Development of an integrated tobacco endgame strategy.

PubMed

van der Eijk, Yvette

2015-07-01

In recent years, various tobacco 'endgame' strategies have been suggested as a means to phase out tobacco consumption. Using country examples, this paper discusses three potential strategies: replacing cigarettes with alternative products (harm reduction), denying tobacco sales to people born after a certain year (the tobacco-free generation proposal), and further implementing measures based on the WHO Framework Convention for Tobacco Control (FCTC) treaty. It is argued that all strategies have potential issues that could be avoided by combining them into an integrated, sequential endgame that, first, using measures recommended in the WHO FCTC, creates a climate that facilitates the phasing out of cigarettes; second, implements a generational phase out of cigarette sales; and third, simultaneously permits the regulated use of alternative nicotine products. Thus, integrating ideas from various endgame strategies will result in a more effective, resilient tobacco endgame policy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Pulmonary infection by Yersinia pestis rapidly establishes a permissive environment for microbial proliferation.

PubMed

Price, Paul A; Jin, Jianping; Goldman, William E

2012-02-21

Disease progression of primary pneumonic plague is biphasic, consisting of a preinflammatory and a proinflammatory phase. During the long preinflammatory phase, bacteria replicate to high levels, seemingly uninhibited by normal pulmonary defenses. In a coinfection model of pneumonic plague, it appears that Yersinia pestis quickly creates a localized, dominant anti-inflammatory state that allows for the survival and rapid growth of both itself and normally avirulent organisms. Yersinia pseudotuberculosis, the relatively recent progenitor of Y. pestis, shows no similar trans-complementation effect, which is unprecedented among other respiratory pathogens. We demonstrate that the effectors secreted by the Ysc type III secretion system are necessary but not sufficient to mediate this apparent immunosuppression. Even an unbiased negative selection screen using a vast pool of Y. pestis mutants revealed no selection against any known virulence genes, demonstrating the transformation of the lung from a highly restrictive to a generally permissive environment during the preinflammatory phase of pneumonic plague.

An acute toxicology study with INGN 007, an oncolytic adenovirus vector, in mice and permissive Syrian hamsters; comparisons with wild-type Ad5 and a replication-defective adenovirus vector

PubMed Central

Lichtenstein, DL; Spencer, JF; Doronin, K; Patra, D; Meyer, JM; Shashkova, EV; Kuppuswamy, M; Dhar, D; Thomas, MA; Tollefson, AE; Zumstein, LA; Wold, WSM; Toth, K

2012-01-01

Oncolytic (replication-competent) adenoviruses as anticancer agents provide new, promising tools to fight cancer. In support of a Phase I clinical trial, here we report safety data with INGN 007 (VRX-007), an oncolytic adenovirus with increased anti-tumor efficacy due to overexpression of the adenovirus-encoded ADP protein. Wild-type adenovirus type 5 (Ad5) and a replication-defective version of Ad5 were also studied as controls. A parallel study investigating the biodistribution of these viruses is described elsewhere in this issue. The toxicology experiments were conducted in two species, the Syrian hamster, which is permissive for INGN 007 and Ad5 replication and the poorly permissive mouse. The studies demonstrated that the safety profile of INGN 007 is similar to Ad5. Both viruses caused transient liver damage upon intravenous injection that resolved by 28 days post-infection. The No-Observable-Adverse-Effect-Level (NOAEL) for INGN 007 in hamsters was 3 × 1010 viral particles per kg. In hamsters, the replication-defective vector caused less toxicity, indicating that replication of Ad vectors in the host is an important factor in pathogenesis. With mice, INGN 007 and Ad5 caused toxicity comparable to the replication-defective adenovirus vector. Partially based on these results, the FDA granted permission to enter into a Phase I clinical trial with INGN 007. PMID:19197324

An acute toxicology study with INGN 007, an oncolytic adenovirus vector, in mice and permissive Syrian hamsters; comparisons with wild-type Ad5 and a replication-defective adenovirus vector.

PubMed

Lichtenstein, D L; Spencer, J F; Doronin, K; Patra, D; Meyer, J M; Shashkova, E V; Kuppuswamy, M; Dhar, D; Thomas, M A; Tollefson, A E; Zumstein, L A; Wold, W S M; Toth, K

2009-08-01

Oncolytic (replication-competent) adenoviruses as anticancer agents provide new, promising tools to fight cancer. In support of a Phase I clinical trial, here we report safety data with INGN 007 (VRX-007), an oncolytic adenovirus with increased anti-tumor efficacy due to overexpression of the adenovirus-encoded ADP protein. Wild-type adenovirus type 5 (Ad5) and a replication-defective version of Ad5 were also studied as controls. A parallel study investigating the biodistribution of these viruses is described elsewhere in this issue. The toxicology experiments were conducted in two species, the Syrian hamster, which is permissive for INGN 007 and Ad5 replication and the poorly permissive mouse. The studies demonstrated that the safety profile of INGN 007 is similar to Ad5. Both viruses caused transient liver damage upon intravenous injection that resolved by 28 days post-infection. The No-Observable-Adverse-Effect-Level (NOAEL) for INGN 007 in hamsters was 3 x 10(10) viral particles per kg. In hamsters, the replication-defective vector caused less toxicity, indicating that replication of Ad vectors in the host is an important factor in pathogenesis. With mice, INGN 007 and Ad5 caused toxicity comparable to the replication-defective adenovirus vector. Partially based on these results, the FDA granted permission to enter into a Phase I clinical trial with INGN 007.

Yeast multistress resistance and lag-phase characterisation during wine fermentation.

PubMed

Ferreira, David; Galeote, Virginie; Sanchez, Isabelle; Legras, Jean-Luc; Ortiz-Julien, Anne; Dequin, Sylvie

2017-09-01

Saccharomyces cerevisiae has been used to perform wine fermentation for several millennia due to its endurance and unmatched qualities. Nevertheless, at the moment of inoculation, wine yeasts must cope with specific stress factors that still challenge wine makers by slowing down or compromising the fermentation process. To better assess the role of genetic and environmental factors that govern multistress resistance during the wine fermentation lag phase, we used a factorial plan to characterise the individual and combined impact of relevant stress factors on eight S. cerevisiae and two non-S. cerevisiae wine yeast strains that are currently commercialised. The S. cerevisiae strains are very genetically diverse, belonging to the wine and flor groups, and frequently contain a previously described XVIVIII translocation that confers increased resistance to sulphites. We found that low temperature and osmotic stress substantially affected all strains, promoting considerably extended lag phases. SO2 addition had a partially temperature-dependent effect, whereas low phytosterol and thiamine concentrations impacted the lag phase in a strain-dependent manner. No major synergic effects of multistress were detected. The diversity of lag-phase durations and stress responses observed among wine strains offer new insights to better control this critical step of fermentation. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Statistical controversies in clinical research: requiem for the 3 + 3 design for phase I trials.

PubMed

Paoletti, X; Ezzalfani, M; Le Tourneau, C

2015-09-01

More than 95% of published phase I trials have used the 3 + 3 design to identify the dose to be recommended for phase II trials. However, the statistical community agrees on the limitations of the 3 + 3 design compared with model-based approaches. Moreover, the mechanisms of action of targeted agents strongly challenge the hypothesis that the maximum tolerated dose constitutes the optimal dose, and more outcomes including clinical and biological activity increasingly need to be taken into account to identify the optimal dose. We review key elements from clinical publications and from the statistical literature to show that the 3 + 3 design lacks the necessary flexibility to address the challenges of targeted agents. The design issues raised by expansion cohorts, new definitions of dose-limiting toxicity and trials of combinations are not easily addressed by the 3 + 3 design or its extensions. Alternative statistical proposals have been developed to make a better use of the complex data generated by phase I trials. Their applications require a close collaboration between all actors of early phase clinical trials. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Permissive tracts for sediment-hosted lead-zinc-silver deposits in the Islamic Republic of Mauritania (phase V, deliverable 73): Chapter J in Second projet de renforcement institutionnel du secteur minier de la République Islamique de Mauritanie (PRISM-II)

USGS Publications Warehouse

Mauk, Jeffrey L.

2015-01-01

Permissive tracts for SEDEX (sedimentary exhalative) deposits coincide with those for MVT deposits. However, the geodynamic setting of the Taoudeni Basin is unlike that of SEDEX ores elsewhere on Earth, and therefore the potential for this class of deposits must be rather low. SEDEX deposits occur along tectonically active, shale dominated passive margins or in intracontinental rift basins.

Spontaneous default mode network phase-locking moderates performance perceptions under stereotype threat.

PubMed

Forbes, Chad E; Leitner, Jordan B; Duran-Jordan, Kelly; Magerman, Adam B; Schmader, Toni; Allen, John J B

2015-07-01

This study assessed whether individual differences in self-oriented neural processing were associated with performance perceptions of minority students under stereotype threat. Resting electroencephalographic activity recorded in white and minority participants was used to predict later estimates of task errors and self-doubt on a presumed measure of intelligence. We assessed spontaneous phase-locking between dipole sources in left lateral parietal cortex (LPC), precuneus/posterior cingulate cortex (P/PCC), and medial prefrontal cortex (MPFC); three regions of the default mode network (DMN) that are integral for self-oriented processing. Results revealed that minorities with greater LPC-P/PCC phase-locking in the theta band reported more accurate error estimations. All individuals experienced less self-doubt to the extent they exhibited greater LPC-MPFC phase-locking in the alpha band but this effect was driven by minorities. Minorities also reported more self-doubt to the extent they overestimated errors. Findings reveal novel neural moderators of stereotype threat effects on subjective experience. Spontaneous synchronization between DMN regions may play a role in anticipatory coping mechanisms that buffer individuals from stereotype threat. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Noise characterization of oil and gas operations.

PubMed

Radtke, Cameron; Autenrieth, Daniel A; Lipsey, Tiffany; Brazile, William J

2017-08-01

In cooperation with The Colorado Oil and Gas Conservation Commission, researchers at Colorado State University performed area noise monitoring at 23 oil and gas sites throughout Northern Colorado. The goals of this study were to: (1) measure and compare the noise levels for the different phases of oil and gas development sites; (2) evaluate the effectiveness of noise barriers; and (3) determine if noise levels exceeded the Colorado Oil and Gas Conservation Commission noise limits. The four phases of oil and gas development include drilling, hydraulic fracturing, completion and production. Noise measurements were collected using the A- and C-weighted sound scales. Octave band analysis was also performed to characterize the frequency spectra of the noise measurements.  Noise measurements were collected using noise dosimeters and a hand-held sound-level meter at specified distances from the development sites in each cardinal direction. At 350 ft (107 m), drilling, hydraulic fracturing, and completion sites without noise barriers exceeded the maximum permissible noise levels for residential and commercial zones (55 dBA and 60 dBA, respectively). In addition, drilling and hydraulic fracturing sites with noise barriers exceeded the maximum permissible noise level for residential zones (55 dBA). However, during drilling, hydraulic fracturing, and completion operations, oil producers are allowed an exception to the noise permissible limits in that they only must comply with the industrial noise limit (80 dBA). It is stated in Rule 604.c.(2)A. that: "Operations involving pipeline or gas facility installation or maintenance, the use of a drilling rig, completion rig, workover rig, or stimulation is subject to the maximum permissible noise levels for industrial zones (80dBA)." [8] Production sites were within the Colorado Oil and Gas Conservation Commission permissible noise level criteria for all zones. At 350 ft (107 m) from the noise source, all drilling, hydraulic fracturing, and completion sites exceeded 65 dBC.  Current noise wall mitigation strategies reduced noise levels in both the A- and C-weighted scale measurements. However, this reduction in noise was not sufficient to reduce the noise below the residential permissible noise level (55 dBA).

Validated LC-MS-MS Method for Multiresidual Analysis of 13 Illicit Phenethylamines in Amniotic Fluid.

PubMed

Burrai, Lucia; Nieddu, Maria; Carta, Antonio; Trignano, Claudia; Sanna, Raimonda; Boatto, Gianpiero

2016-04-01

A multi-residue analytical method was developed for the determination in amniotic fluid (AF) of 13 illicit phenethylamines, including 12 compounds never investigated in this matrix before. Samples were subject to solid-phase extraction using; hydrophilic-lipophilic balance cartridges which gave good recoveries and low matrix effects on analysis of the extracts. The quantification was performed by liquid chromatography electrospray tandem mass spectrometry. The water-acetonitrile mobile phase containing 0.1% formic acid, used with a C18 reversed phase column, provided adequate separation, resolution and signal-to-noise ratio for the analytes and the internal standard. The final optimized method was validated according to international guidelines. A monitoring campaign to assess fetal exposure to these 13 substances of abuse has been performed on AF test samples obtained from pregnant women. All mothers (n = 194) reported no use of drugs of abuse during pregnancy, and this was confirmed by the analytical data. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Thin Layer Chromatographic Resolution of Some β-adrenolytics and a β2-Agonist Using Bovine Serum Albumin as Chiral Additive in Stationary Phase.

PubMed

Malik, Poonam; Bhushan, Ravi

2018-01-01

Direct enantiomeric resolution of commonly used five racemic β-adrenolytics, namely, bisoprolol, atenolol, propranolol, salbutamol and carvedilol has been achieved by thin layer chromatography using bovine serum albumin (BSA) as chiral additive in stationary phase. Successful resolution of the enantiomers of all racemic β-adrenolytics was achieved by use of different composition of simple organic solvents having no buffer or inorganic ions. The effect of variation in pH, temperature, amount of BSA as the additive, and composition of mobile phase on resolution was systematically studied. Spots were visualized in iodine vapors. Native enantiomers for each of the five analytes were isolated and identified and their elution order was determined. The limit of detection was found to be 0.7, 1.2, 0.84, 1.6 and 0.9 μg (per spot) for each enantiomer of bisoprolol, atenolol, propranolol, salbutamol and carvedilol, respectively. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Topical Review: Translating Translational Research in Behavioral Science.

PubMed

Hommel, Kevin A; Modi, Avani C; Piazza-Waggoner, Carrie; Myers, James D

2015-01-01

To present a model of translational research for behavioral science that communicates the role of behavioral research at each phase of translation. A task force identified gaps in knowledge regarding behavioral translational research processes and made recommendations regarding advancement of knowledge. A comprehensive model of translational behavioral research was developed. This model represents T1, T2, and T3 research activities, as well as Phase 1, 2, 3, and 4 clinical trials. Clinical illustrations of translational processes are also offered as support for the model. Behavioral science has struggled with defining a translational research model that effectively articulates each stage of translation and complements biomedical research. Our model defines key activities at each phase of translation from basic discovery to dissemination/implementation. This should be a starting point for communicating the role of behavioral science in translational research and a catalyst for better integration of biomedical and behavioral research. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pedestrian Safety Treatments for Signalized Intersections : Training Course Development

DOT National Transportation Integrated Search

2017-11-01

When drivers make left turns during a permissive turn phase, they must yield to pedestrians as well as oncoming through vehicles. Left-turning drivers sometimes overlook pedestrians in the crosswalk while watching the opposing intersection approach. ...

Development of a composite chiral stationary phase from BSA and β-cyclodextrin-bonded silica.

PubMed

Yao, Bixia; Yang, Xinmei; Guo, Lizhen; Kang, Shanshan; Weng, Wen

2014-01-01

A composite chiral stationary phase (CSP) derived from bovine serum albumin (BSA) and β-cyclodextrin (CD)-bonded silica was prepared. 2,4,6-Trichloro-1,3,5-triazine was used as a cross-linker. The obtained CSP was applied to the enantioseparation of tryptophan, hydrobenzoin, phenylalanine and mandelic acid. The influences of eluent pH value, organic modifier and column temperature on the retention and enantioseparation were discussed. Tryptophan and hydrobenzoin achieved excellent resolution on the composite CSP. For tryptophan, the highest selectivity, 2.79, was achieved with 1% of methanol at pH 8.0. For hydrobenzoin, the selectivity could reach 1.42. The chromatographic results were compared with that on β-CD-bonded or BSA-immobilized CSP. © The Author [2014]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cell cycle re-entry sensitizes podocytes to injury induced death.

PubMed

Hagen, Manuel; Pfister, Eva; Kosel, Andrea; Shankland, Stuart; Pippin, Jeffrey; Amann, Kerstin; Daniel, Christoph

2016-07-17

Podocytes are terminally differentiated renal cells, lacking the ability to regenerate by proliferation. However, during renal injury, podocytes re-enter into the cell cycle but fail to divide. Earlier studies suggested that re-entry into cell cycle results in loss of podocytes, but a direct evidence for this is lacking. Therefore, we established an in vitro model to test the consequences of re-entry into the cell cycle on podocyte survival. A mouse immortalized podocyte cell line was differentiated to non-permissive podocytes and stimulated with e.g. growth factors. Stimulated cells were analyzed for mRNA-expression or stained for cell cycle analysis using flow cytometry and immunocytofluorescence microscopy. After stimulation to re-entry into cell cycle, podocytes were stressed with puromycin aminonucleoside (PAN) and analyzed for survival. During permissive stage more than 40% of immortalized podocytes were in the S-phase. In contrast, S-phase in non-permissive differentiated podocytes was reduced to 5%. Treatment with b-FGF dose dependently induced re-entry into cell cycle increasing the number of podocytes in the S-phase to 10.7% at an optimal bFGF dosage of 10 ng/ml. Forty eight hours after stimulation with bFGF the number of bi-nucleated podocytes significantly increased. A secondary injury stimulus significantly reduced podocyte survival preferentially in bi-nucleated podocytes In conclusion, stimulation of podocytes using bFGF was able to induce re-entry of podocytes into the cell cycle and to sensitize the cells for cell death by secondary injuries. Therefore, this model is appropriate for testing new podocyte protective substances that can be used for therapy.

In vitro susceptibility of Sporothrix brasiliensis: Comparison of yeast and mycelial phases.

PubMed

Sanchotene, Karine Ortiz; Brandolt, Tchana Martinez; Klafke, Gabriel Baracy; Poester, Vanice Rodrigues; Xavier, Melissa Orzechowski

2017-11-01

Sporothrix brasiliensis has emerged as an important cause of sporotrichosis, particularly associated with feline and zoonotic cases. Owing to the paucity of data on antifungal activity against this species, the present study aimed to evaluate the in vitro susceptibility of clinical isolates of S. brasiliensis in the mycelial and yeast phases to itraconazole (ITZ), terbinafine (TRB), and amphotericin B (AMB). Thirty-five isolates from an outbreak of feline sporotrichosis in Southern Brazil were used. All of them were assessed in the yeast and filamentous phases using the broth microdilution technique in accordance with the respective reference protocols M27-A3 and M38-A2 of the Clinical and Laboratory Standards Institute (CLSI). In our study, TRB was the most active antifungal against both the filamentous and yeast phases, showing GM of the MIC of 0.343 μg/ml and 0.127 μg/ml, respectively. In the yeast phase, the GM of the MIC for TRB was significantly lower than that for both ITZ (P = .009) and AMB (P < .001). However, in the filamentous phase, the GM of the MIC for TRB was significantly lower than that of AMB (P < .001), but not different from that of ITZ (P = .091). AMB was the antifungal with the highest GM of the MIC for both phases (1.486 μg/ml for the filamentous phase and 0.660 μg/ml for the yeast). Our results may contribute to a better understanding of antifungal susceptibility profiles of clinical isolates of S. brasiliensis in the mycelial and yeast phases in further studies. © The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Hypertonic saline in the treatment of corneal jellyfish stings.

PubMed

Yu Yao, Hsin; Cho, Ta Hsiung; Lu, Ching Hsiang; Lin, Feng Chi; Horng, Chi Ting

2016-02-01

A 20-year-old male soldier was hit by the jellyfish. The ophthalmic examination revealed that epithelial keratitis and corneal oedema in the right eye. We prescribed 3% NaCl eyedrops and 0.3% Norfloxacin eyedrops in the treatment of the corneal jellyfish stings. Two weeks later, the cornea in the right eye healed. In this case report, 3% NaCl eyedrops was effective in the treatment of acute phase of jellyfish stings of the cornea. © International Society of Travel Medicine, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Identification and Quantification of Pesticides in Environmental Waters With Solid Phase Microextraction and Analysis Using Field-Portable Gas Chromatography-Mass Spectrometry

DTIC Science & Technology

2004-06-10

Microextraction and Analysis using Field-Portable Gas Chromatography-Mass Spectrometry Name of Candidate: CPT Michael J. Nack...and Analysis using Field-Portable Gas Chromatography-Mass Spectrometry Beyond brief excerpts is with the permission of the copyright owner, and...Pesticides in Environmental Waters with Solid Phase Microextraction and Analysis using Field-Portable Gas Chromatography-Mass Spectrometry

Simultaneous quantification of paracetamol, acetylsalicylic acid and papaverine with a validated HPLC method.

PubMed

Kalmár, Eva; Gyuricza, Anett; Kunos-Tóth, Erika; Szakonyi, Gerda; Dombi, György

2014-01-01

Combined drug products have the advantages of better patient compliance and possible synergic effects. The simultaneous application of several active ingredients at a time is therefore frequently chosen. However, the quantitative analysis of such medicines can be challenging. The aim of this study is to provide a validated method for the investigation of a multidose packed oral powder that contained acetylsalicylic acid, paracetamol and papaverine-HCl. Reversed-phase high-pressure liquid chromatography was used. The Agilent Zorbax SB-C18 column was found to be the most suitable of the three different stationary phases tested for the separation of the components of this sample. The key parameters in the method development (apart from the nature of the column) were the pH of the aqueous phase (set to 3.4) and the ratio of the organic (acetonitrile) and the aqueous (25 mM phosphate buffer) phases, which was varied from 7:93 (v/v) to 25:75 (v/v) in a linear gradient, preceded by an initial hold. The method was validated: linearity, precision (repeatability and intermediate precision), accuracy, specificity and robustness were all tested, and the results met the ICH guidelines. © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Improved pedestrian safety at signalized intersections operating the flashing yellow arrow.

DOT National Transportation Integrated Search

2013-04-01

In some jurisdictions, protected left-turn phasing has been replaced with the flashing yellow arrow (FYA) for : protected/permissive left turns (PPLTs) to reduce delay. However, it is important to have a thorough understanding of the : conflict betwe...

Early and late management of type B aortic dissection.

PubMed

Nienaber, Christoph A; Divchev, Dimitar; Palisch, Holger; Clough, Rachel E; Richartz, Barbara

2014-10-01

The management of type B aortic dissection is undergoing profound changes with timely TEVAR accepted as first-line strategy in the setting of complicated dissection; with recent technological advances and in experienced hands this intervention is considered safe and life-saving. With the ability to remodel the dissected aorta as a result of scaffolding even pre-emptive endovascular treatment is being considered and supported by long-term stability and often prevention of aneurysmal expansion. This insight and a growing number of silent risk conditions (resistant hypertension, partial false lumen thrombosis) may lower the threshold for TEVAR in asymptomatic patients in the subacute phase. In the chronic phase of a type B dissection patients are usually free of symptoms, however, with the expanding false lumen at risk of rupture. Advanced TEVAR options (including branches and fenestrations) are likely to be used more often than open surgical replacement of such aneurysmatic segment of the dissected aorta in that chronic phase. All dissection patients should be offered lifelong surveillance. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

European Healthy Cities evaluation: conceptual framework and methodology.

PubMed

de Leeuw, Evelyne; Green, Geoff; Dyakova, Mariana; Spanswick, Lucy; Palmer, Nicola

2015-06-01

This paper presents the methodology, programme logic and conceptual framework that drove the evaluation of the Fifth Phase of the WHO European Healthy Cities Network. Towards the end of the phase, 99 cities were designated progressively through the life of the phase (2009-14). The paper establishes the values, systems and aspirations that these cities sign up for, as foundations for the selection of methodology. We assert that a realist synthesis methodology, driven by a wide range of qualitative and quantitative methods, is the most appropriate perspective to address the wide geopolitical, demographic, population and health diversities of these cities. The paper outlines the rationale for a structured multiple case study approach, the deployment of a comprehensive questionnaire, data mining through existing databases including Eurostat and analysis of management information generation tools used throughout the period. Response rates were considered extremely high for this type of research. Non-response analyses are described, which show that data are representative for cities across the spectrum of diversity. This paper provides a foundation for further analysis on specific areas of interest presented in this supplement. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A randomized controlled Phase III trial comparing 2-weekly docetaxel combined with cisplatin plus fluorouracil (2-weekly DCF) with cisplatin plus fluorouracil (CF) in patients with metastatic or recurrent esophageal cancer: rationale, design and methods of Japan Clinical Oncology Group study JCOG1314 (MIRACLE study).

PubMed

Kataoka, Kozo; Tsushima, Takahiro; Mizusawa, Junki; Hironaka, Shuichi; Tsubosa, Yasuhiro; Kii, Takayuki; Shibuya, Yuichi; Chin, Keisho; Katayama, Hiroshi; Kato, Ken; Fukuda, Haruhiko; Kitagawa, Yuko

2015-05-01

Chemotherapy with cisplatin plus fluorouracil is the current standard treatment for metastatic or recurrent esophageal cancer. We have developed a 2-weekly docetaxel combined with CF regimen and conducted a Phase I/II trial for metastatic or recurrent esophageal cancer (JCOG0807). Promising efficacy and safety were shown in JCOG0807, and we have commenced a Phase III trial in September 2014 to confirm the superiority of 2-weekly DCF to CF for patients with metastatic or recurrent esophageal cancer. A total of 240 patients will be accrued from 41 Japanese institutions over a period of 4 years. The primary end point is overall survival. The secondary end points are progression-free survival, response rate and proportion of adverse events. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000015107 (http://www.umin.ac.jp/ctr/index.htm). © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cell cycle re-entry sensitizes podocytes to injury induced death

PubMed Central

Hagen, Manuel; Pfister, Eva; Kosel, Andrea; Shankland, Stuart; Pippin, Jeffrey; Amann, Kerstin; Daniel, Christoph

2016-01-01

ABSTRACT Podocytes are terminally differentiated renal cells, lacking the ability to regenerate by proliferation. However, during renal injury, podocytes re-enter into the cell cycle but fail to divide. Earlier studies suggested that re-entry into cell cycle results in loss of podocytes, but a direct evidence for this is lacking. Therefore, we established an in vitro model to test the consequences of re-entry into the cell cycle on podocyte survival. A mouse immortalized podocyte cell line was differentiated to non-permissive podocytes and stimulated with e.g. growth factors. Stimulated cells were analyzed for mRNA-expression or stained for cell cycle analysis using flow cytometry and immunocytofluorescence microscopy. After stimulation to re-entry into cell cycle, podocytes were stressed with puromycin aminonucleoside (PAN) and analyzed for survival. During permissive stage more than 40% of immortalized podocytes were in the S-phase. In contrast, S-phase in non-permissive differentiated podocytes was reduced to 5%. Treatment with b-FGF dose dependently induced re-entry into cell cycle increasing the number of podocytes in the S-phase to 10.7% at an optimal bFGF dosage of 10 ng/ml. Forty eight hours after stimulation with bFGF the number of bi-nucleated podocytes significantly increased. A secondary injury stimulus significantly reduced podocyte survival preferentially in bi-nucleated podocytes In conclusion, stimulation of podocytes using bFGF was able to induce re-entry of podocytes into the cell cycle and to sensitize the cells for cell death by secondary injuries. Therefore, this model is appropriate for testing new podocyte protective substances that can be used for therapy. PMID:27232327

Destruction of humic substances by pulsed electrical discharge

NASA Astrophysics Data System (ADS)

Lobanova, G. L.; Yurmazova, T. A.; Shiyan, L. N.; Machekhina, K. I.; Davidenko, M. A.

2017-01-01

Currently, the water recourses in the territory of Tomsk region are groundwater which is limited to the high concentration of iron and manganese ions and organic substances. These impurities present in water in different forms such as soluble salts ant the colloid forms. Therefore, the present work is a part of a continuations researcher of the processes in natural waters containing humic substances at the influence of pulsed electrical discharges in a layer of iron pellets. It is shown that the main stage of water purification process of humic substances during treatment by pulsed electric discharge in the layer of iron granules is a difficult process including several stages such as formation of iron oxyhydroxide colloid particles, sorption and coagulation with humic macromolecules substances, growth of particle dispersed phase and precipitation. The reason for the formation and coagulation of the dispersed phase is a different state of charge of the colloid particles (zeta potentials of (Fe (OH)3) is +8 mV, zeta potentials of (Humic substances) is -70 mV. The most intense permanganate oxidation reduction to the maximum permissible concentration occurs at the processing time equal to 10 seconds. The contact time of active erosion products with sodium humate is established and it equals to 1 hour. The value of permanganate oxidation achieves maximum permissible concentration during this time and iron concentration in solution achieves maximum permissible concentration after filtration.

Development and Validation of a Stability-indicating Reversed-phase UPLC-UV Method for the Assay of Imidacloprid and Estimation of its Related Compounds.

PubMed

Tian, Jingzhi; Rustum, Abu

2018-02-01

Imidacloprid is used as an active pharmaceutical ingredient (API) in veterinary drugs to control fleas and ticks for dogs and cats. Here we are reporting for the first time a validated stability-indicating reversed-phase UPLC-UV method for the assay of imidacloprid and estimation of its related compounds. The stability-indicating capability of this method has been demonstrated by a forced degradation study. All related compounds including processing impurities, imidacloprid API and degradates from stressed samples were well separated from each other. Structures of major degradates from forced degradation study were elucidated through UPLC-MS/MS and key degradation pathways were proposed from the proposed chemical structures of major degradates. The UPLC-UV method is carried out using an HSS T3 column (C18, 2.1 × 30 mm, 1.8 μm particle size) maintained at 30°C with mobile phase A (0.05% v/v of phosphoric acid in water) and mobile phase B (methanol/acetonitrile 75/25 v/v). Analytes are separated by a gradient elution and detected at 270 nm. The UPLC method is green and fast with only 6.5 min run time and about 3.5 ml mobile phase consumption for each sample analysis. The UPLC-UV method was validated according to ICH guidelines. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Employee Engagement Is Vital for the Successful Selection of a Total Laboratory Automation System.

PubMed

Yu, Hoi-Ying E; Wilkerson, Myra L

2017-11-08

To concretely outline a process for selecting a total laboratory automation system that connects clinical chemistry, hematology, and coagulation analyzers and to serve as a reference for other laboratories. In Phase I, a committee including the laboratory's directors and technologists conducted a review of 5 systems based on formal request for information process, site visits, and vendor presentations. We developed evaluation criteria and selected the 2 highest performing systems. In Phase II, we executed a detailed comparison of the 2 vendors based on cost, instrument layout, workflow design, and future potential. In addition to selecting a laboratory automation system, we used the process to ensure employee engagement in preparation for implementation. Selecting a total laboratory automation system is a complicated process. This paper provides practical guide in how a thorough selection process can be done with participation of key stakeholders. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Reinventing clinical trials: a review of innovative biomarker trial designs in cancer therapies.

PubMed

Lin, Ja-An; He, Pei

2015-06-01

Recently, new clinical trial designs involving biomarkers have been studied and proposed in cancer clinical research, in the hope of incorporating the rapid growing basic research into clinical practices. Journal articles related to various biomarkers and their role in cancer clinical trial, articles and books about statistical issues in trial design, and regulatory website, documents, and guidance for submission of targeted cancer therapies. The drug development process involves four phases. The confirmatory Phase III is essential in regulatory approval of a special treatment. Regulatory agency has restrictions on confirmatory trials 'using adaptive designs'. No rule of thumb to pick the most appropriate design for biomarker-related trials. Statistical issues to solve in new designs. Regulatory acceptance of the 'newly proposed trial designs'. Biomarker-related trial designs that can resolve the statistical issues and satisfy the regulatory requirement. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Simultaneous Determination of Potassium Sorbate, Sodium Benzoate, Quinoline Yellow and Sunset Yellow in Lemonades and Lemon Sauces by HPLC Using Experimental Design.

PubMed

Dinç Zor, Şule; Aşçı, Bürge; Aksu Dönmez, Özlem; Yıldırım Küçükkaraca, Dilek

2016-07-01

In this study, development and validation of a HPLC method was described for simultaneous determination of potassium sorbate, sodium benzoate, quinoline yellow and sunset yellow. A Box-Behnken design using three variables at three levels was employed to determine the optimum conditions of chromatographic separation: pH of mobile phase, 6.0-7.0; flow rate, 0.8-1.2 mL min(-1) and the ratio of mobile phase composed of a 0.025 M sodium acetate/acetic acid buffer, 80-90%. Resolution was chosen as a response. The optimized method was validated for linearity, the limits of detection and quantification, accuracy, precision and stability. All the validation parameters were within the acceptance range. The applicability of the developed method to the determination of these food additives in commercial lemonade and lemon sauce samples was successfully demonstrated. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Study of Separation and Identification of the Active Ingredients in Gardenia jasminoides Ellis Based on a Two-Dimensional Liquid Chromatography by Coupling Reversed Phase Liquid Chromatography and Hydrophilic Interaction Liquid Chromatography.

PubMed

Zhou, Xuan; Chen, Cen; Ye, Xiaolan; Song, Fenyun; Fan, Guorong; Wu, Fuhai

2017-01-01

In this paper, by coupling reversed phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC), a two-dimensional liquid chromatography system was developed for separation and identification of the active ingredients in Gardenia jasminoides Ellis (GJE). By applying the semi-preparative C18 column as the first dimension and the core-shell column as the second dimension, a total of 896 peaks of GJE were separated. Among the 896 peaks, 16 active ingredients including geniposide, gardenoside, gardoside, etc. were identified by mass spectrometry analysis. The results indicated that the proposed two-dimensional RPLC/HILIC system was an effective method for the analysis of GJE and might hold a high potential to become a useful tool for analysis of other complex mixtures. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Improved Method for the Qualitative Analyses of Palm Oil Carotenes Using UPLC.

PubMed

Ng, Mei Han; Choo, Yuen May

2016-04-01

Palm oil is the richest source of natural carotenes, comprising 500-700 ppm in crude palm oil (CPO). Its concentration is found to be much higher in oil extracted from palm-pressed fiber, a by-product from the milling of oil palm fruits. There are 11 types of carotenes in palm oil, excluding the cis/trans isomers of some of the carotenes. Qualitative separation of these individual carotenes is particularly useful for the identification and confirmation of different types of oil as the carotenes profile is unique to each type of vegetable oil. Previous studies on HPLC separation of the individual palm carotenes reported a total analyses time of up to 100 min using C30 stationary phase. In this study, the separation was completed in <5 min. The qualitative separation was successfully carried out using a commonly used stationary phase, C18. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Integrating research evidence and physical activity policy making-REPOPA project.

PubMed

Aro, Arja R; Bertram, Maja; Hämäläinen, Riitta-Maija; Van De Goor, Ien; Skovgaard, Thomas; Valente, Adriana; Castellani, Tommaso; Chereches, Razvan; Edwards, Nancy

2016-06-01

Evidence shows that regular physical activity is enhanced by supporting environment. Studies are needed to integrate research evidence into health enhancing, cross-sector physical activity (HEPA) policy making. This article presents the rationale, study design, measurement procedures and the initial results of the first phase of six European countries in a five-year research project (2011-2016), REsearch into POlicy to enhance Physical Activity (REPOPA). REPOPA is programmatic research; it consists of linked studies; the first phase studied the use of evidence in 21 policies in implementation to learn more in depth from the policy making process and carried out 86 qualitative stakeholder interviews. The second, ongoing phase builds on the central findings of the first phase in each country; it consists of two sets of interventions: game simulations to study cross-sector collaboration and organizational change processes in the use of evidence and locally tailored interventions to increase knowledge integration. The results of the first two study phases will be tested and validated among policy makers and other stakeholders in the third phase using a Delphi process. Initial results from the first project phase showed the lack of explicit evidence use in HEPA policy making. Facilitators and barriers of the evidence use were the availability of institutional resources and support but also networking between researchers and policy makers. REPOPA will increase understanding use of research evidence in different contexts; develop guidance and tools and establish sustainable structures such as networks and platforms between academics and policy makers across relevant sectors. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Development and validation of the knowledge and attitudes regarding antibiotics and resistance (KAAR-11) questionnaire for primary care physicians.

PubMed

López-Vázquez, Paula; Vázquez-Lago, Juan Manuel; Gonzalez-Gonzalez, Cristian; Piñeiro-Lamas, María; López-Durán, Ana; Herdeiro, Maria Teresa; Figueiras, Adolfo

2016-10-01

The aim of this study was to develop a novel, self-administered questionnaire to identify primary-care physicians' knowledge and attitudes regarding antibiotics and resistance (KAAR). The study population comprised primary care physicians. The study was conducted in five phases. Phase I consisted of a systematic review and qualitative focus-group study (n = 33 physicians), in which items were formulated so as to be measured on a continuous, visual analogue scale (VAS); in Phase II, content validation and face validity were evaluated by a panel of experts, which reformulated, added and deleted items; Phase III consisted of a pilot study on a population possessing similar characteristics (n = 15); in Phase IV, we analysed reliability by means of a test-retest study (n = 91) and calculated the intraclass correlation coefficients (ICCs); and in Phase V, we assessed construct validity by applying the known-groups technique, measuring the differences between contrasting groups of physicians formed according to antibiotic prescription quality indicators (group 1, n = 156 versus group 2, n = 191). Following Phases I and II, the questionnaire contained 16 knowledge and attitude items. Participants in the pilot study (Phase III) reported no difficulty. The test-retest study (Phase IV) showed that 11 of the 16 initial knowledge and attitude items yielded an ICC > 0.5, while analysis of known-groups validity (Phase V) showed that 13 of the 16 initial items which assessed knowledge and attitudes discriminated between physicians with good and bad indicators of antibiotics prescription. The final 11 item KAAR questionnaire appears to be valid, reliable and responsive. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Brain activation for spontaneous and explicit false belief tasks overlaps: new fMRI evidence on belief processing and violation of expectation.

PubMed

Bardi, Lara; Desmet, Charlotte; Nijhof, Annabel; Wiersema, Jan R; Brass, Marcel

2017-03-01

There is extensive discussion on whether spontaneous and explicit forms of ToM are based on the same cognitive/neural mechanisms or rather reflect qualitatively different processes. For the first time, we analyzed the BOLD signal for false belief processing by directly comparing spontaneous and explicit ToM task versions. In both versions, participants watched videos of a scene including an agent who acquires a true or false belief about the location of an object (belief formation phase). At the end of the movies (outcome phase), participants had to react to the presence of the object. During the belief formation phase, greater activity was found for false vs true belief trials in the right posterior parietal cortex. The ROI analysis of the right temporo-parietal junction (TPJ), confirmed this observation. Moreover, the anterior medial prefrontal cortex (aMPFC) was active during the outcome phase, being sensitive to violation of both the participant's and agent's expectations about the location of the object. Activity in the TPJ and aMPFC was not modulated by the spontaneous/explicit task. Overall, these data show that neural mechanisms for spontaneous and explicit ToM overlap. Interestingly, a dissociation between TPJ and aMPFC for belief tracking and outcome evaluation, respectively, was also found. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Tackling the social determinants of inequalities in health during Phase V of the Healthy Cities Project in Europe.

PubMed

Ritsatakis, Anna; Ostergren, Per-Olof; Webster, Premila

2015-06-01

The WHO European Healthy Cities Network has from its inception aimed at tackling inequalities in health. In carrying out an evaluation of Phase V of the project (2009-13), an attempt was made to examine how far the concept of equity in health is understood and accepted; whether cities had moved further from a disease/medical model to looking at the social determinants of inequalities in health; how far the HC project contributed to cities determining the extent and causes of inequalities in health; what efforts were made to tackle such inequalities and how far inequalities in health may have increased or decreased during Phase V. A broader range of resources was utilized for this evaluation than in previous phases of the project. These indicated that most cities were definitely looking at the broader determinants. Equality in health was better understood and had been included as a value in a range of city policies. This was facilitated by stronger involvement of the HC project in city planning processes. Although almost half the cities participating had prepared a City Health Profile, only few cities had the necessary local level data to monitor changes in inequalities in health. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A randomized phase II/III trial of perioperative chemotherapy with adriamycin plus ifosfamide versus gemcitabine plus docetaxel for high-grade soft tissue sarcoma: Japan Clinical Oncology Group Study JCOG1306.

PubMed

Kataoka, Kozo; Tanaka, Kazuhiro; Mizusawa, Junki; Kimura, Aya; Hiraga, Hiroaki; Kawai, Akira; Matsunobu, Tomoya; Matsumine, Akihiko; Araki, Nobuhito; Oda, Yoshinao; Fukuda, Haruhiko; Iwamoto, Yukihide

2014-08-01

A randomized Phase II/III trial was planned to commence in March 2014. Perioperative chemotherapy with adriamycin plus ifosfamide is the current standard treatment for T2bN0M0 high-grade non-round cell soft tissue sarcoma. The purpose of this study is to confirm the non-inferiority of perioperative chemotherapy with gemcitabine and docetaxel to adriamycin plus ifosfamide for patients with T2bN0M0 or any TN1M0 non-round cell soft tissue sarcoma in the extremities and body wall. A total of 140 patients will be accrued from 28 Japanese institutions over 6 years. The primary endpoint in the Phase II part is the proportion of completion of pre-operative chemotherapy without progressive disease and overall survival in the Phase III part. The secondary endpoints are progression-free survival, response rate of pre-operative chemotherapy, pathological response rate, proportion of preservation of diseased limbs, disease control rate and proportion of adverse events. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000013175 [http://www.umin.ac.jp/ctr/index.htm]. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Overexpression of acetyl-CoA synthetase in Saccharomyces cerevisiae increases acetic acid tolerance.

PubMed

Ding, Jun; Holzwarth, Garrett; Penner, Michael H; Patton-Vogt, Jana; Bakalinsky, Alan T

2015-01-01

Acetic acid-mediated inhibition of the fermentation of lignocellulose-derived sugars impedes development of plant biomass as a source of renewable ethanol. In order to overcome this inhibition, the capacity of Saccharomyces cerevisiae to synthesize acetyl-CoA from acetic acid was increased by overexpressing ACS2 encoding acetyl-coenzyme A synthetase. Overexpression of ACS2 resulted in higher resistance to acetic acid as measured by an increased growth rate and shorter lag phase relative to a wild-type control strain, suggesting that Acs2-mediated consumption of acetic acid during fermentation contributes to acetic acid detoxification. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Wide-range high-resolution transmission electron microscopy reveals morphological and distributional changes of endomembrane compartments during log to stationary transition of growth phase in tobacco BY-2 cells.

PubMed

Toyooka, Kiminori; Sato, Mayuko; Kutsuna, Natsumaro; Higaki, Takumi; Sawaki, Fumie; Wakazaki, Mayumi; Goto, Yumi; Hasezawa, Seiichiro; Nagata, Noriko; Matsuoka, Ken

2014-09-01

Rapid growth of plant cells by cell division and expansion requires an endomembrane trafficking system. The endomembrane compartments, such as the Golgi stacks, endosome and vesicles, are important in the synthesis and trafficking of cell wall materials during cell elongation. However, changes in the morphology, distribution and number of these compartments during the different stages of cell proliferation and differentiation have not yet been clarified. In this study, we examined these changes at the ultrastructural level in tobacco Bright yellow 2 (BY-2) cells during the log and stationary phases of growth. We analyzed images of the BY-2 cells prepared by the high-pressure freezing/freeze substitution technique with the aid of an auto-acquisition transmission electron microscope system. We quantified the distribution of secretory and endosomal compartments in longitudinal sections of whole cells by using wide-range gigapixel-class images obtained by merging thousands of transmission electron micrographs. During the log phase, all Golgi stacks were composed of several thick cisternae. Approximately 20 vesicle clusters (VCs), including the trans-Golgi network and secretory vesicle cluster, were observed throughout the cell. In the stationary-phase cells, Golgi stacks were thin with small cisternae, and only a few VCs were observed. Nearly the same number of multivesicular body and small high-density vesicles were observed in both the stationary and log phases. Results from electron microscopy and live fluorescence imaging indicate that the morphology and distribution of secretory-related compartments dramatically change when cells transition from log to stationary phases of growth. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Ocular and visual status among children in special schools in Wales: the burden of unrecognised visual impairment.

PubMed

Woodhouse, J Margaret; Davies, Nathan; McAvinchey, Aideen; Ryan, Barbara

2014-06-01

The high prevalence of visual defects among children with special needs is well reported and guidelines for vision screening are in place. However, recent research has suggested that vision care for such children is neglected. This study set out to evaluate the current status of vision screening and eye care in special schools in Wales. In phase 1, all 44 special schools in Wales received a questionnaire on current vision screening practices. In phase 2, full eye examinations were conducted with 173 pupils of five schools with no screening service; the pupils were aged 2-21 years. In phase 3, feedback about the service was obtained from all schools and from 15 parents whose children took part. In phase 1, vision screening was patchy and inconsistent among the 39 schools responding. In phase 2, there is a high proportion of pupils (42%) reporting no previous eye examination. Overall, 17% of the pupils in the five schools presented with low vision (WHO definition, poorer than 0.3 LogMAR), 50% needed a first-time or updated spectacle prescription and 51% had some ocular abnormality that was either sight-limiting or warranted action to prevent risk to sight. In phase 3, school staff and parents reported that school-based eye examinations were valuable and, for those children with previous experience, likely to be more successful than clinic-based or practice-based examinations for this particular population. There is an urgent need for a school-based optometric service for this vulnerable group of children and young people. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Isolation of Methoxyfuranocoumarins From Ammi majus by Centrifugal Partition Chromatography.

PubMed

Bartnik, Magdalena; Mazurek, Anna Katarzyna

2016-01-01

Pure methoxyfuranocoumarins were isolated from Ammi majus L. by use of low-pressure column chromatography (LPCC) followed by centrifugal partition chromatography (CPC). The concentrated petroleum ether extract from fruits of A. majus was fractionated on a silica gel column using a gradient of ethyl acetate in dichloromethane (0-80%, v/v). Coumarin-rich fractions were analyzed by thin-layer chromatography (TLC) and high-performance liquid chromatography with diode array detection (HPLC/DAD). Xanthotoxin (8-MOP) and isopimpinellin (isoP), structurally similar compounds, were isolated in one fraction (FR6). To avoid multistep and long-lasting TLC preparation, optimization of CPC conditions has been performed. In one run, an effective separation of 8-MOP and isoP was achieved. The two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (10 : 8 : 10 : 9; v/v) in an ascending mode (the aqueous phase was a stationary phase, and the organic phase was a mobile phase), with flow rate 3 mL/min and rotation speed 1,600 r.p.m., was used. The identification and high purities of isolated 8-MOP (98.7%) and isoP (100%) were confirmed by HPLC/DAD assay, when compared with standards. The developed CPC method could be applied to the effective isolation of 8-MOP and isoP from plant extracts. The high purity of obtained compounds makes possible further exploitation of these components in biological studies. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Development and Optimization of HPLC Analysis of Metronidazole, Diloxanide, Spiramycin and Cliquinol in Pharmaceutical Dosage Forms Using Experimental Design.

PubMed

Elkhoudary, Mahmoud M; Abdel Salam, Randa A; Hadad, Ghada M

2016-11-01

A new simple, sensitive, rapid and accurate gradient reversed-phase high-performance liquid chromatography with photodiode array detector (RP-HPLC-DAD) was developed and validated for simultaneous analysis of Metronidazole (MNZ), Spiramycin (SPY), Diloxanidefuroate (DIX) and Cliquinol (CLQ) using statistical experimental design. Initially, a resolution V fractional factorial design was used in order to screen five independent factors: the column temperature (°C), pH, phosphate buffer concentration (mM), flow rate (ml/min) and the initial fraction of mobile phase B (%). pH, flow rate and initial fraction of mobile phase B were identified as significant, using analysis of variance. The optimum conditions of separation determined with the aid of central composite design were: (1) initial mobile phase concentration: phosphate buffer/methanol (50/50, v/v), (2) phosphate buffer concentration (50 mM), (3) pH (4.72), (4) column temperature 30°C and (5) mobile phase flow rate (0.8 ml min -1 ). Excellent linearity was observed for all of the standard calibration curves, and the correlation coefficients were above 0.9999. Limits of detection for all of the analyzed compounds ranged between 0.02 and 0.11 μg ml -1 ; limits of quantitation ranged between 0.06 and 0.33 μg ml -1 The proposed method showed good prediction ability. The optimized method was validated according to ICH guidelines. Three commercially available tablets were analyzed showing good % recovery and %RSD. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

HPLC Determination of Esculin and Esculetin in Rat Plasma for Pharmacokinetic Studies.

PubMed

Rehman, Shaheed Ur; Kim, In Sook; Kang, Ki Sung; Yoo, Hye Hyun

2015-09-01

An optimized, sensitive and validated reversed-phase high-performance liquid chromatography (RP-HPLC) method with UV detection is described for simultaneous determination of esculin and its aglycone, esculetin, in rat plasma. After addition of internal standard (chrysin), plasma samples were pretreated by solid-phase extraction and introduced into the HPLC system. Analytes were separated on a RP C18 column with a mobile phase of 0.075% acetic acid in water (solvent A) and 90% acetonitrile in solvent A (solvent B) using gradient elution at a flow rate of 1.0 mL/min. The wavelength for UV detection was set at 338 nm. Calibration curves for esculin and esculetin were constructed over a range of 10-1,000 ng/mL. The developed method was found to be specific, precise and accurate. The method was successfully applied to study the pharmacokinetics of esculin and esculetin in rats. After oral administration of 120 mg/kg, the mean Cmax values were 340.3 and 316.5 ng/mL and the AUClast values were 377.3 and 1276.5 h ng/mL for esculin and esculetin, respectively. The bioavailability of esculin was calculated to be 0.62%. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Synchronisms and correlations of spring phenology between apical and lateral meristems in two boreal conifers.

PubMed

Antonucci, Serena; Rossi, Sergio; Deslauriers, Annie; Lombardi, Fabio; Marchetti, Marco; Tognetti, Roberto

2015-10-01

Phenological synchronisms between apical and lateral meristems could clarify some aspects related to the physiological relationships among the different organs of trees. This study correlated the phenological phases of bud development and xylem differentiation during spring 2010-14 in balsam fir (Abies balsamea Mill.) and black spruce [(Picea mariana Mill. (BSP)] of the Monts-Valin National Park (Quebec, Canada) by testing the hypothesis that bud development occurs after the reactivation of xylem growth. From May to September, we conducted weekly monitoring of xylem differentiation using microcores and bud development with direct observations on terminal branches. Synchronism between the beginning of bud development and xylem differentiation was found in both species with significant correlations between the phases of bud and xylem phenology. Degree-day sum was more appropriate in assessing the date of bud growth resumption, while thermal thresholds were more suitable for cambium phenology. Our results provide new knowledge on the dynamics of spring phenology and novel information on the synchronisms between two meristems in coniferous trees. The study demonstrates the importance of precisely defining the phases of bud development in order to correctly analyse the relationships with xylem phenology. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Utilization of Photochemically Induced Fluorescence Detection for HPLC Determination of Genotoxic Impurities in the Vortioxetine Manufacturing Process.

PubMed

Douša, Michal; Doubský, Jan; Srbek, Jan

2016-07-01

An analytical reversed-phase high-performance liquid chromatography (HPLC) method for the detection and quantitative determination of two genotoxic impurities at ppm level present in the vortioxetine manufacturing process is described. Applying the concept of threshold of toxicological concern, a limit of 75 ppm each for both genotoxic impurities was calculated based on the maximum daily dose of active pharmaceutical ingredients. The novel reversed-phase HPLC method with photochemically induced fluorescence detection was developed on XSELECT Charged Surface Hybrid Phenyl-Hexyl column using the mobile phase consisted a mixture of 10 mM ammonium formate pH 3.0 and acetonitrile. The elution was performed using an isocratic composition of 48:52 (v/v) at a flow rate of 1.0 mL/min. The photochemically induced fluorescence detection is based on the use of UV irradiation at 254 nm through measuring the fluorescence intensity at 300 nm and an excitation wavelength of 272 nm to produce fluorescent derivatives of both genotoxic impurities. The online photochemical conversion and detection is easily accomplished for two expected genotoxic impurities and provides a sufficiently low limit detection and quantification for the target analysis. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Phase I/randomized phase II study of afatinib, an irreversible ErbB family blocker, with or without protracted temozolomide in adults with recurrent glioblastoma.

PubMed

Reardon, David A; Nabors, Louis B; Mason, Warren P; Perry, James R; Shapiro, William; Kavan, Petr; Mathieu, David; Phuphanich, Surasak; Cseh, Agnieszka; Fu, Yali; Cong, Julie; Wind, Sven; Eisenstat, David D

2015-03-01

This phase I/II trial evaluated the maximum tolerated dose (MTD) and pharmacokinetics of afatinib plus temozolomide as well as the efficacy and safety of afatinib as monotherapy (A) or with temozolomide (AT) vs temozolomide monotherapy (T) in patients with recurrent glioblastoma (GBM). Phase I followed a traditional 3 + 3 dose-escalation design to determine MTD. Treatment cohorts were: afatinib 20, 40, and 50 mg/day (plus temozolomide 75 mg/m(2)/day for 21 days per 28-day cycle). In phase II, participants were randomized (stratified by age and KPS) to receive A, T or AT; A was dosed at 40 mg/day and T at 75 mg/m(2) for 21 of 28 days. Primary endpoint was progression-free survival rate at 6 months (PFS-6). Participants were treated until intolerable adverse events (AEs) or disease progression. Recommended phase II dose was 40 mg/day (A) + T based on safety data from phase I (n = 32). Most frequent AEs in phase II (n = 119) were diarrhea (71% [A], 82% [AT]) and rash (71% [A] and 69% [AT]). Afatinib and temozolomide pharmacokinetics were unaffected by coadministration. Independently assessed PFS-6 rate was 3% (A), 10% (AT), and 23% (T). Median PFS was longer in afatinib-treated participants with epidermal growth factor receptor (EFGR) vIII-positive tumors versus EGFRvIII-negative tumors. Best overall response included partial response in 1 (A), 2 (AT), and 4 (T) participants and stable disease in 14 (A), 14 (AT), and 21 (T) participants. Afatinib has a manageable safety profile but limited single-agent activity in unselected recurrent GBM patients. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A population-based approach for implementing change from opt-out to opt-in research permissions

PubMed Central

Oates, Jim C.; Shoaibi, Azza; Obeid, Jihad S.; Habrat, Melissa L.; Warren, Robert W.; Brady, Kathleen T.; Lenert, Leslie A.

2017-01-01

Due to recently proposed changes in the Common Rule regarding the collection of research preferences, there is an increased need for efficient methods to document opt-in research preferences at a population level. Previously, our institution developed an opt-out paper-based workflow that could not be utilized for research in a scalable fashion. This project was designed to demonstrate the feasibility of implementing an electronic health record (EHR)-based active opt-in research preferences program. The first phase of implementation required creating and disseminating a patient questionnaire through the EHR portal to populate discreet fields within the EHR indicating patients’ preferences for future research study contact (contact) and their willingness to allow anonymised use of excess tissue and fluid specimens (biobank). In the second phase, the questionnaire was presented within a clinic nurse intake workflow in an obstetrical clinic. These permissions were tabulated in registries for use by investigators for feasibility studies and recruitment. The registry was also used for research patient contact management using a new EHR encounter type to differentiate research from clinical encounters. The research permissions questionnaire was sent to 59,670 patients via the EHR portal. Within four months, 21,814 responses (75% willing to participate in biobanking, and 72% willing to be contacted for future research) were received. Each response was recorded within a patient portal encounter to enable longitudinal analysis of responses. We obtained a significantly lower positive response from the 264 females who completed the questionnaire in the obstetrical clinic (55% volunteers for biobank and 52% for contact). We demonstrate that it is possible to establish a research permissions registry using the EHR portal and clinic-based workflows. This patient-centric, population-based, opt-in approach documents preferences in the EHR, allowing linkage of these preferences to health record information. PMID:28441388

The role of health impact assessment in Phase V of the Healthy Cities European Network.

PubMed

Simos, Jean; Spanswick, Lucy; Palmer, Nicola; Christie, Derek

2015-06-01

Health impact assessment (HIA) is a prospective decision-making aid tool that aims to improve the quality of policies, programmes or projects through recommendations that promote health. It identifies how and through which pathways a decision can impact a wide range of health determinants and seeks to define the distribution of effects within populations, thereby raising the issue of equity. HIA was introduced to the WHO European Healthy Cities Network as one of its four core themes during the Phase IV (2004-08). Here we present an evaluation of the use of HIA during Phase V (2009-13), where HIA was linked with the overarching theme of health and health equity in all local policies and a requirement regarding capacity building. The evaluation was based on 10 case studies contributed by 9 Healthy Cities in five countries (France, Hungary, Italy, Spain and the UK). A Realist Evaluation framework was used to collect and aggregate data obtained through three methods: an HIA factors analysis, a case-study template analysis using Nvivo software and a detailed questionnaire. The main conclusion is that HIA significantly helps promote Health in All Policies (HiAP) and sustainability in Healthy Cities. It is recommended that all Healthy City candidates to Phase VI (2014-18) of the WHO Healthy Cities European Network effectively adopt HIA and HiAP. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

47 CFR 90.733 - Permissible operations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... benchmark for the construction of its land mobile system base stations as prescribed in § 90.725(a); and (2... first meet the requirement to construct its land mobile base station and place it in operation, or... chapter. (f) A Phase I non-nationwide licensee operating a paging base station, or a fixed station...

Electropolymerized fluorinated aniline-based fiber for headspace solid-phase microextraction and gas chromatographic determination of benzaldehyde in injectable pharmaceutical formulations.

PubMed

Mohammadi, Ali; Mohammadi, Somayeh; Bayandori Moghaddam, Abdolmajid; Masoumi, Vahideh; Walker, Roderick B

2014-10-01

In this study, a simple method was developed and validated to detect trace levels of benzaldehyde in injectable pharmaceutical formulations by solid-phase microextraction coupled with gas chromatography-flame ionization detector. Polyaniline was electrodeposited on a platinum wire in trifluoroacetic acid solvent by cyclic voltammetry technique. This fiber shows high thermal and mechanical stability and high performance in extraction of benzaldehyde. Extraction and desorption time and temperature, salt effect and gas chromatography parameters were optimized as key parameters. At the optimum conditions, the fiber shows good linearity between peak area ratio of benzaldehyde/3-chlorobenzaldehyde and benzaldehyde concentration in the range of 50-800 ng/mL with percent relative standard deviation values ranging from 0.75 to 8.64% (n = 3). The limits of quantitation and detection were 50 and 16 ng/mL, respectively. The method has the requisite selectivity, sensitivity, accuracy and precision to assay benzaldehyde in injectable pharmaceutical dosage forms. © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Liquid Chromatographic Analysis of α-Dicarbonyls Using Girard-T Reagent Derivatives.

PubMed

Lawrence, Glen D; Rahmat, Rozaiha; Makahleh, Ahmad; Saad, Bahruddin

2017-11-01

The measurement of α-dicarbonyls and other degradation products of sugars has become important in view of their toxicity. Although there are several methods used for their analysis, most require long reaction times to form UV absorbing or fluorescent derivatives and the nonpolar nature of commonly used derivatives necessitates relatively high concentrations of organic solvents for elution in reverse phase liquid chromatography. The present method describes the use of Girard-T reagent in a simple, one step derivatization of α-dicarbonyls and conjugated aldehydes and analysis using ion-pair reverse phase liquid chromatography. The limit of detection was in the range of 0.06-0.09 μM (4-12 ng/mL) for glyoxal, methylglyoxal, 3-deoxyglucosone and 5-hydroxymethylfurfural with good linear response and reproducibility using UV detection. The hydrazone derivatives were stable for several days in solution. The method was used to study degradation of several sugars and quantification of the target α-dicarbonyls and 5-hydroxymethylfurfural in several soft drinks. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Sex Hormones Coordinate Neutrophil Immunity in the Vagina by Controlling Chemokine Gradients.

PubMed

Lasarte, Sandra; Samaniego, Rafael; Salinas-Muñoz, Laura; Guia-Gonzalez, Mauriel A; Weiss, Linnea A; Mercader, Enrique; Ceballos-García, Elena; Navarro-González, Teresa; Moreno-Ochoa, Laura; Perez-Millan, Federico; Pion, Marjorie; Sanchez-Mateos, Paloma; Hidalgo, Andres; Muñoz-Fernandez, Maria A; Relloso, Miguel

2016-02-01

Estradiol-based contraceptives and hormonal replacement therapy predispose women to Candida albicans infections. Moreover, during the ovulatory phase (high estradiol), neutrophil numbers decrease in the vaginal lumen and increase during the luteal phase (high progesterone). Vaginal secretions contain chemokines that drive neutrophil migration into the lumen. However, their expression during the ovarian cycle or in response to hormonal treatments are controversial and their role in vaginal defense remains unknown.To investigate the transepithelial migration of neutrophils, we used adoptive transfer of Cxcr2(-/-) neutrophils and chemokine immunofluorescence quantitative analysis in response to C. albicans vaginal infection in the presence of hormones.Our data show that the Cxcl1/Cxcr2 axis drives neutrophil transepithelial migration into the vagina. Progesterone promotes the Cxcl1 gradient to favor neutrophil migration. Estradiol disrupts the Cxcl1 gradient and favors neutrophil arrest in the vaginal stroma; as a result, the vagina becomes more vulnerable to pathogens. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

MASS MEDIA COMMUNICATION OF EMERGENCY ISSUES AND COUNTERMEASURES IN A NUCLEAR ACCIDENT: FUKUSHIMA REPORTING IN EUROPEAN NEWSPAPERS.

PubMed

Gallego, Eduardo; Cantone, Marie Claire; Oughton, Deborah H; Perko, Tanja; Prezelj, Iztok; Tomkiv, Yevgeniya

2017-04-01

This paper presents the results of a large study of 1340 articles published by two major newspapers in six European countries (Belgium, Italy, Norway, Slovenia, Spain and Russia) in the first 2 months after the Fukushima Daiichi nuclear disaster. The focus of the analysis is on the application and overall impact of protective actions, both during the emergency phase and later, how the newspapers describe those actions, which differences were apparent between countries and what recommendations can be extracted in order to improve general communication about these issues. A clear lesson is that, even under uncertainty and recognising limitations, responsible authorities need to provide transparent, clear and understandable information to the public and the mass media right from the beginning of the early phase of any nuclear emergency. Clear, concise messages should be given. Mass media could play a key role in reassuring the public if the countermeasures are clearly explained. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Development of cell-cycle checkpoint therapy for solid tumors.

PubMed

Tamura, Kenji

2015-12-01

Cellular proliferation is tightly controlled by several cell-cycle checkpoint proteins. In cancer, the genes encoding these proteins are often disrupted and cause unrestrained cancer growth. The proteins are over-expressed in many malignancies; thus, they are potential targets for anti-cancer therapies. These proteins include cyclin-dependent kinase, checkpoint kinase, WEE1 kinase, aurora kinase and polo-like kinase. Cyclin-dependent kinase inhibitors are the most advanced cell-cycle checkpoint therapeutics available. For instance, palbociclib (PD0332991) is a first-in-class, oral, highly selective inhibitor of CDK4/6 and, in combination with letrozole (Phase II; PALOMA-1) or with fulvestrant (Phase III; PALOMA-3), it has significantly prolonged progression-free survival, in patients with metastatic estrogen receptor-positive, HER2-negative breast cancer, in comparison with that observed in patients using letrozole, or fulvestrant alone, respectively. In this review, we provide an overview of the current compounds available for cell-cycle checkpoint protein-directed therapy for solid tumors. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Electronic monitoring of medication adherence in early maintenance phase treatment for pediatric leukemia and lymphoma: identifying patterns of nonadherence.

PubMed

Rohan, Jennifer M; Drotar, Dennis; Alderfer, Melissa; Donewar, Crista Wetherington; Ewing, Linda; Katz, Ernest R; Muriel, Anna

2015-01-01

To describe patterns of treatment adherence to early maintenance phase therapy for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). Using an objective observational method (electronic monitoring), adherence was examined for 139 patients aged 7-19 years diagnosed with ALL or LBL across 6 centers. The mean adherence percentage was 86.2%. Adherence rates declined over the 1-month of follow-up to 83%. 3 linear trajectories of 6-mercaptopurine adherence were identified: (1) exemplary adherence (n = 99): Averaging nearly 100%; (2) deteriorating (n = 23): Adherence decreased from 100 to 60%; and (3) chronically poor adherence (n = 9): Averaging 40%. Adherence promotion interventions might be tailored to subgroups of patients who demonstrated problematic patterns of treatment adherence that could place them at risk for relapse. This research demonstrates the importance of using objective real-time measures of medication adherence for measuring and documenting adherence patterns. © The Author 2013. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Landsat maps (phase V, deliverable 60), ASTER maps (phase V, deliverable 62), ASTER_DEM maps (phase V, deliverable 63), and spectral remote sensing in support of PRISM-II mineral resource assessment project, Islamic Republic of Mauritania (phase V, deliverables 61 and 64): Chapter E in Second projet de renforcement institutionnel du secteur minier de la République Islamique de Mauritanie (PRISM-II)

USGS Publications Warehouse

Rockwell, Barnaby W.; Knepper, Daniel H.; Horton, John D.

2015-01-01

The image products derived from Landsat TM and ASTER data enable the delineation of mineral groups across wide areas based on color response. Guides are provided that allow users to interpret these colors as to mineral group occurrence over lithologic units and known deposits. This information can be extrapolated to other geologically permissive tracts for various deposit types in the search for similar mineralogic responses that may be indicative of concealed deposits.

Interactive tools for inpatient medication tracking: a multi-phase study with cardiothoracic surgery patients.

PubMed

Wilcox, Lauren; Woollen, Janet; Prey, Jennifer; Restaino, Susan; Bakken, Suzanne; Feiner, Steven; Sackeim, Alexander; Vawdrey, David K

2016-01-01

Prior studies of computing applications that support patients' medication knowledge and self-management offer valuable insights into effective application design, but do not address inpatient settings. This study is the first to explore the design and usefulness of patient-facing tools supporting inpatient medication management and tracking. We designed myNYP Inpatient, a custom personal health record application, through an iterative, user-centered approach. Medication-tracking tools in myNYP Inpatient include interactive views of home and hospital medication data and features for commenting on these data. In a two-phase pilot study, patients used the tools during cardiothoracic postoperative care at Columbia University Medical Center. In Phase One, we provided 20 patients with the application for 24-48 h and conducted a closing interview after this period. In Phase Two, we conducted semi-structured interviews with 12 patients and 5 clinical pharmacists who evaluated refinements to the tools based on the feedback received during Phase One. Patients reported that the medication-tracking tools were useful. During Phase One, 14 of the 20 participants used the tools actively, to review medication lists and log comments and questions about their medications. Patients' interview responses and audit logs revealed that they made frequent use of the hospital medications feature and found electronic reporting of questions and comments useful. We also uncovered important considerations for subsequent design of such tools. In Phase Two, the patients and pharmacists participating in the study confirmed the usability and usefulness of the refined tools. Inpatient medication-tracking tools, when designed to meet patients' needs, can play an important role in fostering patient participation in their own care and patient-provider communication during a hospital stay. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Treatment of FBSS Low Back Pain with a Novel Percutaneous DRG Wireless Stimulator: Pilot and Feasibility Study.

PubMed

Weiner, Richard L; Yeung, Anthony; Montes Garcia, Carlos; Tyler Perryman, Laura; Speck, Benjamin

2016-10-01

Test a miniaturized neurostimulator transforaminally placed at the dorsal root ganglion (DRG) and evaluate the device's safety and efficacy in treating failed back surgery syndrome (FBSS) low back pain. Pilot, two-phase study. Eleven subjects with chronic intractable neuropathic trunk and/or lower limbs pain were included. The system consisted of an implantable, miniaturized stimulator, provided by Stimwave Technologies (Freedom-4) and an external transmitter. Only one stimulator per subject was implanted unilaterally and transforaminally at L1 to L5 levels. During Phase 1 of the study, the stimulators were not anchored. In Phase 2, the stimulators were anchored. Subjects were treated during 45 days after which the stimulator was removed. Pain reduction, implant duration, and stimulator migration were registered. Overall pain reduction was 59.9%, with only one device placed at one location, covering only a portion of the painful areas in the majority of the subjects. In Phase 1, the non-anchored stimulators migrated a mean of 8.80 mm and in Phase 2 a mean of 1.83 mm. Stimulator migration did not correlate with changes in pain relief. Mean time-to-implant duration was 10 minutes and no adverse events were reported during implant, follow-up period, or after explant. The pain reduction results indicate that the Freedom-4 spinal cord stimulation (SCS) Wireless System is a viable treatment of low back pain through stimulation of the DRG, and better overall pain reduction may be achieved by implanting multiple devices. With short percutaneous implant times and excellent safety profile, this new system may offer health cost savings. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Statistical controversies in clinical research: building the bridge to phase II-efficacy estimation in dose-expansion cohorts.

PubMed

Boonstra, P S; Braun, T M; Taylor, J M G; Kidwell, K M; Bellile, E L; Daignault, S; Zhao, L; Griffith, K A; Lawrence, T S; Kalemkerian, G P; Schipper, M J

2017-07-01

Regulatory agencies and others have expressed concern about the uncritical use of dose expansion cohorts (DECs) in phase I oncology trials. Nonetheless, by several metrics-prevalence, size, and number-their popularity is increasing. Although early efficacy estimation in defined populations is a common primary endpoint of DECs, the types of designs best equipped to identify efficacy signals have not been established. We conducted a simulation study of six phase I design templates with multiple DECs: three dose-assignment/adjustment mechanisms multiplied by two analytic approaches for estimating efficacy after the trial is complete. We also investigated the effect of sample size and interim futility analysis on trial performance. Identifying populations in which the treatment is efficacious (true positives) and weeding out inefficacious treatment/populations (true negatives) are competing goals in these trials. Thus, we estimated true and false positive rates for each design. Adaptively updating the MTD during the DEC improved true positive rates by 8-43% compared with fixing the dose during the DEC phase while maintaining false positive rates. Inclusion of an interim futility analysis decreased the number of patients treated under inefficacious DECs without hurting performance. A substantial gain in efficiency is obtainable using a design template that statistically models toxicity and efficacy against dose level during expansion. Design choices for dose expansion should be motivated by and based upon expected performance. Similar to the common practice in single-arm phase II trials, cohort sample sizes should be justified with respect to their primary aim and include interim analyses to allow for early stopping. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A Review of Creative Commons and Science Commons

ERIC Educational Resources Information Center

Garlick, Mia

2005-01-01

With the advent of the widespread adoption of digital technologies and the commercial phase of the Internet in the late 1990s came the empowerment of individuals to copy and redistribute content. Accustomed to equating their permission to use content such as music, books, and movies with the scope of their physical use of the product, people…

A randomized phase II/III study of cabazitaxel versus vinflunine in metastatic or locally advanced transitional cell carcinoma of the urothelium (SECAVIN).

PubMed

Bellmunt, J; Kerst, J M; Vázquez, F; Morales-Barrera, R; Grande, E; Medina, A; González Graguera, M B; Rubio, G; Anido, U; Fernández Calvo, O; González-Billalabeitia, E; Van den Eertwegh, A J M; Pujol, E; Perez-Gracia, J L; González Larriba, J L; Collado, R; Los, M; Maciá, S; De Wit, R

2017-07-01

Despite the advent of immunotherapy in urothelial cancer, there is still a need to find effective cytotoxic agents beyond first and second lines. Vinflunine is the only treatment approved in this setting by the European Medicines Agency and taxanes are also widely used in second line. Cabazitaxel is a taxane with activity in docetaxel-refractory cancers. A randomized study was conducted to compare its efficacy versus vinflunine. This is a multicenter, randomized, open-label, phase II/III study, following a Simon's optimal method with stopping rules based on an interim futility analysis and a formal efficacy analysis at the end of the phase II. ECOG Performance Status, anaemia and liver metastases were stratification factors. Primary objectives were overall response rate for the phase II and overall survival for the phase III. Seventy patients were included in the phase II across 19 institutions in Europe. Baseline characteristics were well balanced between the two arms. Three patients (13%) obtained a partial response on cabazitaxel (95% CI 2.7-32.4) and six patients (30%) in the vinflunine arm (95% CI 11.9-54.3). Median progression-free survival for cabazitaxel was 1.9 versus 2.9 months for vinflunine (P = 0.039). The study did not proceed to phase III since the futility analysis showed a lack of efficacy of cabazitaxel. A trend for overall survival benefit was found favouring vinflunine (median 7.6 versus 5.5 months). Grade 3- to 4-related adverse events were seen in 41% patients with no difference between the two arms. This phase II/III second line bladder study comparing cabazitaxel with vinflunine was closed when the phase II showed a lack of efficacy of the cabazitaxel arm. Vinflunine results were consistent with those known previously. NCT01830231. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Determination of Carvedilol Enantiomers in Pharmaceutical Dosages by SBSE-HPLC Based on Diastereomer Formation.

PubMed

Taraji, Maryam; Talebpour, Zahra; Adib, Nuoshin; Karimi, Shima; Haghighi, Farideh; Aboul-Enein, Hassan Y

2015-09-01

A sensitive, selective and simple method for the simultaneous determination of carvedilol enantiomers in aqueous solution has been developed using stir bar sorptive extraction (SBSE) followed by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. This method is based on the reaction of carvedilol enantiomers with (-)-menthyl chloroformate (MCF) after extraction by the SBSE method to produce diastereomeric derivatives. The separation was achieved by use of a C18 analytical column and the influence of mobile phase composition on the enantioseparation of carvedilol was studied. The applicability of two sorptive phases, poly(methyl methacrylate/ethyleneglycol dimethacrylate) (PA-EG) and polydimethylsiloxane, were tested for extraction of carvedilol enantiomers from aqueous samples. The obtained results showed excellent linear dynamic ranges and precisions for each of them. The least limit of detection for (S)- and (R)-carvedilol obtained 8 and 11 µg L(-1), respectively, using the PA-EG sorptive phase. Inter- and intra-mean recoveries were also satisfactory, ranging from 98 to 103%, with coefficient of variation in the range of 1-5% at three fortified levels using a PA-EG coated stir bar. The proposed SBSE (PA-EG)-MCF derivatization-HPLC-UV method was successfully applied to enantioselective analysis of carvedilol in water and pharmaceutical dosages, confirming the application of this method. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

'A child is also a teacher': exploring the potential for children as change agents in the context of a school-based WASH intervention in rural Eastern Zambia.

PubMed

Bresee, S; Caruso, B A; Sales, J; Lupele, J; Freeman, M C

2016-08-01

As part of water, sanitation and hygiene interventions in low-income settings, it is frequently assumed that pupils can disseminate information and catalyze change at home, yet this assumption has not been rigorously assessed. We employed qualitative research methods in two phases to assess the potential for children to be change agents in five schools in rural Zambia. Phase 1 included role-play and focus group discussions among pupils on their percieved ability to serve as change agents. Children were then given 'homework' that included information on health messages and on how to build a handwashing station, and were encouraged to engage their family. In Phase 2, we conducted separate focus group discussions with pupils and mothers on their experiences with the 'homework'. We found that, in general, pupils were enthusiastic about engaging with parents-typically male heads of household-and were successful at constructing handwashing stations. Mothers reported high levels of trust in children to relay health information learned at school. Pupils were able to enact small changes to behavior, but not larger infrastructure changes, such as construction of latrines. Pupils are capable of communicating knowledge and behaviors to family members; however, discrete activities and guidance is required. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Bayesian hierarchical Poisson models with a hidden Markov structure for the detection of influenza epidemic outbreaks.

PubMed

Conesa, D; Martínez-Beneito, M A; Amorós, R; López-Quílez, A

2015-04-01

Considerable effort has been devoted to the development of statistical algorithms for the automated monitoring of influenza surveillance data. In this article, we introduce a framework of models for the early detection of the onset of an influenza epidemic which is applicable to different kinds of surveillance data. In particular, the process of the observed cases is modelled via a Bayesian Hierarchical Poisson model in which the intensity parameter is a function of the incidence rate. The key point is to consider this incidence rate as a normal distribution in which both parameters (mean and variance) are modelled differently, depending on whether the system is in an epidemic or non-epidemic phase. To do so, we propose a hidden Markov model in which the transition between both phases is modelled as a function of the epidemic state of the previous week. Different options for modelling the rates are described, including the option of modelling the mean at each phase as autoregressive processes of order 0, 1 or 2. Bayesian inference is carried out to provide the probability of being in an epidemic state at any given moment. The methodology is applied to various influenza data sets. The results indicate that our methods outperform previous approaches in terms of sensitivity, specificity and timeliness. © The Author(s) 2011 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Separation and quantitation of three acidic herbicide residues in tobacco and soil by dispersive solid-phase extraction and UPLC-MS/MS.

PubMed

Xiong, Wei; Tao, Xiaoqiu; Pang, Su; Yang, Xue; Tang, GangLing; Bian, Zhaoyang

2014-01-01

A method for the determination of three acidic herbicides, dicamba, 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) in tobacco and soil has been developed based on the use of liquid-liquid extraction and dispersive solid-phase extraction (dispersive-SPE) followed by UPLC-MS/MS. Two percentage of (v/v) formic acid in acetonitrile as the extraction helped partitioning of analytes into the acetonitrile phase. The extract was then cleaned up by dispersive-SPE using primary secondary amine as selective sorbents. Quantitative analysis was done in the multiple-reaction monitoring mode using stable isotope-labeled internal standards for each compound. A separate internal standard for each analyte is required to minimize sample matrix effects on each analyte, which can lead to poor analyte recoveries and decreases in method accuracy and precision. The total analysis time was <4 min. The linear range of the method was from 1 to 100 ng mL(-1) with a limit of detection of each herbicide varied from 0.012 to 0.126 ng g(-1). The proposed method is faster, more sensitive and selective than the traditional methods and more accurate and robust than the published LC-MS/MS methods. © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Rapid Novel HPLC Method for Estimation of Eight Related Compounds in Azilsartan Kamedoxomil and Identification of Degradation Compounds by Using LC-MS.

PubMed

Sreenivasulu, J; Venkata Ramana, P; Sampath Kumar Reddy, G; Nagaraju, Ch V S; Thirumalai Rajan, S; Eswaraiah, S

2015-10-01

A novel, rapid, specific and stability-indicating reverse-phase high-performance liquid chromatography method was developed for the quantitative determination of related compounds, obtained from two different synthetic routes and degradation products of Azilsartan kamedoxomil (AZL). The method was developed by using a YMC-Pack pro C18 (150 × 4.6 mm, 3 µm) column with a mobile phase containing a gradient mobile phase combination. The eluted compounds were measured at wavelength 220 nm. The developed method run time was 25 min, within which AZL and its eight impurities were well separated with minimum 3.0 resolution. The drug substance was subjected to stress conditions of hydrolysis (acid, base and water), oxidation, photolysis, sunlight, 75% relative humidity and thermal degradation as per International Conference on Harmonization (ICH) prescribed stress conditions to ascertain the stability-indicating power of the method. Significant degradation was observed during acid, base, peroxide, water hydrolysis and 75% relative humidity studies. The mass balance of AZL was close to 100% in all the stress condition. The developed method was validated as per the ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Modelling the blast environment and relating this to clinical injury: experience from the 7/7 inquest.

PubMed

Hepper, Alan E; Pope, D J; Bishop, M; Kirkman, E; Sedman, A; Russell, R; Mahoney, P F; Clasper, J

2014-06-01

This paper addresses the computational modelling of a series of specific blast-related incidents and the relationships of clinical and engineering interpretations. The Royal Centre for Defence Medicine and the Defence Science and Technology Laboratory were tasked in 2010 by the UK Ministry of Defence to assist the Coroner's inquests into the 7 July 2005 London bombings. A three phase approach was taken. The first phase included an engineering expert in blast effects on structures reviewing photographs of the damaged carriages and bus to give a view on the likely physical effects on people close to the explosions. The second phase was a clinical review of the evidence by military clinicians to assess blast injury in the casualties. The third phase was to model the blast environment by structural dynamics experts to assess likely blast loading on victims to evaluate the potential blast loading on individuals. This loading information was then assessed by physiology experts. Once all teams (engineering, clinical and modelling/physiological) had separately arrived at their conclusions, the information streams were integrated to arrive at a consensus. The aim of this paper is to describe the methodology used as a potential model for others to consider if faced with a similar investigation, and to show the benefit of the transition of military knowledge to a civilian environment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A qualitative analysis of messages to promote smoking cessation among pregnant women.

PubMed

Hoek, Janet; Gifford, Heather; Maubach, Ninya; Newcombe, Rhiannon

2014-11-27

Although aware that smoking while pregnant presents serious risks to their unborn children, some women continue to smoke and rationalise their dissonance rather than quit. We explored metaphors women used to frame smoking and quitting, then developed cessation messages that drew on these metaphors and examined the perceived effectiveness of these. We used a two-phase qualitative study. Phase one involved 13 in-depth interviews with women who were smoking (or who had smoked) while pregnant. Phase two comprised 22 in-depth interviews with a new sample drawn from the same population. Data were analysed using thematic analysis, which promoted theme identification independently of the research protocol. Participants often described smoking as a choice, a frame that explicitly asserted control over their behaviour. This stance allowed them to counter-argue messages to quit, and distanced them from the risks they created and faced. Messages tested in phase 2 used strong affective appeals as well as themes that stimulated cognitive reflection. Without exception, the messages depicting unwell or distressed children elicited strong emotional responses, were more powerful cessation stimuli, and elicited fewer counter-arguments. Cessation messages that evoke strong affective responses capitalise on the dissonance many women feel when smoking while pregnant and stimulate stronger consideration of quitting. Given the importance of promoting cessation among pregnant women, future campaigns could make greater use of emotional appeals and place less emphasis on informational approaches, which often prompt vigorous counter-arguments. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Sequential Sampling Plan of Anthonomus grandis (Coleoptera: Curculionidae) in Cotton Plants.

PubMed

Grigolli, J F J; Souza, L A; Mota, T A; Fernandes, M G; Busoli, A C

2017-04-01

The boll weevil, Anthonomus grandis grandis Boheman (Coleoptera: Curculionidae), is one of the most important pests of cotton production worldwide. The objective of this work was to develop a sequential sampling plan for the boll weevil. The studies were conducted in Maracaju, MS, Brazil, in two seasons with cotton cultivar FM 993. A 10,000-m2 area of cotton was subdivided into 100 of 10- by 10-m plots, and five plants per plot were evaluated weekly, recording the number of squares with feeding + oviposition punctures of A. grandis in each plant. A sequential sampling plan by the maximum likelihood ratio test was developed, using a 10% threshold level of squares attacked. A 5% security level was adopted for the elaboration of the sequential sampling plan. The type I and type II error used was 0.05, recommended for studies with insects. The adjustment of the frequency distributions used were divided into two phases, so that the model that best fit to the data was the negative binomial distribution up to 85 DAE (Phase I), and from there the best fit was Poisson distribution (Phase II). The equations that define the decision-making for Phase I are S0 = -5.1743 + 0.5730N and S1 = 5.1743 + 0.5730N, and for the Phase II are S0 = -4.2479 + 0.5771N and S1 = 4.2479 + 0.5771N. The sequential sampling plan developed indicated the maximum number of sample units expected for decision-making is ∼39 and 31 samples for Phases I and II, respectively. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

An international study to revise the EORTC questionnaire for assessing quality of life in lung cancer patients.

PubMed

Koller, M; Hjermstad, M J; Tomaszewski, K A; Tomaszewska, I M; Hornslien, K; Harle, A; Arraras, J I; Morag, O; Pompili, C; Ioannidis, G; Georgiou, M; Navarra, C; Chie, W-C; Johnson, C D; Himpel, A; Schulz, C; Bohrer, T; Janssens, A; Kulis, D; Bottomley, A

2017-11-01

The European Organization for Research and Treatment of Cancer (EORTC) QLQ-LC13 was the first module to be used in conjunction with the core questionnaire, the QLQ-C30. Since the publication of the LC13 in 1994, major advances have occurred in the treatment of lung cancer. Given this, an update of the EORTC QLQ-LC13 was undertaken. The study followed phases I to III of the EORTC Module Development Guidelines. Phase I generated relevant quality-of-life issues using a mix of sources including the involvement of 108 lung cancer patients. Phase II transformed issues into questionnaire items. In an international multicenter study (phase III), patients completed both the EORTC QLQ-C30 and the 48-item provisional lung cancer module generated in phases I and II. Patients rated each of the items regarding relevance, comprehensibility, and acceptance. Patient ratings were assessed against a set of prespecified statistical criteria. Descriptive statistics and basic psychometric analyses were carried out. The phase III study enrolled 200 patients with histologically confirmed lung cancer from 12 centers in nine countries (Cyprus, Germany, Italy, Israel, Spain, Norway, Poland, Taiwan, and the UK). Mean age was 64 years (39 - 91), 59% of the patients were male, 82% had non-small-cell lung cancer, and 56% were treated with palliative intent. Twenty-nine of the 48 questions met the criteria for inclusion. The resulting module with 29 questions, thus currently named EORTC QLQ-LC29, retained 12 of the 13 original items, supplemented with 17 items that primarily assess treatment side-effects of traditional and newer therapies. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Infectious Diseases Team for the Early Management of Severe Sepsis and Septic Shock in the Emergency Department.

PubMed

Viale, Pierluigi; Tedeschi, Sara; Scudeller, Luigia; Attard, Luciano; Badia, Lorenzo; Bartoletti, Michele; Cascavilla, Alessandra; Cristini, Francesco; Dentale, Nicola; Fasulo, Giovanni; Legnani, Giorgio; Trapani, Filippo; Tumietto, Fabio; Verucchi, Gabriella; Virgili, Giulio; Berlingeri, Andrea; Ambretti, Simone; De Molo, Chiara; Brizi, Mara; Cavazza, Mario; Giannella, Maddalena

2017-10-15

The impact on patient survival of an infectious disease (ID) team dedicated to the early management of severe sepsis/septic shock (SS/SS) in Emergency Department (ED) has yet to be assessed. A quasiexperimental pre-post study was performed at the general ED of our hospital. During the pre phase (June 2013-July 2014), all consecutive adult patients with SS/SS were managed according to the standard of care, data were prospectively collected. During the post phase (August 2014-October 2015), patients were managed in collaboration with a dedicated ID team performing a bedside patient evaluation within 1 hour of ED arrival. Overall, 382 patients were included, 195 in the pre phase and 187 in the post phase. Median age was 82 years (interquartile range, 70-88). The most common infection sources were lung (43%) and urinary tract (17%); in 22% of cases, infection source remained unknown. During the post phase, overall compliance with the Surviving Sepsis Campaign (SSC) bundle and appropriateness of initial antibiotic therapy improved from 4.6% to 32% (P < .001) and from 30% to 79% (P < .001), respectively. Multivariate analysis showed that predictors of all-cause 14-day mortality were quick sepsis-related organ failure assessment ≥2 (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.15-2.45; P = .007), serum lactate ≥2 mmol/L (HR, 2.13; 95% CI, 1.39-3.25; P < .001), and unknown infection source (HR, 2.07; 95% CI, 1.42-3.02; P < .001); being attended during the post phase was a protective factor (HR, 0.64; 95% CI, 0.43-0.94; P = .026). Implementation of an ID team for the early management of SS/SS in the ED improved the adherence to SSC recommendations and patient survival. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Correlations between chromatographic parameters and bioactivity predictors of potential herbicides.

PubMed

Janicka, Małgorzata

2014-08-01

Different liquid chromatography techniques, including reversed-phase liquid chromatography on Purosphere RP-18e, IAM.PC.DD2 and Cosmosil Cholester columns and micellar liqud chromatography with a Purosphere RP-8e column and using buffered sodium dodecyl sulfate-acetonitrile as the mobile phase, were applied to study the lipophilic properties of 15 newly synthesized phenoxyacetic and carbamic acid derivatives, which are potential herbicides. Chromatographic lipophilicity descriptors were used to extrapolate log k parameters (log kw and log km) and log k values. Partitioning lipophilicity descriptors, i.e., log P coefficients in an n-octanol-water system, were computed from the molecular structures of the tested compounds. Bioactivity descriptors, including partition coefficients in a water-plant cuticle system and water-human serum albumin and coefficients for human skin partition and permeation were calculated in silico by ACD/ADME software using the linear solvation energy relationship of Abraham. Principal component analysis was applied to describe similarities between various chromatographic and partitioning lipophilicities. Highly significant, predictive linear relationships were found between chromatographic parameters and bioactivity descriptors. © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Exposure to airborne asbestos in thermal power plants in Mongolia

PubMed Central

Damiran, Naransukh; Silbergeld, Ellen K; Frank, Arthur L; Lkhasuren, Oyuntogos; Ochir, Chimedsuren; Breysse, Patrick N

2015-01-01

Background: Coal-fired thermal power plants (TPPs) in Mongolia use various types of asbestos-containing materials (ACMs) in thermal insulation of piping systems, furnaces, and other products. Objective: To investigate the occupational exposure of insulation workers to airborne asbestos in Mongolian power plants. Methods: Forty-seven air samples were collected from four power plants in Mongolia during the progress of insulation work. The samples were analyzed by phase contrast microscopy (PCM) and transmission electron microscopy (TEM). Results: The average phase contrast microscopy equivalent (PCME) asbestos fiber concentration was 0.93 f/cm3. Sixteen of the 41 personal and one of the area samples exceeded the United States Occupational Safety and Health Administration (US OSHA) short-term exposure limit of 1.0 f/cm3. If it is assumed that the short-term samples collected are representative of full-shift exposure, then the exposures are approximately 10 times higher than the US OSHA 8-hour permissible exposure limit of 0.1 f/cm3. Conclusion: Power plant insulation workers are exposed to airborne asbestos at concentrations that exceed the US OSHA Permissible Exposure Limit. Action to mitigate the risks should be taken in Mongolia. PMID:25730489

Rapid Determination of Clenbuterol in Pork by Direct Immersion Solid-Phase Microextraction Coupled with Gas Chromatography-Mass Spectrometry.

PubMed

Ye, Diru; Wu, Susu; Xu, Jianqiao; Jiang, Ruifen; Zhu, Fang; Ouyang, Gangfeng

2016-02-01

Direct immersion solid-phase microextraction (DI-SPME) coupled with gas chromatography-mass spectrometry (GC-MS) was developed for rapid analysis of clenbuterol in pork for the first time. In this work, a low-cost homemade 44 µm polydimethylsiloxane (PDMS) SPME fiber was employed to extract clenbuterol in pork. After extraction, derivatization was performed by suspending the fiber in the headspace of the 2 mL sample vial saturated with a vapor of 100 µL hexamethyldisilazane. Lastly, the fiber was directly introduced to GC-MS for analysis. All parameters that influenced absorption (extraction time), derivatization (derivatization reagent, time and temperature) and desorption (desorption time) were optimized. Under optimized conditions, the method offered a wide linear range (10-1000 ng g(-1)) and a low detection limit (3.6 ng g(-1)). Finally, the method was successfully applied in the analysis of pork from the market, and recoveries of the method for spiked pork were 97.4-105.7%. Compared with the traditional solvent extraction method, the proposed method was much cheaper and fast. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Exposure to airborne asbestos in thermal power plants in Mongolia.

PubMed

Damiran, Naransukh; Silbergeld, Ellen K; Frank, Arthur L; Lkhasuren, Oyuntogos; Ochir, Chimedsuren; Breysse, Patrick N

2015-01-01

Coal-fired thermal power plants (TPPs) in Mongolia use various types of asbestos-containing materials (ACMs) in thermal insulation of piping systems, furnaces, and other products. To investigate the occupational exposure of insulation workers to airborne asbestos in Mongolian power plants. Forty-seven air samples were collected from four power plants in Mongolia during the progress of insulation work. The samples were analyzed by phase contrast microscopy (PCM) and transmission electron microscopy (TEM). The average phase contrast microscopy equivalent (PCME) asbestos fiber concentration was 0·93 f/cm(3). Sixteen of the 41 personal and one of the area samples exceeded the United States Occupational Safety and Health Administration (US OSHA) short-term exposure limit of 1·0 f/cm(3). If it is assumed that the short-term samples collected are representative of full-shift exposure, then the exposures are approximately 10 times higher than the US OSHA 8-hour permissible exposure limit of 0·1 f/cm(3). Power plant insulation workers are exposed to airborne asbestos at concentrations that exceed the US OSHA Permissible Exposure Limit. Action to mitigate the risks should be taken in Mongolia.

Periodic Pattern of Genetic and Fitness Diversity during Evolution of an Artificial Cell-Like System.

PubMed

Ichihashi, Norikazu; Aita, Takuyo; Motooka, Daisuke; Nakamura, Shota; Yomo, Tetsuya

2015-12-01

Genetic and phenotypic diversity are the basis of evolution. Despite their importance, however, little is known about how they change over the course of evolution. In this study, we analyzed the dynamics of the adaptive evolution of a simple evolvable artificial cell-like system using single-molecule real-time sequencing technology that reads an entire single artificial genome. We found that the genomic RNA population increases in fitness intermittently, correlating with a periodic pattern of genetic and fitness diversity produced by repeated diversification and domination. In the diversification phase, a genomic RNA population spreads within a genetic space by accumulating mutations until mutants with higher fitness are generated, resulting in an increase in fitness diversity. In the domination phase, the mutants with higher fitness dominate, decreasing both the fitness and genetic diversity. This study reveals the dynamic nature of genetic and fitness diversity during adaptive evolution and demonstrates the utility of a simplified artificial cell-like system to study evolution at an unprecedented resolution. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Simultaneous quantitative determination of six active components in traditional Chinese medicinal preparation Cerebralcare Granule® by RP-HPLC coupled with diode array detection for quality control.

PubMed

Wang, Xiang-yang; Ma, Xiao-hui; Li, Wei; Chu, Yang; Guo, Jia-hua; Zhou, Shui-ping; Zhu, Yong-hong

2014-09-01

A simple, accurate and reliable method for the simultaneous separation and determination of six active components (protocatechuic acid, chlorogenic acid, caffeic acid, paeoniflorin, ferulic acid and rosmarinic acid) in traditional Chinese medicinal preparation Cerebralcare Granule(®) (CG) was developed using reverse-phase high-performance liquid chromatography coupled with diode array detector detection. The chromatographic separation was performed on a Hypersil GOLD C18 column with aqueous formic acid (0.1%, v/v) and acetonitrile as mobile phase at a flow rate of 0.2 ml/min at 30 °C. Because of the different UV characteristics of these components, change detection wavelength method was used for quantitative analysis. All of the analytes showed good linearity (r > 0.9992). The established method showed good precision and relative standard deviations (%) for intra-day and inter-day variations of 0.15-1.81 and 0.11-1.98%, respectively. The validated method was successfully applied to the simultaneously determination of six active components in CG from different batches. © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Ultra-performance liquid chromatographic determination of tocopherols and retinol in human plasma.

PubMed

Bell, Edward C; John, Mathew; Hughes, Rodney J; Pham, Thu

2014-10-01

A rapid, selective and sensitive ultra-performance liquid chromatography method has been developed for the detection and quantification of tocopherols and retinol in human plasma. Alpha-tocopherol, gamma-tocopherol and retinol are assayed using fluorescence detection. Excitation/emission wavelengths are 295/330 nm and 325/470 nm for the analysis of both tocopherols and retinol, respectively. Retinol acetate is employed as the internal standard. The reversed-phase method incorporates gradient elution with a mobile phase consisting of methanol and acetonitrile. Separation of vitamin compounds is achieved using a bridged ethyl hybrid C18 column. The retention times for retinol, retinol acetate, gamma-tocopherol and alpha-tocopherol are 1.6, 1.8, 3.9 and 4.3 min, respectively. The limits of quantification for retinol, gamma-tocopherol and alpha-tocopherol were 0.02, 0.02 and 0.1 µg/mL, respectively. The assay method is suitable for the analysis of tocopherols and retinol in human plasma. The method may be applied following the ingestion of foods fortified with these fat-soluble vitamins. © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Solid-Phase Extraction of Sulfur Mustard Metabolites Using an Activated Carbon Fiber Sorbent.

PubMed

Lee, Jin Young; Lee, Yong Han

2016-01-01

A novel solid-phase extraction method using activated carbon fiber (ACF) was developed and validated. ACF has a vast network of pores of varying sizes and microporous structures that result in rapid adsorption and selective extraction of sulfur mustard metabolites according to the pH of eluting solvents. ACF could not only selectively extract thiodiglycol and 1-methylsulfinyl-2-[2-(methylthio)-ethylsulfonyl]ethane eluting a 9:1 ratio of dichloromethane to acetone, and 1,1'-sulfonylbis[2-(methylsulfinyl)ethane] and 1,1'-sulfonylbis- [2-S-(N-acetylcysteinyl)ethane] eluting 3% hydrogen chloride in methanol, but could also eliminate most interference without loss of analytes during the loading and washing steps. A sample preparation method has been optimized for the extraction of sulfur mustard metabolites from human urine using an ACF sorbent. The newly developed extraction method was applied to the trace analysis of metabolites of sulfur mustard in human urine matrices in a confidence-building exercise for the analysis of biomedical samples provided by the Organisation for the Prohibition of Chemical Weapons. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Optimization of Robust HPLC Method for Quantitation of Ambroxol Hydrochloride and Roxithromycin Using a DoE Approach.

PubMed

Patel, Rashmin B; Patel, Nilay M; Patel, Mrunali R; Solanki, Ajay B

2017-03-01

The aim of this work was to develop and optimize a robust HPLC method for the separation and quantitation of ambroxol hydrochloride and roxithromycin utilizing Design of Experiment (DoE) approach. The Plackett-Burman design was used to assess the impact of independent variables (concentration of organic phase, mobile phase pH, flow rate and column temperature) on peak resolution, USP tailing and number of plates. A central composite design was utilized to evaluate the main, interaction, and quadratic effects of independent variables on the selected dependent variables. The optimized HPLC method was validated based on ICH Q2R1 guideline and was used to separate and quantify ambroxol hydrochloride and roxithromycin in tablet formulations. The findings showed that DoE approach could be effectively applied to optimize a robust HPLC method for quantification of ambroxol hydrochloride and roxithromycin in tablet formulations. Statistical comparison between results of proposed and reported HPLC method revealed no significant difference; indicating the ability of proposed HPLC method for analysis of ambroxol hydrochloride and roxithromycin in pharmaceutical formulations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Determination of Sucrose in Honey with Derivatization/Solid-Phase Microextraction and Gas-Chromatography/Mass Spectrometry.

PubMed

Wang, Haijing; Geppert, Helmut; Fischer, Thomas; Wieprecht, Wolfgang; Möller, Detlev

2015-10-01

A new method for the determination of sucrose in honey with derivatization solid-phase microextraction and gas chromatography/mass spectrometry (D-SPME-GC/MS) was developed. The method incorporates a sample derivatization with acetic anhydride using N-methylimidazole as the catalyst and the subsequent enrichment of the analyte in a Polyacrylate-SPME fiber. Results show that 100 µL N-methylimidazole and 800 µL acetic anhydride were sufficient to complete the acetylation for sucrose in 100 µL aqueous sample at room temperature. For SPME, an enrichment time of 30 min was sufficient. SPME was performed by immersing the fiber into the solution with additional vibration. Then, the analyte was desorbed for 5 min at 280°C in the GC/MS injection port with splitless mode. The present method exhibits good linearity at a concentration range of 0.3-8% of sucrose in honey with excellent regression (R = 0.9993). The method has been successfully applied to the control of sucrose adulteration in honey. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Paternal malparenting and offspring personality disorders: Mediating effect of early maladaptive schemas.

PubMed

Batool, Naila; Shehzadi, Humaira; Riaz, Muhammad Naveed; Riaz, Muhammad Akram

2017-04-01

To examine the mediating role of maladaptive schemas between permissive/authoritarian parenting by fathers and personality disorders, including histrionic, antisocial, narcissistic and depressive attitudes among adults. This cross-sectional study was conducted at the University of Sargodha, Sargodha, Pakistan, and comprised university students. Data was collected by administering the parental authority questionnaire, the young schema questionnaire and the personality diagnostic questionnaire. SPSS 23 was used for data analysis. The study was completed in one year. It was started from June 2014 and ended in June 2015. Of the 200 participants who were handed the questionnaires, 100(50%) returned it fully filled up. Of them, 87(87%) were women and 13(13%) were men. All scales had greater than 0.70 alpha reliability coefficients. The values of skewness for all scales ranged from 0.10 to 0.86.Permissive parenting style had positive correlation with histrionic (p<0.05), narcissistic (p<0.05) and antisocial personality disorders (p<0.01). Authoritarian parenting had positive correlation with early maladaptive schemas (p<0.01) and depressive personality disorder (p<0.05). Both permissive and authoritarian parenting styles led to personality disorders among offspring in the adult phase of their lives.

Security of medical multimedia.

PubMed

Tzelepi, S; Pangalos, G; Nikolacopoulou, G

2002-09-01

The application of information technology to health care has generated growing concern about the privacy and security of medical information. Furthermore, data and communication security requirements in the field of multimedia are higher. In this paper we describe firstly the most important security requirements that must be fulfilled by multimedia medical data, and the security measures used to satisfy these requirements. These security measures are based mainly on modern cryptographic and watermarking mechanisms as well as on security infrastructures. The objective of our work is to complete this picture, exploiting the capabilities of multimedia medical data to define and implement an authorization model for regulating access to the data. In this paper we describe an extended role-based access control model by considering, within the specification of the role-permission relationship phase, the constraints that must be satisfied in order for the holders of the permission to use those permissions. The use of constraints allows role-based access control to be tailored to specifiy very fine-grained and flexible content-, context- and time-based access control policies. Other restrictions, such as role entry restriction also can be captured. Finally, the description of system architecture for a secure DBMS is presented.

Analysis of psilocin, bufotenine and LSD in hair.

PubMed

Martin, Rafaela; Schürenkamp, Jennifer; Gasse, Angela; Pfeiffer, Heidi; Köhler, Helga

2015-03-01

A method for the simultaneous extraction of the hallucinogens psilocin, bufotenine, lysergic acid diethylamide (LSD) as well as iso-LSD, nor-LSD and O-H-LSD from hair with hydrochloride acid and methanol is presented. Clean-up of the hair extracts is performed with solid phase extraction using a mixed-mode cation exchanger. Extracts are measured with liquid chromatography coupled with electrospray tandem mass spectrometry. The method was successfully validated according to the guidelines of the 'Society of Toxicological and Forensic Chemistry' (GTFCh). To obtain reference material hair was soaked in a solution of the analytes in dimethyl sulfoxide/methanol to allow incorporation into the hair. These fortified hair samples were used for method development and can be employed as quality controls. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Development of a rapid and sensitive method for the determination of aluminum by reverse-phase high-performance liquid chromatography using a fluorescence detector.

PubMed

Heena; Kumar, Rajesh; Rani, Susheela; Malik, Ashok Kumar

2015-01-01

This study represents a new analytical high-performance liquid chromatography-fluorescence detector method for the determination of Al(III) as Al(III) complex with 8-hydroxyquinoline-5-sulfonic acid in a tap water sample and a coke sample. A micellar liquid chromatographic method is proposed for the determination of aluminum metal in the presence of cetyltrimethylammonium bromide, a cationic surfactant (0.05 M) used for the solubilization of the aluminum complex. The influence of pH and ligand concentration on the formation of the complex was studied by adding a small amount of 0.1 M sodium hydroxide. The metal chelate was detected at λEx 410 nm and λEm 510 nm. This method eliminates the need for addition of reagent or organic modifier to the mobile phase. The complex was analyzed using an Ascentis Express C18 column and a mobile phase consisting of acetonitrile, methanol and water (55 : 30 : 15). Under the optimized conditions, the linear range was 1-200 µg L(-1) and the limit of detection was 0.05 µg L(-1). The method showed a good detector response over the range of interest and was successfully applied for the determination of trace Al(III) in canned coke and water samples containing excess of Mg(II), Ca(II) and other matrices. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Probabilistic Reversal Learning in Schizophrenia: Stability of Deficits and Potential Causal Mechanisms.

PubMed

Reddy, Lena Felice; Waltz, James A; Green, Michael F; Wynn, Jonathan K; Horan, William P

2016-07-01

Although individuals with schizophrenia show impaired feedback-driven learning on probabilistic reversal learning (PRL) tasks, the specific factors that contribute to these deficits remain unknown. Recent work has suggested several potential causes including neurocognitive impairments, clinical symptoms, and specific types of feedback-related errors. To examine this issue, we administered a PRL task to 126 stable schizophrenia outpatients and 72 matched controls, and patients were retested 4 weeks later. The task involved an initial probabilistic discrimination learning phase and subsequent reversal phases in which subjects had to adjust their responses to sudden shifts in the reinforcement contingencies. Patients showed poorer performance than controls for both the initial discrimination and reversal learning phases of the task, and performance overall showed good test-retest reliability among patients. A subgroup analysis of patients (n = 64) and controls (n = 49) with good initial discrimination learning revealed no between-group differences in reversal learning, indicating that the patients who were able to achieve all of the initial probabilistic discriminations were not impaired in reversal learning. Regarding potential contributors to impaired discrimination learning, several factors were associated with poor PRL, including higher levels of neurocognitive impairment, poor learning from both positive and negative feedback, and higher levels of indiscriminate response shifting. The results suggest that poor PRL performance in schizophrenia can be the product of multiple mechanisms. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Bayesian Analysis of Evolutionary Divergence with Genomic Data under Diverse Demographic Models.

PubMed

Chung, Yujin; Hey, Jody

2017-06-01

We present a new Bayesian method for estimating demographic and phylogenetic history using population genomic data. Several key innovations are introduced that allow the study of diverse models within an Isolation-with-Migration framework. The new method implements a 2-step analysis, with an initial Markov chain Monte Carlo (MCMC) phase that samples simple coalescent trees, followed by the calculation of the joint posterior density for the parameters of a demographic model. In step 1, the MCMC sampling phase, the method uses a reduced state space, consisting of coalescent trees without migration paths, and a simple importance sampling distribution without the demography of interest. Once obtained, a single sample of trees can be used in step 2 to calculate the joint posterior density for model parameters under multiple diverse demographic models, without having to repeat MCMC runs. Because migration paths are not included in the state space of the MCMC phase, but rather are handled by analytic integration in step 2 of the analysis, the method is scalable to a large number of loci with excellent MCMC mixing properties. With an implementation of the new method in the computer program MIST, we demonstrate the method's accuracy, scalability, and other advantages using simulated data and DNA sequences of two common chimpanzee subspecies: Pan troglodytes (P. t.) troglodytes and P. t. verus. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Validation of RP-HPLC method and stress degradation for the combination of metformin HCl, atorvastatin calcium and glimepiride: application to nanoparticles.

PubMed

Gite, Sandip; Patravale, Vandana

2015-01-01

A stability-indicating high-performance liquid chromatography (HPLC) procedure was developed for the determination of metformin HCl (MTH), atorvastatin calcium (AC) and glimepiride (GP) in combination and their main degradation products. The separation and quantization were achieved on a 5-µm Qualisil gold, C18 column (4.6 mm × 250 mm). The mobile phase selected was phosphate buffer (pH 2.9)-organic phase in proportion of 70:30. Organic phase consisted of methanol-acetonitrile (90:10) at a flow rate of 1 mL/min and detection of analytes was carried out at 230 nm. The method exhibited good linearity over the range of 10-60 µg/mL for MTH, 2-20 µg/mL for AC and 5-30 µg/mL for GP. Square of the correlation coefficients was found to be >0.999. Various stress degradation studies were carried out in combination as per International Conference of Harmonization (ICH) guidelines for 4 h. The recovery and precision were determined in terms of intraday and interday precisions and expressed as relative standard deviations. These were <1 and <2%, respectively. Finally, the applicability of the method was evaluated in nanoparticle analysis of MTH, AC and GP as well as in stability studies of nanoformulation. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Factors influencing workplace health promotion intervention: a qualitative systematic review.

PubMed

Rojatz, Daniela; Merchant, Almas; Nitsch, Martina

2017-10-01

Although workplace health promotion (WHP) has evolved over the last 40 years, systematically collected knowledge on factors influencing the functioning of WHP is scarce. Therefore, a qualitative systematic literature review was carried out to systematically identify and synthesize factors influencing the phases of WHP interventions: needs assessment, planning, implementation and evaluation. Research evidence was identified by searching electronic databases (Scopus, PubMed, Social Sciences Citation Index, ASSIA, ERIC, IBBS and PsycINFO) from 1998 to 2013, as well as by cross-checking reference lists of included peer-reviewed articles. The inclusion criteria were: original empirical research, description of WHP, description of barriers to and/or facilitators of the planning, implementation and/or evaluation of WHP. Finally, 54 full texts were included. From these, influencing factors were extracted and summarized using thematic analysis. The majority of influencing factors referred to the implementation phase, few dealt with planning and/or evaluation and none with needs assessment. The influencing factors were condensed into topics with respect to factors at contextual level (e.g. economic crisis); factors at organizational level (e.g. management support); factors at intervention level (e.g. quality of intervention concept); factors at implementer level (e.g. resources); factors at participant level (e.g. commitment to intervention) and factors referring to methodological and data aspects (e.g. data-collection issues). Factors regarding contextual issues and organizational aspects were identified across three phases. Therefore, future research and practice should consider not only the influencing factors at different levels, but also at different phases of WHP interventions. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Molecular regulation of sex change induced by methyltestosterone -feeding and methyltestosterone -feeding withdrawal in the protogynous orange-spotted grouper.

PubMed

Wang, Qing; Liu, Yun; Peng, Cheng; Wang, Xiang; Xiao, Ling; Wang, Dengdong; Chen, Jiaxing; Zhang, Haifa; Zhao, Huihong; Li, Shuisheng; Zhang, Yong; Lin, Haoran

2017-08-01

The sex identity of fish can be easily manipulated by exogenous hormones. Treatment with 17-methyltestosterone (MT) has been widely used to induce a male fate, but the molecular and cellular processes underlying sex changes induced by MT treatments and the withdrawal of MT are not well studied. In this study, we systematically investigated gonadal histology, gene expression profiles, sex steroid hormone levels, and cellular changes during sex changes induced by MT-feeding and MT-feeding withdrawal in the protogynous orange-spotted grouper, Epinephelus coioides. Based on gonadal histology, we demonstrated that MT-feeding-induced sex reversal can be divided into early and late phases: in the early phase, male and female germ cells coexist, and MT-feeding withdrawal leads to a female fate; in the late phase, only male germ cells are observed, and MT-feeding withdrawal does not reverse the process, leading to a male fate. In both the early and late phases, cytochrome P450 family19 subfamily A member 1 (cyp19a1a) gene expression increased in response to MT-feeding withdrawal. Finally, by tracing doublesex- and Mab-3-related transcription factor 1 (dmrt1)-expressing cells, we found that gonia-like cells in the germinal epithelium might be the major germ cell sources for developing testes during sex reversal. Collectively, our findings provide insights into the molecular and cellular mechanisms underlying sex changes induced by exogenous hormones. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Physiological and transcriptional responses to high temperature in Arthrospira (Spirulina) platensis C1.

PubMed

Panyakampol, Jaruta; Cheevadhanarak, Supapon; Sutheeworapong, Sawannee; Chaijaruwanich, Jeerayut; Senachak, Jittisak; Siangdung, Wipawan; Jeamton, Wattana; Tanticharoen, Morakot; Paithoonrangsarid, Kalyanee

2015-03-01

Arthrospira (Spirulina) platensis is a well-known commercial cyanobacterium that is used as a food and in feed supplements. In this study, we examined the physiological changes and whole-genome expression in A. platensis C1 exposed to high temperature. We found that photosynthetic activity was significantly decreased after the temperature was shifted from 35°C to 42°C for 2 h. A reduction in biomass production and protein content, concomitant with the accumulation of carbohydrate content, was observed after prolonged exposure to high temperatures for 24 h. Moreover, the results of the expression profiling in response to high temperature at the designated time points (8 h) revealed two distinct phases of the responses. The first was the immediate response phase, in which the transcript levels of genes involved in different mechanisms, including genes for heat shock proteins; genes involved in signal transduction and carbon and nitrogen metabolism; and genes encoding inorganic ion transporters for magnesium, nitrite and nitrate, were either transiently induced or repressed by the high temperature. In the second phase, the long-term response phase, both the induction and repression of the expression of genes with important roles in translation and photosynthesis were observed. Taken together, the results of our physiological and transcriptional studies suggest that dynamic changes in the transcriptional profiles of these thermal-responsive genes might play a role in maintaining cell homeostasis under high temperatures, as reflected in the growth and biochemical composition, particularly the protein and carbohydrate content, of A. platensis C1. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Inflammatory Milieu and Cardiovascular Homeostasis in Children With Obstructive Sleep Apnea.

PubMed

Smith, David F; Hossain, Md M; Hura, Arjan; Huang, Guixia; McConnell, Keith; Ishman, Stacey L; Amin, Raouf S

2017-04-01

Biomarkers of atherosclerosis (pro-inflammatory cytokines and acute phase reactants) are elevated in children with obstructive sleep apnea (OSA). However, their association with cardiovascular endpoints in children are not understood. We hypothesized that biomarkers of atherosclerosis in children with OSA correlate with pulse transit time (PTT), a surrogate measure of vascular stiffness, with some positively influencing and others negatively influencing PTT. Children with OSA and matched controls were recruited to the study. Pro-inflammatory cytokines and acute phase reactants were measured at 6:00 pm and 6:00 am. Polysomnography with beat-to-beat blood pressure was performed. PTT during wakefulness and stage 2 sleep was calculated. Diurnal variation of biomarkers and their associations with PTT was estimated. Factor analysis was used to determine the effect of groups of cytokines on PTT. One hundred fifty-five children participated in the study; 90 were healthy controls and 65 had OSA. Children with OSA exhibited a different diurnal variation of biomarkers than healthy controls, with pro-inflammatory cytokines peaking in the morning and acute phase reactants peaking in the afternoon. Structural equation modeling demonstrated that interleukins 6 and 8, tumor necrosis factor-α, and sCD40L had a shortening effect, while serum amyloid A, C-reactive protein, and adiponectin had a prolonging effect on PTT. As a result, there was no difference in PTT between the two groups. The differential relationships of acute phase reactants and pro-inflammatory cytokines with PTT suggest that in children with OSA, these mediators may have opposing actions to maintain cardiovascular homeostasis. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Attitudes toward participating in Phase I clinical trials: an investigation with patient-family-physician triads.

PubMed

Shin, Dong Wook; Cho, Juhee; Kim, So Young; Yang, Hyung Kook; Cho, BeLong; Shin, Dong-Bok; Chun, Mi Son; Min, Young Joo; Kim, Young-Woo; Park, Jong Hyock

2016-12-01

Phase I oncology trials have raised concerns that patients' 'unrealistic' optimism could compromise the validity of informed consent, and that patients often participate in trials to conform to physicians' or family members' recommendations. We aimed to determine whether patients or families-given the same information of risk-benefit profile-are more likely to participate in Phase I trials than their physicians and whether people in family or physician situations are more likely to recommend trial participation to patients than they would want for themselves as patients. We conducted a hypothetical vignette study with a patient-caregiver-oncologist. Three groups-725 patient-caregiver pairs recruited by 134 oncologists-were asked to assume three different roles as patients, caregivers and physicians and provided a scenario of a hypothetical patient with treatment-resistant cancer. They were asked questions regarding their intention to participate in or to recommend a Phase I clinical trial. Acceptance rates of the trial were as follows: (a) in the patients' role: patients (54.1), caregivers (62.3) and physicians (63.4%); (b) in the caregivers' role: 55.6, 64.7 and 70.9%; (c) in the physicians' role: 66.1, 70.8 and 76.1%. Patients or caregivers were not more positive to the trial than physicians. All three groups showed more positive attitudes toward the clinical trial when they assumed the role of caregiver or physician than that of patient. Patients and caregivers seem to make as reasonable decisions as physicians; patients seem to take family members' or physicians' recommendation as their legitimate roles rather than as undue pressure. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Phase II study of palonosetron, aprepitant, dexamethasone and olanzapine for the prevention of cisplatin-based chemotherapy-induced nausea and vomiting in patients with thoracic malignancy.

PubMed

Nakashima, Kazuhisa; Murakami, Haruyasu; Yokoyama, Kouichi; Omori, Shota; Wakuda, Kazushige; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Nishiyama, Fumie; Kikugawa, Mami; Kaneko, Masayo; Iwamoto, Yumiko; Koizumi, Satomi; Mori, Keita; Isobe, Takeshi; Takahashi, Toshiaki

2017-09-01

The three-drug combination of a 5-hydroxytryptamine type 3 receptor antagonist, a neurokinin 1 receptor antagonist and dexamethasone is recommended for patients receiving highly emetogenic chemotherapy. However, standard antiemetic therapy is not completely effective in all patients. We conducted an open-label, single-center, single-arm Phase II study to evaluate the efficacy of olanzapine in combination with standard antiemetic therapy in preventing chemotherapy-induced nausea and vomiting in patients with thoracic malignancy receiving their first cycle of cisplatin-based chemotherapy. Patients received 5 mg oral olanzapine on Days 1-5 in combination with standard antiemetic therapy. The primary endpoint was complete response (no vomiting and no use of rescue therapy) during the overall Phase (0-120 h post-chemotherapy). Twenty-three men and seven women were enrolled between May and October 2015. The median age was 64 years (range: 36-75 years). The most common chemotherapy regimen was 75 mg/m2 cisplatin and 500 mg/m2 pemetrexed, which was administered to 14 patients. Complete response rates in acute (0-24 h post-chemotherapy), delayed (24-120 h post-chemotherapy) and overall phases were 100%, 83% and 83% (90% confidence interval: 70-92%; 95% confidence interval: 66-93%), respectively. There were no Grade 3 or Grade 4 adverse events. Although four patients (13%) experienced Grade 1 somnolence, no patients discontinued olanzapine. The addition of 5 mg oral olanzapine to standard antiemetic therapy demonstrates promising efficacy in preventing cisplatin-based chemotherapy-induced nausea and vomiting and an acceptable safety profile in patients with thoracic malignancy. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Physical Basis of the Explosion Source and Generation of Regional Seismic Phases

DTIC Science & Technology

2007-08-31

Randolph Road AIR FORCE MATERIEL COMMAND Hanscom AFB, MA 01731-3010 NOTICE AND SIGNATURE PAGE Using Government drawings...corporation; or convey any rights or permission to manufacture, use , or sell any patented invention that may relate to them. This report was...100 5. An Upper Bound on Rg to Lg Scattering Using Modal Energy Conservation..................... 103 5.1. Summary

The impact of hospital accreditation on clinical documentation compliance: a life cycle explanation using interrupted time series analysis.

PubMed

Devkaran, Subashnie; O'Farrell, Patrick N

2014-08-05

To evaluate whether accredited hospitals maintain quality and patient safety standards over the accreditation cycle by testing a life cycle explanation of accreditation on quality measures. Four distinct phases of the accreditation life cycle were defined based on the Joint Commission International process. Predictions concerning the time series trend of compliance during each phase were specified and tested. Interrupted time series (ITS) regression analysis of 23 quality and accreditation compliance measures. A 150-bed multispecialty hospital in Abu Dhabi, UAE. Each month (over 48 months) a simple random sample of 24% of patient records was audited, resulting in 276,000 observations collected from 12,000 patient records, drawn from a population of 50,000. The impact of hospital accreditation on the 23 quality measures was observed for 48 months, 1 year preaccreditation (2009) and 3-year postaccreditation (2010-2012). The Life Cycle Model was evaluated by aggregating the data for 23 quality measures to produce a composite score (YC) and fitting an ITS regression equation to the unweighted monthly mean of the series. The four phases of the life cycle are as follows: the initiation phase, the presurvey phase, the postaccreditation slump phase and the stagnation phase. The Life Cycle Model explains 87% of the variation in quality compliance measures (R(2)=0.87). The ITS model not only contains three significant variables (β1, β2 and β3) (p≤0.001), but also the size of the coefficients indicates that the effects of these variables are substantial (β1=2.19, β2=-3.95 (95% CI -6.39 to -1.51) and β3=-2.16 (95% CI -2.52 to -1.80). Although there was a reduction in compliance immediately after the accreditation survey, the lack of subsequent fading in quality performance should be a reassurance to researchers, managers, clinicians and accreditors. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Improving outcomes in patients with coexisting multimorbid conditions-the development and evaluation of the combined diabetes and renal control trial (C-DIRECT): study protocol.

PubMed

Griva, Konstadina; Mooppil, Nandakumar; Khoo, Eric; Lee, Vanessa Yin Woan; Kang, Augustine Wee Cheng; Newman, Stanton P

2015-02-12

Diabetes mellitus (DM) is the most common cause of end-stage renal disease (ESRD). Patients with diabetes on dialysis have worse clinical outcomes and increased psychological burden. The need to manage the combined treatment demands for both conditions is particularly challenging yet there is paucity of data of the barriers preventing optimal management to combined therapy for diabetes and kidney failure. The study aims to explore needs of patients and develop an intervention to enable people with diabetes and ESRD to better manage both their conditions. A two-phase study comprising a mixed method observational study (phase I) and a feasibility trial (phase II). Phase I will seek to document outcomes and needs of the population (patients with DM-ESRD) and seek input on preferred delivery/implementation for the programme. Data will be collected with in-depth interviews with patients, caregivers and healthcare providers (N=50), and from a questionnaire-based survey (N=170). Phase 2 will build on these data to design and test the feasibility of a practical, low-intensity, clinic-integrated intervention using a self-management paradigm. The intervention will primarily seek to support behavioural change so as to improve adherence and clinical outcomes for DM as well as for ESRD. For the feasibility trial, we will be evaluating acceptability, retention and completion rates of the programme. The study protocol has been approved by the local ethics committee and written informed consent is required from every participant. Findings will be disseminated through journals, conferences and will be used to create a fully manualised intervention (materials) and training course for facilitators. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Next-Generation Fire Extinguishing Agent. Phase 4. Foundation for New Training Agent Development

DTIC Science & Technology

1989-12-01

Administration PCE perchloroethylene PEL Permissible Exposure Limit QSAR Quantitative Structure Activity Relationship SBUV Solar Backscatter Ultraviolet xi...can pass through the troposphere without destruction to enter the stratosphere. In the stratosphere, they photolyze in the intense solar radiation to...radiation, UV-B, striking the earth. Preliminary data from a Solar Backscatter Ultraviolet (SBUV) instrument aboard NASA’s Nimbus 7 satellite show a

GenPlay Multi-Genome, a tool to compare and analyze multiple human genomes in a graphical interface.

PubMed

Lajugie, Julien; Fourel, Nicolas; Bouhassira, Eric E

2015-01-01

Parallel visualization of multiple individual human genomes is a complex endeavor that is rapidly gaining importance with the increasing number of personal, phased and cancer genomes that are being generated. It requires the display of variants such as SNPs, indels and structural variants that are unique to specific genomes and the introduction of multiple overlapping gaps in the reference sequence. Here, we describe GenPlay Multi-Genome, an application specifically written to visualize and analyze multiple human genomes in parallel. GenPlay Multi-Genome is ideally suited for the comparison of allele-specific expression and functional genomic data obtained from multiple phased genomes in a graphical interface with access to multiple-track operation. It also allows the analysis of data that have been aligned to custom genomes rather than to a standard reference and can be used as a variant calling format file browser and as a tool to compare different genome assembly, such as hg19 and hg38. GenPlay is available under the GNU public license (GPL-3) from http://genplay.einstein.yu.edu. The source code is available at https://github.com/JulienLajugie/GenPlay. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Resting-state networks in healthy adult subjects: a comparison between a 32-element and an 8-element phased array head coil at 3.0 Tesla.

PubMed

Paolini, Marco; Keeser, Daniel; Ingrisch, Michael; Werner, Natalie; Kindermann, Nicole; Reiser, Maximilian; Blautzik, Janusch

2015-05-01

Little research exists on the influence of a magnetic resonance imaging (MRI) head coil's channel count on measured resting-state functional connectivity. To compare a 32-element (32ch) and an 8-element (8ch) phased array head coil with respect to their potential to detect functional connectivity within resting-state networks. Twenty-six healthy adults (mean age, 21.7 years; SD, 2.1 years) underwent resting-state functional MRI at 3.0 Tesla with both coils using equal standard imaging parameters and a counterbalanced design. Independent component analysis (ICA) at different model orders and a dual regression approach were performed. Voxel-wise non-parametric statistical between-group contrasts were determined using permutation-based non-parametric inference. Phantom measurements demonstrated a generally higher image signal-to-noise ratio using the 32ch head coil. However, the results showed no significant differences between corresponding resting-state networks derived from both coils (p < 0.05, FWE-corrected). Using the identical standard acquisition parameters, the 32ch head coil does not offer any significant advantages in detecting ICA-based functional connectivity within RSNs. © The Foundation Acta Radiologica 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Hollow Fiber Supported Ionic Liquids Liquid-Phase Micro-extraction Followed by High-Performance Liquid Chromatography for the Determination of Polycyclic Aromatic Hydrocarbons in Milk Samples.

PubMed

Wang, Meng; Cheng, Chunsheng; Liu, Chunbo; Yang, Yaling

2018-01-01

A rapid, simple, reliable and efficient hollow fiber supported ionic liquids liquid-phase micro-extraction method (IL-HF-LPME) followed by high-performance liquid chromatography was successfully applied to the determination of four kinds of polycyclic aromatic hydrocarbons (PAHs) in milk samples. In the IL-HF-LPME method, a mixture of [OMIM]PF6 and lauric acid, in a ratio of 3:1, was immobilized in the pores of a polypropylene hollow fiber used as extraction solvent. A series of essential parameters influencing the extraction efficiency were investigated and optimized. Under the optimal conditions, the extraction equilibrium is achieved within 3 min, the good linearity was >0.9990, the limits of detection varied from 0.14 to 0.71 ng/mL, the limit of quantification values were between 0.4 and 1.8 ng/mL, and the relative standard deviations were in the range of 1.24-3.27% (n = 5). The proposed method was applied to analyze four PAHs in milk samples and recoveries were between 93.6 and 102.8%. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Validated Method for the Quantification of Baclofen in Human Plasma Using Solid-Phase Extraction and Liquid Chromatography-Tandem Mass Spectrometry.

PubMed

Nahar, Limon Khatun; Cordero, Rosa Elena; Nutt, David; Lingford-Hughes, Anne; Turton, Samuel; Durant, Claire; Wilson, Sue; Paterson, Sue

2016-03-01

A highly sensitive and fully validated method was developed for the quantification of baclofen in human plasma. After adjusting the pH of the plasma samples using a phosphate buffer solution (pH 4), baclofen was purified using mixed mode (C8/cation exchange) solid-phase extraction (SPE) cartridges. Endogenous water-soluble compounds and lipids were removed from the cartridges before the samples were eluted and concentrated. The samples were analyzed using triple-quadrupole liquid chromatography-tandem mass spectrometry (LC-MS-MS) with triggered dynamic multiple reaction monitoring mode for simultaneous quantification and confirmation. The assay was linear from 25 to 1,000 ng/mL (r(2) > 0.999; n = 6). Intraday (n = 6) and interday (n = 15) imprecisions (% relative standard deviation) were <5%, and the average recovery was 30%. The limit of detection of the method was 5 ng/mL, and the limit of quantification was 25 ng/mL. Plasma samples from healthy male volunteers (n = 9, median age: 22) given two single oral doses of baclofen (10 and 60 mg) on nonconsecutive days were analyzed to demonstrate method applicability. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

HPLC/Fluorometric Detection of Carvedilol in Real Human Plasma Samples Using Liquid-Liquid Extraction.

PubMed

Yilmaz, Bilal; Arslan, Sakir

2016-03-01

A simple, rapid and sensitive high-performance liquid chromatography (HPLC) method has been developed to quantify carvedilol in human plasma using an isocratic system with fluorescence detection. The method included a single-step liquid-liquid extraction with diethylether and ethylacetate mixture (3 : 1, v/v). HPLC separation was carried out by reversed-phase chromatography with a mobile phase composed of 20 mM phosphate buffer (pH 7)-acetonitrile (65 : 35, v/v), pumped at a flow rate of 1.0 mL/min. Fluorescence detection was performed at 240 nm (excitation) and 330 nm (emission). The calibration curve for carvedilol was linear from 10 to 250 ng/mL. Intra- and interday precision values for carvedilol in human plasma were <4.93%, and accuracy (relative error) was better than 4.71%. The analytical recovery of carvedilol from human plasma averaged out to 91.8%. The limits of detection and quantification of carvedilol were 3.0 and 10 ng/mL, respectively. Also, the method was successfully applied to three patients with hypertension who had been given an oral tablet of 25 mg carvedilol. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Extracting morphologies from third harmonic generation images of structurally normal human brain tissue.

PubMed

Zhang, Zhiqing; Kuzmin, Nikolay V; Groot, Marie Louise; de Munck, Jan C

2017-06-01

The morphologies contained in 3D third harmonic generation (THG) images of human brain tissue can report on the pathological state of the tissue. However, the complexity of THG brain images makes the usage of modern image processing tools, especially those of image filtering, segmentation and validation, to extract this information challenging. We developed a salient edge-enhancing model of anisotropic diffusion for image filtering, based on higher order statistics. We split the intrinsic 3-phase segmentation problem into two 2-phase segmentation problems, each of which we solved with a dedicated model, active contour weighted by prior extreme. We applied the novel proposed algorithms to THG images of structurally normal ex-vivo human brain tissue, revealing key tissue components-brain cells, microvessels and neuropil, enabling statistical characterization of these components. Comprehensive comparison to manually delineated ground truth validated the proposed algorithms. Quantitative comparison to second harmonic generation/auto-fluorescence images, acquired simultaneously from the same tissue area, confirmed the correctness of the main THG features detected. The software and test datasets are available from the authors. z.zhang@vu.nl. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Validated RP-HPLC/DAD Method for the Quantification of Insect Repellent Ethyl 2-Aminobenzoate in Membrane-Moderated Matrix Type Monolithic Polymeric Device.

PubMed

Islam, Johirul; Zaman, Kamaruz; Chakrabarti, Srijita; Sharma Bora, Nilutpal; Mandal, Santa; Pratim Pathak, Manash; Srinivas Raju, Pakalapati; Chattopadhyay, Pronobesh

2017-07-01

A simple, accurate and sensitive reversed-phase high-performance liquid chromatographic (RP-HPLC) method has been developed for the estimation of ethyl 2-aminobenzoate (EAB) in a matrix type monolithic polymeric device and validated as per the International Conference on Harmonization guidelines. The analysis was performed isocratically on a ZORBAX Eclipse plus C18 analytical column (250 × 4.4 mm, 5 μm) and a diode array detector (DAD) using acetonitrile and water (75:25 v/v) as the mobile phase by keeping the flow-rate constant at 1.0 mL/min. Determination of EAB was not interfered in the presence of excipients. Inter- and intra-day relative standard deviations were not higher than 2%. Mean recovery was between 98.7 and 101.3%. Calibration curve was linear in the concentration range of 0.5-10 µg/mL. Limits of detection and quantification were 0.19 and 0.60 µg/mL, respectively. Thus, the present report put forward a novel method for the estimation of EAB, an emerging insect repellent, by using RP-HPLC technique. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

In situ polymerization of monolith based on poly(Triallyl Isocyanurate-co-trimethylolpropane triacrylate) and its application in high-performance liquid chromatography.

PubMed

Zhong, Jing; Bai, Ligai; Qin, Junxiao; Wang, Jiafei; Hao, Mengbei; Yang, Gengliang

2015-04-01

A novel organic monolithic stationary phase was prepared for high-performance liquid chromatography (HPLC) by in situ copolymerization. In which, triallyl isocyanurate (TAIC) and trimethylolpropane triacrylate (TMPTA) in a binary porogenic solvent consisting of polyethylene glycol 200 and 1, 2-propanediol were used. The resultant monoliths with different column properties (e.g., morphology and pressure) were optimized by adjusting the ratio of TMPTA/TAIC and the composition of porogenic solvent. The resulting poly(TAIC-co-TMPTA) monolith showed a relatively homogeneous structure, good permeability and mechanical stability. The chemical group of the monolith was assayed by the infrared spectra method, the morphology of monolithic material was studied by scanning electron microscopy and the pore size distribution was determined by a mercury porosimeter. A series of small molecules were used to evaluate the column performance in terms of hydrophobic mode. At an optimized flow rate of 1.0 mL min(-1), the theoretical plate number of analyte was >15,000 plates m(-1). These applications demonstrated that the monoliths could be successfully used as the stationary phase in conjunction with HPLC to separate small molecules from the mixture. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Pervasive competition between threat and reward in the brain.

PubMed

Choi, Jong Moon; Padmala, Srikanth; Spechler, Philip; Pessoa, Luiz

2014-06-01

In the current functional MRI study, we investigated interactions between reward and threat processing. Visual cues at the start of each trial informed participants about the chance of winning monetary reward and/or receiving a mild aversive shock. We tested two competing hypothesis: according to the 'salience hypothesis', in the condition involving both reward and threat, enhanced activation would be observed because of increased salience; according to the 'competition hypothesis', the processing of reward and threat would trade-off against each other, leading to reduced activation. Analysis of skin conductance data during a delay phase revealed an interaction between reward and threat processing, such that the effect of reward was reduced during threat and the effect of threat was reduced during reward. Analysis of imaging data during the same task phase revealed interactions between reward and threat processing in several regions, including the midbrain/ventral tegmental area, caudate, putamen, bed nucleus of the stria terminalis, anterior insula, middle frontal gyrus and dorsal anterior cingulate cortex. Taken together, our findings reveal conditions during which reward and threat trade-off against each other across multiple sites. Such interactions are suggestive of competitive processes and may reflect the organization of opponent systems in the brain. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Expansion and retrenchment of the Swedish welfare state: a long-term approach.

PubMed

Buendía, Luis

2015-01-01

In this article, we will undertake a long-term analysis of the evolution of the Swedish welfare state, seeking to explain that evolution through the use of a systemic approach. That is, our approach will consider the interrelations between economic growth (EG), the sociopolitical institutional framework (IF), and the welfare state (WS)-understood as a set of institutions embracing the labor market and its regulation, the tax system, and the so-called social wage-in order to find the main variables that elucidate its evolution. We will show that the expansive phase of the Swedish welfare state can be explained by the symbiotic relationships developed in the WS-EG-IF interaction, whereas the period of welfare state retrenchment is one result of changes operating within the sociopolitical IF and EG bases. © The Author(s) 2015 Reprints and permissions:]br]sagepub.co.uk/journalsPermissions.nav.

CellTracker (not only) for dummies.

PubMed

Piccinini, Filippo; Kiss, Alexa; Horvath, Peter

2016-03-15

Time-lapse experiments play a key role in studying the dynamic behavior of cells. Single-cell tracking is one of the fundamental tools for such analyses. The vast majority of the recently introduced cell tracking methods are limited to fluorescently labeled cells. An equally important limitation is that most software cannot be effectively used by biologists without reasonable expertise in image processing. Here we present CellTracker, a user-friendly open-source software tool for tracking cells imaged with various imaging modalities, including fluorescent, phase contrast and differential interference contrast (DIC) techniques. CellTracker is written in MATLAB (The MathWorks, Inc., USA). It works with Windows, Macintosh and UNIX-based systems. Source code and graphical user interface (GUI) are freely available at: http://celltracker.website/ horvath.peter@brc.mta.hu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Ongoing neural development of affective theory of mind in adolescence.

PubMed

Vetter, Nora C; Weigelt, Sarah; Döhnel, Katrin; Smolka, Michael N; Kliegel, Matthias

2014-07-01

Affective Theory of Mind (ToM), an important aspect of ToM, involves the understanding of affective mental states. This ability is critical in the developmental phase of adolescence, which is often related with socio-emotional problems. Using a developmentally sensitive behavioral task in combination with functional magnetic resonance imaging, the present study investigated the neural development of affective ToM throughout adolescence. Eighteen adolescent (ages 12-14 years) and 18 young adult women (aged 19-25 years) were scanned while evaluating complex affective mental states depicted by actors in video clips. The ventromedial prefrontal cortex (vmPFC) showed significantly stronger activation in adolescents in comparison to adults in the affective ToM condition. Current results indicate that the vmPFC might be involved in the development of affective ToM processing in adolescence. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Phase I study of olaparib plus gemcitabine in patients with advanced solid tumours and comparison with gemcitabine alone in patients with locally advanced/metastatic pancreatic cancer.

PubMed

Bendell, J; O'Reilly, E M; Middleton, M R; Chau, I; Hochster, H; Fielding, A; Burke, W; Burris, H

2015-04-01

Olaparib (Lynparza) is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor that induces synthetic lethality in cancers with homologous recombination defects. In this phase I, dose-escalation trial, patients with advanced solid tumours received olaparib (50-200 mg capsules b.i.d.) continuously or intermittently (days 1-14, per 28-day cycle) plus gemcitabine [i.v. 600-800 mg/m(2); days 1, 8, 15, and 22 (cycle 1), days 1, 8, and 15 (subsequent cycles)] to establish the maximum tolerated dose. A separate dose-escalation phase evaluated olaparib in tablet formulation (100 mg o.d./b.i.d.; days 1-14) plus gemcitabine (600 mg/m(2)). In an expansion phase, patients with genetically unselected locally advanced or metastatic pancreatic cancer were randomised 2 : 1 to the tolerated olaparib capsule combination dose or gemcitabine alone (1000 mg/m(2)). Sixty-six patients were treated [dose-escalation phase, n = 44 (tablet cohort, n = 12); dose-expansion phase, n = 22 (olaparib plus gemcitabine, n = 15; gemcitabine alone, n = 7)]. In the dose-escalation phase, four patients (6%) experienced dose-limiting toxicities (raised alanine aminotransferase, n = 2; neutropenia, n = 1; febrile neutropenia, n = 1). Grade ≥3 adverse events were reported in 38/47 patients (81%) treated with olaparib capsules plus gemcitabine; most common were haematological toxicities (55%). Tolerated combinations were olaparib 100 mg b.i.d. capsule (intermittently, days 1-14) plus gemcitabine 600 mg/m(2) and olaparib 100 mg o.d. tablet (intermittently, days 1-14) plus gemcitabine 600 mg/m(2). There were no differences in efficacy observed during the dose-expansion phase. Olaparib 100 mg b.i.d. (intermittent dosing; capsules) plus gemcitabine 600 mg/m(2) is tolerated in advanced solid tumour patients, with no unmanageable/unexpected toxicities. Continuous dosing of olaparib or combination with gemcitabine at doses >600 mg/m(2) was not considered to have an acceptable tolerability profile for further study. NCT00515866. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

UNderstanding uptake of Immunisations in TravellIng aNd Gypsy communities (UNITING): protocol for an exploratory, qualitative study.

PubMed

Jackson, Cath; Bedford, Helen; Condon, Louise; Crocker, Annie; Emslie, Carol; Dyson, Lisa; Gallagher, Bridget; Kerr, Susan; Lewis, Helen J; Mytton, Julie; Redsell, Sarah A; Schicker, Frieda; Shepherd, Christine; Smith, Lesley; Vousden, Linda; Cheater, Francine M

2015-06-08

Gypsies, Travellers and Roma (referred to here as Travellers) experience significantly poorer health and have shorter life expectancy than the general population. They are also less likely to access health services including immunisation. To improve immunisation rates, we need to understand what helps and hinders individuals in these communities in taking up immunisations. This study has two aims: (1) Investigate the barriers and facilitators to acceptability and uptake of immunisations among six Traveller communities in the UK; (2) Identify potential interventions to increase uptake in these Traveller communities. A three-phase qualitative study with six Traveller communities. PHASE 1: In each community, we will explore up to 45 Travellers' views about the influences on their immunisation behaviours and ideas for improving uptake in their community. PHASE 2: In each community, we will investigate 6-8 service providers' perspectives on barriers and facilitators to childhood and adult immunisations for Traveller communities with whom they work, and ideas to improve uptake. Interview data will be analysed using the Framework approach. PHASE 3: The findings will be discussed and interventions prioritised in six workshops, each with 10-12 phase 1 and 3-4 phase 2 participants. This research received approval from NRES Committee Yorkshire and The Humber-Leeds East (Ref. 13/YH/02). It will produce (1) findings on the barriers and facilitators to uptake of immunisations in six Traveller communities; (2) a prioritised list of potentially feasible and acceptable interventions for increasing uptake in these communities; and (3) methodological development in undertaking research with diverse Traveller communities. The study has the potential to inform new ways of delivering services to ensure high immunisation uptake. Findings will be disseminated to participants, relevant UK organisations with responsibility for the implementation of immunisation policy and Traveller health/welfare; and submitted for publication in academic journals. ISRCTN20019630. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Computer-aided detection system for chest radiography: reducing report turnaround times of examinations with abnormalities.

PubMed

Kao, E-Fong; Liu, Gin-Chung; Lee, Lo-Yeh; Tsai, Huei-Yi; Jaw, Twei-Shiun

2015-06-01

The ability to give high priority to examinations with pathological findings could be very useful to radiologists with large work lists who wish to first evaluate the most critical studies. A computer-aided detection (CAD) system for identifying chest examinations with abnormalities has therefore been developed. To evaluate the effectiveness of a CAD system on report turnaround times of chest examinations with abnormalities. The CAD system was designed to automatically mark chest examinations with possible abnormalities in the work list of radiologists interpreting chest examinations. The system evaluation was performed in two phases: two radiologists interpreted the chest examinations without CAD in phase 1 and with CAD in phase 2. The time information recorded by the radiology information system was then used to calculate the turnaround times. All chest examinations were reviewed by two other radiologists and were divided into normal and abnormal groups. The turnaround times for the examinations with pathological findings with and without the CAD system assistance were compared. The sensitivity and specificity of the CAD for chest abnormalities were 0.790 and 0.697, respectively, and use of the CAD system decreased the turnaround time for chest examinations with abnormalities by 44%. The turnaround times required for radiologists to identify chest examinations with abnormalities could be reduced by using the CAD system. This system could be useful for radiologists with large work lists who wish to first evaluate the most critical studies. © The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Subzero-Temperature Liquid-Liquid Extraction Coupled with UPLC-MS-MS for the Simultaneous Determination of 12 Bioactive Components in Traditional Chinese Medicine Gegen-Qinlian Decoction.

PubMed

Shi, Zhihong; Li, Zhimin; Zhang, Shulan; Fu, Hongna; Zhang, Hongyi

2015-09-01

Based on the phase separation phenomenon of acetonitrile-water system at subzero temperature, a subzero-temperature liquid-liquid extraction coupled with ultra-performance liquid chromatography tandem quadrupole mass spectrometry : UPLC-MS-MS) method was developed for the simultaneous determination of 12 bioactive components in Gegen-Qinlian decoction. After optimization, the extraction conditions were set as follows: 3.0 mL of aqueous sample solution (pH 5.86) was extracted with 2 mL of acetonitrile at -35°C for 35 min. The separated acetonitrile phase was diluted 10-fold with water before UPLC-MS-MS analysis. Separation was performed on a Waters ACQUITY UPLC(®)BEH C18 column (2.1 × 100 mm i.d., 1.7 µm) with ammonium formate buffer solution (20 mmol L(-1), pH 3.2, adjusted by formic acid) and acetonitrile as mobile phase with gradient elution. Twelve target components could be separated within 10 min and quantified in multiple reaction monitoring mode, both positive and negative ionization modes were employed. Limits of detection were in the range of 0.0003-0.0451 μg mL(-1). Relative standard deviation values for intra- and interday precision were <2.71 and 8.94%, respectively. The established method provides a simple and effective framework for the quality control of Gegen-Qinlian decoction and related traditional Chinese medicinal preparations. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Calcium Alginate-Caged Multiwalled Carbon Nanotubes Dispersive Microsolid Phase Extraction Combined With Gas Chromatography-Flame Ionization Detection for the Determination of Polycyclic Aromatic Hydrocarbons in Water Samples.

PubMed

Abboud, Ayad Sami; Sanagi, Mohd Marsin; Ibrahim, Wan Aini Wan; Keyon, Aemi S Abdul; Aboul-Enein, Hassan Y

2018-02-01

In this study, caged calcium alginate-caged multiwalled carbon nanotubes dispersive microsolid phase extraction was described for the first time for the extraction of polycyclic aromatic hydrocarbons (PAHs) from water samples prior to gas chromatographic analysis. Fluorene, phenanthrene and fluoranthene were selected as model compounds. The caged calcium alginate-caged multiwalled carbon nanotubes was characterized by Fourier transform infrared spectroscopy, scanning electron microscopy and thermal gravimetry analyses. The effective parameters namely desorption solvent, solvent volume, extraction time, desorption time, the mass of adsorbent and sample volume were optimized. Under the optimum extraction conditions, the developed method showed good linearity in the range of 0.5-50 ng mL-1 (R2 ≥ 0.996), low limits of detection and quantification (0.42-0.22 ng mL-1) (0.73-1.38 ng mL-1) respectively, good relative recoveries (71.2-104.2%) and reproducibility (RSD 1.8-12.4%, n = 3) for the studied PAHs in water sample. With high enrichment factor (1,000), short extraction time (<30 min), low amounts of adsorbent (100 mg) and low amounts of solvent (0.1 mol) have proven that the microsolid phase extraction method based on calcium alginate-caged multiwalled carbon nanotubes are environmentally friendly and convenient extraction method to use as an alternative adsorbent in the simultaneous preconcentration of PAHs from environmental water samples. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The cell-cycle interactome: a source of growth regulators?

PubMed

Blomme, Jonas; Inzé, Dirk; Gonzalez, Nathalie

2014-06-01

When plants develop, cell proliferation and cell expansion are tightly controlled in order to generate organs with a determinate final size such as leaves. Several studies have demonstrated the importance of the cell proliferation phase for leaf growth, illustrating that cell-cycle regulation is crucial for correct leaf development. A large and complex set of interacting proteins that constitute the cell-cycle interactome controls the transition from one cell-cycle phase to another. Here, we review the current knowledge on cell-cycle regulators from this interactome affecting final leaf size when their expression is altered, mainly in Arabidopsis. In addition to the description of mutants of CYCLIN-DEPENDENT KINASES (CDKs), CYCLINS (CYCs), and their transcriptional and post-translational regulators, a phenotypic analysis of gain- and loss-of-function mutants for 27 genes encoding proteins that interact with cell-cycle proteins is presented. This compilation of information shows that when cell-cycle-related genes are mis-expressed, leaf growth is often altered and that, seemingly, three main trends appear to be crucial in the regulation of final organ size by cell-cycle-related genes: (i) cellular compensation; (ii) gene dosage; and (iii) correct transition through the G2/M phase by ANAPHASE PROMOTING COMPLEX/CYCLOSOME (APC/C) activation. In conclusion, this meta-analysis shows that the cell-cycle interactome is enriched in leaf growth regulators, and illustrates the potential to identify new leaf growth regulators among putative new cell-cycle regulators. © The Author 2013. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

[The youth phase from the viewpoint of children and adolescents: crisis or fun?].

PubMed

Endepohls, M

1995-12-01

Goal of the present study was to analyze by means of a questionnaire how the life phase "youth" is represented in the mind of children and adolescents. The sample consisted of 152 persons aged between 11 and 18. The questionnaire asked not only for the general assumptions about this phase of life but also for their evaluation. The large heterogenity of the answers are in accordance with recent theories form sociology and psychology according to which common assumptions shared by all individuals of a cohort are replaced by individual conceptions. Based on these results, traditional views of the youth phase made by developmental psychologists are criticized. Especially, the thesis of a normative crisis during this life phase has to be rejected. Instead, a high satisfaction with being in this life phase must be acknowledged, this statement being more valid for female than male subjects. Other differences with respect to the conceptions of life phases due to sex or education have not been found important. The answers of the youngest persons made obvious that especially the increase of permissions and status associated with youth make this life phase more attractive.

Trophic or full nutritional support?

PubMed

Arabi, Yaseen M; Al-Dorzi, Hasan M

2018-06-04

Full nutritional support during the acute phase of critical illness has traditionally been recommended to reduce catabolism and prevent malnutrition. Approaches to achieve full nutrition include early initiation of nutritional support, targeting full nutritional requirement as soon as possible and initiation of supplemental parenteral nutrition when enteral nutrition does not reach the target. Existing evidence supports early enteral nutrition over delayed enteral nutrition or early parenteral nutrition. Recent randomized controlled trials have demonstrated that permissive underfeeding or trophic feeding is associated with similar outcomes compared with full feeding in the acute phase of critical illness. In patients with refeeding syndrome, patients with high nutritional risk and patients with shock, early enteral nutrition targeting full nutritional targets may be associated with worse outcomes compared with less aggressive enteral nutrition strategy. A two-phase approach for nutritional support may more appropriately account for the physiologic changes during critical illness than one-phase approach. Further evidence is awaited for the optimal protein amount during critical illness and for feeding patients at high nutritional risk or with acute gastrointestinal injury.

Changes in hospitalization rates for acute coronary syndrome after a two-phase comprehensive smoking ban.

PubMed

Séguret, Fabienne; Ferreira, Christelle; Cambou, Jean-Pierre; Carrière, Isabelle; Thomas, Daniel

2014-12-01

The impact of a comprehensive stepwise smoking ban (2007 and 2008) was assessed by analysing the hospitalization rate for acute coronary syndrome (ACS) in France, between 2003 and 2009. Between 2003 and 2009, 867,164 hospitalizations for ACS were observed among about 23 million administrative reports. The age-and gender-standardized hospitalization rates were calculated and their variation before and after the smoking ban implementation was investigated by Poisson regression that included the ACS seasonal variations and the historical trend. The hospitalization rate decreased by 12.8% (from 269 to 235/100,000) with a significant historical trend reduction (p < 0.10(-3)) in all groups, but in young women. After adjusting for linear trend, reductions linked to the ban remained not significant in all groups: relative risk (RR) from 0.96 (95% CI 0.91-1.01) in men older than 55 years to 0.99 (95% CI 0.93-1.04) in men aged 55 years or less after the first phase, and from 0.96 (95% CI 0.89-1.04) in men older than 55 years to 1.03 (95% CI 0.94-1.12) in women older than 65 years after the second phase of the ban. This study did not demonstrate a significant effect of a two-phases smoking ban on ACS hospitalization rate. A steadily decrease of this rate over the 7-year period, the past preventive measures in France leading to low levels of passive smoking, and the significant increase in active smoking during the studied period may explain this result. Our study highlights the difficulty of proving an effect of smoking bans in a country with an already low ACS incidence. © The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Management of behavioural change in patients presenting with a diagnosis of dementia: a video vignette study with Australian general practitioners.

PubMed

Jiwa, Moyez; Nichols, Pam; Magin, Parker; Pagey, Georgina; Meng, Xingqiong; Parsons, Richard; Pillai, Vinita

2014-09-25

To test the impact of feedback on the proposed management of standardised patients presenting with behavioural change with a diagnosis of dementia in Australian primary care. A video vignette study was performed with Australian general practitioners (GPs) in 2013. Participants viewed six pairs of matched videos depicting people presenting changed behaviour in the context of a dementia diagnosis in two phases. In both phases GPs indicated their diagnosis and management. After phase 1, GPs were offered feedback on management strategies for the patients depicted. Analyses focused on identification of change in management between the two phases of the study. Factors impacting on the intention to coordinate care for such patients were tested in a questionnaire based on the Theory of Planned Behaviour. Forty-five GPs completed the study. There was significant improvement in the proposed management of three of the six scenarios after the intervention. Older GPs were more likely to refer appropriately (OR=1.11 (1.01 to 1.23), p=0.04.). Overall referral to support agencies was more likely after the intervention (OR=2.52 (1.53 to 4.14), p<0.001). Older GPs were less likely to intend to coordinate care for such patients (OR=0.89 (0.81 to 0.98) p=0.02). Participants who felt confident about their ability to coordinate care were more likely to do so (OR=3.79 (1.08 to 13.32) p=0.04). The intervention described in this study promoted multidisciplinary management of patients with behavioural problems with a diagnosis of dementia. Increasing practitioner confidence in their ability to coordinate care may increase the proportion of GPs who will respond to patients and carers in this context. Older GPs may benefit in particular. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Lifetime Prevalence and Correlates of Schizophrenia-Spectrum, Affective, and Other Non-affective Psychotic Disorders in the Chinese Adult Population.

PubMed

Chang, Wing Chung; Wong, Corine Sau Man; Chen, Eric Yu Hai; Lam, Linda Chiu Wa; Chan, Wai Chi; Ng, Roger Man Kin; Hung, Se Fong; Cheung, Eric Fuk Chi; Sham, Pak Chung; Chiu, Helen Fung Kum; Lam, Ming; Lee, Edwin Ho Ming; Chiang, Tin Po; Chan, Lap Kei; Lau, Gary Kar Wai; Lee, Allen Ting Chun; Leung, Grace Tak Yu; Leung, Joey Shuk Yan; Lau, Joseph Tak Fai; van Os, Jim; Lewis, Glyn; Bebbington, Paul

2017-10-21

Lifetime prevalence of psychotic disorders varies widely across studies. Epidemiological surveys have rarely examined prevalences of specific psychotic disorders other than schizophrenia, and the majority used a single-phase design without employing clinical reappraisal interview for diagnostic verification. The current study investigated lifetime prevalence, correlates and service utilization of schizophrenia-spectrum, affective, and other non-affective psychotic disorders in a representative sample of community-dwelling Chinese adult population aged 16-75 years (N = 5719) based on a territory-wide, population-based household survey for mental disorders in Hong Kong. The survey adopted a 2-phase design comprising first-phase psychosis screening and second-phase diagnostic verification incorporating clinical information from psychiatrist-administered semi-structured interview and medical record review to ascertain DSM-IV lifetime diagnosis for psychotic disorders. Data on sociodemographics, psychosocial characteristics and service utilization were collected. Our results showed that lifetime prevalence was 2.47% for psychotic disorder overall, 1.25% for schizophrenia, 0.15% for delusional disorder, 0.38% for psychotic disorder not otherwise specified, 0.31% for bipolar disorder with psychosis, and 0.33% for depressive disorder with psychosis. Schizophrenia-spectrum disorder was associated with family history of psychosis, cigarette smoking and variables indicating socioeconomic disadvantage. Victimization experiences were significantly related to affective psychoses and other non-affective psychoses. Around 80% of participants with any psychotic disorder sought some kind of professional help for mental health problems in the past year. Using comprehensive diagnostic assessment involving interview and record data, our results indicate that approximately 2.5% of Chinese adult population had lifetime psychotic disorder which represents a major public health concern. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Capnogram slope and ventilation dead space parameters: comparison of mainstream and sidestream techniques.

PubMed

Balogh, A L; Petak, F; Fodor, G H; Tolnai, J; Csorba, Z; Babik, B

2016-07-01

Capnography may provide useful non-invasive bedside information concerning heterogeneity in lung ventilation, ventilation-perfusion mismatching and metabolic status. Although the capnogram may be recorded by mainstream and sidestream techniques, the capnogram indices furnished by these approaches have not previously been compared systematically. Simultaneous mainstream and sidestream time and volumetric capnography was performed in anaesthetized, mechanically ventilated patients undergoing elective heart surgery. Time capnography was used to assess the phase II (SII,T) and III slopes (SIII,T). The volumetric method was applied to estimate phase II (SII,V) and III slopes (SIII,V), together with the dead space values according to the Fowler (VDF), Bohr (VDB), and Enghoff (VDE) methods and the volume of CO2 eliminated per breath ([Formula: see text]). The partial pressure of end-tidal CO2 ([Formula: see text]) was registered. Excellent correlation and good agreement were observed in SIII,T measured by the mainstream and sidestream techniques [ratio=1.05 (sem 0.16), R(2)=0.92, P<0.0001]. Although the sidestream technique significantly underestimated [Formula: see text] and overestimated SIII,V [1.32 (0.28), R(2)=0.93, P<0.0001], VDF, VDB, and VDE, the agreement between the mainstream and sidestream techniques in the difference between VDE and VDB, reflecting the intrapulmonary shunt, was excellent [0.97 (0.004), R(2)=0.92, P<0.0001]. The [Formula: see text] exhibited good correlation and mild differences between the mainstream and sidestream approaches [0.025 (0.005) kPa]. Sidestream capnography provides adequate quantitative bedside information about uneven alveolar emptying and ventilation-perfusion mismatching, because it allows reliable assessments of the phase III slope, [Formula: see text] and intrapulmonary shunt. Reliable measurement of volumetric parameters (phase II slope, dead spaces, and eliminated CO2 volumes) requires the application of a mainstream device. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

HIV-1 Transmission During Recent Infection and During Treatment Interruptions as Major Drivers of New Infections in the Swiss HIV Cohort Study.

PubMed

Marzel, Alex; Shilaih, Mohaned; Yang, Wan-Lin; Böni, Jürg; Yerly, Sabine; Klimkait, Thomas; Aubert, Vincent; Braun, Dominique L; Calmy, Alexandra; Furrer, Hansjakob; Cavassini, Matthias; Battegay, Manuel; Vernazza, Pietro L; Bernasconi, Enos; Günthard, Huldrych F; Kouyos, Roger D; Aubert, V; Battegay, M; Bernasconi, E; Böni, J; Bucher, H C; Burton-Jeangros, C; Calmy, A; Cavassini, M; Dollenmaier, G; Egger, M; Elzi, L; Fehr, J; Fellay, J; Furrer, H; Fux, C A; Gorgievski, M; Günthard, H F; Haerry, D; Hasse, B; Hirsch, H H; Hoffmann, M; Hösli, I; Kahlert, C; Kaiser, L; Keiser, O; Klimkait, T; Kouyos, R D; Kovari, H; Ledergerber, B; Martinetti, G; de Tejada, B Martinez; Metzner, K; Müller, N; Nadal, D; Nicca, D; Pantaleo, G; Rauch, A; Regenass, S; Rickenbach, M; Rudin, C; Schöni-Affolter, F; Schmid, P; Schüpbach, J; Speck, R; Tarr, P; Trkola, A; Vernazza, P L; Weber, R; Yerly, S

2016-01-01

Reducing the fraction of transmissions during recent human immunodeficiency virus (HIV) infection is essential for the population-level success of "treatment as prevention". A phylogenetic tree was constructed with 19 604 Swiss sequences and 90 994 non-Swiss background sequences. Swiss transmission pairs were identified using 104 combinations of genetic distance (1%-2.5%) and bootstrap (50%-100%) thresholds, to examine the effect of those criteria. Monophyletic pairs were classified as recent or chronic transmission based on the time interval between estimated seroconversion dates. Logistic regression with adjustment for clinical and demographic characteristics was used to identify risk factors associated with transmission during recent or chronic infection. Seroconversion dates were estimated for 4079 patients on the phylogeny, and comprised between 71 (distance, 1%; bootstrap, 100%) to 378 transmission pairs (distance, 2.5%; bootstrap, 50%). We found that 43.7% (range, 41%-56%) of the transmissions occurred during the first year of infection. Stricter phylogenetic definition of transmission pairs was associated with higher recent-phase transmission fraction. Chronic-phase viral load area under the curve (adjusted odds ratio, 3; 95% confidence interval, 1.64-5.48) and time to antiretroviral therapy (ART) start (adjusted odds ratio 1.4/y; 1.11-1.77) were associated with chronic-phase transmission as opposed to recent transmission. Importantly, at least 14% of the chronic-phase transmission events occurred after the transmitter had interrupted ART. We demonstrate a high fraction of transmission during recent HIV infection but also chronic transmissions after interruption of ART in Switzerland. Both represent key issues for treatment as prevention and underline the importance of early diagnosis and of early and continuous treatment. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Systems to Detect Bacterial Contamination of Banked Blood in a Rapid, Non-Invasive Low Technology Manner. Phase 1.

DTIC Science & Technology

1994-08-25

Department of the Army position, policy or decision unless so designated by other documentation. 94-30800 IIV III !111 IiI I ’ I foron Appr •vedREPORT...copyrighted material is quoted, permission has been obtained to use such material. Where material from documents designated for limited distribution is...Laser Scanning Densitometry for quantitation of the color changes. (6) Narrative: a. Eperimental Methods: 1. Bacteria: Ten bacterial species

Modeling the Combined Effects of Deterministic and Statistical Structure for Optimization of Regional Monitoring

DTIC Science & Technology

2015-06-30

Aberdeen Ave SE AIR FORCE MATERIEL COMMAND KIRTLAND AIR FORCE BASE, NM 87117-5776 DTIC COPY NOTICE AND SIGNATURE PAGE Using Government drawings...or corporation; or convey any rights or permission to manufacture, use , or sell any patented invention that may relate to them. This report was...synthesizing seismograms using a radiative transport technique to predict the high frequency coda (2 to 4 Hz) of regional seismic phases at stations

Determinants of Global Color-Based Selection in Human Visual Cortex.

PubMed

Bartsch, Mandy V; Boehler, Carsten N; Stoppel, Christian M; Merkel, Christian; Heinze, Hans-Jochen; Schoenfeld, Mircea A; Hopf, Jens-Max

2015-09-01

Feature attention operates in a spatially global way, with attended feature values being prioritized for selection outside the focus of attention. Accounts of global feature attention have emphasized feature competition as a determining factor. Here, we use magnetoencephalographic recordings in humans to test whether competition is critical for global feature selection to arise. Subjects performed a color/shape discrimination task in one visual field (VF), while irrelevant color probes were presented in the other unattended VF. Global effects of color attention were assessed by analyzing the response to the probe as a function of whether or not the probe's color was a target-defining color. We find that global color selection involves a sequence of modulations in extrastriate cortex, with an initial phase in higher tier areas (lateral occipital complex) followed by a later phase in lower tier retinotopic areas (V3/V4). Importantly, these modulations appeared with and without color competition in the focus of attention. Moreover, early parts of the modulation emerged for a task-relevant color not even present in the focus of attention. All modulations, however, were eliminated during simple onset-detection of the colored target. These results indicate that global color-based attention depends on target discrimination independent of feature competition in the focus of attention. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Determination of pyrazole and pyrrole pesticides in environmental water samples by solid-phase extraction using multi-walled carbon nanotubes as adsorbent coupled with high-performance liquid chromatography.

PubMed

Ma, Jiping; Lu, Xi; Xia, Yan; Yan, Fengli

2015-02-01

A solid-phase extraction (SPE) method using multi-walled carbon nanotubes as adsorbent coupled with high-performance liquid chromatography was developed for the determination of four pyrazole and pyrrole pesticides (fenpyroximate, chlorfenapyr, fipronil and flusilazole) in environmental water samples. Several parameters, such as extraction adsorbent, elution solvent and volume and sample loading flow rate were optimized to obtain high SPE recoveries and extraction efficiency. The calibration curves for the pesticides extracted were linear in the range of 0.05-10 μg L(-1) for chlorfenapyr and fenpyroximate and 0.05-20 μg L(-1) for fipronil and flusilazole, with the correlation coefficients (r(2)) between 0.9966 and 0.9990. The method gave good precisions (relative standard deviation %) from 2.9 to 10.1% for real spiked samples from reservoir water and seawater; method recoveries ranged 92.2-105.9 and 98.5-103.9% for real spiked samples from reservoir water and seawater, respectively. Limits of detection (S/N = 3) for the method were determined to be 8-19 ng L(-1). The optimized method was successfully applied to the determination of four pesticides of pyrazoles and pyrroles in real environmental water samples. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Stability-Indicating Reversed-Phase UHPLC Method Development and Characterization of Degradation Products of Almotriptan Maleate by LC-QTOF-MS/MS.

PubMed

Saibaba, B; Vishnuvardhan, Ch; Johnsi Rani, P; Satheesh Kumar, N

2018-01-01

Almotriptan maleate (ALMT), a highly selective 5-hydroxy tryptamine 1B/1D (5-HT1B/1D) receptor agonist used in the treatment of migraine headache was subjected to various ICH (Q1A (R2)) specified guidelines. The drug underwent significant degradation under hydrolytic (acid, base and neutral), oxidative and photolytic stress conditions, while it was stable under thermal stress condition. A total of seven significant degradation products (DPs) were obtained. A simple, selective and reliable UPLC method has been developed for the separation of ALMT and its DPs using Acquity UPLC HSS Cyano (100 × 2.1 mm, 1.8 μm) column with mobile phase consisting of ammonium acetate (10 mM, pH 4.4) buffer and acetonitrile in gradient elution mode. Chromatographic analysis was performed at a flow rate of 0.3 mL/min using a PDA detector at a wavelength of 230 nm. All the DPs (DP-1 to DP-7) were characterized using UHPLC-ESI-QTOF based on mass fragmentation pattern and accurate m/z values. The developed UPLC method was validated in terms of specificity, linearity, precision and accuracy. The developed stability-indicating method helps in quantification of drug in the presence of DPs. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Using Global and Regional Species Distribution Models (SDM) to Infer the Invasive Stage of Latrodectus geometricus (Araneae: Theridiidae) in the Americas.

PubMed

Taucare-Ríos, Andrés; Bizama, Gustavo; Bustamante, Ramiro O

2016-12-01

The brown widow spider, Latrodectus geometricus C. L. Koch, 1841, is a large spider of the family Theridiidae that belongs to a genus of medical interest owing to its potent neurotoxic venom, which causes severe pain in humans. In America, this alien spider has been found in virtually all countries in the region, mainly associated with human dwellings, but also in agricultural sectors. However, the invasive process and potential distribution of this invasive species across the American continent are completely unknown. In this context, using a combination of both global and regional niche models, it is possible to hypothesize the invasive phase of the species as well as the geographic space where these different phases occur. By comparing the global and regional niches of L. geometricus, we examined its invasive process and potential distribution across the American continent. This work is an innovative approach to understanding the invasion of the brown widow spider in this area and the ecological processes that underlie this invasion. In this context, the global and regional niche comparison constitutes an appropriate tool to account for the complexities of the invasive process, generating different hypotheses amenable to being tested in future studies. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Female Mice Avoid Male Odor from the Same Strain via the Vomeronasal System in an Estrogen-Dependent Manner.

PubMed

Yano, Saori; Sakamoto, Kentaro Q; Habara, Yoshiaki

2015-11-01

Inbreeding avoidance is essential to providing offspring with genetic diversity. Females' mate choice is more crucial than males' for successful reproduction because of the high cost of producing gametes and limited chances to mate. However, the mechanism of female inbreeding avoidance is still unclear. To elucidate the mechanism underlying inbreeding avoidance by females, we conducted Y-maze behavioral assays using BALB/c and C57BL/6 female mice. In both strains, the avoidance of male urine from the same strain was lower in the low estrogen phase than in the high estrogen phase. The estrous cycle-dependent avoidance was completely prevented by vomeronasal organ (VNO) removal. To assess the regulation of the vomeronasal system by estrogen, the neural excitability was evaluated by immunohistochemistry of the immediate early gene products. Although estrogen did not affect neural excitability in the VNO, estrogen enhanced the neural excitability of the mitral cell layer in the AOB induced by urine from the cognate males. These results suggest that female mice avoid odor from genetically similar males in an estrogen-dependent manner via the vomeronasal system and the excitability of the mitral cells in the AOB is presumed to be regulated by estrogen. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Analysis of Rhizome Development in Oryza longistaminata, a Wild Rice Species.

PubMed

Yoshida, Akiko; Terada, Yasuhiko; Toriba, Taiyo; Kose, Katsumi; Ashikari, Motoyuki; Kyozuka, Junko

2016-10-01

Vegetative reproduction is a form of asexual propagation in plants. A wide range of plants develop rhizomes, modified stems that grow underground horizontally, as a means of vegetative reproduction. In rhizomatous species, despite their distinct developmental patterns, both rhizomes and aerial shoots derive from axillary buds. Therefore, it is of interest to understand the basis of rhizome initiation and development. Oryza longistaminata, a wild rice species, develops rhizomes. We analyzed bud initiation and growth of O. longistaminata rhizomes using various methods of morphological observation. We show that, unlike aerial shoot buds that contain a few leaves only, rhizome buds initiate several leaves and bend to grow at right angles to the original rhizome. Rhizomes are maintained in the juvenile phase irrespective of the developmental phase of the aerial shoot. Stem elongation and reproductive transition are tightly linked in the aerial shoots, but are uncoupled in the rhizome. Our findings indicate that developmental programs operate independently in the rhizomes and aerial shoots. Temporal modification of the developmental pathways that are common to rhizomes and aerial shoots may be the source of developmental plasticity. Furthermore, the creation of new developmental systems appears to be necessary for rhizome development. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Ultra preconcentration of polycyclic aromatic hydrocarbons in smoked bacon by a combination of SPE and DLLME.

PubMed

Liu, Xiaofang; Zhou, Shu; Zhu, Quanfei; Ye, Yong; Chen, Huaixia

2014-09-01

A sample pretreatment method, solid-phase extraction combined with dispersive liquid-liquid microextraction (SPE-DLLME), was established for the sensitive determination of polycyclic aromatic hydrocarbons (PAHs) in smoked bacon samples. In the SPE-DLLME process, three PAHs including naphthalene (Naph), phenanthrene (Phen) and pyrene (Pyr) were extracted from samples and transferred into C18 SPE cartridge. The target analytes were subsequently eluted with 1.2 ml of acetonitrile-dichloromethane (5:1, v/v) mixture solution. The eluent was injected directly into the 5.0 ml ultrapure water in the subsequent DLLME procedure. The sedimented phase was concentrated under a gentle nitrogen flow to 120.0 µl. Finally, the analytes in the extraction solvent were determined by high-performance liquid chromatography with a ultra-violet detector. Some important extraction parameters affecting the performance, such as the sample solution flow rate, breakthrough volume, salt addition as well as the type and volume of the elution solvent were optimized. The developed method provided an ultra enrichment factors for PAHs ranged from 3478 to 3824. The method was applied for the selective extraction and sensitive determination of PAHs in smoked bacon samples. The limits of detection (S/N = 3) were 0.05, 0.01, 0.02 μg kg(-1) for Naph, Phen, Pyr, respectively. © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A phase III randomized trial of adding topical nitroglycerin to first-line chemotherapy for advanced nonsmall-cell lung cancer: the Australasian lung cancer trials group NITRO trial.

PubMed

Davidson, A; Veillard, A-S; Tognela, A; Chan, M M K; Hughes, B G M; Boyer, M; Briscoe, K; Begbie, S; Abdi, E; Crombie, C; Long, J; Boyce, A; Lewis, C R; Varma, S; Broad, A; Muljadi, N; Chinchen, S; Espinoza, D; Coskinas, X; Pavlakis, N; Millward, M; Stockler, M R

2015-11-01

We sought to determine whether the substantial benefits of topical nitroglycerin with first-line, platinum-based, doublet chemotherapy in advanced nonsmall-cell lung cancer (NSCLC) seen in a phase II trial could be corroborated in a rigorous, multicenter, phase III trial. Patients starting one of five, prespecified, platinum-based doublets as first-line chemotherapy for advanced NSCLC were randomly allocated treatment with or without nitroglycerin 25 mg patches for 2 days before, the day of, and 2 days after, each chemotherapy infusion. Progression-free survival (PFS) was the primary end point. Accrual was stopped after the first interim analysis of 270 events. Chemotherapy was predominantly with carboplatin and gemcitabine (79%) or carboplatin and paclitaxel (18%). The final analysis included 345 events in 372 participants with a median follow-up of 33 months. Topical nitroglycerin had no demonstrable effect on PFS [median 5.0 versus 4.8 months, hazard ratio (HR) = 1.07, 95% confidence interval (CI) 0.86-1.32, P = 0.55], overall survival (median 11.0 versus 10.3 months, HR = 0.99, 95% CI 0.79-1.24, P = 0.94), or objective tumor response (31% versus 30%, relative risk = 1.03, 95% CI 0.82-1.29, P = 0.81). Headache, hypotension, syncope, diarrhea, dizziness, and anorexia were more frequent in those allocated nitroglycerin. The addition of topical nitroglycerin to carboplatin-based, doublet chemotherapy in NSCLC had no demonstrable benefit and should not be used or pursued further. Australian New Zealand Clinical Trials Registry Number ACTRN12608000588392. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Development and Validation of an LC-MS-MS Method for Determination of Simvastatin and Simvastatin Acid in Human Plasma: Application to a Pharmacokinetic Study.

PubMed

Partani, Pankaj; Verma, Saurabh Manaswita; Monif, Tausif

2016-09-01

A liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of simvastatin (SV) and simvastatin acid (SVA) in human plasma. To improve assay sensitivity and achieve simultaneous analysis, SVA monitored in (-)ESI (electrospray ionization) mode within the first 4.5 min and SV thereafter in (+)ESI mode. The separation of all compounds was achieved in about 6.2 min using a C18 reverse-phase fused-core(®) column (Ascentis(®) Express C18) and a mobile phase, which was composed of 2.00 ± 0.05 mM ammonium acetate buffer titrated to pH 3.8 with glacial acetic acid-acetonitrile (25:75, v/v), in isocratic mode at a flow rate of 0.500 mL/min. Additionally, a solid-phase extraction step was performed to reduce any ion-suppression and/or enhancement effects. The developed method was linear in the concentration range of 0.100-74.626 ng/mL for SV, and 0.100-48.971 ng/mL for SVA, with correlation coefficient greater than 0.99 for both analytes. The method has shown tremendous reproducibility, with intra- and inter-day precision <7.6%, and intra- and interday accuracy within ±10.9% of nominal values, for the both analytes. The method was successfully applied to characterize the pharmacokinetic profiles of SV and SVA following an oral administration of 40 mg SV tablet to healthy human volunteers. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Novel Chromatographic Methods for Simultaneous Quantification of Fish and Wheat Germ Oils Mixture in Pharmaceutical Dosage Forms.

PubMed

El-Yazbi, Amira F; El-Hawiet, Amr

2017-05-01

Two simple, direct and environment-friendly chromatographic methods, high-performance liquid chromatography (HPLC) and high-performance thin layer chromatographic (HPTLC), were developed for the determination of a binary mixture of fish oil (FO) and wheat germ oil (WGO), for the first time, in their pharmaceutical dosage forms with no need for any sample pretreatment. The HPLC separation was carried out using C-18 stationary phase with mobile phase of 15% formic acid (pH 6), methanol and acetonitrile through gradient-elution, 1.5 mL min-1 flow-rate and detection at 215 nm for FO and 280 nm for WGO. HPTLC separation was carried out on silica-coated plates using diethyl ether-petroleum ether (0.5:9.5, v/v) as mobile phase. Detection was at 215 nm for FO and 240 nm for WGO. Regression analysis showed good linear relationship with r > 0.999 in the concentration-ranges of 0.2-2 mg mL-1 and 2.5-20 μg band-1 for WGO by HPLC and HPTLC methods, respectively, and 0.4-10 mg mL-1 and 25-200 μg band-1 for FO by HPLC and HPTLC methods, respectively. The methods were validated, showed good analytical performance and were successfully applied for the analysis of pharmaceutical formulations and synthetic mixtures of the analytes with good recoveries. Therefore, the two methods could be conveniently adopted for routine analysis of similar products in quality control laboratories of pharmaceutical industries especially that simultaneous determination of FO-WGO mixture has not been reported previously. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

European Healthy City Network Phase V: patterns emerging for healthy urban planning.

PubMed

Grant, Marcus

2015-06-01

There is a tradition of planning cities and their infrastructure to successfully tackle communicable disease arising from urban development. Non-communicable disease follows a different course. Development brings in its wake a basket of adverse health and health equity outcomes that are proving difficult to tackle. In response, within Phase V of the European Healthy Cities Network, municipalities have implemented a range of policy and physical interventions using a settings approach. Owing to the time lag between physical interventions and health outcomes, this research interrogates city activity itself to develop better understanding. Self-reported city case studies and questionnaire data were analysed to reveal patterns using an inductive approach. Findings indicate that some categories of intervention, such as whole city planning and transport, have a systemic impact across the wider determinants of health. Addressing transferability and stakeholder understanding helped cities create conditions for successful outcomes. Cities had varying urban development approaches for tackling climate change. Improvements to current practice are discussed, including; a distinction between supply side and demand side in healthy urban planning; valuing co-benefits and developing integrative approaches to the evidence-base. This evaluative article is important for cities wanting to learn how to maximize benefits to public health through urban development and for researchers exploring, with a systemic approach, the experiences of European cities acting at the interface of urban development and public health. This article also provides recommendations for future phases of the WHO European Healthy Cities programme, posing questions to better address governance and equity in spatial planning. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

User needs analysis and usability assessment of DataMed - a biomedical data discovery index.

PubMed

Dixit, Ram; Rogith, Deevakar; Narayana, Vidya; Salimi, Mandana; Gururaj, Anupama; Ohno-Machado, Lucila; Xu, Hua; Johnson, Todd R

2017-11-30

To present user needs and usability evaluations of DataMed, a Data Discovery Index (DDI) that allows searching for biomedical data from multiple sources. We conducted 2 phases of user studies. Phase 1 was a user needs analysis conducted before the development of DataMed, consisting of interviews with researchers. Phase 2 involved iterative usability evaluations of DataMed prototypes. We analyzed data qualitatively to document researchers' information and user interface needs. Biomedical researchers' information needs in data discovery are complex, multidimensional, and shaped by their context, domain knowledge, and technical experience. User needs analyses validate the need for a DDI, while usability evaluations of DataMed show that even though aggregating metadata into a common search engine and applying traditional information retrieval tools are promising first steps, there remain challenges for DataMed due to incomplete metadata and the complexity of data discovery. Biomedical data poses distinct problems for search when compared to websites or publications. Making data available is not enough to facilitate biomedical data discovery: new retrieval techniques and user interfaces are necessary for dataset exploration. Consistent, complete, and high-quality metadata are vital to enable this process. While available data and researchers' information needs are complex and heterogeneous, a successful DDI must meet those needs and fit into the processes of biomedical researchers. Research directions include formalizing researchers' information needs, standardizing overviews of data to facilitate relevance judgments, implementing user interfaces for concept-based searching, and developing evaluation methods for open-ended discovery systems such as DDIs. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Phase 1 study of ombrabulin in combination with cisplatin (CDDP) in Japanese patients with advanced solid tumors.

PubMed

Takahashi, Shunji; Nakano, Kenji; Yokota, Tomoya; Shitara, Kohei; Muro, Kei; Sunaga, Yoshinori; Ecstein-Fraisse, Evelyne; Ura, Takashi

2016-08-27

In clinical studies in Western countries, the recommended dose of combination ombrabulin a vascular disrupting agent, with cisplatin is 25 mg/m 2 ombrabulin with 75 mg/m 2 cisplatin every 3 weeks. Here, we report the first Phase 1 study of this treatment regimen in Japanese patients with advanced solid tumors. This was an open-label, multicenter, sequential cohort, dose-escalation Phase 1 study of ombrabulin with cisplatin administered once every 3 weeks. The study used a 3 + 3 design without intrapatient dose escalation. The investigated dose levels of ombrabulin were 15.5 and 25 mg/m 2 combined with cisplatin 75 mg/m 2 . The latter dose level was regarded as the maximum administered dose if more than one patient experienced dose-limiting toxicities. Ten patients were treated, but no dose-limiting toxicity was observed at both dose levels. Ombrabulin 25 mg/m 2 with cisplatin 75 mg/m 2 was the maximum administered dose and regarded as the recommended dose in the combination regimen for Japanese patients with cancer. The most frequently reported drug-related adverse events were neutropenia, decreased appetite, constipation, nausea and fatigue. One partial response and five cases of stable disease were reported as the best overall responses. Pharmacokinetic parameters of ombrabulin and cisplatin were comparable with those in non-Japanese patients. Ombrabulin 25 mg/m 2 with cisplatin 75 mg/m 2 once every 3 weeks was well tolerated and established as the recommended dose in Japanese patients with advanced solid tumors. The safety and pharmacokinetic profiles were comparable between Japanese and Caucasian patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Light-Emitting Diode (LED) Traps Improve the Light-Trapping of Anopheline Mosquitoes.

PubMed

Costa-Neta, B M; da Silva, A A; Brito, J M; Moraes, J L P; Rebêlo, J M M; Silva, F S

2017-11-07

Numerous advantages over the standard incandescent lamp favor the use of light-emitting diodes (LEDs) as an alternative and inexpensive light source for sampling medically important insects in surveillance studies. Previously published studies examined the response of mosquitoes to different wavelengths, but data on anopheline mosquito LED attraction are limited. Center for Disease Control and Prevention-type light traps were modified by replacing the standard incandescent lamp with 5-mm LEDs, one emitting at 520 nm (green) and the other at 470 nm (blue). To test the influence of moon luminosity on LED catches, the experiments were conducted during the four lunar phases during each month of the study period. A total of 1,845 specimens representing eight anopheline species were collected. Anopheles (Nyssorhynchus) evansae (35.2%) was the most frequently collected, followed by An. (Nys.) triannulatus (21.9%), An. (Nys.) goeldii (12.9%), and An. (Nys.) argyritarsis (11.5%). The green LED was the most attractive light source, accounting for 43.3% of the individuals collected, followed by the blue (31.8%) and control (24.9%) lights. The LED traps were significantly more attractive than the control, independent of the lunar phase. Light trapping of anopheline mosquitoes was more efficient when the standard incandescent lamp was replaced with LEDs, regardless of the moon phase. The efficiency of LEDs improves light trapping results, and it is suggested that the use of LEDs as an attractant for anopheline mosquitoes should be taken into consideration when sampling anopheline mosquitoes. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Use of Dialectical Behavior Therapy (DBT) in Music Therapy: A Sequential Explanatory Study.

PubMed

Chwalek, Carolyn M; McKinney, Cathy H

2015-01-01

There are published examples of how dialectical behavior therapy (DBT) and music therapy are effectively being used as separate therapies in the treatment of individuals with a variety of mental health disorders. However, research examining DBT-informed music therapy is limited. The purpose of this study was to determine whether music therapists working in mental health settings are implementing components of DBT in their work, and if so, how and why; and if not, why not and what is their level of interest in such work. We used a sequential explanatory mixed-methods research design implemented in two phases. Phase 1 was a quantitative survey of board-certified music therapists (n=260). Due to a low survey response rate (18%), and to enhance the validity of the findings, Phase 2, an embedded qualitative procedure in the form of interviews with clinicians experienced in the DBT approach, was added to the study. Both survey and interviews inquired about DBT training, use of DBT-informed music therapy, music therapy experiences used to address DBT skills, and experiences of implementing DBT-informed music therapy. Respondents indicating they implement DBT-informed music therapy (38.3%) are using components and adaptations of the standard DBT protocol. Advantages of implementing DBT-informed music therapy were identified, and more than half of the respondents who do not implement DBT in their music therapy practice also perceived this work as at least somewhat important. Disadvantages were also identified and support the need for further research. Components of DBT are used in music therapy and are valued, but there is a lack of empirical evidence to inform, refine, and guide practice. © the American Music Therapy Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Phase I trial of p28 (NSC745104), a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in pediatric patients with recurrent or progressive central nervous system tumors: A Pediatric Brain Tumor Consortium Study.

PubMed

Lulla, Rishi R; Goldman, Stewart; Yamada, Tohru; Beattie, Craig W; Bressler, Linda; Pacini, Michael; Pollack, Ian F; Fisher, Paul Graham; Packer, Roger J; Dunkel, Ira J; Dhall, Girish; Wu, Shengjie; Onar, Arzu; Boyett, James M; Fouladi, Maryam

2016-09-01

p53 is a promising target in human cancer. p28 is a cell-penetrating peptide that preferentially enters cancer cells and binds to both wild-type and mutant p53 protein, inhibiting COP1-mediated ubiquitination and proteasomal degradation. This results in increased levels of p53, which induces cell cycle arrest at G2/M. We conducted a phase I study to determine the maximum-tolerated dose (MTD) and describe the dose-limiting toxicities (DLTs) and pharmacokinetics (PKs) of p28 in children. Children aged 3-21 years with recurrent or progressive central nervous system tumors were eligible. Intravenous p28 was administered 3 times weekly for 4 consecutive weeks of a 6-week cycle at 4.16 mg/kg/dose (the adult recommended phase II dose) using a rolling-6 study design. Expression status of p53 was characterized by immunohistochemistry, and serum PK parameters were established on the second dose. Of the 18 eligible patients enrolled in the study, 12 completed the DLT monitoring period and were evaluable for toxicity. p28 was well-tolerated; 7 participants received ≥2 courses, and the most common adverse event attributed to the drug was transient grade 1 infusion-related reaction. PK analysis revealed a profile similar to adults; however, an increased area under the curve was observed in pediatric patients. High p53 expression in tumor cell nuclei was observed in 6 of 12 available tissue samples. There were no objective responses; 2 participants remained stable on the study for >4 cycles. This phase I study demonstrated that p28 is well-tolerated in children with recurrent CNS malignancies at the adult recommended phase II dose. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Managers' use of nursing workforce planning and deployment technologies: protocol for a realist synthesis of implementation and impact.

PubMed

Burton, Christopher; Rycroft-Malone, Jo; Williams, Lynne; Davies, Siân; McBride, Anne; Hall, Beth; Rowlands, Anne-M; Jones, Adrian

2016-08-26

Nursing staffing levels in hospitals appear to be associated with improved patient outcomes. National guidance indicates that the triangulation of information from workforce planning and deployment technologies (WPTs; eg, the Safer Nursing Care Tool) and 'local knowledge' is important for managers to achieve appropriate staffing levels for better patient outcomes. Although WPTs provide managers with predictive information about future staffing requirements, ensuring patient safety and quality care also requires the consideration of information from other sources in real time. Yet little attention has been given to how to support managers to implement WPTs in practice. Given this lack of understanding, this evidence synthesis is designed to address the research question: managers' use of WPTs and their impacts on nurse staffing and patient care: what works, for whom, how and in what circumstances? To explain how WPTs may work and in what contexts, we will conduct a realist evidence synthesis through sourcing relevant evidence, and consulting with stakeholders about the impacts of WPTs on health and relevant public service fields. The review will be in 4 phases over 18 months. Phase 1: we will construct an initial theoretical framework that provides plausible explanations of what works about WPTs. Phase 2: evidence retrieval, review and synthesis guided by the theoretical framework; phase 3: testing and refining of programme theories, to determine their relevance; phase 4: formulating actionable recommendations about how WPTs should be implemented in clinical practice. Ethical approval has been gained from the study's institutional sponsors. Ethical review from the National Health Service (NHS) is not required; however research and development permissions will be obtained. Findings will be disseminated through stakeholder engagement and knowledge mobilisation activities. The synthesis will develop an explanatory programme theory of the implementation and impact of nursing WPTs, and practical guidance for nurse managers. CRD42016038132. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Uterus transplantation: ethical and regulatory challenges.

PubMed

Arora, Kavita Shah; Blake, Valarie

2014-06-01

Moving forward rapidly in the clinical research phase, uterus transplantation may be a future treatment option for women with uterine factor infertility, which accounts for three per cent of all infertility in women. This new method of treatment would allow women, who currently rely on gestational surrogacy or adoption, to gestate and birth their own genetic offspring. Since uterus transplantation carries significant risk when compared with surrogacy and adoption as well as when compared with other organ transplants, it requires greater justification because its goals are quality of life, not life-saving, in their scope. It is important to address questions regarding the physical, psychosocial and ethical risks and benefits of uterus transplantation for all three parties involved--the patient, the donor and the potential child--as well as discuss the regulatory implications as research on uterus transplantations moves forward. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Characterization of resistance to rhabdovirus and retrovirus infection in a human myeloid cell line.

PubMed

Boso, Guney; Somia, Nikunj V

2015-01-01

Viruses interact with various permissive and restrictive factors in host cells throughout their replication cycle. Cell lines that are non-permissive to viral infection have been particularly useful in discovering host cell proteins involved in viral life cycles. Here we describe the characterization of a human myeloid leukemia cell line, KG-1, that is resistant to infection by retroviruses and a Rhabdovirus. We show that KG-1 cells are resistant to infection by Vesicular Stomatits Virus as well as VSV Glycoprotein (VSVG) pseudotyped retroviruses due to a defect in binding. Moreover our results indicate that entry by xenotropic retroviral envelope glycoprotein RD114 is impaired in KG-1 cells. Finally we characterize a post- entry block in the early phase of the retroviral life cycle in KG-1 cells that renders the cell line refractory to infection. This cell line will have utility in discovering proteins involved in infection by VSV and HIV-1.

Use of modified Delphi to plan knowledge translation for decision makers: an application in the field of advanced practice nursing.

PubMed

Carter, Nancy; Lavis, John N; MacDonald-Rencz, Sandra

2014-01-01

Disseminating research to decision makers is difficult. Interaction between researchers and decision makers can identify key messages and processes for dissemination. To gain agreement on the key findings from a synthesis on the integration of advanced practice nurses, we used a modified Delphi process. Nursing decision makers contributed ideas via e-mail, discussed and clarified ideas face to face, and then prioritized statements. Sixteen (89%) participated and 14 (77%) completed the final phase. Priority key messages were around access to care and outcomes. The majority identified "NPs increase access to care" and "NPs and CNSs improve patient and system outcomes" as priority messaging statements. Participants agreed policy makers and the public were target audiences for messages. Consulting with policy makers provided the necessary context to develop tailored policy messages and is a helpful approach for research dissemination. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Medical missionaries to China: the antecedents.

PubMed

Fu, Louis

2015-02-01

Notwithstanding the traditional belief that disciples of Jesus Christ introduced Christianity into China, conclusive evidence showed that it was the Nestorian missionaries who entered China in AD 635. Alongside commercial contacts between the West and China during the prosperous T'ang dynasty (618-906), trepanation, bloodletting and the universal antidote theriac were introduced from the Byzantium Empire. Nestorian Christians built churches throughout China and offered some form of medical services. During the Yuan (Mongol) dynasty (1260-1368), foreign physicians were present in the Royal Court; the most famous was the astronomer, linguist and physician Ai-hsieh (Isaiah), Head of the Imperial Medical Bureau. With the fall of this dynasty, Christianity, being primarily the faith of a foreign community, naturally fell into oblivion. It was not until the sixteenth-century's Age of Discovery when a safe sea route to China was found that a new phase of Christian missionaries began. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Why high-risk, non-expected-utility-maximising gambles can be rational and beneficial: the case of HIV cure studies.

PubMed

Buchak, Lara

2017-02-01

Some early phase clinical studies of candidate HIV cure and remission interventions appear to have adverse medical risk-benefit ratios for participants. Why, then, do people participate? And is it ethically permissible to allow them to participate? Recent work in decision theory sheds light on both of these questions, by casting doubt on the idea that rational individuals prefer choices that maximise expected utility, and therefore by casting doubt on the idea that researchers have an ethical obligation not to enrol participants in studies with high risk-benefit ratios. This work supports the view that researchers should instead defer to the considered preferences of the participants themselves. This essay briefly explains this recent work, and then explores its application to these two questions in more detail. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Anthrax toxin receptor 1 is the cellular receptor for Seneca Valley virus

PubMed Central

Miles, Linde A.; Burga, Laura N.; Gardner, Eric E.; Bostina, Mihnea; Poirier, John T.; Rudin, Charles M.

2017-01-01

Seneca Valley virus (SVV) is an oncolytic picornavirus with selective tropism for neuroendocrine cancers. It has shown promise as a cancer therapeutic in preclinical studies and early-phase clinical trials. Here, we have identified anthrax toxin receptor 1 (ANTXR1) as the receptor for SVV using genome-wide loss-of-function screens. ANTXR1 is necessary for permissivity in vitro and in vivo. However, robust SVV replication requires an additional innate immune defect. We found that SVV interacts directly and specifically with ANTXR1, that this interaction is required for SVV binding to permissive cells, and that ANTXR1 expression is necessary and sufficient for infection in cell lines with decreased expression of antiviral IFN genes at baseline. Finally, we identified the region of the SVV capsid that is responsible for receptor recognition using cryoelectron microscopy of the SVV-ANTXR1-Fc complex. These studies identify ANTXR1, a class of receptor that is shared by a mammalian virus and a bacterial toxin, as the cellular receptor for SVV. PMID:28650343

Experimental evaluation of fingerprint verification system based on double random phase encoding

NASA Astrophysics Data System (ADS)

Suzuki, Hiroyuki; Yamaguchi, Masahiro; Yachida, Masuyoshi; Ohyama, Nagaaki; Tashima, Hideaki; Obi, Takashi

2006-03-01

We proposed a smart card holder authentication system that combines fingerprint verification with PIN verification by applying a double random phase encoding scheme. In this system, the probability of accurate verification of an authorized individual reduces when the fingerprint is shifted significantly. In this paper, a review of the proposed system is presented and preprocessing for improving the false rejection rate is proposed. In the proposed method, the position difference between two fingerprint images is estimated by using an optimized template for core detection. When the estimated difference exceeds the permissible level, the user inputs the fingerprint again. The effectiveness of the proposed method is confirmed by a computational experiment; its results show that the false rejection rate is improved.

Daily low-dose hCG stimulation during the luteal phase combined with GnRHa triggered IVF cycles without exogenous progesterone: a proof of concept trial.

PubMed

Andersen, Claus Yding; Elbaek, Helle Olesen; Alsbjerg, Birgit; Laursen, Rita Jakubcionyte; Povlsen, Betina Boel; Thomsen, Lise; Humaidan, Peter

2015-10-01

Can the luteal phase support be improved in terms of efficacy, hormonal profiles and convenience as compared with today's standard care? Daily low-dose rhCG supplementation in GnRHa triggered IVF cycles can replace the traditional used luteal phase support with exogenous progesterone. A bolus of hCG for final maturation of follicles in connection with COS may induce the risk of OHSS and the luteal phase progesterone levels rise very abruptly in the early luteal phase. This is a proof-of-concept study conducted as a three arm RCT with a total of 93 patients. First patient enrolled in January 2012 and the study finished in January 2014. Normal responder women undergoing IVF/ICSI treatment in a university hospital. One arm served as control, where women followed a standard antagonist protocol. Two study arms were included both having 125 IU hCG daily for luteal phase support without exogenous progesterone after using a GnRHa trigger for ovulation induction. In both study arms exogenous FSH was stopped on stimulation day 6 and replaced by exogenous hCG that was initiated on either stimulation day 2 or day 6. Blood samples were obtained on the day of ovulation induction, on the day of oocyte pickup (OPU) and day OPU + 7. The mean serum levels of hCG did not exceeded the normal physiological range of LH activity in any samples. Mid-luteal progesterone levels were significantly higher in the two study groups receiving daily low-dose hCG for luteal phase support as compared with the control group (control group: 177 ± 27 nmol/l; study group 1: 334 ± 42 nmol/l; study group 2: 277 ± 27 nmol/l; (mean ± SEM). No differences in reproductive outcome were seen between groups. The number of patients included is limited and conclusions need to be verified in a larger RCT. Endogenous production of progesterone may become more attractive as the luteal phase support with levels of LH-like activity only in the physiological range and may, from the patients' point of view, replace inconvenient exogenous progesterone preparation. Further hCG may reduce the cost of stimulation and may collectively be used for stimulation of the follicular phase, ovulation induction and for luteal phase support. An unrestricted grant from ARTS Biologics made this study possible. None of the authors has any competing interests to declare. ClinicalTrial.gov number: NCT01504139. 28 December 2011. © The Author 2015. 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.

Uranium in the Islamic Republic of Mauritania (phase V, deliverable 81): Chapter N in Second projet de renforcement institutionnel du secteur minier de la République Islamique de Mauritanie (PRISM-II)

USGS Publications Warehouse

Fernette, Gregory

2015-01-01

Uranium occurrences are also reported in the Tasiast-Tijirit Terrane of the Archean Rgueïbat Shield, the Mauritanide Belt, and the Coastal Basin. Geologic environments permissive for eight types of uranium deposits are recognized in Mauritania. These deposit types include: calcrete, granite-hosted vein/shear, alkaline intrusive, unconformity-associated, quartz pebble conglomerate, phosphate, sandstone, and red bed-type uranium deposits.

Approximation of a Brittle Fracture Energy with a Constraint of Non-interpenetration

NASA Astrophysics Data System (ADS)

Chambolle, Antonin; Conti, Sergio; Francfort, Gilles A.

2018-06-01

Linear fracture mechanics (or at least the initiation part of that theory) can be framed in a variational context as a minimization problem over an SBD type space. The corresponding functional can in turn be approximated in the sense of {Γ}-convergence by a sequence of functionals involving a phase field as well as the displacement field. We show that a similar approximation persists if additionally imposing a non-interpenetration constraint in the minimization, namely that only nonnegative normal jumps should be permissible.

Pilot-study on the feasibility of sentinel node navigation surgery in combination with thoracolaparoscopic lymphadenectomy without esophagectomy in early esophageal adenocarcinoma patients.

PubMed

Künzli, H T; van Berge Henegouwen, M I; Gisbertz, S S; van Esser, S; Meijer, S L; Bennink, R J; Wiezer, M J; Seldenrijk, C A; Bergman, J J G H M; Weusten, B L A M

2017-11-01

High-risk submucosal esophageal adenocarcinoma's might be treated curatively by means of radical endoscopic resection, followed by thoracolaparoscopic lymphadenectomy without concomitant esophagectomy. A preclinical study has shown the feasibility and safety of this approach; however, no studies are performed in a clinical setting. In addition, sentinel node navigation surgery could be valuable in tailoring the extent of the lymphadenectomy. This study aimed to evaluate the feasibility and safety of thoracolaparoscopic lymphadenectomy without esophagectomy (phase I) and sentinel node navigation surgery (phase II) in patients with early esophageal adenocarcinoma. Patients with T1N0M0 early esophageal adenocarcinoma scheduled for esophagectomy without neoadjuvant therapy were included. Phase I: Two-field, esophagus preserving, thoracolaparoscopic lymphadenectomy was performed, followed by esophagectomy in the same session. Primary outcome parameters were the number of lymph nodes resected, and number of retained lymph nodes in the esophagectomy specimen. Phase II: A radioactive tracer was injected endoscopically the day before surgery. Static imaging was performed 15 and 120 minutes after injection. The day of surgery, sentinel node navigation surgery followed by esophagectomy was performed. Primary outcome parameters were the percentage of patients with a detectable sentinel node, and the concordance between static imaging and probe-based detection of sentinel node. Phase I: Five patients were included, and a median of 30 (IQR: 25-46) lymph nodes was resected. A median of 6 (IQR: 2-9) retained lymph nodes was found in the esophagectomy specimen. No acute adverse events occurred, but near the end of lymphadenectomy esophageal discoloration was observed, possibly indicating ischemia. Phase II: In all five included patients sentinel nodes could be visualized and resected, at a median of 3 (IQR: 2-5) locations. There was a high concordance between imaging and probe-based detection of sentinel nodes. In conclusion, sentinel node navigation surgery followed by lymphadenectomy without concomitant esophagectomy seems feasible in patients with high-risk submucosal early esophageal adenocarcinoma. More evidence is however needed before applying this technique in clinical practice. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2- advanced breast cancer (BELLE-4).

PubMed

Martín, M; Chan, A; Dirix, L; O'Shaughnessy, J; Hegg, R; Manikhas, A; Shtivelband, M; Krivorotko, P; Batista López, N; Campone, M; Ruiz Borrego, M; Khan, Q J; Beck, J T; Ramos Vázquez, M; Urban, P; Goteti, S; Di Tomaso, E; Massacesi, C; Delaloge, S

2017-02-01

Phosphatidylinositol 3-kinase (PI3K) pathway activation in preclinical models of breast cancer is associated with tumor growth and resistance to anticancer therapies, including paclitaxel. Effects of the pan-Class I PI3K inhibitor buparlisib (BKM120) appear synergistic with paclitaxel in preclinical and clinical models. BELLE-4 was a 1:1 randomized, double-blind, placebo-controlled, adaptive phase II/III study investigating the combination of buparlisib or placebo with paclitaxel in women with human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer with no prior chemotherapy for advanced disease. Patients were stratified by PI3K pathway activation and hormone receptor status. The primary endpoint was progression-free survival (PFS) in the full and PI3K pathway-activated populations. An adaptive interim analysis was planned following the phase II part of the study, after ≥125 PFS events had occurred in the full population, to decide whether the study would enter phase III (in the full or PI3K pathway-activated population) or be stopped for futility. As of August 2014, 416 patients were randomized to receive buparlisib (207) or placebo (209) with paclitaxel. At adaptive interim analysis, there was no improvement in PFS with buparlisib versus placebo in the full (median PFS 8.0 versus 9.2 months, hazard ratio [HR] 1.18), or PI3K pathway-activated population (median PFS 9.1 versus 9.2 months, HR 1.17). The study met protocol-specified criteria for futility in both populations, and phase III was not initiated. Median duration of study treatment exposure was 3.5 months in the buparlisib arm versus 4.6 months in the placebo arm. The most frequent adverse events with buparlisib plus paclitaxel (≥40% of patients) were diarrhea, alopecia, rash, nausea, and hyperglycemia. Addition of buparlisib to paclitaxel did not improve PFS in the full or PI3K pathway-activated study population. Consequently, the trial was stopped for futility at the end of phase II. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Laser surface modification of AZ31B Mg alloy for bio-wettability.

PubMed

Ho, Yee-Hsien; Vora, Hitesh D; Dahotre, Narendra B

2015-02-01

Magnesium alloys are the potential degradable materials for load-bearing implant application due to their comparable mechanical properties to human bone, excellent bioactivity, and in vivo non-toxicity. However, for a successful load-bearing implant, the surface of bio-implant must allow protein absorption and layer formation under physiological environment that can assist the cell/osteoblast growth. In this regard, surface wettability of bio-implant plays a key role to dictate the quantity of protein absorption. In light of this, the main objective of the present study was to produce favorable bio-wettability condition of AZ31B Mg alloy bio-implant surface via laser surface modification technique under various laser processing conditions. In the present efforts, the influence of laser surface modification on AZ31B Mg alloy surface on resultant bio-wettability was investigated via contact-angle measurements and the co-relationships among microstructure (grain size), surface roughness, surface energy, and surface chemical composition were established. In addition, the laser surface modification technique was simulated by computational (thermal) model to facilitate the prediction of temperature and its resultant cooling/solidification rates under various laser processing conditions for correlating with their corresponding composition and phase evolution. These predicted thermal properties were later used to correlate with the corresponding microstructure, chemical composition, and phase evolution via experimental analyses (X-ray diffractometer, scanning electron microscope, energy-dispersive spectroscopy). © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Simultaneous determination of enalapril and hydrochlorothiazide in pharmaceutical preparations using microemulsion liquid chromatography.

PubMed

Hammouda, Mohammed E A; Abu El-Enin, Mohamed A; El-Sherbiny, Dina T; El-Wasseef, Dalia R; El-Ashry, Saadia M

2015-01-01

A rapid high-performance liquid chromatography procedure for analytical quality control of mixture containing enalapril maleate (ENM) and hydrochlorothiazide (HCT) in their pharmaceutical preparations was developed using a microemulsion as an eluent. The separation was performed on a column packed with cyano-bonded stationary phase adopting UV detection at 210 nm using a flow rate of 1 mL/min. The optimized microemulsion mobile phase consisted of 0.2 M sodium dodecyl sulfate, 1% octanol, 10% n-propanol and 0.3% triethylamine in 0.02 M phosphoric acid, and pH was adjusted at 3.5. The proposed method was found to be linear over the concentration ranges 1-100 and 0.05-5 μg/mL for ENM and HCT, respectively with a correlation coefficient of 0.9999 for both drugs. The developed method was validated in terms of specificity, linearity, lower limit of quantification, lower limit of detection, precision and accuracy. The proposed method is rapid (5 min), reproducible (relative standard deviation <2.0%) and achieves a satisfactory resolution between ENM and HCT (resolution factor = 3.62). The mean recoveries of the analytes in tablets were in agreement with those obtained from a comparison method, as revealed by statistical analysis of the obtained results using Student's t-test and the variance ratio F-test. © The Author [2014]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Latent Structure and Test-Retest Stability of Connected Language Measures in the Wisconsin Registry for Alzheimer's Prevention (WRAP).

PubMed

Mueller, Kimberly D; Koscik, Rebecca L; Clark, Lindsay R; Hermann, Bruce P; Johnson, Sterling C; Turkstra, Lyn S

2017-11-24

While it is well known that discourse-related language functions are impaired in the dementia phase of Alzheimer's Disease (AD), the presymptomatic temporal course of discourse dysfunction are not known earlier in the course of AD. To conduct discourse-related studies in this phase of AD, validated psychometric instruments are needed. This study investigates the latent structure, validity, and test-retest stability of discourse measures in a late-middle-aged normative group who are relatively free from sporadic AD risk factors. Using a normative sample of 399 participants (mean age = 61), exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were conducted on 18 measures of connected language derived from picture descriptions. Factor invariance across sex and family history and longitudinal test-retest stability measures were calculated. The EFA revealed a four-factor solution, consisting of semantic, syntax, fluency, and lexical constructs. The CFA model substantiated the structure, and factors were invariant across sex and parental history of AD status. Test-retest stability measures were within acceptable ranges. Results confirm a factor structure that is invariant across sex and parental AD history. The factor structure could be useful in similar cohorts designed to detect early language decline in investigations of preclinical or clinical AD or as outcome measures in clinical prevention trials. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Therapeutic Drug Monitoring of Fluoxetine, Norfluoxetine and Paroxetine: A New Tool Based on Microextraction by Packed Sorbent Coupled to Liquid Chromatography.

PubMed

Magalhães, Paulo; Alves, Gilberto; Llerena, Adrián; Falcão, Amílcar

2017-09-01

The present article reports the first liquid chromatography (LC) assay for the simultaneous quantification of fluoxetine (FLU), its metabolite norfluoxetine (NFLU) and paroxetine (PAR) in human plasma, applying the microextraction by packed sorbent (MEPS) technology in sample preparation. Chromatographic analysis of FLU, NFLU and PAR was achieved in <13 min on a reverse-phase C18 column using isocratic elution and fluorescence detection (FLD). The mobile phase was composed by an aqueous solution of 25 mM sodium phosphate monobasic anhydrous and 7.5 mM di-potassium hydrogen phosphate anhydrous (pH 3.0)/acetonitrile/methanol (70:23:7, v/v/v). The detector was set at 240/312 nm for FLU, NFLU and IS and at 295/350 nm for PAR. The method showed linearity in the ranges of 20-750 ng mL-1 for FLU and NFLU, and 5-750 ng mL-1 for PAR (r2 ≥ 0.9919). The overall intra- and interday precision did not exceed 13.6% and the corresponding accuracy (bias) ranged from 0.02 to 16.7%. The method was successfully applied in the analysis of authentic plasma samples. Hence, this new MEPS/LC-FLD assay ensures robust and low-cost analyses representing, therefore, a good alternative to support therapeutic drug monitoring and clinical studies involving these antidepressant drugs. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Simultaneous Determination of Soyasaponins and Isoflavones in Soy (Glycine max L.) Products by HPTLC-densitometry-Multiple Detection.

PubMed

Shawky, Eman; Sallam, Shaimaa M

2017-11-01

A new high-throughput method was developed for the simultaneous analysis of isoflavones and soyasaponnins in Soy (Glycine max L.) products by high-performance thin-layer chromatography with densitometry and multiple detection. Silica gel was used as the stationary phase and ethyl acetate:methanol:water:acetic acid (100:20:16:1, v/v/v/v) as the mobile phase. After chromatographic development, multi-wavelength scanning was carried out by: (i) UV-absorbance measurement at 265 nm for genistin, daidzin and glycitin, (ii) Vis-absorbance measurement at 650 nm for Soyasaponins I and III, after post-chromatographic derivatization with anisaldehyde/sulfuric acid reagent. Validation of the developed method was found to meet the acceptance criteria delineated by ICH guidelines with respect to linearity, accuracy, precision, specificity and robustness. Calibrations were linear with correlation coefficients of >0.994. Intra-day precisions relative standard deviation (RSD)% of all substances in matrix were determined to be between 0.7 and 0.9%, while inter-day precisions (RSD%) ranged between 1.2 and 1.8%. The validated method was successfully applied for determination of the studied analytes in soy-based infant formula and soybean products. The new method compares favorably to other reported methods in being as accurate and precise and in the same time more feasible and cost-effective. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed

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

2016-03-01

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

A maize root tip system to study DNA replication programmes in somatic and endocycling nuclei during plant development.

PubMed

Bass, Hank W; Wear, Emily E; Lee, Tae-Jin; Hoffman, Gregg G; Gumber, Hardeep K; Allen, George C; Thompson, William F; Hanley-Bowdoin, Linda

2014-06-01

The progress of nuclear DNA replication is complex in both time and space, and may reflect several levels of chromatin structure and 3-dimensional organization within the nucleus. To understand the relationship between DNA replication and developmental programmes, it is important to examine replication and nuclear substructure in different developmental contexts including natural cell-cycle progressions in situ. Plant meristems offer an ideal opportunity to analyse such processes in the context of normal growth of an organism. Our current understanding of large-scale chromosomal DNA replication has been limited by the lack of appropriate tools to visualize DNA replication with high resolution at defined points within S phase. In this perspective, we discuss a promising new system that can be used to visualize DNA replication in isolated maize (Zea mays L.) root tip nuclei after in planta pulse labelling with the thymidine analogue, 5-ethynyl-2'-deoxyuridine (EdU). Mixed populations of EdU-labelled nuclei are then separated by flow cytometry into sequential stages of S phase and examined directly using 3-dimensional deconvolution microscopy to characterize spatial patterns of plant DNA replication. Combining spatiotemporal analyses with studies of replication and epigenetic inheritance at the molecular level enables an integrated experimental approach to problems of mitotic inheritance and cellular differentiation. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Value of mechanical dyssynchrony as assessed by radionuclide ventriculography to predict the cardiac resynchronization therapy response.

PubMed

Tournoux, Francois; Chequer, Renata; Sroussi, Marjorie; Hyafil, Fabien; Algalarrondo, Vincent; Cohen-Solal, Alain; Bodson-Clermont, Paule; Le Guludec, Dominique; Rouzet, Francois

2016-11-01

To assess the value of mechanical dyssynchrony measured by equilibrium radionuclide angiography (ERNA) in predicting long-term outcome in cardiac resynchronization therapy (CRT) patients. We reviewed 146 ERNA studies performed in heart failure patients between 2001 and 2011 at our institution. Long-term follow-up focused on death from any cause or heart transplantation. Phase images were computed using the first harmonic Fourier transform. Intra-ventricular dyssynchrony was calculated as the delay between the earliest and most delayed 20% of the left ventricular (LV) (IntraV-20/80) and inter-ventricular dyssynchrony as the difference between LV- and right ventricular (RV)-mode phase angles (InterV). Eighty-three patients (57%) were implanted with a CRT device after ERNA. Median follow-up was 35 [21-50] months. Twenty-four events were observed during the first 41 months. Median baseline ERNA dyssynchrony values were 28 [3 to 46] degrees for intraV-20/80 and 9 [-6 to 24] degrees for interV. Comparing survival between CRT and non-CRT patients according to dyssynchrony status, log-rank tests showed no difference in survival in patients with no ERNA dyssynchrony (P = 0.34) while a significant difference was observed in ERNA patients with high level of mechanical dyssynchrony (P = 0.004). ERNA mechanical dyssynchrony could be of value in CRT patient selection. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

HPTLC and Spectrophotometric Estimation of Febuxostat and Diclofenac Potassium in Their Combined Tablets.

PubMed

El-Yazbi, Fawzi A; Amin, Omayma A; El-Kimary, Eman I; Khamis, Essam F; Younis, Sameh E

2016-08-01

An accurate, precise, rapid, specific and economic high-performance thin-layer chromatographic (HPTLC) method has been developed for the simultaneous quantitative determination of febuxostat (FEB) and diclofenac potassium (DIC). The chromatographic separation was performed on precoated silica gel 60 GF254 plates with chloroform-methanol 7:3 (v/v) as the mobile phase. The developed plates were scanned and quantified at 289 nm. Experimental conditions including band size, mobile phase composition and chamber-saturation time were critically studied, and the optimum conditions were selected. A satisfactory resolution (Rs = 2.67) with RF 0.48 and 0.69 and high sensitivity with limits of detection of 4 and 7 ng/band for FEB and DIC, respectively, were obtained. In addition, derivative ratio and ratio difference spectrophotometric methods were established for the analysis of such a mixture. All methods were validated as per the ICH guidelines. In the HPTLC method, the calibration plots were linear between 0.01-0.55 and 0.02-0.60 µg/band, for FEB and DIC, respectively. For the spectrophotometric methods, the calibration graphs were linear between 2-14 and 4-18 µg/mL for FEB and DIC, respectively. The simplicity and specificity of the proposed methods suggest their application in quality control analysis of FEB and DIC in their raw materials and tablets. A comparison of the proposed methods with the existing methods is presented. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Suppression of Oral Sweet Taste Sensation with Gymnema sylvestre Affects Postprandial Gastrointestinal Blood Flow and Gastric Emptying in Humans.

PubMed

Kashima, Hideaki; Eguchi, Kohei; Miyamoto, Kanae; Fujimoto, Masaki; Endo, Masako Yamaoka; Aso-Someya, Nami; Kobayashi, Toshio; Hayashi, Naoyuki; Fukuba, Yoshiyuki

2017-05-01

An oral sweet taste sensation (OSTS) exaggerates digestive activation transiently, but whether it has a role after swallowing a meal is not known. Gymnema sylvestre (GS) can inhibit the OSTS in humans. We explored the effect of the OSTS of glucose intake on gastrointestinal blood flow, gastric emptying, blood-glucose, and plasma-insulin responses during the postprandial phase. Eight participants ingested 200 g (50 g × 4 times) of 15% glucose solution containing 100 mg of 13C-sodium acetate after rinsing with 25 mL of 2.5% roasted green tea (control) or 2.5% GS solution. During each protocol, gastrointestinal blood flow and gastric emptying were measured by ultrasonography and 13C-sodium acetate breath test, respectively. Decreased subjective sweet taste intensity was observed in all participants in the GS group. The time to attain a peak value of blood flow in the celiac artery and gastric emptying were delayed in the GS group compared with the control group. At the initial phase after glucose intake, blood-glucose and plasma-insulin responses were lower in the GS group than those for the control group. These results suggest that the OSTS itself has a substantial role in controlling postprandial gastrointestinal activities, which may affect subsequent glycemic metabolism. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

RP-HPLC method development and validation for simultaneous estimation of atorvastatin calcium and pioglitazone hydrochloride in pharmaceutical dosage form.

PubMed

Peraman, Ramalingam; Mallikarjuna, Sasikala; Ammineni, Pravalika; Kondreddy, Vinod kumar

2014-10-01

A simple, selective, rapid, precise and economical reversed-phase high-performance liquid chromatographic (RP-HPLC) method has been developed for simultaneous estimation of atorvastatin calcium (ATV) and pioglitazone hydrochloride (PIO) from pharmaceutical formulation. The method is carried out on a C8 (25 cm × 4.6 mm i.d., 5 μm) column with a mobile phase consisting of acetonitrile (ACN):water (pH adjusted to 6.2 using o-phosphoric acid) in the ratio of 45:55 (v/v). The retention time of ATV and PIO is 4.1 and 8.1 min, respectively, with the flow rate of 1 mL/min with diode array detector detection at 232 nm. The linear regression analysis data from the linearity plot showed good linear relationship with a correlation coefficient (R(2)) value for ATV and PIO of 0.9998 and 0.9997 in the concentration range of 10-80 µg mL(-1), respectively. The relative standard deviation for intraday precision has been found to be <2.0%. The method is validated according to the ICH guidelines. The developed method is validated in terms of specificity, selectivity, accuracy, precision, linearity, limit of detection, limit of quantitation and solution stability. The proposed method can be used for simultaneous estimation of these drugs in marketed dosage forms. © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Age-Related Changes in Locomotor Performance Reveal a Similar Pattern for Caenorhabditis elegans, Mus domesticus, Canis familiaris, Equus caballus, and Homo sapiens.

PubMed

Marck, Adrien; Berthelot, Geoffroy; Foulonneau, Vincent; Marc, Andy; Antero-Jacquemin, Juliana; Noirez, Philippe; Bronikowski, Anne M; Morgan, Theodore J; Garland, Theodore; Carter, Patrick A; Hersen, Pascal; Di Meglio, Jean-Marc; Toussaint, Jean-François

2017-04-01

Locomotion is one of the major physiological functions for most animals. Previous studies have described aging mechanisms linked to locomotor performance among different species. However, the precise dynamics of these age-related changes, and their interactions with development and senescence, are largely unknown. Here, we use the same conceptual framework to describe locomotor performances in Caenorhabditis elegans, Mus domesticus, Canis familiaris, Equus caballus, and Homo sapiens. We show that locomotion is a consistent biomarker of age-related changes, with an asymmetrical pattern throughout life, regardless of the type of effort or its duration. However, there is variation (i) among species for the same mode of locomotion, (ii) within species for different modes of locomotion, and (iii) among individuals of the same species for the same mode of locomotion. Age-related patterns are modulated by genetic (such as selective breeding) as well as environmental conditions (such as temperature). However, in all cases, the intersection of the rising developmental phase and the declining senescent phase reveals neither a sharp transition nor a plateau, but a smooth transition, emphasizing a crucial moment: the age at peak performance. This transition may define a specific target for future investigations on the dynamics of such biological interactions. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Development and Validation of a High Pressure Liquid Chromatography-UV Method for the Determination of Treosulfan and Its Epoxy Metabolites in Human Plasma and Its Application in Pharmacokinetic Studies.

PubMed

Koyyalamudi, Sundar R; Kuzhiumparambil, Unnikrishnan; Nath, Christa E; Byrne, Jennifer A; Fraser, Christopher J; O'Brien, Tracey A; Earl, John W; Shaw, Peter J

2016-03-01

Treosulfan (l-threitol-1,4-di-methanesulfonate) is a prodrug of a bifunctional alkylating agent that is being used increasingly in pediatric bone marrow transplantation regimens. The activation pathway is a complex reaction, which consists of two consecutive reactions leading to epoxybutane derivatives which are responsible for DNA alkylation. A simple, sensitive high performance liquid chromatography method for the determination of the sum of treosulfan and its epoxy metabolites by UV detection after derivatization with sodium diethyldithiocarbamate in human plasma was developed and validated. Plasma samples containing treosulfan and epoxy metabolites were converted into thiocarbamate derivative with 10% sodium diethyldithiocarbamate. Dinitrobiphenyl was used as an internal standard. The analysis was carried out using a reversed phase C18 column with a mobile phase consisting of methanol-water (65:35, v/v) at a flow rate of 1 mL/min. The eluent was monitored at 254 nm. The standard calibration curve was established between 2.5 and 50 µg/mL, with a correlation coefficient of 0.9987. Intra- and interday precision and accuracy of the method was <8% and met the analytical criteria. Pharmacokinetic parameters were determined in six children who received intravenous treosulfan (dose range 12-24 g/m(2)) in combination with fludarabine prior to blood or marrow transplantation. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Easy-Assessment of Levofloxacin and Minocycline in Relevant Biomimetic Media by HPLC-UV Analysis.

PubMed

Matos, Ana C; Pinto, Rosana V; Bettencourt, Ana F

2017-08-01

Simple, economic and environmental friendly high-performance liquid chromatography methods for levofloxacin and minocycline quantification in biomimetic media were developed and validate including their stability at body temperature, an often neglected evaluation parameter. Both methods are similar only differing in the wavelength setting, i.e., for levofloxacin and minocycline quantification the UV detection was set at 284 and at 273 nm, respectively. The separation of both antibiotics was achieved using a reversed-phase column and a mobile phase consisting of acetonitrile and water (15:85) with 0.6% triethylamine, adjusted to pH 3. As an internal standard for levofloxacin quantification, minocycline was used and vice versa. The calibration curves for both methods were linear (r = 0.99) over a concentration range of 0.3-16 μg/mL and 0.5-16 μg/mL for levofloxacin and minocycline, respectively, with precision, accuracy and recovery in agreement with international guidelines requirement. Levofloxacin revealed stability in all media and conditions, including at 37°C, with exception to freeze-thaw cycle conditions. Minocycline presented a more accentuated degradation profile over prolonged time courses, when compared to levofloxacin. Reported data is of utmost interest for pharma and biomaterials fields regarding the research and development of new local drug-delivery-systems containing either of these two antibiotics, namely when monitoring the in vitro release studies of those systems. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Screening for anabolic steroids in urine of forensic cases using fully automated solid phase extraction and LC-MS-MS.

PubMed

Andersen, David W; Linnet, Kristian

2014-01-01

A screening method for 18 frequently measured exogenous anabolic steroids and the testosterone/epitestosterone (T/E) ratio in forensic cases has been developed and validated. The method involves a fully automated sample preparation including enzyme treatment, addition of internal standards and solid phase extraction followed by analysis by liquid chromatography-tandem mass spectrometry (LC-MS-MS) using electrospray ionization with adduct formation for two compounds. Urine samples from 580 forensic cases were analyzed to determine the T/E ratio and occurrence of exogenous anabolic steroids. Extraction recoveries ranged from 77 to 95%, matrix effects from 48 to 78%, overall process efficiencies from 40 to 54% and the lower limit of identification ranged from 2 to 40 ng/mL. In the 580 urine samples analyzed from routine forensic cases, 17 (2.9%) were found positive for one or more anabolic steroids. Only seven different steroids including testosterone were found in the material, suggesting that only a small number of common steroids are likely to occur in a forensic context. The steroids were often in high concentrations (>100 ng/mL), and a combination of steroids and/or other drugs of abuse were seen in the majority of cases. The method presented serves as a fast and automated screening procedure, proving the suitability of LC-MS-MS for analyzing anabolic steroids. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Three-dimensional information hierarchical encryption based on computer-generated holograms

NASA Astrophysics Data System (ADS)

Kong, Dezhao; Shen, Xueju; Cao, Liangcai; Zhang, Hao; Zong, Song; Jin, Guofan

2016-12-01

A novel approach for encrypting three-dimensional (3-D) scene information hierarchically based on computer-generated holograms (CGHs) is proposed. The CGHs of the layer-oriented 3-D scene information are produced by angular-spectrum propagation algorithm at different depths. All the CGHs are then modulated by different chaotic random phase masks generated by the logistic map. Hierarchical encryption encoding is applied when all the CGHs are accumulated one by one, and the reconstructed volume of the 3-D scene information depends on permissions of different users. The chaotic random phase masks could be encoded into several parameters of the chaotic sequences to simplify the transmission and preservation of the keys. Optical experiments verify the proposed method and numerical simulations show the high key sensitivity, high security, and application flexibility of the method.

Alterations of DNA content in human endometrial stromal cells transfected with a temperature-sensitive SV40: tetraploidization and physiological consequences.

PubMed

Rinehart, C A; Mayben, J P; Butler, T D; Haskill, J S; Kaufman, D G

1992-01-01

The normal genomic stability of human cells is reversed during neoplastic transformation. The SV40 large T antigen alters the DNA content in human endometrial stromal cells in a manner that relates to neoplastic progression. Human endometrial stromal cells were transfected with a plasmid containing the A209 temperature-sensitive mutant of SV40 (tsSV40), which is also defective in the viral origin of replication. Ninety-seven clonal transfectants from seven different primary cell strains were isolated. Initial analysis revealed that 20% of the clonal populations (19/97) had an apparent diploid DNA content, 35% (34/97) had an apparent tetraploid DNA content, and the remainder were mixed populations of diploid and tetraploid cells. No aneuploid populations were observed. Diploid tsSV40 transformed cells always give rise to a population of cells with a tetraploid DNA content when continuously cultured at the permissive temperature. The doubling of DNA content can be vastly accelerated by the sudden reintroduction of large T antigen activity following a shift from non-permissive to permissive temperature. Tetraploid tsSV40 transfected cells have a lower capacity for anchorage-independent growth and earlier entry into 'crisis' than diploid cells. These results indicate that during the pre-crisis, extended lifespan phase of growth, the SV40 large T antigen causes a doubling of DNA content. This apparent doubling of DNA content does not confer growth advantage during the extended lifespan that precedes 'crisis'.

Novel Validated RP-HPLC Method for Bendamustine Hydrochloride Based on Ion-pair Chromatography: Application in Determining Infusion Stability and Pharmacokinetics.

PubMed

Singh, Yuvraj; Chandrashekar, Anumandla; Pawar, Vivek K; Saravanakumar, Veeramuthu; Meher, Jayagopal; Raval, Kavit; Singh, Pankaj; Kumar, R Dinesh; Chourasia, Manish K

2017-01-01

Ion pair chromatography was used for quantifying bendamustine hydrochloride (BH) in its marketed vial. The permissive objective was to investigate time duration for which highly susceptible drug content of the marketed vial remained stable after reconstitution. However, the method could also be used to measure extremely low levels of drug in rat plasma and a pharmacokinetic study was accordingly conducted to further showcase method's applicability. Optimized separation was achieved on C-18 Purospher ® STAR (250 mm × 4.6 mm, 5 μm particle size) column. Mobile phase flowing at 1.5 mL/min consisted of 5 mM sodium salt of octane sulfonic acid dissolved in methanol, water and glacial acetic acid (55:45:0.075) maintained at pH 6. Detection was carried out at 233 nm with BH eluting after 7.8 min. Validation parameters were determined as per ICH guidelines. Limit of detection and limit of quantification were found to be 0.1 µg/mL and 0.33 µg/mL, respectively. The recoveries were 98-102% in bulk and 85-91% in plasma. The developed method was specific for BH, and utilized for assessing its short-term stability in physiologic solvents and forced degradation products in acid, base, oxidative, light and temperature induced stress environments. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mineral potential tracts for orogenic, Carlin-like, and epithermal gold deposits in the Islamic Republic of Mauritania, (phase V, deliverable 69): Chapter H in Second projet de renforcement institutionnel du secteur minier de la République Islamique de Mauritanie (PRISM-II)

USGS Publications Warehouse

Goldfarb, Richard J.; Marsh, Erin; Anderson, Eric D.; Horton, John D.; Finn, Carol A.; Beaudoin, Georges

2015-01-01

A preliminary evaluation of these gold data can be used to develop broad, firstorder tracts defining favorable and permissive areas for gold resources; detailed metamorphic and structural maps are required for more detailed future tract definition. Such a first-order assessment can, nonetheless, broadly identify four tracts of gold resource potential. Three of these are favorable for discovery of new orogenic gold deposits. One tract, although not favorable, is nevertheless permissive for discovery of epithermal gold deposits. Tract 1 is defined by favorable medium metamorphic grade greenstone belts within vast areas of unfavorable high metamorphic grade, Mesoarchean and Paleoproterozoic granite-gneiss basement of the Rgueïbat Shield. Faults >200 km in length following the general strike of the greenstone belts; lineament intersections with both exposed and buried parts of greenstone belts within 500 m of the surface, as defined by aeromagnetic data (Finn and Anderson, 2015); and areas of banded iron formation (BIF) in the belts are particularly favorable areas for hosting gold resources in orogenic gold deposits within and along the margins of the greenstone belts. Tracts 2 and 3, also for orogenic gold, reflect the favorable Proterozoic-Cambrian metamorphic rocks of the Northern and Southern Mauritanides, with >200-km-long faults following the general strike of the range, and areas underlain by ultramafic and BIF rocks being particularly favorable. Outcrops of Triassic-Jurassic igneous rocks along the margins of the Taoudeni Basin define tract 4, which is permissive for epithermal gold deposits. Although extensive data are lacking for the area, carbonate units along the northern side of the Taoudeni Basin could be considered permissive host rocks for Carlin-type mineralization, but the deep-water carbonate lithologies are typically not favorable for such. 

33 CFR 401.68 - Explosives Permission Letter.

Code of Federal Regulations, 2010 CFR

2010-07-01

... granted and the vessel shall not transit. (c) A written application for a Seaway Explosives Permission... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Explosives Permission Letter. 401... Permission Letter. (a) A Seaway Explosives Permission Letter is required for an explosive vessel in the...

Thermal rearrangement of 7-methylbicyclo

PubMed

Bender; Leber; Lirio; Smith

2000-08-25

The gas-phase thermal rearrangement of exo-7-methylbicyclo[3.2.0]hept-2-ene yields almost exclusively 5-methylnorbornene products. Inversion (i) of configuration dominates this [1,3] sigmatropic shift although some retention (r) is also observed. Because the [1,3] migration can only occur suprafacially (s) in this geometrically constrained system, the si/sr ratio of 7 observed for the migration of C7 in exo-7-methylbicyclo[3.2.0]hept-2-ene indicates that the orbital symmetry rules are somewhat permissive for the [1,3] sigmatropic migration of carbon.

14 CFR 221.122 - Special Tariff Permission to be used in its entirety as granted.

Code of Federal Regulations, 2010 CFR

2010-01-01

... extensive or different permission is desired, a new application for Special Tariff Permission conforming... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Special Tariff Permission to be used in its... TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS TARIFFS Special Tariff Permission To File on Less Than...

21 CFR 1005.22 - Granting permission to bring product into compliance.

Code of Federal Regulations, 2010 CFR

2010-04-01

... amended application for permission with the Secretary. (d) If ownership of a product included in a notice... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Granting permission to bring product into... Procedures § 1005.22 Granting permission to bring product into compliance. (a) When permission contemplated...

After the Liverpool Care Pathway--development of heuristics to guide end of life care for people with dementia: protocol of the ALCP study.

PubMed

Davies, N; Manthorpe, J; Sampson, E L; Iliffe, S

2015-09-02

End of life care guidance for people with dementia is lacking and this has been made more problematic in England with the removal of one of the main end of life care guidelines which offered some structure, the Liverpool Care Pathway. This guidance gap may be eased with the development of heuristics (rules of thumb) which offer a fast and frugal form of decision-making. To develop a toolkit of heuristics (rules of thumb) for practitioners to use when caring for people with dementia at the end of life. A mixed-method study using a co-design approach to develop heuristics in three phases. In phase 1, we will conduct at least six focus groups with family carers, health and social care practitioners from both hospital and community care services, using the 'think-aloud' method to understand decision-making processes and to develop a set of heuristics. The focus group topic guide will be developed from the findings of a previous study of 46 interviews of family carers about quality end-of-life care for people with dementia and a review of the literature. A multidisciplinary development team of health and social care practitioners will synthesise the findings from the focus groups to devise and refine a toolkit of heuristics. Phase 2 will test the use of heuristics in practice in five sites: one general practice, one community nursing team, one hospital ward and two palliative care teams working in the community. Phase 3 will evaluate and further refine the toolkit of heuristics through group interviews, online questionnaires and semistructured interviews. This study has received ethical approval from a local NHS research ethics committee (Rec ref: 15/LO/0156). The findings of this study will be presented in peer-reviewed publications and national and international conferences. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A phase I dose-escalation study of apatorsen (OGX-427), an antisense inhibitor targeting heat shock protein 27 (Hsp27), in patients with castration-resistant prostate cancer and other advanced cancers.

PubMed

Chi, K N; Yu, E Y; Jacobs, C; Bazov, J; Kollmannsberger, C; Higano, C S; Mukherjee, S D; Gleave, M E; Stewart, P S; Hotte, S J

2016-06-01

Heat shock protein 27 (Hsp27) is a chaperone protein that regulates cell survival via androgen receptor and other signaling pathways, thereby mediating cancer progression. Apatorsen (OGX-427) is a 2'-methoxyethyl-modified antisense oligonucleotide that inhibits Hsp27 expression. This study evaluated the safety profile and recommended phase II dosing of apatorsen in patients with advanced cancer. Patients with castration-resistant prostate (CRPC), breast, ovary, lung, or bladder cancer were enrolled to this phase I dose-escalation study. Apatorsen was administered i.v. weekly in 21-day cycles following 3 loading doses and over 5 dose levels (200-1000 mg). Apatorsen plasma concentrations, circulating tumor cells (CTCs) and CTC Hsp27 expression, and serum Hsp27 levels were evaluated. Forty-two patients were accrued, of which 52% had CRPC. Patients were heavily pretreated, with 57% having had ≥3 prior chemotherapy regimens. During the loading dose/cycle 1 and overall study period, 93% and 100% of patients (N = 42) experienced treatment-related adverse events, respectively; most were grade 1-2 and included chills, pruritus, flushing, prolonged aPTT, lymphopenia, and anemia. One patient experienced a dose-limiting toxicity at the 600 mg dose level (intracranial hemorrhage in a previously undiagnosed brain metastasis). A maximum tolerated dose was not defined. Apatorsen Cmax increased proportionally with dose. Decreases in tumor markers and declines in CTCs were observed, with a prostate-specific antigen decline >%50% occurring in 10% of patients with CRPC; 29/39 assessable patients (74%) had reductions from ≥5 CTC/7.5 ml at baseline to <5 CTC/7.5 ml post-treatment. Twelve patients had stable measurable disease as best response. Apatorsen was tolerated at the highest dose evaluated (1000 mg). Single-agent activity was suggested by changes in tumor markers, CTC, and stable measurable disease. Phase II studies evaluating apatorsen are underway. NCT00487786. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Estimation of clinical trial success rates and related parameters.

PubMed

Wong, Chi Heem; Siah, Kien Wei; Lo, Andrew W

2018-01-31

Previous estimates of drug development success rates rely on relatively small samples from databases curated by the pharmaceutical industry and are subject to potential selection biases. Using a sample of 406 038 entries of clinical trial data for over 21 143 compounds from January 1, 2000 to October 31, 2015, we estimate aggregate clinical trial success rates and durations. We also compute disaggregated estimates across several trial features including disease type, clinical phase, industry or academic sponsor, biomarker presence, lead indication status, and time. In several cases, our results differ significantly in detail from widely cited statistics. For example, oncology has a 3.4% success rate in our sample vs. 5.1% in prior studies. However, after declining to 1.7% in 2012, this rate has improved to 2.5% and 8.3% in 2014 and 2015, respectively. In addition, trials that use biomarkers in patient-selection have higher overall success probabilities than trials without biomarkers. © The Author 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Brain activation during anticipatory anxiety in social anxiety disorder.

PubMed

Boehme, Stephanie; Ritter, Viktoria; Tefikow, Susan; Stangier, Ulrich; Strauss, Bernhard; Miltner, Wolfgang H R; Straube, Thomas

2014-09-01

Exaggerated anticipatory anxiety during expectation of performance-related situations is an important feature of the psychopathology of social anxiety disorder (SAD). The neural basis of anticipatory anxiety in SAD has not been investigated in controlled studies. The current study used functional magnetic resonance imaging (fMRI) to investigate the neural correlates during the anticipation of public and evaluated speaking vs a control condition in 17 SAD patients and 17 healthy control subjects. FMRI results show increased activation of the insula and decreased activation of the ventral striatum in SAD patients, compared to control subjects during anticipation of a speech vs the control condition. In addition, an activation of the amygdala in SAD patients during the first half of the anticipation phase in the speech condition was observed. Finally, the amount of anticipatory anxiety of SAD patients was negatively correlated to the activation of the ventral striatum. This suggests an association between incentive function, motivation and anticipatory anxiety when SAD patients expect a performance situation. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

[Calcium and the permissive effect of glucocorticoids: the role of glucocorticoids in an adrenaline-induced increase in the rate of calcium absorption by the ventricular tissue of the rat heart].

PubMed

Seleznev, Iu M; Martynov, A V; Kolpakova, G V; Smirnov, V N

1979-03-01

It was demonstrated in rat experiments that the ability of the myocardial ventricles to increase 45Ca absorption after the injection of adrenaline was disturbed on the 3rd--5th day following adrenalectomy. The decrease in sensitivity to adrenaline occurred in two phases and was delayed essentially after a fall in the concentration of glucocorticoids in circulation. Chronic in vivo injection of hydrocortisone (2.5 mg per rat) into these animals for 3--5 days restored the effect of catecholamine to a great extent. The restorative effect was weaker when the rats were given a single intravenous hydrocortisone infusion 6 hours before being killed. Increase of the single intravenous dose of the hormone to 5 and 7.5 mg per rat reduced its effect. The authors assume that the described permissive effect of glucocorticoids is determined not by their direct interaction with the cytoplasmic membrane but by hormone induced intracellular synthesis of proteins capable of participating in the regulation of permeability to ions.

Must research benefit human subjects if it is to be permissible?

PubMed

Wikler, Daniel

2017-02-01

Must medical experiments with human subjects offer them a 'favourable risk-benefit ratio', that is, more expectation of benefit than harm or burden, if they are to be judged as ethically justified? Ethical justification is easier for experiments that do offer net benefit to subjects, but ethical justification is possible also for some experiments that do not. Basic science experiments with healthy volunteers and 'Phase I' drug trials that seek to determine tolerable dosage levels are routinely approved by ethical review committees; moreover, guidance they receive from government funding agencies specifically asks them to weigh risks to subjects against benefits to subjects and also benefits to those who may benefit from the knowledge gained in the experiment. If a puzzle remains, it is why there remains any assumption that research ethics requires a 'favourable risk-benefit ratio' for the individual research subject. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Extraction and Determination of Quercetin from Ginkgo biloba by DESs-Based Polymer Monolithic Cartridge.

PubMed

Wang, Xiaoqin; Li, Guizhen; Ho Row, Kyung

2017-09-01

Deep eutectic solvents (DES) were formed from choline chloride (ChCl). DES-modified polymer monolithic (DES-M), template molecular polymer monolithic and non-DES-M without a molecular template were synthesized in identical process. These polymer materials were characterized by field emission scanning electron microscopy and Fourier transform infrared spectroscopy. The significant selective adsorption properties of the polymers were assessed by an absorption capacity experiment and solid-phase extraction (SPE). The optimized extraction procedure was as follows: ultrasonic time (30 min), optimal solvent (ethanol) and liquid to material ratio (20 mL g-1). Under this condition, the amount of quercetin extracted from Ginkgo biloba was 290.8 mg g-1. The purification of G. biloba was achieved by the SPE process. Based on the results, DESs-based monolithic cartridges can be used for simple and efficient extraction and as a pre-concentration technique for the purification of bioactive compounds or drugs in aqueous environments with high affinity and selectivity. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Functional relevance of water and glycerol channels in Saccharomyces cerevisiae.

PubMed

Sabir, Farzana; Loureiro-Dias, Maria C; Soveral, Graça; Prista, Catarina

2017-05-01

Our understanding of the functional relevance of orthodox aquaporins and aquaglyceroporins in Saccharomyces cerevisiae is essentially based on phenotypic variations obtained by expression/overexpression/deletion of these major intrinsic proteins in selected strains. These water/glycerol channels are considered crucial during various life-cycle phases, such as sporulation and mating and in some life processes such as rapid freeze-thaw tolerance, osmoregulation and phenomena associated with cell surface. Despite their putative functional roles not only as channels but also as sensors, their underlying mechanisms and their regulation are still poorly understood. In the present review, we summarize and discuss the physiological relevance of S. cerevisiae aquaporins (Aqy1 and Aqy2) and aquaglyceroporins (Fps1 and Yfl054c). In particular, the fact that most S. cerevisiae laboratory strains harbor genes coding for non-functional aquaporins, while wild and industrial strains possess at least one functional aquaporin, suggests that aquaporin activity is required for cell survival under more harsh conditions. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Deviation Management: Key Management Subsystem Driver of Knowledge-Based Continuous Improvement in the Henry Ford Production System.

PubMed

Zarbo, Richard J; Copeland, Jacqueline R; Varney, Ruan C

2017-10-01

To develop a business subsystem fulfilling International Organization for Standardization 15189 nonconformance management regulatory standard, facilitating employee engagement in problem identification and resolution to effect quality improvement and risk mitigation. From 2012 to 2016, the integrated laboratories of the Henry Ford Health System used a quality technical team to develop and improve a management subsystem designed to identify, track, trend, and summarize nonconformances based on frequency, risk, and root cause for elimination at the level of the work. Programmatic improvements and training resulted in markedly increased documentation culminating in 71,641 deviations in 2016 classified by a taxonomy of 281 defect types into preanalytic (74.8%), analytic (23.6%), and postanalytic (1.6%) testing phases. The top 10 deviations accounted for 55,843 (78%) of the total. Deviation management is a key subsystem of managers' standard work whereby knowledge of nonconformities assists in directing corrective actions and continuous improvements that promote consistent execution and higher levels of performance. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Grief and Healing in Young and Middle Age: A Widower's Journey.

PubMed

Lichtenberg, Peter A

2017-02-01

The experience of grief is both uniquely personal and universal. Our personality, our relationship with the deceased, the manner in which the deceased died, our life stage, and many other contextual factors matter and impact grief, and yet there are many experiences, phases, stages of grief that are universal. Those who are grieving deeply or who are farther along in their healing are often trying to understand grief and its realities. It has been said that people die but relationships do not. As a widower twice, once at age 25 and then again nearly 30 years later, I agree with that sentiment, and it is the profound relationships with my wives Becky and Susan that propelled me to share my experiences and reflections on grief and healing. As a clinical psychologist and gerontologist I examined the grief and gerontology literature, learning new things that were useful and not as useful. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Care of the dying: how do we replace the Liverpool Care Pathway?

PubMed

Davis, Charles; Tomas, Jon

2014-12-01

Death is an inescapable certainty of life. Variability in care for dying persons, however, is present. The Liverpool Care Pathway (LCP) sought to guide care for the last days of life but was phased out after intense scrutiny. A governmental report and rapid review of evidence were considered alongside mass and social media reporting. An evidence review of end-of-life care was undertaken. Any person's death is inherently challenging. Much consideration must be given to holistic needs when approaching death. Communication skills may be lacking for professional and patient alike. The LCP became flawed in use rather than intention or principle. Seeming financial gains from death were concerning to all. We have responsibility for making choices prospectively in order for them to influence our care when we are dying. Normalization of death is key on both micro- and macro communication levels. Perceptions of relevant terminology; review of the definition of dying; improved recognition of the dying process and measuring the impact of communication skills training. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Vaccines against malaria.

PubMed

Ouattara, Amed; Laurens, Matthew B

2015-03-15

Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Electronic recording and reporting system for tuberculosis in China: experience and opportunities.

PubMed

Huang, Fei; Cheng, ShiMing; Du, Xin; Chen, Wei; Scano, Fabio; Falzon, Dennis; Wang, Lixia

2014-01-01

Tuberculosis (TB) surveillance in China is organized through a nationwide network of about 3200 hospitals and health facilities. In 2005, an electronic Tuberculosis Information Management System (TBIMS) started to be phased in to replace paper recording. The TBIMS collects key information on TB cases notified in TB care facilities, and exchanges real-time data with the Infectious Disease Reporting System, which covers the country's 37 notifiable diseases. The system is accessible to authorized users at every level of the TB network through a password-protected website. By 2009 the TBIMS achieved nationwide coverage. Completeness of data on patient bacteriological end points improved remarkably over time. Data on about a million active TB cases, including drug-resistant TB, are included each year. The sheer scale of the data handling and the intricate functions that the China TBIMS performs makes it stand apart from the electronic information systems for TB adopted in other countries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Planktonic growth and biofilm formation profiles in Candida haemulonii species complex.

PubMed

Ramos, Lívia S; Oliveira, Simone S C; Souto, Xênia M; Branquinha, Marta H; Santos, André L S

2017-10-01

Candida haemulonii species complex have emerged as multidrug-resistant yeasts able to cause fungemia worldwide. However, very little is known regarding their physiology and virulence factors. In this context, planktonic growth and biofilm formation of Brazilian clinical isolates of Candida haemulonii (n = 5), Candida duobushaemulonii (n = 4), and Candida haemulonii var. vulnera (n = 3) were reported. Overall, the fungal planktonic growth curves in Sabouraud dextrose broth reached the exponential phase in 48 h at 37°C. All the clinical isolates formed biofilm on polystyrene in a time-dependent event, as judged by the parameters evaluated: biomass (crystal violet staining), metabolic activity (XTT reduction), and extracellular matrix (safranin incorporation). No statistically significant differences were observed when the average measurements among the three Candida species were compared regarding both planktonic and biofilm lifestyles; however, typical isolate-specific differences were clearly noticed in fungal growth kinetics. © The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Development and validation of an LC-MS method for determination of Karanjin in rat plasma: application to preclinical pharmacokinetics.

PubMed

Yi, Deliang; Wang, Zhihua; Yi, Longzhi

2015-04-01

A selective and sensitive liquid chromatography-mass spectrometry (MS) method was developed and validated for the determination of karanjin in rat plasma. The target analyte, together with the internal standard (warfarin), was extracted from rat plasma by liquid-liquid extraction with ethyl acetate. Chromatographic separation was performed on a ZORBAX SB-C18 column using a mixture of acetonitrile and 0.1% aqueous formic acid as the mobile phase with linear gradient elution. MS detection was performed on a single quadrupole MS by selected ion monitoring mode via a positive electrospray ionization source. The assay exhibited a linear dynamic range of 2.50-3,000 ng/mL for karanjin. The intra- and inter-day precision was <10.8%, and the intra- and inter-day accuracy was <9.2%. The validated method has been applied to the preclinical pharmacokinetic studies of karanjin following oral administration of 5, 10 and 20 mg/kg karanjin to rats. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Green Chromatographic Separation of Coumarin and Vanillins Using Subcritical Water as the Mobile Phase.

PubMed

Kayan, Berkant; Akay, Sema; Yang, Yu

2016-08-01

Pure water was used as the eluent for separation of coumarin, vanillin and ethyl vanillin at temperatures ranging from 100 to 200°C using a homemade subcritical water chromatography (SBWC) system. Chromatographic separations were performed on five commercial columns including XTerra MS C18, XBridge C18, Zorbax RRHD Eclipse Plus, Zorbax SB-Phenyl and Zorbax SB-C18 columns. The retention time of all three solutes decreased with increasing water temperature. The shortest retention time among all acceptable separations, less than 4 min, was achieved on the Zorbax SB-C18 column at 200°C. While separations on the XTerra MS C18 column resulted in fronting peaks and a degradation peak from ethyl vanillin on the Zorbax RRHD Eclipse Plus column was observed, all three other columns yielded reasonable separations under SBWC conditions. In addition to separation of the standard test mixture, separation of coumarin contained in a skincare cream sample was also carried out using SBWC. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Determination of Flurbiprofen in Human Plasma by High-Performance Liquid Chromatography.

PubMed

Yilmaz, Bilal; Erdem, Ali Fuat

2015-10-01

A simple high-performance liquid chromatography method has been developed for determination of flurbiprofen in human plasma. The method was validated on an Ace C18 column using UV detection. The mobile phase was acetonitrile-0.05 M potassium dihydrogen phosphate solution (60:40, v/v) adjusted to pH 3.5 with phosphoric acid. The calibration curve was linear between the concentration range of 0.10-5.0 μg/mL. Intra- and inter-day precision values for flurbiprofen in plasma were <4.47, and accuracy (relative error) was better than 3.67%. The extraction recoveries of flurbiprofen from human plasma were between 93.0 and 98.9%. The limits of detection and quantification of flurbiprofen were 0.03 and 0.10 μg/mL, respectively. In addition, this assay was applied to determine the pharmacokinetic parameters of flurbiprofen in six healthy Turkish volunteers who had been given 100 mg flurbiprofen. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Multivariate curve resolution-assisted determination of pseudoephedrine and methamphetamine by HPLC-DAD in water samples.

PubMed

Vosough, Maryam; Mohamedian, Hadi; Salemi, Amir; Baheri, Tahmineh

2015-02-01

In the present study, a simple strategy based on solid-phase extraction (SPE) with a cation exchange sorbent (Finisterre SCX) followed by fast high-performance liquid chromatography (HPLC) with diode array detection coupled with chemometrics tools has been proposed for the determination of methamphetamine and pseudoephedrine in ground water and river water. At first, the HPLC and SPE conditions were optimized and the analytical performance of the method was determined. In the case of ground water, determination of analytes was successfully performed through univariate calibration curves. For river water sample, multivariate curve resolution and alternating least squares was implemented and the second-order advantage was achieved in samples containing uncalibrated interferences and uncorrected background signals. The calibration curves showed good linearity (r(2) > 0.994).The limits of detection for pseudoephedrine and methamphetamine were 0.06 and 0.08 μg/L and the average recovery values were 104.7 and 102.3% in river water, respectively. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Evidence-based interventions in pediatric psychology: progress over the decades.

PubMed

Palermo, Tonya M

2014-09-01

This introduction to the special issue on Evidence-Based Interventions in Pediatric Psychology provides background on the process used to develop the special issue, a summary of the key findings from the series of reviews, and discussion of the implications for evidence-based practice. Authors followed a three-phase approach to develop their systematic reviews using rigorous systematic review methodology drawn heavily from the Cochrane Collaboration. The strength of the evidence for each pediatric psychology intervention was evaluated using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The introduction discusses the progress that has been made in the evidence base for pediatric psychology interventions since the first special series published in 1999. Recommendations to stimulate further research and expand and strengthen the quality of the evidence base are described. The introduction concludes with implications from the special issue for pediatric psychology training in evidence-based practice. © The Author 2014. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

GACD: Integrated Software for Genetic Analysis in Clonal F1 and Double Cross Populations.

PubMed

Zhang, Luyan; Meng, Lei; Wu, Wencheng; Wang, Jiankang

2015-01-01

Clonal species are common among plants. Clonal F1 progenies are derived from the hybridization between 2 heterozygous clones. In self- and cross-pollinated species, double crosses can be made from 4 inbred lines. A clonal F1 population can be viewed as a double cross population when the linkage phase is determined. The software package GACD (Genetic Analysis of Clonal F1 and Double cross) is freely available public software, capable of building high-density linkage maps and mapping quantitative trait loci (QTL) in clonal F1 and double cross populations. Three functionalities are integrated in GACD version 1.0: binning of redundant markers (BIN); linkage map construction (CDM); and QTL mapping (CDQ). Output of BIN can be directly used as input of CDM. After adding the phenotypic data, the output of CDM can be used as input of CDQ. Thus, GACD acts as a pipeline for genetic analysis. GACD and example datasets are freely available from www.isbreeding.net. © The American Genetic Association. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Interstitial lung disease induced by alectinib (CH5424802/RO5424802).

PubMed

Ikeda, Satoshi; Yoshioka, Hiroshige; Arita, Machiko; Sakai, Takahiro; Sone, Naoyuki; Nishiyama, Akihiro; Niwa, Takashi; Hotta, Machiko; Tanaka, Tomohiro; Ishida, Tadashi

2015-02-01

A 75-year-old woman with anaplastic lymphoma kinase (ALK)-rearranged Stage IV lung adenocarcinoma was administered the selective anaplastic lymphoma kinase inhibitor, alectinib, as a third-line treatment in a Phase 1-2 study. On the 102nd day, chest computed tomography showed diffuse ground glass opacities. Laboratory data revealed high serum levels of KL-6, SP-D and lactate dehydrogenase without any clinical symptoms. There was no evidence of infection. Marked lymphocytosis was seen in bronchoalveolar lavage fluid analysis, and transbronchial lung biopsy showed mild thickening of alveolar septa and lymphocyte infiltration. Interstitial lung disease was judged to be related to alectinib based on improvements in imaging findings and serum biomarkers after discontinuation of alectinib. To our knowledge, this is the first reported case of alectinib-induced interstitial lung disease. Alectinib is a promising drug for ALK-rearranged non-small cell lung cancer. Clinical trials of this selective anaplastic lymphoma kinase inhibitor will facilitate the meticulous elucidation of its long-term safety profile. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Evaluating the Effects of Function-Based Interventions With Deaf or Hard-of-Hearing Students.

PubMed

Gann, Candace J; Gaines, Sarah E; Antia, Shirin D; Umbreit, John; Liaupsin, Carl J

2015-07-01

This study examined the effectiveness of function-based interventions with students who are deaf or hard of hearing (D/HH). The participants were 3 elementary-aged males attending a center school for the deaf who exhibited chronic off-task behaviors throughout the school day. This study was conducted across 2 phases: (a) a descriptive functional behavior assessment (FBA) was conducted for each participant and (b) individualized function-based interventions were developed based on the results of the FBAs, followed by the implementation of the interventions in each classroom using a single-subject, ABAB reversal design. The function-based interventions significantly improved each participant's on-task behavior in his classroom environment. Furthermore, social validity ratings by each teacher revealed that the interventions were effective, easy to implement, and appropriate for each participant. Implications for application of the procedures used in this study with the D/HH population, limitations, and directions for future research are discussed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Microdosimetry of the full slowing down of protons using Monte Carlo track structure simulations.

PubMed

Liamsuwan, T; Uehara, S; Nikjoo, H

2015-09-01

The article investigates two approaches in microdosimetric calculations based on Monte Carlo track structure (MCTS) simulations of a 160-MeV proton beam. In the first approach, microdosimetric parameters of the proton beam were obtained using the weighted sum of proton energy distributions and microdosimetric parameters of proton track segments (TSMs). In the second approach, phase spaces of energy depositions obtained using MCTS simulations in the full slowing down (FSD) mode were used for the microdosimetric calculations. Targets of interest were water cylinders of 2.3-100 nm in diameters and heights. Frequency-averaged lineal energies ([Formula: see text]) obtained using both approaches agreed within the statistical uncertainties. Discrepancies beyond this level were observed for dose-averaged lineal energies ([Formula: see text]) towards the Bragg peak region due to the small number of proton energies used in the TSM approach and different energy deposition patterns in the TSM and FSD of protons. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The effects of training married men about premenstrual syndrome by pamphlets and short messages on marital satisfaction.

PubMed

Morowatisharifabad, Mohammad Ali; Karimiankakolaki, Zohreh; Bokaie, Mahshid; Fallahzadeh, Hossein; Gerayllo, Sakineh

2014-12-01

Premenstrual syndrome (PMS), which includes physical, psychological and emotional symptoms that occur during the luteal phase of the menstrual cycle, has a negative impact on the quality of the relationship among married couples. The purpose of the study was to examine the effects of educating married men by two methods, pamphlet and short messages (SMS), on marital satisfaction of the couples. The study was experimental in nature. The sample consisted of 80 couples who had visited health centers in Yazd, Iran. The subjects were randomly assigned to the two training methods and pretested and post-tested on the outcome measures. The before to after the training increase in knowledge and practice in men and marital satisfaction of couples were statistically significant. The differences between the two training methods were not statistically significant. Pamphlets and SMS, if designed properly and based on the principles of psychology, can act as influential and almost equally effective educational tools in the context of PMS. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Randomized trial of anaesthetic interventions in external cephalic version for breech presentation.

PubMed

Khaw, K S; Lee, S W Y; Ngan Kee, W D; Law, L W; Lau, T K; Ng, F F; Leung, T Y

2015-06-01

Successful external cephalic version (ECV) for breech presenting fetus reduces the need for Caesarean section (CS). We aimed to compare the success rate of ECV with either spinal anaesthesia (SA) or i.v. analgesia using remifentanil. In a double-phased, stratified randomized blinded controlled study we compared the success rates of ECV, performed under spinal anaesthesia (SA), i.v. analgesia (IVA) using remifentanil or no anaesthetic interventions. In phase I, 189 patients were stratified by parity before randomization to ECV, performed by blinded operators, under SA using either hyperbaric bupivacaine 9 mg with fentanyl 15 µg, i.v. remifentanil infusion 0.1 µg kg min(-1), or Control (no anaesthetic intervention). Operators performing ECV were blinded to the treatment allocation. In phase 2, patients in the Control group in whom the initial ECV failed were further randomized to receive either SA (n=9) or IVA (n=9) for a re-attempt. The primary outcome was the incidence of successful ECV. The success rate in Phase 1 was greatest using SA [52/63 (83%)], compared with IVA [40/63 (64%)] and Control [40/63 (64%)], (P=0.027). Median [IQR] pain scores on a visual analogue scale (range 0-100), were 0 [0-0] with SA, 35 [0-60] with IVA and 50 [30-75] in the Control group (P<0.001). Median [IQR] VAS sedation scores were highest with IVA [75 (50-80)], followed by SA, [0 (0-50)] and Control [0 (0-0)]. In phase 2, 7/9 (78%) of ECV re-attempts were successful with SA, whereas all re-attempts using IVA failed (P=0.0007). The incidence of fetal bradycardia necessitating emergency CS within 30 min, was similar among groups; 1.6% (1/63) in the SA and IVA groups and 3.2% (2/63) in the Control group. SA increased the success rate and reduced pain for both primary and re-attempts of ECV, whereas IVA using remifentanil infusion only reduced the pain. There was no significant increase in the incidence of fetal bradycardia or emergency CS, with ECV performed under anaesthetic interventions. Relaxation of the abdominal muscles from SA appears to underlie the improved outcomes for ECV. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A randomized double-blinded controlled trial of hCG as luteal phase support in natural cycle frozen embryo transfer.

PubMed

Lee, Vivian Chi Yan; Li, Raymond Hang Wun; Yeung, William Shu Biu; Pak Chung, H O; Ng, Ernest Hung Yu

2017-05-01

Does the use of hCG as luteal phase support in natural cycle frozen embryo transfer (FET) increase the ongoing pregnancy rate? The use of hCG in natural cycle FET did not improve the ongoing pregnancy rate. The use of luteal phase support in stimulated cycles has been associated with higher live-birth rates and the results are similar when using hCG or progesterone. This is a randomized double-blinded controlled trial of 450 women recruited between August 2013 and October 2015. Women with regular cycles undergoing natural cycle FET were recruited. Serial serum hormonal concentrations were used to time natural ovulation and at least Day 2 cleavage embryos were replaced. Patients were randomized into either: (i) the treatment group, receiving 1500 IU hCG on the day of FET and 6 days after FET, or (ii) the control group, receiving normal saline on these 2 days. The ongoing pregnancy rate [60/225 (26.7%) in the treatment group vs 70/225 (31.3%) in the control group, odds ratio 1.242 (95% CI 0.825-1.869)], implantation rate and miscarriage rate were comparable between the two groups. In the treatment group, there were significantly more cycles with top quality embryos transferred and a significantly higher serum oestradiol level, but a comparable serum progesterone level, 6 days after FET. However, no significant differences were observed in serum oestradiol and progesterone levels 6 days after FET between the pregnant and non-pregnant women. In the multivariate logistic regression, the number of embryos transferred was the only significant factor predictive of the ongoing pregnancy rate after natural cycle FET. This study only included FET with cleavage stage embryos and only hCG, not vaginal progesterone, was used as luteal phase support. The findings in this study do not support the use of hCG for luteal phase support in natural cycle FET. No external funding was used and there were no competing interests. clinicaltrial.gov identifier: NCT01931384. 23/8/2013. 30/8/2013. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

40 CFR 26.406 - Requirements for permission by parents or guardians and for assent by children.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Requirements for permission by parents... Requirements for permission by parents or guardians and for assent by children. (a) In addition to the... are made for soliciting the permission of each child's parents or guardian. Where parental permission...

40 CFR 26.406 - Requirements for permission by parents or guardians and for assent by children.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Requirements for permission by parents or guardians and for assent by children. (a) In addition to the... are made for soliciting the permission of each child's parents or guardian. Where parental permission... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Requirements for permission by parents...

40 CFR 26.406 - Requirements for permission by parents or guardians and for assent by children.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Requirements for permission by parents or guardians and for assent by children. (a) In addition to the... are made for soliciting the permission of each child's parents or guardian. Where parental permission... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Requirements for permission by parents...

40 CFR 26.406 - Requirements for permission by parents or guardians and for assent by children.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Requirements for permission by parents or guardians and for assent by children. (a) In addition to the... are made for soliciting the permission of each child's parents or guardian. Where parental permission... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Requirements for permission by parents...

40 CFR 26.406 - Requirements for permission by parents or guardians and for assent by children.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Requirements for permission by parents or guardians and for assent by children. (a) In addition to the... are made for soliciting the permission of each child's parents or guardian. Where parental permission... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Requirements for permission by parents...

Building and evaluating an ontology-based tool for reasoning about consent permission

PubMed Central

Grando, Adela; Schwab, Richard

2013-01-01

Given the lack of mechanisms for specifying, sharing and checking the compliance of consent permissions, we focus on building and testing novel approaches to address this gap. In our previous work, we introduced a “permission ontology” to capture in a precise, machine-interpretable form informed consent permissions in research studies. Here we explain how we built and evaluated a framework for specifying subject’s permissions and checking researcher’s resource request in compliance with those permissions. The framework is proposed as an extension of an existing policy engine based on the eXtensible Access Control Markup Language (XACML), incorporating ontology-based reasoning. The framework is evaluated in the context of the UCSD Moores Cancer Center biorepository, modeling permissions from an informed consent and a HIPAA form. The resulting permission ontology and mechanisms to check subject’s permission are implementation and institution independent, and therefore offer the potential to be reusable in other biorepositories and data warehouses. PMID:24551354

Classification of accelerometer wear and non-wear events in seconds for monitoring free-living physical activity.

PubMed

Zhou, Shang-Ming; Hill, Rebecca A; Morgan, Kelly; Stratton, Gareth; Gravenor, Mike B; Bijlsma, Gunnar; Brophy, Sinead

2015-05-11

To classify wear and non-wear time of accelerometer data for accurately quantifying physical activity in public health or population level research. A bi-moving-window-based approach was used to combine acceleration and skin temperature data to identify wear and non-wear time events in triaxial accelerometer data that monitor physical activity. Local residents in Swansea, Wales, UK. 50 participants aged under 16 years (n=23) and over 17 years (n=27) were recruited in two phases: phase 1: design of the wear/non-wear algorithm (n=20) and phase 2: validation of the algorithm (n=30). Participants wore a triaxial accelerometer (GeneActiv) against the skin surface on the wrist (adults) or ankle (children). Participants kept a diary to record the timings of wear and non-wear and were asked to ensure that events of wear/non-wear last for a minimum of 15 min. The overall sensitivity of the proposed method was 0.94 (95% CI 0.90 to 0.98) and specificity 0.91 (95% CI 0.88 to 0.94). It performed equally well for children compared with adults, and females compared with males. Using surface skin temperature data in combination with acceleration data significantly improved the classification of wear/non-wear time when compared with methods that used acceleration data only (p<0.01). Using either accelerometer seismic information or temperature information alone is prone to considerable error. Combining both sources of data can give accurate estimates of non-wear periods thus giving better classification of sedentary behaviour. This method can be used in population studies of physical activity in free-living environments. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Magnetic Solid Phase Extraction Based on Oleic Acid Coated Fe3O4 for the Determination of Benzo[α]pyrene in Cigarette Smoke Coupled with High-Performance Liquid Chromatography.

PubMed

Feng, Shouai; Wei, Kang; Tian, Zhaofu; Li, Xiaolan; Meng, Dongling; Liao, Wenlong; Miao, Mingming; Yang, Yaling

2016-07-29

In this work, a simple and effective method based on magnetic solid-phase extraction combined with high-performance liquid chromatography was developed for the determination of benzo[α]pyrene (BaP) in cigarette smoke. Oleic acid coated Fe 3 O 4 (Fe 3 O 4 -OA) was synthesized and directly used as an efficient sorbent for the first time in magnetic solid-phase extraction (MSPE) procedure for the clean-up of BaP in cigarette smoke extracts. The synthesized Fe 3 O 4 -OA was characterized by transmission electron microscopy, X-ray diffraction and Fourier transformed infrared spectroscopy. The extraction via Fe 3 O 4 -OA was dispersed in the extracts of cigarette smoke followed by the magnetic isolation, acetonitrile-tetrahydrofuran (ACN-THF; v/v = 9:1) was used for desorption of the analyte. The effects of important parameters such as the amount of adsorbent, solution pH, the content of acetonitrile, temperature and sorption time were investigated. The method showed good linearity for the determination of BaP in the concentration range of 0.5-50 ng mL -1 with a regression coefficient (R 2 ) of 0.9987. The limit of detection and limit of quantification for BaP were obtained to be 0.12 and 0.41 ng mL -1 , respectively. The mean recoveries were in the range from 81.0% to 97.6% at low, medium, high spiked levels, and the relative standard deviations were in the range of 2.7-6.8%. Combined with high-performance liquid chromatography and fluorescence detection, a simple and effective method was developed for the analysis of BaP in cigarette smoke. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A randomized controlled study comparing community based with health facility based direct observation of treatment models on patients' satisfaction and TB treatment outcome in Nigeria.

PubMed

Adewole, Olanisun O; Oladele, T; Osunkoya, Arinola H; Erhabor, Greg E; Adewole, Temitayo O; Adeola, Oluwaseun; Obembe, Olufemi; Ota, Martin O C

2015-12-01

Directly observed treatment short-course (DOTS) strategy is an effective mode of treating TB. We aimed to study the cost effectiveness and patients' satisfaction with home based direct observation of treatment (DOT), an innovative approach to community-based DOT (CBDOT) and hospital based DOT (HBDOT). A randomized controlled trial involving 150 newly diagnosed pulmonary TB patients in four TB clinics in Ile Ife , Nigeria, was done. They were randomly assigned to receive treatment with anti TB drugs for the intensive phase administered at home by a TB worker (CBDOT) or at the hospital (HBDOT). Outcome measures were treatment completion/default rates, cost effectiveness and patients' satisfaction with care using a 13 item patients satisfaction questionnaire (PS-13) at 2 months. This trial was registered with pactr.org: number PACTR 201503001058381. At the end of intensive phase, 15/75 (20%) and 2/75 (3%) of patients in the HBDOT and CBDOT, respectively had defaulted from treatment, p= 0.01. Of those with pretreatment positive sputum smear, 97% (68/70) on CBDOT and 54/67 (81%) on HBDOT were sputum negative for AFB at the end of 2 months of treatment, p=0.01. The CBDOT method was associated with a higher patient satisfaction score compared with HBDOT (OR 3.1; 95% CI 1.25-7.70), p=0.001.The total cost for patients was higher in HBDOT (US$159.38) compared with the CBDOT (US$89.52). The incremental cost effectiveness ratio was US$410 per patient who completed the intensive phase treatment with CBDOT. CBDOT is a cost effective approach associated with better compliance to treatment and better patient satisfaction compared to HBDOT. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Long-Term Maintenance of Therapeutic Gains Associated With Cognitive-Behavioral Therapy for Insomnia Delivered Alone or Combined With Zolpidem.

PubMed

Beaulieu-Bonneau, Simon; Ivers, Hans; Guay, Bernard; Morin, Charles M

2017-03-01

To document the long-term sleep outcomes at 12 and 24 months after patients with chronic insomnia were treated with cognitive-behavioral therapy (CBT), either singly or combined with zolpidem medication. Participants were 160 adults with chronic insomnia. They were first randomized for a six-week acute treatment phase involving CBT alone or CBT combined with nightly zolpidem, and randomized for a six-month extended treatment phase involving CBT, no additional treatment, CBT combined with zolpidem as needed, or CBT with zolpidem tapered. This paper reports results of the 12- and 24-month follow-ups on the main outcome measures derived from the Insomnia Severity Index and sleep diaries. Clinical improvements achieved 6 months following the end of treatment were well-maintained in all four conditions, with insomnia remission rates ranging from 48% to 74% at the 12-month follow-up, and from 44% to 63% at the 24-month follow-up. Participants receiving CBT with zolpidem taper in the extended treatment phase had significantly better results than those receiving CBT with continued zolpidem as needed. The magnitude of improvements on sleep diary parameters was similar between conditions, with a slight advantage for the CBT with zolpidem taper condition. The addition of extended CBT did not alter the long-term outcome over improvements obtained during the initial 6-week CBT. The results suggest that CBT for insomnia, when delivered alone or in combination with medication, produce durable sleep improvements up to two years after completion of treatment. These long-term results indicate that even if a combined CBT plus medication approach provide an added benefit immediately after treatment, extending CBT while tapering medication produce better sustained improvements compared to continued use of medication as needed. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Low temperatures are required to induce the development of fertile flowers in transgenic male and female early flowering poplar (Populus tremula L.).

PubMed

Hoenicka, Hans; Lehnhardt, Denise; Briones, Valentina; Nilsson, Ove; Fladung, Matthias

2016-05-01

Until now, artificial early flowering poplar systems have mostly led to the development of sterile flowers. In this study, several strategies aimed at inducting fertile flowers in pHSP::AtFT transgenic poplar were evaluated, in particular the influence of temperature and photoperiod. Our results provide evidence that temperature, and not photoperiod, is the key factor required for the development of fertile flowers in early flowering poplar. Fertile flowers were only obtained when a cold treatment phase of several weeks was used after the heat treatment phase. Heat treatments induced AtFT gene activity through activation of the heat-shock promoter (pHSP). Photoperiod did not show a similar influence on flower fertility as pollen grains were obtained under both long- and short-day conditions. Fertility was confirmed in flowers of both male and female plants. For the first time, crosses were successfully performed with transgenic female early flowering poplar. All mature flowers obtained after 8 weeks of inductive treatments were fertile. Gene expression studies also confirmed that cold temperatures influenced expression of poplar genes homologous to 'pollen development genes' from Arabidopsis thaliana (L.) Heynh. Homology and expression patterns suggested a role for PtTDF1, PtBAM1, PtSERK1/2 and PtMS1 on anther and pollen development in poplar flowers. The system developed in this study allows a fast and very reliable induction of fertile poplar flowers in a very short period of time. The non-reproductive phase, usually 7-10 years, can now be shortened to 6-10 months, and fertile flowers can be obtained independently of the season. This system is a reliable tool for breeding purposes (high-speed breeding technology), genomics and biosafety research. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

International Psychometric Validation of an EORTC Quality of Life Module Measuring Cancer Related Fatigue (EORTC QLQ-FA12).

PubMed

Weis, Joachim; Tomaszewski, Krzysztof A; Hammerlid, Eva; Ignacio Arraras, Juan; Conroy, Thierry; Lanceley, Anne; Schmidt, Heike; Wirtz, Markus; Singer, Susanne; Pinto, Monica; Alm El-Din, Mohamed; Compter, Inge; Holzner, Bernhard; Hofmeister, Dirk; Chie, Wei-Chu; Czeladzki, Marek; Harle, Amelie; Jones, Louise; Ritter, Sabrina; Flechtner, Hans-Henning; Bottomley, Andrew

2017-05-01

The European Organisation for Research and Treatment of Cancer (EORTC) Group has developed a new multidimensional instrument measuring cancer-related fatigue to be used in conjunction with the quality of life core questionnaire (EORTC QLQ-C30). The module EORTC QLQ-FA13 assesses physical, cognitive, and emotional aspects of cancer-related fatigue. The methodology follows the EORTC guidelines for phase IV validation of modules. This paper focuses on the results of the psychometric validation of the factorial structure of the module. For validation and cross-validation confirmatory factor analysis (maximum likelihood estimation), intraclass correlation and Cronbach alpha for internal consistency were employed. The study involved an international multicenter collaboration of 11 European and non-European countries. A total of 946 patients with various tumor diagnoses were enrolled. Based on the confirmatory factor analysis, we could approve the three-dimensional structure of the module. Removing one item and reassigning the factorial mapping of another item resulted in the EORTC QLQ-FA12. For the revised scale, we found evidence supporting good local (indicator reliability ≥ 0.60, factor reliability ≥ 0.82) and global model fit (GFI t1|t2 = 0.965/0.957, CFI t1|t2 = 0.976/0.972, RMSEA t1|t2 = 0.060/0.069) for both measurement points. For each scale, test-retest reliability proved to be very good (intraclass correlation: R t1-t2 = 0.905-0.921) and internal consistency proved to be good to high (Cronbach alpha = .79-.90). Based on the former phase III module, the multidimensional structure was revised as a phase IV module (EORTC FA12) with an improved scale structure. For a comprehensive validation of the EORTC FA12, further aspects of convergent and divergent validity as well as sensitivity to change should be determined. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Quantitative Determination of Four Azo Dyes in Rat Plasma with Solid-Phase Extraction and UFLC-MS-MS Analysis: Application to a Pharmacokinetic Study.

PubMed

Zhu, Hao; Huang, Changshun; Chen, Yijun; Lu, Zihui; Zhou, Haidong; Chen, Chunru; Wu, Jin; Chen, Xiaohong; Jin, Micong

2016-06-05

A rapid and sensitive ultra-fast liquid chromatography tandem mass spectrometry method, followed by simple protein precipitation and solid-phase extraction, has been developed and validated for the quantitative determination of four azo dyes (Para red, Solvent yellow 2, Solvent red 1 and Sudan red 7B) in rat plasma using D 5 -Sudan I as the internal standard. The optimal separation was accomplished on an Agilent Eclipse Plus C18 column (100 × 2.1 mm, 1.8 μm) with gradient elution using the mobile phase including acetonitrile and water (containing 0.1% formic acid). The flow rate was 0.45 mL/min. The detection was conducted by means of electrospray ionization mass spectrometry in positive ion mode with multiple reaction monitoring. The calibration curves showed good linearity, with correlation coefficients >0.998 for all of the analytes within the concentration range. The lower limits of quantification (LLOQs) of Para red, Solvent yellow 2, Solvent red 1 and Sudan red 7B in rat plasma were 1.0, 0.1, 0.1 and 0.1 μg/L, respectively. The intra- and interday relative standard deviations were ≤9.6 and ≤12.4%, respectively, and the accuracy was in the range of -5.8 to -9.5%. The average recoveries were between 81.49 and 118.65%, and the matrix effects were satisfactory in the biological matrices. The fully validated method has been successfully applied in measuring levels of the four azo dyes in rat plasma following oral administration of 20.0 mg/kg of analytes in rats, which was suitable for the pharmacokinetic studies of the azo dyes. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Determination of Aromatic Amines Using Solid-Phase Microextraction Based on an Ionic Liquid-Mediated Sol-Gel Technique.

PubMed

Abbasi, Vajihe; Sarafraz-Yazdi, Ali; Amiri, Amirhassan; Vatani, Hossein

2016-04-01

A headspace solid-phase microextraction (HS-SPME) method was developed for isolation of monocyclic aromatic amines from water samples followed by gas chromatography-flame ionization detector (GC-FID). In this work, the effect of the presence of ionic liquid (namely, 1-hexyl-3-methyl-imidazolium hexafluorophosphate [C6MIM][PF6]) was investigated in the sol-gel coating solutions on the morphology and extraction behavior of the resulting hybrid organic-inorganic sol-gel sorbents utilized in SPME. Hydroxy-terminated poly(dimethylsiloxane) (PDMS) was used as the sol-gel active organic component for sol-gel hybrid coatings. Two different coated fibers that were prepared are PDMS and PDMS-IL ([C6MIM][PF6]) fibers. Under the optimal conditions, the method detection limits (S/N = 3) with PDMS-IL were in the range of 0.001-0.1 ng/mL and the limits of quantification (S/N = 10) between 0.005 and 0.5 ng/mL. The relative standard deviations for one fiber (n = 5) were obtained from 3.1 up to 8.5% and between fibers or batch to batch (n = 3) in the range of 5.3-10.1%. The developed method was successfully applied to real water and juice fruits samples while the relative recovery percentages obtained for the spiked water samples at 0.1 ng/mL were from 83.3 to 95.0%. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Development and validation of a quick, easy, cheap, effective, rugged and safe method for the determination of imidacloprid and its metabolites in soil.

PubMed

Akoijam, Romila; Singh, Balwinder; Mandal, Kousik

2015-04-01

A simplified quick, easy, cheap, effective, rugged and safe method was standardized and validated for the estimation of residues of imidacloprid and its metabolites from different types of soil comprising sandy loam, loamy sand and clay loam soil. The samples were extracted with acetonitrile, clean up by treatment with primary secondary amine sorbent and graphitized carbon. High-performance liquid chromatography (HPLC) is a technique to separate and quantitate residues of polar, nonvolatile and thermolabile chemical compounds, using high-pressure pumps, short and narrow columns packed with microparticulate phases and a detector. The residues were estimated using HPLC equipped with a photodiode array detector system, C18 column. Acetonitrile and water (30 : 70) were used as an isocratic mobile phase at 0.3 mL/min. Imidacloprid and its metabolites presented distinct peaks at retention factors of 4.93 min (6-chloronicotinic acid), 7.91 min (nitroguanidine), 9.12 min (olefin), 11.32 min (nitrosimine), 13.82 min (urea), 15.45 min (5-hydroxy) and 22.47 min (imidacloprid). Consistent recoveries above 80% for imidacloprid and its metabolites were observed when samples were spiked at 0.01, 0.05 and 0.10 mg/kg levels. The limit of quantification of the method was 0.01 mg/kg. The analytical method was validated in terms of parameters including selectivity, linearity, precision and accuracy of the detection system. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Ionic Liquid-Mediated Multi-Walled Carbon Nanotube-Polydimethylsiloxane Fiber for Headspace Solid-Phase Microextraction of Phenolic Compounds in Aqueous Samples by Gas Chromatography Coupled to Flame Ionization Detector.

PubMed

Sadri, Minoo; Vatani, Hossein

2017-02-01

An ionic liquid-mediated multi-walled carbon nanotube (MWCNT)-polydimethylsiloxane (PDMS) sorbent was developed for headspace solid-phase microextraction (HS-SPME) of phenolic compounds from human urine samples. Sol-gel method was used to prepare this sorbent. For this purpose, MWCNTs were functionalized covalently and were attached chemically to the hydroxyl-terminated PDMS. Prepared fiber showed high thermal stability (over than 320°C) and good lifespan (>210 times). These good performances can be attributed to the performance of carbon nanotubes and sol-gel method. Affecting parameters on the efficiency of HS-SPME were investigated and optimized. Under the optimal conditions, linear dynamic ranges were observed over a range of 0.002-200 ng mL -1 with limits of detection from 0.0005 to 0.005 ng mL -1 and limits of quantitation between 0.002 and 0.02 ng mL -1 The relative standard deviations for one fiber (repeatability) (n = 5) at three different concentrations (0.05, 2 and 100 ng mL -1 ) were obtained from 4.6 up to 6.7% and between fibers or batch to batch (n = 3) (reproducibility) in the range of 5.7-7.8%. Urine samples were used as real samples. All real samples were spiked at 0.5 ng mL -1 of understudy analytes and the relative recovery percentages obtained from 90.7 to 102.1%. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Salting-Out Assisted Liquid-Liquid Extraction for Quantification of Febuxostat in Plasma Using RP-HPLC and Its Pharmacokinetic Application.

PubMed

Tandel, Devang; Shah, Purvi; Patel, Kalpana; Thakkar, Vaishali; Patel, Kirti; Gandhi, Tejal

2016-11-01

A rapid and sensitive reversed-phase high-performance liquid chromatography (HPLC) method using novel salting-out assisted liquid-liquid extraction technique has been developed for the quantitative determination of febuxostat (FEB), used for the treatment of gout, in rat plasma. The method was validated according to US FDA guideline. Separation was achieved using a Phenomenex Luna-C 18 (250 × 4.60 mm, 5 µm) column and mobile phase composed of potassium dihydrogen orthophosphate buffer 25 mM, adjusted to pH 6.8 with triethylamine:methanol in a ratio of 35:65 (v/v) showing retention time 5.56 and 8.86 min for FEB and internal standard, respectively. The optimal salting-out parameters; 1 mL of acetonitrile and 200 µL of 2 M ammonium acetate salt showed extraction recovery >90% for FEB from plasma. This extraction procedure afforded clear samples resulting in convenient and cost-saving procedure and showed good linear relationship (r > 0.9997) between peak area ratio and concentration from 0.3 to 20 µg/mL. The results of pharmacokinetic study showed that absorption profile of spherical agglomerate of FEB compared to marketed formulation was higher indicating greater systemic absorption. In conclusion, the developed SALLE-HPLC method with simple ultraviolet detection offered a number of advantages including good quantitative ability, wide linear range, high recovery, short analysis time as well as low cost. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

EACVI/HFA Cardiac Oncology Toxicity Registry in breast cancer patients: rationale, study design, and methodology (EACVI/HFA COT Registry)--EURObservational Research Program of the European Society of Cardiology.

PubMed

Lancellotti, Patrizio; Anker, Stefan D; Donal, Erwan; Edvardsen, Thor; Popescu, Bogdan A; Farmakis, Dimitrios; Filippatos, Gerasimos; Habib, Gilbert; Maggioni, Aldo P; Jerusalem, Guy; Galderisi, Maurizio

2015-05-01

The goal of adjuvant anti-cancer therapies is cure with limited or no side effects, in particular long-term side effects with negative impact on quality of life. In the palliative setting disease control, quality of life and overall survival are important end points. Partly due to improvements in treatment, the population of cancer survivors is large and growing. However, anti-cancer drug-related cardiotoxicity (ADRC) is the leading cause of treatment-associated mortality in cancer survivors. It is one of the most common post-treatment problems among 5- to 10-year survivors of adult cancer. This is particularly true for breast cancer, the most common cancer in women. The EACVI/HFA COT registry is designed for comprehensive data collection and evaluation of the current European practice in terms of diagnosis and management of ADRC in breast cancer patients. The COT registry will be carried out in two continuing phases, the pilot study phase involving 13 countries followed by the long-term registry in which all the 56 ESC countries will be invited to participate. With the COT registry, several critical information will be obtained: on predisposing factors for the development of ADRC, the rate of subclinical LV dysfunction and its transition to overt heart failure, the clinical impact and outcome of ADRC. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

CD81 expression is important for the permissiveness of Huh7 cell clones for heterogeneous hepatitis C virus infection.

PubMed

Akazawa, Daisuke; Date, Tomoko; Morikawa, Kenichi; Murayama, Asako; Miyamoto, Michiko; Kaga, Minako; Barth, Heidi; Baumert, Thomas F; Dubuisson, Jean; Wakita, Takaji

2007-05-01

Huh7 cells constitute a permissive cell line for cell culture of hepatitis C virus (HCV) particles. However, our Huh7 line shows limited permissiveness for HCV. Thus, in this study we set out to determine which host factors are important for conferring permissiveness. To analyze the limited permissiveness of our Huh7 cells, 70 clones were obtained after single-cell cloning of parental Huh7 cells. The cloned Huh7 cells exhibited various levels of HCV pseudoparticles and JFH-1 virus infection efficiency, and some clones were not permissive. A subgenomic replicon was then transfected into the cloned Huh7 cells. While the replication efficiencies differed among the cloned Huh7 cells, these efficiencies did not correlate with infectious permissibility. Flow cytometry showed that CD81, scavenger receptor class B type I, and low-density-lipoprotein receptor expression on the cell surfaces of the Huh7 clones differed among the clones. Interestingly, we found that all of the permissive cell clones expressed CD81 while the nonpermissive cell clones did not. To confirm the importance of CD81 expression for HCV permissiveness, CD81 was then transiently and stably expressed on a nonpermissive Huh7 cell clone, which was consequently restored to HCV infection permissiveness. Furthermore, permissiveness was down-regulated upon transfection of CD81 silencing RNA into a CD81-positive cell clone. In conclusion, CD81 expression is an important determinant of HCV permissiveness of Huh7 cell clones harboring different characteristics.

47 CFR 61.17 - Applications for special permission.

Code of Federal Regulations, 2011 CFR

2011-10-01

... (CONTINUED) TARIFFS Rules for Electronic Filing § 61.17 Applications for special permission. (a) All issuing carriers that file applications for special permission, associated documents, such as transmittal letters, requests for special permission, and supporting information, shall file those documents electronically. (b...

5 CFR 890.1011 - Bases for permissive debarments.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Bases for permissive debarments. 890.1011 Section 890.1011 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... Health Care Providers Permissive Debarments § 890.1011 Bases for permissive debarments. (a) Licensure...

5 CFR 890.1011 - Bases for permissive debarments.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Bases for permissive debarments. 890.1011 Section 890.1011 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... Health Care Providers Permissive Debarments § 890.1011 Bases for permissive debarments. (a) Licensure...

5 CFR 890.1011 - Bases for permissive debarments.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Bases for permissive debarments. 890.1011 Section 890.1011 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... Health Care Providers Permissive Debarments § 890.1011 Bases for permissive debarments. (a) Licensure...

5 CFR 890.1011 - Bases for permissive debarments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Bases for permissive debarments. 890.1011 Section 890.1011 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... Health Care Providers Permissive Debarments § 890.1011 Bases for permissive debarments. (a) Licensure...

'A band of brothers'-an exploration of the range of medical ethical issues faced by British senior military clinicians on deployment to Afghanistan: a qualitative study.

PubMed

Bernthal, Elizabeth M; Draper, H J A; Henning, J; Kelly, J C

2017-06-01

To identify and explore features of ethical issues that senior clinicians faced as deployed medical directors (DMDs) to the British Field Hospital in Afghanistan as well as to determine the ethical training requirements for future deployments. A qualitative study in two phases conducted from November 2014 to June 2015. Phase 1 analysed 60 vignettes of cases that had generated ethical dilemmas for DMDs. Phase 2 included focus groups and an interview with 13 DMDs. Phase 1 identified working with limited resources, dual conflict of meeting both clinical and military obligations and consent of children as the most prevalent ethical challenges. Themes found in Phase 2 included sharing clinical responsibilities with clinicians from other countries and not knowing team members' ways of working, in addition to the themes from Phase 1. This study has drawn together examples of scenarios to form a repository that will aid future training. Recommendations included undertaking ethics training together as a team before, during and after deployment which must include all nationalities who are assigned to the same operational tour, so that different ethical views can be explored beforehand. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

46 CFR 197.515 - Permissible exposure limits (PELs).

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 7 2014-10-01 2014-10-01 false Permissible exposure limits (PELs). 197.515 Section 197.515 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE OCCUPATIONAL SAFETY AND HEALTH STANDARDS GENERAL PROVISIONS Benzene § 197.515 Permissible exposure limits (PELs). The permissible...

46 CFR 197.515 - Permissible exposure limits (PELs).

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 7 2013-10-01 2013-10-01 false Permissible exposure limits (PELs). 197.515 Section 197.515 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE OCCUPATIONAL SAFETY AND HEALTH STANDARDS GENERAL PROVISIONS Benzene § 197.515 Permissible exposure limits (PELs). The permissible...

46 CFR 197.515 - Permissible exposure limits (PELs).

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 7 2012-10-01 2012-10-01 false Permissible exposure limits (PELs). 197.515 Section 197.515 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE OCCUPATIONAL SAFETY AND HEALTH STANDARDS GENERAL PROVISIONS Benzene § 197.515 Permissible exposure limits (PELs). The permissible...

46 CFR 197.515 - Permissible exposure limits (PELs).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Permissible exposure limits (PELs). 197.515 Section 197.515 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE OCCUPATIONAL SAFETY AND HEALTH STANDARDS GENERAL PROVISIONS Benzene § 197.515 Permissible exposure limits (PELs). The permissible...

46 CFR 197.515 - Permissible exposure limits (PELs).

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 7 2011-10-01 2011-10-01 false Permissible exposure limits (PELs). 197.515 Section 197.515 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE OCCUPATIONAL SAFETY AND HEALTH STANDARDS GENERAL PROVISIONS Benzene § 197.515 Permissible exposure limits (PELs). The permissible...

A concept of dynamic permission mechanism on android

NASA Astrophysics Data System (ADS)

Aron, Lukas; Hanacek, Petr

2016-02-01

This paper discuss the main security topic in mobile security area and this topic is protect user against the leakage of data. This work primarily contains the proposal of concept of dynamic permission mechanism for Android operating system. This mechanism deals with assignment or enforcement permissions to the application according to files that the application works with. Application has set of permissions that can use, but if the user opens confident files the application permissions should change its permission set and there should not be possible leakage of this secret data. The permissions set should be stricter according to opened confidential file or more open (without restriction) if the file is not secret file. The concept proposes the solution for protecting this data leakage. Idea covers rule that user should be avoided of change this permissions himself, but this behavior should be dynamic, automatic and independent. This proposal is mainly aimed to Android operating system, but the concept can be applied to other mobile platforms with some implementation changes.

Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry.

PubMed

Zhang, Xinji; Zhang, Yuan; Ye, Xiaofei; Guo, Xiaojing; Zhang, Tianyi; He, Jia

2016-11-23

Phase IV trials are often used to investigate drug safety after approval. However, little is known about the characteristics of contemporary phase IV clinical trials and whether these studies are of sufficient quality to advance medical knowledge in pharmacovigilance. We aimed to determine the fundamental characteristics of phase IV clinical trials that evaluated drug safety using the ClinicalTrials.gov registry data. A data set of 19 359 phase IV clinical studies registered in ClinicalTrials.gov was downloaded. The characteristics of the phase IV trials focusing on safety only were compared with those evaluating both safety and efficacy. We also compared the characteristics of the phase IV trials in three major therapeutic areas (cardiovascular diseases, mental health and oncology). Multivariable logistic regression was used to evaluate factors associated with the use of blinding and randomisation. A total of 4772 phase IV trials were identified, including 330 focusing on drug safety alone and 4392 evaluating both safety and efficacy. Most of the phase IV trials evaluating drug safety (75.9%) had enrolment <300 with 96.5% <3000. Among these trials, 8.2% were terminated or withdrawn. Factors associated with the use of blinding and randomisation included the intervention model, clinical specialty and lead sponsor. Phase IV trials evaluating drug safety in the ClinicalTrials.gov registry were dominated by small trials that might not have sufficient power to detect less common adverse events. An adequate sample size should be emphasised for phase IV trials with safety surveillance as main task. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

30 CFR 75.1002 - Installation of electric equipment and conductors; permissibility.

Code of Federal Regulations, 2012 CFR

2012-07-01

... faces must be— (1) Shielded high-voltage cables supplying power to permissible longwall equipment; (2... intrinsically safe circuits; and (4) Cables and conductors supplying power to low- and medium-voltage permissible equipment. (5) Shielded high-voltage cables supplying power to permissible continuous mining...

30 CFR 75.1002 - Installation of electric equipment and conductors; permissibility.

Code of Federal Regulations, 2013 CFR

2013-07-01

... faces must be— (1) Shielded high-voltage cables supplying power to permissible longwall equipment; (2... intrinsically safe circuits; and (4) Cables and conductors supplying power to low- and medium-voltage permissible equipment. (5) Shielded high-voltage cables supplying power to permissible continuous mining...

30 CFR 75.1002 - Installation of electric equipment and conductors; permissibility.

Code of Federal Regulations, 2014 CFR

2014-07-01

... faces must be— (1) Shielded high-voltage cables supplying power to permissible longwall equipment; (2... intrinsically safe circuits; and (4) Cables and conductors supplying power to low- and medium-voltage permissible equipment. (5) Shielded high-voltage cables supplying power to permissible continuous mining...

26 CFR 1.614-5 - Special rules as to aggregating nonoperating mineral interests.

Code of Federal Regulations, 2010 CFR

2010-04-01

... section. (b) Manner and scope of election—(1) Time for filing application for permission to aggregate separate nonoperating mineral interests under paragraph (a) of this section. The application for permission... and returns under permission. The application for permission to aggregate nonoperating mineral...

30 CFR 75.503 - Permissible electric face equipment; maintenance.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Permissible electric face equipment...-General § 75.503 Permissible electric face equipment; maintenance. [Statutory Provisions] The operator of each coal mine shall maintain in permissible condition all electric face equipment required by §§ 75...

30 CFR 75.503 - Permissible electric face equipment; maintenance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Permissible electric face equipment...-General § 75.503 Permissible electric face equipment; maintenance. [Statutory Provisions] The operator of each coal mine shall maintain in permissible condition all electric face equipment required by §§ 75...

30 CFR 75.503 - Permissible electric face equipment; maintenance.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Permissible electric face equipment...-General § 75.503 Permissible electric face equipment; maintenance. [Statutory Provisions] The operator of each coal mine shall maintain in permissible condition all electric face equipment required by §§ 75...

30 CFR 75.503 - Permissible electric face equipment; maintenance.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Permissible electric face equipment...-General § 75.503 Permissible electric face equipment; maintenance. [Statutory Provisions] The operator of each coal mine shall maintain in permissible condition all electric face equipment required by §§ 75...

30 CFR 75.503 - Permissible electric face equipment; maintenance.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Permissible electric face equipment...-General § 75.503 Permissible electric face equipment; maintenance. [Statutory Provisions] The operator of each coal mine shall maintain in permissible condition all electric face equipment required by §§ 75...

An Ethics of Permission: A Response to the California End of Life Option Act.

PubMed

Nelson, Craig

2016-01-01

An ethics of permission can be helpful in framing a response to the ethical differences surrounding the California End of Life Option Act. Law does not define morality, and reaching a moral understanding demands thorough reflection. An ethics of permission examines the ethical demands of a permissive law for both clinician and patient. Serving the good of the patient, respecting professional conscience, and following the law are three ethical elements. Although developing an ethics of permission includes these three elements, these elements do not exhaust all the moral implications involved. An ethics of permission also includes the importance of exercising professional tolerance in the honoring of clinicians who choose to participate or refuse to participate. In addition, an ethics of permission also provides insight in implementing just and fair behavior among medical professionals.

An Ethics of Permission: A Response to the California End of Life Option Act

PubMed Central

Nelson, Craig

2016-01-01

An ethics of permission can be helpful in framing a response to the ethical differences surrounding the California End of Life Option Act. Law does not define morality, and reaching a moral understanding demands thorough reflection. An ethics of permission examines the ethical demands of a permissive law for both clinician and patient. Serving the good of the patient, respecting professional conscience, and following the law are three ethical elements. Although developing an ethics of permission includes these three elements, these elements do not exhaust all the moral implications involved. An ethics of permission also includes the importance of exercising professional tolerance in the honoring of clinicians who choose to participate or refuse to participate. In addition, an ethics of permission also provides insight in implementing just and fair behavior among medical professionals. PMID:27541320

Algoma-, Superior-, and oolitic-type iron deposits of the Islamic Republic of Mauritania (phase V, deliverable 83): Chapter O in Second projet de renforcement institutionnel du secteur minier de la République Islamique de Mauritanie (PRISM-II)

USGS Publications Warehouse

Taylor, Cliff D.; Finn, Carol A.; Anderson, Eric D.; Joud, M. Y.; Taleb, M. A.; Horton, John D.

2015-01-01

Phanerozoic oolitic ironstones are hosted in the upper Silurian and lower Devonian rocks of the Gara Bouya Ali Group and the Zemmour Group in the Tindouf Basin in northern Mauritania and in the end Ordovician Tichit Group, the Silurian Oued Chig Group, and the lower Devonian Tenemouj Group in the Taoudeni Basin near Tidjikja. These rock groups define 11 permissive tracts for Algoma-, Superior-, and oolitic-type iron deposits in Mauritania.

Notochord alters the permissiveness of myotome for pathfinding by an identified motoneuron in embryonic zebrafish.

PubMed

Beattie, C E; Eisen, J S

1997-02-01

During zebrafish development, identified motoneurons innervate cell-specific regions of each trunk myotome. One motoneuron, CaP, extends an axon along the medial surface of the ventral myotome. To learn how this pathway is established during development, the CaP axon was used as an assay to ask whether other regions of the myotome were permissive for normal CaP pathfinding. Native myotomes were replaced with donor myotomes in normal or reversed dorsoventral orientations and CaP pathfinding was assayed. Ventral myotomes were permissive for CaP axons, even when they were taken from older embryos, suggesting that the CaP pathway remained present on ventral myotome throughout development. Dorsal myotomes from young embryos were also permissive for CaP axons, however, older dorsal myotomes were non-permissive, showing that permissiveness of dorsal myotome for normal CaP pathfinding diminished over time. This process appears to depend on signals from the embryo, since dorsal myotomes matured in vitro remained permissive for CaP axons. Genetic mosaics between wild-type and floating head mutant embryos revealed notochord involvement in dorsal myotome change of permissiveness. Dorsal and ventral myotomes from both younger and older floating head mutant embryos were permissive for CaP axons. These data suggest that initially both dorsal and ventral myotomes are permissive for CaP axons but as development proceeds, there is a notochord-dependent decrease in permissiveness of dorsal myotome for CaP axonal outgrowth. This change participates in restricting the CaP pathway to the ventral myotome and thus to neuromuscular specificity.

47 CFR 61.17 - Method of filing applications for special permission.

Code of Federal Regulations, 2010 CFR

2010-10-01

... special permission. (a) An application for special permission filed electronically must be addressed to... permission applications requiring fees as set forth in part 1, subpart G of this chapter, issuing carriers... 47 Telecommunication 3 2010-10-01 2010-10-01 false Method of filing applications for special...

14 CFR 399.35 - Special tariff permission.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Special tariff permission. (a) Definition. As used in this section, to grant STP means to approve a carrier's application for Special Tariff Permission to file a tariff on less than the statutory notice set... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Special tariff permission. 399.35 Section...

14 CFR 221.120 - Grounds for approving or denying Special Tariff Permission applications.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Tariff Permission applications. 221.120 Section 221.120 Aeronautics and Space OFFICE OF THE SECRETARY... approving applications for Special Tariff Permission to file on less than statutory notice the tariff changes necessary to correct such errors. Each application for Special Tariff Permission based on such...

18 CFR 341.14 - Special permission.

Code of Federal Regulations, 2010 CFR

2010-04-01

... requested waiver. If the application requests permission to make changes in joint tariffs, it must state... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Special permission. 341... COMPANIES SUBJECT TO SECTION 6 OF THE INTERSTATE COMMERCE ACT § 341.14 Special permission. (a) Procedure...

19 CFR 146.9 - Permission of operator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... TREASURY (CONTINUED) FOREIGN TRADE ZONES General Provisions § 146.9 Permission of operator. An application for permission to admit merchandise into a zone, or to manipulate, manufacture, exhibit, or destroy... 19 Customs Duties 2 2010-04-01 2010-04-01 false Permission of operator. 146.9 Section 146.9...

Comment on `A novel experimental method: Electrochemical detection of phase transition in ferroelectric single crystals', Chem. Phys. Lett. 384 (2004) 262 by K. Gatner and R. Jakubas

NASA Astrophysics Data System (ADS)

Ćwikiel, K.; Matlak, M.

2006-03-01

We comment the Letter 'A novel experimental method: electrochemical detection of phase transition in ferroelectric single crystals', Chem. Phys. Lett. 384 (2004) 262 by K. Gatner and R. Jakubas. We indicate that the method used in this Letter is not 'A novel method' but the application of the method described in Refs. [M. Matlak, M. Pietruszka, E. Rówiński, Phys. Rev. B 63 (2001) 52101; M. Matlak, M. Pietruszka, E. Rówiński, Phys. Stat. Sol. A 184 (2001) 335; W. Gaweł, E. Zaleska, Z. Sztuba, Met. Sci. Eng. A 324 (2002) 255], well known to Gatner, but not cited in the commented Letter. Additionally Gatner, cooperating with us, has used our TGS samples and published the results in the commented Letter without our knowledge and permission.

How to keep high-risk studies ethical: classifying candidate solutions.

PubMed

Eyal, Nir

2017-02-01

This article lays out a wide spectrum of candidate ethical solutions for the challenge on which this JME symposium focuses: the benefit:risk ratio challenge to some early-phase HIV cure and remission studies. These candidate solutions fall into four categories: ones that seek to reduce risks in early-phase HIV cure and remission studies, ones that enhance the benefits for these studies' participants (or show that those were adequate in the first place), ones that focus on participants' free and informed consent to participate and ones according to whom the large benefits to non-participants can defeat considerations about individual participant net risks. In so doing, this article also structures the rest of the symposium. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

25 CFR 169.4 - Permission to survey.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 1 2014-04-01 2014-04-01 false Permission to survey. 169.4 Section 169.4 Indians BUREAU... Permission to survey. Anyone desiring to obtain permission to survey for a right-of-way across individually... to cover twice the estimated damages which may be sustained as a result of the survey. With the...

25 CFR 169.4 - Permission to survey.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false Permission to survey. 169.4 Section 169.4 Indians BUREAU... Permission to survey. Anyone desiring to obtain permission to survey for a right-of-way across individually... to cover twice the estimated damages which may be sustained as a result of the survey. With the...

25 CFR 169.4 - Permission to survey.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Permission to survey. 169.4 Section 169.4 Indians BUREAU... Permission to survey. Anyone desiring to obtain permission to survey for a right-of-way across individually... to cover twice the estimated damages which may be sustained as a result of the survey. With the...

12 CFR 211.4 - Permissible activities and investments of foreign branches of member banks.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 2 2010-01-01 2010-01-01 false Permissible activities and investments of... Operations of U.S. Banking Organizations § 211.4 Permissible activities and investments of foreign branches of member banks. (a) Permissible activities and investments. In addition to its general banking...

12 CFR 211.4 - Permissible activities and investments of foreign branches of member banks.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 2 2011-01-01 2011-01-01 false Permissible activities and investments of... Operations of U.S. Banking Organizations § 211.4 Permissible activities and investments of foreign branches of member banks. (a) Permissible activities and investments. In addition to its general banking...

7 CFR 51.1178 - Maximum anhydrous citric acid permissible for corresponding total soluble solids.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 2 2012-01-01 2012-01-01 false Maximum anhydrous citric acid permissible for... Sinensis (l) Osbeck) § 51.1178 Maximum anhydrous citric acid permissible for corresponding total soluble solids. For determining the grade of juice, the maximum permissible anhydrous citric acid content in...

7 CFR 51.1178 - Maximum anhydrous citric acid permissible for corresponding total soluble solids.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 2 2011-01-01 2011-01-01 false Maximum anhydrous citric acid permissible for... Sinensis (l) Osbeck) § 51.1178 Maximum anhydrous citric acid permissible for corresponding total soluble solids. For determining the grade of juice, the maximum permissible anhydrous citric acid content in...

21 CFR 1005.21 - Application for permission to bring product into compliance.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Application for permission to bring product into compliance. 1005.21 Section 1005.21 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... Procedures § 1005.21 Application for permission to bring product into compliance. Application for permission...

12 CFR 543.2 - Application for permission to organize.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Application for permission to organize. 543.2... permission to organize. (a) General. Recommendations by employees of the OTS regarding applications for...), (e), (f) or (g)(2) of this section. (2) Approval of an application for permission to organize an...

30 CFR 75.505 - Mines classed gassy; use and maintenance of permissible electric face equipment.

Code of Federal Regulations, 2014 CFR

2014-07-01

... permissible electric face equipment. 75.505 Section 75.505 Mineral Resources MINE SAFETY AND HEALTH... Electrical Equipment-General § 75.505 Mines classed gassy; use and maintenance of permissible electric face... provision of law and was required to use permissible electric face equipment and to maintain such equipment...

30 CFR 75.505 - Mines classed gassy; use and maintenance of permissible electric face equipment.

Code of Federal Regulations, 2012 CFR

2012-07-01

... permissible electric face equipment. 75.505 Section 75.505 Mineral Resources MINE SAFETY AND HEALTH... Electrical Equipment-General § 75.505 Mines classed gassy; use and maintenance of permissible electric face... provision of law and was required to use permissible electric face equipment and to maintain such equipment...

30 CFR 75.505 - Mines classed gassy; use and maintenance of permissible electric face equipment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... permissible electric face equipment. 75.505 Section 75.505 Mineral Resources MINE SAFETY AND HEALTH... Electrical Equipment-General § 75.505 Mines classed gassy; use and maintenance of permissible electric face... provision of law and was required to use permissible electric face equipment and to maintain such equipment...

30 CFR 75.505 - Mines classed gassy; use and maintenance of permissible electric face equipment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... permissible electric face equipment. 75.505 Section 75.505 Mineral Resources MINE SAFETY AND HEALTH... Electrical Equipment-General § 75.505 Mines classed gassy; use and maintenance of permissible electric face... provision of law and was required to use permissible electric face equipment and to maintain such equipment...

30 CFR 75.505 - Mines classed gassy; use and maintenance of permissible electric face equipment.

Code of Federal Regulations, 2013 CFR

2013-07-01

... permissible electric face equipment. 75.505 Section 75.505 Mineral Resources MINE SAFETY AND HEALTH... Electrical Equipment-General § 75.505 Mines classed gassy; use and maintenance of permissible electric face... provision of law and was required to use permissible electric face equipment and to maintain such equipment...

Globular structure of human ovulatory cervical mucus.

PubMed

Brunelli, Roberto; Papi, Massimiliano; Arcovito, Giuseppe; Bompiani, Adriano; Castagnola, Massimo; Parasassi, Tiziana; Sampaolese, Beatrice; Vincenzoni, Federica; De Spirito, Marco

2007-12-01

Human cervical mucus is a heterogeneous mixture of mucin glycoproteins whose relative concentration changes during the ovulatory phases, thereby producing different mucus aggregation structures that can periodically permit the transit of spermatozoa for fertilization. In preovulatory phase, mucus is arranged in compact fiber-like structures where sperm transit is hindered. Previously, through observations made of fixed and dehydrated samples, a permissive structure in the ovulatory phase was attributed to the larger diameters of pores in the mucus network. Instead, by means of atomic force microscopy, we can show, for the first time, that unfixed ovulatory mucus is composed by floating globules of mucin aggregates. This finding sheds new light on the mechanism that governs spermatozoa transit toward the uterine cavity. In addition, we demonstrate that the switch from globular ovulatory to fibrous preovulatory mucus largely depends on a pH-driven mechanism. Analysis of mucin 5B primary sequence, the main mucin in ovulatory mucus, highlights pH-sensitive domains that are associated to flexible regions prone to drive aggregation. We suggest an involvement of these domains in the fiber-to-globule switch in cervical mucus.

Investigating the Role of Hypothalamic Tumor Involvement in Sleep and Cognitive Outcomes Among Children Treated for Craniopharyngioma.

PubMed

Jacola, Lisa M; Conklin, Heather M; Scoggins, Matthew A; Ashford, Jason M; Merchant, Thomas E; Mandrell, Belinda N; Ogg, Robert J; Curtis, Elizabeth; Wise, Merrill S; Indelicato, Daniel J; Crabtree, Valerie M

2016-07-01

Despite excellent survival prognosis, children treated for craniopharyngioma experience significant morbidity. We examined the role of hypothalamic involvement (HI) in excessive daytime sleepiness (EDS) and attention regulation in children enrolled on a Phase II trial of limited surgery and proton therapy. Participants completed a sleep evaluation (N = 62) and a continuous performance test (CPT) during functional magnetic resonance imaging (fMRI; n = 29) prior to proton therapy. EDS was identified in 76% of the patients and was significantly related to increased HI extent (p = .04). There was no relationship between CPT performance during fMRI and HI or EDS. Visual examination of group composite fMRI images revealed greater spatial extent of activation in frontal cortical regions in patients with EDS, consistent with a compensatory activation hypothesis. Routine screening for sleep problems during therapy is indicated for children with craniopharyngioma, to optimize the timing of interventions and reduce long-term morbidity. © The Author 2016. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Systematic Review: A Reevaluation and Update of the Integrative (Trajectory) Model of Pediatric Medical Traumatic Stress.

PubMed

Price, Julia; Kassam-Adams, Nancy; Alderfer, Melissa A; Christofferson, Jennifer; Kazak, Anne E

2016-01-01

The objective of this systematic review is to reevaluate and update the Integrative Model of Pediatric Medical Traumatic Stress (PMTS; Kazak et al., 2006), which provides a conceptual framework for traumatic stress responses across pediatric illnesses and injuries. Using established systematic review guidelines, we searched PsycINFO, Cumulative Index to Nursing and Allied Health Literature, and PubMed (producing 216 PMTS papers published since 2005), extracted findings for review, and organized and interpreted findings within the Integrative Model framework. Recent PMTS research has included additional pediatric populations, used advanced longitudinal modeling techniques, clarified relations between parent and child PMTS, and considered effects of PMTS on health outcomes. Results support and extend the model's five assumptions, and suggest a sixth assumption related to health outcomes and PMTS. Based on new evidence, the renamed Integrative Trajectory Model includes phases corresponding with medical events, adds family-centered trajectories, reaffirms a competency-based framework, and suggests updated assessment and intervention implications. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Seed birth to death: dual functions of reactive oxygen species in seed physiology.

PubMed

Jeevan Kumar, S P; Rajendra Prasad, S; Banerjee, Rintu; Thammineni, Chakradhar

2015-09-01

Reactive oxygen species (ROS) are considered to be detrimental to seed viability. However, recent studies have demonstrated that ROS have key roles in seed germination particularly in the release of seed dormancy and embryogenesis, as well as in protection from pathogens. This review considers the functions of ROS in seed physiology. ROS are present in all cells and at all phases of the seed life cycle. ROS accumulation is important in breaking seed dormancy, and stimulating seed germination and protection from pathogens. However, excessive ROS accumulation can be detrimental. Therefore, knowledge of the mechanisms by which ROS influence seed physiology will provide insights that may not only allow the development of seed quality markers but also help us understand how dormancy can be broken in several recalcitrant species. Reactive oxygen species have a dual role in seed physiology. Understanding the relative importance of beneficial and detrimental effects of ROS provides great scope for the improvement and maintenance of seed vigour and quality, factors that may ultimately increase crop yields. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Osteoblastic cell response to spark plasma-sintered zirconia/titanium cermets.

PubMed

Fernandez-Garcia, Elisa; Guillem-Marti, Jordi; Gutierrez-Gonzalez, Carlos F; Fernandez, Adolfo; Ginebra, Maria-Pau; Lopez-Esteban, Sonia

2015-01-01

Ceramic/metal composites, cermets, arise from the idea to combine the dissimilar properties in the pure materials. This work aims to study the biocompatibility of new micro-nanostructured 3 Y-TZP/Ti materials with 25, 50 and 75 vol.% Ti, which have been successfully obtained by spark slasma sintering technology, as well as to correlate their surface properties (roughness, wettability and chemical composition) with the osteoblastic cell response. All samples had isotropic and slightly waved microstructure, with sub-micrometric average roughness. Composites with 75 vol.% Ti had the highest surface hydrophilicity. Surface chemical composition of the cermets correlated well with the relative amounts used for their fabrication. A cell viability rate over 80% dismissed any cytotoxicity risk due to manufacturing. Cell adhesion and early differentiation were significantly enhanced on materials containing the nanostructured 3 Y-TZP phase. Proliferation and differentiation of SaOS-2 were significantly improved in their late-stage on the composite with 75 vol.% Ti that, from the osseointegration standpoint, is presented as an excellent biomaterial for bone replacement. Thus, spark plasma sintering is consolidated as a suitable technology for manufacturing nanostructured biomaterials with enhanced bioactivity. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Extraction of three bioactive diterpenoids from Andrographis paniculata: effect of the extraction techniques on extract composition and quantification of three andrographolides using high-performance liquid chromatography.

PubMed

Kumar, Satyanshu; Dhanani, Tushar; Shah, Sonal

2014-10-01

Andrographis paniculata (Burm.f.) wall.ex Nees (Acanthaceae) or Kalmegh is an important medicinal plant finding uses in many Ayurvedic formulations. Diterpenoid compounds andrographolides (APs) are the main bioactive phytochemicals present in leaves and herbage of A. paniculata. The efficiency of supercritical fluid extraction (SFE) using carbon dioxide was compared with the solid-liquid extraction techniques such as solvent extraction, ultrasound-assisted solvent extraction and microwave-assisted solvent extraction with methanol, water and methanol-water as solvents. Also a rapid and validated reverse-phase high-performance liquid chromatography-diode array detection method was developed for the simultaneous determination of the three biologically active compounds, AP, neoandrographolide and andrograpanin, in the extracts of A. paniculata. Under the best SFE conditions tested for diterpenoids, which involved extraction at 60°C and 100 bar, the extractive efficiencies were 132 and 22 µg/g for AP and neoandrographolide, respectively. The modifier percentage significantly affected the extraction efficiency. © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Assessing phagotrophy in the mixotrophic ciliate Paramecium bursaria using GFP-expressing yeast cells.

PubMed

Miura, Takashi; Moriya, Hisao; Iwai, Sosuke

2017-07-03

We used cells of the yeast Saccharomyces cerevisiae expressing green fluorescent protein (GFP) as fluorescently labelled prey to assess the phagocytic activities of the mixotrophic ciliate Paramecium bursaria, which harbours symbiotic Chlorella-like algae. Because of different fluorescence spectra of GFP and algal chlorophyll, ingested GFP-expressing yeast cells can be distinguished from endosymbiotic algal cells and directly counted in individual P. bursaria cells using fluorescence microscopy. By using GFP-expressing yeast cells, we found that P. bursaria altered ingestion activities under different physiological conditions, such as different growth phases or the presence/absence of endosymbionts. Use of GFP-expressing yeast cells allowed us to estimate the digestion rates of live prey of the ciliate. In contrast to the ingestion activities, the digestion rate within food vacuoles was not affected by the presence of endosymbionts, consistent with previous findings that food and perialgal vacuoles are spatially and functionally separated in P. bursaria. Thus, GFP-expressing yeast may provide a valuable tool to assess both ingestion and digestion activities of ciliates that feed on eukaryotic organisms. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Elimination of the last reactions in ergosterol biosynthesis alters the resistance of Saccharomyces cerevisiae to multiple stresses.

PubMed

Liu, Guodong; Chen, Yun; Færgeman, Nils J; Nielsen, Jens

2017-09-01

The sterol composition of membranes is known to influence many phenotypes of yeast. However, a systematic study of the relationship between sterol composition and stress resistances has not been conducted. Here, we therefore constructed single or double gene deletion mutants of the last four enzymes in ergosterol biosynthesis in a prototrophic genetic background of Saccharomyces cerevisiae. Identification of the sterol composition of these mutants revealed a high flexibility of the sterol-processing steps instead of the previously proposed sequential conversion. Compared with the wild type, the mutants showed altered resistances to different exogenous stresses regarding the specific growth rate and duration of lag phase. The erg5 deletion mutant whose sterol has a saturated side chain exhibited overall robust growth under the tested stress conditions. The thermotolerant phenotype of erg5 deletion mutant was reproduced in filamentous fungus Penicillium oxalicum. These results highlight the important role of sterols in the response of yeast cells to environmental stresses, and suggest the possibility of improving the robustness of industrial yeast strains by engineering their sterol composition. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Separation and Purification of Ombuoside from Gynostemma Pentaphyllum by Microwave-Assisted Extraction Coupled with High-Speed Counter-current Chromatography.

PubMed

Jiang, Wenhui; Shan, Hu; Song, Jiying; Lü, Haitao

2017-01-01

A rapid and efficient method for the separation and purification of ombuoside from Gynostemma pentaphyllum by microwave-assisted extraction coupled with high-speed counter-current chromatography (HSCCC) was successfully developed. Using an orthogonal array design L 9 (3 4 ), the extraction conditions, including microwave power, irradiation time, solid-to-liquid ratio and extraction times, were optimized. Ombuoside was isolated and purified from the crude extraction by HSCCC with two-phase solvent system composed of n-hexane:ethyl acetate:ethanol:water (5:6:5:5, v/v) in a single run. A 210 mg quantity of the crude extract containing 2.16% ombuoside was loaded, yielding 3.9 mg of ombuoside at 96.7% purity. The chemical structure of ombuoside was determined by comparison with the high-performance liquid chromatography retention time of standard substance as well as UV, FT-IR, ESI-MS, 1 H NMR and 13 C NMR spectra. The purified ombuoside had strong 1,1-diphenyl-2-picrylhydrazyl and hydroxyl free radical scavenging activities. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Late-instar Behavior of Aedes aegypti (Diptera: Culicidae) Larvae in Different Thermal and Nutritive Environments.

PubMed

Reiskind, Michael H; Janairo, M Shawn

2015-09-01

The effects of temperature on ectotherm growth have been well documented. How temperature affects foraging behavior is less well explored, and has not been studied in larval mosquitoes. We hypothesized that temperature changes foraging behavior in the aquatic larval phase of the mosquito, Aedes aegypti L. Based on empirical results in other systems, we predicted that foraging effort would increase at higher temperatures in these insects. We tested this prediction over three temperature conditions at two food levels. We measured behaviors by video recording replicated cohorts of fourth-instar mosquitoes and assessing individual behavior and time budgets using an ethogram. We found both food level and temperature had significant impacts on larval foraging behavior, with more time spent actively foraging at low food levels and at low temperatures, and more occurrences of active foraging at both temperature extremes. These results are contrary to some of our predictions, but fit into theoretical responses to temperature based upon dynamic energy budget models. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Brucella Intracellular Life Relies on the Transmembrane Protein CD98 Heavy Chain.

PubMed

Keriel, Anne; Botella, Eric; Estrach, Soline; Bragagnolo, Gabriel; Vergunst, Annette C; Feral, Chloe C; O'Callaghan, David

2015-06-01

Brucella are intracellular bacterial pathogens that use a type IV secretion system (T4SS) to escape host defenses and create a niche in which they can multiply. Although the importance of Brucella T4SS is clear, little is known about its interactions with host cell structures. In this study, we identified the eukaryotic protein CD98hc as a partner for Brucella T4SS subunit VirB2. This transmembrane glycoprotein is involved in amino acid transport, modulation of integrin signaling, and cell-to-cell fusion. Knockdown of CD98hc expression in HeLa cells demonstrated that it is essential for Brucella infection. Using knockout dermal fibroblasts, we confirmed its role for Brucella but found that it is not required for Salmonella infection. CD98hc transiently accumulates around the bacteria during the early phases of infection and is required for both optimal bacterial uptake and intracellular multiplication of Brucella. These results provide new insights into the complex interplay between Brucella and its host. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Meeting the goal of concurrent adolescent and adult licensure of HIV prevention and treatment strategies.

PubMed

Hume, Michelle; Lewis, Linda L; Nelson, Robert M

2017-12-01

The ability of adolescents to access safe and effective new products for HIV prevention and treatment is optimised by adolescent licensure at the same time these products are approved and marketed for adults. Many adolescent product development programmes for HIV prevention or treatment products may proceed simultaneously with adult phase III development programmes. Appropriately implemented, this strategy is not expected to delay licensure as information regarding product efficacy can often be extrapolated from adults to adolescents, and pharmacokinetic properties of drugs in adolescents are expected to be similar to those in adults. Finally, adolescents enrolled in therapeutic HIV prevention and treatment research can be considered adults, based on US Food and Drug Administration (FDA) regulations and the appropriate application of state law. The FDA permits local jurisdictions to apply state and local HIV/sexually transmitted infection minor treatment laws so that adolescents who are HIV-positive or at risk of contracting HIV may be enrolled in therapeutic or prevention trials without obtaining parental permission. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Three-dimensional desirability spaces for quality-by-design-based HPLC development.

PubMed

Mokhtar, Hatem I; Abdel-Salam, Randa A; Hadad, Ghada M

2015-04-01

In this study, three-dimensional desirability spaces were introduced as a graphical representation method of design space. This was illustrated in the context of application of quality-by-design concepts on development of a stability indicating gradient reversed-phase high-performance liquid chromatography method for the determination of vinpocetine and α-tocopheryl acetate in a capsule dosage form. A mechanistic retention model to optimize gradient time, initial organic solvent concentration and ternary solvent ratio was constructed for each compound from six experimental runs. Then, desirability function of each optimized criterion and subsequently the global desirability function were calculated throughout the knowledge space. The three-dimensional desirability spaces were plotted as zones exceeding a threshold value of desirability index in space defined by the three optimized method parameters. Probabilistic mapping of desirability index aided selection of design space within the potential desirability subspaces. Three-dimensional desirability spaces offered better visualization and potential design spaces for the method as a function of three method parameters with ability to assign priorities to this critical quality as compared with the corresponding resolution spaces. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Three-dimensional stereotactic atlas of the extracranial vasculature correlated with the intracranial vasculature, cranial nerves, skull and muscles.

PubMed

Nowinski, Wieslaw L; Shoon Let Thaung, Thant; Choon Chua, Beng; Hnin Wut Yi, Su; Yang, Yili; Urbanik, Andrzej

2015-04-01

Our objective was to construct a 3D, interactive, and reference atlas of the extracranial vasculature spatially correlated with the intracranial blood vessels, cranial nerves, skull, glands, and head muscles.The atlas has been constructed from multiple 3T and 7T magnetic resonance angiogram (MRA) brain scans, and 3T phase contrast and inflow MRA neck scans of the same specimen in the following steps: vessel extraction from the scans, building 3D tubular models of the vessels, spatial registration of the extra- and intracranial vessels, vessel editing, vessel naming and color-coding, vessel simplification, and atlas validation.This new atlas contains 48 names of the extracranial vessels (25 arterial and 23 venous) and it has been integrated with the existing brain atlas.The atlas is valuable for medical students and residents to easily get familiarized with the extracranial vasculature with a few clicks; is useful for educators to prepare teaching materials; and potentially can serve as a reference in the diagnosis of vascular disease and treatment, including craniomaxillofacial surgeries and radiologic interventions of the face and neck. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Shorter telomere length in Europeans than in Africans due to polygenetic adaptation.

PubMed

Hansen, Matthew E B; Hunt, Steven C; Stone, Rivka C; Horvath, Kent; Herbig, Utz; Ranciaro, Alessia; Hirbo, Jibril; Beggs, William; Reiner, Alexander P; Wilson, James G; Kimura, Masayuki; De Vivo, Immaculata; Chen, Maxine M; Kark, Jeremy D; Levy, Daniel; Nyambo, Thomas; Tishkoff, Sarah A; Aviv, Abraham

2016-06-01

Leukocyte telomere length (LTL), which reflects telomere length in other somatic tissues, is a complex genetic trait. Eleven SNPs have been shown in genome-wide association studies to be associated with LTL at a genome-wide level of significance within cohorts of European ancestry. It has been observed that LTL is longer in African Americans than in Europeans. The underlying reason for this difference is unknown. Here we show that LTL is significantly longer in sub-Saharan Africans than in both Europeans and African Americans. Based on the 11 LTL-associated alleles and genetic data in phase 3 of the 1000 Genomes Project, we show that the shifts in allele frequency within Europe and between Europe and Africa do not fit the pattern expected by neutral genetic drift. Our findings suggest that differences in LTL within Europeans and between Europeans and Africans is influenced by polygenic adaptation and that differences in LTL between Europeans and Africans might explain, in part, ethnic differences in risks for human diseases that have been linked to LTL. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Ethics and end of life care: the Liverpool Care Pathway and the Neuberger Review.

PubMed

Wrigley, Anthony

2015-08-01

The Liverpool Care Pathway for the Dying has recently been the topic of substantial media interest and also been subject to the independent Neuberger Review. This review has identified clear failings in some areas of care and recommended the Liverpool Care Pathway be phased out. I argue that while the evidence gathered of poor incidences of practice by the Review is of genuine concern for end of life care, the inferences drawn from this evidence are inconsistent with the causes for the concern. Seeking to end an approach that is widely seen as best practice and which can genuinely deliver high quality care because of negative impressions that have been formed from failing to implement it properly is not a good basis for radically overhauling our approach to end of life care. I conclude that improvements in training, communication and ethical decision-making, without the added demand to end the Liverpool Care Pathway, would have resulted in a genuine advance in end of life care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The Development and Validation of Novel, Simple High-Performance Liquid Chromatographic Method with Refractive Index Detector for Quantification of Memantine Hydrochloride in Dissolution Samples.

PubMed

Sawant, Tukaram B; Wakchaure, Vikas S; Rakibe, Udyakumar K; Musmade, Prashant B; Chaudhari, Bhata R; Mane, Dhananjay V

2017-07-01

The present study was aimed to develop an analytical method for quantification of memantine (MEM) hydrochloride in dissolution samples using high-performance liquid chromatography with refractive index (RI) detector. The chromatographic separation was achieved on C18 (250 × 4.5 mm, 5 μm) column using isocratic mobile phase comprises of buffer (pH 5.2):methanol (40:60 v/v) pumped at a flow rate of 1.0 mL/min. The column effluents were monitored using RI detector. The retention time of MEM was found to be ~6.5 ± 0.3 min. The developed chromatographic method was validated and found to be linear over the concentration range of 5.0-45.0 μg/mL for MEM. Mean recovery of MEM was found to be 99.2 ± 0.5% (w/w). The method was found to be simple, fast, precise and accurate, which can be utilized for the quantification of MEM in dissolution samples. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PCSK9 (Proprotein convertase subtilisin/kexin type 9) inhibitors: past, present, and the future.

PubMed

Shimada, Yuichi J; Cannon, Christopher P

2015-09-21

Reduction in low-density lipoprotein cholesterol (LDL-C), mainly with statins, has decreased the risk of cardiovascular events over the last few decades. However, there are several patient populations that warrant further decrease in LDL-C by additional cholesterol-lowering therapy other than statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a new class of drugs that have been shown to further decrease LDL-C by 50-70% when administered as a monotherapy or on a background therapy with statins. Proprotein convertase subtilisin/kexin type 9 inhibitors are also an excellent example of drug development in which discovery of gene mutations and its clinical effects have rapidly progressed into successful preclinical and clinical studies with multiple Phases 1-3 clinical trials completed or ongoing to date. This review summarizes the rapid evolution of the drug from genetic discovery to identification of targets for the drugs, to animal and human testing, and to large clinical outcomes trials, followed by discussion on foreseeable challenges of PCSK9 inhibitors. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

The Emergence of Knowledge and How it Supports the Memory for Novel Related Information.

PubMed

Sommer, Tobias

2017-03-01

Current theories suggest that memories for novel information and events, over time and with repeated retrieval, lose the association to their initial learning context. They are consolidated into a more stable form and transformed into semantic knowledge, that is, semanticized. Novel, related information can then be rapidly integrated into such knowledge, leading to superior memory. We tested these hypotheses in a longitudinal, 302-day, human functional magnetic resonance imaging study in which participants first overlearned and consolidated associative structures. This phase was associated with a shift from hippocampal- to ventrolateral prefrontal cortex (vlPFC)-mediated retrieval, consistent with semanticization. Next, participants encoded novel, related information whose encoding into the already acquired knowledge was orchestrated by the ventromedial prefrontal cortex. Novel related information exhibited reduced forgetting compared with novel control information, which corresponded to a faster shift from hippocampal- to vlPFC-mediated retrieval. In sum, the current results suggest that memory for novel information can be enhanced by anchoring it to prior knowledge via acceleration of the processes observed during semanticization. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

5 CFR 890.1022 - Contesting proposed permissive debarments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Administrative Sanctions Imposed Against Health Care Providers Permissive Debarments § 890.1022 Contesting proposed permissive debarments...

21 CFR 50.55 - Requirements for permission by parents or guardians and for assent by children.

Code of Federal Regulations, 2014 CFR

2014-04-01

... responsibility for the care and custody of the child. (f) Permission by parents or guardians must be documented... Children in Clinical Investigations § 50.55 Requirements for permission by parents or guardians and for... of each child's parents or guardian is granted. (1) Where parental permission is to be obtained, the...

21 CFR 50.55 - Requirements for permission by parents or guardians and for assent by children.

Code of Federal Regulations, 2013 CFR

2013-04-01

... responsibility for the care and custody of the child. (f) Permission by parents or guardians must be documented... Children in Clinical Investigations § 50.55 Requirements for permission by parents or guardians and for... of each child's parents or guardian is granted. (1) Where parental permission is to be obtained, the...

21 CFR 50.55 - Requirements for permission by parents or guardians and for assent by children.

Code of Federal Regulations, 2010 CFR

2010-04-01

... reasonably available, or when only one parent has legal responsibility for the care and custody of the child... Children in Clinical Investigations § 50.55 Requirements for permission by parents or guardians and for... determine that the permission of each child's parents or guardian is granted. (1) Where parental permission...

21 CFR 50.55 - Requirements for permission by parents or guardians and for assent by children.

Code of Federal Regulations, 2011 CFR

2011-04-01

... reasonably available, or when only one parent has legal responsibility for the care and custody of the child... Children in Clinical Investigations § 50.55 Requirements for permission by parents or guardians and for... determine that the permission of each child's parents or guardian is granted. (1) Where parental permission...

21 CFR 50.55 - Requirements for permission by parents or guardians and for assent by children.

Code of Federal Regulations, 2012 CFR

2012-04-01

... reasonably available, or when only one parent has legal responsibility for the care and custody of the child... Children in Clinical Investigations § 50.55 Requirements for permission by parents or guardians and for... determine that the permission of each child's parents or guardian is granted. (1) Where parental permission...

Religiosity and Premarital Sexual Permissiveness: A Response to the Reiss-Heltsley and Broderick Debate

ERIC Educational Resources Information Center

Ruppel, Howard J., Jr.

1970-01-01

When religiosity among college students was measured by Faulkner and DeJong's 5-D Scale of Religiosity" and the Reiss scale was used to measure permissiveness, the expected stronger relationship between religiosity and permissiveness in groups with traditions of low sexual permissiveness than in groups with traditions of high sexual…

46 CFR 502.271 - Special docket application for permission to refund or waive freight charges.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 9 2010-10-01 2010-10-01 false Special docket application for permission to refund or... docket application for permission to refund or waive freight charges. (a)(1) A common carrier or a shipper may file a special docket application seeking permission for a common carrier or conference to...

20 CFR 416.1321 - Suspension for not giving us permission to contact financial institutions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Suspension for not giving us permission to....1321 Suspension for not giving us permission to contact financial institutions. (a) If you don't give us permission to contact any financial institution and request any financial records about you when...

Core clock, SUB1, and ABAR genes mediate flooding and drought responses via alternative splicing in soybean.

PubMed

Syed, Naeem H; Prince, Silvas J; Mutava, Raymond N; Patil, Gunvant; Li, Song; Chen, Wei; Babu, Valliyodan; Joshi, Trupti; Khan, Saad; Nguyen, Henry T

2015-12-01

Circadian clocks are a great evolutionary innovation and provide competitive advantage during the day/night cycle and under changing environmental conditions. The circadian clock mediates expression of a large proportion of genes in plants, achieving a harmonious relationship between energy metabolism, photosynthesis, and biotic and abiotic stress responses. Here it is shown that multiple paralogues of clock genes are present in soybean (Glycine max) and mediate flooding and drought responses. Differential expression of many clock and SUB1 genes was found under flooding and drought conditions. Furthermore, natural variation in the amplitude and phase shifts in PRR7 and TOC1 genes was also discovered under drought and flooding conditions, respectively. PRR3 exhibited flooding- and drought-specific splicing patterns and may work in concert with PRR7 and TOC1 to achieve energy homeostasis under flooding and drought conditions. Higher expression of TOC1 also coincides with elevated levels of abscisic acid (ABA) and variation in glucose levels in the morning and afternoon, indicating that this response to abiotic stress is mediated by ABA, endogenous sugar levels, and the circadian clock to fine-tune photosynthesis and energy utilization under stress conditions. It is proposed that the presence of multiple clock gene paralogues with variation in DNA sequence, phase, and period could be used to screen exotic germplasm to find sources for drought and flooding tolerance. Furthermore, fine tuning of multiple clock gene paralogues (via a genetic engineering approach) should also facilitate the development of flooding- and drought-tolerant soybean varieties. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

From guidelines to practice: a pharmacist-driven prospective audit and feedback improvement model for peri-operative antibiotic prophylaxis in 34 South African hospitals.

PubMed

Brink, Adrian J; Messina, Angeliki P; Feldman, Charles; Richards, Guy A; van den Bergh, Dena

2017-04-01

Few data exist on the implementation of process measures to facilitate adherence to peri-operative antibiotic prophylaxis (PAP) guidelines in Africa. To implement an improvement model for PAP utilizing existing resources, in order to achieve a reduction in surgical site infections (SSIs) across a heterogeneous group of 34 urban and rural South African hospitals. A pharmacist-driven, prospective audit and feedback strategy involving change management and improvement principles was utilized. This 2.5 year intervention involved a pre-implementation phase to test a PAP guideline and a 'toolkit' at pilot sites. Following antimicrobial stewardship committee and clinician endorsement, the model was introduced in all institutions and a survey of baseline SSI and compliance rates with four process measures (antibiotic choice, dose, administration time and duration) was performed. The post-implementation phase involved audit, intervention and monthly feedback to facilitate improvements in compliance. For 70 weeks of standardized measurements and feedback, 24 206 surgical cases were reviewed. There was a significant improvement in compliance with all process measures (composite compliance) from 66.8% (95% CI 64.8-68.7) to 83.3% (95% CI 80.8-85.8), representing a 24.7% increase ( P  <   0.0001). The SSI rate decreased by 19.7% from a mean group rate of 2.46 (95% CI 2.18-2.73) pre-intervention to 1.97 post-intervention (95% CI 1.79-2.15) ( P  =   0.0029). The implementation of process improvement initiatives and principles targeted to institutional needs utilizing pharmacists can effectively improve PAP guideline compliance and sustainable patient outcomes. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

"Dis-able bodied" or "dis-able minded": stakeholders' return-to-work experiences compared between physical and mental health conditions.

PubMed

Vossen, Emmie; Van Gestel, Nicolette; Van der Heijden, Beatrice I J M; Rouwette, Etiënne A J A

2017-05-01

This study aimed to explore if and why the return-to-work (RTW) experiences of various workplace stakeholders in the Netherlands and Denmark differ between physical and mental health conditions, and to understand the consequences of potentially different experiences for the RTW process in both health conditions. We studied 21 cases of long-term sickness absence, and held a total of 61 semi-structured interviews with the various actors involved in these cases. Physical cases were seen as "easy" and mental cases as "difficult" to manage, based on the visibility and predictability of health complaints. On this ground, assessing work ability and following required RTW actions were perceived as more urgent in mental than in physical cases. Despite these perceptions, in practice, the assessment of work ability seemed to impair the RTW process in mental cases (but not in physical ones), and the (non-)uptake of RTW actions appeared to have similar results in both mental and physical cases. With these outcomes, the effectiveness of a differential approach is questioned, and the relevance of a bidirectional dialog on work ability and a phased RTW plan is highlighted, regardless of the absence cause. Our study also demonstrates how policymakers need to strike a balance between obligatory and permissive legislation to better involve workplaces in RTW issues. Implications for rehabilitation Both physically and mentally sick-listed employees could benefit from a bidirectional dialog on work ability as well as from a phased RTW plan. A greater role for employers in the RTW process should be accompanied with a support for sick-listed employees, in both physical and mental sickness absence cases. Dutch and Danish RTW legislation could be improved by carefully balancing obligatory and permissive rules and regulations to involve workplaces in RTW matters.

The reliability of clinical decisions based on the cervical vertebrae maturation staging method.

PubMed

Sohrabi, Aydin; Babay Ahari, Sahar; Moslemzadeh, Hossein; Rafighi, Ali; Aghazadeh, Zahra

2016-02-01

Of the various techniques used to determine the optimum timing for growth modification treatments, the cervical vertebrae maturation method has great advantages, including validity and no need for extra X-ray exposure. Recently, the reproducibility of this method has been questioned. The aim of this study was to investigate the cause of poor reproducibility of this method and to assess the reproducibility of the clinical decisions made based on it. Seventy lateral cephalograms of Iranian patients aged 9‒15 years were observed twice by five experienced orthodontists. In addition to determining the developmental stage, each single parameter involved in this method was assessed in terms of inter- and intra-observer reproducibility. In order to evaluate the reproducibility of clinical decisions based on this method, cervical vertebrae maturation staging (CVMS) I and II were considered as phase 1 and CVMS IV and V were considered as phase 3. By considering the clinical approach of the CVMS method, inter-observer reproducibility of this method increased from 0.48 to 0.61 (moderate to substantial) and intra-observer reproducibility enhanced from 0.72 to 0.74. 1. Complete visualization of the first four cervical vertebrae was an inclusion criterion, which also limits the clinical application of CVMS method. 2. These results can be generalized when determining growth modification treatments solely for Class II patients. Difficulty in determining the morphology of C3 and C4 leads to poor reproducibility of the CVMS method. Despite this, it has acceptable reproducibility in determining the timing of functional treatment for Class II patients. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Habitat Preference of German Mantis religiosa Populations (Mantodea: Mantidae) and Implications for Conservation.

PubMed

Linn, Catherine Anne; Griebeler, Eva Maria

2016-08-01

In Germany, the thermophilic European mantid (Mantis religiosa L.) is endangered. Here, we study habitat requirements during its life, and discuss the applicability of the two conservation measures grazing and mowing to this insect species. At two study sites in south-western Germany, which were each subject to one of these measures, we recorded structural and climatic conditions within different microhabitats. We also conducted capture-mark-recapture studies for adult M. religiosa, and mapped adult roosting, oothecae deposition, egg hatching, and imaginal molting in microhabitats over two vegetation periods. In order to assess microhabitat preference of M. religiosa during its life, and identify climatic conditions driving preferences, we applied the Lille habitat preference index and conducted logistic regression analysis for life phases. Our results suggest that temperature is important for egg and nymph development. For egg deposition, females preferred solid substrates with high heat-storing capacities, as those attenuate the negative influence of cold weather periods on egg development. Being ambush predators, males and females preferred roosting sites with sufficient shelter and high prey abundance. Contrary to our expectation, the conservation measures reduced adult population sizes, and presumably reproduction rates. We thus suggest that mowing during the adult phase should reduce vegetation height to a moderate level to keep prey abundance high. Mowing with a clearing saw or grazing over a short period in small fenced areas should be preferred over prolonged grazing, as grazers collaterally stamp down the vegetation. Grazers indirectly reduce prey availability by deteriorating prevailing microclimatic conditions. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Presymptomatic and longitudinal neuroimaging in neurodegeneration--from snapshots to motion picture: a systematic review.

PubMed

Schuster, Christina; Elamin, Marwa; Hardiman, Orla; Bede, Peter

2015-10-01

Recent quantitative neuroimaging studies have been successful in capturing phenotype and genotype-specific changes in dementia syndromes, amyotrophic lateral sclerosis, Parkinson's disease and other neurodegenerative conditions. However, the majority of imaging studies are cross-sectional, despite the obvious superiority of longitudinal study designs in characterising disease trajectories, response to therapy, progression rates and evaluating the presymptomatic phase of neurodegenerative conditions. The aim of this work is to perform a systematic review of longitudinal imaging initiatives in neurodegeneration focusing on methodology, optimal statistical models, follow-up intervals, attrition rates, primary study outcomes and presymptomatic studies. Longitudinal imaging studies were identified from 'PubMed' and reviewed from 1990 to 2014. The search terms 'longitudinal', 'MRI', 'presymptomatic' and 'imaging' were utilised in combination with one of the following degenerative conditions; Alzheimer's disease, amyotrophic lateral sclerosis/motor neuron disease, frontotemporal dementia, Huntington's disease, multiple sclerosis, Parkinson's disease, ataxia, HIV, alcohol abuse/dependence. A total of 423 longitudinal imaging papers and 103 genotype-based presymptomatic studies were identified and systematically reviewed. Imaging techniques, follow-up intervals and attrition rates showed significant variation depending on the primary diagnosis. Commonly used statistical models included analysis of annualised percentage change, mixed and random effect models, and non-linear cumulative models with acceleration-deceleration components. Although longitudinal imaging studies have the potential to provide crucial insights into the presymptomatic phase and natural trajectory of neurodegenerative processes a standardised design is required to enable meaningful data interpretation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The relationship of neurocognition and negative symptoms to social and role functioning over time in individuals at clinical high risk in the first phase of the North American Prodrome Longitudinal Study.

PubMed

Meyer, Eric C; Carrión, Ricardo E; Cornblatt, Barbara A; Addington, Jean; Cadenhead, Kristin S; Cannon, Tyrone D; McGlashan, Thomas H; Perkins, Diana O; Tsuang, Ming T; Walker, Elaine F; Woods, Scott W; Heinssen, Robert; Seidman, Larry J

2014-11-01

Impaired social, role, and neurocognitive functioning are preillness characteristics of people who later develop psychosis. In people with schizophrenia, neurocognition and negative symptoms are associated with functional impairment. We examined the relative contributions of neurocognition and symptoms to social and role functioning over time in clinically high-risk (CHR) individuals and determined if negative symptoms mediated the influence of cognition on functioning. Social, role, and neurocognitive functioning and positive, negative, and disorganized symptoms were assessed in 167 individuals at CHR for psychosis in the North American Prodrome Longitudinal Study Phase 1 (NAPLS-1), of whom 96 were reassessed at 12 months. Regression analyses indicated that negative symptoms accounted for unique variance in social and role functioning at baseline and follow-up. Composite neurocognition accounted for unique, but modest, variance in social and role functioning at baseline and in role functioning at follow-up. Negative symptoms mediated the relationship between composite neurocognition and social and role functioning across time points. In exploratory analyses, individual tests (IQ estimate, Digit Symbol/Coding, verbal memory) selectively accounted for social and role functioning at baseline and follow-up after accounting for symptoms. When negative symptom items with content overlapping with social and role functioning measures were removed, the relationship between neurocognition and social and role functioning was strengthened. The modest overlap among neurocognition, negative symptoms, and social and role functioning indicates that these domains make substantially separate contributions to CHR individuals. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Demonstration of the Blood-Stage Plasmodium falciparum Controlled Human Malaria Infection Model to Assess Efficacy of the P. falciparum Apical Membrane Antigen 1 Vaccine, FMP2.1/AS01.

PubMed

Payne, Ruth O; Milne, Kathryn H; Elias, Sean C; Edwards, Nick J; Douglas, Alexander D; Brown, Rebecca E; Silk, Sarah E; Biswas, Sumi; Miura, Kazutoyo; Roberts, Rachel; Rampling, Thomas W; Venkatraman, Navin; Hodgson, Susanne H; Labbé, Geneviève M; Halstead, Fenella D; Poulton, Ian D; Nugent, Fay L; de Graaf, Hans; Sukhtankar, Priya; Williams, Nicola C; Ockenhouse, Christian F; Kathcart, April K; Qabar, Aziz N; Waters, Norman C; Soisson, Lorraine A; Birkett, Ashley J; Cooke, Graham S; Faust, Saul N; Woods, Colleen; Ivinson, Karen; McCarthy, James S; Diggs, Carter L; Vekemans, Johan; Long, Carole A; Hill, Adrian V S; Lawrie, Alison M; Dutta, Sheetij; Draper, Simon J

2016-06-01

Models of controlled human malaria infection (CHMI) initiated by mosquito bite have been widely used to assess efficacy of preerythrocytic vaccine candidates in small proof-of-concept phase 2a clinical trials. Efficacy testing of blood-stage malaria parasite vaccines, however, has generally relied on larger-scale phase 2b field trials in malaria-endemic populations. We report the use of a blood-stage P. falciparum CHMI model to assess blood-stage vaccine candidates, using their impact on the parasite multiplication rate (PMR) as the primary efficacy end point. Fifteen healthy United Kingdom adult volunteers were vaccinated with FMP2.1, a protein vaccine that is based on the 3D7 clone sequence of apical membrane antigen 1 (AMA1) and formulated in Adjuvant System 01 (AS01). Twelve vaccinees and 15 infectivity controls subsequently underwent blood-stage CHMI. Parasitemia was monitored by quantitative real-time polymerase chain reaction (PCR) analysis, and PMR was modeled from these data. FMP2.1/AS01 elicited anti-AMA1 T-cell and serum antibody responses. Analysis of purified immunoglobulin G showed functional growth inhibitory activity against P. falciparum in vitro. There were no vaccine- or CHMI-related safety concerns. All volunteers developed blood-stage parasitemia, with no impact of the vaccine on PMR. FMP2.1/AS01 demonstrated no efficacy after blood-stage CHMI. However, the model induced highly reproducible infection in all volunteers and will accelerate proof-of-concept testing of future blood-stage vaccine candidates. NCT02044198. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Expression of C-Reactive Protein and Serum Amyloid A in Early to Late Manifestations of Lyme Disease.

PubMed

Uhde, Melanie; Ajamian, Mary; Li, Xueting; Wormser, Gary P; Marques, Adriana; Alaedini, Armin

2016-12-01

 Infection with Borrelia burgdorferi, the causative agent of Lyme disease, triggers host immune responses that affect the clinical outcome and are a source of biomarkers with diagnostic utility. Although adaptive immunity to B. burgdorferi has been extensively characterized, considerably less information is available about the development of innate acute-phase responses in Lyme disease. Our aim in this study was to evaluate the expression of C-reactive protein (CRP) and serum amyloid A (SAA), the prototype acute-phase response proteins, in the context of the varying manifestations associated with Lyme borreliosis.  Circulating concentrations of CRP and SAA in patients with a range of early to late objective manifestations of Lyme disease and in individuals with post-treatment Lyme disease syndrome were compared with those in healthy control groups.  CRP and SAA levels were significantly elevated in early localized and early disseminated Lyme disease but not in the later stages of active infection. Levels of CRP, but not SAA, were also found to be significantly increased in patients with antibiotic-refractory Lyme arthritis and in those with post-treatment Lyme disease syndrome.  These findings indicate that circulating CRP and SAA levels are highest when the concentration of spirochetes is greatest in skin and/or blood and that levels decline after the dissemination of the organism to extracutaneous sites in subsequent stages of infection. The data also suggest that antibiotic-refractory Lyme arthritis and post-treatment Lyme disease syndrome are associated with elevated CRP responses that are driven by inflammatory mechanisms distinct from those in active infection. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

The Exercise is Medicine Global Health Initiative: a 2014 update.

PubMed

Lobelo, Felipe; Stoutenberg, Mark; Hutber, Adrian

2014-12-01

A third of the world's population does not engage in recommended levels of physical activity (PA), leading to substantial health and economic burdens. The healthcare sector offers a variety of resources that can help counsel, refer and deliver PA promotion programmes for purposes of primordial, primary, secondary and tertiary prevention. Substantial evidence already exists in support of multipronged PA counselling, prescription and referral strategies, in particular those linking healthcare and community-based resources. The Exercise is Medicine (EIM) initiative was introduced in 2007 to advance the implementation of evidence-based strategies to elevate the status of PA in healthcare. In this article, we describe the evolution and global expansion of the EIM initiative, its components, their implementation, an evaluation framework and future initiative activities. Until now, EIM has a presence in 39 countries with EIM Regional Centers established in North America, Latin America, Europe, Africa, Southeast Asia, China and Australasia. The EIM Global Health Initiative is transitioning from its initial phase of infrastructure and awareness building to a phase of programme implementation, with an emphasis in low-to-middle income countries, where 80% of deaths due to non-communicable diseases already occur, but where a large gap in research and implementation of PA strategies exists. Broad implementation of PA counselling and referral systems, as clinical practice standard of care, has the potential to improve PA at the population level by complementing and leveraging other efforts and to contribute to achieving global targets for the reduction of inactivity and related morbidity and mortality. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Safety and pharmacokinetics of ramucirumab in combination with docetaxel in Japanese patients with locally advanced or metastatic breast cancer: a Phase Ib study.

PubMed

Masuda, Norikazu; Iwata, Hiroji; Aogi, Kenjiro; Xu, Yihuan; Ibrahim, Ayman; Gao, Ling; Dalal, Rita; Yoshikawa, Reigetsu; Sasaki, Yasutsuna

2016-12-01

The primary objective of this study was to investigate the safety and tolerability and to confirm the recommended dose of the anti-vascular endothelial growth factor receptor 2 monoclonal antibody ramucirumab in combination with docetaxel in Japanese patients with metastatic/locally advanced breast cancer. In this multicenter, single-arm, Phase Ib trial, eligibility criteria included: 20 years or older, Eastern Cooperative Oncology Group performance status of 0/1 and confirmed diagnosis of human epidermal growth factor receptor 2-negative metastatic/locally recurrent inoperable breast adenocarcinoma. Patients received docetaxel (75 mg/m 2 ) followed by ramucirumab (10 mg/kg) on Day 1 of 21-day cycles. Recommended dose was defined as <33% dose-limiting toxicities in dose-limiting toxicity-evaluable patients in Cycle 1. The safety, pharmacokinetics, immunogenicity and antitumor activity were examined. Seven patients were treated. Most adverse events were mild to moderate. Two patients during Cycle 1 experienced a dose-limiting toxicity; one patient each experienced Grade 3 febrile neutropenia and Grade 3 gingivitis. Both dose-limiting toxicities subsequently resolved. No patients discontinued study therapies during Cycle 1. Four serious adverse events were possibly related to ramucirumab in combination with docetaxel. Anti-ramucirumab antibodies were not detected. Pharmacokinetic analysis revealed low total body clearance and long apparent terminal elimination half-life (~7-12 days). Partial response was reported in four patients. The combination of ramucirumab and docetaxel was tolerable in female Japanese patients with breast cancer. Ramucirumab 10 mg/kg in combination with docetaxel (75 mg/m 2 ) was confirmed as the recommended dose among Japanese patients, supporting its use in future studies. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A modified prebind engagement process reduces biomechanical loading on front row players during scrummaging: a cross-sectional study of 11 elite teams.

PubMed

Cazzola, Dario; Preatoni, Ezio; Stokes, Keith A; England, Michael E; Trewartha, Grant

2015-04-01

Biomechanical studies of the rugby union scrum have typically been conducted using instrumented scrum machines, but a large-scale biomechanical analysis of live contested scrummaging is lacking. We investigated whether the biomechanical loading experienced by professional front row players during the engagement phase of live contested rugby scrums could be reduced using a modified engagement procedure. Eleven professional teams (22 forward packs) performed repeated scrum trials for each of the three engagement techniques, outdoors, on natural turf. The engagement processes were the 2011/2012 (referee calls crouch-touch-pause-engage), 2012/2013 (referee calls crouch-touch-set) and 2013/2014 (props prebind with the opposition prior to the 'Set' command; PreBind) variants. Forces were estimated by pressure sensors on the shoulders of the front row players of one forward pack. Inertial Measurement Units were placed on an upper spine cervical landmark (C7) of the six front row players to record accelerations. Players' motion was captured by multiple video cameras from three viewing perspectives and analysed in transverse and sagittal planes of motion. The PreBind technique reduced biomechanical loading in comparison with the other engagement techniques, with engagement speed, peak forces and peak accelerations of upper spine landmarks reduced by approximately 20%. There were no significant differences between techniques in terms of body kinematics and average force during the sustained push phase. Using a scrum engagement process which involves binding with the opposition prior to the engagement reduces the stresses acting on players and therefore may represent a possible improvement for players' safety. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Use of illicit tobacco following introduction of standardised packaging of tobacco products in Australia: results from a national cross-sectional survey.

PubMed

Scollo, Michelle; Zacher, Meghan; Coomber, Kerri; Wakefield, Melanie

2015-04-01

To assess whether following standardisation of tobacco packaging in Australia, smokers were, as predicted by the tobacco industry, more likely to use illicit tobacco. National cross-sectional telephone surveys conducted continuously from April 2012 (6 months before implementation of plain packaging (PP)) to March 2014 (15 months after) using responses from current cigarette smokers (n=8679). Changes between pre-PP, the transition to PP and PP phase were examined using logistic regression models. Among those whose factory-made cigarettes were purchased in Australia, compared with pre-PP, there were no significant increases in the PP phase in use of: 'cheap whites' (<0.1%; OR=0.24, 95% CI 0.04 to 1.56, p=0.134); international brands purchased for 20% or more below the recommended retail price (0.2%; OR=3.49, 95% CI 0.66 to 18.35, p=0.140); or packs purchased from informal sellers (<0.1%; OR=0.24, 95% CI 0.04 to 1.47, p=0.124). The prevalence of any use of unbranded illicit tobacco remained at about 3% (adjusted OR=0.79, 95% CI 0.58 to 1.08, p=0.141). While unable to quantify the total extent of use of illicit manufactured cigarettes, in this large national survey we found no evidence in Australia of increased use of two categories of manufactured cigarettes likely to be contraband, no increase in purchase from informal sellers and no increased use of unbranded illicit 'chop-chop' tobacco. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Risky driving among UK regular armed forces personnel: changes over time.

PubMed

Sheriff, Rebecca J Syed; Forbes, Harriet J; Wessely, Simon C; Greenberg, Neil; Jones, Norman; Fertout, Mohammed; Harrison, Kate; Fear, Nicola T

2015-09-23

To compare the prevalence of self-reported risky driving in a sample of UK military personnel at 2 different time points (2004 and 2009), and to identify the incidence of new onset risky driving and possible determinants of becoming a new risky driver. Data were used from 2 phases of a military cohort study investigating the health and well-being of UK military personnel between 2004 and 2009. Participants were included if they were undertaking regular (rather than reserve) engagements, had completed both surveys and reported being a driver at both surveys. Univariable and multivariable logistic regression analyses were performed to examine the relationship between risky driving status and sociodemographic and military characteristics. Data analysis was conducted in 2011. The prevalence of risky driving reduced from 18% to 14%, over an average of 3.3 years. The incidence of new onset risky driving was 7%. Predictors for becoming a new risky driver were: younger age, not being in a relationship at phase 2 and harmful alcohol use. Those deployed after 2007 were less likely to become risky drivers following deployment, compared with those deployed before 2007 (adjusted OR 0.62 (95% CI 0.40 to 0.95)). The prevalence of becoming a risky driver appears to have reduced over time. This paper suggests a number of explanations for this reduction, including changes in the way that the UK military have dealt with road safety with the introduction of the road safety campaign (in 2007). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A Phase 2 Trial of Oral Solithromycin 1200 mg or 1000 mg as Single-Dose Oral Therapy for Uncomplicated Gonorrhea.

PubMed

Hook, Edward W; Golden, Matthew; Jamieson, Brian D; Dixon, Paula B; Harbison, Hanne S; Lowens, Sylvan; Fernandes, Prabhavathi

2015-10-01

Progressive resistance to antimicrobial agents has reduced options for gonorrhea therapy worldwide. Solithromycin (CEM-101) is a novel oral fluoroketolide antimicrobial with substantial in vitro activity against Neisseria gonorrhoeae. We conducted a phase 2 trial of 2 oral doses of solithromycin (1200 and 1000 mg) for treatment of uncomplicated gonorrhea. A total of 59 participants were enrolled and treated in this trial; 28 participants received 1200 mg of solithromycin and 31 received 1000 mg. Forty-six (78%) participants had positive cultures for N. gonorrhoeae at the time of enrollment: 24 of the 28 persons (86%) who received 1200 mg of oral solithromycin, and 22 of 31 (71%) who received 1000 mg. In addition, 8 participants had positive pharyngeal gonococcal cultures, and 4 had positive rectal cultures. All patients with positive cultures for N. gonorrhoeae were cured at all sites of infection. Chlamydia trachomatis and Mycoplasma genitalium coinfections were evaluated using nucleic acid amplification tests and were negative at 1 week of follow-up in 9 of 11 (82%) participants positive for C. trachomatis and 7 of 10 (70%) participants positive for M. genitalium. Mild dose-related gastrointestinal side effects (nausea, loose stools, vomiting) were common but did not limit therapy. Oral single-dose solithromycin, in doses of 1000 mg and 1200 mg, was 100% effective for treatment of culture-proven gonorrhea at genital, oral, and rectal sites of infection and is a promising new agent for gonorrhea treatment. NCT01591447. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Surgical outcomes of robot-assisted rectal cancer surgery using the da Vinci Surgical System: a multi-center pilot Phase II study.

PubMed

Tsukamoto, Shunsuke; Nishizawa, Yuji; Ochiai, Hiroki; Tsukada, Yuichiro; Sasaki, Takeshi; Shida, Dai; Ito, Masaaki; Kanemitsu, Yukihide

2017-12-01

We conducted a multi-center pilot Phase II study to examine the safety of robotic rectal cancer surgery performed using the da Vinci Surgical System during the introduction period of robotic rectal surgery at two institutes based on surgical outcomes. This study was conducted with a prospective, multi-center, single-arm, open-label design to assess the safety and feasibility of robotic surgery for rectal cancer (da Vinci Surgical System). The primary endpoint was the rate of adverse events during and after robotic surgery. The secondary endpoint was the completion rate of robotic surgery. Between April 2014 and July 2016, 50 patients were enrolled in this study. Of these, 10 (20%) had rectosigmoid cancer, 17 (34%) had upper rectal cancer, and 23 (46%) had lower rectal cancer; six underwent high anterior resection, 32 underwent low anterior resection, 11 underwent intersphincteric resection, and one underwent abdominoperineal resection. Pathological stages were Stage 0 in 1 patient, Stage I in 28 patients, Stage II in 7 patients and Stage III in 14 patients. Pathologically complete resection was achieved in all patients. There was no intraoperative organ damage or postoperative mortality. Eight (16%) patients developed complications of all grades, of which 2 (4%) were Grade 3 or higher, including anastomotic leakage (2%) and conversion to open surgery (2%). The present study demonstrates the feasibility and safety of robotic rectal cancer surgery, as reflected by low morbidity and low conversion rates, during the introduction period. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Study of the Effectiveness of Multipurpose Solutions on the Bacterial Disinfection of Silicone Hydrogel Contact Lenses In Vitro.

PubMed

Correa, Priscila C; Lui, Aline C F; Silva, Cely B; Gracitelli, Carolina P B; Mimica, Lycia M; Sasagawa, Suzethe M; Netto, Adamo L

2017-10-12

To assess the antimicrobial effectiveness of multipurpose solutions in regard to the disinfection of silicone hydrogel contact lenses (CL) using a study of clinical bacterial isolates from ocular material. Three multipurpose solutions (solution A: polyhexamethylene biguanide 0.00025 g/100 mL; solution B: polyquaternary-1 0.001% and myristamidopropyl dimethylamine 0.0006%; and solution C: polyaminopropyl biguanide 0.00013% and polyquaternary 0.0001%) were used as a 3-phase disinfection on silicone hydrogel CL contaminated with bacteria from clinical isolates that were divided into five groups (group 1: Pseudomonas aeruginosa; group 2: Staphylococcus aureus; group 3: Staphylococcus epidermidis; group 4: Streptococcus spp; and group 5: enterobacteria). No differences were observed between the 24- and 48-hr measurements in any of the samples, and the positivity of microorganisms in T0 was 100% for all solutions; it was 0% in T3. Therefore, only steps T1 (rubbing followed by rinsing) and T2 (rubbing followed by rinsing and immersion of CL into solution) were considered for analysis at the 24-hr measurement time. Throughout the phases, a decrease in the number of bacteria was observed, culminating in the elimination (no recovery) of all microorganisms in the three solutions. At the end of the proposed process, the tested solutions were effective.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Oral and Vaginal Tenofovir for Genital Herpes Simplex Virus Type 2 Shedding in Immunocompetent Women: A Double-Blind, Randomized, Cross-over Trial.

PubMed

Bender Ignacio, Rachel A; Perti, Tara; Magaret, Amalia S; Rajagopal, Sharanya; Stevens, Claire E; Huang, Meei-Li; Selke, Stacy; Johnston, Christine; Marrazzo, Jeanne; Wald, Anna

2015-12-15

Tenofovir is a potent anti-human immunodeficiency virus (HIV) agent that decreased risk of herpes simplex virus type 2 (HSV-2) acquisition in HIV pre-exposure prophylaxis trials. Whether tenofovir has utility in established HSV-2 disease is unclear. We randomized immunocompetent women with symptomatic HSV-2 infection to oral tenofovir disoproxil fumarate (TDF)/placebo vaginal gel, oral placebo/tenofovir (TFV) vaginal gel, or double placebo (ratio 2:2:1) in a one-way cross-over trial. Women collected genital swabs twice daily for HSV PCR during 4-week lead-in and 5-week treatment phases. The primary intent-to-treat end point was within-person comparison of genital HSV shedding and lesion rates. 64 women completed the lead-in phase and were randomized. Neither TDF nor TFV gel decreased overall shedding or lesion rate in the primary analysis; TFV gel decreased quantity of HSV DNA by -0.50 (-0.86-0.13) log10 copies/mL. In the per-protocol analysis, TDF reduced shedding (relative risk [RR] = 0.74, P = .006) and lesion rates (RR = 0.75, P = .032); quantity of virus shed decreased by 0.41 log10 copies/mL. Oral TDF modestly decreased HSV shedding and lesion rate, and quantity of virus shed when used consistently. Vaginal TFV gel decreased quantity of virus shed by 60%. In contrast to effects on HSV-2 acquisition, tenofovir is unlikely to provide clinically meaningful reductions in the frequency of HSV shedding or genital lesions. NCT01448616. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Engagement with the TeenDrivingPlan and diversity of teens' supervised practice driving: lessons for internet-based learner driver interventions.

PubMed

Winston, Flaura K; Mirman, Jessica H; Curry, Allison E; Pfeiffer, Melissa R; Elliott, Michael R; Durbin, Dennis R

2015-02-01

Inexperienced, less-skilled driving characterises many newly licensed drivers and contributes to high crash rates. A randomised trial of TeenDrivingPlan (TDP), a new learner driver phase internet-based intervention, demonstrated effectiveness in improving safety relevant, on-road driving behaviour, primarily through greater driving practice diversity. To inform future learner driver interventions, this analysis examined TDP use and its association with practice diversity. Posthoc analysis of data from teen/parent dyads (n=107), enrolled early in learner phase and assigned to treatment arm in randomised trial. Inserted software beacons captured TDP use data. Electronic surveys completed by parents and teens assessed diversity of practice driving and TDP usability ratings at 24 weeks (end of study period). Most families (84%) used TDP early in the learner period; however, the number of TDP sessions in the first week was three times higher among dyads who achieved greater practice diversity than those with less. By week five many families still engaged with TDP, but differences in TDP use could not be detected between families with high versus low practice diversity. Usability was not a major issue for this sample based on largely positive user ratings. An engaging internet-based intervention, such as TDP, can support families in achieving high practice diversity. Future learner driver interventions should provide important information early in the learner period when engagement is greatest, encourage continued learning as part of logging practice drives, and incorporate monitoring software for further personalisation to meet family needs. NCT01498575. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Budesonide MMX for the Induction of Remission of Mild to Moderate Ulcerative Colitis: A Pooled Safety Analysis.

PubMed

Lichtenstein, Gary R; Travis, Simon; Danese, Silvio; D'Haens, Geert; Moro, Luigi; Jones, Richard; Huang, Michael; Ballard, E David; Bagin, Robert; Hardiman, Yun; Collazo, Raul; Sandborn, William J

2015-09-01

Cumulative safety and tolerability of budesonide MMX, a once-daily oral corticosteroid for inducing mild to moderate ulcerative colitis remission, was examined. Data from three randomized, double-blind, placebo-controlled, phase II or III studies [budesonide MMX 9 mg, 6 mg, or 3mg for 8 weeks]; one phase II study [randomisation to budesonide MMX 9 mg or placebo for 4 weeks, then open-label budesonide MMX 9 mg for 4 weeks]; and one open-label study [budesonide MMX 9 mg for 8 weeks] were pooled. Patients randomised to budesonide MMX 9 mg [n = 288], 6 mg [n = 254], or placebo [n = 293] had similar rates of adverse events [AEs] [27.1%, 24.8%, and 23.9%, respectively] and serious AEs [2.4%, 2.0%, and 2.7%, respectively]; treatment-related AEs and serious AEs were reported by 11.8% and 13.5%, and 5.9% and 2.2%, respectively, of patients receiving budesonide MMX 3mg [n = 17] or open-label budesonide MMX 9 mg [n = 89]. Mean morning plasma cortisol concentrations were normal from baseline to final visit across randomised groups; in patients receiving open-label budesonide, mean cortisol concentration was 129.9 nmol/l after 4 weeks, returning to normal concentrations at final visit. Budesonide MMX was not associated with an overall increased risk for glucocorticoid-related adverse effects. Budesonide MMX 9 mg was associated with normal mean cortisol concentrations at final visit and an AE incidence comparable to placebo. Overall, budesonide MMX was safe and well tolerated for inducing remission of patients with mild to moderate ulcerative colitis. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Cysticidal Efficacy of Combined Treatment With Praziquantel and Albendazole for Parenchymal Brain Cysticercosis.

PubMed

Garcia, Hector H; Lescano, Andres G; Gonzales, Isidro; Bustos, Javier A; Pretell, E Javier; Horton, John; Saavedra, Herbert; Gonzalez, Armando E; Gilman, Robert H

2016-06-01

The efficacy of current antiparasitic treatment for cerebral Taenia solium cysticercosis with either albendazole (ABZ) or praziquantel (PZQ) is suboptimal. A recent study demonstrated that combining these 2 antiparasitic drugs improves antiparasitic efficacy. We present here the parasiticidal efficacy data obtained during a previous phase II pharmacokinetic study that compared combined ABZ plus PZQ with ABZ alone. The study was a randomized, double-blinded, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ (15 mg/k/d, for 10 days) and PZQ (50 mg/k/d, for 10 days) in intraparenchymal brain cysticercosis. Patients received the usual concomitant medications, including an antiepileptic drug (phenytoin or carbamazepine), dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug. Patients underwent safety laboratory evaluations at days 4, 7, and 11, as well as magnetic resonance (MR) imaging at 6 months to assess parasiticidal efficacy. Thirty-two patients were included, 16 in each arm. All of them completed antiparasitic treatment and underwent follow-up brain MR imaging. Cysticidal efficacy was strikingly higher in the combined ABZ-plus-PZQ group than in the ABZ-alone group (proportion of cysts resolved, 78 of 82 [95%] vs 23 of 77 [30%] [relative risk {RR}, 3.18; 95% confidence interval {CI}, 2.08-4.88; P < .001]; patients with complete cyst clearance, 12 of 16 [75%] vs 4 of 16 [25%] [RR, 3.00; 95% CI, 1.23-7.34; P = .005]). The combination of ABZ plus PZQ is more effective in destroying viable brain cysticercosis cysts than ABZ alone. NCT00441285. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Safety and Immunogenicity of a Tetravalent Dengue Vaccine Candidate in Healthy Children and Adults in Dengue-Endemic Regions: A Randomized, Placebo-Controlled Phase 2 Study.

PubMed

Sirivichayakul, Chukiat; Barranco-Santana, Elizabeth A; Esquilin-Rivera, Inés; Oh, Helen M L; Raanan, Marsha; Sariol, Carlos A; Shek, Lynette P; Simasathien, Sriluck; Smith, Mary Kathryn; Velez, Ivan Dario; Wallace, Derek; Gordon, Gilad S; Stinchcomb, Dan T

2016-05-15

A safe, effective tetravalent dengue vaccine is a global health priority. The safety and immunogenicity of a live attenuated, recombinant tetravalent dengue vaccine candidate (TDV) were evaluated in healthy volunteers from dengue-endemic countries. This multicenter, double-blind, phase 2 study was conducted in Puerto Rico, Colombia, Singapore, and Thailand. During stage I, 148 volunteers aged 1.5-45 years were sequentially enrolled into 4 age-descending groups and randomized at a ratio of 2:1 to receive TDV or placebo. In stage II (group 5), 212 children aged 1.5-11 years were randomized at a ratio of 3:1 to receive TDV or placebo. Participants received a subcutaneous injection of TDV or placebo on days 0 and 90 and were followed for analysis of safety, seropositivity, and neutralizing antibodies to DENV-1-4. Injection site pain, itching, and erythema (mostly mild) were the only solicited adverse events more frequently reported with TDV than with placebo in all age groups. After 2 TDV doses, seropositivity was >95% in all 5 groups for DENV-1-3 and 72.7%-100% for DENV-4; geometric mean titers ranged from 582 to 1187 for DENV-1, from 582 to 1187 for DENV-2, from 196 to 630 for DENV-3, and from 41 to 210 for DENV-4 among the 5 groups. TDV was well tolerated and immunogenic in volunteers aged 1.5-45 years, irrespective of prevaccination dengue exposure. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mailjournals.permissions@oup.com.

Coordination of Slow Waves With Sleep Spindles Predicts Sleep-Dependent Memory Consolidation in Schizophrenia.

PubMed

Demanuele, Charmaine; Bartsch, Ullrich; Baran, Bengi; Khan, Sheraz; Vangel, Mark G; Cox, Roy; Hämäläinen, Matti; Jones, Matthew W; Stickgold, Robert; Manoach, Dara S

2017-01-01

Schizophrenia patients have correlated deficits in sleep spindle density and sleep-dependent memory consolidation. In addition to spindle density, memory consolidation is thought to rely on the precise temporal coordination of spindles with slow waves (SWs). We investigated whether this coordination is intact in schizophrenia and its relation to motor procedural memory consolidation. Twenty-one chronic medicated schizophrenia patients and 17 demographically matched healthy controls underwent two nights of polysomnography, with training on the finger tapping motor sequence task (MST) on the second night and testing the following morning. We detected SWs (0.5-4 Hz) and spindles during non-rapid eye movement (NREM) sleep. We measured SW-spindle phase-amplitude coupling and its relation with overnight improvement in MST performance. Patients did not differ from controls in the timing of SW-spindle coupling. In both the groups, spindles peaked during the SW upstate. For patients alone, the later in the SW upstate that spindles peaked and the more reliable this phase relationship, the greater the overnight MST improvement. Regression models that included both spindle density and SW-spindle coordination predicted overnight improvement significantly better than either parameter alone, suggesting that both contribute to memory consolidation. Schizophrenia patients show intact spindle-SW temporal coordination, and these timing relationships, together with spindle density, predict sleep-dependent memory consolidation. These relations were seen only in patients suggesting that their memory is more dependent on optimal spindle-SW timing, possibly due to reduced spindle density. Interventions to improve memory may need to increase spindle density while preserving or enhancing the coordination of NREM oscillations. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Substitution scenario in follow-up of chronic cancer patients in primary care: prevalence, disease duration and estimated extra consultation time.

PubMed

van Dipten, C; Olde Hartman, T C; Biermans, M C J; Assendelft, W J J

2016-02-01

The incidence of cancer as well as survival rates for it are increasing. It is debated whether care in the chronic phase of cancer can be positioned in primary care due to doubts about capacity and workload. To estimate GPs' extra consultation time if they assume responsibility for the care in the chronic phase of cancer. Retrospective cohort study. Estimation of extra consultation time by quantifying prevalence, incidence, survival, number of chronic cancer patients, current practice contacts and registration of risk factors in patients with all types of cancers. The most prevalent types of cancer (with 5-year survival rates) are as follows: breast cancer (91.5%), colorectal cancer (63.8%), prostate cancer (78.3%), melanoma (91.9%) and bladder and urinary tract cancer (77.3%). Primary care practices include ~32 chronic cancer patients, with a potential extra consultation time of ~19 hours per year per 1000 patients. One-third (35%) are already in a chronic disease management programme and 57% were diagnosed >5 years ago. Registration of risk factors for cancer is incomplete, but of better quality when comorbidity is present. Numbers of chronic cancer patients and possible time investment by primary care professionals in the case of a substitution scenario should not be a limiting factor for transition of follow-up from secondary to primary care, as most of the patients were diagnosed >5 years ago and a large proportion of these patients are already monitored in an existing chronic care programme. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Characterization of an fungal l-fucokinase involved in Mortierella alpina GDP-l-fucose salvage pathway.

PubMed

Wang, Hongchao; Zhang, Chen; Chen, Haiqin; Yang, Qin; Zhou, Xin; Gu, Zhennan; Zhang, Hao; Chen, Wei; Chen, Yong Q

2016-08-01

GDP-l-fucose functions as a biological donor for fucosyltransferases, which are required for the catalysis of l-fucose to various acceptor molecules including oligosaccharides, glycoproteins and glycolipids. Mortierella alpina is one of the highest lipid-producing fungi and can biosynthesis GDP-l-fucose in the de novo pathway. Analysis of the M. alpina genome suggests that there is a gene encoding l-fucokinase (FUK) for the conversion of fucose to l-fucose-1-phosphate in the GDP-l-fucose salvage pathway, which has never been found in fungi before. This gene was characterized to explore its role in GDP-l-fucose synthesis. The yield of GDP-l-fucose is relatively higher in lipid accumulation phase (0.096 mg per g cell) than that in cell multiplication phase (0.074 mg per g cell) of M. alpina Additionally, the transcript level of FUK is up regulated by nitrogen exhaustion when M. alpina starts to accumulate lipid, highlights the functional significance of FUK in the GDP-l-fucose biosynthesis in M. alpina Gene encoding FUK was expressed heterologously in Escherichia coli and the resulting protein was purified to homogeneity. The product of FUK reaction was analyzed by liquid chromatography and mass spectrometry. Kinetic parameters and other properties of FUK were investigated. Comparative analyses between the FUK protein and other homologous proteins were performed. To our knowledge, this study is the first to report a comprehensive characterization of FUK in a fungus. Mortierella alpina could be used as an alternative source for the production of GDP-l-fucose. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Autologous CD34+ cell therapy improves exercise capacity, angina frequency and reduces mortality in no-option refractory angina: a patient-level pooled analysis of randomized double-blinded trials.

PubMed

Henry, Timothy D; Losordo, Douglas W; Traverse, Jay H; Schatz, Richard A; Jolicoeur, E Marc; Schaer, Gary L; Clare, Robert; Chiswell, Karen; White, Christopher J; Fortuin, F David; Kereiakes, Dean J; Zeiher, Andreas M; Sherman, Warren; Hunt, Andrea S; Povsic, Thomas J

2018-01-05

Autologous CD34+ (auto-CD34+) cells represent an attractive option for the treatment of refractory angina. Three double-blinded randomized trials (n = 304) compared intramyocardial (IM) auto-CD34+ cells with IM placebo injections to affect total exercise time (TET), angina frequency (AF), and major adverse cardiac events (MACE). Patient-level data were pooled from the Phase I, Phase II ACT-34, ACT-34 extension, and Phase III RENEW trials to determine the efficacy and safety of auto-CD34+ cells. Treatment effects for TET were analysed using an analysis of covariance mixed-effects model and for AF using Poisson regression in a log linear model with repeated measures. The Kaplan-Meier rate estimates for MACE were compared using the log-rank test. Autologous CD34+ cell therapy improved TET by 46.6 s [3 months, 95% confidence interval (CI) 13.0 s-80.3 s; P = 0.007], 49.5 s (6 months, 95% CI 9.3-89.7; P = 0.016), and 44.7 s (12 months, 95% CI - 2.7 s-92.1 s; P = 0.065). The relative frequency of angina was 0.78 (95% CI 0.63-0.98; P = 0.032), 0.66 (0.48-0.91; P = 0.012), and 0.58 (0.38-0.88; P = 0.011) at 3-, 6- and 12-months in auto-CD34+ compared with placebo patients. Results remained concordant when analysed by treatment received and when confined to the Phase III dose of 1 × 105 cells/kg. Autologous CD34 + cell therapy significantly decreased mortality (12.1% vs. 2.5%; P = 0.0025) and numerically reduced MACE (38.9% vs. 30.0; P = 0.14) at 24 months. Treatment with auto-CD34+ cells resulted in clinically meaningful durable improvements in TET and AF at 3-, 6- and 12-months, as well as a reduction in 24-month mortality in this patient-level meta-analysis. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.

34 CFR 97.408 - Requirements for permission by parents or guardians and for assent by children.

Code of Federal Regulations, 2012 CFR

2012-07-01

... reasonably available, or if only one parent has legal responsibility for the care and custody of the child... § 97.408 Requirements for permission by parents or guardians and for assent by children. (a) In... permission of each child's parent(s) or guardian(s). If parental permission is to be obtained, the IRB may...

34 CFR 97.408 - Requirements for permission by parents or guardians and for assent by children.

Code of Federal Regulations, 2014 CFR

2014-07-01

... reasonably available, or if only one parent has legal responsibility for the care and custody of the child... § 97.408 Requirements for permission by parents or guardians and for assent by children. (a) In... permission of each child's parent(s) or guardian(s). If parental permission is to be obtained, the IRB may...

34 CFR 97.408 - Requirements for permission by parents or guardians and for assent by children.

Code of Federal Regulations, 2011 CFR

2011-07-01

... reasonably available, or if only one parent has legal responsibility for the care and custody of the child... § 97.408 Requirements for permission by parents or guardians and for assent by children. (a) In... permission of each child's parent(s) or guardian(s). If parental permission is to be obtained, the IRB may...

34 CFR 97.408 - Requirements for permission by parents or guardians and for assent by children.

Code of Federal Regulations, 2010 CFR

2010-07-01

... reasonably available, or if only one parent has legal responsibility for the care and custody of the child... § 97.408 Requirements for permission by parents or guardians and for assent by children. (a) In... permission of each child's parent(s) or guardian(s). If parental permission is to be obtained, the IRB may...

34 CFR 97.408 - Requirements for permission by parents or guardians and for assent by children.

Code of Federal Regulations, 2013 CFR

2013-07-01

... reasonably available, or if only one parent has legal responsibility for the care and custody of the child... § 97.408 Requirements for permission by parents or guardians and for assent by children. (a) In... permission of each child's parent(s) or guardian(s). If parental permission is to be obtained, the IRB may...

20 CFR 416.207 - You do not give us permission to contact financial institutions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false You do not give us permission to contact... Benefits for Which You Are Otherwise Eligible § 416.207 You do not give us permission to contact financial institutions. (a) To be eligible for SSI payments you must give us permission to contact any financial...

Pluronic lecithin organogel (PLO) of diltiazem hydrochloride: effect of solvents/penetration enhancers on ex vivo permeation.

PubMed

Parhi, Rabinarayan; Suresh, Podilam; Pattnaik, Subasini

2016-06-01

In the present study, pluronic lecithin organogel (PLO) of diltiazem hydrochloride (DZH) was developed by taking different ratios of organic phase to aqueous phase (1:3, 1:4, and 1:5) with varying concentration of soya lecithin (20, 30, and 40 % w/w) in organic phase (isopropyl myristate, IPM) and pluronic (20, 25, and 30 % w/w) in aqueous phase, respectively, and characterized for in vitro parameters and ex vivo permeation study. The results of in vitro parameters were found to be within permissible limit and all the PLOs were physically stable at refrigeration and ambient temperature. The influence of phase ratio and different concentrations of soya lecithin on DZH release from the PLOs was found to be significant (p < 0.05), whereas the influences of different concentrations of pluronic were insignificant. The effect of different solvents/penetration enhancers viz. IPM, propylene glycol (PG), dimethyl sulphoxide (DMSO), and D-limonene, in combination and alone, on the permeation of DZH across the dorsal skin of rat was studied. Among all, formulation containing IPM (PLO6) exhibited highest flux of 147.317 μg/cm(2)/h. Furthermore, histopathology section of treated skin sample illustrated that lipid bilayer disruption was the mechanism for the DZH permeation. The above results indicated that PLO6 may serve as a promising alternative delivery system for DZH in the effective treatment of hypertension.

Cdc7 is required throughout the yeast S phase to activate replication origins.

PubMed

Donaldson, A D; Fangman, W L; Brewer, B J

1998-02-15

The long-standing conclusion that the Cdc7 kinase of Saccharomyces cerevisiae is required only to trigger S phase has been challenged by recent data that suggests it acts directly on individual replication origins. We tested the possibility that early- and late-activated origins have different requirements for Cdc7 activity. Cells carrying a cdc7(ts) allele were first arrested in G1 at the cdc7 block by incubation at 37 degrees C, and then were allowed to enter S phase by brief incubation at 23 degrees C. During the S phase, after return to 37 degrees C, early-firing replication origins were activated, but late origins failed to fire. Similarly, a plasmid with a late-activated origin was defective in replication. As a consequence of the origin activation defect, duplication of chromosomal sequences that are normally replicated from late origins was greatly delayed. Early-replicating regions of the genome duplicated at approximately their normal time. The requirements of early and late origins for Cdc7 appear to be temporally rather than quantitatively different, as reducing overall levels of Cdc7 by growth at semi-permissive temperature reduced activation at early and late origins approximately equally. Our results show that Cdc7 activates early and late origins separately, with late origins requiring the activity later in S phase to permit replication initiation.

Challenges to obtaining parental permission for child participation in a school-based waterpipe tobacco smoking prevention intervention in Qatar.

PubMed

Nakkash, Rima T; Al Mulla, Ahmad; Torossian, Lena; Karhily, Roubina; Shuayb, Lama; Mahfoud, Ziyad R; Janahi, Ibrahim; Al Ansari, Al Anoud; Afifi, Rema A

2014-09-30

Involving children in research studies requires obtaining parental permission. A school-based intervention to delay/prevent waterpipe use for 7th and 8th graders in Qatar was developed, and parental permission requested. Fifty three percent (2308/4314) of the parents returned permission forms; of those 19.5% of the total (840/4314) granted permission. This paper describes the challenges to obtaining parental permission. No research to date has described such challenges in the Arab world. A random sample of 40 schools in Doha, Qatar was selected for inclusion in the original intervention. Permission forms were distributed to parents for approval of their child's participation. The permission forms requested that parents indicate their reasons for non-permission if they declined. These were categorized into themes. In order to understand reasons for non-permission, interviews with parents were conducted. Phone numbers of parents were requested from the school administration; 12 of the 40 schools (30%) agreed to provide the contact information. A random sample of 28 parents from 12 schools was interviewed to reach data saturation. Thematic analysis was used to analyze their responses. Reasons for non-permission documented in both the forms and interviews included: poor timing; lack of interest; the child not wanting to participate; and the child living in a smoke-free environment. Interviews provided information on important topics to include in the consent forms, parents' decision-making processes regarding their child's participation, and considerations for communicating with parents. Many parents also indicated that this was the first time they had been asked to give an informed consent for their child's participation in a study. Results indicate that more attention needs to be given to the informed parental consent process. Researchers should consider enhancing both the methods of communicating information as well the specific information provided. Before embarking on recruitment of children for studies, formative research on the parental consent process is suggested.

Coding, Constant Comparisons, and Core Categories: A Worked Example for Novice Constructivist Grounded Theorists.

PubMed

Giles, Tracey M; de Lacey, Sheryl; Muir-Cochrane, Eimear

2016-01-01

Grounded theory method has been described extensively in the literature. Yet, the varying processes portrayed can be confusing for novice grounded theorists. This article provides a worked example of the data analysis phase of a constructivist grounded theory study that examined family presence during resuscitation in acute health care settings. Core grounded theory methods are exemplified, including initial and focused coding, constant comparative analysis, memo writing, theoretical sampling, and theoretical saturation. The article traces the construction of the core category "Conditional Permission" from initial and focused codes, subcategories, and properties, through to its position in the final substantive grounded theory.

A phase 2, randomised, placebo-controlled clinical trial of blisibimod, an inhibitor of B cell activating factor, in patients with moderate-to-severe systemic lupus erythematosus, the PEARL-SC study.

PubMed

Furie, R A; Leon, G; Thomas, M; Petri, M A; Chu, A D; Hislop, C; Martin, R S; Scheinberg, M A

2015-09-01

To evaluate the efficacy and safety of subcutaneous blisibimod, an inhibitor of B cell activating factor, in patients with systemic lupus erythematosus (SLE) in a dose-ranging Phase 2b clinical trial. 547 patients with SLE with anti-double stranded DNA or antinuclear antibodies and Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score ≥6 at baseline were randomised to receive placebo or blisibimod at one of 3 dose levels. The primary end point, measured at Week 24, was the SLE Responder Index-5 (SRI-5, meeting established SRI criteria but with ≥5 point improvement in SELENA-SLEDAI). Although SRI-5 response rates were not significantly improved in the pooled blisibimod groups compared with placebo, they were higher in subjects randomised to the highest dose of blisibimod (200 mg once-weekly (QW)) compared with pooled placebo, from Week 16 to Week 24, reaching statistical significance at Week 20 (p=0.02). SRI response rates compared with placebo were higher still in subjects who attained SELENA-SLEDAI improvements of ≥8, and in a subgroup of patients with severe disease (SELENA-SLEDAI ≥10 and receiving corticosteroids at baseline). In subjects with protein:creatine ratios of 1-6 at baseline, significant reductions in proteinuria were observed with blisibimod. Significant (p<0.01) changes in anti-double stranded DNA antibodies, complement C3 and C4, and reductions in B cells were observed with blisibimod.No imbalances in serious adverse events or infections (4/280 and 3/266), deaths (4/280 and 3/266) and malignancies (2/280 and 2/266) were reported for blisibimod compared with placebo. This study successfully identified a safe, effective and convenient dose, study population and end point for evaluation of blisibimod effect in Phase 3. NCT01162681. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Biased ligand of the angiotensin II type 1 receptor in patients with acute heart failure: a randomized, double-blind, placebo-controlled, phase IIB, dose ranging trial (BLAST-AHF).

PubMed

Pang, Peter S; Butler, Javed; Collins, Sean P; Cotter, Gad; Davison, Beth A; Ezekowitz, Justin A; Filippatos, Gerasimos; Levy, Phillip D; Metra, Marco; Ponikowski, Piotr; Teerlink, John R; Voors, Adriaan A; Bharucha, David; Goin, Kathleen; Soergel, David G; Felker, G Michael

2017-08-07

Currently, no acute heart failure (AHF) therapy definitively improves outcomes. Reducing morbidity and mortality from acute heart failure (AHF) remains an unmet need. TRV027 is a novel 'biased' ligand of the angiotensin II type 1 receptor (AT1R), selectively antagonizing the negative effects of angiotensin II, while preserving the potential pro-contractility effects of AT1R stimulation. BLAST-AHF was designed to determine the safety, efficacy, and optimal dose of TRV027 to advance into future studies. BLAST-AHF was a multi-centre, international, randomized, double-blind, placebo-controlled, parallel group, phase IIb dose-ranging study, enrolling patients with AHF into 4 groups: placebo, 1, 5, or 25 mg/h of TRV027. Treatment was by IV infusion for 48-96 h. The primary composite endpoint was comprised of the following: (i) time from baseline to death through day 30, (ii) time from baseline to heart failure re-hospitalization through day 30, (iii) the first assessment time point following worsening heart failure through day 5, (iv) change in dyspnea visual analogue scale (VAS) score calculated as the area under the curve (AUC) representing the change from baseline over time from baseline through day 5, and (v) length of initial hospital stay (in days) from baseline. Analyses were by modified intention-to-treat. Overall, 621 patients were enrolled. After 254 patients, a pre-specified interim analysis resulted in several protocol changes, including a lower blood pressure inclusion criterion as well as a new allocation scheme of 2:1:2:1, overweighting both placebo, and the 5 mg/h dose. TRV027 did not confer any benefit over placebo at any dose with regards to the primary composite endpoint or any of the individual components. There were no significant safety issues with TRV027. In this phase IIb dose-ranging AHF study, TRV027 did not improve clinical status through 30-day follow-up compared with placebo. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Increased brainstem perfusion, but no blood-brain barrier disruption, during attacks of migraine with aura.

PubMed

Hougaard, Anders; Amin, Faisal M; Christensen, Casper E; Younis, Samaira; Wolfram, Frauke; Cramer, Stig P; Larsson, Henrik B W; Ashina, Messoud

2017-06-01

See Moskowitz (doi:10.1093/brain/awx099) for a scientific commentary on this article.The migraine aura is characterized by transient focal cortical disturbances causing dramatic neurological symptoms that are usually followed by migraine headache. It is currently not understood how the aura symptoms are related to the headache phase of migraine. Animal studies suggest that cortical spreading depression, the likely mechanism of migraine aura, causes disruption of the blood-brain barrier and noxious stimulation of trigeminal afferents leading to activation of brainstem nuclei and triggering of migraine headache. We used the sensitive and validated technique of dynamic contrast-enhanced high-field magnetic resonance imaging to simultaneously investigate blood-brain barrier permeability and tissue perfusion in the brainstem (at the level of the lower pons), visual cortex, and brain areas of the anterior, middle and posterior circulation during spontaneous attacks of migraine with aura. Patients reported to our institution to undergo magnetic resonance imaging during the headache phase after presenting with typical visual aura. Nineteen patients were scanned during attacks and on an attack-free day. The mean time from attack onset to scanning was 7.6 h. We found increased brainstem perfusion bilaterally during migraine with aura attacks. Perfusion also increased in the visual cortex and posterior white matter following migraine aura. We found no increase in blood-brain barrier permeability in any of the investigated regions. There was no correlation between blood-brain barrier permeability, brain perfusion, and time from symptom onset to examination or pain intensity. Our findings demonstrate hyperperfusion in brainstem during the headache phase of migraine with aura, while the blood-brain barrier remains intact during attacks of migraine with aura. These data thus contradict the preclinical hypothesis of cortical spreading depression-induced blood-brain barrier disruption as a possible mechanism linking aura and headache.awx089media15422686892001. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Relative Impact of Sleep and Circadian Drive on Motor Skill Acquisition and Memory Consolidation.

PubMed

Tucker, Matthew A; Morris, Christopher J; Morgan, Alexandra; Yang, Jessica; Myers, Samantha; Pierce, Joanna Garcia; Stickgold, Robert; Scheer, Frank A J L

2017-04-01

Sleep during the biological night facilitates memory consolidation. Here we determined the impact of sleep and wake on motor skill learning (acquisition) and subsequent off-line skill improvement (memory consolidation), independent of circadian phase, and compared this to the impact of the endogenous circadian system, independent of whether sleep occurred during the biological night or day. Participants completed two 8-day sleep laboratory visits, adhering on one visit to a circadian aligned ("normal") sleep schedule for the full duration of the protocol, and on the other to a circadian misaligned (12-hour inverted) schedule, with alignment during the first 3 days, a 12-hour 'slam shift' on Day 4, followed by circadian misalignment during the last 4 days of the protocol. Participants were repeatedly trained and tested on different versions of the finger-tapping motor sequence task across each visit. Sleep facilitated offline memory consolidation regardless of whether it occurred during the biological day or night, while circadian phase had no significant impact. These sleep-related benefits remained after accounting for general motor speed, measured in the absence of learning. In addition, motor skill acquisition was facilitated when the training session followed shortly after sleep, without significant impact of circadian phase (biological morning vs. evening). This effect was largely driven by heightened acquisition in participants who slept during the day and were trained shortly thereafter, that is, when acquisition occurred during the biological evening. These benefits were also retained after controlling for general motor speed. Sleep benefits both the acquisition and consolidation of motor skill regardless of whether they occur during the biological day or night. After controlling for general motor speed, a critical adjustment that few studies perform, these sleep benefits remain intact. Our findings have clear implications for night shift workers who obtain their sleep during the day. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Determination of Alkaloid Contents in Various Tissues of Coptis Chinensis Franch. by Reversed Phase-High Performance Liquid Chromatography and Ultraviolet Spectrophotometry.

PubMed

Yang, Yanfang; Peng, Jingling; Li, Fangping; Liu, Xin; Deng, Meng; Wu, Hezhen

2017-05-01

A simple and intuitive method for optimizing the chemical constituents of Coptis Chinensis Franch. is important to assess its quality and clinical efficacy. An high performance liquid chromatography and ultraviolet spectrophotometry method was developed for the determination of berberine hydrochloride, palmatine chloride, jatrorrhizine hydrochloride, epiberberine, coptisine, columbamine and magnoflorine in various tissues (i.e., phloem, xylem and medulla) and rizhome of C. Chinensis Franch. The transection of rhizome from outside-in includes cork layer, cortex, phloem, cambium, xylem and medulla. Cork layer consists of dead cells, and therefore is not of any research significance. Cortex, phloem and cambium were almost impossible to separate, therefore they were studied as a whole in our experiments. They were collectively referred to as "phloem". The analytes were separated on a Gemini-NX C18 (250 mm × 4.6 mm, 5 μm) reversed phase column using a gradient elution of acetonitrile-0.03 mol/L ammonium acetate solution (containing 0.1% triethylamine and 0.6% ammonium hydroxide) as the mobile phase at a flow rate of 1.0 mL/min and UV detection at 270 nm. The method allowing the simultaneous quantification of seven major active constituents was optimized and validated for linearity, precision, accuracy, limits of detection (LOD) and quantification. The LOD ranged from 0.102 to 0.651 mg/mL (r ≥ 0.9993). Accuracy, precision and recovery were all within the required limits. The average recovery was between 100.14% and 102.75% and the relative standard deviations were <3.34%. At the same time, the absorbance was determined by ultraviolet spectrophotometry at 345 nm wavelength. Based on contents of the seven constituents and clustering result, this investigation suggests that there are significant differences in the distribution of seven alkaloids in the tissues examined. Furthermore, the total alkaloid content in xylem is relatively lower than that in phloem, medulla and rhizome. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A phase II study of axitinib (AG-013736) in patients with incurable adenoid cystic carcinoma.

PubMed

Ho, A L; Dunn, L; Sherman, E J; Fury, M G; Baxi, S S; Chandramohan, R; Dogan, S; Morris, L G T; Cullen, G D; Haque, S; Sima, C S; Ni, A; Antonescu, C R; Katabi, N; Pfister, D G

2016-10-01

Recurrent/metastatic adenoid cystic carcinoma (ACC) is an incurable disease with no standard treatments. The majority of ACCs express the oncogenic transcription factor MYB (also c-myb), often in the context of a MYB gene rearrangement. This phase II trial of the tyrosine kinase inhibitor (TKI) axitinib (Pfizer) tested the hypothesis that targeting pathways activated by MYB can be therapeutically effective for ACC. This is a minimax two-stage, phase II trial that enrolled patients with incurable ACC of any primary site. Progressive or symptomatic disease was required. Patients were treated with axitinib 5 mg oral twice daily; dose escalation was allowed. The primary end point was best overall response (BOR). An exploratory analysis correlating biomarkers to drug benefit was conducted, including next-generation sequencing (NGS) in 11 patients. Thirty-three patients were registered and evaluable for response. Fifteen patients had the axitinib dose increased. Tumor shrinkage was achieved in 22 (66.7%); 3 (9.1%) had confirmed partial responses. Twenty-five (75.8%) patients had stable disease, 10 of whom had disease stability for >6 months. The median progression-free survival (PFS) was 5.7 months (range 0.92-21.8 months). Grade 3 axitinib-related toxicities included hypertension, oral pain and fatigue. A trend toward superior PFS was noted with the MYB/NFIB rearrangement, although this was not statistically significant. NGS revealed three tumors with 4q12 amplification, producing increased copies of axitinib-targeted genes PDGFR/KDR/KIT. Two 4q12 amplified patients achieved stable disease for >6 months, including one with significant tumor reduction and the longest PFS on study (21.8 months). Although the primary end point was not met, axitinib exhibited clinical activity with tumor shrinkage achieved in the majority of patients with progressive disease before trial enrollment. Analysis of MYB biomarkers and genomic profiling suggests the hypothesis that 4q12 amplified ACCs are a disease subset that benefit from TKI therapy. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A protocol for an exploratory phase I mixed-methods study of enhanced integrated care for care home residents with advanced dementia: the Compassion Intervention.

PubMed

Elliott, Margaret; Harrington, Jane; Moore, Kirsten; Davis, Sarah; Kupeli, Nuriye; Vickerstaff, Victoria; Gola, Anna; Candy, Bridget; Sampson, Elizabeth L; Jones, Louise

2014-06-17

In the UK approximately 700,000 people are living with, and a third of people aged over 65 will die with, dementia. People with dementia may receive poor quality care towards the end of life. We applied a realist approach and used mixed methods to develop a complex intervention to improve care for people with advanced dementia and their family carers. Consensus on intervention content was achieved using the RAND UCLA appropriateness method and mapped to sociological theories of process and impact. Core components are: (1) facilitation of integrated care, (2) education, training and support, (3) investment from commissioners and care providers. We present the protocol for an exploratory phase I study to implement components 1 and 2 in order to understand how the intervention operates in practice and to assess feasibility and acceptability. An 'Interdisciplinary Care Leader (ICL)' will work within two care homes, alongside staff and associated professionals to facilitate service integration, encourage structured needs assessment, develop the use of personal and advance care plans and support staff training. We will use qualitative and quantitative methods to collect data for a range of outcome and process measures to detect effects on individual residents, family carers, care home staff, the intervention team, the interdisciplinary team and wider systems. Analysis will include descriptive statistics summarising process and care home level data, individual demographic and clinical characteristics and data on symptom burden, clinical events and quality of care. Qualitative data will be explored using thematic analysis. Findings will inform a future phase II trial. Ethical approval was granted (REC reference 14/LO/0370). We shall publish findings at conferences, in peer-reviewed journals, on the Marie Curie Cancer Care website and prepare reports for dissemination by organisations involved with end-of-life care and dementia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Motilin-induced gastric contractions signal hunger in man.

PubMed

Tack, J; Deloose, E; Ang, D; Scarpellini, E; Vanuytsel, T; Van Oudenhove, L; Depoortere, I

2016-02-01

Hunger is controlled by the brain, which receives input from signals of the GI tract (GIT). During fasting, GIT displays a cyclical motor pattern, the migrating motor complex (MMC), regulated by motilin. To study the relationship between hunger and MMC phases (I-III), focusing on spontaneous and pharmacologically induced phase III and the correlation with plasma motilin and ghrelin levels. The role of phase III was also studied in the return of hunger after a meal in healthy individuals and in patients with loss of appetite. In fasting healthy volunteers, mean hunger ratings during a gastric (62.5±7.5) but not a duodenal (40.4±5.4) phase III were higher (p<0.0005) than during phase I (27.4±4.7) and phase II (37±4.5). The motilin agonist erythromycin, but not the cholinesterase inhibitor neostigmine, induced a premature gastric phase III, which coincided with an increase in hunger scores from 29.2±7 to 61.7±8. The somatostatin analogue octreotide induced a premature intestinal phase III without a rise in hunger scores. Hunger ratings significantly correlated (β=0.05; p=0.01) with motilin plasma levels, and this relationship was lost after erythromycin administration. Motilin, but not ghrelin administration, induced a premature gastric phase III and a rise in hunger scores. In contrast to octreotide, postprandial administration of erythromycin induced a premature gastric phase III accompanied by an early rise in hunger ratings. In patients with unexplained loss of appetite, gastric phase III was absent and hunger ratings were lower. Motilin-induced gastric phase III is a hunger signal from GIT in man. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

5 CFR 890.1022 - Contesting proposed permissive debarments.

Code of Federal Regulations, 2014 CFR

2014-01-01

.... 890.1022 Section 890.1022 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Administrative Sanctions Imposed Against Health Care Providers Permissive Debarments § 890.1022 Contesting proposed permissive debarments...

5 CFR 890.1022 - Contesting proposed permissive debarments.

Code of Federal Regulations, 2013 CFR

2013-01-01

.... 890.1022 Section 890.1022 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Administrative Sanctions Imposed Against Health Care Providers Permissive Debarments § 890.1022 Contesting proposed permissive debarments...

47 CFR 27.902 - Permissible communications.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Permissible communications. 27.902 Section 27.902 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 1670-1675 MHz Band § 27.902 Permissible communications. Licensees...

47 CFR 27.902 - Permissible communications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Permissible communications. 27.902 Section 27.902 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 1670-1675 MHz Band § 27.902 Permissible communications. Licensees...

47 CFR 22.1025 - Permissible communications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Permissible communications. 22.1025 Section 22.1025 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Offshore Radiotelephone Service § 22.1025 Permissible communications. Offshore central...

47 CFR 101.1307 - Permissible communications.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false Permissible communications. 101.1307 Section 101.1307 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Multiple Address Systems General Provisions § 101.1307 Permissible...

47 CFR 101.1307 - Permissible communications.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false Permissible communications. 101.1307 Section 101.1307 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Multiple Address Systems General Provisions § 101.1307 Permissible...

47 CFR 101.1307 - Permissible communications.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Permissible communications. 101.1307 Section 101.1307 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Multiple Address Systems General Provisions § 101.1307 Permissible...

5 CFR 890.1011 - Bases for permissive debarments.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Section 890.1011 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Administrative Sanctions Imposed Against Health Care Providers Permissive Debarments § 890.1011 Bases for permissive debarments. (a) Licensure...

47 CFR 27.802 - Permissible communications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Permissible communications. 27.802 Section 27.802 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 1.4 GHz Band § 27.802 Permissible communications. Licensees in...

47 CFR 27.802 - Permissible communications.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Permissible communications. 27.802 Section 27.802 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 1.4 GHz Band § 27.802 Permissible communications. Licensees in...

Development of guidelines for pedestrian safety treatments at signalized intersections.

DOT National Transportation Integrated Search

2012-01-01

For intersections with a permissive or protected-permissive left-turn mode, pedestrians cross during the : permissive period. This operation requires the left-turn driver to yield to both opposing vehicles and : pedestrians, prior to accepting a gap ...

47 CFR 22.515 - Permissible communications paths.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 2 2014-10-01 2014-10-01 false Permissible communications paths. 22.515 Section 22.515 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Paging and Radiotelephone Service § 22.515 Permissible communications paths...

47 CFR 22.515 - Permissible communications paths.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Permissible communications paths. 22.515 Section 22.515 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Paging and Radiotelephone Service § 22.515 Permissible communications paths...

47 CFR 22.515 - Permissible communications paths.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 2 2013-10-01 2013-10-01 false Permissible communications paths. 22.515 Section 22.515 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Paging and Radiotelephone Service § 22.515 Permissible communications paths...

47 CFR 22.515 - Permissible communications paths.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Permissible communications paths. 22.515 Section 22.515 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Paging and Radiotelephone Service § 22.515 Permissible communications paths...

47 CFR 101.1013 - Permissible communications services.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Permissible communications services. 101.1013 Section 101.1013 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Local Multipoint Distribution Service § 101.1013 Permissible...

47 CFR 101.1013 - Permissible communications services.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false Permissible communications services. 101.1013 Section 101.1013 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Local Multipoint Distribution Service § 101.1013 Permissible...

47 CFR 101.1013 - Permissible communications services.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Permissible communications services. 101.1013 Section 101.1013 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Local Multipoint Distribution Service § 101.1013 Permissible...

47 CFR 101.1013 - Permissible communications services.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Permissible communications services. 101.1013 Section 101.1013 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Local Multipoint Distribution Service § 101.1013 Permissible...

47 CFR 101.1013 - Permissible communications services.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false Permissible communications services. 101.1013 Section 101.1013 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Local Multipoint Distribution Service § 101.1013 Permissible...

5 CFR 890.1014 - Notice of proposed permissive debarment.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... 890.1014 Section 890.1014 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Administrative Sanctions Imposed Against Health Care Providers Permissive Debarments § 890.1014 Notice of proposed permissive debarment...

5 CFR 890.1014 - Notice of proposed permissive debarment.

Code of Federal Regulations, 2013 CFR

2013-01-01

.... 890.1014 Section 890.1014 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Administrative Sanctions Imposed Against Health Care Providers Permissive Debarments § 890.1014 Notice of proposed permissive debarment...

5 CFR 890.1014 - Notice of proposed permissive debarment.

Code of Federal Regulations, 2012 CFR

2012-01-01

.... 890.1014 Section 890.1014 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Administrative Sanctions Imposed Against Health Care Providers Permissive Debarments § 890.1014 Notice of proposed permissive debarment...

5 CFR 890.1014 - Notice of proposed permissive debarment.

Code of Federal Regulations, 2014 CFR

2014-01-01

.... 890.1014 Section 890.1014 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Administrative Sanctions Imposed Against Health Care Providers Permissive Debarments § 890.1014 Notice of proposed permissive debarment...

5 CFR 890.1014 - Notice of proposed permissive debarment.

Code of Federal Regulations, 2011 CFR

2011-01-01

.... 890.1014 Section 890.1014 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Administrative Sanctions Imposed Against Health Care Providers Permissive Debarments § 890.1014 Notice of proposed permissive debarment...

Observational research with adolescents: a framework for the management of the parental permission

PubMed Central

2013-01-01

Background Waiving parent permission can be an option in some epidemiological and social research with adolescents. However, exemptions have not been uniformly considered or applied. Our aim is to critically assess the different factors that could be taken into account when making decisions about waiving active parental permission in observational research with adolescents. Discussion In some cases alternatives to parental permission could be applied to protect the rights of both adolescents and parents and also to assure the benefits to adolescents as a group that can come from appropriately conducted studies. However, the criteria of ensuring minimal risk can be difficult to define and apply and a distinction between harm and discomfort is reviewed. Waiving active parental permission could be acceptable when the risk of harm is minimal; when the research questions are related to an activity for which adolescents are not legally considered to be children; when the risk of harm or discomfort may increase if parental permission is required; and when risk of discomfort is low because the questionnaire is not potentially offensive for some adolescents and/or for some parents. Summary Stringent rules concerning parental permission in some studies could be detrimental to adolescents. A framework and a decision tree guide are proposed to help researchers and Research Ethics Committees in their decisions on whether active parental permission must be obtained. PMID:23286743

30 CFR 22.10 - Approval plate.

Code of Federal Regulations, 2010 CFR

2010-07-01

... MINING PRODUCTS PORTABLE METHANE DETECTORS § 22.10 Approval plate. (a) Attachment to be made by manufacturers. (1) Manufacturers shall attach, stamp, or mold an approval plate on each permissible methane... follows: Permissible Methane Detector (or Permissible Methane Indicating Detector) Approval No. ___ issued...

47 CFR 61.153 - Method of filing applications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... (CONTINUED) TARIFFS Applications for Special Permission § 61.153 Method of filing applications. (a) An application for special permission must be addressed to “Secretary, Federal Communication Commission... for issuing carriers filing tariffing fees electronically, for all special permission applications...

47 CFR 101.703 - Permissible communications.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false Permissible communications. 101.703 Section 101.703 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Common Carrier Fixed Point-to-Point Microwave Service § 101.703 Permissible...

47 CFR 101.703 - Permissible communications.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Permissible communications. 101.703 Section 101.703 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Common Carrier Fixed Point-to-Point Microwave Service § 101.703 Permissible...

47 CFR 101.703 - Permissible communications.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false Permissible communications. 101.703 Section 101.703 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Common Carrier Fixed Point-to-Point Microwave Service § 101.703 Permissible...

47 CFR 101.703 - Permissible communications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Permissible communications. 101.703 Section 101.703 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Common Carrier Fixed Point-to-Point Microwave Service § 101.703 Permissible...

47 CFR 101.703 - Permissible communications.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Permissible communications. 101.703 Section 101.703 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Common Carrier Fixed Point-to-Point Microwave Service § 101.703 Permissible...

Contrasting amino acid profiles among permissive and non-permissive hosts of Candidatus Liberibacter asiaticus, putative causal agent of Huanglongbing

PubMed Central

Alabi, Olufemi J.; Simpson, Catherine R.; Jifon, John L.

2017-01-01

Huanglongbing is a devastating disease of citrus. In this study, a comprehensive profile of phloem sap amino acids (AA) in four permissive host plants of Candidatus Liberibacter asiaticus (CLas) and three non-permissive Rutaceae plants was conducted to gain a better understanding of host factors that may promote or suppress the bacterium. The AA profiles of Diaphorina citri nymphs and adults were similarly analyzed. A total of 38 unique AAs were detected in phloem sap of the various plants and D. citri samples, with phloem sap of young shoots containing more AAs and at higher concentrations than their mature counterparts. All AAs detected in phloem sap of non-permissive plants were also present in CLas -permissive hosts plus additional AAs in the latter class of plants. However, the relative composition of 18 commonly shared AAs varied between CLas -permissive hosts and non-permissive plants. Multivariate analysis with a partial least square discriminant methodology revealed a total of 12 AAs as major factors affecting CLas host status, of which seven were positively related to CLas tolerance/resistance and five positively associated with CLas susceptibility. Most of the AAs positively associated with CLas susceptibility were predominantly of the glutamate family, notably stressed-induced AAs such as arginine, GABA and proline. In contrast, AAs positively correlated with CLas tolerance/resistance were mainly of the serine family. Further analysis revealed that whereas the relative proportions of AAs positively associated with CLas susceptibility did not vary with host developmental stages, those associated with CLas tolerance/resistance increased with flush shoot maturity. Significantly, the proline-to-glycine ratio was determined to be an important discriminating factor for CLas permissivity with higher values characteristic of CLas -permissive hosts. This ratio could be exploited as a biomarker in HLB-resistance breeding programs. PMID:29236706

Bordetella pertussis modulates human macrophage defense gene expression.

PubMed

Valdez, Hugo Alberto; Oviedo, Juan Marcos; Gorgojo, Juan Pablo; Lamberti, Yanina; Rodriguez, Maria Eugenia

2016-08-01

Bordetella pertussis, the etiological agent of whooping cough, still causes outbreaks. We recently found evidence that B. pertussis can survive and even replicate inside human macrophages, indicating that this host cell might serve as a niche for persistence. In this work, we examined the interaction of B. pertussis with a human monocyte cell line (THP-1) that differentiates into macrophages in culture in order to investigate the host cell response to the infection and the mechanisms that promote that intracellular survival. To that end, we investigated the expression profile of a selected number of genes involved in cellular bactericidal activity and the inflammatory response during the early and late phases of infection. The bactericidal and inflammatory response of infected macrophages was progressively downregulated, while the number of THP-1 cells heavily loaded with live bacteria increased over time postinfection. Two of the main toxins of B. pertussis, pertussis toxin (Ptx) and adenylate cyclase (CyaA), were found to be involved in manipulating the host cell response. Therefore, failure to express either toxin proved detrimental to the development of intracellular infections by those bacteria. Taken together, these results support the relevance of host defense gene manipulation to the outcome of the interaction between B. pertussis and macrophages. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Neural substrates of defensive reactivity in two subtypes of specific phobia.

PubMed

Lueken, Ulrike; Hilbert, Kevin; Stolyar, Veronika; Maslowski, Nina I; Beesdo-Baum, Katja; Wittchen, Hans-Ulrich

2014-11-01

Depending on threat proximity, different defensive behaviours are mediated by a descending neural network involving forebrain (distal threat) vs midbrain areas (proximal threat). Compared to healthy subjects, it can be assumed that phobics are characterized by shortened defensive distances on a behavioural and neural level. This study aimed at characterizing defensive reactivity in two subtypes of specific phobia [snake (SP) and dental phobics (DP)]. Using functional magnetic resonance imaging (fMRI), n = 39 subjects (13 healthy controls, HC; 13 SP; 13 DP) underwent an event-related fMRI task employing an anticipation (5-10 s) and immediate perception phase (phobic pictures and matched neutral stimuli; 1250 ms) to modulate defensive distance. Although no differential brain activity in any comparisons was observed in DP, areas associated with defensive behaviours (e.g. amygdala, hippocampus, midbrain) were activated in SP. Decreasing defensive distance in SP was characterized by a shift to midbrain activity. Present findings substantiate differences between phobia types in their physiological and neural organization that can be expanded to early stages of defensive behaviours. Findings may contribute to a better understanding of the dynamic organization of defensive reactivity in different types of phobic fear. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Biologic treatment in Sjögren's syndrome.

PubMed

Sada, Pablo Ruiz; Isenberg, David; Ciurtin, Coziana

2015-02-01

SS is a chronic systemic autoimmune disease characterized by decreased exocrine gland function. A variety of other disease manifestations may also be present, including general constitutional symptoms and extraglandular features. A multidisciplinary approach focused on both local and systemic medical therapies is needed as the disease has a wide clinical spectrum. The current treatment for SS is mainly symptomatic. However, there is evidence that systemic drugs are effective in controlling extraglandular manifestations of the disease. Overall evidence for the role of conventional immunosuppressive therapy is limited. A number of attempts to use biologic therapies have led to variable results. Biologic agents targeting B cells, such as rituximab, epratuzumab and belimumab, have shown promising results, but further studies are needed to validate the findings. Early-phase studies with abatacept and alefacept proved that T cell stimulation inhibition is another potentially effective target for SS treatment. Modulation or inhibition of other targets such as IFN, IL-6 and Toll-like receptor are also currently being investigated. We have summarized the available evidence regarding the efficacy of biologic treatments and discuss other potential therapies targeting pathways or molecules recognized as being involved in the pathogenesis of SS. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Too ill to will? Deathbed wills: assessing testamentary capacity near the end of life.

PubMed

Purser, Kelly; Rosenfeld, Tuly

2016-05-01

Assessing testamentary capacity in the terminal phase of an illness or at a person's deathbed is fraught with challenges for both doctors and lawyers. Numerous issues need to be considered when assessing capacity for a will. These issues are exacerbated when such an assessment needs to be undertaken at the bedside of a dying patient. The nature and severity of the illness, effects on cognition of the terminal illness, effects of medication, urgency, psychological and emotional factors, interactions with carers, family and lawyers, and a range of other issues confound and complicate the assessment of capacity. What is the doctor's role in properly assessing capacity in this context and how does this role intersect with the legal issues? Doctors will play an increasing role in assessing testamentary capacity in this setting. The ageing of society, more effective treatment of acute illness and, often, the prolongation of dying are only some of the factors leading to this increasing need. However, despite its importance and increasing prevalence, the literature addressing this challenging practical area is scarce and offers limited guidance. This paper examines these challenges and discusses some practical approaches. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Acute 5-(2-aminopropyl)benzofuran (5-APB) intoxication and fatality: a case report with postmortem concentrations.

PubMed

McIntyre, Iain M; Gary, Ray D; Trochta, Amber; Stolberg, Susan; Stabley, Robert

2015-03-01

A 20-year-old man, a college student, became unresponsive in front of his girlfriend. He was known to consume alcohol and take an unknown drug at some point while in attendance at a local music festival earlier in the day/evening. Upon arrival of emergency personnel, he was noted to be asystolic and apneic. Despite aggressive medical intervention by emergency personnel and at a local hospital emergency room, he was pronounced deceased within 1.25 h of initial medical attention. Postmortem blood initially screened positive for methamphetamine by ELISA. An alkaline drug screen detected 5-(2-aminopropyl)benzofuran (5-APB) which was subsequently confirmed and quantified by a specific GC-MS SIM analysis following solid-phase extraction. Concentrations were determined in the peripheral blood (2.5 mg/L), central blood (2.9 mg/L), liver (16 mg/kg), vitreous (1.3 mg/L), urine (23 mg/L) and gastric contents (6 mg). No other common amphetamine-like compound was detected, although 5-(2-aminopropyl)-2,3-dihydrobenzofuran (5-APDB) was presumptively identified in both peripheral blood and urine. Alcohol, the only other drug identified, was confirmed at a concentration of 0.02% (w/v). © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Isolation of Flavonoids From Wild Aquilaria sinensis Leaves by an Improved Preparative High-Speed Counter-Current Chromatography Apparatus.

PubMed

Yang, Mao-Xun; Liang, Yao-Guang; Chen, He-Ru; Huang, Yong-Fang; Gong, Hai-Guang; Zhang, Tian-You; Ito, Yoichiro

2018-01-01

Four flavonoids including apigenin-7,4'-dimethylether, genkwanin, quercetin, and kaempferol were isolated in a preparative or semi-preparative scale from the leaves of wild Aquilaria sinensis using an improved preparative high-speed counter-current chromatography apparatus. The separations were performed with a two-phase solvent system composed of hexane-ethyl acetate, methanol-water at suitable volume ratios. The obtained fractions were analyzed by HPLC, and the identification of each target compound was carried out by ESI-MS and NMR. The yields of the above four target flavonoids were 4.7, 10.0, 11.0 and 4.4%, respectively. All these four flavonoids exhibited nitrite scavenging activities with the clearance rate of 12.40 ± 0.20%, 5.84 ± 0.03%, 28.10 ± 0.17% and 5.19 ± 0.11%, respectively. Quercetin was originally isolated from the Thymelaeaceae family, while kaempferol was isolated from the Aquilaria genus for the first time. In cytotoxicity test these two flavonoids exhibited moderate inhibitory activities against HepG2 cells with the IC50 values of 12.54 ± 1.37 and 38.63 ± 4.05 μM, respectively. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Simultaneous Determination of Hydrochlorothiazide and Losartan Potassium in Osmotic Pump Tablets by Microemulsion Liquid Chromatography.

PubMed

Li, Liangxing; Lai, Caiyun; Xuan, Xueyi; Gao, Chongkai; Li, Ning

2016-09-01

A rapid and efficient oil-in-water microemulsion liquid chromatographic (MELC) method has been optimized and validated for the determination of hydrochlorothiazide (HCT) and losartan potassium (LOP) in osmotic pump tablets. Samples were injected into a C18 (150 mm × 4.6 mm ID, 5 µm particle size) analytical column, which was maintained at 30°C. The most effective MELC system had a mobile phase consisting of 95% (v/v) of 3.0% (w/w) SDS, 6.0% (w/w) n-butanol, 0.8% (w/w) n-octane, 90.2% (w/w) water and 5% (v/v) acetonitrile (pH 5). The flow rate was 1.0 mL min(-1) and UV detection was performed at 265 nm. Linearity ranged from 2.5 to 12.5 µg mL(-1) for HCT and 10.0-60.0 µg mL(-1) for LOP (r > 0.999 for both drugs). The proposed method was rapid, precise (RSDs < 1.4%) and accurate (98.9% recovery for HCT and 101% recovery for LOP). It is applicable to simultaneous determination of HCT and LOP in osmotic pump tablets. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Validation and Application of a Simple UHPLC-MS-MS Method for the Enantiospecific Determination of Warfarin in Human Urine.

PubMed

Alshogran, Osama Y; Ocque, Andrew J; Leblond, François A; Pichette, Vincent; Nolin, Thomas D

2016-04-01

A simple and rapid liquid chromatographic-tandem mass spectrometric method has been developed and validated for the enantiospecific determination of R- and S-warfarin in human urine. Warfarin enantiomers were extracted from urine using methyl tert-butyl ether. Chromatographic separation of warfarin enantiomers and the internal standard d5-warfarin was achieved using a Astec Chirobiotic V column with gradient mobile phase at a flow rate of 400 µL/min over 10 min. Detection was performed on a TSQ Quantum Ultra triple quadrupole mass spectrometer equipped with a heated electrospray ionization source. Analytes were detected in negative ionization mode using selected reaction monitoring. Calibration curves were linear with a correlation coefficient of ≥0.996 for both enantiomers over a concentration range of 5-500 ng/mL. The intra- and interday accuracy and precision for both analytes were within ±9.0%. Excellent extraction efficiency and negligible matrix effects were observed. The applicability of the method was demonstrated by successful measurement of warfarin enantiomers in urine of patients with kidney disease. The method is simple, accurate and reproducible and is currently being used to support warfarin pharmacokinetic studies. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Promoting mental wellbeing: developing a theoretically and empirically sound complex intervention.

PubMed

Millar, S L; Donnelly, M

2014-06-01

This paper describes the development of a complex intervention to promote mental wellbeing using the revised framework for developing and evaluating complex interventions produced by the UK Medical Research Council (UKMRC). Application of the first two phases of the framework is described--development and feasibility and piloting. The theoretical case and evidence base were examined analytically to explicate the theoretical and empirical foundations of the intervention. These findings informed the design of a 12-week mental wellbeing promotion programme providing early intervention for people showing signs of mental health difficulties. The programme is based on the theoretical constructs of self-efficacy, self-esteem, purpose in life, resilience and social support and comprises 10 steps. A mixed methods approach was used to conduct a feasibility study with community and voluntary sector service users and in primary care. A significant increase in mental wellbeing was observed following participation in the intervention. Qualitative data corroborated this finding and suggested that the intervention was feasible to deliver and acceptable to participants, facilitators and health professionals. The revised UKMRC framework can be successfully applied to the development of public health interventions. © The Author 2013. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Convection-enhanced delivery for the treatment of glioblastoma.

PubMed

Vogelbaum, Michael A; Aghi, Manish K

2015-03-01

Effective treatment of glioblastoma (GBM) remains a formidable challenge. Survival rates remain poor despite decades of clinical trials of conventional and novel, biologically targeted therapeutics. There is considerable evidence that most of these therapeutics do not reach their targets in the brain when administered via conventional routes (intravenous or oral). Hence, direct delivery of therapeutics to the brain and to brain tumors is an active area of investigation. One of these techniques, convection-enhanced delivery (CED), involves the implantation of catheters through which conventional and novel therapeutic formulations can be delivered using continuous, low-positive-pressure bulk flow. Investigation in preclinical and clinical settings has demonstrated that CED can produce effective delivery of therapeutics to substantial volumes of brain and brain tumor. However, limitations in catheter technology and imaging of delivery have prevented this technique from being reliable and reproducible, and the only completed phase III study in GBM did not show a survival benefit for patients treated with an investigational therapeutic delivered via CED. Further development of CED is ongoing, with novel catheter designs and imaging approaches that may allow CED to become a more effective therapeutic delivery technique. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Valorisation of CO2-rich off-gases to biopolymers through biotechnological process.

PubMed

Garcia-Gonzalez, Linsey; De Wever, Heleen

2017-11-01

As one of the key enabling technologies, industrial biotechnology has a high potential to tackle harmful CO2 emissions and to turn CO2 into a valuable commodity. So far, experimental work mainly focused on the bioconversion of pure CO2 to chemicals and plastics and little is known about the tolerance of the bioprocesses to the presence of impurities. This work is the first to investigate the impact of real CO2-rich off-gases on autotrophic production of polyhydroxybutyrate. To this end, two-phase heterotrophic-autotrophic fermentation experiments were set up, consisting of heterothrophic cell mass growth using glucose as substrate followed by autotrophic biopolymer production using either pure synthetic CO2 or industrial off-gases sampled at two point sources. The use of real off-gases did not affect the bacterial performance. High biopolymer content (up to 73%) and productivities (up to 0.227 g/lh) were obtained. Characterisation of the polymers showed that all biopolymers had similar properties, independent of the CO2 source. Moreover, the CO2-derived biopolymers' properties were comparable to commercial ones and biopolymers reported in literature, which are all produced from organic carbon sources. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Intraneuronal Amyloid Beta Accumulation Disrupts Hippocampal CRTC1-Dependent Gene Expression and Cognitive Function in a Rat Model of Alzheimer Disease.

PubMed

Wilson, Edward N; Abela, Andrew R; Do Carmo, Sonia; Allard, Simon; Marks, Adam R; Welikovitch, Lindsay A; Ducatenzeiler, Adriana; Chudasama, Yogita; Cuello, A Claudio

2017-02-01

In Alzheimer disease (AD), the accumulation of amyloid beta (Aβ) begins decades before cognitive symptoms and progresses from intraneuronal material to extracellular plaques. To date, however, the precise mechanism by which the early buildup of Aβ peptides leads to cognitive dysfunction remains unknown. Here, we investigate the impact of the early Aβ accumulation on temporal and frontal lobe dysfunction. We compared the performance of McGill-R-Thy1-APP transgenic AD rats with wild-type littermate controls on a visual discrimination task using a touchscreen operant platform. Subsequently, we conducted studies to establish the biochemical and molecular basis for the behavioral alterations. It was found that the presence of intraneuronal Aβ caused a severe associative learning deficit in the AD rats. This coincided with reduced nuclear translocation and genomic occupancy of the CREB co-activator, CRTC1, and decreased production of synaptic plasticity-associated transcripts Arc, c-fos, Egr1, and Bdnf. Thus, blockade of CRTC1-dependent gene expression in the early, preplaque phase of AD-like pathology provides a molecular basis for the cognitive deficits that figure so prominently in early AD. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Detection of local chemical states of lithium and their spatial mapping by scanning transmission electron microscopy, electron energy-loss spectroscopy and hyperspectral image analysis.

PubMed

Muto, Shunsuke; Tatsumi, Kazuyoshi

2017-02-08

Advancements in the field of renewable energy resources have led to a growing demand for the analysis of light elements at the nanometer scale. Detection of lithium is one of the key issues to be resolved for providing guiding principles for the synthesis of cathode active materials, and degradation analysis after repeated use of those materials. We have reviewed the different techniques currently used for the characterization of light elements such as high-resolution transmission electron microscopy, scanning transmission electron microscopy (STEM) and electron energy-loss spectroscopy (EELS). In the present study, we have introduced a methodology to detect lithium in solid materials, particularly for cathode active materials used in lithium-ion battery. The chemical states of lithium were isolated and analyzed from the overlapping multiple spectral profiles, using a suite of STEM, EELS and hyperspectral image analysis. The method was successfully applied in the chemical state analyses of hetero-phases near the surface and grain boundary regions of the active material particles formed by chemical reactions between the electrolyte and the active materials. © The Author 2016. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Are Age-Related Differences Uniform Across Different Inhibitory Functions?

PubMed

Vadaga, Kiran K; Blair, Mervin; Li, Karen Z H

2016-07-01

In the current experiment, we examined the relative age-sensitivity of 3 inhibitory functions: access, deletion, and restraint by taking into consideration their underlying control processes: proactive and reactive control. The 3 inhibitory functions were measured using a sequential flanker task. Young (age: 18-35, n = 24) and older adults (age: 60-75, n = 25) first memorized a series of 8 animal words in a fixed order. In the test phase, these stimuli were presented randomly either singly or with flankers and participants responded "yes" or "no" based on the prelearned sequence. In the access trials, flankers were either ahead of the current target or unrelated. In the deletion trials, flankers were previous target items. In the restraint trials, the flanker cues (XXXX) prompted the participants to withhold responses occasionally. Unflanked trials served as the baseline condition. Age-related differences in the magnitude of inhibition effects were largest in restraint, followed by deletion. No age-related differences were observed in access. Our findings suggest that the magnitude of age-related differences in inhibitory functions is contingent on the degree of proactive control recruited by a given inhibitory function. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Staff Experiences Forming and Sustaining Palliative Care Teams in Nursing Homes.

PubMed

Norton, Sally A; Ladwig, Susan; Caprio, Thomas V; Quill, Timothy E; Temkin-Greener, Helena

2018-01-03

Building palliative care (PC) capacity in nursing homes (NH) is a national priority and essential to providing high quality care for residents with advanced illness. We report on NH staff experiences in developing and sustaining Palliative Care Teams (PCTeams) as part of a randomized clinical trial to "Improve Palliative Care through Teamwork" (IMPACTT). We conducted rapid ethnographic assessments of all NH (N = 14) in the intervention arm. Data included semistructured interviews with direct care and administrative staff (n = 41), field observations, and written materials. We used a phased approach to data analysis including open coding and comparative analyses within and across homes. We found four key structural themes in our analysis including: administrative support, financial considerations, turnover and staffing, and competing priorities. The development and sustainability of the nascent PCTeams were constantly threatened by competing priorities and the key factor in their success was consistent and tangible administrative support. While improving PC in NHs is a recognized priority, lack of stable infrastructure and unintended consequences of reimbursement policies created conditions which often thwarted the sustainability of the PCTeams. © The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Amyloidosis and spontaneous hepatic bleeding, transcatheter therapy for hepatic parenchymal bleeding with massive intraperitoneal hemorrhage: a case report and review of the literature.

PubMed

Mousa, Albeir Y; Abu-Halimah, Shadi; Alhalbouni, Saadi; Hass, Stephen M; Yang, Calvin; Gill, Gurpreet; AbuRahma, Ali F; Bates, Mark

2014-10-01

Hepatic hemorrhage can be devastating, especially in patients with underlying hepatic pathology. This is a case report of a 50-year-old man who presented to the emergency room with Stage 3 shock as evidenced by a systolic blood pressure of 90 mmHg, a heart rate of 125 beats per minute, respiration of 32, with delayed capillary refill and agitation. At this time, he was found to have a massive spontaneous intra-abdominal hemorrhage with an advanced stage of amyloidosis with multiple organ malfunctions. The initial diagnosis was based on an abdominal computed tomography scan and the patient was taken expeditiously to a hybrid angiography suite for a celiac angiogram. An intraoperative diagnosis of extravasation from amyloid related vasculopathy was made based on the angiographic appearance of hepatic circulation. Coil embolization of the feeding branch of the bleeder was achieved using the interlock coil system and a completion angiogram was done showing complete cessation of active bleeding. The postoperative phase was uneventful and the patient was discharged home on postoperative day three. His postoperative visit at five months later was unremarkable. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Validation of a Stability-Indicating Method for Methylseleno-L-Cysteine (L-SeMC).

PubMed

Canady, Kristin; Cobb, Johnathan; Deardorff, Peter; Larson, Jami; White, Jonathan M; Boring, Dan

2016-01-01

Methylseleno-L-cysteine (L-SeMC) is a naturally occurring amino acid analogue used as a general dietary supplement and is being explored as a chemopreventive agent. As a known dietary supplement, L-SeMC is not regulated as a pharmaceutical and there is a paucity of analytical methods available. To address the lack of methodology, a stability-indicating method was developed and validated to evaluate L-SeMC as both the bulk drug and formulated drug product (400 µg Se/capsule). The analytical approach presented is a simple, nonderivatization method that utilizes HPLC with ultraviolet detection at 220 nm. A C18 column with a volatile ion-pair agent and methanol mobile phase was used for the separation. The method accuracy was 99-100% from 0.05 to 0.15 mg/mL L-SeMC for the bulk drug, and 98-99% from 0.075 to 0.15 mg/mL L-SeMC for the drug product. Method precision was <1% for the bulk drug and was 3% for the drug product. The LOQ was 0.1 µg/mL L-SeMC or 0.002 µg L-SeMC on column. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Stability-Indicating TLC-Densitometric Assay for Methyltestosterone and Quantum Chemical Calculations.

PubMed

Musharraf, Syed Ghulam; Ul Arfeen, Qamar; Ul Haq, Faraz; Khatoon, Aliya; Azher Ali, Rahat

2017-10-01

Methyltestosterone is a synthetic testosterone derivative commonly used for the treatment of testosterone deficiency in males and one the anabolic steroids whose use is banned by World Anti-Doping Agency (WADA). This study presents a simple, cost-effective and rapid stability-indicating assay for densitometric quantification of methyltestosterone in pharmaceutical formulation. The developed method employed pre-coated TLC plates with mobile phase hexane:acetone (6.5:3.5 v/v). Limit of detection and limit of quantitation were found to be 2.06 and 6.24 ng/spot, respectively. Stress degradation study of methyltestosterone was conducted by applying various stress conditions such as hydrolysis under acidic, basic and neutral conditions, heating in anhydrous conditions and exposure to light. Methyltestosterone was found to be susceptible to photodegradation, acidic and basic hydrolysis. Degraded products were well resolved with significantly different Rf values. Acid degraded product was identified as 17,17-dimethyl-18-norandrosta-4,13(14)-dien-3-one through spectroscopic methods. The reactivity of methyltestosterone under applied stress conditions was also explained by quantum chemical calculations. The developed method is found to be repeatable, selective and accurate for quantification of methyltestosterone and can be employed for routine analysis. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Lactobacilli-lactoferrin interplay in Chlamydia trachomatis infection.

PubMed

Sessa, Rosa; Di Pietro, Marisa; Filardo, Simone; Bressan, Alessia; Mastromarino, Paola; Biasucci, Alessandra Vittoria; Rosa, Luigi; Cutone, Antimo; Berlutti, Francesca; Paesano, Rosalba; Valenti, Piera

2017-07-31

In the cervicovaginal microenvironment, lactobacilli are known to protect against genital infections and, amongst the host defence compounds, lactoferrin has recently acquired importance for its anti-microbial and anti-inflammatory properties. An abnormal genital microenvironment facilitates the acquisition of pathogens like Chlamydia trachomatis, the leading cause of bacterial sexually transmitted infections worldwide. The aim of our study is to investigate the effects of Lactobacillus crispatus, Lactobacillus brevis and bovine lactoferrin on chlamydial infection, in order to shed light on the complex interplay between host defence mechanisms and C. trachomatis. We have also evaluated the effect of these defence factors to modulate the chlamydia-mediated inflammatory state. To this purpose, we have determined the infectivity and progeny production of C. trachomatis as well as interleukin-8 and interleukin-6 synthesis. The main result of our study is that the combination of L. brevis and bovine lactoferrin is the most effective in inhibiting the early phases (adhesion and invasion) of C. trachomatis infection of cervical epithelial cells and in decreasing the levels of both cytokines. In conclusion, the interaction between L. brevis and lactoferrin seems to play a role in the protection against C. trachomatis, reducing the infection and regulating the immunomodulatory activity, thus decreasing the risk of severe complications. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Analysis of fentanyl in urine by DLLME-GC-MS.

PubMed

Gardner, Michael A; Sampsel, Sheena; Jenkins, Werner W; Owens, Janel E

2015-03-01

Fentanyl is a synthetic narcotic anesthetic ∼80-100 times more potent than morphine. Owing to the potential for its abuse, the drug may be included in a forensic toxicology work-up, which requires fast, precise and accurate measurements. Here, the stability of fentanyl was assessed when stored at three different temperatures (-20, 4 and 25°C) in synthetic urine. Stability at those three temperatures was demonstrated over 12 weeks upon analysis by gas chromatography-mass spectrometry with a deuterated internal standard (fentanyl-D5) utilizing three different extraction techniques: liquid-liquid extraction (LLE), solid-phase extraction and dispersed liquid-liquid microextraction (DLLME). The DLLME method was then optimized before use in the analysis of fentanyl in urine samples obtained from autopsy cases at the El Paso County Coroner's Office. Accuracy of the DLLME method was assessed by completing spike and recovery studies at three different fortification levels (10, 100 and 250 ng/mL) with excellent recovery (89.9-102.6%). The excellent comparability between DLLME and LLE is demonstrated (Bland-Altman difference plot with a mean difference of 4.9 ng/mL) and the use of this methodology in the analysis of forensically relevant samples is discussed. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Microwave-Assisted Extraction and Purification of Arctiin and Arctigenin from Fructus Arctii by High-Speed Countercurrent Chromatography.

PubMed

Lü, Haitao; Sun, Zhaoyun; Shan, Hu; Song, Jiying

2016-03-01

An efficient method for the rapid extraction, separation and purification of bioactive lignans, arctiin and arctigenin, from Fructus arctii by microwave-assisted extraction coupled with high-speed countercurrent chromatography was developed. The optimal extraction conditions of arctiin and arctigenin were evaluated by orthogonal array. Arctigenin could be converted from arctiin by hydrochloric acid hydrolysis. The separations were performed at a preparative scale with two-phase solvents composed of ethyl acetate-ethanol-water (5 : 1 : 5, v/v/v) for arctiin, and n-hexane-ethyl acetate-ethanol-water (4 : 4 : 3 : 4, v/v/v/v) for arctigenin. From 500 mg of crude extract sample, 122.3 mg of arctiin and 45.7 mg of arctigenin were obtained with the purity of 98.46 and 96.57%, and the recovery of 94.3 and 81.6%, respectively. Their structures were determined by comparison with the high-performance liquid chromatography retention time of standard substance as well as UV, FT-IR, electrospray ion source (ESI)-MS, (1)H-NMR and (13)C-NMR spectrum. According to the antioxidant activity assay, arctigenin had stronger 1,1-diphenyl-2-picrylhydrazyl free radicals scavenging activity. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

7 CFR 29.39 - Permissive inspection.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Permissive inspection. 29.39 Section 29.39 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... INSPECTION Regulations Definitions § 29.39 Permissive inspection. Inspection authorized under section 6 of...

7 CFR 29.39 - Permissive inspection.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 2 2011-01-01 2011-01-01 false Permissive inspection. 29.39 Section 29.39 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... INSPECTION Regulations Definitions § 29.39 Permissive inspection. Inspection authorized under section 6 of...

12 CFR 703.14 - Permissible investments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Permissible investments. 703.14 Section 703.14 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS INVESTMENT AND DEPOSIT ACTIVITIES § 703.14 Permissible investments. (a) Variable rate investment. A Federal...

47 CFR 90.1305 - Permissible operations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Permissible operations. 90.1305 Section 90.1305 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Wireless Broadband Services in the 3650-3700 MHz Band § 90.1305 Permissible...

47 CFR 90.1305 - Permissible operations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Permissible operations. 90.1305 Section 90.1305 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Wireless Broadband Services in the 3650-3700 MHz Band § 90.1305 Permissible...

47 CFR 90.1305 - Permissible operations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Permissible operations. 90.1305 Section 90.1305 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Wireless Broadband Services in the 3650-3700 MHz Band § 90.1305 Permissible...

46 CFR 169.235 - Permission required.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 7 2011-10-01 2011-10-01 false Permission required. 169.235 Section 169.235 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Inspection and Certification Repairs and Alterations § 169.235 Permission required. (a) Repairs or...

46 CFR 169.235 - Permission required.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Permission required. 169.235 Section 169.235 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Inspection and Certification Repairs and Alterations § 169.235 Permission required. (a) Repairs or...

21 CFR 610.17 - Permissible combinations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Permissible combinations. 610.17 Section 610.17 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS GENERAL BIOLOGICAL PRODUCTS STANDARDS General Provisions § 610.17 Permissible combinations...

12 CFR 703.13 - Permissible investment activities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Permissible investment activities. 703.13... INVESTMENT AND DEPOSIT ACTIVITIES § 703.13 Permissible investment activities. (a) Regular way settlement and... funds transactions. (c) Investment repurchase transaction. A Federal credit union may enter into an...

12 CFR 703.13 - Permissible investment activities.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Permissible investment activities. 703.13... INVESTMENT AND DEPOSIT ACTIVITIES § 703.13 Permissible investment activities. (a) Regular way settlement and... funds transactions. (c) Investment repurchase transaction. A Federal credit union may enter into an...

30 CFR 75.500 - Permissible electric equipment.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Permissible electric equipment. 75.500 Section... AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Electrical Equipment-General § 75.500 Permissible electric equipment. [Statutory Provision] On and after March 30, 1971: (a) All junction or...

30 CFR 75.500 - Permissible electric equipment.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Permissible electric equipment. 75.500 Section... AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Electrical Equipment-General § 75.500 Permissible electric equipment. [Statutory Provision] On and after March 30, 1971: (a) All junction or...

30 CFR 75.500 - Permissible electric equipment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Permissible electric equipment. 75.500 Section... AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Electrical Equipment-General § 75.500 Permissible electric equipment. [Statutory Provision] On and after March 30, 1971: (a) All junction or...

30 CFR 75.500 - Permissible electric equipment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Permissible electric equipment. 75.500 Section... AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Electrical Equipment-General § 75.500 Permissible electric equipment. [Statutory Provision] On and after March 30, 1971: (a) All junction or...

30 CFR 75.500 - Permissible electric equipment.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Permissible electric equipment. 75.500 Section... AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Electrical Equipment-General § 75.500 Permissible electric equipment. [Statutory Provision] On and after March 30, 1971: (a) All junction or...

47 CFR 1.772 - Application for special tariff permission.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Application for special tariff permission. 1... Complaints, Applications, Tariffs, and Reports Involving Common Carriers Tariffs § 1.772 Application for special tariff permission. Applications under section 203 of the Communications Act for special tariff...

5 CFR 890.1012 - Time limits for OPM to initiate permissive debarments.

Code of Federal Regulations, 2014 CFR

2014-01-01

... permissive debarments. 890.1012 Section 890.1012 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Administrative Sanctions Imposed Against Health Care Providers Permissive Debarments § 890.1012 Time limits for OPM to...

5 CFR 890.1012 - Time limits for OPM to initiate permissive debarments.

Code of Federal Regulations, 2013 CFR

2013-01-01

... permissive debarments. 890.1012 Section 890.1012 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Administrative Sanctions Imposed Against Health Care Providers Permissive Debarments § 890.1012 Time limits for OPM to...

5 CFR 890.1012 - Time limits for OPM to initiate permissive debarments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... permissive debarments. 890.1012 Section 890.1012 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Administrative Sanctions Imposed Against Health Care Providers Permissive Debarments § 890.1012 Time limits for OPM to...

47 CFR 24.3 - Permissible communications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SERVICES General Information § 24.3 Permissible communications. PCS licensees may provide any mobile... mobile operations. Broadcasting as defined in the Communications Act is prohibited. [61 FR 45356, Aug. 29... 47 Telecommunication 2 2010-10-01 2010-10-01 false Permissible communications. 24.3 Section 24.3...

Water-wetting surfaces as hydrate promoters during transport of carbon dioxide with impurities.

PubMed

Kuznetsova, Tatiana; Jensen, Bjørnar; Kvamme, Bjørn; Sjøblom, Sara

2015-05-21

Water condensing as liquid drops within the fluid bulk has traditionally been the only scenario accepted in the industrial analysis of hydrate risks. We have applied a combination of absolute thermodynamics and molecular dynamics modeling to analyze the five primary routes of hydrate formation in a rusty pipeline carrying dense carbon dioxide with methane, hydrogen sulfide, argon, and nitrogen as additional impurities. We have revised the risk analysis of all possible routes in accordance with the combination of the first and the second laws of thermodynamics to determine the highest permissible content of water. It was found that at concentrations lower than five percent, hydrogen sulfide will only support the formation of carbon dioxide-dominated hydrate from adsorbed water and hydrate formers from carbon dioxide phase rather than formation in the aqueous phase. Our results indicate that hydrogen sulfide leaving carbon dioxide for the aqueous phase will be able to create an additional hydrate phase in the aqueous region adjacent to the first adsorbed water layer. The growth of hydrate from different phases will decrease the induction time by substantially reducing the kinetically limiting mass transport across the hydrate films. Hydrate formation via adsorption of water on rusty walls will play the decisive role in hydrate formation risk, with the initial concentration of hydrogen sulfide being the critical factor. We concluded that the safest way to eliminate hydrate risks is to ensure that the water content of carbon dioxide is low enough to prevent water dropout via the adsorption mechanism.

Concept analysis of moral courage in nursing: A hybrid model.

PubMed

Sadooghiasl, Afsaneh; Parvizy, Soroor; Ebadi, Abbas

2018-02-01

Moral courage is one of the most fundamental virtues in the nursing profession, however, little attention has been paid to it. As a result, no exact and clear definition of moral courage has ever been accessible. This study is carried out for the purposes of defining and clarifying its concept in the nursing profession. This study used a hybrid model of concept analysis comprising three phases, namely, a theoretical phase, field work phase, and a final analysis phase. To find relevant literature, electronic search of valid databases was utilized using keywords related to the concept of courage. Field work data were collected over an 11 months' time period from 2013 to 2014. In the field work phase, in-depth interviews were performed with 10 nurses. The conventional content analysis was used in two theoretical and field work phases using Graneheim and Lundman stages, and the results were combined in the final analysis phase. Ethical consideration: Permission for this study was obtained from the ethics committee of Tehran University of Medical Sciences. Oral and written informed consent was received from the participants. From the sum of 750 gained titles in theoretical phase, 26 texts were analyzed. The analysis resulted in 494 codes in text analysis and 226 codes in interview analysis. The literature review in the theoretical phase revealed two features of inherent-transcendental characteristics, two of which possessed a difficult nature. Working in the field phase added moral self-actualization characteristic, rationalism, spiritual beliefs, and scientific-professional qualifications to the feature of the concept. Moral courage is a pure and prominent characteristic of human beings. The antecedents of moral courage include model orientation, model acceptance, rationalism, individual excellence, acquiring academic and professional qualification, spiritual beliefs, organizational support, organizational repression, and internal and external personal barriers. Professional excellence resulting from moral courage can be crystallized in the form of provision of professional care, creating peace of mind, and the nurse's decision making and proper functioning.

New stimulation regimens: endogenous and exogenous progesterone use to block the LH surge during ovarian stimulation for IVF.

PubMed

Massin, Nathalie

2017-03-01

The advent of embryo and oocyte vitrification today gives reproductive specialists an opportunity to consider new strategies for improving the practice and results of IVF attempts. As the freezing of entire cohorts does not compromise, and may even improve, the results of IVF attempts, it is possible to break away from the standard sequence of stimulation-retrieval-transfer. The constraints associated with ovarian stimulation in relation to the potential harmful effects of the hormonal environment on endometrial receptivity can be avoided. This review will look at the new stimulation protocols where progesterone is used to block the LH surge. Thanks to 'freeze all' strategies, the increase in progesterone could actually be no longer a cause for concern. There are two ways of using progesterone, whether it be endogenous, as in luteal phase stimulation, or exogenous, as in the use of progesterone in the follicular phase i.e. progestin primed ovarian stimulation. A literature search was carried out (until September 2016) on MEDLINE. The following text words were utilized to generate the list of citations: progestin primed ovarian stimulation, luteal phase stimulation, luteal stimulation, duostim, double stimulation, random start. Articles and their references were then examined in order to identify other potential studies. All of the articles are reported in this review. The use of progesterone during ovarian stimulation is effective in blocking the LH surge, whether endogenous or exogenous, and it does not affect the number of oocytes collected or the quality of the embryos obtained. Its main constraint is that it requires total freezing and delayed transfer. A variety of stimulation protocols can be derived from these two methods, and their implications are discussed, from fertility preservation to ovarian response profiles to organization for the patients and clincs. These new regimens enable more flexibility and are of emerging interest in daily practice. However, their medical and economic significance remains to be demonstrated. The use of luteal phase or follicular phase protocols with progestins could rapidly develop in the context of oocyte donation and fertility preservation not related to oncology. Their place could develop even more in the general population of patients in IVF programs. The strategy of total freezing continues to develop, thanks to technical improvements, in particular vitrification and PGS on blastocysts, and thanks to studies showing improvements in embryo implantation when the transfer take place far removed from the hormonal changes caused by ovarian stimulation. © The Author 2016. 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

50 CFR 217.82 - Permissible methods of taking.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Permissible methods of taking. 217.82 Section 217.82 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC... School (NEODS) Training Operations § 217.82 Permissible methods of taking. (a) Under Letters of...

50 CFR 217.172 - Permissible methods of taking.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Permissible methods of taking. 217.172 Section 217.172 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC... Neptune Liquefied Natural Gas Facility Off Massachusetts § 217.172 Permissible methods of taking. (a...

50 CFR 217.202 - Permissible methods of taking.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Permissible methods of taking. 217.202 Section 217.202 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC... Redevelopment Project § 217.202 Permissible methods of taking. (a) Under Letters of Authorization issued...

50 CFR 217.82 - Permissible methods of taking.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Permissible methods of taking. 217.82 Section 217.82 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC... School (NEODS) Training Operations § 217.82 Permissible methods of taking. (a) Under Letters of...

50 CFR 217.172 - Permissible methods of taking.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Permissible methods of taking. 217.172 Section 217.172 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC... Neptune Liquefied Natural Gas Facility Off Massachusetts § 217.172 Permissible methods of taking. (a...

42 CFR 441.482 - Permissible purchases.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Permissible purchases. 441.482 Section 441.482... Optional Self-Directed Personal Assistance Services Program § 441.482 Permissible purchases. (a... assistance. (b) The services, supports and items that are purchased with a service budget must be linked to...

50 CFR 217.202 - Permissible methods of taking.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Permissible methods of taking. 217.202 Section 217.202 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC... Redevelopment Project § 217.202 Permissible methods of taking. (a) Under Letters of Authorization issued...

42 CFR 433.66 - Permissible provider-related donations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Permissible provider-related donations. 433.66... Requirements State Financial Participation § 433.66 Permissible provider-related donations. (a) General rule... provider-related donations without a reduction in FFP, only in accordance with the requirements of this...

42 CFR 433.66 - Permissible provider-related donations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 4 2013-10-01 2013-10-01 false Permissible provider-related donations. 433.66... Requirements State Financial Participation § 433.66 Permissible provider-related donations. (a) General rule... provider-related donations without a reduction in FFP, only in accordance with the requirements of this...

42 CFR 433.66 - Permissible provider-related donations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 4 2012-10-01 2012-10-01 false Permissible provider-related donations. 433.66... Requirements State Financial Participation § 433.66 Permissible provider-related donations. (a) General rule... provider-related donations without a reduction in FFP, only in accordance with the requirements of this...

42 CFR 433.66 - Permissible provider-related donations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 4 2011-10-01 2011-10-01 false Permissible provider-related donations. 433.66... Requirements State Financial Participation § 433.66 Permissible provider-related donations. (a) General rule... provider-related donations without a reduction in FFP, only in accordance with the requirements of this...

42 CFR 433.66 - Permissible provider-related donations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 4 2014-10-01 2014-10-01 false Permissible provider-related donations. 433.66... Requirements State Financial Participation § 433.66 Permissible provider-related donations. (a) General rule... provider-related donations without a reduction in FFP, only in accordance with the requirements of this...

47 CFR 73.525 - TV Channel 6 protection.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... (4) The maximum permissible effective radiated power (ERP) and antenna height may be adjusted for..., the maximum permissible vertically polarized ERP will be the maximum horizontally polarized ERP... it does not. (ii) If the applicant chooses to use mixed polarity, the permissible ERP is as follows...

45 CFR 1639.4 - Permissible representation of eligible clients.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Permissible representation of eligible clients... CORPORATION WELFARE REFORM § 1639.4 Permissible representation of eligible clients. Recipients may represent an individual eligible client who is seeking specific relief from a welfare agency. [62 FR 30766...

42 CFR 1002.210 - Permissive exclusions; general authority.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Permissive exclusions; general authority. 1002.210 Section 1002.210 Public Health OFFICE OF INSPECTOR GENERAL-HEALTH CARE, DEPARTMENT OF HEALTH AND HUMAN... § 1002.210 Permissive exclusions; general authority. The State agency must have administrative procedures...

30 CFR 75.1103-7 - Electrical components; permissibility requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Electrical components; permissibility... Protection § 75.1103-7 Electrical components; permissibility requirements. The electrical components of each... dust when the electrical power is deenergized as required by § 75.313, but these components shall be...

30 CFR 75.1103-7 - Electrical components; permissibility requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electrical components; permissibility... Protection § 75.1103-7 Electrical components; permissibility requirements. The electrical components of each... dust when the electrical power is deenergized as required by § 75.313, but these components shall be...

30 CFR 75.1103-7 - Electrical components; permissibility requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Electrical components; permissibility... Protection § 75.1103-7 Electrical components; permissibility requirements. The electrical components of each... dust when the electrical power is deenergized as required by § 75.313, but these components shall be...

30 CFR 75.1103-7 - Electrical components; permissibility requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Electrical components; permissibility... Protection § 75.1103-7 Electrical components; permissibility requirements. The electrical components of each... dust when the electrical power is deenergized as required by § 75.313, but these components shall be...

30 CFR 75.1103-7 - Electrical components; permissibility requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Electrical components; permissibility... Protection § 75.1103-7 Electrical components; permissibility requirements. The electrical components of each... dust when the electrical power is deenergized as required by § 75.313, but these components shall be...

36 CFR 264.12 - Use without permission.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Use without permission. 264.12 Section 264.12 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE PROPERTY MANAGEMENT Mount St. Helens National Volcanic Monument Symbol § 264.12 Use without permission...

78 FR 16519 - Agency Information Collection Activities: Application for Advance Permission To Return to...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-15

...-0016] Agency Information Collection Activities: Application for Advance Permission To Return to... Currently Approved Collection. (2) Title of the Form/Collection: Application for Advance Permission to..., 10 minutes for reading the instructions, and 35 minutes for completing and submitting the application...

78 FR 14585 - Agency Information Collection Activities: Application for Advance Permission to Enter as...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-06

... DEPARTMENT OF HOMELAND SECURITY U.S. Citizenship and Immigration Services [OMB Control Number 1615-0017] Agency Information Collection Activities: Application for Advance Permission to Enter as... Collection. (2) Title of the Form/Collection: Application for Advance Permission to Enter as Nonimmigrant...

46 CFR 565.8 - Special permission.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 9 2010-10-01 2010-10-01 false Special permission. 565.8 Section 565.8 Shipping FEDERAL MARITIME COMMISSION REGULATIONS AND ACTIONS TO ADDRESS RESTRICTIVE FOREIGN MARITIME PRACTICES CONTROLLED CARRIERS § 565.8 Special permission. Section 8(d) of the Shipping Act of 1984 (46 U.S.C. 40501(e...

10 CFR 850.22 - Permissible exposure limit.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Permissible exposure limit. 850.22 Section 850.22 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.22 Permissible exposure limit. The responsible employer must assure that no worker is exposed to an airborne...

50 CFR 218.11 - Permissible methods of taking.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Permissible methods of taking. 218.11... Range Complex) § 218.11 Permissible methods of taking. (a) Under Letters of Authorization issued... following species, by the indicated method of take and the indicated number of times: (1) Level B Harassment...

50 CFR 217.72 - Permissible methods of taking.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Permissible methods of taking. 217.72 Section 217.72 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC... Kodiak Launch Complex, Alaska § 217.72 Permissible methods of taking. (a) Under a Letter of Authorization...

50 CFR 217.13 - Permissible methods of taking.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Permissible methods of taking. 217.13 Section 217.13 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC... at Monterey Bay National Marine Sanctuary, CA § 217.13 Permissible methods of taking. (a) Under LOAs...

50 CFR 217.153 - Permissible methods of taking.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Permissible methods of taking. 217.153 Section 217.153 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC... Natural Gas Deepwater Port in the Gulf of Mexico § 217.153 Permissible methods of taking. (a) Under LOAs...

50 CFR 218.171 - Permissible methods of taking.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Permissible methods of taking. 218.171 Section 218.171 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC... Complex and the Associated Proposed Extensions Study Area § 218.171 Permissible methods of taking. (a...

50 CFR 217.13 - Permissible methods of taking.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Permissible methods of taking. 217.13 Section 217.13 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC... at Monterey Bay National Marine Sanctuary, CA § 217.13 Permissible methods of taking. (a) Under LOAs...

50 CFR 216.152 - Permissible methods of taking.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Permissible methods of taking. 216.152 Section 216.152 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC....152 Permissible methods of taking. (a) Under Letters of Authorization issued pursuant to §§ 216.106...

50 CFR 217.72 - Permissible methods of taking.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Permissible methods of taking. 217.72 Section 217.72 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC... Kodiak Launch Complex, Alaska § 217.72 Permissible methods of taking. (a) Under a Letter of Authorization...

50 CFR 216.122 - Permissible methods of taking.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Permissible methods of taking. 216.122 Section 216.122 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC... Permissible methods of taking. (a) Under Letters of Authorization issued pursuant to § 216.106 and 216.127...

50 CFR 216.152 - Permissible methods of taking.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Permissible methods of taking. 216.152 Section 216.152 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC....152 Permissible methods of taking. (a) Under Letters of Authorization issued pursuant to §§ 216.106...

50 CFR 216.122 - Permissible methods of taking.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Permissible methods of taking. 216.122 Section 216.122 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC... Permissible methods of taking. (a) Under Letters of Authorization issued pursuant to § 216.106 and 216.127...

42 CFR 433.68 - Permissible health care-related taxes.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 4 2012-10-01 2012-10-01 false Permissible health care-related taxes. 433.68 Section 433.68 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... Requirements State Financial Participation § 433.68 Permissible health care-related taxes. (a) General rule. A...

42 CFR 433.68 - Permissible health care-related taxes.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 4 2014-10-01 2014-10-01 false Permissible health care-related taxes. 433.68 Section 433.68 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... Requirements State Financial Participation § 433.68 Permissible health care-related taxes. (a) General rule. A...

46 CFR 115.700 - Permission for repairs and alterations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... replacement in kind, of electrical wiring, fuel lines, tanks, boilers and other pressure vessels, and steering... 46 Shipping 4 2011-10-01 2011-10-01 false Permission for repairs and alterations. 115.700 Section... AND CERTIFICATION Repairs and Alterations § 115.700 Permission for repairs and alterations. (a...

46 CFR 176.700 - Permission for repairs and alterations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... repair or replacement, other than replacement in kind, of electrical wiring, fuel lines, tanks, boilers... 46 Shipping 7 2012-10-01 2012-10-01 false Permission for repairs and alterations. 176.700 Section... (UNDER 100 GROSS TONS) INSPECTION AND CERTIFICATION Repairs and Alterations § 176.700 Permission for...

46 CFR 176.700 - Permission for repairs and alterations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... repair or replacement, other than replacement in kind, of electrical wiring, fuel lines, tanks, boilers... 46 Shipping 7 2013-10-01 2013-10-01 false Permission for repairs and alterations. 176.700 Section... (UNDER 100 GROSS TONS) INSPECTION AND CERTIFICATION Repairs and Alterations § 176.700 Permission for...

46 CFR 115.700 - Permission for repairs and alterations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... replacement in kind, of electrical wiring, fuel lines, tanks, boilers and other pressure vessels, and steering... 46 Shipping 4 2013-10-01 2013-10-01 false Permission for repairs and alterations. 115.700 Section... AND CERTIFICATION Repairs and Alterations § 115.700 Permission for repairs and alterations. (a...

46 CFR 115.700 - Permission for repairs and alterations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... replacement in kind, of electrical wiring, fuel lines, tanks, boilers and other pressure vessels, and steering... 46 Shipping 4 2012-10-01 2012-10-01 false Permission for repairs and alterations. 115.700 Section... AND CERTIFICATION Repairs and Alterations § 115.700 Permission for repairs and alterations. (a...

46 CFR 176.700 - Permission for repairs and alterations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... repair or replacement, other than replacement in kind, of electrical wiring, fuel lines, tanks, boilers... 46 Shipping 7 2014-10-01 2014-10-01 false Permission for repairs and alterations. 176.700 Section... (UNDER 100 GROSS TONS) INSPECTION AND CERTIFICATION Repairs and Alterations § 176.700 Permission for...

46 CFR 176.700 - Permission for repairs and alterations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... repair or replacement, other than replacement in kind, of electrical wiring, fuel lines, tanks, boilers... 46 Shipping 7 2011-10-01 2011-10-01 false Permission for repairs and alterations. 176.700 Section... (UNDER 100 GROSS TONS) INSPECTION AND CERTIFICATION Repairs and Alterations § 176.700 Permission for...

46 CFR 115.700 - Permission for repairs and alterations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... replacement in kind, of electrical wiring, fuel lines, tanks, boilers and other pressure vessels, and steering... 46 Shipping 4 2014-10-01 2014-10-01 false Permission for repairs and alterations. 115.700 Section... AND CERTIFICATION Repairs and Alterations § 115.700 Permission for repairs and alterations. (a...

30 CFR 77.1902-1 - Permissible diesel-powered equipment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Permissible diesel-powered equipment. 77.1902-1 Section 77.1902-1 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE... COAL MINES Slope and Shaft Sinking § 77.1902-1 Permissible diesel-powered equipment. Diesel-powered...

30 CFR 77.1902-1 - Permissible diesel-powered equipment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Permissible diesel-powered equipment. 77.1902-1 Section 77.1902-1 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE... COAL MINES Slope and Shaft Sinking § 77.1902-1 Permissible diesel-powered equipment. Diesel-powered...

Permissive Parenting and Mental Health in College Students: Mediating Effects of Academic Entitlement

ERIC Educational Resources Information Center

Barton, Alison L.; Hirsch, Jameson K.

2016-01-01

Objective: Student mental health may suffer due to unreasonable expectations associated with academic entitlement; permissive parenting may be one source of these expectations. The authors examined the role of academic entitlement as a mediator of the relationship between permissive parenting and psychological functioning. Participants:…

25 CFR 225.32 - Permission to start operations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false Permission to start operations. 225.32 Section 225.32 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS OIL AND GAS, GEOTHERMAL, AND SOLID MINERALS AGREEMENTS Minerals Agreements § 225.32 Permission to start operations. (a) No...

25 CFR 225.32 - Permission to start operations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Permission to start operations. 225.32 Section 225.32 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS OIL AND GAS, GEOTHERMAL, AND SOLID MINERALS AGREEMENTS Minerals Agreements § 225.32 Permission to start operations. (a) No...

30 CFR 75.501-2 - Permissible electric face equipment.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Permissible electric face equipment. 75.501-2... SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Electrical Equipment-General § 75.501-2 Permissible electric face equipment. (a) On and after March 30, 1971, in mines operated entirely...

30 CFR 75.501-2 - Permissible electric face equipment.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Permissible electric face equipment. 75.501-2... SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Electrical Equipment-General § 75.501-2 Permissible electric face equipment. (a) On and after March 30, 1971, in mines operated entirely...

30 CFR 75.501-2 - Permissible electric face equipment.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Permissible electric face equipment. 75.501-2... SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Electrical Equipment-General § 75.501-2 Permissible electric face equipment. (a) On and after March 30, 1971, in mines operated entirely...

32 CFR 643.115 - Contractors-Permission to erect structures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Contractors-Permission to erect structures. 643... (CONTINUED) REAL PROPERTY REAL ESTATE Additional Authority of Commanders § 643.115 Contractors—Permission to... the structure is to be used for any purpose other than the fulfillment of the contract, application...

78 FR 62645 - Agency Information Collection Activities: Application for Permission to Reapply for Admission...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-22

...-0018] Agency Information Collection Activities: Application for Permission to Reapply for Admission.... (2) Title of the Form/Collection: Application for Permission To Reapply for Admission Into the United... I-212 is used by USCIS to adjudicate applications filed by aliens requesting consent to reapply for...

43 CFR 23.4 - Application for permission to conduct exploration operations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Application for permission to conduct... SURFACE EXPLORATION, MINING AND RECLAMATION OF LANDS § 23.4 Application for permission to conduct... disposition under the mineral leasing acts without first filing an application for, and obtaining, a permit...

78 FR 77696 - Agency Information Collection Activities: Application for Permission To Reapply for Admission...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-24

...-0018] Agency Information Collection Activities: Application for Permission To Reapply for Admission... Collection. (2) Title of the Form/Collection: Application for Permission to Reapply for Admission into the... on Form I-212 is used by USCIS to adjudicate applications filed by aliens requesting consent to...

77 FR 43346 - Agency Information Collection Activities: Application for Permission To Reapply for Admission...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-24

...-0018] Agency Information Collection Activities: Application for Permission To Reapply for Admission... the Form/Collection: Application for Permission To Reapply for Admission Into the United States After...: Individuals or households. USCIS uses the information provided on Form I-212 to adjudicate applications filed...

30 CFR 75.506-1 - Electric face equipment; permissible condition; maintenance requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Electric face equipment; permissible condition... Equipment-General § 75.506-1 Electric face equipment; permissible condition; maintenance requirements. (a) Except as provided in paragraph (b) of this section, electric face equipment which meets the requirements...