Half-life of the superallowed β+ emitter Ne18

NASA Astrophysics Data System (ADS)

Grinyer, G. F.; Smith, M. B.; Andreoiu, C.; Andreyev, A. N.; Ball, G. C.; Bricault, P.; Chakrawarthy, R. S.; Daoud, J. J.; Finlay, P.; Garrett, P. E.; Hackman, G.; Hyland, B.; Leslie, J. R.; Morton, A. C.; Pearson, C. J.; Phillips, A. A.; Schumaker, M. A.; Svensson, C. E.; Valiente-Dobón, J. J.; Williams, S. J.; Zganjar, E. F.

2007-08-01

The half-life of Ne18 has been determined by detecting 1042-keV γ rays in the daughter F18 following the superallowed-Fermi β+ decay of samples implanted at the center of the 8πγ-ray spectrometer, a spherical array of 20 HPGe detectors. Radioactive Ne18 beams were produced on-line, mass-separated, and ionized using an electron-cyclotron-resonance ionization source at the ISAC facility at TRIUMF in Vancouver, Canada. This is the first high-precision half-life measurement of a superallowed Fermi β decay to utilize both a large-scale HPGe spectrometer and the isotope separation on-line technique. The half-life of Ne18, 1.6656 ± 0.0019 s, deduced following a 1.4σ correction for detector pulse pile-up, is four times more precise than the previous world average. As part of an investigation into potential systematic effects, the half-life of the heavier isotope Ne23 was determined to be 37.11 ± 0.06 s, a factor of 2 improvement over the previous precision.

Settling the half-life of 60Fe: fundamental for a versatile astrophysical chronometer.

PubMed

Wallner, A; Bichler, M; Buczak, K; Dressler, R; Fifield, L K; Schumann, D; Sterba, J H; Tims, S G; Wallner, G; Kutschera, W

2015-01-30

In order to resolve a recent discrepancy in the half-life of 60Fe, we performed an independent measurement with a new method that determines the 60Fe content of a material relative to 55Fe (t1/2=2.744  yr) with accelerator mass spectrometry. Our result of (2.50±0.12)×10(6)  yr clearly favors the recently reported value (2.62±0.04)×10(6)  yr, and rules out the older result of (1.49±0.27)×10(6)  yr. The present weighted mean half-life value of (2.60±0.05)×10(6)  yr substantially improves the reliability as an important chronometer for astrophysical applications in the million-year time range. This includes its use as a sensitive probe for studying recent chemical evolution of our Galaxy, the formation of the early Solar System, nucleosynthesis processes in massive stars, and as an indicator of a recent nearby supernova.

Stable isotope turnover and half-life in animal tissues: a literature synthesis.

PubMed

Vander Zanden, M Jake; Clayton, Murray K; Moody, Eric K; Solomon, Christopher T; Weidel, Brian C

2015-01-01

Stable isotopes of carbon, nitrogen, and sulfur are used as ecological tracers for a variety of applications, such as studies of animal migrations, energy sources, and food web pathways. Yet uncertainty relating to the time period integrated by isotopic measurement of animal tissues can confound the interpretation of isotopic data. There have been a large number of experimental isotopic diet shift studies aimed at quantifying animal tissue isotopic turnover rate λ (%·day(-1), often expressed as isotopic half-life, ln(2)/λ, days). Yet no studies have evaluated or summarized the many individual half-life estimates in an effort to both seek broad-scale patterns and characterize the degree of variability. Here, we collect previously published half-life estimates, examine how half-life is related to body size, and test for tissue- and taxa-varying allometric relationships. Half-life generally increases with animal body mass, and is longer in muscle and blood compared to plasma and internal organs. Half-life was longest in ecotherms, followed by mammals, and finally birds. For ectotherms, different taxa-tissue combinations had similar allometric slopes that generally matched predictions of metabolic theory. Half-life for ectotherms can be approximated as: ln (half-life) = 0.22*ln (body mass) + group-specific intercept; n = 261, p<0.0001, r2 = 0.63. For endothermic groups, relationships with body mass were weak and model slopes and intercepts were heterogeneous. While isotopic half-life can be approximated using simple allometric relationships for some taxa and tissue types, there is also a high degree of unexplained variation in our models. Our study highlights several strong and general patterns, though accurate prediction of isotopic half-life from readily available variables such as animal body mass remains elusive.

Intrinsically disordered segments and the evolution of protein half-life

NASA Astrophysics Data System (ADS)

Babu, M.

2013-03-01

Precise turnover of proteins is essential for cellular homeostasis and is primarily mediated by the proteasome. Thus, a fundamental question is: What features make a protein an efficient substrate for degradation? Here I will present results that proteins with a long terminal disordered segment or internal disordered segments have a significantly shorter half-life in yeast. This relationship appears to be evolutionarily conserved in mouse and human. Furthermore, upon gene duplication, divergence in the length of terminal disorder or variation in the number of internal disordered segments results in significant alteration of the half-life of yeast paralogs. Many proteins that exhibit such changes participate in signaling, where altered protein half-life will likely influence their activity. We suggest that variation in the length and number of disordered segments could serve as a remarkably simple means to evolve protein half-life and may serve as an underappreciated source of genetic variation with important phenotypic consequences. MMB acknowledges the Medical Research Council for funding his research program.

Fab-dsFv: A bispecific antibody format with extended serum half-life through albumin binding.

PubMed

Davé, Emma; Adams, Ralph; Zaccheo, Oliver; Carrington, Bruce; Compson, Joanne E; Dugdale, Sarah; Airey, Michael; Malcolm, Sarah; Hailu, Hanna; Wild, Gavin; Turner, Alison; Heads, James; Sarkar, Kaushik; Ventom, Andrew; Marshall, Diane; Jairaj, Mark; Kopotsha, Tim; Christodoulou, Louis; Zamacona, Miren; Lawson, Alastair D; Heywood, Sam; Humphreys, David P

2016-10-01

An antibody format, termed Fab-dsFv, has been designed for clinical indications that require monovalent target binding in the absence of direct Fc receptor (FcR) binding while retaining substantial serum presence. The variable fragment (Fv) domain of a humanized albumin-binding antibody was fused to the C-termini of Fab constant domains, such that the VL and VH domains were individually connected to the Cκ and CH1 domains by peptide linkers, respectively. The anti-albumin Fv was selected for properties thought to be desirable to ensure a durable serum half-life mediated via FcRn. The Fv domain was further stabilized by an inter-domain disulfide bond. The bispecific format was shown to be thermodynamically and biophysically stable, and retained good affinity and efficacy to both antigens simultaneously. In in vivo studies, the serum half-life of Fab-dsFv, 2.6 d in mice and 7.9 d in cynomolgus monkeys, was equivalent to Fab'-PEG.

Fab-dsFv: A bispecific antibody format with extended serum half-life through albumin binding

PubMed Central

Davé, Emma; Adams, Ralph; Zaccheo, Oliver; Carrington, Bruce; Compson, Joanne E.; Dugdale, Sarah; Airey, Michael; Malcolm, Sarah; Hailu, Hanna; Wild, Gavin; Turner, Alison; Heads, James; Sarkar, Kaushik; Ventom, Andrew; Marshall, Diane; Jairaj, Mark; Kopotsha, Tim; Christodoulou, Louis; Zamacona, Miren; Lawson, Alastair D.; Heywood, Sam; Humphreys, David P.

2016-01-01

ABSTRACT An antibody format, termed Fab-dsFv, has been designed for clinical indications that require monovalent target binding in the absence of direct Fc receptor (FcR) binding while retaining substantial serum presence. The variable fragment (Fv) domain of a humanized albumin-binding antibody was fused to the C-termini of Fab constant domains, such that the VL and VH domains were individually connected to the Cκ and CH1 domains by peptide linkers, respectively. The anti-albumin Fv was selected for properties thought to be desirable to ensure a durable serum half-life mediated via FcRn. The Fv domain was further stabilized by an inter-domain disulfide bond. The bispecific format was shown to be thermodynamically and biophysically stable, and retained good affinity and efficacy to both antigens simultaneously. In in vivo studies, the serum half-life of Fab-dsFv, 2.6 d in mice and 7.9 d in cynomolgus monkeys, was equivalent to Fab'-PEG. PMID:27532598

Designing of peptides with desired half-life in intestine-like environment.

PubMed

Sharma, Arun; Singla, Deepak; Rashid, Mamoon; Raghava, Gajendra Pal Singh

2014-08-20

In past, a number of peptides have been reported to possess highly diverse properties ranging from cell penetrating, tumor homing, anticancer, anti-hypertensive, antiviral to antimicrobials. Owing to their excellent specificity, low-toxicity, rich chemical diversity and availability from natural sources, FDA has successfully approved a number of peptide-based drugs and several are in various stages of drug development. Though peptides are proven good drug candidates, their usage is still hindered mainly because of their high susceptibility towards proteases degradation. We have developed an in silico method to predict the half-life of peptides in intestine-like environment and to design better peptides having optimized physicochemical properties and half-life. In this study, we have used 10mer (HL10) and 16mer (HL16) peptides dataset to develop prediction models for peptide half-life in intestine-like environment. First, SVM based models were developed on HL10 dataset which achieved maximum correlation R/R2 of 0.57/0.32, 0.68/0.46, and 0.69/0.47 using amino acid, dipeptide and tripeptide composition, respectively. Secondly, models developed on HL16 dataset showed maximum R/R2 of 0.91/0.82, 0.90/0.39, and 0.90/0.31 using amino acid, dipeptide and tripeptide composition, respectively. Furthermore, models that were developed on selected features, achieved a correlation (R) of 0.70 and 0.98 on HL10 and HL16 dataset, respectively. Preliminary analysis suggests the role of charged residue and amino acid size in peptide half-life/stability. Based on above models, we have developed a web server named HLP (Half Life Prediction), for predicting and designing peptides with desired half-life. The web server provides three facilities; i) half-life prediction, ii) physicochemical properties calculation and iii) designing mutant peptides. In summary, this study describes a web server 'HLP' that has been developed for assisting scientific community for predicting intestinal half-life

The interaction between thermodynamic stability and buried free cysteines in regulating the functional half-life of fibroblast growth factor-1.

PubMed

Lee, Jihun; Blaber, Michael

2009-10-16

Protein biopharmaceuticals are an important and growing area of human therapeutics; however, the intrinsic property of proteins to adopt alternative conformations (such as during protein unfolding and aggregation) presents numerous challenges, limiting their effective application as biopharmaceuticals. Using fibroblast growth factor-1 as model system, we describe a cooperative interaction between the intrinsic property of thermostability and the reactivity of buried free-cysteine residues that can substantially modulate protein functional half-life. A mutational strategy that combines elimination of buried free cysteines and secondary mutations that enhance thermostability to achieve a substantial gain in functional half-life is described. Furthermore, the implementation of this design strategy utilizing stabilizing mutations within the core region resulted in a mutant protein that is essentially indistinguishable from wild type as regard protein surface and solvent structure, thus minimizing the immunogenic potential of the mutations. This design strategy should be generally applicable to soluble globular proteins containing buried free-cysteine residues.

Leadership in Higher Education and the Second Half of Life

ERIC Educational Resources Information Center

Mills, Roxanne

2006-01-01

Research indicates that little is understood about the impact of what has been called "the second half of life" on administrators in higher education, such as deans and department chairs. This study addresses this lack of knowledge by reviewing research on the second half of life phenomena, especially its possible impact on university/college…

High-precision half-life determination for the superallowed β+ emitter Ga62

NASA Astrophysics Data System (ADS)

Grinyer, G. F.; Finlay, P.; Svensson, C. E.; Ball, G. C.; Leslie, J. R.; Austin, R. A. E.; Bandyopadhyay, D.; Chaffey, A.; Chakrawarthy, R. S.; Garrett, P. E.; Hackman, G.; Hyland, B.; Kanungo, R.; Leach, K. G.; Mattoon, C. M.; Morton, A. C.; Pearson, C. J.; Phillips, A. A.; Ressler, J. J.; Sarazin, F.; Savajols, H.; Schumaker, M. A.; Wong, J.

2008-01-01

The half-life of the superallowed β+ emitter Ga62 has been measured at TRIUMF's Isotope Separator and Accelerator facility using a fast-tape-transport system and 4π continuous-flow gas proportional counter to detect the positrons from the decay of Ga62 to the daughter Zn62. The result, T1/2=116.100±0.025 ms, represents the most precise measurement to date (0.022%) for any superallowed β-decay half-life. When combined with six previous measurements of the Ga62 half-life, a new world average of T1/2=116.121±0.021 ms is obtained. This new half-life measurement results in a 20% improvement in the precision of the Ga62 superallowed ft value while reducing its mean by 0.9σ to ft=3074.3(12) s. The impact of this half-life measurement on precision tests of the CVC hypothesis and isospin symmetry breaking corrections for A⩾62 superallowed decays is discussed.

A biomimetic approach for enhancing the in vivo half-life of peptides

PubMed Central

Penchala, Sravan C; Miller, Mark R; Pal, Arindom; Dong, Jin; Madadi, Nikhil R.; Xie, Jinghang; Joo, Hyun; Tsai, Jerry; Batoon, Patrick; Samoshin, Vyacheslav; Franz, Andreas; Cox, Trever; Miles, Jesse; Chan, William K; Park, Miki S; Alhamadsheh, Mamoun M

2015-01-01

The tremendous therapeutic potential of peptides has not yet been realized, mainly due to their short in vivo half-life. While conjugation to macromolecules has been a mainstay approach for enhancing the half-life of proteins, the steric hindrance of macromolecules often harms the binding of peptides to target receptors, compromising the in vivo efficacy. Here we report a new strategy for enhancing the in vivo half-life of peptides without compromising their potency. Our approach involves endowing peptides with a small-molecule that binds reversibly to the serum protein, transthyretin. Although there are few reversible albumin-binding molecules, we are unaware of designed small molecules that bind reversibly to other serum proteins and are used for half-life extension in vivo. We show here that our strategy was indeed effective in enhancing the half-life of an agonist for GnRH receptor while maintaining its binding affinity, which was translated into superior in vivo efficacy. PMID:26344696

Precision half-life measurement of 17F

NASA Astrophysics Data System (ADS)

Brodeur, M.; Nicoloff, C.; Ahn, T.; Allen, J.; Bardayan, D. W.; Becchetti, F. D.; Gupta, Y. K.; Hall, M. R.; Hall, O.; Hu, J.; Kelly, J. M.; Kolata, J. J.; Long, J.; O'Malley, P.; Schultz, B. E.

2016-02-01

Background: The precise determination of f t values for superallowed mixed transitions between mirror nuclide are gaining attention as they could provide an avenue to test the theoretical corrections used to extract the Vu d matrix element from superallowed pure Fermi transitions. The 17F decay is particularly interesting as it proceeds completely to the ground state of 17O, removing the need for branching ratio measurements. The dominant uncertainty on the f t value of the 17F mirror transition stems from a number of conflicting half-life measurements. Purpose: A precision half-life measurement of 17F was performed and compared to previous results. Methods: The life-time was determined from the β counting of implanted 17F on a Ta foil that was removed from the beam for counting. The 17F beam was produced by transfers reaction and separated by the TwinSol facility of the Nuclear Science Laboratory of the University of Notre Dame. Results: The measured value of t1/2 new=64.402 (42) s is in agreement with several past measurements and represents one of the most precise measurements to date. In anticipation of future measurements of the correlation parameters for the decay and using the new world average t1/2 world=64.398 (61) s, we present a new estimate of the mixing ratio ρ for the mixed transition as well as the correlation parameters based on assuming Standard Model validity. Conclusions: The relative uncertainty on the new world average for the half-life is dominated by the large χ2=31 of the existing measurements. More precision measurements with different systematics are needed to remedy to the situation.

Strategies to improve plasma half life time of peptide and protein drugs.

PubMed

Werle, M; Bernkop-Schnürch, A

2006-06-01

Due to the obvious advantages of long-acting peptide and protein drugs, strategies to prolong plasma half life time of such compounds are highly on demand. Short plasma half life times are commonly due to fast renal clearance as well as to enzymatic degradation occurring during systemic circulation. Modifications of the peptide/protein can lead to prolonged plasma half life times. By shortening the overall amino acid amount of somatostatin and replacing L: -analogue amino acids with D: -amino acids, plasma half life time of the derivate octreotide was 1.5 hours in comparison to only few minutes of somatostatin. A PEG(2,40 K) conjugate of INF-alpha-2b exhibited a 330-fold prolonged plasma half life time compared to the native protein. It was the aim of this review to provide an overview of possible strategies to prolong plasma half life time such as modification of N- and C-terminus or PEGylation as well as methods to evaluate the effectiveness of drug modifications. Furthermore, fundamental data about most important proteolytic enzymes of human blood, liver and kidney as well as their cleavage specificity and inhibitors for them are provided in order to predict enzymatic cleavage of peptide and protein drugs during systemic circulation.

New Measurement of the 60Fe Half-Life.

PubMed

Rugel, G; Faestermann, T; Knie, K; Korschinek, G; Poutivtsev, M; Schumann, D; Kivel, N; Günther-Leopold, I; Weinreich, R; Wohlmuther, M

2009-08-14

We have made a new determination of the half-life of the radioactive isotope 60Fe using high precision measurements of the number of 60Fe atoms and their activity in a sample containing over 10(15) 60Fe atoms. Our new value for the half-life of 60Fe is (2.62+/-0.04) x 10(6) yr, significantly above the previously reported value of (1.49+/-0.27) x 10(6) yr. Our new measurement for the lifetime of 60Fe has significant implications for interpretations of galactic nucleosynthesis, for determinations of formation time scales of solids in the early Solar System, and for the interpretation of live 60Fe measurements from supernova-ejecta deposits on Earth.

Variation in absorption and half-life of hydrocortisone influence plasma cortisol concentrations.

PubMed

Hindmarsh, Peter C; Charmandari, Evangelia

2015-04-01

Hydrocortisone therapy should be individualized in congenital adrenal hyperplasia (CAH) patients to avoid over and under replacement. We have assessed how differences in absorption and half-life of cortisol influence glucocorticoid exposure. Forty-eight patients (21 M) aged between 6·1 and 20·3 years with CAH due to CYP21A2 deficiency were studied. Each patient underwent a 24-h plasma cortisol profile with the morning dose used to calculate absorption parameters along with an intravenous (IV) hydrocortisone (15 mg/m(2) body surface area) bolus assessment of half-life. Parameters derived were maximum plasma concentration (Cmax ), time of maximum plasma concentration (tmax ), time to attaining plasma cortisol concentration <100 nmol/l and half-life of cortisol. Mean half-life was 76·5 ± 5·2 (range 40-225·3) min, Cmax 780·7 ± 61·6 nmol/l and tmax 66·7 (range 20-118) min. Time taken to a plasma cortisol concentration less than 100 nmol/l was 289 (range 140-540) min. Those with a fast half-life and slow tmax took longest to reach a plasma cortisol concentration less than 100 nmol/l (380 ± 34·6 min), compared to those with a slow half-life and fast tmax (298 ± 34·8 min) and those with a fast half-life and fast tmax (249·5 ± 14·4 min) (One-way anovaF = 4·52; P = 0·009). Both rate of absorption and half-life of cortisol in the circulation play important roles in determining overall exposure to oral glucocorticoid. Dose regimens need to incorporate estimates of these parameters into determining the optimum dosing schedule for individuals. © 2014 John Wiley & Sons Ltd.

HALO--a Java framework for precise transcript half-life determination.

PubMed

Friedel, Caroline C; Kaufmann, Stefanie; Dölken, Lars; Zimmer, Ralf

2010-05-01

Recent improvements in experimental technologies now allow measurements of de novo transcription and/or RNA decay at whole transcriptome level and determination of precise transcript half-lives. Such transcript half-lives provide important insights into the regulation of biological processes and the relative contributions of RNA decay and de novo transcription to differential gene expression. In this article, we present HALO (Half-life Organizer), the first software for the precise determination of transcript half-lives from measurements of RNA de novo transcription or decay determined with microarrays or RNA-seq. In addition, methods for quality control, filtering and normalization are supplied. HALO provides a graphical user interface, command-line tools and a well-documented Java application programming interface (API). Thus, it can be used both by biologists to determine transcript half-lives fast and reliably with the provided user interfaces as well as software developers integrating transcript half-life analysis into other gene expression profiling pipelines. Source code, executables and documentation are available at http://www.bio.ifi.lmu.de/software/halo.

Half-life of Si-32 from tandem-accelerator mass spectrometry

NASA Technical Reports Server (NTRS)

Elmore, D.; Anantaraman, N.; Fulbright, H. W.; Gove, H. E.; Nishiizumi, K.; Murrell, M. T.; Honda, M.; Hans, H. S.

1980-01-01

A newly developed mass-spectrometry technique employing a tandem Van de Graaff accelerator together with a special beam-transport system and heavy-ion detector has been used to determine the half-life of Si-32. The result obtained, 108 plus or minus 18 yr, disagrees with the accepted value of 330 plus or minus 40 yr. The implications of the new half-life of Si-32, which is used for dating studies, are discussed.

Using gamma distribution to determine half-life of rotenone, applied in freshwater.

PubMed

Rohan, Maheswaran; Fairweather, Alastair; Grainger, Natasha

2015-09-15

Following the use of rotenone to eradicate invasive pest fish, a dynamic first-order kinetic model is usually used to determine the half-life and rate at which rotenone dissipated from the treated waterbody. In this study, we investigate the use of a stochastic gamma model for determining the half-life and rate at which rotenone dissipates from waterbodies. The first-order kinetic and gamma models produced similar values for the half-life (4.45 days and 5.33 days respectively) and days to complete dissipation (51.2 days and 52.48 days respectively). However, the gamma model fitted the data better and was more flexible than the first-order kinetic model, allowing us to use covariates and to predict a possible range for the half-life of rotenone. These benefits are particularly important when examining the influence that different environmental factors have on rotenone dissipation and when trying to predict the rate at which rotenone will dissipate during future operations. We therefore recommend that in future the gamma distribution model is used when calculating the half-life of rotenone in preference to the dynamic first-order kinetics model. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of the 129I Half-Life Value Through Analyses of Primitive Meteorites

NASA Astrophysics Data System (ADS)

Pravdivtseva, Olga; Meshik, Alex; Hohenberg, Charles M.

The preserved record of decay of now-extinct 129I into 129Xe forms the basis of the I-Xe chronometer. Comparison of the high precision I-Xe and Pb-Pb ages of chondrules and pure mineral phases separated from eight meteorites suggests the 17.5 ÷ 14.6 Ma range for the 129I half-life, assuming that the 235U and 238U half-lives are correct. The mean value of 16 Ma indicates that the 15.7 Ma half-life of 129I used here for the I-Xe age calculations is most probably correct. Since the 129I half-life value only affects the relative I-Xe ages, the few Ma relative to the Shallowater standard, the absolute I-Xe ages are almost immune to this uncertainty in the 129I half-life.

Half-life of the superallowed {beta}{sup +} emitter {sup 18}Ne

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

Grinyer, G. F.; Andreoiu, C.; Finlay, P.

The half-life of {sup 18}Ne has been determined by detecting 1042-keV {gamma} rays in the daughter {sup 18}F following the superallowed-Fermi {beta}{sup +} decay of samples implanted at the center of the 8{pi}{gamma}-ray spectrometer, a spherical array of 20 HPGe detectors. Radioactive {sup 18}Ne beams were produced on-line, mass-separated, and ionized using an electron-cyclotron-resonance ionization source at the ISAC facility at TRIUMF in Vancouver, Canada. This is the first high-precision half-life measurement of a superallowed Fermi {beta} decay to utilize both a large-scale HPGe spectrometer and the isotope separation on-line technique. The half-life of {sup 18}Ne, 1.6656 {+-} 0.0019 s,more » deduced following a 1.4{sigma} correction for detector pulse pile-up, is four times more precise than the previous world average. As part of an investigation into potential systematic effects, the half-life of the heavier isotope {sup 23}Ne was determined to be 37.11 {+-} 0.06 s, a factor of 2 improvement over the previous precision.« less

Estimation of Monocrotophos renal elimination half-life in humans.

PubMed

Jose, Arun; Selvakumar, Ratnasamy; Peter, John Victor; Karthik, Gunasekaran; Fleming, Denise Helen; Fleming, Jude Joseph

2015-01-01

Monocrotophos, implicated in about 1/4th of organophosphate poisonings in our centre, is associated with the highest mortality (24%). Yet data on its pharmacokinetics in humans is limited. We estimated the renal elimination half-life of monocrotophos. Consecutive patients presenting with monocrotophos overdose over a 2-month period who had normal renal function were recruited. Monocrotophos in plasma and urine were quantitated by high-performance liquid chromatography. Urine was obtained from catheterised samples at 0-2, 2-4, 4-6, 6-8, 8-12 and 12-24 h. Plasma specimens were collected at the time of admission, and at the midpoint of the urine sample collections at 1, 3, 5, 7, 10, 15 and 21 h. Renal elimination half-life was calculated from the cumulative amount excreted in the urine. The cohort of 5 male patients, aged 35.8 ± 2.94 years, presented with typical organophosphate (cholinergic) toxidrome following intentional monocrotophos overdose. All patients required mechanical ventilation; one patient died. Plasma data was available from 5 patients and urine data from 3 patients. The median renal elimination half-life was 3.3 (range: 1.9-5.0 h). Plasma monocrotophos values, as natural log, fell in a linear fashion up to around 10 h after admission. After the 10-hour period, there was a secondary rise in values in all the 3 patients in whom sampling was continued after 10 h. A renal elimination half-life of 3.3 h for monocrotophos is consistent with a water-soluble compound which is rapidly cleared from the plasma. The secondary rise in plasma monocrotophos values suggests possible re-distribution. Determining the elimination profile of this compound will help develop better strategies for treatment.

Potential fitness benefits of the half-pounder life history in Klamath River steelhead

USGS Publications Warehouse

Hodge, Brian W.; Wilzbach, Peggy; Duffy, Walter G.

2014-01-01

Steelhead Oncorhynchus mykiss from several of the world's rivers display the half-pounder life history, a variant characterized by an amphidromous (and, less often, anadromous) return to freshwater in the year of initial ocean entry. We evaluated factors related to expression of the half-pounder life history in wild steelhead from the lower Klamath River basin, California. We also evaluated fitness consequences of the half-pounder phenotype using a simple life history model that was parameterized with our empirical data and outputs from a regional survival equation. The incidence of the half-pounder life history differed among subbasins of origin and smolt ages. Precocious maturation occurred in approximately 8% of half-pounders and was best predicted by individual length in freshwater preceding ocean entry. Adult steelhead of the half-pounder phenotype were smaller and less fecund at age than adult steelhead of the alternative (ocean contingent) phenotype. However, our data suggest that fish of the half-pounder phenotype are more likely to spawn repeatedly than are fish of the ocean contingent phenotype. Models predicted that if lifetime survivorship were equal between phenotypes, the fitness of the half-pounder phenotype would be 17–28% lower than that of the ocean contingent phenotype. To meet the condition of equal fitness between phenotypes would require that first-year ocean survival be 21–40% higher among half-pounders in freshwater than among their cohorts at sea. We concluded that continued expression of the half-pounder phenotype is favored by precocious maturation and increased survival relative to that of the ocean contingent phenotype.

Advances in Therapeutic Fc Engineering – Modulation of IgG-Associated Effector Functions and Serum Half-life

PubMed Central

Saxena, Abhishek; Wu, Donghui

2016-01-01

Today, monoclonal immunoglobulin gamma (IgG) antibodies have become a major option in cancer therapy especially for the patients with advanced or metastatic cancers. Efficacy of monoclonal antibodies (mAbs) is achieved through both its antigen-binding fragment (Fab) and crystallizable fragment (Fc). Fab can specifically recognize tumor-associated antigen (TAA) and thus modulate TAA-linked downstream signaling pathways that may lead to the inhibition of tumor growth, induction of tumor apoptosis, and differentiation. The Fc region can further improve mAbs’ efficacy by mediating effector functions such as antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cell-mediated phagocytosis. Moreover, Fc is the region interacting with the neonatal Fc receptor in a pH-dependent manner that can slow down IgG’s degradation and extend its serum half-life. Loss of the antibody Fc region dramatically shortens its serum half-life and weakens its anticancer effects. Given the essential roles that the Fc region plays in the modulation of the efficacy of mAb in cancer treatment, Fc engineering has been extensively studied in the past years. This review focuses on the recent advances in therapeutic Fc engineering that modulates its related effector functions and serum half-life. We also discuss the progress made in aglycosylated mAb development that may substantially reduce the cost of manufacture but maintain similar efficacies as conventional glycosylated mAb. Finally, we highlight several Fc engineering-based mAbs under clinical trials. PMID:28018347

On the half-life of luminescence signals in dosimetric applications: A unified presentation

NASA Astrophysics Data System (ADS)

Pagonis, V.; Kitis, G.; Polymeris, G. S.

2018-06-01

Luminescence signals from natural and man-made materials are widely used in dosimetric and dating applications. In general, there are two types of half-lives of luminescence signals which are of importance to experimental and modeling work in this research area. The first type of half-life is the time required for the population of the trapped charge in a single trap to decay to half its initial value. The second type of half-life is the time required for the luminescence intensity to drop to half of its initial value. While there a handful of analytical expressions available in the literature for the first type of half-life, there are no corresponding analytical expressions for the second type. In this work new analytical expressions are derived for the half-life of luminescence signals during continuous wave optical stimulation luminescence (CW-OSL) or isothermal luminescence (ITL) experiments. The analytical expressions are derived for several commonly used luminescence models which are based on delocalized transitions involving the conduction band: first and second order kinetics, empirical general order kinetics (GOK), mixed order kinetics (MOK) and the one-trap one-recombination center (OTOR) model. In addition, half-life expressions are derived for a different type of luminescence model, which is based on localized transitions in a random distribution of charges. The new half-life expressions contain two parts. The first part is inversely proportional to the thermal or optical excitation rate, and depends on the experimental conditions and on the cross section of the relevant luminescence process. The second part is characteristic of the optical and/or thermal properties of the material, as expressed by the parameters in the model. A new simple and quick method for analyzing luminescence signals is developed, and examples are given of applying the new method to a variety of dosimetric materials. The new test allows quick determination of whether a set of

Food at checkouts in non-food stores: a cross-sectional study of a large indoor shopping mall.

PubMed

Wright, James; Kamp, Erin; White, Martin; Adams, Jean; Sowden, Sarah

2015-10-01

To investigate the display of food at non-food store checkouts; and to classify foods by type and nutrient content, presence of price promotions and whether food was at child height. Cross-sectional survey of checkout displays at non-food stores. Foods were classified as 'less healthy' or healthier using the UK Food Standards Agency's Nutrient Profile Model. Written price promotions were recorded. Child height was defined as the sight line of an 11-year-old approximated from UK growth charts. A large indoor shopping mall, Gateshead, UK, February-March 2014. Two hundred and five out of 219 non-food stores in the shopping mall directory which were open for trading. Thirty-two (15·6%) of 205 non-food stores displayed food at the checkout. All displayed less healthy foods, and fourteen (43·8%) had healthier foods. Overall, 5911 checkout foods were identified. Of these, 4763 (80·6%) were 'less healthy'. No fruits, vegetables, nuts or seeds were found. Of 4763 less healthy foods displayed, 195 (4·1%) were subject to price promotions, compared with twelve of 1148 (1·0%) healthier foods (χ 2(df=1)=25·4, P<0·0001). There was no difference in the proportion of less healthy (95·1%) and healthier (96·2%) foods displayed at child height. Almost one-sixth of non-food stores displayed checkout food, the majority of which was 'less healthy' and displayed at child height. Less healthy food was more likely to be subject to a written price promotion than healthier food. Further research into the drivers and consequences of checkout food in non-food stores is needed. Public health regulation may be warranted.

Extending Serum Half-life of Albumin by Engineering Neonatal Fc Receptor (FcRn) Binding*

PubMed Central

Andersen, Jan Terje; Dalhus, Bjørn; Viuff, Dorthe; Ravn, Birgitte Thue; Gunnarsen, Kristin Støen; Plumridge, Andrew; Bunting, Karen; Antunes, Filipa; Williamson, Rebecca; Athwal, Steven; Allan, Elizabeth; Evans, Leslie; Bjørås, Magnar; Kjærulff, Søren; Sleep, Darrell; Sandlie, Inger; Cameron, Jason

2014-01-01

A major challenge for the therapeutic use of many peptides and proteins is their short circulatory half-life. Albumin has an extended serum half-life of 3 weeks because of its size and FcRn-mediated recycling that prevents intracellular degradation, properties shared with IgG antibodies. Engineering the strictly pH-dependent IgG-FcRn interaction is known to extend IgG half-life. However, this principle has not been extensively explored for albumin. We have engineered human albumin by introducing single point mutations in the C-terminal end that generated a panel of variants with greatly improved affinities for FcRn. One variant (K573P) with 12-fold improved affinity showed extended serum half-life in normal mice, mice transgenic for human FcRn, and cynomolgus monkeys. Importantly, favorable binding to FcRn was maintained when a single-chain fragment variable antibody was genetically fused to either the N- or the C-terminal end. The engineered albumin variants may be attractive for improving the serum half-life of biopharmaceuticals. PMID:24652290

High-Precision Half-Life Measurement for the Superallowed β+ Emitter 22Mg

NASA Astrophysics Data System (ADS)

Dunlop, Michelle

2017-09-01

High precision measurements of the Ft values for superallowed Fermi beta transitions between 0+ isobaric analogue states allow for stringent tests of the electroweak interaction. These transitions provide an experimental probe of the Conserved-Vector-Current hypothesis, the most precise determination of the up-down element of the Cabibbo-Kobayashi-Maskawa matrix, and set stringent limits on the existence of scalar currents in the weak interaction. To calculate the Ft values several theoretical corrections must be applied to the experimental data, some of which have large model dependent variations. Precise experimental determinations of the ft values can be used to help constrain the different models. The uncertainty in the 22Mg superallowed Ft value is dominated by the uncertainty in the experimental ft value. The adopted half-life of 22Mg is determined from two measurements which disagree with one another, resulting in the inflation of the weighted-average half-life uncertainty by a factor of 2. The 22Mg half-life was measured with a precision of 0.02% via direct β counting at TRIUMF's ISAC facility, leading to an improvement in the world-average half-life by more than a factor of 3.

40 CFR 158.510 - Tiered testing options for nonfood pesticides.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Toxicology § 158.510 Tiered testing options for nonfood... required toxicology (§ 158.500) and human exposure (§ 158.1020, § 158.1070, and § 158.1410) studies... studies on the active ingredient must be submitted together. The specific makeup of the set of toxicology...

40 CFR 158.510 - Tiered testing options for nonfood pesticides.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Toxicology § 158.510 Tiered testing options for nonfood... required toxicology (§ 158.500) and human exposure (§ 158.1020, § 158.1070, and § 158.1410) studies... studies on the active ingredient must be submitted together. The specific makeup of the set of toxicology...

40 CFR 158.510 - Tiered testing options for nonfood pesticides.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Toxicology § 158.510 Tiered testing options for nonfood... required toxicology (§ 158.500) and human exposure (§ 158.1020, § 158.1070, and § 158.1410) studies... studies on the active ingredient must be submitted together. The specific makeup of the set of toxicology...

40 CFR 158.510 - Tiered testing options for nonfood pesticides.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Toxicology § 158.510 Tiered testing options for nonfood... required toxicology (§ 158.500) and human exposure (§ 158.1020, § 158.1070, and § 158.1410) studies... studies on the active ingredient must be submitted together. The specific makeup of the set of toxicology...

Prevalence of non-food allergies among non-immigrants, long-time immigrants and recent immigrants in Canada.

PubMed

Yao, Jiayun; Sbihi, Hind

2016-12-27

The prevalence of allergic conditions has been increasing worldwide, with the highest rates seen in Western countries like Canada. The development of allergies is known to be related to both genetic and environmental factors, but the causal pathways remain unclear. Studies on immigrants provide a unique opportunity to disentangle these two factors and provide a better understanding of the disease aetiology. The aim of this study was to investigate the relationship between immigration status and prevalence of non-food allergies in a population-based study of Canadians. Data of 116,232 respondents from the Canadian Community Health Survey (Cycle 3.1, 2005) were used in a multivariable logistic regression to assess the association between immigration status (non-immigrant, long-time immigrant [>10 years] and recent immigrant [≤10 years]) and self-reported doctor-diagnosed non-food allergies, adjusting for potential confounders. The highest prevalence of non-food allergies was found among non-immigrants (29.6%), followed by long-time immigrants (23.9%) and then recent immigrants (14.3%). The odds of non-food allergies were reduced by 60% (OR = 0.40, 95% CI: 0.35, 0.45) among recent immigrants and 25% (OR = 0.75, 95% CI: 0.70, 0.80) among long-time immigrants, compared with non-immigrants, after adjusting for sex, age, socio-economic status and rurality. This study finds a distinctly lower prevalence of non-food allergies among immigrants compared with non-immigrants, with the difference diminishing with longer duration of residence in Canada. The findings highlight the potential of environmental determinants of allergy development that warrant further investigation, and demonstrate the need for multicultural strategies to manage the public health burden of allergic conditions.

β+ decay and cosmic-ray half-life of 91Nb

NASA Astrophysics Data System (ADS)

Hindi, M. M.; Sur, Bhaskar; Wedding, Kristin L.; Bardayan, D. W.; Czerwinski, K. R.; da Cruz, M. T. F.; Hoffman, D. C.; Larimer, R.-M.; Lesko, K. T.; Norman, Eric B.

1993-06-01

In the laboratory, 91Nb decays by electron capture with a 680-yr half-life. However, as a high energy cosmic ray, it would be stripped of its atomic electrons and would be able to undergo only β+ decay. We produced and chemically purified a sample of 91Nb and observed its decay with an array of Ge and NaI detectors. By following the β+ annihilation radiation, we were able to determine the β+ branching ratios of both the 105-keV, 61-d isomer and the ground state of 91Nb. The ground-state branch is (7.7+/-0.8)×10-3% leading to a β+ partial half-like of (8.8+/-1.9)×106 yr. Such a value of the half-life makes 91Nb a good candidate for determining the confinement time of this secondary component of the cosmic rays.

Extending the half-life of a fab fragment through generation of a humanized anti-human serum albumin Fv domain: An investigation into the correlation between affinity and serum half-life.

PubMed

Adams, Ralph; Griffin, Laura; Compson, Joanne E; Jairaj, Mark; Baker, Terry; Ceska, Tom; West, Shauna; Zaccheo, Oliver; Davé, Emma; Lawson, Alastair Dg; Humphreys, David P; Heywood, Sam

2016-10-01

We generated an anti-albumin antibody, CA645, to link its Fv domain to an antigen-binding fragment (Fab), thereby extending the serum half-life of the Fab. CA645 was demonstrated to bind human, cynomolgus, and mouse serum albumin with similar affinity (1-7 nM), and to bind human serum albumin (HSA) when it is in complex with common known ligands. Importantly for half-life extension, CA645 binds HSA with similar affinity within the physiologically relevant range of pH 5.0 - pH 7.4, and does not have a deleterious effect on the binding of HSA to neonatal Fc receptor (FcRn). A crystal structure of humanized CA645 Fab in complex with HSA was solved and showed that CA645 Fab binds to domain II of HSA. Superimposition with the crystal structure of FcRn bound to HSA confirmed that CA645 does not block HSA binding to FcRn. In mice, the serum half-life of humanized CA645 Fab is 84.2 h. This is a significant extension in comparison with < 1 h for a non-HSA binding CA645 Fab variant. The Fab-HSA structure was used to design a series of mutants with reduced affinity to investigate the correlation between the affinity for albumin and serum half-life. Reduction in the affinity for MSA by 144-fold from 2.2 nM to 316 nM had no effect on serum half-life. Strikingly, despite a reduction in affinity to 62 µM, an extension in serum half-life of 26.4 h was still obtained. CA645 Fab and the CA645 Fab-HSA complex have been deposited in the Protein Data Bank (PDB) with accession codes, 5FUZ and 5FUO, respectively.

Update of NIST half-life results corrected for ionization chamber source-holder instability.

PubMed

Unterweger, M P; Fitzgerald, R

2014-05-01

As reported at the ICRM 2011, it was discovered that the source holder used for calibrations in the NIST 4πγ ionization chamber (IC) was not stable. This has affected a large number of half-life measurement results previously reported and used in compilations of nuclear data. Corrections have been made on all of the half-life data based on the assumption that the changes to the ionization chamber response were gradual. The corrections are energy dependent and therefore radionuclide specific. This presentation will review our results and present the recommended changes in half-life values and/or uncertainties. © 2013 Published by Elsevier Ltd.

Neutron activation analyses and half-life measurements at the usgs triga reactor

NASA Astrophysics Data System (ADS)

Larson, Robert E.

Neutron activation of materials followed by gamma spectroscopy using high-purity germanium detectors is an effective method for making measurements of nuclear beta decay half-lives and for detecting trace amounts of elements present in materials. This research explores applications of neutron activation analysis (NAA) in two parts. Part 1. High Precision Methods for Measuring Decay Half-Lives, Chapters 1 through 8 Part one develops research methods and data analysis techniques for making high precision measurements of nuclear beta decay half-lives. The change in the electron capture half-life of 51Cr in pure chromium versus chromium mixed in a gold lattice structure is explored, and the 97Ru electron capture decay half-life are compared for ruthenium in a pure crystal versus ruthenium in a rutile oxide state, RuO2. In addition, the beta-minus decay half-life of 71mZn is measured and compared with new high precision findings. Density Functional Theory is used to explain the measured magnitude of changes in electron capture half-life from changes in the surrounding lattice electron configuration. Part 2. Debris Collection Nuclear Diagnostic at the National Ignition Facility, Chapters 9 through 11 Part two explores the design and development of a solid debris collector for use as a diagnostic tool at the National Ignition Facility (NIF). NAA measurements are performed on NIF post-shot debris collected on witness plates in the NIF chamber. In this application NAA is used to detect and quantify the amount of trace amounts of gold from the hohlraum and germanium from the pellet present in the debris collected after a NIF shot. The design of a solid debris collector based on material x-ray ablation properties is given, and calculations are done to predict performance and results for the collection and measurements of trace amounts of gold and germanium from dissociated hohlraum debris.

Superior serum half life of albumin tagged TNF ligands

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

Mueller, Nicole; Schneider, Britta; Pfizenmaier, Klaus

2010-06-11

Due to their immune stimulating and apoptosis inducing properties, ligands of the TNF family attract increasing interest as therapeutic proteins. A general limitation of in vivo applications of recombinant soluble TNF ligands is their notoriously rapid clearance from circulation. To improve the serum half life of the TNF family members TNF, TWEAK and TRAIL, we genetically fused soluble variants of these molecules to human serum albumin (HSA). The serum albumin-TNF ligand fusion proteins were found to be of similar bioactivity as the corresponding HSA-less counterparts. Upon intravenous injection (i.v.), serum half life of HSA-TNF ligand fusion proteins, as determined bymore » ELISA, was around 15 h as compared to approximately 1 h for all of the recombinant control TNF ligands without HSA domain. Moreover, serum samples collected 6 or 24 h after i.v. injection still contained high TNF ligand bioactivity, demonstrating that there is only limited degradation/inactivation of circulating HSA-TNF ligand fusion proteins in vivo. In a xenotransplantation model, significantly less of the HSA-TRAIL fusion protein compared to the respective control TRAIL protein was required to achieve inhibition of tumor growth indicating that the increased half life of HSA-TNF ligand fusion proteins translates into better therapeutic action in vivo. In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands.« less

High-precision half-life determination for 21Na using a 4 π gas-proportional counter

NASA Astrophysics Data System (ADS)

Finlay, P.; Laffoley, A. T.; Ball, G. C.; Bender, P. C.; Dunlop, M. R.; Dunlop, R.; Hackman, G.; Leslie, J. R.; MacLean, A. D.; Miller, D.; Moukaddam, M.; Olaizola, B.; Severijns, N.; Smith, J. K.; Southall, D.; Svensson, C. E.

2017-08-01

A high-precision half-life measurement for the superallowed β+ transition between the isospin T =1 /2 mirror nuclei 21Na and 21Ne has been performed at the TRIUMF-ISAC radioactive ion beam facility yielding T1 /2=22.4506 (33 ) s, a result that is a factor of 4 more precise than the previous world-average half-life for 21Na and represents the single most precisely determined half-life for a transition between mirror nuclei to date. The contribution to the uncertainty in the 21Na F tmirror value due to the half-life is now reduced to the level of the nuclear-structure-dependent theoretical corrections, leaving the branching ratio as the dominant experimental uncertainty.

Geochemical constraints on the half-life of {sup 130}Te

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

Thomas, H. V.; Pattrick, R. A. D.; Crowther, S. A.

2008-11-15

To determine the half-life of {sup 130}Te we have analyzed multiple aliquots of geological telluride samples 100 times smaller than those previously reported using a unique resonance ionization mass spectrometer. We employ a low-fluence neutron irradiation that allows determination of parent and daughter from the same xenon isotopic analysis. Step heating of these irradiated samples allows the {sup 130}Xe/{sup 132}Xe ratio of fluids trapped inside the tellurides to be determined. Considering only samples where the trapped {sup 130}Xe/{sup 132}Xe ratio is demonstrably consistent with atmospheric xenon, we can avoid over- or under-estimating the half-life due to redistribution or inheritance ofmore » radiogenic {sup 130}Xe. Combining our work with literature data, it is clear that several relatively young samples have retained xenon quantitatively since formation, allowing the half-life to be determined as (8.0{+-}1.1)x10{sup 20} yr. Older samples have clearly been affected by post-formation processing. This suggests that there is little hope of monitoring solar luminosity through the geological record of {sup 126}Xe production by solar neutrinos, but it is possible that geologically useful chronological information can be obtained from this system.« less

Half-life of leu-enkephalin in the serum of infants of the first year of life on different types of feeding: relationship with temperament.

PubMed

Sokolov, O Yu; Kurasova, O B; Kost, N V; Gabaeva, M V; Korneeva, E V; Mikheeva, I G; Zozulya, A A

2004-04-01

The half-life of leu-enkephalin in the serum of infants aged under 1 year is significantly shorter than in adults. In girls leu-enkephalin half-life is significantly longer than in boys. The half-life of leu-enkephalin is different in infants on breast and formula feeding. Nine characteristics of temperament in infants of the first year of life were determined using EITQ and ITQ questionnaires. Serum leu-enkephalin half-life directly correlated with temperament characteristics (activity, perception, threshold), but not with the level psychomotor development.

Site-Specific Albumination as an Alternative to PEGylation for the Enhanced Serum Half-Life in Vivo.

PubMed

Yang, Byungseop; Lim, Sung In; Kim, Jong Chul; Tae, Giyoong; Kwon, Inchan

2016-05-09

Polyethylene glycol (PEG) has been widely used as a serum half-life extender of therapeutic proteins. However, due to immune responses and low degradability of PEG, developing serum half-life extender alternatives to PEG is required. Human serum albumin (HSA) has several beneficial features as a serum half-life extender, including a very long serum half-life, good degradability, and low immune responses. In order to further evaluate the efficacy of HSA, we compared the extent of serum half-life extension of a target protein, superfolder green fluorescent protein (sfGFP), upon HSA conjugation with PEG conjugation side-by-side. Combination of site-specific incorporation of p-azido-l-phenylalanine into sfGFP and copper-free click chemistry achieved the site-specific conjugation of a single HSA, 20 kDa PEG, or 30 kDa PEG to sfGFP. These sfGFP conjugates exhibited the fluorescence comparable to or even greater than that of wild-type sfGFP (sfGFP-WT). In mice, HSA-conjugation to sfGFP extended the serum half-life 9.0 times compared to that of unmodified sfGFP, which is comparable to those of PEG-conjugated sfGFPs (7.3 times for 20 kDa PEG and 9.5 times for 30 kDa PEG). These results clearly demonstrated that HSA was as effective as PEG in extending the serum half-life of a target protein. Therefore, with the additional favorable features, HSA is a good serum half-life extender of a (therapeutic) protein as an alternative to PEG.

β-decay half-life of V50 calculated by the shell model

NASA Astrophysics Data System (ADS)

Haaranen, M.; Srivastava, P. C.; Suhonen, J.; Zuber, K.

2014-10-01

In this work we survey the detectability of the β- channel of 2350V leading to the first excited 2+ state in 2450Cr. The electron-capture (EC) half-life corresponding to the transition of 2350V to the first excited 2+ state in 2250Ti had been measured earlier. Both of the mentioned transitions are 4th-forbidden non-unique. We have performed calculations of all the involved wave functions by using the nuclear shell model with the GXPF1A interaction in the full f-p shell. The computed half-life of the EC branch is in good agreement with the measured one. The predicted half-life for the β- branch is in the range ≈2×1019 yr whereas the present experimental lower limit is 1.5×1018 yr. We discuss also the experimental lay-out needed to detect the β--branch decay.

The impact of extended half-life versus conventional factor product on hemophilia caregiver burden.

PubMed

Schwartz, Carolyn E; Powell, Victoria E; Su, Jun; Zhang, Jie; Eldar-Lissai, Adi

2018-05-01

Extended half-life factor products have reduced annualized bleeding rates in hemophilia patients. The impact of extended half-life versus conventional factor products on hemophilia caregiver burden has not been investigated. This study aimed to evaluate caregiver burden in extended half-life versus conventional factor products for hemophilia A and B. This cross-sectional web-based study of caregivers of people with hemophilia A or B was recruited from a panel research company and by word of mouth. Participants completed the Hemophilia Caregiver Impact measure, the PedsQL Family Impact Module (PedsQL), and the Work Productivity and Activity Impairment Questionnaire (WPAI). We also collected demographic, insurance coverage, and medical information related to the hemophilia patient(s). Burden differences were assessed using linear regression and matched cohort analyses. The sample (n = 448) included 49 people who were caring for people on extended half-life factor products. Worse caregiver burden was associated with more infusions per week and more bleeds in the past 6 months. Regression analyses suggested that caring for someone who is on a extended half-life factor product is associated with lower emotional impact (β = - 0.11, p < 0.05, Adjusted R 2  = 0.06), and shows a trend association with lower practical impact (β = - 0.09, p < 0.10, Adjusted R 2  = 0.05). The matched cohort analysis also revealed that people on extended half-life factor product had lower Emotional Impact and Practical Impact scores (t = - 2.95 and - 2.94, respectively, p < 0.05 in both cases). No differences were detected on the PedsQL or the WPAI. The reduced required frequency of factor product infusions of extended half-life factor products appears to reduce the emotional distress and practical burden of caregiving. Future work should evaluate the longitudinal impact.

Precise measurement of the {sup 19}Ne half-life

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

Triambak, S.; TRIUMF, 4004 Wesbrook Mall, Vancouver, BC V6T 2A3

2011-11-30

We describe a high-precision measurement of the half-life of the T = 1/2 nucleus {sup 19}Ne, performed at TRIUMF, Canada's National Laboratory for Nuclear and Particle Physics, Vancouver, Canada. Some implications of this measurement related to tests of the Standard Model are discussed.

Tests of a Fast Plastic Scintillator for High-Precision Half-Life Measurements

NASA Astrophysics Data System (ADS)

Laffoley, A. T.; Dunlop, R.; Finlay, P.; Leach, K. G.; Michetti-Wilson, J.; Rand, E. T.; Svensson, C. E.; Grinyer, G. F.; Thomas, J. C.; Ball, G.; Garnsworthy, A. B.; Hackman, G.; Orce, J. N.; Triambak, S.; Williams, S. J.; Andreoiu, C.; Cross, D.

2013-03-01

A fast plastic scintillator detector is evaluated for possible use in an ongoing program of high-precision half-life measurements of short lived β emitters. Using data taken at TRI-UMF's Isotope Separator and Accelerator Facility with a radioactive 26Na beam, a detailed investigation of potential systematic effects with this new detector setup is being performed. The technique will then be applied to other β-decay half-life measurements including the superallowed Fermi β emitters 10C, 14O, and T = 1/2 decay of 15O.

A calculation model to half-life estimate of two-proton radioactive decay process

NASA Astrophysics Data System (ADS)

Tavares, O. A. P.; Medeiros, E. L.

2018-04-01

Partial half-life of the radioactive decay by the two-proton emission mode has been estimated for proton-rich nuclei of mass number 18 < A < 68 by a model based on the quantum mechanical tunneling mechanism through a potential barrier. The Coulomb, centrifugal and overlapping contributions to the barrier have been considered within the spherical nucleus approximation. The present calculation method has been shown to be adequate in reproducing the existing experimental half-life data for 19Mg, 45Fe, 48Ni, and 54Zn 2p-emitter nuclides within a factor six. For 67Kr parent nucleus the calculated partial 2p-decay half-life has been found to be ten times greater than the recent, unique measured value at RIKEN Nishina Center. Prediction for new, yet unmeasured cases of two-proton radioactivity are also reported.

Precision half-life measurement of 11C: The most precise mirror transition F t value

NASA Astrophysics Data System (ADS)

Valverde, A. A.; Brodeur, M.; Ahn, T.; Allen, J.; Bardayan, D. W.; Becchetti, F. D.; Blankstein, D.; Brown, G.; Burdette, D. P.; Frentz, B.; Gilardy, G.; Hall, M. R.; King, S.; Kolata, J. J.; Long, J.; Macon, K. T.; Nelson, A.; O'Malley, P. D.; Skulski, M.; Strauss, S. Y.; Vande Kolk, B.

2018-03-01

Background: The precise determination of the F t value in T =1 /2 mixed mirror decays is an important avenue for testing the standard model of the electroweak interaction through the determination of Vu d in nuclear β decays. 11C is an interesting case, as its low mass and small QE C value make it particularly sensitive to violations of the conserved vector current hypothesis. The present dominant source of uncertainty in the 11CF t value is the half-life. Purpose: A high-precision measurement of the 11C half-life was performed, and a new world average half-life was calculated. Method: 11C was created by transfer reactions and separated using the TwinSol facility at the Nuclear Science Laboratory at the University of Notre Dame. It was then implanted into a tantalum foil, and β counting was used to determine the half-life. Results: The new half-life, t1 /2=1220.27 (26 ) s, is consistent with the previous values but significantly more precise. A new world average was calculated, t1/2 world=1220.41 (32 ) s, and a new estimate for the Gamow-Teller to Fermi mixing ratio ρ is presented along with standard model correlation parameters. Conclusions: The new 11C world average half-life allows the calculation of a F tmirror value that is now the most precise value for all superallowed mixed mirror transitions. This gives a strong impetus for an experimental determination of ρ , to allow for the determination of Vu d from this decay.

Interspecies scaling: predicting volumes, mean residence time and elimination half-life. Some suggestions.

PubMed

Mahmood, I

1998-05-01

Extrapolation of animal data to assess pharmacokinetic parameters in man is an important tool in drug development. Clearance, volume of distribution and elimination half-life are the three most frequently extrapolated pharmacokinetic parameters. Extensive work has been done to improve the predictive performance of allometric scaling for clearance. In general there is good correlation between body weight and volume, hence volume in man can be predicted with reasonable accuracy from animal data. Besides the volume of distribution in the central compartment (Vc), two other volume terms, the volume of distribution by area (Vbeta) and the volume of distribution at steady state (VdSS), are also extrapolated from animals to man. This report compares the predictive performance of allometric scaling for Vc, Vbeta and VdSS in man from animal data. The relationship between elimination half-life (t(1/2)) and body weight across species results in poor correlation, most probably because of the hybrid nature of this parameter. To predict half-life in man from animal data, an indirect method (CL=VK, where CL=clearance, V is volume and K is elimination rate constant) has been proposed. This report proposes another indirect method which uses the mean residence time (MRT). After establishing that MRT can be predicted across species, it was used to predict half-life using the equation MRT=1.44 x t(1/2). The results of the study indicate that Vc is predicted more accurately than Vbeta and VdSS in man. It should be emphasized that for first-time dosing in man, Vc is a more important pharmacokinetic parameter than Vbeta or VdSS. Furthermore, MRT can be predicted reasonably well for man and can be used for prediction of half-life.

Half-life measurement of the medical radioisotope 177Lu produced from the 176Yb(n,γ) reaction

NASA Astrophysics Data System (ADS)

Ferreira, K. M.; Collins, S. M.; Fenwick, A. J.

2017-09-01

177Lu is a medium energy beta-emitter commonly used in Nuclear Medicine for radiotherapeutic applications. In this work, the half-life of 177Lu has been measured using a re-entrant ionisation chamber over a period of 82 days (approximately 12 half-lives). Unlike the majority of previous studies, the material used in this work was produced via the 176Yb(n,γ)177Yb reaction followed by the β-decay to 177Lu, producing insignificant quantities of 177mLu. This has resulted in the most precise half-life measurement of 177Lu to date. A half-life of 6.6430 (11) days has been determined. This value is in statistical agreement with the currently recommended half-life of 6.6463 (15) days (z-score = 1.8).

Half-life Measurements of Excited Levels in Fission Products around Mass Number 150

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

Kojima, Y., E-mail: kojima.yasuaki@f.mbox.nagoya-u.ac.jp; Shima, Y.; Hayashi, H.

2014-06-15

A spectrometer to measure nuclear level half-lives has been installed at the on-line isotope separator of the Kyoto University Reactor. This spectrometer consists of a LaBr3 scintillator, a thin plastic scintillator and an HPGe detector. Half-lives are deduced using the β-γ-γ delayed coincidence method. The prompt-time distribution curves measured with the spectrometer give a time resolution (FWHM) of 600 ps for 100-keV γ rays. This resolution means that half-lives down to the subnanosecond range or shorter can be measured. We reported recent measurements of the half-life of {sup 149}Pr and {sup 149}Nd. Some of the more interesting results include themore » first determination of the half-lives of {sup 149}Pr levels at 86.5 and 125.6 keV, which are 4.2(5) ns and 1.0(2) ns, respectively. In addition, the data indicate that the half-life of the 270.8-keV level in {sup 149}Nd is not 5.1(3) ns as reported previously, but 0.42(3) ns.« less

Half-life determination for {sup 108}Ag and {sup 110}Ag

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

Zahn, Guilherme S.; Genezini, Frederico A.

2014-11-11

In this work, the half-life of the short-lived silver radionuclides {sup 108}Ag and {sup 110}Ag were measured by following the activity of samples after they were irradiated in the IEA-R1 reactor. The results were then fitted using a non-paralizable dead time correction to the regular exponential decay and the individual half-life values obtained were then analyzed using both the Normalized Residuals and the Rajeval techniques, in order to reach the most exact and precise final values. To check the validity of dead-time correction, a second correction method was also employed by means of counting a long-lived {sup 60}Co radioactive sourcemore » together with the samples as a livetime chronometer. The final half-live values obtained using both dead-time correction methods were in good agreement, showing that the correction was properly assessed. The results obtained are partially compatible with the literature values, but with a lower uncertainty, and allow a discussion on the last ENSDF compilations' values.« less

Half-life of Th232 and the branching ratio of Bi212

USGS Publications Warehouse

Senftle, F.E.; Farley, T.A.; Lazar, N.

1956-01-01

The half-life of Th232 has been calculated by determining an absolute gamma-disintegration rate for Tl208 in equilibrium with Th232 for three old thorium nitrate salts and one natural thorite sample. The branching ratio, ??(??+??), for Bi212, a necessary parameter in the calculation, was also measured. The half-life of Th232 was found to be 1.42??1010 years within an estimated error of 5%, which is essentially in agreement with the presently accepted value. The branching ratio, ??(??+??), of Bi212 was found to be 0.362??0.006, about 7.4% higher than the currently accepted value. ?? 1956 The American Physical Society.

Contribution of amygdalar and lateral hypothalamic neurons to visual information processing of food and nonfood in monkey.

PubMed

Ono, T; Tamura, R; Nishijo, H; Nakamura, K; Tabuchi, E

1989-02-01

Visual information processing was investigated in the inferotemporal cortical (ITCx)-amygdalar (AM)-lateral hypothalamic (LHA) axis which contributes to food-nonfood discrimination. Neuronal activity was recorded from monkey AM and LHA during discrimination of sensory stimuli including sight of food or nonfood. The task had four phases: control, visual, bar press, and ingestion. Of 710 AM neurons tested, 220 (31.0%) responded during visual phase: 48 to only visual stimulation, 13 (1.9%) to visual plus oral sensory stimulation, 142 (20.0%) to multimodal stimulation and 17 (2.4%) to one affectively significant item. Of 669 LHA neurons tested, 106 (15.8%) responded in the visual phase. Of 80 visual-related neurons tested systematically, 33 (41.2%) responded selectively to the sight of any object predicting the availability of reward, and 47 (58.8%) responded nondifferentially to both food and nonfood. Many of AM neuron responses were graded according to the degree of affective significance of sensory stimuli (sensory-affective association), but responses of LHA food responsive neurons did not depend on the kind of reward indicated by the sensory stimuli (stimulus-reinforcement association). Some AM and LHA food responses were modulated by extinction or reversal. Dynamic information processing in ITCx-AM-LHA axis was investigated by reversible deficits of bilateral ITCx or AM by cooling. ITCx cooling suppressed discrimination by vision responding AM neurons (8/17). AM cooling suppressed LHA responses to food (9/22). We suggest deep AM-LHA involvement in food-nonfood discrimination based on AM sensory-affective association and LHA stimulus-reinforcement association.

Measurement of the {sup 214}Po half-life by the DEVIS track setup

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

Belov, V. A.; Brakhman, E. V.; Zeldovich, O. Ya.

2013-04-15

Measurement of the {sup 214}Po half-life with the DEVIS track setup at the Institute of Theoretical and Experimental Physics (ITEP, Moscow) by means of a procedure based on determining lifetimes of individual nuclei is described. The value obtained for the {sup 214}Po half-life is 163.8 {+-} 3.0 Micro-Sign s. The possibility of reaching the accuracy of the measurements that is required for testing the statement that the decay of some nuclei has a nonexponential character and the source intensity necessary for this are discussed.

Pharmacokinetic-based prediction of real-life dosing of extended half-life clotting factor concentrates on hemophilia

PubMed Central

Gherardini, Stefano

2018-01-01

The improvement of clotting factor concentrates (CFCs) has undergone an impressive boost during the last six years. Since 2010, several new recombinant factor (rF)VIII/IX concentrates entered phase I/II/III clinical trials. The improvements are related to the culture of human embryonic kidney (HEK) cells, post-translational glycosylation, PEGylation, and co-expression of the fragment crystallizable (Fc) region of immunoglobulin (Ig)G1 or albumin genes in the manufacturing procedures. The extended half-life (EHL) CFCs allow an increase of the interval between bolus administrations during prophylaxis, a very important advantage for patients with difficulties in venous access. Although the inhibitor risk has not been fully established, phase III studies have provided standard prophylaxis protocols, which, compared with on-demand treatment, have achieved very low annualized bleeding rates (ABRs). The key pharmacokinetics (PK) parameter to tailor patient therapy is clearance, which is more reliable than the half-life of CFCs; the clearance considers the decay rate of the drug concentration–time profile, while the half-life considers only the half concentration of the drug at a given time. To tailor the prophylaxis of hemophilia patients in real-life, we propose two formulae (expressed in terms of the clearance, trough and dose interval between prophylaxis), respectively based on the one- and two-compartmental models (CMs), for the prediction of the optimal single dose of EHL CFCs. Once the data from the time decay of the CFCs are fitted by the one- or two-CMs after an individual PK analysis, such formulae provide to the treater the optimal trade-off among trough and time-intervals between boluses. In this way, a sufficiently long time-interval between bolus administration could be guaranteed for a wider class of patients, with a preassigned level of the trough. Finally, a PK approach using repeated dosing is discussed, and some examples with new EHL CFCs are shown

[beta][sup +] decay and cosmic-ray half-life of [sup 91]Nb

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

Hindi, M.M.; Sur, B.; Wedding, K.L.

1993-06-01

In the laboratory, [sup 91]Nb decays by electron capture with a 680-yr half-life. However, as a high energy cosmic ray, it would be stripped of its atomic electrons and would be able to undergo only [beta][sup +] decay. We produced and chemically purified a sample of [sup 91]Nb and observed its decay with an array of Ge and NaI detectors. By following the [beta][sup +] annihilation radiation, we were able to determine the [beta][sup +] branching ratios of both the 105-keV, 61-d isomer and the ground state of [sup 91]Nb. The ground-state branch is (7.7[plus minus]0.8)[times]10[sup [minus]3]% leading to amore » [beta][sup +] partial half-like of (8.8[plus minus]1.9)[times]10[sup 6] yr. Such a value of the half-life makes [sup 91]Nb a good candidate for determining the confinement time of this secondary component of the cosmic rays.« less

Standardisation and half-life of 89Zr.

PubMed

García-Toraño, E; Peyrés, V; Roteta, M; Mejuto, M; Sánchez-Cabezudo, A; Romero, E

2018-04-01

The nuclide 89 Zr is being tested for the labelling of compounds with long blood circulation times. It decays by beta plus emission (22.8%) and by electron capture (77.2%) to 89 Y. Its half-life has been determined by following the decay rate with two measurement systems; an Ionisation Chamber and an HPGe detector. The combination of six results gives a value of T 1/2 = 78.333 (38) h, slightly lower than the DDEP recommended value of 78.42 (13) h. This radionuclide has also been standardised by liquid scintillation counting, 4πγ counting and coincidence techniques. Copyright © 2017 Elsevier Ltd. All rights reserved.

Half-life of {sup 221}Fr in Si and Au at 4 K and at millikelvin temperatures

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

Wauters, F.; Breitenfeldt, M.; De Leebeeck, V.

2010-12-15

The half-life of the {alpha}-decaying nucleus {sup 221}Fr was determined in different environments, that is, embedded in Si at 4 K, and embedded in Au at 4 K and about 20 mK. No differences in half-life for these different conditions were observed within 0.1%. Furthermore, we quote a value for the absolute half-life of {sup 221}Fr of t{sub 1/2}=286.1(10) s that is of comparable precision to the most precise value available in the literature.

Measurement of the half-life of 79Se with accelerator mass spectrometry

DOE PAGES

Dou, Liang; Jiang, Shan; Wang, Xiao-Bo; ...

2014-10-01

The accelerator mass spectrometry (AMS) is an effective method for the determination of the half-life of long-lived radionuclides. In this paper, we report a method for measurement of the half-life of 79Se. The number of 79Se atoms was determined from measured 79Se/Se absolute ratios with the AMS system at the China Institute of Atomic Energy and the decay rate of 79Se was determined by counting the emitted β-rays with a liquid scintillation spectrometer. The major improvements of our measurements include using the high abundance of an 79Se sample which was cooled for many years to exclude the interference of short-livedmore » nuclides, the extraction of SeO 2 - molecular ions, that results in a suppression of the 79 Br background by as much as about five orders of magnitude. Also, an AMS measurement of the absolute ratio of 79 Se/Se was developed to avoid systematic errors. The results show that 79 Se/Se is (2.35±0.12)×10 -7 in the reference sample and the radioactivity of 79Se is (1.24±0.05) Bq/g, so the half-life of 79Se is (2.78±0.18)×10 5 a.« less

Metabolic half-life of somatostatin and peptidase activities are altered in Alzheimer's disease.

PubMed

Weber, S J; Louis, R B; Trombley, L; Bissette, G; Davies, P; Davis, T P

1992-01-01

Several reports have described decreased immunoreactive somatostatin levels in specific regions of post-mortem brain tissue from patients diagnosed with senile dementia of the Alzheimer type (SDAT). In an attempt to determine if the metabolism of somatostatin is also altered as a result of SDAT, we examined the regional metabolic half-life of somatostatin-28 (SS-28) and somatostatin-14 (SS-14). The activity of the following peptidases was also determined: neutral endopeptidase E.C. 3.4.24.11; metalloendopeptidase E.C. 3.4.24.15; carboxypeptidase E (E.C. 3.4.17.10); and trypsin-like serine protease. The metabolic half-life of SS-28 was significantly reduced in post-mortem Brodmann Area 22 of SDAT tissue. This decrease in SS-28 metabolic half-life was correlated with a significant increase in trypsin-like serine protease activity in the same SDAT brain region. The formation rate of SS-14 from SS-28 incubated with Brodmann Area 22 homogenates was also increased in SDAT tissues as compared to controls. A regional variation in neutral endopeptidase E.C. 3.4.24.11 was also noted in both controls and SDAT samples. Although postmortem intervals of samples varied significantly, no effect was seen on any biochemical parameter measured. Results from this study provide evidence that a correlation can be made between changes in metabolic half-life somatostatin and alterations in neuropeptidase activities due to SDAT. As these data show alterations in both proteolytic metabolism and peptidase activities, many other biologically active peptide substrates could also be affected in SDAT.

A formula for half-life of proton radioactivity

NASA Astrophysics Data System (ADS)

Zhang, Zhi-Xing; Dong, Jian-Min

2018-01-01

We present a formula for proton radioactivity half-lives of spherical proton emitters with the inclusion of the spectroscopic factor. The coefficients in the formula are calibrated with the available experimental data. As an input to calculate the half-life, the spectroscopic factor that characterizes the important information on nuclear structure should be obtained with a nuclear many-body approach. This formula is found to work quite well, and in better agreement with experimental measurements than other theoretical models. Therefore, it can be used as a powerful tool in the investigation of proton emission, in particular for experimentalists. Supported by National Natural Science Foundation of China (11435014, 11405223, 11675265, 11575112), the 973 Program of China (2013CB834401, 2013CB834405), National Key Program for S&T Research and Development (2016YFA0400501), the Knowledge Innovation Project (KJCX2-EW-N01) of Chinese Academy of Sciences, the Funds for Creative Research Groups of China (11321064) and the Youth Innovation Promotion Association of Chinese Academy of Sciences

Half-life and magnetic moment of the first excited state in {sup 132}I

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

Tanigaki, M.; Ohkubo, Y.; Izumi, S.

2009-09-15

The half-life and the magnetic moment were measured for the first excited state in {sup 132}I, of which the inconsistent results on the half-life have been reported by several other groups. This time, measurements were performed on {sup 132}I obtained as a decay product of a {sup 132}Te radioactive beam from the ion guide at Tohoku University. The half-life of this level was determined to be T{sub 1/2}=1.120{+-}0.015 ns using a conventional coincidence technique with a pair of BaF{sub 2} detectors. The time-differential perturbed angular correlation technique was successfully applied to the first excited state in {sup 132}I implanted intomore » nickel foils. The magnetic moment of this state was determined to be {mu}=+(2.06{+-}0.18){mu}{sub N}. The present results are consistent with values reported by Gorodetzky et al. and Singh et al.« less

Anxiety Trajectories in the Second Half of Life: Genetic and Environmental Contributions over Age

PubMed Central

Lee, Lewina O.; Gatz, Margaret; Pedersen, Nancy L.; Prescott, Carol A.

2015-01-01

Clinically significant anxiety symptoms are prevalent among the elderly, yet knowledge about the longitudinal course of anxiety symptoms in later life remains scarce. The goals of this study were to (1) characterize age trajectories of state anxiety symptoms in the second half of life, and (2) estimate genetic and environmental contributions to individual differences in the age trajectory of state anxiety. This study was based on data from 1,482 participants in the Swedish Adoption/Twin Study of Aging who were aged 50 and older at their first occasion (512 complete twin pairs, 458 singletons) and had up to six measurement occasions spanning 11 years. Consistent with lifespan developmental theories of age-related emotional change, anxiety symptom levels declined during the transition from midlife to the mid −60s, followed by a mild increase that gradually plateaued in the 80s. There were substantial individual differences in the age trajectory of anxiety. After accounting for effects of sex, cohort, mode of testing and proximity to death, this longitudinal variation was partitioned into biometric sources. Nonshared environmental variance was highest in the late 60s and declined thereafter, whereas genetic variance increased at an accelerated pace from approximately age 60 onward. There was no evidence for effects of rearing or other shared environment on anxiety symptoms in later life. These findings highlight how the etiology of anxiety symptoms changes from midlife to old age. PMID:26751006

All half-lives are wrong, but some half-lives are useful.

PubMed

Wright, J G; Boddy, A V

2001-01-01

The half-life of a drug, which expresses a change in concentration in units of time, is perhaps the most easily understood pharmacokinetic parameter and provides a succinct description of many concentration-time profiles. The calculation of a half-life implies a linear, first-order, time-invariant process. No drug perfectly obeys such assumptions, although in practise this is often a valid approximation and provides invaluable quantitative information. Nevertheless, the physiological processes underlying half-life should not be forgotten. The concept of clearance facilitates the interpretation of factors affecting drug elimination, such as enzyme inhibition or renal impairment. Relating clearance to the observed concentration-time profile is not as naturally intuitive as is the case with half-life. As such, these 2 approaches to parameterising a linear pharmacokinetic model should be viewed as complementary rather than alternatives. The interpretation of pharmacokinetic parameters when there are multiple disposition phases is more challenging. Indeed, in any pharmacokinetic model, the half-lives are only one component of the parameters required to specify the concentration-time profile. Furthermore, pharmacokinetic parameters are of little use without a dose history. Other factors influencing the relevance of each disposition phase to clinical end-points must also be considered. In summarising the pharmacokinetics of a drug, statistical aspects of the estimation of a half-life are often overlooked. Half-lives are rarely reported with confidence intervals or measures of variability in the population, and some approaches to this problem are suggested. Half-life is an important summary statistic in pharmacokinetics, but care must be taken to employ it appropriately in the context of dose history and clinically relevant pharmacodynamic end-points.

High-Precision Half-Life Measurement for the Superallowed β+ Emitter Alm26

NASA Astrophysics Data System (ADS)

Finlay, P.; Ettenauer, S.; Ball, G. C.; Leslie, J. R.; Svensson, C. E.; Andreoiu, C.; Austin, R. A. E.; Bandyopadhyay, D.; Cross, D. S.; Demand, G.; Djongolov, M.; Garrett, P. E.; Green, K. L.; Grinyer, G. F.; Hackman, G.; Leach, K. G.; Pearson, C. J.; Phillips, A. A.; Sumithrarachchi, C. S.; Triambak, S.; Williams, S. J.

2011-01-01

A high-precision half-life measurement for the superallowed β+ emitter Alm26 was performed at the TRIUMF-ISAC radioactive ion beam facility yielding T1/2=6346.54±0.46stat±0.60systms, consistent with, but 2.5 times more precise than, the previous world average. The Alm26 half-life and ft value, 3037.53(61) s, are now the most precisely determined for any superallowed β decay. Combined with recent theoretical corrections for isospin-symmetry-breaking and radiative effects, the corrected Ft value for Alm26, 3073.0(12) s, sets a new benchmark for the high-precision superallowed Fermi β-decay studies used to test the conserved vector current hypothesis and determine the Vud element of the Cabibbo-Kobayashi-Maskawa quark mixing matrix.

Half-life of the electron-capture decay of {sup 97}Ru: Precision measurement shows no temperature dependence

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

Goodwin, J. R.; Golovko, V. V.; Iacob, V. E.

2009-10-15

We have measured the half-life of the electron-capture (ec) decay of {sup 97}Ru in a metallic environment, both at low temperature (19 K), and also at room temperature. We find the half-lives at both temperatures to be the same within 0.1%. This demonstrates that a recent claim that the ec decay half-life for {sup 7}Be changes by 0.9%{+-}0.2% under similar circumstances certainly cannot be generalized to other ec decays. Our results for the half-life of {sup 97}Ru, 2.8370(14) d at room temperature and 2.8382(14) d at 19 K, are consistent with, but much more precise than, previous room-temperature measurements. Inmore » addition, we have also measured the half-lives of the {beta}{sup -}-emitters {sup 103}Ru and {sup 105}Rh at both temperatures, and found them also to be unchanged.« less

The Use of Gene Ontology Term and KEGG Pathway Enrichment for Analysis of Drug Half-Life

PubMed Central

Chen, Lei; Lu, Jing; Kong, XiangYin; Huang, Tao; Li, HaiPeng

2016-01-01

A drug’s biological half-life is defined as the time required for the human body to metabolize or eliminate 50% of the initial drug dosage. Correctly measuring the half-life of a given drug is helpful for the safe and accurate usage of the drug. In this study, we investigated which gene ontology (GO) terms and biological pathways were highly related to the determination of drug half-life. The investigated drugs, with known half-lives, were analyzed based on their enrichment scores for associated GO terms and KEGG pathways. These scores indicate which GO terms or KEGG pathways the drug targets. The feature selection method, minimum redundancy maximum relevance, was used to analyze these GO terms and KEGG pathways and to identify important GO terms and pathways, such as sodium-independent organic anion transmembrane transporter activity (GO:0015347), monoamine transmembrane transporter activity (GO:0008504), negative regulation of synaptic transmission (GO:0050805), neuroactive ligand-receptor interaction (hsa04080), serotonergic synapse (hsa04726), and linoleic acid metabolism (hsa00591), among others. This analysis confirmed our results and may show evidence for a new method in studying drug half-lives and building effective computational methods for the prediction of drug half-lives. PMID:27780226

The Next Big Thing We Won't Be Able to Live Without? Fulbright's Half-Life Theory Gives Us Some Ideas

ERIC Educational Resources Information Center

Fulbright, Ron

2015-01-01

My great-grandparents lived one-half of their lives without electricity. My grandparents lived one-half of their lives without a telephone. My parents lived one-half of their lives without a television. My sister has lived one-half of her life without a computer and I have lived one-half of my life without Google. Today, we could not imagine life…

Ubiquitin-fusion as a strategy to modulate protein half-life: A3G antiviral activity revisited

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

Cadima-Couto, Iris; Freitas-Vieira, Acilino; Instituto de Medicina Molecular, Lisboa

2009-10-25

The human APOBEC3G (A3G) is a potent inhibitor of HIV-1 replication and its activity is suppressed by HIV-1 virion infectivity factor (Vif). Vif neutralizes A3G mainly by inducing its degradation in the proteasome and blocking its incorporation into HIV-1 virions. Assessing the time needed for A3G incorporation into virions is, therefore, important to determine how quickly Vif must act to induce its degradation. We show that modelling the intracellular half-life of A3G can induce its Vif-independent targeting to the ubiquitin-proteasome system. By using various amino acids (X) in a cleavable ubiquitin-X-A3G fusion, we demonstrate that the half-life (t1/2) of X-A3Gmore » can be manipulated. We show that A3G molecules with a half-life of 13 min are incorporated into virions, whereas those with a half-life shorter than 5 min were not. The amount of X-A3G incorporated into virions increases from 13 min (Phe-A3G) to 85 min (Asn-A3G) and remains constant after this time period. Interestingly, despite the presence of similar levels of Arg-A3G (t1/2 = 28 min) and Asp-A3G (t1/2 = 65 min) into HIV-1 DELTAvif virions, inhibition of viral infectivity was only evident in the presence of A3G proteins with a longer half-life (t1/2 >= 65 min).« less

Predicting the impacts of climate change on the potential distribution of major native non-food bioenergy plants in China.

PubMed

Wang, Wenguo; Tang, Xiaoyu; Zhu, Qili; Pan, Ke; Hu, Qichun; He, Mingxiong; Li, Jiatang

2014-01-01

Planting non-food bioenergy crops on marginal lands is an alternative bioenergy development solution in China. Native non-food bioenergy plants are also considered to be a wise choice to reduce the threat of invasive plants. In this study, the impacts of climate change (a consensus of IPCC scenarios A2a for 2080) on the potential distribution of nine non-food bioenergy plants native to China (viz., Pistacia chinensis, Cornus wilsoniana, Xanthoceras sorbifolia, Vernicia fordii, Sapium sebiferum, Miscanthus sinensis, M. floridulus, M. sacchariflorus and Arundo donax) were analyzed using a MaxEnt species distribution model. The suitable habitats of the nine non-food plants were distributed in the regions east of the Mongolian Plateau and the Tibetan Plateau, where the arable land is primarily used for food production. Thus, the large-scale cultivation of those plants for energy production will have to rely on the marginal lands. The variables of "precipitation of the warmest quarter" and "annual mean temperature" were the most important bioclimatic variables for most of the nine plants according to the MaxEnt modeling results. Global warming in coming decades may result in a decrease in the extent of suitable habitat in the tropics but will have little effect on the total distribution area of each plant. The results indicated that it will be possible to grow these plants on marginal lands within these areas in the future. This work should be beneficial for the domestication and cultivation of those bioenergy plants and should facilitate land-use planning for bioenergy crops in China.

Predicting the Impacts of Climate Change on the Potential Distribution of Major Native Non-Food Bioenergy Plants in China

PubMed Central

Wang, Wenguo; Tang, Xiaoyu; Zhu, Qili; Pan, Ke; Hu, Qichun; He, Mingxiong; Li, Jiatang

2014-01-01

Planting non-food bioenergy crops on marginal lands is an alternative bioenergy development solution in China. Native non-food bioenergy plants are also considered to be a wise choice to reduce the threat of invasive plants. In this study, the impacts of climate change (a consensus of IPCC scenarios A2a for 2080) on the potential distribution of nine non-food bioenergy plants native to China (viz., Pistacia chinensis, Cornus wilsoniana, Xanthoceras sorbifolia, Vernicia fordii, Sapium sebiferum, Miscanthus sinensis, M. floridulus, M. sacchariflorus and Arundo donax) were analyzed using a MaxEnt species distribution model. The suitable habitats of the nine non-food plants were distributed in the regions east of the Mongolian Plateau and the Tibetan Plateau, where the arable land is primarily used for food production. Thus, the large-scale cultivation of those plants for energy production will have to rely on the marginal lands. The variables of “precipitation of the warmest quarter” and “annual mean temperature” were the most important bioclimatic variables for most of the nine plants according to the MaxEnt modeling results. Global warming in coming decades may result in a decrease in the extent of suitable habitat in the tropics but will have little effect on the total distribution area of each plant. The results indicated that it will be possible to grow these plants on marginal lands within these areas in the future. This work should be beneficial for the domestication and cultivation of those bioenergy plants and should facilitate land-use planning for bioenergy crops in China. PMID:25365425

Measurement of the half-life of {sup 198}Au in a nonmetal: High-precision measurement shows no host-material dependence

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

Goodwin, J. R.; Nica, N.; Iacob, V. E.

2010-10-15

We have measured the half-life of the {beta}{sup -} decay of {sup 198}Au to be 2.6948(9) d, with the nuclide sited in an insulating environment. Comparing this result with the half-life we measured previously with a metallic environment, we find the half-lives in both environments to be the same within 0.04%, thus contradicting a prediction that screening from a ''plasma'' of quasifree electrons in a metal increases the half-life by as much as 7%.

Persistence and Effective Half-Life of Chemical Warfare Agent VX on Grass Foliage

DTIC Science & Technology

2017-08-01

obtain results applicable to VX- contaminated battlefields. The Effective Half-Life of VX on grass foliage was determined as the net effect of factors...Soldiers on VX- contaminated battlefields. 15. SUBJECT TERMS Chemical warfare agent (CWA) Agent–plant Echinochloa crus-galli Foliage Effective Half...The use of either trade or manufacturers ’ names in this report does not constitute an official endorsement of any commercial products. This report may

High-precision half-life measurements of the T =1 /2 mirror β decays 17F and 33Cl

NASA Astrophysics Data System (ADS)

Grinyer, J.; Grinyer, G. F.; Babo, M.; Bouzomita, H.; Chauveau, P.; Delahaye, P.; Dubois, M.; Frigot, R.; Jardin, P.; Leboucher, C.; Maunoury, L.; Seiffert, C.; Thomas, J. C.; Traykov, E.

2015-10-01

Background: Measurements of the f t values for T =1 /2 mirror β+ decays offer a method to test the conserved vector current hypothesis and to determine Vud, the up-down matrix element of the Cabibbo-Kobayashi-Maskawa matrix. In most mirror decays used for these tests, uncertainties in the f t values are dominated by the uncertainties in the half-lives. Purpose: Two precision half-life measurements were performed for the T =1 /2 β+ emitters, 17F and 33Cl, in order to eliminate the half-life as the leading source of uncertainty in their f t values. Method: Half-lives of 17F and 33Cl were determined using β counting of implanted radioactive ion beam samples on a moving tape transport system at the Système de Production d'Ions Radioactifs Accélérés en Ligne low-energy identification station at the Grand Accélérateur National d'Ions Lourds. Results: The 17F half-life result, 64.347 (35) s, precise to ±0.05 % , is a factor of 5 times more precise than the previous world average. The half-life of 33Cl was determined to be 2.5038 (22) s. The current precision of ±0.09 % is nearly 2 times more precise compared to the previous world average. Conclusions: The precision achieved during the present measurements implies that the half-life no longer dominates the uncertainty of the f t values for both T =1 /2 mirror decays 17F and 33Cl.

9 CFR 314.9 - Specimens for educational, research, and other nonfood purposes; permits for, required.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Specimens for educational, research, and other nonfood purposes; permits for, required. 314.9 Section 314.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY...

9 CFR 314.9 - Specimens for educational, research, and other nonfood purposes; permits for, required.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Specimens for educational, research, and other nonfood purposes; permits for, required. 314.9 Section 314.9 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY...

Quantification of 60Fe atoms by MC-ICP-MS for the redetermination of the half-life.

PubMed

Kivel, Niko; Schumann, Dorothea; Günther-Leopold, Ines

2013-03-01

In many scientific fields, the half-life of radionuclides plays an important role. The accurate knowledge of this parameter has direct impact on, e.g., age determination of archeological artifacts and of the elemental synthesis in the universe. In order to derive the half-life of a long-lived radionuclide, the activity and the absolute number of atoms have to be analyzed. Whereas conventional radiation measurement methods are typically applied for activity determinations, the latter can be determined with high accuracy by mass spectrometric techniques. Over the past years, the half-lives of several radionuclides have been specified by means of multiple-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) complementary to the earlier reported values mainly derived by accelerator mass spectrometry. The present paper discusses all critical aspects (amount of material, radiochemical sample preparation, interference correction, isotope dilution mass spectrometry, calculation of measurement uncertainty) for a precise analysis of the number of atoms by MC-ICP-MS exemplified for the recently published half-life determination of 60Fe (Rugel et al, Phys Rev Lett 103:072502, 2009).

High-Precision Half-life Measurements for the Superallowed β+ Emitter 14O

NASA Astrophysics Data System (ADS)

Laffoley, A. T.; Svensson, C. E.; Andreoiu, C.; Austin, R. A. E.; Ball, G. C.; Blank, B.; Bouzomita, H.; Cross, D. S.; Diaz Varela, A.; Dunlop, R.; Finlay, P.; Garnsworthy, A. B.; Garrett, P. E.; Giovinazzo, J.; Grinyer, G. F.; Hackman, G.; Hadinia, B.; Jamieson, D. S.; Ketelhut, S.; Leach, K. G.; Leslie, J. R.; Tardiff, E. R.; Thomas, J. C.; Unsworth, C.

2014-03-01

The half-life of 14O, a superallowed Fermi β+ emitter, has been determined via simultaneous γ and β counting experiments at TRIUMF's Isotope Separator and Accelerator facility. Following the implantation of 14O samples at the center of the 8π spectrometer, a γ counting measurement was performed by detecting the 2313 keV γ-rays emitted from the first excited state of the daughter 14N using 20 high-purity germanium (HPGe) detectors. A simultaneous β counting experiment was performed using a fast plastic scintillator positioned directly behind the implantation site. The results, T½(γ) = 70:632 ± 0:094 s and T½(β) = 70:610 ± 0:030 s, are consistent with one another and, together with eight previous measurements, establish a new average for the 14O half-life of T½ = 70:619 ± 0:011 s with a reduced χ2 of 0.99.

A New Method to Determine the Half-Life for Penicillin Using Microcalorimeter

NASA Astrophysics Data System (ADS)

Li, Z. X.; Zhao, W. W.

2015-01-01

The dissolution process of penicillin in normal saline and isotonic glucose solution was reported using a microcalorimeter. Both the integral and differential heats of solution were measured. The quantitative relationships between the amount of heat released and the quantity of dissolved penicillin were established. Meanwhile, the kinetics and the half-life of the dissolution processes as well as the enthalpy of solution, the entropy of dissolution, and the free energy of dissolution were determined. The results showed that a change of the solvent from normal saline to isotonic glucose solution had little effect on the half-life of penicillin in the dissolution process, and there was no significant difference between the stabilities of penicillin in isotonic glucose solution and normal saline. Moreover, the dissolution process of penicillin in isotonic glucose solution followed the first-order kinetics. These results could provide a theoretical basis for the clinical applications of penicillin.

Predictors of 25(OH)D half-life and plasma 25(OH)D concentration in The Gambia and the UK.

PubMed

Jones, K S; Assar, S; Vanderschueren, D; Bouillon, R; Prentice, A; Schoenmakers, I

2015-03-01

Predictors of 25(OH)D3 half-life were factors associated with vitamin D metabolism, but were different between people in The Gambia and the UK. Country was the strongest predictor of plasma 25(OH)D concentration, probably as a marker of UVB exposure. 25(OH)D3 half-life may be applied as a tool to investigate vitamin D expenditure. The aim of this study was to investigate predictors of 25(OH)D3 half-life and plasma 25(OH)D concentration. Plasma half-life of an oral tracer dose of deuterated-25(OH)D3 was measured in healthy men aged 24-39 years, resident in The Gambia, West Africa (n = 18) and in the UK during the winter (n = 18), countries that differ in calcium intake and vitamin D status. Plasma and urinary markers of vitamin D, calcium, phosphate and bone metabolism, nutrient intakes and anthropometry were measured. Normally distributed data are presented as mean (SD) and non-normal data as geometric mean (95% CI). Gambian compared to UK men had higher plasma concentrations of 25(OH)D (69 (13) vs. 29 (11) nmol/L; P < 0.0001); 1,25(OH)2D (181 (165, 197) vs. 120 (109, 132) pmol/L; P < 0.01); and parathyroid hormone (PTH) (50 (42, 60) vs. 33 (27, 39); P < 0.0001). There was no difference in 25(OH)D3 half-life (14.7 (3.5) days vs. 15.6 (2.5) days) between countries (P = 0.2). In multivariate analyses, 25(OH)D, 1,25(OH)2D, vitamin D binding protein and albumin-adjusted calcium (Caalb) explained 79% of variance in 25(OH)D3 half-life in Gambians, but no significant predictors were found in UK participants. For the countries combined, Caalb, PTH and plasma phosphate explained 39 % of half-life variability. 1,25(OH)2D, weight, PTH and country explained 81% of variability in 25(OH)D concentration; however, country alone explained 74%. Factors known to affect 25(OH)D metabolism predict 25(OH)D3 half-life, but these differed between countries. Country predicted 25(OH)D, probably as a proxy measure for UVB exposure and vitamin D supply. This study supports the use of 25(OH

Half life of chromium in serum and urine in a former plasma cutter of stainless steel

PubMed Central

Petersen, R.; Thomsen, J. F.; Jorgensen, N. K.; Mikkelsen, S.

2000-01-01

For 8 years chromium in serum and urine has been followed up in a former plasma cutter of stainless steel who was exposed to airborne dust and fumes containing chromium during this work. After the first examination for serum chromium the exposure ended. Serum chromium concentration has been measured seven times during the period and was initially very high and has subsequently dropped slowly. The half life was 40 months in serum. Urinary chromium has been measured five times. The half life was 129 months in urine. The study shows that exposure to airborne dust and fumes containing chromium may cause accumulation of chromium in the body, and that when exposure ends, elimination of chromium is very slow. Previous studies suggest that chromium mainly accumulates in the lungs.


Keywords: chromium half life; plasma cutting; stainless steel PMID:10711283

Determination of photon emission probability for the main gamma ray and half-life measurements of 64Cu.

PubMed

Pibida, L; Zimmerman, B; Bergeron, D E; Fitzgerald, R; Cessna, J T; King, L

2017-11-01

The National Institute of Standards and Technology (NIST) performed new standardization measurements for 64 Cu. As part of this work the photon emission probability for the main gamma-ray line and the half-life were determined using several high-purity germanium (HPGe) detectors. Half-life determinations were also carried out with a NaI(Tl) well counter and two pressurized ionization chambers. Published by Elsevier Ltd.

High-precision half-life and branching-ratio measurements for superallowed Fermi β+ emitters at TRIUMF - ISAC

NASA Astrophysics Data System (ADS)

Laffoley, A. T.; Dunlop, R.; Finlay, P.; Grinyer, G. F.; Andreoiu, C.; Austin, R. A. E.; Ball, G. C.; Bandyopadhyay, D.; Blank, B.; Bouzomita, H.; Chagnon-Lessard, S.; Chester, A.; Cross, D. S.; Demand, G.; Diaz Varela, A.; Djongolov, M.; Ettenauer, S.; Garnsworthy, A. B.; Garrett, P. E.; Giovinazzo, J.; Glister, J.; Green, K. L.; Hackman, G.; Hadinia, B.; Jamieson, D. S.; Ketelhut, S.; Leach, K. G.; Leslie, J. R.; Pearson, C. J.; Phillips, A. A.; Rand, E. T.; Starosta, K.; Sumithrarachchi, C. S.; Svensson, C. E.; Tardiff, E. R.; Thomas, J. C.; Towner, I. S.; Triambak, S.; Unsworth, C.; Williams, S. J.; Wong, J.; Yates, S. W.; Zganjar, E. F.

2014-03-01

A program of high-precision half-life and branching-ratio measurements for superallowed Fermi β emitters is being carried out at TRIUMF's Isotope Separator and Accelerator (ISAC) radioactive ion beam facility. Recent half-life measurements for the superallowed decays of 14O, 18Ne, and 26Alm, as well as branching-ratio measurements for 26Alm and 74Rb are reported. These results provide demanding tests of the Standard Model and the theoretical isospin symmetry breaking (ISB) corrections in superallowed Fermi β decays.

Measurement of the BB Decay Half-Life of 130Te with the NEMO-3 Detector

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

A. J. Caffrey

2011-08-01

We report results from the NEMO-3 experiment based on an exposure of 1275 days with 661 g of 130Te in the form of enriched and natural tellurium foils. The double B decay rate of 130Te is found to be greater than zero with a significance of 7.7 standard deviations and the half-life is measured to be T2v 1/2 = [7.0 +/- 0.9(stat) +/- 1.1 (syst)] x 10{sup 20} yr. This represents the most precise measurement of this half-life yet published and the first real-time observation of this decay.

Incorporation of Half-Cycle Theory Into Ko Aging Theory for Aerostructural Flight-Life Predictions

NASA Technical Reports Server (NTRS)

Ko, William L.; Tran, Van T.; Chen, Tony

2007-01-01

The half-cycle crack growth theory was incorporated into the Ko closed-form aging theory to improve accuracy in the predictions of operational flight life of failure-critical aerostructural components. A new crack growth computer program was written for reading the maximum and minimum loads of each half-cycle from the random loading spectra for crack growth calculations and generation of in-flight crack growth curves. The unified theories were then applied to calculate the number of flights (operational life) permitted for B-52B pylon hooks and Pegasus adapter pylon hooks to carry the Hyper-X launching vehicle that air launches the X-43 Hyper-X research vehicle. A crack growth curve for each hook was generated for visual observation of the crack growth behavior during the entire air-launching or captive flight. It was found that taxiing and the takeoff run induced a major portion of the total crack growth per flight. The operational life theory presented can be applied to estimate the service life of any failure-critical structural components.

Work Dissatisfaction and Sleep Problems among Canadians in the Latter Half of Life.

PubMed

Brown, Kyla; Bierman, Alex

2017-09-01

This study examined the relationship between work dissatisfaction and sleep problems among Canadian adults in the latter half of life, as well as how gender and social contact moderate this relationship. Data were obtained from the Canadian General Social Survey, Cycle 21 (2007), which sampled adults aged 45 and older in 2007. Analyses focused on individuals with employment as their main activity. Analyses show that work dissatisfaction positively predicts trouble sleeping. There are no significant gender differences in this relationship. Social contact with friends buffers this relationship, but social contact with family does not, and buffering does not vary significantly between men and women. This research contributes to knowledge on sleep problems by showing that work dissatisfaction is adversely associated with sleep problems among Canadians in the latter half of life, but social contact with friends can weaken this deleterious relationship.

Lexical-semantic deficits in processing food and non-food items.

PubMed

Rumiati, Raffaella I; Foroni, Francesco; Pergola, Giulio; Rossi, Paola; Silveri, Maria Caterina

2016-12-01

The study of category specific deficits in brain-damaged patients has been instrumental in explaining how knowledge about different types of objects is organized in the brain. Much of this research focused on testing putative semantic sensory/functional subsystems that could explain the observed dissociations in performance between living things (e.g., animals and fruits/vegetables) and non-living things (e.g., tools). As neuropsychological patterns that did not fit the original living/non-living distinction were observed, an alternative organization of semantic memory in domains constrained by evolutionary pressure was hypothesized. However, the category of food, that contains both living-natural items, such as an apple, and nonliving-manufactured items as in the case of a hamburger, has never been systematically investigated. As such, food category could turn out to be very useful to test whether the brain organizes the knowledge about food in sensory/functional subsystems, in a specific domain, or whether both approaches might need to be integrated. In the present study we tested the ability of patients with Alzheimer dementia (AD) and with Primary Progressive Aphasias (PPA) as well as healthy controls to perform a confrontation naming task, a categorization task, and a comprehension of edible (natural and manufactured food) and non edible items (tools and non-edible natural things) task (Tasks 1-3). The same photographs of natural and manufactured food were presented together with a description of food's sensory or functional property that could be either congruent or incongruent with that particular food (Task 4). Patients were overall less accurate than healthy individuals, and PPA patients were generally more impaired than AD patients, especially on the naming task. Food tended to be processed better than non-food in two out of three tasks (categorization and comprehension tasks). Patient groups showed no difference in naming food and non-food items, while

Estimates of the half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Vietnam veterans of operation ranch hand

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

Pirkle, J.L.; Wolfe, W.H.; Patterson, D.G.

1989-01-01

A half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD; commonly known as dioxin) in serum has been measured in 36 Air Force Vietnam Veterans of Operation Ranch Hand, which was the operation that aerially sprayed the herbicide Agent Orange in Vietnam. From serum specimens taken in 1982 and 1987, the median half-life of 2,3,7,8-TCDD in these Ranch Hand veterans was found to be 7.1 yr (95% confidence interval about the median of 5.8-9.6 yr). These veterans reported no civilian exposure to dioxin or herbicides. Concentrations of 2,3,7,8-TCDD in the 1982 serum specimens from these veterans ranged from 16.9 to 423 parts per trillion onmore » a lipid weight basis. The half-life estimates were not associated with the concentration of 2,3,7,8-TCDD in the 1982 serum specimens. This half-life of 7.1 yr is much longer than the half-life of 2,3,7,8-TCDD reported in animals but is consistent with recent evidence from other human exposures to 2,3,7,8-TCDD.« less

Heart rate reactivity associated to positive and negative food and non-food visual stimuli.

PubMed

Kuoppa, Pekka; Tarvainen, Mika P; Karhunen, Leila; Narvainen, Johanna

2016-08-01

Using food as a stimuli is known to cause multiple psychophysiological reactions. Heart rate variability (HRV) is common tool for assessing physiological reactions in autonomic nervous system. However, the findings in HRV related to food stimuli have not been consistent. In this paper the quick changes in HRV related to positive and negative food and non-food visual stimuli are investigated. Electrocardiogram (ECG) was measured from 18 healthy females while being stimulated with the pictures. Subjects also filled Three-Factor Eating Questionnaire to determine their eating behavior. The inter-beat-interval time series and the HRV parameters were extracted from the ECG. The quick change in HRV parameters were studied by calculating the change from baseline value (10 s window before stimulus) to value after the onset of the stimulus (10 s window during stimulus). The paired t-test showed significant difference between positive and negative food pictures but not between positive and negative non-food pictures. All the HRV parameters decreased for positive food pictures while they stayed the same or increased a little for negative food pictures. The eating behavior characteristic cognitive restraint was negatively correlated with HRV parameters that describe decreasing of heart rate.

New isomer and decay half-life of {sup 115}Ru

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

Kurpeta, J.; Plochocki, A.; Rissanen, J.

2010-12-15

Exotic, neutron-rich nuclei of mass A=115 produced in proton-induced fission of {sup 238}U were extracted using the IGISOL mass separator. The beam of isobars was transferred to the JYFLTRAP Penning trap system for further separation to the isotopic level. Monoisotopic samples of {sup 115}Ru nuclei were used for {gamma}and {beta} coincidence spectroscopy. In {sup 115}Ru we have observed excited levels, including an isomer with a half-life of 76(6) ms and (7/2{sup -}) spin and parity. The first excited 61.7-keV level in {sup 115}Ru with spins and parity (3/2{sup +}) may correspond to an oblate 3/2{sup +}[431] Nilsson orbital. A half-lifemore » of 318(19) ms for the {beta}{sup -} decay of the (1/2{sup +}) ground state in {sup 115}Ru has been firmly established in two independent measurements, a value which is significantly shorter than that previously reported.« less

Improved half-life determination and β-delayed γ-ray spectroscopy for 18Ne decay

NASA Astrophysics Data System (ADS)

Grinyer, G. F.; Ball, G. C.; Bouzomita, H.; Ettenauer, S.; Finlay, P.; Garnsworthy, A. B.; Garrett, P. E.; Green, K. L.; Hackman, G.; Leslie, J. R.; Pearson, C. J.; Rand, E. T.; Sumithrarachchi, C. S.; Svensson, C. E.; Thomas, J. C.; Triambak, S.; Williams, S. J.

2013-04-01

The half-life of the superallowed Fermi β+ emitter 18Ne has been determined to ±0.07% precision by counting 1042 keV delayed γ rays that follow approximately 8% of all β decays. The deduced half-life, T1/2=1.6648(11) s, includes a 0.7% correction that accounts for systematic losses associated with rate-dependent detector pulse pileup that was determined using a recently developed γ-ray photopeak-counting technique. This result is a factor of two times more precise than, and in excellent agreement with, a previous lower-statistics measurement that employed the same experimental setup. High-resolution β-delayed γ-ray spectroscopy results for the relative γ-ray intensities and β-decay branching ratios to excited states in the daughter 18F are also presented.

High-precision half-life measurements for the superallowed Fermi β+ emitter 14O

NASA Astrophysics Data System (ADS)

Laffoley, A. T.; Svensson, C. E.; Andreoiu, C.; Austin, R. A. E.; Ball, G. C.; Blank, B.; Bouzomita, H.; Cross, D. S.; Diaz Varela, A.; Dunlop, R.; Finlay, P.; Garnsworthy, A. B.; Garrett, P. E.; Giovinazzo, J.; Grinyer, G. F.; Hackman, G.; Hadinia, B.; Jamieson, D. S.; Ketelhut, S.; Leach, K. G.; Leslie, J. R.; Tardiff, E.; Thomas, J. C.; Unsworth, C.

2013-07-01

The half-life of the superallowed Fermi β+ emitter 14O has been determined via simultaneous direct β and γ counting experiments at TRIUMF's Isotope Separator and Accelerator (ISAC) facility. A γ-ray counting measurement was performed by detecting the 2312.6-keV γ rays emitted from an excited state of the daughter 14N following the implantation of samples at the center of the 8π γ-ray spectrometer, a spherical array of 20 high-purity germanium (HPGe) detectors. A simultaneous β counting experiment was performed using a fast plastic scintillator positioned behind the implantation site with a solid angle coverage of ˜20%. The results, T1/2(β)=70.610±0.030s and T1/2(γ)=70.632±0.094s, form a consistent set and, together with eight previous measurements, establish a new average for the 14O half-life of T1/2=70.619±0.011s with a reduced χ2 of 0.99.

Hour Glass Half-Full or Half-Empty? Future Time Perspective and Preoccupation with Negative Events Across the Life Span

PubMed Central

Strough, JoNell; de Bruin, Wändi Bruine; Parker, Andrew M.; Lemaster, Philip; Pichayayothin, Nipat; Delaney, Rebecca

2016-01-01

According to socioemotional selectivity theory, older adults' emotional well-being stems from having limited future time perspective that motivates them to maximize well-being in the “here and now.” Presumably, then, older adults' time horizons are associated with emotional competencies that boost positive affect and dampen negative affect, but little research has addressed this. Using a US national adult life-span sample (N= 3,933, 18-93 yrs), we found that a two-factor model of future time perspective (focus on future opportunities; focus on limited time) fit the data better than a one-factor model. Through middle age, people perceived the life-span hourglass as half full—they focused more on future opportunities than limited time. Around age 60, the balance changed to increasingly perceiving the life-span hourglass as half empty—they focused less on future opportunities and more on limited time. This pattern held even after accounting for perceived health, self-reported decision-making ability, and retirement status. At all ages, women's time horizons focused more on future opportunities compared to men's, and men's focused more on limited time. Focusing on future opportunities was associated with reporting less preoccupation with negative events, whereas focusing on limited time was associated with reporting more preoccupation. Older adults reported less preoccupation with negative events and this association was stronger after controlling for their perceptions of limited time and fewer future opportunities, suggesting that other pathways may explain older adults' reports of their ability to disengage from negative events. Insights gained and questions raised by measuring future time perspective as two dimensions are discussed. PMID:27267222

Hour glass half full or half empty? Future time perspective and preoccupation with negative events across the life span.

PubMed

Strough, JoNell; Bruine de Bruin, Wändi; Parker, Andrew M; Lemaster, Philip; Pichayayothin, Nipat; Delaney, Rebecca

2016-09-01

According to socioemotional selectivity theory, older adults' emotional well-being stems from having a limited future time perspective that motivates them to maximize well-being in the "here and now." Presumably, then, older adults' time horizons are associated with emotional competencies that boost positive affect and dampen negative affect, but little research has addressed this. Using a U.S. adult life-span sample (N = 3,933; 18-93 years), we found that a 2-factor model of future time perspective (future opportunities; limited time) fit the data better than a 1-factor model. Through middle age, people perceived the life-span hourglass as half full-they focused more on future opportunities than limited time. Around Age 60, the balance changed to increasingly perceiving the life-span hourglass as half empty-they focused less on future opportunities and more on limited time, even after accounting for perceived health, self-reported decision-making ability, and retirement status. At all ages, women's time horizons focused more on future opportunities compared with men's, and men's focused more on limited time. Focusing on future opportunities was associated with reporting less preoccupation with negative events, whereas focusing on limited time was associated with reporting more preoccupation. Older adults reported less preoccupation with negative events, and this association was stronger after controlling for their perceptions of limited time and fewer future opportunities, suggesting that other pathways may explain older adults' reports of their ability to disengage from negative events. Insights gained and questions raised by measuring future time perspective as 2 dimensions are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Label-free Fab and Fc affinity/avidity profiling of the antibody complex half-life for polyclonal and monoclonal efficacy screening.

PubMed

Read, Thomas; Olkhov, Rouslan V; Williamson, E Diane; Shaw, Andrew M

2015-09-01

A unified approach to affinity screening for Fab and Fc interactions of an antibody for its antigen and FcγR receptor has been developed. An antigen array is used for the Fab affinity and cross-reactivity screening and protein A/G proxy is the FcγR receptor. The affinities are derived using a simple 1:1 binding model with a consistent error analysis. The association and dissociation kinetics are measured over optimised times for accurate determination. The Fab/Fc affinities are derived for ten antibodies: mAb-actin (mouse), pAb-BSA (sheep), pAb-collagen V (rabbit), pAb-CRP (goat), mAb-F1 (mouse), mAbs (mouse) 7.3, 12.3, 29.3, 36.3 and 46.3 raised against LcrV in Yersinia pestis. The rate of the dissociation of antigen-antibody complexes relates directly to their immunological function as does the Fc-FcγR complex and a new half-life plot has been defined with a Fab/Fc half-life range of 17-470 min. The upper half-life value points to surface avidity. Two antibodies that are protective as an immunotherapy define a Fab half-life >250 min and an Fc half-life >50 min as characteristics of ideal interactions which can form the basis of an antibody screen for immunotherapy.

Precise measurement of the half-life of the Fermi {beta} decay of {sup 26}Al{sup m}

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

Scott, Rebecca J.; Thompson, Maxwell N.; Rassool, Roger P.

2011-08-15

State-of-the-art signal digitization and analysis techniques have been used to measure the half-life of the Fermi {beta} decay of {sup 26}Al{sup m}. The half-life was determined to be 6347.8 {+-} 2.5 ms. This new datum contributes to the experimental testing of the conserved-vector-current hypothesis and the required unitarity of the Cabibbo-Kobayashi-Maskawa matrix: two essential components of the standard model. Detailed discussion of the experimental techniques and data analysis and a thorough investigation of the statistical and systematic uncertainties are presented.

High-Precision Half-Life Measurements for the Superallowed Fermi β+ Emitters 14O and 18Ne

NASA Astrophysics Data System (ADS)

Laffoley, A. T.; Andreoiu, C.; Austin, R. A. E.; Ball, G. C.; Bender, P. C.; Bidaman, H.; Bildstein, V.; Blank, B.; Bouzomita, H.; Cross, D. S.; Deng, G.; Diaz Varela, A.; Dunlop, M. R.; Dunlop, R.; Finlay, P.; Garnsworthy, A. B.; Garrett, P.; Giovinazzo, J.; Grinyer, G. F.; Grinyer, J.; Hadinia, B.; Jamieson, D. S.; Jigmeddorj, B.; Ketelhut, S.; Kisliuk, D.; Leach, K. G.; Leslie, J. R.; MacLean, A.; Miller, D.; Mills, B.; Moukaddam, M.; Radich, A. J.; Rajabali, M. M.; Rand, E. T.; Svensson, C. E.; Tardiff, E.; Thomas, J. C.; Turko, J.; Voss, P.; Unsworth, C.

High-precision half-life measurements, at the level of ±0.04%, for the superallowed Fermi emitters 14O and 18Ne have been performed at TRIUMF's Isotope Separator and Accelerator facility. Using 3 independent detector systems, a gas-proportional counter, a fast plastic scintillator, and a high-purity germanium array, a series of direct β and γ counting measurements were performed for each of the isotopes. In the case of 14O, these measurements were made to help resolve an existing discrepancy between detection methods, whereas for 18Ne the half-life precision has been improved in anticipation of forthcoming high-precision branching ratio measurements.

L: (+)-Lactic acid production from non-food carbohydrates by thermotolerant Bacillus coagulans.

PubMed

Ou, Mark S; Ingram, Lonnie O; Shanmugam, K T

2011-05-01

Lactic acid is used as an additive in foods, pharmaceuticals, and cosmetics, and is also an industrial chemical. Optically pure lactic acid is increasingly used as a renewable bio-based product to replace petroleum-based plastics. However, current production of lactic acid depends on carbohydrate feedstocks that have alternate uses as foods. The use of non-food feedstocks by current commercial biocatalysts is limited by inefficient pathways for pentose utilization. B. coagulans strain 36D1 is a thermotolerant bacterium that can grow and efficiently ferment pentoses using the pentose-phosphate pathway and all other sugar constituents of lignocellulosic biomass at 50°C and pH 5.0, conditions that also favor simultaneous enzymatic saccharification and fermentation (SSF) of cellulose. Using this bacterial biocatalyst, high levels (150-180 g l(-1)) of lactic acid were produced from xylose and glucose with minimal by-products in mineral salts medium. In a fed-batch SSF of crystalline cellulose with fungal enzymes and B. coagulans, lactic acid titer was 80 g l(-1) and the yield was close to 80%. These results demonstrate that B. coagulans can effectively ferment non-food carbohydrates from lignocellulose to L: (+)-lactic acid at sufficient concentrations for commercial application. The high temperature fermentation of pentoses and hexoses to lactic acid by B. coagulans has these additional advantages: reduction in cellulase loading in SSF of cellulose with a decrease in enzyme cost in the process and a reduction in contamination of large-scale fermentations.

Extending the Serum Half-Life of G-CSF via Fusion with the Domain III of Human Serum Albumin

PubMed Central

Zhao, Shuqiang; Zhang, Yu; Tian, Hong; Chen, Xiaofei; Cai, Di; Yao, Wenbing; Gao, Xiangdong

2013-01-01

Protein fusion technology is one of the most commonly used methods to extend the half-life of therapeutic proteins. In this study, in order to prolong the half-life of Granulocyte colony stimulating factor (G-CSF), the domain III of human serum albumin (3DHSA) was genetically fused to the N-terminal of G-CSF. The 3DHSA-G-CSF fusion gene was cloned into pPICZαA along with the open reading frame of the α-factor signal under the control of the AOX1 promoter. The recombinant expression vector was transformed into Pichia pastoris GS115, and the recombinant strains were screened by SDS-PAGE. As expected, the 3DHSA-G-CSF showed high binding affinity with HSA antibody and G-CSF antibody, and the natural N-terminal of 3DHSA was detected by N-terminal sequencing. The bioactivity and pharmacokinetic studies of 3DHSA-G-CSF were respectively determined using neutropenia model mice and human G-CSF ELISA kit. The results demonstrated that 3DHSA-G-CSF has the ability to increase the peripheral white blood cell (WBC) counts of neutropenia model mice, and the half-life of 3DHSA-G-CSF is longer than that of native G-CSF. In conclusion, 3DHSA can be used to extend the half-life of G-CSF. PMID:24151579

Combined glyco- and protein-Fc engineering simultaneously enhance cytotoxicity and half-life of a therapeutic antibody.

PubMed

Monnet, Céline; Jorieux, Sylvie; Souyris, Nathalie; Zaki, Ouafa; Jacquet, Alexandra; Fournier, Nathalie; Crozet, Fabien; de Romeuf, Christophe; Bouayadi, Khalil; Urbain, Rémi; Behrens, Christian K; Mondon, Philippe; Fontayne, Alexandre

2014-01-01

While glyco-engineered monoclonal antibodies (mAbs) with improved antibody-dependent cell-mediated cytotoxicity (ADCC) are reaching the market, extensive efforts have also been made to improve their pharmacokinetic properties to generate biologically superior molecules. Most therapeutic mAbs are human or humanized IgG molecules whose half-life is dependent on the neonatal Fc receptor FcRn. FcRn reduces IgG catabolism by binding to the Fc domain of endocytosed IgG in acidic lysosomal compartments, allowing them to be recycled into the blood. Fc-engineered mAbs with increased FcRn affinity resulted in longer in vivo half-life in animal models, but also in healthy humans. These Fc-engineered mAbs were obtained by alanine scanning, directed mutagenesis or in silico approach of the FcRn binding site. In our approach, we applied a random mutagenesis technology (MutaGen™) to generate mutations evenly distributed over the whole Fc sequence of human IgG1. IgG variants with improved FcRn-binding were then isolated from these Fc-libraries using a pH-dependent phage display selection process. Two successive rounds of mutagenesis and selection were performed to identify several mutations that dramatically improve FcRn binding. Notably, many of these mutations were unpredictable by rational design as they were located distantly from the FcRn binding site, validating our random molecular approach. When produced on the EMABling(®) platform allowing effector function increase, our IgG variants retained both higher ADCC and higher FcRn binding. Moreover, these IgG variants exhibited longer half-life in human FcRn transgenic mice. These results clearly demonstrate that glyco-engineering to improve cytotoxicity and protein-engineering to increase half-life can be combined to further optimize therapeutic mAbs.

Measurement of the double- β decay half-life of 136 Xe with the KamLAND-Zen experiment

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

Gando, A.; Gando, Y.; Hanakago, H.

2012-04-19

We present results from the KamLAND-Zen double-beta decay experiment based on an exposure of 77.6 days with 129 kg of 136Xe. The measured two-neutrino double-beta decay half-life of 136Xe is Tmore » $$2ν\\atop{1/2}$$ = 2.38 ± 0.02(stat) ± 0.14(syst) x10 21 yr, consistent with a recent measurement by EXO-200. We also obtain a lower limit for the neutrinoless double-beta decay half-life, T$$0ν\\atop{1/2}$$ > 5.7 x 10 24 yr at 90% C.L.« less

Ultra-High Precision Half-Life Measurement for the Superallowed &+circ; Emitter ^26Al^m

NASA Astrophysics Data System (ADS)

Finlay, P.; Demand, G.; Garrett, P. E.; Leach, K. G.; Phillips, A. A.; Sumithrarachchi, C. S.; Svensson, C. E.; Triambak, S.; Grinyer, G. F.; Leslie, J. R.; Andreoiu, C.; Cross, D.; Austin, R. A. E.; Ball, G. C.; Bandyopadhyay, D.; Djongolov, M.; Ettenauer, S.; Hackman, G.; Pearson, C. J.; Williams, S. J.

2009-10-01

The calculated nuclear structure dependent correction for ^26Al^m (δC-δNS= 0.305(27)% [1]) is smaller by nearly a factor of two than the other twelve precision superallowed cases, making it an ideal case to pursue a reduction in the experimental errors contributing to the Ft value. An ultra-high precision half-life measurement for the superallowed &+circ; emitter ^26Al^m has been made at the Isotope Separator and Accelerator (ISAC) facility at TRIUMF in Vancouver, Canada. A beam of ˜10^5 ^26Al^m/s was delivered in October 2007 and its decay was observed using a 4π continuous gas flow proportional counter as part of an ongoing experimental program in superallowed Fermi β decay studies. With a statistical precision of ˜0.008%, the present work represents the single most precise measurement of any superallowed half-life to date. [4pt] [1] I.S. Towner and J.C. Hardy, Phys. Rev. C 79, 055502 (2009).

Ultra-High Precision Half-Life Measurement for the Superallowed &+circ; Emitter ^26Al^m

NASA Astrophysics Data System (ADS)

Finlay, P.; Demand, G.; Garrett, P. E.; Leach, K. G.; Phillips, A. A.; Sumithrarachchi, C. S.; Svensson, C. E.; Triambak, S.; Ball, G. C.; Bandyopadhyay, D.; Djongolov, M.; Ettenauer, S.; Hackman, G.; Pearson, C. J.; Williams, S. J.; Andreoiu, C.; Cross, D.; Austin, R. A. E.; Grinyer, G. F.; Leslie, J. R.

2008-10-01

The calculated nuclear structure dependent correction for ^26Al^m (δC-δNS= 0.305(27)% [1]) is smaller by nearly a factor of two than the other twelve precision superallowed cases, making it an ideal case to pursue a reduction in the experimental errors contributing to the Ft value. An ultra-high precision half-life measurement for the superallowed &+circ; emitter ^26Al^m has been made using a 4π continuous gas flow proportional counter as part of an ongoing experimental program in superallowed Fermi β decay studies at the Isotope Separator and Accelerator (ISAC) facility at TRIUMF in Vancouver, Canada, which delivered a beam of ˜10^5 ^26Al^m/s in October 2007. With a statistical precision of ˜0.008%, the present work represents the single most precise measurement of any superallowed half-life to date. [1] I.S. Towner and J.C. Hardy, Phys. Rev. C 77, 025501 (2008).

Precision half-life measurement of the 4-fold forbidden {beta} decay of {sup 50}V

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

Dombrowski, H.; Neumaier, S.; Zuber, K.

2011-05-15

A sensitive search of the 4-fold forbidden nonunique decay of {sup 50}V has been performed. A total mass measuring time product of 186 kg d has been accumulated. A reliable half-life value with the highest precision so far of (2.29{+-}0.25)x10{sup 17} years of the electron capture decay of {sup 50}V into the first excited state of {sup 50}Ti could be obtained. A photon emission line following the {beta} decay into the first excited state of {sup 50}Cr could not be observed, resulting in a lower limit on the half-life of the {beta}-decay branch of 1.7x10{sup 18} years. This is notmore » in good agreement with a claimed observation of this decay branch published in 1989.« less

Biological half-life of gaseous elemental iodine deposited onto rice grains

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

Uchida, S.; Muramatsu, Y.; Sumiya, M.

In order to obtain the biological half-life (Tb) of iodine deposited on rough rice grains, rice plants of four different growing stages--heading, milky, dough, and yellow ripe--were exposed to elemental gaseous iodine. After the exposure, the rough rice samples were collected at different intervals and analyzed for iodine to estimate the value of Tb. The average value of Tb obtained by the experiments at the dough and yellow ripe stages was about 200 d. This value is considerably larger than those for pasture grass and leafy vegetables.

Oclacitinib in feline nonflea-, nonfood-induced hypersensitivity dermatitis: results of a small prospective pilot study of client-owned cats.

PubMed

Ortalda, Christian; Noli, Chiara; Colombo, Silvia; Borio, Stefano

2015-08-01

Oclacitinib is a Janus kinase inhibitor that decreases pruritus and lesions in allergic dogs. In cats, it is able to inhibit interleukin-31-induced pruritus; no information is available on its clinical effectiveness. To evaluate the efficacy, ease of administration and tolerability of oclacitinib in feline nonflea-, nonfood-induced hypersensitivity dermatitis. Cats >12 months of age and >3 kg body weight with a diagnosis of nonflea-, nonfood-induced hypersensitivity dermatitis were treated with oclacitinib, 0.4-0.6 mg/kg orally (p.o.) twice daily for 2 weeks, then once daily for an additional 14 days. Clinical lesions were evaluated with the Scoring Feline Allergic Dermatitis (SCORFAD) system and pruritus was evaluated with a 10-cm-long visual analog scale (VAS) before and at the end of the study. Owners assessed global efficacy, ease of administration and tolerability with a four-point scale. Twelve cats were treated with a mean initial oclacitinib dose of 0.47 mg/kg p.o. twice daily. There was good improvement in SCORFAD and VAS pruritus scores in five of 12 cases, while the other cats were unchanged, deteriorated or dropped out due to treatment failure. Owners scored global efficacy as good/excellent in four of 12 cases and ease of administration and tolerability as good/excellent in 10 of 12. Oclacitinib at 0.4-0.6 mg/kg p.o. may be an effective and safe drug for some cats with nonflea-, nonfood-induced hypersensitivity dermatitis. Further studies are needed to identify the most effective dose range for this species. © 2015 ESVD and ACVD.

Protein half-life determines expression of proteostatic networks in podocyte differentiation.

PubMed

Schroeter, Christina B; Koehler, Sybille; Kann, Martin; Schermer, Bernhard; Benzing, Thomas; Brinkkoetter, Paul T; Rinschen, Markus M

2018-04-25

Podocytes are highly specialized, epithelial, postmitotic cells, which maintain the renal filtration barrier. When adapting to considerable metabolic and mechanical stress, podocytes need to accurately maintain their proteome. Immortalized podocyte cell lines are a widely used model for studying podocyte biology in health and disease in vitro. In this study, we performed a comprehensive proteomic analysis of the cultured human podocyte proteome in both proliferative and differentiated conditions at a depth of >7000 proteins. Similar to mouse podocytes, human podocyte differentiation involved a shift in proteostasis: undifferentiated podocytes have high expression of proteasomal proteins, whereas differentiated podocytes have high expression of lysosomal proteins. Additional analyses with pulsed stable-isotope labeling by amino acids in cell culture and protein degradation assays determined protein dynamics and half-lives. These studies unraveled a globally increased stability of proteins in differentiated podocytes. Mitochondrial, cytoskeletal, and membrane proteins were stabilized, particularly in differentiated podocytes. Importantly, protein half-lives strongly contributed to protein abundance in each state. These data suggest that regulation of protein turnover of particular cellular functions determines podocyte differentiation, a paradigm involving mitophagy and, potentially, of importance in conditions of increased podocyte stress and damage.-Schroeter, C. B., Koehler, S., Kann, M., Schermer, B., Benzing, T., Brinkkoetter, P. T., Rinschen, M. M. Protein half-life determines expression of proteostatic networks in podocyte differentiation.

A Case Controlled Examination of the Interpersonal Theory of Suicide in the Second Half of Life.

PubMed

Van Orden, Kimberly A; Smith, Phillip N; Chen, Tian; Conwell, Yeates

2016-07-02

The interpersonal theory of suicide proposes that the most proximal cause of suicide is the combination of thwarted belongingness and perceived burdensomeness coupled with a pre-existing vulnerability of reduced fear of death and increased pain tolerance. This pre-existing vulnerability develops in response to painful and provocative life events. According to the theory, empirically demonstrated risk factors for suicide operate by increasing the likelihood of one or more of the theory's constructs. The current study examined the relations of the major constructs of the interpersonal theory with suicide case status compared to living controls in the second half of life. The current study used a pre-existing psychological autopsy database to compare suicide decedents to living controls 50 years and older. Theory constructs were measured by composite scores of thwarted belongingness, perceived burdensomeness, and painful and provocative experiences using an a priori selection of items comprising each construct. Suicide decedents experienced greater levels of all three of the theory's constructs when examined independently compared to living controls. When examined simultaneously while also controlling for Major Depression, greater perceived burdensomeness and painful and provocative experiences were associated with suicide case status (vs. control). The interpersonal theory is a comprehensive framework that may be useful in understanding risk for death by suicide in the second half of life. Clinical management of suicide risk for adults in the second half of life could include a focus on perceived burdensomeness, as the IPTS proposes that this psychological state is amenable to change via therapeutic intervention.

The Plasma Disappearance Time and Catabolic Half-Life of I 131-Labelled Normal Human Gamma Globulin in Amyloidosis and in Rheumatoid Arthritis

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

Mills, John A.; Calkins, Evan; Cohen, Alan S.

1961-10-01

The serum survival time and catabclic half-life of intravenously injected I 131-labeled pooled human gamma globulin - were studied in three patients with amyloidosis, four patients with rheumatoid arthritis, and three normal controls. The half-time of gamma globulin survival in the controsubjects ranged from 16.5 to 30 days. Two patients with amyloidosis, one primary and one secondary, both with the nephrotic syndrome, exhibited shortened serum half-times of 4.5 and 11 days, respectively. The serum half-time of the latter patient, before the appearance of clinical amyloidosis, was 14 days. One patient with primary amyloidosis but without nephrosis exhibited a half-time ofmore » serum gamma globulin disappearance of 21 days. The half-time of gamma globulin disappearance in four patients with chronic active rheumatoid arthritis varied between 19.5 and 8.5 days. The lower figure was found in a patient having a high titer of rheumatoid factor. If this subject is excepted, the average half- time in three rheumatoid subjects is 17 days. The catabolic half-life of the iodinated gamma globulin agreed in most instances with the serum half-time. The calculated distribution space of the injected gamma globulin showed no consistent alteration in either amyloidosis or rheumatoid arthritis as compared with the control subjects. Since the nephrotic syndrome from other causes may produce an accelerated catabolic half-life, a similar finding on these subjects cannot be ascribed to amyloidosis.« less

The national employment guarantee scheme and inequities in household spending on food and non-food determinants of health in rural India.

PubMed

Dilip, T R; Dandona, Rakhi; Dandona, Lalit

2013-10-15

Inequities in a population in spending on food and non-food items can contribute to disparities in health status. The Mahatma Gandhi National Rural Employment Guarantee Scheme (MGNREGS) was launched in rural India in 2006, aimed at providing at least 100 days of manual work to a member in needy households. We used nationally representative data from the consumer expenditure surveys of 2004-05 and 2009-10 and the employment survey of 2009-10 conducted by National Sample Survey Organisation to assess the effect of MGNREGS in reducing inequities in consumption of food and non-food items between poor and non-poor households in the states of India. Variations among the states in implementation of MGNREGS were examined using the employment and unemployment survey data, and compared with official programme data up to 2012-13. Inequity in spending on food and non-food items was assessed using the ratio of monthly per capita consumer expenditure (MPCE) between the most vulnerable (labourer) and least vulnerable categories of households. The survey data suggested 1.42 billion person-days of MGNRGES employment in the 2009-10 financial year, whereas the official programme data reported 2.84 billion person-days. According to the official data, the person-days of MGNRGES employment decreased by 43.3% from 2009-10 to 2012-13 for the 9 large less developed states of India. Survey data revealed that the average number of MGNREGS work days in a year per household varied from 42 days in Rajasthan to less than 10 days in 14 of the 20 major states in India in 2009-10. Rajasthan with the highest implementation of MGNRGES among the 9 less developed states of India had the highest relative decline of 10.4% in the food spending inequity from 2004-05 to 2009-10 between the most vulnerable and less vulnerable households. The changes in inequity for non-food spending did not have any particular pattern across the less developed states. In the most vulnerable category, the households in

High-Precision Half-Life and Branching Ratio Measurements for the Superallowed β+ Emitter 26Alm

NASA Astrophysics Data System (ADS)

Finlay, P.; Svensson, C. E.; Demand, G. A.; Garrett, P. E.; Green, K. L.; Leach, K. G.; Phillips, A. A.; Rand, E. T.; Ball, G.; Bandyopadhyay, D.; Djongolov, M.; Ettenauer, S.; Hackman, G.; Pearson, C. J.; Leslie, J. R.; Andreoiu, C.; Cross, D.; Austin, R. A. E.; Grinyer, G. F.; Sumithrarachchi, C. S.; Williams, S. J.; Triambak, S.

2013-03-01

High-precision half-life and branching-ratio measurements for the superallowed β+ emitter 26Alm were performed at the TRIUMF-ISAC radioactive ion beam facility. An upper limit of ≤ 15 ppm at 90% C.L. was determined for the sum of all possible non-analogue β+/EC decay branches of 26Alm, yielding a superallowed branching ratio of 100.0000+0-0.0015%. A value of T1/2 = 6:34654(76) s was determined for the 26Alm half-life which is consistent with, but 2.5 times more precise than, the previous world average. Combining these results with world-average measurements yields an ft value of 3037.58(60) s, the most precisely determined for any superallowed emitting nucleus to date. This high-precision ft value for 26Alm provides a new benchmark to refine theoretical models of isospin-symmetry-breaking effects in superallowed β decays.

When do star clusters become multiple star systems? II. Toward a half-life formalism with four bodies

NASA Astrophysics Data System (ADS)

Ibragimov, Timur; Leigh, Nathan W. C.; Ryu, Taeho; Panurach, Teresa; Perna, Rosalba

2018-03-01

We present a half-life formalism for describing the disruption of gravitationally-bound few-body systems, with a focus on binary-binary scattering. For negative total encounter energies, the four-body problem has three possible decay products in the point particle limit. For each decay product and a given set of initial conditions, we obtain directly from numerical scattering simulations the half-life for the distribution of disruption times. As in radioactive decay, the half-lives should provide a direct prediction for the relative fractions of each decay product. We test this prediction with simulated data and find good agreement with our hypothesis. We briefly discuss applications of this feature of the gravitational four-body problem to populations of black holes in globular clusters. This paper, the second in the series, builds on extending the remarkable similarity between gravitational chaos at the macroscopic scale and radioactive decay at the microscopic scale to larger-N systems.

When do star clusters become multiple star systems? II. Towards a half-life formalism with four bodies

NASA Astrophysics Data System (ADS)

Ibragimov, Timur; Leigh, Nathan W. C.; Ryu, Taeho; Panurach, Teresa; Perna, Rosalba

2018-07-01

We present a half-life formalism for describing the disruption of gravitationally bound few-body systems, with a focus on binary-binary scattering. For negative total encounter energies, the four-body problem has three possible decay products in the point-particle limit. For each decay product and a given set of initial conditions, we obtain directly from numerical scattering simulations the half-life for the distribution of disruption times. As in radioactive decay, the half-lives should provide a direct prediction for the relative fractions of each decay product. We test this prediction with simulated data and find good agreement with our hypothesis. We briefly discuss applications of this feature of the gravitational four-body problem to populations of black holes in globular clusters. This paper, the second in the series, builds on extending the remarkable similarity between gravitational chaos at the macroscopic scale and radioactive decay at the microscopic scale to larger-N systems.

Measurement of the two-neutrino double-beta decay half-life of $$^{130}$$Te with the CUORE-0 experiment

DOE PAGES

Alduino, C.; Alfonso, K.; Artusa, D. R.; ...

2017-01-06

Here, we report on the measurement of the two-neutrino double-beta decay half-life of 130Te with the CUORE-0 detector. From an exposure of 33.4 kg year of TeO 2, the half-life is determined to be T 2ν 1/2 = [8.2 ± 0.2 (stat.) ± 0.6 (syst.)] × 10 20 year. This result is obtained after a detailed reconstruction of the sources responsible for the CUORE-0 counting rate, with a specific study of those contributing to the 130Te neutrinoless double-beta decay region of interest.

Real-World Analysis of Dispensed IUs of Coagulation Factor IX and Resultant Expenditures in Hemophilia B Patients Receiving Standard Half-life Versus Extended Half-life Products and Those Switching from Standard Half-life to Extended Half-life Products.

PubMed

Tortella, Bartholomew J; Alvir, José; McDonald, Margaret; Spurden, Dean; Fogarty, Patrick F; Chhabra, Amit; Pleil, Andreas M

2018-01-24

Hemophilia B requires replacement therapy with factor IX (FIX) coagulation products to treat and prevent bleeding episodes. A recently introduced extended half-life (EHL) recombinant FIX replacement product provided the opportunity to compare the amount of dispensed factor and expenditures for EHL treatment compared with a standard half-life (SHL) product. To determine factor international units (IUs) dispensed and expenditures associated with switching from nonacog alfa, the most commonly used SHL replacement product, to eftrenonacog alfa, an EHL FIX replacement product. Two U.S. claims databases were analyzed. A large national specialty pharmacy dispensation claims database was used to identify the number of IUs dispensed and monthly charges for all patients with hemophilia B from April 2015 to June 2016. Truven Health MarketScan Research Databases (January 2010-July 2016) were used to identify IUs and expenditures for patients with claims data for at least 3 months before and after switching from the SHL to the EHL product. Medians for IUs and expenditures are presented to accommodate for skewness of data distribution. The national specialty pharmacy database analysis included 296 patients with moderate or severe hemophilia B (233 on SHL; 94 on EHL). Median monthly factor dispensed was 11% lower (2,142 IU) in the EHL versus SHL cohort over the study period, while individual monthly reductions ranged from 32% to 47% (9,838 IU to 16,514 IU). Using the wholesale acquisition cost, the median per-patient monthly factor expenditures over the 15-month study period were 94% higher ($23,005) for the EHL than for the SHL product. Individual median monthly expenditure differences ranged from 15% ($6,562) to 49% ($19,624). In the Truven database, 14 patients switched from the SHL to the EHL product. The amount of factor dispensed was variable; in the 1-year period before and after the switch from the SHL to the EHL product, mean IUs dispensed decreased by 3,005 IU, while

Pile-up corrections for high-precision superallowed β decay half-life measurements via γ-ray photopeak counting

NASA Astrophysics Data System (ADS)

Grinyer, G. F.; Svensson, C. E.; Andreoiu, C.; Andreyev, A. N.; Austin, R. A. E.; Ball, G. C.; Bandyopadhyay, D.; Chakrawarthy, R. S.; Finlay, P.; Garrett, P. E.; Hackman, G.; Hyland, B.; Kulp, W. D.; Leach, K. G.; Leslie, J. R.; Morton, A. C.; Pearson, C. J.; Phillips, A. A.; Sarazin, F.; Schumaker, M. A.; Smith, M. B.; Valiente-Dobón, J. J.; Waddington, J. C.; Williams, S. J.; Wong, J.; Wood, J. L.; Zganjar, E. F.

2007-09-01

A general technique that corrects γ-ray gated β decay-curve data for detector pulse pile-up is presented. The method includes corrections for non-zero time-resolution and energy-threshold effects in addition to a special treatment of saturating events due to cosmic rays. This technique is verified through a Monte Carlo simulation and experimental data using radioactive beams of Na26 implanted at the center of the 8π γ-ray spectrometer at the ISAC facility at TRIUMF in Vancouver, Canada. The β-decay half-life of Na26 obtained from counting 1809-keV γ-ray photopeaks emitted by the daughter Mg26 was determined to be T=1.07167±0.00055 s following a 27σ correction for detector pulse pile-up. This result is in excellent agreement with the result of a previous measurement that employed direct β counting and demonstrates the feasibility of high-precision β-decay half-life measurements through the use of high-purity germanium γ-ray detectors. The technique presented here, while motivated by superallowed-Fermi β decay studies, is general and can be used for all half-life determinations (e.g. α-, β-, X-ray, fission) in which a γ-ray photopeak is used to select the decays of a particular isotope.

Extension of in vivo half-life of biologically active peptides via chemical conjugation to XTEN protein polymer.

PubMed

Podust, Vladimir N; Sim, Bee-Cheng; Kothari, Dharti; Henthorn, Lana; Gu, Chen; Wang, Chia-wei; McLaughlin, Bryant; Schellenberger, Volker

2013-11-01

XTEN, unstructured biodegradable proteins, have been used to extend the in vivo half-life of genetically fused therapeutic proteins and peptides. To expand the applications of XTEN technology to half-life extension of other classes of molecules, XTEN protein polymers and methods for chemical XTENylation were developed. Two XTEN precursors were engineered to contain enzymatically removable purification tags. The proteins were readily expressed in bacteria and purified to homogeneity by chromatography techniques. As proof-of-principle, GLP2-2G peptide was chemically conjugated to each of the two XTEN protein polymers using maleimide-thiol chemistry. The monodisperse nature of XTEN protein polymer enabled reaction monitoring as well as the detection of peptide modifications in the conjugated state using reverse phase-high performance liquid chromatography (RP-HPLC) and electrospray ionization mass spectrometry. The resulting GLP2-2G-XTEN conjugates were purified by preparative RP-HPLC to homogeneity. In comparison with recombinantly fused GLP2-2G-XTEN, chemically conjugated GLP2-2G-XTEN molecules exhibited comparable in vitro activity, in vitro plasma stability and pharmacokinetics in rats. These data suggest that chemical XTENylation could effectively extend the half-life of a wide spectrum of biologically active molecules, therefore broadening its applicability.

Dexamethasone promotes granulocyte mobilization by prolonging the half-life of granulocyte-colony-stimulating factor in healthy donors for granulocyte transfusions.

PubMed

Hiemstra, Ida H; van Hamme, John L; Janssen, Machiel H; van den Berg, Timo K; Kuijpers, Taco W

2017-03-01

Granulocyte transfusion (GTX) is a potential approach to correcting neutropenia and relieving the increased risk of infection in patients who are refractory to antibiotics. To mobilize enough granulocytes for transfusion, healthy donors are premedicated with granulocyte-colony-stimulating factor (G-CSF) and dexamethasone. Granulocytes have a short circulatory half-life. Consequently, patients need to receive GTX every other day to keep circulating granulocyte counts at an acceptable level. We investigated whether plasma from premedicated donors was capable of prolonging neutrophil survival and, if so, which factor could be held responsible. The effects of plasma from G-CSF/dexamethasone-treated donors on neutrophil survival were assessed by annexin-V, CD16. and CXCR4 staining and nuclear morphology. We isolated an albumin-bound protein using α-chymotrypsin and albumin-depletion and further characterized it using protein analysis. The effects of dexamethasone and G-CSF were assessed using mifepristone and G-CSF-neutralizing antibody. G-CSF plasma concentrations were determined by Western blot and Luminex analyses. G-CSF/dexamethasone plasma contained a survival-promoting factor for at least 2 days. This factor was recognized as an albumin-associated protein and was identified as G-CSF itself, which was surprising considering its reported half-life of only 4.5 hours. Compared with coadministration of dexamethasone, administration of G-CSF alone to the same GTX donors led to a faster decline in circulating G-CSF levels, whereas dexamethasone itself did not induce any G-CSF, demonstrating a role for dexamethasone in increasing G-CSF half-life. Dexamethasone increases granulocyte yield upon coadministration with G-CSF by extending G-CSF half-life. This observation might also be exploited in the coadministration of dexamethasone with other recombinant proteins to modulate their half-life. © 2016 AABB.

The beta(+) decay and cosmic-ray half-life of Mn-54

NASA Astrophysics Data System (ADS)

Dacruz, M. T. F.; Norman, E. B.; Chan, Y. D.; Garcia, A.; Larimer, R. M.; Lesko, K. T.; Stokstad, R. G.; Wietfeldt, F. E.

1993-03-01

We performed a search for the beta(+) branch of Mn-54 decay. As a cosmic ray, Mn-54, deprived of its atomic electrons, can decay only via beta(+) and beta(-) decay, with a half-life of the order of 106 yr. This turns Mn-54 into a suitable cosmic chronometer for the study of cosmic-ray confinement times. We searched for coincident back-to-back 511-keV gamma-rays using two germanium detectors inside a Nal(Tl) annulus. An upper limit of 2 x 10-8 was found for the beta(+) decay branch, corresponding to a lower limit of 13.7 for the log ft value.

Urinary excretion half life of trichloroacetic acid as a biomarker of exposure to chlorinated drinking water disinfection by-products

PubMed Central

Bader, E; Hrudey, S; Froese, K

2004-01-01

Methods: A longitudinal pilot exposure/intervention study measured the elimination half life of TCAA in urine. Beverage consumption was limited to a public water supply and bottled water of known TCAA concentration, and ingestion volume was managed. The five participants limited fluid consumption to only the water provided. Consumption journals were kept by each participant and their daily first morning urine (FMU) samples were analysed for TCAA and creatinine. TCAA elimination half life curves were generated from a two week washout period using TCAA-free bottled water. Results: Individual elimination half lives ranged from 2.1 to 6.3 days, for single compartment exponential decay, the model which fit the data. Conclusion: Urinary TCAA is persistent enough to be viable as a biomarker of medium term (days) exposure to drinking water TCAA ingestion within a range of realistic concentrations. PMID:15258281

High-Precision Half-Life Measurement for the Superallowed {beta}{sup +} Emitter {sup 26}Al{sup m}

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

Finlay, P.; Svensson, C. E.; Green, K. L.

2011-01-21

A high-precision half-life measurement for the superallowed {beta}{sup +} emitter {sup 26}Al{sup m} was performed at the TRIUMF-ISAC radioactive ion beam facility yielding T{sub 1/2}=6346.54{+-}0.46{sub stat{+-}}0.60{sub syst} ms, consistent with, but 2.5 times more precise than, the previous world average. The {sup 26}Al{sup m} half-life and ft value, 3037.53(61) s, are now the most precisely determined for any superallowed {beta} decay. Combined with recent theoretical corrections for isospin-symmetry-breaking and radiative effects, the corrected Ft value for {sup 26}Al{sup m}, 3073.0(12) s, sets a new benchmark for the high-precision superallowed Fermi {beta}-decay studies used to test the conserved vector current hypothesismore » and determine the V{sub ud} element of the Cabibbo-Kobayashi-Maskawa quark mixing matrix.« less

3-O sulfation of heparin leads to hepatotropism and longer circulatory half-life.

PubMed

Miller, Colton M; Xu, Yongmei; Kudrna, Katrina M; Hass, Blake E; Kellar, Brianna M; Egger, Andrew W; Liu, Jian; Harris, Edward N

2018-05-17

Heparins are common blood anticoagulants that are critical for many surgical and biomedical procedures used in modern medicine. In contrast to natural heparin derived from porcine gut mucosa, synthetic heparins are homogenous by mass, polymer length, and chemistry. Stable cell lines expressing the human and mouse Stabilin receptors were used to evaluate endocytosis of natural and synthetic heparin. We chemoenzymatically produced synthetic heparin consisting of 12 sugars (dodecamers) containing 14 sulfate groups resulting in a non-3-O sulfated structure (n12mer). Half of the n12mer was modified with a 3-O sulfate on a single GlcNS sugar producing the 3-O sulfated heparin (12mer). Wildtype (WT), Stabilin-1 knock-out (KO), and Stabilin-2 KO C57BL/6 mice were developed and used for metabolic studies and provided as a source for primary liver sinusoidal endothelial cells. Human and mouse Stabilin-2 receptors had very similar endocytosis rates of both the 12mer and n12mer, suggesting that they are functionally similar in primary cells. Subcutaneous injections of the n12mer and 12mer revealed that the 12mer had a much longer half-life in circulation and a higher accumulation in liver. The n12mer never accumulated in circulation and was readily excreted by the kidneys before liver accumulation could occur. Liver sinusoidal endothelial cells from the Stabilin-2 KO mice had lower uptake rates for both dodecamers, whereas, the Stabilin-1 KO mice had lower endocytosis rates for the 12mer than the n12mer. 3-O sulfation of heparin is correlated to both a longer circulatory half-life and hepatotropism which is largely performed by the Stabilin receptors. Copyright © 2018 Elsevier Ltd. All rights reserved.

A new measurement of the half-life of (166m)Ho.

PubMed

Nedjadi, Y; Bailat, C; Caffari, Y; Froidevaux, P; Wastiel, C; Kivel, N; Guenther-Leopold, I; Triscone, G; Jaquenod, F; Bochud, F

2012-09-01

The work presented here is a new and precise measurement of the half-life of (166m)Ho by determining the activity concentration, using an ionisation chamber calibrated for this nuclide, and measuring the number of (166m)Ho atoms using multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS). Since the isotope (166)Er interferes with the mass spectrometric measurement, Er has to be eliminated from the (166m)Ho radioactive solution. The elimination was achieved using ion-exchange chromatography with the cation exchange resin Dowex AG 50W-X8 and 2-Hydroxybutanoic acid as the mobile phase. After a first transit through the chromatographic column, the purified (166m)Ho eluate was spiked with natural Er to get a resulting Er isotopic composition close to that of natural Er at better than 99.5%, and then it underwent two further separations to eliminate the Er. The activity concentration of this Er-free radioactive (166m)Ho solution was measured in our reference ionisation chamber calibrated for this nuclide by means of the 4πβ(PC)-γ and 4πβ(PS)-4πγ coincidence techniques and integral counting with a well-type NaI(Tl) detector and Monte Carlo efficiencies. An aliquot of this standardized solution was sent to the Paul Scherrer Institute (PSI) for mass concentration determination using an isotope dilution MC-ICP-MS approach. The mass concentration of (166m)Ho in this solution was determined with 0.25% relative standard uncertainty. This value was corroborated by two other independent measurements. The new half-life of (166m)Ho, 1132.6(39) years (k=1), is compatible with the value determined in 1965, but is 5.6% shorter and about 43 times more precise. Copyright © 2012 Elsevier Ltd. All rights reserved.

Vitamin E plasma kinetics in swine show low bioavailability and short half-life of -α-tocopheryl acetate.

PubMed

van Kempen, T A T G; Reijersen, M H; de Bruijn, C; De Smet, S; Michiels, J; Traber, M G; Lauridsen, C

2016-10-01

Vitamin E is important for animal production because of its effects on health and product quality, but the amount and form required remains controversial. Our objective was to quantify the absolute bioavailability of oral -α-tocopheryl acetate (α-TAc) in swine (22 ± 1 kg and 8 wk old, fitted with jugular catheters) adapted to a diet supplemented with 75 mg/kg -α-TAc; 75 mg/kg was chosen because this level represents the nonweighted average inclusion level in piglet diets across Western key swine-producing countries. For this, a 350-g test meal (6% fat) was supplied at time 0 containing 75 mg deuterated (D9) -α-TAc to 9 animals, and 8 animals received an intravenous () dose containing deuterated (D6) RRR-α-tocopherol (α-T) at one-eighth the oral dose and a test meal without supplemental vitamin E. Plasma samples (12 to 13 per animal) were obtained at incremental intervals over 75 h for analysis of deuterated α-T using liquid chromatography-tandem mass spectrometry. Surprisingly, the i.v. dose rapidly disappeared from plasma and then reappeared. The half-life for this first peak was only 1.7 ± 0.3 min. The second peak had an appearance rate (Ka) of 0.10 ± 0.06 d and a half-life of 5.9 ± 1.2 h. Oral dosing resulted, after a lag of 56 min, in a Ka of 0.91 ± 0.21 d and a half-life of 2.6 ± 0.8 h. The bioavailability for oral α-TAc was 12.5%, whereas the area under the curve was only 5.4%. This low bioavailability, small area under the curve, and short half-life are likely because of various factors, that is, the use of only 6% fat in the diet, the use of the acetate ester and , and the high dose relative to requirements. In conclusion, i.v. dosed vitamin E shows both a rapid and a very slow pool, whereas orally dosed vitamin E shows a single slow pool. The oral material has a very short half-live (44% of i.v. or 2.6 h), low bioavailability (12.5%), and a very small area under the curve (5.4%), bringing into question the efficacy of typical doses of vitamin

Improved measurement of the half-life of the J π = 8 - nuclear isomer 152m2 Eu

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

Humby, Peter; Simon, Anna; Beausang, C. W.

2015-02-23

The standard γ-ray energy calibration source 152Eu is well known based on the 13.5 y decay of its ground state. Nevertheless, in addition to this decay 152Eu also has two relatively long-lived isomeric states: a 9 h J π=0 - state at E *=46 keV and a 96 min J π=8 - state at E *=148 keV. Here we report a new measurement of the half-lives of both of these isomeric states. Excited states in 152Eu were populated following the 154Sm (p,3n) reaction using a 25 MeV proton beam from the K-150 cyclotron at the Cyclotron Institute of Texas A&Mmore » University. Post irradiation, γ rays from the de-excitation of the long lived isomeric states were measured using the six BGO shielded high-purity germanium (HPGe) clover detectors that are part of the STARLiTeR array. The half-life of the J π=8 - isomer 152m2Eu was obtained by measuring the decrease in intensity of the 90 keV γ ray from the cascade to the ground state. The half-life of this state was measured to be 95.8(4) min which is in agreement with and significantly more precise than the previously measured value of 96(1) min. In a manner similar to the ground state the second long-lived isomer 151m1Eu, the J π=0 - state at 46 keV, β decays to excited states in 152Gd and 152Sm. Also, the half-life of this state was measured to be 9.39(7) h using five γ-ray transitions.« less

Standard Operating Procedure for Using the NAFTA Guidance to Calculate Representative Half-life Values and Characterizing Pesticide Degradation

EPA Pesticide Factsheets

Results of the degradation kinetics project and describes a general approach for calculating and selecting representative half-life values from soil and aquatic transformation studies for risk assessment and exposure modeling purposes.

Eawag-Soil in enviPath: a new resource for exploring regulatory pesticide soil biodegradation pathways and half-life data.

PubMed

Latino, Diogo A R S; Wicker, Jörg; Gütlein, Martin; Schmid, Emanuel; Kramer, Stefan; Fenner, Kathrin

2017-03-22

Developing models for the prediction of microbial biotransformation pathways and half-lives of trace organic contaminants in different environments requires as training data easily accessible and sufficiently large collections of respective biotransformation data that are annotated with metadata on study conditions. Here, we present the Eawag-Soil package, a public database that has been developed to contain all freely accessible regulatory data on pesticide degradation in laboratory soil simulation studies for pesticides registered in the EU (282 degradation pathways, 1535 reactions, 1619 compounds and 4716 biotransformation half-life values with corresponding metadata on study conditions). We provide a thorough description of this novel data resource, and discuss important features of the pesticide soil degradation data that are relevant for model development. Most notably, the variability of half-life values for individual compounds is large and only about one order of magnitude lower than the entire range of median half-life values spanned by all compounds, demonstrating the need to consider study conditions in the development of more accurate models for biotransformation prediction. We further show how the data can be used to find missing rules relevant for predicting soil biotransformation pathways. From this analysis, eight examples of reaction types were presented that should trigger the formulation of new biotransformation rules, e.g., Ar-OH methylation, or the extension of existing rules, e.g., hydroxylation in aliphatic rings. The data were also used to exemplarily explore the dependence of half-lives of different amide pesticides on chemical class and experimental parameters. This analysis highlighted the value of considering initial transformation reactions for the development of meaningful quantitative-structure biotransformation relationships (QSBR), which is a novel opportunity offered by the simultaneous encoding of transformation reactions and

Half-life of porcine antibodies absorbed from a colostrum supplement containing porcine immunoglobulins.

PubMed

Polo, J; Campbell, J M; Crenshaw, J; Rodríguez, C; Pujol, N; Navarro, N; Pujols, J

2012-12-01

Absorption of immunoglobulins (Ig) at birth from colostrum is essential for piglet survival. The objective was to evaluate the half-life of antibodies absorbed in the bloodstream of newborn piglets orally fed a colostrum supplement (CS) containing energy (fat and carbohydrates) and IgG from porcine plasma. Viable piglets (n = 23; 900 to 1,800 g BW) from 6 sows were colostrum deprived and blood sampled and within the next 2 h of life randomly allocated to either control group (n = 9) providing 30 mL of Ig-free milk replacer or a group (n = 14) receiving 30 mL of CS by oral gavage. Piglets were transported to a Biosafety Level 3 facility (Centre de Recerca en Sanitat Animal, Spain) and fed Ig-free milk replacer every 3 to 4 h for 15 d. Survival, weight, plasma IgG content by radial immunodiffusion (RID), and antibodies against porcine circovirus type 2 (PCV2), porcine parvovirus (PPV), porcine reproductive and respiratory syndrome (PRRS), Mycoplasma hyopneumoniae (Mhy), and swine influenza virus (SIV) were determined by specific ELISA before treatment administration, at 24 h, and weekly for 56 d. Clinical symptoms were not observed for either group. Mortality index was lower (17 vs. 38%; P < 0.02) and BW higher (17.7 vs. 15.3 kg; P = 0.035) for pigs supplemented with CS than piglets in the control group. At 24 h postadministration, the CS group had a plasma IgG mean of 7.6 ± 0.06 vs. 0.14 ± 0.03 mg/mL for the control group. The IgG levels in the CS group decayed until day 21 when de novo synthesis of IgG was detected in 25% of piglets. Half-life of antibody concentration (HLAC) by RID was 6.2 d. In the CS group, efficiency of PCV2 and PPV antibody transfer was high. For PCV2, all animals remained positive by day 56 and the calculated HLAC was 17.7 d. For PPV, 72.7% of piglets were ELISA positive by day 35 and HLAC was 12.0 d. For PRRS, all piglets remained positive by day 14 and the calculated HLAC was 11.9 d. For Mhy and SIV the calculated HLAC were 8.4 and 3.0 d

Innovative methodology for intercomparison of radionuclide calibrators using short half-life in situ prepared radioactive sources

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

Oliveira, P. A.; Santos, J. A. M., E-mail: joao.santos@ipoporto.min-saude.pt; Serviço de Física Médica do Instituto Português de Oncologia do Porto Francisco Gentil, EPE, Porto

2014-07-15

Purpose: An original radionuclide calibrator method for activity determination is presented. The method could be used for intercomparison surveys for short half-life radioactive sources used in Nuclear Medicine, such as{sup 99m}Tc or most positron emission tomography radiopharmaceuticals. Methods: By evaluation of the resulting net optical density (netOD) using a standardized scanning method of irradiated Gafchromic XRQA2 film, a comparison of the netOD measurement with a previously determined calibration curve can be made and the difference between the tested radionuclide calibrator and a radionuclide calibrator used as reference device can be calculated. To estimate the total expected measurement uncertainties, a carefulmore » analysis of the methodology, for the case of{sup 99m}Tc, was performed: reproducibility determination, scanning conditions, and possible fadeout effects. Since every factor of the activity measurement procedure can influence the final result, the method also evaluates correct syringe positioning inside the radionuclide calibrator. Results: As an alternative to using a calibrated source sent to the surveyed site, which requires a relatively long half-life of the nuclide, or sending a portable calibrated radionuclide calibrator, the proposed method uses a source preparedin situ. An indirect activity determination is achieved by the irradiation of a radiochromic film using {sup 99m}Tc under strictly controlled conditions, and cumulated activity calculation from the initial activity and total irradiation time. The irradiated Gafchromic film and the irradiator, without the source, can then be sent to a National Metrology Institute for evaluation of the results. Conclusions: The methodology described in this paper showed to have a good potential for accurate (3%) radionuclide calibrators intercomparison studies for{sup 99m}Tc between Nuclear Medicine centers without source transfer and can easily be adapted to other short half-life

Hair-to-blood ratio and biological half-life of mercury: experimental study of methylmercury exposure through fish consumption in humans.

PubMed

Yaginuma-Sakurai, Kozue; Murata, Katsuyuki; Iwai-Shimada, Miyuki; Nakai, Kunihiko; Kurokawa, Naoyuki; Tatsuta, Nozomi; Satoh, Hiroshi

2012-02-01

The hair-to-blood ratio and biological half-life of methylmercury in a one-compartment model seem to differ between past and recent studies. To reevaluate them, 27 healthy volunteers were exposed to methylmercury at the provisional tolerable weekly intake (3.4 µg/kg body weight/week) for adults through fish consumption for 14 weeks, followed by a 15-week washout period after the cessation of exposure. Blood was collected every 1 or 2 weeks, and hair was cut every 4 weeks. Total mercury (T-Hg) concentrations were analyzed in blood and hair. The T-Hg levels of blood and hair changed with time (p < 0.001). The mean concentrations increased from 6.7 ng/g at week 0 to 26.9 ng/g at week 14 in blood, and from 2.3 to 8.8 µg/g in hair. The mean hair-to-blood ratio after the adjustment for the time lag from blood to hair was 344 ± 54 (S.D.) for the entire period. The half-lives of T-Hg were calculated from raw data to be 94 ± 23 days for blood and 102 ± 31 days for hair, but the half-lives recalculated after subtracting the background levels from the raw data were 57 ± 18 and 64 ± 22 days, respectively. In conclusion, the hair-to-blood ratio of methylmercury, based on past studies, appears to be underestimated in light of recent studies. The crude half-life may be preferred rather than the recalculated one because of the practicability and uncertainties of the background level, though the latter half-life may approximate the conventional one.

Consideration on the Long Ecological Half-Life Component of (137)Cs in Demersal Fish Based on Field Observation Results Obtained after the Fukushima Accident.

PubMed

Tagami, Keiko; Uchida, Shigeo

2016-02-16

Radiocesium concentrations in most marine fish collected off the coast of Fukushima and surrounding prefectures have decreased with time, and four years after the Fukushima Daiichi Nuclear Power Plant accident occurred, radiocesium concentrations have generally fallen below the detectable level (ca. < 10 Bq kg(-1)-raw). Only in some demersal fish species have detectable concentration levels still been found, and even these species have showed slow radiocesium decreases. The food web was considered as the major factor causing this phenomenon; however, slow elimination rates of radiocesium from these fish species also could be the cause. The latter effect was examined by considering that the (137)Cs concentration decreasing trend in fish could be fit with a set of three exponentially decreasing components; that is, having short, intermediate, and long biological half-lives. The long ecological half-life component was calculated using a 400-1500 d period of monitoring results for Japanese rockfish (Sebastes cheni) and compared with previous reported laboratory results for biological half-life. The obtained ecological half-lives ranged from 274-365 d, and these values agreed with the biological half-life of this fish species. This result implied that the long biological half-lives of radiocesium in some demersal fish species made their radiocesium contamination periods longer.

RBC-/Cr-51/ half-life and albumin turnover in growing Beagle dogs during chronic radial acceleration

NASA Technical Reports Server (NTRS)

Beckman, D. A.; Evans, J. W.; Oyama, J.

1979-01-01

The effects of chronic centrifugation on growing Beagle dogs exposed to -2 or -2.6 Gx on albumin and RBC turnover rates, albumin concentration and space, and total blood volume were determined and compared with caged and run control of animals. Albumin-(I-125) and autologous RBC-(Cr-51) preparations were injected into all dogs at day 82 of the centrifugation periods, and the disappearance curves were determined by successive bleedings of the animals over the next 35 d, during which the centrifugation was continued. There were no differences in albumin turnover rates or space. Two populations of RBCs were found in both centrifugated groups, one with a normal half-life of 27 + or - 1 S.E.M. d, and one with a significantly (p less than 0.01) shorter half-life of 15 + or - 2 S.E.M. d. An absolute polycythemia was also observed in both centrifuged groups. The results suggest that chronic centrifugation acts through some as-yet unknown mechanism to affect RBC population kinetics.

Recovery of nearly 8,000 metagenome-assembled genomes substantially expands the tree of life.

PubMed

Parks, Donovan H; Rinke, Christian; Chuvochina, Maria; Chaumeil, Pierre-Alain; Woodcroft, Ben J; Evans, Paul N; Hugenholtz, Philip; Tyson, Gene W

2017-11-01

Challenges in cultivating microorganisms have limited the phylogenetic diversity of currently available microbial genomes. This is being addressed by advances in sequencing throughput and computational techniques that allow for the cultivation-independent recovery of genomes from metagenomes. Here, we report the reconstruction of 7,903 bacterial and archaeal genomes from >1,500 public metagenomes. All genomes are estimated to be ≥50% complete and nearly half are ≥90% complete with ≤5% contamination. These genomes increase the phylogenetic diversity of bacterial and archaeal genome trees by >30% and provide the first representatives of 17 bacterial and three archaeal candidate phyla. We also recovered 245 genomes from the Patescibacteria superphylum (also known as the Candidate Phyla Radiation) and find that the relative diversity of this group varies substantially with different protein marker sets. The scale and quality of this data set demonstrate that recovering genomes from metagenomes provides an expedient path forward to exploring microbial dark matter.

Half-life, branching-ratio, and Q-value measurement for the superallowed 0{sup +}{yields}0{sup +}{beta}{sup +} emitter {sup 42}Ti

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

Nieto, T. Kurtukian; Souin, J.; Audirac, L.

2009-09-15

The half-life, the branching ratio, and the decay Q value of the superallowed {beta} emitter {sup 42}Ti were measured in an experiment performed at the JYFLTRAP facility of the Accelerator Laboratory of the University of Jyvaeskylae. {sup 42}Ti is the heaviest T{sub z}=-1 nucleus for which high-precision measurements of these quantities have been tried. The half-life (T{sub 1/2}=208.14{+-}0.45 ms) and the Q value [Q{sub EC}=7016.83(25) keV] are close to or reach the required precision of about 0.1%. The branching ratio for the superallowed decay branch [BR=47.7(12)%], a by-product of the half-life measurement, does not reach the necessary precision yet. Nonetheless,more » these results allow one to determine the experimental ft value and the corrected Ft value to be 3114(79) and 3122(79) s, respectively.« less

Thirty years after Chernobyl: Long-term determination of 137Cs effective half-life in the lichen Stereocaulon vesuvianum.

PubMed

Savino, F; Pugliese, M; Quarto, M; Adamo, P; Loffredo, F; De Cicco, F; Roca, V

2017-06-01

It has been widely shown that nuclear fallout includes substances, which accumulate in organisms such as crustaceans, fish, mushrooms and lichens, helping to evaluate the activity concentration of contaminants accumulated on a long time. In this context, radiocaesium deposited in soil following the Chernobyl accident on 26 April 1986 is known to have remained persistently available for plant uptake in many areas of Europe. Studies on the lichen Stereocaulon vesuvianum show the plant's high capacity to retain radionuclides from the substrate and the air. After the Chernobyl accident, starting from September 1986, at the Radioactivity Laboratory (LaRa) of the University of Naples Federico II, four monitoring campaigns to evaluate the activity concentration of four isotopes of the two elements caesium and ruthenium ( 134 Cs, 137 Cs, 103 Ru and 106 Ru) were carried out until 1999. This study allowed the effective half-life of 134 Cs and 137 Cs to be estimated. Twenty-eight years after the accident, in December 2014, a further sampling was carried out; only 137 Cs was revealed beyond the detection limits, measuring activity concentrations ranging from 20 to 40 Bq/kg, while the other radionuclides were no longer observed due to their shorter half-life. The last sampling allowed more precise determination of the effective half-life of 137 Cs (6.2 ± 0.1 year), due to the larger dataset on a large time period. Copyright © 2017 Elsevier Ltd. All rights reserved.

Determination of the half-life of the ground state of {sup 229}Th by using {sup 232}U and {sup 233}U decay series

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

Kikunaga, H.; Nishina Center for Accelerator-Based Science, RIKEN, Wako, Saitama 351-0198; Suzuki, T.

2011-07-15

The half-life of the ground state of {sup 229}Th ({sup 229}Th{sup g}) has become an important factor in nuclear technology, for example, in the geological disposal of nuclear spent fuel. However, the values reported in two previous studies are not in agreement. This study reevaluates the half-life of {sup 229}Th{sup g} by using a simple and reliable method. The {sup 232}U/{sup 233}U activity ratio of a {sup 232,233}U sample was measured by high-resolution {alpha}-particle spectrometry. Next, the {sup 228}Th/{sup 229}Th{sup g} activity ratio of the Th sample, which was grown from the {sup 232,233}U sample, was also measured. The half-lifemore » of {sup 229}Th{sup g} was calculated from these activity ratios, the growth time, and the half-lives of {sup 232}U, {sup 233}U, and {sup 228}Th. From the results of these five measurements, the half-life of {sup 229}Th{sup g} is determined to be 7932 {+-} 55 yr at a confidence level of 2{sigma}.« less

Development of a time-variable nuclear pulser for half life measurements

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

Zahn, Guilherme S.; Domienikan, Claudio; Carvalhaes, Roberto P. M.

2013-05-06

In this work a time-variable pulser system with an exponentially-decaying pulse frequency is presented, which was developed using the low-cost, open-source Arduino microcontroler plataform. In this system, the microcontroller produces a TTL signal in the selected rate and a pulse shaper board adjusts it to be entered in an amplifier as a conventional pulser signal; both the decay constant and the initial pulse rate can be adjusted using a user-friendly control software, and the pulse amplitude can be adjusted using a potentiometer in the pulse shaper board. The pulser was tested using several combinations of initial pulse rate and decaymore » constant, and the results show that the system is stable and reliable, and is suitable to be used in half-life measurements.« less

Perfluorooctane Sulfonate Plasma Half-Life Determination and Long-Term Tissue Distribution in Beef Cattle (Bos taurus).

PubMed

Lupton, Sara J; Dearfield, Kerry L; Johnston, John J; Wagner, Sarah; Huwe, Janice K

2015-12-30

Perfluorooctane sulfonate (PFOS) is used in consumer products as a surfactant and is found in industrial and consumer waste, which ends up in wastewater treatment plants (WWTPs). PFOS does not breakdown during WWTP processes and accumulates in the biosolids. Common practices include application of biosolids to pastures and croplands used for feed, and as a result, animals such as beef cattle are exposed to PFOS. To determine plasma and tissue depletion kinetics in cattle, 2 steers and 4 heifers were dosed with PFOS at 0.098 mg/kg body weight and 9.1 mg/kg, respectively. Plasma depletion half-lives for steers and heifers were 120 ± 4.1 and 106 ± 23.1 days, respectively. Specific tissue depletion half-lives ranged from 36 to 385 days for intraperitoneal fat, back fat, muscle, liver, bone, and kidney. These data indicate that PFOS in beef cattle has a sufficiently long depletion half-life to permit accumulation in edible tissues.

Observation of daily and annular variations in the 214Po half-life

NASA Astrophysics Data System (ADS)

Alexeev, E. N.; Gavrilyuk, Yu. M.; Gangapshev, A. M.; Gezhaev, A. M.; Kazalov, V. V.; Kuzminov, V. V.; Panasenko, S. I.; Ratkevich, S. S.

2017-11-01

Results of the analysis of a time series of values of the half-life (τ) of the 214Po nucleus with a different time step obtained from the TAU-1 (354 days) and TAU-2 (973 days) installations are presented. The annual variation with an amplitude of (9.8 ± 0.6) × 10-4 and daily variations in the solar, lunar, and sidereal times with amplitudes of (5.3 ± 0.3) × 10-4, (6.9 ± 2.0) × 10-4, and (7.2 ± 1.2) × 10-4, respectively, are found in the series of τ values. It is shown that variations in microclimatic parameters cannot be a cause of τ variations.

Half-lives of 214Pb and 214Bi.

PubMed

Martz, D E; Langner, G H; Johnson, P R

1991-10-01

New measurements on chemically separated samples of 214Bi have yielded a mean half-life value of 19.71 +/- 0.02 min, where the error quoted is twice the standard deviation of the mean based on 23 decay runs. This result provides strong support for the historic 19.72 +/- 0.04 min half-life value and essentially excludes the 19.9-min value, both reported in previous studies. New measurements of the decay rate of 222Rn progeny activity initially in radioactive equilibrium have yielded a value of 26.89 +/- 0.03 min for the half-life of 214Pb, where the error quoted is twice the standard deviation of the mean based on 12 decay runs. This value is 0.1 min longer than the currently accepted 214Pb half-value of 26.8 min.

Measurement of the double-{beta} decay half-life of {sup 150}Nd and search for neutrinoless decay modes with the NEMO-3 detector

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

Argyriades, J.; Augier, C.; Bongrand, M.

2009-09-15

The half-life for double-{beta} decay of {sup 150}Nd has been measured by the NEMO-3 experiment at the Modane Underground Laboratory. Using 924.7 days of data recorded with 36.55 g of {sup 150}Nd, we measured the half-life for 2{nu}{beta}{beta} decay to be T{sub 1/2}{sup 2{nu}}=(9.11{sub -0.22}{sup +0.25}(stat.){+-}0.63(syst.))x10{sup 18} yr. The observed limit on the half-life for neutrinoless double-{beta} decay is found to be T{sub 1/2}{sup 0{nu}}>1.8x10{sup 22} yr at 90% confidence level. This translates into a limit on the effective Majorana neutrino mass of <4.0-6.3 eV if the nuclear deformation is taken into account. We also set limits on modelsmore » involving Majoron emission, right-handed currents, and transitions to excited states.« less

Isolation of human anti-serum albumin Fab antibodies with an extended serum-half life.

PubMed

Kang, Hyeon-Ju; Kim, Hye-Jin; Cha, Sang-Hoon

2016-01-01

The serum albumin (SA) has been exploited to generate long-acting biotherapeutics by taking advantage of the FcRn-mediated recycling mechanism in a direct or an indirect way. Since Fab fragments have been proven to be clinically safe for human usage, we assumed that human anti-SA Fab antibodies could have a great potential as a carrier molecule to extend the serum half-life of therapeutic proteins. We, herein, had attempted to isolate anti-SA Fab antibodies from HuDVFab-8L antibody library via a phage display technology, and identified eight discrete human Fab antibodies. One of the Fab antibodies, SL335, showed the strongest binding reactivity to human SA with nM range of affinity at both pH 6 and pH 7.4, and cross-reacted to SAs from various species including rat, mouse, canine and monkey. The in vivo pharmacokinetic assay using a rat model indicated that SL335 has approximately 10 fold longer serum half-life and 26 to 44-fold increase in AUC0 → ∞ compared to the negative control Fab molecule in both intravenous and subcutaneous administrations. Knowing that Fabs have proven to be safe in clinics for a long time, SL335 seems to have a great potential in generating long-acting protein drugs by tagging effector molecules with either chemical conjugation or genetic fusion. Copyright © 2015 Elsevier B.V. All rights reserved.

Genome-wide gene expression and RNA half-life measurements allow predictions of regulation and metabolic behavior in Methanosarcina acetivorans

DOE PAGES

Peterson, Joseph R.; Thor, ShengShee; Kohler, Lars; ...

2016-11-16

Here, while a few studies on the variations in mRNA expression and half-lives measured under different growth conditions have been used to predict patterns of regulation in bacterial organisms, the extent to which this information can also play a role in defining metabolic phenotypes has yet to be examined systematically. Here we present the first comprehensive study for a model methanogen. As a result, we use expression and half-life data for the methanogen Methanosarcina acetivorans growing on fast- and slow-growth substrates to examine the regulation of its genes. Unlike Escherichia coli where only small shifts in half-lives were observed, wemore » found that most mRNA have significantly longer half-lives for slow growth on acetate compared to fast growth on methanol or trimethylamine. Interestingly, half-life shifts are not uniform across functional classes of enzymes, suggesting the existence of a selective stabilization mechanism for mRNAs. Using the transcriptomics data we determined whether transcription or degradation rate controls the change in transcript abundance. Degradation was found to control abundance for about half of the metabolic genes underscoring its role in regulating metabolism. Genes involved in half of the metabolic reactions were found to be differentially expressed among the substrates suggesting the existence of drastically different metabolic phenotypes that extend beyond just the methanogenesis pathways. By integrating expression data with an updated metabolic model of the organism (iST807) significant differences in pathway flux and production of metabolites were predicted for the three growth substrates. In conclusion, this study provides the first global picture of differential expression and half-lives for a class II methanogen, as well as provides the first evidence in a single organism that drastic genome-wide shifts in RNA half-lives can be modulated by growth substrate. We determined which genes in each metabolic pathway

Genome-wide gene expression and RNA half-life measurements allow predictions of regulation and metabolic behavior in Methanosarcina acetivorans

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

Peterson, Joseph R.; Thor, ShengShee; Kohler, Lars

Here, while a few studies on the variations in mRNA expression and half-lives measured under different growth conditions have been used to predict patterns of regulation in bacterial organisms, the extent to which this information can also play a role in defining metabolic phenotypes has yet to be examined systematically. Here we present the first comprehensive study for a model methanogen. As a result, we use expression and half-life data for the methanogen Methanosarcina acetivorans growing on fast- and slow-growth substrates to examine the regulation of its genes. Unlike Escherichia coli where only small shifts in half-lives were observed, wemore » found that most mRNA have significantly longer half-lives for slow growth on acetate compared to fast growth on methanol or trimethylamine. Interestingly, half-life shifts are not uniform across functional classes of enzymes, suggesting the existence of a selective stabilization mechanism for mRNAs. Using the transcriptomics data we determined whether transcription or degradation rate controls the change in transcript abundance. Degradation was found to control abundance for about half of the metabolic genes underscoring its role in regulating metabolism. Genes involved in half of the metabolic reactions were found to be differentially expressed among the substrates suggesting the existence of drastically different metabolic phenotypes that extend beyond just the methanogenesis pathways. By integrating expression data with an updated metabolic model of the organism (iST807) significant differences in pathway flux and production of metabolites were predicted for the three growth substrates. In conclusion, this study provides the first global picture of differential expression and half-lives for a class II methanogen, as well as provides the first evidence in a single organism that drastic genome-wide shifts in RNA half-lives can be modulated by growth substrate. We determined which genes in each metabolic pathway

Re-measuring the half-life of ^60Fe

NASA Astrophysics Data System (ADS)

Collon, Philippe; Stolz, Andreas; Austin, Sam; Couder, Manoel; Ahmad, Irshad; Greene, John; Robertson, Daniel; Schmitt, Chris; Bowers, Matt; Lu, Wenting; Post, Kirk; Carilli, Michael

2009-10-01

A recent experiment both at PSI and at Munich on the ^60Fe lifetime points to a T1/2 for ^60Fe that is possibly 70% higher (i.e. ˜2.6x10^6 years) than the presently accepted value (1.5x10^6 years). ^60Fe is mainly produced in core collapse supernovae explosions and these new results open up a number of questions as many factors scale with this number; from the ^60Fe abundance determination with gamma ray telescope measurements to recent ^60Fe(n, γ) cross section studies. We are presently working on a double-pronged attempt at re-measuring this half-life using the ``old'' AMS technique used by the Kutschera group in 1984 as well as a low-background activity measurement on the growth of ^60Co from the decay of ^60Fe. Both rely however on a clean production of a ^60Fe sample as measurements rely on measuring the ^60Co decay γ-line from ^60Co produced by the decay of ^60Fe. Beam time was made available at the NSCL to produce a well characterized ^60Fe sample at the focal plane of the A1900. The ^60Fe ions were implanted in a high purity Al target. We will report the results from this run as well as from the chemical separation of the ^60Fe and first measurements of the sample.

Half-life measurement of 212Pb by means of a liquid scintillator-based 220Rn trap.

PubMed

Kossert, Karsten

2017-07-01

A beaker was filled with a liquid mineral oil scintillator to catch 220 Rn from a 228 Th source. The liquid scintillator was then transferred to a polyethylene vial which was measured in a custom-built triple-to-double coincidence ratio (TDCR) counter. The measurements were used to determine the 212 Pb half-life which was found to be 10.622(7) hours. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Two-pronged Binding Mechanism of IgG to the Neonatal Fc Receptor Controls Complex Stability and IgG Serum Half-life*

PubMed Central

Schoch, Angela; Larraillet, Vincent; Hilger, Maximiliane; Schlothauer, Tilman; Emrich, Thomas

2017-01-01

The success of recombinant monoclonal immunoglobulins (IgG) is rooted in their ability to target distinct antigens with high affinity combined with an extraordinarily long serum half-life, typically around 3 weeks. The pharmacokinetics of IgGs is intimately linked to the recycling mechanism of the neonatal Fc receptor (FcRn). For long serum half-life of therapeutic IgGs, the highly pH-dependent interaction with FcRn needs to be balanced to allow efficient FcRn binding and release at slightly acidic pH and physiological pH, respectively. Some IgGs, like the antibody briakinumab has an unusually short half-life of ∼8 days. Here we dissect the molecular origins of excessive FcRn binding in therapeutic IgGs using a combination of hydrogen/deuterium exchange mass spectrometry and FcRn affinity chromatography. We provide experimental evidence for a two-pronged IgG-FcRn binding mechanism involving direct FcRn interactions with both the Fc region and the Fab regions of briakinumab, and correlate the occurrence of excessive FcRn binding to an unusually strong Fab-FcRn interaction. PMID:28062799

Phenobarbital administration every eight hours: improvement of seizure management in idiopathic epileptic dogs with decreased phenobarbital elimination half-life.

PubMed

Stabile, F; Barnett, C R; De Risio, L

2017-02-18

Estimated prevalence of canine idiopathic epilepsy is 0.6 per cent in the first-opinion canine population in the UK. Phenobarbital monotherapy has been reported to reduce/eradicate seizure activity in 60-93 per cent of idiopathic epileptic dogs (IEDs). The objective of this study was to evaluate safety and efficacy of the administration of phenobarbital orally every eight hours in IEDs with phenobarbital elimination half-life less than 20 hours. Medical records of 10 IEDs in which steady state trough serum phenobarbital levels were within the reference range and phenobarbital elimination half-life had become less than 20 hours following prolonged administration every 12 hours were reviewed. Side effects and seizure frequency when phenobarbital was administered every 12 hours or 8 hours were compared. In all dogs the side effects of the antiepileptic medication treatment improved. When phenobarbital was administered every eight hours, 9/10 dogs experienced improvement in seizure frequency and 8/10 dogs maintained seizure freedom for a period three times longer than the longest interictal interval period previously recorded. Reduction in the severity and number of clusters of seizures was recorded in one of the remaining two dogs. The administration of phenobarbital orally every eight hours in IEDs with decreased phenobarbital elimination half-life appears safe and can improve seizure management. The results of this study were presented in abstract form (poster) for the 28th symposium of the European Society of Veterinary Neurology - European College of Veterinary Neurology (ESVN), September 18-19, 2015, Amsterdam, Netherlands. British Veterinary Association.

The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: The second clinical candidate having a shorter and favorable human half-life

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

Wang, Jane L.; Limburg, David; Graneto, Matthew J.

2012-05-29

In this Letter, we provide the structure-activity relationships, optimization of design, testing criteria, and human half-life data for a series of selective COX-2 inhibitors. During the course of our structure-based drug design efforts, we discovered two distinct binding modes within the COX-2 active site for differently substituted members of this class. The challenge of a undesirably long human half-life for the first clinical candidate 1t{sub 1/2} = 360 h was addressed by multiple strategies, leading to the discovery of 29b-(S) (SC-75416) with t{sub 1/2} = 34 h.

Biological half-life and organ distribution of [3H]8-arginine vasopressin following administration of vasopressin receptor antagonist OPC-31260.

PubMed

Molnár, Andor H; Varga, Csaba; Janáky, Tamás; Tóth, Gábor; Tóth, Géza; Farkas, Judit; László, Ferenc; László, Ferenc A

2007-06-07

The effects of the antidiuretic (V(2)) non-peptide receptor antagonist OPC-31260 on the plasma vasopressin level and the biological half-life and organ distribution of radiochemically pure, biologically active [(3)H]8-arginine vasopressin [spec. act.: 15.9 mCi/mmol (588 GBq/mmol)] were studied in Wistar rats. The plasma vasopressin level increased significantly throughout the whole experimental period (24 h). There was no change in the fast phase of the curves of total radioactivity disappearance from the plasma after the administration of [(3)H]arginine vasopressin (control: 1.51+/-0.17 min, OPC-31260-treated: 1.42+/-0.12 min, n=10). The fast phase of the disappearance curves of intact [(3)H]arginine vasopressin did not change either following the administration of OPC-31260 in a dose of 30 mg/kg p.o. (control: 1.06+/-0.19 min, OPC-31260-treated: 1.00+/-0.15 min, n=6). The slow phase of the biological half-life, which is characteristic for the examined compound, proved to be significantly longer (total radioactivity control: 9.29+/-0.61 min, OPC-31260-treated: 12.33+/-0.42 min, P<0.05, n=10; [(3)H]arginine vasopressin radioactivity: control: 5.96+/-0.58 min, OPC-31260-treated: 8.90+/-0.37 min, P<0.05, n=6). In the control rats, the radioactivity was accumulated to the greatest extent in the neurohypophysis, adenohypophysis and kidney. Following OPC-31260 administration, significantly more radioactive compounds accumulated in the kidney (control: 0.30+/-0.052 total radioactivity %/100 mg organ weight, OPC-31260-treated: 0.50+/-0.133 total radioactivity %/100 mg organ weight, P<0.05, n=10) and neurohypophysis (control: 0.37+/-0.053 total radioactivity %/100 mg organ weight, OPC-31260-treated: 0.52+/-0.076 total radioactivity %/100 mg organ weight, P<0.05, n=10). Our results permit the conclusion that the antidiuretic antagonist OPC-31260 not only blocks the V(2) receptors, but also increases the biological half-life of vasopressin. The longer biological half-life of

Enhanced circulation half-life of site-specific PEGylated rhG-CSF: optimization of PEG molecular weight.

PubMed

Zhai, Yanqin; Zhao, Yongjiang; Lei, Jiandu; Su, Zhiguo; Ma, Guanghui

2009-07-15

Recombinant human granulocyte colony stimulating factor (rhG-CSF) and its PEGylated product "mono-PEG20-GCSF" have already been widely used for treatment of all kinds of neutropenia. However, the high required dosage of mono-PEG20-GCSF made it relatively expensive in clinical use. We postulated that an N-terminal site-specific PEGylated rhG-CSF with higher PEG Mw (PEG30 kDa) might be able to achieve longer circulation half-life while retaining its bioactivity, allowing the reduction of dosage for clinical use. rhG-CSF was PEGylated at the N-terminus by 5 kDa, 10 kDa, 20 kDa and 30 kDa methoxy-poly(ethylene glycol)-propionaldehyde (mPEG-ALD), and the four PEGylates were compared with respect to reaction, separation, characterization and also in vivo/in vitro activity, results showed that the mPEG-ALD of higher Mw demonstrated better N-terminal site-specific selectivity, separation purity and yield. The production cost and in vitro activity of mono-PEG30-GCSF and mono-PEG20-GCSF were almost the same, while mono-PEG30-GCSF showed longer in vivo circulation half-life and 60% higher drug bioavailability than mono-PEG20-GCSF. Consequently, mono-PEG30-GCSF shall be administered at a lower dosage than mono-PEG20-GCSF while retaining the same therapeutic efficacy.

Immunoglobulin Fc domain fusion to TRAIL significantly prolongs its plasma half-life and enhances its antitumor activity.

PubMed

Wang, Haizhen; Davis, Jennifer S; Wu, Xiangwei

2014-03-01

TRAIL (Apo2L) is a potent inducer of cell death. Interest in TRAIL has increased, following the observation that TRAIL can selectively kill a wide variety of human cancer cells without killing normal cells both in vitro and when grown as xenografts. Therefore, TRAIL has been proposed as a promising anticancer agent and currently is being tested in clinical trials. However, recombinant TRAIL has a very short plasma half-life, which limits its therapeutic potential. To overcome this limitation, we investigated the ability of the human IgG1 fragment crystallizable region (Fc) to enhance TRAIL stability. In this report, we show that Fc-TRAIL chimeric protein displays higher specific activity in vitro and a significantly longer half-life in mice than recombinant human TRAIL (rh-TRAIL). No short-term toxicity, especially liver toxicity, was observed. More importantly, Fc-TRAIL was much more effective in inhibiting tumor growth in a xenograft tumor model compared with rh-TRAIL. Our data suggest that fusion of Fc to TRAIL is able to improve the bioavailability and activity of TRAIL both in vitro and in vivo, and Fc-TRAIL may be explored for future clinical applications in cancer treatment and prevention. ©2014 AACR.

Does substantiated childhood maltreatment lead to poor quality of life in young adulthood? Evidence from an Australian birth cohort study.

PubMed

Abajobir, Amanuel Alemu; Kisely, Steve; Williams, Gail; Strathearn, Lane; Clavarino, Alexandra; Najman, Jake Moses

2017-07-01

To examine the independent effect of single and multiple forms of substantiated childhood maltreatment (CM) on quality of life (QoL), controlling for selected potential confounders and/or covariates, and concurrent depressive symptoms. We used data from a prospective pre-birth cohort of 8556 mothers recruited consecutively during their first antenatal clinic visit at the Mater Hospital from 1981 to 1983 in Brisbane, Australia. The data were linked to substantiated cases of CM reported to the child protection government agency up to the age of 14 years. The sample consisted of 3730 (49.7% female) young adults for whom there were complete data on QoL at the 21-year follow-up. The mean age of participants was 20.6 years. Logistic regression models were used to assess the association between CM and QoL measured at the 21-year follow-up. There were statistically significant associations between exposure to substantiated CM and poorer QoL. This also applied to the subcategories of childhood physical abuse, childhood emotional abuse (CEA), and neglect. These associations were generally stable after adjusting for confounders/covariates and concurrent depressive symptoms, except physical abuse. CEA with or without neglect significantly and particularly predicted worse subsequent QoL. Exposure to any substantiated maltreatment substantially contributed to worse QoL in young adulthood, with a particular association with CEA and neglect. Prior experiences of CM may have a substantial association with subsequent poorer QoL.

Unfounded Attribution of the "Half-Life" Index-Number of Literature Obsolescence to Burton and Kebler: A Literature Science Study.

ERIC Educational Resources Information Center

Szava-Kovats, Endre

2002-01-01

The term and notion of the "half-life" index-number of literature obsolescence, and their borrowing from nuclear physics and adaptation into the literature of literature obsolescence, have up to now been attributed to the librarian Burton and the physicist Kebler and to their 1960 journal article. This article presents evidence to show it is…

High-Precision Measurement of the Ne19 Half-Life and Implications for Right-Handed Weak Currents

NASA Astrophysics Data System (ADS)

Triambak, S.; Finlay, P.; Sumithrarachchi, C. S.; Hackman, G.; Ball, G. C.; Garrett, P. E.; Svensson, C. E.; Cross, D. S.; Garnsworthy, A. B.; Kshetri, R.; Orce, J. N.; Pearson, M. R.; Tardiff, E. R.; Al-Falou, H.; Austin, R. A. E.; Churchman, R.; Djongolov, M. K.; D'Entremont, R.; Kierans, C.; Milovanovic, L.; O'Hagan, S.; Reeve, S.; Sjue, S. K. L.; Williams, S. J.

2012-07-01

We report a precise determination of the Ne19 half-life to be T1/2=17.262±0.007s. This result disagrees with the most recent precision measurements and is important for placing bounds on predicted right-handed interactions that are absent in the current standard model. We are able to identify and disentangle two competing systematic effects that influence the accuracy of such measurements. Our findings prompt a reassessment of results from previous high-precision lifetime measurements that used similar equipment and methods.

High-precision measurement of the 19Ne half-life and implications for right-handed weak currents.

PubMed

Triambak, S; Finlay, P; Sumithrarachchi, C S; Hackman, G; Ball, G C; Garrett, P E; Svensson, C E; Cross, D S; Garnsworthy, A B; Kshetri, R; Orce, J N; Pearson, M R; Tardiff, E R; Al-Falou, H; Austin, R A E; Churchman, R; Djongolov, M K; D'Entremont, R; Kierans, C; Milovanovic, L; O'Hagan, S; Reeve, S; Sjue, S K L; Williams, S J

2012-07-27

We report a precise determination of the (19)Ne half-life to be T(1/2)=17.262±0.007 s. This result disagrees with the most recent precision measurements and is important for placing bounds on predicted right-handed interactions that are absent in the current standard model. We are able to identify and disentangle two competing systematic effects that influence the accuracy of such measurements. Our findings prompt a reassessment of results from previous high-precision lifetime measurements that used similar equipment and methods.

The antitumor agent 3-bromopyruvate has a short half-life at physiological conditions.

PubMed

Glick, Matthew; Biddle, Perry; Jantzi, Josh; Weaver, Samantha; Schirch, Doug

2014-09-12

Clinical research is currently exploring the validity of the anti-tumor candidate 3-bromopyruvate (3-BP) as a novel treatment for several types of cancer. However, recent publications have overlooked rarely-cited earlier work about the instability of 3-BP and its decay to 3-hydroxypyruvate (3-HP) which have obvious implications for its mechanism of action against tumors, how it is administered, and for precautions when preparing solutions of 3-BP. This study found the first-order decay rate of 3-BP at physiological temperature and pH has a half-life of only 77 min. Lower buffer pH decreases the decay rate, while choice of buffer and concentration do not affect it. A method for preparing more stable solutions is also reported. Copyright © 2014 Elsevier Inc. All rights reserved.

Health status and suicide in the second half of life

PubMed Central

Conwell, Yeates; Duberstein, Paul R.; Hirsch, Jameson K.; Conner, Kenneth R.; Eberly, Shirley; Caine, Eric D.

2010-01-01

Objective To examine the associations of suicide in the second half of life with medical and psychiatric illness, functional limitations, and reported use of inpatient, ambulatory, and home health care services. Method A retrospective case-control design was used to compare 86 people over age 50 years who died by suicide with a comparison group of 86 living community participants that were individually matched on age, gender, race, and county of residence. Results Suicide decedents had more Axis I diagnoses, including current mood and anxiety disorders, worse physical health status, and greater impairment in functional capacity. They were more likely to have required psychiatric treatment, medical, or surgical hospitalization in the last year, and visiting nurse or home health aide services. In a multivariate model, the presence of any active Axis I disorder and any impairment in instrumental activities of daily living (IADL) made independent contributions to suicide risk. Conclusions Mental illness, physical illness, and associated functional impairments represent domains of risk for suicide in this age group. In addition to individuals with psychiatric illness, those with severe or comorbid physical illness and functional disability who require inpatient and home care services should be targeted for screening and preventive interventions. PMID:19582758

The effective and environmental half-life of 137Cs at Coral Islands at the former US nuclear test site.

PubMed

Robison, William L; Conrado, Cynthia L; Bogen, Kenneth T; Stoker, A Carol

2003-01-01

The United States (US) conducted nuclear weapons testing from 1946 to 1958 at Bikini and Enewetak Atolls in the northern Marshall Islands. Based on previous detailed dose assessments for Bikini, Enewetak, Rongelap, and Utirik Atolls over a period of 28 years, cesium-137 (137Cs) at Bikini Atoll contributes about 85-89% of the total estimated dose through the terrestrial food chain as a result of uptake of 137Cs by food crops. The estimated integral 30, 50, and 70-year doses were based on the radiological decay of 137Cs (30-year half-life) and other radionuclides. However, there is a continuing inventory of 137Cs and 90Sr in the fresh water portion of the groundwater at all contaminated atolls even though the turnover rate of the fresh groundwater is about 5 years. This is evidence that a portion of the soluble fraction of 137Cs and 90Sr inventory in the soil is lost by transport to groundwater when rainfall is heavy enough to cause recharge of the lens, resulting in loss of 137Cs from the soil column and root zone of the plants. This loss is in addition to that caused by radioactive decay. The effective rate of loss was determined by two methods: (1) indirectly, from time-dependent studies of the 137Cs concentration in leaves of Pisonia grandis, Guettarda specosia, Tournefortia argentea (also called Messerschmidia), Scaevola taccada, and fruit from Pandanus and coconut trees (Cocos nucifera L.), and (2) more directly, by evaluating the 137Cs/90Sr ratios at Bikini Atoll. The mean (and its lower and upper 95% confidence limits) for effective half-life and for environmental-loss half-life (ELH) based on all the trees studied on Rongelap, Bikini, and Enewetak Atolls are 8.5 years (8.0 years, 9.8 years), and 12 years (11 years, 15 years), respectively. The ELH based on the 137Cs/90Sr ratios in soil in 1987 relative to the 137Cs/90Sr ratios at the time of deposition in 1954 is less than 17 years. The magnitude of the decrease below 17 years depends on the ELH for 90Sr

A substantial proportion of life-threatening injuries are sport-related.

PubMed

Meehan, William P; Mannix, Rebekah

2013-05-01

This study aimed to assess the proportion of all life-threatening injuries that are sport-related. We conducted a cross-sectional study of patients included in the National Hospital Ambulatory Medical Care Survey during the years 1999 to 2008. Life-threatening injuries were defined according to the International Classification of Diseases, Ninth Revision codes: skull fracture (800.x-802.xx, 803.x-804.xx), cervical spine fractures (805.xx-806.10), intracranial hemorrhage (852.xx-853.xx), traumatic pneumothorax/hemothorax (860.00-860.05), liver lacerations (864.xx), spleen lacerations (865.xx), aortic rupture (901.0; 902.0), gastric/duodenal rupture (537.89), heat stroke (992.0), and commotio cordis/heart contusion (861.01). Sport-related was defined by the external cause of injury codes, confirmed by text search. There were 300,394 observed emergency department visits during the study period. An estimated 0.5% (95% confidence interval [CI], 0.5%-0.6%) of all emergency department visits nationally were for life-threatening injuries. Of the life-threatening injuries, 14% (95% CI, 12%-17) were sport-related, representing 926,805 sport-related, life-threatening injuries nationally. A higher percentage (32%; 95% CI, 27%-38%) of life-threatening injuries sustained by children was sport-related when compared with adults (9%; 95% CI, 7%-11%). For adults aged 19 to 44 years, 12% (95% CI, 9%-15%) of life-threatening injuries were sport-related. For children aged 6 to 18 years, 39% (95% CI, 33%-46%) of life-threatening injuries were sport-related. Nearly a quarter (23%; 95% CI, 7%-55%) of pediatric cervical spine fractures was sport-related. The percentage of cervical spine fractures that were sport-related was lower for adults (7%; 95% CI, 4%-11%). Efforts should be made to prevent the number of sport-related, life-threatening injuries.

A Substantial Proportion of Life-Threatening Injuries are Sport-Related

PubMed Central

Meehan, William P.; Mannix, Rebekah

2013-01-01

Objective To assess the proportion of all life-threatening injuries that are sport-related. Methods We conducted a cross-sectional study of patients included in the National Hospital Ambulatory Medical Care Survey (NHAMCS) during the years 1999–2008. Life-threatening injuries were defined as International Classification of Diseases 9 codes: skull fracture [800.x–802.xx, 803.x–804.xx], cervical spine fractures [805.xx–806.10], intracranial hemorrhage [852.xx–853.xx], traumatic pneumothorax/hemothorax [860.00–860.05], liver lacerations [864.xx], spleen lacerations [865.xx], aortic rupture [901.0; 902.0], gastric/duodenal rupture [537.89], heat stroke [992.0], and commotio cordis/heart contusion [861.01]. Sport-related was defined by external cause of injury codes, confirmed by text search. Results There were 300,394 observed emergency department visits during the study period. An estimated 0.5% (95% CI, 0.5 – 0.6) of all ED visits nationally were for life-threatening injuries. Of life-threatening injuries, 14% (95% CI, 12 – 17) were sport-related, representing 926,805 sport-related, life-threatening injuries nationally. A higher percentage (32%; 95% CI, 27 – 38) of life-threatening injuries sustained by children was sport-related when compared with adults (9%; 95% CI, 7 – 11). For adults aged 19–44 years, 12% (95% CI, 9 – 15) of life-threatening injuries were sport-related. For children aged 6–18 years, 39% (95% CI, 33 – 46) of life-threatening injuries were sport-related. Nearly a quarter (23%; 95% CI, 7 – 55) of pediatric cervical spine fractures was sport-related. The percentage of cervical spine fractures that were sport-related was lower for adults (7%; 95% CI, 4 – 11). Conclusion Efforts should be made to prevent the number of sport-related, life-threatening injuries. PMID:23603654

Chitosan-decorated selenium nanoparticles as protein carriers to improve the in vivo half-life of the peptide therapeutic BAY 55-9837 for type 2 diabetes mellitus.

PubMed

Rao, Lei; Ma, Yi; Zhuang, Manjiao; Luo, Tianjie; Wang, Yayu; Hong, An

2014-01-01

As a potential protein therapeutic for type 2 diabetes mellitus (T2DM), BAY 55-9837 is limited by poor stability and a very short half-life in vivo. The purpose of this study was to construct a novel nanostructured biomaterial by conjugating BAY 55-9837 to chitosan-decorated selenium nanoparticles (CS-SeNPs) to prolong the in vivo half-life of BAY 55-9837 by reducing its renal clearance rate. BAY 55-9837-loaded CS-SeNPs (BAY-CS-SeNPs) were prepared, and their surface morphology, particle size, zeta potential, and structure were characterized. The stability, protein-loading rate, and in vitro release of BAY 55-9837 from CS-SeNPs were also quantified. Additionally, a sensitive high-performance liquid chromatography (HPLC) assay was developed for the quantification of BAY 55-9837 in mouse plasma. Thereafter, mice were injected via the tail vein with either BAY 55-9837 or BAY-CS-SeNPs, and the plasma concentration of BAY 55-9837 was determined via our validated HPLC method at different time intervals postinjection. Relevant in vivo pharmacokinetic parameters (half-life, area under the curve from time 0 to last sampling point, observed clearance) were then calculated and analyzed. BAY-CS-SeNPs were successfully synthesized, with diameters of approximately 200 nm. BAY-CS-SeNPs displayed good stability with a high protein-loading rate, and the release process of BAY 55-9837 from the CS-SeNPs lasted for over 70 hours, with the cumulative release reaching 78.9%. Moreover, the conjugation of CS-SeNPs to BAY 55-9837 significantly reduced its renal clearance to a rate of 1.56 mL/h and extended its half-life to 20.81 hours. In summary, our work provides a simple method for reducing the renal clearance rate and extending the half-life of BAY 55-9837 in vivo by utilizing CS-SeNPs as nanocarriers.

Application of fracture mechanics and half-cycle method to the prediction of fatigue life of B-52 aircraft pylon components

NASA Technical Reports Server (NTRS)

Ko, W. L.; Carter, A. L.; Totton, W. W.; Ficke, J. M.

1989-01-01

Stress intensity levels at various parts of the NASA B-52 carrier aircraft pylon were examined for the case when the pylon store was the space shuttle solid rocket booster drop test vehicle. Eight critical stress points were selected for the pylon fatigue analysis. Using fracture mechanics and the half-cycle theory (directly or indirectly) for the calculations of fatigue-crack growth ,the remaining fatigue life (number of flights left) was estimated for each critical part. It was found that the two rear hooks had relatively short fatigue life and that the front hook had the shortest fatigue life of all the parts analyzed. The rest of the pylon parts were found to be noncritical because of their extremely long fatigue life associated with the low operational stress levels.

Increased volume of distribution for recombinant activated factor VII and longer plasma-derived factor VII half-life may explain their long lasting prophylactic effect.

PubMed

Mathijssen, Natascha C J; Masereeuw, Rosalinde; Holme, Pal Andre; van Kraaij, Marian G J; Laros-van Gorkom, Britta A P; Peyvandi, Flora; van Heerde, Waander L

2013-08-01

Prophylaxis with plasma-derived or recombinant activated factor VII is beneficial in severe factor VII deficiency. To understand why prophylactic treatment with both products is efficacious, we conducted a pharmacokinetic study. Ten factor VII deficient patients were treated with either recombinant activated (20 μg/kg) or plasma-derived (25 IU/kg) factor VII in a cross-over design. Pharmacokinetic parameters were analyzed through activated factor VII activity, factor VII clotting activity, and factor VII antigen levels on depicted time points. Factor VII activity half-lifes, determined by non-compartmental and one-compartmental analysis (results in brackets), were shorter for recombinant activated (1.4h; 0.7h) than for plasma-derived factor VII (6.8h; 3.2h); both recombinant activated (5.1h; 2.1h and plasma-derived factor VII (5.8h; 3.2h) resulted in longer half-lives of factor VII antigen. Activated factor VII half-lives (based on activated factor VII activity levels) were significantly higher compared to factor VII clotting activity (1.6h; 0.9h). Volumes of distribution were significantly higher for activated factor VII (236 ml/kg; 175 ml/kg, measured by activated factor VII) as compared to plasma-derived factor VII (206 ml/kg; 64 ml/kg, measured by factor FVII activity), suggesting a plasma- and extracellular fluid distribution for recombinant activated factor VII. Recombinant activated factor VII showed significantly shorter half-lifes than plasma-derived factor VII. Volumes of distribution were significantly higher for treatment with recombinant activated factor VII. The longer half-life for plasma-derived factor VII, compared to recombinant activated factor VII, and the increased volume of distribution for recombinant activated factor VII, compared to plasma-derived factor VII may further elucidate the beneficial effect of prophylactic treatment of both products. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparison between the clot-protecting activity of a mutant plasminogen activator inhibitor-1 with a very long half-life and 6-aminocaproic acid.

PubMed

Kindell, Daniel Glenn; Keck, Rick Wayne; Jankun, Jerzy

2015-06-01

Plasminogen activator inhibitor (PAI)-1 is a serpin glycoprotein that can stabilize blood clots by inhibiting fibrinolysis. However, wild-type PAI-1 has the disadvantage of a short half-life of ∼2 h. A very long half-life (VLHL) PAI-1 mutant was developed previously with an active-form half-life of >700 h, making it a possible candidate for use in hemorrhagic therapy. Current treatments for mitigating hemorrhage, other than inducers of blood clotting, are limited to lysine analog antifibrinolytics, including 6-aminocaproic acid and tranexamic acid. VLHL PAI-1 has been previously demonstrated to limit bleeding; however, the efficacy of this protein compared with lysine analog antifibrinolytics has not been investigated. The aim of the current study was to compare the clot stabilizing properties of the novel antifibrinolytic VLHL PAI-1 with those of 6-aminocaproic acid in reference plasma. Using thromboelastographic analysis, VLHL PAI-1 exhibited an IC 50 (half maximal inhibitory concentration) of 8.8×10 -8 mol/l, while 6-aminocaproic acid showed an IC 50 of 1.6×10 -4 mol/l. However, at doses of >9.0×10 -7 mol/l, VLHL PAI-1 exhibited a delay in the onset of clot formation, which may be attributed to thrombin inhibition by excess PAI-1. The inhibition of tissue plasminogen activator by VLHL PAI-1 demonstrated improved efficacy over 6-aminocaproic acid in mitigating hemorrhage. In addition, patients with a PAI-1 deficiency, which causes blood clots to lyse rapidly resulting in profuse bleeding, may benefit from the application of VLHL PAI-1 as an antihemorrhagic therapy.

Comparison between the clot-protecting activity of a mutant plasminogen activator inhibitor-1 with a very long half-life and 6-aminocaproic acid

PubMed Central

KINDELL, DANIEL GLENN; KECK, RICK WAYNE; JANKUN, JERZY

2015-01-01

Plasminogen activator inhibitor (PAI)-1 is a serpin glycoprotein that can stabilize blood clots by inhibiting fibrinolysis. However, wild-type PAI-1 has the disadvantage of a short half-life of ∼2 h. A very long half-life (VLHL) PAI-1 mutant was developed previously with an active-form half-life of >700 h, making it a possible candidate for use in hemorrhagic therapy. Current treatments for mitigating hemorrhage, other than inducers of blood clotting, are limited to lysine analog antifibrinolytics, including 6-aminocaproic acid and tranexamic acid. VLHL PAI-1 has been previously demonstrated to limit bleeding; however, the efficacy of this protein compared with lysine analog antifibrinolytics has not been investigated. The aim of the current study was to compare the clot stabilizing properties of the novel antifibrinolytic VLHL PAI-1 with those of 6-aminocaproic acid in reference plasma. Using thromboelastographic analysis, VLHL PAI-1 exhibited an IC50 (half maximal inhibitory concentration) of 8.8×10−8 mol/l, while 6-aminocaproic acid showed an IC50 of 1.6×10−4 mol/l. However, at doses of >9.0×10−7 mol/l, VLHL PAI-1 exhibited a delay in the onset of clot formation, which may be attributed to thrombin inhibition by excess PAI-1. The inhibition of tissue plasminogen activator by VLHL PAI-1 demonstrated improved efficacy over 6-aminocaproic acid in mitigating hemorrhage. In addition, patients with a PAI-1 deficiency, which causes blood clots to lyse rapidly resulting in profuse bleeding, may benefit from the application of VLHL PAI-1 as an antihemorrhagic therapy. PMID:26136983

Substantial Goodness and Nascent Human Life.

PubMed

Floyd, Shawn

2015-09-01

Many believe that moral value is--at least to some extent--dependent on the developmental states necessary for supporting rational activity. My paper rejects this view, but does not aim simply to register objections to it. Rather, my essay aims to answer the following question: if a human being's developmental state and occurrent capacities do not bequeath moral standing, what does? The question is intended to prompt careful consideration of what makes human beings objects of moral value, dignity, or (to employ my preferred term) goodness. Not only do I think we can answer this question, I think we can show that nascent human life possesses goodness of precisely this sort. I appeal to Aquinas's metaethics to establish the conclusion that the goodness of a human being--even if that being is an embryo or fetus--resides at the substratum of her existence. If she possesses goodness, it is because human existence is good.

Phase I study of BAY 94-9027, a PEGylated B-domain-deleted recombinant factor VIII with an extended half-life, in subjects with hemophilia A.

PubMed

Coyle, T E; Reding, M T; Lin, J C; Michaels, L A; Shah, A; Powell, J

2014-04-01

BAY 94-9027 is a B-domain-deleted recombinant factor VIII (rFVIII) with site-specific attachment of poly(ethylene glycol) that has shown an extended half-life in animal models of hemophilia. To assess the pharmacokinetics and safety of BAY 94-9027 after single and repeated administration in subjects with severe hemophilia A. This 8-week, prospective, multicenter, open-label, phase I trial was conducted in 14 subjects aged 21–58 years with FVIII of < 1%, ≥ 150 days of exposure to FVIII, and no history of FVIII inhibitors. After a ≥ 3-day washout, subjects received a single dose of sucrose-formulated rFVIII (rFVIII-FS) (cohort 1 [n = 7], 25 IU kg−1; cohort 2 [n = 7], 50 IU kg−1) for a 48-h pharmacokinetic (PK) study. After another ≥ 3-day washout, cohort 1 received twice-weekly BAY 94-9027 at 25 IU kg−1 (16 doses), and cohort 2 received once-weekly BAY 94-9027 at 60 IU kg−1 (nine doses). A 168-h PK study was performed after the first and last BAY 94-9027 doses. BAY 94-9027 showed equivalent recovery and an improved PK profile vs. rFVIII-FS, with a half-life of ~ 19 h (vs. ~ 13.0 h for rFVIII-FS). BAY 94-9027 was well tolerated, and no immunogenicity was observed. This phase I study demonstrates that BAY 94-9027 has an extended half-life in subjects with hemophilia A and, after multiple dosing, was well tolerated with no immunogenicity during the 8-week trial. A phase III study in a larger number of subjects is underway to fully characterize how this prolonged half-life will permit less frequent prophylaxis dosing for patients with hemophilia.

Crosslinking of micropatterned collagen-based nerve guides to modulate the expected half-life.

PubMed

Salvatore, L; Madaghiele, M; Parisi, C; Gatti, F; Sannino, A

2014-12-01

The microstructural, mechanical, compositional, and degradative properties of a nerve conduit are known to strongly affect the regenerative process of the injured peripheral nerve. Starting from the fabrication of micropatterned collagen-based nerve guides, according to a spin-casting process reported in the literature, this study further investigates the possibility to modulate the degradation rate of the scaffolds over a wide time frame, in an attempt to match different rates of nerve regeneration that might be encountered in vivo. To this aim, three different crosslinking methods, that is, dehydrothermal (DHT), carbodiimide-based (EDAC), and glutaraldehyde-based (GTA) crosslinking, were selected. The elastically effective degree of crosslinking, attained by each method and evaluated according to the classical rubber elasticity theory, was found to significantly tune the in vitro half-life (t1/2 ) of the matrices, with an exponential dependence of the latter on the crosslink density. The high crosslinking efficacy of EDAC and GTA treatments, respectively threefold and fourfold when compared to the one attained by DHT, led to a sharp increase of the corresponding in vitro half-lives (ca., 10, 172, and 690 h, for DHT, EDAC, and GTA treated matrices, respectively). As shown by cell viability assays, the cytocompatibility of both DHT and EDAC treatments, as opposed to the toxicity of GTA, suggests that such methods are suitable to crosslink collagen-based scaffolds conceived for clinical use. In particular, nerve guides with expected high residence times in vivo might be produced by finely controlling the biocompatible reaction(s) adopted for crosslinking. © 2014 Wiley Periodicals, Inc.

Dual Constant Domain-Fab: A novel strategy to improve half-life and potency of a Met therapeutic antibody.

PubMed

Cignetto, Simona; Modica, Chiara; Chiriaco, Cristina; Fontani, Lara; Milla, Paola; Michieli, Paolo; Comoglio, Paolo M; Vigna, Elisa

2016-06-01

The kinase receptor encoded by the Met oncogene is a sensible target for cancer therapy. The chimeric monovalent Fab fragment of the DN30 monoclonal antibody (MvDN30) has an odd mechanism of action, based on cell surface removal of Met via activation of specific plasma membrane proteases. However, the short half-life of the Fab, due to its low molecular weight, is a severe limitation for the deployment in therapy. This issue was addressed by increasing the Fab molecular weight above the glomerular filtration threshold through the duplication of the constant domains, in tandem (DCD-1) or reciprocally swapped (DCD-2). The two newly engineered molecules showed biochemical properties comparable to the original MvDN30 in vitro, acting as full Met antagonists, impairing Met phosphorylation and activation of downstream signaling pathways. As a consequence, Met-mediated biological responses were inhibited, including anchorage-dependent and -independent cell growth. In vivo DCD-1 and DCD-2 showed a pharmacokinetic profile significantly improved over the original MvDN30, doubling the circulating half-life and reducing the clearance. In pre-clinical models of cancer, generated by injection of tumor cells or implant of patient-derived samples, systemic administration of the engineered molecules inhibited the growth of Met-addicted tumors. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Development and in vivo characterization of a novel peptide drug delivery system providing extended plasma half life.

PubMed

Shahnaz, Gul; Iqbal, Javed; Rahmat, Deni; Perera, Glen; Laffleur, Flavia; Rossi, Denise; Bernkop-Schnürch, Andreas

2012-02-10

It was the aim of this study to develop a sustained parenteral peptide (DALCE) delivery system by the immobilization of DALCE to thiolated carboxymethyl dextran-cysteine (CMD-Cys) via disulfide bond formation. The resulting CMD-Cys-DALCE conjugate displayed a 22.6±7.9% (m/m) of DALCE (mean±S.D.; n=3). The conjugation of DALCE with CMD-Cys was confirmed by FTIR-ATR spectroscopy. In vitro release studies of conjugate CMD-Cys-DALCE in the presence of 2 μM/ml reduced glutathione (GSH) being also available in the plasma showed a sustained peptide release over a time period of 8 h, because of thiol/disulfide exchange reactions. For in vivo pharmacokinetic study, DALCE and CMD-Cys-DALCE were administered intravenously to male Sprague-Dawley rats at a dose of 1mg/kg. The AUC(0-8) (ng.min/ml) was determined to be 268848±924 and 40019±495 for CMD-Cys-DALCE and DALCE, respectively. The mean residence time (MRT) was determined to be 256±8 and 53.1±9.5 min for CMD-Cys-DALCE and for DALCE, respectively. CMD-Cys-DALCE showed a more than 5-fold increased elimination half-life (p<0.01), 3-fold decreased volume of distribution (p<0.01) and a 6.7-fold decreased plasma clearance rate (p<0.01) compared to DALCE. According to these findings, CMD-Cys-DALCE seems to act as prodrug by improving half-life and decreasing plasma clearance. Copyright © 2011 Elsevier B.V. All rights reserved.

Estimation of renal allograft half-life: fact or fiction?

PubMed

Azancot, M Antonieta; Cantarell, Carme; Perelló, Manel; Torres, Irina B; Serón, Daniel; Seron, Daniel; Moreso, Francesc; Arias, Manuel; Campistol, Josep M; Curto, Jordi; Hernandez, Domingo; Morales, José M; Sanchez-Fructuoso, Ana; Abraira, Victor

2011-09-01

Renal allograft half-life time (t½) is the most straightforward representation of long-term graft survival. Since some statistical models overestimate this parameter, we compare different approaches to evaluate t½. Patients with a 1-year functioning graft transplanted in Spain during 1990, 1994, 1998 and 2002 were included. Exponential, Weibull, gamma, lognormal and log-logistic models censoring the last year of follow-up were evaluated. The goodness of fit of these models was evaluated according to the Cox-Snell residuals and the Akaike's information criterion (AIC) was employed to compare these models. We included 4842 patients. Real t½ in 1990 was 14.2 years. Median t½ (95% confidence interval) in 1990 and 2002 was 15.8 (14.2-17.5) versus 52.6 (35.6-69.5) according to the exponential model (P < 0.001). No differences between 1990 and 2002 were observed when t½ was estimated with the other models. In 1990 and 2002, t½ was 14.0 (13.1-15.0) versus 18.0 (13.7-22.4) according to Weibull, 15.5 (13.9-17.1) versus 19.1 (15.6-22.6) according to gamma, 14.4 (13.3-15.6) versus 18.3 (14.2-22.3) according to the log-logistic and 15.2 (13.8-16.6) versus 18.8 (15.3-22.3) according to the lognormal models. The AIC confirmed that the exponential model had the lowest goodness of fit, while the other models yielded a similar result. The exponential model overestimates t½, especially in cohorts of patients with a short follow-up, while any of the other studied models allow a better estimation even in cohorts with short follow-up.

Utilization of in vitro Caco-2 permeability and liver microsomal half-life screens in discovering BMS-488043, a novel HIV-1 attachment inhibitor with improved pharmacokinetic properties.

PubMed

Yang, Zheng; Zadjura, Lisa M; Marino, Anthony M; D'Arienzo, Celia J; Malinowski, Jacek; Gesenberg, Christoph; Lin, Pin-Fang; Colonno, Richard J; Wang, Tao; Kadow, John F; Meanwell, Nicholas A; Hansel, Steven B

2010-04-01

Optimizing pharmacokinetic properties to improve oral exposure is a common theme in modern drug discovery. In the present work, in vitro Caco-2 permeability and microsomal half-life screens were utilized in an effort to guide the structure-activity relationship in order to improve the pharmacokinetic properties of novel HIV-1 attachment inhibitors. The relevance of the in vitro screens to in vivo pharmacokinetic properties was first demonstrated with a number of program compounds at the early stage of lead optimization. The Caco-2 permeability, tested at 200 microM, was quantitatively predictive of in vivo oral absorption, with complete absorption occurring at a Caco-2 permeability of 100 nm/s or higher. The liver microsomal half-life screen, conducted at 1 microM substrate concentration, can readily differentiate low-, intermediate-, and high-clearance compounds in rats, with a nearly 1:1 correlation in 12 out of 13 program compounds tested. Among the >100 compounds evaluated, BMS-488043 emerged as a lead, exhibiting a Caco-2 permeability of 178 nm/s and a microsomal half-life predictive of a low clearance (4 mL/min/kg) in humans. These in vitro characteristics translated well to the in vivo setting. The oral bioavailability of BMS-488043 in rats, dogs, and monkeys was 90%, 57%, and 60%, respectively. The clearance was low in all three species tested, with a terminal half-life ranging from 2.4 to 4.7 h. Furthermore, the oral exposure of BMS-488043 was significantly improved (6- to 12-fold in rats and monkeys) compared to the prototype compound BMS-378806 that had a suboptimal Caco-2 permeability (51 nm/s) and microsomal half-life. More importantly, the improvements in preclinical pharmacokinetics translated well to humans, leading to a >15-fold increase in the human oral exposure of BMS-488043 than BMS-378806 and enabling a clinical proof-of-concept for this novel class of anti-HIV agents. The current studies demonstrated the valuable role of in vitro ADME screens

A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants.

PubMed

Zhu, Qing; McLellan, Jason S; Kallewaard, Nicole L; Ulbrandt, Nancy D; Palaszynski, Susan; Zhang, Jing; Moldt, Brian; Khan, Anis; Svabek, Catherine; McAuliffe, Josephine M; Wrapp, Daniel; Patel, Nita K; Cook, Kimberly E; Richter, Bettina W M; Ryan, Patricia C; Yuan, Andy Q; Suzich, JoAnn A

2017-05-03

Prevention of respiratory syncytial virus (RSV) illness in all infants is a major public health priority. However, no vaccine is currently available to protect this vulnerable population. Palivizumab, the only approved agent for RSV prophylaxis, is limited to high-risk infants, and the cost associated with the requirement for dosing throughout the RSV season makes its use impractical for all infants. We describe the development of a monoclonal antibody as potential RSV prophylaxis for all infants with a single intramuscular dose. MEDI8897*, a highly potent human antibody, was optimized from antibody D25, which targets the prefusion conformation of the RSV fusion (F) protein. Crystallographic analysis of Fab in complex with RSV F from subtypes A and B reveals that MEDI8897* binds a highly conserved epitope. MEDI8897* neutralizes a diverse panel of RSV A and B strains with >50-fold higher activity than palivizumab. At similar serum concentrations, prophylactic administration of MEDI8897* was ninefold more potent than palivizumab at reducing pulmonary viral loads by >3 logs in cotton rats infected with either RSV A or B subtypes. MEDI8897 was generated by the introduction of triple amino acid substitutions (YTE) into the Fc domain of MEDI8897*, which led to more than threefold increased half-life in cynomolgus monkeys compared to non-YTE antibody. Considering the pharmacokinetics of palivizumab in infants, which necessitates five monthly doses for protection during an RSV season, the high potency and extended half-life of MEDI8897 support its development as a cost-effective option to protect all infants from RSV disease with once-per-RSV-season dosing in the clinic. Copyright © 2017, American Association for the Advancement of Science.

Development of CANDLES low background HPGe detector and half-life measurement of 180Tam

NASA Astrophysics Data System (ADS)

Chan, W. M.; Kishimoto, T.; Umehara, S.; Matsuoka, K.; Suzuki, K.; Yoshida, S.; Nakajima, K.; Iida, T.; Fushimi, K.; Nomachi, M.; Ogawa, I.; Tamagawa, Y.; Hazama, R.; Takemoto, Y.; Nakatani, N.; Takihira, Y.; Tozawa, M.; Kakubata, H.; Trang, V. T. T.; Ohata, T.; Tetsuno, K.; Maeda, T.; Khai, B. T.; Li, X. L.; Batpurev, T.

2018-01-01

A low background HPGe detector system was developed at CANDLES Experimental Hall for multipurpose use. Various low background techniques were employed, including hermatic shield design, radon gas suppression, and background reduction analysis. A new pulse shape discrimination (PSD) method was specially created for coaxial Ge detector. Using this PSD method, microphonics noise and background event at low energy region less than 200 keV can be rejected effectively. Monte Carlo simulation by GEANT4 was performed to acquire the detection efficiency and study the interaction of gamma-rays with detector system. For rare decay measurement, the detector was utilized to detect the nature's most stable isomer tantalum-180m (180Tam) decay. Two phases of tantalum physics run were completed with total livetime of 358.2 days, which Phase II has upgraded shield configuration. The world most stringent half-life limit of 180Tam has been successfully achieved.

Omalizumab substantially improves dermatology-related quality of life in patients with chronic spontaneous urticaria.

PubMed

Finlay, A Y; Kaplan, A P; Beck, L A; Antonova, E N; Balp, M-M; Zazzali, J; Khalil, S; Maurer, M

2017-10-01

Chronic spontaneous/idiopathic urticaria (CSU/CIU) has substantial detrimental effects on health-related quality of life (HRQoL) with an effect comparable to or worse than many other skin diseases. To assess the effect of omalizumab on CSU patients' HRQoL, measured by the Dermatology Life Quality Index (DLQI) in three phase III studies ASTERIA I, ASTERIA II and GLACIAL. A post hoc analysis examined changes in DLQI scores, distribution of patients across DLQI bands and the proportion reaching minimal clinically important difference (MCID) following omalizumab vs. placebo. Omalizumab 300 mg significantly improved total DLQI scores vs. placebo, with a mean decrease from baseline to week 12 of -10.3 vs. -6.1 (P < 0.0001) in ASTERIA I, -10.2 vs. -6.1 (P = 0.0004) in ASTERIA II and -9.7 vs. -5.1 (P < 0.0001) in GLACIAL. A significant shift from high disease impact on life at baseline towards less impact at week 12 was seen with omalizumab 300 mg vs. placebo (P < 0.001; all studies). The proportion of patients where change in mean total DLQI score from baseline to week 12 reached an MCID of ≥4 was 74.1%, 76.0% and 77.2% in ASTERIA I, II and GLACIAL, respectively (P < 0.01; all studies). Maximum duration of omalizumab treatment was 24 weeks. This additional analysis assessed the impact of CSU and benefit of treatment with omalizumab by exploring different facets of DLQI data by treatment arm at multiple assessment points. The original aspects of analysis included applying the concept of the recently validated score for the MCID of the DLQI, changes in DLQI domain scores and in the distribution of subjects based on validated total DLQI score bands. It showed consistently that omalizumab provides significant and clinically relevant improvements in many aspects of HRQoL that are important to patients with CSU. These results contribute to a better understanding of the impact of CSU and its treatment on patients and can support clinical decision-making in routine medical

Comparison of 75SeHCAT retention half-life and fecal content of individual bile acids in patients with chronic diarrheal disorders.

PubMed

Scheurlen, C; Kruis, W; Büll, U; Stellaard, F; Lang, P; Paumgartner, G

1986-01-01

Measurement of the retention of 23-75Se-25-homotaurocholic acid (SeHCAT) has been suggested as a new test for ileal function. We investigated 31 patients with chronic diarrhea, 10 with ileal Crohn's disease and 21 with diarrhea but without ileal disease. The whole-body retention half-life of 1 mu Ci SeHCAT was determined and compared to the fecal content of total and individual bile acids. Patients with ileal disease had increased primary fecal bile acids (chenodeoxycholic acid: mean 6.95 mg/g dry weight, range 3.15-10.6 mg/g; cholic acid: mean 18.15 mg/g, range 10.3-33.9 mg/g) and a short SeHCAT retention (mean 11.9 h, range 2-24 h), whereas patients with intact ileum had normal fecal bile acids and a SeHCAT retention of 85.9 h (range 28-216 h). SeHCAT retention half-life differentiated well between patients with ileal disease and patients with normal ileum, thus indicating the SeHCAT test as a valid investigation method for detection of primary bile acid malabsorption in patients with chronic diarrhea and ileal dysfunction.

Do radioactive half-lives vary with the Earth-to-Sun distance?

PubMed

Hardy, J C; Goodwin, J R; Iacob, V E

2012-09-01

Recently, Jenkins, Fischbach and collaborators have claimed evidence that radionuclide half-lives vary systematically over a ±0.1% range as a function of the oscillating distance between the Earth and the Sun, based on multi-year activity measurements. We have avoided the time-dependent instabilities to which such measurements are susceptible by directly measuring the half-life of (198)Au (t(1/2)=2.695 d) on seven occasions spread out in time to cover the complete range of Earth-Sun distances. We observe no systematic oscillations in half-life and can set an upper limit on their amplitude of ±0.02%. Copyright © 2012 Elsevier Ltd. All rights reserved.

Estimating biodegradation half-lives for use in chemical screening.

PubMed

Aronson, Dallas; Boethling, Robert; Howard, Philip; Stiteler, William

2006-06-01

Biodegradation half-lives are needed for many applications in chemical screening, but these data are not available for most chemicals. To address this, in phase one of this work we correlated the much more abundant ready and inherent biodegradation test data with measured half-lives for water and soil. In phase two, we explored the utility of the BIOWIN models (in EPI Suite) and molecular fragments for predicting half-lives. BIOWIN model output was correlated directly with measured half-lives, and new models were developed by re-regressing the BIOWIN fragments against the half-lives. All of these approaches gave the best results when used for binary (fast/slow) classification of half-lives, with accuracy generally in the 70-80% range. In the last phase, we used the collected half-life data to examine the default half-lives assigned by EPI Suite and the PBT Profiler for use as input to their level III multimedia models. It is concluded that estimated half-lives should not be used for purposes other than binning or prioritizing chemicals unless accuracy improves significantly.

Intermittent Drug Dosing Intervals Guided by the Operational Multiple Dosing Half Lives for Predictable Plasma Accumulation and Fluctuation

PubMed Central

Grover, Anita; Benet, Leslie Z.

2013-01-01

Intermittent drug dosing intervals are usually initially guided by the terminal pharmacokinetic half life and are dependent on drug formulation. For chronic multiple dosing and for extended release dosage forms, the terminal half life often does not predict the plasma drug accumulation or fluctuation observed. We define and advance applications for the operational multiple dosing half lives for drug accumulation and fluctuation after multiple oral dosing at steady-state. Using Monte Carlo simulation, our results predict a way to maximize the operational multiple dosing half lives relative to the terminal half life by using a first-order absorption rate constant close to the terminal elimination rate constant in the design of extended release dosage forms. In this way, drugs that may be eliminated early in the development pipeline due to a relatively short half life can be formulated to be dosed at intervals three times the terminal half life, maximizing compliance, while maintaining tight plasma concentration accumulation and fluctuation ranges. We also present situations in which the operational multiple dosing half lives will be especially relevant in the determination of dosing intervals, including for drugs that follow a direct PKPD model and have a narrow therapeutic index, as the rate of concentration decrease after chronic multiple dosing (that is not the terminal half life) can be determined via simulation. These principles are illustrated with case studies on valproic acid, diazepam, and anti-hypertensives. PMID:21499748

Clinical utility and patient perspectives on the use of extended half-life rFIXFc in the management of hemophilia B

PubMed Central

Miguelino, Maricel G; Powell, Jerry S

2014-01-01

Hemophilia B is an X-linked genetic disease caused by mutation of the gene for coagulation protein factor IX (FIX), with an incidence of approximately once every 30,000 male births in all populations and ethnic groups. When severe, the disease leads to spontaneous life threatening bleeding episodes. When untreated, most patients die from bleeding complications before 25 years of age. Current therapy requires frequent intravenous infusions of therapeutic recombinant or plasma-derived protein concentrates containing FIX. Most patients administer the infusions at home every few days, and must limit their physical activities to avoid abnormal bleeding when the FIX activity levels are below normal. After completing the pivotal Phase III clinical trial, a new therapeutic FIX preparation that has been engineered for an extended half-life in circulation, received regulatory approval in March 2014 in Canada and the US. This new FIX represents a major therapeutic advance for patients with hemophilia B. The half-life is prolonged due to fusion of the native FIX molecule with the normal constant region of immunoglobulin G. This fusion molecule then follows the normal immunoglobulin recirculation pathways through endothelial cells, resulting in prolonged times in circulation. In the clinical trials, over 150 patients successfully used eftrenonacog alfa regularly for more than 1 year to prevent spontaneous bleeding, to successfully treat any bleeding episodes, and to provide effective coagulation for major surgery. All infusions were well tolerated and effective, with no inhibitors detected and no safety concerns. This promising therapy should allow patients to use fewer infusions to maintain appropriate FIX activity levels in all clinical settings. PMID:25143713

Estimation of elimination half-lives of organic chemicals in humans using gradient boosting machine.

PubMed

Lu, Jing; Lu, Dong; Zhang, Xiaochen; Bi, Yi; Cheng, Keguang; Zheng, Mingyue; Luo, Xiaomin

2016-11-01

Elimination half-life is an important pharmacokinetic parameter that determines exposure duration to approach steady state of drugs and regulates drug administration. The experimental evaluation of half-life is time-consuming and costly. Thus, it is attractive to build an accurate prediction model for half-life. In this study, several machine learning methods, including gradient boosting machine (GBM), support vector regressions (RBF-SVR and Linear-SVR), local lazy regression (LLR), SA, SR, and GP, were employed to build high-quality prediction models. Two strategies of building consensus models were explored to improve the accuracy of prediction. Moreover, the applicability domains (ADs) of the models were determined by using the distance-based threshold. Among seven individual models, GBM showed the best performance (R(2)=0.820 and RMSE=0.555 for the test set), and Linear-SVR produced the inferior prediction accuracy (R(2)=0.738 and RMSE=0.672). The use of distance-based ADs effectively determined the scope of QSAR models. However, the consensus models by combing the individual models could not improve the prediction performance. Some essential descriptors relevant to half-life were identified and analyzed. An accurate prediction model for elimination half-life was built by GBM, which was superior to the reference model (R(2)=0.723 and RMSE=0.698). Encouraged by the promising results, we expect that the GBM model for elimination half-life would have potential applications for the early pharmacokinetic evaluations, and provide guidance for designing drug candidates with favorable in vivo exposure profile. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang. Copyright © 2016 Elsevier B.V. All rights reserved.

Half-lives of 132La and 135La

NASA Astrophysics Data System (ADS)

Abel, E. P.; Clause, H. K.; Fonslet, J.; Nickles, R. J.; Severin, G. W.

2018-03-01

The half-lives of 135La and 132La were determined via serial gamma spectroscopy, and the half-life of 135La was further determined by a high-precision ionization-chamber measurement. The results are 18.91(2) hr for 135La and 4.59(4) hr for 132La compared with the previously compiled values of 19.5(2) hr and 4.8(2) hr, respectively. These lanthanum isotopes comprise a medically interesting system with positron emitter 132La and Auger-electron emitter 135La forming a theranostic pair for internal diagnostics and therapeutics. The precise half-lives are necessary for proper evaluation of their value in medicine and for a more representative tabulation of nuclear data.

Apparent Half-Lives of Dioxins, Furans, and Polychlorinated Biphenyls as a Function of Age, Body Fat, Smoking Status, and Breast-Feeding

PubMed Central

Milbrath, Meghan O’Grady; Wenger, Yvan; Chang, Chiung-Wen; Emond, Claude; Garabrant, David; Gillespie, Brenda W.; Jolliet, Olivier

2009-01-01

Objective In this study we reviewed the half-life data in the literature for the 29 dioxin, furan, and polychlorinated biphenyl congeners named in the World Health Organization toxic equivalency factor scheme, with the aim of providing a reference value for the half-life of each congener in the human body and a method of half-life estimation that accounts for an individual’s personal characteristics. Data sources and extraction We compared data from > 30 studies containing congener-specific elimination rates. Half-life data were extracted and compiled into a summary table. We then created a subset of these data based on defined exclusionary criteria. Data synthesis We defined values for each congener that approximate the half-life in an infant and in an adult. A linear interpolation of these values was used to examine the relationship between half-life and age, percent body fat, and absolute body fat. We developed predictive equations based on these relationships and adjustments for individual characteristics. Conclusions The half-life of dioxins in the body can be predicted using a linear relationship with age adjusted for body fat, smoking, and breast-feeding. Data suggest an alternative method based on a linear relationship between half-life and total body fat, but this approach requires further testing and validation with individual measurements. PMID:19337517

Safety and efficacy of BAY 94-9027, a prolonged-half-life factor VIII.

PubMed

Reding, M T; Ng, H J; Poulsen, L H; Eyster, M E; Pabinger, I; Shin, H-J; Walsch, R; Lederman, M; Wang, M; Hardtke, M; Michaels, L A

2017-03-01

Essentials Recombinant factor VIII BAY 94-9027 conjugates in a site-specific manner with polyethylene glycol. BAY 94-9027 was given to patients with severe hemophilia A as prophylaxis and to treat bleeds. BAY 94-9027 prevented bleeds at dose intervals up to every 7 days and effectively treated bleeds. BAY 94-9027 treatment was mainly well tolerated and no patient developed factor VIII inhibitors. Click to hear Dr Tiede's perspective on half-life extended factor VIII for the treatment of hemophilia A SUMMARY: Background BAY 94-9027 is a B-domain-deleted prolonged-half-life recombinant factor VIII (FVIII) that conjugates in a site-specific manner with polyethylene glycol. Objective Assess efficacy and safety of BAY 94-9027 for prophylaxis and treatment of bleeds in patients with severe hemophilia A. Patients/methods In this multinational, phase 2/3, partially randomized, open-label trial, men aged 12-65 years with FVIII < 1% and ≥ 150 exposure days to FVIII received BAY 94-9027 for 36 weeks on demand or prophylactically at intervals determined following a 10-week run-in period on 25 IU kg -1 body weight two times per week. Patients with > 1 bleed during the run-in subsequently received 30-40 IU kg -1 two times per week; patients with ≤ 1 bleed were eligible for randomization to every-5-days (45-60 IU kg -1 ) or every-7-days (60 IU kg -1 ) prophylaxis (1 : 1) for 26 additional weeks until randomization arms were filled. Patients who were eligible but not randomized continued twice-weekly prophylaxis. The primary efficacy outcome was annualized bleeding rate (ABR). Results The intent-to-treat population included 132 patients (prophylaxis, n = 112; on demand, n = 20). Median ABR (quartile [Q1; Q3]) for patients treated two times per week who were not eligible for randomization (n = 13) improved after dose increase (17.4 [14.3; 26.0] to 4.1 [2.0; 10.6]). Median ABR for patients randomized to every-5-days treatment (n = 43) was 1.9 (0; 4.2), similar to patients

Tailoring treatment of haemophilia B: accounting for the distribution and clearance of standard and extended half-life FIX concentrates.

PubMed

Iorio, Alfonso; Fischer, Kathelijn; Blanchette, Victor; Rangarajan, Savita; Young, Guy; Morfini, Massimo

2017-06-02

The prophylactic administration of factor IX (FIX) is considered the most effective treatment for haemophilia B. The inter-individual variability and complexity of the pharmacokinetics (PK) of FIX, and the rarity of the disease have hampered identification of an optimal treatment regimens. The recent introduction of extended half-life recombinant FIX molecules (EHL-rFIX), has prompted a thorough reassessment of the clinical efficacy, PK and pharmacodynamics of plasma-derived and recombinant FIX. First, using longer sampling times and multi-compartmental PK models has led to more precise (and favourable) PK for FIX than was appreciated in the past. Second, investigating the distribution of FIX in the body beyond the vascular space (which is implied by its complex kinetics) has opened a new research field on the role for extravascular FIX. Third, measuring plasma levels of EHL-rFIX has shown that different aPTT reagents have different accuracy in measuring different FIX molecules. How will this new knowledge reflect on clinical practice? Clinical decision making in haemophilia B requires some caution and expertise. First, comparisons between different FIX molecules must be assessed taking into consideration the comparability of the populations studied and the PK models used. Second, individual PK estimates must rely on multi-compartmental models, and would benefit from adopting a population PK approach. Optimal sampling times need to be adapted to the prolonged half-life of the new EHL FIX products. Finally, costs considerations may apply, which is beyond the scope of this manuscript but might be deeply connected with the PK considerations discussed in this communication.

Human neutrophil kinetics: modeling of stable isotope labeling data supports short blood neutrophil half-lives.

PubMed

Lahoz-Beneytez, Julio; Elemans, Marjet; Zhang, Yan; Ahmed, Raya; Salam, Arafa; Block, Michael; Niederalt, Christoph; Asquith, Becca; Macallan, Derek

2016-06-30

Human neutrophils have traditionally been thought to have a short half-life in blood; estimates vary from 4 to 18 hours. This dogma was recently challenged by stable isotope labeling studies with heavy water, which yielded estimates in excess of 3 days. To investigate this disparity, we generated new stable isotope labeling data in healthy adult subjects using both heavy water (n = 4) and deuterium-labeled glucose (n = 9), a compound with more rapid labeling kinetics. To interpret results, we developed a novel mechanistic model and applied it to previously published (n = 5) and newly generated data. We initially constrained the ratio of the blood neutrophil pool to the marrow precursor pool (ratio = 0.26; from published values). Analysis of heavy water data sets yielded turnover rates consistent with a short blood half-life, but parameters, particularly marrow transit time, were poorly defined. Analysis of glucose-labeling data yielded more precise estimates of half-life (0.79 ± 0.25 days; 19 hours) and marrow transit time (5.80 ± 0.42 days). Substitution of this marrow transit time in the heavy water analysis gave a better-defined blood half-life of 0.77 ± 0.14 days (18.5 hours), close to glucose-derived values. Allowing the ratio of blood neutrophils to mitotic neutrophil precursors (R) to vary yielded a best-fit value of 0.19. Reanalysis of the previously published model and data also revealed the origin of their long estimates for neutrophil half-life: an implicit assumption that R is very large, which is physiologically untenable. We conclude that stable isotope labeling in healthy humans is consistent with a blood neutrophil half-life of less than 1 day. © 2016 by The American Society of Hematology.

Adenosine monophosphate deaminase 3 activation shortens erythrocyte half-life and provides malaria resistance in mice.

PubMed

Hortle, Elinor; Nijagal, Brunda; Bauer, Denis C; Jensen, Lora M; Ahn, Seong Beom; Cockburn, Ian A; Lampkin, Shelley; Tull, Dedreia; McConville, Malcolm J; McMorran, Brendan J; Foote, Simon J; Burgio, Gaetan

2016-09-01

The factors that determine red blood cell (RBC) lifespan and the rate of RBC aging have not been fully elucidated. In several genetic conditions, including sickle cell disease, thalassemia, and G6PD deficiency, erythrocyte lifespan is significantly shortened. Many of these diseases are also associated with protection from severe malaria, suggesting a role for accelerated RBC senescence and clearance in malaria resistance. Here, we report a novel, N-ethyl-N-nitrosourea-induced mutation that causes a gain of function in adenosine 5'-monophosphate deaminase (AMPD3). Mice carrying the mutation exhibit rapid RBC turnover, with increased erythropoiesis, dramatically shortened RBC lifespan, and signs of increased RBC senescence/eryptosis, suggesting a key role for AMPD3 in determining RBC half-life. Mice were also found to be resistant to infection with the rodent malaria Plasmodium chabaudi. We propose that resistance to P. chabaudi is mediated by increased RBC turnover and higher rates of erythropoiesis during infection. © 2016 by The American Society of Hematology.

Whole-genome analysis of mRNA decay in Plasmodium falciparum reveals a global lengthening of mRNA half-life during the intra-erythrocytic development cycle.

PubMed

Shock, Jennifer L; Fischer, Kael F; DeRisi, Joseph L

2007-01-01

The rate of mRNA decay is an essential element of post-transcriptional regulation in all organisms. Previously, studies in several organisms found that the specific half-life of each mRNA is precisely related to its physiologic role, and plays an important role in determining levels of gene expression. We used a genome-wide approach to characterize mRNA decay in Plasmodium falciparum. We found that, globally, rates of mRNA decay increase dramatically during the asexual intra-erythrocytic developmental cycle. During the ring stage of the cycle, the average mRNA half-life was 9.5 min, but this was extended to an average of 65 min during the late schizont stage of development. Thus, a major determinant of mRNA decay rate appears to be linked to the stage of intra-erythrocytic development. Furthermore, we found specific variations in decay patterns superimposed upon the dominant trend of progressive half-life lengthening. These variations in decay pattern were frequently enriched for genes with specific cellular functions or processes. Elucidation of Plasmodium mRNA decay rates provides a key element for deciphering mechanisms of genetic control in this parasite, by complementing and extending previous mRNA abundance studies. Our results indicate that progressive stage-dependent decreases in mRNA decay rate function are a major determinant of mRNA accumulation during the schizont stage of intra-erythrocytic development. This type of genome-wide change in mRNA decay rate has not been observed in any other organism to date, and indicates that post-transcriptional regulation may be the dominant mechanism of gene regulation in P. falciparum.

Topology and Oligomerization of Mono- and Oligomeric Proteins Regulate Their Half-Lives in the Cell.

PubMed

Mallik, Saurav; Kundu, Sudip

2018-06-05

To find additional structural constraints (besides disordered segments) that regulate protein half-life in the cell, we herein assess the influence of native topology of monomeric and sequestration of oligomeric proteins into multimeric complexes in yeast, human, and mouse. Native topology acts as a molecular marker of globular protein's mechanical resistance and consequently captures their half-life variations on genome scale. Sequestration into multimeric complexes elongates oligomeric protein half-life in the cell, presumably by burying ubiquitinoylation sites and disordered segments required for proteasomal recognition. The latter effect is stronger for proteins associated with multiple complexes and for those binding early during complex self-assembly, including proteins that oligomerize with large proportions of surface buried. After gene duplication, diversification of topology and sequestration into non-identical sets of complexes alter half-lives of paralogous proteins during the course of evolution. Thus, native topology and sequestration into multimeric complexes reflect designing principles of proteins to regulate their half-lives. Copyright © 2018 Elsevier Ltd. All rights reserved.

Is obesity associated with a decline in intelligence quotient during the first half of the life course?

PubMed

Belsky, Daniel W; Caspi, Avshalom; Goldman-Mellor, Sidra; Meier, Madeline H; Ramrakha, Sandhya; Poulton, Richie; Moffitt, Terrie E

2013-11-01

Cross-sectional studies have found that obesity is associated with low intellectual ability and neuroimaging abnormalities in adolescence and adulthood. Some have interpreted these associations to suggest that obesity causes intellectual decline in the first half of the life course. We analyzed data from a prospective longitudinal study to test whether becoming obese was associated with intellectual decline from childhood to midlife. We used data from the ongoing Dunedin Multidisciplinary Health and Development Study, a population-representative birth cohort study of 1,037 children in New Zealand who were followed prospectively from birth (1972-1973) through their fourth decade of life with a 95% retention rate. Intelligence quotient (IQ) was measured in childhood and adulthood. Anthropometric measurements were taken at birth and at 12 subsequent in-person assessments. As expected, cohort members who became obese had lower adulthood IQ scores. However, obese cohort members exhibited no excess decline in IQ. Instead, these cohort members had lower IQ scores since childhood. This pattern remained consistent when we accounted for children's birth weights and growth during the first years of life, as well as for childhood-onset obesity. Lower IQ scores among children who later developed obesity were present as early as 3 years of age. We observed no evidence that obesity contributed to a decline in IQ, even among obese individuals who displayed evidence of the metabolic syndrome and/or elevated systemic inflammation.

Is Obesity Associated With a Decline in Intelligence Quotient During the First Half of the Life Course?

PubMed Central

Belsky, Daniel W.; Caspi, Avshalom; Goldman-Mellor, Sidra; Meier, Madeline H.; Ramrakha, Sandhya; Poulton, Richie; Moffitt, Terrie E.

2013-01-01

Cross-sectional studies have found that obesity is associated with low intellectual ability and neuroimaging abnormalities in adolescence and adulthood. Some have interpreted these associations to suggest that obesity causes intellectual decline in the first half of the life course. We analyzed data from a prospective longitudinal study to test whether becoming obese was associated with intellectual decline from childhood to midlife. We used data from the ongoing Dunedin Multidisciplinary Health and Development Study, a population-representative birth cohort study of 1,037 children in New Zealand who were followed prospectively from birth (1972–1973) through their fourth decade of life with a 95% retention rate. Intelligence quotient (IQ) was measured in childhood and adulthood. Anthropometric measurements were taken at birth and at 12 subsequent in-person assessments. As expected, cohort members who became obese had lower adulthood IQ scores. However, obese cohort members exhibited no excess decline in IQ. Instead, these cohort members had lower IQ scores since childhood. This pattern remained consistent when we accounted for children's birth weights and growth during the first years of life, as well as for childhood-onset obesity. Lower IQ scores among children who later developed obesity were present as early as 3 years of age. We observed no evidence that obesity contributed to a decline in IQ, even among obese individuals who displayed evidence of the metabolic syndrome and/or elevated systemic inflammation. PMID:24029684

Movement Complexity and Neuromechanical Factors Affect the Entropic Half-Life of Myoelectric Signals

PubMed Central

Hodson-Tole, Emma F.; Wakeling, James M.

2017-01-01

Appropriate neuromuscular functioning is essential for survival and features underpinning motor control are present in myoelectric signals recorded from skeletal muscles. One approach to quantify control processes related to function is to assess signal variability using measures such as Sample Entropy. Here we developed a theoretical framework to simulate the effect of variability in burst duration, activation duty cycle, and intensity on the Entropic Half-Life (EnHL) in myoelectric signals. EnHLs were predicted to be <40 ms, and to vary with fluctuations in myoelectric signal amplitude and activation duty cycle. Comparison with myoelectic data from rats walking and running at a range of speeds and inclines confirmed the range of EnHLs, however, the direction of EnHL change in response to altered locomotor demand was not correctly predicted. The discrepancy reflected different associations between the ratio of the standard deviation and mean signal intensity (Ist:It¯) and duty factor in simulated and physiological data, likely reflecting additional information in the signals from the physiological data (e.g., quiescent phase content; variation in action potential shapes). EnHL could have significant value as a novel marker of neuromuscular responses to alterations in perceived locomotor task complexity and intensity. PMID:28974932

Family losses following truncation selection in populations of half-sib families

Treesearch

J. H. Roberds; G. Namkoong; H. Kang

1980-01-01

Family losses during truncation selection may be sizable in populations of half-sib families. Substantial losses may occur even in populations containing little or no variation among families. Heavier losses will occur, however, under conditions of high heritability where there is considerable family variation. Standard deviations and therefore variances of family loss...

Half-Lives of 101Rh and 108m Ag

NASA Astrophysics Data System (ADS)

Norman, Eric; Browne, Edgardo; Shugart, Howard

2014-09-01

Half-lives of short-lived nuclei can easily be measured by direct counting techniques, whereas those of long-lived naturally-occurring nuclei are usually determined by specific activity measurements. However, half-lives in the range of 1 - 1,000,000 years are notoriously difficult to determine. For example, published values for the half-life of 101Rh range from 3.0 +/- 0.4 years to 10 +/- 1 years, and for 108m Ag published values range from 127 +/- 21 years to 438 +/- 9 years. In order to resolve the issues of what the half-lives of these isotopes actually are, we set up two separate long-term gamma-ray counting experiments. Gamma-ray data were collected in time bins using high-purity Ge detectors and ORTEC PC-based data acquisition systems. We counted in this manner for a period of approximately 5 years for 101Rh and 3 years for 108mAg. In this talk we will describe the details of these experiments and will present the final results for the half-lives of 101Rh and 108mAg determined from these measurements. Half-lives of short-lived nuclei can easily be measured by direct counting techniques, whereas those of long-lived naturally-occurring nuclei are usually determined by specific activity measurements. However, half-lives in the range of 1 - 1,000,000 years are notoriously difficult to determine. For example, published values for the half-life of 101Rh range from 3.0 +/- 0.4 years to 10 +/- 1 years, and for 108m Ag published values range from 127 +/- 21 years to 438 +/- 9 years. In order to resolve the issues of what the half-lives of these isotopes actually are, we set up two separate long-term gamma-ray counting experiments. Gamma-ray data were collected in time bins using high-purity Ge detectors and ORTEC PC-based data acquisition systems. We counted in this manner for a period of approximately 5 years for 101Rh and 3 years for 108mAg. In this talk we will describe the details of these experiments and will present the final results for the half-lives of 101Rh

Simplified half-life methods for the analysis of kinetic data

NASA Technical Reports Server (NTRS)

Eberhart, J. G.; Levin, E.

1988-01-01

The analysis of reaction rate data has as its goal the determination of the order rate constant which characterize the data. Chemical reactions with one reactant and present simplified methods for accomplishing this goal are considered. The approaches presented involve the use of half lives or other fractional lives. These methods are particularly useful for the more elementary discussions of kinetics found in general and physical chemistry courses.

Assessment of biological half life using in silico QSPkR approach: a self organizing molecular field analysis (SOMFA) on a series of antimicrobial quinolone drugs.

PubMed

Goel, Honey; Sinha, V R; Thareja, Suresh; Aggarwal, Saurabh; Kumar, Manoj

2011-08-30

The quinolones belong to a family of synthetic potent broad-spectrum antibiotics and particularly active against gram-negative organisms, especially Pseudomonas aeruginosa. A 3D-QSPkR approach has been used to obtain the quantitative structure pharmacokinetic relationship for a series of quinolone drugs using SOMFA. The series consisting of 28 molecules have been investigated for their pharmacokinetic performance using biological half life (t(1/2)). A statistically validated robust model for a diverse group of quinolone drugs having flexibility in structure and pharmacokinetic profile (t(1/2)) obtained using SOMFA having good cross-validated correlation coefficient r(cv)(2) (0.6847), non cross-validated correlation coefficient r(2) values (0.7310) and high F-test value (33.9663). Analysis of 3D-QSPkR models through electrostatic and shape grids provide useful information about the shape and electrostatic potential contributions on t(1/2). The analysis of SOMFA results provide an insight for the generation of novel molecular architecture of quinolones with optimal half life and improved biological profile. Copyright © 2011 Elsevier B.V. All rights reserved.

Influence of three artificial light sources on oviposition and half-life of the Black Soldier Fly, Hermetia illucens (Diptera: Stratiomyidae): Improving small-scale indoor rearing.

PubMed

Heussler, Carina D; Walter, Andreas; Oberkofler, Hannes; Insam, Heribert; Arthofer, Wolfgang; Schlick-Steiner, Birgit C; Steiner, Florian M

2018-01-01

Hermetia illucens (L.), the Black Soldier Fly, has received increased scientific attention for its potential in circular waste management where larvae can serve as feedstuff for livestock and for biodiesel production. The flies occur naturally in (sub)-tropical and warm-temperate climates, and their mating depends on space and sunlight. Small-scale indoor rearing of Black Soldier Flies has been challenging because they react sensitive to artificial light sources and cage sizes, but recent studies have shown that small-scale rearing under artificial light is feasible. Here, we test the influence of three artificial light sources (light-emitting diodes, fluorescent lamps, and halogen lamps) on small-scale indoor rearing. Three experiments were conducted to compare oviposition traits (pre-oviposition period, total oviposition-period, and egg mass per female) and half-life among the three light sources. Oviposition did not differ among the three light sources, but male and female half-life did. Based on the performance of the light-emitting diodes and their outstanding energy efficiency, we recommend this light source for small-scale indoor rearing of Black Soldier Flies.

A latent class analysis of friendship network types and their predictors in the second half of life.

PubMed

Miche, Martina; Huxhold, Oliver; Stevens, Nan L

2013-07-01

Friendships contribute uniquely to well-being in (late) adulthood. However, studies on friendship often ignore interindividual differences in friendship patterns. The aim of this study was to investigate such differences including their predictors. The study builds on Matthews's qualitative model of friendship styles. Matthews distinguished 3 approaches to friendship differing by number of friends, duration of friendships, and emotional closeness. We used latent class analysis to identify friendship network types in a sample of middle-aged and older adults aged 40-85 years (N = 1,876). Data came from the German Aging Survey (DEAS). Our analysis revealed 4 distinct friendship network types that were in high congruence with Matthews's typology. We identified these as a discerning style, which focuses on few close relationships, an independent style, which refrains from close engagements, and 2 acquisitive styles that both acquire new friends across their whole life course but differ regarding the emotional closeness of their friendships. Socioeconomic status, gender, health, and network-disturbing and network-sustaining variables predicted affiliations with network types. We argue that future studies should consider a holistic view of friendships in order to better understand the association between friendships and well-being in the second half of life.

For better and for worse: the relationship between future expectations and functioning in the second half of life.

PubMed

Shrira, Amit; Palgi, Yuval; Ben-Ezra, Menachem; Spalter, Tal; Kavé, Gitit; Shmotkin, Dov

2011-03-01

To examine age group differences in the relationship between future expectations about standards of living and physical, mental, and cognitive functioning in the second half of life. Data from the Survey of Health, Ageing, and Retirement in Europe (N=27,687, mean age=64.44). First, with increasing age, the expectation to improve (ETI) and the expectation to worsen (ETW) in standards of living became more independent of each other. Second, with increasing age, ETI was less strongly correlated with functioning whereas ETW was more strongly correlated with it. Third, with increasing age, the relationship between ETI and functioning was more strongly moderated by ETW, so that adaptive functioning was associated with expectations that no major change is to occur and with expectations for both growth and decline. Late-life positive and negative expectancies are less interdependent than they are in younger age, probably due to their stronger interaction when associating with functioning. Expectancies interact either to reflect an attempt to preserve the functional status quo (low expectancy to improve and to decline) or may signal a highly complex mental organization (high expectancy to improve and to decline).

For Better and for Worse: The Relationship between Future Expectations and Functioning in the Second Half of Life

PubMed Central

Palgi, Yuval; Ben-Ezra, Menachem; Spalter, Tal; Kavé, Gitit; Shmotkin, Dov

2011-01-01

Objectives. To examine age group differences in the relationship between future expectations about standards of living and physical, mental, and cognitive functioning in the second half of life. Method. Data from the Survey of Health, Ageing, and Retirement in Europe (N = 27,687, mean age = 64.44). Results. First, with increasing age, the expectation to improve (ETI) and the expectation to worsen (ETW) in standards of living became more independent of each other. Second, with increasing age, ETI was less strongly correlated with functioning whereas ETW was more strongly correlated with it. Third, with increasing age, the relationship between ETI and functioning was more strongly moderated by ETW, so that adaptive functioning was associated with expectations that no major change is to occur and with expectations for both growth and decline. Discussion. Late-life positive and negative expectancies are less interdependent than they are in younger age, probably due to their stronger interaction when associating with functioning. Expectancies interact either to reflect an attempt to preserve the functional status quo (low expectancy to improve and to decline) or may signal a highly complex mental organization (high expectancy to improve and to decline). PMID:21296870

Prediction of thyroidal 131I effective half-life in patients with Graves' disease.

PubMed

Zhang, Ruiguo; Zhang, Guizhi; Wang, Renfei; Tan, Jian; He, Yajing; Meng, Zhaowei

2017-10-06

Calculation of effective thyroidal half-life (Teff) of iodine-131( 131 I) is cumbersome and tedious. The aim of this study was to investigate factors that could be used to predict Teff and to develop a Teff prediction model in Graves' disease patients. A total of 256 patients with GD were involved in this study. We investigated the influences of age, gender, disease duration, thyroid weight, antithyroid drugs, antithyroid drugs discontinuation period (ADP), thyroid function indexes, thyroid autoantibodies, thyroid-stimulating hormone receptor antibody (TRAb) level and radioactive iodine uptake (RAIU) values before 131 I therapy on Teff, applying univariate and multivariate analyses. Teff correlated negatively with thyroid peroxidase antibody, TRAb and thyroid weight, as well as positively with 24-hour, 48-hour, and 72-hour RAIU. Additionally, a longer ADP (especially≥ 14d) or without antithyroid drugs before 131 I therapy led to a longer Teff. Stepwise multiple linear regression analysis showed that 24-hour and 72-hour RAIU were statistically significant predictors of Teff ( P <0.001). The relationship was: predictive Teff=5.277+0.295×72-hour RAIU-0.217×24-hour RAIU (r =0.865, P < 0.001). The present results indicate that prediction of Teff from 24-hour and 72-hour RAIU is feasible in patients with Graves' disease, with high prediction accuracy.

PASylation: a biological alternative to PEGylation for extending the plasma half-life of pharmaceutically active proteins

PubMed Central

Schlapschy, Martin; Binder, Uli; Börger, Claudia; Theobald, Ina; Wachinger, Klaus; Kisling, Sigrid; Haller, Dirk; Skerra, Arne

2013-01-01

A major limitation of biopharmaceutical proteins is their fast clearance from circulation via kidney filtration, which strongly hampers efficacy both in animal studies and in human therapy. We have developed conformationally disordered polypeptide chains with expanded hydrodynamic volume comprising the small residues Pro, Ala and Ser (PAS). PAS sequences are hydrophilic, uncharged biological polymers with biophysical properties very similar to poly-ethylene glycol (PEG), whose chemical conjugation to drugs is an established method for plasma half-life extension. In contrast, PAS polypeptides offer fusion to a therapeutic protein on the genetic level, permitting Escherichia coli production of fully active proteins and obviating in vitro coupling or modification steps. Furthermore, they are biodegradable, thus avoiding organ accumulation, while showing stability in serum and lacking toxicity or immunogenicity in mice. We demonstrate that PASylation bestows typical biologics, such as interferon, growth hormone or Fab fragments, with considerably prolonged circulation and boosts bioactivity in vivo. PMID:23754528

High-precision {beta} decay half-life measurements of proton-rich nuclei for testing the CVC hypothesis

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

Kurtukian-Nieto, T.; Collaboration: NEX Group of CENBG

2011-11-30

The experimental study of super-allowed nuclear {beta} decays serves as a sensitive probe of the conservation of the weak vector current (CVC) and allows tight limits to be set on the presence of scalar or right-handed currents. Once CVC is verified, it is possible to determine the V{sub ud} element of the CKM quark-mixing matrix. Similarly, the study of nuclear mirror {beta} decays allows to arrive at the same final quantity V{sub ud}. Whereas dedicated studies of 0{sup +}{yields}0{sup +} decays are performed for several decades now, the potential of mirror transitions was only rediscovered recently. Therefore, it can bemore » expected that important progress is possible with high-precision studies of different mirror {beta} decays. In the present piece of work the half-life measurements performed by the CENBG group of the proton-rich nuclei {sup 42}Ti, {sup 38-39}Ca, {sup 30-31}S and {sup 29}P are summarised.« less

Half-and-Half Palatoplasty.

PubMed

Han, Hyun Ho; Kang, In Sook; Rhie, Jong Won

2014-08-01

A 14-month-old child was diagnosed with a Veau Class II cleft palate. Von Langenbeck palatoplasty was performed for the right palate, and V-Y pushback palatoplasty was performed for the left palate. The child did not have a special problem during the surgery, and the authors were able to elongate the cleft by 10 mm. Contrary to preoperative concerns regarding the hybrid use of palatoplasties, the uvula and midline incisions remained balanced in the middle. The authors named this combination method "half-and-half palatoplasty" and plan to conduct a long-term follow up study as a potential solution that minimizes the complications of palatoplasty.

Half-and-Half Palatoplasty

PubMed Central

Han, Hyun Ho; Kang, In Sook

2014-01-01

A 14-month-old child was diagnosed with a Veau Class II cleft palate. Von Langenbeck palatoplasty was performed for the right palate, and V-Y pushback palatoplasty was performed for the left palate. The child did not have a special problem during the surgery, and the authors were able to elongate the cleft by 10 mm. Contrary to preoperative concerns regarding the hybrid use of palatoplasties, the uvula and midline incisions remained balanced in the middle. The authors named this combination method "half-and-half palatoplasty" and plan to conduct a long-term follow up study as a potential solution that minimizes the complications of palatoplasty. PMID:28913201

Average and recommended half-life values for two neutrino double beta decay: Upgrade-2013

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

Barabash, A. S.

2013-12-30

All existing positive results on two neutrino double beta decay in different nuclei were analyzed. Using the procedure recommended by the Particle Data Group, weighted average values for half-lives of {sup 48}Ca, {sup 76}Ge, {sup 82}Se, {sup 96}Zr, {sup 100}Mo, {sup 100}Mo−{sup 100}Ru (0{sub 1}{sup +}), {sup 116}Cd, {sup 130}Te, {sup 136}Xe, {sup 150}Nd, {sup 150}Nd−{sup 150}Sm (0{sub 1}{sup +}) and {sup 238}U were obtained. Existing geochemical data were analyzed and recommended values for half-lives of {sup 128}Te and {sup 130}Ba are proposed. I recommend the use of these results as the most currently reliable values for half-lives.

Importance of neonatal FcR in regulating the serum half-life of therapeutic proteins containing the Fc domain of human IgG1: a comparative study of the affinity of monoclonal antibodies and Fc-fusion proteins to human neonatal FcR.

PubMed

Suzuki, Takuo; Ishii-Watabe, Akiko; Tada, Minoru; Kobayashi, Tetsu; Kanayasu-Toyoda, Toshie; Kawanishi, Toru; Yamaguchi, Teruhide

2010-02-15

The neonatal FcR (FcRn) binds to the Fc domain of IgG at acidic pH in the endosome and protects IgG from degradation, thereby contributing to the long serum half-life of IgG. To date, more than 20 mAb products and 5 Fc-fusion protein products have received marketing authorization approval in the United States, the European Union, or Japan. Many of these therapeutic proteins have the Fc domain of human IgG1; however, the serum half-lives differ in each protein. To elucidate the role of FcRn in the pharmacokinetics of Fc domain-containing therapeutic proteins, we evaluated the affinity of the clinically used human, humanized, chimeric, or mouse mAbs and Fc-fusion proteins to recombinant human FcRn by surface plasmon resonance analysis. The affinities of these therapeutic proteins to FcRn were found to be closely correlated with the serum half-lives reported from clinical studies, suggesting the important role of FcRn in regulating their serum half-lives. The relatively short serum half-life of Fc-fusion proteins was thought to arise from the low affinity to FcRn. The existence of some mAbs having high affinity to FcRn and a short serum half-life, however, suggested the involvement of other critical factor(s) in determining the serum half-life of such Abs. We further investigated the reason for the relatively low affinity of Fc-fusion proteins to FcRn and suggested the possibility that the receptor domain of Fc-fusion protein influences the structural environment of the FcRn binding region but not of the FcgammaRI binding region of the Fc domain.

The detectability half-life in arthropod predator-prey research: what it is, why we need it, how to measure it, and how to use it.

PubMed

Greenstone, Matthew H; Payton, Mark E; Weber, Donald C; Simmons, Alvin M

2014-08-01

Molecular gut-content analysis enables detection of arthropod predation with minimal disruption of ecosystem processes. Most assays produce only qualitative results, with each predator testing either positive or negative for target prey remains. Nevertheless, they have yielded important insights into community processes. For example, they have confirmed the long-hypothesized role of generalist predators in retarding early-season build-up of pest populations prior to the arrival of more specialized predators and parasitoids and documented the ubiquity of secondary and intraguild predation. However, raw qualitative gut-content data cannot be used to assess the relative impact of different predator taxa on prey population dynamics: they must first be weighted by the relative detectability periods for molecular prey remains for each predator-prey combination. If this is not carried out, interpretations of predator impact will be biased towards those with the longest detectabilities. We review the challenges in determining detectability half-lives, including unstated assumptions that have often been ignored in the performance of feeding trials. We also show how detectability half-lives can be used to properly weight assay data to rank predators by their importance in prey population suppression, and how sets of half-lives can be used to test hypotheses concerning predator ecology and physiology. We use data from 32 publications, comprising 97 half-lives, to generate and test hypotheses on taxonomic differences in detectability half-lives and discuss the possible role of the detectability half-life in interpreting qPCR and next-generation sequencing data. © 2013 John Wiley & Sons Ltd.

21 CFR 131.180 - Half-and-half.

Code of Federal Regulations, 2010 CFR

2010-04-01

...). (ii) Natural and artificial food flavoring. (c) Methods of analysis. The milkfat content is determined... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Half-and-half. 131.180 Section 131.180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 131.180 - Half-and-half.

Code of Federal Regulations, 2013 CFR

2013-04-01

...). (ii) Natural and artificial food flavoring. (c) Methods of analysis. The milkfat content is determined... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Half-and-half. 131.180 Section 131.180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 131.180 - Half-and-half.

Code of Federal Regulations, 2014 CFR

2014-04-01

...). (ii) Natural and artificial food flavoring. (c) Methods of analysis. The milkfat content is determined... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Half-and-half. 131.180 Section 131.180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 131.180 - Half-and-half.

Code of Federal Regulations, 2011 CFR

2011-04-01

...). (ii) Natural and artificial food flavoring. (c) Methods of analysis. The milkfat content is determined... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Half-and-half. 131.180 Section 131.180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 131.180 - Half-and-half.

Code of Federal Regulations, 2012 CFR

2012-04-01

...). (ii) Natural and artificial food flavoring. (c) Methods of analysis. The milkfat content is determined... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Half-and-half. 131.180 Section 131.180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

Half-Life of Sulfonylureas in HNF1A and HNF4A Human MODY Patients is not Prolonged as Suggested by the Mouse Hnf1a(-/-) Model.

PubMed

Urbanova, Jana; Andel, Michal; Potockova, Jana; Klima, Josef; Macek, Jan; Ptacek, Pavel; Mat'oska, Vaclav; Kumstyrova, Tereza; Heneberg, Petr

2015-01-01

Sulfonylurea derivatives are widely used for clinical treatment of human subjects with Maturity Onset Diabetes of the Young (MODY) caused by mutations in HNF-1α or HNF-4α despite the mechanism leading to their hypersensitivity is incompletely understood. In Hnf1a(-/-) mice, serum concentrations and half-life of sulfonylurea derivatives are strongly increased. We thus hypothesized that reduced sulfonylurea derivatives clearance stands behind their therapeutic potential in human HNF1A/HNF4A MODY subjects. Single doses of 3 mg glipizide and 5 mg glibenclamide/glyburide were administered sequentially to seven HNF1A/HNF4A MODY subjects and six control individuals matched for their age, BMI and CYP2C9 genotype. Pharmacokinetic (plasma concentration levels, Cmax, tmax, t1/2, AUC) and pharmacodynamic parameters (glycemia, C-peptide and insulin plasma levels) were followed for 24 hours after drug administration. We provide the first evidence on the pharmacokinetics and pharmacodynamics of sulfonylurea derivatives in human MODY subjects. The half-life of glipizide did not change, and reached 3.8±0.7 and 3.7±1.8 h in the MODY and control subjects, respectively. The half-life of glibenclamide was increased only in some MODY subjects (t1/2 9.5±6.7 and 5.0±1.4 h, respectively). Importantly, the intra- individual responses of MODY (but control) subjects to glipizide and glibenclamide treatment were highly correlated. With regards to pharmacodynamics, we observed a differential response of control but not MODY subjects to the doses of glipizide and glibenclamide applied. We rejected the hypothesis that all human MODY-associated mutations in HNF1A / HNF4A induce changes in the pharmacokinetics of sulfonylureas in humans analogically to the Hnf1a(-/-) mouse model.

CYP2C8 activity recovers within 96 hours after gemfibrozil dosing: estimation of CYP2C8 half-life using repaglinide as an in vivo probe.

PubMed

Backman, Janne T; Honkalammi, Johanna; Neuvonen, Mikko; Kurkinen, Kaisa J; Tornio, Aleksi; Niemi, Mikko; Neuvonen, Pertti J

2009-12-01

Gemfibrozil 1-O-beta-glucuronide is a mechanism-based inhibitor of cytochrome P450 2C8. We studied the recovery of CYP2C8 activity after discontinuation of gemfibrozil treatment using repaglinide as a probe drug, to estimate the in vivo turnover half-life of CYP2C8. In a randomized five-phase crossover study, nine healthy volunteers ingested 0.25 mg of repaglinide alone or after different time intervals after a 3-day treatment with 600 mg of gemfibrozil twice daily. The area under the plasma concentration-time curve (AUC) from time 0 to infinity of repaglinide was 7.6-, 2.9-, 1.4- and 1.0-fold compared with the control phase when it was administered 1, 24, 48, or 96 h after the last gemfibrozil dose, respectively (P < 0.001 versus control for 1, 24, and 48 h after gemfibrozil). Thus, a strong CYP2C8 inhibitory effect persisted even after gemfibrozil and gemfibrozil 1-O-beta-glucuronide concentrations had decreased to less than 1% of their maximum (24-h dosing interval). In addition, the metabolite to repaglinide AUC ratios indicated that significant (P < 0.05) inhibition of repaglinide metabolism continued up to 48 h after gemfibrozil administration. Based on the recovery of repaglinide oral clearance, the in vivo turnover half-life of CYP2C8 was estimated to average 22 +/- 6 h (mean +/- S.D.). In summary, CYP2C8 activity is recovered gradually during days 1 to 4 after gemfibrozil discontinuation, which should be considered when CYP2C8 substrate dosing is planned. The estimated CYP2C8 half-life will be useful for in vitro-in vivo extrapolations of drug-drug interactions involving induction or mechanism-based inhibition of CYP2C8.

Effective Half-Life of Caesium-137 in Various Environmental Media at the Savannah River Site

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

Paller, M. H.; Jannik, G. T.; Baker, R. A.

2014-05-01

During the operational history of the Savannah River Site (SRS), many different radionuclides have been released from site facilities into the SRS environment. However, only a relatively small number of pathways, most importantly 137Cs in fish and deer, have contributed significantly to doses and risks to the public. The “effective” half-lives (T e) of 137Cs (which include both physical decay and environmental dispersion) in Savannah River floodplain soil and vegetation and in fish and white-tailed deer from the SRS were estimated using long-term monitoring data. For 1974–2011, the T es of 137Cs in Savannah River floodplain soil and vegetation weremore » 17.0 years (95% CI = 14.2–19.9) and 13.4 years (95% CI = 10.8–16.0), respectively. These T es were greater than in a previous study that used data collected only through 2005 as a likely result of changes in the flood regime of the Savannah River. Field analyses of 137Cs concentrations in deer collected during yearly controlled hunts at the SRS indicated an overall T e of 15.9 years (95% CI = 12.3–19.6) for 1965–2011; however, the T e for 1990–2011 was significantly shorter (11.8 years, 95% CI = 4.8–18.8) due to an increase in the rate of 137Cs removal. The shortest T es were for fish in SRS streams and the Savannah River (3.5–9.0 years), where dilution and dispersal resulted in rapid 137Cs removal. Long-term data show that T es are significantly shorter than the physical half-life of 137Cs in the SRS environment but that they can change over time. Therefore, it is desirable have a long period of record for calculating Tes and risky to extrapolate T es beyond this period unless the processes governing 137Cs removal are clearly understood.« less

An improved method for determination of fumigant degradation half-life in soil

USDA-ARS?s Scientific Manuscript database

Using the current approach, measurement of fumigant degradation half-lives under realistic soil conditions is problematic due to the large headspace that is necessary above the soil during incubation. This results in a poor degree of contact between the fumigant and the soil’s degrading surfaces; di...

Half-lives of PFOS, PFHxS and PFOA after end of exposure to contaminated drinking water.

PubMed

Li, Ying; Fletcher, Tony; Mucs, Daniel; Scott, Kristin; Lindh, Christian H; Tallving, Pia; Jakobsson, Kristina

2018-01-01

Municipal drinking water contaminated with perfluorinated alkyl acids had been distributed to one-third of households in Ronneby, Sweden. The source was firefighting foam used in a nearby airfield since the mid-1980s. Clean water was provided from 16 December 2013. To determine the rates of decline in serum perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), and their corresponding half-lives. Up to seven blood samples were collected between June 2014 and September 2016 from 106 participants (age 4-84 years, 53% female). Median initial serum concentrations were PFHxS, 277 ng/mL (range 12-1660); PFOS, 345 ng/mL (range 24-1500); and PFOA, 18 ng/mL (range 2.4-92). The covariate-adjusted average rates of decrease in serum were PFHxS, 13% per year (95% CI 12% to 15%); PFOS, 20% per year (95% CI 19% to 22%); and PFOA, 26% per year (95% CI 24% to 28%). The observed data are consistent with a first-order elimination model. The mean estimated half-life was 5.3 years (95% CI 4.6 to 6.0) for PFHxS, 3.4 years (95% CI 3.1 to 3.7) for PFOS and 2.7 years (95% CI 2.5 to 2.9) for PFOA. The interindividual variation of half-life was around threefold when comparing the 5th and 95th percentiles. There was a marked sex difference with more rapid elimination in women for PFHxS and PFOS, but only marginally for PFOA. The estimated half-life for PFHxS was considerably longer than for PFOS and PFOA. For PFHxS and PFOS, the average half-life is shorter than the previously published estimates. For PFOA the half-life is in line with the range of published estimates. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Half-lives of PFOS, PFHxS and PFOA after end of exposure to contaminated drinking water

PubMed Central

Li, Ying; Fletcher, Tony; Mucs, Daniel; Scott, Kristin; Lindh, Christian H; Tallving, Pia; Jakobsson, Kristina

2018-01-01

Background Municipal drinking water contaminated with perfluorinated alkyl acids had been distributed to one-third of households in Ronneby, Sweden. The source was firefighting foam used in a nearby airfield since the mid-1980s. Clean water was provided from 16 December 2013. Objective To determine the rates of decline in serum perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), and their corresponding half-lives. Methods Up to seven blood samples were collected between June 2014 and September 2016 from 106 participants (age 4–84 years, 53% female). Results Median initial serum concentrations were PFHxS, 277 ng/mL (range 12–1660); PFOS, 345 ng/mL (range 24–1500); and PFOA, 18 ng/mL (range 2.4–92). The covariate-adjusted average rates of decrease in serum were PFHxS, 13% per year (95% CI 12% to 15%); PFOS, 20% per year (95% CI 19% to 22%); and PFOA, 26% per year (95% CI 24% to 28%). The observed data are consistent with a first-order elimination model. The mean estimated half-life was 5.3 years (95% CI 4.6 to 6.0) for PFHxS, 3.4 years (95% CI 3.1 to 3.7) for PFOS and 2.7 years (95% CI 2.5 to 2.9) for PFOA. The interindividual variation of half-life was around threefold when comparing the 5th and 95th percentiles. There was a marked sex difference with more rapid elimination in women for PFHxS and PFOS, but only marginally for PFOA. Conclusions The estimated half-life for PFHxS was considerably longer than for PFOS and PFOA. For PFHxS and PFOS, the average half-life is shorter than the previously published estimates. For PFOA the half-life is in line with the range of published estimates. PMID:29133598

Shiga toxin type 2 (Stx2), a potential agent of bioterrorism, has a short distribution and a long elimination half-life, and induces kidney and thymus lesions in rats.

PubMed

Liu, Yue-Nan; Wang, Sheng-Han; Li, Tao; Wang, Qin; Tu, Wei; Cai, Kun; Hou, Xiao-Jun; Tian, Ren-Mao; Gao, Xiang; Liu, Hao; Xiao, Le; Shi, Jing; Cheng, Yuan-Guo; Li, Jian-Chun; Wang, Hui

2011-09-01

Shiga toxin type 2, a major virulence factor produced by the Shiga toxin-producing Escherichia coli, is a potential toxin agent of bioterrorism. In this study, iodine-125 (125I) was used as an indicator to describe the in vivo Stx2 biodistribution profile. The rats were injected intravenously (i.v.) with 125I-Stx2 at three doses of 5.1-127.5 μg/kg body weight. Stx2 had a short distribution half-life (t (1/2)α, less than 6 min) and a long elimination half-life in rat. The toxicokinetics of Stx2 in rats was dose dependent and nonlinear. Stx2 concentrations in various tissues were detected at 5-min, 0.5-h, and 72-h postinjection. High radioactivity was found in the lungs, kidneys, nasal turbinates, and sometimes in the eyes, which has never been reported in previous studies. In a preliminary assessment, lesions were found in the kidney and thymus.

The elimination half-life of benzodiazepines and fall risk: two prospective observational studies.

PubMed

de Vries, Oscar J; Peeters, Geeske; Elders, Petra; Sonnenberg, Caroline; Muller, Majon; Deeg, Dorly J H; Lips, Paul

2013-11-01

the STOPP criteria advise against the use of long-acting benzodiazepines (LBs). to study whether LBs are associated with a higher fall risk than short-acting benzodiazepines (SBs) (elimination half-life ≤ 10 h). we used base-line data and prospective fall follow-up from the Longitudinal Aging Study Amsterdam, a longitudinal cohort study including 1,509 community-dwelling older persons (Study 1) and from a separate fall prevention study with 564 older persons after a fall (Study 2). Time to the first fall after inclusion and number of falls in the first year after inclusion were the primary endpoints. both in Study 1 and Study 2 the use of SBs was associated with time to the first fall, hazard ratio (HR) 1.62 (95% CI: 1.03-2.56) and HR 1.64 (95% CI: 1.19-2.26),respectively. LBs were not significantly associated with time to first fall, HR 1.40 (0.85-2.31) and HR 1.08 (0.72-1.62). In both studies, the use of SBs was also associated with number of falls, odds ratio (OR) 1.28 (95% CI: 1.01-1.61) and OR 1.37 (95% CI: 1.10-1.70). LBs were not significantly associated with number of falls, OR 1.23 (0.96-1.57) and 1.10 (0.82-1.48). the use of SBs is not associated with a lower fall risk compared with LBs. The use of both SBs and LBs by old persons should be strongly discouraged.

Starship Life Support

NASA Technical Reports Server (NTRS)

Jones, Harry W.

2009-01-01

The design and mass cost of a starship and its life support system are investigated. The mission plan for a multi generational interstellar voyage to colonize a new planet is used to describe the starship design, including the crew habitat, accommodations, and life support. Only current technology is assumed. Highly reliable life support systems can be provided with reasonably small additional mass, suggesting that they can support long duration missions. Bioregenerative life support, growing crop plants that provide food, water, and oxygen, has been thought to need less mass than providing stored food for long duration missions. The large initial mass of hydroponics systems is paid for over time by saving the mass of stored food. However, the yearly logistics mass required to support a bioregenerative system exceeds the mass of food solids it produces, so that supplying stored dehydrated food always requires less mass than bioregenerative food production. A mixed system that grows about half the food and supplies the other half dehydrated has advantages that allow it to breakeven with stored dehydrated food in about 66 years. However, moderate increases in the hydroponics system mass to achieve high reliability, such as adding spares that double the system mass and replacing the initial system every 100 years, increase the mass cost of bioregenerative life support. In this case, the high reliability half food growing, half food supplying system does not breakeven for 389 years. An even higher reliability half and half system, with three times original system mass and replacing the system every 50 years, never breaks even. Growing food for starship life support requires more mass than providing dehydrated food, even for multigeneration voyages of hundreds of years. The benefits of growing some food may justify the added mass cost. Much more efficient recycling food production is wanted but may not be possible. A single multigenerational interstellar voyage to

Kinetic modeling and half life study on bioremediation of crude oil dispersed by Corexit 9500.

PubMed

Zahed, Mohammad Ali; Aziz, Hamidi Abdul; Isa, Mohamed Hasnain; Mohajeri, Leila; Mohajeri, Soraya; Kutty, Shamsul Rahman Mohamed

2011-01-30

Hydrocarbon pollution in marine ecosystems occurs mainly by accidental oil spills, deliberate discharge of ballast waters from oil tankers and bilge waste discharges; causing site pollution and serious adverse effects on aquatic environments as well as human health. A large number of petroleum hydrocarbons are biodegradable, thus bioremediation has become an important method for the restoration of oil polluted areas. In this research, a series of natural attenuation, crude oil (CO) and dispersed crude oil (DCO) bioremediation experiments of artificially crude oil contaminated seawater was carried out. Bacterial consortiums were identified as Acinetobacter, Alcaligenes, Bacillus, Pseudomonas and Vibrio. First order kinetics described the biodegradation of crude oil. Under abiotic conditions, oil removal was 19.9% while a maximum of 31.8% total petroleum hydrocarbons (TPH) removal was obtained in natural attenuation experiment. All DCO bioreactors demonstrated higher and faster removal than CO bioreactors. Half life times were 28, 32, 38 and 58 days for DCO and 31, 40, 50 and 75 days for CO with oil concentrations of 100, 500, 1000 and 2000 mg/L, respectively. The effectiveness of Corexit 9500 dispersant was monitored in the 45 day study; the results indicated that it improved the crude oil biodegradation rate. Copyright © 2010 Elsevier B.V. All rights reserved.

SUDOQU: a new dose model to derive criteria for surface contamination of non-food (consumer) goods, containers and conveyances.

PubMed

van Dillen, Teun

2015-04-01

The Fukushima nuclear accident (Japan, 11 March 2011) revealed the need for well-founded criteria for surface contamination and associated screening levels related to the import of non-food (consumer) goods, containers and conveyances. The only available European-harmonised criteria are those laid down in the IAEA transport regulations, but these criteria date back from the early 1960s and only apply to the safe transport of radioactive materials. The main problem is that a generic dose-assessment model for consumer products is missing. Therefore, RIVM (National Institute for Public Health and the Environment) developed a new methodology entitled SUDOQU (SUrface DOse QUantification) to calculate the annual effective dose for both consumers and non-radiological workers, addressing issues of removability of surface contamination. The methodology can be used to derive criteria and screening levels for surface contamination and could serve as a useful tool for policy-makers and radiation-protection specialists. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Alcohol in the second half of life: do usual quantity and frequency of drinking to intoxication increase with increased drinking frequency?

PubMed

Brunborg, Geir Scott; Østhus, Ståle

2015-02-01

We investigated if increased drinking frequency among adults in the second half of life co-occurred with increased usual quantity and increased intoxication frequency. Two-wave panel study. Norway. Norwegian adults (1017 women and 959 men) aged 40-79 years. Drinking frequency, usual quantity and intoxication frequency was measured by self-report in 2002/03 and again in 2007/08. Information about gender, age and level of education was obtained from the public register. Health was collected by self-report. Because of a significant gender × change in drinking frequency interaction effect on change in intoxication frequency (b = 0.02, P = 0.013), women and men were analysed separately. After adjusting for covariates, women who increase their drinking frequency showed a non-significant decrease in usual quantity [low initial usual quantity (LIUQ): β = -0.01, P = 0.879; high initial usual quantity (HIUQ): β = -0.06, P = 0.164] and a non-significant increase in intoxication frequency (LIUQ: β = 0.04, P = 0.569; HIUQ: β = 0.09, P = 0.251). Men who increased their drinking frequency showed a small decrease in usual quantity (LIUQ: β = -0.06, P = 0.049; HIUQ: β = -0.05, P = 0.002) and a small increase in intoxication frequency (LIUQ: β = 0.05, P = 0.035; HIUQ: β = 0.13, P = 0.004). Among Norwegian adults in the second half of life, increased drinking frequency appears to be associated with a small reduction in usual quantity, and a small increase in frequency of drinking to intoxication. © 2014 Society for the Study of Addiction.

Determination of the energy transitions and half-lives of Rubidium nuclei

NASA Astrophysics Data System (ADS)

Biçer, Ahmet; Manisa, Kaan; Engin Çalık, Abdullah; Erdoğan, Mehmet; Şen, Mürsel; Bircan, Hasan; Dapo, Haris; Boztosun, Ismail

2018-03-01

The photonuclear reactions, first extensively studied in the 1970's and performed using the gamma rays obtained via bremsstrahlung, are a standard nuclear physics experiment. In this study, a non-enriched Rubidium sample was irradiated with photons produced by a clinical linear electron accelerator (cLINACs) with energies up to 18 MeV with the aim of activating it through photonuclear reactions. The activated sample was measured with a high purity germanium detector (HPGe) with the aim of measuring the transition energies and half-lives. The spectroscopic analysis performed on the obtained data yielded high quality results for the transition energies with precision matching or surpassing the literature data. For the half-lives the results were consistent with the literature, most notably the half-life of 84mRb decay was determined as 20.28(2) m. The results for both energies and half-lives further show that the clinical linear accelerators can be successfully used as an efficient tool in experimental nuclear research endeavors.

10 CFR 140.84 - Criterion I-Substantial discharge of radioactive material or substantial radiation levels offsite.

Code of Federal Regulations, 2013 CFR

2013-01-01

... or substantial radiation levels offsite. 140.84 Section 140.84 Energy NUCLEAR REGULATORY COMMISSION... § 140.84 Criterion I—Substantial discharge of radioactive material or substantial radiation levels... radioactive material offsite, or that there have been substantial levels of radiation offsite, when, as a...

10 CFR 140.84 - Criterion I-Substantial discharge of radioactive material or substantial radiation levels offsite.

Code of Federal Regulations, 2014 CFR

2014-01-01

... or substantial radiation levels offsite. 140.84 Section 140.84 Energy NUCLEAR REGULATORY COMMISSION... § 140.84 Criterion I—Substantial discharge of radioactive material or substantial radiation levels... radioactive material offsite, or that there have been substantial levels of radiation offsite, when, as a...

40 CFR 350.27 - Substantiation form to accompany claims of trade secrecy, instructions to substantiation form.

Code of Federal Regulations, 2010 CFR

2010-07-01

... TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.27 Substantiation form to... Secret Substantiation Form General Information EPA requires that the information requested in a trade secret substantiation be completed using this substantiation form in order to ensure that all facility...

40 CFR 350.27 - Substantiation form to accompany claims of trade secrecy, instructions to substantiation form.

Code of Federal Regulations, 2014 CFR

2014-07-01

... TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.27 Substantiation form to... Secret Substantiation Form General Information EPA requires that the information requested in a trade secret substantiation be completed using this substantiation form in order to ensure that all facility...

40 CFR 350.27 - Substantiation form to accompany claims of trade secrecy, instructions to substantiation form.

Code of Federal Regulations, 2011 CFR

2011-07-01

... TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.27 Substantiation form to... Secret Substantiation Form General Information EPA requires that the information requested in a trade secret substantiation be completed using this substantiation form in order to ensure that all facility...

40 CFR 350.27 - Substantiation form to accompany claims of trade secrecy, instructions to substantiation form.

Code of Federal Regulations, 2012 CFR

2012-07-01

... TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.27 Substantiation form to... Secret Substantiation Form General Information EPA requires that the information requested in a trade secret substantiation be completed using this substantiation form in order to ensure that all facility...

40 CFR 350.27 - Substantiation form to accompany claims of trade secrecy, instructions to substantiation form.

Code of Federal Regulations, 2013 CFR

2013-07-01

... TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.27 Substantiation form to... Secret Substantiation Form General Information EPA requires that the information requested in a trade secret substantiation be completed using this substantiation form in order to ensure that all facility...

NS5A inhibitors unmask differences in functional replicase complex half-life between different hepatitis C virus strains

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

Benzine, Tiffany; Brandt, Ryan; Lovell, William C.

We synthesized the Hepatitis C virus (HCV) RNA by the replicase complex (RC), a macromolecular assembly composed of viral non-structural proteins and cellular co-factors. Inhibitors of the HCV NS5A protein block formation of new RCs but do not affect RNA synthesis by preformed RCs. Without new RC formation, existing RCs turn over and are eventually lost from the cell. We aimed to use NS5A inhibitors to estimate the half-life of the functional RC of HCV. We compared different cell culture-infectious strains of HCV that may be grouped based on their sensitivity to lipid peroxidation: robustly replicating, lipid peroxidation resistant (LPOmore » R) viruses (e.g. JFH-1 or H77D) and more slowly replicating, lipid peroxidation sensitive (LPO S) viruses (e.g. H77S.3 and N.2). Furthermore, in luciferase assays, LPO S HCV strains declined under NS5A inhibitor therapy with much slower kinetics compared to LPO R HCV strains. This difference in rate of decline was not observed for inhibitors of the NS5B RNAdependent RNA polymerase suggesting that the difference was not simply a consequence of differences in RNA stability. In further analyses, we compared two isoclonal HCV variants: the LPO S H77S.3 and the LPO R H77D that differ only by 12 amino acids. Differences in rate of decline between H77S.3 and H77D following NS5A inhibitor addition were not due to amino acid sequences in NS5A but rather due to a combination of amino acid differences in the non-structural proteins that make up the HCV RC. The mathematical modeling of intracellular HCV RNA dynamics suggested that differences in RC stability (half-lives of 3.5 and 9.9 hours, for H77D and H77S.3, respectively) are responsible for the different kinetics of antiviral suppression between LPO S and LPO R viruses. In nascent RNA capture assays, the rate of RNA synthesis decline following NS5A inhibitor addition was significantly faster for H77D compared to H77S.3 indicating different half-lives of functional RCs.« less

NS5A inhibitors unmask differences in functional replicase complex half-life between different hepatitis C virus strains

DOE PAGES

Benzine, Tiffany; Brandt, Ryan; Lovell, William C.; ...

2017-06-08

We synthesized the Hepatitis C virus (HCV) RNA by the replicase complex (RC), a macromolecular assembly composed of viral non-structural proteins and cellular co-factors. Inhibitors of the HCV NS5A protein block formation of new RCs but do not affect RNA synthesis by preformed RCs. Without new RC formation, existing RCs turn over and are eventually lost from the cell. We aimed to use NS5A inhibitors to estimate the half-life of the functional RC of HCV. We compared different cell culture-infectious strains of HCV that may be grouped based on their sensitivity to lipid peroxidation: robustly replicating, lipid peroxidation resistant (LPOmore » R) viruses (e.g. JFH-1 or H77D) and more slowly replicating, lipid peroxidation sensitive (LPO S) viruses (e.g. H77S.3 and N.2). Furthermore, in luciferase assays, LPO S HCV strains declined under NS5A inhibitor therapy with much slower kinetics compared to LPO R HCV strains. This difference in rate of decline was not observed for inhibitors of the NS5B RNAdependent RNA polymerase suggesting that the difference was not simply a consequence of differences in RNA stability. In further analyses, we compared two isoclonal HCV variants: the LPO S H77S.3 and the LPO R H77D that differ only by 12 amino acids. Differences in rate of decline between H77S.3 and H77D following NS5A inhibitor addition were not due to amino acid sequences in NS5A but rather due to a combination of amino acid differences in the non-structural proteins that make up the HCV RC. The mathematical modeling of intracellular HCV RNA dynamics suggested that differences in RC stability (half-lives of 3.5 and 9.9 hours, for H77D and H77S.3, respectively) are responsible for the different kinetics of antiviral suppression between LPO S and LPO R viruses. In nascent RNA capture assays, the rate of RNA synthesis decline following NS5A inhibitor addition was significantly faster for H77D compared to H77S.3 indicating different half-lives of functional RCs.« less

Assessment of Minimum Important Difference and Substantial Clinical Benefit with the Vascular Quality of Life Questionnaire-6 when Evaluating Revascularisation Procedures in Peripheral Arterial Disease.

PubMed

Nordanstig, J; Pettersson, M; Morgan, M; Falkenberg, M; Kumlien, C

2017-09-01

Patient reported outcomes are increasingly used to assess outcomes after peripheral arterial disease (PAD) interventions. VascuQoL-6 (VQ-6) is a PAD specific health-related quality of life (HRQoL) instrument for routine clinical practice and clinical research. This study assessed the minimum important difference for the VQ-6 and determined thresholds for the minimum important difference and substantial clinical benefit following PAD revascularisation. This was a population-based observational cohort study. VQ-6 data from the Swedvasc Registry (January 2014 to September 2016) was analysed for revascularised PAD patients. The minimum important difference was determined using a combination of a distribution based and an anchor-based method, while receiver operating characteristic curve analysis (ROC) was used to determine optimal thresholds for a substantial clinical benefit following revascularisation. A total of 3194 revascularised PAD patients with complete VQ-6 baseline recordings (intermittent claudication (IC) n = 1622 and critical limb ischaemia (CLI) n = 1572) were studied, of which 2996 had complete VQ-6 recordings 30 days and 1092 a year after the vascular intervention. The minimum important difference 1 year after revascularisation for IC patients ranged from 1.7 to 2.2 scale steps, depending on the method of analysis. Among CLI patients, the minimum important difference after 1 year was 1.9 scale steps. ROC analyses demonstrated that the VQ-6 discriminative properties for a substantial clinical benefit was excellent for IC patients (area under curve (AUC) 0.87, sensitivity 0.81, specificity 0.76) and acceptable in CLI (AUC 0.736, sensitivity 0.63, specificity 0.72). An optimal VQ-6 threshold for a substantial clinical benefit was determined at 3.5 scale steps among IC patients and 4.5 in CLI patients. The suggested thresholds for minimum important difference and substantial clinical benefit could be used when evaluating VQ-6 outcomes following

Trends In Rhode Island Forests: A Half-Century of Change

Treesearch

Northeastern Research Station and Rhode Island Department of Environmental Management Division of Forest Environment

2002-01-01

Forests provide watershed protection, settings for recreation, wildlife habitat, biodiversity, wood and other products, and much more. Forests contribute to the quality of life of each Rhode Island resident making the State a better place in which to live. Some of the significant trends that have occurred in Rhode Island's forests over the last half century are...

Enhanced in Vivo Efficacy of a Type I Interferon Superagonist with Extended Plasma Half-life in a Mouse Model of Multiple Sclerosis*

PubMed Central

Harari, Daniel; Kuhn, Nadine; Abramovich, Renne; Sasson, Keren; Zozulya, Alla L.; Smith, Paul; Schlapschy, Martin; Aharoni, Rina; Köster, Mario; Eilam, Raya; Skerra, Arne; Schreiber, Gideon

2014-01-01

IFNβ is a common therapeutic option to treat multiple sclerosis. It is unique among the family of type I IFNs in that it binds to the interferon receptors with high affinity, conferring exceptional biological properties. We have previously reported the generation of an interferon superagonist (dubbed YNSα8) that is built on the backbone of a low affinity IFNα but modified to exhibit higher receptor affinity than even for IFNβ. Here, YNSα8 was fused with a 600-residue hydrophilic, unstructured N-terminal polypeptide chain comprising proline, alanine, and serine (PAS) to prolong its plasma half-life via “PASylation.” PAS-YNSα8 exhibited a 10-fold increased half-life in both pharmacodynamic and pharmacokinetic assays in a transgenic mouse model harboring the human receptors, notably without any detectable loss in biological potency or bioavailability. This long-lived superagonist conferred significantly improved protection from MOG35–55-induced experimental autoimmune encephalomyelitis compared with IFNβ, despite being injected with a 4-fold less frequency and at an overall 16-fold lower dosage. These data were corroborated by FACS measurements showing a decrease of CD11b+/CD45hi myeloid lineage cells detectable in the CNS, as well as a decrease in IBA+ cells in spinal cord sections determined by immunohistochemistry for PAS-YNSα8-treated animals. Importantly, PAS-YNSα8 did not induce antibodies upon repeated administration, and its biological efficacy remained unchanged after 21 days of treatment. A striking correlation between increased levels of CD274 (PD-L1) transcripts from spleen-derived CD4+ cells and improved clinical response to autoimmune encephalomyelitis was observed, indicating that, at least in this mouse model of multiple sclerosis, CD274 may serve as a biomarker to predict the effectiveness of IFN therapy to treat this complex disease. PMID:25193661

Nearly half of families in high-deductible health plans whose members have chronic conditions face substantial financial burden.

PubMed

Galbraith, Alison A; Ross-Degnan, Dennis; Soumerai, Stephen B; Rosenthal, Meredith B; Gay, Charlene; Lieu, Tracy A

2011-02-01

High-deductible health plans-typically with deductibles of at least $1,000 per individual and $2,000 per family-require greater enrollee cost sharing than traditional plans. But they also may provide more affordable premiums and may be the lowest-cost, or only, coverage option for many families with members who are chronically ill. We surveyed families with chronic conditions in high-deductible plans and families in traditional plans to compare health care-related financial burden-such as experiencing difficulty paying medical or basic bills or having to set up payment plans. Almost half (48 percent) of the families with chronic conditions in high-deductible plans reported health care-related financial burden, compared to 21 percent of families in traditional plans. Almost twice as many lower-income families in high-deductible plans spent more than 3 percent of income on health care expenses as lower-income families in traditional plans (53 percent versus 29 percent). As health reform efforts advance, policy makers must consider how to modify high-deductible plans to reduce the financial burden for families with chronic conditions.

Catalytic conversion of nonfood woody biomass solids to organic liquids.

PubMed

Barta, Katalin; Ford, Peter C

2014-05-20

This Account outlines recent efforts in our laboratories addressing a fundamental challenge of sustainability chemistry, the effective utilization of biomass for production of chemicals and fuels. Efficient methods for converting renewable biomass solids to chemicals and liquid fuels would reduce society's dependence on nonrenewable petroleum resources while easing the atmospheric carbon dioxide burden. The major nonfood component of biomass is lignocellulose, a matrix of the biopolymers cellulose, hemicellulose, and lignin. New approaches are needed to effect facile conversion of lignocellulose solids to liquid fuels and to other chemical precursors without the formation of intractable side products and with sufficient specificity to give economically sustainable product streams. We have devised a novel catalytic system whereby the renewable feedstocks cellulose, organosolv lignin, and even lignocellulose composites such as sawdust are transformed into organic liquids. The reaction medium is supercritical methanol (sc-MeOH), while the catalyst is a copper-doped porous metal oxide (PMO) prepared from inexpensive, Earth-abundant starting materials. This transformation occurs in a single stage reactor operating at 300-320 °C and 160-220 bar. The reducing equivalents for these transformations are derived by the reforming of MeOH (to H2 and CO), which thereby serves as a "liquid syngas" in the present case. Water generated by deoxygenation processes is quickly removed by the water-gas shift reaction. The Cu-doped PMO serves multiple purposes, catalyzing substrate hydrogenolysis and hydrogenation as well as the methanol reforming and shift reactions. This one-pot "UCSB process" is quantitative, giving little or no biochar residual. Provided is an overview of these catalysis studies beginning with reactions of the model compound dihydrobenzofuran that help define the key processes occurring. The initial step is phenyl-ether bond hydrogenolysis, and this is followed by

Studies of a urinary biomarker of dietary inorganic sulphur in subjects on diets containing 1-38 mmol sulphur/day and of the half-life of ingested 34SO4(2-).

PubMed

Curno, R; Magee, E A; Edmond, L M; Cummings, J H

2008-09-01

Sulphites are widely used food additives that may damage health, hence limits are set on their use. They are excreted in urine as sulphate, along with sulphate derived from sulphur amino acids. Dietary intakes of sulphites are hard to determine, so we have tested the utility of urinary nitrogen:sulphate ratio as a biomarker of inorganic sulphur (IS) intake. Additionally we determined the half-life of ingested (34)SO(4)(2-) from its urinary excretion. Twenty healthy adult subjects were recruited by poster advertisement, for a 24-h study where they ate specified foods, which were high in IS, in addition to their normal diet. The half-life of ingested (34)SO(4)(2-) was assessed in five healthy volunteers, given 5.9 mmols of Na(2)(34)SO(4) as a single dose and collecting all urine specimens for 72-96 h. Urine and duplicate diets from three previously conducted studies were analysed for nitrogen and sulphate content, thus expanding the range of IS intakes for evaluation. Duplicate diets were analysed for IS content by ion exchange chromatography, while IS intake was predicted from urinary sulphate (g/day S)-(urinary nitrogen (g/day)/18.89). (32)S:(34)S ratios were determined by liquid chromatography mass spectrometry/mass spectrometry. The range of IS intake was 1.3-37.5 mmol S/day. Actual and predicted IS intakes were mmol/day+/-s.e. 9.2+/-0.65 and 7.0+/-0.45, respectively, and were correlated r=0.60 (n=108). The mean half-life of ingested (34)SO(4)(2-) was 8.2 h. From a 24-h urine collection, IS intake from the habitual diet can be determined for groups of individuals. To predict individual intakes of IS, which may include high sporadic amounts from beer and wine, at least 48 h of urine collection would be required.

Co-Inheritance Analysis within the Domains of Life Substantially Improves Network Inference by Phylogenetic Profiling

PubMed Central

Shin, Junha; Lee, Insuk

2015-01-01

Phylogenetic profiling, a network inference method based on gene inheritance profiles, has been widely used to construct functional gene networks in microbes. However, its utility for network inference in higher eukaryotes has been limited. An improved algorithm with an in-depth understanding of pathway evolution may overcome this limitation. In this study, we investigated the effects of taxonomic structures on co-inheritance analysis using 2,144 reference species in four query species: Escherichia coli, Saccharomyces cerevisiae, Arabidopsis thaliana, and Homo sapiens. We observed three clusters of reference species based on a principal component analysis of the phylogenetic profiles, which correspond to the three domains of life—Archaea, Bacteria, and Eukaryota—suggesting that pathways inherit primarily within specific domains or lower-ranked taxonomic groups during speciation. Hence, the co-inheritance pattern within a taxonomic group may be eroded by confounding inheritance patterns from irrelevant taxonomic groups. We demonstrated that co-inheritance analysis within domains substantially improved network inference not only in microbe species but also in the higher eukaryotes, including humans. Although we observed two sub-domain clusters of reference species within Eukaryota, co-inheritance analysis within these sub-domain taxonomic groups only marginally improved network inference. Therefore, we conclude that co-inheritance analysis within domains is the optimal approach to network inference with the given reference species. The construction of a series of human gene networks with increasing sample sizes of the reference species for each domain revealed that the size of the high-accuracy networks increased as additional reference species genomes were included, suggesting that within-domain co-inheritance analysis will continue to expand human gene networks as genomes of additional species are sequenced. Taken together, we propose that co

External radiation exposure, excretion, and effective half-life in 177Lu-PSMA-targeted therapies.

PubMed

Kurth, J; Krause, B J; Schwarzenböck, S M; Stegger, L; Schäfers, M; Rahbar, K

2018-04-12

Prostate-specific membrane antigen (PSMA)-targeted therapy with 177 Lu-PSMA-617 is a therapeutic option for patients with metastatic castration-resistant prostate cancer (mCRPC). To optimize the therapy procedure, it is necessary to determine relevant parameters to define radiation protection and safety necessities. Therefore, this study aimed at estimating the ambient radiation exposure received by the patient. Moreover, the excreted activity was quantified. In total, 50 patients with mCRPC and treated with 177 Lu-PSMA-617 (mean administered activity 6.3 ± 0.5 GBq) were retrospectively included in a bi-centric study. Whole-body dose rates were measured at a distance of 2 m at various time points after application of 177 Lu-PSMA-617, and effective half-lives for different time points were calculated and compared. Radiation exposure to the public was approximated using the dose integral. For the estimation of the excreted activity, whole body measurements of 25 patients were performed at 7 time points. Unbound 177 Lu-PSMA-617 was rapidly cleared from the body. After 4 h, approximately 50% and, after 12 h, approximately 70% of the administered activity were excreted, primarily via urine. The mean dose rates were the following: 3.6 ± 0.7 μSv/h at 2 h p. i., 1.6 ± 0.6 μSv/h at 24 h, 1.1 ± 0.5 μSv/h at 48 h, and 0.7 ± 0.4 μSv/h at 72 h. The mean effective half-life of the cohort was 40.5 ± 9.6 h (min 21.7 h; max 85.7 h). The maximum dose to individual members of the public per treatment cycle was ~ 250 ± 55 μSv when the patient was discharged from the clinic after 48 h and ~ 190 ± 36 μSv when the patient was discharged after 72 h. In terms of the radiation exposure to the public, 177 Lu-PSMA is a safe option of radionuclide therapy. As usually four (sometimes more) cycles of the therapy are performed, it must be conducted in a way that ensures that applicable legal requirements can be followed. In

Half Lives for ``Irradiated'' Nonscience Majors

NASA Astrophysics Data System (ADS)

Geise, Kathleen; Hallam, Peter; Rattray, Rebecca; Stencel, Robert; Wolfe, Tristan

2014-03-01

We launched new hands-on radiation labs to supplement lecture material for undergraduate, non-science majors at the University of Denver to reinforce learning objectives during winter quarter 2014 and in order to help educate the public about nuclear energy decisions. Our learning objectives included: 1. differentiate between particle radiation and electro-magnetic radiation, 2. understand that particle radiation comes in alpha, beta and gamma types, 3. atomic and nuclear structure, 4. decay and half-life, 5. understand safe vs. unsafe doses and issues surrounding nuclear waste disposal. We used prelab surveys, prelab assessments, laboratory write-ups and quizzes to measure success with the learning objectives.

Psychosocial correlates of unintentional weight loss in the second half of life in the German general population

PubMed Central

König, Hans-Helmut

2017-01-01

Background Unintentional weight loss (UWL) is common in older age and associated with adverse outcomes including mortality. The aim of the present study was to determine psychosocial correlates of UWL. Methods Data were derived from a large, nationally representative study of community-dwelling individuals in the second half of life (40 years and over) in Germany in 2014 (n = 7,933). Data on UWL were assessed in face-to-face interviews as unintentional loss of more than 5kg (11 pounds) in weight in the past 12 months, and data on psychosocial factors were recorded in self-administered questionnaires. Results Multiple logistic regressions revealed that UWL was positively associated with depressive symptoms and positive affect, whereas it was negatively associated with self-esteem. Individuals with UWL were more likely to feel lonely and perceive themselves as socially excluded. Conclusion The findings of important psychosocial correlates of UWL may help to identify individuals at risk for UWL in older age. This is in particular important since interventions to treat this phenomenon in older age are available that reduce adverse consequences resulting from UWL. PMID:28968437

Differences in the half-lives of some mitochondrial rat liver enzymes may derive partially from hepatocyte heterogeneity.

PubMed

Vargas, J L; Roche, E; Knecht, E; Grisolía, S

1987-11-16

The different turnover rates of rat liver mitochondrial enzymes make autophagy unlikely to be the main mechanism for degradation of mitochondria. Although alternatives have been presented, hepatocyte heterogeneity has not been considered. Lighter hepatocytes isolated in a discontinuous Percoll gradient contain more glutamate dehydrogenase (GDH) (half-life 1 day) and a more active autophagic system than heavier hepatocytes. The latter contain more carbamoyl phosphate synthase (CPS) and ornithine carbamoyl transferase (OTC) (half-lives 8 days) but less lysosomal activity. As expected, isolated autophagic vacuoles contain, relative to the mitochondrial content, 3-times less OTC and CPS than GDH, probably reflecting a faster lysosomal engulfment of mitochondria in the light hepatocytes (which contain more GDH). These data may explain some of the half-life differences of the enzymes studied.

The truly remarkable universality of half a standard deviation: confirmation through another look.

PubMed

Norman, Geoffrey R; Sloan, Jeff A; Wyrwich, Kathleen W

2004-10-01

In this issue of Expert Review of Pharmacoeconomics and Outcomes Research, Farivar, Liu, and Hays present their findings in 'Another look at the half standard deviation estimate of the minimally important difference in health-related quality of life scores (hereafter referred to as 'Another look') . These researchers have re-examined the May 2003 Medical Care article 'Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation' (hereafter referred to as 'Remarkable') in the hope of supporting their hypothesis that the minimally important difference in health-related quality of life measures is undoubtedly closer to 0.3 standard deviations than 0.5. Nonetheless, despite their extensive wranglings with the exclusion of many articles that we included in our review; the inclusion of articles that we did not include in our review; and the recalculation of effect sizes using the absolute value of the mean differences, in our opinion, the results of the 'Another look' article confirm the same findings in the 'Remarkable' paper.

10 CFR 840.4 - Criterion I-Substantial discharge of radioactive material or substantial radiation levels offsite.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Criterion I-Substantial discharge of radioactive material or substantial radiation levels offsite. 840.4 Section 840.4 Energy DEPARTMENT OF ENERGY EXTRAORDINARY NUCLEAR OCCURRENCES § 840.4 Criterion I—Substantial discharge of radioactive material or...

10 CFR 840.4 - Criterion I-Substantial discharge of radioactive material or substantial radiation levels offsite.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Criterion I-Substantial discharge of radioactive material or substantial radiation levels offsite. 840.4 Section 840.4 Energy DEPARTMENT OF ENERGY EXTRAORDINARY NUCLEAR OCCURRENCES § 840.4 Criterion I—Substantial discharge of radioactive material or...

10 CFR 840.4 - Criterion I-Substantial discharge of radioactive material or substantial radiation levels offsite.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Criterion I-Substantial discharge of radioactive material or substantial radiation levels offsite. 840.4 Section 840.4 Energy DEPARTMENT OF ENERGY EXTRAORDINARY NUCLEAR OCCURRENCES § 840.4 Criterion I—Substantial discharge of radioactive material or...

10 CFR 840.4 - Criterion I-Substantial discharge of radioactive material or substantial radiation levels offsite.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Criterion I-Substantial discharge of radioactive material or substantial radiation levels offsite. 840.4 Section 840.4 Energy DEPARTMENT OF ENERGY EXTRAORDINARY NUCLEAR OCCURRENCES § 840.4 Criterion I—Substantial discharge of radioactive material or...

Half-Lives of Proton Emitters With a Deformed Density-Dependent Model

NASA Astrophysics Data System (ADS)

Qian, Yi-Bin; Ren, Zhong-Zhou; Ni, Dong-Dong; Sheng, Zong-Qiang

2010-11-01

Half-lives of proton radioactivity are investigated with a deformed density-dependent model. The single folding potential which is dependent on deformation and orientation is employed to calculate the proton decay width through the deformed potential barrier. In addition, the spectroscopic factor is taken into account in the calculation, which is obtained in the relativistic mean field theory with NL3. The calculated results of semi-spherical nuclei are found to be in good agreement with the experimental data, and the results of well-deformed nuclei are also satisfactory. Moreover, a formula for the spherical proton emission half-life based on the Gamow quantum tunneling theory is presented.

Substantial global carbon uptake by cement carbonation

NASA Astrophysics Data System (ADS)

Xi, Fengming; Davis, Steven J.; Ciais, Philippe; Crawford-Brown, Douglas; Guan, Dabo; Pade, Claus; Shi, Tiemao; Syddall, Mark; Lv, Jie; Ji, Lanzhu; Bing, Longfei; Wang, Jiaoyue; Wei, Wei; Yang, Keun-Hyeok; Lagerblad, Björn; Galan, Isabel; Andrade, Carmen; Zhang, Ying; Liu, Zhu

2016-12-01

Calcination of carbonate rocks during the manufacture of cement produced 5% of global CO2 emissions from all industrial process and fossil-fuel combustion in 2013. Considerable attention has been paid to quantifying these industrial process emissions from cement production, but the natural reversal of the process--carbonation--has received little attention in carbon cycle studies. Here, we use new and existing data on cement materials during cement service life, demolition, and secondary use of concrete waste to estimate regional and global CO2 uptake between 1930 and 2013 using an analytical model describing carbonation chemistry. We find that carbonation of cement materials over their life cycle represents a large and growing net sink of CO2, increasing from 0.10 GtC yr-1 in 1998 to 0.25 GtC yr-1 in 2013. In total, we estimate that a cumulative amount of 4.5 GtC has been sequestered in carbonating cement materials from 1930 to 2013, offsetting 43% of the CO2 emissions from production of cement over the same period, not including emissions associated with fossil use during cement production. We conclude that carbonation of cement products represents a substantial carbon sink that is not currently considered in emissions inventories.

The correlation between reading and mathematics ability at age twelve has a substantial genetic component.

PubMed

Davis, Oliver S P; Band, Gavin; Pirinen, Matti; Haworth, Claire M A; Meaburn, Emma L; Kovas, Yulia; Harlaar, Nicole; Docherty, Sophia J; Hanscombe, Ken B; Trzaskowski, Maciej; Curtis, Charles J C; Strange, Amy; Freeman, Colin; Bellenguez, Céline; Su, Zhan; Pearson, Richard; Vukcevic, Damjan; Langford, Cordelia; Deloukas, Panos; Hunt, Sarah; Gray, Emma; Dronov, Serge; Potter, Simon C; Tashakkori-Ghanbaria, Avazeh; Edkins, Sarah; Bumpstead, Suzannah J; Blackwell, Jenefer M; Bramon, Elvira; Brown, Matthew A; Casas, Juan P; Corvin, Aiden; Duncanson, Audrey; Jankowski, Janusz A Z; Markus, Hugh S; Mathew, Christopher G; Palmer, Colin N A; Rautanen, Anna; Sawcer, Stephen J; Trembath, Richard C; Viswanathan, Ananth C; Wood, Nicholas W; Barroso, Ines; Peltonen, Leena; Dale, Philip S; Petrill, Stephen A; Schalkwyk, Leonard S; Craig, Ian W; Lewis, Cathryn M; Price, Thomas S; Donnelly, Peter; Plomin, Robert; Spencer, Chris C A

2014-07-08

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children's ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child's cognitive abilities at age twelve.

Carboxyhemoglobin half-life during hyperbaric oxygen in a patient with lung dysfunction: a case report.

PubMed

Weaver, Lindell K; Deru, Kayla

2017-01-01

The carboxyhemoglobin half-life (COHb t1/2) during hyperbaric oxygen (HBO₂) is often quoted as 23 minutes, derived from the average of two adult male volunteers breathing HBO₂ at 3 atmospheres absolute (ATA). However, the mean COHb t1/2 of 12 male volunteer smokers was 26.3 minutes at 1.58 ATA and in 12 non-intubated carbon monoxide (CO) poisoned patients treated at 3 ATA, was 43 minutes. An 81-year old male, poisoned by an improperly ventilated natural gas heater, was intubated for coma, then treated with HBO₂. His PaO₂/FiO₂ = 283 from aspiration. His initial COHb was 34.4%, and 18 minutes before HBO₂, 5.9%. After a compression interval of 17 minutes, the COHb measured after 22 minutes at 3 ATA was 3.3%. By exponential decay, his COHb t1/2 before HBO₂ was 95 minutes. We estimate the range for COHb t1/2 during compression as 62-81 minutes and for the 3-ATA interval, 58 to 49 minutes, respectively. The mid-point estimate of COHb t1/2 at 3 ATA was 53 minutes. The COHb t1/2 we calculated is greater than previously reported, but longer in our patient possibly because of concomitant respiratory failure, lung dysfunction, and mechanical ventilation. The often-cited COHb t1/2 of 23 minutes, likely underestimates the actual COHb t1/2 in CO-poisoned patients, especially those with cardiopulmonary dysfunction.

Nearly Half of Families In High-Deductible Health Plans Whose Members Have Chronic Conditions Face Substantial Financial Burden

PubMed Central

Galbraith, Alison A.; Ross-Degnan, Dennis; Soumerai, Stephen B.; Rosenthal, Meredith B.; Gay, Charlene; Lieu, Tracy A.

2015-01-01

High-deductible health plans – typically with deductibles of at least $1,000 per individual and $2,000 per family -- require greater enrollee cost sharing than traditional plans. But they also may provide more affordable premiums and may be the lowest-cost, or only, coverage option for many families with members who are chronically ill. We surveyed families with chronic conditions in high-deductible plans and families in traditional plans to compare health care-related financial burden – such as experiencing difficulty paying medical or basic bills or having to set up payment plans. Almost half (48 percent) of the families with chronic conditions in high-deductible plans reported health care-related financial burden, compared to a fifth of families (21 percent) in traditional plans. Almost twice as many lower-income families in high-deductible plans spent more than 3 percent of income on health care expenses as lower-income families in traditional plans (53 percent versus 29 percent). As health reform efforts advance, policy makers must consider how to modify high-deductible plans to reduce the financial burden for families with chronic conditions. PMID:21289354

Establishing Substantial Equivalence: Transcriptomics

NASA Astrophysics Data System (ADS)

Baudo, María Marcela; Powers, Stephen J.; Mitchell, Rowan A. C.; Shewry, Peter R.

Regulatory authorities in Western Europe require transgenic crops to be substantially equivalent to conventionally bred forms if they are to be approved for commercial production. One way to establish substantial equivalence is to compare the transcript profiles of developing grain and other tissues of transgenic and conventionally bred lines, in order to identify any unintended effects of the transformation process. We present detailed protocols for transcriptomic comparisons of developing wheat grain and leaf material, and illustrate their use by reference to our own studies of lines transformed to express additional gluten protein genes controlled by their own endosperm-specific promoters. The results show that the transgenes present in these lines (which included those encoding marker genes) did not have any significant unpredicted effects on the expression of endogenous genes and that the transgenic plants were therefore substantially equivalent to the corresponding parental lines.

77 FR 34887 - Substantial Business Activities

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-12

... Substantial Business Activities AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of proposed... regarding whether a foreign corporation has substantial business activities in a foreign country. These... provide guidance regarding whether a foreign corporation has substantial business activities in a foreign...

The correlation between reading and mathematics ability at age twelve has a substantial genetic component

PubMed Central

Davis, Oliver S. P.; Band, Gavin; Pirinen, Matti; Haworth, Claire M. A.; Meaburn, Emma L.; Kovas, Yulia; Harlaar, Nicole; Docherty, Sophia J.; Hanscombe, Ken B.; Trzaskowski, Maciej; Curtis, Charles J. C.; Strange, Amy; Freeman, Colin; Bellenguez, Céline; Su, Zhan; Pearson, Richard; Vukcevic, Damjan; Langford, Cordelia; Deloukas, Panos; Hunt, Sarah; Gray, Emma; Dronov, Serge; Potter, Simon C.; Tashakkori-Ghanbaria, Avazeh; Edkins, Sarah; Bumpstead, Suzannah J.; Blackwell, Jenefer M.; Bramon, Elvira; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden; Duncanson, Audrey; Jankowski, Janusz A. Z.; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N. A.; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Viswanathan, Ananth C.; Wood, Nicholas W.; Barroso, Ines; Peltonen, Leena; Dale, Philip S.; Petrill, Stephen A.; Schalkwyk, Leonard S.; Craig, Ian W.; Lewis, Cathryn M.; Price, Thomas S.; Donnelly, Peter; Plomin, Robert; Spencer, Chris C. A.

2014-01-01

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children’s ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child’s cognitive abilities at age twelve. PMID:25003214

Sub-nanosecond Half-life Measurement of the Yrast I{sup π}=5{sup −} State in the N=78 Nucleus {sup 136}{sub 58}Ce using Fast-timing Coincident Gamma-ray Spectroscopy

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

Alharbi, T.; Department of Physics, Faculty of Science in Zulfi, Almajmaah University, P.O. Box 1712, 11932; Regan, P.H., E-mail: p.regan@surrey.ac.uk

2014-06-15

We report on the measurement of the half-life of the yrast I{sup π}=5{sup −} state in the transitional nucleus {sup 136}Ce using a combined HPGe-LaBr3(Ce) scintillator gamma-ray detection array. The measured value for the E1 decay is approximately half a nanosecond, which corresponds to an E1 decay strength of approximately 2×10{sup −6} Wu. This value is in line with single-particle type E1 decays in this mass region and suggests no sign of additional K-hindrance associated with axially symmetric quadrupole deformations observed for lighter cerium isotopes.

Enzymatic transformation of nonfood biomass to starch

PubMed Central

You, Chun; Chen, Hongge; Myung, Suwan; Sathitsuksanoh, Noppadon; Ma, Hui; Zhang, Xiao-Zhou; Li, Jianyong; Zhang, Y.-H. Percival

2013-01-01

The global demand for food could double in another 40 y owing to growth in the population and food consumption per capita. To meet the world’s future food and sustainability needs for biofuels and renewable materials, the production of starch-rich cereals and cellulose-rich bioenergy plants must grow substantially while minimizing agriculture’s environmental footprint and conserving biodiversity. Here we demonstrate one-pot enzymatic conversion of pretreated biomass to starch through a nonnatural synthetic enzymatic pathway composed of endoglucanase, cellobiohydrolyase, cellobiose phosphorylase, and alpha-glucan phosphorylase originating from bacterial, fungal, and plant sources. A special polypeptide cap in potato alpha-glucan phosphorylase was essential to push a partially hydrolyzed intermediate of cellulose forward to the synthesis of amylose. Up to 30% of the anhydroglucose units in cellulose were converted to starch; the remaining cellulose was hydrolyzed to glucose suitable for ethanol production by yeast in the same bioreactor. Next-generation biorefineries based on simultaneous enzymatic biotransformation and microbial fermentation could address the food, biofuels, and environment trilemma. PMID:23589840

[Gerotranscendence in the second half of life: first empirical investigation in Flanders].

PubMed

Raes, F; Marcoen, A

2001-08-01

Tornstam regards gerotranscendence as the final stage in a natural process towards maturity and wisdom, that can be described as a shift in meta-perspective which accompanies the process of aging: from a materialistic and rational perspective to a more cosmic and transcendent one. The present study contributes to the development of a by Tornstam used gerotranscendence scale, and looks for theoretically expected relations between gerotranscendence and psychosocial variables such as life satisfaction, death attitude, and recently experienced life crises. The relation between gerotranscendence and dimensions of religion and faith will also be examined. Participants were 120 older adults, 58 men and 62 women, aged 45-92 years. The scores on the gerotranscendence scale were not congruent, neither with the hypothetical threefold apriori scales, nor with the factor structure Tornstam had found in his research. An exploratory factor analysis yielded three factors which were to a certain extent reconcilable with the gerotranscendence theory. The subscales are Transcendent connection, Active involvement and coherence, and Attachment to life and material goods. Older respondents and respondents who experienced one or more life crises, have higher scores on Transcendent connection. The experience of connection seems to be related to dimensions of religion and faith. The results warrant further research into a measurement of gerotranscendence and the relation with dimensions of religion and faith.

Substantial Physician Turnover And Beneficiary 'Churn' In A Large Medicare Pioneer ACO.

PubMed

Hsu, John; Vogeli, Christine; Price, Mary; Brand, Richard; Chernew, Michael E; Mohta, Namita; Chaguturu, Sreekanth K; Weil, Eric; Ferris, Timothy G

2017-04-01

Alternative payment models, such as accountable care organizations (ACOs), attempt to stimulate improvements in care delivery by better alignment of payer and provider incentives. However, limited attention has been paid to the physicians who actually deliver the care. In a large Medicare Pioneer ACO, we found that the number of beneficiaries per physician was low (median of seventy beneficiaries per physician, or less than 5 percent of a typical panel). We also found substantial physician turnover: More than half of physicians either joined (41 percent) or left (18 percent) the ACO during the 2012-14 contract period studied. When physicians left the ACO, most of their attributed beneficiaries also left the ACO. Conversely, about half of the growth in the beneficiary population was because of new physicians affiliating with the ACO; the remainder joined after switching physicians. These findings may help explain the muted financial impact ACOs have had overall, and they raise the possibility of future gaming on the part of ACOs to artificially control spending. Policy refinements include coordinated and standardized risk-sharing parameters across payers to prevent any dilution of the payment incentives or confusion from a cacophony of incentives across payers. Project HOPE—The People-to-People Health Foundation, Inc.

Hong Kong Chinese teachers' attitudes towards life-sustaining treatment in the dying patients.

PubMed

Lee, J C Y; Chen, P P; Yeo, J K S; So, H Y

2003-06-01

To evaluate the attitudes of Hong Kong Chinese teachers towards life-sustaining treatment in the dying patients. Prospective structured questionnaire survey. Hong Kong Institute of Education. All teaching staff at the Hong Kong Institute of Education were sent the survey questionnaire. The questionnaire gathered demographic data, information on experience of 'life and death' decision-making, and views on life-sustaining treatment decisions. Respondents were also requested to respond to statements on life-sustaining treatment using a 5-point Likert Scale (1 representing strong disagreement and 5 representing strong agreement). A total of 436 questionnaires were sent to teaching staff at the Hong Kong Institute of Education. The response rate was 27.8%. More than half (65.8%) of the respondents were aged between 30 and 49 years. There was an equal proportion of men and women among respondents. The respondents agreed with statements supporting end-of-life decisions (mean aggregate score, 3.13; standard deviation, 1.24; P<0.0001), and disagreed with statements against such decisions (mean aggregate score, 2.81; standard deviation, 1.22; P<0.0001). If the patient is competent, half of the respondents agreed that the patient alone should make the decision, while 27.2% believed that it should be a joint decision made by the patient, the family, and the doctor. Conversely, if the patient is incompetent, 52.6% agreed that it should be a joint decision made by the family and the doctor. There was strong support for advanced directives, whereby decisions in relation to life-sustaining treatment were legally recorded in advance (mean score, 3.62; P=0.0001). The teachers in this survey appear to support the practice of withdrawing and withholding life-sustaining treatment in the dying patients when medical treatment is considered futile. Although patient autonomy in decision-making was supported by the greatest number of respondents, joint decision-making by the patient, family

Half-life measurements of isomeric states populated in projectile fragmentation

NASA Astrophysics Data System (ADS)

Bowry, M.; Podolyák, Zs.; Kurcewicz, J.; Pietri, S.; Bunce, M.; Regan, P. H.; Farinon, F.; Geissel, H.; Nociforo, C.; Prochazka, A.; Weick, H.; Allegro, P.; Benlliure, J.; Benzoni, G.; Boutachkov, P.; Gerl, J.; Gorska, M.; Gottardo, A.; Gregor, N.; Janik, R.; Knöbel, R.; Kojouharov, I.; Kubo, T.; Litvinov, Y. A.; Merchan, E.; Mukha, I.; Naqvi, F.; Pfeiffer, B.; Pfützner, M.; Plaß, W.; Pomorski, M.; Riese, B.; Ricciardi, M. V.; Schmidt, K.-H.; Schaffner, H.; Kurz, N.; Denis Bacelar, A. M.; Bruce, A. M.; Farrelly, G. F.; Alkhomashi, N.; Al-Dahan, N.; Scheidenberger, C.; Sitar, B.; Spiller, P.; Stadlmann, J.; Strmen, P.; Sun, B.; Takeda, H.; Tanihata, I.; Terashima, S.; Valiente Dobon, J. J.; Winfield, J. S.; Wollersheim, H.-J.; Woods, P. J.

2012-10-01

The half-lives of excited isomeric states observed in 195Au, 201Tl and 215Rn are reported for the first time. Delayed γ-rays were correlated with nuclei produced in the projectile fragmentation of relativistic 238U ions, unambiguously identified in terms of their atomic number (Z) and mass-to-charge ratio (A/Q) after traversing an in-flight separator. The observation of a long-lived isomeric state in 195Au with t1/2 = 16-4+8 μs is presented. Two shorter-lived isomeric states were detected in 201Tl and 215Rn with t1/2 = 95-21+39 and 57-12+21 ns respectively. In total 24 isomeric states were identified in different nuclei from Pt to Rn (A ˜ 200) during the current study, the majority of which were previously reported. The wealth of spectroscopic data provides the opportunity to determine the isomeric ratios over a wide range of Z, A and angular momentum (I ħ) of the reaction products. In particular, high-spin states with I ≳ 18 ħ provide a robust test of theoretical models of fragmentation.

Looking East at BottomHalf of Reactor Number One and TopHalf ...

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

Looking East at Bottom-Half of Reactor Number One and Top-Half of Reactor Number 2 Including Weigh Hopper on Third Floor of Oxide Building - Hematite Fuel Fabrication Facility, Oxide Building & Oxide Loading Dock, 3300 State Road P, Festus, Jefferson County, MO

20 CFR 220.141 - Substantial gainful activity, defined.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Substantial work activity. Substantial work activity is work activity that involves doing significant physical... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Substantial gainful activity, defined. 220... RETIREMENT ACT DETERMINING DISABILITY Substantial Gainful Activity § 220.141 Substantial gainful activity...

20 CFR 220.141 - Substantial gainful activity, defined.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) Substantial work activity. Substantial work activity is work activity that involves doing significant physical... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Substantial gainful activity, defined. 220... RETIREMENT ACT DETERMINING DISABILITY Substantial Gainful Activity § 220.141 Substantial gainful activity...

Half-life of the 15 /2+ state of 135I: A test of E 2 seniority relations

NASA Astrophysics Data System (ADS)

Spagnoletti, P.; Simpson, G. S.; Carroll, R.; Régis, J.-M.; Blanc, A.; Jentschel, M.; Köster, U.; Mutti, P.; Soldner, T.; de France, G.; Ur, C. A.; Urban, W.; Bruce, A. M.; Drouet, F.; Fraile, L. M.; Gaffney, L. P.; Ghitǎ, D. G.; Ilieva, S.; Jolie, J.; Korten, W.; Kröll, T.; Larijarni, C.; Lalkovski, S.; Licǎ, R.; Mach, H.; Mǎrginean, N.; Paziy, V.; Podolyák, Zs.; Regan, P. H.; Scheck, M.; Saed-Samii, N.; Thiamova, G.; Townsley, C.; Vancraeyenest, A.; Vedia, V.; Gargano, A.; Van Isacker, P.

2017-02-01

The half-life of the 15 /21+ state of the 3-valence-proton nucleus 135I has been measured to be 1.74(8) ns using the EXILL-FATIMA mixed array of Ge and LaBr3 detectors. The nuclei were produced following the cold neutron-induced fission of a 235U target at the PF1B beam line of the Institut Laue-Langevin. The extracted B (E 2 ;15 /2+→11 /2+) value enabled a test of seniority relations for the first time between E 2 transition rates. Large-scale shell-model calculations were performed for 134Te and 135I, and reinterpreted in a single-orbit approach. The results show that the two-body component of the E 2 operator can be large whereas energy shifts due to the three-body component of the effective interaction are small.

PREPARATION, IN VITRO AND IN VIVO CHARACTERIZATION OF HYDROPHOBIC PATCHES OF A HIGHLY WATER SOLUBLE DRUG FOR PROLONGED PLASMA HALF LIFE: EFFECT OF PERMEATION ENHANCERS.

PubMed

Yaqoob, Ayesha; Ahmad, Mahmood; Mahmood, Asif; Sarfraz, Rai Muhammad

2016-11-01

Aim of present study was to develop metoprolol matrix patches using different enhancers. Combination of two hydrophobic polymers, ethyl cellulose and eudragit RL 100 (8 : 2) were used for preparation of unilaminated matrix patch. 10% w/w of isopropyl myristate (IPM), dimethyl sulfoxide (DMSO), span (20 (S20), Tween 20 (T20) and eucalyptus oil as enhancers and 40% of dibutyl phthalate as plasticizer were used. Prepared patches were evaluated for physical appearance, weight uniformity and thickness. FTIR studies were performed to assess compatibility among ingredients and developed formulation. Dissolution and permeation studies were performed to compare effects of enhancers. Surface morphology after release was examined by scanning electron microscopy. Selected formulation was subjected to in vivo studies by randomized crossover design in rabbits (n = 6) for pharmacokinetic comparison with oral solution administration. Physical evaluation revealed that translucent, flexible, non brittle patches of uniform weight and thickness were prepared. Release from patches followed Higuchi model. Mechanism of release was Fickian. Formulation containing IPM showed that release was by anomalous transport. Highest permeation flux was observed for formulation containing IPM with 2-fold enhancement in permeation. Permeation flux for patches was in order of formulation with no enhancer > IPM > T20 > S20 > DMSO = eucalyptus oil. Plasma concentration from in vivo studies exhibited sustained plasma levels of metoprolol after transdermal patch application in comparison to oral solution administration. Pharmacokinetic analysis of in vivo data elucidated that half life was increased 8 times when compared to oral administration, due to controlled release of drug for longer period of time. These findings suggested that hydrophobic transdermal patches of highly water soluble drug metoprolol were successfully prepared with 10% of IPM for sustained systemic delivery for prolonged half life.

Collimated thermal radiation transfer via half Maxwell's fish-eye lens for thermophotovoltaics

NASA Astrophysics Data System (ADS)

Chung, Haejun; Zhou, Zhiguang; Bermel, Peter

2017-05-01

Thermophotovoltaics (TPV) convert heat into electricity by capturing thermal radiation with a photovoltaic (PV) cell, ideally at efficiencies of 50% or more. However, excess heating of the PV cell from close proximity to the emitter substantially reduces the system efficiency. In this work, we theoretically develop and numerically demonstrate an approach to fundamentally improving TPV systems that allow for a much greater separation of an emitter and a receiver. Thus, we solve the excess heating dilemma, required for achieving theoretically high efficiencies. It consists of a spherically graded index lens known as Maxwell's Fish-Eye (MFE) structure, capable of collimating hemispherical emission into a much narrower range of angles, close to the normal direction. To fully characterize the power radiation profile of the MFE, we perform finite-difference time-domain simulations for a quarter MFE and then map it onto a Gaussian beam approximation. The modeled beam properties are subsequently used to study a half MFE. In an optimized half MFE design, 90% of all thermal photons reach a receiver at a distance of 100 λ; by comparison, only 15.6% of a blackbody emitter reach a receiver in the same geometry. It is also shown that the emission achieved by a half MFE can lead to a photon recycling rate above 95% for below bandgap photons at an emitter-receiver separation of 100 λ. By applying a half MFE, the absolute TPV efficiency can be improved from 5.74% to 37.15%, which represents a significant step forward in realizing high-efficiency TPV systems.

Influence of ethacrynic acid on glutathione S-transferase pi transcript and protein half-lives in human colon cancer cells.

PubMed

Shen, H; Ranganathan, S; Kuzmich, S; Tew, K D

1995-10-12

Ethacrynic acid (EA) is a plant phenolic acid that is both an inhibitor and an inducer of glutathione S-transferase (GST) activity. To determine contributory factors in the increased GST activity caused by EA treatment, human colon carcinoma HT29 cells were compared with a cloned EA-resistant population (HT6-8) maintained in medium containing 72 microM EA. Several factors are involved in the increased expression of GST pi in HT6-8. For example, nuclear run-on experiments showed an approximately 2-fold increase in the rate of transcription of GST pi. In addition, the half-life of GST pi transcript was increased from 4.1 (wild type, HT29, HT4-1) to 8.4 hr. The half-life of GST pi protein was 1-2 hr in HT4-1 cells versus 8-9 hr in HT6-8 cells. When either human ovarian carcinoma cells (SKOV3) or human prostatic carcinoma cells (DU145) were treated with EA, the half-life of the GST pi transcript was also increased. The transcript half-lives of another thiol-metabolism enzyme, gamma-glutamylcysteine synthetase (gamma-GCS), and a phase II detoxification enzyme, dihydrodiol dehydrogenase (DDH), were also increased in HT6-8, SKOV3 and DU145 cells treated with EA. However, the half-lives of transcripts from "housekeeping genes," such as glyceraldehyde 3-phosphate dehydrogenase (G3PDH), beta-actin and beta-tubulin, were not changed in these cell lines following EA. Apparently, a number of coordinated factors are involved in EA-enhanced expression of GST pi and other detoxification enzymes.

Structural Basis of Conserved Cysteine in the Fibroblast Growth Factor Family: Evidence for a Vestigial Half-Cystine

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

Lee, Jihun; Blaber, Michael; FSU)

2010-11-09

The 22 members of the mouse/human fibroblast growth factor (FGF) family of proteins contain a conserved cysteine residue at position 83 (numbering scheme of the 140-residue form of FGF-1). Sequence and structure information suggests that this position is a free cysteine in 16 members and participates as a half-cystine in at least 3 (and perhaps as many as 6) other members. While a structural role as a half-cystine provides a stability basis for possible selective pressure, it is less clear why this residue is conserved as a free cysteine (although free buried thiols can limit protein functional half-life). To probemore » the structural role of the free cysteine at position 83 in FGF-1, we constructed Ala, Ser, Thr, Val, and Ile mutations and determined their effects on structure and stability. These results show that position 83 in FGF-1 is thermodynamically optimized to accept a free cysteine. A second cysteine mutation was introduced into wild-type FGF-1 at adjacent position Ala66, which is known to participate as a half-cystine with position 83 in FGF-8, FGF-19, and FGF-23. Results show that, unlike position 83, a free cysteine at position 66 destabilizes FGF-1; however, upon oxidation, a near-optimal disulfide bond is formed between Cys66 and Cys83, resulting in {approx} 14 kJ/mol of increased thermostability. Thus, while the conserved free cysteine at position 83 in the majority of the FGF proteins may have a principal role in limiting functional half-life, evidence suggests that it is a vestigial half-cystine.« less

7 CFR 51.2295 - Half kernel.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Half kernel. 51.2295 Section 51.2295 Agriculture... Standards for Shelled English Walnuts (Juglans Regia) Definitions § 51.2295 Half kernel. Half kernel means the separated half of a kernel with not more than one-eighth broken off. ...

Capillary reference half-cell

DOEpatents

Hall, Stephen H.

1996-01-01

The present invention is a reference half-cell electrode wherein intermingling of test fluid with reference fluid does not affect the performance of the reference half-cell over a long time. This intermingling reference half-cell may be used as a single or double junction submersible or surface reference electrode. The intermingling reference half-cell relies on a capillary tube having a first end open to reference fluid and a second end open to test fluid wherein the small diameter of the capillary tube limits free motion of fluid within the capillary to diffusion. The electrode is placed near the first end of the capillary in contact with the reference fluid. The method of operation of the present invention begins with filling the capillary tube with a reference solution. After closing the first end of the capillary, the capillary tube may be fully submerged or partially submerged with the second open end inserted into test fluid. Since the electrode is placed near the first end of the capillary, and since the test fluid may intermingle with the reference fluid through the second open end only by diffusion, this intermingling capillary reference half-cell provides a stable voltage potential for long time periods.

Capillary reference half-cell

DOEpatents

Hall, S.H.

1996-02-13

The present invention is a reference half-cell electrode wherein intermingling of test fluid with reference fluid does not affect the performance of the reference half-cell over a long time. This intermingling reference half-cell may be used as a single or double junction submersible or surface reference electrode. The intermingling reference half-cell relies on a capillary tube having a first end open to reference fluid and a second end open to test fluid wherein the small diameter of the capillary tube limits free motion of fluid within the capillary to diffusion. The electrode is placed near the first end of the capillary in contact with the reference fluid. The method of operation of the present invention begins with filling the capillary tube with a reference solution. After closing the first end of the capillary, the capillary tube may be fully submerged or partially submerged with the second open end inserted into test fluid. Since the electrode is placed near the first end of the capillary, and since the test fluid may intermingle with the reference fluid through the second open end only by diffusion, this intermingling capillary reference half-cell provides a stable voltage potential for long time periods. 11 figs.

Improvement in health-related quality of life in patients with haemophilia B treated with nonacog beta pegol, a new extended half-life recombinant FIX product.

PubMed

Chowdary, P; Kearney, S; Regnault, A; Hoxer, C S; Yee, D L

2016-07-01

Health-related quality of life (HRQoL) of individuals with haemophilia has greatly improved with the use of factor replacement and routine prophylaxis. To explore the HRQoL of individuals with haemophilia B treated with nonacog beta pegol, an extended half-life recombinant factor IX, in a single-blind, randomized multinational phase III pivotal trial (paradigm(™) 2) and its open-label extension (paradigm(™) 4). In the pivotal trial, adolescents and adults with haemophilia B were allocated to 28-week on-demand treatment or randomized to 52 weeks of prophylaxis with 10 or 40 IU kg(-1) nonacog beta pegol administered every seven days. In the extension trial, patients could continue on the same treatment or switch to the alternate dosing regimen at any time. HRQoL was assessed with the HAEMO-QOL/HAEM-A-QOL age-specific questionnaires and the EQ-5D. In the pivotal trial, adults receiving 40 IU kg(-1) prophylaxis reported significant improvements in the 'HAEM-A-QOL Total' score (-6.4 ± 8.5, P = 0.017) and in 'Sport' (-15.3 ± 8.5, P = 0.020), 'Feeling' (-15.2 ± 18.3, P = 0.010) and 'Partnership' (-9.6 ± 15.5, P = 0.046) domain scores; no significant improvements were seen in the other arms. At the pivotal trial end, fewer patients reported problems in the EQ-5D 'Mobility' and 'Pain/Discomfort' dimensions, in particular those receiving prophylaxis. In the extension trial, adult patients switching from 10 to 40 IU kg(-1) prophylaxis showed significant improvements in 'HAEM-A-QOL Total' score (-12.5 ± 8.7, P = 0.016) and 'Physical health' domain (-23.1 ± 14.4, P = 0.016). Prophylactic treatment with nonacog beta pegol 40 IU kg(-1) once weekly leads to HRQoL benefits in individuals with haemophilia B; this might be related to fewer bleeding episodes and higher FIX activity levels. © 2016 John Wiley & Sons Ltd.

Degradation and half-life of DNA present in biomass from a genetically-modified organism during land application.

PubMed

Halter, Mathew C; Zahn, James A

2017-02-01

White biotechnology has made a positive impact on the chemical industry by providing safer, more efficient chemical manufacturing processes that have reduced the use of toxic chemicals, harsh reaction conditions, and expensive metal catalysts, which has improved alignment with the principles of Green Chemistry. The genetically-modified (GM) biocatalysts that are utilized in these processes are typically separated from high-value products and then recycled, or eliminated. Elimination routes include disposal in sanitary landfills, incineration, use as a fuel, animal feed, or reuse as an agricultural soil amendment or other value-added products. Elimination routes that have the potential to impact the food chain or environment have been more heavily scrutinized for the fate and persistence of biological products. In this study, we developed and optimized a method for monitoring the degradation of strain-specific DNA markers from a genetically-modified organism (GMO) used for the commercial production of 1,3-propanediol. Laboratory and field tests showed that a marker for heterologous DNA in the GM organism was no longer detectable by end-point polymerase chain reaction (PCR) after 14 days. The half-life of heterologous DNA was increased by 17% (from 42.4 to 49.7 h) after sterilization of the soil from a field plot, which indicated that abiotic factors were important in degradation of DNA under field conditions. There was no evidence for horizontal transfer of DNA target sequences from the GMO to viable organisms present in the soil.

Control of phosphorothioate stereochemistry substantially increases the efficacy of antisense oligonucleotides.

PubMed

Iwamoto, Naoki; Butler, David C D; Svrzikapa, Nenad; Mohapatra, Susovan; Zlatev, Ivan; Sah, Dinah W Y; Meena; Standley, Stephany M; Lu, Genliang; Apponi, Luciano H; Frank-Kamenetsky, Maria; Zhang, Jason Jingxin; Vargeese, Chandra; Verdine, Gregory L

2017-09-01

Whereas stereochemical purity in drugs has become the standard for small molecules, stereoisomeric mixtures containing as many as a half million components persist in antisense oligonucleotide (ASO) therapeutics because it has been feasible neither to separate the individual stereoisomers, nor to synthesize stereochemically pure ASOs. Here we report the development of a scalable synthetic process that yields therapeutic ASOs having high stereochemical and chemical purity. Using this method, we synthesized rationally designed stereopure components of mipomersen, a drug comprising 524,288 stereoisomers. We demonstrate that phosphorothioate (PS) stereochemistry substantially affects the pharmacologic properties of ASOs. We report that Sp-configured PS linkages are stabilized relative to Rp, providing stereochemical protection from pharmacologic inactivation of the drug. Further, we elucidated a triplet stereochemical code in the stereopure ASOs, 3'-SpSpRp, that promotes target RNA cleavage by RNase H1 in vitro and provides a more durable response in mice than stereorandom ASOs.

20 CFR 404.1675 - Finding of substantial failure.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Finding of substantial failure. 404.1675... DISABILITY INSURANCE (1950- ) Determinations of Disability Substantial Failure § 404.1675 Finding of substantial failure. A finding of substantial failure with respect to a State may not be made unless and until...

20 CFR 404.1675 - Finding of substantial failure.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Finding of substantial failure. 404.1675... DISABILITY INSURANCE (1950- ) Determinations of Disability Substantial Failure § 404.1675 Finding of substantial failure. A finding of substantial failure with respect to a State may not be made unless and until...

20 CFR 404.1675 - Finding of substantial failure.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Finding of substantial failure. 404.1675... DISABILITY INSURANCE (1950- ) Determinations of Disability Substantial Failure § 404.1675 Finding of substantial failure. A finding of substantial failure with respect to a State may not be made unless and until...

20 CFR 404.1675 - Finding of substantial failure.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Finding of substantial failure. 404.1675... DISABILITY INSURANCE (1950- ) Determinations of Disability Substantial Failure § 404.1675 Finding of substantial failure. A finding of substantial failure with respect to a State may not be made unless and until...

20 CFR 404.1675 - Finding of substantial failure.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Finding of substantial failure. 404.1675... DISABILITY INSURANCE (1950- ) Determinations of Disability Substantial Failure § 404.1675 Finding of substantial failure. A finding of substantial failure with respect to a State may not be made unless and until...

Extraterrestrial Life: Life on Mars - Then and Now

NASA Technical Reports Server (NTRS)

Arrhenius, Gustaf; Mojzsis, Stephen

1996-01-01

The recent claim to have identified possible signs of ancient life on Mars has been widely publicized and discussed. The authors conceded that none of the half-dozen pieces of evidence adduced in their paper individually provided strong support for extraterrestrial life, though they argued that the pieces added up to a case worth considering. Most - perhaps all - of the observed phenomena have counterparts in the inorganic world, so even the combination does not make a compelling case that there was ever life on Mars. Nevertheless, the importance of the problem has justified bringing the results to general attention. The paper has focussed interest on the origin and possible ubiquity of life, and on how we can design techniques capable of giving a more definitive answer to the question of whether there is, or has ever been, life elsewhere in the Universe.

Half the entanglement in critical systems is distillable from a single specimen

NASA Astrophysics Data System (ADS)

Orús, R.; Latorre, J. I.; Eisert, J.; Cramer, M.

2006-06-01

We establish a quantitative relationship between the entanglement content of a single quantum chain at a critical point and the corresponding entropy of entanglement. We find that, surprisingly, the leading critical scaling of the single-copy entanglement with respect to any bipartitioning is exactly one-half of the entropy of entanglement, in a general setting of conformal field theory and quasifree systems. Conformal symmetry imposes that the single-copy entanglement scales as E1(ρL)=(c/6)lnL-(c/6)(π2/lnL)+O(1/L) , where L is the number of constituents in a block of an infinite chain and c denotes the central charge. This shows that from a single specimen of a critical chain, already half the entanglement can be distilled compared to the rate that is asymptotically available. The result is substantiated by a quantitative analysis for all translationally invariant quantum spin chains corresponding to all isotropic quasifree fermionic models. An example of the XY spin chain shows that away from criticality the above relation is maintained only near the quantum phase transition.

20 CFR 416.1075 - Finding of substantial failure.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Finding of substantial failure. 416.1075... AGED, BLIND, AND DISABLED Determinations of Disability Substantial Failure § 416.1075 Finding of substantial failure. A finding of substantial failure with respect to a State may not be made unless and until...

20 CFR 416.1075 - Finding of substantial failure.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Finding of substantial failure. 416.1075... AGED, BLIND, AND DISABLED Determinations of Disability Substantial Failure § 416.1075 Finding of substantial failure. A finding of substantial failure with respect to a State may not be made unless and until...

20 CFR 416.1075 - Finding of substantial failure.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Finding of substantial failure. 416.1075... AGED, BLIND, AND DISABLED Determinations of Disability Substantial Failure § 416.1075 Finding of substantial failure. A finding of substantial failure with respect to a State may not be made unless and until...

20 CFR 416.1075 - Finding of substantial failure.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Finding of substantial failure. 416.1075... AGED, BLIND, AND DISABLED Determinations of Disability Substantial Failure § 416.1075 Finding of substantial failure. A finding of substantial failure with respect to a State may not be made unless and until...

20 CFR 416.1075 - Finding of substantial failure.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Finding of substantial failure. 416.1075... AGED, BLIND, AND DISABLED Determinations of Disability Substantial Failure § 416.1075 Finding of substantial failure. A finding of substantial failure with respect to a State may not be made unless and until...

Application of simple mathematical expressions to relate the half-lives of xenobiotics in rats to values in humans.

PubMed

Ward, Keith W; Erhardt, Paul; Bachmann, Kenneth

2005-01-01

Previous publications from GlaxoSmithKline and University of Toledo laboratories convey our independent attempts to predict the half-lives of xenobiotics in humans using data obtained from rats. The present investigation was conducted to compare the performance of our published models against a common dataset obtained by merging the two sets of rat versus human half-life (hHL) data previously used by each laboratory. After combining data, mathematical analyses were undertaken by deploying both of our previous models, namely the use of an empirical algorithm based on a best-fit model and the use of rat-to-human liver blood flow ratios as a half-life correction factor. Both qualitative and quantitative analyses were performed, as well as evaluation of the impact of molecular properties on predictability. The merged dataset was remarkably diverse with respect to physiochemical and pharmacokinetic (PK) properties. Application of both models revealed similar predictability, depending upon the measure of stipulated accuracy. Certain molecular features, particularly rotatable bond count and pK(a), appeared to influence the accuracy of prediction. This collaborative effort has resulted in an improved understanding and appreciation of the value of rats to serve as a surrogate for the prediction of xenobiotic half-lives in humans when clinical pharmacokinetic studies are not possible or practicable.

Campground marketing: the heavy-half strategy

Treesearch

Wilbur F. LaPage

1969-01-01

When we arrayed camping frequencies in order from the lowest to the highest number of days spent camping per year we found that half of the campers do much more than half of the camping. Campers in this heavy half consistently camp more, year after year, and are increasing their annual participation as well. Heavy-half campers have larger investments in camping...

Ceramide binding to anandamide increases its half-life and potentiates its cytotoxicity in human neuroblastoma cells.

PubMed

Di Scala, Coralie; Mazzarino, Morgane; Yahi, Nouara; Varini, Karine; Garmy, Nicolas; Fantini, Jacques; Chahinian, Henri

2017-06-01

Anandamide (AEA) is a ubiquitous lipid that exerts neurotransmitter functions but also controls important biological functions such as proliferation, survival, or programmed cell death. The latter effects are also regulated by ceramide, a lipid enzymatically generated from sphingomyelin hydrolysis by sphingomyelinase. Ceramide has been shown to increase the cellular toxicity of AEA, but the mechanisms controlling this potentiating effect remained unclear. Here we have used a panel of in silico, physicochemical, biochemical and cellular approaches to study the crosstalk between AEA and ceramide apoptotic pathways. Molecular dynamics simulations indicated that AEA and ceramide could form a stable complex in phosphatidylcholine membranes. Consistent with these data, we showed that AEA can specifically insert into ceramide monolayers whereas it did not penetrate into sphingomyelin membranes. Then we have studied the effects of ceramide on AEA-induced toxicity of human neuroblastoma cells. In these experiments, the cells have been either naturally enriched in ceramide by neutral sphingomyelinase pre-incubation or treated with C2-ceramide, a biologically active ceramide analog. Both treatments significantly increased the cytotoxicity of AEA as assessed by the MTS mitochondrial toxicity assay. This effect was correlated with the concomitant accumulation of natural ceramide (or its synthetic analog) and AEA in the cells. A kinetic study of AEA hydrolysis showed that ceramide inhibited the fatty acid amino hydrolase (FAAH) activity in cell extracts. Taken together, these data suggested that ceramide binds to AEA, increases its half-life and potentiates its cytotoxicity. Overall, these mechanisms account for a functional cross-talk between AEA and ceramide apoptotic pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

Heinz Werner: His Life, Ideas, and Contributions to Developmental Psychology in the First Half of the 20th Century.

PubMed

Ostler, Teresa

2016-01-01

The author provides an overview of Heinz Werner's life and contributions to the field of developmental psychology during the first half of the 20th century. She focuses on his early work in Vienna and Munich as well as his tenure at the Psychological Institute in Hamburg, up through the time when he became a named Professor in Psychology at Clark University. Recognized as one of the founders of developmental psychology, Heinz Werner worked in the areas of perceptual development, comparative psychology, and symbol formation. Versatile in rigorous experimental methodologies, and in observational and phenomenological methodologies, Werner's approach to development stood in contrast to other approaches of development, both past and current. For Werner, development was a heuristic, a way of looking at processes in a variety of domains, including ontogeny, phylogeny, microgenesis, biology, developmental psychopathology, neuropsychology, and comparative psychology. Werner viewed development as proceeding from a state of relative globality and lack of differentiation to a state of increasing differentiation, articulation, and hierarchical integration, but he also stressed that individuals can function at different developmental levels under different times and conditions. Werner's holistic, organismic, comparative, and contextual approach to development transcended interdisciplinary boundaries, allowing him to study the interrelatedness between thought, language, feeling, perception, and culture.

Extrinsic doping of the half-Heusler compounds

NASA Astrophysics Data System (ADS)

Stern, Robin; Dongre, Bonny; Madsen, Georg K. H.

2016-08-01

Controlling the p- and n-type doping is a key tool to improve the power-factor of thermoelectric materials. In the present work we provide a detailed understanding of the defect thermochemistry in half-Heusler compounds. We calculate the formation energies of intrinsic and extrinsic defects in state of the art n-type TiNiSn and p-type TiCoSb thermoelectric materials. It is shown how the incorporation of online repositories can reduce the workload in these calculations. In TiNiSn we find that Ni- and Ti-interstitial defects play a crucial role in the carrier concentration of TiNiSn. Furthermore, we find that extrinsic doping with Sb can substantially enhance the carrier concentration, in agreement with experiment. In case of TiCoSb, we find ScTi, FeCo and SnSb being possible p-type dopants. While experimental work has mainly focussed on Sn-doping of the Sb site, the present result underlines the possibility to p-dope TiCoSb on all lattice sites.

29 CFR 1990.145 - Consideration of substantial new issues or substantial new evidence.

Code of Federal Regulations, 2010 CFR

2010-07-01

... substance any substantial new issues upon which the Secretary did not reach a conclusion in the rulemaking... or an Advance Notice of Proposed Rulemaking; (v) A detailed statement and analysis as to why the...

29 CFR 1990.145 - Consideration of substantial new issues or substantial new evidence.

Code of Federal Regulations, 2011 CFR

2011-07-01

... substance any substantial new issues upon which the Secretary did not reach a conclusion in the rulemaking... or an Advance Notice of Proposed Rulemaking; (v) A detailed statement and analysis as to why the...

Emotions and physical health in the second half of life: interindividual differences in age-related trajectories and dynamic associations according to socioeconomic status.

PubMed

Schöllgen, Ina; Huxhold, Oliver; Schmiedek, Florian

2012-06-01

The importance of socioeconomic status (SES) for psychological functioning over the life span is increasingly acknowledged in psychological research. The Reserve Capacity Model by Gallo and Matthews (2003) suggests that SES is not only linked to physical health but also to the experience of positive and negative emotions. Moreover, due to differential amounts of psychosocial resources, cross-domain associations between emotions and health might differ according to SES. The present study examined age-related developments in positive affect (PA), negative affect (NA), and physical health, as well as dynamic associations between health and emotions in the second half of life. We looked at differences in these trajectories and their interrelationships according to education as one aspect of SES. We used data of up to three waves spanning 12 years from the nationally representative German Ageing Survey (N = 3,847, AgeT1 = 40-85 years). Applying multiple-group dual change score models, we found differential age-related change in PA and physical health, but not in NA, in two groups differing in level of education. NA did only predict change in physical health in low-educated individuals, whereas physical health was equally strongly related to change in PA in both education groups. These results indicate that SES not only affects changes in physical health and emotional functioning but also their interrelationships. PsycINFO Database Record (c) 2012 APA, all rights reserved

Half-time strategies to enhance second-half performance in team-sports players: a review and recommendations.

PubMed

Russell, Mark; West, Daniel J; Harper, Liam D; Cook, Christian J; Kilduff, Liam P

2015-03-01

A number of intermittent team sports require that two consecutive periods of play (lasting for ~30-45 min) are separated by a 10-20 min half-time break. The half-time practices employed by team-sports players generally include returning to the changing rooms, temporarily relaxing from the cognitive and physical demands of the first half, rehydration and re-fuelling strategies, addressing injury or equipment concerns, and receiving tactical instruction and coach feedback. However, the typically passive nature of these actions has been associated with physiological changes that impair performance during the second half. Both physical and cognitive performances have been found to decline in the initial stages of subsequent exercise that follows half-time. An increased risk of injury has also been observed during this period. Therefore, half-time provides sports scientists and strength and conditioning coaches with an opportunity to optimise second-half performance. An overview of strategies thought to benefit team-sports athletes is presented; specifically, the efficacy of heat maintenance strategies (including passive and active methods), post-activation potentiation, hormonal priming, and modified hydro-nutritional practices are discussed. A theoretical model of applying these strategies in a manner that compliments current practice is also offered.

Synchronous Half-Wave Rectifier

NASA Technical Reports Server (NTRS)

Rippel, Wally E.

1989-01-01

Synchronous rectifying circuit behaves like diode having unusually low voltage drop during forward-voltage half cycles. Circuit particularly useful in power supplies with potentials of 5 Vdc or less, where normal forward-voltage drops in ordinary diodes unacceptably large. Fabricated as monolithic assembly or as hybrid. Synchronous half-wave rectifier includes active circuits to attain low forward voltage drop and high rectification efficiency.

Grip strength and quality of life in the second half of life: hope as a moderator.

PubMed

Gum, Amber M; Segal-Karpas, Dikla; Avidor, Sharon; Ayalon, Liat; Bodner, Ehud; Palgi, Yuval

2017-09-28

The purpose of the current study was to investigate grip strength, hope, and their interaction as predictors of quality of life four years later in a nationally representative sample of older adults. Data were derived from the first (2005-2006) and second wave (2009) of the Israeli component of the Survey of Health Ageing and Retirement in Europe (SHARE; N = 344). Hope was measured by three items from the Hope   Scale, and quality of life was measured by the CASP-12 (Control, Autonomy, Self-Realization, and Pleasure). Multiple regression analyses were conducted. Grip strength at T1 predicted QoL in T2, but hope was not a significant predictor. Furthermore, hope moderated the effect of handgrip on QoL, such that the effect was weaker for higher levels of hope. As hypothesized, hope acted as a moderator, such that poor grip strength was associated with worse QoL for less hopeful older adults, but grip strength was not associated with QoL for more hopeful older adults. Findings are consistent with a theoretical conceptualization of hope as a buffer between physical challenges and negative outcomes like QoL. Encouraging a hopeful perspective could enhance QoL for older adults with decreased muscle strength.

Coupling complement regulators to immunoglobulin domains generates effective anti-complement reagents with extended half-life in vivo

PubMed Central

HARRIS, C L; WILLIAMS, A S; LINTON, S M; MORGAN, B P

2002-01-01

Complement activation and subsequent generation of inflammatory molecules and membrane attack complex contributes to the pathology of a number of inflammatory and degenerative diseases, including arthritis, glomerulonephritis and demyelination. Agents that specifically inhibit complement activation might prove beneficial in the treatment of these diseases. Soluble recombinant forms of the naturally occurring membrane complement regulatory proteins (CRP) have been exploited for this purpose. We have undertaken to design better therapeutics based on CRP. Here we describe the generation of soluble, recombinant CRP comprising rat decay accelerating factor (DAF) or rat CD59 expressed as Fc fusion proteins, antibody-like molecules comprising two CRP moieties in place of the antibody Fab arms (CRP-Ig). Reagents bearing DAF on each arm (DAF-Ig), CD59 on each arm (CD59-Ig) and a hybrid reagent containing both DAF and CD59 were generated. All three reagents inhibited C activation in vitro. Compared with soluble CRP lacking Fc domains, activity was reduced, but was fully restored by enzymatic release of the regulator from the Ig moiety, implicating steric constraints in reducing functional activity. In vivo studies showed that DAF-Ig, when compared to soluble DAF, had a much extended half-life in the circulation in rats and concomitantly caused a sustained reduction in plasma complement activity. When given intra-articularly to rats in a model of arthritis, DAF-Ig significantly reduced severity of disease. The data demonstrate the potential of CRP-Ig as reagents for sustained therapy of inflammatory disorders, including arthritis, but emphasize the need for careful design of fusion proteins to retain function. PMID:12165074

Factor Activity Assays for Monitoring Extended Half-Life FVIII and Factor IX Replacement Therapies.

PubMed

Kitchen, Steve; Tiefenbacher, Stefan; Gosselin, Robert

2017-04-01

The advent of modified factor VIII (FVIII) and factor IX (FIX) molecules with extended half-lives (EHLs) compared with native FVIII and FIX represents a major advance in the field of hemophilia care, with the potential to reduce the frequency of prophylactic injections and/or to increase the trough level prior to subsequent injections. Monitoring treatment through laboratory assays will be an important part of ensuring patient safety, including any tailoring of prophylaxis. Several approaches have been used to extend half-lives, including PEGylation, and fusion to albumin or immunoglobulin. Some of these modifications affect factor assays as routinely performed in hemophilia centers; so, laboratories will need to use FVIII and FIX assays which have been shown to be suitable on a product-by-product basis. For some products, there are marked differences between results obtained using one-stage or chromogenic assays and results obtained using different reagents in the one-stage assay. The laboratory should use an assay in which the recovery of the product closely aligns with the assay used by the pharmaceutical company to assign potency to the product, so that the units reported by the laboratory agree with those used to demonstrate efficacy of the product during clinical trials. Reported assay differences in relation to several of the EHL FVIII and FIX molecules will be reviewed in this article. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Self-esteem across the second half of life: The role of socioeconomic status, physical health, social relationships, and personality factors.

PubMed

von Soest, Tilmann; Wagner, Jenny; Hansen, Thomas; Gerstorf, Denis

2018-06-01

Self-esteem development across adulthood has been in the center of interest for some time now. However, not much is known about factors that shape self-esteem and its development in the second half of life and whether the factors differ with age and gender. To examine these questions, this study uses 2-wave data from the population-based NorLAG study in Norway (N = 5,555; M age = 58 years; 51% women) and combines self-report data on self-esteem and personality with registry-based information on socioeconomic status (education, income, unemployment), health problems (sick leave, lifetime history of disability), and social relationships (cohabiting partner, lifetime history of divorce and widowhood). Results from latent change score models revealed that self-esteem peaked at around age 50 and declined thereafter. More importantly, lower socioeconomic status, not having a cohabiting partner, unemployment, and disability were each uniquely associated with lower levels of self-esteem and/or steeper declines in self-esteem over the 5-year study period. Over and above registry-based information, personality characteristics were relevant, with a more mature personality being associated with higher self-esteem level. Emotionally stable participants also showed less pronounced declines in self-esteem. Moreover, associations of disability and of emotional stability with self-esteem level were weaker with advancing age. Among women, self-esteem level was more strongly associated with emotional stability and less strongly with openness, compared to men. Our findings demonstrate the utility of registry-based information and suggest that physical health, social relationships, and personality factors are in manifold ways uniquely associated with self-esteem and its development later in life. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Budget Impact Analysis of Prolonged Half-Life Recombinant FVIII Therapy for Hemophilia in the United States.

PubMed

McMullen, Suzanne; Buckley, Brieana; Hall, Eric; Kendter, Jon; Johnston, Karissa

2017-01-01

Hemophilia A is a factor VIII deficiency, associated with spontaneous, recurrent bleeding episodes. This may lead to comorbidities such as arthropathy and joint replacement, which contribute to morbidity and increased health care expenditure. Recombinant factor VIII Fc fusion protein (rFVIIIFc), a prolonged half-life factor therapy, requires fewer infusions, resulting in reduced treatment burden. Use a budget impact analysis to assess the potential economic impact of introducing rFVIIIFc to a formulary from the perspective of a private payer in the United States. The budget impact model was developed to estimate the potential economic impact of adding rFVIIIFc to a private payer formulary across a 2-year time period. The eligible patient population consisted of inhibitor-free adults with severe hemophilia A, receiving recombinant-based episodic or prophylaxis treatment regimens. Patients were assumed to switch from conventional recombinant factor treatment to rFVIIIFc. Only medication costs were included in the model. The introduction of rFVIIIFc is estimated to have a budget impact of 1.4% ($0.12 per member per month) across 2 years for a private payer population of 1,000,000 (estimated 19.7 individuals receiving treatment for hemophilia A). The introduction of rFVIIIFc is estimated to prevent 124 bleeds across 2 years at a cost of $1891 per bleed avoided. Hemophilia A is a rare disease with a low prevalence; therefore, the overall cost to society of introducing rFVIIIFc is small. Considerations for comprehensively assessing the budget impact of introducing rFVIIIFc should include episodic and prophylaxis regimens, bleed avoidance, and annual factor consumption required under alternative scenarios. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

76 FR 63846 - Substantially Underserved Trust Areas (SUTA)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-14

... CFR Part 1700 RIN 0572-AC23 Substantially Underserved Trust Areas (SUTA) AGENCY: Rural Utilities... of infrastructure projects in Substantially Underserved Trust Areas (SUTA). The intent is to..., Washington, DC 20250-1522. Title: Substantially Underserved Trust Areas. Type of Request: Approval of a new...

pH-selective mutagenesis of protein-protein interfaces: in silico design of therapeutic antibodies with prolonged half-life.

PubMed

Spassov, Velin Z; Yan, Lisa

2013-04-01

Understanding the effects of mutation on pH-dependent protein binding affinity is important in protein design, especially in the area of protein therapeutics. We propose a novel method for fast in silico mutagenesis of protein-protein complexes to calculate the effect of mutation as a function of pH. The free energy differences between the wild type and mutants are evaluated from a molecular mechanics model, combined with calculations of the equilibria of proton binding. The predicted pH-dependent energy profiles demonstrate excellent agreement with experimentally measured pH-dependency of the effect of mutations on the dissociation constants for the complex of turkey ovomucoid third domain (OMTKY3) and proteinase B. The virtual scanning mutagenesis identifies all hotspots responsible for pH-dependent binding of immunoglobulin G (IgG) to neonatal Fc receptor (FcRn) and the results support the current understanding of the salvage mechanism of the antibody by FcRn based on pH-selective binding. The method can be used to select mutations that change the pH-dependent binding profiles of proteins and guide the time consuming and expensive protein engineering experiments. As an application of this method, we propose a computational strategy to search for mutations that can alter the pH-dependent binding behavior of IgG to FcRn with the aim of improving the half-life of therapeutic antibodies in the target organism. Copyright © 2013 Wiley Periodicals, Inc.

A Novel Long-Acting Human Growth Hormone Fusion Protein (VRS-317): Enhanced In Vivo Potency and Half-Life

PubMed Central

Cleland, Jeffrey L; Geething, Nathan C; Moore, Jerome A; Rogers, Brian C; Spink, Benjamin J; Wang, Chai-Wei; Alters, Susan E; Stemmer, Willem P C; Schellenberger, Volker

2012-01-01

A novel recombinant human growth hormone (rhGH) fusion protein (VRS-317) was designed to minimize receptor-mediated clearance through a reduction in receptor binding without mutations to rhGH by genetically fusing with XTEN amino acid sequences to the N-terminus and the C-terminus of the native hGH sequence. Although in vitro potency of VRS-317 was reduced approximately 12-fold compared with rhGH, in vivo potency was increased because of the greatly prolonged exposure to the target tissues and organs. VRS-317 was threefold more potent than daily rhGH in hypophysectomized rats and fivefold more potent than daily rhGH in juvenile monkeys. In juvenile monkeys, a monthly dose of 1.4 mg/kg VRS-317 (equivalent to 0.26 mg/kg rhGH) caused a sustained pharmacodynamic response for 1 month equivalent to 0.05 mg/kg/day rhGH (1.4 mg/kg rhGH total over 28 days). In monkeys, VRS-317, having a terminal elimination half-life of approximately 110 h, was rapidly and near-completely absorbed, and was well tolerated with no observed adverse effects after every alternate week subcutaneous dosing for 14 weeks. VRS-317 also did not cause lipoatrophy in pig and monkey studies. VRS-317 is currently being studied in GH-deficient patients to confirm the observations in these animal studies. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:2744–2754, 2012 PMID:22678811

24 CFR 907.7 - Remedies for substantial default.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Remedies for substantial default... URBAN DEVELOPMENT SUBSTANTIAL DEFAULT BY A PUBLIC HOUSING AGENCY § 907.7 Remedies for substantial... staff; or (3) Provide assistance deemed necessary, in the discretion of HUD, to remedy emergency...

Establishing Substantial Equivalence: Metabolomics

NASA Astrophysics Data System (ADS)

Beale, Michael H.; Ward, Jane L.; Baker, John M.

Modern ‘metabolomic’ methods allow us to compare levels of many structurally diverse compounds in an automated fashion across a large number of samples. This technology is ideally suited to screening of populations of plants, including trials where the aim is the determination of unintended effects introduced by GM. A number of metabolomic methods have been devised for the determination of substantial equivalence. We have developed a methodology, using [1H]-NMR fingerprinting, for metabolomic screening of plants and have applied it to the study of substantial equivalence of field-grown GM wheat. We describe here the principles and detail of that protocol as applied to the analysis of flour generated from field plots of wheat. Particular emphasis is given to the downstream data processing and comparison of spectra by multivariate analysis, from which conclusions regarding metabolome changes due to the GM can be assessed against the background of natural variation due to environment.

24 CFR 907.3 - Bases for substantial default.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false Bases for substantial default. 907.3 Section 907.3 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN DEVELOPMENT... DEVELOPMENT SUBSTANTIAL DEFAULT BY A PUBLIC HOUSING AGENCY § 907.3 Bases for substantial default. (a...

24 CFR 907.3 - Bases for substantial default.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Bases for substantial default. 907.3 Section 907.3 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN DEVELOPMENT... DEVELOPMENT SUBSTANTIAL DEFAULT BY A PUBLIC HOUSING AGENCY § 907.3 Bases for substantial default. (a...

24 CFR 907.3 - Bases for substantial default.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false Bases for substantial default. 907.3 Section 907.3 Housing and Urban Development REGULATIONS RELATING TO HOUSING AND URBAN DEVELOPMENT... DEVELOPMENT SUBSTANTIAL DEFAULT BY A PUBLIC HOUSING AGENCY § 907.3 Bases for substantial default. (a...

19 CFR 10.7 - Substantial containers or holders.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Substantial containers or holders. 10.7 Section 10... Exported and Returned § 10.7 Substantial containers or holders. (a) Substantial containers or holders... domestic products exported and returned. When such containers or holders are imported not containing or...

Excretion Profiles and Half-Lives of Ten Urinary Polycyclic Aromatic Hydrocarbon Metabolites after Dietary Exposure

PubMed Central

Li, Zheng; Romanoff, Lovisa; Bartell, Scott; Pittman, Erin N.; Trinidad, Debra A.; McClean, Michael; Webster, Thomas F.; Sjödin, Andreas

2015-01-01

Human exposure to polycyclic aromatic hydrocarbons (PAHs) can be assessed by biomonitoring of their urinary mono-hydroxylated metabolites (OH-PAHs). Limited information exists on the human pharmacokinetics of OH-PAHs. This study aimed to investigate the excretion half-life of 1-hydroxypyrene (1-PYR), the most used biomarker for PAH exposure, and 9 other OH-PAHs following a dietary exposure in 9 non-smoking volunteers with no occupational exposure to PAHs. Each person avoided food with known high PAH-content during the study period, except for a high PAH-containing lunch (barbecued chicken) on the first day. Individual urine samples (n = 217) were collected from 15 hours before to 60 hours following the dietary exposure. Levels of all OH-PAHs in all subjects increased rapidly by 9–141 fold after the exposure, followed by a decrease consistent with first order kinetics, and returned to background levels 24–48 hours after the exposure. The average time to reach maximal concentration ranged from 3.1 h (1-naphthol) to 5.5 h (1-PYR). Creatinine-adjusted urine concentrations for each metabolite were analyzed using a non-linear mixed effects model including a term to estimate background exposure. The background-adjusted half-life estimate was 3.9 h for 1-PYR and ranged 2.5–6.1 h for the other 9 OH-PAHs, which in general, were shorter than those previously reported. The maximum concentrations after the barbecued chicken consumption were comparable to the levels found in reported occupational settings with known high PAH exposures. It is essential to consider the relatively short half-life, the timing of samples relative to exposures, and the effect of diet when conducting PAH exposure biomonitoring studies. PMID:22663094

7 CFR 51.1441 - Half-kernel.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Half-kernel. 51.1441 Section 51.1441 Agriculture... Standards for Grades of Shelled Pecans Definitions § 51.1441 Half-kernel. Half-kernel means one of the separated halves of an entire pecan kernel with not more than one-eighth of its original volume missing...

49 CFR 384.301 - Substantial compliance-general requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... personnel), and enforcement practices. (b)(1) A State must come into substantial compliance with the... come into substantial compliance with 49 CFR 383.123 not later than September 30, 2006. (c) A State must come into substantial compliance with the requirements of subpart B of this part in effect as of...

49 CFR 384.301 - Substantial compliance-general requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... personnel), and enforcement practices. (b)(1) A State must come into substantial compliance with the... come into substantial compliance with 49 CFR 383.123 not later than September 30, 2006. (c) A State must come into substantial compliance with the requirements of subpart B of this part in effect as of...

49 CFR 384.301 - Substantial compliance-general requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... personnel), and enforcement practices. (b)(1) A State must come into substantial compliance with the... come into substantial compliance with 49 CFR 383.123 not later than September 30, 2006. (c) A State must come into substantial compliance with the requirements of subpart B of this part in effect as of...

49 CFR 384.301 - Substantial compliance-general requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... personnel), and enforcement practices. (b)(1) A State must come into substantial compliance with the... come into substantial compliance with 49 CFR 383.123 not later than September 30, 2006. (c) A State must come into substantial compliance with the requirements of subpart B of this part in effect as of...

Perceived parental food controlling practices are related to obesogenic or leptogenic child life style behaviors.

PubMed

Van Strien, Tatjana; van Niekerk, Rianne; Ouwens, Machteld A

2009-08-01

To better understand whether the parental food controlling practices pressure and restriction to eat are obesity preventing or obesity promoting, this study examined whether these parenting practices are related to other (food or non-food) areas that are generally regarded as obesogenic or leptogenic. Are these foods controlling practices more indicative of obesogenic or leptogenic child life style behaviors? In a sample of 7-12-year-old boys and girls (n = 943) the perceived parental food controlling practices were related to various measures for unhealthy life style. Using factor analysis we assessed whether there is a constellation of lifestyle behaviors that is potentially obesogenic or leptogenic. Remarkably, perceived parental restriction and pressure loaded on two different factors. Perceived parental restriction to eat had a negative loading on a factor that further comprised potential obesogenic child life style behaviors, such as snacking (positive loading), time spend with screen media (television or computer) (positive loadings) and frequency of fruit consumption (negative loading). Perceived parental pressure to eat had a positive loading on a factor that further comprised potential leptogenic life style behaviors such as frequency of eating a breakfast meal and sporting (positive loadings). It is concluded that low perceived parental restriction in regard to food may perhaps be a sign of more uninvolved 'neglecting' or indulgent parenting/obesogenic home environment, whereas high perceived parental pressure to eat may be sign of a more 'concerned' leptogenic parenting/home environment, though more research into style of parenting is needed.

49 CFR 384.301 - Substantial compliance-general requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... State must come into substantial compliance with the requirements of subpart B of this part in effect as..., not later than September 30, 2005. (2) Exception. A State must come into substantial compliance with 49 CFR 383.123 not later than September 30, 2006. (c) A State must come into substantial compliance...

Modification of the Fc Region of a Human Anti-oncostatin M Monoclonal Antibody for Higher Affinity to FcRn Receptor and Extension of Half-life in Cynomolgus Monkeys.

PubMed

Nnane, Ivo P; Han, Chao; Jiao, Qun; Tam, Susan H; Davis, Hugh M; Xu, Zhenhua

2017-07-01

The purpose of this study was to evaluate the pharmacokinetics (PK) of anti-oncostatin M (OSM) IgG1 monoclonal antibodies, CNTO 1119 and its Fc variant (CNTO 8212), which incorporates the LS(Xtend) mutation to extend terminal half-life (T 1/2 ), after a single intravenous (IV) or subcutaneous (SC) administration in cynomolgus monkeys, and to predict human PK. In study 1, single doses of CNTO 1119 and CNTO 8212 were administered IV or SC at 3 mg/kg to cynomolgus monkeys (n = 3 per group). In study 2, single doses of CNTO 8212 were administered IV at 1, 5 or 20 mg/kg, or SC at 5 mg/kg to cynomolgus monkeys (n = 5 per group). Serial blood samples were collected for assessment of serum concentrations of CNTO 1119 and/or CNTO 8212. A two-compartment population PK model with first-order elimination was utilized to simultaneously describe the serum concentrations of CNTO 1119 and CNTO 8212 over time after IV and SC administration in cynomolgus monkeys. The typical population PK parameter estimates for CNTO 1119 in cynomolgus monkeys were clearance (CL) = 2.81 mL/day/kg, volume of distribution of central compartment (V 1 ) = 31.3 mL/kg, volume of distribution of peripheral compartment (V 2 ) = 23.3 mL/kg, absolute bioavailability (F) = 0.84 and T 1/2 = 13.4 days. In comparison, the typical population PK parameter estimates for CNTO 8212 in cynomolgus monkeys were CL = 1.41 mL/day/kg, V 1 = 39.8 mL/kg, V 2 = 32.6 mL/kg, F = 0.75 and T 1/2 = 35.7 days. The mean CL of CNTO 8212 was ~50% lower compared with that for CNTO 1119 in cynomolgus monkeys. The overall volume of distribution (V 1 +V 2 ) for CNTO 8212 was about 32% larger compared with that for CNTO 1119, but generally similar to the vascular volume in cynomolgus monkeys. The T 1/2 of CNTO 8212 was significantly (p < 0.05) longer by about 2.7-fold than that for CNTO 1119 in cynomolgus monkeys. Thus, the modification of the Fc portion of an anti-OSM IgG1 mAb for higher FcRn binding affinity resulted in lower systemic

77 FR 39452 - Substantial Business Activities; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-03

... Substantial Business Activities; Correction AGENCY: Internal Revenue Service (IRS), Treasury. ACTION... whether a foreign corporation has substantial business activities in a foreign country. FOR FURTHER... the Code, the regulations have been submitted to the Chief Counsel for Advocacy of the Small Business...

76 FR 37641 - Safety Zone; Independence Day Fireworks Celebration for the City of Half Moon Bay, Half Moon Bay, CA

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-28

...-AA00 Safety Zone; Independence Day Fireworks Celebration for the City of Half Moon Bay, Half Moon Bay... temporary safety zone in the navigable waters of Half Moon Bay, off of Pillar Point Harbor beach, Half Moon Bay, CA in support of the Independence Day Fireworks Celebration for the City of Half Moon Bay...

Metric half-span model support system

NASA Technical Reports Server (NTRS)

Jackson, C. M., Jr.; Dollyhigh, S. M.; Shaw, D. S. (Inventor)

1982-01-01

A model support system used to support a model in a wind tunnel test section is described. The model comprises a metric, or measured, half-span supported by a nonmetric, or nonmeasured half-span which is connected to a sting support. Moments and forces acting on the metric half-span are measured without interference from the support system during a wind tunnel test.

First report on the safety and efficacy of an extended half-life glycoPEGylated recombinant FVIII for major surgery in severe haemophilia A.

PubMed

Hampton, K; Chowdary, P; Dunkley, S; Ehrenforth, S; Jacobsen, L; Neff, A; Santagostino, E; Sathar, J; Takedani, H; Takemoto, C M; Négrier, C

2017-09-01

N8-GP (turoctocog alfa pegol) is an extended half-life glycoPEGylated recombinant factor VIII (FVIII) product developed for the prevention and treatment of bleeds in haemophilia A patients. This is a planned interim analysis of pathfinder™3, an international, open-label, Phase 3 trial evaluating the efficacy and safety (including immunogenicity) of N8-GP administered before, during and after major surgery in severe haemophilia A patients aged ≥12 years. Sixteen patients who underwent 18 major surgical procedures (including synovectomy, joint replacement and ankle arthrodesis) were included here. Postoperative assessments were conducted daily for days 1-6, and once for days 7-14. Primary endpoint was N8-GP haemostatic efficacy, assessed after completion of surgery using a four-point scale ('excellent', 'good', 'moderate', 'none'). Haemostasis was successful (rated 'excellent' or 'good') on completion of surgery in 17 (94.4%) procedures and rated as 'moderate' (5.6%) for one surgery in a patient with multiple comorbidities who needed an intraoperative N8-GP dose (20.7 IU kg -1 ). In the postoperative period, three bleeds occurred (one during days 1-6; two during days 7-14); all were successfully treated with N8-GP. Mean N8-GP consumption on day of surgery was 80.0 IU kg -1 ; patients received a mean of 1.7 doses (median: 2, range: 1-3). No safety concerns were identified. The data showed that N8-GP was effective and well tolerated for the prevention and treatment of bleeds during major surgery; such FVIII products with extended half-lives may modify current treatment schedules, enabling fewer infusions and earlier patient discharge. © 2017 John Wiley & Sons Ltd.

5 CFR 550.183 - Substantial hours requirement.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Substantial hours requirement. 550.183 Section 550.183 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY ADMINISTRATION (GENERAL) Premium Pay Law Enforcement Availability Pay § 550.183 Substantial hours requirement. (a...

5 CFR 550.183 - Substantial hours requirement.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Substantial hours requirement. 550.183 Section 550.183 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY ADMINISTRATION (GENERAL) Premium Pay Law Enforcement Availability Pay § 550.183 Substantial hours requirement. (a...

5 CFR 550.183 - Substantial hours requirement.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Substantial hours requirement. 550.183 Section 550.183 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY ADMINISTRATION (GENERAL) Premium Pay Law Enforcement Availability Pay § 550.183 Substantial hours requirement. (a...

5 CFR 550.183 - Substantial hours requirement.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Substantial hours requirement. 550.183 Section 550.183 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY ADMINISTRATION (GENERAL) Premium Pay Law Enforcement Availability Pay § 550.183 Substantial hours requirement. (a...

Half-Fan-Based Intensity-Weighted Region-of-Interest Imaging for Low-Dose Cone-Beam CT in Image-Guided Radiation Therapy.

PubMed

Yoo, Boyeol; Son, Kihong; Pua, Rizza; Kim, Jinsung; Solodov, Alexander; Cho, Seungryong

2016-10-01

With the increased use of computed tomography (CT) in clinics, dose reduction is the most important feature people seek when considering new CT techniques or applications. We developed an intensity-weighted region-of-interest (IWROI) imaging method in an exact half-fan geometry to reduce the imaging radiation dose to patients in cone-beam CT (CBCT) for image-guided radiation therapy (IGRT). While dose reduction is highly desirable, preserving the high-quality images of the ROI is also important for target localization in IGRT. An intensity-weighting (IW) filter made of copper was mounted in place of a bowtie filter on the X-ray tube unit of an on-board imager (OBI) system such that the filter can substantially reduce radiation exposure to the outer ROI. In addition to mounting the IW filter, the lead-blade collimation of the OBI was adjusted to produce an exact half-fan scanning geometry for a further reduction of the radiation dose. The chord-based rebinned backprojection-filtration (BPF) algorithm in circular CBCT was implemented for image reconstruction, and a humanoid pelvis phantom was used for the IWROI imaging experiment. The IWROI image of the phantom was successfully reconstructed after beam-quality correction, and it was registered to the reference image within an acceptable level of tolerance. Dosimetric measurements revealed that the dose is reduced by approximately 61% in the inner ROI and by 73% in the outer ROI compared to the conventional bowtie filter-based half-fan scan. The IWROI method substantially reduces the imaging radiation dose and provides reconstructed images with an acceptable level of quality for patient setup and target localization. The proposed half-fan-based IWROI imaging technique can add a valuable option to CBCT in IGRT applications.

Family, money, and health: Regional differences in the determinants of life satisfaction over the life course

PubMed Central

Margolis, Rachel; Myrskylä, Mikko

2013-01-01

We examine how family, money, and health explain variation in life satisfaction over the life cycle across seven global regions using data from the World Values Survey. With a life domain approach, we study whether the importance of the life domains varies by region and age groups and whether the variation explained by each factor is due to the magnitude or prevalence of each factor. Globally, family, money, and health explain a substantial fraction of life satisfaction, increasing from 12 percent in young adulthood to 15 percent in mature adulthood. Health is the most important factor, and its importance increases with age. Income is unimportant above age 50. Remarkably, the contribution of family is small across ages. Across regions health is most important in the wealthier, and income in the poorer regions of the world. Family explains a substantial fraction of life satisfaction only in Western Europe and Anglophone countries. Findings highlight that the population-level importance of family, money, and health in explaining variation in life satisfaction across regions is mainly attributable to the individual-level life satisfaction differences between people of different statuses rather than differences in the distribution of various states such as poor health across regions. PMID:24796263

GRAPHIC REANALYSIS OF THE TWO NINDS-TPA TRIALS CONFIRMS SUBSTANTIAL TREATMENT BENEFIT

PubMed Central

Saver, Jeffrey L.; Gornbein, Jeffrey; Starkman, Sidney

2010-01-01

Background of Comment/Review Multiple statistical analyses of the two NINDS-TPA Trials have confirmed study findings of benefit of fibrinolytic therapy. A recent graphic analysis departed from best practices in the visual display of quantitative information by failing to take into account the skewed functional importance NIH Stroke Scale raw scores and by scaling change axes at up to twenty times the range achievable by individual patients. Methods Using the publicly available datasets of the 2 NINDS-TPA Trials, we generated a variety of figures appropriate to the characteristics of acute stroke trial data. Results A diverse array of figures all visually delineated substantial benefits of fibrinolytic therapy, including: bar charts of normalized gain and loss; stacked bar, bar, and matrix plots of clinically relevant ordinal ranks; a time series stacked line plot of continuous scale disability weights; and line plot, bubble chart, and person icon array graphs of joint outcome table analysis. The achievable change figure showed substantially greater improvement among TPA than placebo patients, median 66.7% (IQR 0–92.0) vs 50.0% (IQR −7.1 – 80.0), p=0.003. Conclusions On average, under 3 hour patients treated with TPA recovered two-thirds while placebo patients improved only half of the way towards fully normal. Graphical analyses of the two NINDS-TPA trials, when performed according to best practices, is a useful means of conveying details about patient response to therapy not fully delineated by summary statistics, and confirms a valuable treatment benefit of under 3 hour fibrinolytic therapy in acute stroke. PMID:20829518

Changes in extremes due to half a degree warming in observations and models

NASA Astrophysics Data System (ADS)

Fischer, E. M.; Schleussner, C. F.; Pfleiderer, P.

2017-12-01

Assessing the climate impacts of half-a-degree warming increments is high on the post-Paris science agenda. Discriminating those effects is particularly challenging for climate extremes such as heavy precipitation and heat extremes for which model uncertainties are generally large, and for which internal variability is so important that it can easily offset or strongly amplify the forced local changes induced by half a degree warming. Despite these challenges we provide evidence for large-scale changes in the intensity and frequency of climate extremes due to half a degree warming. We first assess the difference in extreme climate indicators in observational data for the 1960s and 1970s versus the recent past, two periods differ by half a degree. We identify distinct differences for the global and continental-scale occurrence of heat and heavy precipitation extremes. We show that those observed changes in heavy precipitation and heat extremes broadly agree with simulated historical differences and are informative for the projected differences between 1.5 and 2°C warming despite different radiative forcings. We therefore argue that evidence from the observational record can inform the debate about discernible climate impacts in the light of model uncertainty by providing a conservative estimate of the implications of 0.5°C warming. A limitation of using the observational record arises from potential non-linearities in the response of climate extremes to a certain level of warming. We test for potential non-linearities in the response of heat and heavy precipitation extremes in a large ensemble of transient climate simulations. We further quantify differences between a time-window approach in a coupled model large ensemble vs. time-slice experiments using prescribed SST experiments performed in the context of the HAPPI-MIP project. Thereby we provide different lines of evidence that half a degree warming leads to substantial changes in the expected occurrence of

A tetraethylene glycol coat gives gold nanoparticles long in vivo half-lives with minimal increase in size

PubMed Central

Willett, Julian DS; Lawrence, Marlon G; Wilder, Jennifer C; Smithies, Oliver

2017-01-01

In this study, we describe the experiments determining whether coating gold nanoparticles with tetraethylene glycol (TEG) provides pharmacologically relevant advantages, such as increased serum half-life and resistance to protein adsorption. Monodisperse TEG-coated, NaBH4-reduced gold nanoparticles with a hydrodynamic size comparable to albumin were synthesized by reducing gold chloride with NaBH4 under alkaline conditions in the presence of TEG-SH. The particles were characterized by gel electrophoresis, column chromatography, and transmission electron microscopy. The nanoparticles were subsequently injected intravenously into mice, and their half-lives and final destinations were determined via photometric analysis, light microscopy (LM), and transmission electron microscopy. The TEG particles had a long half-life (~400 minutes) that was not influenced by splenectomy. After 500 minutes of injection, TEG particles were found in kidney proximal tubule cell vesicles and in spleen red and white pulp. The particles induced apoptosis in the spleen red pulp but not in white pulp or the kidney. Some of the TEG particles appeared to have undergone ligand exchange reactions that increased their charge. The TEG particles were shown to be resistant to nonspecific protein adsorption, as judged by gel electrophoresis and column chromatography. These results demonstrate that naturally monodisperse, small-sized gold nanoparticles coated with TEG have long in vivo plasma half-lives, are minimally toxic, and are resistant to protein adsorption. This suggests that a TEG coating should be considered as an alternative to a polyethylene glycol coating, which is polydisperse and of much larger size. PMID:28408825

26 CFR 1.528-4 - Substantiality test.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 7 2014-04-01 2013-04-01 true Substantiality test. 1.528-4 Section 1.528-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Homeowners Associations § 1.528-4 Substantiality test. (a) In general. In order...

A half-metallic half-Heusler alloy having the largest atomic-like magnetic moment at optimized lattice constant

DOE PAGES

Zhang, R. L.; Damewood, L.; Fong, C. Y.; ...

2016-11-02

For half-Heusler alloys, the general formula is XYZ, where X can be a transition or alkali metal element, Y is another transition metal element, typically Mn or Cr, and Z is a group IV element or a pnicitide. The atomic arrangements within a unit-cell show three configurations. Before this study, most of the predictions of half-metallic properties of half-Heusler alloys at the lattice constants differing from their optimized lattice constant. Based on the electropositivity of X and electronegativity of Z for half-Heusler alloys, we found that one of the configurations of LiCrS exhibits half-metallic properties at its optimized lattice constantmore » of 5.803Å, and has the maximum atomic-like magnetic moment of 5μ B. In conclusion, the challenges of its growth and the effects of the spin-orbit effect in this alloy will be discussed.« less

Evaluating the environmental parameters that determine aerobic biodegradation half-lives of pesticides in soil with a multivariable approach.

PubMed

Wang, Yuxin; Lai, Adelene; Latino, Diogo; Fenner, Kathrin; Helbling, Damian E

2018-06-14

Aerobic biodegradation half-lives (half-lives) are key parameters used to evaluate pesticide persistence in soil. However, half-life estimates for individual pesticides often span several orders of magnitude, reflecting the impact that various environmental or experimental parameters have on half-lives in soil. In this work, we collected literature-reported half-lives for eleven pesticides along with associated metadata describing the environmental or experimental conditions under which they were derived. We then developed a multivariable framework to discover relationships between the half-lives and associated metadata. We first compared data for the herbicide atrazine collected from 95 laboratory and 65 field studies. We discovered that atrazine application history and soil texture were the parameters that have the largest influence on the observed half-lives in both types of studies. We then extended the analysis to include ten additional pesticides with data collected exclusively from laboratory studies. We found that, when data were available, pesticide application history and biomass concentrations were always positively associated with half-lives. The relevance of other parameters varied among the pesticides, but in some cases the variability could be explained by the physicochemical properties of the pesticides. For example, we found that the relative significance of the organic carbon content of soil for determining half-lives depends on the relative solubility of the pesticide. Altogether, our analyses highlight the reciprocal influence of both environmental parameters and intrinsic physicochemical properties for determining half-lives in soil. Copyright © 2018 Elsevier Ltd. All rights reserved.

EARLY CHILDHOOD INVESTMENTS SUBSTANTIALLY BOOST ADULT HEALTH

PubMed Central

Campbell, Frances; Conti, Gabriella; Heckman, James J.; Moon, Seong Hyeok; Pinto, Rodrigo; Pungello, Elizabeth; Pan, Yi

2014-01-01

High-quality early childhood programs have been shown to have substantial benefits in reducing crime, raising earnings, and promoting education. Much less is known about their benefits for adult health. We report the long-term health impacts of one of the oldest and most heavily cited early childhood interventions with long-term follow-up evaluated by the method of randomization: the Carolina Abecedarian Project (ABC). Using recently collected biomedical data, we find that disadvantaged children randomly assigned to treatment have significantly lower prevalence of risk factors for cardiovascular and metabolic diseases in their mid-30s. The evidence is especially strong for males. The mean systolic blood pressure among the control males is 143, while only 126 among the treated. One in four males in the control group is affected by metabolic syndrome, while none in the treatment group is. To reach these conclusions, we address several statistical challenges. We use exact permutation tests to account for small sample sizes and conduct a parallel bootstrap confidence interval analysis to confirm the permutation analysis. We adjust inference to account for the multiple hypotheses tested and for nonrandom attrition. Our evidence shows the potential of early life interventions for preventing disease and promoting health. PMID:24675955

Prehension of Half-Full and Half-Empty Glasses: Time and History Effects on Multi-Digit Coordination

PubMed Central

Sun, Yao; Zatsiorsky, Vladimir M.; Latash, Mark L.

2011-01-01

We explored how digit forces and indices of digit coordination depend on the history of getting to a particular set of task parameters during static prehension tasks. The participants held in the right hand an instrumented handle with a light-weight container attached on top of the handle. At the beginning of each trial, the container could be empty, filled to the half with water (0.4 l) or filled to the top (0.8 l). The water was pumped in/out of the container at a constant, slow rate over 10 s. At the end of each trial, the participants always held a half-filled container that has just been filled (Empty-Half), emptied (Full-Half), or stayed half-filled throughout the trial (Half-Only). Indices of co-variation (synergy indices) of elemental variables (forces and moments of force produced by individual digits) stabilizing such performance variables as total normal force, total tangetial force, and total moment of force were computed at two levels of an assumed control hierarchy. At the upper level, the task is shared between the thumb and virtual finger (an imagined digit with the mechanical action equal to that of the four fingers), while at the lower level, action of the virtual finger is shared among the actual four fingers. Filling or emptying the container led to a drop in the safety margin (proportion of grip force over the slipping threshold) below the values observed in the Half-Only condition. Synergy indices at both levels of the hierarchy showed changes over the Full-Half and Empty-Half condition. These changes could be monotonic (typical of moment of force and normal force) or non-monotonic (typical of tangential force). For both normal and tangential forces, higher synergy indices at the higher level of the hierarchy corresponded to lower indices at the lower level. Significant differences in synergy indices across conditions were seen at the final steady-state showing that digit coordination during steady holding an object is history dependent. The

Determining thyroid {sup 131}I effective half-life for the treatment planning of Graves' disease

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

Willegaignon, Jose; Sapienza, Marcelo T.; Barberio Coura Filho, George

2013-02-15

Purpose: Thyroid {sup 131}I effective half-life (T{sub eff}) is an essential parameter in patient therapy when accurate radiation dose is desirable for producing an intended therapeutic outcome. Multiple {sup 131}I uptake measurements and resources from patients themselves and from nuclear medicine facilities are requisites for determining T{sub eff}, these being limiting factors when implementing the treatment planning of Graves' disease (GD) in radionuclide therapy. With the aim of optimizing this process, this study presents a practical, propitious, and accurate method of determining T{sub eff} for dosimetric purposes. Methods: A total of 50 patients with GD were included in this prospectivemore » study. Thyroidal {sup 131}I uptake was measured at 2-h, 6-h, 24-h, 48-h, 96-h, and 220-h postradioiodine administration. T{sub eff} was calculated by considering sets of two measured points (24-48-h, 24-96-h, and 24-220-h), sets of three (24-48-96-h, 24-48-220-h, and 24-96-220-h), and sets of four (24-48-96-220-h). Results: When considering all the measured points, the representative T{sub eff} for all the patients was 6.95 ({+-}0.81) days, whereas when using such sets of points as (24-220-h), (24-96-220-h), and (24-48-220-h), this was 6.85 ({+-}0.81), 6.90 ({+-}0.81), and 6.95 ({+-}0.81) days, respectively. According to the mean deviations 2.2 ({+-}2.4)%, 2.1 ({+-}2.0)%, and 0.04 ({+-}0.09)% found in T{sub eff}, calculated based on all the measured points in time, and with methods using the (24-220-h), (24-48-220-h), and (24-96-220-h) sets, respectively, no meaningful statistical difference was noted among the three methods (p > 0.500, t test). Conclusions: T{sub eff} obtained from only two thyroid {sup 131}I uptakes measured at 24-h and 220-h, besides proving to be sufficient, accurate enough, and easily applicable, attributes additional major cost-benefits for patients, and facilitates the application of the method for dosimetric purposes in the treatment planning

Orange juice substantially reduces the bioavailability of the beta-adrenergic-blocking agent celiprolol.

PubMed

Lilja, Jari J; Juntti-Patinen, Laura; Neuvonen, Pertti J

2004-03-01

Grapefruit juice was recently found to decrease plasma concentrations of the beta-adrenergic receptor-blocking agent celiprolol. Our objective was to investigate the effect of orange juice on the pharmacokinetics of celiprolol in healthy subjects. In a randomized crossover study with 2 phases and a washout of 2 weeks, 10 healthy volunteers ingested either 200 mL normal-strength orange juice or water 3 times a day for 2 days. On the morning of day 3, 1 hour after ingestion of 200 mL orange juice or water, each subject ingested 100 mg celiprolol with either 200 mL orange juice or water. In addition, 200 mL orange juice or water was ingested at 4, 10, 22, and 27 hours after celiprolol intake. The concentrations of celiprolol in plasma and its excretion into urine were measured up to 33 hours after its dosing. Systolic and diastolic blood pressures and heart rate were recorded up to 10 hours. Orange juice reduced the mean peak plasma concentration of celiprolol by 89% (P <.01) and the mean area under the plasma celiprolol concentration-time curve by 83% (P <.01). The time to peak concentration of celiprolol increased from 4 to 6 hours (P <.05), and the half-life was prolonged from 4.6 to 10.8 hours (P =.05) after ingestion of orange juice. Orange juice reduced the urinary excretion of celiprolol by 77% (P <.01). No significant differences were observed in the hemodynamic variables between the phases. Orange juice substantially reduces the bioavailability of celiprolol, but the mechanism of this interaction remains to be resolved. For example, modulation of intestinal pH and of function of transporters implicated in the absorption of celiprolol may be involved. Because of the great extent of the orange juice-celiprolol interaction and a wide use of orange juice, this interaction is likely to have clinical importance in some patients, although hemodynamic consequences were not seen in young healthy subjects.

Years of life lost due to infectious diseases in Poland

PubMed Central

Bryla, Marek; Dziankowska-Zaborszczyk, Elzbieta; Bryla, Pawel; Pikala, Malgorzata

2017-01-01

Purpose An evaluation of mortality due to infectious diseases in Poland in 1999–2012 and an analysis of standard expected years of life lost due to the above diseases. Methods The study material included a database created on the basis of 5,219,205 death certificates of Polish inhabitants, gathered between 1999 and 2012 and provided by the Central Statistical Office. Crude Death Rates (CDR), Standardized Death Rates (SDR) and Standard Expected Years of Life Lost (SEYLL) due to infectious and parasitic diseases were also evaluated in the study period as well as Standard Expected Years of Life Lost per living person (SEYLLp) and Standard Expected Years of Life Lost per dead person (SEYLLd). Time trends were evaluated with the application of joinpoint models and an annual percentage change in their values. Results Death certificates report that 38,261 people died due to infectious diseases in Poland in the period 1999–2012, which made up 0.73% of the total number of deaths. SDR caused by these diseases decreased, particularly in the male group: Annual Percentage Change (APC = -1.05; 95% CI:-2.0 to -0.2; p<0.05). The most positive trends were observed in mortality caused by tuberculosis (A15-A19) (APC = -5.40; 95% CI:-6.3 to -4.5; p<0.05) and also meningitis, encephalitis, myelitis and encephalomyelitis (G03-G04) (APC = -3.42; 95% CI:-4.7 to -2.1; p<0.05). The most negative mortality trends were observed for intestinal infectious diseases (A00-A09) Annual Average Percentage Change (AAPC = 7.3; 95% CI:3.1 to 11.7; p<0.05). SDR substantially decreased in the first half of the study period, but then significantly increased in the second half. Infectious and parasitic diseases contributed to a loss of around 37,000 standard expected years of life in 1999 and more than 28,000 in 2012. During the study period, the SEYLLp index decreased from 9.59 to 7.39 per 10,000 population and the SEYLLd index decreased from 14.26 to 10.34 years (AAPC = 2.3; 95% CI:-2,9 to -1.7; p<0

20 CFR 416.910 - Meaning of substantial gainful activity.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Meaning of substantial gainful activity. 416....910 Meaning of substantial gainful activity. Substantial gainful activity means work that— (a) Involves doing significant and productive physical or mental duties; and (b) Is done (or intended) for pay...

20 CFR 416.910 - Meaning of substantial gainful activity.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Meaning of substantial gainful activity. 416....910 Meaning of substantial gainful activity. Substantial gainful activity means work that— (a) Involves doing significant and productive physical or mental duties; and (b) Is done (or intended) for pay...

20 CFR 404.1510 - Meaning of substantial gainful activity.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Meaning of substantial gainful activity. 404... Meaning of substantial gainful activity. Substantial gainful activity means work that— (a) Involves doing significant and productive physical or mental duties; and (b) Is done (or intended) for pay or profit. (See...

20 CFR 404.1510 - Meaning of substantial gainful activity.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Meaning of substantial gainful activity. 404... Meaning of substantial gainful activity. Substantial gainful activity means work that— (a) Involves doing significant and productive physical or mental duties; and (b) Is done (or intended) for pay or profit. (See...

7 CFR 51.2296 - Three-fourths half kernel.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Three-fourths half kernel. 51.2296 Section 51.2296 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards...-fourths half kernel. Three-fourths half kernel means a portion of a half of a kernel which has more than...

Production of substantially pure fructose

DOEpatents

Hatcher, Herbert J.; Gallian, John J.; Leeper, Stephen A.

1990-01-01

A process is disclosed for the production of substantially pure fructose from sucrose-containing substrates. The process comprises converting the sucrose to levan and glucose, purifying the levan by membrane technology, hydrolyzing the levan to form fructose monomers, and recovering the fructose.

The Prolonged Life-Span of Alveolar Macrophages

PubMed Central

Murphy, Jaime; Summer, Ross; Wilson, Andrew A.; Kotton, Darrell N.; Fine, Alan

2008-01-01

To further examine the half-life of alveolar macrophages, chimeric CD 45.2 mice were generated through bone marrow transplantation of donor CD 45.1 cells. Before administration of donor cells, recipient mice were divided into two cohorts: the first cohort received total body irradiation; the second cohort also received irradiation—however, the thorax, head, and upper extremities were shielded with lead. Flow cytometric analysis was then performed on blood, peritoneal, and bronchoalveolar lavage cells over time to quantify engraftment. The data generated for the unshielded cohort of mice revealed a macrophage half-life of 30 days. In the shielded cohort, however, we found that by 8 months there was negligible replacement of recipient alveolar macrophages by donor cells, despite reconstitution of the blood and peritoneum by donor bone marrow. Consistent with these findings, the mean fluorescent intensity of alveolar macrophages remained stable over a 4-week period after in vivo PKH26 dye loading. Together, these data show that previous alveolar macrophage half-life studies were confounded by the fact that they did not account for the toxic effects of irradiation conditioning regimens, and demonstrate that the bone marrow does not significantly contribute to the alveolar macrophage compartment during steady-state conditions. PMID:18192503

29 CFR 825.218 - Substantial and grievous economic injury.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Substantial and grievous economic injury. 825.218 Section... Medical Leave Act § 825.218 Substantial and grievous economic injury. (a) In order to deny restoration to... cause “substantial and grievous economic injury” to the operations of the employer, not whether the...

Defining futile life-prolonging treatments through Neo-Socratic Dialogue.

PubMed

Aizawa, Kuniko; Asai, Atsushi; Bito, Seiji

2013-12-09

In Japan, people are negative towards life-prolonging treatments. Laws that regulate withholding or discontinuing life-prolonging treatments and advance directives do not exist. Physicians, however, view discontinuing life-prolonging treatments negatively due to fears of police investigations. Although ministerial guidelines were announced regarding the decision process for end-of-life care in 2007, a consensus could not be reached on the definition of end-of-life and conditions for withholding treatment. We established a forum for extended discussions and consensus building on this topic. We used the Neo-Socratic Dialogue (NSD) method which promotes philosophical discussion based on a case-study to address a question and formulate a consensus and answer in a group. The question chosen for the dialogue was: "What is a life-prolonging treatment?" A series of dialogues took place over a period of one and a half days. It was carried out by three groups in 2010 and 2011. Seven participants with diverse backgrounds were recruited per group. We analyzed the content of the discussion. Based on three case studies concerning different opinions about treatment options for an older dementia patient, a patient demanding chemotherapy, and a severely ill neonate, conditions for futile life-prolonging treatment were elucidated through NSD. Such treatments are those carried out for the sole purpose of prolonging life and are detrimental to the patient, and should be decided based foremost on the patient's lack of desire for treatment, the consensus of those involved, and through social acceptance. These arguments are essentially consistent with ones on medical futility in the United States. By expressing the objective of healthcare and the requirement of social acceptance, participants were also able to elucidate issues related to the awareness of those involved and the medical environment. Compared to the end-of-life guidelines in Japan, the objective of treatment, its effects

Defining futile life-prolonging treatments through Neo-Socratic Dialogue

PubMed Central

2013-01-01

Background In Japan, people are negative towards life-prolonging treatments. Laws that regulate withholding or discontinuing life-prolonging treatments and advance directives do not exist. Physicians, however, view discontinuing life-prolonging treatments negatively due to fears of police investigations. Although ministerial guidelines were announced regarding the decision process for end-of-life care in 2007, a consensus could not be reached on the definition of end-of-life and conditions for withholding treatment. We established a forum for extended discussions and consensus building on this topic. Methods We used the Neo-Socratic Dialogue (NSD) method which promotes philosophical discussion based on a case-study to address a question and formulate a consensus and answer in a group. The question chosen for the dialogue was: “What is a life-prolonging treatment?” A series of dialogues took place over a period of one and a half days. It was carried out by three groups in 2010 and 2011. Seven participants with diverse backgrounds were recruited per group. We analyzed the content of the discussion. Results Based on three case studies concerning different opinions about treatment options for an older dementia patient, a patient demanding chemotherapy, and a severely ill neonate, conditions for futile life-prolonging treatment were elucidated through NSD. Such treatments are those carried out for the sole purpose of prolonging life and are detrimental to the patient, and should be decided based foremost on the patient’s lack of desire for treatment, the consensus of those involved, and through social acceptance. These arguments are essentially consistent with ones on medical futility in the United States. By expressing the objective of healthcare and the requirement of social acceptance, participants were also able to elucidate issues related to the awareness of those involved and the medical environment. Compared to the end-of-life guidelines in Japan, the

Substantially oxygen-free contact tube

NASA Technical Reports Server (NTRS)

Pike, James F. (Inventor)

1993-01-01

A device for arc welding is provided in which a continuously-fed electrode wire is in electrical contact with a contact tube. The contact tube is improved by using a substantially oxygen-free conductive alloy in order to reduce the amount of electrical erosion.

Substantially Oxygen-Free Contact Tube

NASA Technical Reports Server (NTRS)

Pike, James F. (Inventor)

1991-01-01

A device for arc welding is provided in which a continuously-fed electrode wire is in electrical contact with a contact tube. The contact tube is improved by using a substantially oxygen-free conductive alloy in order to reduce the amount of electrical erosion.

Solar geoengineering could substantially reduce climate risks—A research hypothesis for the next decade

NASA Astrophysics Data System (ADS)

Keith, David W.; Irvine, Peter J.

2016-11-01

We offer a hypothesis that if solar geoengineering (SG) were deployed to offset half of the increase in global-mean temperature from the date of deployment using a technology and deployment method chosen to approximate a reduction in the solar constant then, over the 21st century, it would (a) substantially reduce the global aggregate risks of climate change, (b) without making any country worse off, and (c) with the aggregate risks from side-effects being small in comparison to the reduction in climate risks. We do not set out to demonstrate this hypothesis; rather we propose it with the goal of stimulating a strategic engagement of the SG research community with policy-relevant questions. We elaborate seven sub-hypotheses on the effects of our scenario for key risks of climate change that could be assessed in future modeling work. As an example, we provide a defence of one of our sub-hypotheses, that our scenario of SG would reduce the risk of drought in dry regions, but also identify issues that may undermine this sub-hypothesis and how future work could resolve this question. SG cannot substitute for emissions mitigation but it may be a useful supplement. It is our hope that scientific and technical research over the next decade focuses more closely on well-articulated variants of the key policy-relevant question: could SG be designed and deployed in such a way that it could substantially and equitably reduce climate risks?

Anisotropy in layered half-metallic Heusler alloy superlattices

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

Azadani, Javad G.; Munira, Kamaram; Sivakumar, Chockalingam

2016-01-28

We show that when two Heusler alloys are layered in the [001], [110], or [111] directions for various thicknesses to form a superlattice, the Slater-Pauling rule may still be satisfied and the resulting superlattice is often half-metallic with gaps comparable to or larger than those of its constituents. In addition, uniaxial magnetocrystalline anisotropy is induced because of the differences in the electronic structure of the two Heuslers in the superlattice. Various full-full, full-half, and half-half Heusler superlattices are studied, and potential half-metallic superlattices with perpendicular magnetocrystalline anisotropy are identified.

40 CFR 158.1100 - Spray drift data requirements table.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the general use patterns of terrestrial food crop and terrestrial nonfood crop. The aquatic use pattern includes products classified under the general use patterns of aquatic food crop and aquatic... Pattern Terrestrial Food Crop Nonfood Crop Aquatic Food Nonfood Greenhouse Food Crop Nonfood Crop Forestry...

40 CFR 158.1100 - Spray drift data requirements table.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the general use patterns of terrestrial food crop and terrestrial nonfood crop. The aquatic use pattern includes products classified under the general use patterns of aquatic food crop and aquatic... Pattern Terrestrial Food Crop Nonfood Crop Aquatic Food Nonfood Greenhouse Food Crop Nonfood Crop Forestry...

Relationship among aqueous copper half-lives and responses of Pimephales promelas to a series of copper sulfate pentahydrate concentrations.

PubMed

Calomeni, Alyssa J; Kinley, Ciera M; Geer, Tyler D; Iwinski, Kyla J; Hendrikse, Maas; Rodgers, John H

2018-04-01

Copper algaecide exposures in situ are often of shorter duration than exposures for static toxicity experiments because aqueous concentrations in situ dissipate as a function of site-specific fate processes. Consequently, responses of organisms to static copper exposures may overestimate effects following in situ exposures. To understand the role of exposure duration for altering responses, Pimephales promelas survival was compared following static (96 h) and pulse (1.5, 4, 8, and 15 h half-lives) exposures of CuSO 4 •5H 2 O. Copper concentrations sorbed by fry indicated a consequence of different exposures. Responses of P. promelas to static exposures resulted in 96 h LC 50 s of 166 µgCu/L (95% confidence interval [CI], 142-189 µgCu/L) as soluble copper and 162 µgCu/L (CI, 140-183 µgCu/L) as acid soluble copper. Relative to static 96 h LC 50 s, exposures with half-lives of 1.5, 4 and 8 h resulted in LC 50 s 10, 3 and 2 times greater, respectively, for responses measured 96 h after exposure initiation. Copper concentrations extracted from fry exposed for 1.5, 4 and 8 h half-lives were less than the static experiment. However, copper sorbed by fry in the 15 h half-life experiment was not different than the static experiment. The relationship between 96 h LC 50 and 1/half-life was expressed using the equations y = 116 + 1360 × (R 2  = 0.97) for soluble copper and y = 147 + 1620 × (R 2  = 0.98) for acid soluble copper. Incorporation of exposure duration for predictions of P. promelas responses to copper pulse exposures increases prediction accuracy by an order of magnitude.

The Constitution of the Human Embryo as Substantial Change

PubMed Central

Alvargonzález, David

2016-01-01

This paper analyzes the transformation from the human zygote to the implanted embryo under the prism of substantial change. After a brief introduction, it vindicates the Aristotelian ideas of substance and accident, and those of substantial and accidental change. It then claims that the transformation from the multicelled zygote to the implanted embryo amounts to a substantial change. Pushing further, it contends that this substantial change cannot be explained following patterns of genetic reductionism, emergence, and self-organization, and proposes Gustavo Bueno’s idea of anamorphosis as a means to encapsulate criticism against such positions. PMID:26850033

Fetal Adrenal Gland in the Second Half of Gestation: Morphometrical Assessment with 3.0T Post-Mortem MRI

PubMed Central

Hou, Zhongyu; Ma, Jun; Feng, Lei; Lin, Xiangtao; Tang, Yuchun; Zhang, Xiaoli; Liu, Qingwei; Liu, Shuwei

2013-01-01

Background The morphometry of fetal adrenal gland is rarely described with MRI of high magnetic field. The purpose of this study is to assess the normal fetal adrenal gland length (AL), width (AW), height (AH), surface area (AS) and volume (AV) in the second half of gestation with 3.0T post-mortem MRI. Methods and Findings Fifty-two fetal specimens of 23–40 weeks gestational age (GA) were scanned by 3.0T MRI. Morphological changes and quantitative measurements of the fetal adrenal gland were analyzed. Asymmetry and sexual dimorphism were also obtained. The shape of the fetal adrenal gland did not change substantially from 23 to 40 weeks GA. The bilateral adrenal glands appeared as a ‘Y’, pyramidal or half-moon shape after reconstruction. There was a highly linear correlation between AL, AW, AH, AS, AV and GA. AW, AH, AS and AV were larger for the left adrenal gland than the right. No sexual dimorphism was found. Conclusions Our data delineated the normal fetal adrenal gland during the second half of gestation, and can serve as a useful precise reference for anatomy or in vivo fetus. PMID:24116052

Work and the Perceived Quality of Life. A Final Report.

DTIC Science & Technology

1986-12-01

The experience of work has the potential to substantially influence the perceived quality of life (pQL). The goal of this research program was to...Job satisfaction, life satisfaction, quality of life , quality of work life, unemployment, work-family conflict, job involvement, family involvement, job importance.

Life Cycle Assessment of Bioenergy from Lignocellulosic Crops Cultivated on Marginal Land in Europe

NASA Astrophysics Data System (ADS)

Rettenmaier, Nils; Schmidt, Tobias; Gärtner, Sven; Reinhardt, Guido

2017-04-01

Population growth and changing diets due to economic development lead to an additional demand for land for food and feed production. Slowly but surely turning into a mass market, also the cultivation of non-food biomass crops for fibre (bio-based products) and fuel (biofuels and bioenergy) is increasingly contributing to the pressure on global agricultural land. As a consequence, the already prevailing competition for land might even intensify over the next decades. Against this background, the possibilities of shifting the cultivation of non-food biomass crops to so-called 'marginal lands' are investigated. The EC-funded project 'Sustainable exploitation of biomass for bioenergy from marginal lands in Europe' (SEEMLA) aims at the establishment of suitable innovative land-use strategies for a sustainable production of bioenergy from lignocellulosic crops on marginal lands while improving general ecosystem services. For a complete understanding of the environmental benefits and drawbacks of the envisioned cultivation of bioenergy crops on marginal land, life cycle assessments (LCA) have proven to be a suitable and valuable tool. Thus, embedded into a comprehensive sustainability assessment, a screening LCA is carried out for the entire life cycles of the bioenergy carriers researched in SEEMLA. Investigated systems, on the one hand, include the specific field trials carried out by the SEEMLA partners in Ukraine, Greece and Germany. On the other hand, generic scenarios are investigated in order to derive reliable general statements on the environmental impacts of bioenergy from marginal lands in Europe. Investigated crops include woody and herbaceous species such as black locust, poplar, pine, willow and Miscanthus. Conversion technologies cover the use in a domestic or a district heating plant, power plant, CHP as well as the production of Fischer-Tropsch diesel (FT diesel) and lignocellulosic ethanol. Environmental impacts are compared to conventional reference

Half-marathoners are younger and slower than marathoners.

PubMed

Knechtle, Beat; Nikolaidis, Pantelis T; Zingg, Matthias A; Rosemann, Thomas; Rüst, Christoph A

2016-01-01

Age and performance trends of elite and recreational marathoners are well investigated, but not for half-marathoners. We analysed age and performance trends in 508,108 age group runners (125,894 female and 328,430 male half-marathoners and 10,205 female and 43,489 male marathoners) competing between 1999 and 2014 in all flat half-marathons and marathons held in Switzerland using single linear regression analyses, mixed-effects regression analyses and analyses of variance. The number of women and men increased across years in both half-marathons and marathons. There were 12.3 times more female half-marathoners than female marathoners and 7.5 times more male half-marathoners than male marathoners. For both half-marathons and marathons, most of the female and male finishers were recorded in age group 40-44 years. In half-marathons, women (10.29 ± 3.03 km/h) were running 0.07 ± 0.06 km/h faster (p < 0.001) than men (10.22 ± 3.06 km/h). Also in marathon, women (14.77 ± 4.13 km/h) were running 0.28 ± 0.16 km/h faster (p < 0.001) than men (14.48 ± 4.07 km/h). In marathon, women (42.18 ± 10.63 years) were at the same age than men (42.06 ± 10.45 years) (p > 0.05). Also in half-marathon, women (41.40 ± 10.63 years) were at the same age than men (41.31 ± 10.30 years) (p > 0.05). However, women and men marathon runners were older than their counterpart half-marathon runners (p < 0.001). In summary, (1) more athletes competed in half-marathons than in marathons, (2) women were running faster than men, (3) half-marathoners were running slower than marathoners, and (4) half-marathoners were younger than marathoners.

The Identification and Assessment of Late-life ADHD in Memory Clinics

PubMed Central

Fischer, Barbara L.; Gunter-Hunt, Gail; Steinhafel, Courtney Holm; Howell, Timothy

2013-01-01

INTRODUCTION Little data exists about attention deficit hyperactivity disorder (ADHD) in late life. While evaluating patients’ memory problems, our Memory Clinic staff has periodically identified ADHD in previously undiagnosed adults. We conducted a survey to assess the extent to which other memory clinics view ADHD as a relevant clinical issue. METHOD We developed and sent a questionnaire to Memory Clinics in the United States to ascertain how ADHD was identified and addressed. The percentage of responding memory clinics’ means of assessing and managing late-life ADHD comprised the measurements for this study. RESULTS Approximately one-half of responding memory clinics reported seeing ADHD patients. Of these, one-half reported identifying previously diagnosed cases, and almost one-half reported diagnosing ADHD themselves. One fifth of clinics reported screening regularly for ADHD, and few clinics described treatment methods. CONCLUSION Our results suggest that U.S. memory clinics may not adequately identify and address ADHD in late life. PMID:22173147

Intelligibility in microbial complex systems: Wittgenstein and the score of life.

PubMed

Baquero, Fernando; Moya, Andrés

2012-01-01

Knowledge in microbiology is reaching an extreme level of diversification and complexity, which paradoxically results in a strong reduction in the intelligibility of microbial life. In our days, the "score of life" metaphor is more accurate to express the complexity of living systems than the classic "book of life." Music and life can be represented at lower hierarchical levels by music scores and genomic sequences, and such representations have a generational influence in the reproduction of music and life. If music can be considered as a representation of life, such representation remains as unthinkable as life itself. The analysis of scores and genomic sequences might provide mechanistic, phylogenetic, and evolutionary insights into music and life, but not about their real dynamics and nature, which is still maintained unthinkable, as was proposed by Wittgenstein. As complex systems, life or music is composed by thinkable and only showable parts, and a strategy of half-thinking, half-seeing is needed to expand knowledge. Complex models for complex systems, based on experiences on trans-hierarchical integrations, should be developed in order to provide a mixture of legibility and imageability of biological processes, which should lead to higher levels of intelligibility of microbial life.

Calculation of pressure half-time.

PubMed

Oyama, Mark A; Weidman, Jess A; Cole, Steven G

2008-06-01

Doppler echocardiography is useful in assessing the severity of obstructive cardiac lesions, such as mitral valve stenosis. The Doppler study can be used to calculate pressure half-time (PHT), which is defined as the time required for the pressure gradient across an obstruction to decrease to half of its maximal value. Thus, PHT increases as the severity of stenosis increases. In this report, we describe the methodology involved in measuring PHT in a dog with mitral valve stenosis before and after balloon valvuloplasty.

Visual Search Across the Life Span

ERIC Educational Resources Information Center

Hommel, Bernhard; Li, Karen Z. H.; Li, Shu-Chen

2004-01-01

Gains and losses in visual search were studied across the life span in a representative sample of 298 individuals from 6 to 89 years of age. Participants searched for single-feature and conjunction targets of high or low eccentricity. Search was substantially slowed early and late in life, age gradients were more pronounced in conjunction than in…

Neutron activation of natural materials in a PWR spectrum: feedback on {sup 116m}In relative γ emission intensities and half-life

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

Gruel, Adrien; Geslot, Benoit; Di Salvo, Jacques

2015-07-01

During the MAESTRO program, carried out between 2011 and 2014 in MINERVE zero power reactor, common Gen-II and Gen-III light water reactor materials were irradiated. For some of these materials, the decay of their activation products was also measured by γ spectrometry. Initially devoted to the measurement of the integral capture cross section by activation and reactivity-oscillation method, these results can also provide useful information on decay data of various radionuclides. This approach of this experiment led to a common roadmap shared by the Experimental Physics Section and the Henri Becquerel National Laboratory to improve decay data in nuclear datamore » libraries. Results discussed in this paper concern the relative emission intensities of the main γ rays of {sup 116m}In. Six irradiations of samples with various physical forms of {sup nat}In were carried out. Measurements were analyzed using decay data from several evaluations and it is shown that γ ray activities are not consistent. Analyses were carried out to provide new relative γ emission intensities from these measurements. The {sup 116m}In half-life has also been measured and shows a good agreement with existing values. Finally, an overview of the foreseen results on additional decay data from the MAESTRO program is given. (authors)« less

Behavioral Interventions to Reduce the Pica of Persons with Developmental Disabilities

ERIC Educational Resources Information Center

McAdam, David B.; Sherman, James A.; Sheldon, Jan B.; Napolitano, Deborah A.

2004-01-01

The consumption of nonfood items (i. e., pica) frequently occurs in persons with developmental disabilities. Pica may result in the puncture or blockage of the digestive tract, infestation by gastrointestinal parasites, and can interfere with an individuals daily learning, occupational performance, and quality of life. Twenty-six published studies…

β-decay half-lives of new neutron-rich rare-earth isotopes 159Pm,162Sm, and 166Gd

NASA Astrophysics Data System (ADS)

Ichikawa, S.; Asai, M.; Tsukada, K.; Haba, H.; Nagame, Y.; Shibata, M.; Sakama, M.; Kojima, Y.

2005-06-01

The new neutron-rich rare-earth isotopes 159Pm, 162Sm, and 166Gd produced in the proton-induced fission of 238U were identified using the JAERI on-line isotope separator (JAERI-ISOL) coupled to a gas-jet transport system. The half-lives of 159Pm, 162Sm, and 166Gd were determined to be 1.5 ± 0.2, 2.4 ± 0.5, and 4.8 ± 1.0 s respectively. The partial decay scheme of 166Gd was constructed from γγ-coincidence data. A more accurate half-life value of 25.6 ± 2.2 s was obtained for the previously identified isotope 166Tb. The half-lives measured in the present study are in good agreement with the theoretical predictions calculated by the second generation of the gross theory with the atomic masses evaluated by Audi and Wapstra.

Ecological half-lives of radiocesium in 16 species in marine biota after the TEPCO's Fukushima Daiichi nuclear power plant accident.

PubMed

Iwata, Kayoko; Tagami, Keiko; Uchida, Shigeo

2013-07-16

TEPCO's Fukushima Daiichi Nuclear Power Plant (FDNPP) accident of March 2011 caused the discharge of a considerable quantity of radionuclides, including (137)Cs. Because of its long half-life (30.17 years), the fate of (137)Cs in the marine biota is of great interest. This study aims to evaluate, using food monitoring data, ecological half-lives (Teco) of (137)Cs in marine biota caught offshore of Fukushima. The data were categorized into two regional groups (north and south) with respect to the FDNPP site, and the regional (137)Cs concentration trend and estimated Teco in the marine biota were appraised. Although the (137)Cs concentration in the seawater in the south was higher than that in the north, Teco values remained relatively consistent among common species of both regions. Teco was then compared to biological half-life (Tb) estimated in laboratory settings. The ratios of Teco/Tb were inconsistent among different groups of marine species. The ratios of Teco/Tb for brown seaweed and bivalves were approximately 1, and the ratios of Teco/Tb for demersal fish ranged from 4.4 to 16.1. The reasons for different ratios of Teco and Tb values may be attributed to environmental and ecological factors, such as different trophic levels.

[From Bonghan system to primo vascular system:the thought on the substantial study on meridian points].

PubMed

Lin, Dong; Huang, Xiaozhen; Zhuang, Wanyu; Lin, Lili

2017-01-12

Through the systematic analysis on the primo vascular system (PVS) in recent years, we believe that in recent years, more and more studies have indicated that PVS is distributed in reticulate structure in every part of body, such as vessels, lymphangions, nerves, brain, spinal cords and internal organs, and it contains a large amount of immunocytes and has involved in the physiological or pathological process of the immunity and circulation in the body. There are the evidences to prove that in morphology and cytobiology. But, nowadays, there is no way to explain its effect characters. On the basis of the study on living matter characteristics, a breakthrough is possibly made through the systematic cooperation even though it is the difficulty to detect the life function effect. It is especially displayed in the substantial study on meridian points. Hence, the study on the law of meridian point effects on the basis of clinical practice has to be focused on in the substantial study on meridian points.

26 CFR 1.7874-3T - Substantial business activities (temporary).

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 13 2013-04-01 2013-04-01 false Substantial business activities (temporary). 1... Substantial business activities (temporary). (a) Scope. This section provides rules regarding whether a foreign corporation has substantial business activities in the relevant foreign country when compared to...

Potential years lost and life expectancy in adults with newly diagnosed epilepsy.

PubMed

Granbichler, Claudia A; Zimmermann, Georg; Oberaigner, Willi; Kuchukhidze, Giorgi; Ndayisaba, Jean-Pierre; Taylor, Alexandra; Luef, Gerhard; Bathke, Arne C; Trinka, Eugen

2017-11-01

Studies using relative measures, such as standardized mortality ratios, have shown that patients with epilepsy have an increased mortality. Reports on more direct and absolute measure such as life expectancy are sparse. We report potential years lost and how life expectancy has changed over 40 years in a cohort of patients with newly diagnosed epilepsy. We analyzed life expectancy in a cohort of adult patients diagnosed with definite epilepsy between 1970 and 2010. Those with brain tumor as cause of epilepsy were excluded. By retrospective probabilistic record linkage, living or death status was derived from the national death registry. We estimated life expectancy by a Weibull regression model using gender, age at diagnosis, epilepsy etiology, and year of diagnosis as covariates at time of epilepsy diagnosis, and 5, 10, 15, and 20 years after diagnosis. Results were compared to the general population, and 95% confidence intervals are given. There were 249 deaths (105 women, age at death 19.0-104.0 years) in 1,112 patients (11,978.4 person-years, 474 women, 638 men). A substantial decrease in life expectancy was observed for only a few subgroups, strongly depending on epilepsy etiology and time of diagnosis: time of life lost was highest in patients with symptomatic epilepsy diagnosed between 1970 and 1980; the impact declined with increasing time from diagnosis. Over half of the analyzed subgroups did not differ significantly from the general population. This effect was reversed in the later decades, and life expectancy was prolonged in some subgroups, reaching a maximum in those with newly diagnosed idiopathic and cryptogenic epilepsy between 2001 and 2010. Life expectancy is reduced in symptomatic epilepsies. However, in other subgroups, a prolonged life expectancy was found, which has not been reported previously. Reasons may be manifold and call for further study. © 2017 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International

The "House" in Half Hollow Hills

ERIC Educational Resources Information Center

Karnilow, Sheldon

2006-01-01

In this article, the author relates how he initiated a systemic improvement to Half Hollow Hills school district when he became its superintendent. He relates that although he came to Half Hollow Hills with a deep understanding of the models of systemic change, he did not bring with him a specific prescriptive plan for improvement. His plan for…

Half-lit Dione

NASA Image and Video Library

2017-10-16

Saturn's moon Dione is captured in this view from NASA's Cassini spacecraft, half in shadow and half in light. Sinuous canyons carve interconnected paths across the moon's icy landscape. Subtle variations in brightness hint at differences in composition, as well as the size and shape of grains in Dione's surface material, or regolith. Cassini spent more than a decade at Saturn studying Dione (698 miles or 1,123 kilometers across) and the planet's many other moons as part of the quest to understand how the moons formed and evolved, and how they are connected. This view looks toward the side of Dione that faces away from Saturn. North is up and rotated 59 degrees to the right. The image was taken in visible light with the Cassini spacecraft narrow-angle camera on June 22, 2017. The view was obtained at a distance of approximately 224,000 miles (360,000 kilometers) from Dione. Image scale is 1.4 mile (2.2 kilometers) per pixel. The Cassini spacecraft ended its mission on Sept. 15, 2017. https://photojournal.jpl.nasa.gov/catalog/PIA21349

20 CFR 654.13 - Determination of areas of substantial unemployment.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Determination of areas of substantial unemployment. 654.13 Section 654.13 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF... 10582 § 654.13 Determination of areas of substantial unemployment. An area of substantial unemployment...

20 CFR 654.13 - Determination of areas of substantial unemployment.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false Determination of areas of substantial unemployment. 654.13 Section 654.13 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF... 10582 § 654.13 Determination of areas of substantial unemployment. An area of substantial unemployment...

20 CFR 654.13 - Determination of areas of substantial unemployment.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Determination of areas of substantial unemployment. 654.13 Section 654.13 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF... 10582 § 654.13 Determination of areas of substantial unemployment. An area of substantial unemployment...

20 CFR 654.13 - Determination of areas of substantial unemployment.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false Determination of areas of substantial unemployment. 654.13 Section 654.13 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF... 10582 § 654.13 Determination of areas of substantial unemployment. An area of substantial unemployment...

20 CFR 654.13 - Determination of areas of substantial unemployment.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Determination of areas of substantial unemployment. 654.13 Section 654.13 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF... 10582 § 654.13 Determination of areas of substantial unemployment. An area of substantial unemployment...

Life Events, Public Policy and the Economic Vulnerability of Children and the Elderly.

ERIC Educational Resources Information Center

Burkhauser, Richard V.; Duncan, Greg J.

This report uses longitudinal data to provide a dynamic picture of the family income experiences of children and the elderly. In contrast to the image of fairly stable incomes during most life-cycle stages, findings show substantial income volatility at all points in the life span, placing substantial numbers of the population at risk of suffering…

The cognitive therapy of depression rests on substantial theoretical, empirical and clinical foundations: a reply to Dr Gipps

PubMed Central

Moorey, Stirling

2017-01-01

Dr Gipps claims that the cognitive therapy for depression rests on a mistake. But his anachronistic analysis of Beck's early research from the perspective of current psychoanalytic theory misses the point. The value of the research was not that it disproved psychoanalytic theory, but that it generated a model of depression that has revolutionised psychotherapy research. Psychoanalysts are belatedly adopting research methods that Beck pioneered half a century ago. The cognitive model of depression has explanatory power for both maintenance and vulnerability and has substantial research underpinning it. Cognitive therapy for depression has a larger body of evidence for its efficacy and relapse prevention effect than any other psychotherapy. Transference-focused approaches to depression have yet to establish themselves in the same way. PMID:29018552

Half-Truths on the Half Shell.

ERIC Educational Resources Information Center

White, Randy Wayne

1993-01-01

Recounts the author's experiences investigating the oyster fisheries off the panhandle of Florida. Describes the life of an oyster fisherman whose business has declined because of media claims of fishery contamination, and discusses those claims with an environmental administrator, a university professor, and a biologist. (MDH)

The Cost of Uncertain Life Span*

PubMed Central

Edwards, Ryan D.

2012-01-01

A considerable amount of uncertainty surrounds the length of human life. The standard deviation in adult life span is about 15 years in the U.S., and theory and evidence suggest it is costly. I calibrate a utility-theoretic model of preferences over length of life and show that one fewer year in standard deviation is worth about half a mean life year. Differences in the standard deviation exacerbate cross-sectional differences in life expectancy between the U.S. and other industrialized countries, between rich and poor countries, and among poor countries. Accounting for the cost of life-span variance also appears to amplify recently discovered patterns of convergence in world average human well-being. This is partly for methodological reasons and partly because unconditional variance in human length of life, primarily the component due to infant mortality, has exhibited even more convergence than life expectancy. PMID:22368324

Technical and economic assessments of storage techniques for long-term retention of industrial-beet sugar for non-food industrial fermentations

NASA Astrophysics Data System (ADS)

Vargas-Ramirez, Juan Manuel

Industrial beets may compete against corn grain as an important source of sugars for non-food industrial fermentations. However, dependable and energy-efficient systems for beet sugar storage and processing are necessary to help establish industrial beets as a viable sugar feedstock. Therefore, technical and economic aspects of beet sugar storage and processing were evaluated. First, sugar retention was evaluated in whole beets treated externally with either one of two antimicrobials or a senescence inhibitor and stored for 36 wk at different temperature and atmosphere combinations. Although surface treatment did not improve sugar retention, full retention was enabled by beet dehydration caused by ambient air at 25 °C and with a relative humidity of 37%. This insight led to the evaluation of sugar retention in ground-beet tissue ensiled for 8 wk at different combinations of acidic pH, moisture content (MC), and sugar:solids. Some combinations of pH ≤ 4.0 and MC ≤ 67.5% enabled retentions of at least 90%. Yeast fermentability was also evaluated in non-purified beet juice acidified to enable long-term storage and partially neutralized before fermentation. None of the salts synthesized through juice acidification and partial neutralization inhibited yeast fermentation at the levels evaluated in that work. Conversely, yeast fermentation rates significantly improved in the presence of ammonium salts, which appeared to compensate for nitrogen deficiencies. Capital and operating costs for production and storage of concentrated beet juice for an ethanol plant with a production capacity of 76 x 106 L y-1 were estimated on a dry-sugar basis as U.S. ¢34.0 kg-1 and ¢2.2 kg-1, respectively. Storage and processing techniques evaluated thus far prove that industrial beets are a technically-feasible sugar feedstock for ethanol production.

High performance p-type half-Heusler thermoelectric materials

NASA Astrophysics Data System (ADS)

Yu, Junjie; Xia, Kaiyang; Zhao, Xinbing; Zhu, Tiejun

2018-03-01

Half-Heusler compounds, which possess robust mechanical strength, good high temperature thermal stability and multifaceted physical properties, have been verified as a class of promising thermoelectric materials. During the last two decades, great progress has been made in half-Heusler thermoelectrics. In this review, we summarize some representative work of p-type half-Heusler materials, the thermoelectric performance of which has been remarkably enhanced in recent years. We introduce the features of the crystal and electronic structures of half-Heusler compounds, and successful strategies for optimizing electrical and thermal transport in the p-type RFeSb (R  =  V, Nb, Ta) and MCoSb (M  =  Ti, Zr, Hf) based systems, including band engineering, the formation of solid solutions and hierarchical phonon scattering. The outlook for future research directions of half-Heusler thermoelectrics is also presented.

Intelligibility in microbial complex systems: Wittgenstein and the score of life

PubMed Central

Baquero, Fernando; Moya, Andrés

2012-01-01

Knowledge in microbiology is reaching an extreme level of diversification and complexity, which paradoxically results in a strong reduction in the intelligibility of microbial life. In our days, the “score of life” metaphor is more accurate to express the complexity of living systems than the classic “book of life.” Music and life can be represented at lower hierarchical levels by music scores and genomic sequences, and such representations have a generational influence in the reproduction of music and life. If music can be considered as a representation of life, such representation remains as unthinkable as life itself. The analysis of scores and genomic sequences might provide mechanistic, phylogenetic, and evolutionary insights into music and life, but not about their real dynamics and nature, which is still maintained unthinkable, as was proposed by Wittgenstein. As complex systems, life or music is composed by thinkable and only showable parts, and a strategy of half-thinking, half-seeing is needed to expand knowledge. Complex models for complex systems, based on experiences on trans-hierarchical integrations, should be developed in order to provide a mixture of legibility and imageability of biological processes, which should lead to higher levels of intelligibility of microbial life. PMID:22919679

The association between substantiated childhood maltreatment, asthma and lung function: A prospective investigation.

PubMed

Abajobir, Amanuel Alemu; Kisely, Steve; Williams, Gail; Strathearn, Lane; Suresh, Sadasivam; Najman, Jake Moses

2017-10-01

Asthma reflects multiple and likely complex causal pathways. We investigate the possibility that childhood maltreatment is one such causal pathway. Childhood maltreatment can be interpreted as a form of early life adversity and like other life adversities may predict a range of negative health outcomes, including asthma. A total of 3762 young adults (52.63% female) from the Mater Hospital-University of Queensland Study of Pregnancy (MUSP) participated in this study. MUSP is a prospective Australian birth cohort study of mothers consecutively recruited during their first antenatal clinic visit at Brisbane's Mater Hospital from 1981 to 1983. The study followed both mother-child dyads to the age of 21years after birth. Participants reported whether they had been diagnosed by a physician with asthma by the 21-year follow-up. Trained research assistants also performed gender- and height-standardized lung function tests using a Spirobank G spirometer system attached to a laptop computer. We linked this dataset with data obtained from the child protection services and which comprised all substantiated cases of childhood maltreatment in the MUSP cohort. Substantiations of childhood maltreatment included children in an age range of 0-14years. The experience of any childhood maltreatment, particularly emotional abuse, was independently associated with self-reported physician-diagnosed asthma by the 21-year follow-up. The association was no longer significant after adjustment for a range of confounders and covariates in neglected children. Childhood maltreatment, including multiple events, was not associated with lung function in adjusted models. Childhood maltreatment, including emotional abuse, was associated with lifetime ever asthma. This was in contrast to the absence of an association with objective measures of lung function. More research is indicated on the effect of childhood maltreatment on lung function using objective measures. In the meantime, there should be a

Hyperhidrosis Substantially Reduces Quality of Life in Children: A Retrospective Study Describing Symptoms, Consequences and Treatment with Botulinum Toxin.

PubMed

Mirkovic, Sandra Eriksson; Rystedt, Alma; Balling, Mie; Swartling, Carl

2018-01-12

Studies on children with hyperhidrosis are sparse. This retrospective study presents clinical data and quality of life, along with treatment effect and safety of botulinum toxin (BTX). Case reports from 366 children were included to capture the medical history of hyperhidrosis. The total median score of the Dermatology Life Quality Index before treatment was 11 for children aged 16-17 years and 12 for children younger than 16 years. The children described physical, psychosocial and consequence-related symptoms. More than 70% had multifocal hyperhidrosis. BTX-A and/or BTX-B were given to 323 children, 193 of whom received repeated treatments. The highest score in a 5-grade scale concerning treatment effect was reported by 176/193 children, i.e. their "sweating disappeared completely". No severe adverse events occurred. Focal and multifocal hyperhidrosis in children reduces quality of life considerably. Treatment with BTX-A and/or BTX-B has been performed with success.

Core-protective half-metallicity in trilayer graphene nanoribbons

NASA Astrophysics Data System (ADS)

Jeon, Gi Wan; Lee, Kyu Won; Lee, Cheol Eui

2017-07-01

Half-metals, playing an important role in spintronics, can be described as materials that enable fully spin-polarized electrical current. Taking place in graphene-based materials, half-metallicity has been shown in zigzag-edged graphene nanoribbons (ZGNRs) under an electric field. Localized electron states on the edge carbons are a key to enabling half-metallicity in ZGNRs. Thus, modification of the localized electron states is instrumental to the carbon-based spintronics. Our simple model shows that in a trilayer ZGNRs (triZGNRs) only the middle layer may become half-metallic leaving the outer layers insulating in an electric field, as confirmed by our density functional theory (DFT) calculations. Due to the different circumstances of the edge carbons, the electron energies at the edge carbons are different near the Fermi level, leading to a layer-selective half-metallicity. We believe that triZGNRs can be the tiniest electric cable (nanocable) form and can open a route to graphene-based spintronics applications.

Nonlinear instability of half-solitons on star graphs

NASA Astrophysics Data System (ADS)

Kairzhan, Adilbek; Pelinovsky, Dmitry E.

2018-06-01

We consider a half-soliton stationary state of the nonlinear Schrödinger equation with the power nonlinearity on a star graph consisting of N edges and a single vertex. For the subcritical power nonlinearity, the half-soliton state is a degenerate critical point of the action functional under the mass constraint such that the second variation is nonnegative. By using normal forms, we prove that the degenerate critical point is a saddle point, for which the small perturbations to the half-soliton state grow slowly in time resulting in the nonlinear instability of the half-soliton state. The result holds for any N ≥ 3 and arbitrary subcritical power nonlinearity. It gives a precise dynamical characterization of the previous result of Adami et al. (2012) [2], where the half-soliton state was shown to be a saddle point of the action functional under the mass constraint for N = 3 and for cubic nonlinearity.

24 CFR 902.79 - Substantial default.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Substantial default. 902.79 Section 902.79 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR PUBLIC AND INDIAN HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT...

19 CFR 134.35 - Articles substantially changed by manufacture.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 1 2012-04-01 2012-04-01 false Articles substantially changed by manufacture. 134...; DEPARTMENT OF THE TREASURY COUNTRY OF ORIGIN MARKING Exceptions to Marking Requirements § 134.35 Articles substantially changed by manufacture. (a) Articles other than goods of a NAFTA country. An article used in the...

19 CFR 134.35 - Articles substantially changed by manufacture.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Articles substantially changed by manufacture. 134...; DEPARTMENT OF THE TREASURY COUNTRY OF ORIGIN MARKING Exceptions to Marking Requirements § 134.35 Articles substantially changed by manufacture. (a) Articles other than goods of a NAFTA country. An article used in the...

19 CFR 134.35 - Articles substantially changed by manufacture.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 1 2011-04-01 2011-04-01 false Articles substantially changed by manufacture. 134...; DEPARTMENT OF THE TREASURY COUNTRY OF ORIGIN MARKING Exceptions to Marking Requirements § 134.35 Articles substantially changed by manufacture. (a) Articles other than goods of a NAFTA country. An article used in the...

The Social and Recreational Characteristics of Adults with Intellectual Disability and Pica Living in Institutions

ERIC Educational Resources Information Center

Ashworth, Melody; Hirdes, John P.; Martin, Lynn

2009-01-01

This paper reports on the social life of adults with intellectual disability (ID) who engage in pica behaviour (i.e., ingestion of non-food items). Secondary analyses were conducted on the population of adults residing in Ontario's three remaining specialized institutions for persons with ID (N = 1008); 220 individuals (21.8%) had pica. All…

29 CFR 825.218 - Substantial and grievous economic injury.

Code of Federal Regulations, 2013 CFR

2013-07-01

... sustained. If the reinstatement of a key employee threatens the economic viability of the firm, that would... 29 Labor 3 2013-07-01 2013-07-01 false Substantial and grievous economic injury. 825.218 Section... Medical Leave Act § 825.218 Substantial and grievous economic injury. (a) In order to deny restoration to...

29 CFR 825.218 - Substantial and grievous economic injury.

Code of Federal Regulations, 2014 CFR

2014-07-01

... sustained. If the reinstatement of a key employee threatens the economic viability of the firm, that would... 29 Labor 3 2014-07-01 2014-07-01 false Substantial and grievous economic injury. 825.218 Section... Medical Leave Act § 825.218 Substantial and grievous economic injury. (a) In order to deny restoration to...

The crowded life is a slow life: Population density and life history strategy.

PubMed

Sng, Oliver; Neuberg, Steven L; Varnum, Michael E W; Kenrick, Douglas T

2017-05-01

The world population has doubled over the last half century. Yet, research on the psychological effects of human population density, once a popular topic, has decreased over the past few decades. Applying a fresh perspective to an old topic, we draw upon life history theory to examine the effects of population density. Across nations and across the U.S. states (Studies 1 and 2), we find that dense populations exhibit behaviors corresponding to a slower life history strategy, including greater future-orientation, greater investment in education, more long-term mating orientation, later marriage age, lower fertility, and greater parental investment. In Studies 3 and 4, experimentally manipulating perceptions of high density led individuals to become more future-oriented. Finally, in Studies 5 and 6, experimentally manipulating perceptions of high density seemed to lead to life-stage-specific slower strategies, with college students preferring to invest in fewer rather than more relationship partners, and an older MTurk sample preferring to invest in fewer rather than more children. This research sheds new insight on the effects of density and its implications for human cultural variation and society at large. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Outlier detection in a new half-circular distribution

NASA Astrophysics Data System (ADS)

Rambli, Adzhar; Mohamed, Ibrahim Bin; Shimizu, Kunio; Khalidin, Nurliza

2015-10-01

In this paper, we use a discordancy test based on spacing theory to detect outlier in a half-circular data. Up to now, numerous discordancy tests have been proposed to detect outlier in circular distributions which are defined in [0,2π). However, some circular data lie within just half of this range. Therefore, first we introduce a new half-circular distribution developed using the inverse stereographic projection technique on a gamma distributed variable. Then, we develop a new discordancy test to detect single or multiple outliers in the half-circular data based on the spacing theory. We show the practical value of the test by applying it to an eye data set obtained from a glaucoma clinic at the University of Malaya Medical Centre, Malaysia.

29 CFR 825.218 - Substantial and grievous economic injury.

Code of Federal Regulations, 2012 CFR

2012-07-01

... sustained. If the reinstatement of a “key employee” threatens the economic viability of the firm, that would... 29 Labor 3 2012-07-01 2012-07-01 false Substantial and grievous economic injury. 825.218 Section... Medical Leave Act § 825.218 Substantial and grievous economic injury. (a) In order to deny restoration to...

29 CFR 825.218 - Substantial and grievous economic injury.

Code of Federal Regulations, 2011 CFR

2011-07-01

... sustained. If the reinstatement of a “key employee” threatens the economic viability of the firm, that would... 29 Labor 3 2011-07-01 2011-07-01 false Substantial and grievous economic injury. 825.218 Section... Medical Leave Act § 825.218 Substantial and grievous economic injury. (a) In order to deny restoration to...

Half Sinful Words: Disguised Grief in "Ulysses."

ERIC Educational Resources Information Center

Hobbs, Michael

As a shrewd technician of the language, A. L. Tennyson rightly understood that words are not controllable; they do not always obey rules. As Tennyson said, words "half reveal and half conceal the soul within." In "Ulysses," the title character's speech to his fellow mariners--where he attempts to explain why he has decided to…

Sleep, Cognition, and Normal Aging: Integrating a Half-Century of Multidisciplinary Research

PubMed Central

Scullin, Michael K.; Bliwise, Donald L.

2014-01-01

Sleep is implicated in cognitive functioning in young adults. With increasing age there are substantial changes to sleep quantity and quality including changes to slow wave sleep, spindle density, and sleep continuity/fragmentation. A provocative question for the field of cognitive aging is whether such changes in sleep physiology affect cognition (e.g., memory consolidation). We review nearly a half-century of research studies across 7 diverse correlational and experimental literature domains, which historically have had little crosstalk. Broadly speaking, sleep and cognitive functions are often related in advancing age, though the prevalence of null effects (including correlations in the unexpected, negative direction) in healthy older adults indicates that age may be an effect modifier of these associations. We interpret the literature as suggesting that maintaining good sleep quality, at least in young adulthood and middle age, promotes better cognitive functioning and serves to protect against age-related cognitive declines. PMID:25620997

Early-life disruption of amphibian microbiota decreases later-life resistance to parasites.

PubMed

Knutie, Sarah A; Wilkinson, Christina L; Kohl, Kevin D; Rohr, Jason R

2017-07-20

Changes in the early-life microbiota of hosts might affect infectious disease risk throughout life, if such disruptions during formative times alter immune system development. Here, we test whether an early-life disruption of host-associated microbiota affects later-life resistance to infections by manipulating the microbiota of tadpoles and challenging them with parasitic gut worms as adults. We find that tadpole bacterial diversity is negatively correlated with parasite establishment in adult frogs: adult frogs that had reduced bacterial diversity as tadpoles have three times more worms than adults without their microbiota manipulated as tadpoles. In contrast, adult bacterial diversity during parasite exposure is not correlated with parasite establishment in adult frogs. Thus, in this experimental setup, an early-life disruption of the microbiota has lasting reductions on host resistance to infections, which is possibly mediated by its effects on immune system development. Our results support the idea that preventing early-life disruption of host-associated microbiota might confer protection against diseases later in life.Early-life microbiota alterations can affect infection susceptibility later in life, in animal models. Here, Knutie et al. show that manipulating the microbiota of tadpoles leads to increased susceptibility to parasitic infection in adult frogs, in the absence of substantial changes in the adults' microbiota.

Sometimes Getting There Is Half the Fun

ERIC Educational Resources Information Center

Hanlon, Kerri

2008-01-01

Vacations for exceptional families require flexibility, persistence, a sense of humor, and a view of the world as the glass being half full. In this article, the author shares her family's summer vacation experience. If "getting there is half the fun," the author's family has had more than their share of fun times. She has learned the…

Are Global and Regional Improvements in Life Expectancy and in Child, Adult and Senior Survival Slowing?

PubMed Central

Hum, Ryan J.; Verguet, Stéphane; Cheng, Yu-Ling; McGahan, Anita M.; Jha, Prabhat

2015-01-01

Improvements in life expectancy have been considerable over the past hundred years. Forecasters have taken to applying historical trends under an assumption of continuing improvements in life expectancy in the future. A linear mixed effects model was used to estimate the trends in global and regional rates of improvements in life expectancy, child, adult, and senior survival, in 166 countries between 1950 and 2010. Global improvements in life expectancy, including both child and adult survival rates, decelerated significantly over the study period. Overall life expectancy gains were estimated to have declined from 5.9 to 4.0 months per year for a mean deceleration of -0.07 months/year2; annual child survival gains declined from 4.4 to 1.6 deaths averted per 1000 for a mean deceleration of -0.06 deaths/1000/year2; adult survival gains were estimated to decline from 4.8 to 3.7 deaths averted per 1000 per year for a mean deceleration of -0.08 deaths/1000/year2. Senior survival gains however increased from 2.4 to 4.2 deaths averted per 1000 per year for an acceleration of 0.03 deaths/1000/year2. Regional variation in the four measures was substantial. The rates of global improvements in life expectancy, child survival, and adult survival have declined since 1950 despite an increase in the rate of improvements among seniors. We postulate that low-cost innovation, related to the last half-century progress in health–primarily devoted to children and middle age, is reaping diminishing returns on its investments. Trends are uneven across regions and measures, which may be due in part to the state of epidemiological transition between countries and regions and disparities in the diffusion of innovation, accessible only in high-income countries where life expectancy is already highest. PMID:25992949

20 CFR 404.1572 - What we mean by substantial gainful activity.

Code of Federal Regulations, 2011 CFR

2011-04-01

... work activity that involves doing significant physical or mental activities. Your work may be... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false What we mean by substantial gainful activity... Activity § 404.1572 What we mean by substantial gainful activity. Substantial gainful activity is work...

20 CFR 416.972 - What we mean by substantial gainful activity.

Code of Federal Regulations, 2011 CFR

2011-04-01

... work activity that involves doing significant physical or mental activities. Your work may be... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false What we mean by substantial gainful activity... Activity § 416.972 What we mean by substantial gainful activity. Substantial gainful activity is work...

20 CFR 416.972 - What we mean by substantial gainful activity.

Code of Federal Regulations, 2010 CFR

2010-04-01

... work activity that involves doing significant physical or mental activities. Your work may be... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What we mean by substantial gainful activity... Activity § 416.972 What we mean by substantial gainful activity. Substantial gainful activity is work...

20 CFR 404.1572 - What we mean by substantial gainful activity.

Code of Federal Regulations, 2010 CFR

2010-04-01

... work activity that involves doing significant physical or mental activities. Your work may be... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What we mean by substantial gainful activity... Activity § 404.1572 What we mean by substantial gainful activity. Substantial gainful activity is work...

21 CFR 514.4 - Substantial evidence.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUG APPLICATIONS General Provisions § 514.4 Substantial evidence... adequate and well-controlled studies, such as a study in a target species, study in laboratory animals... effectiveness of the new animal drug involved that the new animal drug will have the effect it purports or is...

21 CFR 514.4 - Substantial evidence.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUG APPLICATIONS General Provisions § 514.4 Substantial evidence... adequate and well-controlled studies, such as a study in a target species, study in laboratory animals... effectiveness of the new animal drug involved that the new animal drug will have the effect it purports or is...

21 CFR 514.4 - Substantial evidence.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUG APPLICATIONS General Provisions § 514.4 Substantial evidence... adequate and well-controlled studies, such as a study in a target species, study in laboratory animals... effectiveness of the new animal drug involved that the new animal drug will have the effect it purports or is...

21 CFR 514.4 - Substantial evidence.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUG APPLICATIONS General Provisions § 514.4 Substantial evidence... adequate and well-controlled studies, such as a study in a target species, study in laboratory animals... effectiveness of the new animal drug involved that the new animal drug will have the effect it purports or is...

21 CFR 514.4 - Substantial evidence.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUG APPLICATIONS General Provisions § 514.4 Substantial evidence... adequate and well-controlled studies, such as a study in a target species, study in laboratory animals... effectiveness of the new animal drug involved that the new animal drug will have the effect it purports or is...

Improved half-metallic gap of zincblende half-metal superlattices with the Tran-Blaha modified Becke-Johnson density functional

NASA Astrophysics Data System (ADS)

Guo, San-Dong

2016-08-01

Binary transition-metal pnictides and chalcogenides half-metallic ferromagnetic materials with zincblende structure, being compatible with current semiconductor technology, can be used to make high-performance spintronic devices. Here, we investigate electronic structures and magnetic properties of composite structure ((CrX)2 /(YX)2 (X=As, Sb; Se, Te and Y=Ga; Zn) superlattices) of zincblende half-metallic ferromagnetism and semiconductor by using Tran and Blaha's modified Becke and Johnson (mBJ) exchange potential. Calculated results show that they all are half-metallic ferromagnets with both generalized gradient approximation (GGA) and mBJ, and the total magnetic moment per formula unit follows a Slater-Pauling-like "rule of 8". The key half-metallic gaps by using mBJ are enhanced with respect to GGA results, which is because mBJ makes the occupied minority-spin p-bands move toward lower energy, but toward higher energy for empty minority-spin Cr-d bands. When the spin-orbit coupling (SOC) is included, the spin polarization deviates from 100%, and a most reduced polarization of 98.3% for (CrSb)2 /(GaSb)2, which indicates that SOC has small effects, of the order of 1%, in the considered four kinds of superlattice.

Transgender Youth and Life-Threatening Behaviors

ERIC Educational Resources Information Center

Grossman, Arnold H.; D'Augelli, Anthony R.

2007-01-01

Sexual minority status is a key risk factor for suicide among lesbian, gay, and bisexual youth; however, it has not been studied among transgender youth. Fifty-five transgender youth reported on their life-threatening behaviors. Nearly half of the sample reported having seriously thought about taking their lives and one quarter reported suicide…

Online Farsi digit recognition using their upper half structure

NASA Astrophysics Data System (ADS)

Ghods, Vahid; Sohrabi, Mohammad Karim

2015-03-01

In this paper, we investigated the efficiency of upper half Farsi numerical digit structure. In other words, half of data (upper half of the digit shapes) was exploited for the recognition of Farsi numerical digits. This method can be used for both offline and online recognition. Half of data is more effective in speed process, data transfer and in this application accuracy. Hidden Markov model (HMM) was used to classify online Farsi digits. Evaluation was performed by TMU dataset. This dataset contains more than 1200 samples of online handwritten Farsi digits. The proposed method yielded more accuracy in recognition rate.

Determination of life for a polyimide-epoxy alternator insulation system

NASA Technical Reports Server (NTRS)

Penn, W. B.; Schaefer, R. F.; Balke, R. L.

1974-01-01

Tests were conducted to predict remaining electrical insulation life of a polyimide epoxy insulated 60 KW, 208 volt homopolar inductor alternator, following completion of 23,130 hours of turbo-alternator endurance tests. The sectioned armature winding of this alternator stator was used as means to evaluate and measure end-life at several aging temperatures for development of an Arrhenius plot. A one-half life rate of 11.3 C was established from these data with a predicted remaining life of 60,000 hours at an armature winding temperature of 248 C and a total life, including endurance test time, of 61,645 hours.

77 FR 11482 - Notice of Revision and Request for Extension of Approval of an Information Collection...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

... Nonfood Animal and Poultry Products and Byproducts Into the United States AGENCY: Animal and Plant Health... regulations for restricted and controlled importation of nonfood animal and poultry products and byproducts...: For information on restricted and controlled importation of nonfood animal and poultry products and...

Life Skills-Based HIV Education: Some Virtues and Errors

ERIC Educational Resources Information Center

Clarke, David; Yankah, Ekua; Aggleton, Peter

2015-01-01

Since the early 1990s, life skills education has benefitted substantially from international agency advocacy and support, linked to its implementation in several countries as a key component of the education sector response to sexual health and HIV. The concept of life skills was first promoted by the World Health Organization through its…

Establishing Substantial Equivalence: Proteomics

NASA Astrophysics Data System (ADS)

Lovegrove, Alison; Salt, Louise; Shewry, Peter R.

Wheat is a major crop in world agriculture and is consumed after processing into a range of food products. It is therefore of great importance to determine the consequences (intended and unintended) of transgenesis in wheat and whether genetically modified lines are substantially equivalent to those produced by conventional plant breeding. Proteomic analysis is one of several approaches which can be used to address these questions. Two-dimensional PAGE (2D PAGE) remains the most widely available method for proteomic analysis, but is notoriously difficult to reproduce between laboratories. We therefore describe methods which have been developed as standard operating procedures in our laboratory to ensure the reproducibility of proteomic analyses of wheat using 2D PAGE analysis of grain proteins.

Preventive Interventions for the Second Half of Life: A Systematic Review.

PubMed

Hajat, Cother; Selwyn, Adriana; Harris, Mark; Yach, Derek

2018-05-01

Recent improvements in life expectancy globally require intensified focus on noncommunicable diseases and age-related conditions. The purpose of this article is to inform the development of age-specific prevention guidelines for adults aged 50 and above, which are currently lacking. PubMed, Cochrane database, and Google Scholar and explicit outreach to experts in the field. Meta-analyses, intervention-based, and prospective cohort studies that reported all-cause mortality, disease-specific mortality, or morbidity in adults were included. A systematic review was undertaken in 2015 using search terms of a combination of and "intervention," "mortality," "reduction," "improvement," "death," and "morbidity." Interventions were categorized according to the Center for Evidence-Based Medicine Level of Evidence framework. A summary table reports for each intervention the impact, strength of evidence, initiation, duration, and details of the intervention. Age-decade-specific preventive recommendations have been proposed relating to physical activity, diet, tobacco and alcohol use, medication adherence, screening and vaccination, and mental and cognitive health. Clear recommendations have been made according to the existing evidence base, but further research investment is needed to fill the many gaps. Further, personalized approaches to healthy aging complemented by population-wide approaches and broader cross-sector partnerships will help to ensure greater longevity is an opportunity, rather than a burden, for society.

Fat Content Modulates Rapid Detection of Food: A Visual Search Study Using Fast Food and Japanese Diet

PubMed Central

Sawada, Reiko; Sato, Wataru; Toichi, Motomi; Fushiki, Tohru

2017-01-01

Rapid detection of food is crucial for the survival of organisms. However, previous visual search studies have reported discrepant results regarding the detection speeds for food vs. non-food items; some experiments showed faster detection of food than non-food, whereas others reported null findings concerning any speed advantage for the detection of food vs. non-food. Moreover, although some previous studies showed that fat content can affect visual attention for food, the effect of fat content on the detection of food remains unclear. To investigate these issues, we measured reaction times (RTs) during a visual search task in which participants with normal weight detected high-fat food (i.e., fast food), low-fat food (i.e., Japanese diet), and non-food (i.e., kitchen utensils) targets within crowds of non-food distractors (i.e., cars). Results showed that RTs for food targets were shorter than those for non-food targets. Moreover, the RTs for high-fat food were shorter than those for low-fat food. These results suggest that food is more rapidly detected than non-food within the environment and that a higher fat content in food facilitates rapid detection. PMID:28690568

Fat Content Modulates Rapid Detection of Food: A Visual Search Study Using Fast Food and Japanese Diet.

PubMed

Sawada, Reiko; Sato, Wataru; Toichi, Motomi; Fushiki, Tohru

2017-01-01

Rapid detection of food is crucial for the survival of organisms. However, previous visual search studies have reported discrepant results regarding the detection speeds for food vs. non-food items; some experiments showed faster detection of food than non-food, whereas others reported null findings concerning any speed advantage for the detection of food vs. non-food. Moreover, although some previous studies showed that fat content can affect visual attention for food, the effect of fat content on the detection of food remains unclear. To investigate these issues, we measured reaction times (RTs) during a visual search task in which participants with normal weight detected high-fat food (i.e., fast food), low-fat food (i.e., Japanese diet), and non-food (i.e., kitchen utensils) targets within crowds of non-food distractors (i.e., cars). Results showed that RTs for food targets were shorter than those for non-food targets. Moreover, the RTs for high-fat food were shorter than those for low-fat food. These results suggest that food is more rapidly detected than non-food within the environment and that a higher fat content in food facilitates rapid detection.

Lack of Substantial Post-Cessation Weight Increase in Electronic Cigarettes Users.

PubMed

Russo, Cristina; Cibella, Fabio; Mondati, Enrico; Caponnetto, Pasquale; Frazzetto, Evelise; Caruso, Massimo; Caci, Grazia; Polosa, Riccardo

2018-03-23

Minimization of post-cessation weight gain in quitters is important, but existing approaches (e.g., antismoking medications) shows only limited success. We investigated changes in body weight in smokers who quit or reduced substantially their cigarette consumption by switching to electronic cigarettes (ECs) use. Body weight and smoking/vaping history were extracted from medical records of smokers and ex-smokers to match three study groups: (1) regular EC users on at least two consecutive follow-up visits; (2) regular smokers (and not using ECs); (3) subjects who reported sustained smoking abstinence after completing a cessation program. Review of their medical records was conducted at two follow-up visits at 6- (F/U 6m) and 12-months (F/U 12m). A total of 86 EC users, 93 regular smokers, and 44 quitters were studied. In the EC users study group, cigarettes/day use decreased from 21.1 at baseline to 1.8 at F/U 12m ( p < 0.0001). Dual usage was reported by approximately 50% of EC users. Both within factor (time, p < 0.0001) and between factor (study groups, p < 0.0001) produced significant effect on weight (% change from baseline), with a significant 4.8% weight gain from baseline in the quitters study group at F/U 12m. For the EC users, weight gain at F/U 12m was only 1.5% of baseline. There was no evidence of post-cessation weight increase in those who reduced substantially cigarette consumption by switching to ECs (i.e., dual users) and only modest post-cessation weight increase was reported in exclusive EC users at F/U 12m. By reducing weight gain and tobacco consumption, EC-based interventions may promote an overall improvement in quality of life.

Engineering half-Heusler thermoelectric materials using Zintl chemistry

NASA Astrophysics Data System (ADS)

Zeier, Wolfgang G.; Schmitt, Jennifer; Hautier, Geoffroy; Aydemir, Umut; Gibbs, Zachary M.; Felser, Claudia; Snyder, G. Jeffrey

2016-06-01

Half-Heusler compounds based on XNiSn and XCoSb (X = Ti, Zr or Hf) have rapidly become important thermoelectric materials for converting waste heat into electricity. In this Review, we provide an overview on the electronic properties of half-Heusler compounds in an attempt to understand their basic structural chemistry and physical properties, and to guide their further development. Half-Heusler compounds can exhibit semiconducting transport behaviour even though they are described as ‘intermetallic’ compounds. Therefore, it is most useful to consider these systems as rigid-band semiconductors within the framework of Zintl (or valence-precise) compounds. These considerations aid our understanding of their properties, such as the bandgap and low hole mobility because of interstitial Ni defects in XNiSn. Understanding the structural and bonding characteristics, including the presence of defects, will help to develop different strategies to improve and design better half-Heusler thermoelectric materials.

Life Goals in Patients with Cancer: A Systematic Review of the Literature

PubMed Central

Hullmann, Stephanie E.; Robb, Sheri L.; Rand, Kevin L.

2015-01-01

Objective Purposes of this systematic review of life goal research in cancer patients were to: 1) identify life goal characteristics and processes being examined, 2) describe instruments used to assess life goal constructs, 3) identify theoretical models being used to guide research, and 4) summarize what is known about the impact of the cancer experience on life goal characteristics, processes, and psychological outcomes. Methods We conducted this systematic review using MEDLINE, PubMed, CINAHL, and PsycINFO databases. Inclusion criteria were: 1) published between 1993 and 2014, 2) English language, 3) cancer patient population, and 4) original research articles that assessed life goal characteristics and/or goal processes. One-hundred ninety-seven articles were screened and 27 included in the final review. Results Seven life goal characteristics and seven life goal processes were identified, and less than half of studies investigated associations between goal characteristics and processes. Conceptual definitions were not provided for about half of the identified life goal constructs. Studies used both validated and author-developed instruments to assess goal constructs. Twenty-four different theoretical models were identified, with self-regulation theory most frequently cited. Overall, the literature suggests that cancer impacts patients’ life goal characteristics and processes, and life goal disturbance is related to poorer psychological outcomes. Conclusions The impact of the cancer experience on life goals is an important and emerging area of research that would benefit from conceptual and theoretical clarity and measurement consistency. PMID:25990641

LibHalfSpace: A C++ object-oriented library to study deformation and stress in elastic half-spaces

NASA Astrophysics Data System (ADS)

Ferrari, Claudio; Bonafede, Maurizio; Belardinelli, Maria Elina

2016-11-01

The study of deformation processes in elastic half-spaces is widely employed for many purposes (e.g. didactic, scientific investigation of real processes, inversion of geodetic data, etc.). We present a coherent programming interface containing a set of tools designed to make easier and faster the study of processes in an elastic half-space. LibHalfSpace is presented in the form of an object-oriented library. A set of well known and frequently used source models (Mogi source, penny shaped horizontal crack, inflating spheroid, Okada rectangular dislocation, etc.) are implemented to describe the potential usage and the versatility of the library. The common interface given to library tools enables us to switch easily among the effects produced by different deformation sources that can be monitored at the free surface. Furthermore, the library also offers an interface which simplifies the creation of new source models exploiting the features of object-oriented programming (OOP). These source models can be built as distributions of rectangular boundary elements. In order to better explain how new models can be deployed some examples are included in the library.

LCIA framework and cross-cutting issues guidance within the UNEP/SETAC Life Cycle Initiative

EPA Science Inventory

Increasing needs for decision support and advances in scientific knowledge within life cycle assessment (LCA) led to substantial efforts to provide global guidance on environmental life cycle impact assessment (LCIA) indicators under the auspices of the UNEP-SETAC Life Cycle Init...

Acylated heptapeptide binds albumin with high affinity and application as tag furnishes long-acting peptides

NASA Astrophysics Data System (ADS)

Zorzi, Alessandro; Middendorp, Simon J.; Wilbs, Jonas; Deyle, Kaycie; Heinis, Christian

2017-07-01

The rapid renal clearance of peptides in vivo limits this attractive platform for the treatment of a broad range of diseases that require prolonged drug half-lives. An intriguing approach for extending peptide circulation times works through a `piggy-back' strategy in which peptides bind via a ligand to the long-lived serum protein albumin. In accordance with this strategy, we developed an easily synthesized albumin-binding ligand based on a peptide-fatty acid chimera that has a high affinity for human albumin (Kd=39 nM). This ligand prolongs the elimination half-life of cyclic peptides in rats 25-fold to over seven hours. Conjugation to a peptide factor XII inhibitor developed for anti-thrombotic therapy extends the half-life from 13 minutes to over five hours, inhibiting coagulation for eight hours in rabbits. This high-affinity albumin ligand could potentially extend the half-life of peptides in human to several days, substantially broadening the application range of peptides as therapeutics.

Assessing the difference of tolerance and phytoremediation potential in mercury contaminated soil of a non-food energy crop, Helianthus tuberosus L. (Jerusalem artichoke).

PubMed

Lv, Shiqi; Yang, Bin; Kou, Yixuan; Zeng, Jun; Wang, Ruixiong; Xiao, Yumeng; Li, Fencan; Lu, Ying; Mu, Yuwen; Zhao, Changming

2018-01-01

This study was conducted to evaluate the effects of mercury stress on growth, photosynthesis and mercury accumulation in different cultivars of a non-food energy crop, Jerusalem artichoke, and to screen appropriate cultivars for their efficacy in the phytoremediation of mercury (Hg 2+ ) contaminated soil. Cultivars LZJ033 (high above-ground biomass and nutrient content, and strongly sexual reproduction) and LZJ119 (a long period of vegetative growth) exhibited more tolerance to mercury stress than LZJ047 (the highest tuber yield and total sugar content). The lines LZJ119 and LZJ047 showed delays in emergence time of about four weeks, and LZJ047 exhibited the highest mortality rate, 85.19%, under treatment with 10 mg kg -1 mercury. The MDA (malondialdehyde) content increased whereas and the P n (net photosynthetic rate), F v ∕ F m (the maximum quantum yield of PSII photochemistry) and chlorophyll content decreased in response to mercury stress. The stem diameter, stem biomass and photosynthetic rate of Jerusalem artichoke showed some modest increases in response to mercury stress and exhibited hormesis at least 1 mg kg -1 mercury treatment. Overall, LZJ119 produced more biomass under mercury stress, whereas LZJ033 exhibited a greater capacity for mercury bioaccumulation. Accordingly, LZJ119 may be a good candidate cultivar for use in cases of moderate-low mercury contamination, whereas LZJ033 may be a better candidate under conditions of high mercury contamination. When Jerusalem artichoke was cultivated in mercury contaminated soil, it not only removed the mercury from soil but also produced large amounts of tubers and shoots which could be used as feedstock for the production of bioethanol.

Assessing the difference of tolerance and phytoremediation potential in mercury contaminated soil of a non-food energy crop, Helianthus tuberosus L. (Jerusalem artichoke)

PubMed Central

Lv, Shiqi; Yang, Bin; Kou, Yixuan; Zeng, Jun; Wang, Ruixiong; Xiao, Yumeng; Li, Fencan; Lu, Ying; Mu, Yuwen

2018-01-01

This study was conducted to evaluate the effects of mercury stress on growth, photosynthesis and mercury accumulation in different cultivars of a non-food energy crop, Jerusalem artichoke, and to screen appropriate cultivars for their efficacy in the phytoremediation of mercury (Hg2+) contaminated soil. Cultivars LZJ033 (high above-ground biomass and nutrient content, and strongly sexual reproduction) and LZJ119 (a long period of vegetative growth) exhibited more tolerance to mercury stress than LZJ047 (the highest tuber yield and total sugar content). The lines LZJ119 and LZJ047 showed delays in emergence time of about four weeks, and LZJ047 exhibited the highest mortality rate, 85.19%, under treatment with 10 mg kg-1 mercury. The MDA (malondialdehyde) content increased whereas and the Pn (net photosynthetic rate), Fv∕Fm (the maximum quantum yield of PSII photochemistry) and chlorophyll content decreased in response to mercury stress. The stem diameter, stem biomass and photosynthetic rate of Jerusalem artichoke showed some modest increases in response to mercury stress and exhibited hormesis at least 1 mg kg-1 mercury treatment. Overall, LZJ119 produced more biomass under mercury stress, whereas LZJ033 exhibited a greater capacity for mercury bioaccumulation. Accordingly, LZJ119 may be a good candidate cultivar for use in cases of moderate—low mercury contamination, whereas LZJ033 may be a better candidate under conditions of high mercury contamination. When Jerusalem artichoke was cultivated in mercury contaminated soil, it not only removed the mercury from soil but also produced large amounts of tubers and shoots which could be used as feedstock for the production of bioethanol. PMID:29404218

Online Vape Shop Customers Who Use E-Cigarettes Report Abstinence from Smoking and Improved Quality of Life, But a Substantial Minority Still Have Vaping-Related Health Concerns

PubMed Central

Van Gucht, Dinska; Adriaens, Karolien; Baeyens, Frank

2017-01-01

(1) Background: Characteristics and usage patterns of vapers (e-cigarette users) have mainly been studied in web-based convenience samples or in visitors of brick-and-mortar vape shops. We extended this by targeting customers of one particular online vape shop in the Netherlands; (2) Methods: Customers were questioned on their smoking history, current smoking and vaping status, reasons for vaping, perceived harmfulness, and potential health changes due to vaping; (3) Results: Almost everyone (99%, 95% CI 0.96, 1.00) smoked before they started vaping. A great majority agreed that unlike with other smoking-cessation aids, they could quit smoking (81%, 95% CI 0.79, 0.90) due to vaping. Almost all customers were regular vapers (93.6%, 95% CI 0.89, 0.96) who used state-of-the-art open system devices without modifications and e-liquid with 10 mg/mL nicotine on average. Vapers reported using e-cigs to quit smoking, because e-cigs are healthier, and for financial reasons. The majority (52.6%, 95% CI 0.46, 0.60) perceived vaping as not that harmful to not harmful at all, but one fifth (21.8%, 95% CI 0.16, 0.28) believed vaping to be harmful. More than half (57.8%, 95% CI 0.50, 0.65) reported gaining more pleasure from vaping than from smoking. A substantial majority (84.2%, 95% CI 0.78, 0.89) agreed that their health had improved since they started vaping; (4) Conclusions: Findings are similar to those obtained in other vape shop studies, but also to the results of convenience samples of less-well-defined populations. PMID:28714914

Online Vape Shop Customers Who Use E-Cigarettes Report Abstinence from Smoking and Improved Quality of Life, But a Substantial Minority Still Have Vaping-Related Health Concerns.

PubMed

Gucht, Dinska Van; Adriaens, Karolien; Baeyens, Frank

2017-07-17

(1) Background: Characteristics and usage patterns of vapers (e-cigarette users) have mainly been studied in web-based convenience samples or in visitors of brick-and-mortar vape shops. We extended this by targeting customers of one particular online vape shop in the Netherlands; (2) Methods: Customers were questioned on their smoking history, current smoking and vaping status, reasons for vaping, perceived harmfulness, and potential health changes due to vaping; (3) Results: Almost everyone (99%, 95% CI 0.96, 1.00) smoked before they started vaping. A great majority agreed that unlike with other smoking-cessation aids, they could quit smoking (81%, 95% CI 0.79, 0.90) due to vaping. Almost all customers were regular vapers (93.6%, 95% CI 0.89, 0.96) who used state-of-the-art open system devices without modifications and e-liquid with 10 mg/mL nicotine on average. Vapers reported using e-cigs to quit smoking, because e-cigs are healthier, and for financial reasons. The majority (52.6%, 95% CI 0.46, 0.60) perceived vaping as not that harmful to not harmful at all , but one fifth (21.8%, 95% CI 0.16, 0.28) believed vaping to be harmful. More than half (57.8%, 95% CI 0.50, 0.65) reported gaining more pleasure from vaping than from smoking. A substantial majority (84.2%, 95% CI 0.78, 0.89) agreed that their health had improved since they started vaping; (4) Conclusions: Findings are similar to those obtained in other vape shop studies, but also to the results of convenience samples of less-well-defined populations.

Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial

PubMed Central

Griffiths, Roland R; Johnson, Matthew W; Carducci, Michael A; Umbricht, Annie; Richards, William A; Richards, Brian D; Cosimano, Mary P; Klinedinst, Margaret A

2016-01-01

Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes. Trial Registration ClinicalTrials.gov identifier: NCT00465595 PMID:27909165

Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial.

PubMed

Griffiths, Roland R; Johnson, Matthew W; Carducci, Michael A; Umbricht, Annie; Richards, William A; Richards, Brian D; Cosimano, Mary P; Klinedinst, Margaret A

2016-12-01

Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes. ClinicalTrials.gov identifier: NCT00465595. © The Author(s) 2016.

40 CFR 158.2174 - Experimental use permit microbial pesticides nontarget organisms and environmental fate data...

Code of Federal Regulations, 2014 CFR

2014-07-01

..., residential, and industrial). Terrestrial uses include: Food, Feed, Non-Food, Forestry, Residential outdoor, greenhouse (food and food), Indoor (food and nonfood), and Industrial. (c) Key. R=Required; CR=Conditionally... Indoor Food/Nonfood Industrial Test Substance Test Notes 885.4050 Avian oraltoxicity NR R R R R NR NR NR...

40 CFR 158.2174 - Experimental use permit microbial pesticides nontarget organisms and environmental fate data...

Code of Federal Regulations, 2013 CFR

2013-07-01

..., residential, and industrial). Terrestrial uses include: Food, Feed, Non-Food, Forestry, Residential outdoor, greenhouse (food and food), Indoor (food and nonfood), and Industrial. (c) Key. R=Required; CR=Conditionally... Indoor Food/Nonfood Industrial Test Substance Test Notes 885.4050 Avian oraltoxicity NR R R R R NR NR NR...

40 CFR 158.2174 - Experimental use permit microbial pesticides nontarget organisms and environmental fate data...

Code of Federal Regulations, 2012 CFR

2012-07-01

..., residential, and industrial). Terrestrial uses include: Food, Feed, Non-Food, Forestry, Residential outdoor, greenhouse (food and food), Indoor (food and nonfood), and Industrial. (c) Key. R=Required; CR=Conditionally... Indoor Food/Nonfood Industrial Test Substance Test Notes 885.4050 Avian oraltoxicity NR R R R R NR NR NR...

Predictive Variables of Half-Marathon Performance for Male Runners

PubMed Central

Gómez-Molina, Josué; Ogueta-Alday, Ana; Camara, Jesus; Stickley, Christoper; Rodríguez-Marroyo, José A.; García-López, Juan

2017-01-01

The aims of this study were to establish and validate various predictive equations of half-marathon performance. Seventy-eight half-marathon male runners participated in two different phases. Phase 1 (n = 48) was used to establish the equations for estimating half-marathon performance, and Phase 2 (n = 30) to validate these equations. Apart from half-marathon performance, training-related and anthropometric variables were recorded, and an incremental test on a treadmill was performed, in which physiological (VO2max, speed at the anaerobic threshold, peak speed) and biomechanical variables (contact and flight times, step length and step rate) were registered. In Phase 1, half-marathon performance could be predicted to 90.3% by variables related to training and anthropometry (Equation 1), 94.9% by physiological variables (Equation 2), 93.7% by biomechanical parameters (Equation 3) and 96.2% by a general equation (Equation 4). Using these equations, in Phase 2 the predicted time was significantly correlated with performance (r = 0.78, 0.92, 0.90 and 0.95, respectively). The proposed equations and their validation showed a high prediction of half-marathon performance in long distance male runners, considered from different approaches. Furthermore, they improved the prediction performance of previous studies, which makes them a highly practical application in the field of training and performance. Key points The present study obtained four equations involving anthropometric, training, physiological and biomechanical variables to estimate half-marathon performance. These equations were validated in a different population, demonstrating narrows ranges of prediction than previous studies and also their consistency. As a novelty, some biomechanical variables (i.e. step length and step rate at RCT, and maximal step length) have been related to half-marathon performance. PMID:28630571

Life stress and risk of precancerous cervical lesions: a pretest directed by the life stress model.

PubMed

Lovejoy, N C; Roche, N; McLean, D

1997-01-01

To present the results of a pilot study to pretest instruments designed to measure selected variables named in the Life Stress Model, a model of health outcomes. Additional aims were to determine the effect of completing personal risk assessments for precancerous squamous-cell intraepithelial lesions of the cervic (SIL) on receptivity to cervical cancer prevention information and to extend knowledge of stressful life events experienced by inner-city women attending high-risk health clinics. Cross-sectional. 20 adult women attending high-risk prenatal or human immunodeficiency virus (HIV) outpatient clinics in one of two New York City hospitals. Most were recovering drugs abusers; half were diagnosed with HIV infections. Data were collected by self-report using standard measures. Demographics, medical histories of immunosuppressive states, and investigator-developed screening inventories of behavioral and dietary risk factors associated with SIL also were administered. Life event stressors, psychological state, social support, symptom distress, and SIL diagnosis. Instruments met acceptable psychometric standards for internal consistency, but the standard measure of stressful life events did not capture the full range of stressors experienced by this group of patients: hovering relatives, abusive spouses, HIV diagnosis, changes in welfare benefits, the HIV status of the unborn, and mandatory foster care. Although unable to recall cancer histories of family members, about half of the women who completed study instruments were interested in receiving more information cervical cancer. Exploratory analyses suggest that women diagnosed with SIL experience more psychological distress and family disfunction than women without SIL. Completing personal SIL risk assessments may stimulate patients' receptivity to cancer risk factor information. Health outcomes studies guided by the Life Stress Model may prove fruitful. Cancer risk factor assessments may be an important method

Conceptual Principles of Quality of Life: An Empirical Exploration

ERIC Educational Resources Information Center

Bramston, P.; Chipuer, H.; Pretty, G.

2005-01-01

Background: Quality of life is a popular measure of outcomes and its widespread use has led to recent calls for a better understanding of the construct, emphasizing the need to build a substantial body of knowledge around what determines perceptions of life quality. Three widely reported and used conceptual principles are examined in this study.…

26 CFR 1.42-7 - Substantially bond-financed buildings. [Reserved

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Substantially bond-financed buildings. [Reserved] 1.42-7 Section 1.42-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY INCOME TAX INCOME TAXES Credits Against Tax § 1.42-7 Substantially bond-financed buildings. [Reserved] ...

Predictive Variables of Half-Marathon Performance for Male Runners.

PubMed

Gómez-Molina, Josué; Ogueta-Alday, Ana; Camara, Jesus; Stickley, Christoper; Rodríguez-Marroyo, José A; García-López, Juan

2017-06-01

The aims of this study were to establish and validate various predictive equations of half-marathon performance. Seventy-eight half-marathon male runners participated in two different phases. Phase 1 (n = 48) was used to establish the equations for estimating half-marathon performance, and Phase 2 (n = 30) to validate these equations. Apart from half-marathon performance, training-related and anthropometric variables were recorded, and an incremental test on a treadmill was performed, in which physiological (VO 2max , speed at the anaerobic threshold, peak speed) and biomechanical variables (contact and flight times, step length and step rate) were registered. In Phase 1, half-marathon performance could be predicted to 90.3% by variables related to training and anthropometry (Equation 1), 94.9% by physiological variables (Equation 2), 93.7% by biomechanical parameters (Equation 3) and 96.2% by a general equation (Equation 4). Using these equations, in Phase 2 the predicted time was significantly correlated with performance (r = 0.78, 0.92, 0.90 and 0.95, respectively). The proposed equations and their validation showed a high prediction of half-marathon performance in long distance male runners, considered from different approaches. Furthermore, they improved the prediction performance of previous studies, which makes them a highly practical application in the field of training and performance.

{beta}-decay half-lives of new neutron-rich rare-earth isotopes {sup 159}Pm,{sup 162}Sm, and {sup 166}Gd

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

Ichikawa, S.; Asai, M.; Tsukada, K.

The new neutron-rich rare-earth isotopes {sup 159}Pm, {sup 162}Sm, and {sup 166}Gd produced in the proton-induced fission of {sup 238}U were identified using the JAERI on-line isotope separator (JAERI-ISOL) coupled to a gas-jet transport system. The half-lives of {sup 159}Pm, {sup 162}Sm, and {sup 166}Gd were determined to be 1.5 {+-} 0.2, 2.4 {+-} 0.5, and 4.8 {+-} 1.0 s respectively. The partial decay scheme of {sup 166}Gd was constructed from {gamma}{gamma}-coincidence data. A more accurate half-life value of 25.6 {+-} 2.2 s was obtained for the previously identified isotope {sup 166}Tb. The half-lives measured in the present study aremore » in good agreement with the theoretical predictions calculated by the second generation of the gross theory with the atomic masses evaluated by Audi and Wapstra.« less

Computational investigation of half-Heusler compounds for spintronics applications

NASA Astrophysics Data System (ADS)

Ma, Jianhua; Hegde, Vinay I.; Munira, Kamaram; Xie, Yunkun; Keshavarz, Sahar; Mildebrath, David T.; Wolverton, C.; Ghosh, Avik W.; Butler, W. H.

2017-01-01

We present first-principles density functional calculations of the electronic structure, magnetism, and structural stability of 378 XYZ half-Heusler compounds (with X = Cr, Mn, Fe, Co, Ni, Ru, Rh; Y = Ti, V, Cr, Mn, Fe, Ni; Z = Al, Ga, In, Si, Ge, Sn, P, As, Sb). We find that a "Slater-Pauling gap" in the density of states (i.e., a gap or pseudogap after nine states in the three atom primitive cell) in at least one spin channel is a common feature in half-Heusler compounds. We find that the presence of such a gap at the Fermi energy in one or both spin channels contributes significantly to the stability of a half-Heusler compound. We calculate the formation energy of each compound and systematically investigate its stability against all other phases in the open quantum materials database (OQMD). We represent the thermodynamic phase stability of each compound as its distance from the convex hull of stable phases in the respective chemical space and show that the hull distance of a compound is a good measure of the likelihood of its experimental synthesis. We find low formation energies and mostly correspondingly low hull distances for compounds with X = Co, Rh, or Ni, Y = Ti or V, and Z = P, As, Sb, or Si. We identify 26 18-electron semiconductors, 45 half-metals, and 34 near half-metals with negative formation energy that follow the Slater-Pauling rule of three electrons per atom. Our calculations predict several new, as-yet unknown, thermodynamically stable phases, which merit further experimental exploration—RuVAs, CoVGe, FeVAs in the half-Heusler structure, and NiScAs, RuVP, RhTiP in the orthorhombic MgSrSi-type structure. Further, two interesting zero-moment half-metals, CrMnAs and MnCrAs, are calculated to have negative formation energy. In addition, our calculations predict a number of hitherto unreported semiconducting (e.g., CoVSn and RhVGe), half-metallic (e.g., RhVSb), and near half-metallic (e.g., CoFeSb and CoVP) half-Heusler compounds to lie close to

Waste recycling issues in bioregenerative life support

NASA Technical Reports Server (NTRS)

Macelroy, R. D.; Wang, D.

1989-01-01

Research and technology development issues centering on the recycling of materials within a bioregenerative life support system are reviewed. The importance of recovering waste materials for subsequent use is emphasized. Such material reclamation will substantially decrease the energy penalty paid for bioregenerative life support systems, and can potentially decrease the size of the system and its power demands by a significant amount. Reclamation of fixed nitrogen and the sugars in cellulosic materials is discussed.

Work-life balance and welfare.

PubMed

Evans, Lois; Young, Greg

2017-04-01

An online survey and focus groups were conducted, providing qualitative information on the work-life balance of psychiatrists and trainees in Australasia. An invitation to participate in an anonymous online welfare survey was emailed to all the Royal Australian and New Zealand College of Psychiatrists trainees, Fellows, and Affiliates. Following this, nine focus groups were held across Australia and New Zealand. Responses received were thematically analysed. The emergent patterns are presented in this report. Our research suggests that work-life balance can be subjectively and objectively measured. There are phases of good and bad work-life balance, depending on stage of career and other commitments. Work-life balance may be an indicator of the health of individuals and organisations. Due to its complexity, with intrinsic and extrinsic factors involved, solutions are unlikely to be simple. Further studies are needed to substantiate our findings.

Time scale dependence of the center of pressure entropy: What characteristics of the neuromuscular postural control system influence stabilographic entropic half-life?

PubMed

Federolf, Peter; Zandiyeh, Payam; von Tscharner, Vinzenz

2015-12-01

The center of pressure (COP) movement in studies of postural control reveals a highly regular structure (low entropy) over short time periods and a highly irregular structure over large time scales (high entropy). Entropic half-life (EnHL) is a novel measure that quantifies the time over which short-term temporal correlations in a time series deteriorate to an uncorrelated, random structure. The current study suggested and tested three hypotheses about how characteristics of the neuromuscular postural control system may affect stabilometric EnHL: (H1) control system activity hypothesis: EnHL decreases with increased frequency of control system interventions adjusting COP motion; (H2) abundance of states hypothesis: EnHL decreases with increased number of mechanically equivalent states available to the postural system; and (H3) neurologic process hierarchy hypothesis: EnHL increases if postural control functions shift from the spinal level to the motor cortex. Thirty healthy participants performed quiet stance tests for 90 s in 18 different conditions: stance (bipedal, one-legged, and tandem); footwear (bare foot, regular sports shoe, and rocker sole shoes); and simultaneous cognitive task (two-back working memory task, no challenge). A four-way repeated-measures ANOVA revealed significant changes in EnHL for the different stance positions and for different movement directions (medio-lateral, anterior-posterior). These changes support H1 and H2. Significant differences were also found between rocker sole shoes and normal or barefoot standing, which supports H3. This study contributes to the understanding of how and why EnHL is a useful measure to monitor neuromuscular control of balance.

Fusion to Human Serum Albumin Extends the Circulatory Half-Life and Duration of Antithrombotic Action of the Kunitz Protease Inhibitor Domain of Protease Nexin 2.

PubMed

Sheffield, William P; Eltringham-Smith, Louise J; Bhakta, Varsha

2018-01-01

The Kunitz Protease Inhibitor (KPI) domain of protease nexin 2 (PN2) potently inhibits coagulation factor XIa. Recombinant KPI has been shown to inhibit thrombosis in mouse models, but its clearance from the murine circulation remains uncharacterized. The present study explored the pharmacokinetic and pharmacodynamic effects of fusing KPI to human serum albumin (HSA) in fusion protein KPIHSA. Hexahistidine-tagged KPI (63 amino acids) and KPIHSA (656 amino acids) were expressed in Pichia pastoris yeast and purified by nickel-chelate chromatography. Clearance profiles in mice were determined, as well as the effects of KPI or KPIHSA administration on FeCl3-induced vena cava thrombus size or carotid artery time to occlusion, respectively. Fusion to HSA increased the mean terminal half-life of KPI by 8-fold and eliminated its interaction with the low density lipoprotein receptor-related protein. KPI and KPIHSA similarly reduced thrombus size and occlusion in both venous and arterial thrombosis models when administered at the time of injury, but only KPI was effective when administered one hour before injury. Albumin fusion deflects KPI from rapid in vivo clearance without impairing its antithrombotic properties and widens its potential therapeutic window. © 2018 The Author(s). Published by S. Karger AG, Basel.

Fuel from Tobacco and Arundo Donax: Synthetic Crop for Direct Drop-in Biofuel Production through Re-routing the Photorespiration Intermediates and Engineering Terpenoid Pathways

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

None

PETRO Project: Biofuels offer renewable alternatives to petroleum-based fuels that reduce net greenhouse gas emissions to nearly zero. However, traditional biofuels production is limited not only by the small amount of solar energy that plants convert through photosynthesis into biological materials, but also by inefficient processes for converting these biological materials into fuels. Farm-ready, non-food crops are needed that produce fuels or fuel-like precursors at significantly lower costs with significantly higher productivity. To make biofuels cost-competitive with petroleum-based fuels, biofuels production costs must be cut in half.

Half-lives of 221Fr, 217At, 213Bi, 213Po and 209Pb from the 225Ac decay series.

PubMed

Suliman, G; Pommé, S; Marouli, M; Van Ammel, R; Stroh, H; Jobbágy, V; Paepen, J; Dirican, A; Bruchertseifer, F; Apostolidis, C; Morgenstern, A

2013-07-01

The half-lives of (221)Fr, (217)At, (213)Bi, (213)Po, and (209)Pb were measured by means of an ion-implanted planar Si detector for alpha and beta particles emitted from weak (225)Ac sources or from recoil sources, which were placed in a quasi-2π counting geometry. Recoil sources were prepared by collecting atoms from an open (225)Ac source onto a glass substrate. The (221)Fr and (213)Bi half-lives were determined by following the alpha particle emission rate of recoil sources as a function of time. Similarly, the (209)Pb half-life was determined from the beta particle count rate. The shorter half-lives of (217)At and (213)Po were deduced from delayed coincidence measurements on weak (225)Ac sources using digital data acquisition in list mode. The resulting values: T1/2((221)Fr)=4.806 (6) min, T1/2((217)At)=32.8 (3)ms, T1/2((213)Bi)=45.62 (6)min, T1/2((213)Po)=3.708 (8) μs, and T1/2((209)Pb)=3.232 (5)h were in agreement only with the best literature data. Copyright © 2013 Elsevier Ltd. All rights reserved.

Assessment of the Maximal Split-Half Coefficient to Estimate Reliability

ERIC Educational Resources Information Center

Thompson, Barry L.; Green, Samuel B.; Yang, Yanyun

2010-01-01

The maximal split-half coefficient is computed by calculating all possible split-half reliability estimates for a scale and then choosing the maximal value as the reliability estimate. Osburn compared the maximal split-half coefficient with 10 other internal consistency estimates of reliability and concluded that it yielded the most consistently…

Forecasting Spanish natural life expectancy.

PubMed

Guillen, Montserrat; Vidiella-i-Anguera, Antoni

2005-10-01

Knowledge of trends in life expectancy is of major importance for policy planning. It is also a key indicator for assessing future development of life insurance products, substantiality of existing retirement schemes, and long-term care for the elderly. This article examines the feasibility of decomposing age-gender-specific accidental and natural mortality rates. We study this decomposition by using the Lee and Carter model. In particular, we fit the Poisson log-bilinear version of this model proposed by Wilmoth and Brouhns et al. to historical (1975-1998) Spanish mortality rates. In addition, by using the model introduced by Wilmoth and Valkonen we analyze mortality-gender differentials for accidental and natural rates. We present aggregated life expectancy forecasts compared with those constructed using nondecomposed mortality rates.

"Peek-a-Boo. How "Can" You Be There?" Analytic Work with a Severely Traumatised Two-and-a-Half-Year-Old Girl

ERIC Educational Resources Information Center

Strati, Katerina

2010-01-01

This paper traces the analytic work with a severely traumatised two-and-a-half-year-old girl Phoebe, whose early life was marked by chronic abuse and a violent murder she witnessed a few months prior to the beginning of treatment. Bringing the trauma in the room in a dissociative form, in line with post-traumatic stress disorder presentation, was…

Half-State Readout In Vertical-Bloch-Line Memory

NASA Technical Reports Server (NTRS)

Katti, Romney R.; Wu, Jiin-Chuan; Stadler, Henry L.

1994-01-01

Potentially narrow margins of chirality-based chopping of magnetic stripes avoided. Half-state readout is experimental method of readout in Vertical-Bloch-Line (VBL) memory. Based on differential deflections of magnetic stripe domains in which data bits stored. To give meaning to explanation of half-state readout, see "Vertical-Bloch-Line Memory" (NPO-18467).

Large rainfall changes consistently projected over substantial areas of tropical land

NASA Astrophysics Data System (ADS)

Chadwick, Robin; Good, Peter; Martin, Gill; Rowell, David P.

2016-02-01

Many tropical countries are exceptionally vulnerable to changes in rainfall patterns, with floods or droughts often severely affecting human life and health, food and water supplies, ecosystems and infrastructure. There is widespread disagreement among climate model projections of how and where rainfall will change over tropical land at the regional scales relevant to impacts, with different models predicting the position of current tropical wet and dry regions to shift in different ways. Here we show that despite uncertainty in the location of future rainfall shifts, climate models consistently project that large rainfall changes will occur for a considerable proportion of tropical land over the twenty-first century. The area of semi-arid land affected by large changes under a higher emissions scenario is likely to be greater than during even the most extreme regional wet or dry periods of the twentieth century, such as the Sahel drought of the late 1960s to 1990s. Substantial changes are projected to occur by mid-century--earlier than previously expected--and to intensify in line with global temperature rise. Therefore, current climate projections contain quantitative, decision-relevant information on future regional rainfall changes, particularly with regard to climate change mitigation policy.

Sex- and age-related differences in half-marathon performance and competitiveness in the world's largest half-marathon - the GöteborgsVarvet.

PubMed

Knechtle, B; Nikolaidis, P T

2018-01-01

In road runners, the age-related performance decline has been well investigated for marathoners, but little is known for half-marathoners. We analysed data from 138,616 runners (48,148 women and 90,469 men) competing between 2014 and 2016 in GöteborgsVarvet, the world's largest half-marathon. The men-to-women ratio in participants increased with age, the fastest race times were observed in age groups ˂35 and 35-39 years in women and in age group 35-39 years in men, the main effect of sex and the sex × age group interaction on race time were trivial, and the competitiveness was denser in men and in the younger age groups. In summary, in half-marathon running in the largest half-marathon in the world, the GöteborgsVarvet, women achieved the fastest race time at an earlier age compared to men where the fastest race times were observed in women in age groups ˂35 and 35-39 years and in men in age group 35-39 years.

The Quality of Life in China

ERIC Educational Resources Information Center

Shu, Xiaoling; Zhu, Yifei

2009-01-01

The Asia Barometer Survey of 2,000 respondents reveals that substantial majorities of the Chinese people experience feelings of happiness, enjoyment, and accomplishment. In fact, the proportion experiencing these indicators of a high quality of life are larger in China than in some more prosperous countries. Favorable historical comparison,…

"End-of-Life Care? I'm not Going to Worry About That Yet." Health Literacy Gaps and End-of-Life Planning Among Elderly Dialysis Patients.

PubMed

Ladin, Keren; Buttafarro, Katie; Hahn, Emily; Koch-Weser, Susan; Weiner, Daniel E

2018-03-19

Between 2000 and 2012, the incident dialysis population in the United States increased by nearly 60%, most sharply among adults 75 years and older. End-of-life (EOL) conversations among dialysis patients are associated with better patient-centered outcomes and lower use of aggressive interventions in the last month of life. This study examined how health literacy may affect engagement, comprehension, and satisfaction with EOL conversations among elderly dialysis patients. Qualitative/descriptive study with semi-structured interviews about health literacy, EOL conversations, and goals of care with 31 elderly dialysis patients at 2 centers in Boston. Themes were interpreted in the context of Nutbeam's health literacy framework. Despite high mortality risk in this population, only 13% of patients had discussed EOL preferences with physicians, half had discussed EOL with their social network, and 25% of participants explicitly stated that they had never considered EOL preferences. Less than 30% of participants could correctly define terminology commonly used in EOL conversations. Analyses yielded 5 themes: (1) Misunderstanding EOL terminology; (2) Nephrologists reluctant to discuss EOL; (3) Patients conforming to socially constructed roles; (4) Discordant expectations and dialysis experiences; and (5) Reconciling EOL values and future care. Patients had limited understanding of EOL terminology, lacked of opportunities for meaningful EOL discussion with providers and family, resulting in uncertainty about future care. Limited health literacy presents a substantial barrier to communication and could lead to older adults committing to an intensive pattern of care without adequate information. Clinicians should consider health literacy when discussing dialysis initiation.

Displacement field for an edge dislocation in a layered half-space

USGS Publications Warehouse

Savage, J.C.

1998-01-01

The displacement field for an edge dislocation in an Earth model consisting of a layer welded to a half-space of different material is found in the form of a Fourier integral following the method given by Weeks et al. [1968]. There are four elementary solutions to be considered: the dislocation is either in the half-space or the layer and the Burgers vector is either parallel or perpendicular to the layer. A general two-dimensional solution for a dip-slip faulting or dike injection (arbitrary dip) can be constructed from a superposition of these elementary solutions. Surface deformations have been calculated for an edge dislocation located at the interface with Burgers vector inclined 0??, 30??, 60??, and 90?? to the interface for the case where the rigidity of the layer is half of that of the half-space and the Poisson ratios are the same. Those displacement fields have been compared to the displacement fields generated by similarly situated edge dislocations in a uniform half-space. The surface displacement field produced by the edge dislocation in the layered half-space is very similar to that produced by an edge dislocation at a different depth in a uniform half-space. In general, a low-modulus (high-modulus) layer causes the half-space equivalent dislocation to appear shallower (deeper) than the actual dislocation in the layered half-space.

Skill Acquisition and Use across the Life Course: Current Trends, Future Prospects

ERIC Educational Resources Information Center

Martin, Bill

2007-01-01

People's life pathways are no longer as predictable as they were in the second half of the 20th century. It is no longer as simple as moving from school to work, probably via tertiary education, to living independently, then getting married and starting a family. Changes in how people combine education with life-course transitions will influence…

Method of sealing an ultracapacitor substantially free of water

DOEpatents

Chapman-Irwin, Patricia; Feist, Thomas Paul

2002-04-02

A method of sealing an ultracapacitor substantially free of water is disclosed. The method includes providing a multilayer cell comprising two solid, non porous current collectors, separated by two porous electrodes with a separator between the two electrodes, sealing the cell with a reclosable hermetic closure. Water inside the closure is dissociated by an applied voltage to the cell and escapes in the form of hydrogen and oxygen when the closure is unmated, the closure is then mated to hermetically seal the cell which is substantially free of water.

Toward More Substantial Theories of Language Acquisition

ERIC Educational Resources Information Center

Jenson, Cinnamon Ann

2015-01-01

Cognitive linguists argue that certain sets of knowledge of language are innate. However, critics have argued that the theoretical concept of "innateness" should be eliminated since it is ambiguous and insubstantial. In response, I aim to strengthen theories of language acquisition and identify ways to make them more substantial. I…

Determining the Economic Feasibility of Using Produced Water for Agriculture in Colorado Through Life Cycle Cost Analyses

NASA Astrophysics Data System (ADS)

Dolan, F.; Blaine, A. C.; Hogue, T. S.

2016-12-01

To combat the need for new sources of water in Colorado, the current research looks to produced water as a potential source. Produced water, the water produced alongside oil and gas in a well, is currently viewed as a high-volume waste product; however, this water can potentially be used to irrigate food or non-food crops after treatment. Kern County in California has been using produced water for this purpose for over 20 years and a town in Colorado has followed suit. Our research seeks to determine how Wellington, CO overcame economic, legal, social, and technological barriers in order to put produced water to beneficial use. Life cycle cost analyses of produced water in three counties in Colorado are conducted to determine the economic feasibility of using produced water for irrigation on a broad scale. The current study is chosen based on the quality and quantity of the region's produced water as well as the need for new sources of water within the county. The results of this research will help in the transition between viewing produced water as a waste product and using it as a tool to help secure Colorado's water future.

Life Goals Matter to Happiness: A Revision of Set-Point Theory

ERIC Educational Resources Information Center

Headey, Bruce

2008-01-01

Using data from the long-running German Socio-Economic Panel Survey (SOEP), this paper provides evidence that life goals matter substantially to subjective well-being (SWB). Non-zero sum goals, which include commitment to family, friends and social and political involvement, promote life satisfaction. Zero sum goals, including commitment to career…

Changes in Burnout and Satisfaction With Work-Life Balance in Physicians and the General US Working Population Between 2011 and 2014.

PubMed

Shanafelt, Tait D; Hasan, Omar; Dyrbye, Lotte N; Sinsky, Christine; Satele, Daniel; Sloan, Jeff; West, Colin P

2015-12-01

To evaluate the prevalence of burnout and satisfaction with work-life balance in physicians and US workers in 2014 relative to 2011. From August 28, 2014, to October 6, 2014, we surveyed both US physicians and a probability-based sample of the general US population using the methods and measures used in our 2011 study. Burnout was measured using validated metrics, and satisfaction with work-life balance was assessed using standard tools. Of the 35,922 physicians who received an invitation to participate, 6880 (19.2%) completed surveys. When assessed using the Maslach Burnout Inventory, 54.4% (n=3680) of the physicians reported at least 1 symptom of burnout in 2014 compared with 45.5% (n=3310) in 2011 (P<.001). Satisfaction with work-life balance also declined in physicians between 2011 and 2014 (48.5% vs 40.9%; P<.001). Substantial differences in rates of burnout and satisfaction with work-life balance were observed by specialty. In contrast to the trends in physicians, minimal changes in burnout or satisfaction with work-life balance were observed between 2011 and 2014 in probability-based samples of working US adults, resulting in an increasing disparity in burnout and satisfaction with work-life balance in physicians relative to the general US working population. After pooled multivariate analysis adjusting for age, sex, relationship status, and hours worked per week, physicians remained at an increased risk of burnout (odds ratio, 1.97; 95% CI, 1.80-2.16; P<.001) and were less likely to be satisfied with work-life balance (odds ratio, 0.68; 95% CI, 0.62-0.75; P<.001). Burnout and satisfaction with work-life balance in US physicians worsened from 2011 to 2014. More than half of US physicians are now experiencing professional burnout. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Half wavelength dipole antennas over stratified media

NASA Technical Reports Server (NTRS)

Latorraca, G. A.

1972-01-01

Theoretical solutions of the fields induced by half-wavelength, horizontal, electric field dipoles (HEDS) are determined based on studies of infinitesimal, horizontal, electric field dipoles over low loss plane-stratified media. To determine these solutions, an approximation to the current distribution of a half-wavelength HED is derived and experimentally verified. Traverse and antenna measurements obtained on the Athabasca Glacier in the summer of 1971 are related to the characteristics of the transmitting antenna design, and the measurement techniques and field equipment used in the glacier trials are described and evaluated.

"Then It Will Be Good": Negative Life Events and Resilience in Ugandan Youth

ERIC Educational Resources Information Center

Eggum, Natalie D.; Sallquist, Julie; Eisenberg, Nancy

2011-01-01

Youths (N = 57; mean age = 13.83 years) residing near Tororo, Uganda, were interviewed to obtain quantitative and qualitative data pertaining to negative life events, adjustment problems, coping, social support, self-worth, and hope. On average, they experienced nearly half of the 22 negative life events assessed. The experience of negative life…

Biological Half-Life of Cardiolite[R

ERIC Educational Resources Information Center

Jesse, Kenneth

2008-01-01

I recently had a cardiac stress test. It was my fourth. Its purpose was to determine whether my heart is pumping an adequate quantity of blood during exercise. Additionally, is there a partial arterial blockage or damaged heart muscle? The test involves the patient receiving an injection of Cardiolite[R], a substance containing a molecule to which…

Gettysburg College Takes Work-Life Balance Seriously

ERIC Educational Resources Information Center

Wilson, Robin

2009-01-01

This article describes the work-life benefits Gettysburg College offers its employees. 400 of Gettysburg's 725 full-time employees participate in the college's wellness program. About half of them stick with it long enough to earn discounts of up to $500 a year on their health-insurance premiums. The wellness program--which includes free on-campus…

Half-Metallic Ferromagnetism and Stability of Transition Metal Pnictides and Chalcogenides

NASA Astrophysics Data System (ADS)

Liu, Bang-Gui

It is highly desirable to explore robust half-metallic ferromagnetic materials compatible with important semiconductors for spintronic applications. A state-of-the-art full potential augmented plane wave method within the densityfunctional theory is reliable enough for this purpose. In this chapter we review theoretical research on half-metallic ferromagnetism and structural stability of transition metal pnictides and chalcogenides. We show that some zincblende transition metal pnictides are half-metallic and the half-metallic gap can be fairly wide, which is consistent with experiment. Systematic calculations reveal that zincblende phases of CrTe, CrSe, and VTe are excellent half-metallic ferromagnets. These three materials have wide half-metallic gaps, are low in total energy with respect to the corresponding ground-state phases, and, importantly, are structurally stable. Halfmetallic ferromagnetism is also found in wurtzite transition metal pnictides and chalcogenides and in transition-metal doped semiconductors as well as deformed structures. Some of these half-metallic materials could be grown epitaxially in the form of ultrathin .lms or layers suitable for real spintronic applications.