decline in overall dropout rates. The introduction of a GED certification program in high schools in Oregon produced a four percent decrease in graduation rates. Introduction of GED certificates in California increased dropout rates by 3 points. The GED program induces high school students to drop out.

Taking the Easy Way Out: How the GED Testing Program Induces Students to Drop Out

PubMed Central

Heckman, James J.; Humphries, John Eric; LaFontaine, Paul A.; Rodríguez, Pedro L.

2011-01-01

The option to obtain a General Education Development (GED) certificate changes the incentives facing high school students. This paper evaluates the effect of three different GED policy innovations on high school graduation rates. A six point decrease in the GED pass rate due to an increase in passing standards produced a 1.3 point decline in overall dropout rates. The introduction of a GED certification program in high schools in Oregon produced a four percent decrease in graduation rates. Introduction of GED certificates in California increased dropout rates by 3 points. The GED program induces high school students to drop out. PMID:24634564

Self-calibration of a W/Re thermocouple using a miniature Ru-C (1954 °C) eutectic cell

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

Ongrai, O.; University of Surrey, Guildford, Surrey; National Institute of Metrology, Klong 5, Klong Luang, Pathumthani

2013-09-11

Previous successful investigations of miniature cobalt-carbon (Co-C, 1324 °C) and palladium-carbon (Pd-C, 1492 °C) high temperature fixed-point cells for thermocouple self-calibration have been reported [1-2]. In the present work, we describe a series of measurements of a miniature ruthenium-carbon (Ru-C) eutectic cell (melting point 1954 °C) to evaluate the repeatability and stability of a W/Re thermocouple (type C) by means of in-situ calibration. A miniature Ru-C eutectic fixed-point cell with outside diameter 14 mm and length 30 mm was fabricated to be used as a self-calibrating device. The performance of the miniature Ru-C cell and the type C thermocouple ismore » presented, including characterization of the stability, repeatability, thermal environment influence, ITS-90 temperature realization and measurement uncertainty.« less

GUIDANCE FOR STATISTICAL DETERMINATION OF APPROPRIATE PERCENT MINORITY AND PERCENT POVERTY DISTRIBUTIONAL CUTOFF VALUES USING CENSUS DATA FOR AND EPA REGION II ENVIRONMENTAL JUSTICE PROJECT

EPA Science Inventory

The purpose of this report is to assist Region H by providing a statistical analysis identifying the areas with minority and below poverty populations known as "Community of Concern" (COC). The aim was to find a cutoff value as a threshold to identify a COC using demographic data...

Efficacy of ormeloxifene versus oral contraceptive in the management of abnormal uterine bleeding due to uterine leiomyoma.

PubMed

Kriplani, Alka; Srivastava, Astha; Kulshrestha, Vidushi; Kachhawa, Garima; Agarwal, Nutan; Bhatla, Neerja; Hari, Smriti

2016-12-01

To compare ormeloxifene with combined oral contraceptive (COC) in abnormal uterine bleeding (AUB) due to leiomyoma (AUB-L). Fifty women with AUB-L were randomized after informed consent and institute ethics clearance. Group I (n = 25) was given ormeloxifene (a SERM i.e. selective estrogen receptor modulator) 60 mg twice per week and group II (n = 25) was given COC (ethinyl estradiol 30 μg with desogestrel 150 μg) on days 1-21 for 6 months. Menstrual blood loss was assessed on pictorial blood loss assessment chart (PBAC) score and leiomyoma volume was assessed on ultrasound. Fibroids were classified according to FIGO-PALM-COEIN classification for AUB where leiomyomas were further sub-classified as types 0 to 8 according to their location. Follow up was done at 1, 3, 6 and 9 months. Mean PBAC score reduced by 81% with ormeloxifene (group I) compared with 43.8% for COC (group II). After 6 months, 18 patients (72%) in group I had PBAC score in the non-menorrhagic range (<100) compared with only two (8%) in group II. In group I, PBAC score in FIGO-PALM-COEIN leiomyoma types 2, 3, 4, 5, 6 reduced by 90.2%, 82.5%, 93.3%, 56.4% and 100%, respectively and 14 (56%) developed amenorrhea; compared with reduction of 64%, 27.5%, 25.9% in types 4, 5 and 6, respectively in group II. Dysmenorrhea visual analog scale score decreased in both groups. Mean leiomyoma volume increased in both groups: by 25.7% with ormeloxifene versus 16.9% with COC; only grade 2 leiomyoma in group I reduced by 44%. One patient in group II with grade 2 leiomyoma discontinued treatment at 3 months. Seven patients (28%) developed ovarian cyst in group I with no other major adverse effect in either group. Ormeloxifene with its convenient twice-weekly dosage schedule was effective in treating AUB-L, with 72% of patients responding to 6-month treatment compared with 8% with COC, even though leiomyoma volume increased insignificantly with both ormeloxifene and COCs. © 2016 Japan Society of Obstetrics and Gynecology.

The effect of bearing friction torques on the primary stability of press-fit acetabular cups: A novel in vitro method.

PubMed

Alexander, Jahnke; Stefan, Schroeder; Alfonso, Fonseca Ulloa Carlos; Adam, Ahmed Gafar; Alexander, Ishaque Bernd; Markus, Rickert

2018-05-10

Aseptic loosening is the main reason for revision of total hip arthroplasty, and relative micromotions between cementless acetabular cups and bone play an important role regarding their comparatively high loosening rate. Therefore, the aim of the present study was to analyze the influence of resulting frictional torques on the primary stability of press-fit acetabular cups subjected to two different bearing partners. A cementless press-fit cup was implanted in bone-like foam. Primary stability of the cup was analyzed by determining spatial total, translational and rotational interface micromotions by means of an eddy current sensor measuring system. Torque transmission into the cup was realized by three synchronous servomotors considering resultant friction torques based on constant friction for ceramic-on-ceramic (CoC: µ = 0.044; max. resultant torque: 1.5 Nm) and for ceramic-on-polyethylene (CoP: µ = 0.063; max. resultant torque: 1.9 Nm) bearing partners. Rotational micromotion of CoC was 8.99 ± 0.85µm and of CoP 13.39 ± 1.43µm. Translational micromotion of CoC was 29.93 ± 1.44µm and of CoP 39.91 ± 2.25µm. Maximum total relative micromotions were 37.10 ± 1.07µm for CoC and 51.64 ± 2.18µm for CoP. Micromotions resulting from CoC were statistically lower than those resulting from CoP (p < 0.05). The described 3D-measuring set-up offers a novel in vitro method of measuring primary stability of acetabular cups. We can therefore conclude, that primary stability of acetabular cup systems can be observed using either the lower friction curve (CoC) or the higher friction curve (CoP). In future studies different cup designs or cup fixation mechanisms may be tested and compared in vitro and assessed prior to implantation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Comparison of daily urine, sweat, and skin swabs among cocaine users.

PubMed

Kidwell, D A; Kidwell, J D; Shinohara, F; Harper, C; Roarty, K; Bernadt, K; McCaulley, R A; Smith, F P

2003-04-23

This study (1) compares urine, skin swabs, and PharmChek sweat patches for monitoring drug use; (2) measures possible environmental contamination in recent cocaine (COC) users; and (3) evaluates various immunoassays (IA) for screening COC in diverse matrices. Unique aspects include daily urine monitoring of 10 participants for 4 weeks, multiple monitoring methods, analysis for all specimens by IA and gas chromatography (GC)/mass spectrometry (MS), and the potential for continued illicit drug use by participants. Urine served as the "gold standard" specimen for determining drug use. Only cocaine and related substances were detected. Trace amounts of drugs were found on the skin (<50 ng per swab) of urine-negative participants' hands or forehead. In contrast, larger quantities of COC were found on the skin of individuals with BE-positive urines or individuals living with drug users (up to 20 microg per swab). Patch COC amounts among the three regular users (250-9000, 0-240, 160-22,000 ng per patch) exceeded BE (50-950, none, 30-2200 ng per patch). Pre-swabs, valuable for interpreting the source or time frame of positive patch results, contained substantial COC (38-1160, 0-152, 34-762 ng per swab) prior to patch application; therefore, patch results may represent current use, prior use, contamination, or a combination. In three individuals with no indication of cocaine use, false positives (defined as sweat patch positive when urine specimens were <300ng BE/ml) occurred at a 7% rate. Proposed cut-off concentrations of 75 ng cocaine per patch and 300 ng BE/ml urine curtail the incidence of false positives in this limited population. Three immunoassays were compared to screen specimens for cocaine: a modified, manual Microgenics CEDIA; a Cozart ELISA; and an OraSure ELISA. CEDIA's limit of detection (LOD) was 81ng/ml, compared with LODs of 4 ng/ml for the Cozart ELISA and 1.5 ng/ml for the OraSure ELISA. Cozart correlated with OraSure results for COC concentrations <2000 ng per swab (n=117), r(2)=0.79.

Ethinyl estradiol and levonorgestrel pharmacokinetics with a low-dose transdermal contraceptive delivery system, AG200-15: a randomized controlled trial.

PubMed

Archer, David F; Stanczyk, Frank Z; Rubin, Arkady; Foegh, Marie

2012-06-01

This study evaluated the ethinyl estradiol (EE) and levonorgestrel (LNG) pharmacokinetic profiles of AG200-15, a transdermal contraceptive delivery system, compared with a combination oral contraceptive (COC) containing EE 35 mcg and norgestimate 250 mcg. A Phase 1, open-label, single-center study in 36 healthy women was conducted over three cycles with a randomized crossover design. After a run-in cycle of 21 days on and 7 days off with AG200-15, participants were randomized to receive one of two treatments: a 21/7-day cycle of AG200-15 either followed or preceded by one cycle of the COC. This trial is registered on ClinicalTrials.gov under the identifier NCT01243580. During the third week of AG200-15 use, mean (±standard deviation) maximum serum concentration (C(max)), area under the curve(0-168 h) and steady-state concentration (C(ss48-168 h)) for EE were 51.3 ± 17.3 pg/mL, 6.26 ± 2.46 ng h/mL and 35.7 ± 14.5 pg/mL, respectively; for LNG, the corresponding values were 2400 ± 1140 pg/mL, 317 ± 159 ng h/mL and 1847 ± 930 pg/mL, respectively. The AG200-15 EE C(max) was approximately 60% lower and the EE C(ss) was 15%-20% lower than those obtained with the COC. The calculated daily dose of AG200-15 was equivalent to a 30-mcg EE COC. The most common adverse events (AEs; >10%) in the AG200-15 group were headache, nausea and application-site irritation. All drug-related AEs were mild, and no serious AEs were reported. EE and LNG daily exposure during AG200-15 treatment was within the range reported for a low-dose COC. The daily EE dose with AG 200-15 was equivalent to a 30-mcg COC and was safe and well tolerated. Copyright © 2012 Elsevier Inc. All rights reserved.

Is there any difference in survivorship of total hip arthroplasty with different bearing surfaces? A systematic review and network meta-analysis.

PubMed

Yin, Si; Zhang, Dangfeng; Du, Hui; Du, Heng; Yin, Zhanhai; Qiu, Yusheng

2015-01-01

Although many total hip bearing implants are widely used all over the world, simultaneous comparisons across the numerous available bearing surfaces are rare. The purpose of this study was to compare the survivorship of total hip arthroplasty (THA) with six available bearing implants. We conducted a systematic review of randomized controlled trials (RCTs) reporting survivorship or revision of ceramic-on-ceramic (CoC), ceramic-on-conventional polyethylene (CoPc), ceramic-on-highly-crosslinked polyethylene (CoPxl), metal-on-conventional polyethylene (MoPc), metal-on-highly-crosslinked polyethylene (MoPxl), or metal-on-metal (MoM) bearing implants. The synthesis of present evidence was performed by both the traditional direct-comparison meta-analysis and network meta-analysis. In total, 40 RCTs involving a total of 5321 THAs were identified. The pooled data of network meta-analysis showed no difference in relative risk (RR) of revision across CoC, CoPc, CoPxl and MoPxl bearings. However, the MoM bearing was demonstrated with a significant higher risk of revision compared with CoC (RR 5.10; 95% CI=1.62 to 16.81), CoPc (RR 4.80; 95% CI=1.29 to 17.09), or MoPxl (RR 3.85; 95% CI=1.16 to 14.29), and the MoPc bearing was indicated with a higher risk of revision compared with CoC (RR 2.83; 95% CI=1.20 to 6.63). The ranking probabilities of the effective interventions also revealed the inferiority of the MoM and MoPc implants in survivorship (both 0%, 95% CI=0% to 0%) compared with CoC (39%, 95% CI=0% to 100%), CoPc (33%, 95% CI=0% to 100%), CoPxl (7%, 95% CI=0% to 100%) or MoPxl (21%, 95% CI=0% to 100%). The present evidence indicated the similar performance in survivorship among CoC, CoPc, CoPxl and MoPxl bearing implants, and that all likely have superiority compared with the MoM and MoPc bearing implants in THA procedures. Long-term RCT data are required to confirm these conclusions and better inform clinical decisions.

Associations of hormonal contraceptive use with measures of HIV disease progression and antiretroviral therapy effectiveness.

PubMed

Whiteman, Maura K; Jeng, Gary; Samarina, Anna; Akatova, Natalia; Martirosyan, Margarita; Kissin, Dmitry M; Curtis, Kathryn M; Marchbanks, Polly A; Hillis, Susan D; Mandel, Michele G; Jamieson, Denise J

2016-01-01

To examine the associations between hormonal contraceptive use and measures of HIV disease progression and antiretroviral treatment (ART) effectiveness. A prospective cohort study of women with prevalent HIV infection in St. Petersburg, Russia, was conducted. After contraceptive counseling, participants chose to use combined oral contraceptives (COCs), depot-medroxyprogesterone acetate (DMPA), a copper intrauterine device (IUD) or male condoms for pregnancy prevention. Among participants not using ART at enrollment, we used multivariate Cox regression to assess the association between current (time-varying) contraceptive use and disease progression, measured by the primary composite outcome of CD4 decline to <350 cells/mm(3), ART initiation or death. Among participants using ART at enrollment, we used linear mixed models to estimate the predicted mean CD4 change at select time points by contraceptive method. During a total of 5233 months follow-up among participants not using ART with enrollment CD4 ≥350 cells/mm(3) (n=315), 97 experienced disease progression. Neither current use of COCs [adjusted hazard ratio (aHR) 0.91, 95% confidence interval (CI) 0.56-1.48] nor DMPA (aHR 1.28, 95% CI 0.71-2.31) was associated with a statistically significant increased risk for disease progression compared with use of nonhormonal methods (IUD or condoms). Among participants using ART at enrollment (n=77), we found no statistically significant differences in the predicted mean changes in CD4 cell count comparing current use of COCs (p=.1) or DMPA (p=.3) with nonhormonal methods. Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. Published by Elsevier Inc.

14 CFR 119.49 - Contents of operations specifications.

Code of Federal Regulations, 2010 CFR

2010-01-01

... primary point of contact for correspondence between the FAA and the certificate holder and the name and..., appliances, and emergency equipment. (9) Authorization for the method of controlling weight and balance of... shall serve as the primary point of contact for correspondence between the FAA and the certificate...

Nonesterified Fatty Acid-Induced Endoplasmic Reticulum Stress in Cattle Cumulus Oocyte Complexes Alters Cell Metabolism and Developmental Competence.

PubMed

Sutton-McDowall, Melanie L; Wu, Linda L Y; Purdey, Malcolm; Abell, Andrew D; Goldys, Ewa M; MacMillan, Keith L; Thompson, Jeremy G; Robker, Rebecca L

2016-01-01

Reduced oocyte quality has been associated with poor fertility of high-performance dairy cows during peak lactation, due to negative energy balance. We examined the role of nonesterified fatty acids (NEFAs), known to accumulate within follicular fluid during under- and overnutrition scenarios, in causing endoplasmic reticulum (ER) stress of in vitro maturated cattle cumulus-oocyte complexes (COCs). NEFA concentrations were: palmitic acid (150 μM), oleic acid (200 μM), and steric acid (75 μM). Abattoir-derived COCs were randomly matured for 24 h in the presence of NEFAs and/or an ER stress inhibitor, salubrinal. Total and hatched blastocyst yields were negatively impacted by NEFA treatment compared with controls, but this was reversed by salubrinal. ER stress markers, activating transcription factor 4 (Atf4) and heat shock protein 5 (Hspa5), but not Atf6, were significantly up-regulated by NEFA treatment within whole COCs but reversed by coincubation with salubrinal. Likewise, glucose uptake and lactate production, measured in spent medium samples, showed a similar pattern, suggesting that cumulus cell metabolism is sensitive to NEFAs via an ER stress-mediated process. In contrast, while mitochondrial DNA copy number was recovered in NEFA-treated oocytes, oocyte autofluorescence of the respiratory chain cofactor, FAD, was lower following NEFA treatment of COCs, and this was not reversed by salubrinal, suggesting the negative impact was via reduced mitochondrial function. These results reveal the significance of NEFA-induced ER stress on bovine COC developmental competence, revealing a potential therapeutic target for improving oocyte quality during peak lactation. © 2016 by the Society for the Study of Reproduction, Inc.

The effect of cinnarizine and cocculus indicus on simulator sickness.

PubMed

Lucertini, Marco; Mirante, Nadia; Casagrande, Maria; Trivelloni, Pierandrea; Lugli, Vittoria

2007-05-16

Pensacola Simulator Sickness Questionnaire (SSQ) is a valuable method to analyse symptoms evoked by exposure to a flight simulator environment that can also be adopted to evaluate the effectiveness of preventive tools, aiming at reducing simulator sickness (SS). In this study we analysed SSQ data in subjects undergoing a standard ground based spatial disorientation training inside a flight simulator, in order to evaluate the SS prevention obtained with two different pharmacological tools. Twelve males volunteers participated to an experimental design based on a double-blind, balanced administration of either 30 mg cinnarizine (CIN), or Cocculus Indicus 6CH (COC), or placebo (PLC) before one trial of about one hour spent inside a spatial disorientation trainer. All subjects underwent the three different conditions (CIN, COC, PLC) during 3 non-consecutive days separated by at least 2 weeks. During each experimental day, all subjects filled in SSQ. In addition, both postural instability (with the use of a static stabilometric platform), and sleepiness symptoms were evaluated. All the tests were performed before and after the simulated flight, at different times, in one-and-half-hour intervals. Results indicated a strong increase of sickness after flight simulation that linearly decreased, showing pre-simulator scores after 1.30 hours. In contrast to both PLC and COC, CIN showed significant side effects immediately following flight simulation, with no benefit at the simultaneous SSQ scores. Globally, no highly significant differences between COC and PLC were observed, although a minor degree of postural instability could be detected after COC administration. As far as the present exposure to a simulator environment is concerned, none of the pharmacological tools administered in this study resulted effective in reducing SS symptoms as detected by the SSQ. Moreover, CIN significantly increased sleepiness and postural instability in most subjects.

Combined hormonal contraceptive (CHC) use among obese women and contraceptive effectiveness: a systematic review.

PubMed

Dragoman, Monica V; Simmons, Katharine B; Paulen, Melissa E; Curtis, Kathryn M

2017-02-01

To evaluate from the literature whether combined hormonal contraception (CHC), including combined oral contraception pills (COCs), transdermal patch, vaginal ring or combined injectables, have different effectiveness or failure rates by body weight or body mass index (BMI). We searched PubMed and the Cochrane Library databases for all articles in all languages published between inception and February 2016, for evidence relevant to body weight or BMI, CHC use and contraceptive effectiveness. The quality of each individual study was assessed using the system for evaluating evidence developed by the United States Preventive Services Task Force. From 2874 articles, we identified 15 reports for inclusion, all of fair to poor quality. Fourteen studies measured the association of obesity status and contraceptive failure among COC users. Three fair quality and one poor quality study reported increased COC failure among a heterogeneous population of overweight and obese women compared with normal weight women, while eight fair quality and two poor quality studies did not find an association. Two fair quality studies reported on contraceptive transdermal patches. One pooled analysis described a higher proportion of pregnancies among women using the patch who weighed ≥90 kg; another secondary analysis suggested BMI>30 was associated with increased failure. No studies directly compared contraceptive effectiveness using the combined vaginal ring or combined injectable. Current available evidence addressing the risk of CHC failure in obese compared to normal weight women is limited to fair and poor quality studies. Studies of COCs show mixed results, though absolute differences in COC failure by body weight and BMI are small. Based on limited evidence, it appears that increasing body weight and BMI may contribute to decreasing contraceptive patch effectiveness. Copyright © 2017. Published by Elsevier Inc.

Cyclic AMP-elevating Agents Promote Cumulus Cell Survival and Hyaluronan Matrix Stability, Thereby Prolonging the Time of Mouse Oocyte Fertilizability*

PubMed Central

Di Giacomo, Monica; Camaioni, Antonella; Klinger, Francesca G.; Bonfiglio, Rita; Salustri, Antonietta

2016-01-01

Cumulus cells sustain the development and fertilization of the mammalian oocyte. These cells are retained around the oocyte by a hyaluronan-rich extracellular matrix synthesized before ovulation, a process called cumulus cell-oocyte complex (COC) expansion. Hyaluronan release and dispersion of the cumulus cells progressively occur after ovulation, paralleling the decline of oocyte fertilization. We show here that, in mice, postovulatory changes of matrix are temporally correlated to cumulus cell death. Cumulus cell apoptosis and matrix disassembly also occurred in ovulated COCs cultured in vitro. COCs expanded in vitro with FSH or EGF underwent the same changes, whereas those expanded with 8-bromo-adenosine-3′,5′-cyclic monophosphate (8-Br-cAMP) maintained integrity for a longer time. It is noteworthy that 8-Br-cAMP treatment was also effective on ovulated COCs cultured in vitro, prolonging the vitality of the cumulus cells and the stability of the matrix from a few hours to >2 days. Stimulation of endogenous adenylate cyclase with forskolin or inhibition of phosphodiesterase with rolipram produced similar effects. The treatment with selective cAMP analogues suggests that the effects of cAMP elevation are exerted through an EPAC-independent, PKA type II-dependent signaling pathway, probably acting at the post-transcriptional level. Finally, overnight culture of ovulated COCs with 8-Br-cAMP significantly counteracted the decrease of fertilization rate, doubling the number of fertilized oocytes compared with control conditions. In conclusion, these studies suggest that cAMP-elevating agents prevent cumulus cell senescence and allow them to continue to exert beneficial effects on oocyte and sperm, thereby extending in vitro the time frame of oocyte fertilizability. PMID:26694612

Contraceptive Use and Pregnancy Incidence Among Women Participating in an HIV Prevention Trial.

PubMed

Akello, Carolyne A; Bunge, Katherine E; Nakabiito, Clemensia; Mirembe, Brenda G; Fowler, Mary Glenn; Mishra, Anupam; Marrazzo, Jeanne; Chirenje, Zvavahera M; Celum, Connie; Balkus, Jennifer E

2017-06-01

Recent HIV prevention trials required use of effective contraceptive methods to fulfill eligibility for enrollment. We compared pregnancy rates in a subset of participants enrolled in the Microbicide Trials Network protocol (MTN-003), a randomized trial of chemoprophylaxis to prevent HIV acquisition among women aged 18-45 years who initiated depot medroxyprogesterone acetate (DMPA) or combined oral contraceptives (COCs) at enrollment, relative to those already using DMPA or COCs. Data were analyzed from MTN-003 participants from Uganda. Before enrollment, information on contraceptive type and initiation date was obtained. Urine pregnancy tests were performed at monthly follow-up visits. Cox proportional hazards models were used to compare pregnancy incidence among new users (initiated ≤60 days before enrollment) and established users (initiated >60 days before enrollment). Of 322 women enrolled, 296 were COC or DMPA users, 82 (28%) were new users, and 214 (72%) were established users. Pregnancy incidence was higher among new contraceptive users compared to established users (20.70% vs. 10.55%; adjusted hazard ratio [HR] = 1.66; 95% confidence interval [95% CI] 0.93-2.96). Among DMPA users, pregnancy incidence was 10.20% in new users versus 3.48% in established users (HR = 2.56; 95% CI 0.86-7.65). Among new COC users, pregnancy incidence was 42.67% in new users versus 23.67% in established COC users (adjusted HR = 1.74; 95% CI 0.87-3.48). New contraceptive users, regardless of method, at the Uganda MTN-003 site had an increased pregnancy risk compared to established users, which may be due to contraceptive initiation primarily for trial eligibility. New users may benefit from intensive contraceptive counseling and additional contraceptive options, including longer acting reversible contraceptives.

Cocaine hydrolase encoded in viral vector blocks the reinstatement of cocaine seeking in rats for 6 months

PubMed Central

Anker, Justin J.; Brimijoin, Stephen; Gao, Yang; Geng, Liyi; Zlebnik, Natalie E.; Parks, Robin J.; Carroll, Marilyn E.

2011-01-01

Background Cocaine dependence is a pervasive disorder with high rates of relapse. In a previous study, direct administration of a quadruple mutant albumin-fused butyrylcholinesterase (BChE) that efficiently catalyzes hydrolysis of cocaine to benzoic acid and ecgonine methyl ester acutely blocked cocaine seeking in an animal model of relapse. In the present experiments these results were extended to achieve a long duration blockade of cocaine seeking with a gene transfer paradigm using a related BChE-based cocaine hydrolase, termed “CocH”. Methods Male and female rats were allowed to self-administer cocaine under a fixed-ratio 1 schedule of reinforcement for approximately 14 days. Following the final self-administration session, rats were injected with CocH vector or a control injection (empty vector or saline), and their cocaine solutions were replaced with saline for 14 days to allow for extinction of lever pressing. Subsequently, they were tested for drug-primed reinstatement by administering i.p. injections of saline (S), cocaine (5, 10, and 15 mg/kg, C), and d-amphetamine (A) according to the following sequence: S, C, S, C, S, C, S, A. Rats then received cocaine-priming injections once weekly for 4 weeks, and subsequently, once monthly for up to 6 months. Results Administration of CocH vector produced substantial and sustained CocH activity in plasma that corresponded with diminished cocaine- (but not amphetamine-) induced reinstatement responding for up to 6 months following treatment (compared to high responding controls). Conclusion These results demonstrate that viral transfer of CocH may be useful in promoting long-term resistance to relapse to cocaine addiction. PMID:22209637

TD-DFT Insight into Photodissociation of Co-C Bond in Coenzyme B12

NASA Astrophysics Data System (ADS)

Kozlowski, Pawel; Liu, Hui; Kornobis, Karina; Lodowski, Piotr; Jaworska, Maria

2013-12-01

Coenzyme B12 (AdoCbl) is one of the most biologically active forms of vitamin B12, and continues to be a topic of active research interest. The mechanism of Co-C bond cleavage in AdoCbl, and the corresponding enzymatic reactions are however, not well understood at the molecular level. In this work, time-dependent density functional theory (TD-DFT) has been applied to investigate the photodissociation of coenzyme B12. To reduce computational cost, while retaining the major spectroscopic features of AdoCbl, a truncated model based on ribosylcobalamin (RibCbl) was used to simulate Co-C photodissociation. Equilibrium geometries of RibCbl were obtained by optimization at the DFT/BP86/TZVP level of theory, and low-lying excited states were calculated by TD-DFT using the same functional and basis set. The calculated singlet states, and absorption spectra were simulated in both the gas phase, and water, using the polarizable continuum model (PCM). Both spectra were in reasonable agreement with experimental data, and potential energy curves based on vertical excitations were plotted to explore the nature of Co-C bond dissociation. It was found that a repulsive 3(σCo-C → σ*Co-C) triplet state became dissociative at large Co-C bond distance, similar to a previous observation for methylcobalamin (MeCbl). Furthermore, potential energy surfaces (PESs) obtained as a function of both Co-CRib and Co-NIm distances, identify the S1 state as a key intermediate generated during photoexcitation of RibCbl, attributed to a mixture of a MLCT (metal-to-ligand charge transfer) and a σ bonding-ligand charge transfer (SBLCT) states.

Wafer-scale fabrication of polymer-based microdevices via injection molding and photolithographic micropatterning protocols.

PubMed

Lee, Dae-Sik; Yang, Haesik; Chung, Kwang-Hyo; Pyo, Hyeon-Bong

2005-08-15

Because of their broad applications in biomedical analysis, integrated, polymer-based microdevices incorporating micropatterned metallic and insulating layers are significant in contemporary research. In this study, micropatterns for temperature sensing and microelectrode sets for electroanalysis have been implemented on an injection-molded thin polymer membrane by employing conventional semiconductor processing techniques (i.e., standard photolithographic methods). Cyclic olefin copolymer (COC) is chosen as the polymer substrate because of its high chemical and thermal stability. A COC 5-in. wafer (1-mm thickness) is manufactured using an injection molding method, in which polymer membranes (approximately 130 microm thick and 3 mm x 6 mm in area) are implemented simultaneously in order to reduce local thermal mass around micropatterned heaters and temperature sensors. The highly polished surface (approximately 4 nm within 40 microm x 40 microm area) of the fabricated COC wafer as well as its good resistance to typical process chemicals makes it possible to use the standard photolithographic and etching protocols on the COC wafer. Gold micropatterns with a minimum 5-microm line width are fabricated for making microheaters, temperature sensors, and microelectrodes. An insulating layer of aluminum oxide (Al2O3) is prepared at a COC-endurable low temperature (approximately 120 degrees C) by using atomic layer deposition and micropatterning for the electrode contacts. The fabricated microdevice for heating and temperature sensing shows improved performance of thermal isolation, and microelectrodes display good electrochemical performances for electrochemical sensors. Thus, this novel 5-in. wafer-level microfabrication method is a simple and cost-effective protocol to prepare polymer substrate and demonstrates good potential for application to highly integrated and miniaturized biomedical devices.

The Epidemiology and National Trends of Bearing Surface Usage in Primary Total Hip Arthroplasty in Korea

PubMed Central

Yoon, Pil Whan; Kim, Yunjung; Yoo, Seungmi; Lee, Sahnghoon; Kim, Hee Joong

2016-01-01

Background We analyzed the data for primary total hip arthroplasty (THA) in the Korean nationwide database to assess (1) the epidemiology and national trends of bearing surface usage in THAs and (2) the prevalence of each type of bearing surface according to age, gender, hospital type, primary payer, and hospital procedure volume. Methods A total of 30,881 THAs were analyzed using the Korean Health Insurance Review and Assessment Service database for 2007 through 2011. Bearing surfaces were sub-grouped according to device code for national health insurance claims and consisted of ceramic-on-ceramic (CoC), metal-on-polyethylene (MoP), ceramic-on-polyethylene (CoP), and metal-on-metal (MoM). The prevalence of each type of bearing surface was calculated and stratified by age, gender, hospital type, primary payer, and procedure volume of each hospital. Results CoC was the most frequently used bearing surface (76.7%), followed by MoP (11.9%), CoP (7.3%), and MoM (4.1%). The proportion of THAs using a CoC bearing surface increased steadily from 71.6% in 2007 to 81.4% in 2011, whereas the proportions using CoP, MoP, and MoM bearing surfaces decreased. The order of prevalence was identical to that in the general population regardless of age, gender, hospital type, primary payer, and hospital procedure volume. Conclusions The trends and epidemiology of bearing surface usage in THAs in Korea are different from those in other countries, and the CoC bearing surface is the most prevalent articulation. In future, the results of a large-scale study using nationwide data of THAs involving a CoC bearing surface will be reported in Korea. PMID:26929796

A risk-based approach for identifying constituents of concern in oil sands process-affected water from the Athabasca Oil Sands region.

PubMed

McQueen, Andrew D; Kinley, Ciera M; Hendrikse, Maas; Gaspari, Daniel P; Calomeni, Alyssa J; Iwinski, Kyla J; Castle, James W; Haakensen, Monique C; Peru, Kerry M; Headley, John V; Rodgers, John H

2017-04-01

Mining leases in the Athabasca Oil Sands (AOS) region produce large volumes of oil sands process-affected water (OSPW) containing constituents that limit beneficial uses and discharge into receiving systems. The aim of this research is to identify constituents of concern (COCs) in OSPW sourced from an active settling basin with the goal of providing a sound rational for developing mitigation strategies for using constructed treatment wetlands for COCs contained in OSPW. COCs were identified through several lines of evidence: 1) chemical and physical characterization of OSPW and comparisons with numeric water quality guidelines and toxicity endpoints, 2) measuring toxicity of OSPW using a taxonomic range of sentinel organisms (i.e. fish, aquatic invertebrates, and a macrophyte), 3) conducting process-based manipulations (PBMs) of OSPW to alter toxicity and inform treatment processes, and 4) discerning potential treatment pathways to mitigate ecological risks of OSPW based on identification of COCs, toxicological analyses, and PBM results. COCs identified in OSPW included organics (naphthenic acids [NAs], oil and grease [O/G]), metals/metalloids, and suspended solids. In terms of species sensitivities to undiluted OSPW, fish ≥ aquatic invertebrates > macrophytes. Bench-scale manipulations of the organic fractions of OSPW via PBMs (i.e. H 2 O 2 +UV 254 and granular activated charcoal treatments) eliminated toxicity to Ceriodaphnia dubia (7-8 d), in terms of mortality and reproduction. Results from this study provide critical information to inform mitigation strategies using passive or semi-passive treatment processes (e.g., constructed treatment wetlands) to mitigate ecological risks of OSPW to aquatic organisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Field metabolomics and laboratory assessments of anaerobic intrinsic bioremediation of hydrocarbons at a petroleum‐contaminated site

PubMed Central

Parisi, Victoria A.; Brubaker, Gaylen R.; Zenker, Matthew J.; Prince, Roger C.; Gieg, Lisa M.; Da Silva, Marcio L.B.; Alvarez, Pedro J. J.; Suflita, Joseph M.

2009-01-01

Summary Field metabolomics and laboratory assays were used to assess the in situ anaerobic attenuation of hydrocarbons in a contaminated aquifer underlying a former refinery. Benzene, ethylbenzene, 2‐methylnaphthalene, 1,2,4‐ and 1,3,5‐trimethylbenzene were targeted as contaminants of greatest regulatory concern (COC) whose intrinsic remediation has been previously reported. Metabolite profiles associated with anaerobic hydrocarbon decay revealed the microbial utilization of alkylbenzenes, including the trimethylbenzene COC, PAHs and several n‐alkanes in the contaminated portions of the aquifer. Anaerobic biodegradation experiments designed to mimic in situ conditions showed no loss of exogenously amended COC; however, a substantive rate of endogenous electron acceptor reduction was measured (55 ± 8 µM SO4 day−1). An assessment of hydrocarbon loss in laboratory experiments relative to a conserved internal marker revealed that non‐COC hydrocarbons were being metabolized. Purge and trap analysis of laboratory assays showed a substantial loss of toluene, m‐ and o‐xylene, as well as several alkanes (C6–C12). Multiple lines of evidence suggest that benzene is persistent under the prevailing site anaerobic conditions. We could find no in situ benzene intermediates (phenol or benzoate), the parent molecule proved recalcitrant in laboratory assays and low copy numbers of Desulfobacterium were found, a genus previously implicated in anaerobic benzene biodegradation. This study also showed that there was a reasonable correlation between field and laboratory findings, although with notable exception. Thus, while the intrinsic anaerobic bioremediation was clearly evident at the site, non‐COC hydrocarbons were preferentially metabolized, even though there was ample literature precedence for the biodegradation of the target molecules. PMID:21261914

Occurrence of cocaine and benzoylecgonine in drinking and source water in the São Paulo State region, Brazil.

PubMed

Campestrini, Iolana; Jardim, Wilson F

2017-01-15

The occurrence of illicit drugs in natural waters (surface, source and drinking water) is of interest due to the poor sanitation coverage and the high consumption of drugs of abuse in Brazil. In addition, little is known about the effects of these compounds on aquatic organisms and human health. This work investigates the occurrence of cocaine (COC) and its major metabolite, benzoylecgonine (BE), in surface and drinking water collected in rivers from a populated geographic area in Brazil. Surface water samples were collected in 22 locations from 16 different rivers and one dam from São Paulo State, whereas drinking water samples were collected in 5 locations. Samples were collected during the dry and wet season. Among the 34 surface water samples analyzed, BE was detected above the LOD in 94%, while COC in 85%. BE concentrations ranged from 10ngL -1 to 1019ngL -1 and COC concentrations from 6ngL -1 to 62ngL -1 . In the drinking water samples analyzed, BE and COC were found in 100% of the samples analyzed. For BE, concentrations were found in the range from 10ngL -1 to 652ngL -1 , and COC was quantified in concentrations between 6 and 22ngL -1 . These concentrations are one of the highest found in urban surface waters and may pose some risk to aquatic species. However, no human health risk was identified using the Hazard Quotient. BE is proposed as a reliable indicator of sewage contamination in both source and drinking water. Copyright © 2016 Elsevier B.V. All rights reserved.

The Epidemiology and National Trends of Bearing Surface Usage in Primary Total Hip Arthroplasty in Korea.

PubMed

Yoon, Pil Whan; Yoo, Jeong Joon; Kim, Yunjung; Yoo, Seungmi; Lee, Sahnghoon; Kim, Hee Joong

2016-03-01

We analyzed the data for primary total hip arthroplasty (THA) in the Korean nationwide database to assess (1) the epidemiology and national trends of bearing surface usage in THAs and (2) the prevalence of each type of bearing surface according to age, gender, hospital type, primary payer, and hospital procedure volume. A total of 30,881 THAs were analyzed using the Korean Health Insurance Review and Assessment Service database for 2007 through 2011. Bearing surfaces were sub-grouped according to device code for national health insurance claims and consisted of ceramic-on-ceramic (CoC), metal-on-polyethylene (MoP), ceramic-on-polyethylene (CoP), and metal-on-metal (MoM). The prevalence of each type of bearing surface was calculated and stratified by age, gender, hospital type, primary payer, and procedure volume of each hospital. CoC was the most frequently used bearing surface (76.7%), followed by MoP (11.9%), CoP (7.3%), and MoM (4.1%). The proportion of THAs using a CoC bearing surface increased steadily from 71.6% in 2007 to 81.4% in 2011, whereas the proportions using CoP, MoP, and MoM bearing surfaces decreased. The order of prevalence was identical to that in the general population regardless of age, gender, hospital type, primary payer, and hospital procedure volume. The trends and epidemiology of bearing surface usage in THAs in Korea are different from those in other countries, and the CoC bearing surface is the most prevalent articulation. In future, the results of a large-scale study using nationwide data of THAs involving a CoC bearing surface will be reported in Korea.

Incorporation of Pentraxin 3 into Hyaluronan Matrices Is Tightly Regulated and Promotes Matrix Cross-linking

PubMed Central

Baranova, Natalia S.; Inforzato, Antonio; Briggs, David C.; Tilakaratna, Viranga; Enghild, Jan J.; Thakar, Dhruv; Milner, Caroline M.; Day, Anthony J.; Richter, Ralf P.

2014-01-01

Mammalian oocytes are surrounded by a highly hydrated hyaluronan (HA)-rich extracellular matrix with embedded cumulus cells, forming the cumulus cell·oocyte complex (COC) matrix. The correct assembly, stability, and mechanical properties of this matrix, which are crucial for successful ovulation, transport of the COC to the oviduct, and its fertilization, depend on the interaction between HA and specific HA-organizing proteins. Although the proteins inter-α-inhibitor (IαI), pentraxin 3 (PTX3), and TNF-stimulated gene-6 (TSG-6) have been identified as being critical for COC matrix formation, its supramolecular organization and the molecular mechanism of COC matrix stabilization remain unknown. Here we used films of end-grafted HA as a model system to investigate the molecular interactions involved in the formation and stabilization of HA matrices containing TSG-6, IαI, and PTX3. We found that PTX3 binds neither to HA alone nor to HA films containing TSG-6. This long pentraxin also failed to bind to products of the interaction between IαI, TSG-6, and HA, among which are the covalent heavy chain (HC)·HA and HC·TSG-6 complexes, despite the fact that both IαI and TSG-6 are ligands of PTX3. Interestingly, prior encounter with IαI was required for effective incorporation of PTX3 into TSG-6-loaded HA films. Moreover, we demonstrated that this ternary protein mixture made of IαI, PTX3, and TSG-6 is sufficient to promote formation of a stable (i.e. cross-linked) yet highly hydrated HA matrix. We propose that this mechanism is essential for correct assembly of the COC matrix and may also have general implications in other inflammatory processes that are associated with HA cross-linking. PMID:25190808

Reliability of High-Temperature Fixed-Point Installations over 8 Years

NASA Astrophysics Data System (ADS)

Elliott, C. J.; Ford, T.; Ongrai, O.; Pearce, J. V.

2017-12-01

At NPL, high-temperature metal-carbon eutectic fixed points have been set up for thermocouple calibration purposes since 2006, for realising reference temperatures above the highest point specified in the International Temperature Scale of 1990 for contact thermometer calibrations. Additionally, cells of the same design have been provided by NPL to other national measurement institutes (NMIs) and calibration laboratories over this period, creating traceable and ISO 17025 accredited facilities around the world for calibrating noble metal thermocouples at 1324 {°}C (Co-C) and 1492 {°}C (Pd-C). This paper shows collections of thermocouple calibration results obtained during use of the high-temperature fixed-point cells at NPL and, as further examples, the use of cells installed at CCPI Europe (UK) and NIMT (Thailand). The lifetime of the cells can now be shown to be in excess of 7 years, whether used on a weekly or monthly basis, and whether used in an NMI or industrial calibration laboratory.

Approximating dose and risk for contaminants in groundwater from the underground nuclear test areas of the Nevada National Security Site (NNSS)

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

Daniels, Jeffrey I.; Chapman, Jenny; Pohlmann, Karl F.

As part of the Environmental Management Program at the Nevada National Security Site (NNSS), the Underground Test Area (UGTA) Activity investigates the potential impacts of radionuclides that were introduced into groundwater from the underground nuclear tests conducted near or below the NNSS water table between 1951 and 1992. Groundwater models are being used to simulate contaminant transport and forecast contaminant boundaries that encompass areas where the groundwater has a five percent or greater probability of containing contaminants above the Safe Drinking Water Act Maximum Contaminant Levels (SDWA MCLs) at any time during the next 1,000 years. Transport modeling conducted formore » the Frenchman Flat Corrective Action Unit (CAU) at the NNSS identified the beta/photon-emitting radionuclides tritium (3H), carbon-14 (14C), chlorine-36 (36Cl), technetium-99 (99Tc), and iodine-129 (129I) as having the greatest influence in defining the farthest extent of the modeled CAU contaminant boundary. These same radionuclides are assumed here as the contaminants of concern (COCs) for all underground nuclear tests at the NNSS because models are not yet complete for the other CAUs.Potential public exposure to the COCs will only occur and be of concern if the COCs migrate into the groundwater beneath public or private lands at levels that exceed either individual SDWA MCLs or dose and risk limits. Groundwater flow directions strongly suggest that any contaminant boundary predicted by contaminant fate and transport modeling to overlap public or private lands is more likely to occur to the west and/or southwest of the NNSS and the adjacent Nevada Test and Training Range (NTTR). Well-established, rural communities exist in these directions. Estimates of representative activity concentrations at the applicable SDWA MCL were developed for the five COCs. It is assumed that these COC concentrations may collectively occur at some public or private location in the future, but that situation does not exist today. These representative activity concentrations are evaluated with respect to conforming collectively to a modern annual committed effective dose (CED) and lifetime excess cancer morbidity risk for a hypothetical reasonably maximally exposed individual (RMEI). This approach goes beyond the SDWA MCL focus of the contaminant boundary because individual COC concentrations may comply with the SDWA MCL but not collectively meet the modern health-protection metrics and the SDWA language, especially if future modeling studies or monitoring activities show multiple radionuclides from different SDWA MCL categories to be COCs. For the drinking water exposure pathway alone, the annual committed effective dose (CED) for the RMEI from all five COCs that are collectively at estimated activity concentrations equal to their SDWA MCL is well below the U.S. Department of Energy health-protective CED limit of 100 millirem (mrem)/yr. This is consistent using both the NNSS unclassified, 1992 decay-corrected radionuclide atom inventory and the atom inventory based on radionuclides measured in groundwater obtained from the ALMENDRO cavity in 2009 to calculate the SDWA MCL activity concentrations in groundwater. The RMEI’s total lifetime excess cancer risk from the drinking water exposure pathway for both atom inventories is within the range of 1 × 10 -4 to ≤ 1 × 10 -6, which is considered health protective according to modern SDWA MCL regulatory language. The biosphere exposure pathways are drinking water, garden produce, animal products, inadvertent soil ingestion, and indoor and outdoor air inhalation. The exposure parameters for communities west and southwest of the NNSS were developed when the Yucca Mountain high-level, nuclear-waste disposal facility was under consideration. For all biosphere exposure pathways, calculations of the annual CED and lifetime excess cancer morbidity risk for the RMEI revealed that: 1) The annual CED is well within health-protective guidance (<< 100 mrem CED/yr) for the COC activity concentrations at the SDWA MCL, regardless of the atom inventory used. 2) The calculated 70-year lifetime excess cancer morbidity risk (6 x 10 -5) is within the health-protective range when the five COC activity concentrations are derived using the NNSS 1992 atom inventory, but it is at the upper limit of the acceptable range (1 x 10 -4) using the ALMENDRO 2009 atom inventory. 3) Tritium (3H) is the principal COC for producing annual dose and lifetime excess cancer risk, regardless of the atom inventory used. 4) Overall, the drinking water ingestion pathway is the dominant exposure pathway contributing to the total annual CED and lifetime excess cancer risk, followed by eating locally grown produce and animal products. 5) When tritium completely decays (after about 100 years), the RMEI’s lifetime risk will fall well within the health-protective range (i.e., 1 × 10-4 to ≤ 1 × 10 -6) and 36Cl will then become the most important contributor to the RMEI’s total annual CED and lifetime excess cancer morbidity risk from eating local produce and animal products. In the event that radionuclide concentrations begin to approach SDWA MCLs, a reasonable risk-management strategy for keeping lifetime risk more in compliance with regulatory guidance would be to use local sources of groundwater that are below SDWA MCLs or to limit the consumption of local produce and animal products that have ingested COC-contaminated groundwater. The viability of the latter strategy increases where the annual CED due to 36Cl approaches that of 3H.The dose and risk values calculated here for an RMEI are specific to the assumption that the five COCs occur in groundwater beneath public or private lands at concentrations that are collectively at the SDWA MCL. Currently, these COCs are essentially absent from groundwater beneath public or private lands beyond the boundaries of the NNSS and NTTR other than at very low, naturally occurring concentrations. The analyses presented here can be readily applied to determine dose and risk for COC concentrations actually measured in future monitoring samples.« less

Development of a Distributed Breach for the Conical Shock Tube.

DTIC Science & Technology

1983-01-01

Ti - «<M’»<Mosm —vocvicocviosm —VO(VI cr»—vo •*— ro cvi ro • * m m is. vo N OO CO OS <c<c<c<c<r<c<coc<c<E<c«<c<c<coc<coi hht-HHI-1-Khhhl- hHhhHh

Photodynamic action of LED-activated pyropheophorbide-α methyl ester in cisplatin-resistant human ovarian carcinoma cells

NASA Astrophysics Data System (ADS)

Tan, Y.; Xu, C. S.; Xia, X. S.; Yu, H. P.; Bai, D. Q.; He, Y.; Leung, A. W. N.

2009-04-01

Cisplatin-resistance is a major obstacle for the successful therapy to ovarian cancer, and exploring novel approach to deactivate cisplatin-resistant ovarian cells will improve the clinical outcomes. Our present study showed that there was no dark cytotoxicity of MPPa in the COC1/DDP cells at the dose of 0.25 - 4 μM, and LED-activated MPPa resulted in drug dose- and light-dependent cytotoxicity. Apoptotic rate 6 h after LED-activated MPPa (2 μM) increased to 16.71% under the light energy of 1 J/cm2. Confocal laser scanning microscopy showed that MPPa mainly localized in the intracellular membrane system, namely the endoplasmic reticulum, Golgi apparatus, lysosomes and mitochondria in the COC1/DDP cells. Mitochondrial membrane potential (ΔΨm) was collapsed when COC1/DDP cells were exposed to 2 μM MPPa for 20 h and then 1 J/cm2 irradiation of LED source. These data demonstrated that LED-activated MPPa significantly deactivated cisplatin-resistant ovarian cell line COC1/DDP cells and enhanced apoptosis and decreased ΔΨm, which suggests LED is an efficient light source for PDT and LED-activated MPPa can be developed as new modality for treating cisplatin-resistant ovarian.

Oral contraceptives and venous thromboembolism: pill scares and public health.

PubMed

Reid, Robert L

2011-11-01

Post-marketing surveillance of combined oral contraceptives (COCs) for rare complications such as venous thromboembolism (VTE) presents unique challenges. Prospective studies, which are costly and time consuming, have to date been undertaken by only a few contraceptive manufacturers willing to commit to full evaluation of product safety. Often such studies are conducted with the approval of regulatory authorities as a precondition for marketing. Alternatively, independent investigators with access to large databases have conducted retrospective studies to compare the incidence of VTE between new and older products. Such studies, however, run the risk of erroneous conclusions if they cannot ensure comparable risk profiles for users of these different products. Often database studies are unable to access information on important confounders, and medical records may not be available to validate the actual diagnosis of VTE. "Pill scares" generated following publication and media dissemination of worrisome findings, when the conclusions are in doubt and not corroborated by stronger prospective study designs, are frequently damaging to public health. From a review of recent publications on the VTE risk with drospirenone-containing COCs, it can be concluded that the best quality evidence does not support a difference in risk between users of COCs containing drospirenone and those of COCs containing levonorgestrel.

Assisting in vitro fertilization by manipulating cumulus-oocyte-complexes either mechanically or enzymatically does not prevent IVF failure

PubMed Central

Ebner, Thomas; Moser, Marianne; Shebl, Omar; Mayer, Richard; Tews, Gernot

2011-01-01

Objective This prospective study was set up in order to analyze whether additional treatment (cutting off supernumerous cumulus cells; adding hyaluronidase) of the cumulus-oocyte-complex (COC) would help to improve treatment outcome. Material and Methods COCs from 50 patients were prospectively subdivided into a control group A (no manipulation of COC) and two study groups. In group B, surplus cumulus cells were cut off using syringes, and in the second study group COCs were incubated with a 1:11 dilution of hyaluronidase (final concentration 7 IU/l). Main outcome measures were fertilization rate, embryo development, as well as rates of implantation, pregnancy, and live birth. Results Fertilization was higher in group C as compared to the untreated control group A (p<0.05). However, complete fertilization failure could not be avoided by any of the modified IVF approaches. Compaction on day 4 and blastocyst quality on day 5 were significantly improved in group C as compared to group B (but not to group A). Rates of implantation, pregnancy, and live birth were not affected by any of the methods. Conclusion ICSI seems to be the only choice for avoiding the vast majority of fertilization failures after IVF. PMID:24591979

Electrochemical monitoring-on-chip (E-MoC) of HIV-infection in presence of cocaine and therapeutics.

PubMed

Kaushik, Ajeet; Vabbina, Phani Kiran; Atluri, Venkata; Shah, Pratikkumar; Vashist, Arti; Jayant, Rahul Dev; Yandart, Adriana; Nair, Madhavan

2016-12-15

Electrochemical monitoring-on-chip (E-MoC)-based approach for rapid assessment of human immunodeficiency virus (HIV)-infection in the presence of cocaine (Coc) and specific drugs namely i.e., tenofovir (Tef), rimcazole (RA) is demonstrated here, for the first time, using electrochemical impedance spectroscopy (EIS). An in-vitro primary human astrocytes (HA) model was developed using a cultureware chip (CC, used for E-MoC) for HIV-infection, Coc exposure and treatment with anti-HIV drug i.e., Tef, and Coc antagonist i.e., RA. The charge transfer resistance (Rct) value of each CC well varies with respect to infection and treatment demonstrated highly responsive sensitivity of developed chip. The results of E-MoC, a proof-of-the concept, suggested that HIV-infection progression due to Coc ingestion and therapeutic effects of highly specific drugs are measurable on the basis of cell electrophysiology. Though, this work needs various molecular biology-based optimizations to promote this technology as an analytical tool for the rapid assessment of HIV-infection in a patient to manage HIV diseases for timely diagnosis. The presented study is based on using CNS cells and efforts are being made to perform this method using peripheral cells such as monocytes derived dendritic cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Pharmacodynamics of combined estrogen-progestin oral contraceptives: 2. effects on hemostasis.

PubMed

Farris, Manuela; Bastianelli, Carlo; Rosato, Elena; Brosens, Ivo; Benagiano, Giuseppe

2017-10-01

The pharmacodynamic effects of various combined oral estrogen-progestin combinations (COC) are examined for their components alone or in the various combined formulations. Special emphasis is given to products containing natural estrogens. Areas covered: Recent information on the effect of androgens, estrogens, progestins, as well as various COC combinations on the coagulation cascade will be reviewed aiming at providing an updated picture. The present article reviews hemostatic changes occurring during use of classic and modern combinations of estrogens (ethinyl estradiol, estradiol, estradiol valerate and estetrol) and new progestins (desogestrel, gestodene, dienogest, drospirenone, nomegestrol acetate), compared to classic compounds, such as levonorgestrel. Both pro- and anti-coagulatory effects of COC in healthy women are detailed and possible links with incidence of thromboembolic events are discussed. Expert commentary: Overall, the picture is reassuring: the use of natural estrogens and of new generation progestins has reduced pro-coagulatory changes in healthy subjects, although the observed differences in the risk of venous thromboembolism between second and third generation progestins is still incompletely understood. At the same time, there still is a need for large comparative and surveillance studies before firm conclusions can be drawn. At any rate, available evidence indicates that hemostatic effects of the newer COC, especially those utilizing natural estrogens, are minimal and often remain with the normal range.

Interrelated effects of substance use diagnosis, race, and smoking severity on abstinence initiation in dually dependent male smokers: results of a retrospective chart review.

PubMed

Heffner, Jaimee L; Blom, Thomas J; Camerota, Elaine; Sansone, Linda E; Bodie, Linda; Smith, Joshua; Lin, Show; Drake, J Michael; Meyer, Corey; Anthenelli, Robert M

2007-12-01

: Study goals were 2-fold: 1) to examine differences in demographic and clinical characteristics of smokers who fell into 3 diagnostic groups: alcohol abuse/dependence only (ALC), cocaine abuse/dependence only (COC), and mixed alcohol and cocaine abuse/dependence (ALC + COC); and 2) to determine the degree to which diagnostic grouping predicted short-term abstinence from smoking. : Retrospective chart reviews were conducted by using the treatment records of male veterans (N = 175) who participated in a voluntary smoking cessation program during their stay in residential substance dependence treatment. : The ALC group smoked more heavily, had higher levels of nicotine dependence, and reported more emotional problems than the other 2 groups. Short-term abstinence rates were high across the 3 groups (38%, 58%, and 57% for the ALC, COC, and ALC + COC groups, respectively). Lighter smoking at treatment entry, non-white race, and a diagnosis of cocaine abuse/dependence (with or without alcohol abuse/dependence) predicted short-term abstinence in the program. : Substance misusers motivated to quit smoking can initiate smoking abstinence at relatively high rates with the aid of combined pharmacotherapy and intensive group counseling. White subjects who smoke more heavily and have a diagnosis of alcohol abuse/dependence only have lower success rates for abstinence initiation.

Neurosurgery certification in member societies of the World Federation of Neurosurgical Societies: Asia.

PubMed

Gasco, Jaime; Braun, Jonathan D; McCutcheon, Ian E; Black, Peter M

2011-01-01

To objectively compare the complexity and diversity of the certification process in neurological surgery in member societies of the World Federation of Neurosurgical Societies. This study centers in continental Asia. We provide here an analysis based on the responses provided to a 13-item survey. The data received were analyzed, and three Regional Complexity Scores (RCS) were designed. To compare national board experience, eligibility requirements for access to the certification process, and the obligatory nature of the examinations, an RCS-Organizational score was created (20 points maximum). To analyze the complexity of the examination, an RCS-Components score was designed (20 points maximum). The sum of both is presented in a Global RCS score. Only those countries that responded to the survey and presented nationwide homogeneity in the conduction of neurosurgery examinations could be included within the scoring system. In addition, a descriptive summary of the certification process per responding society is also provided. On the basis of the data provided by our RCS system, the highest global RCS was achieved by South Korea and Malaysia (21/40 points) followed by the joint examination of Singapore and Hong-Kong (FRCS-Ed) (20/40 points), Japan (17/40 points), the Philippines (15/40 points), and Taiwan (13 points). The experience from these leading countries should be of value to all countries within Asia. Copyright © 2011 Elsevier Inc. All rights reserved.

Repair Air Conditioning, COC Bldg 2605, First Floor Plan. By ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Repair Air Conditioning, COC Bldg 2605, First Floor Plan. By Strategic Air Command, Civil Engineering. Drawing no. R-156, sheet no. 2 of 4, 15 August 1968; project no. MAR-125-8;CE-572; file drawer 2605-6. Scale one-eighth inch to one foot. 29x41 inches. pencil on paper 405 - March Air Force Base, Strategic Air Command, Combat Operations Center, 5220 Riverside Drive, Moreno Valley, Riverside County, CA

Determination of cocaine, benzoylecgonine and cocaethylene in human hair by solid-phase microextraction and gas chromatography-mass spectrometry.

PubMed

de Toledo, Fernanda Crossi Pereira; Yonamine, Mauricio; de Moraes Moreau, Regina Lucia; Silva, Ovandir Alves

2003-12-25

The present work describes a highly precise and sensitive method developed to detect cocaine (COC), benzoylecgonine (BE, its main metabolite) and cocaethylene (CE, transesterification product of the coingestion of COC with ethanol) in human head hair samples. The method was based on an alkylchloroformate derivatization of benzoylecgonine and the extraction of the analytes by solid-phase microextraction (SPME). Gas chromatography-mass spectrometry (GC-MS) was used to identify and quantify the analytes in selected ion monitoring mode (SIM). The limits of quantification and detection (LOQ and LOD) were: 0.1 ng/mg for COC and CE, and 0.5 ng/mg for BE. Good inter- and intra-assay precision was observed. The dynamic range of the assay was 0.1-50 ng/mg. The method is not time consuming and was shown to be easy to perform.

Carbon Nanotube Based Groundwater Remediation: The Case of Trichloroethylene.

PubMed

Jha, Kshitij C; Liu, Zhuonan; Vijwani, Hema; Nadagouda, Mallikarjuna; Mukhopadhyay, Sharmila M; Tsige, Mesfin

2016-07-21

Adsorption of chlorinated organic contaminants (COCs) on carbon nanotubes (CNTs) has been gaining ground as a remedial platform for groundwater treatment. Applications depend on our mechanistic understanding of COC adsorption on CNTs. This paper lays out the nature of competing interactions at play in hybrid, membrane, and pure CNT based systems and presents results with the perspective of existing gaps in design strategies. First, current remediation approaches to trichloroethylene (TCE), the most ubiquitous of the COCs, is presented along with examination of forces contributing to adsorption of analogous contaminants at the molecular level. Second, we present results on TCE adsorption and remediation on pure and hybrid CNT systems with a stress on the specific nature of substrate and molecular architecture that would contribute to competitive adsorption. The delineation of intermolecular interactions that contribute to efficient remediation is needed for custom, scalable field design of purification systems for a wide range of contaminants.

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

Takahashi, Ryo, E-mail: inter.takahashi@gmail.com; Todo, Yasuyuki, E-mail: yastodo@k.u-tokyo.ac.jp

In recent years, shade coffee certification programs have attracted increasing attention from forest conservation and development organizations. The certification programs could be expected to promote forest conservation by providing a premium price to shade coffee producers. However, little is known about the significance of the conservation efforts generated by certification programs. In particular, the relationship between the impact of the certification and producer characteristics has yet to be examined. The purpose of this study, which was conducted in Ethiopia, was to examine the impact of a shade coffee certification program on forest conservation and its relationship with the socioeconomic characteristicsmore » of the producers. Remote sensing data of 2005 and 2010 was used to gauge the changes in forest area. Employing a probit model, we found that a forest coffee area being certified increased the probability of forest conservation by 19.3 percentage points relative to forest coffee areas lacking certification. We also found that although economically poor producers tended to engage in forest clearing, the forest coffee certification program had a significant impact on these producers. This result suggests that the certification program significantly affects the behaviors of economically poor producers and motivates these producers to conserve the forest. -- Highlights: • We employed the probit mode to evaluate the impact of the shade coffee certification on forest conservation in Ethiopia. • We estimated how the impact of the certification varied among producers with different characteristics. • The certification increased the probability of conserving forest by 19.3 percentage points. • Certification program motivated the economically poor producers to conserve the forest.« less

48 CFR 301.603-72 - FAC-C and HHS SAC certification requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HUMAN SERVICES GENERAL HHS ACQUISITION REGULATION SYSTEM Career Development, Contracting Authority, and... retention of certification, including the requirement to earn continuous learning points (CLPs). FAC-C... to employees for the first time at a department or agency.) (c) The FAC-C certification is based on...

The Predictive Validity of the ABFM's In-Training Examination.

PubMed

O'Neill, Thomas R; Li, Zijia; Peabody, Michael R; Lybarger, Melanie; Royal, Kenneth; Puffer, James C

2015-05-01

Our objective was to examine the predictive validity of the American Board of Family Medicine's (ABFM) In-Training Examination (ITE) with regard to predicting outcomes on the ABFM certification examination. This study used a repeated measures design across three levels of medical training (PGY1--PGY2, PGY2--PGY3, and PGY3--initial certification) with three different cohorts (2010--2011, 2011--2012, and 2012--2013) to examine: (1) how well the residents' ITE scores correlated with their test scores in the following year, (2) what the typical score increase was across training years, and (3) what was the sensitivity, specificity, positive predictive value, and negative predictive value of the PGY3 scores with regard to predicting future results on the MC-FP Examination. ITE scores generally correlate at about .7 with the following year's ITE or with the following year's certification examination. The mean growth from PGY1 to PGY2 was 52 points, from PGY2 to PGY3 was 34 points, and from PGY3 to initial certification was 27 points. The sensitivity, specificity, positive predictive value, and negative predictive value were .91, .47, .96, and .27, respectively. The ITE is a useful predictor of future ITE and initial certification examination performance.

Effect of different shipping temperatures (∼22 °C vs. ∼7 °C) and holding media on blastocyst development after overnight holding of immature equine cumulus-oocyte complexes.

PubMed

Diaw, Mouhamadou; Salgado, Renato M; Canesin, Heloísa S; Gridley, Nell; Hinrichs, Katrin

2018-04-15

Intracytoplasmic sperm injection (ICSI) is an important tool for equine embryo production in both clinical and research settings. In clinical ICSI programs, immature equine cumulus-oocyte complexes (COCs) are often collected at the mare's location and shipped to the ICSI laboratory. To simplify shipment and aid scheduling of subsequent procedures, COCs can be held overnight at room temperature (∼22 °C) before placement into maturation culture, with no detrimental effect on meiotic or developmental competence. A recent study indicated that it might be possible to hold COCs overnight at cold (∼4 °C) temperatures. If so, this might allow longer holding periods that would ease shipping requirements. In this study, we compared oocyte maturation rates, as well as cleavage and blastocyst rates after ICSI, for COCs held at either room or cold temperatures overnight before the onset of in vitro maturation. In Exp. 1, COCs were shipped overnight in a commercial embryo holding medium, ViGRO (Vg), in insulated containers designed to hold at either room temperature (RT, ∼22 °C) or cold temperatures (Cold, ∼7 °C). Subsequent rates of in vitro maturation, cleavage and blastocyst formation were significantly higher in the RT treatment (39%, 90% and 41%, respectively) than in the Cold treatment (23%, 60% and 17%, respectively, P < .05). In Exp. 2, we compared Vg medium with a second commercial embryo holding medium, SYNGRO (Sy). There was no significant difference between Vg and Sy groups in any evaluated parameter within either RT or Cold treatments. Within each medium group and for both media combined, the rates of in vitro maturation, cleavage and blastocyst formation were significantly higher in the RT treatment (42%, 81% and 42%, respectively for the combined media) than in the Cold treatment (29%, 54% and 10%, respectively for the combined media, P < .05). We conclude that shipment of immature equine COCs at cold temperatures (∼7 °C) is detrimental to subsequent in vitro maturation and embryo production. Copyright © 2018 Elsevier Inc. All rights reserved.

The role of cGMP as a mediator of lipolysis in bovine oocytes and its effects on embryo development and cryopreservation.

PubMed

Schwarz, Kátia R L; de Castro, Fernanda C; Schefer, Letícia; Botigelli, Ramon C; Paschoal, Daniela M; Fernandes, Hugo; Leal, Cláudia L V

2018-01-01

This study aimed to determine the influence of cyclic guanosine 3'5'-monophosphate (cGMP) and cGMP-dependent kinase (PKG) during in vitro maturation (IVM) on lipolysis-related parameters in bovine cumulus-oocyte complexes (COCs), and on embryo development and cryosurvival. COCs were matured with cGMP/PKG modulators and assessed for metaphase II rates (MII), cGMP levels, lipid content in oocytes (OO), transcript abundance for genes involved in lipolysis (ATGL) and lipid droplets (PLIN2) in cumulus cells (CC) and OO, and presence of phosphorylated (active) hormone sensitive lipase (HSLser563) in OO. Embryo development, lipid contents and survival to vitrification were also assessed. Phosphodiesterase 5 inhibition (PDE5; cGMP-hydrolyzing enzyme) with 10-5M sildenafil (SDF) during 24 h IVM increased cGMP in COCs (56.9 vs 9.5 fMol/COC in untreated controls, p<0.05) and did not affect on maturation rate (84.3±6.4% MII). Fetal calf serum (FCS) in IVM medium decreased cGMP in COCs compared to bovine serum albumin (BSA) + SDF (19.6 vs 66.5 fMol/COC, respectively, p<0.05). FCS increased lipid content in OO (40.1 FI, p<0.05) compared to BSA (34.6 FI), while SDF decreased (29.8 and 29.6 FI, with BSA or FCS, respectively p<0.05). PKG inhibitor (KT5823) reversed this effect (38.9 FI, p<0.05). ATGL and PLIN2 transcripts were detected in CC and OO, but were affected by cGMP and PKG only in CC. HSLser563 was detected in OO matured with or without modulators. Reduced lipid content in embryos were observed only when SDF was added during IVM and IVC (27.6 FI) compared to its use in either or none of the culture periods (34.2 FI, p<0.05). Survival to vitrification was unaffected by SDF. In conclusion, cGMP and PKG are involved in lipolysis in OO and possibly in CC and embryos; serum negatively affects this pathway, contributing to lipid accumulation, and cGMP modulation may reduce lipid contents in oocytes and embryos, but without improving embryo cryotolerance.

An active recombinant cocoonase from the silkworm Bombyx mori: bleaching, degumming and sericin degrading activities.

PubMed

Unajak, Sasimanas; Aroonluke, Suradet; Promboon, Amornrat

2015-04-01

Cocoonase is a serine protease produced by silk moths and used for softening the cocoons so that they can escape. Degumming is one of the important steps in silk processing. This research aimed to produce an active recombinant Bombyx mori cocoonase (BmCoc) for the silk degumming process. A recombinant BmCoc was successfully expressed in a Pichia pastoris system. The purified enzyme showed specific activity of 227 U mg(-1) protein, 2.4-fold purification, 95% yield and a molecular weight of 26 kDa. The enzyme exhibited optimal temperature at 40 °C and optimal pH at 8, and showed thermal stability at 25-45 °C and pH stability at 5-9. The recombinant enzyme exhibited sericin degumming ability and color bleaching characteristics, and did not affect the fibroin fiber. The enzyme also degraded sericin substrate with a product size about 30-70 kDa. In this study, we successfully produced the active recombinant BmCoc in P. pastoris with promising functions for the Thai silk degumming process, which includes degumming, sericin degrading and color bleaching activities. Our data clearly indicated that the recombinant enzyme had proteolytic activity on sericin but not on fibroin proteins. The recombinant BmCoc has proven to be suitable for numerous applications in the silk industry. © 2014 Society of Chemical Industry.

Women's ability to self-screen for contraindications to combined oral contraceptive pills in Tanzanian drug shops.

PubMed

Chin-Quee, Dawn; Ngadaya, Esther; Kahwa, Amos; Mwinyiheri, Thomas; Otterness, Conrad; Mfinanga, Sayoki; Nanda, Kavita

2013-10-01

To estimate the accuracy of self-screening for contraindications to combined oral contraceptive pills (COCs) and to estimate the proportion of women with contraindications to hormonal methods among those using drug shops in Tanzania. Trained nurses interviewed 1651 women aged 18-39 years who self-screened for contraindications to COCs with the help of a poster at drug shops in Tanzania. Nurse assessment of the women served as the gold standard for comparison with self-assessment. Blood pressure was also measured onsite. Nurses reported that 437 (26.5%) women were not eligible to use COCs, compared with 485 (29.4%) according to self-report. Overall, 133 (8.1%) women who said that they were eligible were deemed ineligible by nurses. The rate of ineligibility was artificially high owing to participant and nurse assessments that were incorrectly based on adverse effects of pill use and cultural reasons, and because of the sampling procedure, which intercepted women regardless of their reasons for visiting the drug shop. Adjusted rates of ineligibility were 8.6% and 12.7%, respectively, according to nurse and participant assessment. Both nurses and women underestimated the prevalence of hypertension in the present group. Self-screening among women in rural and peri-urban Tanzania with regard to contraindications to COC use was comparable to assessment by trained nurses. © 2013.

A phase 1, multicentre, open-label study to evaluate ovarian follicular activity and hormone levels with an extended-regimen combined oral contraceptive with low-dose ethinyl estradiol supplementation.

PubMed

Kroll, Robin; Seidman, Larry; Ricciotti, Nancy; Howard, Brandon; Weiss, Herman

2015-01-01

To evaluate the effect on ovarian follicular activity of the 91-day extended-regimen combined oral contraceptive (COC), consisting of 84 days of levonorgestrel (LNG)/ethinylestradiol (EE) 150 μg/30 μg tablets plus seven days of EE 10 μg tablets in place of placebo. This was a phase 1, open-label study. Ovarian follicular activity was classified via the Hoogland and Skouby method. Safety and tolerability as well as return to ovulation were assessed. Of the 35 subjects included in the efficacy analysis, luteinized, unruptured follicles, or ovulation were detected in 0 of 35 cycles during the first 28-day interval; 1 of 35 cycles (2.9%) in the second 28-day interval; and 2 of 35 cycles (5.7%) in the final 35-day interval. The ovarian activity rate over the entire 91-day treatment period was 2.9%. There was a low incidence of treatment-emergent adverse events. Ovulation returned in most subjects (77.1%, 27/35) within 32 days following the last dose of COC. The 91-day extended-regimen COC with low-dose EE supplementation was found to be effective in suppressing ovarian activity and inhibiting ovulation and was well tolerated. Return to ovulation was rapid, occurring within approximately one month after discontinuation of COC.

Thermal modeling of head disk interface system in heat assisted magnetic recording

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

Vemuri, Sesha Hari; Seung Chung, Pil; Jhon, Myung S., E-mail: mj3a@andrew.cmu.edu

2014-05-07

A thorough understanding of the temperature profiles introduced by the heat assisted magnetic recording is required to maintain the hotspot at the desired location on the disk with minimal heat damage to other components. Here, we implement a transient mesoscale modeling methodology termed lattice Boltzmann method (LBM) for phonons (which are primary carriers of energy) in the thermal modeling of the head disk interface (HDI) components, namely, carbon overcoat (COC). The LBM can provide more accurate results compared to conventional Fourier methodology by capturing the nanoscale phenomena due to ballistic heat transfer. We examine the in-plane and out-of-plane heat transfermore » in the COC via analyzing the temperature profiles with a continuously focused and pulsed laser beam on a moving disk. Larger in-plane hotspot widening is observed in continuously focused laser beam compared to a pulsed laser. A pulsed laser surface develops steeper temperature gradients compared to continuous hotspot. Furthermore, out-of-plane heat transfer from the COC to the media is enhanced with a continuous laser beam then a pulsed laser, while the temperature takes around 140 fs to reach the bottom surface of the COC. Our study can lead to a realistic thermal model describing novel HDI material design criteria for the next generation of hard disk drives with ultra high recording densities.« less

Combined oral contraceptives: health benefits beyond contraception.

PubMed

Caserta, D; Ralli, E; Matteucci, E; Bordi, G; Mallozzi, M; Moscarini, M

2014-09-01

It has been recognized for over 50 years that combined oral contraceptives (COCs) are also capable of offering health benefits beyond contraception through the treatment and prevention of several gynaecological and medical disorders. During the last years a constant attention was given to the adverse effects of COCs, whereas their non-contraceptive benefits were underestimated. To date, most women are still unaware of the therapeutic uses of hormonal contraceptives, while on the contrary there is an extensive and constantly increasing of these non-contraceptive health benefits. This review summarizes the conditions of special interest for physicians, including dysmenorrhoea, menorrhagia, hyperandrogenism (acne, hirsutism, polycystic ovary syndrome), functional ovarian cysts, endometriosis, premenstrual syndrome, myomas, pelvic inflammatory disease, bone mineral density, benign breast disease and endometrial/ovarian and colorectal cancer. The benefits of COCs in rheumatoid arthritis, multiple sclerosis, menstrual migraine and in perimenopause have also been treated for more comprehensive information. Using COCs specifically for non-contraceptive indications is still outside the product licence in the majority of cases. We strongly believe that these aspects are not of minor relevance and they deserve a special consideration by health providers and by the mass media, which have the main responsibility in the diffusion of scientific information. Thus, counseling and education are necessary to help women make well-informed health-care decisions and it is also crucial to increase awareness among general practitioners and gynaecologists.

76 FR 31992 - In the Matter of Nine Mile Point Nuclear Station, LLC; Nine Mile Point Nuclear Station...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-02

... Secretary by e-mail at [email protected] , or by telephone at 301-415-1677, to request (1) a digital...-issued digital ID certificate). Based upon this information, the Secretary will establish an electronic... docket. Information about applying for a digital ID certificate is available on the NRC's public Web site...

75 FR 24998 - In the Matter of Florida Power and Light Company: Turkey Point Nuclear Plant; Independent Spent...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-06

..., to request (1) a digital ID certificate, which allows the participant (or its counsel or... NRC- issued digital ID certificate). Based upon this information, the Secretary will establish an... electronic docket. Information about applying for a digital ID certificate is available on NRC's public Web...

Internists' Views of Maintenance of Certification: A Stages-of-Change Perspective

ERIC Educational Resources Information Center

Arnold, Gerald K.; Hess, Brian J.; Lipner, Rebecca S.

2013-01-01

Introduction: Board certification has evolved from a "point-in-time" event to a process of periodic learning and reevaluation of medical competence through maintenance of certification (MOC). To better understand MOC participation, the transtheoretical model (TTM) was used to describe physicians' perceptions of MOC as a sequence of…

Combined hormonal contraceptive use among women with known dyslipidemias: a systematic review of critical safety outcomes.

PubMed

Dragoman, Monica; Curtis, Kathryn M; Gaffield, Mary E

2016-09-01

Dyslipidemias represent a spectrum of lipid disorders that are important risk factors for cardiovascular disease. In addition, elevated triglycerides are known to be associated with pancreatitis. Though less clear, it is possible that dyslipidemias may also contribute to risk for venous thromboembolism (VTE). Ethinyl estradiol and progestogen, contained within combined hormonal contraception, are known to impact lipid metabolism. To evaluate from the literature whether use of combined hormonal contraception (CHC), including combined oral contraception (COC) pills, transdermal patch, vaginal ring or injectables, modifies the relative risk of acute myocardial infarction (MI), stroke, VTE or pancreatitis among women with known dyslipidemias and to determine if existing lipid abnormalities worsen with CHC use. PubMed and the Cochrane Library databases were searched for all articles in all languages published between inception and September 2014 relevant to dyslipidemia, CHC use and serious adverse events (MI, stroke, VTE or pancreatitis). The quality of each individual study was assessed using the system for grading evidence developed by the United States Preventive Services Task Force. From 306 articles identified by our search strategy, 3 articles met inclusion criteria. In a poor-quality case-control study, women with hypercholesterolemia but no COC use had an increased risk of MI (adjusted odds ratio [adj OR] 3.3, 95% confidence interval [CI] 1.6-6.8), as did women who used COCs but did not have hypercholesterolemia (adj OR 2.0, 95% CI 1.4-2.8), compared with non-COC users without hypercholesterolemia; women with both COC use and hypercholesterolemia had an adjusted OR of 24.7 (95% CI 5.6-108.5) compared with women with neither risk factor. A poor-quality cohort study examined COC users and reported that women with dyslipidemia had increased risk for VTE [crude risk ratio (RR) 1.39, 95% CI 1.04-1.85] and transient ischemic attacks or cerebrovascular accidents (CVAs) (RR 1.76, 95% CI 1.51-2.06) compared to those without dyslipidemia. Another poor-quality cohort study provided direct evidence on changes in lipid levels among COC users with dyslipidemia. A minority of women with elevated total cholesterol or triglyceride levels at baseline showed normal results (25% and 28%, respectively) after 6 cycles of COC use. No evidence regarding risks associated with use of other CHC methods was identified. No evidence was identified for the outcome of pancreatitis. Limited data from poor-quality observational studies suggest that women with known dyslipidemias using CHC may be at increased risk for MI and may experience a minimal increase in risk for CVA or VTE. No evidence was identified on risk for pancreatitis in this context. The impact of CHC exposure on the status of lipid abnormalities over time, an intermediate marker for disease, is also unclear. Given the significant limitations of this body of evidence, the importance of access to effective contraception and theoretical concerns raised about the use of CHCs by women with known dyslipidemias, additional rigorous studies are needed to best estimate true associations. Contraceptive decision making should include consideration of both the known and theoretical risks of a given CHC method, safety and acceptability of alternative contraceptive methods, and risks associated with unintended pregnancy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Ovarian follicular dynamics, follicle deviation, and oocyte yield in Gyr breed (Bos indicus) cows undergoing repeated ovum pick-up.

PubMed

Viana, J H M; Palhao, M P; Siqueira, L G B; Fonseca, J F; Camargo, L S A

2010-04-15

The objective of this study was to evaluate ovarian follicular dynamics during intervals between successive ovum pick-up (OPU) and determine its effects on the number and quality of recovered cumulus-oocyte complexes (COCs) in Zebu cows (Bos indicus). Pluriparous nonlactating Gyr cows (Bos indicus; n=10) underwent four consecutive OPU sessions at 96-h intervals. The dynamics of ovarian follicular growth between OPU sessions was monitored by twice-daily ultrasonographic examinations. A single dominant follicle (DF) or two codominant (CDF) follicles (>9mm) were present in 63.3% (19 of 30) of intervals studied, with follicle deviation beginning when the future dominant follicle (F1) achieved a diameter of 6.2+/-0.3mm. The phenomenon of codominance was observed in four (13.3%) of the inter-OPU intervals. The remaining intervals (36.6%, 11 of 30) were characterized by a greater follicular population, lower rate of follicular growth, and a smaller diameter F1 (P<0.0001). There was a tendency (P=0.08) toward an increase in the number of recovered COCs when dominant follicles were not present (NDF). The quality of COCs was not affected by the presence of a single dominant follicle, but codominant follicles resulted in recovery of a lower proportion of viable embryos (40.0%, 62.1%, and 63.6%; P<0.05) and higher proportions of degenerate COCs (56.0%, 30.3%, and 28.6%; P<0.05) for CDF, NDF, and DF respectively. We concluded that, in Zebu cows, (a) repeated follicle aspirations altered ovarian follicular dynamics, perhaps by increasing follicular growth rate; (b) follicular dominance could be established in cows undergoing twice-a-week OPU; and (c) the presence of a dominant follicle during short inter-OPU intervals may not affect COC quality, except when a codominant follicle was present. Copyright 2010 Elsevier Inc. All rights reserved.

Bioleaching characteristics, influencing factors of Cu solubilization and survival of Herbaspirillum sp. GW103 in Cu contaminated mine soil.

PubMed

Govarthanan, Muthusamy; Lee, Gun-Woong; Park, Jung-Hee; Kim, Jae Su; Lim, Sung-Sik; Seo, Sang-Ki; Cho, Min; Myung, Hyun; Kamala-Kannan, Seralathan; Oh, Byung-Taek

2014-08-01

This study was aimed at assess the potential of diazotrophic bacteria, Herbaspirillum sp. GW103, for bioleaching of Cu in mine soil. The strain exhibited resistance to As (550mgL(-1)), Cu (350mgL(-1)), Zn (300mgL(-1)) and Pb (200mgL(-1)). The copper resistance was further confirmed by locating copA and copB genes. The survival of the isolate GW103 during bioleaching was analyzed using green fluorescent protein tagged GW103. Response surface methodology based Box-Behnken design was used to optimize the physical and chemical conditions for Cu bioleaching. Five significant variables (temperature, incubation time, CaCO3, coconut oil cake (COC), agitation rate) were selected for the optimization. Second-order polynomials were established to identify the relationship between Cu bioleaching and variables. The optimal conditions for maximum Cu bioleaching (66%) were 30°C, 60h of incubation with 1.75% of CaCO3 and 3% COC at 140rpm. The results of Cu sequential extraction studies indicated that the isolate GW103 leached Cu from ion-exchangeable, reducible, strong organic and residual fractions. Obtained results point out that the isolate GW103 could be used for bioleaching of Cu from mine soils. Copyright © 2014 Elsevier Ltd. All rights reserved.

Repair Air Conditioning, COC Bldg 2605, Basement Plan. By Strategic ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Repair Air Conditioning, COC Bldg 2605, Basement Plan. By Strategic Air Command, Civil Engineering. Drawing no. R-156, sheet no. 1 of 4, 15 August 1968; project no. MAR-125-8;CE-572; file drawer 2605-5. Last revised 31 August 1968?. Scale one-eighth inch and one-quarter inch to one foot. 29x41 inches. pencil on paper - March Air Force Base, Strategic Air Command, Combat Operations Center, 5220 Riverside Drive, Moreno Valley, Riverside County, CA

77 FR 9696 - Notice of Proposed Reinstatement of Terminated Oil and Gas Lease COC30486

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-17

...Under the provisions of 30 U.S.C. 188(d) and (e), and 43 CFR 3108.2-3(a) and (b)(1), the Bureau of Land Management (BLM) received a petition for reinstatement of oil and gas lease COC30486 from Encana Oil & Gas (USA) Inc., for lands in Mesa County, Colorado. The petition was filed on time and was accompanied by all the rentals due since the date the lease terminated under the law.

United States Air Force 611th Air Support Group/Civil Engineering Squadron, Elmendorf AFB, Alaska. Risk assessment Point Lonely Radar Installation, Alaska. Final report

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

Karmi, S.

1996-04-01

This document contains the baseline human health risk assessment and the ecological risk assessment (ERA) for the Point Lonely Distant Early Warning (DEW) Line radar installation. Twelve sites at the Point Lonely radar installation underwent remedial investigations (RIs) during the summer of 1993. The Vehicle Storage Area (SS14) was combined with the Inactive Landfill because the two sites were essentially co-located and were sampled during the RI as a single unit. Therefore, 11 sites are discussed in this risk assessment. The presence of chemical contamination in the soil, sediments, and surface water at the installation was evaluated and reported inmore » the Point Lonely Remedial Investigation/Feasibility Study (RI/FS). The analytical data reported in the RI/FS form the basis for the human health and ecological risk assessments. The primary chemicals of concern (COCs) at the 11 sites are diesel and gasoline from past spills and/or leaks, chlorinated solvents, and manganese. The 11 sites investigated and the types of samples collected at each site are presented.« less

Between Technocracy and Democracy: An Experimental Approach to Certification of Food Products by Japanese Consumer Cooperative Women

ERIC Educational Resources Information Center

Kimura, Aya Hirata

2010-01-01

Voluntary food certification systems have emerged as a prominent mechanism of food governance in recent years. However, critics have exposed certifications' inability to secure independence, quality, consumer trust, and costs. Recent criticism is even more pointed in that some theorists have critiqued "alternative" systems such as Fair…

Design and implementation of PKI-based certification authority

NASA Astrophysics Data System (ADS)

Zheng, Ying; Bai, Qinghai; Zhao, Linna; Chun, Hua; Chen, Jing

2015-12-01

PKI achieves the management of public key by certificates. It combines the user's public key and his or her identification formation through a trusted third-party organization CA, in order to authenticate the user's identity on the Internet, thus ensuring the authenticity, integrity, confidentiality, and non- repudiation of the information transmitted on the Internet. CA is the most critical agency in the PKI system, mainly responsible for issuing and managing certificates. On the basis of the actual needs of an enterprise, in this paper the author designs and develops a small-sized PKI-based Certification Authority equipped with the functions of root CA initialization, certificate application, certificate issuance, certificate revocation, and the generation of certificate revocation list. The author also points out the problems that need to be mentioned in the design and development.

Pressure-enhanced superconductivity in quasi-1D cobalt carbide Sc3CoC4

NASA Astrophysics Data System (ADS)

Wang, Enyu; Zhu, Xiyu; Wen, Hai-Hu

2016-07-01

We have successfully synthesized the quasi-1D cobalt carbide Sc3CoC4 by using the arc-melting technique which is similar to that of the previous reports. An incomplete superconducting transition is detected at ambient pressure. In addition, two anomalies have been observed at 72 K and 143 K both from resistivity and magnetic susceptibility measurements. According to previous studies, it was argued that they correspond to the 1D Peierls-type distortion and charge-density-wave transitions, respectively. By applying a pressure, the transition at about 72 K is quickly suppressed, which is accompanied by the occurrence of a complete superconducting transition at about 4.5 K. Moreover, the DC magnetic susceptibility under high pressures also reveals the enhancement of superconductivity. We attribute this enhancement of superconductivity to the suppression of the Peierls-type distortion at about 72 K and probably together with the promoted Josephson coupling between the [CoC4] ∞ one-dimensional ribbons.

Bacterial cocaine esterase: a protein-based therapy for cocaine overdose and addiction

PubMed Central

Narasimhan, Diwahar; Woods, James H; Sunahara, Roger K

2012-01-01

Cocaine is highly addictive and there are no pharmacotherapeutic drugs available to treat acute cocaine toxicity or chronic abuse. Antagonizing an inhibitor such as cocaine using a small molecule has proven difficult. The alternative approach is to modify cocaine’s pharmacokinetic properties by sequestering or hydrolyzing it in serum and limiting access to its sites of action. We took advantage of a bacterial esterase (CocE) that has evolved to hydrolyze cocaine and have developed it as a therapeutic that rapidly and specifically clears cocaine from the subject. Native enzyme was unstable at 37°C, thus limiting CocE’s potential. Innovative computational methods based on the protein’s structure helped elucidate its mechanism of destabilization. Novel protein engineering methodologies were applied to substantially improve its stability in vitro and in vivo. These improvements rendered CocE as a powerful and efficacious therapeutic to treat cocaine intoxication and lead the way towards developing a therapy for addiction. PMID:22300094

Expression of apoptotic genes in immature and in vitro matured equine oocytes and cumulus cells.

PubMed

Leon, P M M; Campos, V F; Kaefer, C; Begnini, K R; McBride, A J A; Dellagostin, O A; Seixas, F K; Deschamps, J C; Collares, T

2013-08-01

The gene expression of Bax, Bcl-2, survivin and p53, following in vitro maturation of equine oocytes, was compared in morphologically distinct oocytes and cumulus cells. Cumulus-oocyte complexes (COC) were harvested and divided into two groups: G1 - morphologically healthy cells; and G2 - less viable cells or cells with some degree of atresia. Total RNA was isolated from both immature and in vitro matured COC and real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to quantify gene expression. Our results showed there was significantly higher expression of survivin (P < 0.05) and lower expression of p53 (P < 0.01) in oocytes compared with cumulus cells in G1. No significant difference in gene expression was observed following in vitro maturation or in COC derived from G1 and G2. However, expression of the Bax gene was significantly higher in cumulus cells from G1 (P < 0.02).

An overview of the development of combined oral contraceptives containing estradiol: focus on estradiol valerate/dienogest

PubMed Central

Fruzzetti, Franca; Trémollieres, Florence; Bitzer, Johannes

2012-01-01

Natural estrogens such as estradiol (E2) or its valerate ester (E2V) offer an alternative to ethinyl estradiol (EE). E2-containing combined oral contraceptives (COCs) have demonstrated sufficient ovulation inhibition and acceptable contraceptive efficacy. However, earlier formulations were generally associated with unacceptable bleeding profiles. Two E2V-containing preparations have been approved to date for contraceptive use: E2V/cypro-terone acetate (CPA) (Femilar®; only approved in Finland and only in women >40 years or women aged 35–40 years in whom a COC containing EE is not appropriate) and E2V/dienogest (DNG; Qlaira®/Natazia®). The objective of the current review is to provide an overview of the development of COCs containing natural estrogen, highlighting past issues and challenges faced by earlier formulations, as well as the current status and future directions. The majority of information to date pertains to the development of E2V/DNG. PMID:22468839

Structural analysis of thermostabilizing mutations of cocaine esterase

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

Narasimhan, Diwahar; Nance, Mark R.; Gao, Daquan

Cocaine is considered to be the most addictive of all substances of abuse and mediates its effects by inhibiting monoamine transporters, primarily the dopamine transporters. There are currently no small molecules that can be used to combat its toxic and addictive properties, in part because of the difficulty of developing compounds that inhibit cocaine binding without having intrinsic effects on dopamine transport. Most of the effective cocaine inhibitors also display addictive properties. We have recently reported the use of cocaine esterase (CocE) to accelerate the removal of systemic cocaine and to prevent cocaine-induced lethality. However, wild-type CocE is relatively unstablemore » at physiological temperatures ({tau}{sub 1/2} {approx} 13 min at 37 C), presenting challenges for its development as a viable therapeutic agent. We applied computational approaches to predict mutations to stabilize CocE and showed that several of these have increased stability both in vitro and in vivo, with the most efficacious mutant (T172R/G173Q) extending half-life up to 370 min. Here we present novel X-ray crystallographic data on these mutants that provide a plausible model for the observed enhanced stability. We also more extensively characterize the previously reported variants and report on a new stabilizing mutant, L169K. The improved stability of these engineered CocE enzymes will have a profound influence on the use of this protein to combat cocaine-induced toxicity and addiction in humans.« less

Polycystic ovary syndrome and combined oral contraceptive use: a comparison of clinical practice in the United States to treatment guidelines.

PubMed

Bird, Steven T; Hartzema, Abraham G; Etminan, Mahyar; Brophy, James M; Delaney, Joseph A C

2013-04-01

The October 2010 ESHRE/ASRM polycystic ovary syndrome (PCOS) workshop concluded: (1) all combined oral contraceptives (COC) appear to have equal efficacy for PCOS, (2) addition of antiandrogens (spironolactone) to COCs has little treatment benefit and (3) metformin does not improve the live-birth rate and should only be used with impaired glucose tolerance. We compared these guidelines to current practice in the United States IMS claims-database. Time-series analyses were conducted by calendar-year in women with PCOS to evaluate prescribing preferences for COCs, concomitant use of spironolactone, and utilization of metformin. Trends were analyzed with linear regression. Our cohort included 1.6 million women taking COCs, 46 780 with a PCOS claim. Drospirenone utilization increased by 1.52% (SE:0.48%, p = 0.007) per-year more in women with PCOS (4.16%, SE:0.45%, p < 0.001) than in women without PCOS (2.64%, SE:0.17%, p < 0.001)). Concomitant use of drospirenone and spironolactone was common (14.26%) and increased by 0.75% (SE:0.15%, p = 0.002) per-year. Although plasma glucose tests were unavailable, women with PCOS were more likely to take metformin than have a diabetes claim (45.8% versus 15.2%, p < 0.001), indicating some women likely receive metformin solely for PCOS. Our data suggests further attention is needed to medication management of PCOS to bridge the gap between guidelines and practice.

Follicular development in a 7-day versus 4-day hormone-free interval with an oral contraceptive containing 20 mcg ethinyl estradiol and 1 mg norethindrone acetate.

PubMed

Rible, Radhika D; Taylor, DeShawn; Wilson, Melissa L; Stanczyk, Frank Z; Mishell, Daniel R

2009-03-01

Combined oral contraceptive (COC) formulations with 20 mcg ethinyl estradiol (EE) have a greater incidence of ovarian hormone production and follicular development, which can be managed by shortening the number of hormone-free days per COC cycle. This study evaluates differences in follicular development during a 7-day versus 4-day hormone-free interval in a COC regimen with 20 mcg EE and 1 mg norethindrone acetate. Forty-one healthy women were randomized in an open-label fashion to this formulation in either a 24/4 or a 21/7 day regimen for three cycles. Estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone and inhibin B were measured daily from Cycle 2, Day 21 to Cycle 3, Day 3 and on Day 7 of Cycle 3. Follicular diameter and Hoogland score were calculated on Cycle 2, Days 21, 24 and 28 and Cycle 3, Days 3 and 7. Sixty-six percent of subjects in the 21/7 group and 70% of the subjects in the 24/4 group developed a follicle greater than 10 mm diameter. Ovarian steroid hormone levels, Hoogland scores and bleeding patterns were not statistically significant between the groups. In contrast to prior studies, this analysis suggests no difference in follicle development or bleeding patterns among women receiving a 21/7 or 24/4 regimen of a 20-mcg EE/1-mg norethindrone acetate COC.

Haemostatic and metabolic impact of estradiol pills and drospirenone-containing ethinylestradiol pills vs. levonorgestrel-containing ethinylestradiol pills: A literature review.

PubMed

Lete, Iñaki; Chabbert-Buffet, Nathalie; Jamin, Christian; Lello, Stefano; Lobo, Paloma; Nappi, Rossella E; Pintiaux, Axelle

2015-01-01

Since its introduction 50 years ago, the contraceptive pill has continuously evolved to decrease the risk of venous thromboembolism (VTE) associated with its use. An increased risk of VTE still remains, however. Other concerns, such as effects on lipid and carbohydrate metabolism, have also been reported. In this study we compared two reference combined oral contraceptives (COCs) containing ethinylestradiol (EE)/levonorgestrel (LNG) and EE/drospirenone (DRSP) with COCs containing estradiol (E2) (estradiol valerate [E2V]/dienogest [DNG] and E2/nomegestrol acetate [NOMAC]). They were evaluated according to their influence on recognised haemostatic and metabolic markers. A literature search of the MEDLINE/PubMed database was conducted for head-to-head studies. EE/LNG was chosen as the comparator pill. The haemostatic impact of E2 pills and EE/LNG has been extensively compared, in contrast to that of EE/DRSP and EE/LNG. Changes in haemostatic and metabolic marker levels between EE/LNG and E2V/DNG were generally not statistically significant. E2/NOMAC showed statistically significantly favourable results on haemostatic markers and had a neutral effect on carbohydrate and lipid metabolism when compared with EE/LNG. E2/NOMAC exhibits less haemostatic and metabolic impact than EE/LNG and other COCs, suggesting that it may be a promising candidate to reduce residual VTE risk associated with COC use. Confirmation from a well-powered prospective clinical trial is, however, needed.

Effects of a combined oral contraceptive containing 20 mcg of ethinylestradiol and 3 mg of drospirenone on the blood pressure, renin-angiotensin-aldosterone system, insulin resistance, and androgenic profile of healthy young women.

PubMed

Giribela, Cassiana Rosa Galvão; Consolim-Colombo, Fernanda Marciano; Nisenbaum, Marcelo Gil; Moraes, Tercio Lemos de; Giribela, Aricia Helena Galvão; Baracat, Edmund Chada; Melo, Nilson Roberto de

2015-01-01

Combined oral contraceptives (COCs) may increase the risk for cardiovascular disease depending on the ethynyl estradiol (EE) dose and the androgenicity of the progestogens. Our objective was to evaluate the impact of a COC containing 20 mcg EE + 3 mg drospirenone on blood pressure (BP), renin-angiotensin-aldosterone system, insulin resistance, and androgenic profile of healthy young women. Eighty-one healthy young women aged 30 ± 1 years (case group, n = 49, received COC; control group, n = 32, used no COC) were assessed twice, before and after the 6-month study. Statistical analysis employed the paired t-tests and expressed the data in mean and standard deviation. Results were as follows: no changes in BP or in BMI; a significant increase in aldosterone, plasma renin activity, triglycerides, and total cholesterol levels, but a non-significant increase in HDL and no significant changes in LDL levels (these parameters remained within normal ranges); a significant increase in the HOMA-IR index and a significant decrease in dehydroepiandrosterone sulfate (SDHEA), androstenedione, total testosterone, and free testosterone levels; no significant variations in the control group parameters. An oral contraceptive combination of a low EE dose and an anti-androgenic progestogen does not negatively influence the risk factors for a cardiovascular disease.

Thermal effect on structure organizations in cobalt-fullerene nanocomposition.

PubMed

Lavrentiev, Vasily; Vacik, Jiri; Naramoto, Hiroshi; Sakai, Seiji

2010-04-01

Effect of deposition temperature (Ts) on structure of Co-C60 nanocomposite (NC) prepared by simultaneous deposition of cobalt and fullerene on sapphire is presented. The NC structure variations with Ts increasing from room temperature (RT) to 400 degrees C have been analyzed using scanning electron microscopy (SEM), atomic force microscopy (AFM) and Raman spectroscopy. AFM and SEM show granule-like structure of the Co-C60 film. The mixture film deposited at RT includes the hills on the surface suggesting accumulation of internal stress during phase separation. Raman spectra show 25 cm(-1) downshift of Ag(2) C60 peak suggesting -Co-C60- polymerization in C60-based matrix of the NC film. Analysis of Raman spectra has revealed existence of amorphous carbon (a-C) in the NC matrix that argues C60 decomposition. The Ts increase to 200 degrees C causes the surface hills smoothing. In parallel, downshift of the Ag(2) peak decreases to 16 cm(-1) that implies more pronounced phase separation and lower -Co-C60- polymerization efficiency. Also, amount of a-C content slightly increases. Further Ts increasing to 400 degrees C changes the NC structure dramatically. AFM shows evident enlargement of the granules. According to Raman spectra the high Ts deposition yields pronounced C60 decomposition increasing the a-C content. Features of a-C Raman peak imply nucleation of graphitic islands at the NC interfaces. Abundant decomposition of C60 in the mixture film deposited at 400 degrees C is referred to cobalt catalytic effect.

Holding equine oocytes in a commercial embryo-holding medium: New perspective on holding temperature and maturation time.

PubMed

Dini, Pouya; Bogado Pascottini, Osvaldo; Ducheyne, Kaatje; Hostens, Miel; Daels, Peter

2016-09-15

In the present study, we examined the effect of holding equine oocytes in Syngro embryo holding medium (EHM) overnight at either 4 °C, 17 °C, or 22 °C to 25 °C, on the time to maturation and developmental competence. We also examined the effect of placing denuded oocyte without extruded polar body back in maturation condition on subsequent maturation rate. In experiment 1, cumulus-oocyte complexes (COCs) were recovered postmortem and placed in EHM at 22 °C to 25 °C for 18 to 20 hours (OH) or placed directly in maturation (DM). The maturation rate was assessed after 22, 24, or 28 hours of culture. After denuding cumulus cells at 22 or 24 hours, oocytes without obvious polar body were placed back into culture and reassessed at subsequent time points. At 22 hours, a higher proportion of oocytes placed in OH achieved nuclear maturation than those placed in DM (63% and 37%, respectively, P = 0.008). At 24 and 28 hours, no significant differences in the % MII stage oocytes were observed between OH and DM. The nuclear maturation rate for OH oocytes was similar at 22, 24, and 28 hours, indicating that the maximum maturation rate was reached at an earlier time than that in DM. Oocytes fertilized by intracytoplasmic sperm injection resulted in a 7.1% and 6.3% blastocyst rate for OH and DM, respectively. Denuding oocytes after 22 hours or more of culture did not have an adverse effect on the final nuclear maturation rate. After 28 hours of culture, the same nuclear maturation rate (MII) was reached for nondenuded oocytes and oocytes denuded after 22 hours of 24 hours of culture. In experiment 2, COCs were held overnight at room temperature in EHM, then placed in maturation for 20, 22, and 28 hours. Nuclear maturation rate was significantly lower at 20 hours than 22 and 28 hours of culture and was similar at 22 and 28 hours, suggesting that at least 22 hours of culture is required to reach maximal maturation rate for stored oocytes (43%, 62%, and 65% at 20, 22, and 28 hours, respectively. P < 0.001). In experiment 3, COCs were either placed directly in culture or held at 22 °C to 25 °C, 17 °C, or 4 °C overnight. After 24 hours of culture, maturation rate was similar for all groups, suggesting that COCs can be stored in conventional 4 °C transport condition or 17 °C. In preliminary studies, COCs were held at 4 °C followed by 24 hours of culture, and mature oocytes were fertilized using intracytoplasmic sperm injection. Twenty-three injected oocytes yielded four blastocysts. In conclusion, we reported that oocytes can be placed in a commercial EHM and stored overnight without a detrimental effect on maturation rates or blastocyst development. Oocytes held in holding medium require less time to reach the MII stage than oocytes placed in culture directly. Removing the cumulus cells from oocytes that have been cultured for at least 22 hours does not seem to alter the final nuclear maturation rate. Finally, we observed no detrimental effect of storing oocytes at 4 °C for up to 18 hours, and oocytes appeared to maintain developmental competence and blastocyst potential. Copyright © 2016 Elsevier Inc. All rights reserved.

Self-validating type C thermocouples to 2300 °C using high temperature fixed points

NASA Astrophysics Data System (ADS)

Pearce, J. V.; Elliott, C. J.; Machin, G.; Ongrai, O.

2013-09-01

Above 1500 °C, tungsten-rhenium (W-Re) thermocouples are the most commonly used contact thermometers because they are practical and inexpensive. However in general loss of calibration is very rapid, and, due to their embrittlement at high temperature, it is generally not possible to remove them for recalibration from the process environments in which they are used. Even if removal for recalibration was possible this would be of, at best, very limited use due to large inhomogeneity effects. Ideally, these thermocouples require some mechanism to monitor their drift in-situ. In this study, we describe self-validation of Type C (W5%Re/W26%Re) thermocouples by means of miniature high temperature fixed points comprising crucibles containing respectively Co-C, Pt-C, Ru-C, and Ir-C eutectic alloys. An overview of developments in this area is presented.

Progress report for the CCT-WG5 high temperature fixed point research plan

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

Machin, G.; Woolliams, E. R.; Anhalt, K.

2013-09-11

An overview of the progress in High Temperature Fixed Point (HTFP) research conducted under the auspices of the CCT-WG5 research plan is reported. In brief highlights are: Provisional long term stability of HTFPs has been demonstrated. Optimum construction methods for HTFPs have been established and high quality HTFPs of Co-C, Pt-C and Re-C have been constructed for thermodynamic temperature assignment. The major sources of uncertainty in the assignment of thermodynamic temperature have been identified and quantified. The status of absolute radiometric temperature measurement has been quantified through the circulation of a set of HTFPs. The measurement campaign to assign lowmore » uncertainty thermodynamic temperatures to a selected set of HTFPs will begin in mid-2012. It is envisaged that this will be complete by 2015 leading to HTFPs becoming routine reference standards for radiometry and high temperature metrology.« less

Enhanced performance of a structured cyclo olefin copolymer-based amorphous silicon solar cell

NASA Astrophysics Data System (ADS)

Zhan, Xinghua; Chen, Fei; Gao, Mengyu; Tie, Shengnian; Gao, Wei

2017-07-01

The submicron array was fabricated onto a cyclo olefin copolymer (COC) film by a hot embossing method. An amorphous silicon p-i-n junction and transparent conductive layers were then deposited onto it through a plasma enhanced chemical vapor deposition (PECVD) and magnetron sputtering. The efficiency of the fabricated COC-based solar cell was measured and the result demonstrated 18.6% increase of the solar cell efficiency when compared to the sample without array structure. The imprinted polymer solar cells with submicron array indeed increase their efficiency.

Magnetic state and phase composition of carbon-encapsulated Co@C nanoparticles according to 59Co, 13C NMR data and Raman spectroscopy

NASA Astrophysics Data System (ADS)

Mikhalev, K. N.; Germov, A. Yu; Uimin, M. A.; Yermakov, A. E.; Konev, A. S.; Novikov, S. I.; Gaviko, V. S.; Ponosov, Yu S.

2018-05-01

59Co, 13C NMR spectra, magnetization and Raman spectra of Co@C nanoparticles encapsulated in carbon have been analyzed. It has been shown that the cores of the nanoparticles consist of metallic cobalt with FCC structure and perhaps the carbide of cobalt Co3C. Carbon shell have been characterized as a highly defective structure similar to amorphous or glassy-like carbon, however, it may include a small amount of the carbon nanotubes.

Aircraft Certification Service Field Office Listing

DOT National Transportation Integrated Search

1997-08-12

This advisory circular is issued to the general public and industry. It : provides the nearest points of contact for information on issuance of type and : supplemental type certificates and changes, as well as issuance of production : and/or airworth...

Combined hormonal versus nonhormonal versus progestin-only contraception in lactation.

PubMed

Lopez, Laureen M; Grey, Thomas W; Stuebe, Alison M; Chen, Mario; Truitt, Sarah T; Gallo, Maria F

2015-03-20

Postpartum contraception improves the health of mothers and children by lengthening birth intervals. For lactating women, contraception choices are limited by concerns about hormonal effects on milk quality and quantity and passage of hormones to the infant. Ideally, the contraceptive chosen should not interfere with lactation or infant growth. Timing of contraception initiation is also important. Immediately postpartum, most women have contact with a health professional, but many do not return for follow-up contraceptive counseling. However, immediate initiation of hormonal methods may disrupt the onset of milk production. To determine the effects of hormonal contraceptives on lactation and infant growth We searched for eligible trials until 2 March 2015. Sources included the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, POPLINE, Web of Science, LILACS, ClinicalTrials.gov, and ICTRP. We also examined review articles and contacted investigators. We sought randomized controlled trials in any language that compared hormonal contraception versus another form of hormonal contraception, nonhormonal contraception, or placebo during lactation. Hormonal contraception includes combined or progestin-only oral contraceptives, injectable contraceptives, implants, and intrauterine devices.Trials had to have one of our primary outcomes: breast milk quantity or biochemical composition; lactation initiation, maintenance, or duration; infant growth; or timing of contraception initiation and effect on lactation. Secondary outcomes included contraceptive efficacy while breastfeeding and birth interval. For continuous variables, we calculated the mean difference (MD) with 95% confidence interval (CI). For dichotomous outcomes, we computed the Mantel-Haenszel odds ratio (OR) with 95% CI. Due to differing interventions and outcome measures, we did not aggregate the data in a meta-analysis. In 2014, we added seven trials for a new total of 11. Five reports were published before 1985 and six from 2005 to 2014. They included 1482 women. Four trials examined combined oral contraceptives (COCs), and three studied a levonorgestrel-releasing intrauterine system (LNG-IUS). We found two trials of progestin-only pills (POPs) and two of the etonogestrel-releasing implant. Older studies often lacked quantified results. Most trials did not report significant differences between the study arms in breastfeeding duration, breast milk composition, or infant growth. Exceptions were seen mainly in older studies with limited information.For breastfeeding duration, two of eight trials indicated a negative effect on lactation. A COC study reported a negative effect on lactation duration compared to placebo but did not quantify results. Another trial showed a lower percentage of the LNG-IUS group breastfeeding at 75 days versus the nonhormonal IUD group (reported P < 0.05) but no significant difference at one year.For breast milk volume, two older studies indicated lower volume for the COC group versus the placebo group. One trial did not quantify results. The other showed lower means (mL) for the COC group, e.g. at 16 weeks (MD -24.00, 95% CI -34.53 to -13.47) and at 24 weeks (MD -24.90, 95% CI -36.01 to -13.79). Another four trials did not report any significant difference between the study groups in milk volume or composition with two POPs, a COC, or the etonogestrel implant.Seven trials studied infant growth; one showed greater weight gain (grams) for the etonogestrel implant versus no method for six weeks (MD 426.00, 95% CI 58.94 to 793.06) but less compared with depot medroxyprogesterone acetate (DMPA) from 6 to 12 weeks (MD -271.00, 95% CI -355.10 to -186.90). The others studied POPs, COCs versus POPs, or an LNG-IUS. Results were not consistent across the 11 trials. The evidence was limited for any particular hormonal method. The quality of evidence was moderate overall and low for three of four placebo-controlled trials of COCs or POPs. The sensitivity analysis included six trials with moderate quality evidence and sufficient outcome data. Five trials indicated no significant difference between groups in breastfeeding duration (etonogestrel implant insertion times, COC versus POP, and LNG-IUS). For breast milk volume or composition, a COC study showed a negative effect, while an implant trial showed no significant difference. Of four trials that assessed infant growth, three indicated no significant difference between groups. One showed greater weight gain in the etonogestrel implant group versus no method but less versus DMPA.

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

Dutton, Spencer M.; Chan, Wanyu R.; Mendell, Mark J.

California's building efficiency standards (Title 24) mandate minimum prescribed ventilation rates (VRs) for commercial buildings. Title 24 standards currently include a prescriptive procedure similar to ASHRAE’s prescriptive “ventilation rate procedure”, but does not include an alternative procedure, akin to ASHRAE’s non-prescriptive “indoor air quality procedure” (IAQP). The IAQP determines minimum VRs based on objectively and subjectively evaluated indoor air quality (IAQ). The first primary goal of this study was to determine, in a set of California retail stores, the adequacy of Title 24 VRs and observed current measured VRs in providing the level of IAQ specified through an IAQP process,more » The second primary goal was to evaluate whether several VRs implemented experimentally in a big box store would achieve adequate IAQ, assessed objectively and subjectively. For the first goal, a list of contaminants of concern (CoCs) and reference exposure levels (RELs) were selected for evaluating IAQ. Ventilation rates and indoor and outdoor CoC concentrations were measured in 13 stores, including one “big box” store. Mass balance models were employed to calculate indoor contaminant source strengths for CoCs in each store. Using these source strengths and typical outdoor air contaminant concentrations, mass balance models were again used to calculate for each store the “IAQP” VR that would maintain indoor CoC concentrations below selected RELs. These IAQP VRs were compared to the observed VRs and to the Title 24- prescribed VRs. For the second goal, a VR intervention study was performed in the big box store to determine how objectively assessed indoor contaminant levels and subjectively assessed IAQ varied with VR. The three intervention study VRs included an approximation of the store’s current VR [0.24 air changes per hour (ACH)], the Title 24-prescribed VR [0.69 ACH], and the calculated IAQPbased VR [1.51 ACH]). Calculations of IAQP-based VRs showed that for the big box store and 11 of the 12 other stores, neither current measured VRs nor the Title 24-prescribed VRs would be sufficient to maintain indoor concentrations of all CoCs below RELs. In the intervention study, with the IAQP-based VR applied in the big box store, all CoCs were controlled below RELs (within margins of error). Also, at all three VRs in this store, the percentage of subjects reporting acceptable air quality exceeded an 80% criterion of acceptability. The IAQP allows consideration of outdoor air ventilation as just one of several possible tools for achieving adequate IAQ. In two of the 13 surveyed buildings, applying the IAQP to allow lower VRs could have saved energy whilst still maintaining acceptable indoor air quality. In the remaining 11 buildings, saving energy through lower VRs would require combination with other strategies, either reducing indoor sources of CoCs such as formaldehyde, or use of gas phase air cleaning technologies. Based on the findings from applying the IAQP calculations to retail stores and the IAQP-based intervention study, recommendations are made regarding the potential introduction of a comparable procedure in Title 24.« less

Behavioral effects of ketamine and toxic interactions with psychostimulants

PubMed Central

Hayase, Tamaki; Yamamoto, Yoshiko; Yamamoto, Keiichi

2006-01-01

Background The anesthetic drug ketamine (KT) has been reported to be an abused drug and fatal cases have been observed in polydrug users. In the present study, considering the possibility of KT-enhanced toxic effects of other drugs, and KT-induced promotion of an overdose without making the subject aware of the danger due to the attenuation of several painful subjective symptoms, the intraperitoneal (i.p.) KT-induced alterations in behaviors and toxic interactions with popular co-abused drugs, the psychostimulants cocaine (COC) and methamphetamine (MA), were examined in ICR mice. Results A single dose of KT caused hyperlocomotion in a low (30 mg/kg, i.p.) dose group, and hypolocomotion followed by hyperlocomotion in a high (100 mg/kg, i.p.) dose group. However, no behavioral alterations derived from enhanced stress-related depression or anxiety were observed in the forced swimming or the elevated plus-maze test. A single non-fatal dose of COC (30 mg/kg, i.p.) or MA (4 mg/kg, i.p.) caused hyperlocomotion, stress-related depression in swimming behaviors in the forced swimming test, and anxiety-related behavioral changes (preference for closed arms) in the elevated plus-maze test. For the COC (30 mg/kg) or MA (4 mg/kg) groups of mice simultaneously co-treated with KT, the psychostimulant-induced hyperlocomotion was suppressed by the high dose KT, and the psychostimulant-induced behavioral alterations in the above tests were reversed by both low and high doses of KT. For the toxic dose COC (70 mg/kg, i.p.)- or MA (15 mg/kg, i.p.)-only group, mortality and severe seizures were observed in some animals. In the toxic dose psychostimulant-KT groups, KT attenuated the severity of seizures dose-dependently. Nevertheless, the mortality rate was significantly increased by co-treatment with the high dose KT. Conclusion Our results demonstrated that, in spite of the absence of stress-related depressive and anxiety-related behavioral alterations following a single dose of KT treatment, and in spite of the KT-induced anticonvulsant effects and attenuation of stress- and anxiety-related behaviors caused by COC or MA, the lethal effects of these psychostimulants were increased by KT. PMID:16542420

ESTABLISHING A LIVE CARTILAGE-ON-CARTILAGE INTERFACE FOR TRIBOLOGICAL TESTING.

PubMed

Trevino, Robert L; Stoia, Jonathan; Laurent, Michel P; Pacione, Carol A; Chubinskaya, Susan; Wimmer, Markus A

2017-03-01

Mechano-biochemical wear encompasses the tribological interplay between biological and mechanical mechanisms responsible for cartilage wear and degradation. The aim of this study was to develop and start validating a novel tribological testing system, which better resembles the natural joint environment through incorporating a live cartilage-on-cartilage articulating interface, joint specific kinematics, and the application of controlled mechanical stimuli for the measurement of biological responses in order to study the mechano-biochemical wear of cartilage. The study entailed two parts. In Part 1, the novel testing rig was used to compare two bearing systems: (a) cartilage articulating against cartilage (CoC) and (b) metal articulating against cartilage (MoC). The clinically relevant MoC, which is also a common tribological interface for evaluating cartilage wear, should produce more wear to agree with clinical observations. In Part II, the novel testing system was used to determine how wear is affected by tissue viability in live and dead CoC articulations. For both parts, bovine cartilage explants were harvested and tribologically tested for three consecutive days. Wear was defined as release of glycosaminoglycans into the media and as evaluation of the tissue structure. For Part I, we found that the live CoC articulation did not cause damage to the cartilage, to the extent of being comparable to the free swelling controls, whereas the MoC articulation caused decreased cell viability, extracellular matrix disruption, and increased wear when compared to CoC, and consistent with clinical data. These results provided confidence that this novel testing system will be adequate to screen new biomaterials for articulation against cartilage, such as in hemiarthroplasty. For Part II, the live and dead cartilage articulation yielded similar wear as determined by the release of proteoglycans and aggrecan fragments, suggesting that keeping the cartilage alive may not be essential for short term wear tests. However, the biosynthesis of glycosaminoglycans was significantly higher due to live CoC articulation than due to the corresponding live free swelling controls, indicating that articulation stimulated cell activity. Moving forward, the cell response to mechanical stimuli and the underlying mechano-biochemical wear mechanisms need to be further studied for a complete picture of tissue degradation.

Self-reported and verified compliance in a phase 3 clinical trial of a novel low-dose contraceptive patch and pill.

PubMed

Kaunitz, Andrew M; Portman, David; Westhoff, Carolyn L; Archer, David F; Mishell, Daniel R; Foegh, Marie

2015-03-01

Pregnancy rates in US contraceptive clinical trials are increasing due to decreased treatment compliance. This study compared compliance with a new low-dose levonorgestrel (LNG) and ethinyl estradiol (EE) contraceptive patch (CP, Twirla™) with that of a low-dose combination oral contraceptive (COC) in a demographically diverse population. This analysis was part of an open-label, parallel-group, multicenter phase 3 study that randomized healthy sexually active women (17-40years) to 13cycles of LNG/EE CP or 6cycles of COC, then 7cycles of LNG/EE CP. We defined self-reported compliance as cycles that, according to diaries, show 21days of patch wear without missed days or any patch worn >7days or 21days of pill-taking without missed pill days. We verified compliance by detectable plasma presence of LNG and EE at cycles 2, 6, and 13. Of the intention-to-treat population with diary information (N=1328, mean age 26.4years, 46% minorities, 33% obese), 10.0% of the CP (n=998) versus 21.2% of the COC group (n=330) self-reported noncompliance after 6cycles (p<.001). Laboratory assessments verified 10-14% of participants in both groups as noncompliant. Self-reported perfect use did not vary between obese [body mass index (BMI) ≥30kg/m(2)] versus nonobese (BMI <30kg/m(2)) participants in both groups or when stratified by age, education, or race/ethnicity in the CP group. Self-reported compliance was significantly greater in the CP than COC group and did not vary by obesity status. Discrepancies between self-reported and verified compliance question reliability of patient diaries. This paper, based on an analysis of a phase 3 trial, shows that compliance was significantly greater with a new weekly transdermal CP than with a once-daily COC in obese as well as nonobese participants. Discrepancies between self-reported compliance and laboratory-verified compliance raise questions regarding the reliability of patient diaries. Copyright © 2015 Elsevier Inc. All rights reserved.

Side effects unrelated to disease activity and acceptability of highly effective contraceptive methods in women with systemic lupus erythematosus: a randomized, clinical trial.

PubMed

Cravioto, María-del-Carmen; Jiménez-Santana, Luisa; Mayorga, Julio; Seuc, Armando H

2014-08-01

To assess the side effects unrelated to disease activity and the acceptability of combined oral contraceptives (COCs), progestin-only pills (POPs) and copper-releasing intrauterine devices (IUDs) in women with systemic lupus erythematosus (SLE). A randomized clinical trial including 162 women with SLE, assigned to COC (n=54), POP (n=54) or IUD (n=54). Follow-up visits were conducted after 1, 2, 3, 6, 9 and 12 months of treatment to monitor the presence of symptoms, changes in body weight and blood pressure as well as the development of health problems other than those relating to lupus. Reasons for discontinuation and satisfaction with the use of the assigned method were recorded at the end of treatment. Statistical analysis included descriptive statistics, repeated measure analyses and Kaplan-Meier curves. Significantly different discontinuation rates due to any reason [35%, 55%, 29% (p<0.01)] or nonmedical reasons [(11%, 31%, 4% (p<0.05)] were observed among the COC, POP and IUD groups. Nausea was most frequent among COC users, dysmenorrhea among IUD users and acne and hirsutism among POP users. Mean blood pressures remained unchanged. Mild increases in body weight were observed over time in all treatment groups. Most women were satisfied with the use of the assigned contraceptive method. Oral contraceptives and IUD are acceptable birth control methods for patients with lupus, when counseling and specialized health attention are provided; however, the acceptability of POP appears to be inferior. Side effects unrelated to lupus disease activity are not frequent reasons to discontinue the contraceptive methods. This study delves into an area that has not been explored among patients with lupus. Our findings on the associated side effects and reasons for discontinuing COCs, POPs or copper-bearing IUDs may be useful in improving contraceptive counseling for women with lupus. Furthermore, they also heighten our knowledge on the reasons that may preclude the widespread use of effective contraceptives among lupus patients. Copyright © 2014. Published by Elsevier Inc.

46 CFR 154.1802 - Certificates, letters and endorsements: Foreign flag vessels.

Code of Federal Regulations, 2010 CFR

2010-10-01

... information which except for the certificates under paragraph (c)(1) of this section, are in English: (1) The... sampling points. (6) If the vessel carries methane, a description of the systems for cargo temperature and...

Electrochromatography on acrylate-based monolith in cyclic olefin copolymer microchip: a cost-effective and easy-to-use technology.

PubMed

Ladner, Yoann; Crétier, Gérard; Faure, Karine

2012-10-01

This article shows that there is great interest in using an electrochromatographic microchip made of hexyl acrylate (HA) based porous monolith cast within the channel of a cyclic olefin copolymer (COC) device. The monolith is simultaneously in situ synthesized and anchored to the inner walls of the channel in less than 10 min. By appropriate choice of light intensity used during the synthesis, the separation efficiency obtained for nonpolar solutes such as polycyclic aromatic hydrocarbons (PAH) is increased up to 250 000 plates/m. The performance of this HA-filled COC microchip was investigated for a wide range of analytes of varying nature. The reversed-phase separation of four aflatoxins is obtained in less than 2 min. The baseline separation of a mixture of neurotransmitters including six amino acids and two catecholamines is possible thanks to the superimposition of the differences in electrophoretic mobility on the chromatographic process. The durability of the system at pH 13 allows the separation of five biogenic amines and the quantitative determination of two of them in numerous wine samples. The feasibility of on-line preconcentration is also demonstrated. Hydrophilic surface modification of COC channel via UV-photografting with poly(ethylene glycol) methacrylate (PEGMA) before in situ synthesis of HA, is necessary to reduce the adsorption of very hydrophobic solutes such as PAH during enrichment. The detection limit of fluoranthene is decreased down to less than 1 ppb with a preconcentration of 4.5 h on the HA-filled PEGMA functionalized COC microchip. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preliminary studies on LED-activated pyropheophorbide-α methyl ester killing cisplatin-resistant ovarian carcinoma cells

NASA Astrophysics Data System (ADS)

Tan, Yong; Xu, Chuan Shan; Xia, Xin Shu; Yu, He Ping; Bai, Ding Qun; He, Yong; Xu, Jing; Wang, Ping; Wang, Xin Na; Leung, Albert Wing Nang

2009-05-01

In the present study, a novel LED source was applied for activating pyropheophorbids-a methyl ester (MPPa) in cisplatin-resistant ovarian cell line COC1/DDP cells. MPPa concentration was 2 μM and light energy from 0.125-8 J/cm2. Cytotoxicity was investigated 24 h using MTT reduction assay and light microscopy after treatment. Cellular ultrastructure was observed using transmission electron microscopy (TEM) and nuclear chromatin by fluorescent microscope with Hoechst33258 staining. MTT reduction assay showed that the cytotoxicity of LED-activated MPPa in the COC1/DDP cells increased along with the light dose of LED source and LED-activated MPPa resulted in light-dependent cytotoxicity. The observations from light microscopy reinforced the above results. TEM showed that necrotic cells with the disruption of karyotheca, karyorrhexis, and karyolysis of nucleus and apoptotic cells, especially the apoptotic body, can be seen post LED-activated MPPa. Hoechst33258 staining showed that condensation of chromatin and nuclear fragmentations could be found in many treated cells and some of them formed the structure of apoptotic bodies when COC1/DDP cells were exposed to 2 μM MPPa for 20 h and then 1 J/cm2 irradiation of LED source. The findings demonstrated that the novel LED source could efficiently activated MPPa and LED-activated MPPa could significantly kill cisplatin-resistant ovarian cell line COC1/DDP cells through two major pathways including necrosis and apoptosis, suggesting that LED is a novel and efficient light source and LED-activated MPPa might be potential therapeutic modality for treating cisplatin-resistant ovarian carcinoma.

Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol compared with one containing levonorgestrel and ethinylestradiol on haemostasis, lipids and carbohydrate metabolism

PubMed Central

Ågren, Ulla M; Anttilat, Marjatta; Mäenpää-Liukko, Kristiina; Rantala, Maija-Liisa; Rautiainen, Hilkka; Sommer, Werner F; Mommers, Ellen

2011-01-01

Objectives To compare the effects of a combined oral contraceptive (COC) containing nomegestrol acetate and 17β-oestradiol (NOMAC/E2) on haemostasis, lipids, carbohydrate metabolism, C-reactive protein (CRP) and sex hormone-binding globulin (SHBG) with those of a COC containing levonorgestrel and ethinylestradiol (LNG/EE). Methods In a randomised, open-label study, 121 healthy women, 18-50 years of age, were randomly assigned to receive NOMAC/E2 (2.5 mg/1.5 mg) in a 24/4-day regimen (n = 60) or LNG/EE (150 μg/30 μg) in a 21/7-day regimen (n = 61) for six cycles. The primary outcome was the change from baseline to cycle 6 for all indices. Results All parameters were similar at baseline between the two groups. Over six cycles, NOMAC/E2 had less effect on most haemostatic indices than LNG/EE. Lipids were essentially unchanged with NOMAC/E2, whereas with LNG/EE high-density lipoprotein cholesterol decreased and low-density lipoprotein cholesterol and triglycerides slightly increased. NOMAC/E2 induced negligible changes in glucose and insulin parameters, in contrast to LNG/EE. A much smaller increase in CRP was observed with NOMAC/E2 than with LNG/EE. NOMAC/E2 was associated with a greater increase in SHBG. Conclusions The monophasic COC NOMAC/E2 had less influence on haemostasis, lipids and carbohydrate metabolism than the COC LNG/EE. PMID:22066891

Reward and Toxicity of Cocaine Metabolites Generated by Cocaine Hydrolase.

PubMed

Murthy, Vishakantha; Geng, Liyi; Gao, Yang; Zhang, Bin; Miller, Jordan D; Reyes, Santiago; Brimijoin, Stephen

2015-08-01

Butyrylcholinesterase (BChE) gene therapy is emerging as a promising concept for treatment of cocaine addiction. BChE levels after gene transfer can rise 1000-fold above those in untreated mice, making this enzyme the second most abundant plasma protein. For months or years, gene transfer of a BChE mutated into a cocaine hydrolase (CocH) can maintain enzyme levels that destroy cocaine within seconds after appearance in the blood stream, allowing little to reach the brain. Rapid enzyme action causes a sharp rise in plasma levels of two cocaine metabolites, benzoic acid (BA) and ecgonine methyl ester (EME), a smooth muscle relaxant that is mildly hypotensive and, at best, only weakly rewarding. The present study, utilizing Balb/c mice, tested reward effects and cardiovascular effects of administering EME and BA together at molar levels equivalent to those generated by a given dose of cocaine. Reward was evaluated by conditioned place preference. In this paradigm, cocaine (20 mg/kg) induced a robust positive response but the equivalent combined dose of EME + BA failed to induce either place preference or aversion. Likewise, mice that had undergone gene transfer with mouse CocH (mCocH) showed no place preference or aversion after repeated treatments with a near-lethal 80 mg/kg cocaine dose. Furthermore, a single administration of that same high cocaine dose failed to affect blood pressure as measured using the noninvasive tail-cuff method. These observations confirm that the drug metabolites generated after CocH gene transfer therapy are safe even after a dose of cocaine that would ordinarily be lethal.

[Endometriosis medical treatment: Hormonal treatment for the management of pain and endometriotic lesions recurrence. CNGOF-HAS Endometriosis Guidelines].

PubMed

Geoffron, S; Cohen, J; Sauvan, M; Legendre, G; Wattier, J M; Daraï, E; Fernandez, H; Chabbert-Buffet, N

2018-03-01

The available literature, from 2006 to 2017, on hormonal treatment has been analysed as a contribution to the HAS-CNGOF task force for the treatment of endometriosis. Available data are heterogeneous and the general level of evidence is moderate. Hormonal treatment is usually offered as the primary option to women suffering from endometriosis. It cannot be used in women willing to conceive. In women who have not been operated, the first line of hormonal treatment includes combined oral contraceptives (COC) and the levonorgestrel-releasing intra uterine system (52mg LNG-IUS). As a second line, desogestrel progestin only pills, etonogestrel implants, GnRH analogs (GnRHa) with add back therapy and dienogest can be offered. Add back therapy should include estrogens to prevent bone loss and improve quality of life, it can be introduced before the third month of treatment to prevent side effects. The literature does not support preoperative hormonal treatment for the sole purpose of reducing complications or recurrence, or facilitating surgical procedures. After surgical treatment, hormonal treatment is recommended to prevent pain recurrence and improve quality of life. COCs or LNG IUS are recommended as a first line. To prevent recurrence of endometriomas COC is advised and maintained as long as tolerance is good in the absence of pregnancy plans. In case of dysmenorrhea, postoperative COC should be used in a continuous scheme. GnRHa are not recommended in the sole purpose of reducing endometrioma recurrence risk. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Spectroscopic and computational studies of cobalamin species with variable lower axial ligation: implications for the mechanism of Co-C bond activation by class I cobalamin-dependent isomerases.

PubMed

Conrad, Karen S; Jordan, Christopher D; Brown, Kenneth L; Brunold, Thomas C

2015-04-20

5'-deoxyadenosylcobalamin (coenzyme B12, AdoCbl) serves as the cofactor for several enzymes that play important roles in fermentation and catabolism. All of these enzymes initiate catalysis by promoting homolytic cleavage of the cofactor's Co-C bond in response to substrate binding to their active sites. Despite considerable research efforts, the role of the lower axial ligand in facilitating Co-C bond homolysis remains incompletely understood. In the present study, we characterized several derivatives of AdoCbl and its one-electron reduced form, Co(II)Cbl, by using electronic absorption and magnetic circular dichroism spectroscopies. To complement our experimental data, we performed computations on these species, as well as additional Co(II)Cbl analogues. The geometries of all species investigated were optimized using a quantum mechanics/molecular mechanics method, and the optimized geometries were used to compute absorption spectra with time-dependent density functional theory. Collectively, our results indicate that a reduction in the basicity of the lower axial ligand causes changes to the cofactor's electronic structure in the Co(II) state that replicate the effects seen upon binding of Co(II)Cbl to Class I isomerases, which replace the lower axial dimethylbenzimidazole ligand of AdoCbl with a protein-derived histidine (His) residue. Such a reduction of the basicity of the His ligand in the enzyme active site may be achieved through proton uptake by the catalytic triad of conserved residues, DXHXGXK, during Co-C bond homolysis.

AAVrh.10-mediated expression of an anti-cocaine antibody mediates persistent passive immunization that suppresses cocaine-induced behavior.

PubMed

Rosenberg, Jonathan B; Hicks, Martin J; De, Bishnu P; Pagovich, Odelya; Frenk, Esther; Janda, Kim D; Wee, Sunmee; Koob, George F; Hackett, Neil R; Kaminsky, Stephen M; Worgall, Stefan; Tignor, Nicole; Mezey, Jason G; Crystal, Ronald G

2012-05-01

Cocaine addiction is a major problem affecting all societal and economic classes for which there is no effective therapy. We hypothesized an effective anti-cocaine vaccine could be developed by using an adeno-associated virus (AAV) gene transfer vector as the delivery vehicle to persistently express an anti-cocaine monoclonal antibody in vivo, which would sequester cocaine in the blood, preventing access to cognate receptors in the brain. To accomplish this, we constructed AAVrh.10antiCoc.Mab, an AAVrh.10 gene transfer vector expressing the heavy and light chains of the high affinity anti-cocaine monoclonal antibody GNC92H2. Intravenous administration of AAVrh.10antiCoc.Mab to mice mediated high, persistent serum levels of high-affinity, cocaine-specific antibodies that sequestered intravenously administered cocaine in the blood. With repeated intravenous cocaine challenge, naive mice exhibited hyperactivity, while the AAVrh.10antiCoc.Mab-vaccinated mice were completely resistant to the cocaine. These observations demonstrate a novel strategy for cocaine addiction by requiring only a single administration of an AAV vector mediating persistent, systemic anti-cocaine passive immunity.

Analysis of cocaine and three of its metabolites in hair by gas chromatography-mass spectrometry using ion-trap detection for CI/MS/MS.

PubMed

Cognard, Emmanuelle; Rudaz, Serge; Bouchonnet, Stéphane; Staub, Christian

2005-11-05

A sensitive GC/CI/MS/MS method was developed for the simultaneous determination of cocaine (COC), anhydroecgonine methylester (cocaine pyrolysis product, AEME), ecgonine methylester (cocaine enzymatic hydrolysis product, EME) and cocaethylene (cocaine with ethanol trans-esterification product, COET) in human hair samples. After acid hydrolysis, hair samples were extracted with an automated solid phase extraction (SPE). The analysis of cocaine and its three metabolites was performed using an ion-trap spectrometer in positive chemical ionization with isobutane as gas reagent. The procedure was validated. Weighted linear regression was found appropriate in a concentration range of 0.10-5.00 ng/mg for AEME, 0.05-5.00 ng/mg for COC, EME and COET. The limit of detection was estimated at 0.005 ng/mg for COC and COET, at 0.025 ng/mg for EME, and at 0.050 ng/mg for AEME. Method performance was evaluated in terms of trueness and precision using quality control (QC) samples over the investigated ranges. Method selectivity and robustness were also demonstrated.

A comparison of the pharmacokinetic profile of an ascending-dose, extended-regimen combined oral contraceptive to those of other extended regimens.

PubMed

Darwish, Mona; Bond, Mary; Ricciotti, Nancy; Hsieh, Jennifer; Fiedler-Kelly, Jill; Grasela, Thaddeus

2014-11-01

Quartette (levonorgestrel [LNG]/ethinyl estradiol [EE] and EE) is an ascending-dose, extended-regimen combined oral contraceptive (COC) that consists of a constant dose of LNG 150 µg on days 1 to 84 with EE 20 µg on days 1 to 42, 25 µg on days 43 to 63, 30 µg on days 64 to 84, and 10 µg of EE monotherapy on days 85 to 91. A population pharmacokinetic (PK) model for EE was developed using nonlinear mixed-effects modeling to characterize the PK profile of EE administered in Quartette and other extended-regimen LNG/EE COCs. Model-predicted plasma concentration-time profiles demonstrated a stepwise increase in systemic exposure to EE during the first 84 days of the cycle following each EE dose change. Lower concentrations of EE were noted during the final 7-day period of EE 10 µg. Gradual increases in EE seen with Quartette may decrease the incidence of unscheduled bleeding frequently observed during early cycles of extended-regimen COCs. © The Author(s) 2014.

Ab initio calculations for the spectral analysis of dimethyl ether (CH_3OCH_3) and their isotopologues

NASA Astrophysics Data System (ADS)

Senent, M. L.; Villa, M.; Dominguez-Gomez, R.; Alvarez-Bajo, O.; Carvajal, M.

2011-05-01

Dimethyl ether is a complex interstellar molecule with two internal rotors, which has a high abundance in the star-forming regions. This point, jointed with the recent development of the last-generation observatories operating at the sub-mm and mm wavelengths, has motivated a new laboratory spectral recording in this frequency range. In spite of that, the rotational spectra was only analysed in depth within its vibrational ground state and a new spectral analysis within the fundamental torsional states is in progress. These analysis were carried out with ERHAM, a global model that takes into account the large amplitude motions owing to the two equivalent internal CH3 tops. Nevertheless, their torsional modes in principle interact with the bending COC mode and an appropiate torsional-bending description would be needed in order to analyse the rotational spectra within higher excited states. In this work, a new analysis of the COC bending and the CH3 torsional degrees of freedom has been carried out by means of ab initio calculations. A new and more accurate three-dimensional Potential Energy Surface (PES), is obtained using the CCSD(T) level of theory. This approach has also been applied to other isotopologues of interest, as 13C-dimethyl ether and the monodeuterated species. The purpose of this study is to help in the assignment of new spectral lines of these species and hence to contribute in the spectral cleaning of the astronomical observations to the interstellar medium.

Aboveground Injection Sytem Construction and Mecahnical Integrity Test Plan

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

Li, Jun

An In-Situ Bioremediation (ISB) Pilot Test Treatability Study is planned at Sandia National Laboratories, New Mexico (SNL/NM) Technical Area-V (TA-V) Groundwater Area of Concern. The Treatability Study is designed to gravity inject an electron-donor substrate and bioaugmentation bacteria into groundwater using an injection well. The constituents of concern (COCs) are nitrate and trichloroethene (TCE). The Pilot Test Treatability Study will evaluate the effectiveness of bioremediation and COC treatment over a prescribed period of time. Results of the pilot test will provide data that will be used to evaluate the cost and effectiveness of a fullscale system.

Perceived value of national certification for pediatric nurses.

PubMed

Messmer, Patricia R; Hill-Rodriguez, Deborah; Williams, Arthur R; Ernst, Mary E; Tahmooressi, Jill

2011-09-01

This study evaluated whether pediatric nurses who were certified valued national certifications to a greater degree than those who were not certified. The Gaberson, Schroeter, Killen, and Valentine (2003) Perceived Value of Certification Tool (PVCT) was used to measure nurses' perceptions of certification. The PVCT includes 18 certification-related value statements, using a five-point Likert scale response ranging from strongly agree to strongly disagree. A principal factor analysis was performed to identify clusters of related variables. Certified pediatric nurses valued national certifications to a greater degree than those who were not certified. More favorable views of certification were moderately associated with favorable views of the effects of certification on salary. The PVCT was found to have one factor, not two, as previously reported in the literature. Lower perceived relationships were reported between certification and salary, clinical competence, and consumer confidence compared with feelings of professionalism and personal satisfaction. Efforts to improve the relationship between certification and its perceived value at one institution were addressed. More attention may be needed to strengthen relationships, perceived or otherwise, between certification and competency skills, public awareness, and compensation of nurses for holding national certification. Copyright 2011, SLACK Incorporated.

Optimization of the thermogauge furnace for realizing high temperature fixed points

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

Wang, T.; Dong, W.; Liu, F.

2013-09-11

The thermogauge furnace was commonly used in many NMIs as a blackbody source for calibration of the radiation thermometer. It can also be used for realizing the high temperature fixed point(HTFP). According to our experience, when realizing HTFP we need the furnace provide relative good temperature uniformity to avoid the possible damage to the HTFP. To improve temperature uniformity in the furnace, the furnace tube was machined near the tube ends with a help of a simulation analysis by 'ansys workbench'. Temperature distributions before and after optimization were measured and compared at 1300 °C, 1700°C, 2500 °C, which roughly correspondmore » to Co-C(1324 °C), Pt-C(1738 °C) and Re-C(2474 °C), respectively. The results clearly indicate that through machining the tube the temperature uniformity of the Thermogage furnace can be remarkably improved. A Pt-C high temperature fixed point was realized in the modified Thermogauge furnace subsequently, the plateaus were compared with what obtained using old heater, and the results were presented in this paper.« less

Thermodynamic temperature assignment to the point of inflection of the melting curve of high-temperature fixed points.

PubMed

Woolliams, E R; Anhalt, K; Ballico, M; Bloembergen, P; Bourson, F; Briaudeau, S; Campos, J; Cox, M G; del Campo, D; Dong, W; Dury, M R; Gavrilov, V; Grigoryeva, I; Hernanz, M L; Jahan, F; Khlevnoy, B; Khromchenko, V; Lowe, D H; Lu, X; Machin, G; Mantilla, J M; Martin, M J; McEvoy, H C; Rougié, B; Sadli, M; Salim, S G R; Sasajima, N; Taubert, D R; Todd, A D W; Van den Bossche, R; van der Ham, E; Wang, T; Whittam, A; Wilthan, B; Woods, D J; Woodward, J T; Yamada, Y; Yamaguchi, Y; Yoon, H W; Yuan, Z

2016-03-28

The thermodynamic temperature of the point of inflection of the melting transition of Re-C, Pt-C and Co-C eutectics has been determined to be 2747.84 ± 0.35 K, 2011.43 ± 0.18 K and 1597.39 ± 0.13 K, respectively, and the thermodynamic temperature of the freezing transition of Cu has been determined to be 1357.80 ± 0.08 K, where the ± symbol represents 95% coverage. These results are the best consensus estimates obtained from measurements made using various spectroradiometric primary thermometry techniques by nine different national metrology institutes. The good agreement between the institutes suggests that spectroradiometric thermometry techniques are sufficiently mature (at least in those institutes) to allow the direct realization of thermodynamic temperature above 1234 K (rather than the use of a temperature scale) and that metal-carbon eutectics can be used as high-temperature fixed points for thermodynamic temperature dissemination. The results directly support the developing mise en pratique for the definition of the kelvin to include direct measurement of thermodynamic temperature. © 2016 The Author(s).

CHROMASSI: a therapy advice system based on chrono-massage and acupression using the method of ZiWuLiuZhu.

PubMed

Nguyen, H P; Le, D L; Tran, Q M; Nguyen, V T; Nguyen, N O

1995-01-01

Massage and Acupression have a history of many years of use by the Vietnamese people in the treatment of diseases, and they can give wonderful therapeutic effects in painful syndromes and chronic diseases, etc. On the other hand, some methods of Chrono-Acupuncture based on chronobiological theory and the holistic concept of traditional medicine are studied and applied in clinical applications. This paper presents the therapy advice system based on Chrono-Massage and Acupression using the method of ZiWuLiuZhu called CHROMASSI. The system includes four major parts. Massage and Acupression Teaching: This part can provide the user with some background in Massage and Acupression theory such as the pathology of the meridians, the classification of points and their function, the therapeutic properties of points, the methods of Massage and Acupression (including Pression, Friction, Rubbing, Light Massage, Petrissage, Rolling and Rubbing, Percussion and Vibration), and the direction of the meridians circulation, displaying AcuPoints represented by color pictures of the 12 main meridians and 2 vessels. More than 330 popular AcuPoints are used in the system. Open AcuPoint Calculating: This module can help us to calculate open AcuPoints based on data about days, months, years and hours using the special method of ZiWuLiuZhu. The Points adopted by ZiWuLiuZhu are the Five Shu Points and Source Points including 66 points (all of them are located below the elbows and knees). The effectiveness of these points becomes particularly evident when they are needled or punctured at optimum time intervals. For example, at 9:00 a.m., September 22, 1994, the open Points by the ZiWuLiuZhu method will be the points K2 (Nhien Coc) and K10 (Am Coc). According to the chronotherapeutic method, first we have to pressure (or puncture) the above points in order to attain the sensation RDac KhiS (arrival of energy), then pressure the other treating points as in ordinary Massage and Acupression. Therapy Consultation: Knowledge of the system was provided by Prof. Nguyen Van Thang and Doctor Nguyen Nhu Oanh at the Vietnam National Institute of Oriental Medicine. CHROMASSI is able to advise on ways to treat about 153 diseases and symptoms in the following fields: Aches and Pains, Insomnia, Common Cold and Influenza, Sexual Disturbances, Medical Aesthetics in Face, Breast and Buttock, Hygiene, Cardio-Vascular Tract, Digestive Tract, Urinary Tract, Respiratory Tract, Genital Tract, Ear-Nose-Throat Tract, Nervous Tract. The system can provide information about Remarks, Acupoints formulas for treating by Massage and Acupression with colour pictures of meridians. Explanation: The CHROMASSI system can explain why the AcuPoints are used for treating diseases based on the theoretical bases of traditional Vietnamese medicine and on the meridians and collaterals system theory. The colour pictures representing the circulation of vital energy in the meridians are used for explanation. The CHROMASSI system was developed in TURBO-PROLOG and TURBO-PASCAL and can run on IBM PC/AT computers and compatibles. The system can be used for teaching and for clinics of Massage and Acupression combined with Chronotherapeutics. At present the system is used by some physicians for clinical applications. The first results indicate that, in 20 cases of generalized headache compared with the control group, the combining of chronoacupression using the ZiWuLiuZhu method and ordinary Massage and Acupression gave better effects than that obtained by either method alone.

National Center for Standards and Certification Information: Service and programs

NASA Technical Reports Server (NTRS)

Overman, Joanne

1994-01-01

The National Center for Standards and Certification Information (NCSCI) provides information on U.S., foreign and international voluntary standards, government regulations, and conformity assessment procedures for non-agricultural products. The Center serves as a referral service and focal point in the United States for information on standards and standards-related information. NCSCI staff respond to inquiries, maintain a reference collection of standards and standards-related documents, and serve as the U.S. inquiry point for information to and from foreign countries.

14 CFR 36.801 - Noise measurement.

Code of Federal Regulations, 2014 CFR

2014-01-01

...: AIRCRAFT TYPE AND AIRWORTHINESS CERTIFICATION Helicopters § 36.801 Noise measurement. For primary, normal, transport, or restricted category helicopters for which certification is sought under appendix H of this part, the noise generated by the helicopter must be measured at the noise measuring points and under...

14 CFR 36.801 - Noise measurement.

Code of Federal Regulations, 2012 CFR

2012-01-01

...: AIRCRAFT TYPE AND AIRWORTHINESS CERTIFICATION Helicopters § 36.801 Noise measurement. For primary, normal, transport, or restricted category helicopters for which certification is sought under appendix H of this part, the noise generated by the helicopter must be measured at the noise measuring points and under...

14 CFR 36.801 - Noise measurement.

Code of Federal Regulations, 2013 CFR

2013-01-01

...: AIRCRAFT TYPE AND AIRWORTHINESS CERTIFICATION Helicopters § 36.801 Noise measurement. For primary, normal, transport, or restricted category helicopters for which certification is sought under appendix H of this part, the noise generated by the helicopter must be measured at the noise measuring points and under...

The effect of bearing type on the outcome of total hip arthroplasty.

PubMed

Peters, Rinne M; Van Steenbergen, Liza N; Stevens, Martin; Rijk, Paul C; Bulstra, Sjoerd K; Zijlstra, Wierd P

2018-04-01

Background and purpose - Alternative bearing surfaces such as ceramics and highly crosslinked polyethylene (HXLPE) were developed in order to further improve implant performance of total hip arthroplasties (THAs). Whether these alternative bearing surfaces result in increased longevity is subject to debate. Patients and methods - Using the Dutch Arthroplasty Register (LROI), we identified all patients with a primary, non-metal-on-metal THA implanted in the Netherlands in the period 2007-2016 (n = 209,912). Cumulative incidence of revision was calculated to determine differences in survivorship of THAs according to bearing type: metal-on-polyethylene (MoPE), metal-on-HXLPE (MoHXLPE), ceramic-on-polyethylene (CoPE), ceramic-on-HXLPE (CoHXLPE), ceramic-on-ceramic (CoC), and oxidized-zirconium-on-(HXL)polyethylene (Ox(HXL)PE). Multivariable Cox proportional hazard regression ratios (HRs) were used for comparisons. Results - After adjustment for confounders, CoHXLPE, CoC, and Ox(HXL)PE resulted in a statistically significantly lower risk of revision compared with MoPE after 9 years follow-up (HR =0.8-0.9 respectively, compared with HR =1.0). For small (22-28 mm) femoral head THAs, lower revision rates were found for CoPE and CoHXLPE (HR =0.9). In the 36 mm femoral head subgroup, CoC-bearing THAs had a lower HR compared with MoHXLPE (HR =0.7 versus 1.0). Crude revision rates in young patients (< 60 years) for CoHXLPE, CoC, and Ox(HXL)PE (HR =0.7) were lower than MoPE (HR =1.0). However, after adjustment for case mix and confounders these differences were not statistically significant. Interpretation - We found a mid-term lower risk of revision for CoHXLPE, CoC, and Ox(HXL)PE bearings compared with traditional MoPE-bearing surfaces.

MISSED WELL-CHILD CARE VISITS, LOW CONTINUITY OF CARE, AND RISK FOR AMBULATORY CARE SENSITIVE HOSPITALIZATIONS IN YOUNG CHILDREN

PubMed Central

Tom, Jeffrey; Tseng, Chien-Wen; Davis, James; Solomon, Cam; Zhou, Chuan; Mangione-Smith, Rita

2013-01-01

Objectives To determine if adherence to the recommended well-child care (WCC) visit schedule, independent of continuity of care (COC), is associated with lower risk for Ambulatory Care Sensitive Hospitalizations (ACSH) and whether this association varies by chronic disease status. Design Population-based, retrospective cohort study Setting Hawaii’s largest health plan from 1999 to 2006 Patients/Participants 36,944 children ≤ 3.5 years-old who were eligible if they were enrolled prior to 2 months-old, had ≥ 4 outpatient visits during the study period, and had an enrollment period that overlapped with ≥ 1 WCC visit interval. Main Exposure(s) WCC visit adherence and COC Index Main Outcome Measure(s) Risk for ACSH (Hazard Ratio [HR]) Results Overall, 8,921 (24%) children had ≥ 1 chronic disease. The proportions of ACSH among healthy children versus those with ≥ 1 chronic disease were 3% (n= 751) and 7% (n= 645), respectively. For children with chronic disease, those with the lowest WCC visit adherence (0–25%) had 1.9 times (HR: 1.9, 95% Confidence Interval [CI]: 1.5–2.5) the risk of ACSH compared to those in the highest category (75–100%). The risk of ACSH for children with chronic disease who fell into the lowest COC category (0–0.25) was 2.4 times (HR 2.4, 95% CI: 1.7–3.5) higher than for those who fell into the highest category (0.75–1.0). Conclusions For children with chronic disease, both low WCC visit adherence and COC are independently associated with an increased risk of ACSH. Providing access to a consistent source of primary care appears important for this vulnerable population. PMID:21041598

Combined Cocaine Hydrolase Gene Transfer and Anti-Cocaine Vaccine Synergistically Block Cocaine-Induced Locomotion

PubMed Central

Carroll, Marilyn E.; Zlebnik, Natalie E.; Anker, Justin J.; Kosten, Thomas R.; Orson, Frank M.; Shen, Xiaoyun; Kinsey, Berma; Parks, Robin J.; Gao, Yang; Brimijoin, Stephen

2012-01-01

Mice and rats were tested for reduced sensitivity to cocaine-induced hyper-locomotion after pretreatment with anti-cocaine antibody or cocaine hydrolase (CocH) derived from human butyrylcholinesterase (BChE). In Balb/c mice, direct i.p. injection of CocH protein (1 mg/kg) had no effect on spontaneous locomotion, but it suppressed responses to i.p. cocaine up to 80 mg/kg. When CocH was injected i.p. along with a murine cocaine antiserum that also did not affect spontaneous locomotion, there was no response to any cocaine dose. This suppression of locomotor activity required active enzyme, as it was lost after pretreatment with iso-OMPA, a selective BChE inhibitor. Comparable results were obtained in rats that developed high levels of CocH by gene transfer with helper-dependent adenoviral vector, and/or high levels of anti-cocaine antibody by vaccination with norcocaine hapten conjugated to keyhole limpet hemocyanin (KLH). After these treatments, rats were subjected to a locomotor sensitization paradigm involving a “training phase" with an initial i.p. saline injection on day 1 followed by 8 days of repeated cocaine injections (10 mg/kg, i.p.). A 15-day rest period then ensued, followed by a final “challenge" cocaine injection. As in mice, the individual treatment interventions reduced cocaine-stimulated hyperactivity to a modest extent, while combined treatment produced a greater reduction during all phases of testing compared to control rats (with only saline pretreatment). Overall, the present results strongly support the view that anti-cocaine vaccine and cocaine hydrolase vector treatments together provide enhanced protection against the stimulatory actions of cocaine in rodents. A similar combination therapy in human cocaine users might provide a robust therapy to help maintain abstinence. PMID:22912888

Pregnancy and contraceptive use among women participating in the FEM-PrEP trial.

PubMed

Callahan, Rebecca; Nanda, Kavita; Kapiga, Saidi; Malahleha, Mookho; Mandala, Justin; Ogada, Teresa; Van Damme, Lut; Taylor, Douglas

2015-02-01

Pregnancy among study participants remains a challenge for trials of new HIV prevention agents despite promotion and provision of contraception. We evaluated contraceptive use, pregnancy incidence, and study drug adherence by contraceptive method among women enrolled in the FEM-PrEP trial of once-daily oral tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) for HIV prevention. We required women to be using effective non-barrier contraception at enrollment. At each monthly follow-up visit, women were counseled on contraceptive use and tested for pregnancy. TDF-FTC adherence was determined by measuring plasma drug concentrations at 4-week intervals. We used Cox proportional hazards models to assess factors associated with incident pregnancy and multivariate logistic regression to examine the relationship between contraceptive method used at enrollment and TDF-FTC adherence. More than half of women were not using effective contraception before enrollment. Ninety-eight percent of these women adopted either injectable (55%) or oral (43%) contraceptives. The overall pregnancy rate was 9.6 per 100 woman-years. Among injectable users and new users of combined oral contraceptives (COCs), the rates were 1.6 and 35.1, respectively. New users of injectables had significantly greater odds of adhering to TDF-FTC than new COC users [odds ratio (95% confidence interval): 4.4 (1.7 to 11.6), P = 0.002], existing COC users [3.1 (1.3 to 7.3), P = 0.01], and existing injectable users [2.4 (1.1 to 5.6), P = 0.04]. Women using COCs during FEM-PrEP, particularly new adopters, were more likely to become pregnant and less likely to adhere to study product than injectable users. HIV prevention trials should consider requiring long-acting methods, including injectables, for study participation.

Heat stress and antioxidant enzyme activity in bubaline ( Bubalus bubalis) oocytes during in vitro maturation

NASA Astrophysics Data System (ADS)

Waiz, Syma Ashraf; Raies-ul-Haq, Mohammad; Dhanda, Suman; Kumar, Anil; Goud, T. Sridhar; Chauhan, M. S.; Upadhyay, R. C.

2016-09-01

In vitro environments like heat stress usually increase the production of reactive oxygen species in bubaline oocytes which have been implicated as one of the major causes for reduced developmental competence. Oocytes during meiotic maturation are sensitive to oxidative stress, and heat stress accelerates cellular metabolism, resulting in the higher production of free radicals. Therefore, the aim of present work was to assess the impact of heat stress during meiotic maturation on bubaline cumulus-oocyte complexes (COC), denuded oocytes (DO), and cumulus cell mass in terms of their oxidative status. Accordingly, for control group, COC were matured at 38.5 °C for complete 24 h of meiotic maturation and heat stress of 40.5 and 41.5 °C was applied to COC during the first 12 h of maturation and then moved to 38.5 °C for rest of the 12 h. In another group, COC after maturation were denuded from the surrounding cumulus cells by manual pipetting. Results indicated that the production of reactive oxygen species (ROS), lipid peroxides, and nitric oxide (NO) was significantly ( P < 0.05) higher in the oocytes subjected to heat stress (40.5 and 41.5 °C) during meiotic maturation compared to the oocytes matured under standard in vitro culture conditions (38.5 °C). Also, the antioxidant enzymatic activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were significantly ( P < 0.05) increased in all the treatment groups compared to the control group. Therefore, the present study clearly establishes that heat stress ensues oxidative stress in bubaline oocytes which triggers the induction of antioxidant enzymatic defense system for scavenging the ROS.

Dark production of carbon monoxide (CO) from dissolved organic matter in the St. Lawrence estuarine system: Implication for the global coastal and blue water CO budgets

NASA Astrophysics Data System (ADS)

Zhang, Yong; Xie, Huixiang; Fichot, CéDric G.; Chen, Guohua

2008-12-01

We investigated the thermal (dark) production of carbon monoxide (CO) from dissolved organic matter (DOM) in the water column of the St. Lawrence estuarine system in spring 2007. The production rate, Qco, decreased seaward horizontally and downward vertically. Qco exhibited a positive, linear correlation with the abundance of chromophoric dissolved organic matter (CDOM). Terrestrial DOM was more efficient at producing CO than marine DOM. The temperature dependence of Qco can be characterized by the Arrhenius equation with the activation energies of freshwater samples being higher than those of salty samples. Qco remained relatively constant between pH 4-6, increased slowly between pH 6-8 and then rapidly with further rising pH. Ionic strength and iron chemistry had little influence on Qco. An empirical equation, describing Qco as a function of CDOM abundance, temperature, pH, and salinity, was established to evaluate CO dark production in the global coastal waters (depth < 200 m). The total coastal CO dark production from DOM was estimated to be from 0.46 to 1.50 Tg CO-C a-1 (Tg carbon from CO a-1). We speculated the global oceanic (coastal plus open ocean) CO dark production to be in the range from 4.87 to 15.8 Tg CO-C a-1 by extrapolating the coastal water-based results to blue waters (depth > 200 m). Both the coastal and global dark source strengths are significant compared to the corresponding photochemical CO source strengths (coastal: ˜2.9 Tg CO-C a-1; global: ˜50 Tg CO-C a-1). Steady state deepwater CO concentrations inferred from Qco and microbial CO uptake rates are <0.1 nmol L-1.

Metabolites involved in cellular communication among human cumulus-oocyte-complex and sperm during in vitro fertilization.

PubMed

Gómez-Torres, María José; García, Eva María; Guerrero, Jaime; Medina, Sonia; Izquierdo-Rico, María José; Gil-Izquierdo, Ángel; Orduna, Jesús; Savirón, María; González-Brusi, Leopoldo; Ten, Jorge; Bernabeu, Rafael; Avilés, Manuel

2015-11-09

Fertilization is a key physiological process for the preservation of the species. Consequently, different mechanisms affecting the sperm and the oocyte have been developed to ensure a successful fertilization. Thus, sperm acrosome reaction is necessary for the egg coat penetration and sperm-oolema fusion. Several molecules are able to induce the sperm acrosome reaction; however, this process should be produced coordinately in time and in the space to allow the success of fertilization between gametes. The goal of this study was to analyze the metabolites secreted by cumulus-oocyte-complex (COC) to find out new components that could contribute to the induction of the human sperm acrosome reaction and other physiological processes at the time of gamete interaction and fertilization. For the metabolomic analysis, eighteen aliquots of medium were used in each group, containing: a) only COC before insemination and after 3 h of incubation; b) COC and capacitated spermatozoa after insemination and incubated for 16-20 hours; c) only capacitated sperm after 16-20 h in culture and d) only fertilization medium as control. Six patients undergoing assisted reproduction whose male partners provided normozoospermic samples were included in the study. Seventy-two COC were inseminated. The metabolites identified were monoacylglycerol (MAG), lysophosphatidylcholine (LPC) and phytosphingosine (PHS). Analysis by PCR and in silico of the gene expression strongly suggests that the cumulus cells contribute to the formation of the PHS and LPC. LPC and PHS are secreted by cumulus cells during in vitro fertilization and they could be involved in the induction of human acrosome reaction (AR). The identification of new molecules with a paracrine effect on oocytes, cumulus cells and spermatozoa will provide a better understanding of gamete interaction.

Cocaine induces state-dependent learning of sexual conditioning in male Japanese quail.

PubMed

Gill, Karin E; Rice, Beth Ann; Akins, Chana K

2015-01-01

State dependent learning effects have been widely studied in a variety of drugs of abuse. However, they have yet to be studied in relation to sexual motivation. The current study investigated state-dependent learning effects of cocaine in male Japanese quail (Coturnix japonica) using a sexual conditioning paradigm. Cocaine-induced state-dependent learning effects were investigated using a 2×2 factorial design with training state as one factor and test state as the other factor. During a 14-day training phase, male quail were injected once daily with 10mg/kg cocaine or saline and then placed in a test chamber after 15min. In the test chamber, sexual conditioning trials consisted of presentation of a light conditioned stimulus (CS) followed by sexual reinforcement. During the state dependent test, half of the birds received a shift in drug state from training to testing (Coc→Sal or Sal→Coc) while the other half remained in the same drug state (Coc→Coc or Sal→Sal). Results showed that male quail that were trained and tested in the same state (Coc→Coc or Sal→Sal) showed greater sexual conditioning than male quail that were trained and tested in different states (Sal→Coc) except when cocaine was administered chronically prior to the test (Coc→Sal). For the latter condition, sexual conditioning persisted from cocaine training to the saline test. The findings suggest that state dependent effects may alter sexual motivation and that repeated exposure to cocaine during sexual activity may increase sexual motivation which, in turn, may lead to high risk sexual activities. An alternative explanation for the findings is also discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

Osteocalcin is not a strong determinant of serum testosterone and sperm count in men from infertile couples.

PubMed

Schwetz, V; Gumpold, R; Graupp, M; Hacker, N; Schweighofer, N; Trummer, O; Pieber, T R; Ballon, M; Lerchbaum, E; Obermayer-Pietsch, B

2013-07-01

Osteocalcin (OC) - released by osteoblasts and known as a marker of bone turnover - has been suggested to influence male fertility in murine models by enhancing testosterone production and sperm count. Results from clinical studies are scarce, however. The aim of this cross-sectional study was to investigate the proposed association of OC, undercarboxylated osteocalcin (ucOC) or carboxylated osteocalcin (cOC) with testosterone and sperm count in a cohort of 159 young male adults from infertile couples. Semen analysis was performed. Testosterone, free testosterone, LH, OC and ucOC were measured in serum samples after an overnight fast. cOC and OC correlated weakly but significantly with testosterone (OC: r = 0.165, p = 0.040, cOC: r = 0.193, p = 0.017), but not after adjusting for age and body mass index (BMI) or waist-hip ratio (WHR). %ucOC (ucOC levels expressed as percentage of total OC) correlated inversely with LH (r = -0.184, p = 0.023) and remained significant after the same adjustment. No significant correlations were observed between OC, cOC, ucOC, %ucOC and sperm count, semen volume and number of vital spermatozoa. In binary logistic regression analyses, none of the parameters of OC were predictors of oligozoospermia after adjusting for age and BMI or WHR. The weak association between %ucOC and LH has marginal clinical importance because of the lack of associations of parameters of OC with testosterone and sperm count. The current data thus cannot support the notion that OC is associated with male fertility in young men from infertile couples. © 2013 American Society of Andrology and European Academy of Andrology.

Presence of encircling granulosa cells protects against oxidative stress-induced apoptosis in rat eggs cultured in vitro.

PubMed

Tiwari, Meenakshi; Tripathi, Anima; Chaube, Shail K

2017-01-01

Increased oxidative stress (OS) due to in vitro culture conditions can affect the quality of denuded eggs during various assisted reproductive technologies (ARTs). Presence of intact granulosa cells may protect eggs from OS damage under in vitro culture conditions. The present study was aimed to investigate whether encircling granulosa cells could protect against hydrogen peroxide (H 2 O 2 )-induced egg apoptosis in ovulated cumulus oocyte complexes (COCs) cultured in vitro. The OS was induced by exposing COCs as well as denuded eggs with various concentrations of H 2 O 2 for 3 h in vitro. The morphological changes, total reactive oxygen species (ROS) as well as catalase expression, Bax/Bcl-2, cytochrome c levels and DNA fragmentation were analysed in COCs as well as denuded eggs. Our results suggest that H 2 O 2 treatment induced morphological apoptotic features in a concentration-dependent manner in denuded eggs cultured in vitro. The 20 µM of H 2 O 2 treatment induced OS by elevating total ROS level, reduced catalase and Bcl-2 expression levels with overexpression of Bax and cytochrome c and induced DNA fragmentation in denuded eggs cultured in vitro. The presence of encircling granulosa cells protected H 2 O 2 -induced morphological apoptotic features by preventing the increase of Bax, cytochrome c expression levels and DNA fragmentation in associated egg. However, 20 µM of H 2 O 2 was sufficient to induce peripheral granulosa cell apoptosis in COCs and degeneration in few denuded eggs cultured in vitro. Taken together our data suggest that the presence of encircling granulosa cells could be beneficial to protect ovulated eggs from OS damage under in vitro culture conditions during various ART programs.

Drospirenone-containing oral contraceptive pills and the risk of venous thromboembolism: a systematic review of observational studies.

PubMed

Larivée, N; Suissa, S; Khosrow-Khavar, F; Tagalakis, V; Filion, K B

2017-09-01

The effects of fourth-generation drospirenone-containing combined oral contraceptives (COCs) on the risk of venous thromboembolism (VTE) are controversial. To assess the methodological strengths and limitations of the evidence on the VTE risk of these COCs. We searched CINAHL, the Cochrane Library, EMBASE, HealthStar, Medline, and the Science Citation Index. Studies were included if they were cohort and case-control studies, reported a venous thrombotic outcome, had a comparator group, reported an effect measure of the association of interest, and were published in English or French. We assessed study quality using the ROBINS-I tool and assessed the presence of four common sources of bias: prevalent user bias, inappropriate choice of comparator, VTE misclassification, and confounding. Our systematic review included 17 studies. The relative risks of VTE associated with drospirenone- versus second-generation levonorgestrel-containing COCs ranged from 1.0 to 3.3. Based on ROBINS-I, three studies had a moderate risk, ten had a serious risk, and four had a critical risk. Nine studies included prevalent users, four included inappropriate comparators, four had VTE misclassification, and five did not account for two or more important confounding factors. The three highest quality studies had relative risks ranging from 1.0 to 1.57. As a result of the methodological limitations of the individual studies, the VTE risk of drospirenone-containing COCs remains unknown. The highest quality studies suggest there are no or slightly increased harmful effects, but their confidence limits do not rule out an almost doubling of the risk. Systematic review of drospirenone: best studies show no or slightly increased VTE risk (versus levonorgestrel). © 2017 Royal College of Obstetricians and Gynaecologists.

In search of the economic sustainability of Hadron therapy: the real cost of setting up and operating a Hadron facility.

PubMed

Vanderstraeten, Barbara; Verstraete, Jan; De Croock, Roger; De Neve, Wilfried; Lievens, Yolande

2014-05-01

To determine the treatment cost and required reimbursement for a new hadron therapy facility, considering different technical solutions and financing methods. The 3 technical solutions analyzed are a carbon only (COC), proton only (POC), and combined (CC) center, each operating 2 treatment rooms and assumed to function at full capacity. A business model defines the required reimbursement and analyzes the financial implications of setting up a facility over time; activity-based costing (ABC) calculates the treatment costs per type of patient for a center in a steady state of operation. Both models compare a private, full-cost approach with public sponsoring, only taking into account operational costs. Yearly operational costs range between €10.0M (M = million) for a publicly sponsored POC to €24.8M for a CC with private financing. Disregarding inflation, the average treatment cost calculated with ABC (COC: €29,450; POC: €46,342; CC: €46,443 for private financing; respectively €16,059, €28,296, and €23,956 for public sponsoring) is slightly lower than the required reimbursement based on the business model (between €51,200 in a privately funded POC and €18,400 in COC with public sponsoring). Reimbursement for privately financed centers is very sensitive to a delay in commissioning and to the interest rate. Higher throughput and hypofractionation have a positive impact on the treatment costs. Both calculation methods are valid and complementary. The financially most attractive option of a publicly sponsored COC should be balanced to the clinical necessities and the sociopolitical context. Copyright © 2014 Elsevier Inc. All rights reserved.

A survey of bonobo (Pan paniscus) oral contraceptive pill use in North American zoos.

PubMed

Agnew, Mary K; Asa, Cheryl S; Clyde, Victoria L; Keller, Dominique L; Meinelt, Audra

2016-09-01

Contraception is an essential tool in reproductive management of captive species. The Association of Zoos and Aquariums (AZA) Reproductive Management Center (RMC) gathers data on contraception use and provides recommendations. Although apes have been given oral contraceptive pills (OCPs) for at least 30 years, there have been no published reports with basic information on why the pill is administered, formulations and brands used, and effects on physiology and behavior. Here, we report survey results characterizing OCP use in bonobos (Pan paniscus) housed in North American zoos, as well as information accumulated in the RMC's Contraception Database. Of 26 females treated, there have been no failures and nine reversals. The most commonly administered OCP formulation in bonobos contained ethinyl estradiol (EE) 35 μg/norethindrone 1 mg. Few females on combined oral contraceptives (COCs) were given a continuous active pill regimen; a hormone-free interval of at least 5 days was allowed in most. Crushing the pill and mixing with juice or food was common. Females on COCs seldom experienced breakthrough estrus or bleeding, while these conditions were sometimes observed for females on continuous COCs. All females on COCs exhibited some degree of perineal swelling, with a mean score of 3 or 3+ most commonly reported. Behavioral changes included less sexual behavior, dominant females becoming subordinate, and a negative effect on mood. No appreciable change in weight was noted. Taken together, these results indicate that OCPs are an effective and reversible contraceptive option for bonobos that can be used by zoos and sanctuaries to limit reproduction. Zoo Biol. 35:444-453, 2016. © Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effect of oral contraceptive containing ethinyl estradiol combined with drospirenone vs. desogestrel on clinical and biochemical parameters in patients with polycystic ovary syndrome.

PubMed

Kriplani, Alka; Periyasamy, Anurekha Janaki; Agarwal, Nutan; Kulshrestha, Vidushi; Kumar, Anand; Ammini, Ariachery Chinnama

2010-08-01

A prospective randomized trial was conducted to compare efficacy of a drospirenone-containing combined oral contraceptives (COC) with desogestrel-containing COC in women with polycystic ovary-syndrome (PCOS) not desirous of child-bearing. Sixty women were randomized into study group [ethinylestradiol (EE) 30 mcg+drospirenone 3 mg] and control group (EE 30 mcg+desogestrel 150 mcg), treated for 6 months and followed up at 1 month, 3 months, 6 months, during treatment and 3 and 6 months post-treatment. Acne and hirsutism scoring, bodyweight, body mass index (BMI), blood pressure (BP), ultrasound parameters, lipid profile, glycemic profile and hormonal profile were compared. Cycles were regular in both groups during treatment. Effect of regular cycles persisted in 44.83% (13/30) vs. 17.24% (5/30) in study vs. control group at 6 months post-treatment with 33.3% decreased hirsutism score in the study group (versus no change in control group) even at 6 months after stopping treatment. With treatment, BMI fell by 0.52 kg/m(2) in the study group; systolic and diastolic BP fell in the study group while it rose in the control group. Low-density lipoprotein significantly decreased and high-density lipoprotein was elevated in the study group (p<.05). The study group showed a significant fall in fasting/postprandial blood sugar and insulin and total testosterone against a rise in the control group. In women with PCOS, a drospirenone containing COC has better outcome in terms of persistent regular cycles, antiandrogenic effect, fall in BMI and BP, better lipid profile, favorable glycemic and hormonal profile than desogestrel-containing COC. Copyright 2010 Elsevier Inc. All rights reserved.

Relationship between Aircraft Noise Contour Area and Noise Levels at Certification Points

NASA Technical Reports Server (NTRS)

Powell, Clemans A.

2003-01-01

The use of sound exposure level contour area reduction has been proposed as an alternative or supplemental metric of progress and success for the NASA Quiet Aircraft Technology program, which currently uses the average of predicted noise reductions at three community locations. As the program has expanded to include reductions in airframe noise as well as reduction due to optimization of operating procedures for lower noise, there is concern that the three-point methodology may not represent a fair measure of benefit to airport communities. This paper addresses several topics related to this proposal: (1) an analytical basis for a relationship between certification noise levels and noise contour areas for departure operations is developed, (2) the relationship between predicted noise contour area and the noise levels measured or predicted at the certification measurement points is examined for a wide range of commercial and business aircraft, and (3) reductions in contour area for low-noise approach scenarios are predicted and equivalent reductions in source noise are determined.

40 CFR 1042.655 - Special certification provisions for-Category 3 engines with aftertreatment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... demonstrating for certification that catalyst-equipped engines (or engines equipped with other aftertreatment... engine-out emissions comply with the Tier 2 standards. The catalyst material or other aftertreatment... points. This catalyst or aftertreatment testing may be performed on a benchscale. (c) Engineering...

75 FR 79070 - Notice of Applications for Certificates of Public Convenience and Necessity and Foreign Air...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-17

... transportation of persons, property and mail from any point or points behind any Member State of the European Union via any point or points in any Member State and via intermediate points to any point or points in... between any point or points in the United States and any point or points in any member of the European...

75 FR 16226 - Notice of Applications for Certificates of Public Convenience and Necessity and Foreign Air...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-31

... transportation of persons, property and mail from any point or points behind any Member State of the European Union, via any point or points in any Member State and via intermediate points to any point or points in... between any point or points in the United States and any point or points in any member of the European...

An EXAFS study on the so-called {open_quotes}Co-Mo-S{close_quotes} phase in Co/C and CoMo/C, compared with a Moessbauer emission spectroscopy study

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

Craje, M.W.J.; Kraan, A.M. van der; Louwers, S.P.A.

1992-06-25

EXAFS was used in this paper to study 4 sulfided catalysts that have the same structure as their {sup 57}Co counterparts characterized by Mossbauer emission spectroscopy. The {open_quotes}Co-Mo-S{close_quotes} phase in Co/C is similar to CoMo/C due to a very highly dispersed Co species. Without Mo, the sulfidic Co results in a Co{sub 9}S{sub 8} phase during sulfidation at 673K, Mo prevents Co sintering in CoMo/C. 37 refs., 6 figs., 2 tabs.

AAVrh.10-Mediated Expression of an Anti-Cocaine Antibody Mediates Persistent Passive Immunization That Suppresses Cocaine-Induced Behavior

PubMed Central

Rosenberg, Jonathan B.; Hicks, Martin J.; De, Bishnu P.; Pagovich, Odelya; Frenk, Esther; Janda, Kim D.; Wee, Sunmee; Koob, George F.; Hackett, Neil R.; Kaminsky, Stephen M.; Worgall, Stefan; Tignor, Nicole; Mezey, Jason G.

2012-01-01

Abstract Cocaine addiction is a major problem affecting all societal and economic classes for which there is no effective therapy. We hypothesized an effective anti-cocaine vaccine could be developed by using an adeno-associated virus (AAV) gene transfer vector as the delivery vehicle to persistently express an anti-cocaine monoclonal antibody in vivo, which would sequester cocaine in the blood, preventing access to cognate receptors in the brain. To accomplish this, we constructed AAVrh.10antiCoc.Mab, an AAVrh.10 gene transfer vector expressing the heavy and light chains of the high affinity anti-cocaine monoclonal antibody GNC92H2. Intravenous administration of AAVrh.10antiCoc.Mab to mice mediated high, persistent serum levels of high-affinity, cocaine-specific antibodies that sequestered intravenously administered cocaine in the blood. With repeated intravenous cocaine challenge, naive mice exhibited hyperactivity, while the AAVrh.10antiCoc.Mab-vaccinated mice were completely resistant to the cocaine. These observations demonstrate a novel strategy for cocaine addiction by requiring only a single administration of an AAV vector mediating persistent, systemic anti-cocaine passive immunity. PMID:22486244

Ceramic on ceramic arthroplasty of the hip: new materials confirm appropriate use in young patients.

PubMed

Sentuerk, U; von Roth, P; Perka, C

2016-01-01

The leading indication for revision total hip arthroplasty (THA) remains aseptic loosening owing to wear. The younger, more active patients currently undergoing THA present unprecedented demands on the bearings. Ceramic-on-ceramic (CoC) bearings have consistently shown the lowest rates of wear. The recent advances, especially involving alumina/zirconia composite ceramic, have led to substantial improvements and good results in vitro. Alumina/zirconia composite ceramics are extremely hard, scratch resistant and biocompatible. They offer a low co-efficient of friction and superior lubrication and lower rates of wear compared with other bearings. The major disadvantage is the risk of fracture of the ceramic. The new composite ceramic has reduced the risk of fracture of the femoral head to 0.002%. The risk of fracture of the liner is slightly higher (0.02%). Assuming that the components are introduced without impingement, CoC bearings have major advantages over other bearings. Owing to the superior hardness, they produce less third body wear and are less vulnerable to intra-operative damage. The improved tribology means that CoC bearings are an excellent choice for young, active patients requiring THA. ©2016 The British Editorial Society of Bone & Joint Surgery.

JWST center of curvature test method and results

NASA Astrophysics Data System (ADS)

Saif, Babak; Chaney, David; Greenfield, Perry; Van Gorkom, Kyle; Brooks, Keira; Hack, Warren; Bluth, Marcel; Bluth, Josh; Sanders, James; Smith, Koby; Carey, Larkin; Chaung, Sze; Keski-Kuha, Ritva; Feinberg, Lee; Tournois, Severine; Smith, W. Scott; Kradinov, Vladimir

2017-09-01

The James Webb Space Telescope (JWST) recently saw the completion of the assembly process for the Optical Telescope Element and Integrated Science Instrument Module (OTIS). This integration effort was performed at Goddard Space Flight Center (GSFC) in Greenbelt, Maryland. In conjunction with this assembly process a series of vibration and acoustic tests were performed. To help assure the telescope's primary mirror was not adversely impacted by this environmental testing an optical center of curvature (CoC) test was performed to measure changes in the mirror's optical performance. The primary is a 6.5 meter diameter mirror consisting of 18 individual hexagonal segments. Each segment is an off-axis asphere. There are a total of three prescriptions repeated six times each. As part of the CoC test each segment was individually measured using a high-speed interferometer (HSI) designed and built specifically for this test. This interferometer is capable of characterizing both static and dynamic characteristics of the mirrors. The latter capability was used, with the aid of a vibration stinger applying a low-level input force, to measure the dynamic characteristic changes of the PM backplane structure. This paper describes the CoC test setup, an innovative alignment method, and both static and dynamic test results.

Pituitary and ovarian hormone activity during the 7-day hormone-free interval of various combined oral contraceptive regimens.

PubMed

Cho, Michael; Atrio, Jessica; Lim, Aaron H; Azen, Colleen; Stanczyk, Frank Z

2014-07-01

The objective was to investigate changes in luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) and progesterone (P) during the hormone-free interval (HFI) of 6 combined oral contraceptives (COCs). Blood samples were obtained from 62 women. When COCs were grouped by ethinyl estradiol (EE) dose, there was a significant positive mean slope for LH and FSH during the HFI for the 30- and 35 mcg-EE doses, whereas 20 showed a gradual nonsignificant slope. All E2 slopes were significant. P remained suppressed with all doses. A more rapid rebound of gonadotropin levels is found with higher doses of EE during the HFI. This study showed a more rapid rebound of pituitary hormone levels among women using higher-EE-dosage formulations, which was demonstrated by the statistically significant slope for mean LH and FSH from day 1 to day 7 of the HFI. The degree of suppression did not vary across progestin generations. It remains to be established whether women who experience side effects during their HFI may benefit from using a COC with a lower EE dose to minimize changes in endogenous pituitary hormone levels. Copyright © 2014 Elsevier Inc. All rights reserved.

A Comparative Efficacy of Low-Dose Combined Oral Contraceptives Containing Desogestrel and Drospirenone in Premenstrual Symptoms

PubMed Central

Wichianpitaya, Jirath; Taneepanichskul, Surasak

2013-01-01

Objective. To compare the efficacy of low-dose COC containing desogestrel (DSG) with drospirenone (DRSP) in the changes of premenstrual symptoms. Methods. In an open-label randomized controlled trial, 90 women with premenstrual syndrome who required COC were randomly recruited and allocated equally to receive either 6 cycles of 20 micrograms ethinyl estradiol (EE)/150 micrograms DSG (DSG group) or 20 micrograms EE/3 mg DRSP (DRSP group) in 24/4 extended regimen. Analysis of covariance and repeated analysis of variance were used to determine the difference of mean Women's Health Assessment Questionnaire (WHAQ) scores changes between groups, within group, and in premenstrual, menstrual, and postmenstrual phases. Results. Baseline characteristics and WHAQ scores were comparable. At the ends of the 3rd and the 6th cycles, mean WHAQ scores of all the 3 phases in DRSP group showed significant reduction and were significantly lower than those in DSG group. DSG group showed significant reduction in both premenstrual and menstrual phases after the 6th cycle. Adverse effects were comparable in both groups. In conclusion, low-dose COC containing either DSG or DRSP reduced premenstrual symptoms, but the latter showed greater efficacy and earlier reduction. PMID:23577032

Potassium ferrate treatment of RFETS` contaminated groundwater

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

NONE

1995-01-01

The potassium ferrate treatment study of Rocky Flats Environmental Technology Site (RFETS) groundwater was performed under the Sitewide Treatability Studies Program (STSP). This study was undertaken to determine the effectiveness of potassium ferrate in a water treatment system to remove the contaminants of concern (COCS) from groundwater at the RFETS. Potassium ferrate is a simple salt where the iron is in the plus six valence state. It is the iron at the plus six valence state (Fe {sup +6}) that makes it an unique water treatment chemical, especially in waters where the pH is greater than seven. In basic solutionsmore » where the solubility of the oxides/hydroxides of many of the COCs is low, solids are formed as the pH is raised. By using ferrate these solids are agglomerated so they can be effectively removed by sedimentation in conventional water treatment equipment. The objective of this study was to determine the quality of water after treatment with potassium ferrate and to determine if the Colorado Water Quality Control Commission (CWQCC) discharge limits for the COCs listed in Table 1.0-1 could be met. Radionuclides in the groundwater were of special concern.« less

Ceramic-on-ceramic bearing fractures in total hip arthroplasty: an analysis of data from the National Joint Registry.

PubMed

Howard, D P; Wall, P D H; Fernandez, M A; Parsons, H; Howard, P W

2017-08-01

Ceramic-on-ceramic (CoC) bearings in total hip arthroplasty (THA) are commonly used, but concerns exist regarding ceramic fracture. This study aims to report the risk of revision for fracture of modern CoC bearings and identify factors that might influence this risk, using data from the National Joint Registry (NJR) for England, Wales, Northern Ireland and the Isle of Man. We analysed data on 223 362 bearings from 111 681 primary CoC THAs and 182 linked revisions for bearing fracture recorded in the NJR. We used implant codes to identify ceramic bearing composition and generated Kaplan-Meier estimates for implant survivorship. Logistic regression analyses were performed for implant size and patient specific variables to determine any associated risks for revision. A total of 222 852 bearings (99.8%) were CeramTec Biolox products. Revisions for fracture were linked to seven of 79 442 (0.009%) Biolox Delta heads, 38 of 31 982 (0.119%) Biolox Forte heads, 101 of 80 170 (0.126%) Biolox Delta liners and 35 of 31 258 (0.112%) Biolox Forte liners. Regression analysis of implant size revealed smaller heads had significantly higher odds of fracture (chi-squared 68.0, p < 0.001). The highest fracture risk was observed in the 28 mm Biolox Forte subgroup (0.382%). There were no fractures in the 40 mm head group for either ceramic type. Liner thickness was not predictive of fracture (p = 0.67). Body mass index (BMI) was independently associated with revision for both head fractures (odds ratio (OR) 1.09 per unit increase, p = 0.031) and liner fractures (OR 1.06 per unit increase, p = 0.006). We report the largest independent study of CoC bearing fractures to date. The risk of revision for CoC bearing fracture is very low but previous studies have underestimated this risk. There is good evidence that the latest generation of ceramic has greatly reduced the odds of head fracture but not of liner fracture. Small head size and high patient BMI are associated with an increased risk of ceramic bearing fracture. Cite this article: Bone Joint J 2017;99-B:1012-19. ©2017 The British Editorial Society of Bone & Joint Surgery.

Ovine secondary follicles vitrified out the ovarian tissue grow and develop in vitro better than those vitrified into the ovarian fragments.

PubMed

Lunardi, Franciele Osmarini; de Aguiar, Francisco Leo Nascimento; Duarte, Ana Beatriz Graça; Araújo, Valdevane Rocha; de Lima, Laritza Ferreira; Ribeiro de Sá, Naiza Arcângela; Vieira Correia, Hudson Henrique; Domingues, Sheyla Farhayldes Souza; Campello, Cláudio Cabral; Smitz, Johan; de Figueiredo, José Ricardo; Ribeiro Rodrigues, Ana Paula

2016-04-15

Cryopreservation of preantral follicles is a promising technique to preserve female fertility. The aim of this study was to evaluate the effect of vitrification on the development of secondary follicles included in ovarian tissue or isolated after microdissection. An important end point included is the capacity of grown oocytes to resume meiosis. Sheep ovarian cortexes were cut into fragments and split into three different groups: (1) fresh (control): secondary follicles isolated without any previous vitrification; (2) follicle-vitrification (follicle-vit): secondary follicles vitrified in isolated form; and (3) tissue-vitrification (tissue-vit): secondary follicles vitrified within fragments of ovarian tissue (in situ former) and subsequently subjected to isolation. From the three groups, isolated secondary follicles were submitted to IVC for 18 days. After IVC, cumulus-oocyte complexes (COCs) were harvested from follicles. As an additional control group, in vivo grown, in vivo-grown COCs were collected from antral ovarian follicles. All, recovered COCs were matured and the chromatin configuration was evaluated. Data were analyzed by ANOVA, and the means were compared by Student-Newman-Keuls test, and by chi-square. Differences were considered to be significant when P < 0.05. Isolated preantral follicles from all treatments had normal morphology, antrum formation, and low follicle degeneration after IVC. The growth rate between control and follicle-vit did not differ (P > 0.05), and was higher (P < 0.05) than for tissue-vit. The percentage of follicles that decreased diameter during IVC was significantly higher in tissue-vit than the in follicle-vit. Recovery rate of oocytes from normal follicles was higher in follicle-vit than in tissue-vit. Furthermore, oocyte viability was lower in tissue-vit than other treatments, and follicle-vit did not differ from control and in vivo grown. The percentage of oocytes meiosis resuming was not different between treatments except for in vivo grown. After vitrification, only follicle-vit showed metaphase I oocyte. We conclude that secondary follicles vitrified after isolation displayed a better follicular growth rate, oocyte viability, percentage of oocytes reaching the metaphase I stage, and fewer follicles with decreased diameter after IVC. Copyright © 2016 Elsevier Inc. All rights reserved.

Professionalization and Certification for Teachers in Adult Basic Education

ERIC Educational Resources Information Center

Sabatini, John P.; Ginsburg, Lynda; Russell, Mary

2002-01-01

When Shanahan, Meehan, and Mogge (1994) reviewed the issue of professionalization, they characterized previous discussions and debates as controversial, negative, and heated, marked more by discord than unity. A key point of disagreement was whether or under what conditions certification could be considered necessary or desirable. They found only…

Standards for Elementary Teacher Certification: A Fifty State Study.

ERIC Educational Resources Information Center

Dumas, Wayne; Weible, Thomas

A study of the minimum program standards established by 50 state education agencies for preparation and certification of elementary school teachers focused on the status of general education requirements, professional education requirements, and requirements for areas of concentration. Two reference points were employed in analysis of the…

78 FR 76701 - Certificates of Public Convenience and Necessity and Foreign Air Carrier Permits

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-18

... may be granted to European Union carriers under the U.S.-E.U. Open Skies Agreement. Barbara J... of persons, property and mail from any point or points behind any Member State(s) of the European Union, via any point or points in any Member State and via intermediate points, to any point(s) in the...

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2011-04-12

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Cardiovascular disease incidence among females in South Carolina by type of oral contraceptives, 2000-2013: a retrospective cohort study.

PubMed

Samson, Marsha E; Adams, Swann A; Merchant, Anwar T; Maxwell, Whitney D; Zhang, Jiajia; Bennett, Charles L; Hebert, James R

2016-11-01

Certain types of oral contraceptives can produce favorable effects on lipid metabolism and vascular tone, while others have potentially detrimental effects. Endogenous and exogenous hormones exert different effects on high-density lipoprotein (HDL) and low-density lipoprotein (LDL) depending on the type, combination, and dose of the hormone. The estrogenic and progestogenic effects of exogenous hormones on HDL and LDL are inconsistent. Studying surrogate end points (LDL, HDL levels) may provide a misleading picture of OCs. Medicaid data from 2000 to 2013 were used to assess the relationship between the type of OCs and CVD incidence. Multivariable logistic regression was used to model relationships between cardiovascular disease and OC use adjusting for potential confounders. Compared to combined oral contraceptives (COC), progestin-only oral contraceptives (POC) were associated with decreased heart disease and stroke incidence after adjusting for important covariates (OR 0.74; 95 % CI 0.57, 0.97 and OR 0.39; 95 % CI 0.16, 0.95, respectively). However, there was a positive association between POC + COC and both heart disease and stroke incidence (OR 2.28; 95 % CI 1.92, 2.70 and OR 2.12; 95 % CI 1.34, 3.35, respectively). In light of an association between POC use and decreased heart disease and stroke, women's CVD risk factors should be carefully considered when choosing which OC to use. Baseline CVD risk should be a part of the discussion between women and their primary care providers when making choices regarding OCs.

Spherulitic Growth of Coral Skeletons and Synthetic Aragonite: Nature’s Three-Dimensional Printing

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

Sun, Chang-Yu; Marcus, Matthew A.; Frazier, Matthew J.

Coral skeletons were long assumed to have a spherulitic structure, that is, a radial distribution of acicular aragonite (CaCO 3) crystals with their c-axes radiating from series of points, termed centers of calcification (CoCs). This assumption was based on morphology alone, not on crystallography. In this paper, we measure the orientation of crystals and nanocrystals and confirm that corals grow their skeletons in bundles of aragonite crystals, with their c-axes and long axes oriented radially and at an angle from the CoCs, thus precisely as expected for feather-like or “plumose” spherulites. Furthermore, we find that in both synthetic and coralmore » aragonite spherulites at the nanoscale adjacent crystals have similar but not identical orientations, thus demonstrating by direct observation that even at nanoscale the mechanism of spherulite formation is non-crystallographic branching (NCB), as predicted by theory. Finally, synthetic aragonite spherulites and coral skeletons have similar angle spreads, and angular distances of adjacent crystals, further confirming that coral skeletons are spherulites. This is important because aragonite grows anisotropically, 10 times faster along the c-axis than along the a-axis direction, and spherulites fill space with crystals growing almost exclusively along the c-axis, thus they can fill space faster than any other aragonite growth geometry, and create isotropic materials from anisotropic crystals. Greater space filling rate and isotropic mechanical behavior are key to the skeleton’s supporting function and therefore to its evolutionary success. Finally, in this sense, spherulitic growth is Nature’s 3D printing.« less

Spherulitic Growth of Coral Skeletons and Synthetic Aragonite: Nature’s Three-Dimensional Printing

DOE PAGES

Sun, Chang-Yu; Marcus, Matthew A.; Frazier, Matthew J.; ...

2017-05-31

Coral skeletons were long assumed to have a spherulitic structure, that is, a radial distribution of acicular aragonite (CaCO 3) crystals with their c-axes radiating from series of points, termed centers of calcification (CoCs). This assumption was based on morphology alone, not on crystallography. In this paper, we measure the orientation of crystals and nanocrystals and confirm that corals grow their skeletons in bundles of aragonite crystals, with their c-axes and long axes oriented radially and at an angle from the CoCs, thus precisely as expected for feather-like or “plumose” spherulites. Furthermore, we find that in both synthetic and coralmore » aragonite spherulites at the nanoscale adjacent crystals have similar but not identical orientations, thus demonstrating by direct observation that even at nanoscale the mechanism of spherulite formation is non-crystallographic branching (NCB), as predicted by theory. Finally, synthetic aragonite spherulites and coral skeletons have similar angle spreads, and angular distances of adjacent crystals, further confirming that coral skeletons are spherulites. This is important because aragonite grows anisotropically, 10 times faster along the c-axis than along the a-axis direction, and spherulites fill space with crystals growing almost exclusively along the c-axis, thus they can fill space faster than any other aragonite growth geometry, and create isotropic materials from anisotropic crystals. Greater space filling rate and isotropic mechanical behavior are key to the skeleton’s supporting function and therefore to its evolutionary success. Finally, in this sense, spherulitic growth is Nature’s 3D printing.« less

14 CFR 93.321 - Transfer and termination of allocations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... commercial air tours outside the Dragon and Zuni Point corridors may not be transferred into the Dragon and Zuni Point corridors. Allocations authorizing commercial air tours within the Dragon and Zuni Point corridors may be transferred outside of the Dragon and Zuni Point corridors. (iii) A certificate holder must...

14 CFR 93.321 - Transfer and termination of allocations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... commercial air tours outside the Dragon and Zuni Point corridors may not be transferred into the Dragon and Zuni Point corridors. Allocations authorizing commercial air tours within the Dragon and Zuni Point corridors may be transferred outside of the Dragon and Zuni Point corridors. (iii) A certificate holder must...

14 CFR 93.321 - Transfer and termination of allocations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... commercial air tours outside the Dragon and Zuni Point corridors may not be transferred into the Dragon and Zuni Point corridors. Allocations authorizing commercial air tours within the Dragon and Zuni Point corridors may be transferred outside of the Dragon and Zuni Point corridors. (iii) A certificate holder must...

14 CFR 93.321 - Transfer and termination of allocations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... commercial air tours outside the Dragon and Zuni Point corridors may not be transferred into the Dragon and Zuni Point corridors. Allocations authorizing commercial air tours within the Dragon and Zuni Point corridors may be transferred outside of the Dragon and Zuni Point corridors. (iii) A certificate holder must...

[The assesment of cranio-cerebral injuries in the aspect of neurological, psychiatric and certification criteria].

PubMed

Maksymowicz, Krzysztof; Piechocki, Dariusz; Drozd, Radosław

2005-01-01

In this paper an effort has been made to explain and systemize the notions of encephalopathy, psycho organic syndrome, characteropathy, seen as consequences of cranio-cerebral injuries, and regarding neurological, psychiatric and certificating criteria. The main aim of this classification is to define the necessary conditions needed to confirm or exclude the presence of neurological changes mentioned above. The conditions should be acceptable from the neurological, psychiatric and certificating points of view. The certificating experience of the authors shows that there are vast differences among criteria applied by neurologists, psychiatrists and certificating doctors in assessing the consequences of cranio-cerebral injuries. Moreover, in the above paper various injury and disease factors have been presented and discussed. Although they do not remain in any causal connection with the assessed event, they have a significant influence on the final result of the medical certification.

Describing Elementary Certification Methods across the Elementary Music Career Cycle

ERIC Educational Resources Information Center

Svec, Christina L.

2017-01-01

The purpose of the study was to describe elementary music method choice and certification method choice overall and across the elementary music career cycle. Participants (N = 254) were categorized as Level I or Elementary Division in a southwestern music education association database. The questionnaire included 25 four-point Likert-type items…

78 FR 35352 - Applications for Certificates of Public Convenience and Necessity and Foreign Air Carrier Permits

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-12

... transportation of persons and property from any point or points behind any Member State of the European Union via... point or points in the United States and any point or points in any member of the European Common... available to European Community carries in the future. Barbara J. Hairston, Acting Program Manager, Docket...

78 FR 2710 - Applications for Certificates of Public Convenience and Necessity and Foreign Air Carrier Permits

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... points behind the European Union, via any point or points in the European Union and intermediate points... under the U.S.-European Union agreements, as amended. Docket Number: DOT-OST-2012-0212. Date Filed... European Common Aviation Area and any point or points in the United States; (c) pursuant to the prior...

77 FR 59243 - Notice of Applications for Certificates of Public Convenience and Necessity and Foreign Air...

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2012-10-17

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77 FR 70208 - Notice of Applications for Certificates of Public Convenience and Necessity and Foreign Air...

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76 FR 35939 - Notice of Applications for Certificates of Public Convenience and Necessity and Foreign Air...

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..., property, and mail from any point or points behind any Member State of the European Union, via any point or... any additional route rights made available to European Union carriers in the future, to the extent... or points in the United States and any point or points in any member of the European Common Aviation...

76 FR 33400 - Notice of Applications for Certificates of Public Convenience and Necessity and Foreign Air...

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76 FR 42762 - Notice of Applications for Certificates of Public Convenience and Necessity and Foreign Air...

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78 FR 4586 - Applications for Certificates of Public Convenience and Necessity and Foreign Air Carrier Permits

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2013-01-22

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77 FR 47670 - RG Steel Sparrows Point LLC, Formerly Known as Severstal Sparrows Point LLC, a Subsidiary of RG...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-09

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-74,919] RG Steel Sparrows Point LLC, Formerly Known as Severstal Sparrows Point LLC, a Subsidiary of RG Steel LLC, Including All On-Site Leased Workers, Sparrows Point, MD; Amended Certification Regarding Eligibility To Apply for...

Vital effects in coral skeletal composition display strict three-dimensional control

USGS Publications Warehouse

Meibom, A.; Yurimoto, H.; Cuif, J.-P.; Domart-Coulon, I.; Houlbreque, F.; Constantz, B.; Dauphin, Y.; Tambutte, E.; Tambutte, S.; Allemand, D.; Wooden, J.; Dunbar, R.

2006-01-01

Biological control over coral skeletal composition is poorly understood but critically important to paleoenvironmental reconstructions. We present microanalytical measurements of trace-element abundances as well as oxygen and carbon isotopic compositions of individual skeletal components in the zooxanthellate coral Colpophyllia sp. Our data show that centers of calcification (COC) have higher trace element concentrations and distinctly lighter isotopic compositions than the fibrous components of the skeleton. These observations necessitate that COC and the fibrous skeleton are precipitated by different mechanisms, which are controlled by specialized domains of the calicoblastic cell-layer. Biological processes control the composition of the skeleton even at the ultra-structure level. Copyright 2006 by the American Geophysical Union.

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

Chan, Wanyu R.; Sidheswaran, Meera; sullivan, Douglas

The HZEB research program aims to generate information needed to develop new science-based commercial building ventilation rate (VR) standards that balance the dual objectives of increasing energy efficiency and maintaining acceptable indoor air quality. This interim report describes the preliminary results from one HZEB field study on retail stores. The primary purpose of this study is to estimate the whole-building source strengths of contaminant of concerns (COCs). This information is needed to determine the VRs necessary to maintain indoor concentrations of COCs below applicable health guidelines.The goal of this study is to identify contaminants in retail stores that should bemore » controlled via ventilation, and to determine the minimum VRs that would satisfy the occupant health and odor criteria.« less

Weather support area, floor plan and details. ("Alter COC, Bldg. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Weather support area, floor plan and details. ("Alter COC, Bldg. 2605, Weather Support Area, Floor Plan & Details" Also includes a site plan and a finish schedule. The exact location of this construction is obscure, but it appears to be the enclosure of space at the north end of room 101, the "Display Area" or "War Room") Strategic Air Command, Civil Engineering. Drawing no. B-1081, sheet no. 1 of 2, 9 July 1968; project no. MAR-132-8; CE-562; file drawer 2605-9, also 1315. Various scales. 29x41 inches. pencil on paper - March Air Force Base, Strategic Air Command, Combat Operations Center, 5220 Riverside Drive, Moreno Valley, Riverside County, CA

Preparation and characterization of ligand types intermediate in the metal catalyzed conversion of coal to methane, methanol, and higher alkanes and alcohols. Second technical progress report, September 1, 1979-February 28, 1981

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

Gladysz, J. A.

1980-11-10

Mechanistic studies of anionic formyl complexes were made. The rate of decomposition of the formyl (CO)/sub 4/Mn(COC/sub 6/H/sub 5/)(CHO)/sup -/ anion as a function of counter-ion and trialkylborane present was examined. The deuterated formyl (CO)/sub 4/Mn(COC/sub 6/H/sub 5/)(CDO)/sup -/ was prepared and its decomposition was monitored by H/sup 2/ NMR. The data obtained indicate that the formyl decomposes by a disproportionative pathway not by initial CO loss, as commonly noted for formyl complexes.

A rhinocerotid-dominated megafauna at the MIS6-5 transition: The late Middle Pleistocene Coc Muoi assemblage, Lang Son province, Vietnam

NASA Astrophysics Data System (ADS)

Bacon, Anne-Marie; Antoine, Pierre-Olivier; Huong, Nguyen Thi Mai; Westaway, Kira; Tuan, Nguyen Anh; Duringer, Philippe; Zhao, Jian-xin; Ponche, Jean-Luc; Dung, Sam Canh; Nghia, Truong Huu; Minh, Tran Thi; Son, Pham Thanh; Boyon, Marc; Thuy, Nguyen Thi Kim; Blin, Amandine; Demeter, Fabrice

2018-04-01

Little is known about the ecosystems in the north of the Indochinese peninsula at the Middle-Late Pleistocene transition. In this paper, we analyzed the new fauna from Coc Muoi cave, Lang Son province, northeast Vietnam. In comparison with other well-documented faunas from the region, that of Coc Muoi is distinguished by the predominance of rhinoceroses among diverse large-bodied herbivores. The results of the OSL and pIR-IRSL dating of the cave sediments and U-series dating of flowstones indicate a potential age range of 148-117 ka for the fauna (MIS6-5). The analysis of age-at-death distributions of rhinoceroses, wild cattle, sambar deer, and wild pig, does not show any apparent selectivity of age classes. We also focused our study on rhinoceroses, tapirs, and wild cattle by analyzing the prevalence of hypoplastic defects on deciduous and permanent teeth, in an attempt to assess the health status of the taxa during their first years of growth. The health status of large-bodied herbivores (kouprey and rhinoceros) reveals the importance of stressors (biotic and abiotic) in the rainforest environment during a period of marked climatic transition (MIS6-5) in comparison with other MIS5-4 well-documented faunas from the region.

CD56 Expression in Odontogenic Cysts and Tumors.

PubMed

Jaafari-Ashkavandi, Zohreh; Dehghani-Nazhvani, Ali; Razmjouyi, Faranak

2014-01-01

Background and aims. Odontogenic cysts and tumors have a wide spectrum of clinical characteristics that lead to the different management strategies. Since definite diagnosis is difficult in some cases, it has been suggested that CD56 may be a candidate marker for definitive diagnosis of some odontogenic tumors. The present study was designed to examine CD56 expression in lesions with histopathological similarities. Materials and methods. In this cross-sectional, analytical study the subjects were 22 ameloblastomas, 13 dentigerous cysts, 10 keratocystic odontogenic tumors (KCOT), 4 adenomatoid odontogenic tumors (AOT), 3 orthokeratinized odonto-genic cysts, 3 calcifying odontogenic cysts (COC) and one glandular odontogenic cyst (GOC). All the samples were examined for CD56 immunoreactivity. Data were analyzed using chi-square test. Results. Twenty cases (91%) of ameloblastomas, 3 (75%) AOT, 4 (40%) KCOT and one case of GOC were positive for CD56. None of the dentigerous cysts, COC and orthokeratinized odontogenic cysts was CD56-positive. There was a significant difference in the CD56 expression between ameloblastoma and dentigerous cyst, as well as COC. Also, KCOT showed significantly higher expression than orthokeratinized odontogenic cyst. Conclusion. In this study CD56 expression was limited to the odontogenic tumors and more aggressive cystic lesions. This marker can be a useful aid for distinguishing cysts and tumors from similar lesions.

Perceived competence and contraceptive use during adolescence.

PubMed

Hillman, Jennifer B; Negriff, Sonya; Dorn, Lorah D

2010-03-01

Little is known about psychosocial correlates of different contraceptive methods in adolescence. Cross-sectional analyses of 209 postmenarcheal girls [mean age (years)+/-SD=15.68+/-1.74], primarily Caucasian (62.8%) or African American (32.8%). Competence (activities and social) and rule-breaking behavior were assessed by the Youth Self Report (YSR; adolescent) and the Child Behavior Checklist (CBCL; parent). Three contraceptive-use groups were created: no hormonal contraceptive (n=142), combined oral contraceptives or the transdermal patch (COCs/patch, n=41), and depot medroxyprogesterone acetate (DMPA, n=20). There was a significant effect of contraceptive-use group on competence (p=.003). The DMPA group had lower competence (CBCL activities and social; YSR social) than the no-hormonal-contraceptive and COCs/patch groups. The COCs/patch group scored lower than the no-hormonal-contraceptive group on YSR activities competence, but was not different from the DMPA group. Lastly, there was an effect of contraceptive-use group on CBCL (but not YSR) rule-breaking behavior (p=.029) with the DMPA group having higher rule-breaking behavior than the other groups. Type of contraceptive method was associated with parent and adolescent's perceived competence. For rule-breaking behavior, parental perception may be more relevant to contraceptive use. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Evaluation of solid-phase microextraction desorption parameters for fast GC analysis of cocaine in coca leaves.

PubMed

Ilias, Yara; Bieri, Stefan; Christen, Philippe; Veuthey, Jean-Luc

2006-08-01

By its simplicity and rapidity, solid-phase microextraction (SPME) appears as an interesting alternative for sample introduction in fast gas chromatography (fast GC). This combination depends on numerous parameters affecting the desorption step (i.e., the release of compounds from the SPME fiber coating to the GC column). In this study, different liner diameters, injection temperatures, and gas flow rates are evaluated to accelerate the thermal desorption process in the injection port. This process is followed with real-time direct coupling a split/splitless injector to a mass spectrometer by means of a short capillary. It is shown that an effective, quantitative, and rapid transfer of cocaine (COC) and cocaethylene (CE) is performed with a 0.75-mm i.d. liner, at 280 degrees C and 4 mL/min gas flow rate. The 7-microm polydimethylsiloxane (PDMS) coating is selected for combination with fast GC because the 100-microm PDMS fiber presents some limitations caused by fiber bleeding. Finally, the developed SPME-fast GC method is applied to perform in less than 5 min, the quantitation of COC extracted from coca leaves by focused microwave-assisted extraction. An amount of 7.6 +/- 0.5 mg of COC per gram of dry mass is found, which is in good agreement with previously published results.

77 FR 59243 - Notice of Applications for Certificates of Public Convenience and Necessity and Foreign Air...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-26

... persons, property, and mail from any point or points behind any Member State of the European Union, via... rights made available to European Union carriers in the future, to the extent permitted by Elit'Avia's... any point or points in the United States and any point orpoints in any member of the European Common...

Randomized comparison of bleeding patterns in women using a combined contraceptive vaginal ring or a low-dose combined oral contraceptive on a menstrually signaled regimen.

PubMed

Weisberg, Edith; Merki-Feld, Gabriele S; McGeechan, Kevin; Fraser, Ian S

2015-02-01

To compare bleeding patterns for 12 months continuous use of a contraceptive ring [contraceptive vaginal ring (CVR)] and pill [combined oral contraceptive (COC)] on a menstrually signaled regimen and the effectiveness of 4 days "treatment withdrawal" to stop bleeding. Women, 66 to each group, were randomized to continuous use of a CVR (15 mcg ethinyl estradiol/150 mcg etonogestrel) or a low-dose pill (20 mcg ethinyl estradiol/100 mcg levonorgestrel) for 360 days on a menstrually signaled regimen. Bleeding/spotting days, daily use of ring or pill, was recorded. Endpoint was the total number of bleeding/spotting days for each method over four 90-day reference periods (RP) plus the analysis of bleeding patterns using modified World Health Organization criteria. There was a reduction in the mean (±S.D.) number of bleeding/spotting days from RP1 (CVR 14.2±10; pill 16.6±10.9) to RP4 (CVR 8.8±9.6; pill 8.8±9.1). Fifteen percent of CVR and 4% COC users experienced amenorrhea or infrequent bleeding throughout the study. Amenorrhea increased over time (RP1 vs. RP4: CVR 10% vs. 21% and COC 2% vs. 30%). Compliance with the menstrually signaled regimen was poor. Ceasing hormones for 4 days stopped a bleeding episode within 5 days in the majority of episodes and many stopped spontaneously. Bleeding patterns with continuous use of the CVR and COC are similar and improve over 1 year of use. The unpredictability, but short duration, of bleeding episodes should be stressed during counseling. This information for clinicians and women about breakthrough bleeding patterns with use of a CVR or combined pill over 12 months using a menstrually signaled regimen will give women an indication of what to expect with continuous use. Copyright © 2015 Elsevier Inc. All rights reserved.

Probabilistic assessment of compliance with the numerical criteria for fecal coliforms in rivers

NASA Astrophysics Data System (ADS)

Cha, YoonKyung

2017-04-01

Most guidelines for assessing fecal contamination in surface waters suggest that a waterbody is impaired if a certain percent or the geometric mean of samples exceeds the numerical criteria for fecal indicator organisms. However, this raw score approach is not able to account for the uncertainty and variability in the sample statistics. In a Bayesian hierarchical modeling approach, the uncertainty in the mean parameter is expressed as a posterior distribution, and the probability of not violating the criterion is referred to as the confidence of compliance (COC). Further, the spatiotemporal variability in the mean parameter can be quantified by imposing the hierarchical structure on the model. The monitoring data spanning 91 sites across the four major rivers (the Han, Geum, Yeongsan, and Nakdong) of South Korea for the years 2007-2016 were used. The Bayesian hierarchical model was developed for each river to predict the COC with the criteria for fecal coliforms. The established criteria for fecal coliforms are less than 10, 100, 200, and 1,000 CFU/100mL in the river whose water quality goal corresponds to Class Ia, Ib, II, and III, respectively. The model results suggested that the COC varied significantly by site, ranging from 0.0 to 98.9 percent across the four rivers. In the Geum, Yeongsan, and Nakdong Rivers, COC values in the upper river sections were substantially lower than those in the upper river sections. The model suggested that for all four rivers the spatial component, compared with annual and seasonal components, made the largest contribution to the variability in mean fecal coliforms. In all four rivers, mean levels for fecal coliform during the summer (July to September) were distinctly higher than those during other seasons. A decreasing pattern was clearly shown in the Yeongsan River over the recent decade, while monotonic increases or decreases were not shown in other three rivers.

Human Chorionic Gonadotropin Mediated Generation of Reactive Oxygen Species Is Sufficient to Induce Meiotic Exit but Not Apoptosis in Rat Oocytes

PubMed Central

Tiwari, Meenakshi; Chaube, Shail K.

2017-01-01

Abstract Generation of reactive oxygen species (ROS) is associated with final stages of follicular development and ovulation in mammals. The human chorionic gonadotropin (hCG) mimics the action of luteinizing hormone and triggers follicular development and ovulation. However, it remains unclear whether hCG induces generation of ROS, if yes, whether hCG-mediated increased level of ROS could induce meiotic exit and/or apoptosis in rat oocytes. For this purpose, cumulus–oocyte complexes (COCs) were collected from ovary of experimental rats injected with 20 IU pregnant mare's serum gonadotropin for 48 h followed by 20 IU hCG for 0, 7, 14, and 21 h. The morphological changes in COCs, meiotic status of oocyte, total ROS, hydrogen peroxide (H2O2), inducible nitric oxide synthase (iNOS), nitric oxide (NO), Bax, Bcl-2, cytochrome c, telomerase reverse transcriptase (TERT) expression levels, and DNA fragmentation were analyzed in COCs. Our data suggest that hCG surge increased total ROS as well as H2O2 levels but decreased iNOS expression and total NO level in oocytes. The hCG-mediated increased level of ROS was sufficient to induce meiotic cell cycle resumption in majority of oocytes as evidenced by meiotic exit from diplotene as well as metaphase-II (M-II) arrest and their meiotic status. However, increase of ROS level due to hCG surge was not sufficient to trigger Bax and cytochrome c expression levels and DNA fragmentation in COCs. In addition, increased TERT activity was observed in oocytes collected 21 h post-hCG surge showing onset of oocyte aging. Taken together, these results suggest that hCG induces generation of ROS sufficient to trigger meiotic exit from diplotene, as well as M-II arrest, but not good enough to induce apoptosis in rat oocytes. PMID:29098117

Determination of cocaine and its derivatives in hair samples by liquid phase microextraction (LPME) and gas chromatography-mass spectrometry (GC-MS).

PubMed

Pego, A M F; Roveri, F L; Kuninari, R Y; Leyton, V; Miziara, I D; Yonamine, M

2017-05-01

Hair testing is a recognized approach when it comes to accessing historical drug use. According to the World Drug Report of United Nations Office on Drugs and Crime (UNODC) 2015, Brazil is the largest cocaine (COC) market in South America. New analytical methodologies to detect crack/cocaine analytes in hair samples are highly desirable. Here, a method consisting of a liquid-phase microextraction (LPME) as a clean-up step, followed by gas chromatography-mass spectrometry (GC-MS) analysis has been proposed. The new validated method consisted of a washing step; an overnight incubation with methanol and a quick derivatization with butylchloroformate. Once derivatized, the samples were then submitted to the LPME procedure. Limits of detection (LoD) and quantitation (LoQ) obtained were of 0.1 and 0.5ng/mg for COC 0.4 and 0.5ng/mg for anhydroecgonine methyl ester (AEME); 0.03 and 0.05 for cocaethylene (CE), respectively and 0.05ng/mg for both LoD and LoQ for benzoylecgonine (BZE). All calibration curves were linear over the scope applied, from LoQ up to 20ng/mg, with a r 2 >0.99. Precision and accuracy assays showed acceptable %RSD values, according to international guidelines. Twelve postmortem head hair samples stemming from the Institute of Legal Medicine of Sao Paulo (IML-SP) have been analyzed, from which seven have shown to be positive for COC (0.75->20ng/mg) and BZE (0.1->20ng/mg). Apart from COC's main metabolite, four samples were also positive for CE (0.1-3.9ng/mg) and three samples for AEME (0.5-4.9ng/mg). To conclude, the LPME technique together with GC-MS analysis have shown promising results and were able to meet the demand of the laboratory of analyzing postmortem hair samples to look for all four analytes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Contribution of Cervicovaginal Infections to the Immunomodulatory Effects of Hormonal Contraception

PubMed Central

Chen, Pai-Lien; Morrison, Charles S.; Doncel, Gustavo F.; Mendonca, Kevin; Kwok, Cynthia; Chipato, Tsungai; Salata, Robert; Mauck, Christine

2015-01-01

ABSTRACT Particular types of hormonal contraceptives (HCs) and genital tract infections have been independently associated with risk of HIV-1 acquisition. We examined whether immunity in women using injectable depot medroxyprogesterone acetate (DMPA), combined oral contraceptives (COC), or no HCs differs by the presence of cervicovaginal infections. Immune mediators were quantified in cervical swabs from 832 HIV-uninfected reproductive-age Ugandans and Zimbabweans. Bacterial infections and HIV were diagnosed by PCR, genital herpes serostatus by enzyme-linked immunosorbent assay (ELISA), altered microflora by Nugent score, and Trichomonas vaginalis and Candida albicans infection by wet mount. Generalized linear models utilizing Box-Cox-Power transformation examined associations between levels of mediators, infection status, and HCs. In no-HC users, T. vaginalis was associated with broadest spectrum of aberrant immunity (higher interleukin 1β [IL-1β], IL-8, macrophage inflammatory protein 3α [MIP-3α], β-defensin 2 [BD2], and IL-1 receptor antigen [IL-1RA]). In women with a normal Nugent score and no genital infection, compared to the no-HC group, COC users showed higher levels of IL-1β, IL-6, IL-8, and IL-1RA, while DMPA users showed higher levels of RANTES and lower levels of BD2, both associated with HIV seroconversion. These effects of COC were blunted in the presence of gonorrhea, chlamydia, trichomoniasis, candidiasis, and an abnormal Nugent score; however, RANTES was increased among COC users with herpes, chlamydia, and abnormal Nugent scores. The effect of DMPA was exacerbated by lower levels of IL-1RA in gonorrhea, chlamydia, or herpes, SLPI in gonorrhea, and IL-1β, MIP-3α, and IL-1RA/IL1β ratio in trichomoniasis. Thus, the effects of HC on cervical immunity depend on the genital tract microenvironment, and a weakened mucosal barrier against HIV may be a combined resultant of genital tract infections and HC use. PMID:26330510

Continuous Norethisterone Acetate versus Cyclical Drospirenone 3 mg/Ethinyl Estradiol 20 μg for the Management of Primary Dysmenorrhea in Young Adult Women.

PubMed

Al-Jefout, Moamar; Nawaiseh, Nedal

2016-04-01

To evaluate the efficacy of continuous norethisterone acetate (NET-A), 5 mg (group N) vs cyclical combined oral contraceptive pill (COC) consisting of drospirenone 3 mg/ethinyl estradiol 20 μg pills (group P) in treating dysmenorrhea in young adult women. This prospective, open-label, nonrandomized study included 38 Jordanian patients: 20 patients in group N and 18 patients in group P. Continuous NET-A 5 mg daily or cyclical COC. Pain scores, adverse effects, analgesic use, school absence, and cost. Thirty-eight patients used NET-A or COC for 6 months. All participants had almost the same starting levels of visual analogue scale (VAS) scores. Both drugs were similar in suppressing dysmenorrhea at the 3-month follow-up visit; VAS score mean (±SD) in group N and P were 1.30 ± 1.22 and 1.28 ± 0.83 (P = .22), respectively, and after 6 months, with mean VAS scores (±SD) of 1.30 ± 1.22 and 1.28 ± 0.83, respectively (P = .95). The cost of the treatment in the N group was much less than in the P group. Participants in the N group were less likely to use pain killers: 20% and 44% in the N and P groups, respectively (P = .006) in the first month and only 5% and 17% (P = .019) in the N and P groups, respectively, at the 3-month follow-up, and none of them used any analgesics at the 6-month follow-up. A continuous NET-A regimen is a well tolerated, effective, and inexpensive option for dysmenorrhea treatment and was as good as COC. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Hormonal Contraception and the Risk of HIV Acquisition: An Individual Participant Data Meta-analysis

PubMed Central

Morrison, Charles S.; Chen, Pai-Lien; Kwok, Cynthia; Baeten, Jared M.; Brown, Joelle; Crook, Angela M.; Van Damme, Lut; Delany-Moretlwe, Sinead; Francis, Suzanna C.; Friedland, Barbara A.; Hayes, Richard J.; Heffron, Renee; Kapiga, Saidi; Karim, Quarraisha Abdool; Karpoff, Stephanie; Kaul, Rupert; McClelland, R. Scott; McCormack, Sheena; McGrath, Nuala; Myer, Landon; Rees, Helen; van der Straten, Ariane; Watson-Jones, Deborah; van de Wijgert, Janneke H. H. M.; Stalter, Randy; Low, Nicola

2015-01-01

Background Observational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC. Methods and Findings Eligible studies measured HC exposure and incident HIV infection prospectively using standardized measures, enrolled women aged 15–49 y, recorded ≥15 incident HIV infections, and measured prespecified covariates. Our primary analysis estimated the adjusted hazard ratio (aHR) using two-stage random effects meta-analysis, controlling for region, marital status, age, number of sex partners, and condom use. We included 18 studies, including 37,124 women (43,613 woman-years) and 1,830 incident HIV infections. Relative to no HC use, the aHR for HIV acquisition was 1.50 (95% CI 1.24–1.83) for DMPA use, 1.24 (95% CI 0.84–1.82) for NET-EN use, and 1.03 (95% CI 0.88–1.20) for COC use. Between-study heterogeneity was mild (I2 < 50%). DMPA use was associated with increased HIV acquisition compared with COC use (aHR 1.43, 95% CI 1.23–1.67) and NET-EN use (aHR 1.32, 95% CI 1.08–1.61). Effect estimates were attenuated for studies at lower risk of methodological bias (compared with no HC use, aHR for DMPA use 1.22, 95% CI 0.99–1.50; for NET-EN use 0.67, 95% CI 0.47–0.96; and for COC use 0.91, 95% CI 0.73–1.41) compared to those at higher risk of bias (pinteraction = 0.003). Neither age nor herpes simplex virus type 2 infection status modified the HC–HIV relationship. Conclusions This IPD meta-analysis found no evidence that COC or NET-EN use increases women’s risk of HIV but adds to the evidence that DMPA may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk. A randomized controlled trial would provide more definitive evidence about the effects of hormonal contraception, particularly DMPA, on HIV risk. PMID:25612136

Validation of a heterologous fertilization assay and comparison of fertilization rates of equine oocytes using in vitro fertilization, perivitelline, and intracytoplasmic sperm injections.

PubMed

Sessions-Bresnahan, D R; Graham, J K; Carnevale, E M

2014-07-15

IVF in horses is rarely successful. One reason for this could be the failure of sperm to fully capacitate or exhibit hyperactive motility. We hypothesized that the zona pellucida (ZP) of equine oocytes prevents fertilization in vitro, and bypassing the ZP would increase fertilization rates. Limited availability of equine oocytes for research has necessitated the use of heterologous oocyte binding assays using bovine oocytes. We sought to validate an assay using bovine oocytes and equine sperm and then to demonstrate that bypassing the ZP using perivitelline sperm injections (PVIs) with equine sperm capacitated with dilauroyl phosphatidylcholine would result in higher fertilization rates than standard IVF in bovine and equine oocytes. In experiment 1, bovine oocytes were used for (1) IVF with bovine sperm, (2) IVF with equine sperm, and (3) intracytoplasmic sperm injections (ICSIs) with equine sperm. Presumptive zygotes were either stained with 4',6-diamidino-2-phenylindole from 18 to 26 hours at 2-hour intervals or evaluated for cleavage at 56 hours after addition of sperm. Equine sperm fertilized bovine oocytes; however, pronuclei formation was delayed compared with bovine sperm after IVF. The delayed pronuclear formation was not seen after ICSI. In experiment 2, bovine oocytes were assigned to the following five groups: (1) cumulus oocyte complexes (COCs) coincubated with bovine sperm; (2) COC exposed to sucrose then coincubated with bovine sperm; (3) COC coincubated with equine sperm; (4) COC exposed to sucrose, and coincubated with equine sperm; and (5) oocytes exposed to sucrose, and 10 to 15 equine sperm injected into the perivitelline (PV) space. Equine sperm tended (P = 0.08) to fertilize more bovine oocytes when injected into the PV space than after IVF. In experiment 3, oocytes were assigned to the following four groups: (1) IVF, equine, and bovine COC coincubated with equine sperm; (2) PVI of equine and bovine oocytes; (3) PVI with equine oocytes pretreated with sucrose; and (4) ICSI of equine oocytes. Oocytes were examined at 24 hours for cleavage. No equine oocytes cleaved after IVF or PVI. However, ICSI conducted with equine sperm treated with dilauroyl phosphatidylcholine resulted in 85% of the oocytes cleaving. Sperm injected into the PV space of equine oocytes did not appear to enter the ooplasm. This study validated the use of bovine oocytes for equine sperm studies and indicates that failure of equine IVF is more than an inability of equine sperm to penetrate the ZP. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of obesity on the effectiveness of hormonal contraceptives: an individual participant data meta-analysis.

PubMed

Yamazaki, Michiyo; Dwyer, Kate; Sobhan, Mahboob; Davis, Daniel; Kim, Myong-Jin; Soule, Lisa; Willett, Gerald; Yu, Chongwoo

2015-11-01

The objective of this investigation was to assess the potential effect of obesity on the effectiveness of hormonal contraceptives (HCs). A meta-analysis was conducted using individual participant data directly from the Phase 3 clinical trials of combination oral contraceptives (COCs) rather than extracting summary data from literature. Trials selected were reviewed by the US Food and Drug Administration (FDA) between 2000 and 2012, conducted in North America, had more than six 28-day cycle equivalents of exposure, and had readily retrievable participant-level data. Contraceptive effectiveness was measured by the Pearl Index (PI: the number of pregnancies per 100 woman-years) in women aged 18-35 at risk of unintended pregnancy. The incidence rate ratio (IRR), a ratio of PIs for obese women (defined as body mass index [BMI] ≥30 kg/m(2)) compared to non-obese women (BMI <30 kg/m(2)) was calculated. A Cox proportional-hazard regression model with fixed and random-effects were used to estimate hazard ratios (HRs) for unintended pregnancy in obese women compared to non-obese women. Seven clinical trials with COCs (N=14,024: 2707 obese and 11,317 non-obese women) met the inclusion criteria for the meta-analysis. The PI for each trial varied: 2.05-5.08 for obese and 1.84-3.80 for non-obese women. The pooled PI estimated using direct weighted average method was 3.14 (95% CI: 2.33-4.22) for obese and 2.53 (95% CI: 1.88-3.41) for non-obese women. The pooled IRRs estimated using direct weighted average and Mantel-Haenszel adjustment methods were comparable: 1.37 (95% CI: 1.02-1.84) and 1.43 (95% CI: 1.07-1.92), respectively. The overall HR of 1.44 (95% CI: 1.06-1.95; p=.018) in the meta-analysis suggested a 44% higher pregnancy rate during COC use for obese women after adjusting for age and race. Obesity may increase the risk of unintended pregnancy in women using COCs; more data on obese women from ongoing and future Phase 3 clinical trials are necessary to allow further evaluation of this topic. Results of this meta-analysis suggest that obese women may have a higher pregnancy rate during COC use compared to non-obese women. Future analysis should assess differences in pharmacodynamics or compliance that could potentially account for the observed difference in unintended pregnancy rates. Published by Elsevier Inc.

Technical Approach for Determining Key Parameters Needed for Modeling the Performance of Cast Stone for the Integrated Disposal Facility Performance Assessment

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

Yabusaki, Steven B.; Serne, R. Jeffrey; Rockhold, Mark L.

2015-03-30

Washington River Protection Solutions (WRPS) and its contractors at Pacific Northwest National Laboratory (PNNL) and Savannah River National Laboratory (SRNL) are conducting a development program to develop / refine the cementitious waste form for the wastes treated at the ETF and to provide the data needed to support the IDF PA. This technical approach document is intended to provide guidance to the cementitious waste form development program with respect to the waste form characterization and testing information needed to support the IDF PA. At the time of the preparation of this technical approach document, the IDF PA effort is justmore » getting started and the approach to analyze the performance of the cementitious waste form has not been determined. Therefore, this document looks at a number of different approaches for evaluating the waste form performance and describes the testing needed to provide data for each approach. Though the approach addresses a cementitious secondary aqueous waste form, it is applicable to other waste forms such as Cast Stone for supplemental immobilization of Hanford LAW. The performance of Cast Stone as a physical and chemical barrier to the release of contaminants of concern (COCs) from solidification of Hanford liquid low activity waste (LAW) and secondary wastes processed through the Effluent Treatment Facility (ETF) is of critical importance to the Hanford Integrated Disposal Facility (IDF) total system performance assessment (TSPA). The effectiveness of cementitious waste forms as a barrier to COC release is expected to evolve with time. PA modeling must therefore anticipate and address processes, properties, and conditions that alter the physical and chemical controls on COC transport in the cementitious waste forms over time. Most organizations responsible for disposal facility operation and their regulators support an iterative hierarchical safety/performance assessment approach with a general philosophy that modeling provides the critical link between the short-term understanding from laboratory and field tests, and the prediction of repository performance over repository time frames and scales. One common recommendation is that experiments be designed to permit the appropriate scaling in the models. There is a large contrast in the physical and chemical properties between the Cast Stone waste package and the IDF backfill and surrounding sediments. Cast Stone exhibits low permeability, high tortuosity, low carbonate, high pH, and low Eh whereas the backfill and native sediments have high permeability, low tortuosity, high carbonate, circumneutral pH, and high Eh. These contrasts have important implications for flow, transport, and reactions across the Cast Stone – backfill interface. Over time with transport across the interface and subsequent reactions, the sharp geochemical contrast will blur and there will be a range of spatially-distributed conditions. In general, COC mobility and transport will be sensitive to these geochemical variations, which also include physical changes in porosity and permeability from mineral reactions. Therefore, PA modeling must address processes, properties, and conditions that alter the physical and chemical controls on COC transport in the cementitious waste forms over time. Section 2 of this document reviews past Hanford PAs and SRS Saltstone PAs, which to date have mostly relied on the lumped parameter COC release conceptual models for TSPA predictions, and provides some details on the chosen values for the lumped parameters. Section 3 provides more details on the hierarchical modeling strategy and processes and mechanisms that control COC release. Section 4 summarizes and lists the key parameters for which numerical values are needed to perform PAs. Section 5 provides brief summaries of the methods used to measure the needed parameters and references to get more details.« less

77 FR 43368 - Joerns Healthcare, LLC, Stevens Point, Wisconsin Division, Including On-Site Leased Workers From...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-24

.... The Department has determined that these workers were sufficiently under the control of the subject..., Stevens Point, Wisconsin Division, Including On-Site Leased Workers From ABR, Aerotek, and Manpower, Stevens Point, WI; Amended Certification Regarding Eligibility To Apply for Worker Adjustment Assistance...

TiO2 surface functionalization of COC based planar waveguide Bragg gratings for refractive index sensing

NASA Astrophysics Data System (ADS)

Rosenberger, M.; Girschikofsky, M.; Förthner, M.; Belle, S.; Rommel, M.; Frey, L.; Schmauss, B.; Hellmann, R.

2018-01-01

We demonstrate the applicability of a planar waveguide Bragg grating in cyclo-olefin copolymer (COC) for refractive index sensing. The polymer planar waveguide Bragg grating fabricated using a single writing step technique is coated with a high-index layer of titanium dioxide (TiO2) leading to a distinct birefringence. This in turn results in the splitting of the Bragg reflection into two distinct Bragg wavelengths, which strongly differ regarding their refractive index sensitivities. Where one wavelength is only slightly affected by the ambient refractive index, the second Bragg peak shows a strong sensitivity. Furthermore, we investigate the temperature behaviour of the functionalized sensor and discuss it with respect to applications in refractive index sensing.

Enhanced microwave absorbing performance of CoNi alloy nanoparticles anchored on a spherical carbon monolith.

PubMed

Li, Na; Hu, Changwen; Cao, Minhua

2013-05-28

CoNi alloy nanoparticles anchored on a spherical carbon monolith (CoNi-C) were prepared by a solvothermal route and subsequent heat treatment without any templates. Their permittivity and permeability behaviors were studied in the frequency range of 2-18 GHz. The CoNi-C composites showed the best microwave absorbing performances compared to those of Co-C and Ni-C. The maximum reflection loss of the CoNi-C nanocomposites can reach -50.2 dB at 7.7 GHz with samples of 4 mm in thickness, better than that of the Ni-C composites, while the Co-C composites showed almost no absorption at all. The absorption mechanism of the three absorbents was also discussed.

[Regulations of sickness certification as a factor for increased health care utilization in Germany].

PubMed

Herrmann, Wolfram J; Haarmann, Alexander; Bærheim, Anders

2015-01-01

In Germany, utilization of ambulatory health care is high compared to other countries. Classical models of health care utilization cannot sufficiently explain these differences. The aim of this study was to explore relevant factors which can explain the higher health care utilization in Germany. In this article, we focus on regulations regarding sickness certification as a potential factor. An explorative qualitative study design. We conducted episodic interviews with 20 patients in Germany and 20 patients in Norway and participant observation in four primary care practices each. Additionally, we conducted a context analysis of relevant health care system related factors which emerged during the study. Qualitative data analysis was done by thematic coding in the framework of grounded theory. The need for a sickness certificate was an important reason for encounter in Germany, especially regarding minor illnesses. Sickness certification is a societal topic. GPs play a double role regarding sickness certification, both as the patients' advocate and as an expert witness for social security services. In Norway, longer periods of self-administered sickness certification and more differentiated possibilities of sickness certification have been introduced successfully. Our results point to regulations regarding sickness certification as a relevant factor for higher health care utilization in Germany. In pilot studies, the effect of extended self-certification of sickness and part-time sickness certification should be further assessed. Copyright © 2015. Published by Elsevier GmbH.

Social and Environmental Impacts of Forest Management Certification in Indonesia

PubMed Central

Miteva, Daniela A.; Loucks, Colby J.; Pattanayak, Subhrendu K.

2015-01-01

In response to unsustainable timber production in tropical forest concessions, voluntary forest management certification programs such as the Forest Stewardship Council (FSC) have been introduced to improve environmental, social, and economic performance over existing management practices. However, despite the proliferation of forest certification over the past two decades, few studies have evaluated its effectiveness. Using temporally and spatially explicit village-level data on environmental and socio-economic indicators in Kalimantan (Indonesia), we evaluate the performance of the FSC-certified timber concessions compared to non-certified logging concessions. Employing triple difference matching estimators, we find that between 2000 and 2008 FSC reduced aggregate deforestation by 5 percentage points and the incidence of air pollution by 31%. It had no statistically significant impacts on fire incidence or core areas, but increased forest perforation by 4 km2 on average. In addition, we find that FSC reduced firewood dependence (by 33%), respiratory infections (by 32%) and malnutrition (by 1 person) on average. By conducting a rigorous statistical evaluation of FSC certification in a biodiversity hotspot such as Indonesia, we provide a reference point and offer methodological and data lessons that could aid the design of ongoing and future evaluations of a potentially critical conservation policy. PMID:26132491

Optical testing of the LSST combined primary/tertiary mirror

NASA Astrophysics Data System (ADS)

Tuell, Michael T.; Martin, Hubert M.; Burge, James H.; Gressler, William J.; Zhao, Chunyu

2010-07-01

The Large Synoptic Survey Telescope (LSST) utilizes a three-mirror design in which the primary (M1) and tertiary (M3) mirrors are two concentric aspheric surfaces on one monolithic substrate. The substrate material is Ohara E6 borosilicate glass, in a honeycomb sandwich configuration, currently in production at The University of Arizona's Steward Observatory Mirror Lab. In addition to the normal requirements for smooth surfaces of the appropriate prescriptions, the alignment of the two surfaces must be accurately measured and controlled in the production lab. Both the pointing and centration of the two optical axes are important parameters, in addition to the axial spacing of the two vertices. This paper describes the basic metrology systems for each surface, with particular attention to the alignment of the two surfaces. These surfaces are aspheric enough to require null correctors for each wavefront. Both M1 and M3 are concave surfaces with both non-zero conic constants and higher-order terms (6th order for M1 and both 6th and 8th orders for M3). M1 is hyperboloidal and can utilize a standard Offner null corrector. M3 is an oblate ellipsoid, so has positive spherical aberration. We have chosen to place a phase-etched computer-generated hologram (CGH) between the mirror surface and the center-of-curvature (CoC), whereas the M1 null lens is beyond the CoC. One relatively new metrology tool is the laser tracker, which is relied upon to measure the alignment and spacings. A separate laser tracker system will be used to measure both surfaces during loose abrasive grinding and initial polishing.

77 FR 68196 - Notice of Applications for Certificates of Public Convenience and Necessity and Foreign Air...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-15

... carrier permit to enable GSS, consistent with the open skies, U.S.-European Union (``EU'') Air Transport... point or points behind any Member State of the European Union, via any point or points in any Member... European Union carriers in the future. GSS also requests (i) exemption authority, to the extent necessary...

75 FR 39324 - Notice of Applications for Certificates of Public Convenience and Necessity and Foreign Air...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-08

... foreign air transportation of persons, property and mail between a point or points in the European Community and the Member States of the European Union, and a point or points in the United States, to the... community and the Member States of the European Union. Docket Number: DOT-OST-2010-0150. Date Filed: June 9...

Photographic copy of Mr. T. L. Macon’s July 23, 1872 ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Photographic copy of Mr. T. L. Macon’s July 23, 1872 stockholder’s certificate no. 109 in the Public Belt Railroad Association of New Orleans, Louisiana. Original certificate located in the New Orleans Public Belt Railroad administrative offices at 5100 Jefferson Highway, Jefferson, LA 70123. MR. T. L. MACON’S JULY 23, 1872 STOCKHOLDER’S CERTIFICATE NO. 109 IN THE PUBLIC BELT RAILROAD ASSOCIATION OF NEW ORLEANS, LOUISIANA. - Huey P. Long Bridge, Spanning Mississippi River approximately midway between nine & twelve mile points upstream from & west of New Orleans, Jefferson, Jefferson Parish, LA

A miniature high-temperature fixed point for self-validation of type C thermocouples

NASA Astrophysics Data System (ADS)

Ongrai, O.; Pearce, J. V.; Machin, G.; Sweeney, S. J.

2011-10-01

Reliable high-temperature (>1500 °C) measurement is crucial for a wide range of industrial processes as well as specialized applications, e.g. aerospace. The most common type of sensor used for high-temperature measurement is the thermocouple. At and above 1500 °C, tungsten-rhenium (W-Re) thermocouples are the most commonly used temperature sensors due to their utility up to 2300 °C. However, the achievable accuracy of W-Re thermocouples is seriously limited by the effects of their inhomogeneity, drift and hysteresis. Furthermore, due to their embrittlement at high temperature, the removal of these thermocouples from environments such as nuclear power plants or materials processing furnaces for recalibration is generally not possible. Even if removal for recalibration were possible, this would be of, at best, very limited use due to large inhomogeneity effects. Ideally, these thermocouples require some mechanism to monitor their drift in situ. In this study, we describe a miniature Co-C eutectic fixed-point cell to evaluate the stability of type C (W5%Re/W26%Re) thermocouples by means of in situ calibration.

Coupling effect of topological states and Chern insulators in two-dimensional triangular lattices

NASA Astrophysics Data System (ADS)

Zhang, Jiayong; Zhao, Bao; Xue, Yang; Zhou, Tong; Yang, Zhongqin

2018-03-01

We investigate topological states of two-dimensional (2D) triangular lattices with multiorbitals. Tight-binding model calculations of a 2D triangular lattice based on px and py orbitals exhibit very interesting doubly degenerate energy points at different positions (Γ and K /K' ) in momentum space, with quadratic non-Dirac and linear Dirac band dispersions, respectively. Counterintuitively, the system shows a global topologically trivial rather than nontrivial state with consideration of spin-orbit coupling due to the "destructive interference effect" between the topological states at the Γ and K /K' points. The topologically nontrivial state can emerge by introducing another set of triangular lattices to the system (bitriangular lattices) due to the breakdown of the interference effect. With first-principles calculations, we predict an intrinsic Chern insulating behavior (quantum anomalous Hall effect) in a family of the 2D triangular lattice metal-organic framework of Co(C21N3H15) (TPyB-Co) from this scheme. Our results provide a different path and theoretical guidance for the search for and design of new 2D topological quantum materials.

Droplet evaporation and spread on waxy and hairy leaves associated with type and concentration of adjuvants.

PubMed

Xu, Linyun; Zhu, Heping; Ozkan, H Erdal; Bagley, William E; Krause, Charles R

2011-07-01

Adjuvants can improve pesticide application efficiency and effectiveness. However, quantifications of the adjuvant-amended pesticide droplet actions on foliage, which could affect application efficiencies, are largely unknown. Droplet evaporation rates and spread on waxy or hairy leaves varied greatly with the adjuvant types tested. On waxy leaves, the wetted areas of droplets containing crop oil concentrate (COC) were significantly smaller than those containing modified seed oil (MSO), non-ionic surfactant (NIS) or oil surfactant blend (OSB), whereas the evaporation rates of COC-amended droplets were significantly higher. On hairy leaves, COC-amended droplets remained on top of the hairs without wetting the epidermis. When the relative concentration was 1.50, the wetted area of droplets with NIS was 9.2 times lower than that with MSO and 6.1 times lower than that with OSB. The wetted area increased as the adjuvant concentration increased. MSO- or OSB-amended droplets spread extensively on the hairy leaf surface until they were completely dried. These results demonstrated that the proper concentration of MSO, NIS or OSB in spray mixtures improved the homogeneity of spray coverage on both waxy and hairy leaf surfaces and could reduce pesticide use. This article is a US Government work and is in the public domain in the USA. Published 2011 by John Wiley & Sons, Ltd.

Effect of sericin supplementation during in vitro maturation on the maturation, fertilization and development of porcine oocytes.

PubMed

Do, L T K; Namula, Z; Luu, V V; Sato, Y; Taniguchi, M; Isobe, T; Kikuchi, K; Otoi, T

2014-04-01

This study aimed to examine the effects of sericin supplementation during in vitro oocyte maturation on the nuclear maturation, fertilization and development of porcine oocytes. Cumulus-oocyte complexes (COCs) were cultured in maturation medium supplemented with 0 (control), 0.1, 0.5, 1.0, 2.5 or 5.0% sericin and were then subjected to in vitro fertilization and embryo culture. More COCs matured with 1.0% sericin underwent germinal vesicle breakdown and reached metaphase II compared with the control COCs matured without sericin (p < 0.01). The proportions of oocytes with DNA-fragmented nuclei did not differ between the groups, regardless of the sericin level. The total fertilization rate of oocytes matured with 1.0% sericin was higher (p < 0.05) than that of oocytes matured with 0.1%, 2.5% and 5.0% sericin. Supplementation with more than 1.0% sericin decreased the DNA fragmentation index of the blastocysts compared with the control group (p < 0.05). However, the supplementation of the maturation medium with sericin had no beneficial effects on the cleavage, development to the blastocyst stage and the total cell number of the embryos. Our findings indicate that supplementation with 1.0% sericin during maturation culture may improve the nuclear maturation and the quality of the embryos but does not affect blastocyst formation. © 2014 Blackwell Verlag GmbH.

Dynamic behaviour of river colloidal and dissolved organic matter through cross-flow ultrafiltration system.

PubMed

Wilding, Andrew; Liu, Ruixia; Zhou, John L

2005-07-01

Through cross-flow filtration (CFF) with a 1-kDa regenerated cellulose Pellicon 2 module, the ultrafiltration characteristics of river organic matter from Longford Stream, UK, were investigated. The concentration of organic carbon (OC) in the retentate in the Longford Stream samples increased substantially with the concentration factor (cf), reaching approximately 40 mg/L at cf 15. The results of dissolved organic carbon (DOC) and colloidal organic carbon (COC) analysis, tracking the isolation of colloids from river waters, show that 2 mg/L of COC was present in those samples and good OC mass balance (77-101%) was achieved. Fluorescence measurements were carried out for the investigation of retentate and permeate behaviour of coloured dissolved organic materials (CDOM). The concentrations of CDOM in both the retentate and permeate increased with increasing cf, although CDOM were significantly more concentrated in the retentate. The permeation model expressing the correlation between log[CDOM] in the permeate and logcf was able to describe the permeation behaviour of CDOM in the river water with regression coefficients (r(2)) of 0.94 and 0.98. Dry weight analysis indicated that the levels of organic colloidal particles were from 49 to 71%, and between 29 and 51% of colloidal particles present were inorganic. COC as a percentage of DOC was found to be 10-16% for Longford Stream samples.

Differential modulatory effects of cocaine on marmoset monkey recognition memory.

PubMed

Melamed, Jonathan L; de Jesus, Fernando M; Aquino, Jéssica; Vannuchi, Clarissa R S; Duarte, Renata B M; Maior, Rafael S; Tomaz, Carlos; Barros, Marilia

2017-01-01

Acute and repeated exposure to cocaine alters the cognitive performance of humans and animals. How each administration schedule affects the same memory task has yet to be properly established in nonhuman primates. Therefore, we assessed the performance of marmoset monkeys in a spontaneous object-location (SOL) recognition memory task after acute and repeated exposure to cocaine (COC; 5mg/kg, ip). Two identical neutral stimuli were explored on the 10-min sample trial, after which preferential exploration of the displaced vs the stationary object was analyzed on the 10-min test trial. For the acute treatment, cocaine was given immediately after the sample presentation, and spatial recognition was then tested after a 24-h interval. For the repeated exposure schedule, daily cocaine injections were given on 7 consecutive days. After a 7-day drug-free period, the SOL task was carried out with a 10-min intertrial interval. When given acutely postsample, COC improved the marmosets' recognition memory, whereas it had a detrimental effect after the repeated exposure. Thus, depending on the administration schedule, COC exerted opposing effects on the marmosets' ability to recognize spatial changes. This agrees with recent studies in rodents and the recognition impairment seen in human addicts. Further studies related to the effects of cocaine's acute×prior drug history on the same cognitive domain are warranted. © 2017 Elsevier B.V. All rights reserved.

Phytoremedial Potential of Typha latifolia, Eichornia crassipes and Monochoria hastata found in Contaminated Water Bodies Across Ranchi City (India).

PubMed

Hazra, Moushumi; Avishek, Kirti; Pathak, Gopal

2015-01-01

Phytoremediation is an emerging technology that uses green plants (living machines) for removal of contaminants of concern (COC). These plant species have the potential to remove the COC, thereby restoring the original condition of soil or water environment. The present study focuses on assessing the heavy metals (COC) present in the contaminated water bodies of Ranchi city, Jharkhand, India. Phytoremedial potential of three plant species: Typha latifolia, Eichornia crassipes and Monochoria hastata were assessed in the present study. Heterogenous accumulation of metals was found in the three plant species. It was observed that the ratio of heavy metal concentration was different in different parts, i.e., shoots and roots. Positive results were also obtained for translocation factor of all species with minimum of 0.10 and maximum of 1. It was found experimentally that M. hastata has the maximum BFC for root as 4.32 and shoot as 2.70 (for Manganese). For T. latifolia, BCF of maximum was observed for root (163.5) and respective shoot 86.46 (for Iron), followed by 7.3 and 5.8 for root and shoot (for Manganese) respectively. E. crassipes was found to possess a maximum BCF of 278.6 (for Manganese and 151 (for Iron) and shoot as 142 (for Manganese) and 36.13 (for Iron).

Microporous Co@C Nanoparticles Prepared by Dealloying CoAl@C Precursors: Achieving Strong Wideband Microwave Absorption via Controlling Carbon Shell Thickness.

PubMed

Li, Da; Liao, Haoyan; Kikuchi, Hiroaki; Liu, Tong

2017-12-27

Excellent magnetic features make Co-based materials promising candidates as high-performance microwave absorbers. However, it is still a significant challenge for Co-based absorbers to possess high-intensity and broadband absorption simultaneously, owing to the lack of dielectric loss and impedance matching. Herein, microporous Co@C nanoparticles (NPs) with carbon shell thicknesses ranging from 1.8-4.9 nm have been successfully synthesized by dealloying CoAl@C precursors. All of the samples exhibit high microwave absorption performance. The microporous Co@C sample possessing a carbon shell of 1.8 nm exhibits the highest absorption intensity among these samples with a minimum reflection loss (RL) of -141.1 dB, whose absorption bandwidth for RL ≤ -10 dB is 7.3 GHz. As the thickness of the carbon shell increases, the absorption bandwidth of the NPs becomes wider. For the sample with the carbon shell thickness of 4.9 nm, the absorption bandwidth for RL ≤ -10 dB reaches a record high of 13.2 GHz. The outstanding microwave attenuation properties are attributed to the dielectric loss of the carbon shell, the magnetic loss of the Co core, and the cooperation of the core-shell structure and microporous morphology. The strong wideband microwave absorption of the carbon-coated microporous Co NPs highlights their potential applications in microwave absorbing systems.

Risk factors for recurrence of venous thromboembolism associated with the use of oral contraceptives.

PubMed

Vaillant-Roussel, Hélène; Ouchchane, Lemlih; Dauphin, Claire; Philippe, Pierre; Ruivard, Marc

2011-11-01

Combined oral contraceptives (COC) increase the risk of venous thromboembolism (VTE), but the risk of recurrent VTE is not precisely determined. In this retrospective cohort study, we sought the risk factors for recurrence after a first VTE that occurred in women taking COC. Time-to-event analysis was done with Kaplan-Meier estimates. In total, 172 patients were included (43% with pulmonary embolism): 82% had no other clinical risk factor for VTE. Among the 160 patients who stopped anticoagulation, the cumulative incidence of recurrent VTE was 5.1% after 1 year and 14.2% after 5 years. Significant factors associated with recurrence were renewed use of COC [hazard ratio (HR)=8.2 (2.1-32.2)], antiphospholipid syndrome [HR=4.1 (1.3-12.5)] and protein C deficiency or factor II G20210A [HR=2.7 (1.1-7)]. Pure-progestin contraception [HR=1.3 (0.5-3.0)] or factor V Leiden [HR=1.3 (0.5-3.4)] did not increase recurrence. Postsurgical VTE had a lower risk of recurrence [HR=0.1 (0.0-0.9)]. Further studies are warranted to determine whether testing for antiphospholipid syndrome, protein C deficiency or the factor II G20210A could modify the duration of anticoagulation. This study confirms the safety of pure-progestin contraception. Copyright © 2011 Elsevier Inc. All rights reserved.

Efficacy and tolerability of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol in a 24/4 regimen, in comparison to an oral contraceptive containing ethinylestradiol and drospirenone in a 21/7 regimen.

PubMed

Mansour, Diana; Verhoeven, Carole; Sommer, Werner; Weisberg, Edith; Taneepanichskul, Surasak; Melis, Gian Benedetto; Sundström-Poromaa, Inger; Korver, Tjeerd

2011-12-01

The primary objective was to assess the efficacy, cycle control and tolerability of a monophasic combined oral contraceptive (COC) containing nomegestrol acetate (NOMAC) and 17β-oestradiol (E2). Effects on acne were evaluated as a secondary objective. Results were compared to those of a COC containing drospirenone (DRSP) and ethinylestradiol (EE). Women (aged 18-50 years) were randomised to receive NOMAC/E2 (2.5 mg/1.5 mg) in a 24/4-day regimen (n=1591) or DRSP/EE (3 mg/30 μg) in a 21/7-day regimen (n=535) for 13 cycles. Estimated Pearl Indices for NOMAC/E2 and DRSP/EE were 0.38 and 0.81 in women aged≤35 years and 0.31 and 0.66 for all women (18-50 years), respectively. Scheduled withdrawal bleedings were shorter and lighter among users of NOMAC/E2 and were sometimes absent altogether. Intracyclic bleeding/spotting was infrequent in both groups, and decreased over time. Type and frequency of adverse events were similar to those typically reported for COCs. These data show that NOMAC/E2 provides high contraceptive efficacy with acceptable cycle control as well as an overall adverse event profile similar to that of DRSP/EE.

Redox Biology Final Examination 2016 | Center for Cancer Research

Cancer.gov

Numerous registrants have requested a certificate upon completion of the Redox Biology (RB) course. In order to obtain a certificate, you must answer 8 of the 12 questions below correctly. In the final examination, 1 question is derived from each of the 1-hour lectures. It is highly recommended that you have a copy of each PowerPoint presentation prior to taking the examination.

The Certification of Teachers' Language Competence in Quebec in French and English: Two Different Perspectives?

ERIC Educational Resources Information Center

Laurier, Michel; Baker, Beverly

2015-01-01

Language tools are reflections of the academic traditions of assessment developers, as well as the perceptions of language quality as held by a society. The certification of Quebec's teachers offers an interesting case in point: the Québec Government's "ministère de l'Éducation, du Loisir et du Sport" (MELS) requires that all students in…

Redox Biology Final Examination 2016 | Center for Cancer Research

Cancer.gov

Numerous registrants have requested a certificate upon completion of the Redox Biology (RB) course. In order to obtain a certificate, you must answer 8 of the 12 questions below correctly. In the final examination, 1 question is derived from each of the 1-hour lectures. It is highly recommended that you have a copy of each PowerPoint presentation prior to taking the

Development of a Professional Certification in Cancer Patient Education.

PubMed

Papadakos, Janet; D'souza, Anna; Masse, Adeline; Boyko, Susan; Clarke, Susan; Giuliani, Meredith; MacKinnon, Keira; McBain, Sarah; McCallum, Meg; MacVinnie, Jan; Papadakos, Tina

2018-04-19

Patient educators come into the field from diverse professional backgrounds and often lack training in how to teach and develop patient education resources since no formal patient education professional certification program exists. A professional certification program for patient educators would further define the professional scope of practice and reduce variability in performance. The purpose of this study was to (1) determine the level of interest among Canadian cancer patient educators in a patient education professional certification program and (2) determine the competencies to be included in the professional certification program. A 12-item survey was designed by executive members of the Canadian Chapter of the Cancer Patient Education Network. The survey included a list of competencies associated with patient education, and a 4-point Likert scale ranging from "slightly important" to "very important" was used to determine the rank of each competency. The survey was sent to 53 patient educators across Canada. Ninety-two percent of the patient educators are interested in a professional certification program. Patient educators indicated that competencies related to developing patient resources, collaboration, plain language expertise, and health literacy were of most importance. Patient educators support the development of a patient education professional certification program and endorsed the competencies proposed. This information provides the foundation for the creation of a professional certification program for cancer patient educators.

Theoretical analysis of factors controlling the nonalternating CO/C(2)H(4) copolymerization.

PubMed

Haras, Alicja; Michalak, Artur; Rieger, Bernhard; Ziegler, Tom

2005-06-22

A [P-O]Pd catalyst based on o-alkoxy derivatives of diphenylphosphinobenzene sulfonic acid (I) has recently been shown by Drent et al. to perform nonalternating CO/C(2)H(4) copolymerization with subsequent incorporation of ethylene units into the polyketone chain. The origin of the nonalternation is investigated in a theoretical study of I, where calculated activation barriers and reaction heats of all involved elementary steps are used to generate a complete kinetic model. The kinetic model is able to account for the observed productivity and degree of nonalternation as a function of temperature. Consistent with the energy changes obtained for the real catalyst model, the selectivity toward a nonalternating distribution of both comonomers appears to be mainly a result of a strong destabilization of the Pd-acyl complex.

[(S)-1-Carbamoylethyl]bis(dimethylglyoximato-kappa2N,N')[(S)-1-phenylethylamine]cobalt(III) and bis(dimethylglyoximato-kappa2N,N')[(R)-1-(N-methylcarbamoyl)ethyl][(R)-1-phenylethylamine]cobalt(III) monohydrate.

PubMed

Orisaku, Keiko Komori; Hagiwara, Mieko; Ohgo, Yoshiki; Arai, Yoshifusa; Ohgo, Yoshiaki

2005-04-01

The title complexes, [Co(C3H6NO)(C4H7N2O2)2(C8H11N)] and [Co(C4H8NO)(C4H7N2O2)2(C8H11N)].H2O, were resolved from [(RS)-1-carbamoylethyl]bis(dimethylglyoximato)[(S)-1-phenylethylamine]cobalt(III) and bis(dimethylglyoximato)[(RS)-1-(N-methylcarbamoyl)ethyl][(R)-1-phenylethylamine]cobalt(III), respectively, and their crystal structures were determined in order to reveal the absolute configuration of the major enantiomer produced in the photoisomerization of each series of 2-carbamoylethyl and 2-(N-methylcarbamoyl)ethyl cobaloxime complexes.

Corifollitropin alfa compared with follitropin beta in poor responders undergoing ICSI: a randomized controlled trial.

PubMed

Kolibianakis, E M; Venetis, C A; Bosdou, J K; Zepiridis, L; Chatzimeletiou, K; Makedos, A; Masouridou, S; Triantafillidis, S; Mitsoli, A; Tarlatzis, B C

2015-02-01

Does substituting 150 µg corifollitropin alfa for 450 IU follitropin beta during the first 7 days of ovarian stimulation in proven poor responders, result in retrieval of a non-inferior number (<1.5 fewer) of cumulus oocyte complexes (COCs)? A single s.c. dose of 150 µg corifollitropin alfa on the first day of ovarian stimulation, followed if necessary, from Day 8 onwards, with 450 IU of follitropin beta/day, is not inferior to daily doses of 450 IU follitropin beta. The 95% CI of the difference between medians in the number of oocytes retrieved was -1 to +1 within the safety margin of 1.5. Recent data from retrospective studies suggest that the use of corifollitropin alfa in poor responders is promising since it could simplify ovarian stimulation without compromising its outcome. Seventy-nine women with previous poor ovarian response undergoing ICSI treatment were enrolled in this open label, non-inferiority, randomized clinical trial (RCT). Inclusion criteria were: previous poor response to ovarian stimulation (≤4 COCs) after maximal stimulation, age <45 years, regular spontaneous menstrual cycle, body mass index: 18-32 kg/m(2) and basal follicle stimulating hormone ≤20 IU/l. On Day 2 of the menstrual cycle, patients were administered either a single s.c dose of 150 µg corifollitropin alfa (n = 40) or a fixed daily dose of 450 IU of follitropin beta (n = 39). In the corifollitropin alfa group, 450 IU of follitropin beta were administered from Day 8 of stimulation until the day of human chorionic gonadotrophin (hCG) administration, if necessary. To inhibit premature luteinizing hormone surge, the gonadotrophin releasing hormone antagonist ganirelix was used. Triggering of final oocyte maturation was performed using 250 µg of recombinant hCG, when at least two follicles reached 17 mm in mean diameter. The number of COCs retrieved was not statistically different between the corifollitropin alfa and the follitropin beta groups [Median 3 versus 2, 95% CI 2-4, 2-3, respectively, P = 0.26]. The 95% CI of the difference between medians in the number of oocytes retrieved was -1 to +1. A multivariable analysis adjusting for all the potential baseline differences confirmed this finding. No significant difference was observed regarding the probability of live birth between the corifollitropin alfa and the follitropin beta group (live birth per patient reaching oocyte retrieval: 7.9 versus 2.6%, respectively, difference +5.3%, 95% CI: -6.8 to +18.3). The present study was not powered to test a smaller difference (e.g. 1 COC) in terms of COCs retrieved as well as to show potential differences in the probability of pregnancy. Moreover, it would be interesting to assess whether the continuation of stimulation in the long acting FSH arm, where necessary, with 200 IU instead of 450 IU of follitropin beta would have altered the direction or the magnitude of the effect of the type of FSH, observed on the number of COCs retrieved. Corifollitropin alfa simplifies IVF treatment because it is administered in a GnRH antagonist protocol and replaces seven daily FSH injections with a single one of a long acting FSH without compromising the outcome. It could greatly reduce the burden of treatment for poor responders and this deserves further investigation. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

75 FR 6432 - Notice of Applications for Certificates of Public Convenience and Necessity and Foreign Air...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-09

... in the European Community and the Member States of the European Union, and a point or points in the... the European Community and the Member States of the European Union. Barbara J. Hairston, Supervisory...

75 FR 53015 - Notice of Applications for Certificates of Public Convenience and Necessity and Foreign Air...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-30

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78 FR 68134 - Certificates of Public Convenience and Necessity and Foreign Air Carrier Permits

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-13

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77 FR 37732 - Notice of Applications for Certificates of Public Convenience and Necessity and Foreign Air...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-22

... any Member State of the European Union via any point or points in any Member State and via... points in any member of the European Common Aviation Area; (iii) other charters; and (iv) transportation authorized by any additional route rights made available to European Community carriers in the future. HLE...

77 FR 32172 - Notice of Applications for Certificates of Public Convenience and Necessity and Foreign Air...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-31

... Member State of the European Union via any point or points in any Member State and via intermediate... points in any member of the European Common Aviation Area; (c) foreign scheduled and charter all-cargo... (d) transportation authorized by any additional route rights made available to European Community...

76 FR 38265 - Notice of Applications for Certificates of Public Convenience and Necessity and Foreign Air...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

... Member State of the European Union via any point or points in any Member State and via intermediate... points in any member of the European Common Aviation Area (``ECAA''); (c) other charters pursuant to the... available to European Community carriers in the future. Renee V. Wright, Program Manager, Docket Operations...

Managing aging effects on dry cask storage systems for extended long-term storage and transportation of used fuel - rev. 0

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

Chopra, O.K.; Diercks, D.; Fabian, R.

The cancellation of the Yucca Mountain repository program in the United States raises the prospect of extended long-term storage (i.e., >120 years) and deferred transportation of used fuel at operating and decommissioned nuclear power plant sites. Under U.S. federal regulations contained in Title 10 of the Code of Federal Regulations (CFR) 72.42, the initial license term for an Independent Spent Fuel Storage Installation (ISFSI) must not exceed 40 years from the date of issuance. Licenses may be renewed by the U.S. Nuclear Regulatory Commission (NRC) at the expiration of the license term upon application by the licensee for a periodmore » not to exceed 40 years. Application for ISFSI license renewals must include the following: (1) Time-limited aging analyses (TLAAs) that demonstrate that structures, systems, and components (SSCs) important to safety will continue to perform their intended function for the requested period of extended operation; and (2) a description of the aging management program (AMP) for management of issues associated with aging that could adversely affect SSCs important to safety. In addition, the application must also include design bases information as documented in the most recent updated final safety analysis report as required by 10 CFR 72.70. Information contained in previous applications, statements, or reports filed with the Commission under the license may be incorporated by reference provided that those references are clear and specific. The NRC has recently issued the Standard Review Plan (SRP) for renewal of used-fuel dry cask storage system (DCSS) licenses and Certificates of Compliance (CoCs), NUREG-1927, under which NRC may renew a specific license or a CoC for a term not to exceed 40 years. Both the license and the CoC renewal applications must contain revised technical requirements and operating conditions (fuel storage, surveillance and maintenance, and other requirements) for the ISFSI and DCSS that address aging effects that could affect the safe storage of the used fuel. The information contained in the license and CoC renewal applications will require NRC review to verify that the aging effects on the SSCs in DCSSs/ ISFSIs are adequately managed for the period of extended operation. To date, all of the ISFSIs located across the United States with more than 1,500 dry casks loaded with used fuel have initial license terms of 20 years; three ISFSIs (Surry, H.B. Robinson and Oconee) have received their renewed licenses for 20 years, and two other ISFSIs (Calvert Cliffs and Prairie Island) have applied for license renewal for 40 years. This report examines issues related to managing aging effects on the SSCs in DCSSs/ISFSIs for extended long-term storage and transportation of used fuels, following an approach similar to that of the Generic Aging Lessons Learned (GALL) report, NUREG-1801, for the aging management and license renewal of nuclear power plants. The report contains five chapters and an appendix on quality assurance for aging management programs for used-fuel dry storage systems. Chapter I of the report provides an overview of the ISFSI license renewal process based on 10 CFR 72 and the guidance provided in NUREG-1927. Chapter II contains definitions and terms for structures and components in DCSSs, materials, environments, aging effects, and aging mechanisms. Chapter III and Chapter IV contain generic TLAAs and AMPs, respectively, that have been developed for managing aging effects on the SSCs important to safety in the dry cask storage system designs described in Chapter V. The summary descriptions and tabulations of evaluations of AMPs and TLAAs for the SSCs that are important to safety in Chapter V include DCSS designs (i.e., NUHOMS{reg_sign}, HI-STORM 100, Transnuclear (TN) metal cask, NAC International S/T storage cask, ventilated storage cask (VSC-24), and the Westinghouse MC-10 metal dry storage cask) that have been and continue to be used by utilities across the country for dry storage of used fuel to date. The goal of this report is to help establish the technical basis for extended long-term storage and transportation of used fuel.« less

The impact of a male or female thrombotic family history on contraceptive counseling: a cohort study.

PubMed

van Vlijmen, E F W; Veeger, N J G M; Middeldorp, S; Hamulyák, K; Prins, M H; Kluin-Nelemans, H C; Meijer, K

2016-09-01

Essentials It is unknown if a male or female thrombotic family history influences risk in female relatives. We assessed thrombotic risk in female relatives of male and female patients with thrombosis. A hormonally related female thrombotic family history further increases risk in female relatives. This information could be important in counseling women on contraceptive options. Click to hear Prof. Rosendaal's perspective on venous thrombosis: etiology, pathogenesis, and prognosis Background Women from thrombophilic families have increased risk of venous thromboembolism (VTE), which increases further during oral contraceptive (COC) use and pregnancy-postpartum. Whether this additional risk differs between relatives of male and female patients, or is different when that female patient had a hormonally related VTE (during COC use/pregnancy), is unknown. Methods One thousand five female relatives of consecutive patients with VTE from a family-based cohort were retrospectively followed for incident VTE from ages 15 to 50, first VTE, or study inclusion. Absolute and relative VTE risks adjusted for factors of patients (sex, age) and relatives (thrombophilia, COC use, pregnancy) were estimated in relatives of female and male patients and in relatives of female patients with and without hormonally related VTE. Results Absolute risk in relatives of female (0.32 [95% confidence interval [CI] 0.23-0.43]) vs. male patients (0.39 [95% CI 0.28-0.53]) was comparable. However, the heterogeneity analysis of risk estimates suggested that in relatives of female vs. male patients, the contribution of pregnancy-postpartum (hazard ratio [HR] 11.6 [95% CI 6.3-21.3] vs. HR6.6 [95% CI 2.8-15.2]) and, to a lesser extent, COC use (HR3.6 [95% CI 1.8-7.1] vs. HR2.7 [95% CI 1.5-5.0]) to the VTE risk differs. Absolute risk was significantly higher in relatives of female patients with hormonally related VTE (0.43 [95% CI 0.3-0.6]) vs. relatives of female patients without hormonally related VTE (0.13 [95% CI 0.05-0.27]), HR3.28 [95% CI 1.5-7.9]). The higher contribution of pregnancy-postpartum and COC use to the VTE risk was mainly observed in relatives of patients with hormonally related VTE. Conclusions These findings suggest that a family history from a female patient, especially when VTE was hormonally related, may further increase VTE risk in her female relatives. This information could be important in counseling women on contraceptive options. © 2016 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Possibilities for discrimination between chewing of coca leaves and abuse of cocaine by hair analysis including hygrine, cuscohygrine, cinnamoylcocaine and cocaine metabolite/cocaine ratios.

PubMed

Rubio, Nelida Cristina; Hastedt, Martin; Gonzalez, Jorge; Pragst, Fritz

2015-01-01

Contrary to the illegal use of any form of manufactured cocaine, chewing of coca leaves and drinking of coca tea are allowed and are very common and socially integrated in several South American countries. Because of this different legal state, an analytical method for discrimination between use of coca leaves and abuse of processed cocaine preparations is required. In this study, the applicability of hair analysis for this purpose was examined. Hair samples from 26 Argentinean coca chewers and 22 German cocaine users were analysed for cocaine (COC), norcocaine (NC), benzoylecgonine (BE), ecgonine methyl ester (EME), cocaethylene (CE), cinnamoylcocaine (CIN), tropacocaine (TRO), cuscohygrine (CUS) and hygrine (HYG) by hydrophilic interaction liquid chromatography (HILIC) in combination with triplequad mass spectrometry (MS/MS) and hybrid quadrupole time-of-flight mass spectrometry (QTOF-MS). The following concentrations (range, median, ng/mg) were determined in hair of the coca chewers: COC 0.085-75.5, 17.0; NC 0.03-1.15, 0.12; BE 0.046-35.5, 6.1; EME 0.014-6.0, 0.66; CE 0.00-13.8, 0.38; CIN 0.005-16.8, 0.79; TRO 0.02-0.16, 0.023; CUS 0.026-26.7, 0.31. In lack of a reference substance, only qualitative data were obtained for HYG, and two metabolites of CUS were detected which were not found in hair of the cocaine users. For interpretation, the concentrations of the metabolites and of the coca alkaloids in relation to cocaine were statistically compared between coca chewers and cocaine users. By analysis of variance (ANOVA) significant differences were found for all analytes (α = 0.000 to 0.030) with the exception of TRO (α = 0.218). The ratios CUS/COC, CIN/COC and EME/COC appeared to be the most suitable criteria for discrimination between both groups with the means and medians 5-fold to 10-fold higher for coca chewers and a low overlap of the ranges between both groups. The same was qualitatively found for HYG. However, these criteria cannot exclude cocaine use in addition to coca chewing. In this regard screening for typical cutting agents can be helpful and led to the detection of levamisole (21×), lidocaine (6×) and paracetamol (3×) in the 22 samples from German cocaine users, whereas no levamisole, lidocaine (3×) and paracetamol (1×) were found in hair from the Argentinean coca chewers. These criteria have to be confirmed for South American cocaine consumers including smokers of coca paste and may be different because of different composition of the drug and other use habits.

10 CFR 72.158 - Control of special processes.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., and applicant for a CoC shall establish measures to ensure that special processes, including welding, heat treating, and nondestructive testing, are controlled and accomplished by qualified personnel using...

The ecological sustainability of tropical forest management: evaluation of the national forest management standards of Costa Rica and Nicaragua, with emphasis on the need for adaptive. management

Treesearch

Kathleen McGinleya; Bryan Fineganb

2003-01-01

From a conceptual point of view, national forest management standards in Latin American countries have progressed significantly in recent years.Examples include the Costa Rican Standards and Procedures for Sustainable Forest Management and Certification, developed by the National Commission for Forest Certification and in Nicaragua, the National Institute of Forestry...

78 FR 17389 - Texas Eastern Transmission, LP; Notice of Application for Certificate of Public Convenience and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-21

... Regulatory Commission an application under Sections 7(b) and 7(c) of the Natural Gas Act (NGA) for its... day from supply points in the Marcellus Shale region to delivery points in New York, New Jersey, Ohio...

77 FR 47691 - Notice of Applications for Certificates of Public Convenience and Necessity and Foreign Air...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-09

...: Application of Rizon Qatar Company W.L.L. (``Rizon Jet'') requesting a foreign air carrier permit to engage in... States and any point or points in Qatar. Rizon Jet also requests exemption authority to engage in the...

Cycle control with an extended-regimen oral contraceptive combining levonorgestrel and ethinyl estradiol that includes continuous low-dose ethinyl estradiol instead of the traditional hormone-free interval.

PubMed

Nappi, Rossella E; Lobo Abascal, Paloma; Hsieh, Jennifer; Micheletti, Marie-Christine

2017-01-01

To evaluate scheduled and unscheduled bleeding and spotting over 1 year of treatment with 91-day extended-regimen combined oral contraception (COC) providing continuous low-dose ethinyl estradiol (EE) in place of the traditional 7-day hormone-free interval (HFI). This post hoc analysis of a multicenter, open-label, 1-year, Phase 3 study of extended-regimen COC with 30 µg EE/150 µg levonorgestrel (LNG) for 84 days and EE 10 µg for 7 days included 799 sexually active, adult women who completed at least one 91-day cycle of therapy. Subjects recorded bleeding and spotting episodes daily using electronic diaries. Logistic regression analyses are reported as ORs with 95% CIs. There was a 10% increase (OR =1.102; 95% CI: 1.006-1.206) in the likelihood of reporting no scheduled bleeding for each additional 91-day cycle completed. From the third 91-day cycle, more than one fifth of women reported no scheduled bleeding (third cycle =23% [121/533]; fourth cycle =22% [97/446]). Among women who reported no scheduled bleeding at Cycle 1 (136/758 [18%]), ≥45% showed sustained lack of scheduled bleeding in later cycles. There were increases of 53% (OR =1.531; 95% CI: 1.393-1.683) and 31% (OR =1.307; 95% CI: 1.205-1.418) in the likelihood of reporting 0 to ≤6 days vs >6 days of unscheduled bleeding and spotting, respectively, for each additional 91-day cycle. By Cycle 2, more than 80% of women reported no unscheduled bleeding or ≤6 days of unscheduled bleeding during each 91-day cycle. Improved cycle control with decreased bleeding over time was shown during extended-regimen COC with 30 µg EE/150 µg LNG for 84 days and continuous low-dose EE instead of the traditional 7-day HFI. Women considering this regimen should be informed that those who complete at least one 91-day COC cycle will likely experience less bleeding/spotting in future cycles.

A liquid chromatography-tandem mass spectrometry method for the determination of cocaine and metabolites in blood and in dried blood spots collected from postmortem samples and evaluation of the stability over a 3-month period.

PubMed

Moretti, Matteo; Visonà, Silvia Damiana; Freni, Francesca; Tomaciello, Ilaria; Vignali, Claudia; Groppi, Angelo; Tajana, Luca; Osculati, Antonio Marco Maria; Morini, Luca

2018-05-04

The aims of this study were (1) to identify and quantify cocaine (COC), benzoylecgonine (BE), ecgonine methyl ester (EME), and cocaethylene (CE) in DBS; (2) to compare dried blood spots (DBSs) analytical results with the routine blood analyses; (3) to monitor analytes stability on DBS within a 3-month period. Eighty-five μL of blood from postmortem cases were put on a card for DBS analysis and kept in the dark, at room temperature. Samples were extracted through solid-phase extraction (SPE) cartridges and injected in the liquid chromatography-tandem mass spectrometry (LC-MS/MS) system. The analytical procedure is simple, sensitive, and specific. Limits of detection (LODs) and quantification (LOQs) were calculated at 1.0 and 5.0 ng/mL(g) for COC and CE, and at 0.5 and 2 ng/mL for EME and BE, respectively. Validation parameters fulfilled all the acceptance criteria. Fifty-five postmortem cases were evaluated. Eighteen cases were positive for COC (44-2456 ng/mL) and BE (228-4700 ng/mL), 12 for EME (92-1500 ng/mL), and 11 cases for CE (11-273 ng/mL). Stability was evaluated on 8 cases collected in the period January 2017-January 2018. For each case, 5 DBSs were collected at T0. Four DBSs were analyzed within the 4 following weeks and 1 sample was analyzed after 3 months. The concentrations on DBSs, stored at room temperature, always matched the ones obtained on blood samples kept at -20°C (<20% variation, both at T0 and after 3 months). BE and COC concentrations remained stable after a 3-month storage, EME concentrations slightly increased after 3 weeks in the 2 analyzed samples, while CE provided a less homogeneous stability depending on the sample. Copyright © 2018 John Wiley & Sons, Ltd.

Ovulatory effects of three oral contraceptive regimens: a randomized, open-label, descriptive trial.

PubMed

Seidman, Larry; Kroll, Robin; Howard, Brandon; Ricciotti, Nancy; Hsieh, Jennifer; Weiss, Herman

2015-06-01

This study describes ovarian activity suppression of a 21/7-active low-dose combined oral contraceptive (COC) regimen that included only ethinyl estradiol (EE) during the traditional hormone-free interval (HFI) and two commercially available 28-day regimens, a 24/4 and a 21/7 regimen. The randomized, open-label, parallel-group descriptive study was conducted at two US sites. Healthy, reproductive-aged women (n=146) were randomized to one of three groups for three consecutive 28-day cycles, as follows: treatment 1 (n=39 completed): 21/7-active COC [21 days of 150 mcg desogestrel (DSG)/20 mcg EE, followed by 7 days of 10 mcg EE (DSG/EE+7 days EE)], treatment 2 (n=39 completed): 24 days of 3mg drospirenone (DRSP)/20 mcg EE, followed by 4 placebo (PBO)-pill days (DRSP/EE+4 days PBO) and treatment 3 (n=42 completed): 21 days of 100 mcg levonorgestrel (LNG)/20 mcg EE, followed by 7 PBO-pill days (LNG/EE+7 days PBO). The primary outcome was ovarian activity suppression assessed by transvaginal ultrasound and serum hormone concentrations and classified using the Hoogland and Skouby (H/S) method. Ovarian activity rate (H/S grade 4 or 5) was low for all three treatments: 0% [95% confidence interval (CI) 0-2.8] for DSG/EE+7 days EE, 1% (95% CI 0.2-5.2) for DRSP/EE+4days PBO and 1% (95% CI 0-3.9) for LNG/EE+7 days PBO. All three treatments showed similar suppression of serum progesterone, 17β-estradiol, follicle-stimulating hormone and luteinizing hormone levels. The 21/7-active low-dose COC regimen (DSG/EE+7 days EE) showed ovarian activity suppression that was similar to the 24/4 (DRSP/EE+4 days PBO) and 21/7 (LNG/EE+7days PBO) regimens. The 21/7-active low-dose COC regimen (DSG/EE+7 days EE) that included only EE during the traditional HFI showed suppression of ovarian follicular activity that was similar to the 24/4 (DRSP/EE+4days PBO) and the 21/7 (LNG/EE+7 days PBO) comparator regimens. Copyright © 2015 Elsevier Inc. All rights reserved.

Drugs of abuse and alcohol consumption among different groups of population on the Greek Island of Lesvos through sewage-based epidemiology.

PubMed

Gatidou, Georgia; Kinyua, Juliet; van Nuijs, Alexander L N; Gracia-Lor, Emma; Castiglioni, Sara; Covaci, Adrian; Stasinakis, Athanasios S

2016-09-01

The occurrence of 22 drugs of abuse, their metabolites, and the alcohol metabolite ethyl sulphate was investigated in raw sewage samples collected during the non-touristic season from three sewage treatment plants (STPs), which serve different sizes and types of population in the Greek island of Lesvos. Using the sewage-based epidemiology approach, the consumption of these substances was estimated. Five target analytes, cocaine (COC), benzoylecgonine (BE), 3,4-methylenedioxymethamphetamine (MDMA), 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH) and ethyl sulphate (EtS) were detected at concentrations above their limit of quantification, whereas the rest eighteen target compounds were not detected. THC-COOH was detected in most of the samples with concentrations ranging between <20 and 90ngL(-1), followed by EtS (range <1700-12,243ngL(-1)). COC, BE, and MDMA were present only in the STP that serves Mytilene (the main city of the island), at mean concentrations of 3.9ngL(-1) for COC (95% CI: 1.7-6.1), 9.4ngL(-1) for BE (95% CI: -1.6-23) and 3.2ngL(-1) for MDMA (95% CI: 1.2-5.1). Back-calculations to an amount of used substance indicated more intense use of drugs among city population than rural and University population with average values of 9.5 and 1.2mgday(-1) per 1000 inhabitants for COC (95% CI: -1.43-20.4) and MDMA (95% CI: 0.52-1.85), respectively, and 2.8gday(-1) per 1000 inhabitants for tetrahydrocannabinol (THC) (95% CI: 2.4-3.1), the active ingredient of cannabis. Alcohol consumption was observed to be higher in the city population (5.4mL pure alcohol per day per inhabitant) than in the rural population (3.4mL pure alcohol per day per inhabitant), but the difference was not statistically significant. Consumption of THC differed significantly among the three STPs. Copyright © 2016 Elsevier B.V. All rights reserved.

Cumulus cell expansion and first polar body extrusion during in vitro oocyte maturation in relation to morphological and morphometric characteristics of the dromedary camel ovary.

PubMed

Mesbah, F; Kafi, M; Nili, H

2016-12-01

The morphological and morphometric characteristics of the ovary are fundamental properties for in vitro oocyte maturation. Nuclear maturation, including first polar body (1PB) extrusion, cytoplasmic maturation and cumulus cell (CC) expansion are the criteria for in vitro maturation (IVM) of oocyte. This study was designed to determine the effect of morphological and morphometric features of the ovary on CC expansion and 1PB extrusion during IVM of oocyte in the adult female dromedary camel. The weight, volume and three dimensions of ovaries from slaughtered dromedary camels and oocytes inside zona diameter and zona pellucida thickness were measured. The follicles were classified in regard to the size and oocytes according to their ooplasm appearance and CC compactness. Aspirated cumulus oocyte complexes (COCs) were incubated for 48 hr (with a 6-hr interval) in Hams-F10, and CC expansion and 1PB extrusion were assessed. Significant differences were seen in the shape, weight, volume and three dimensions of the ovaries between ≤4-year-old and >4-year-old dromedary camel (p < .5). Approximately, 95.82% of follicles were 2-4 mm in diameter. The mean (±SD) of inside zona diameter of the oocyte and zona pellucida thickness was 132.22 ± 13.8 and 14.64 ± 2.24 μm, respectively, in >4-year-old dromedary camel. The CC expansion and 1PB extrusion were seen in 86% and 21.88% of COCs, respectively. Age and sexual conditions of dromedary camel influence the morphological and morphometric characteristics of the ovary. Most COCs retrieved from 2-6 mm follicles are cultivable. The most slaughterhouse-derived COCs retrieved from 2-6 mm follicles of non-pregnant dromedary camels are excellent and good and yielding a most favourable diameter to achieve the developmental competence for IVM in an optimal time of 24-30 hr; the optimal time for CC expansion is 24-30 hr in this species. However, the CC expansion is a prerequisite process, but not sufficient for IVM. © 2016 Blackwell Verlag GmbH.

Rovibronically selected and resolved two-color laser photoionization and photoelectron study of cobalt carbide cation.

PubMed

Huang, Huang; Chang, Yih Chung; Luo, Zhihong; Shi, Xiaoyu; Lam, Chow-Shing; Lau, Kai-Chung; Ng, C Y

2013-03-07

We have conducted a two-color visible-ultraviolet (VIS-UV) resonance-enhanced laser photoionization efficiency and pulsed field ionization-photoelectron (PFI-PE) study of gaseous cobalt carbide (CoC) near its ionization onset in the total energy range of 61,200-64,510 cm(-1). The cold gaseous CoC sample was prepared by a laser ablation supersonically cooled beam source. By exciting CoC molecules thus generated to single N' rotational levels of the intermediate CoC∗((2)Σ(+); v') state using a VIS dye laser prior to UV laser photoionization, we have obtained N(+) rotationally resolved PFI-PE spectra for the CoC(+)(X(1)Σ(+); v(+) = 0 and 1) ion vibrational bands free from interference by impurity species except Co atoms produced in the ablation source. The rotationally selected and resolved PFI-PE spectra have made possible unambiguous rotational assignments, yielding accurate values for the adiabatic ionization energy of CoC(X(2)Σ(+)), IE(CoC) = 62,384.3 ± 0.6 cm(-1) (7.73467 ± 0.00007 eV), the vibrational frequency ωe (+) = 985.6 ± 0.6 cm(-1), the anharmonicity constant ωe (+)χe (+) = 6.3 ± 0.6 cm(-1), the rotational constants (Be (+) = 0.7196 ± 0.0005 cm(-1), αe (+) = 0.0056 ± 0.0008 cm(-1)), and the equilibrium bond length re (+) = 1.534 Å for CoC(+)(X(1)Σ(+)). The observation of the N(+) = 0 level in the PFI-PE measurement indicates that the CoC(+) ground state is of (1)Σ(+) symmetry. Large ΔN(+) = N(+) - N' changes up to 6 are observed for the photoionization transitions CoC(+)(X(1)Σ(+); v(+) = 0-2; N(+)) ← CoC∗((2)Σ(+); v'; N' = 6, 7, 8, and 9). The highly precise energetic and spectroscopic data obtained in the present study have served as a benchmark for testing theoretical predictions based on state-of-the-art ab initio quantum calculations at the CCSDTQ∕CBS level of theory as presented in the companion article.

Cycle control with an extended-regimen oral contraceptive combining levonorgestrel and ethinyl estradiol that includes continuous low-dose ethinyl estradiol instead of the traditional hormone-free interval

PubMed Central

Nappi, Rossella E; Lobo Abascal, Paloma; Hsieh, Jennifer; Micheletti, Marie-Christine

2017-01-01

Purpose To evaluate scheduled and unscheduled bleeding and spotting over 1 year of treatment with 91-day extended-regimen combined oral contraception (COC) providing continuous low-dose ethinyl estradiol (EE) in place of the traditional 7-day hormone-free interval (HFI). Patients and methods This post hoc analysis of a multicenter, open-label, 1-year, Phase 3 study of extended-regimen COC with 30 µg EE/150 µg levonorgestrel (LNG) for 84 days and EE 10 µg for 7 days included 799 sexually active, adult women who completed at least one 91-day cycle of therapy. Subjects recorded bleeding and spotting episodes daily using electronic diaries. Logistic regression analyses are reported as ORs with 95% CIs. Results There was a 10% increase (OR =1.102; 95% CI: 1.006–1.206) in the likelihood of reporting no scheduled bleeding for each additional 91-day cycle completed. From the third 91-day cycle, more than one fifth of women reported no scheduled bleeding (third cycle =23% [121/533]; fourth cycle =22% [97/446]). Among women who reported no scheduled bleeding at Cycle 1 (136/758 [18%]), ≥45% showed sustained lack of scheduled bleeding in later cycles. There were increases of 53% (OR =1.531; 95% CI: 1.393–1.683) and 31% (OR =1.307; 95% CI: 1.205–1.418) in the likelihood of reporting 0 to ≤6 days vs >6 days of unscheduled bleeding and spotting, respectively, for each additional 91-day cycle. By Cycle 2, more than 80% of women reported no unscheduled bleeding or ≤6 days of unscheduled bleeding during each 91-day cycle. Conclusion Improved cycle control with decreased bleeding over time was shown during extended-regimen COC with 30 µg EE/150 µg LNG for 84 days and continuous low-dose EE instead of the traditional 7-day HFI. Women considering this regimen should be informed that those who complete at least one 91-day COC cycle will likely experience less bleeding/spotting in future cycles. PMID:29042818

Nomegestrol acetate/17-beta estradiol: a review of efficacy, safety, and patient acceptability

PubMed Central

Akintomide, Hannat; Panicker, Sabeena

2015-01-01

Nomegestrol acetate (NOMAC) 2.5 mg with 17-beta estradiol (E2) 1.5 mg is a new combined oral contraceptive (COC) formulation and is the first monophasic E2 pill to be marketed, having been licensed for use in Europe in 2011. It is available to be taken daily in a regimen of 24 active pills followed by four placebo pills. NOMAC is a highly selective 19-nor progestogen derivative with specific binding to progesterone receptors, anti-estrogenic activity and no androgenic, mineralocorticoid nor glucocorticoid effects. E2 is an estrogen that is identical to endogenous estrogen. While it has been in use for only a short period of time, current evidence suggests that NOMAC/E2 is just as effective, safe, and acceptable as existing COC preparations. Two large Phase III trials conducted in the Americas and across Europe, Australia, and Asia showed lower cumulative pregnancy rates in the NOMAC/E2 groups compared to the drospirenone (DRSP) 3 mg in combination with ethinyl estradiol (EE) 30 µg (DRSP/EE) groups but this difference was not statistically significant. NOMAC/E2 exhibits a good safety profile and has less effects on cardiovascular risk, hemostatic, metabolic, and endocrine factors in comparison to COCs containing EE in combination with levonorgestrel (LNG) or DRSP. NOMAC/E2 has also been found to cause less breast cell proliferation when compared to E2 alone and has some anti-proliferative effect on human breast cancer cells. NOMAC/E2 is considered acceptable as its compliance, continuation rates, and bleeding patterns were similar to COCs containing DRSP/EE and LNG 150 µg combined with EE 30 µg or LNG 100 µg combined with EE 20 µg (LNG/EE). However, discontinuation was found to be slightly higher in the NOMAC/E2 groups in the two large Phase III trials comparing NOMAC/E2 use with DRSP/EE. As the scientific literature has limited information on NOMAC/E2, further experience with NOMAC/E2 is required. PMID:29386925

10 CFR 72.158 - Control of special processes.

Code of Federal Regulations, 2013 CFR

2013-01-01

... NUCLEAR FUEL, HIGH-LEVEL RADIOACTIVE WASTE, AND REACTOR-RELATED GREATER THAN CLASS C WASTE Quality..., and applicant for a CoC shall establish measures to ensure that special processes, including welding...