Therapeutic interventions for increasing ankle dorsiflexion after ankle sprain: a systematic review.

Science.gov (United States)

Terada, Masafumi; Pietrosimone, Brian G; Gribble, Phillip A

2013-01-01

Clinicians perform therapeutic interventions, such as stretching, manual therapy, electrotherapy, ultrasound, and exercises, to increase ankle dorsiflexion. However, authors of previous studies have not determined which intervention or combination of interventions is most effective. To determine the magnitude of therapeutic intervention effects on and the most effective therapeutic interventions for restoring normal ankle dorsiflexion after ankle sprain. We performed a comprehensive literature search in Web of Science and EBSCO HOST from 1965 to May 29, 2011, with 19 search terms related to ankle sprain, dorsiflexion, and intervention and by cross-referencing pertinent articles. Eligible studies had to be written in English and include the means and standard deviations of both pretreatment and posttreatment in patients with acute, subacute, or chronic ankle sprains. Outcomes of interest included various joint mobilizations, stretching, local vibration, hyperbaric oxygen therapy, electrical stimulation, and mental-relaxation interventions. We extracted data on dorsiflexion improvements among various therapeutic applications by calculating Cohen d effect sizes with associated 95% confidence intervals (CIs) and evaluated the methodologic quality using the Physiotherapy Evidence Database (PEDro) scale. In total, 9 studies (PEDro score = 5.22 ± 1.92) met the inclusion criteria. Static-stretching interventions with a home exercise program had the strongest effects on increasing dorsiflexion in patients 2 weeks after acute ankle sprains (Cohen d = 1.06; 95% CI = 0.12, 2.42). The range of effect sizes for movement with mobilization on ankle dorsiflexion among individuals with recurrent ankle sprains was small (Cohen d range = 0.14 to 0.39). Static-stretching intervention as a part of standardized care yielded the strongest effects on dorsiflexion after acute ankle sprains. The existing evidence suggests that clinicians need to consider what may be the limiting factor of

Hybrid discrete choice models: Gained insights versus increasing effort

Energy Technology Data Exchange (ETDEWEB)

Mariel, Petr, E-mail: petr.mariel@ehu.es [UPV/EHU, Economía Aplicada III, Avda. Lehendakari Aguire, 83, 48015 Bilbao (Spain); Meyerhoff, Jürgen [Institute for Landscape Architecture and Environmental Planning, Technical University of Berlin, D-10623 Berlin, Germany and The Kiel Institute for the World Economy, Duesternbrooker Weg 120, 24105 Kiel (Germany)

2016-10-15

Hybrid choice models expand the standard models in discrete choice modelling by incorporating psychological factors as latent variables. They could therefore provide further insights into choice processes and underlying taste heterogeneity but the costs of estimating these models often significantly increase. This paper aims at comparing the results from a hybrid choice model and a classical random parameter logit. Point of departure for this analysis is whether researchers and practitioners should add hybrid choice models to their suite of models routinely estimated. Our comparison reveals, in line with the few prior studies, that hybrid models gain in efficiency by the inclusion of additional information. The use of one of the two proposed approaches, however, depends on the objective of the analysis. If disentangling preference heterogeneity is most important, hybrid model seems to be preferable. If the focus is on predictive power, a standard random parameter logit model might be the better choice. Finally, we give recommendations for an adequate use of hybrid choice models based on known principles of elementary scientific inference. - Highlights: • The paper compares performance of a Hybrid Choice Model (HCM) and a classical Random Parameter Logit (RPL) model. • The HCM indeed provides insights regarding preference heterogeneity not gained from the RPL. • The RPL has similar predictive power as the HCM in our data. • The costs of estimating HCM seem to be justified when learning more on taste heterogeneity is a major study objective.

Hybrid discrete choice models: Gained insights versus increasing effort

International Nuclear Information System (INIS)

Mariel, Petr; Meyerhoff, Jürgen

2016-01-01

Hybrid choice models expand the standard models in discrete choice modelling by incorporating psychological factors as latent variables. They could therefore provide further insights into choice processes and underlying taste heterogeneity but the costs of estimating these models often significantly increase. This paper aims at comparing the results from a hybrid choice model and a classical random parameter logit. Point of departure for this analysis is whether researchers and practitioners should add hybrid choice models to their suite of models routinely estimated. Our comparison reveals, in line with the few prior studies, that hybrid models gain in efficiency by the inclusion of additional information. The use of one of the two proposed approaches, however, depends on the objective of the analysis. If disentangling preference heterogeneity is most important, hybrid model seems to be preferable. If the focus is on predictive power, a standard random parameter logit model might be the better choice. Finally, we give recommendations for an adequate use of hybrid choice models based on known principles of elementary scientific inference. - Highlights: • The paper compares performance of a Hybrid Choice Model (HCM) and a classical Random Parameter Logit (RPL) model. • The HCM indeed provides insights regarding preference heterogeneity not gained from the RPL. • The RPL has similar predictive power as the HCM in our data. • The costs of estimating HCM seem to be justified when learning more on taste heterogeneity is a major study objective.

A randomized controlled trial of the therapeutic workplace for community methadone patients: a partial failure to engage.

Science.gov (United States)

Knealing, Todd W; Wong, Conrad J; Diemer, Karly N; Hampton, Jacqueline; Silverman, Kenneth

2006-08-01

The Therapeutic Workplace is an employment-based treatment for drug addiction that uses wages for work to reinforce drug abstinence. The Therapeutic Workplace has promoted abstinence from heroin and cocaine in treatment-resistant mothers in methadone treatment. This study attempted to replicate that effect in crack cocaine users recruited from community-based methadone programs. Participants were randomly assigned to a Therapeutic Workplace (n=22) or usual care control (n=25) group. Therapeutic Workplace participants were invited to work in the workplace and earn vouchers every weekday for 9 months contingent on documented opiate and cocaine abstinence. The two groups did not differ significantly on measures of cocaine or opiate use collected during study participation. Daily attendance and urinalysis results of the Therapeutic Workplace group were analyzed, and only 7 of the 22 participants initiated consistent periods of abstinence and workplace attendance. Two individuals gained access to the workplace on a few days, and 9 participants attempted to gain access to the workplace but never provided a drug-negative urine sample. Possible reasons for differences between the current study and the previous Therapeutic Workplace study are considered. Procedures that increase participant contact with the Therapeutic Workplace and its reinforcement contingencies might increase the likelihood of these individuals being successful in the treatment program.

Dynamic loop gain increases upon adopting the supine body position during sleep in patients with obstructive sleep apnoea.

Science.gov (United States)

Joosten, Simon A; Landry, Shane A; Sands, Scott A; Terrill, Philip I; Mann, Dwayne; Andara, Christopher; Skuza, Elizabeth; Turton, Anthony; Berger, Philip; Hamilton, Garun S; Edwards, Bradley A

2017-11-01

Obstructive sleep apnoea (OSA) is typically worse in the supine versus lateral sleeping position. One potential factor driving this observation is a decrease in lung volume in the supine position which is expected by theory to increase a key OSA pathogenic factor: dynamic ventilatory control instability (i.e. loop gain). We aimed to quantify dynamic loop gain in OSA patients in the lateral and supine positions, and to explore the relationship between change in dynamic loop gain and change in lung volume with position. Data from 20 patients enrolled in previous studies on the effect of body position on OSA pathogenesis were retrospectively analysed. Dynamic loop gain was calculated from routinely collected polysomnographic signals using a previously validated mathematical model. Lung volumes were measured in the awake state with a nitrogen washout technique. Dynamic loop gain was significantly higher in the supine than in the lateral position (0.77 ± 0.15 vs 0.68 ± 0.14, P = 0.012). Supine functional residual capacity (FRC) was significantly lower than lateral FRC (81.0 ± 15.4% vs 87.3 ± 18.4% of the seated FRC, P = 0.021). The reduced FRC we observed on moving to the supine position was predicted by theory to increase loop gain by 10.2 (0.6, 17.1)%, a value similar to the observed increase of 8.4 (-1.5, 31.0)%. Dynamic loop gain increased by a small but statistically significant amount when moving from the lateral to supine position and this may, in part, contribute to the worsening of OSA in the supine sleeping position. © 2017 Asian Pacific Society of Respirology.

Blood Outgrowth Endothelial Cells Increase Tumor Growth Rates and Modify Tumor Physiology: Relevance for Therapeutic Targeting

Energy Technology Data Exchange (ETDEWEB)

Pagan, Jonathan, E-mail: jdpagan@uams.edu; Przybyla, Beata; Jamshidi-Parsian, Azemat [Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Gupta, Kalpna [Vascular Biology Center and Division of Hematology-Oncology Transplantation, Department of Medicine, University of Minnesota Medical School, MN 72223 (United States); Griffin, Robert J. [Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States)

2013-02-18

oxygenation and subsequent radiation response of tumors. We surmise that these cells are preferentially stimulated to divide in the tumor microenvironment, thereby inducing the significant increase in tumor growth observed and that the use of injected BOECs could be a viable approach to modulate the tumor microenvironment for therapeutic gain. Conversely, agents or approaches to block their recruitment and integration of BOECs into primary or metastatic lesions may be an effective way to restrain cancer progression before or after other treatments are applied.

Blood Outgrowth Endothelial Cells Increase Tumor Growth Rates and Modify Tumor Physiology: Relevance for Therapeutic Targeting

International Nuclear Information System (INIS)

Pagan, Jonathan; Przybyla, Beata; Jamshidi-Parsian, Azemat; Gupta, Kalpna; Griffin, Robert J.

2013-01-01

oxygenation and subsequent radiation response of tumors. We surmise that these cells are preferentially stimulated to divide in the tumor microenvironment, thereby inducing the significant increase in tumor growth observed and that the use of injected BOECs could be a viable approach to modulate the tumor microenvironment for therapeutic gain. Conversely, agents or approaches to block their recruitment and integration of BOECs into primary or metastatic lesions may be an effective way to restrain cancer progression before or after other treatments are applied

A reinforcement-based therapeutic workplace for the treatment of drug abuse: three-year abstinence outcomes.

Science.gov (United States)

Silverman, Kenneth; Svikis, Dace; Wong, Conrad J; Hampton, Jacqueline; Stitzer, Maxine L; Bigelow, George E

2002-08-01

Long-term Therapeutic Workplace effects were evaluated in heroin- and cocaine-dependent, unemployed, treatment-resistant young mothers. Participants were paid to work or to train in the Therapeutic Workplace but had to provide drug-free urine samples to gain daily access. Participants (N = 40) were randomly assigned to a Therapeutic Workplace or usual care control group. Therapeutic Workplace participants could work for 3 years. Relative to controls, Therapeutic Workplace participants increased cocaine (28% vs. 54% negative; p = .04) and opiate (37% vs. 60% negative; p = .05) abstinence on the basis of monthly urine samples collected until 3 years after intake. The Therapeutic Workplace can be an effective long-term treatment of cocaine and heroin addiction in poor and chronically unemployed young mothers.

Influences of finite gain bandwidth on pulse propagation in parabolic fiber amplifiers with distributed gain profiles

International Nuclear Information System (INIS)

Zhao Jia-Sheng; Li Pan; Chen Xiao-Dong; Feng Su-Juan; Mao Qing-He

2012-01-01

The evolutions of the pulses propagating in decreasing and increasing gain distributed fiber amplifiers with finite gain bandwidths are investigated by simulations with the nonlinear Schrödinger equation. The results show that the parabolic pulse propagations in both the decreasing and the increasing gain amplifiers are restricted by the finite gain bandwidth. For a given input pulse, by choosing a small initial gain coefficient and gain variation rate, the whole gain for the pulse amplification limited by the gain bandwidth may be higher, which is helpful for the enhancement of the output linearly chirped pulse energy. Compared to the decreasing gain distributed fiber amplifier, the increasing gain distributed amplifier may be more conducive to suppress the pulse spectral broadening and increase the critical amplifier length for achieving a larger output linearly chirped pulse energy

Possibility of Recombination Gain Increase in CV Ions at 4.0 nm Via Coherence

Science.gov (United States)

Luo, Y.; Morozov, A.; Gordon, D.; Sprangle, P.; Svidzinsky, A.; Xia, H.; Scully, M.; Suckewer, S.

This paper is about the recent experimental results on amplification of the CV line in the "water window" at 4.03 nm from resonance transition to the ground level of He-like ions in recombination scheme. The indication of the amplification of the CV line has been observed when an elongated narrow plasma channel was created, where high intensity 100 fs beams, optimal for creating CV ions in high density plasma, was propagated up to 0.5-0.6 mm. Without channeling the effective plasma length was much shorter and there was no indication of amplification.The large interest in gain generation in He-like ions in the transition to ground state is due to the possibility of applying a recently developed theory of Lasing Without Inversion (LWI) in XUV and X-ray regions to largely increase the gain for such transitions. The presented results of the indication of CV line amplifications are being discussed from the point of view of using LWI as a superradiance gain increase, hence to construct a very compact soft X-ray laser in the "water window".The last part of the paper is related to the application of the ultra-intensive fs plasma laser, which is currently in the process of development by using stimulated Raman backscattering (SRBS) to create a plasma amplifier and compressor, as the pump for compact laser operating in the "water window" and also at shorter wavelengths.

Early pair housing increases solid feed intake and weight gains in dairy calves.

Science.gov (United States)

Costa, J H C; Meagher, R K; von Keyserlingk, M A G; Weary, D M

2015-09-01

Dairy calves have traditionally been kept in individual pens throughout the milk-feeding period. Social rearing is associated with increased solid feed intake and, hence, higher weight gains before and after weaning. Little is known about the effect of the age at which social housing begins. The aim of this study was to assess the effects of early versus late pairing on feeding behavior and weight gain before and after weaning. Holstein bull calves were reared individually (n=8 calves) or paired with another calf at 6±3 d (n=8 pairs) or 43±3 d of age (n=8 pairs). All calves were fed 8 L of milk/d for 4 wk, 6 L/d from 4 to 7 wk, and then milk was reduced by 20%/d until calves were completely weaned at 8 wk of age. Calves were provided ad libitumaccess to calf starter and a total mixed ration (TMR). Body weight and feed intake were measured weekly from 3 to 10 wk of age.Intake of calf starter was significantly higher for the early-paired calves than for individually reared and late-paired calves throughout the experimental period. At 10 wk of age, starter dry matter intake averaged 2.20±0.22, 1.09±0.25, and 1.26±0.33kg/d for early-paired, late-paired, and individually housed calves, respectively. Intake of TMR did not differ among treatments, TMR dry matter intake averaged 3.27±0.72, 3.08±0.46, and 2.89±0.54kg/d for the same 3 treatments. Calves in the early paired treatment also showed significantly higher average daily gain over the experimental period (0.89±0.04 vs. 0.76±0.04 and 0.73±0.04kg/d for the early-paired, individual, and late-paired calves, respectively). These results indicate that social housing soon after birth can increase weight gains and intake of solid feed. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Sweet taste of saccharin induces weight gain without increasing caloric intake, not related to insulin-resistance in Wistar rats.

Science.gov (United States)

Foletto, Kelly Carraro; Melo Batista, Bruna Aparecida; Neves, Alice Magagnin; de Matos Feijó, Fernanda; Ballard, Cíntia Reis; Marques Ribeiro, Maria Flávia; Bertoluci, Marcello Casaccia

2016-01-01

In a previous study, we showed that saccharin can induce weight gain when compared with sucrose in Wistar rats despite similar total caloric intake. We now question whether it could be due to the sweet taste of saccharin per se. We also aimed to address if this weight gain is associated with insulin-resistance and to increases in gut peptides such as leptin and PYY in the fasting state. In a 14 week experiment, 16 male Wistar rats received either saccharin-sweetened yogurt or non-sweetened yogurt daily in addition to chow and water ad lib. We measured daily food intake and weight gain weekly. At the end of the experiment, we evaluated fasting leptin, glucose, insulin, PYY and determined insulin resistance through HOMA-IR. Cumulative weight gain and food intake were evaluated through linear mixed models. Results showed that saccharin induced greater weight gain when compared with non-sweetened control (p = 0.027) despite a similar total caloric intake. There were no differences in HOMA-IR, fasting leptin or PYY levels between groups. We conclude that saccharin sweet taste can induce mild weight gain in Wistar rats without increasing total caloric intake. This weight gain was not related with insulin-resistance nor changes in fasting leptin or PYY in Wistar rats. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genetic Gain Increases by Applying the Usefulness Criterion with Improved Variance Prediction in Selection of Crosses.

Science.gov (United States)

Lehermeier, Christina; Teyssèdre, Simon; Schön, Chris-Carolin

2017-12-01

A crucial step in plant breeding is the selection and combination of parents to form new crosses. Genome-based prediction guides the selection of high-performing parental lines in many crop breeding programs which ensures a high mean performance of progeny. To warrant maximum selection progress, a new cross should also provide a large progeny variance. The usefulness concept as measure of the gain that can be obtained from a specific cross accounts for variation in progeny variance. Here, it is shown that genetic gain can be considerably increased when crosses are selected based on their genomic usefulness criterion compared to selection based on mean genomic estimated breeding values. An efficient and improved method to predict the genetic variance of a cross based on Markov chain Monte Carlo samples of marker effects from a whole-genome regression model is suggested. In simulations representing selection procedures in crop breeding programs, the performance of this novel approach is compared with existing methods, like selection based on mean genomic estimated breeding values and optimal haploid values. In all cases, higher genetic gain was obtained compared with previously suggested methods. When 1% of progenies per cross were selected, the genetic gain based on the estimated usefulness criterion increased by 0.14 genetic standard deviation compared to a selection based on mean genomic estimated breeding values. Analytical derivations of the progeny genotypic variance-covariance matrix based on parental genotypes and genetic map information make simulations of progeny dispensable, and allow fast implementation in large-scale breeding programs. Copyright © 2017 by the Genetics Society of America.

Exploring the therapeutic effects of yoga and its ability to increase quality of life

Directory of Open Access Journals (Sweden)

Catherine Woodyard

2011-01-01

Full Text Available The objective of this study is to assess the findings of selected articles regarding the therapeutic effects of yoga and to provide a comprehensive review of the benefits of regular yoga practice. As participation rates in mind-body fitness programs such as yoga continue to increase, it is important for health care professionals to be informed about the nature of yoga and the evidence of its many therapeutic effects. Thus, this manuscript provides information regarding the therapeutic effects of yoga as it has been studied in various populations concerning a multitude of different ailments and conditions. Therapeutic yoga is defined as the application of yoga postures and practice to the treatment of health conditions and involves instruction in yogic practices and teachings to prevent reduce or alleviate structural, physiological, emotional and spiritual pain, suffering or limitations. Results from this study show that yogic practices enhance muscular strength and body flexibility, promote and improve respiratory and cardiovascular function, promote recovery from and treatment of addiction, reduce stress, anxiety, depression, and chronic pain, improve sleep patterns, and enhance overall well-being and quality of life.

Aging increases the susceptibility to motor memory interference and reduces off-line gains in motor skill learning

DEFF Research Database (Denmark)

Roig, Marc; Ritterband-Rosenbaum, Anina; Jensen, Jesper Lundbye

2014-01-01

Declines in the ability to learn motor skills in older adults are commonly attributed to deficits in the encoding of sensorimotor information during motor practice. We investigated whether aging also impairs motor memory consolidation by assessing the susceptibility to memory interference and off...... greater susceptibility to memory interference and no off-line gains in motor skill learning. Performing B produced memory interference and reduced off-line gains only in the older group. However, older adults also showed deficits in memory consolidation independent of the interfering effects of B. Age......-related declines in motor skill learning are not produced exclusively by deficits in the encoding of sensorimotor information during practice. Aging also increases the susceptibility to memory interference and reduces off-line gains in motor skill learning after practice....

Detective quantum efficiency gains compared with speed gains for hypersensitized astronomical plates

International Nuclear Information System (INIS)

Kaye, A.L.

1977-01-01

It is reasonable to assume that gains in detective quantum efficiency (DQE) are far better criteria for assessing the performance of hypersensitizing techniques than gains in speed. It is shown here that gains in speed can be misleading, for some methods of hypersensitization give plates of increased speed but reduced detective quantum efficiency. (author)

Chemopreventive and therapeutic activity of dietary blueberry against estrogen-mediated breast cancer.

Science.gov (United States)

Jeyabalan, Jeyaprakash; Aqil, Farrukh; Munagala, Radha; Annamalai, Lakshmanan; Vadhanam, Manicka V; Gupta, Ramesh C

2014-05-07

Berries are gaining increasing importance lately for their chemopreventive and therapeutic potential against several cancers. In earlier studies, a blueberry-supplemented diet has shown protection against 17β-estradiol (E2)-mediated mammary tumorigenesis. This study tested both preventive and therapeutic activities of diet supplemented with whole blueberry powder (50:50 blend of Tifblue and Rubel). Animals received 5% blueberry diet, either 2 weeks prior to or 12 weeks after E2 treatment in preventive and therapeutic groups, respectively. Both interventions delayed the tumor latency for palpable mammary tumors by 28 and 37 days, respectively. Tumor volume and multiplicity were also reduced significantly in both modes. The effect on mammary tumorigenesis was largely due to down-regulation of CYP 1A1 and ER-α gene expression and also favorable modulation of microRNA (miR-18a and miR-34c) levels. These data suggest that the blueberry blend tested is effective in inhibiting E2-mediated mammary tumorigenesis in both preventive and therapeutic modes.

Analysis of the therapeutic gain in the treatment of human osteosarcoma microcolonies in vitro with 211At-labelled monoclonal antibody.

Science.gov (United States)

Larsen, R H; Bruland, O S; Hoff, P; Alstad, J; Rofstad, E K

1994-06-01

Microcolonies were obtained by culturing cells of two human osteosarcoma lines (OHS and KPDX) and one human melanoma line (WIX-c) for either 24 or 72 h. The microcolonies were treated with either alpha-particle radiation emitted by the 211At-labelled monoclonal antibody (MAb) TP-3 or external beam X-rays. Survival of microcolonies was assayed by colony formation. Therapeutic gain factor (TGF) values were calculated for two survival levels, 50% and 20% microcolony regeneration (i.e. at least one cell in 50% or 20% of the colonies survived the treatments). The TGF values were affected by the specific activity of the 211At-MAb conjugate, the antigen expression of the cells and the size and growth pattern of the microcolonies. Treatment with 211At-TP-3 gave TGF values that varied from 1.3 +/- 0.4 to 4.5 +/- 0.7 (mean +/- s.e.). The antigen-rich OHS cell line had on average 1.6 times higher TGF than the antigen-poor KPDX cell line. The TGF increased significantly with colony size for the densely packed colonies of the KPDX cell line but not for the OHS cell line, which had colonies with cells growing in a more scattered pattern. Control experiments with the two non-specific 211At forms, free 211At and 211At-labelled bovine serum albumin, gave TGF values from 0.6 +/- 0.1 to 1.0 +/- 0.3. This study suggests that in vivo evaluation of 211At-MAbs using relevant tumour models is desirable.

Exploring the therapeutic potential of Ayahuasca: acute intake increases mindfulness-related capacities.

Science.gov (United States)

Soler, Joaquim; Elices, Matilde; Franquesa, Alba; Barker, Steven; Friedlander, Pablo; Feilding, Amanda; Pascual, Juan C; Riba, Jordi

2016-03-01

Ayahuasca is a psychotropic plant tea used for ritual purposes by the indigenous populations of the Amazon. In the last two decades, its use has expanded worldwide. The tea contains the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT), plus β-carboline alkaloids with monoamine-oxidase-inhibiting properties. Acute administration induces an introspective dream-like experience characterized by visions and autobiographic and emotional memories. Studies of long-term users have suggested its therapeutic potential, reporting that its use has helped individuals abandon the consumption of addictive drugs. Furthermore, recent open-label studies in patients with treatment-resistant depression found that a single ayahuasca dose induced a rapid antidepressant effect that was maintained weeks after administration. Here, we conducted an exploratory study of the psychological mechanisms that could underlie the beneficial effects of ayahuasca. We assessed a group of 25 individuals before and 24 h after an ayahuasca session using two instruments designed to measure mindfulness capacities: The Five Facets Mindfulness Questionnaire (FFMQ) and the Experiences Questionnaire (EQ). Ayahuasca intake led to significant increases in two facets of the FFMQ indicating a reduction in judgmental processing of experiences and in inner reactivity. It also led to a significant increase in decentering ability as measured by the EQ. These changes are classic goals of conventional mindfulness training, and the scores obtained are in the range of those observed after extensive mindfulness practice. The present findings support the claim that ayahuasca has therapeutic potential and suggest that this potential is due to an increase in mindfulness capacities.

Hope-inspiring therapeutic relationships, professional expectations and social inclusion for young people with psychosis.

Science.gov (United States)

Berry, Clio; Greenwood, Kathryn

2015-10-01

Personal recovery accounts suggest that a positive therapeutic relationship with an optimistic mental health professional may facilitate social inclusion. However, little empirical research has investigated the role of the therapeutic relationship in social outcomes or explored potential mechanisms of change within community psychosis care. This study investigated the direct predictive associations of the therapeutic relationship and professional expectancies for social inclusion and vocational activity for young people with psychosis, and indirect associations through hopefulness. Young people with psychosis and their main mental health professional (n=51 dyads) participated across two time points. Measures of therapeutic relationships, professional expectancies, and vocational activity were obtained at baseline. Measures of hopefulness, social inclusion and vocational activity were obtained at follow-up. Direct and indirect associations between variables were analysed using path modelling. Directed path models were consistent with a positive therapeutic relationship and positive professional expectancies predicting social inclusion and vocational activity through mediation by increased patient domain-specific hopefulness. The professional-rated therapeutic relationship more directly predicts change in vocational activity status. Change in vocational activity status predicts increased patient hopefulness. The therapeutic relationship between professionals and young people with psychosis appears hope-inspiring and important to patients' social inclusion and vocational outcomes. Vocational activity may produce reciprocal gains in hopefulness. Copyright © 2015 Elsevier B.V. All rights reserved.

Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy

OpenAIRE

Wagner, Mark T; Mithoefer, Michael C; Mithoefer, Ann T; MacAulay, Rebecca K; Jerome, Lisa; Yazar-Klosinski, Berra; Doblin, Rick

2017-01-01

A growing body of research suggests that traumatic events lead to persisting personality change characterized by increased neuroticism. Relevantly, enduring improvements in Post-Traumatic Stress Disorder (PTSD) symptoms have been found in response to 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. There is evidence that lasting changes in the personality feature of ?openness? occur in response to hallucinogens, and that this may potentially act as a therapeutic mechanism of c...

Therapeutic potential of abalone and status of bioactive molecules: A comprehensive review.

Science.gov (United States)

Suleria, H A R; Masci, P P; Gobe, G C; Osborne, S A

2017-05-24

Marine organisms are increasingly being investigated as sources of bioactive molecules with therapeutic applications as nutraceuticals and pharmaceuticals. In particular, nutraceuticals are gaining popularity worldwide owing to their therapeutic potential and incorporation in functional foods and dietary supplements. Abalone, a marine gastropod, contains a variety of bioactive compounds with anti-oxidant, anti-thrombotic, anti-inflammatory, anti-microbial, and anti-cancer activities. For thousands of years different cultures have used abalone as a traditional functional food believing consumption provides health benefits. Abalone meat is one of the most precious commodities in Asian markets where it is considered a culinary delicacy. Recent research has revealed that abalone is composed of many vital moieties like polysaccharides, proteins, and fatty acids that provide health benefits beyond basic nutrition. A review of past and present research is presented with relevance to the therapeutic potential of bioactive molecules from abalone.

Increased Plasma Colloid Osmotic Pressure Facilitates the Uptake of Therapeutic Macromolecules in a Xenograft Tumor Model

Directory of Open Access Journals (Sweden)

Matthias Hofmann

2009-08-01

Full Text Available Elevated tumor interstitial fluid pressure (TIFP is a characteristic of most solid tumors. Clinically, TIFP may hamper the uptake of chemotherapeutic drugs into the tumor tissue reducing their therapeutic efficacy. In this study, a means of modulating TIFP to increase the flux of macromolecules into tumor tissue is presented, which is based on the rationale that elevated plasma colloid osmotic pressure (COP pulls water from tumor interstitium lowering the TIFP. Concentrated human serum albumin: (20% HSA, used as an agent to enhance COP, reduced the TIFP time-dependently from 8 to 2 mm Hg in human tumor xenograft models bearing A431 epidermoid vulva carcinomas. To evaluate whether this reduction facilitates the uptake of macromolecules, the intratumoral distribution of fluorescently conjugated dextrans (2.5 mg/ml and cetuximab (2.0 mg/ml was probed using novel time domain nearinfrared fluorescence imaging. This method permitted discrimination and semiquantification of tumor-accumulated conjugate from background and unspecific probe fluorescence. The coadministration of 20% HSA together with either dextrans or cetuximab was found to lower the TIFP significantly and increase the concentration of the substances within the tumor tissue in comparison to control tumors. Furthermore, combined administration of 20%HSA plus cetuximab reduced the tumor growth significantly in comparison to standard cetuximab treatment. These data demonstrate that increased COP lowers the TIFP within hours and increases the uptake of therapeutic macromolecules into the tumor interstitium leading to reduced tumor growth. This model represents a novel approach to facilitate the delivery of therapeutics into tumor tissue, particularly monoclonal antibodies.

A model to obtain an optimum erbium desity for gain increasing in EDFA

Directory of Open Access Journals (Sweden)

E. Arzi

2003-12-01

Full Text Available   In this paper, we suggest a novel model, based on input pump power and wave guidestructure, to calculate the Er-density profile in Erbium doped fiber amplifiers. This optimization is carried out for both SMF and DSF fibers. These optimized profiles have a Gaussian-like shape. Using the SMF optimized Er-density profile, high gain enhancement is obtained in a relatively short length of fibers. On the other hand, the DSF optimized profile shows small changes in the gain, which agrees with the previously report on other method of gain enhancement. This model is applicable to all active waveguides and any other dopant as well .

Optimal weight gain in triplet pregnancies.

Science.gov (United States)

Johnston, Robert C; Erfani, Hadi; Shamshirsaz, Amir A; Spiel, Melissa; Ravangard, Sam F; Shaman, Majid; Allaf, M Baraa; Shamshirsaz, Alireza A; Haeri, Sina

2017-08-01

To identify appropriate weight gain in triplet gestations, which may aid in reducing the risk of perinatal morbidity within this high-risk cohort. This retrospective cohort study evaluated all non-anomalous triplet pregnancies between 23 and 40 weeks' gestation resulting in live births at five tertiary-care medical centers between 1991 and 2011. Subjects were divided by pre-pregnancy BMI into underweight, normal-weight, overweight, and obese groups, and then stratified by low (gain (≥1.5 lbs/week). Primary outcomes included spontaneous preterm birth and preeclampsia. We included 116 mothers and 348 corresponding neonates for final analysis. The incidence of preeclampsia and preterm delivery less than 32 weeks' gestation was 37% and 41%, respectively. The incidence of preeclampsia increased with weight gain per week, but was not statistically different from subjects who gained less weight. We found no statistical correlation between weight gain per week and preterm delivery. We found no association between preeclampsia or preterm delivery and increasing weight gain in triplet pregnancies. The association with increased risk for preeclampsia was predominantly due to BMI effect. Based on the current study, recommendations for optimal weight gain in mothers with triplet gestations could not be defined.

Digital Therapeutics: An Integral Component of Digital Innovation in Drug Development.

Science.gov (United States)

Sverdlov, Oleksandr; van Dam, Joris; Hannesdottir, Kristin; Thornton-Wells, Tricia

2018-07-01

Digital therapeutics represent a new treatment modality in which digital systems such as smartphone apps are used as regulatory-approved, prescribed therapeutic interventions to treat medical conditions. In this article we provide a critical overview of the rationale for investing in such novel modalities, including the unmet medical needs addressed by digital therapeutics and the potential for reducing current costs of medical care. We also discuss emerging pathways to regulatory approval and how innovative business models are enabling further growth in the development of digital therapeutics. We conclude by providing some recent examples of digital therapeutics that have gained regulatory approval and highlight opportunities for the near future. © 2018 American Society for Clinical Pharmacology and Therapeutics.

Greater early and mid-pregnancy gestational weight gain are associated with increased risk of gestational diabetes mellitus: A prospective cohort study.

Science.gov (United States)

Zhong, Chunrong; Li, Xiating; Chen, Renjuan; Zhou, Xuezhen; Liu, Chaoqun; Wu, Jiangyue; Xu, Shangzhi; Wang, Weiye; Xiao, Mei; Xiong, Guoping; Wang, Jing; Yang, Xuefeng; Hao, Liping; Yang, Nianhong

2017-12-01

Gestational diabetes mellitus is associated with adverse short- and long-term consequences for both the mother and the offspring. To examine the relationship between the rates of gestational weight gain (RGWG) during early and mid-pregnancy and the risk of gestational diabetes mellitus (GDM). 2090 singleton pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC) without overt diabetes before pregnancy were analyzed in our study. Gestational weight were measured regularly in every antenatal visit. Gestational diabetes mellitus was assessed with the 75-g, 2-h oral glucose tolerance test at 24-28 weeks of gestation. Multivariable logistic regression was performed to estimate effect of RGWG on GDM. A total of 8.3% (n = 173) of pregnant women were diagnosed with GDM. Women with elevated rate of gestational weight gain prior to glucose screening test (RGWG-PG) increased the risk of GDM (adjusted p-trend = 0.004; odds ratios (OR) 1.64, 95% confidence intervals (CI) 1.01-2.68 and OR 2.30,95% CI 1.44-3.66 for 0.297-0.384 kg/wk and 0.385 kg/wk or more vs. 0.213 kg/wk or less, respectively). Women with greater rate of gestational weight gain in the first trimester (RGWG-F) increased the risk of GDM (adjusted p-trend = 0.048; OR 1.83, 95% CI 1.14-2.94 and OR 1.76, 95% CI 1.10-2.83 for 0.086-0.200 kg/wk and 0.201 kg/wk or more vs. -0.025 kg/wk or less, respectively). The rate of gestational weight gain in the second trimester (RGWG-S) was significantly associated with GDM only among women with RGWG-F more than 0.086 kg/wk (adjusted p-trend = 0.035; OR 2.04, 95% CI 1.16-3.59 for 0.658 kg/wk or more vs. 0.418 kg/wk or less). Greater early pregnancy weight gain are associated with increased risk of GDM. Elevated weight gain in mid-pregnancy increased the risk of GDM only among pregnant women with greater weight gain in the first trimester. Copyright © 2017 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All

Energy Gaining Windows for Residental Buildings

DEFF Research Database (Denmark)

Kragh, Jesper; Laustsen, Jacob Birck; Svendsen, Svend

2008-01-01

This paper presents some of the research done during the last 8 years at the Technical University of Denmark developing improved low-energy window solutions. The focus has been on maximizing the net energy gain of windows for residential buildings. The net energy gain of windows is the solar gain...... minus the heat loss integrated over the heating season. It is assumed that in northern cold climates all of the solar gain during the heating season can be utilized for space heating. Problems with overheating in the summer period must be solved with overhang or moveable solar shading devices. Two...... and longer durability of the window. The glazing in these fiber reinforced polyester windows is both unsealed and sealed triple glazing units. To increase the net energy gain slim frame profiles have been developed to increase the glazing area and thereby the solar gain. The challenge when developing slim...

PAI-1 gain-of-function genotype, factors increasing PAI-1 levels, and airway obstruction: The GALA II Cohort.

Science.gov (United States)

Sherenian, M G; Cho, S H; Levin, A; Min, J-Y; Oh, S S; Hu, D; Galanter, J; Sen, S; Huntsman, S; Eng, C; Rodriguez-Santana, J R; Serebrisky, D; Avila, P C; Kalhan, R; Smith, L J; Borrell, L N; Seibold, M A; Keoki Williams, L; Burchard, E G; Kumar, R

2017-09-01

PAI-1 gain-of-function variants promote airway fibrosis and are associated with asthma and with worse lung function in subjects with asthma. We sought to determine whether the association of a gain-of-function polymorphism in plasminogen activator inhibitor-1 (PAI-1) with airway obstruction is modified by asthma status, and whether any genotype effect persists after accounting for common exposures that increase PAI-1 level. We studied 2070 Latino children (8-21y) with genotypic and pulmonary function data from the GALA II cohort. We estimated the relationship of the PAI-1 risk allele with FEV1/FVC by multivariate linear regression, stratified by asthma status. We examined the association of the polymorphism with asthma and airway obstruction within asthmatics via multivariate logistic regression. We replicated associations in the SAPPHIRE cohort of African Americans (n=1056). Secondary analysis included the effect of the at-risk polymorphism on postbronchodilator lung function. There was an interaction between asthma status and the PAI-1 polymorphism on FEV 1 /FVC (P=.03). The gain-of-function variants, genotypes (AA/AG), were associated with lower FEV 1 /FVC in subjects with asthma (β=-1.25, CI: -2.14,-0.35, P=.006), but not in controls. Subjects with asthma and the AA/AG genotypes had a 5% decrease in FEV 1 /FVC (P<.001). In asthmatics, the risk genotype (AA/AG) was associated with a 39% increase in risk of clinically relevant airway obstruction (OR=1.39, CI: 1.01, 1.92, P=.04). These associations persisted after exclusion of factors that increase PAI-1 including tobacco exposure and obesity. The decrease in the FEV 1 /FVC ratio associated with the risk genotype was modified by asthma status. The genotype increased the odds of airway obstruction by 75% within asthmatics only. As exposures known to increase PAI-1 levels did not mitigate this association, PAI-1 may contribute to airway obstruction in the context of chronic asthmatic airway inflammation. © 2017

Sociocultural influences on strategies to lose weight, gain weight, and increase muscles among ten cultural groups.

Science.gov (United States)

McCabe, Marita P; Busija, Lucy; Fuller-Tyszkiewicz, Matthew; Ricciardelli, Lina; Mellor, David; Mussap, Alexander

2015-01-01

This study determined how sociocultural messages to change one's body are perceived by adolescents from different cultural groups. In total, 4904 adolescents, including Australian, Chilean, Chinese, Indo-Fijian, Indigenous Fijian, Greek, Malaysian, Chinese Malaysian, Tongans in New Zealand, and Tongans in Tonga, were surveyed about messages from family, peers, and the media to lose weight, gain weight, and increase muscles. Groups were best differentiated by family pressure to gain weight. Girls were more likely to receive the messages from multiple sociocultural sources whereas boys were more likely to receive the messages from the family. Some participants in a cultural group indicated higher, and others lower, levels of these sociocultural messages. These findings highlight the differences in sociocultural messages across cultural groups, but also that adolescents receive contrasting messages within a cultural group. These results demonstrate the difficulty in representing a particular message as being characteristic of each cultural group. Copyright © 2014 Elsevier Ltd. All rights reserved.

Developmental gains in visuospatial memory predict gains in mathematics achievement.

Directory of Open Access Journals (Sweden)

Yaoran Li

Full Text Available Visuospatial competencies are related to performance in mathematical domains in adulthood, but are not consistently related to mathematics achievement in children. We confirmed the latter for first graders and demonstrated that children who show above average first-to-fifth grade gains in visuospatial memory have an advantage over other children in mathematics. The study involved the assessment of the mathematics and reading achievement of 177 children in kindergarten to fifth grade, inclusive, and their working memory capacity and processing speed in first and fifth grade. Intelligence was assessed in first grade and their second to fourth grade teachers reported on their in-class attentive behavior. Developmental gains in visuospatial memory span (d = 2.4 were larger than gains in the capacity of the central executive (d = 1.6 that in turn were larger than gains in phonological memory span (d = 1.1. First to fifth grade gains in visuospatial memory and in speed of numeral processing predicted end of fifth grade mathematics achievement, as did first grade central executive scores, intelligence, and in-class attentive behavior. The results suggest there are important individual differences in the rate of growth of visuospatial memory during childhood and that these differences become increasingly important for mathematics learning.

Developmental gains in visuospatial memory predict gains in mathematics achievement.

Science.gov (United States)

Li, Yaoran; Geary, David C

2013-01-01

Visuospatial competencies are related to performance in mathematical domains in adulthood, but are not consistently related to mathematics achievement in children. We confirmed the latter for first graders and demonstrated that children who show above average first-to-fifth grade gains in visuospatial memory have an advantage over other children in mathematics. The study involved the assessment of the mathematics and reading achievement of 177 children in kindergarten to fifth grade, inclusive, and their working memory capacity and processing speed in first and fifth grade. Intelligence was assessed in first grade and their second to fourth grade teachers reported on their in-class attentive behavior. Developmental gains in visuospatial memory span (d = 2.4) were larger than gains in the capacity of the central executive (d = 1.6) that in turn were larger than gains in phonological memory span (d = 1.1). First to fifth grade gains in visuospatial memory and in speed of numeral processing predicted end of fifth grade mathematics achievement, as did first grade central executive scores, intelligence, and in-class attentive behavior. The results suggest there are important individual differences in the rate of growth of visuospatial memory during childhood and that these differences become increasingly important for mathematics learning.

Developmental Gains in Visuospatial Memory Predict Gains in Mathematics Achievement

Science.gov (United States)

Li, Yaoran; Geary, David C.

2013-01-01

Visuospatial competencies are related to performance in mathematical domains in adulthood, but are not consistently related to mathematics achievement in children. We confirmed the latter for first graders and demonstrated that children who show above average first-to-fifth grade gains in visuospatial memory have an advantage over other children in mathematics. The study involved the assessment of the mathematics and reading achievement of 177 children in kindergarten to fifth grade, inclusive, and their working memory capacity and processing speed in first and fifth grade. Intelligence was assessed in first grade and their second to fourth grade teachers reported on their in-class attentive behavior. Developmental gains in visuospatial memory span (d = 2.4) were larger than gains in the capacity of the central executive (d = 1.6) that in turn were larger than gains in phonological memory span (d = 1.1). First to fifth grade gains in visuospatial memory and in speed of numeral processing predicted end of fifth grade mathematics achievement, as did first grade central executive scores, intelligence, and in-class attentive behavior. The results suggest there are important individual differences in the rate of growth of visuospatial memory during childhood and that these differences become increasingly important for mathematics learning. PMID:23936154

Adolescent Metabolic Syndrome Risk Is Increased with Higher Infancy Weight Gain and Decreased with Longer Breast Feeding

Directory of Open Access Journals (Sweden)

Kim Khuc

2012-01-01

Full Text Available Background. Prevalence of the metabolic syndrome is increasing in pediatric age groups worldwide. Meeting the criteria for the metabolic syndrome puts children at risk for later cardiovascular and metabolic disease. Methods. Using linear regression, we examined the association between infant weight gain from birth to 3 months and risk for the metabolic syndrome among 16- to 17-year-old Chilean adolescents (n=357, accounting for the extent of breastfeeding in infancy and known covariates including gender, birth weight, and socioeconomic status. Results. Participants were approximately half male (51%, born at 40 weeks of gestation weighing 3.5 kg, and 48% were exclusively breastfed for ≥90 days. Factors independently associated with increased risk of metabolic syndrome in adolescence were faster weight gain in the first 3 months of life (B=0.16, P<0.05 and male gender (B=0.24, P<0.05. Breastfeeding as the sole source of milk for ≥90 days was associated with significantly decreased risk of metabolic syndrome (B=−0.16. Conclusion. This study adds to current knowledge about early infant growth and breastfeeding and their long-term health effects.

Increase in H-reflex gain following 1 week of immobilization

DEFF Research Database (Denmark)

Jensen, Jesper Lundbye; Sørensen, Mie; Nielsen, Jens Bo

It is well established that motor experience induces structural and functional plasticity within the central nervous system. It is less well investigated whether reduced motor activity in relation to immobilization is also associated with plastic neuronal changes. The present experiment examined ...... removal all measurements had returned to preimmobilization levels. These results show that immobilization of only one week duration is associated with reversible adaptive changes in the gain of the central part of the monosynaptic stretch reflex....

A model to obtain an optimum erbium desity for gain increasing in EDFA

OpenAIRE

E. Arzi; A. Hassani; F. E. Seraji

2003-01-01

  In this paper, we suggest a novel model, based on input pump power and wave guidestructure, to calculate the Er-density profile in Erbium doped fiber amplifiers. This optimization is carried out for both SMF and DSF fibers. These optimized profiles have a Gaussian-like shape. Using the SMF optimized Er-density profile, high gain enhancement is obtained in a relatively short length of fibers. On the other hand, the DSF optimized profile shows small changes in the gain, which agrees with the ...

Excessive signal transduction of gain-of-function variants of the calcium-sensing receptor (CaSR are associated with increased ER to cytosol calcium gradient.

Directory of Open Access Journals (Sweden)

Marianna Ranieri

Full Text Available In humans, gain-of-function mutations of the calcium-sensing receptor (CASR gene are the cause of autosomal dominant hypocalcemia or type 5 Bartter syndrome characterized by an abnormality of calcium metabolism with low parathyroid hormone levels and excessive renal calcium excretion. Functional characterization of CaSR activating variants has been so far limited at demonstrating an increased sensitivity to external calcium leading to lower Ca-EC50. Here we combine high resolution fluorescence based techniques and provide evidence that for the efficiency of calcium signaling system, cells expressing gain-of-function variants of CaSR monitor cytosolic and ER calcium levels increasing the expression of the Sarco-Endoplasmic Reticulum Calcium-ATPase (SERCA and reducing expression of Plasma Membrane Calcium-ATPase (PMCA. Wild-type CaSR (hCaSR-wt and its gain-of-function (hCaSR-R990G; hCaSR-N124K variants were transiently transfected in HEK-293 cells. Basal intracellular calcium concentration was significantly lower in cells expressing hCaSR-wt and its gain of function variants compared to mock. In line, FRET studies using the D1ER probe, which detects [Ca2+]ER directly, demonstrated significantly higher calcium accumulation in cells expressing the gain of function CaSR variants compared to hCaSR-wt. Consistently, cells expressing activating CaSR variants showed a significant increase in SERCA activity and expression and a reduced PMCA expression. This combined parallel regulation in protein expression increases the ER to cytosol calcium gradient explaining the higher sensitivity of CaSR gain-of-function variants to external calcium. This control principle provides a general explanation of how cells reliably connect (and exacerbate receptor inputs to cell function.

Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease.

Science.gov (United States)

Barage, Sagar H; Sonawane, Kailas D

2015-08-01

Alzheimer's disease is an irreversible, progressive neurodegenerative disorder. Various therapeutic approaches are being used to improve the cholinergic neurotransmission, but their role in AD pathogenesis is still unknown. Although, an increase in tau protein concentration in CSF has been described in AD, but several issues remains unclear. Extensive and accurate analysis of CSF could be helpful to define presence of tau proteins in physiological conditions, or released during the progression of neurodegenerative disease. The amyloid cascade hypothesis postulates that the neurodegeneration in AD caused by abnormal accumulation of amyloid beta (Aβ) plaques in various areas of the brain. The amyloid hypothesis has continued to gain support over the last two decades, particularly from genetic studies. Therefore, current research progress in several areas of therapies shall provide an effective treatment to cure this devastating disease. This review critically evaluates general biochemical and physiological functions of Aβ directed therapeutics and their relevance. Copyright © 2015 Elsevier Ltd. All rights reserved.

An output amplitude configurable wideband automatic gain control with high gain step accuracy

International Nuclear Information System (INIS)

He Xiaofeng; Ye Tianchun; Mo Taishan; Ma Chengyan

2012-01-01

An output amplitude configurable wideband automatic gain control (AGC) with high gain step accuracy for the GNSS receiver is presented. The amplitude of an AGC is configurable in order to cooperate with baseband chips to achieve interference suppression and be compatible with different full range ADCs. And what's more, the gain-boosting technology is introduced and the circuit is improved to increase the step accuracy. A zero, which is composed by the source feedback resistance and the source capacity, is introduced to compensate for the pole. The AGC is fabricated in a 0.18 μm CMOS process. The AGC shows a 62 dB gain control range by 1 dB each step with a gain error of less than 0.2 dB. The AGC provides 3 dB bandwidth larger than 80 MHz and the overall power consumption is less than 1.8 mA, and the die area is 800 × 300 μm 2 . (semiconductor integrated circuits)

Receiver gain function: the actual NMR receiver gain

OpenAIRE

Mo, Huaping; Harwood, John S.; Raftery, Daniel

2010-01-01

The observed NMR signal size depends on the receiver gain parameter. We propose a receiver gain function to characterize how much the raw FID is amplified by the receiver as a function of the receiver gain setting. Although the receiver is linear for a fixed gain setting, the actual gain of the receiver may differ from what the gain setting suggests. Nevertheless, for a given receiver, we demonstrate that the receiver gain function can be calibrated. Such a calibration enables accurate compar...

Efficiency of selection methods for increased ratio of pupal-larval to adult-larval weight gains in Tribolium.

Science.gov (United States)

Campo, J L; Cobos, P

1994-01-12

Four lines of Tribolium castaneum were selected in each of three replicates for increased ratio of (pupal-larval) to (adult-larval) weight gains, using selection for increased (pupal-larval) weight gain (PL), selection for decreased (adult-larval) weight gain (AL), direct selection for the ratio (R) and linear selection index of larval, pupal and adult weights (I), respectively, for four generations. Linear index was calculated with economic weights of m(2) -m(3) , m(3) -m(1) and m(1) -m(2) , respectively, with m(1) , m(2) and m(3) being the means for larval, pupal and adult weights. Selection to increase the ratio is considered to be a method to maximize the mean response in (adult-larval) weight while controlling the response in (pupal-adult) weight, and as a form of antagonistic selection to increase the weight gain during a given age period relative to the gain at another age period. Larval, pupal and adult weights were measured at 14, 21 and 28 days after adult emergence, respectively. The selected proportion was 20 % in all lines. The response observed for the ratio differed significantly among lines (p adulto-peso de larva en Tribolium Cuatro líneas de Tribolium castaneum fueron seleccionadas en cada una de tres repeticiones para incrementar el cociente (peso de pupa-peso de larva)/(peso de adulto-peso de larva); la línea PL fue seleccionada para aumentar la diferencia (peso de pupa-pesp de larva), la línea AL fue seleccionada para disminuir la diferencia (peso de adulto-peso de larva), fa línea R fue seleccionada directamente para el cociente, y la línea I fue seleccionada por medio de un índice lineal basado en los pesos de larva, pupa y adulto, durante cuatro generaciones. El índice lineal se calculó con pesos económicos de (m(2) -m(3) ), (m(3) -m(1) ), y (m(1) -m(2) ) respectivamentee, siendo m(1) , m(2) , y m(3) los valores medios para el peso de larva, pupa y adulto. La selección para aumentar el cociente indicado es un método para maximizar

Gain attenuation of gated framing camera

International Nuclear Information System (INIS)

Xiao Shali; Liu Shenye; Cao Zhurong; Li Hang; Zhang Haiying; Yuan Zheng; Wang Liwei

2009-01-01

The theoretic model of framing camera's gain attenuation is analyzed. The exponential attenuation curve of the gain along the pulse propagation time is simulated. An experiment to measure the coefficient of gain attenuation based on the gain attenuation theory is designed. Experiment result shows that the gain follows an exponential attenuation rule with a quotient of 0.0249 nm -1 , the attenuation coefficient of the pulse is 0.00356 mm -1 . The loss of the pulse propagation along the MCP stripline is the leading reason of gain attenuation. But in the figure of a single stripline, the gain dose not follow the rule of exponential attenuation completely, instead, there is a gain increase at the stripline bottom. That is caused by the reflection of the pulse. The reflectance is about 24.2%. Combining the experiment and theory, which design of the stripline MCP can improved the gain attenuation. (authors)

A critical view on singular therapeutic projects

Directory of Open Access Journals (Sweden)

Fernando Sfair Kinker

2016-04-01

Full Text Available This article discusses the issue of unique therapeutic projects within the mental health services built in the Brazilian psychiatric reform process. Starting from the concepts that have gained strength in both the psychiatric reform as in the collective health, this study proposes that current notions of the therapeutic project still are influenced by biological, psychological or social paradigms that simplify the complexity of the experience suffered by the subjects. Despite therapeutic projects are an essential achievement for the qualification of mental health care, it is still necessary to produce an epistemological rupture in the relationship with mental suffering so that they can achieve the greatest potential for transformation. Therefore, the article suggests that the practice of therapeutic projects should hold discussions with the reality of users life of and their relationships in the territories of existence, to transform the relations of power and knowledge that reproduce the subjects annulment. Thus, it is possible to dialogue with the complexity of the mental suffering experience, producing changes in the scenes that produce it.

Manufacturing of recombinant therapeutic proteins in microbial systems.

Science.gov (United States)

Graumann, Klaus; Premstaller, Andreas

2006-02-01

Recombinant therapeutic proteins have gained enormous importance for clinical applications. The first recombinant products have been produced in E. coli more than 20 years ago. Although with the advent of antibody-based therapeutics mammalian expression systems have experienced a major boost, microbial expression systems continue to be widely used in industry. Their intrinsic advantages, such as rapid growth, high yields and ease of manipulation, make them the premier choice for expression of non-glycosylated peptides and proteins. Innovative product classes such as antibody fragments or alternative binding molecules will further expand the use of microbial systems. Even more, novel, engineered production hosts and integrated technology platforms hold enormous potential for future applications. This review summarizes current applications and trends for development, production and analytical characterization of recombinant therapeutic proteins in microbial systems.

Weight gain following treatment of hyperthyroidism.

Science.gov (United States)

Dale, J; Daykin, J; Holder, R; Sheppard, M C; Franklyn, J A

2001-08-01

Patients frequently express concern that treating hyperthyroidism will lead to excessive weight gain. This study aimed to determine the extent of, and risk factors for, weight gain in an unselected group of hyperthyroid patients. We investigated 162 consecutive hyperthyroid patients followed for at least 6 months. Height, weight, clinical features, biochemistry and management were recorded at each clinic visit. Documented weight gain was 5.42 +/- 0.46 kg (mean +/- SE) and increase in BMI was 8.49 +/- 0.71%, over a mean 24.2 +/- 1.6 months. Pre-existing obesity, Graves' disease causing hyperthyroidism, weight loss before presentation and length of follow-up each independently predicted weight gain. Patients treated with thionamides or radioiodine gained a similar amount of weight (thionamides, n = 87, 5.16 +/- 0.63 kg vs. radioiodine, n = 62, 4.75 +/- 0.57 kg, P = 0.645), but patients who underwent thyroidectomy (n = 13) gained more weight (10.27 +/- 2.56 kg vs. others, P = 0.007). Development of hypothyroidism (even transiently) was associated with weight gain (never hypothyroid, n = 102, 4.57 +/- 0.52 kg, transiently hypothyroid, n = 29, 5.37 +/- 0.85 kg, on T4, n = 31, 8.06 +/- 1.42 kg, P = 0.014). This difference remained after correcting for length of follow-up. In the whole cohort, weight increased by 3.95 +/- 0.40 kg at 1 year (n = 144) to 9.91 +/- 1.62 kg after 4 years (n = 27) (P = 0.008), representing a mean weight gain of 3.66 +/- 0.44 kg/year. We have demonstrated marked weight gain after treatment of hyperthyroidism. Pre-existing obesity, a diagnosis of Graves' disease and prior weight loss independently predicted weight gain and weight continued to rise with time. Patients who became hypothyroid, despite T4 replacement, gained most weight.

Gain control mechanisms in spinal motoneurons

Directory of Open Access Journals (Sweden)

Michael David Johnson

2014-07-01

Full Text Available Motoneurons provide the only conduit for motor commands to reach muscles. For many years, motoneurons were in fact considered to be little more than passive wires. Systematic studies in the past 25 years however have clearly demonstrated that the intrinsic electrical properties of motoneurons are under strong neuromodulatory control via multiple sources. The discovery of potent neuromodulation from the brainstem and its ability to change the gain of motoneurons shows that the passive view of the motor output stage is no longer tenable. A mechanism for gain control at the motor output stage makes good functional sense considering our capability of generating an enormous range of forces, from very delicate (e.g. putting in a contact lens to highly forceful (emergency reactions. Just as sensory systems need gain control to deal with a wide dynamic range of inputs, so to might motor output need gain control to deal with the wide dynamic range of the normal movement repertoire. Two problems emerge from the potential use of the brainstem monoaminergic projection to motoneurons for gain control. First, the projection is highly diffuse anatomically, so that independent control of the gains of different motor pools is not feasible. In fact, the system is so diffuse that gain for all the motor pools in a limb likely increases in concert. Second, if there is a system that increases gain, probably a system to reduce gain is also needed. In this review, we summarize recent studies that show local inhibitory circuits within the spinal cord, especially reciprocal and recurrent inhibition, have the potential to solve both of these problems as well as constitute another source of gain modulation.

Improving the user experience through practical data analytics gain meaningful insight and increase your bottom line

CERN Document Server

Fritz, Mike

2015-01-01

Improving the User Experience through Practical Data Analytics is your must-have resource for making UX design decisions based on data, rather than hunches. Authors Fritz and Berger help the UX professional recognize and understand the enormous potential of the ever-increasing user data that is often accumulated as a by-product of routine UX tasks, such as conducting usability tests, launching surveys, or reviewing clickstream information. Then, step-by-step, they explain how to utilize both descriptive and predictive statistical techniques to gain meaningful insight with that data. You'll be

Therapeutic targeting strategies using endogenous cells and proteins.

Science.gov (United States)

Parayath, Neha N; Amiji, Mansoor M

2017-07-28

Targeted drug delivery has become extremely important in enhancing efficacy and reducing the toxicity of therapeutics in the treatment of various disease conditions. Current approaches include passive targeting, which relies on naturally occurring differences between healthy and diseased tissues, and active targeting, which utilizes various ligands that can recognize targets expressed preferentially at the diseased site. Clinical translation of these mechanisms faces many challenges including the immunogenic and toxic effects of these non-natural systems. Thus, use of endogenous targeting systems is increasingly gaining momentum. This review is focused on strategies for employing endogenous moieties, which could serve as safe and efficient carriers for targeted drug delivery. The first part of the review involves cells and cellular components as endogenous carriers for therapeutics in multiple disease states, while the second part discusses the use of endogenous plasma components as endogenous carriers. Further understanding of the biological tropism with cells and proteins and the newer generation of delivery strategies that exploits these endogenous approaches promises to provide better solutions for site-specific delivery and could further facilitate clinical translations. Copyright © 2017 Elsevier B.V. All rights reserved.

Gestational weight gain in overweight and obese women enrolled in a healthy lifestyle and eating habits program.

Science.gov (United States)

Petrella, E; Malavolti, M; Bertarini, V; Pignatti, L; Neri, I; Battistini, N C; Facchinetti, F

2014-09-01

To determine whether changes in lifestyle in women with BMI > 25 could decrease gestational weight gain and unfavorable pregnancy outcomes. Women with BMI > 25 were randomized at 1st trimester to no intervention or a Therapeutic Lifestyle Changes (TLC) Program including diet (overweight: 1700 kcal/day, obese: 1800 kcal/day) and mild physical activity (30 min/day, 3 times/week). At baseline and at the 36th week women filled-in a Food Frequency Questionnaire. gestational weight gain, gestational diabetes mellitus, gestational hypertension, preterm delivery. Data stratified by BMI categories. Socio-demographic features were similar between groups (TLC: 33 cases, 28 cases). At term, gestational weight gain in obese women randomized to TLC group was lower (6.7 ± 4.3 kg) versus controls (10.1 ± 5.6 kg, p = 0.047). Gestational diabetes mellitus, gestational hypertension and preterm delivery were also significantly lower. TLC was an independent factor in preventing gestational weight gain, gestational diabetes mellitus, gestational hypertension. Significant changes in eating habits occurred in the TLC group, which increased the number of snacks, the intake of fruits-vegetables and decreased the consumption of sugar. A caloric restriction associated to changes in eating behavior and constant physical activity, is able to reduce gestational weight gain and related pregnancy complications in obese women.

Loss restlessness and gain calmness: durable effects of losses and gains on choice switching.

Science.gov (United States)

Yechiam, Eldad; Zahavi, Gal; Arditi, Eli

2015-08-01

While the traditional conceptualization of the effect of losses focuses on bias in the subjective weight of losses compared with respective gains, some accounts suggest more global task-related effects of losses. Based on a recent attentional theory, we predicted a positive after-effect of losses on choice switching in later tasks. In two experimental studies, we found increased choice switching rates in tasks with losses compared to tasks with no losses. Additionally, this heightened shifting behavior was maintained in subsequent tasks that do not include losses, a phenomenon we refer to as "loss restlessness." Conversely, gains were found to have an opposite "calming" effect on choice switching. Surprisingly, the loss restlessness phenomenon was observed following an all-losses payoff regime but not after a task with symmetric mixed gains and losses. This suggests that the unresolved mental account following an all-losses regime increases search behavior. Potential implications to macro level phenomena, such as the leverage effect, are discussed.

Temporal trends in pregnancy weight gain and birth weight in Bavaria 2000–2007: slightly decreasing birth weight with increasing weight gain in pregnancy

OpenAIRE

Schiessl, Barbara; Beyerlein, Andreas; Lack, Nicholas; Kries, Rüdiger von

2009-01-01

Aims: To assess temporal trends in birth weight and pregnancy weight gain in Bavaria from 2000 to 2007. Methods: Data on 695,707 mother and infant pairs (singleton term births) were available from a compulsory reporting system for quality assurance, including information on birth weight, maternal weight at delivery and at booking, maternal smoking, age, and further anthropometric and lifestyle factors. Pregnancy weight gain was defined as: weight prior to delivery minus weight at first booki...

Is the GAIN Act a turning point in new antibiotic discovery?

Science.gov (United States)

Brown, Eric D

2013-03-01

The United States GAIN (Generating Antibiotic Incentives Now) Act is a call to action for new antibiotic discovery and development that arises from a ground swell of concern over declining activity in this therapeutic area in the pharmaceutical sector. The GAIN Act aims to provide economic incentives for antibiotic drug discovery in the form of market exclusivity and accelerated drug approval processes. The legislation comes on the heels of nearly two decades of failure using the tools of modern drug discovery to find new antibiotic drugs. The lessons of failure are examined herein as are the prospects for a renewed effort in antibiotic drug discovery and development stimulated by new investments in both the public and private sector.

The Therapeutic Utility of Employment in Treating Drug Addiction: Science to Application

OpenAIRE

Silverman, Kenneth; Holtyn, August F.; Morrison, Reed

2016-01-01

Research on a model Therapeutic Workplace has allowed for evaluation of the use of employment in the treatment of drug addiction. Under the Therapeutic Workplace intervention, adults with histories of drug addiction are hired and paid to work. To promote drug abstinence or adherence to addiction medications, participants are required to provide drug-free urine samples or take prescribed addiction medications, respectively, to gain access to the workplace and/or to maintain their maximum rate ...

Yeast synthetic biology for the production of recombinant therapeutic proteins.

Science.gov (United States)

Kim, Hyunah; Yoo, Su Jin; Kang, Hyun Ah

2015-02-01

The production of recombinant therapeutic proteins is one of the fast-growing areas of molecular medicine and currently plays an important role in treatment of several diseases. Yeasts are unicellular eukaryotic microbial host cells that offer unique advantages in producing biopharmaceutical proteins. Yeasts are capable of robust growth on simple media, readily accommodate genetic modifications, and incorporate typical eukaryotic post-translational modifications. Saccharomyces cerevisiae is a traditional baker's yeast that has been used as a major host for the production of biopharmaceuticals; however, several nonconventional yeast species including Hansenula polymorpha, Pichia pastoris, and Yarrowia lipolytica have gained increasing attention as alternative hosts for the industrial production of recombinant proteins. In this review, we address the established and emerging genetic tools and host strains suitable for recombinant protein production in various yeast expression systems, particularly focusing on current efforts toward synthetic biology approaches in developing yeast cell factories for the production of therapeutic recombinant proteins. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

Innate heart regeneration: endogenous cellular sources and exogenous therapeutic amplification.

Science.gov (United States)

Malliaras, Konstantinos; Vakrou, Styliani; Kapelios, Chris J; Nanas, John N

2016-11-01

The -once viewed as heretical- concept of the adult mammalian heart as a dynamic organ capable of endogenous regeneration has recently gained traction. However, estimated rates of myocyte turnover vary wildly and the underlying mechanisms of cardiac plasticity remain controversial. It is still unclear whether the adult mammalian heart gives birth to new myocytes through proliferation of resident myocytes, through cardiomyogenic differentiation of endogenous progenitors or through both mechanisms. In this review, the authors discuss the cellular origins of postnatal mammalian cardiomyogenesis and touch upon therapeutic strategies that could potentially amplify innate cardiac regeneration. The adult mammalian heart harbors a limited but detectable capacity for spontaneous endogenous regeneration. During normal aging, proliferation of pre-existing cardiomyocytes is the dominant mechanism for generation of new cardiomyocytes. Following myocardial injury, myocyte proliferation increases modestly, but differentiation of endogenous progenitor cells appears to also contribute to cardiomyogenesis (although agreement on the latter point is not universal). Since cardiomyocyte deficiency underlies almost all types of heart disease, development of therapeutic strategies that amplify endogenous regeneration to a clinically-meaningful degree is of utmost importance.

Therapeutic potential of paclitaxel-radiation treatment of a murine ovarian carcinoma

International Nuclear Information System (INIS)

Milas, Luka; Saito, Yoshihiro; Hunter, Nancy; Milross, Christopher G.; Mason, Kathryn A.

1996-01-01

Background. Paclitaxel has been shown to radiosensitize tumor cells in culture by arresting them in the most radiosensitive G 2 and M cell cycle phases. In vivo preclinical studies are now necessary to obtain full insight into the radiopotentiating potential of this drug and its ability to increase the therapeutic gain of radiotherapy. We tested its ability to enhance the tumor radioresponse of an ovarian carcinoma and to influence the normal tissue radioresponse of recipient mice. Methods. Mice bearing 8-mm isotransplants of a syngeneic ovarian carcinoma, designated OCA-I, in their legs were treated with 40 mg/kg paclitaxel i.v., 14-60 Gy single-dose local tumor irradiation, or both; radiation was given under ambient conditions 1-96 h after paclitaxel. Tumor growth delay, tumor cure rate (TCD 50 assay), and delay in tumor recurrences were measured. Normal tissue radioresponse was determined using jejunal crypt cell survival at 3.5 days after exposure of mice to 9-14 Gy single dose of total body irradiation; the mice were untreated or treated with 40 mg/kg i.v. paclitaxel 4-96 h before irradiation. Results. Paclitaxel alone was effective against OCA-I, but its combination with irradiation produced supra-additive tumor growth delay. It also reduced TCD 50 values and delayed tumor recurrences. The enhancement of tumor radioresponse ranged from 1.33 to 1.96; the value increased as the time between paclitaxel administration and tumor irradiation increased up to 48 h, but then decreased again at 96 h. In contrast, paclitaxel protected jejunum against radiation damage by factors of 1.03 to 1.07 when given 24-96 h before irradiation. It showed some potentiation of damage (by a factor of 1.07), but only when given 4 h before irradiation. Conclusions. Paclitaxel potentiated tumor radioresponse if given within 4 days before irradiation, whereas it caused radioprotection of normal tissue (jejunum) at that time. Therefore, paclitaxel significantly increased therapeutic gain

Higher gestational weight gain is associated with increasing offspring birth weight independent of maternal glycemic control in women with type 1 diabetes

DEFF Research Database (Denmark)

Secher, Anna L; Parellada, Clara B; Ringholm, Lene

2014-01-01

; P = 0.02) and birth weight SD score (β = 0.06; P = 0.008) when adjusted for prepregnancy BMI, HbA1c at 36 weeks, smoking, parity, and ethnicity. CONCLUSIONS: Higher gestational weight gain in women with type 1 diabetes was associated with increasing offspring birth weight independent of glycemic......OBJECTIVE: We evaluate the association between gestational weight gain and offspring birth weight in singleton term pregnancies of women with type 1 diabetes. RESEARCH DESIGN AND METHODS: One hundred fifteen consecutive women referred at ... (prepregnancy BMI Women...

Perspectives on Phytochemicals as Antibacterial Agents: An Outstanding Contribution to Modern Therapeutics.

Science.gov (United States)

Khatri, Savita; Kumar, Manish; Phougat, Neetu; Chaudhary, Renu; Chhillar, Anil Kumar

2016-01-01

Despite the considerable advancements in the development of antimicrobial agents, incidents of epidemics due to multi drug resistance in microorganisms have created a massive hazard to mankind. Due to increased resistance against conventional antibiotics, researchers and pharmaceutical industries are more concerned about novel therapeutic agents for the prevention of bacterial infections. Enormous wealth of traditional system of medicine gains importance in health therapies over again. With ancient credentials of potent medicinal plants, various herbal remedies came forward for the management of bacterial infections. The Ayurvedic approach facilitates the development of new therapeutic agents due to structural and functional diversity among phytochemicals. The abundance and diversity is responsible for the characterization of new lead structures from medicinal plants. Industrial interest has increased due to recent research advancements viz. synergistic and high-throughput screening approach for the evaluation of vast variety of phytochemicals. The review certainly emphasizes on the traditional medicines as alternatives to conventional chemotherapeutic drugs. The review briefly describes mode of action of various antibiotics and resistance mechanisms. This review focuses on the chemical diversity and various mechanisms of action of phytochemicals against bacterial pathogens.

Personality type influence the gestational weight gain.

Science.gov (United States)

Franik, Grzegorz; Lipka, Nela; Kopyto, Katarzyna; Kopocińska, Joanna; Owczarek, Aleksander; Sikora, Jerzy; Madej, Paweł; Chudek, Jerzy; Olszanecka-Glinianowicz, Magdalena

2017-08-01

Pregnancy is frequently followed by the development of obesity. Aside from psychological factors, hormonal changes influence weight gain in pregnant women. We attempted to assess the potential association between personality type and the extent of gestational weight gain. The study group involved 773 women after term delivery (age 26.3 ± 3.9 years, body mass before pregnancy 61.2 ± 11.1 kg). Weight gain during pregnancy was calculated by using self-reported body mass prior to and during the 38th week of pregnancy. Personality type was assessed using the Polish version of the Framingham Type A Behavior Patterns Questionnaire (adapted by Juczynski). Two hundred forty-six (31.8%) study subjects represented type A personalities, 272 (35.2%) type B and 255 (33.0%) an indirect type. Gestational weight gain was related to the behavior patterns questionnaire score and age. In women gain was higher than in women with type B behavior of the same age. In women >30, the gestational weight gain was larger for type B personalities. Type A personality and increased urgency in younger pregnant women increases the risk of developing obesity during pregnancy in women below 30 years old. A higher level of competitiveness demonstrates a risk factor of excessive weight gain during pregnancy regardless of age.

The therapeutic potential of allosteric ligands for free fatty acid sensitive GPCRs

DEFF Research Database (Denmark)

Hudson, Brian D; Ulven, Trond; Milligan, Graeme

2013-01-01

G protein coupled receptors (GPCRs) are the most historically successful therapeutic targets. Despite this success there are many important aspects of GPCR pharmacology and function that have yet to be exploited to their full therapeutic potential. One in particular that has been gaining attention...... safety, more physiologically appropriate responses, better target selectivity, and reduced likelihood of desensitisation and tachyphylaxis. Despite these advantages, the development of allosteric ligands is often difficult from a medicinal chemistry standpoint due to the more complex challenge...

Genetic gain in dairy cattle populations is increased using sexed semen in commercial herds

DEFF Research Database (Denmark)

Sørensen, Morten Kargo; Andersen, Jakob Voergaard; Pedersen, Louise Dybdahl

2011-01-01

Using stochastic simulation, the effect of using sexed semen to cow dams (CD) in a dairy cattle breeding scheme, with or without use of multiple ovulation and embryo transfer (MOET) to bull dams (BD), on annual genetic gain at the population level was examined. Three levels of sexed semen were...... combined with three levels of MOET: no sexed semen, sexed semen to the best CD and sexed semen to all heifers, combined with no MOET, MOET on all BD and MOET randomly on 20% of the BD. In total, nine scenarios were compared. The simulated population was monitored for 30 years and included 450 herds...... with 100 cows each. Each year 50 young bulls (YB), 10 active sires and 215 BD were selected on best linear unbiased prediction estimated breeding values by truncation selection across the simulated population, and the YB were tested within the population. Use of sexed semen alone gave a positive increase...

Low-Gain Circularly Polarized Antenna with Torus-Shaped Pattern

Science.gov (United States)

Amaro, Luis R.; Kruid, Ronald C.; Vacchione, Joseph D.; Prata, Aluizio

2012-01-01

The Juno mission to Jupiter requires an antenna with a torus-shaped antenna pattern with approximately 6 dBic gain and circular polarization over the Deep Space Network (DSN) 7-GHz transmit frequency and the 8-GHz receive frequency. Given the large distances that accumulate en-route to Jupiter and the limited power afforded by the solar-powered vehicle, this toroidal low-gain antenna requires as much gain as possible while maintaining a beam width that could facilitate a +/-10deg edge of coverage. The natural antenna that produces a toroidal antenna pattern is the dipole, but the limited approx. = 2.2 dB peak gain would be insufficient. Here a shaped variation of the standard bicone antenna is proposed that could achieve the required gains and bandwidths while maintaining a size that was not excessive. The final geometry that was settled on consisted of a corrugated, shaped bicone, which is fed by a WR112 waveguide-to-coaxial- waveguide transition. This toroidal low-gain antenna (TLGA) geometry produced the requisite gain, moderate sidelobes, and the torus-shaped antenna pattern while maintaining a very good match over the entire required frequency range. Its "horn" geometry is also low-loss and capable of handling higher powers with large margins against multipactor breakdown. The final requirement for the antenna was to link with the DSN with circular polarization. A four-layer meander-line array polarizer was implemented; an approach that was fairly well suited to the TLGA geometry. The principal development of this work was to adapt the standard linear bicone such that its aperture could be increased in order to increase the available gain of the antenna. As one increases the aperture of a standard bicone, the phase variation across the aperture begins to increase, so the larger the aperture becomes, the greater the phase variation. In order to maximize the gain from any aperture antenna, the phase should be kept as uniform as possible. Thus, as the standard

Controlling gain one photon at a time

Science.gov (United States)

Schwartz, Gregory W; Rieke, Fred

2013-01-01

Adaptation is a salient property of sensory processing. All adaptational or gain control mechanisms face the challenge of obtaining a reliable estimate of the property of the input to be adapted to and obtaining this estimate sufficiently rapidly to be useful. Here, we explore how the primate retina balances the need to change gain rapidly and reliably when photons arrive rarely at individual rod photoreceptors. We find that the weakest backgrounds that decrease the gain of the retinal output signals are similar to those that increase human behavioral threshold, and identify a novel site of gain control in the retinal circuitry. Thus, surprisingly, the gain of retinal signals begins to decrease essentially as soon as background lights are detectable; under these conditions, gain control does not rely on a highly averaged estimate of the photon count, but instead signals from individual photon absorptions trigger changes in gain. DOI: http://dx.doi.org/10.7554/eLife.00467.001 PMID:23682314

Gain control network conditions in early sensory coding.

Directory of Open Access Journals (Sweden)

Eduardo Serrano

Full Text Available Gain control is essential for the proper function of any sensory system. However, the precise mechanisms for achieving effective gain control in the brain are unknown. Based on our understanding of the existence and strength of connections in the insect olfactory system, we analyze the conditions that lead to controlled gain in a randomly connected network of excitatory and inhibitory neurons. We consider two scenarios for the variation of input into the system. In the first case, the intensity of the sensory input controls the input currents to a fixed proportion of neurons of the excitatory and inhibitory populations. In the second case, increasing intensity of the sensory stimulus will both, recruit an increasing number of neurons that receive input and change the input current that they receive. Using a mean field approximation for the network activity we derive relationships between the parameters of the network that ensure that the overall level of activity of the excitatory population remains unchanged for increasing intensity of the external stimulation. We find that, first, the main parameters that regulate network gain are the probabilities of connections from the inhibitory population to the excitatory population and of the connections within the inhibitory population. Second, we show that strict gain control is not achievable in a random network in the second case, when the input recruits an increasing number of neurons. Finally, we confirm that the gain control conditions derived from the mean field approximation are valid in simulations of firing rate models and Hodgkin-Huxley conductance based models.

Rethinking Therapeutic Misconception in Biobanking

DEFF Research Database (Denmark)

Tupasela, Aaro; Snell, Karoliina; Cañada, Jose

2017-01-01

Some authors have noted that in biobank research participants may be guided by what is called therapeutic misconception, whereby participants attribute therapeutic intent to research procedures.This article argues that the notion of therapeutic misconception is increasingly less justified when...... underpinnings for the need to separate research and treatment, and thus the notion of therapeutic misconception in the fi rst place. We call this tension between research and treatment ambivalent research advancement to highlight the difficulties that various actors have in managing such shifts within...

Optimal weight gain in obese and overweight pregnant Japanese women.

Science.gov (United States)

Hirooka-Nakama, Junko; Enomoto, Kimiko; Sakamaki, Kentaro; Kurasawa, Kentaro; Miyagi, Etsuko; Aoki, Shigeru

2018-03-20

We aimed to determine the optimal gestational weight gain (GWG) in Japanese women with a Body Mass Index (BMI) ≥25 kg/m 2 . The present retrospective study investigated singleton pregnancies in 6,781 Japanese women registered in the Japan Society of Obstetrics and Gynecology system in 2013. We divided overweight and obese women into four GWG categories based on the Institute of Medicine (IOM) recommended: weight loss, small weight gain, within IOM criteria, and above IOM criteria. The adjusted odds ratios and predicted probabilities of maternal and neonatal outcomes of interest with weight change were calculated. In overweight women, GWG was associated with neonatal birth weight. In the loss and small gain subgroups, there was a significant increase in small for gestational age (SGA) and low birth weight neonates (LBW). Predicted probabilities showed the lowest risk was observed in a weight gain of 0 kg; the risk sharply increased at a gain of 11.5 kg. In obese women, weight gain increased the prevalence of large for gestational age (LGA) neonates; however; SGA was not associated with GWG. Predicted probabilities showed an increase in the risk with weight gain. The observed optimal GWG was 0 to 11.5 kg in overweight, and weight loss in obese, pregnant Japanese women.

Energy Gaining Windows for Residental Buildings

DEFF Research Database (Denmark)

Kragh, Jesper; Laustsen, Jacob Birck; Svendsen, Svend

2008-01-01

window is made of fiber-reinforced plastic (plastic reinforced by fine fibers made of glass). This composite material is a weatherproof material with very low thermal conductivity and high mechanical strength. These properties make the material very suitable for frame profiles due to lower heat loss...... minus the heat loss integrated over the heating season. It is assumed that in northern cold climates all of the solar gain during the heating season can be utilized for space heating. Problems with overheating in the summer period must be solved with overhang or moveable solar shading devices. Two...... and longer durability of the window. The glazing in these fiber reinforced polyester windows is both unsealed and sealed triple glazing units. To increase the net energy gain slim frame profiles have been developed to increase the glazing area and thereby the solar gain. The challenge when developing slim...

A generic whole body physiologically based pharmacokinetic model for therapeutic proteins in PK-Sim.

Science.gov (United States)

Niederalt, Christoph; Kuepfer, Lars; Solodenko, Juri; Eissing, Thomas; Siegmund, Hans-Ulrich; Block, Michael; Willmann, Stefan; Lippert, Jörg

2018-04-01

Proteins are an increasingly important class of drugs used as therapeutic as well as diagnostic agents. A generic physiologically based pharmacokinetic (PBPK) model was developed in order to represent at whole body level the fundamental mechanisms driving the distribution and clearance of large molecules like therapeutic proteins. The model was built as an extension of the PK-Sim model for small molecules incorporating (i) the two-pore formalism for drug extravasation from blood plasma to interstitial space, (ii) lymph flow, (iii) endosomal clearance and (iv) protection from endosomal clearance by neonatal Fc receptor (FcRn) mediated recycling as especially relevant for antibodies. For model development and evaluation, PK data was used for compounds with a wide range of solute radii. The model supports the integration of knowledge gained during all development phases of therapeutic proteins, enables translation from pre-clinical species to human and allows predictions of tissue concentration profiles which are of relevance for the analysis of on-target pharmacodynamic effects as well as off-target toxicity. The current implementation of the model replaces the generic protein PBPK model available in PK-Sim since version 4.2 and becomes part of the Open Systems Pharmacology Suite.

Capacity gains of buffer-aided moving relays

KAUST Repository

Zafar, Ammar

2017-03-14

This work investigates the gain due to reduction in path loss by deploying buffer-aided moving relaying. In particular, the increase in gain due to moving relays is studied for dual-hop broadcast channels and the bidirectional relay channel. It is shown that the exploited gains in these channels due to buffer-aided relaying can be enhanced by utilizing the fact that a moving relay can communicate with the terminal closest to it and store the data in the buffer and then forward the data to the intended destination when it comes in close proximity with the destination. Numerical results show that for both the considered channels the achievable rates are increased as compared to the case of stationary relays. Numerical results also show that more significant increase in performance is seen when the relay moves to-and-fro between the source and the relay.

Capacity gains of buffer-aided moving relays

KAUST Repository

Zafar, Ammar; Shaqfeh, Mohammad; Alnuweiri, Hussein; Alouini, Mohamed-Slim

2017-01-01

This work investigates the gain due to reduction in path loss by deploying buffer-aided moving relaying. In particular, the increase in gain due to moving relays is studied for dual-hop broadcast channels and the bidirectional relay channel. It is shown that the exploited gains in these channels due to buffer-aided relaying can be enhanced by utilizing the fact that a moving relay can communicate with the terminal closest to it and store the data in the buffer and then forward the data to the intended destination when it comes in close proximity with the destination. Numerical results show that for both the considered channels the achievable rates are increased as compared to the case of stationary relays. Numerical results also show that more significant increase in performance is seen when the relay moves to-and-fro between the source and the relay.

Gain maximization in a probabilistic entanglement protocol

Science.gov (United States)

di Lorenzo, Antonio; Esteves de Queiroz, Johnny Hebert

Entanglement is a resource. We can therefore define gain as a monotonic function of entanglement G (E) . If a pair with entanglement E is produced with probability P, the net gain is N = PG (E) - (1 - P) C , where C is the cost of a failed attempt. We study a protocol where a pair of quantum systems is produced in a maximally entangled state ρm with probability Pm, while it is produced in a partially entangled state ρp with the complementary probability 1 -Pm . We mix a fraction w of the partially entangled pairs with the maximally entangled ones, i.e. we take the state to be ρ = (ρm + wUlocρpUloc+) / (1 + w) , where Uloc is an appropriate unitary local operation designed to maximize the entanglement of ρ. This procedure on one hand reduces the entanglement E, and hence the gain, but on the other hand it increases the probability of success to P =Pm + w (1 -Pm) , therefore the net gain N may increase. There may be hence, a priori, an optimal value for w, the fraction of failed attempts that we mix in. We show that, in the hypothesis of a linear gain G (E) = E , even assuming a vanishing cost C -> 0 , the net gain N is increasing with w, therefore the best strategy is to always mix the partially entangled states. Work supported by CNPq, Conselho Nacional de Desenvolvimento Científico e Tecnológico, proc. 311288/2014-6, and by FAPEMIG, Fundação de Amparo à Pesquisa de Minas Gerais, proc. IC-FAPEMIG2016-0269 and PPM-00607-16.

Enhancing optical gains in Si nanocrystals via hydrogenation and cerium ion doping

International Nuclear Information System (INIS)

Wang, Dong-Chen; Li, Yan-Li; Song, Sheng-Chi; Guo, Wen-Ping; Lu, Ming; Chen, Jia-Rong

2014-01-01

We report optical gain enhancements in Si nanocrystals (Si-NCs) via hydrogenation and Ce 3+ ion doping. Variable stripe length technique was used to obtain gains. At 0.3 W/cm 2 pumping power density of pulsed laser, net gains were observed together with gain enhancements after hydrogenation and/or Ce 3+ ion doping; gains after loss corrections were between 89.52 and 341.95 cm −1 ; and the photoluminescence (PL) lifetime was found to decrease with the increasing gain enhancement. At 0.04 W/cm 2 power density, however, no net gain was found and the PL lifetime increased with the increasing PL enhancement. The results were discussed according to stimulated and spontaneous excitation and de-excitation mechanisms of Si-NCs.

Reactor-produced therapeutic radioisotopes

International Nuclear Information System (INIS)

Knapp, F.F. Jr.

2002-01-01

The significant worldwide increase in therapeutic radioisotope applications in nuclear medicine, oncology and interventional cardiology requires the dependable production of sufficient levels of radioisotopes for these applications (Reba, 2000; J. Nucl. Med., 1998; Nuclear News, 1999; Adelstein and Manning, 1994). The issues associated with both accelerator- and reactor-production of therapeutic radioisotopes is important. Clinical applications of therapeutic radioisotopes include the use of both sealed sources and unsealed radiopharmaceutical sources. Targeted radiopharmaceutical agents include those for cancer therapy and palliation of bone pain from metastatic disease, ablation of bone marrow prior to stem cell transplantation, treatment modalities for mono and oligo- and polyarthritis, for cancer therapy (including brachytherapy) and for the inhibition of the hyperplastic response following coronary angioplasty and other interventional procedures (For example, see Volkert and Hoffman, 1999). Sealed sources involve the use of radiolabeled devices for cancer therapy (brachytherapy) and also for the inhibition of the hyperplasia which is often encountered after angioplasty, especially with the exponential increase in the use of coronary stents and stents for the peripheral vasculature and other anatomical applications. Since neutron-rich radioisotopes often decay by beta decay or decay to beta-emitting daughter radioisotopes which serve as the basis for radionuclide generator systems, reactors are expected to play an increasingly important role for the production of a large variety of therapeutic radioisotopes required for these and other developing therapeutic applications. Because of the importance of the availability of reactor-produced radioisotopes for these applications, an understanding of the contribution of neutron spectra for radioisotope production and determination of those cross sections which have not yet been established is important. This

Assessment of Learning Gains in a Flipped Biochemistry Classroom

Science.gov (United States)

Ojennus, Deanna Dahlke

2016-01-01

The flipped classroom has become an increasingly popular pedagogical approach to teaching and learning. In this study, learning gains were assessed in a flipped biochemistry course and compared to gains in a traditional lecture. Although measured learning gains were not significantly different between the two courses, student perception of…

Commercially available interactive video games in burn rehabilitation: therapeutic potential.

Science.gov (United States)

Parry, Ingrid S; Bagley, Anita; Kawada, Jason; Sen, Soman; Greenhalgh, David G; Palmieri, Tina L

2012-06-01

Commercially available interactive video games (IVG) like the Nintendo Wii™ (NW) and PlayStation™II Eye Toy (PE) are increasingly used in the rehabilitation of patients with burn. Such games have gained popularity in burn rehabilitation because they encourage range of motion (ROM) while distracting from pain. However, IVGs were not originally designed for rehabilitation purposes but rather for entertainment and may lack specificity for achieving rehabilitative goals. Objectively evaluating the specific demands of IVGs in relation to common burn therapy goals will determine their true therapeutic benefit and guide their use in burn rehabilitation. Upper extremity (UE) motion of 24 normal children was measured using 3D motion analysis during play with the two types of IVGs most commonly described for use after burn: NW and PE. Data was analyzed using t-tests and One-way Analysis of Variance. Active range of motion for shoulder flexion and abduction during play with both PE and NW was within functional range, thus supporting the idea that IVGs offer activities with therapeutic potential to improve ROM. PE resulted in higher demands and longer duration of UE motion than NW, and therefore may be the preferred tool when UE ROM or muscular endurance are the goals of rehabilitation. When choosing a suitable IVG for application in rehabilitation, the user's impairment together with the therapeutic attributes of the IVG should be considered to optimize outcome. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

Fetal Programming of Obesity: Maternal Obesity and Excessive Weight Gain

Directory of Open Access Journals (Sweden)

Seray Kabaran

2014-10-01

Full Text Available The prevalence of obesity is an increasing health problem throughout the world. Maternal pre-pregnancy weight, maternal nutrition and maternal weight gain are among the factors that can cause childhood obesity. Both maternal obesity and excessive weight gain increase the risks of excessive fetal weight gain and high birth weight. Rapid weight gain during fetal period leads to changes in the newborn body composition. Specifically, the increase in body fat ratio in the early periods is associated with an increased risk of obesity in the later periods. It was reported that over-nutrition during fetal period could cause excessive food intake during postpartum period as a result of metabolic programming. By influencing the fetal metabolism and tissue development, maternal obesity and excessive weight gain change the amounts of nutrients and metabolites that pass to the fetus, thus causing excessive fetal weight gain which in turn increases the risk of obesity. Fetal over-nutrition and excessive weight gain cause permanent metabolic and physiologic changes in developing organs. While mechanisms that affect these organs are not fully understood, it is thought that the changes may occur as a result of the changes in fetal energy metabolism, appetite control, neuroendocrine functions, adipose tissue mass, epigenetic mechanisms and gene expression. In this review article, the effects of maternal body weight and weight gain on fetal development, newborn birth weight and risk of obesity were evaluated, and additionally potential mechanisms that can explain the effects of fetal over-nutrition on the risk of obesity were investigated [TAF Prev Med Bull 2014; 13(5.000: 427-434

Enhanced Gain in Photonic Crystal Amplifiers

DEFF Research Database (Denmark)

Ek, Sara; Semenova, Elizaveta; Hansen, Per Lunnemann

2012-01-01

We experimentally demonstrate enhanced gain in the slow-light regime of quantum well photonic crystal amplifiers. A strong gain enhancement is observed with the increase of the group refractive index, due to light slow-down. The slow light enhancement is shown in a amplified spontaneous emission....... These results are promising for short and efficient semiconductor optical amplifiers. This effect will also benefit other devices, such as mode locked lasers....

Evaluating realized genetic gains from tree improvement.

Science.gov (United States)

J.B. St. Clair

1993-01-01

Tree improvement has become an essential part of the management of forest lands for wood production, and predicting yields and realized gains from forests planted with genetically-improved trees will become increasingly important. This paper discusses concepts of tree improvement and genetic gain important to growth and yield modeling, and reviews previous studies of...

Discovery, clinical development, and therapeutic uses of bisphosphonates.

Science.gov (United States)

Licata, Angelo A

2005-04-01

To review the literature concerning the history, development, and therapeutic uses of bisphosphonates. English-language articles were identified through a search of MEDLINE (through December 2004) using the key word bisphosphonate. Reference lists of pivotal studies, reviews, and full prescribing information for the approved agents were also examined. Selected studies included those that discussed the discovery and initial applications of bisphosphonates, as well as their historical development, pharmacokinetic and pharmacodynamic properties, and current therapeutic uses. Bisphosphonates structurally resemble pyrophosphates (naturally occurring polyphosphates) and have demonstrated similar physicochemical effects to pyrophosphates. In addition, bisphosphonates reduce bone turnover and resist hydrolysis when administered orally. The information gained from initial work with etidronate generated a considerable scientific effort to design new and more effective bisphosphonates. The PCP moiety in the general bisphosphonate structure is essential for binding to hydroxyapatite and allows for a number of chemical variations by changing the 2 lateral side chains (designated R(1) and R(2)). The R(1) side chain determines binding affinity to hydroxyapatite, and the R(2) side chain determines antiresorptive potency. Accordingly, each bisphosphonate has its own characteristic profile of activity. The bisphosphonates reduce bone turnover, increase bone mass, and decrease fracture risk and therefore have a significant place in the management of skeletal disorders including osteoporosis, Paget's disease, bone metastases, osteogenesis imperfecta, and heterotopic ossification.

Assessment of learning gains in a flipped biochemistry classroom.

Science.gov (United States)

Ojennus, Deanna Dahlke

2016-01-01

The flipped classroom has become an increasingly popular pedagogical approach to teaching and learning. In this study, learning gains were assessed in a flipped biochemistry course and compared to gains in a traditional lecture. Although measured learning gains were not significantly different between the two courses, student perception of learning gains did differ and indicates a higher level of satisfaction with the flipped lecture format. © 2015 The International Union of Biochemistry and Molecular Biology.

Therapeutic enhancement: nursing intervention category for patients diagnosed with Readiness for Therapeutic Regimen Management.

Science.gov (United States)

Kelly, Cynthia W

2008-04-01

To present a new nursing intervention category called therapeutic enhancement. Fewer than half of North Americans follow their physician's recommendations for diet and exercise, even when such are crucial to their health or recovery. It is imperative that nurses consider new ways to promote healthy behaviours. Therapeutic enhancement is intended to provide such a fresh approach. Traditional intervention techniques focusing on education, contracts, social support and more frequent interaction with physicians appear not to be effective when used alone. Successful strategies have been multidisciplinary; and have included interventions by professional nurses who assist patients to understand their disease and the disease process and that helps them to develop disease-management and self-management skills. Therapeutic enhancement incorporates The Stages of Change Theory, Commitment to Health Theory, Motivational Interviewing techniques and instrumentation specifically designed for process evaluation of health-promoting interventions. This is a critical review of approaches that, heretofore, have not been synthesised in a single published article. Based on the commonly used Stages of Change model, therapeutic enhancement is useful for patients who are at the action stage of change. Using therapeutic enhancement as well as therapeutic strategies identified in Stages of Change Theory, such as contingency management, helping relationships, counterconditioning, stimulus control and Motivational Interviewing techniques, nursing professionals can significantly increase the chances of patients moving from action to the maintenance stage of change for a specific health behaviour. Using the nursing intervention category, therapeutic enhancement can increase caregivers' success in helping patients maintain healthy behaviours.

Net energy gain from DT fusion

International Nuclear Information System (INIS)

Buende, R.

1985-01-01

The net energy which can be gained from an energy raw material by means of a certain conversion system is deduced as the figure-of-merit which adequately characterizes the net energy balance of utilizing an energy source. This potential net energy gain is determined for DT fusion power plants. It is represented as a function of the degree of exploitation of the energy raw material lithium ore and is compared with the net energy which can be gained with LW and FBR power plants by exploiting uranium ore. The comparison clearly demonstrates the net energetic advantage of DT fusion. A sensitivity study shows that this holds even if the energy expenditure for constructing and operating is drastically increased

Toxoplasmosis Complications and Novel Therapeutic Synergism Combination of Diclazuril plus Atovaquone

Directory of Open Access Journals (Sweden)

Helieh S Oz

2014-09-01

Full Text Available Toxoplasmosis is a major cause of foodborne disease, congenital complication and morbidity. There is an urgent need for safe and effective therapies to encounter congenital and persisting toxoplasmosis. The hypothesis was: Combination Diclazuril plus Atovaquone to exert a novel therapeutic synergy to prevent toxoplasmosis syndromes. Methods. Pregnant dams were treated with Diclazuril and Atovaquone monotherapy or combination therapy and infected intraperitoneally with Toxoplasma tachyzoites (600. Results. Infected dams developed severe toxoplasmosis associated syndrome with increases in the abdominal adiposity surrounding uteri, gansterointestinal and other internal organs and excessive weight gain. Numerous organisms along with infiltration of inflammatory cells were detected scattered into adipose tissues. Combination therapy (p< 0.01 and to a lesser extent Diclazuril (p< 0.05 protected dams from inflammatory fat and excess weight gains. This was consistent with pancreatitis development in infected dams (versus normal p< 0.05 with infiltration of inflammatory cells, degeneration and necrosis of pancreatic cells followed by the degeneration and loss of islets. Combination and monotherapy protected dams from these inflammatory and pathological aspects of pancreatitis. Infected dams exhibited severe colitis, and colonic tissues significantly shortened in length. Brush border epithelial cells were replaced with infiltration of lymphocytes, granulocytes, and microabscess formations into cryptic microstructures. Combination therapy synergistically preserved colonic structure and normalized pathological damages (p< 0.001 and to a lesser degree Diclazuril monotherapy protected dams from colitis (p< 0.05 and gastrointestinal toxoplasmosis. Other complications included severe splenitis (p<0.001 and hepatitis (p<0.001 which were normalized with combination therapy. Conclusions. Combination Diclazuril plus Atovaquone was safe and with a novel therapeutic

The effect of holiday weight gain on body weight.

Science.gov (United States)

Schoeller, Dale A

2014-07-01

The topic of holiday weight gain has been a frequent subject of the lay media; however, scientific interest has only been recent. Multiple studies in Western societies have reported average weight gains among adults during the period between mid-November and mid-January that were about 0.5 kg. The range in individual weight changes was large, however, and the already overweight and obese gain more weight than those who are healthy weight. When the average gain across the year was also measured, the holiday weight was the major contributor to annual excess weight gain. Efforts patterned to increase awareness to energy balance and body weight have been shown to be successful at reducing such gain. An exception to holiday weight gain being a major contributor to annual excess gain has been children, in whom summer weight gains have been observed to be the major contributor to average excess weight gain. Copyright © 2014 Elsevier Inc. All rights reserved.

[Body weight gain after radioiodine therapy in hyperthyroidism].

Science.gov (United States)

Scheidhauer, K; Odatzidu, L; Kiencke, P; Schicha, H

2002-02-01

Analysis and follow up of body weight after radioiodine therapy (RITh) of hyperthyroidism, since excessive weight gain is a common complaint among these patients. Therapy and body weight related data of 100 consecutive RITh-patients were retrospectively analysed from the time before up to three years after RITh. All patients suffered from hyperthyroidism (Graves' disease or autonomy), but were adjusted to euthyroid levels after RITh. Patients' data were compared to a control group of 48 euthyroid patients out of the same ambulance and during the same time scale. All patients (RITh and controls) gained weight over the time. There was no statistically significant difference in BMI development over three years between RITh-patients and controls (5.5% resp. 4.9% increase). In the first year after RITh, weight gain of the RITh patients was higher indeed, but lower in the follow up, resulting in the same range of weight gain after three years as the controls. Besides that women showed a slightly higher increase of BMI than men, and so did younger patients compared to elder as well as patients with overweight already before RITh. An initially distinct increase of body weight after RITh of hyperthyroidism is mainly a compensation of pretherapeutic weight loss due to hyperthyroidism. Presupposing adequate euthyroid adjustment of thyroid metabolism after therapy, RITh is not responsible for later weight gain and adipositas.

Determinants of Weight Gain During Adjuvant Endocrine Therapy and Association of Such Weight Gain With Recurrence in Long-term Breast Cancer Survivors.

Science.gov (United States)

Raghavendra, Akshara; Sinha, Arup K; Valle-Goffin, Janeiro; Shen, Yu; Tripathy, Debu; Barcenas, Carlos H

2018-02-01

Weight gain is a negative prognostic factor in breast cancer (BC) patients. The risk factors for weight gain during adjuvant endocrine therapy (ET) and the extent to which such weight gain is associated with disease recurrence remain unclear. We retrospectively identified a cohort of women with a diagnosis of stage I-III, hormone receptor-positive, human epidermal growth factor receptor 2-negative BC from January 1997 to August 2008, who had received initial treatment at the MD Anderson Cancer Center, had completed 5 years of ET, and had remained free of locoregional or distant relapse or contralateral BC for ≥ 5 years after diagnosis. The weight change at the end of 5 years of ET was measured as the percentage of the change in weight from the start of ET, with a weight gain of > 5% considered clinically significant. Multivariable logistic regression and Cox proportional hazards models were used to assess the determinants of such weight gain and the risk of recurrence after 5 years. Of 1282 long-term BC survivors, 432 (33.7%) had a weight gain of > 5% after 5 years of ET. Women who were premenopausal at diagnosis were 1.40 times more likely than women who were postmenopausal at diagnosis to have a weight gain of > 5%. Asian women had the lowest risk of gaining weight. The recurrence risks of patients who had gained weight and those who had not were not significantly different. Premenopausal BC patients had an increased risk of weight gain after 5 years of ET; however, BC patients with a weight gain of > 5% did not have an increased risk of disease recurrence. Copyright © 2017 Elsevier Inc. All rights reserved.

Gain uniformity experimental study performed on triple-GEM gas detector

International Nuclear Information System (INIS)

Dong Liyuan; Qi Huirong; Lu Xinyu; Ouyang Qun; Chen Yuanbo; Li Yuhong

2012-01-01

With the application of the two-dimensional GEM gaseous detector in X-ray imaging, the correction method of gain uniformity caused by triple-GEM avalanche structures and electric field uniformity should be studied. The paper reported the study of the triple-GEM detector with effective area 100 mm × 100 mm used the Pad's size of 9.5 mm × 9.5 mm. In the test, 100 readout channels were designed. Results showed that gain remained stable over time; at air flow increases, gain from increases obviously to changes very little. Particularly, triple-GEM's gain uniformity was very good (more than 80%) and the range of energy resolution was from 0.18 to 0.2. To improve gain consistency of results, the difference value revised was obtained to be about 0.1 by the least square method. It provided a better method to improve gain uniformity of GEM detector. (authors)

Quercetin: A wonder bioflvonoid with therapeutic potential in disease management

Directory of Open Access Journals (Sweden)

Alka Gupta

2016-03-01

Full Text Available In the last decade, considerable efforts have been made to develop health promising nutritional supplements. Quercetin is a plant-derived bioflavonoid which is recently gaining scientific interest for its antioxidant free radical scavenging effects and anti-inflammatory properties. This wonder flavanol exhibits therapeutic potential in various ailments like cancer, coronary artery, asthma and alzheimer (neurodegeneration diseases. Additional clinical uses include treatment of inflammatory conditions like gout, pancreatitis and prostatitis. It has been extensively studied for its gastroprotective effects, anti-obesity action, immune booster, reducing risk of cataract and reduction of diabetic complications. The present review briefly discusses about biological activity, mechanism of action and therapeutic potential of quercetin in prevention and mitigation of diseases.

Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy.

Science.gov (United States)

Wagner, Mark T; Mithoefer, Michael C; Mithoefer, Ann T; MacAulay, Rebecca K; Jerome, Lisa; Yazar-Klosinski, Berra; Doblin, Rick

2017-08-01

A growing body of research suggests that traumatic events lead to persisting personality change characterized by increased neuroticism. Relevantly, enduring improvements in Post-Traumatic Stress Disorder (PTSD) symptoms have been found in response to 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. There is evidence that lasting changes in the personality feature of "openness" occur in response to hallucinogens, and that this may potentially act as a therapeutic mechanism of change. The present study investigated whether heightened Openness and decreased Neuroticism served as a mechanism of change within a randomized trial of MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD. The Clinician-Administered PTSD Scale (CAPS) Global Scores and NEO PI-R Personality Inventory (NEO) Openness and Neuroticism Scales served as outcome measures. Results indicated that changes in Openness but not Neuroticism played a moderating role in the relationship between reduced PTSD symptoms and MDMA treatment. Following MDMA-assisted psychotherapy, increased Openness and decreased Neuroticism when comparing baseline personality traits with long-term follow-up traits also were found. These preliminary findings suggest that the effect of MDMA-assisted psychotherapy extends beyond specific PTSD symptomatology and fundamentally alters personality structure, resulting in long-term persisting personality change. Results are discussed in terms of possible mechanisms of psychotherapeutic change.

Determining productivity gains from herbaceous vegetation management with 'age-shift' calculations

Science.gov (United States)

David B. South; James H. Miller; Mark O. Kimberley; Curtis L. Vanderschaaf

2006-01-01

Gains in stand volume that result from competition control and fertilization are sometimes reported as 'percentage gains'. Because percentage gains arithmetically decline over time asstand volume increases, plantation managers have difficultyin using percentage gains to project growth and revenues. The 'age-shift' method quantifies the year...

Gestational weight gain.

Science.gov (United States)

Kominiarek, Michelle A; Peaceman, Alan M

2017-12-01

Prenatal care providers are advised to evaluate maternal weight at each regularly scheduled prenatal visit, monitor progress toward meeting weight gain goals, and provide individualized counseling if significant deviations from a woman's goals occur. Today, nearly 50% of women exceed their weight gain goals with overweight and obese women having the highest prevalence of excessive weight gain. Risks of inadequate weight gain include low birthweight and failure to initiate breast-feeding whereas the risks of excessive weight gain include cesarean deliveries and postpartum weight retention for the mother and large-for-gestational-age infants, macrosomia, and childhood overweight or obesity for the offspring. Prenatal care providers have many resources and tools to incorporate weight and other health behavior counseling into routine prenatal practices. Because many women are motivated to improve health behaviors, pregnancy is often considered the optimal time to intervene for issues related to eating habits and physical activity to prevent excessive weight gain. Gestational weight gain is a potentially modifiable risk factor for a number of adverse maternal and neonatal outcomes and meta-analyses of randomized controlled trials report that diet or exercise interventions during pregnancy can help reduce excessive weight gain. However, health behavior interventions for gestational weight gain have not significantly improved other maternal and neonatal outcomes and have limited effectiveness in overweight and obese women. Copyright © 2017 Elsevier Inc. All rights reserved.

[Predictors of the therapeutic discharge in patients with dual pathology admitted to a therapeutic community with a psychiatric unit].

Science.gov (United States)

Madoz-Gúrpide, Agustín; García Vicent, Vicente; Luque Fuentes, Encarnación; Ochoa Mangado, Enriqueta

2013-01-01

This study aims to analyze the variables on which depends therapeutic discharge, in patients with a severe dual diagnosis admitted to a professional therapeutic community where their pathology is treated. 325 patients admitted between June 2000 and June 2009 to the therapeutic community. This is a retrospective, cross-sectional study with no control group, based on the detailed analysis of the information collected in a model of semi-structured clinical interview designed in the therapeutic community. The 29.5% of the individuals included in the sample were therapeutically discharged. Of all the variables introduced in this analysis the most significant ones were gender, age at the beginning of treatment, education level, opiate dependence, polidrug abuse, and the presence of psychotic disorders and borderline personality disorder. In our study, gender determines the type of discharge, being therapeutic discharge more frequent among women. A higher educational also increases a better prognosis with a higher rate of therapeutic discharge among individuals with higher education level. A later age at the beginning of the treatment reduces the likelihood of therapeutic discharge. Likewise, polidrug abuse, diagnosis of psychotic disorders and borderline personality disorder are associated to a lower rate of therapeutic discharge. Recognizing these characteristics will allow the early identification of those patients more at risk of dropping treatment hastily, while trying to prevent it by increasing the therapeutic intensity.

Optical properties of nanowire metamaterials with gain

DEFF Research Database (Denmark)

Isidio de Lima, Joaquim Junior; Adam, Jost; Rego, Davi

2016-01-01

The transmittance, reflectance and absorption of a nanowire metamaterial with optical gain are numerically simulated and investigated. It is assumed that the metamaterial is represented by aligned silver nanowires embedded into a semiconductor matrix, made of either silicon or gallium phosphide....... The gain in the matrix is modeled by adding a negative imaginary part to the dielectric function of the semiconductor. It is found that the optical coefficients of the metamaterial depend on the gain magnitude in a non-trivial way: they can both increase and decrease with gain depending on the lattice...... constant of the metamaterial. This peculiar behavior is explained by the field redistribution between the lossy metal nanowires and the amplifying matrix material. These findings are significant for a proper design of nanowire metamaterials with low optical losses for diverse applications....

FEL gain optimisation and spontaneous radiation

Energy Technology Data Exchange (ETDEWEB)

Bali, L.M.; Srivastava, A.; Pandya, T.P. [Lucknow Univ. (India)] [and others

1995-12-31

Colson have evaluated FEL gains for small deviations from perfect electron beam injection, with radiation of the same polarisation as that of the wiggler fields. We find that for optimum gain the polarisation of the optical field should be the same as that of the spontaneous emission under these conditions. With a helical wiggler the axial oscillations resulting from small departures from perfect electron beam injection lead to injection dependent unequal amplitudes and phases of the spontaneous radiation in the two transverse directions. Viewed along the axis therefore the spontaneous emission is elliptically polarised. The azimuth of the ellipse varies with the difference of phase of the two transverse components of spontaneous emission but the eccentricity remains the same. With planar wigglers the spontaneous emission viewed in the axial direction is linearly polarised, again with an injection dependent azimuth. For optimum coherent gain of a radiation field its polarisation characteristics must be the same as those of the spontaneous radiation with both types of wiggler. Thus, with a helical wiggler and the data reported earlier, an increase of 10% in the FEL gain at the fundamental frequency and of 11% at the fifth harmonic has been calculated in the small gain per pass limit. Larger enhancements in gain may result from more favourable values of input parameters.

The increase of Lactobacillus species in the gut flora of newborn broiler chicks and ducks is associated with weight gain.

Directory of Open Access Journals (Sweden)

Emmanouil Angelakis

Full Text Available BACKGROUND: A bacterial role in the obesity pandemic has been suspected based on the ingestion of probiotics that can modify the gut flora. The objective of our study was to determine if increased Lactobacillus sp. in the gut flora of newborn broiler chicks and ducks could result in weight gain increase. METHODOLOGY: Female broiler chicks (Gallus gallus domesticus and ducks (Anas platyrhynchos domestica were separated into one control and two experimental groups, and inoculated once or twice with 4x10(10Lactobacillus spp. per animal in PBS, or with PBS alone. Fecal samples were collected before and at 24 hours, 2, 4, 8, 16 and 30 days after the inoculation. DNA was extracted from the stools, and qPCR assays were performed on a MX3000 system for the detection and quantification of Lactobacillus sp., Bacteroidetes and Firmicutes, using a quantification plasmid. Animals were measured and sacrificed 60 days after the beginning of the experiment, and livers were collected and measured. PRINCIPAL FINDINGS: Chicks inoculated once and twice with Lactobacillus weighed 10.2% (p = 0.0162 and 13.5% (p = 0.0064 more than the control group animals, respectively. Similarly, ducks inoculated once and twice weighed 7.7% (p = 0.05 and 14% (p = 0.035 more than those in the control group, respectively. Liver mass was also significantly higher in inoculated animals compared to the control group. Inoculation with Lactobacillus sp. increased the DNA copies of Lactobacillus spp. and Firmicutes in the stools. Bacteroidetes remained stable, and only the second Lactobacillus sp. inoculation significantly decreased its population in chicks. The ratio of DNA copies of Firmicutes to those of Bacteroidetes increased to as much as 6,4 in chicks and 8,3 in ducks. CONCLUSIONS: Differences in the intestinal microbiota may precede weight increase, as we found that an increase of Lactobacillus sp. in newborn ducks and chicks preceded the development of weight gain.

Variety Gains and the Extensive Margin of Trade

OpenAIRE

Mohler, Lukas

2012-01-01

Findings from the literature suggest that previous estimates of the variety gains from trade are too small because of the imprecise measurement of the imported variety set under the Armington assumption. In this contribution, I use results from the literature on multi-product firms to obtain variety gain estimates that account for the entry and exit of firms as well as for product turnover within firms and find that welfare gains increase by a factor of 2.5 compared to the baseline Armington ...

Identification of coexistence of BRAF V600E mutation and EZH2 gain specifically in melanoma as a promising target for combination therapy.

Science.gov (United States)

Yu, Huan; Ma, Meng; Yan, Junya; Xu, Longwen; Yu, Jiayi; Dai, Jie; Xu, Tianxiao; Tang, Huan; Wu, Xiaowen; Li, Siming; Lian, Bin; Mao, Lili; Chi, Zhihong; Cui, Chuanliang; Guo, Jun; Kong, Yan

2017-12-04

Coexistence of enhancer of zeste homolog 2 (EZH2) and BRAF gene aberrations has been described in many cancer types. In this study, we aim to explore the coexistence status of BRAF V600E mutation and the copy number variation of EZH2 and explore the potential of this combination as a therapeutic target. A total of 138 cases of melanoma samples harboring BRAF V600E mutation were included, and EZH2 copy numbers were examined by QuantiGenePlex DNA Assays. Clinical pathological distinction between patient groups with or without EZH2 amplification (hereafter referred to as EZH2 gain) was statistically analyzed. The sensitivity of melanoma cell lines and patient-derived xenograft (PDX) models containing BRAF V600E mutation with or without EZH2 gain to vemurafenib (BRAF inhibitor), GSK2816126 (EZH2 inhibitor) and a combination of both agents was evaluated. In our cohort, the coexistence rate of BRAF V600E mutation and EZH2 gain was up to 29.0%, and significant differences in overall survival and disease-free survival were found between no EZH2 copy number gain and gain groups (P = 0.038, P = 0.030), gain and high EZH2 copy number gain groups (P = 0.006, P = 0.010). Combination with BRAF and EZH2 inhibition showed better inhibitory efficacy in melanoma prevention compared with vemurafenib monotherapy. More importantly, this improved therapeutic effect was observed especially in melanoma cell lines and PDX models containing concurrently BRAF V600E mutation and EZH2 gain. Coexistence of BRAF V600E mutation and EZH2 gain is rather prevalent in melanoma. Our findings provided evidence for the feasibility of combination therapy with EZH2 and BRAF inhibitors in melanoma with concurrent BRAF V600E mutation and EZH2 gain.

Body weight gain after radioiodine therapy of hyperthyroidism

International Nuclear Information System (INIS)

Scheidhauer, K.; Odatzidu, L.; Schicha, H.

2002-01-01

Aim: Analysis and follow up of body weight after radioiodine therapy (RITh) of hyperthyroidism, since excessive weight gain is a common complaint among these patients. Methods: Therapy and body weight related data of 100 consecutive RITh-patients were retrospectively analysed from the time before up to three years after RITh. All patients suffered from hyperthyroidism (Graves' disease or autonomy), but were adjusted to euthyroid levels after RITh. Patients' data were compared to a control group of 48 euthyroid patients out of the same ambulance and during the same time scale. Results: All patients (RITh and controls) gained weight over the time. There was no statistically significant difference in BMI development over three years between RITh-patients and controls (5.5% resp. 4.9% increase). In the first year after RITh, weight gain of the RITh patients was higher indeed, but lower in the follow up, resulting in the same range of weight gain after three years as the controls. Besides that women showed a slightly higher increase of BMI than men, and so did younger patients compared to elder as well as patients with overweight already before RITh. Conclusions: An initially distinct increase of body weight after RITh of hyperthyroidism is mainly a compensation of pretherapeutic weight loss due to hyperthyroidism. Presupposing adequate euthyroid adjustment of thyroid metabolism after therapy, RITh is not responsible for later weight gain and adipositas. (orig.) [de

Maternal Obesity, Gestational Weight Gain, and Asthma in Offspring.

Science.gov (United States)

Polinski, Kristen J; Liu, Jihong; Boghossian, Nansi S; McLain, Alexander C

2017-11-09

Obesity is common among women of childbearing age; intrauterine exposure to maternal obesity or gestational weight gain may influence the development of asthma in early childhood. We examined the relationships of maternal obesity and gestational weight gain with asthma in offspring. We used data from the Early Childhood Longitudinal Study-Birth Cohort, which has a nationally representative sample of children followed from birth in 2001 through age 4 (n = 6,450). Asthma was based on parental report of a medical professional's diagnosis. We used generalized estimating equation binomial models to compute adjusted odds ratios (ORs) of childhood asthma with maternal obesity and 4 measures of gestational weight gain. Compared with children of normal-weight mothers, children of obese mothers had increased risk of asthma (adjusted OR, 1.63; 95% confidence interval [CI], 1.26-2.12) by age 4, and children born to overweight mothers had similar risk (adjusted OR, 1.25; 95% CI, 0.99-1.59). Extreme-low weight gain (gain (≥25 kg) were associated with increased risk of asthma; however, the following measures were not significant predictors of asthma: meeting gestational weight gain recommendations of the Institute of Medicine, total gestational weight gain, and weekly rate of weight gain in the second and third trimesters. Extreme-low or extreme-high gestational weight gain and maternal obesity are risk factors for early childhood asthma, further evidence of the long-term impact of intrauterine exposure on children and the need to target preconception care to improve child health indicators.

Short communication: The gain-of-function Y581S polymorphism of the ABCG2 transporter increases secretion into milk of danofloxacin at the therapeutic dose for mastitis treatment.

Science.gov (United States)

Otero, J A; Barrera, B; de la Fuente, A; Prieto, J G; Marqués, M; Álvarez, A I; Merino, G

2015-01-01

The ATP-binding cassette transporter ABCG2 restricts the exposure of certain drugs and natural compounds in different tissues and organs. Its expression in the mammary gland is induced during lactation and is responsible for the active secretion of many compounds into milk, including antimicrobial agents. This particular function of ABCG2 may affect drug efficacy against mastitis and the potential presence of drug residues in the milk. Previous in vitro and in vivo studies showed increased transport of several compounds, including fluoroquinolones, by the bovine ABCG2 Y581S polymorphism. Our main purpose was to study the potential effect of this bovine ABCG2 polymorphism on the secretion into milk of the antimicrobial danofloxacin administered at the therapeutic dose of 6mg/kg used for mastitis treatment. In addition, the effect of this polymorphism on the relative mRNA and protein levels of ABCG2 by quantitative real-time PCR and Western blot were studied. Danofloxacin 18% (6mg/kg) was administered to 6 Y/Y homozygous and 5 Y/S heterozygous cows. Danofloxacin levels in milk and milk-to-plasma concentration ratios were almost 1.5- and 2-fold higher, respectively, in Y/S cows compared with the Y/Y cows, showing a higher capacity of this variant to transport danofloxacin into milk. Furthermore, the higher activity of this polymorphism is not linked to higher ABCG2 mRNA or protein levels. These results demonstrate the relevant effect of the Y581S polymorphism of the bovine ABCG2 transporter in the secretion into milk of danofloxacin after administration of 6mg/kg, with potentially important consequences for mastitis treatment and for milk residue handling. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Operational gain : measuring the capture of genetic gain ...

African Journals Online (AJOL)

The concept of operational gain is more than the weighted average of the genetic quality of planted hectares, and encompasses tree breeding efficiencies, propagation efficiencies, matching of species and genotype to site, plant use efficiency and early measures of stand density and growth. To test the operational gain ...

Central gain control in tinnitus and hyperacusis

Directory of Open Access Journals (Sweden)

Benjamin D Auerbach

2014-10-01

Full Text Available Sensorineural hearing loss induced by noise or ototoxic drug exposure reduces the neural activity transmitted from the cochlea to the central auditory system. Despite a reduced cochlear output, neural activity from more central auditory structures is paradoxically enhanced at suprathreshold intensities. This compensatory increase in the central auditory activity in response to the loss of sensory input is referred to as central gain enhancement. Enhanced central gain is hypothesized to be a potential mechanism that gives rise to hyperacusis and tinnitus, two debilitating auditory perceptual disorders that afflict millions of individuals. This review will examine the evidence for gain enhancement in the central auditory system in response to cochlear damage. Further, it will address the potential cellular and molecular mechanisms underlying this enhancement and discuss the contribution of central gain enhancement to tinnitus and hyperacusis. Current evidence suggests that multiple mechanisms with distinct temporal and spectral profiles are likely to contribute to central gain enhancement. Dissecting the contributions of these different mechanisms at different levels of the central auditory system is essential for elucidating the role of central gain enhancement in tinnitus and hyperacusis and, most importantly, the development of novel treatments for these disorders.

Central Gain Control in Tinnitus and Hyperacusis

Science.gov (United States)

Auerbach, Benjamin D.; Rodrigues, Paulo V.; Salvi, Richard J.

2014-01-01

Sensorineural hearing loss induced by noise or ototoxic drug exposure reduces the neural activity transmitted from the cochlea to the central auditory system. Despite a reduced cochlear output, neural activity from more central auditory structures is paradoxically enhanced at suprathreshold intensities. This compensatory increase in the central auditory activity in response to the loss of sensory input is referred to as central gain enhancement. Enhanced central gain is hypothesized to be a potential mechanism that gives rise to hyperacusis and tinnitus, two debilitating auditory perceptual disorders that afflict millions of individuals. This review will examine the evidence for gain enhancement in the central auditory system in response to cochlear damage. Further, it will address the potential cellular and molecular mechanisms underlying this enhancement and discuss the contribution of central gain enhancement to tinnitus and hyperacusis. Current evidence suggests that multiple mechanisms with distinct temporal and spectral profiles are likely to contribute to central gain enhancement. Dissecting the contributions of these different mechanisms at different levels of the central auditory system is essential for elucidating the role of central gain enhancement in tinnitus and hyperacusis and, most importantly, the development of novel treatments for these disorders. PMID:25386157

TCAD simulation of Low Gain Avalanche Detectors

Science.gov (United States)

Dalal, Ranjeet; Jain, Geetika; Bhardwaj, Ashutosh; Ranjan, Kirti

2016-11-01

In the present work, detailed simulation using Technology Computer Aided Design (TCAD) tool, Silvaco for non-irradiated and irradiated LGAD (Low Gain Avalanche Detector) devices has been carried out. The effects of different design parameters and proton irradiation on LGAD operation are discussed in detail. An already published effective two trap bulk damage model is used to simulate the radiation damage without implementing any acceptor removal term. The TCAD simulation for irradiated LGAD devices produce decreasing gain with increasing fluence, similar to the measurement results. The space charge density and electric field distribution are used to illustrate the possible reasons for the degradation of gain of the irradiated LGAD devices.

TCAD simulation of Low Gain Avalanche Detectors

Energy Technology Data Exchange (ETDEWEB)

Dalal, Ranjeet; Jain, Geetika; Bhardwaj, Ashutosh, E-mail: ashutosh.bhardwaj@cern.ch; Ranjan, Kirti

2016-11-11

In the present work, detailed simulation using Technology Computer Aided Design (TCAD) tool, Silvaco for non-irradiated and irradiated LGAD (Low Gain Avalanche Detector) devices has been carried out. The effects of different design parameters and proton irradiation on LGAD operation are discussed in detail. An already published effective two trap bulk damage model is used to simulate the radiation damage without implementing any acceptor removal term. The TCAD simulation for irradiated LGAD devices produce decreasing gain with increasing fluence, similar to the measurement results. The space charge density and electric field distribution are used to illustrate the possible reasons for the degradation of gain of the irradiated LGAD devices.

TCAD simulation of Low Gain Avalanche Detectors

International Nuclear Information System (INIS)

Dalal, Ranjeet; Jain, Geetika; Bhardwaj, Ashutosh; Ranjan, Kirti

2016-01-01

In the present work, detailed simulation using Technology Computer Aided Design (TCAD) tool, Silvaco for non-irradiated and irradiated LGAD (Low Gain Avalanche Detector) devices has been carried out. The effects of different design parameters and proton irradiation on LGAD operation are discussed in detail. An already published effective two trap bulk damage model is used to simulate the radiation damage without implementing any acceptor removal term. The TCAD simulation for irradiated LGAD devices produce decreasing gain with increasing fluence, similar to the measurement results. The space charge density and electric field distribution are used to illustrate the possible reasons for the degradation of gain of the irradiated LGAD devices.

Therapist Self-Disclosure and the Therapeutic Relationship: A Phenomenological Study from the Client Perspective

Science.gov (United States)

Audet, Cristelle T.; Everall, Robin D.

2010-01-01

Therapist self-disclosure is gaining empirical attention amidst theoretical discourse and ethical debate, particularly with regards to its influence on the therapeutic relationship. This paper presents part of a larger qualitative study that explored client experiences of therapist self-disclosure and specifically focuses on the therapeutic…

Tributyltin exposure induces gut microbiome dysbiosis with increased body weight gain and dyslipidemia in mice.

Science.gov (United States)

Guo, Hao; Yan, Haotian; Cheng, Dong; Wei, Xinglong; Kou, Ruirui; Si, Jiliang

2018-05-03

Gut microbiome dysbiosis plays a profound role in the pathogenesis of obesity and tributyltin (TBT) has been found as an environmental obesogen. However, whether TBT could disturb gut microbiome and the relationship between obesity induced by TBT exposure and alteration in gut microbiota are still unknown. In order to assess the association between them, mice were exposed to TBTCl (50 μg kg -1 ) once every three days from postnatal days (PNDs) 24 to 54. The results demonstrated that TBT exposure resulted in increased body weight gain, lager visceral fat accumulation and dyslipidemia in male mice on PND 84. Correspondingly, 16S rRNA gene sequencing revealed that TBT treatment decreased gut microbial species and perturbed the microbiome composition in mice. Furthermore, Pearson's corelation coefficient analysis showed a significantly negative correlation between the body weight and the alpha diversity of gut microbiome. These results suggested that TBT exposure could induce gut microbiome dysbiosis in mice, which might contribute to the obesity pathogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

Could Nutritional Rehabilitation at Home Complement or Replace Centre-based Therapeutic Feeding Programmes for Severe Malnutrition?

OpenAIRE

Gaboulaud, Valérie; Dan-Bouzoua, N; Brasher, C; Fedida, G; Gergonne, B; Brown, Vincent

2007-01-01

To measure the success rate of three different strategies used in Médecins Sans Frontières large-scale therapeutic nutritional rehabilitation programme in Niger, we analysed three cohorts of severely malnourished patients in terms of daily weight gain, length of stay, recovery, case fatality and defaulting. A total of 1937 children aged 6-59 months were followed prospectively from 15 August 2002 to 21 October 2003. For the three cohorts, 660 children were maintained in the therapeutic feeding...

Emerging Therapeutic Enhancement Enabling Health Technologies and Their Discourses: What Is Discussed within the Health Domain?

Science.gov (United States)

Wolbring, Gregor; Diep, Lucy; Yumakulov, Sophya; Ball, Natalie; Leopatra, Verlyn; Yergens, Dean

2013-01-01

So far, the very meaning of health and therefore, treatment and rehabilitation is benchmarked to the normal or species-typical body. We expect certain abilities in members of a species; we expect humans to walk but not to fly, but a bird we expect to fly. However, increasingly therapeutic interventions have the potential to give recipients beyond species-typical body related abilities (therapeutic enhancements, TE). We believe that the perfect storm of TE, the shift in ability expectations toward beyond species-typical body abilities, and the increasing desire of health consumers to shape the health system will increasingly influence various aspects of health care practice, policy, and scholarship. We employed qualitative and quantitative methods to investigate among others how human enhancement, neuro/cognitive enhancement, brain machine interfaces, and social robot discourses cover (a) healthcare, healthcare policy, and healthcare ethics, (b) disability and (c) health consumers and how visible various assessment fields are within Neuro/Cogno/Human enhancement and within the BMI and social robotics discourse. We found that health care, as such, is little discussed, as are health care policy and ethics; that the term consumers (but not health consumers) is used; that technology, impact and needs assessment is absent; and that the imagery of disabled people is primarily a medical one. We submit that now, at this early stage, is the time to gain a good understanding of what drives the push for the enhancement agenda and enhancement-enabling devices, and the dynamics around acceptance and diffusion of therapeutic enhancements. PMID:27429129

Emerging Therapeutic Enhancement Enabling Health Technologies and Their Discourses: What Is Discussed within the Health Domain?

Directory of Open Access Journals (Sweden)

Gregor Wolbring

2013-07-01

Full Text Available So far, the very meaning of health and therefore, treatment and rehabilitation is benchmarked to the normal or species-typical body. We expect certain abilities in members of a species; we expect humans to walk but not to fly, but a bird we expect to fly. However, increasingly therapeutic interventions have the potential to give recipients beyond species-typical body related abilities (therapeutic enhancements, TE. We believe that the perfect storm of TE, the shift in ability expectations toward beyond species-typical body abilities, and the increasing desire of health consumers to shape the health system will increasingly influence various aspects of health care practice, policy, and scholarship. We employed qualitative and quantitative methods to investigate among others how human enhancement, neuro/cognitive enhancement, brain machine interfaces, and social robot discourses cover (a healthcare, healthcare policy, and healthcare ethics, (b disability and (c health consumers and how visible various assessment fields are within Neuro/Cogno/ Human enhancement and within the BMI and social robotics discourse. We found that health care, as such, is little discussed, as are health care policy and ethics; that the term consumers (but not health consumers is used; that technology, impact and needs assessment is absent; and that the imagery of disabled people is primarily a medical one. We submit that now, at this early stage, is the time to gain a good understanding of what drives the push for the enhancement agenda and enhancement-enabling devices, and the dynamics around acceptance and diffusion of therapeutic enhancements.

Causes and Consequences of Interdialytic weight gain

NARCIS (Netherlands)

Ipema, Karin J. R.; Kuipers, Johanna; Westerhuis, Ralf; Gaillard, Carlo A. J. M.; Schans, van der Cees P.; Krijnen, Wim P.; Franssen, Casper F. M.

2016-01-01

Background/Aims: Higher interdialytic weight gain (IDWG) is associated with higher predialysis blood pressure and increased mortality. IDWG is also increasingly being recognized as an indicator of nutritional status. We studied in detail the associations of various patient factors and nutritional

[Therapeutic goals and indications: psychotherapy patient's self-reports during diagnostic assessment].

Science.gov (United States)

Faller, H

2000-07-01

Although individual therapeutic goals are considered to be important factors motivating patients to engage in therapeutic work, they have gained little attention in empirical research. In the present study, patients were given a questionnaire containing 24 therapeutic goals which could be rated according to their subjective relevance on a 5-point scale. N = 152 patients (mean age 34.5 years, 59.2% female) who presented at a university psychotherapy outpatient department to attend a diagnostic interview participated in the study. "To solve my problems" and "to get relief from my complaints" were the goals that were rated as most important. Goals pertaining to mental health such as more contentness and calmness, self-assertion and insight scored high, too. Three rational scales were constructed: 1. insight, 2. sociability, and 3. self-assertion. These scales were correlated with both patients' causal attributions and therapy expectations in plausible ways. However, the general strength of intercorrelations point of the conception patients goals were not very succinct at the time of the intake interview. Indication groups regarding specific therapeutic measures did not differ with respect to therapy goals. Only the general decision whether to recommend a psychotherapeutic intervention or not seemed to be influenced by patients' therapeutic aims.

MOS current gain cells with electronically variable gain and constant bandwidth

NARCIS (Netherlands)

Klumperink, Eric A.M.; Seevinck, Evert

1989-01-01

Two MOS current gain cells are proposed that provide linear amplification of currents supplied by several linear MOS V-I converters. The gain is electronically variable by a voltage or a current and can be made insensitive to temperature and IC processing. The gain cells have a constant

Polarization dependence of the optical modal gain in ZnO

International Nuclear Information System (INIS)

Kim, Bumjin; Kyhm, Kwangseuk; Cho, Chaeryong

2010-01-01

The modal gain spectrum due to the electron-hole plasma in ZnO was measured using a variable stripe length method. A modal gain contour map for energy and stripe length allowed the modal gain saturation to be analyzed in terms of the spectral and the stripe length dependences. The modal gain was observed to be more significant in the TE mode than in the TM mode due to the polarization asymmetry of the wurtzite structure. We also found that the degree of polarization are enhanced as the stripe length increased, despite of modal gain saturation.

Changes in job strain and subsequent weight gain

DEFF Research Database (Denmark)

Vesterlund, Gitte Kingo; Keller, Amélie Cléo; Heitmann, Berit Lilienthal

2018-01-01

in 1999 between those who were rarely v. sometimes v. often busy in 1993 (P=0·03), with the largest weight gain in individuals with sustained high busyness in both years. Loss of influence between 1993 and 1999 was associated with larger subsequent weight gain than sustained high influence (P=0......Objective: Obesity as well as job strain is increasing, and job strain might contribute to weight gain. The objective of the current study was to examine associations between longitudinal alterations in the components of job strain and subsequent weight gain. Design: The study was designed...... as a prospective cohort study with three questionnaire surveys enabling measurement of job-strain alterations over 6 years and subsequent measurements of weight gain after further 10 years of follow-up. ANCOVA and trend analyses were conducted. Job demands were measured as job busyness and speed, and control...

A simple method to increase effective PMT gain by amplifier circuit powered from voltage divider

International Nuclear Information System (INIS)

Popov, V.; Majewski, S.; Wojtsekhowski, B.; Guerin, D

2001-01-01

A novel concept is introduced of additional effective signal amplification by employing a dedicated circuit to process anode or dynode signals prior to sending them through a standard 50 /spl Omega/ line/cable. The circuit is entirely powered by the current flowing through the base voltage divider. Additional gain factors of 2-10 were easily achieved with preserved operation speed and rate capability up to several MHz. This additional signal boost can be used in many applications where higher gain and/or lower PMT operational voltages are desirable. For example, in the case of a PMT employed in a low input light signal (such as a Cherenkov counter), this technique will permit operation at a lower voltage and, therefore, will result in better operational PMT stability and longer PMT lifetime. At present, two experimental set-ups at Jefferson Lab are using PMT bases using this concept

Achieving the Promise of Therapeutic Extracellular Vesicles: The Devil is in Details of Therapeutic Loading.

Science.gov (United States)

Sutaria, Dhruvitkumar S; Badawi, Mohamed; Phelps, Mitch A; Schmittgen, Thomas D

2017-05-01

Extracellular vesicles (EVs) represent a class of cell secreted organelles which naturally contain biomolecular cargo such as miRNA, mRNA and proteins. EVs mediate intercellular communication, enabling the transfer of functional nucleic acids from the cell of origin to the recipient cells. In addition, EVs make an attractive delivery vehicle for therapeutics owing to their increased stability in circulation, biocompatibility, low immunogenicity and toxicity profiles. EVs can also be engineered to display targeting moieties on their surfaces which enables targeting to desired tissues, organs or cells. While much has been learned on the role of EVs as cell communicators, the field of therapeutic EV application is currently under development. Critical to the future success of EV delivery system is the description of methods by which therapeutics can be successfully and efficiently loaded within the EVs. Two methods of loading of EVs with therapeutic cargo exist, endogenous and exogenous loading. We have therefore focused this review on describing the various published approaches for loading EVs with therapeutics.

The effect of the Thanksgiving Holiday on weight gain

Directory of Open Access Journals (Sweden)

Dinger Mary K

2006-11-01

Full Text Available Abstract Background More people than ever are considered obese and the resulting health problems are evident. These facts highlight the need for identification of critical time periods for weight gain. Therefore the purpose was to assess potential changes that occur in body weight during the Thanksgiving holiday break in college students. Methods 94 college students (23.0 ± 4.6 yrs, 72.1 ± 14.0 kg, 172.6 ± 9.3 cm, 24.0 ± 3.9 kg/m2 reported to the human body composition laboratory at the University of Oklahoma following a 6-hour fast with testing occurring prior to, and immediately following the Thanksgiving holiday break (13 ± 3 days. Body weight (BW was assessed using a balance beam scale while participants were dressed in minimal clothing. Paired t-tests were used to assess changes in BW pre and post Thanksgiving holiday with additional analysis by gender, body mass index (BMI, and class standing (i.e. undergraduate vs. graduate. Results Overall, a significant (P P P 2 group compared to a non significant 0.2 kg gain in the normal group (2. Conclusion These data indicate that participants in our study gained a significant amount of BW (0.5 kg during the Thanksgiving holiday. While an increase in BW of half a kilogram may not be cause for alarm, the increase could have potential long-term health consequences if participants retained this weight gain throughout the college year. Additionally, because the overweight/obese participants gained the greatest amount of BW, this group may be at increased risk for weight gain and further obesity development during the holiday season.

Optical gain and gain suppression of quantum-well lasers with valence band mixing

International Nuclear Information System (INIS)

Ahn, D.; Chuang, S.L.

1990-01-01

The effects of valence band mixing on the nonlinear gains of quantum-well lasers are studied theoretically. The authors' analysis is based on the multiband effective-mass theory and the density matrix formalism with intraband relaxation taken into account. The gain and the gain-suppression coefficient of a quantum-well laser are calculated from the complex optical susceptibility obtained by the density matrix formulation with the theoretical dipole moments obtained from the multiband effective-mass theory. The calculated gain spectrum shows that there are remarkable differences (both in peak amplitude and spectral shape) between our model with valence band mixing and the conventional parabolic band model. The shape of the gain spectrum calculated by the authors' model becomes more symmetric due to intraband relaxation together with nonparabolic energy dispersions and is closer to the experimental observations when compared with the conventional method using the parabolic band model and the multiband effective-mass calculation without intraband relaxation. Both give quite asymmetric gain spectra. Optical intensity in the GaAs active region is estimated by solving rate equations for the stationary states with nonlinear gain suppression. The authors calculate the mode gain for the resonant mode including the gain suppression, which results in spectral hole burning of the gain spectrum

Selection on Optimal Haploid Value Increases Genetic Gain and Preserves More Genetic Diversity Relative to Genomic Selection.

Science.gov (United States)

Daetwyler, Hans D; Hayden, Matthew J; Spangenberg, German C; Hayes, Ben J

2015-08-01

Doubled haploids are routinely created and phenotypically selected in plant breeding programs to accelerate the breeding cycle. Genomic selection, which makes use of both phenotypes and genotypes, has been shown to further improve genetic gain through prediction of performance before or without phenotypic characterization of novel germplasm. Additional opportunities exist to combine genomic prediction methods with the creation of doubled haploids. Here we propose an extension to genomic selection, optimal haploid value (OHV) selection, which predicts the best doubled haploid that can be produced from a segregating plant. This method focuses selection on the haplotype and optimizes the breeding program toward its end goal of generating an elite fixed line. We rigorously tested OHV selection breeding programs, using computer simulation, and show that it results in up to 0.6 standard deviations more genetic gain than genomic selection. At the same time, OHV selection preserved a substantially greater amount of genetic diversity in the population than genomic selection, which is important to achieve long-term genetic gain in breeding populations. Copyright © 2015 by the Genetics Society of America.

Hypothalamic over-expression of VGF in the Siberian hamster increases energy expenditure and reduces body weight gain.

Science.gov (United States)

Lewis, Jo E; Brameld, John M; Hill, Phil; Cocco, Cristina; Noli, Barbara; Ferri, Gian-Luca; Barrett, Perry; Ebling, Francis J P; Jethwa, Preeti H

2017-01-01

VGF (non-acronymic) was first highlighted to have a role in energy homeostasis through experiments involving dietary manipulation in mice. Fasting increased VGF mRNA in the Arc and levels were subsequently reduced upon refeeding. This anabolic role for VGF was supported by observations in a VGF null (VGF-/-) mouse and in the diet-induced and gold-thioglucose obese mice. However, this anabolic role for VGF has not been supported by a number of subsequent studies investigating the physiological effects of VGF-derived peptides. Intracerebroventricular (ICV) infusion of TLQP-21 increased resting energy expenditure and rectal temperature in mice and protected against diet-induced obesity. Similarly, ICV infusion of TLQP-21 into Siberian hamsters significantly reduced body weight, but this was due to a decrease in food intake, with no effect on energy expenditure. Subsequently NERP-2 was shown to increase food intake in rats via the orexin system, suggesting opposing roles for these VGF-derived peptides. Thus to further elucidate the role of hypothalamic VGF in the regulation of energy homeostasis we utilised a recombinant adeno-associated viral vector to over-express VGF in adult male Siberian hamsters, thus avoiding any developmental effects or associated functional compensation. Initially, hypothalamic over-expression of VGF in adult Siberian hamsters produced no effect on metabolic parameters, but by 12 weeks post-infusion hamsters had increased oxygen consumption and a tendency to increased carbon dioxide production; this attenuated body weight gain, reduced interscapular white adipose tissue and resulted in a compensatory increase in food intake. These observed changes in energy expenditure and food intake were associated with an increase in the hypothalamic contents of the VGF-derived peptides AQEE, TLQP and NERP-2. The complex phenotype of the VGF-/- mice is a likely consequence of global ablation of the gene and its derived peptides during development, as well

The contribution of fat component to gestational weight gain

Directory of Open Access Journals (Sweden)

2013-12-01

Full Text Available Objective: to estimate the role of adipose tissue in gestational weight gain (GWG and preferential fat deposition among normal-weight women. Subjects and methods: prospective cohort study of 84 pregnancies: maternal body mass index 18,5–24,9 kg/m2, singleton term pregnancy, nondiabetic women, somatically well. GWG and skinfold thickness were evaluated in the 1st, 2nd, 3d trimesters, on the 3d day after delivery. Results: fat mass gain in low GWG was similar to recommended GWG and in the high-GWG group was greater one. Women with recommended and low GWG returned to their initial fat level on the 3d day after delivery, in excessive weight gain fat significantly increased (р=0,025. Compared to initial recommended GWG resulted in triceps skinfold thicknesses loss (р=0,001, in abdominal skinfold gained nothing and in thighs skinfold thicknesses increasing (р=0,021. Inadequate GWG leads to fat loss in arms (р=0,017, fat of abdominal area and thighs return to initial level. In excessive GWG fat in the upper trunk and arms not changed, in the lower area (thighs significantly increased compared to initial level (р=0,001 or other groups (р=0,001. Conclusion: excessive GWG was associated with greater adipose tissue cumulation and its deposition preferentially over the thighs. Inadequate GWG was clearly linked to low fat-free mass gain.

Abnormal Auditory Gain in Hyperacusis: Investigation with a Computational Model

Directory of Open Access Journals (Sweden)

Peter U. Diehl

2015-07-01

Full Text Available Hyperacusis is a frequent auditory disorder that is characterized by abnormal loudness perception where sounds of relatively normal volume are perceived as too loud or even painfully loud. As Hyperacusis patients show decreased loudness discomfort levels (LDLs and steeper loudness growth functions, it has been hypothesized that hyperacusis might be caused by an increase in neuronal response gain in the auditory system. Moreover, since about 85% of hyperacusis patients also experience tinnitus, the conditions might be caused by a common mechanism. However, the mechanisms that give rise to hyperacusis have remained unclear.Here we have used a computational model of the auditory system to investigate candidate mechanisms for hyperacusis. Assuming that perceived loudness is proportional to the summed activity of all auditory nerve fibers, the model was tuned to reproduce normal loudness perception. We then evaluated a variety of potential hyperacusis gain mechanisms by determining their effects on model equal-loudness contours and comparing the results to the LDLs of hyperacusis patients with normal hearing thresholds. Hyperacusis was best accounted for by an increase in nonlinear gain in the central auditory system. Good fits to the average patient LDLs were obtained for a general increase in gain that affected all frequency channels to the same degree, and also for a frequency-specific gain increase in the high-frequency range. Moreover, the gain needed to be applied after subtraction of spontaneous activity of the auditory nerve, which is in contrast to current theories of tinnitus generation based on amplification of spontaneous activity. Hyperacusis and tinnitus might therefore be caused by different changes in neuronal processing in the central auditory system.

Therapeutic nanomedicine surmounts the limitations of pharmacotherapy

Directory of Open Access Journals (Sweden)

Odiba Arome

2017-09-01

Full Text Available Science always strives to find an improved way of doing things and nanoscience is one such approach. Nanomaterials are suitable for pharmaceutical applications mostly because of their size which facilitates absorption, distribution, metabolism and excretion of the nanoparticles. Whether labile or insoluble nanoparticles, their cytotoxic effect on malignant cells has moved the use of nanomedicine into focus. Since nanomedicine can be described as the science and technology of diagnosing, treating and preventing diseases towards ultimately improving human health, a lot of nanotechnology options have received approval by various regulatory agencies. Nanodrugs also have been discovered to be more precise in targeting the desired site, hence maximizing the therapeutic effects, while minimizing side-effects on the rest of the body. This unique property and more has made nanomedicine popular in therapeutic medicine employing nanotechnology in genetic therapy, drug encapsulation, enzyme manipulation and control, tissue engineering, target drug delivery, pharmacogenomics, stem cell and cloning, and even virus-based hybrids. This review highlights nanoproducts that are in development and have gained approval through one clinical trial stage or the other.

Weight gain in women diagnosed with breast cancer.

Science.gov (United States)

Demark-Wahnefried, W; Rimer, B K; Winer, E P

1997-05-01

This review of the literature indicates that weight gain is a common observation among women after the diagnosis of breast cancer. Gains in weight range from 0 to 50 lb and are influenced by menopausal status; nodal status; and the type, duration, and intensity of treatment. Weight gain appears to be greater among premenopausal women; among those who are node positive; and among those receiving higher dose, longer duration, and multiagent regimens. Psychosocial research suggests that weight gain has a profoundly negative impact on quality of life in patients with breast cancer. Recent findings also suggest that weight gain during therapy may increase the risk of recurrence and decrease survival. Although weight gain in patients with breast cancer is clinically well appreciated, little research has been conducted to investigate the underlying mechanisms of energy imbalance. Changes in rates of metabolism, physical activity, and dietary intake are all plausible mechanisms and call for more research. Further study will provide valuable insight into the problem of weight gain and encourage effective interventions to improve the quality and quantity of life for the woman with breast cancer. Until more is known, however, dietetics practitioners will have to monitor and work individually with patients with breast cancer and use empirical approaches to achieve the important goal of weight management.

Optimizing oncology therapeutics through quantitative translational and clinical pharmacology: challenges and opportunities.

Science.gov (United States)

Venkatakrishnan, K; Friberg, L E; Ouellet, D; Mettetal, J T; Stein, A; Trocóniz, I F; Bruno, R; Mehrotra, N; Gobburu, J; Mould, D R

2015-01-01

Despite advances in biomedical research that have deepened our understanding of cancer hallmarks, resulting in the discovery and development of targeted therapies, the success rates of oncology drug development remain low. Opportunities remain for objective dose selection informed by exposure-response understanding to optimize the benefit-risk balance of novel therapies for cancer patients. This review article discusses the principles and applications of modeling and simulation approaches across the lifecycle of development of oncology therapeutics. Illustrative examples are used to convey the value gained from integration of quantitative clinical pharmacology strategies from the preclinical-translational phase through confirmatory clinical evaluation of efficacy and safety. © 2014 American Society for Clinical Pharmacology and Therapeutics.

Does Increased Body Mass Index Effect the Gains of Pulmonary Rehabilitation in Chronic Obstructive Pulmonary Disease Patients?

Directory of Open Access Journals (Sweden)

Hülya Doğan Şahin

2017-12-01

Full Text Available Objective: We aimed to compare the gain of pulmonary rehabilitation (PR in obese, pre-obese, and normal-weight patients with chronic obstructive pulmonary disease (COPD who underwent a PR program. Methods: COPD patients (n=137 underwent pulmonary and cardiac system examination and pulmonary function tests (PFTs before PR. Chest X-rays, arterial blood gases, body mass index, quality of life (QOL questionnaires, anxiety and depression scores, and Modified Medical Research Council dyspnea scale (MMRC scores were evaluated in all patients. A 6-min walk test was performed to determine the exercise capacity of the patients. All patients underwent an 8-week outpatient PR program. The patients were reevaluated at the end of 8th week in terms of all parameters. Results: The study group consisted of 44 normal-weight, 52 pre-obese, and 41 obese COPD patients. Before PR, there was no significant difference in terms of 6-min walk distance (6MWD, PFT, MMRC, or QOL scores between the groups (p>0.05 for all. After PR, partial arterial oxygen pressure and arterial saturation, MMRC, and QOL scores improved significantly in all three groups (p<0.05 for all. 6MWD and walkwork significantly increased after PR in all three groups (p<0.001 for all, but the gain in 6MWD was significantly lower in obese patients compared to pre-obese and normal-weight patients (p=0.049. Conclusion: Pre-obese and obese patients benefit from PR similarly to the normal-weight patients in terms of gas exchange, dyspnea perception, and QOL. But it seems to be that exercise capacity improves less in obese COPD patients compared to pre-obese and normal- weight patients.

A Mathematical Model to Investigate Gain-Induced Oscillation in the ...

African Journals Online (AJOL)

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that increase in the gain of the baroreflex feedback loop controlling venous volume ... The existence of fluctuations in blood pressure has been known since the ...... Thus, young adults, with high gain and small D2, are in the unstable region,.

Immunogenicity of therapeutic proteins: the use of animal models.

Science.gov (United States)

Brinks, Vera; Jiskoot, Wim; Schellekens, Huub

2011-10-01

Immunogenicity of therapeutic proteins lowers patient well-being and drastically increases therapeutic costs. Preventing immunogenicity is an important issue to consider when developing novel therapeutic proteins and applying them in the clinic. Animal models are increasingly used to study immunogenicity of therapeutic proteins. They are employed as predictive tools to assess different aspects of immunogenicity during drug development and have become vital in studying the mechanisms underlying immunogenicity of therapeutic proteins. However, the use of animal models needs critical evaluation. Because of species differences, predictive value of such models is limited, and mechanistic studies can be restricted. This review addresses the suitability of animal models for immunogenicity prediction and summarizes the insights in immunogenicity that they have given so far.

Overexpression of Jazf1 reduces body weight gain and regulates lipid metabolism in high fat diet

International Nuclear Information System (INIS)

Jang, Woo Young; Bae, Ki Beom; Kim, Sung Hyun; Yu, Dong Hun; Kim, Hei Jung; Ji, Young Rae; Park, Seo Jin; Park, Si Jun; Kang, Min-Cheol; Jeong, Ja In; Park, Sang-Joon; Lee, Sang Gyu; Lee, Inkyu; Kim, Myoung Ok; Yoon, Duhak; Ryoo, Zae Young

2014-01-01

Highlights: • The expression of Jazf1 in the liver suppressed lipid accumulation. • Jazf1 significantly increases transcription of fatty acid synthase. • Jazf1 plays a critical role in the regulation of energy and lipid homeostasis. • Jazf1 associates the development of metabolic disorder. • Jazf1 may provide a new therapeutic target in the management of metabolic disorder. - Abstract: Jazf1 is a 27 kDa nuclear protein containing three putative zinc finger motifs that is associated with diabetes mellitus and prostate cancer; however, little is known about the role that this gene plays in regulation of metabolism. Recent evidence indicates that Jazf1 transcription factors bind to the nuclear orphan receptor TR4. This receptor regulates PEPCK, the key enzyme involved in gluconeogenesis. To elucidate Jazf1’s role in metabolism, we fed a 60% fat diet for up to 15 weeks. In Jazf1 overexpression mice, weight gain was found to be significantly decreased. The expression of Jazf1 in the liver also suppressed lipid accumulation and decreased droplet size. These results suggest that Jazf1 plays a critical role in the regulation of lipid homeostasis. Finally, Jazf1 may provide a new therapeutic target in the management of obesity and diabetes

Overexpression of Jazf1 reduces body weight gain and regulates lipid metabolism in high fat diet

Energy Technology Data Exchange (ETDEWEB)

Jang, Woo Young; Bae, Ki Beom; Kim, Sung Hyun; Yu, Dong Hun; Kim, Hei Jung; Ji, Young Rae; Park, Seo Jin; Park, Si Jun; Kang, Min-Cheol; Jeong, Ja In [School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of); Park, Sang-Joon [College of Veterinary Medicine, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of); Lee, Sang Gyu [School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of); Lee, Inkyu [School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 700-842 (Korea, Republic of); Kim, Myoung Ok [School of Animal BT Sciences, Sangju Campus, Kyungpook National University, 386 Gajang-dong, Sangju, Gyeongsangbuk-do 742-211 (Korea, Republic of); Yoon, Duhak, E-mail: dhyoon@knu.ac.kr [School of Animal BT Sciences, Sangju Campus, Kyungpook National University, 386 Gajang-dong, Sangju, Gyeongsangbuk-do 742-211 (Korea, Republic of); Ryoo, Zae Young, E-mail: jaewoong64@hanmail.net [School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of)

2014-02-14

Highlights: • The expression of Jazf1 in the liver suppressed lipid accumulation. • Jazf1 significantly increases transcription of fatty acid synthase. • Jazf1 plays a critical role in the regulation of energy and lipid homeostasis. • Jazf1 associates the development of metabolic disorder. • Jazf1 may provide a new therapeutic target in the management of metabolic disorder. - Abstract: Jazf1 is a 27 kDa nuclear protein containing three putative zinc finger motifs that is associated with diabetes mellitus and prostate cancer; however, little is known about the role that this gene plays in regulation of metabolism. Recent evidence indicates that Jazf1 transcription factors bind to the nuclear orphan receptor TR4. This receptor regulates PEPCK, the key enzyme involved in gluconeogenesis. To elucidate Jazf1’s role in metabolism, we fed a 60% fat diet for up to 15 weeks. In Jazf1 overexpression mice, weight gain was found to be significantly decreased. The expression of Jazf1 in the liver also suppressed lipid accumulation and decreased droplet size. These results suggest that Jazf1 plays a critical role in the regulation of lipid homeostasis. Finally, Jazf1 may provide a new therapeutic target in the management of obesity and diabetes.

Skin temperature increase mediated by wearable, long duration, low-intensity therapeutic ultrasound

Science.gov (United States)

Langer, Matthew D.; Huang, Wenyi; Ghanem, Angi; Guo, Yuan; Lewis, George K.

2017-03-01

One of the safety concerns with the delivery of therapeutic ultrasound is overheating of the transducer-skin interface due to poor or improper coupling. The objective of this research was to define a model that could be used to calculate the heating in the skin as a result of a novel, wearable long-duration ultrasound device. This model was used to determine that the maximum heating in the skin remained below the minimum threshold necessary to cause thermal injury over multiple hours of use. In addition to this model data, a human clinical study used wire thermocouples on the skin surface to measure heating characteristics during treatment with the sustained ultrasound system. Parametric analysis of the model determined that the maximum temperature increase is at the surface of the skin ranged from 40-41.8° C when perfusion was taken into account. The clinical data agreed well with the model predictions. The average steady state temperature observed across all 44 subjects was 40°C. The maximum temperature observed was less than 44° C, which is clinically safe for over 5 hours of human skin contact. The resultant clinical temperature data paired well with the model data suggesting the model can be used for future transducer and ultrasound system design simulation. As a result, the device was validated for thermal safety for typical users and use conditions.

A reinforcement-based therapeutic workplace for the treatment of drug abuse: six-month abstinence outcomes.

Science.gov (United States)

Silverman, K; Svikis, D; Robles, E; Stitzer, M L; Bigelow, G E

2001-02-01

This study evaluated a novel drug abuse treatment, the Therapeutic Workplace. In this treatment, patients are paid to perform jobs or to participate in job training. Salary is linked to abstinence by requiring patients to provide drug-free urine samples to gain access to the workplace. Pregnant and postpartum drug abuse patients (N = 40) were randomly assigned to a Therapeutic Workplace or usual care control group. Therapeutic Workplace participants were invited to work 3 hr every weekday for 6 months and could earn up to $4,030 in vouchers for abstinence, workplace attendance, and performance. On average, 45% of participants attended the workplace per day. Relative to controls, the Therapeutic Workplace nearly doubled patients' abstinence from opiates and cocaine (33% vs. 59% of thrice-weekly urine samples drug negative, respectively, p Workplace can effectively treat heroin and cocaine abuse in pregnant and postpartum women.

Analysis and Evaluation of Performance Gains and Tradeoffs for Massive MIMO Systems

Directory of Open Access Journals (Sweden)

Saba Qasim Jabbar

2016-09-01

Full Text Available Massive MIMO technique offers significant performance gains for the future of wireless communications via improving the spectral efficiency, energy efficiency and the channel quality with simple linear processing such as maximum-ratio transmission (MRT or zero-forcing (ZF by providing each user a large degree of freedom. In this paper, the system performance gains are studied in a multi-cell downlink massive MIMO system under the main considerations such as perfect channel estimation, imperfect channel estimation and the effect of interference among cells due to pilot sequences contamination. Then, mathematical expressions are derived for these gains i.e., spatial multiplexing gain, array gain and spatial diversity gain. After that, essential tradeoffs among these gains are considered under the effect of non-orthogonal interference, these tradeoffs are: spatial diversity gain vs. spatial multiplexing gain and array gain vs. spatial multiplexing gain. Simulation results show that the unbounded number of base station antennas boosts the array gain through concentrating the energy to spatial directions where users are sited, hence diminishing loss in array gain due to pilot contamination. The simulation results reveal also that massive MIMO strengthens the spatial multiplexing gain through increasing the number of served users via the same system resources in spite the effect of inter-cell interference. Finally, the spatial diversity gain is measured in term of outage probability and the simulation results show that raising the number of antennas will improve the outage probability. Meanwhile increasing the number of served users will lead to degrade the outage probability per user due to non-orthogonal interference from other cells.

Influence of tiamulin therapy on weight gain in Brachyspira dysentery in piglets

Directory of Open Access Journals (Sweden)

Alexandru Octavian Doma

2014-05-01

Full Text Available The aim of research was to evaluate the therapeutic and economic efficiency (daily individual weight gain / observation period of two available tiamulin fumarate antibiotic conditionings (one oral and one injectable in a farm environment, were Brachyspira evolution was suspicioned and confirmed. The experiment was conducted in a pig growing and fattening unit from Timis County, constituted as an intensive system. The sick piglets manifested acute clinical signs, mainly: drowsiness, enophtalmia, kyphosis and the sanguinolent diarrhoea in all cases. Clinical and morphopathologic suspicion was confirmed by the laboratory and bacterioscopic examination, which ascertained the presence of Brachyspira hyodysenteriae. Consequently, were chosen 48 ill piglets from the age group of 35 to 45 days and three experimental therapeutic (T and one Control (C groups were constituted as follows: group T1 - oral way treatment for five consecutive days with Tiamutin 45% soluble granules (Ceva, at doses of 6 and 8 mg.kg.bw., (for group T2 and respectively Tiamutin 10% injectable (Dopharma (T3, 8mg.kg.bw-1 I.M., four consecutive days. Study duration was 21 days, revealing the economic superiority of the oral conditionings vs. injectable of tiamulin fumarate and also the therapeutic efficiency of this form as primal choice in the enteric disease outbreaks.

Slow-light-enhanced gain in active photonic crystal waveguides

DEFF Research Database (Denmark)

Ek, Sara; Hansen, Per Lunnemann; Chen, Yaohui

2014-01-01

Passive photonic crystals have been shown to exhibit a multitude of interesting phenomena, including slow-light propagation in line-defect waveguides. It was suggested that by incorporating an active material in the waveguide, slow light could be used to enhance the effective gain of the material......, which would have interesting application prospects, for example enabling ultra-compact optical amplifiers for integration in photonic chips. Here we experi- mentally investigate the gain of a photonic crystal membrane structure with embedded quantum wells. We find that by solely changing the photonic...... crystal structural parameters, the maximum value of the gain coefficient can be increased compared with a ridge waveguide structure and at the same time the spectral position of the peak gain be controlled. The experimental results are in qualitative agreement with theory and show that gain values similar...

Analysis of NRAS gain in 657 patients with melanoma and evaluation of its sensitivity to a MEK inhibitor.

Science.gov (United States)

Yan, Junya; Wu, Xiaowen; Yu, Jiayi; Yu, Huan; Xu, Tianxiao; Brown, Kevin M; Bai, Xue; Dai, Jie; Ma, Meng; Tang, Huan; Si, Lu; Chi, Zhihong; Sheng, Xinan; Cui, Chuanliang; Kong, Yan; Guo, Jun

2018-01-01

Neuroblastoma rat-sarcoma (NRAS) mutations have been described in Chinese patients with melanoma. However, the status and the clinical significance of NRAS gain have not been investigated on a large scale. A total of 657 melanoma samples were included in the study. NRAS copy number was examined using the QuantiGene Plex DNA assay. The sensitivities of cell lines and patient-derived xenograft (PDX) models containing NRAS gain to a MAP/ERK kinase (MEK) inhibitor (binimetinib) were also evaluated. The overall incidence of NRAS gain was 14.0% (92 of 657). Incidence of NRAS gain in acral, mucosal, chronic sun-induced damage (CSD) and non-CSD melanomas was 12.2%, 15.8%, 9.5% and 19.4%, respectively. NRAS gain was mutually exclusive to NRAS mutations (P = 0.036). The median survival time for melanoma patients with NRAS gain was significantly shorter than that for patients with normal NRAS copy number (P = 0.006). For patients containing NRAS gain, the median survival time for higher copy number (>4 copies) was significantly shorter than those with lower copy number (2-4 copies; P = 0.002). The MEK inhibitor (binimetinib) inhibited the proliferation of melanoma cells and the tumour growth of PDX models with NRAS gain. NRAS gain is frequent in patients with melanoma and may predict a poor prognosis of melanoma. The melanoma cells and PDX models containing NRAS gain are sensitive to MEK inhibitor (binimetinib), indicating that NRAS gain might be a new therapeutic target for melanoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

GAIN Technology Workshops Summary Report

Energy Technology Data Exchange (ETDEWEB)

Braase, Lori Ann [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2016-08-01

National and global demand for nuclear energy is increasing and United States (U.S.) global leadership is eroding. There is a sense of urgency with respect to the deployment of the innovative nuclear energy technologies. The Gateway for Accelerated Innovation in Nuclear (GAIN) initiative is based on the simultaneous achievement of three strategic goals. The first is maintaining global technology leadership within the U.S. Department of Energy (DOE). The second is enabling global industrial leadership for nuclear vendors and suppliers. The third is focused on utility optimization of nuclear energy within the clean energy portfolio. An effective public-private partnership is required to achieve these goals. DOEs recognizes the recent sense of urgency new developers and investors have in getting their concepts to market. They know that time to market for nuclear technology takes too long and the facilities needed to conduct the necessary research, development and demonstration (RD&D) activities are very expensive to develop and maintain. Early technologies, in the lower technology readiness levels (TRL) need materials testing, analysis, modeling, code development, etc., most of which currently exists in the DOE national laboratory system. However, mature technologies typically need large component testing and demonstration facilities, which are expensive and long-lead efforts. By understanding the needs of advanced nuclear technology developers, GAIN will connect DOE national laboratory capabilities (e.g., facilities, expertise, materials, and data) with industry RD&D needs. In addition, GAIN is working with the Nuclear Regulatory Commission (NRC) to streamline processes and increase understanding of the licensing requirements for advanced reactors.

GAIN Technology Workshops Summary Report

International Nuclear Information System (INIS)

Braase, Lori Ann

2016-01-01

National and global demand for nuclear energy is increasing and United States (U.S.) global leadership is eroding. There is a sense of urgency with respect to the deployment of the innovative nuclear energy technologies. The Gateway for Accelerated Innovation in Nuclear (GAIN) initiative is based on the simultaneous achievement of three strategic goals. The first is maintaining global technology leadership within the U.S. Department of Energy (DOE). The second is enabling global industrial leadership for nuclear vendors and suppliers. The third is focused on utility optimization of nuclear energy within the clean energy portfolio. An effective public-private partnership is required to achieve these goals. DOEs recognizes the recent sense of urgency new developers and investors have in getting their concepts to market. They know that time to market for nuclear technology takes too long and the facilities needed to conduct the necessary research, development and demonstration (RD&D) activities are very expensive to develop and maintain. Early technologies, in the lower technology readiness levels (TRL) need materials testing, analysis, modeling, code development, etc., most of which currently exists in the DOE national laboratory system. However, mature technologies typically need large component testing and demonstration facilities, which are expensive and long-lead efforts. By understanding the needs of advanced nuclear technology developers, GAIN will connect DOE national laboratory capabilities (e.g., facilities, expertise, materials, and data) with industry RD&D needs. In addition, GAIN is working with the Nuclear Regulatory Commission (NRC) to streamline processes and increase understanding of the licensing requirements for advanced reactors.

A narrative literature review of the therapeutic effects of music upon childbearing women and neonates.

Science.gov (United States)

Hollins Martin, Caroline J

2014-11-01

Therapeutic effects of music are well recognised within the literature, with benefits for a variety of health problems documented. This narrative review summarises benefits in terms of reducing stress, anxiety, labour pain and depression in childbearing women. For neonates, music has been shown to reduce number of days to discharge, reduce pain response behaviours, increase weight gain, improve Brazelton scores, improve parent/infant intimacy, improve oxygen saturation, increase formula intake, stabilize vital signs and increase parental reports of calmed infants. The main criticism of the studies reviewed is lack of categorisation of the particulars of the variables within the music that directly influenced outcome variables. A recommendation is made that a music package be developed and relationships with variables rigorously evaluated. The validated product may then be made available for use. Since evidence supports advantages from listening to music, it is suggested that maternity professionals use it in more creative ways. Copyright © 2014 Elsevier Ltd. All rights reserved.

Should I Gain Weight?

Science.gov (United States)

... Videos for Educators Search English Español Should I Gain Weight? KidsHealth / For Teens / Should I Gain Weight? ... something about it. Why Do People Want to Gain Weight? Some of the reasons people give for ...

Targeting Potassium Channels for Increasing Delivery of Imaging Agents and Therapeutics to Brain Tumors

Directory of Open Access Journals (Sweden)

Nagendra Sanyasihally Ningaraj

2013-05-01

Full Text Available Every year in the US, 20,000 new primary and nearly 200,000 metastatic brain tumor cases are reported. The cerebral microvessels/ capillaries that form the blood–brain barrier (BBB not only protect the brain from toxic agents in the blood but also pose a significant hindrance to the delivery of small and large therapeutic molecules. Different strategies have been employed to circumvent the physiological barrier posed by blood-brain tumor barrier (BTB. Studies in our laboratory have identified significant differences in the expression levels of certain genes and proteins between normal and brain tumor capillary endothelial cells. In this study, we validated the non-invasive and clinically relevant Dynamic Contrast Enhancing-Magnetic Resonance Imaging (DCE-MRI method with invasive, clinically irrelevant but highly accurate Quantitative Autoradiography (QAR method using rat glioma model. We also showed that DCE-MRI metric of tissue vessel perfusion-permeability is sensitive to changes in blood vessel permeability following administration of calcium-activated potassium (BKCa channel activator NS-1619. Our results show that human gliomas and brain tumor endothelial cells that overexpress BKCa channels can be targeted for increased BTB permeability for MRI enhancing agents to brain tumors. We conclude that monitoring the outcome of increased MRI enhancing agents’ delivery to microsatellites and leading tumor edges in glioma patients would lead to beneficial clinical outcome.

Contrast gain control in first- and second-order motion perception.

Science.gov (United States)

Lu, Z L; Sperling, G

1996-12-01

A novel pedestal-plus-test paradigm is used to determine the nonlinear gain-control properties of the first-order (luminance) and the second-order (texture-contrast) motion systems, that is, how these systems' responses to motion stimuli are reduced by pedestals and other masking stimuli. Motion-direction thresholds were measured for test stimuli consisting of drifting luminance and texture-contrast-modulation stimuli superimposed on pedestals of various amplitudes. (A pedestal is a static sine-wave grating of the same type and same spatial frequency as the moving test grating.) It was found that first-order motion-direction thresholds are unaffected by small pedestals, but at pedestal contrasts above 1-2% (5-10 x pedestal threshold), motion thresholds increase proportionally to pedestal amplitude (a Weber law). For first-order stimuli, pedestal masking is specific to the spatial frequency of the test. On the other hand, motion-direction thresholds for texture-contrast stimuli are independent of pedestal amplitude (no gain control whatever) throughout the accessible pedestal amplitude range (from 0 to 40%). However, when baseline carrier contrast increases (with constant pedestal modulation amplitude), motion thresholds increase, showing that gain control in second-order motion is determined not by the modulator (as in first-order motion) but by the carrier. Note that baseline contrast of the carrier is inherently independent of spatial frequency of the modulator. The drastically different gain-control properties of the two motion systems and prior observations of motion masking and motion saturation are all encompassed in a functional theory. The stimulus inputs to both first- and second-order motion process are normalized by feedforward, shunting gain control. The different properties arise because the modulator is used to control the first-order gain and the carrier is used to control the second-order gain.

THE CONSUMPTION OF RED PUPUNHA (BACTRIS GASIPAES KUNTH) INCREASES HDL CHOLESTEROL AND REDUCES WEIGHT GAIN OF LACTATING AND POST-LACTATING WISTAR RATS.

Science.gov (United States)

Carvalho, R Piccolotto; Lemos, J R Gonzaga; de Aquino Sales, R Souza; Martins, M Gassen; Nascimento, C H; Bayona, M; Marcon, J L; Monteiro, J Barros

2013-09-01

The lactating and post-lactating periods are marked by large metabolic change. Production of milk is 60% lipid dependent. We reported in a recent scientific meeting that Red pupunha palm tree fruit increases HDL cholesterol in lactating rats. This study evaluated if consumption of Red Pupunha by adult female rats has a beneficial impact on the lipid metabolism of lacting and post-lacting adult rats. Evaluate if consumption of red pupunha has a beneficial effect in the lipid metabolism of lacting and post-lacting adult Wistar rats. Four groups including two for control; (1) control adult lactating rats, (2) control adults post-lactating rats; and two experimental groups; (3) pupunha adults lactating rats and (4) pupunha adult post-lactating rats were evaluated and compared regarding: weight gain, food consumption, plasma total protein, glucose, total lipid, triglycerides, total cholesterol and HDL-cholesterol levels. The mean difference and its 95% confidence intervals were used for group comparisons. Group comparisons were evaluated by using analysis of variance (one-way ANOVA). The statistical significance of the pairwise differences among groups was assessed by using the two-sided Tukey test. There were no important differences in food consumption, plasma glucose, total lipids and triglycerides among groups. The red pupunha lactating group gain less weight showing lower body mass index (BMI) than controls (p < 0.05). Total cholesterol was lower in red pupunha lactating than in controls but not in the red pupunha post-lactating group as compared to controls. Triglycerides were lower in the post-lactating red pupunha group as compared to the control group (p = 0.039) but not for the lactating groups. Red pupunha lactating and post-lactating groups had higher HDL-cholesterol than their corresponding control groups (p ≤ 0.01). Original findings include the beneficial effect of red pupunha in post-lactating rats increasing the HDL-cholesterol and lowering the BMI

Increasing Possibilities of Nano suspension

International Nuclear Information System (INIS)

Sutradhar, K.B.; Khatun, S.; Luna, I.P.

2013-01-01

Nowadays, a very large proportion of new drug candidates emerging from drug discovery programmes are water insoluble and thus poorly bioavailable. To avoid this problem, nano technology for drug delivery has gained much interest as a way to improve the solubility problems. Nano refers to particles size range of 1-1000 nm. The reduction of drug particles into the submicron range leads to a significant increase in the dissolution rate and therefore enhances bioavailability. Nanosuspensions are part of nano technology. This interacts with the body at subcellular (i.e., molecular) scales with a high degree of specificity and can be potentially translated into targeted cellular and tissue-specific clinical applications designed to achieve maximal therapeutic efficacy with minimal side effects. Production of drugs as nanosuspensions can be developed for drug delivery systems as an oral formulation and no noral administration. Here, this review describes the methods of pharmaceutical nano suspension production including advantages and disadvantages, potential benefits, characterization tests, and pharmaceutical applications in drug delivery

A therapeutic skating intervention for children with autism spectrum disorder.

Science.gov (United States)

Casey, Amanda Faith; Quenneville-Himbeault, Gabriel; Normore, Alexa; Davis, Hanna; Martell, Stephen G

2015-01-01

The purpose of this study was to evaluate the effects of a highly structured therapeutic skating intervention on motor outcomes and functional capacity in 2 boys with autism spectrum disorder aged 7 and 10 years. This multiple-baseline, single-subject study assigned participants to three 1-hour skating sessions per week for 12 weeks focusing on skill and motor development. Multiple data points assessed (a) fidelity to the intervention and (b) outcomes measures including the Pediatric Balance Scale, Timed Up and Go, floor to stand, Six-Minute Walk Test, goal attainment, and weekly on-ice testing. Improvements were found in balance, motor behavior, and functional capacity by posttest with gains remaining above pretest levels at follow-up. Therapeutic skating may produce physical benefits for children with autism spectrum disorder and offer a viable, inexpensive community-based alternative to other forms of physical activity.

Sub-therapeutic doses of fluvastatin and valsartan are more effective than therapeutic doses in providing beneficial cardiovascular pleiotropic effects in rats: A proof of concept study.

Science.gov (United States)

Janić, Miodrag; Lunder, Mojca; France Štiglic, Alenka; Jerin, Aleš; Skitek, Milan; Černe, Darko; Marc, Janja; Drevenšek, Gorazd; Šabovič, Mišo

2017-12-01

Statins and sartans can, in therapeutic doses, induce pleiotropic cardiovascular effects. Similar has recently been shown also for sub-therapeutic doses. We thus explored and compared the cardiovascular pleiotropic efficacy of sub-therapeutic vs. therapeutic doses. Wistar rats were randomly divided into 7 groups receiving fluvastatin, valsartan and their combination in sub-therapeutic and therapeutic doses, or saline. After 6weeks, the animals were euthanised, their hearts and thoracic aortas isolated, and blood samples taken. Endothelium-dependent relaxation of the thoracic aortae and ischaemic-reperfusion injury of the isolated hearts were assessed along with the related serum parameters and genes expression. Fluvastatin and valsartan alone or in combination were significantly more effective in sub-therapeutic than therapeutic doses. The sub-therapeutic combination greatly increased thoracic aorta endothelium-dependent relaxation and maximally protected the isolated hearts against ischaemia-reperfusion injury and was thus most effective. Beneficial effects were accompanied by increased levels of nitric oxide (NO) and decreased levels of asymmetric dimethylarginine (ADMA) in the serum (again prominently induced by the sub-therapeutic combination). Furthermore, nitric oxide synthase 3 (NOS3) and endothelin receptor type A (EDNRA) genes expression increased, but only in both combination groups and without significant differences between them. In the therapeutic dose groups, fluvastatin and valsartan decreased cholesterol values and systolic blood pressure. Sub-therapeutic doses of fluvastatin and valsartan are more effective in expressing cardiovascular pleiotropic effects than therapeutic doses of fluvastatin and/or valsartan. These results could be of significant clinical relevance. Copyright © 2017 Elsevier Inc. All rights reserved.

Gaining Relational Competitive Advantages

DEFF Research Database (Denmark)

Hu, Yimei; Zhang, Si; Li, Jizhen

2015-01-01

Establishing strategic technological partnerships (STPs) with foreign partners is an increasingly studied topic within the innovation management literature. Partnering firms can jointly create sources of relational competitive advantage. Chinese firms often lack research and development (R......&D) capabilities but are increasingly becoming preferred technological partners for transnational corporations. We investigate an STP between a Scandinavian and a Chinese firm and try to explore how to gain relational competitive advantage by focusing on its two essential stages: relational rent generation...... and appropriation. Based on an explorative case study, we develop a conceptual framework that consists of process, organizational alliance factors, and coordination modes that we propose lead to relational competitive advantage....

The History of Therapeutic Aerosols: A Chronological Review.

Science.gov (United States)

Stein, Stephen W; Thiel, Charles G

2017-02-01

In 1956, Riker Laboratories, Inc., (now 3 M Drug Delivery Systems) introduced the first pressurized metered dose inhaler (MDI). In many respects, the introduction of the MDI marked the beginning of the modern pharmaceutical aerosol industry. The MDI was the first truly portable and convenient inhaler that effectively delivered drug to the lung and quickly gained widespread acceptance. Since 1956, the pharmaceutical aerosol industry has experienced dramatic growth. The signing of the Montreal Protocol in 1987 led to a surge in innovation that resulted in the diversification of inhaler technologies with significantly enhanced delivery efficiency, including modern MDIs, dry powder inhalers, and nebulizer systems. The innovative inhalers and drugs discovered by the pharmaceutical aerosol industry, particularly since 1956, have improved the quality of life of literally hundreds of millions of people. Yet, the delivery of therapeutic aerosols has a surprisingly rich history dating back more than 3500 years to ancient Egypt. The delivery of atropine and related compounds has been a crucial inhalation therapy throughout this period and the delivery of associated structural analogs remains an important therapy today. Over the centuries, discoveries from many cultures have advanced the delivery of therapeutic aerosols. For thousands of years, therapeutic aerosols were prepared by the patient or a physician with direct oversight of the patient using custom-made delivery systems. However, starting with the Industrial Revolution, advancements in manufacturing resulted in the bulk production of therapeutic aerosol delivery systems produced by people completely disconnected from contact with the patient. This trend continued and accelerated in the 20th century with the mass commercialization of modern pharmaceutical inhaler products. In this article, we will provide a summary of therapeutic aerosol delivery from ancient times to the present along with a look to the future. We

High gain multigap avalanche detectors for Cerenkov ring imaging

Energy Technology Data Exchange (ETDEWEB)

Gilmore, R.S.; Lavender, W.M.; Leith, D.W.G.S.; Williams, S.H.

1980-10-01

We report on a continuing study of multigap parallel plate avalanche chambers, primarily as photoelectron detectors for use with Cerenkov ring imaging counters. By suitable control of the fields in successive gaps and by introducing screens to reduce photon feedback to the cathode the gain many be increased considerably. We have obtained gains in excess of 6 x 10/sup 7/ for photoelectrons with a good pulse height spectrum and expect to increase this further. We discuss the use of resistive anodes to give avalanche positions in two dimensions by charge division.

Theoretical and experimental studies on the daily accumulative heat gain from cool roofs

International Nuclear Information System (INIS)

Qin, Yinghong; Zhang, Mingyi; Hiller, Jacob E.

2017-01-01

Cool roofs are gaining popularity as passive building cooling techniques, but the correlation between energy savings and rooftop albedo has not been understood completely. Here we theoretically model the daily accumulative inward heat (DAIH) from building roofs with different albedo values, correlating the heat gain of the building roof to both the rooftop albedo and the incident solar radiation. According to this model, the DAIH increases linearly with the daily zenith solar radiation, but decreases linearly with the rooftop albedo. A small building cell was constructed to monitor the heat gain of the building under the conditions of non-insulated and insulated roofs. The observational DAIH is highly coincident with the theoretical one, validating the theoretical model. It was found that insulating the roof, increasing the rooftop albedo, or both options can effectively curtail the heat gain in buildings during the summer season. The proposed theoretical model would be a powerful tool for evaluating the heat gain of the buildings and estimating the energy savings potential of high-reflective cool roofs. - Highlights: • Daily accumulative heat gain from a building roof is theoretically modeled. • Daily accumulative heat gain from a building roof increases linearly with rooftop absorptivity. • Increasing the roof insulation tapers the effect of the rooftop absorptivity. • The theoretical model is powerful for estimating energy savings of reflective roofs.

Therapeutic miRNA and siRNA: Moving from Bench to Clinic as Next Generation Medicine

Directory of Open Access Journals (Sweden)

Chiranjib Chakraborty

2017-09-01

Full Text Available In the past few years, therapeutic microRNA (miRNA and small interfering RNA (siRNA are some of the most important biopharmaceuticals that are in commercial space as future medicines. This review summarizes the patents of miRNA- and siRNA-based new drugs, and also provides a snapshot about significant biopharmaceutical companies that are investing for the therapeutic development of miRNA and siRNA molecules. An insightful view about individual siRNA and miRNA drugs has been depicted with their present status, which is gaining attention in the therapeutic landscape. The efforts of the biopharmaceuticals are discussed with the status of their preclinical and/or clinical trials. Here, some of the setbacks have been highlighted during the biopharmaceutical development of miRNA and siRNA as individual therapeutics. Finally, a snapshot is illustrated about pharmacokinetics, pharmacodynamics with absorption, distribution, metabolism, and excretion (ADME, which is the fundamental development process of these therapeutics, as well as the delivery system for miRNA- and siRNA-based drugs. Keywords: miRNA, siRNA, drug development

Preventing Weight Gain

Science.gov (United States)

... Local Programs Related Topics Diabetes Nutrition Preventing Weight Gain Language: English (US) Español (Spanish) Recommend on Facebook ... cancer. Choosing an Eating Plan to Prevent Weight Gain So, how do you choose a healthful eating ...

c-Fms signaling mediates neurofibromatosis Type-1 osteoclast gain-in-functions.

Directory of Open Access Journals (Sweden)

Yongzheng He

Full Text Available Skeletal abnormalities including osteoporosis and osteopenia occur frequently in both pediatric and adult neurofibromatosis type 1 (NF1 patients. NF1 (Nf1 haploinsufficient osteoclasts and osteoclast progenitors derived from both NF1 patients and Nf1(+/- mice exhibit increased differentiation, migration, and bone resorptive capacity in vitro, mediated by hyperactivation of p21(Ras in response to limiting concentrations of macrophage-colony stimulating factor (M-CSF. Here, we show that M-CSF binding to its receptor, c-Fms, results in increased c-Fms activation in Nf1(+/ (- osteoclast progenitors, mediating multiple gain-in-functions through the downstream effectors Erk1/2 and p90RSK. PLX3397, a potent and selective c-Fms inhibitor, attenuated M-CSF mediated Nf1(+/- osteoclast migration by 50%, adhesion by 70%, and pit formation by 60%. In vivo, we administered PLX3397 to Nf1(+/- osteoporotic mice induced by ovariectomy (OVX and evaluated changes in bone mass and skeletal architecture. We found that PLX3397 prevented bone loss in Nf1(+/--OVX mice by reducing osteoclast differentiation and bone resorptive activity in vivo. Collectively, these results implicate the M-CSF/c-Fms signaling axis as a critical pathway underlying the aberrant functioning of Nf1 haploinsufficient osteoclasts and may provide a potential therapeutic target for treating NF1 associated osteoporosis and osteopenia.

New concepts in therapeutic photomedicine: photochemistry, optical targeting and the therapeutic window

International Nuclear Information System (INIS)

Parrish, J.A.

1981-01-01

Advances in optics technology, synthetic photochemistry, and the science of photobiology make it possible to think beyond phototherapy and photochemotherapy which is dependent on direct photochemical alteration of metabolites or direct phototoxic insult to cells. This report discusses another gender of photomedicine therapy which includes in vivo photoactivation of medicines, photon-dependent drug delivery, and manipulation of host and exposure source to maximize therapeutic index. These therapeutic manipulations are made possible because the skin is highly overperfused and because non-ionizing electromagnetic radiation that enters skin and blood has adequate photon energy to cause electronic excitation. Radiation of 320-800 nm is not very directly phototoxic, is absorbed by a variety of relatively nontoxic photolabile molecules and has an internal dosimetric depth profile. This radiation can therefore be used to activate, deactivate, bind, release or biotransform medications in vivo in skin or other organs. The photochemist, synthetic chemist and photobiologist can collaborate to significantly increase therapeutic possibilities

Mechanisms of therapeutic resistance in cancer (stem cells with emphasis on thyroid cancer cells.

Directory of Open Access Journals (Sweden)

Sabine eHombach-Klonisch

2014-03-01

Full Text Available Tissue invasion, metastasis and therapeutic resistance to anti-cancer treatments are common and main causes of death in cancer patients. Tumor cells mount complex and still poorly understood molecular defense mechanisms to counteract and evade oxygen deprivation, nutritional restrictions as well as radio- and chemotherapeutic treatment regimens aimed at destabilizing their genomes and important cellular processes. In thyroid cancer, as in other tumors, such defense strategies include the reactivation in cancer cells of early developmental programs normally active exclusively in stem cells, the stimulation of cancer stem-like cells resident within the tumor tissue and the recruitment of bone marrow-derived progenitors into the tumor (Thomas et al., 2008;Klonisch et al., 2009;Derwahl, 2011. Metastasis and therapeutic resistance in cancer (stem cells involves the epithelial-to-mesenchymal transition- (EMT- mediated enhancement in cellular plasticity, which includes coordinated dynamic biochemical and nuclear changes (Ahmed et al., 2010. The purpose of the present review is to provide an overview of the role of DNA repair mechanisms contributing to therapeutic resistance in thyroid cancer and highlight the emerging roles of autophagy and damage associated molecular pattern (DAMP responses in EMT and chemoresistance in tumor cells. Finally, we use the stem cell factor and nucleoprotein High Mobility Group A2 (HMGA2 as an example to demonstrate how factors intended to protect stem cells are wielded by cancer (stem cells to gain increased transformative cell plasticity which enhances metastasis, therapeutic resistance and cell survival. Wherever possible, we have included information on these cellular processes and associated factors as they relate to thyroid cancer cells.

Discovery and design of carbohydrate-based therapeutics.

Science.gov (United States)

Cipolla, Laura; Araújo, Ana C; Bini, Davide; Gabrielli, Luca; Russo, Laura; Shaikh, Nasrin

2010-08-01

Till now, the importance of carbohydrates has been underscored, if compared with the two other major classes of biopolymers such as oligonucleotides and proteins. Recent advances in glycobiology and glycochemistry have imparted a strong interest in the study of this enormous family of biomolecules. Carbohydrates have been shown to be implicated in recognition processes, such as cell-cell adhesion, cell-extracellular matrix adhesion and cell-intruder recognition phenomena. In addition, carbohydrates are recognized as differentiation markers and as antigenic determinants. Due to their relevant biological role, carbohydrates are promising candidates for drug design and disease treatment. However, the growing number of human disorders known as congenital disorders of glycosylation that are being identified as resulting from abnormalities in glycan structures and protein glycosylation strongly indicates that a fast development of glycobiology, glycochemistry and glycomedicine is highly desirable. The topics give an overview of different approaches that have been used to date for the design of carbohydrate-based therapeutics; this includes the use of native synthetic carbohydrates, the use of carbohydrate mimics designed on the basis of their native counterpart, the use of carbohydrates as scaffolds and finally the design of glyco-fused therapeutics, one of the most recent approaches. The review covers mainly literature that has appeared since 2000, except for a few papers cited for historical reasons. The reader will gain an overview of the current strategies applied to the design of carbohydrate-based therapeutics; in particular, the advantages/disadvantages of different approaches are highlighted. The topic is presented in a general, basic manner and will hopefully be a useful resource for all readers who are not familiar with it. In addition, in order to stress the potentialities of carbohydrates, several examples of carbohydrate-based marketed therapeutics are given

Prepregnancy body mass index, gestational weight gain, and birth weight in the BRISA cohort.

Science.gov (United States)

Lima, Raina Jansen Cutrim Propp; Batista, Rosângela Fernandes Lucena; Ribeiro, Marizélia Rodrigues Costa; Ribeiro, Cecília Cláudia Costa; Simões, Vanda Maria Ferreira; Lima Neto, Pedro Martins; Silva, Antônio Augusto Moura da; Bettiol, Heloisa

2018-01-01

OBJECTIVE To analyze the effects of maternal pre-pregnancy body mass index and weight gain during pregnancy on the baby's birth weight. METHODS We conducted a cross-sectional study with 5,024 mothers and their newborns using a Brazilian birth cohort study. In the proposed model, estimated by structural equation modeling, we tested socioeconomic status, age, marital status, pre-pregnancy body mass index, smoking habit and alcohol consumption during pregnancy, hypertension and gestational diabetes, gestational weight gain, and type of delivery as determinants of the baby's birth weight. RESULTS For a gain of 4 kg/m2 (1 Standard Deviation [SD]) in pre-pregnancy body mass index, there was a 0.126 SD increase in birth weight, corresponding to 68 grams (p gestational weight gain represented a 0.280 SD increase in newborn weight, correponding to 151.2 grams (p weight was direct (standardized coefficient [SC] = 0.202; p weight gain during pregnancy (SC = -0.070, p weight gain during pregnany on birth weight was predominantly direct (SC = 0.269, p gained less weight during pregnancy (p gestational weight gain on the increase in birth weight was greater than that of pre-pregnancy body mass index.

Therapeutic applications of radiopharmaceuticals

International Nuclear Information System (INIS)

Baker, W.J.; Datz, F.L.; Beightol, R.W.

1987-01-01

Whether a radiopharmaceutical has diagnostic or therapeutic application depends on both the isotope and pharmaceutical used. For diagnostic applications, the isotope should undergo only γ-decay, since usually only γ-radiation is detected by nuclear medicine cameras. The half-life should be just long enough to allow the procedure to be performed. In contrast, the isotope needed for therapeutic purposes should have particulate radiation, such as a β-particle (electron), since these are locally absorbed an increase the local radiation dose. γ-Radiation, which penetrates the tissues, produces less radiation dose than do Β-particles. Several references dealing with radioactive decay, particulate interactions, and diagnostic and therapeutic applications of radiopharmaceuticals are available. Radiopharmaceuticals can legally be used only by physicians who are qualified by specific training in the safe handling of radionuclides. The experience and training of these physicians must be approved by the Nuclear Regulatory Commission or Agreement State Agency authorized to license the use of radiopharmaceuticals. A list of all byproduct material and procedures is available in the Code of Federal Regulations. Of the many radiopharmaceuticals available for diagnostic and therapeutic use, only those commonly used are discussed in this chapter

Textural gain and subsequent loss in irradiated apples, carrots and potatoes with increase in dose from 0.03 to 1.0 kGy

International Nuclear Information System (INIS)

Cathalin, J.; McNulty, P.

1996-01-01

Cored samples (16mm X 15mm diameter) of apples, carrots and potatoes were irradiated in an Isomedix Gammacell 1000 irradiator at a dose rate of approximately 9Gy/min. Texture was measured using unrestrained uniaxial compression to microrupture on the JJ Universal Testing Machine. The loading rate was 6mm/min. Texture or firmness was assessed as the force to microrupture; the force required for various microrupture sample deformations (25%, 50% and 75%); the apparent Young's Modulus (ratio of the average stress to the average strain to microrupture); and the microrupture energy (area under the force-deformation curve). As the dose increased from 0.03 up to about 0.1 kGy, a gain in texture generally occurred in all products ranging from 3% to 16%. A transition area from gain to loss occurred within the 0.1 to 0.3 kGy range. Loss of texture occurred in all products as the dose increased from 0.3 to 1.0kGy, the loss ranging from 4% to 30%. The greatest loss of texture occurred in apples and the least loss in carrots. There textural trends may have commercial significance in low dose irradiation processes such as sprout inhibition, senescence delay and disinfestation

Therapeutic inertia amongst general practitioners with interest in diabetes.

Science.gov (United States)

Seidu, Samuel; Than, Tun; Kar, Deb; Lamba, Amrit; Brown, Pam; Zafar, Azhar; Hussain, Rizwan; Amjad, Ahmed; Capehorn, Mathew; Martin, Elizabeth; Fernando, Kevin; McMoran, Jim; Millar-Jones, David; Kahn, Shahzada; Campbell, Nigel; Brice, Richard; Mohan, Rahul; Mistry, Mukesh; Kanumilli, Naresh; St John, Joan; Quigley, Richard; Kenny, Colin; Khunti, Kamlesh

2018-02-01

As the therapeutic options in the management of type 2 diabetes increase, there is an increase confusion among health care professionals, thus leading to the phenomenon of therapeutic inertia. This is the failure to escalate or de-escalate treatment when the clinical need for this is required. It has been studied extensively in various settings, however, it has never been reported in any studies focusing solely on primary care physicians with an interest in diabetes. This group is increasingly becoming the focus of managing complex diabetes care in the community, albeit with the support from specialists. In this retrospective audit, we assessed the prevalence of the phenomenon of therapeutic inertia amongst primary care physicians with an interest in diabetes in UK. We also assessed the predictive abilities of various patient level characteristics on therapeutic inertia amongst this group of clinicians. Out of the 240 patients reported on, therapeutic inertia was judged to have occurred in 53 (22.1%) of patients. The full model containing all the selected variables was not statistically significant, p=0.59. So the model was not able to distinguish between situations in which therapeutic inertia occurred and when it did not occur. None of the patient level characteristics on its own was predictive of therapeutic inertia. Therapeutic inertia was present only in about a fifth of patient patients with diabetes being managed by primary care physicians with an interest in diabetes. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Pushed by Symptoms, Pulled by Values: Promotion Goals Increase Motivation in Therapeutic Tasks.

Science.gov (United States)

Katz, Benjamin A; Catane, Sara; Yovel, Iftah

2016-03-01

While many therapies focus on the reduction of disturbing symptoms, others pursue behavior consistent with personally held values. Based on regulatory focus theory (Higgins, 1997), reducing symptoms is a type of prevention goal while pursuing values is a promotion goal. In the current study, 123 undergraduate students elicited a negative, self-focused emotion-laden cognition. They were then randomly assigned to construe their negative thought as either (a) an impediment to valued behaviors, (b) a cause of unpleasant symptoms, or to one of two control conditions: (c) distraction or (d) no intervention. Then, participants in all groups completed a series of repetitive therapeutic tasks that targeted their elicited negative cognitions. Results showed that participants who construed treatment in terms of valued behavior promotion spent more time on a therapeutic task than all other groups. The group in the unpleasant symptom promotion condition did not differ from either control group. The motivational advantage of value promotion was not accounted for by differences in mood. The present findings suggest that clients may be better motivated through value promotion goals, as opposed to symptom prevention goals. Copyright © 2015. Published by Elsevier Ltd.

Necroptosis: Modules and molecular switches with therapeutic implications.

Science.gov (United States)

Arora, Deepika; Sharma, Pradeep Kumar; Siddiqui, Mohammed Haris; Shukla, Yogeshwer

2017-06-01

Among the various programmed cell death (PCD) pathways, "Necroptosis" has gained much importance as a novel paradigm of cell death. This pathway has emerged as a backup mechanism when physiologically conserved PCD (apoptosis) is non-functional either genetically or pathogenically. The expanding spectrum of necroptosis from physiological development to diverse patho-physiological disorders, including xenobiotics-mediated toxicity has now grabbed the attention worldwide. The efficient role of necroptosis regulators in disease development and management are under constant examination. In fact, few regulators (e.g. MLKL) have already paved their way towards clinical trials and others are in queue. In this review, emphasis has been paid to the various contributing factors and molecular switches that can regulate necroptosis. Here we linked the overview of current knowledge of this enigmatic signaling with magnitude of therapeutics that may underpin the opportunities for novel therapeutic approaches to suppress the pathogenesis of necroptosis-driven disorders. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Review of health and productivity gains from better IEQ

Energy Technology Data Exchange (ETDEWEB)

Fisk, William J.

2000-08-01

The available scientific data suggest that existing technologies and procedures can improve indoor environmental quality (IEQ) in a manner that significantly increases productivity and health. While there is considerable uncertainty in the estimates of the magnitudes of productivity gains that may be obtained, the projected gains are very large. For the U.S., the estimated potential annual savings and productivity gains are $6 to $14 billion from reduced respiratory disease, $2 to $4 billion from reduced allergies and asthma, $10 to $30 billion from reduced sick building syndrome symptoms, and $20 to $160 billion from direct improvements in worker performance that are unrelated to health. Productivity gains that are quantified and demonstrated could serve as a strong stimulus for energy efficiency measures that simultaneously improve the indoor environment.

Weight Gain: A Possible Side Effect of All Antiretrovirals

Science.gov (United States)

Ricci, Elena; Menzaghi, Barbara; Orofino, Giancarlo; Passerini, Simone; Madeddu, Giordano; Martinelli, Canio Vito; De Socio, Giuseppe Vittorio; Squillace, Nicola; Rusconi, Stefano; Bonfanti, Paolo; Di Biagio, Antonio; Quirino, T; Bonfanti, P; Ricci, E; Bellacosa, C; Maggi, P; Calza, L; Abeli, C; Menzaghi, B; Celesia, B M; Grosso, C; Stagno, A; Vichi, F; Mazzotta, F; Martinelli, C; Penco, G; Cassola, G; Di Biagio, A; Taramasso, L; Nicolini, L A; Dentone, C; Molteni, C; Palvarini, L; Scalzini, A; Carenzi, L; Rizzardini, G; Valsecchi, L; Cordier, L; Rusconi, S; Colombo, V; Galli, M; Franzetti, M; De Socio, G V; Mazzotta, E; Parruti, G; Madeddu, G; Bagella, P; S. Mura, M; Libertone, R; Antinori, A; Di Giambenedetto, S; Orofino, G; Guastavigna, M; Caramell, P

2017-01-01

Abstract Weight gain and body mass index (BMI) increase are central issues in patients living with HIV who need to minimize the risk of metabolic disease. Information collected through the SCOLTA cohort revealed significant 1-year BMI increase in patients treated with dolutegravir (P = .004), raltegravir (P = .0004), elvitegravir (P = .004), darunavir (P = .0006), and rilpivirine (P = .029). BMI gain correlated with low baseline BMI (P = .002) and older age (P = .0007) in Centers for Disease Control and Prevention stages A/B, with lower BMI (P = .005) and CD4+ T-cell count (P = .007) at enrollment in stage C. PMID:29255735

Improving the in vivo therapeutic index of siRNA polymer conjugates through increasing pH responsiveness.

Science.gov (United States)

Guidry, Erin N; Farand, Julie; Soheili, Arash; Parish, Craig A; Kevin, Nancy J; Pipik, Brenda; Calati, Kathleen B; Ikemoto, Nori; Waldman, Jacob H; Latham, Andrew H; Howell, Bonnie J; Leone, Anthony; Garbaccio, Robert M; Barrett, Stephanie E; Parmar, Rubina Giare; Truong, Quang T; Mao, Bing; Davies, Ian W; Colletti, Steven L; Sepp-Lorenzino, Laura

2014-02-19

Polymer based carriers that aid in endosomal escape have proven to be efficacious siRNA delivery agents in vitro and in vivo; however, most suffer from cytotoxicity due in part to a lack of selectivity for endosomal versus cell membrane lysis. For polymer based carriers to move beyond the laboratory and into the clinic, it is critical to find carriers that are not only efficacious, but also have margins that are clinically relevant. In this paper we report three distinct categories of polymer conjugates that improve the selectivity of endosomal membrane lysis by relying on the change in pH associated with endosomal trafficking, including incorporation of low pKa heterocycles, acid cleavable amino side chains, or carboxylic acid pH sensitive charge switches. Additionally, we determine the therapeutic index of our polymer conjugates in vivo and demonstrate that the incorporation of pH responsive elements dramatically expands the therapeutic index to 10-15, beyond that of the therapeutic index (less than 3), for polymer conjugates previously reported.

Intracellular and extracellular microtubule associated protein tau as a therapeutic target in Alzheimer disease and other tauopathies.

Science.gov (United States)

Avila, Jesús; Pallas, Noemí; Bolós, Marta; Sayas, C Laura; Hernandez, Felix

2016-06-01

Microtubule associated protein tau, a protein mainly expressed in neurons, plays an important role in several diseases related to dementia, named tauopathies. Alzheimer disease is the most relevant tauopathy. The role of tau protein in dementia is now a topic under discussion, and is the focus of this review. We have covered two major areas: tau pathology and tau as a therapeutic target. Tau pathology is mainly related to a gain of toxic function due to an abnormal accumulation, aberrant modifications (such as hyperphosphorylation and truncation, among others) and self-aggregation of tau into oligomers or larger structures. Also, tau can be found extracellularly in a toxic form. Tau-based therapy is mainly centered on avoiding the gain of these toxic functions of tau. Tau therapies are focused on lowering tau levels, mainly of modified tau species that could be toxic for neurons (phosphorylated, truncated or aggregated tau), in intracellular or extracellular form. Decreasing the levels of those toxic species is a possible therapeutic strategy.

76 FR 65634 - Redetermination of the Consolidated Net Unrealized Built-In Gain and Loss

Science.gov (United States)

2011-10-24

... Redetermination of the Consolidated Net Unrealized Built-In Gain and Loss AGENCY: Internal Revenue Service (IRS... consolidated net unrealized built-in gain and loss in certain circumstances. This document also invites... gain (NUBIG) at the time of its ownership change, recognized built-in gains will increase the section...

Interdelivery weight gain and risk of cesarean delivery following a prior vaginal delivery.

Science.gov (United States)

Dude, Annie M; Lane-Cordova, Abbi D; Grobman, William A

2017-09-01

Approximately one third of all deliveries in the United States are via cesarean. Previous research indicates weight gain during pregnancy is associated with an increased risk of cesarean delivery. It remains unclear, however, whether and to what degree weight gain between deliveries (ie, interdelivery weight gain) is associated with cesarean delivery in a subsequent pregnancy following a vaginal delivery. The objective of the study was to determine whether interdelivery weight gain is associated with an increased risk of intrapartum cesarean delivery following a vaginal delivery. This was a case-control study of women who had 2 consecutive singleton births of at least 36 weeks' gestation between 2005 and 2016, with a vaginal delivery in the index pregnancy. Women were excluded if they had a contraindication to a trial of labor (eg, fetal malpresentation or placenta previa) in the subsequent pregnancy. Maternal characteristics and delivery outcomes for both pregnancies were abstracted from the medical record. Maternal weight gain between deliveries was measured as the change in body mass index at delivery. Women who underwent a subsequent cesarean delivery were compared with those who had a repeat vaginal delivery using χ 2 statistics for categorical variables and Student t tests or analysis of variance for continuous variables. Multivariable logistic regression was used to determine whether interdelivery weight gain remained independently associated with intrapartum cesarean delivery after adjusting for potential confounders. Of 10,396 women who met eligibility criteria and had complete data, 218 (2.1%) had a cesarean delivery in the subsequent pregnancy. Interdelivery weight gain was significantly associated with cesarean delivery and remained significant in multivariable analysis for women with a body mass index increase of at least 2 kg/m 2 (adjusted odds ratio, 1.53, 95% confidence interval, 1.03-2.27 for a body mass index increase of 2 kg/m 2 to gained 2 kg

Gains in Life Expectancy Associated with Higher Education in Men.

Science.gov (United States)

Bijwaard, Govert E; van Poppel, Frans; Ekamper, Peter; Lumey, L H

2015-01-01

Many studies show large differences in life expectancy across the range of education, intelligence, and socio-economic status. As educational attainment, intelligence, and socio-economic status are highly interrelated, appropriate methods are required to disentangle their separate effects. The aim of this paper is to present a novel method to estimate gains in life expectancy specifically associated with increased education. Our analysis is based on a structural model in which education level, IQ at age 18 and mortality all depend on (latent) intelligence. The model allows for (selective) educational choices based on observed factors and on an unobserved factor capturing intelligence. Our estimates are based on information from health examinations of military conscripts born in 1944-1947 in The Netherlands and their vital status through age 66 (n = 39,798). Our empirical results show that men with higher education have lower mortality. Using structural models to account for education choice, the estimated gain in life expectancy for men moving up one educational level ranges from 0.3 to 2 years. The estimated gain in months alive over the observational period ranges from -1.2 to 5.7 months. The selection effect is positive and amounts to a gain of one to two months. Decomposition of the selection effect shows that the gain from selection on (latent) intelligence is larger than the gain from selection on observed factors and amounts to 1.0 to 1.7 additional months alive. Our findings confirm the strong selection into education based on socio-economic status and intelligence. They also show significant higher life expectancy among individuals with higher education after the selectivity of education choice has been taken into account. Based on these estimates, it is plausible therefore that increases in education could lead to increases in life expectancy.

Tuning of gravity-dependent and gravity-independent vertical angular VOR gain changes by frequency of adaptation.

Science.gov (United States)

Yakushin, Sergei B

2012-06-01

The gain of the vertical angular vestibulo-ocular reflex (aVOR) was adaptively increased and decreased in a side-down head orientation for 4 h in two cynomolgus monkeys. Adaptation was performed at 0.25, 1, 2, or 4 Hz. The gravity-dependent and -independent gain changes were determined over a range of head orientations from left-side-down to right-side-down at frequencies from 0.25 to 10 Hz, before and after adaptation. Gain changes vs. frequency data were fit with a Gaussian to determine the frequency at which the peak gain change occurred, as well as the tuning width. The frequency at which the peak gravity-dependent gain change occurred was approximately equal to the frequency of adaptation, and the width increased monotonically with increases in the frequency of adaptation. The gravity-independent component was tuned to the adaptive frequency of 0.25 Hz but was uniformly distributed over all frequencies when the adaptation frequency was 1-4 Hz. The amplitude of the gravity-independent gain changes was larger after the aVOR gain decrease than after the gain increase across all tested frequencies. For the aVOR gain decrease, the phase lagged about 4° for frequencies below the adaptation frequency and led for frequencies above the adaptation frequency. For gain increases, the phase relationship as a function of frequency was inverted. This study demonstrates that the previously described dependence of aVOR gain adaptation on frequency is a property of the gravity-dependent component of the aVOR only. The gravity-independent component of the aVOR had a substantial tuning curve only at an adaptation frequency of 0.25 Hz.

Gain characteristics of a multiatmosphere uv-preionized CO2 laser

International Nuclear Information System (INIS)

Alcock, A.J.; Fedosejevs, R.; Walker, A.C.

1975-01-01

The small-signal gain of a transverse-discharge UV-preionized CO 2 laser was investigated at pressures in the 1 to 15-atm range. Measurements were carried out on the P(18) and R(16) lines of both the 10.4- and 9.4-μm bands, and data on the pressure dependence of the peak gain and gain rise time are presented. The results demonstrate that small-signal gains in excess of 5-percent cm -1 are readily obtained at pressures of approximately 12 atm and confirm that the relaxation times of the energy levels relevant to laser action scale inversely with pressure. In addition, it is found that the gain of both R branches increases more rapidly with pressure than that of the P branches, while there are indications that the 9.4- and 10.4-μm gain values become comparable at pressures of approximately 15 atm. The experimental results are compared with the dependence of gain on pressure predicted by a relatively simple theoretical model. On the basis of this model it is found that the experimentally determined gain rises more rapidly with pressure than one would expect and a number of possible reasons for this discrepancy are discussed

Advances in the delivery of RNA therapeutics: from concept to clinical reality.

Science.gov (United States)

Kaczmarek, James C; Kowalski, Piotr S; Anderson, Daniel G

2017-06-27

The rapid expansion of the available genomic data continues to greatly impact biomedical science and medicine. Fulfilling the clinical potential of genetic discoveries requires the development of therapeutics that can specifically modulate the expression of disease-relevant genes. RNA-based drugs, including short interfering RNAs and antisense oligonucleotides, are particularly promising examples of this newer class of biologics. For over two decades, researchers have been trying to overcome major challenges for utilizing such RNAs in a therapeutic context, including intracellular delivery, stability, and immune response activation. This research is finally beginning to bear fruit as the first RNA drugs gain FDA approval and more advance to the final phases of clinical trials. Furthermore, the recent advent of CRISPR, an RNA-guided gene-editing technology, as well as new strides in the delivery of messenger RNA transcribed in vitro, have triggered a major expansion of the RNA-therapeutics field. In this review, we discuss the challenges for clinical translation of RNA-based therapeutics, with an emphasis on recent advances in delivery technologies, and present an overview of the applications of RNA-based drugs for modulation of gene/protein expression and genome editing that are currently being investigated both in the laboratory as well as in the clinic.

Measurement of in-vivo dosage increase due to dental alloys during therapeutic irradiation of the mouth cavity

International Nuclear Information System (INIS)

Thilmann, C.; Mose, S.; Saran, F.; Schopohl, B.; Boettcher, H.D.

1995-01-01

The degree of dosage increase in the immediate surrounding of metallic dental materials was measured in an in-vivo study during therapeutic irradiation with 60 Co gamma rays in the area of mouth cavity of 11 patients. Measurements were carried out by thermoluminescent dosimetry at permamently fixed golden teeth and alloy specimens containing gold and palladium and amalgam. The following relative dodage values according to a simultanelusly measured reference value were measured at the surface of the different dental materials: 161% near fixed golden caps, 168% near the specimen containing gold in a high percentage, 133% near the specimen of palladium and 161% near the specimen of amalgam. The in vivo measured dosage increases due to metallic dental prosthesis are less than values obtained using back scatter arramgements for irradiating phantoms. Despite this, they could be of clinical relevance. Thus the usage of a mucous membrane protection during irradiation with 60 Co, as a means of preventing local lesions of the oral mucosa, due to dental alloys within the treatment volume remains inevitable. (orig.) [de

Dot gain compensation in the blue noise mask

Science.gov (United States)

Yao, Meng; Parker, Kevin J.

1995-04-01

Frequency modulated (FM) halftoning or 'stochastic screening,' has attracted a great deal of attention in the printing industry in recent years. It has several advantages over conventional halftoning. But one serious problem that arises in FM halftoning is dot gain. One approach to stochastic screening uses a specially constructed halftone screen, the blue noise mask (BNM), to produce an unstructured and visually appealing pattern of halftone dots at any gray level. In this paper, we will present methods to correct dot gain with the BNM. Dot gain is related to the area-to-perimeter ration of printed spots. We can exploit this feature in different ways. At a medium level, a B>NM pattern will have 'connected' as well as 'isolated' dots. Normally, as we build down BNM patterns to lower levels, a specific number of white dots will be replace by black dots. Since connected white dots are more likely to be picked than isolated white dots, this will results in substantial dot gain because of the increasing number of isolated white dots. We show that it is possible to constrain the process of constructing a BNM such that isolated dots are preferentially removes, thus significantly reducing dot gain in a BNM.

Active rc filter permits easy trade-off of amplifier gain and sensitivity to gain

Science.gov (United States)

Kerwin, W. J.; Shaffer, C. V.

1968-01-01

Passive RC network was designed with zeros of transmission in the right half of the complex frequency plane in the feedback loop of a simple negative-gain amplifier. The proper positioning provides any desired trade-off between amplifier gain and sensitivity to amplifier gain.

Mechanisms of Gain Control by Voltage-Gated Channels in Intrinsically-Firing Neurons

Science.gov (United States)

Patel, Ameera X.; Burdakov, Denis

2015-01-01

Gain modulation is a key feature of neural information processing, but underlying mechanisms remain unclear. In single neurons, gain can be measured as the slope of the current-frequency (input-output) relationship over any given range of inputs. While much work has focused on the control of basal firing rates and spike rate adaptation, gain control has been relatively unstudied. Of the limited studies on gain control, some have examined the roles of synaptic noise and passive somatic currents, but the roles of voltage-gated channels present ubiquitously in neurons have been less explored. Here, we systematically examined the relationship between gain and voltage-gated ion channels in a conductance-based, tonically-active, model neuron. Changes in expression (conductance density) of voltage-gated channels increased (Ca2+ channel), reduced (K+ channels), or produced little effect (h-type channel) on gain. We found that the gain-controlling ability of channels increased exponentially with the steepness of their activation within the dynamic voltage window (voltage range associated with firing). For depolarization-activated channels, this produced a greater channel current per action potential at higher firing rates. This allowed these channels to modulate gain by contributing to firing preferentially at states of higher excitation. A finer analysis of the current-voltage relationship during tonic firing identified narrow voltage windows at which the gain-modulating channels exerted their effects. As a proof of concept, we show that h-type channels can be tuned to modulate gain by changing the steepness of their activation within the dynamic voltage window. These results show how the impact of an ion channel on gain can be predicted from the relationship between channel kinetics and the membrane potential during firing. This is potentially relevant to understanding input-output scaling in a wide class of neurons found throughout the brain and other nervous systems

Maternal pre-pregnancy body mass index, gestational weight gain influence birth weight.

Science.gov (United States)

Zhao, R; Xu, L; Wu, M L; Huang, S H; Cao, X J

2018-02-01

Evidence suggests that pre-pregnancy body mass index and gestational weight gain have impact on pregnancy and birth weight, yet whether maternal gestational weight gain has a differential effect on the rates of adverse birth weight among women with different pre-pregnancy body mass index categories are unknown. We selected 1617 children matched with their mothers as study subjects. The subjects were divided into three categories: weight gain below the American Institute of Medicine guidelines, weight gain within the American Institute of Medicine guidelines and weight gain above the American Institute of Medicine guidelines. The prevalence of pre-pregnancy underweight and overweight/obese women was 16.3% and 12.3%. And nearly 15.2% of the women had gestational weight gain below American Institute of Medicine guideline, 52.1% of the women had gestational weight gain above American Institute of Medicine guideline. Maternal overweight and obese was associated with increased risk for macrosomia and large-for-gestational age. Women had gestational weight gain below American Institute of Medicine guideline were more likely to have low birth weight and small-for-gestational age than women who had gestational weight gain within American Institute of Medicine guideline. Furthermore, the risks for macrosomia and large-for-gestational age were increased in women with above American Institute of Medicine guideline. And for women with a normal weight before pregnancy, gestational weight gain above the American Institute of Medicine guidelines were associated with higher rates of macrosomia and large-for-gestational age, compared with the women of similar pre-pregnancy weight category but with gestational weight gain within the American Institute of Medicine guidelines. Women with abnormal pre-pregnancy body mass index and gestational weight gain are at risk for adverse birth weight outcomes. Moreover, gestational weight gain has a differential effect on the rates of adverse

Maximizing gain in high-throughput screening using conformal prediction.

Science.gov (United States)

Svensson, Fredrik; Afzal, Avid M; Norinder, Ulf; Bender, Andreas

2018-02-21

Iterative screening has emerged as a promising approach to increase the efficiency of screening campaigns compared to traditional high throughput approaches. By learning from a subset of the compound library, inferences on what compounds to screen next can be made by predictive models, resulting in more efficient screening. One way to evaluate screening is to consider the cost of screening compared to the gain associated with finding an active compound. In this work, we introduce a conformal predictor coupled with a gain-cost function with the aim to maximise gain in iterative screening. Using this setup we were able to show that by evaluating the predictions on the training data, very accurate predictions on what settings will produce the highest gain on the test data can be made. We evaluate the approach on 12 bioactivity datasets from PubChem training the models using 20% of the data. Depending on the settings of the gain-cost function, the settings generating the maximum gain were accurately identified in 8-10 out of the 12 datasets. Broadly, our approach can predict what strategy generates the highest gain based on the results of the cost-gain evaluation: to screen the compounds predicted to be active, to screen all the remaining data, or not to screen any additional compounds. When the algorithm indicates that the predicted active compounds should be screened, our approach also indicates what confidence level to apply in order to maximize gain. Hence, our approach facilitates decision-making and allocation of the resources where they deliver the most value by indicating in advance the likely outcome of a screening campaign.

Factors affecting pregnancy weight gain and relationships with maternal/fetal outcomes in Turkey

Directory of Open Access Journals (Sweden)

Nilufer Akgun

2017-05-01

Full Text Available Objectives: To determine the effects of pre-pregnancy body mass index (BMI and gestational weight gain on maternal and fetal complications, and to examine whether Turkish women achieve the recommended gestational weight gain. We also investigated the relationship between pregnancy weight gain and mode of delivery, with an examination of maternal anthropometry. Methods: A retrospective cross-sectional study was conducted on a population of 986 pregnant women between November 2011 and November 2015 at Atatürk Education and Research Hospital, Ankara, Turkey. Maternal age, BMI, monthly weight gain during pregnancy, infant birth weight, gender, and maternal and fetal adverse outcomes were evaluated. Results: The frequency of maternal complications was positively associated with elevated pre-pregnancy BMI (p less than 0.05, and weight gain during pregnancy was associated with parity and increased infant birth weight (p less than 0.05. However, no correlations were observed between mean pregnancy weight gain and maternal complications (p greater than 0.05. The percentage of women who gained the Institute of Medicine (IOM-recommended amount of weight was the highest in the underweight BMI group (54.1% and the lowest in the obese BMI group (24.3%. Pregnancy weight gain exceeded IOM recommendations in the overweight (56.3% and obese (52.5% groups. Conclusions: While maternal weight gain during pregnancy affects neonatal body weight, higher pre-pregnancy BMI has an adverse effect on recommended weight gain during pregnancy, with increased maternal complications.

Predicting the Uncertain Future of Aptamer-Based Diagnostics and Therapeutics.

Science.gov (United States)

Bruno, John G

2015-04-16

Despite the great promise of nucleic acid aptamers in the areas of diagnostics and therapeutics for their facile in vitro development, lack of immunogenicity and other desirable properties, few truly successful aptamer-based products exist in the clinical or other markets. Core reasons for these commercial deficiencies probably stem from industrial commitment to antibodies including a huge financial investment in humanized monoclonal antibodies and a general ignorance about aptamers and their performance among the research and development community. Given the early failures of some strong commercial efforts to gain government approval and bring aptamer-based products to market, it may seem that aptamers are doomed to take a backseat to antibodies forever. However, the key advantages of aptamers over antibodies coupled with niche market needs that only aptamers can fill and more recent published data still point to a bright commercial future for aptamers in areas such as infectious disease and cancer diagnostics and therapeutics. As more researchers and entrepreneurs become familiar with aptamers, it seems inevitable that aptamers will at least be considered for expanded roles in diagnostics and therapeutics. This review also examines new aptamer modifications and attempts to predict new aptamer applications that could revolutionize biomedical technology in the future and lead to marketed products.

[Fast food promotes weight gain].

Science.gov (United States)

Stender, Steen; Dyerberg, Jørn; Astrup, Arne V

2007-05-07

The total amounts of fat in a fast food menu consisting of French fries and fried Chicken Nuggets from McDonald's and KFC, respectively, bought in 35 different countries vary from 41 to 71 gram. In most countries the menu contained unacceptably high amounts of industrially-produced trans fat which contributes to an increased risk of ischaemic heart disease, weight gain, abdominal fat accumulation and type 2 diabetes. The quality of the ingredients in fast food ought to be better and the size of the portions smaller and less energy-dense so that frequent fast food meals do not increase the risk of obesity and diseases among customers.

PYTHIOSIS: A THERAPEUTIC APPROACH

Directory of Open Access Journals (Sweden)

C. M. C. Falcão

2015-10-01

Full Text Available Pythiosis, a disease caused by the oomycete Pythium insidiosum, often presents inefficient response to chemotherapy. It is a consensus that, in spite the several therapeutic protocols, a combination of surgery, chemotherapy and immunotherapy should be used. Surgical excision requires the removal of the entire affected area, with a wide margin of safety. The use of antifungal drugs has resulted in variable results, both in vitro and in vivo, and presents low therapeutic efficiency due to differences in the agent characteristics, which differ from true fungi. Immunotherapy is a non-invasive alternative for the treatment of pythiosis, which aims at modifying the immune response of the host, thereby producing an effective response to the agent. Photodynamic therapy has emerged as a promising technique, with good activity against P. insidiosum in vitro and in vivo. However, more studies are necessary to increase the efficiency of the current treatment protocols and consequently improve the cure rates. This paper aims to conduct a review covering the conventional and recent therapeutic methods against P. insidiosum infections

Disease-Associated Particulates and Joint Inflammation; Mechanistic Insights and Potential Therapeutic Targets

Directory of Open Access Journals (Sweden)

Olwyn R. Mahon

2018-05-01

Full Text Available It is now well established that intra-articular deposition of endogenous particulates, such as osteoarthritis-associated basic calcium phosphate crystals, gout-associated monosodium urate crystals, and calcium deposition disease-associated calcium pyrophosphate crystals, contributes to joint destruction through the production of cartilage-degrading enzymes and pro-inflammatory cytokines. Furthermore, exogenous wear-debris particles, generated from prosthetic implants, drive periprosthetic osteolysis which impacts on the longevity of total joint replacements. Over the last few years, significant insight has been gained into the mechanisms through which these particulates exert their effects. Not only has this increased our understanding of the pathological processes associated with crystal deposition but it has also led to the identification of a number of therapeutic targets to treat particulate-associated disease. In this review, we discuss recent developments regarding the cellular events triggered by joint-associated particulates, as well as future directions in therapy for particulate-related arthropathies.

Therapeutic efficacy of a therapeutic cooking group from the patients' perspective.

Science.gov (United States)

Hill, Kimberly H; O'Brien, Kimberly A; Yurt, Roger W

2007-01-01

The purpose of this study was to evaluate the therapeutic efficacy of the cooking group from the burn survivors' perspective. By incorporating concepts of kitchen skills, energy conservation, and desensitization techniques, the cooking group can assist patients with the functional use of their hands, standing tolerance, return to former vocational activities, and socialization with other patients. A questionnaire was developed based on commonly expressed benefits of cooking group. Areas of interest included decreasing anxiety in the kitchen, distraction from their burns, socializing with other burn survivors, and the physical benefits of participating in the group. The results of this study indicate that participants regard the therapeutic cooking group as a valuable treatment modality that effectively combines functional activities with socialization to decrease burn related anxiety and increase motion in a supportive environment for patients with burns.

Multimodal Pilot Behavior in Multi-Axis Tracking Tasks with Time-Varying Motion Cueing Gains

Science.gov (United States)

Zaal, P. M. T; Pool, D. M.

2014-01-01

In a large number of motion-base simulators, adaptive motion filters are utilized to maximize the use of the available motion envelope of the motion system. However, not much is known about how the time-varying characteristics of such adaptive filters affect pilots when performing manual aircraft control. This paper presents the results of a study investigating the effects of time-varying motion filter gains on pilot control behavior and performance. An experiment was performed in a motion-base simulator where participants performed a simultaneous roll and pitch tracking task, while the roll and/or pitch motion filter gains changed over time. Results indicate that performance increases over time with increasing motion gains. This increase is a result of a time-varying adaptation of pilots' equalization dynamics, characterized by increased visual and motion response gains and decreased visual lead time constants. Opposite trends are found for decreasing motion filter gains. Even though the trends in both controlled axes are found to be largely the same, effects are less significant in roll. In addition, results indicate minor cross-coupling effects between pitch and roll, where a cueing variation in one axis affects the behavior adopted in the other axis.

Metformin and berberine prevent olanzapine-induced weight gain in rats.

Directory of Open Access Journals (Sweden)

Yueshan Hu

Full Text Available Olanzapine is a first line medication for the treatment of schizophrenia, but it is also one of the atypical antipsychotics carrying the highest risk of weight gain. Metformin was reported to produce significant attenuation of antipsychotic-induced weight gain in patients, while the study of preventing olanzapine-induced weight gain in an animal model is absent. Berberine, an herbal alkaloid, was shown in our previous studies to prevent fat accumulation in vitro and in vivo. Utilizing a well-replicated rat model of olanzapine-induced weight gain, here we demonstrated that two weeks of metformin or berberine treatment significantly prevented the olanzapine-induced weight gain and white fat accumulation. Neither metformin nor berberine treatment demonstrated a significant inhibition of olanzapine-increased food intake. But interestingly, a significant loss of brown adipose tissue caused by olanzapine treatment was prevented by the addition of metformin or berberine. Our gene expression analysis also demonstrated that the weight gain prevention efficacy of metformin or berberine treatment was associated with changes in the expression of multiple key genes controlling energy expenditure. This study not only demonstrates a significant preventive efficacy of metformin and berberine treatment on olanzapine-induced weight gain in rats, but also suggests a potential mechanism of action for preventing olanzapine-reduced energy expenditure.

Weight Gain during Pregnancy

Science.gov (United States)

... Global Map Premature Birth Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal ... fitness > Weight gain during pregnancy Weight gain during pregnancy E-mail to a friend Please fill in ...

Weight gain after subthalamic nucleus deep brain stimulation in Parkinson's disease is influenced by dyskinesias' reduction and electrodes' position.

Science.gov (United States)

Balestrino, Roberta; Baroncini, Damiano; Fichera, Mario; Donofrio, Carmine Antonio; Franzin, Alberto; Mortini, Pietro; Comi, Giancarlo; Volontè, Maria Antonietta

2017-12-01

Parkinson's disease is a common neurodegenerative disease that can be treated with pharmacological or surgical therapy. Subthalamic nucleus (STN) deep brain stimulation is a commonly used surgical option. A reported side effect of STN-DBS is weight gain: the aim of our study was to find those factors that determine weight gain, through one year-long observation of 32 patients that underwent surgery in our centre. During the follow-up, we considered: anthropometric features, hormonal levels, motor outcome, neuropsychological and quality of life outcomes, therapeutic parameters and electrodes position. The majority (84%) of our patients gained weight (6.7 kg in 12 months); more than a half of the cohort became overweight. At 12th month, weight gain showed a correlation with dyskinesias reduction, electrodes voltage and distance on the lateral axis. In the multivariate regression analysis, the determinants of weight gain were dyskinesias reduction and electrodes position. In this study, we identified dyskinesias reduction and distance between the active electrodes and the third ventricle as determining factors of weight gain after STN-DBS implantation in PD patients. The first finding could be linked to a decrease in energy consumption, while the second one could be due to a lower stimulation of the lateral hypothalamic area, known for its important role in metabolism and body weight control. Weight gain is a common finding after STN-DBS implantation, and it should be carefully monitored given the potential harmful consequences of overweight.

The Gain Estimation of a Fabry-Perot Cavity (FPC Antenna with a Finite Dimension

Directory of Open Access Journals (Sweden)

Taek-Sun Kwon

2017-10-01

Full Text Available In this paper, we have presented an equation for estimating the gain of a Fabry-Perot cavity (FPC antenna with a finite dimension. When an FPC antenna has an infinite dimension and its height is half of a wavelength, the maximum gain of that FPC antenna can be obtained theoretically. If the FPC antenna does not have a dimension sufficient for multiple reflections between a partially reflective surface (PRS and the ground, its gain must be less than that of an FPC antenna that has an infinite dimension. In addition, the gain of an FPC antenna increases as the dimension of a PRS increases and becomes saturated from a specific dimension. The specific dimension where the gain starts to saturate also gets larger as the reflection magnitude of the PRS becomes closer to one. Thus, it would be convenient to have a gain equation when considering the dimension of an FPC antenna in order to estimate the exact gain of the FPC antenna with a specific dimension. A gain versus the dimension of the FPC antenna for various reflection magnitudes of PRS has been simulated, and the modified gain equation is produced through the curve fitting of the full-wave simulation results. The resulting empirical gain equation of an FPC antenna whose PRS dimension is larger than 1.5λ0 has been obtained.

Antipsychotic-associated weight gain: management strategies and impact on treatment adherence

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Dayabandara M

2017-08-01

Full Text Available Madhubhashinee Dayabandara, Raveen Hanwella, Suhashini Ratnatunga, Sudarshi Seneviratne, Chathurie Suraweera, Varuni A de Silva Department of Psychiatry, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka Abstract: Antipsychotic-induced weight gain is a major management problem for clinicians. It has been shown that weight gain and obesity lead to increased cardiovascular and cerebrovascular morbidity and mortality, reduced quality of life and poor drug compliance. This narrative review discusses the propensity of various antipsychotics to cause weight gain, the pharmacologic and nonpharmacologic interventions available to counteract this effect and its impact on adherence. Most antipsychotics cause weight gain. The risk appears to be highest with olanzapine and clozapine. Weight increases rapidly in the initial period after starting antipsychotics. Patients continue to gain weight in the long term. Children appear to be particularly vulnerable to antipsychotic-induced weight gain. Tailoring antipsychotics according to the needs of the individual and close monitoring of weight and other metabolic parameters are the best preventive strategies at the outset. Switching to an agent with lesser tendency to cause weight gain is an option, but carries the risk of relapse of the illness. Nonpharmacologic interventions of dietary counseling, exercise programs and cognitive and behavioral strategies appear to be equally effective in individual and group therapy formats. Both nonpharmacologic prevention and intervention strategies have shown modest effects on weight. Multiple compounds have been investigated as add-on medications to cause weight loss. Metformin has the best evidence in this respect. Burden of side effects needs to be considered when prescribing weight loss medications. There is no strong evidence to recommend routine prescription of add-on medication for weight reduction. Heterogeneity of study methodologies and other

Gain in Body Fat Is Associated with Increased Striatal Response to Palatable Food Cues, whereas Body Fat Stability Is Associated with Decreased Striatal Response

OpenAIRE

Stice, Eric; Yokum, Sonja

2016-01-01

Cross-sectional brain-imaging studies reveal that obese versus lean humans show greater responsivity of reward and attention regions to palatable food cues, but lower responsivity of reward regions to palatable food receipt. However, these individual differences in responsivity may result from a period of overeating. We conducted a repeated-measures fMRI study to test whether healthy weight adolescent humans who gained body fat over a 2 or 3 year follow-up period show an increase in responsiv...

Laugh Away the Fat? Therapeutic Humor in the Control of Stress-induced Emotional Eating

Directory of Open Access Journals (Sweden)

Elizabeth S. Bast

2014-01-01

Full Text Available This review explores the potential overlap between the fields of nutrition and therapeutic humor, together with the role of humor as a possible tool for aiding those in whom emotions, particularly negative ones, trigger eating as a means to improve mood. We review emotional eating, obesity, and the hypothesized mechanisms of emotional eating. We then review the field of therapeutic humor and its ability to de-stress individuals, possibly through endorphin and opioid systems, both of which are also involved in eating behavior. Finally, we present a novel hypothesis that people may be trained to use humor as a “food substitute” at best, or to blunt hunger stimuli, to achieve similar advantages, without the side effect of weight gain.

Laugh Away the Fat? Therapeutic Humor in the Control of Stress-induced Emotional Eating

Science.gov (United States)

Bast, Elizabeth S.; Berry, Elliot M.

2014-01-01

This review explores the potential overlap between the fields of nutrition and therapeutic humor, together with the role of humor as a possible tool for aiding those in whom emotions, particularly negative ones, trigger eating as a means to improve mood. We review emotional eating, obesity, and the hypothesized mechanisms of emotional eating. We then review the field of therapeutic humor and its ability to de-stress individuals, possibly through endorphin and opioid systems, both of which are also involved in eating behavior. Finally, we present a novel hypothesis that people may be trained to use humor as a “food substitute” at best, or to blunt hunger stimuli, to achieve similar advantages, without the side effect of weight gain. PMID:24498514

Prepregnancy body mass index, gestational weight gain, and birth weight in the BRISA cohort

Directory of Open Access Journals (Sweden)

Raina Jansen Cutrim Propp Lima

2018-05-01

Full Text Available ABSTRACT OBJECTIVE To analyze the effects of maternal pre-pregnancy body mass index and weight gain during pregnancy on the baby's birth weight. METHODS We conducted a cross-sectional study with 5,024 mothers and their newborns using a Brazilian birth cohort study. In the proposed model, estimated by structural equation modeling, we tested socioeconomic status, age, marital status, pre-pregnancy body mass index, smoking habit and alcohol consumption during pregnancy, hypertension and gestational diabetes, gestational weight gain, and type of delivery as determinants of the baby's birth weight. RESULTS For a gain of 4 kg/m2 (1 Standard Deviation [SD] in pre-pregnancy body mass index, there was a 0.126 SD increase in birth weight, corresponding to 68 grams (p < 0.001. A 6 kg increase (1 SD in gestational weight gain represented a 0.280 SD increase in newborn weight, correponding to 151.2 grams (p < 0.001. The positive effect of pre-pregnancy body mass index on birth weight was direct (standardized coefficient [SC] = 0.202; p < 0.001, but the negative indirect effect was small (SC = -0.076, p < 0.001 and partially mediated by the lower weight gain during pregnancy (SC = -0.070, p < 0.001. The positive effect of weight gain during pregnany on birth weight was predominantly direct (SC = 0.269, p < 0.001, with a small indirect effect of cesarean delivery (SC = 0.011; p < 0.001. Women with a higher pre-pregnancy body mass index gained less weight during pregnancy (p < 0.001. CONCLUSIONS The effect of gestational weight gain on the increase in birth weight was greater than that of pre-pregnancy body mass index.

Effect of simvastatin in the autonomic system is dependent on the increased gain/sensitivity of the baroreceptors

Science.gov (United States)

Moreira, Edson D; Mostarda, Cristiano T; Moraes-Silva, Ivana C; Ferreira, Janaina B; dos Santos, Fernando; Lacchini, Silvia; De Angelis, Kátia; Rodrigues, Bruno; Irigoyen, Maria Cláudia

2013-01-01

A number of mechanisms have been proposed to explain the pleiotropic effect of statin therapy to reduce sympathetic outflow in cardiovascular disease. We tested the hypothesis that statin treatment could improve baroreflex gain-sensitivity triggered by morphological adaptations in the mechanoreceptor site, thus reducing sympathetic activity, regardless of arterial pressure (AP) level reduction. Male spontaneously hypertensive rats (SHR) were divided into control (SHR, n = 8) and SHR-simvastatin (5 mg/kg/day, for 7 days) (SHR-S, n = 8). After treatment, AP, baroreflex sensitivity (BRS) in response to AP-induced changes, aortic depressor nerve activity, and spectral analyses of pulse interval (PI) and AP variabilities were performed. Internal and external carotids were prepared for morphoquantitative evaluation. Although AP was similar between groups, sympathetic modulation, represented by the low frequency band of PI (SHR: 6.84 ± 3.19 vs. SHR-S: 2.41 ± 0.96 msec2) and from systolic AP variability (SHR: 3.95 ± 0.36 vs. SHR-S: 2.86 ± 0.18 mmHg2), were reduced in treated animals. In parallel, simvastatin induced an increase of 26% and 21% in the number of elastic lamellae as well as a decrease of 9% and 25% in the carotid thickness in both, external and internal carotid, respectively. Moreover, improved baroreceptor function (SHR: 0.78 ± 0.03 vs. SHR-S: 1.06 ± 0.04% mv/mmHg) was observed in addition to a 115% increase in aortic depressor nerve activity in SHR-S rats. Therefore, our data suggest that the reduction of sympathetic outflow in hypertension by simvastatin treatment may be triggered by structural changes in the carotid arteries and increased BRS in response to an improvement of the baroreceptors discharge and consequently of the afferent pathway of the baroreflex arch. PMID:24303130

Employment, work hours and weight gain among middle-aged women.

Science.gov (United States)

Au, N; Hauck, K; Hollingsworth, B

2013-05-01

To investigate the influence of employment and work hours on weight gain and weight loss among middle-aged women. Quantile regression techniques were used to estimate the influence of employment and hours worked on percentage weight change over 2 years across the entire distribution of weight change in a cohort of middle-aged women. A range of controls was included in the models to isolate the effect of work status. A total of 9276 women aged 45-50 years at baseline who were present in both the 1996 and 1998 surveys of the Australian Longitudinal Study of Women's Health. The women were a representative sample of the Australian population. Being out of the labour force or unemployed was associated with lower weight gain and higher weight loss than being employed. The association was stronger at low to moderate levels of weight gain. Among employed women, working regular (35-40), long (41-48) or very long (49+) hours was associated with increasingly higher levels of weight gain compared with working part-time hours. The association was stronger for women with greater weight gain overall. The association between unemployment and weight change became insignificant when health status was controlled for. Employment was associated with more weight gain and less weight loss. Among the employed, working longer hours was associated with more weight gain, especially at the higher levels of weight gain where the health consequences are more serious. These findings suggest that as women work longer hours they are more likely to make lifestyle choices that are associated with weight gain.

Gestational weight gain among minority adolescents predicts term birth weight.

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Ekambaram, Maheswari; Irigoyen, Matilde; DeFreitas, Johelin; Rajbhandari, Sharina; Geaney, Jessica Lynn; Braitman, Leonard Edward

2018-03-07

In adolescents, there is limited evidence on the independent and additive effect of prepregnancy body mass index (BMI) and gestational weight gain on infant birth weight. Data also show that this effect may vary by race. We sought to examine the impact of maternal prepregnancy BMI and gestational weight gain on birth weight and risk of large for gestational age (LGA) in term newborns of minority adolescent mothers. This was a retrospective cohort study of 411 singleton live term infants born to mothers ≤ 18 years. Data were abstracted from electronic medical records. Gestational weight gain was related to infant birth weight (ρ = 0.36, P gain, gestational age and Hispanic ethnicity were independent predictors of birth weight, controlling for maternal age, BMI, parity, tobacco/drug use and preeclampsia. The probability of having an LGA infant increased with weight gain [adjusted odds ratio (aOR) 1.14, 95% confidence interval (CI) 1.07-1.21] but not with BMI. Mothers who gained weight in excess of 2009 Institute of Medicine (IOM) recommendations had a greater risk of having an LGA infant compared to those who gained within recommendations (aOR 5.7, 95% CI 1.6-19.5). Minority adolescents with greater gestational weight gain had infants with higher birth weight and greater risk of LGA; BMI was not associated with either outcome. Further studies are needed to examine the applicability of the 2009 BMI-specific IOM gestational weight gain recommendations to adolescents in minority populations.

A high gain modified SEPIC DC-to-DC boost converter for renewable energy application

DEFF Research Database (Denmark)

Maroti, Pandav Kiran; Padmanaban, Sanjeevikumar; Bhaskar, Mahajan Sagar

2017-01-01

The proposed work present the modified high gain Single Ended Primary Inductance Converter (SEPIC) for renewable energy applications. The voltage gain of proposed converter is very highly related to conventional dc-to-dc converter and recently projected converter based on conventional converter....... The key feature of projected converter is only one controlled device and voltage gain is increased without using a transformer and coupled inductor structure. The voltage gain of projected converter is increased by 10 times compared to the SEPIC converter by adding one extra inductor and capacitor...... in SEPIC converter for a duty ratio of 90%. The detailed analysis of the voltage gain with the voltage drop across passive device and working of projected converter is deliberated in details in the paper. The projected converter is simulated in Matrix Laboratory software (2014). The simulation results...

The modulation of neural gain facilitates a transition between functional segregation and integration in the brain.

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Shine, James M; Aburn, Matthew J; Breakspear, Michael; Poldrack, Russell A

2018-01-29

Cognitive function relies on a dynamic, context-sensitive balance between functional integration and segregation in the brain. Previous work has proposed that this balance is mediated by global fluctuations in neural gain by projections from ascending neuromodulatory nuclei. To test this hypothesis in silico, we studied the effects of neural gain on network dynamics in a model of large-scale neuronal dynamics. We found that increases in neural gain directed the network through an abrupt dynamical transition, leading to an integrated network topology that was maximal in frontoparietal 'rich club' regions. This gain-mediated transition was also associated with increased topological complexity, as well as increased variability in time-resolved topological structure, further highlighting the potential computational benefits of the gain-mediated network transition. These results support the hypothesis that neural gain modulation has the computational capacity to mediate the balance between integration and segregation in the brain. © 2018, Shine et al.

Weight gain in children on oxcarbazepine monotherapy.

Science.gov (United States)

Garoufi, Anastasia; Vartzelis, George; Tsentidis, Charalambos; Attilakos, Achilleas; Koemtzidou, Evangelia; Kossiva, Lydia; Katsarou, Eustathia; Soldatou, Alexandra

2016-05-01

Studies of the effect of oxcarbazepine (OXC) on body growth of children with epilepsy are rare and their results are controversial. To the contrary, many studies have shown significant weight gain following valproate (VPA) treatment. To prospectively evaluate the effect of OXC monotherapy on growth patterns of children with epilepsy and compare it with the effect of VPA monotherapy. Fifty-nine otherwise healthy children, aged 3.7-15.9 years, with primary generalized, partial or partial with secondary generalization seizure disorder, were included in the study. Twenty six children were placed on OXC and thirty three on VPA monotherapy. Body weight (BW), height and body mass index (BMI) as well as their standard deviation scores (SDS), were evaluated prior to as well as 8 months post initiation of OXC or VPA therapy. Eight months post OXC-treatment, BW, SDS-BW, BMI and SDS-BMI increased significantly. The increase was similar to that observed in the VPA group. An additional 15.4% of children in the OXC group and 21.2% in the VPA group became overweight or obese. The effect of both OXC and VPA therapy on linear growth did not reach statistical significance. Similarly to VPA, OXC monotherapy resulted in a significant weight gain in children with epilepsy. Careful monitoring for excess weight gain along with counseling on adapting a healthy lifestyle should be offered to children on OXC therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Enhancing genetic gain in the era of molecular breeding.

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Xu, Yunbi; Li, Ping; Zou, Cheng; Lu, Yanli; Xie, Chuanxiao; Zhang, Xuecai; Prasanna, Boddupalli M; Olsen, Michael S

2017-05-17

As one of the important concepts in conventional quantitative genetics and breeding, genetic gain can be defined as the amount of increase in performance that is achieved annually through artificial selection. To develop pro ducts that meet the increasing demand of mankind, especially for food and feed, in addition to various industrial uses, breeders are challenged to enhance the potential of genetic gain continuously, at ever higher rates, while they close the gaps that remain between the yield potential in breeders' demonstration trials and the actual yield in farmers' fields. Factors affecting genetic gain include genetic variation available in breeding materials, heritability for traits of interest, selection intensity, and the time required to complete a breeding cycle. Genetic gain can be improved through enhancing the potential and closing the gaps, which has been evolving and complemented with modern breeding techniques and platforms, mainly driven by molecular and genomic tools, combined with improved agronomic practice. Several key strategies are reviewed in this article. Favorable genetic variation can be unlocked and created through molecular and genomic approaches including mutation, gene mapping and discovery, and transgene and genome editing. Estimation of heritability can be improved by refining field experiments through well-controlled and precisely assayed environmental factors or envirotyping, particularly for understanding and controlling spatial heterogeneity at the field level. Selection intensity can be significantly heightened through improvements in the scale and precision of genotyping and phenotyping. The breeding cycle time can be shortened by accelerating breeding procedures through integrated breeding approaches such as marker-assisted selection and doubled haploid development. All the strategies can be integrated with other widely used conventional approaches in breeding programs to enhance genetic gain. More transdisciplinary

Leading Gainful Employment Metric Reporting

Science.gov (United States)

Powers, Kristina; MacPherson, Derek

2016-01-01

This chapter will address the importance of intercampus involvement in reporting of gainful employment student-level data that will be used in the calculation of gainful employment metrics by the U.S. Department of Education. The authors will discuss why building relationships within the institution is critical for effective gainful employment…

Can Beta Blockers Cause Weight Gain?

Science.gov (United States)

... cause weight gain? Can beta blockers cause weight gain? Answers from Sheldon G. Sheps, M.D. Yes. Weight gain can occur as a side effect of some ... and metoprolol (Lopressor, Toprol-XL). The average weight gain is about 2.6 pounds (about 1.2 ...

Changes in working conditions and major weight gain among normal- and overweight midlife employees.

Science.gov (United States)

Niskanen, Riikka; Holstila, Ansku; Rahkonen, Ossi; Lallukka, Tea

2017-11-01

Objectives We aimed to examine the association between changes in psychosocial working conditions and major weight gain among midlife women and men. Furthermore, we examined the associations separately among normal- and overweight participants. Methods We used survey data among employees of the City of Helsinki, Finland, from 2000-2002 (phase 1, N=8960), 2007 (phase 2, N=7332), and 2012 (phase 3, N=6814), with a final study sample of 4369 participants. We examined changes in job strain, job demands, and job control from phase 1 to 2. We defined major weight gain as ≥10% weight gain between phases 1 and 3 based on self-reported weight (kg). We performed logistic regression analysis adjusting for baseline age, marital status, and occupational class, stratifying by gender and by baseline body mass index. Results Job demands among both genders and job strain among women was associated with major weight gain. Furthermore, increased job demands [odds ratio (OR) 1.52, 95% CI 1.05-2.20] or increased job strain (OR 1.53, 95% CI 1.11-2.11) was associated with major weight gain among overweight women. Normal-weight men reporting decreased job demands (OR 4.11, 95% CI 1.48-11.40) and overweight men reporting increasing job demands (OR 2.93, 95% CI 1.26-6.82) exhibited higher odds of major weight gain. Conclusions Associations between working conditions and weight gain appeared primarily weak. Our study suggests that overweight individuals might be at a higher risk of weight gain when facing psychosocial strain in the workplace.

Therapeutic neuroprotective agents for amyotrophic lateral sclerosis

Science.gov (United States)

Pandya, Rachna S.; Zhu, Haining; Li, Wei; Bowser, Robert; Friedlander, Robert M.

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal chronic neurodegenerative disease whose hallmark is proteinaceous, ubiquitinated, cytoplasmic inclusions in motor neurons and surrounding cells. Multiple mechanisms proposed as responsible for ALS pathogenesis include dysfunction of protein degradation, glutamate excitotoxicity, mitochondrial dysfunction, apoptosis, oxidative stress, and inflammation. It is therefore essential to gain a better understanding of the underlying disease etiology and search for neuroprotective agents that might delay disease onset, slow progression, prolong survival, and ultimately reduce the burden of disease. Because riluzole, the only Food and Drug Administration (FDA)-approved treatment, prolongs the ALS patient’s life by only 3 months, new therapeutic agents are urgently needed. In this review, we focus on studies of various small pharmacological compounds targeting the proposed pathogenic mechanisms of ALS and discuss their impact on disease progression. PMID:23864030

Association between gestational weight gain and perinatal outcomes in women with chronic hypertension.

Science.gov (United States)

Yee, Lynn M; Caughey, Aaron B; Cheng, Yvonne W

2017-09-01

Gestational weight gain above or below the 2009 National Academy of Medicine guidelines has been associated with adverse maternal and neonatal outcomes. Although it has been well established that excess gestational weight gain is associated with the development of gestational hypertension and preeclampsia, the relationship between gestational weight gain and adverse perinatal outcomes among women with pregestational (chronic) hypertension is less clear. The objective of this study was to examine the relationship between gestational weight gain above and below National Academy of Medicine guidelines and perinatal outcomes in a large, population-based cohort of women with chronic hypertension. This is a population-based retrospective cohort study of women with chronic hypertension who had term, singleton, vertex births in the United States from 2012 through 2014. Prepregnancy body mass index was calculated using self-reported prepregnancy weight and height. Women were categorized into 4 groups based on gestational weight gain and prepregnancy body mass index: (1) weight gain less than, (2) weight gain within, (3) weight gain 1-19 lb in excess of, and (4) weight gain ≥20 lb in excess of the National Academy of Medicine guidelines. The χ 2 tests and multivariable logistic regression analysis were used for statistical comparisons. Stratified analyses by body mass index category were additionally performed. In this large birth cohort, 101,259 women met criteria for inclusion. Compared to hypertensive women who had gestational weight gain within guidelines, hypertensive women with weight gain ≥20 lb over National Academy of Medicine guidelines were more likely to have eclampsia (adjusted odds ratio, 1.93; 95% confidence interval, 1.54-2.42) and cesarean delivery (adjusted odds ratio, 1.60; 95% confidence interval, 1.50-1.70). Excess weight gain ≥20 lb over National Academy of Medicine guidelines was also associated with increased odds of 5-minute Apgar gain 1-19 lb

EPO Receptor Gain-of-Function Causes Hereditary Polycythemia, Alters CD34+ Cell Differentiation and Increases Circulating Endothelial Precursors

Science.gov (United States)

Perrotta, Silverio; Cucciolla, Valeria; Ferraro, Marcella; Ronzoni, Luisa; Tramontano, Annunziata; Rossi, Francesca; Scudieri, Anna Chiara; Borriello, Adriana; Roberti, Domenico; Nobili, Bruno; Cappellini, Maria Domenica; Oliva, Adriana; Amendola, Giovanni; Migliaccio, Anna Rita; Mancuso, Patrizia; Martin-Padura, Ines; Bertolini, Francesco; Yoon, Donghoon; Prchal, Josef T.; Della Ragione, Fulvio

2010-01-01

Background Gain-of-function of erythropoietin receptor (EPOR) mutations represent the major cause of primary hereditary polycythemia. EPOR is also found in non-erythroid tissues, although its physiological role is still undefined. Methodology/Principal Findings We describe a family with polycythemia due to a heterozygous mutation of the EPOR gene that causes a G→T change at nucleotide 1251 of exon 8. The novel EPOR G1251T mutation results in the replacement of a glutamate residue by a stop codon at amino acid 393. Differently from polycythemia vera, EPOR G1251T CD34+ cells proliferate and differentiate towards the erythroid phenotype in the presence of minimal amounts of EPO. Moreover, the affected individuals show a 20-fold increase of circulating endothelial precursors. The analysis of erythroid precursor membranes demonstrates a heretofore undescribed accumulation of the truncated EPOR, probably due to the absence of residues involved in the EPO-dependent receptor internalization and degradation. Mutated receptor expression in EPOR-negative cells results in EPOR and Stat5 phosphorylation. Moreover, patient erythroid precursors present an increased activation of EPOR and its effectors, including Stat5 and Erk1/2 pathway. Conclusions/Significance Our data provide an unanticipated mechanism for autosomal dominant inherited polycythemia due to a heterozygous EPOR mutation and suggest a regulatory role of EPO/EPOR pathway in human circulating endothelial precursors homeostasis. PMID:20700488

Leaving home for college and gaining independence

NARCIS (Netherlands)

Mulder, C.H.; Clark, W.A.V.

2002-01-01

As more and more young US adults attend college it has become an increasingly important filter in the process of becoming an independent household. Now for a large number of young adults living in the USA, living away at college is a first step in the process of gaining residential and economic

Estimating the potential gains from mergers

DEFF Research Database (Denmark)

Bogetoft, Peter; Wang, Dexiang

2005-01-01

We introduce simple production economic models to estimate the potential gains from mergers. We decompose the gains into technical ef¿ciency, size (scale) and harmony (mix) gains, and we discuss alternative ways to capture these gains. We propose to approximate the production processes using...... the non-parametric. Data Envelopment Analysis (DEA) approach, and we use the resulting operational approach to estimate the potential gains from merging agricultural extension of¿ces in Denmark....

Variations in resting energy expenditure: impact on gestational weight gain.

Science.gov (United States)

Berggren, E K; O'Tierney-Ginn, P; Lewis, S; Presley, L; De-Mouzon, S Hauguel; Catalano, P M

2017-10-01

There are significant variations in gestational weight gain, with many women gaining in excess of the Institute of Medicine guidelines. Unfortunately, efforts to improve appropriate gestational weight gain have had only limited success. To date, interventions have focused primarily on decreasing energy intake and/or increasing physical activity. Maternal resting energy expenditure, which comprises ∼60% of total energy expenditure compared with the ∼20% that comes from physical activity, may be an important consideration in understanding variations in gestational weight gain. Our objective was to quantify the changes in resting energy expenditure during pregnancy and their relationship to gestational weight gain and body composition changes among healthy women. We hypothesized that greater gestational weight gain, and fat mass accrual in particular, are inversely related to variations in resting energy expenditure. We conducted a secondary analysis of a prospective cohort studied before conception and late pregnancy (34-36 weeks). Body composition (estimated using hydrodensitometry) and resting energy expenditure (estimated using indirect calorimetry) were measured. The relationship between the changes in resting energy expenditure and gestational weight gain and the change in fat mass and fat-free mass were quantified. Resting energy expenditure was expressed as kilocalories per kilogram of fat-free mass per day (kilocalories per kilogram of fat-free mass -1 /day -1 ) and kilocalories per day. Correlations are reported as r. Among 51 women, preconception body mass index was 23.0 (4.7) kg/m 2 ; gestational weight gain was 12.8 (4.7) kg. Preconception and late pregnancy resting energy expenditure (kilocalories per day) correlated positively with the change in fat-free mass (r = 0.37, P = .008; r = 0.51, P = .001). Late-pregnancy resting energy expenditure (kilocalories per kilogram of fat-free mass -1 /day -1 ) was inversely associated with the change in fat

Pregnancy Weight Gain by Gestational Age in Women with Uncomplicated Dichorionic Twin Pregnancies.

Science.gov (United States)

Hutcheon, Jennifer A; Platt, Robert W; Abrams, Barbara; Braxter, Betty J; Eckhardt, Cara L; Himes, Katherine P; Bodnar, Lisa M

2018-03-01

Twin pregnancies are at increased risk for adverse outcomes and are associated with greater gestational weight gain compared to singleton pregnancies. Studies that disentangle the relationship between gestational duration, weight gain and adverse outcomes are needed to inform weight gain guidelines. We created charts of the mean, standard deviation and select percentiles of maternal weight gain-for-gestational age in twin pregnancies and compared them to singleton curves. We abstracted serial prenatal weight measurements of women delivering uncomplicated twin pregnancies at Magee-Womens Hospital (Pittsburgh, PA, 1998-2013) and merged them with the hospital's perinatal database. Hierarchical linear regression was used to express pregnancy weight gain as a smoothed function of gestational age according to pre-pregnancy BMI category. Charts of week- and day-specific values for the mean, standard deviation, and percentiles of maternal weight gain were created. Prenatal weight measurements (median: 11 [interquartile range: 9, 13] per woman) were available for 1109 women (573 normal weight, 287 overweight, and 249 obese). The slope of weight gain was most pronounced in normal weight women and flattened with increasing pre-pregnancy BMI (e.g. 50th percentiles of 6.8, 5.7, and 3.6 kg at 20 weeks and 19.8, 18.1, and 14.4 at 37 weeks in normal weight, overweight, and obese women, respectively). Weight gain patterns in twins diverged from singletons after 17-19 weeks. Our charts provide a tool for the classification of maternal weight gain in twin pregnancies. Future work is needed to identify the range of weight gain associated with optimal pregnancy health outcomes. © 2018 John Wiley & Sons Ltd.

Gestational Weight Gain and Pregnancy Outcomes in 481 Obese Glucose-Tolerant Women

DEFF Research Database (Denmark)

Jensen, Dorte Møller; Ovesen, Per; Beck-Nielsen, Henning

2005-01-01

OBJECTIVE: To investigate the effect of gestational weight gain in obese glucose-tolerant women. RESEARCH DESIGN AND METHODS: We performed a historical cohort study of 481 women with prepregnancy BMI > or = 30 kg/m2 and a normal 2-h 75-g oral glucose tolerance test (OGTT) during the third trimester......-weight women (3,478 g). In multivariate analyses, increasing weight gain was associated with significantly higher rates of hypertension (OR 4.8 [95% CI for group 4 vs. group 1: 1.7-13.1]), cesarean section (3.5 [1.6-7.8]), induction of labor (3.7 [1.7-8.0]), and large-for-gestational-age infants (4.7 [2.......0-11.0]). There was no difference in rates of small-for-gestational-age infants. Significant predictors for birth weight (determined by multiple linear regression) were gestational weight gain, 2-h OGTT result, pre-gestational BMI, maternal age, gestational age, and smoking. CONCLUSIONS: Increasing weight gain in obese women...

Physiologically Based Pharmacokinetic Modeling of Therapeutic Proteins.

Science.gov (United States)

Wong, Harvey; Chow, Timothy W

2017-09-01

Biologics or therapeutic proteins are becoming increasingly important as treatments for disease. The most common class of biologics are monoclonal antibodies (mAbs). Recently, there has been an increase in the use of physiologically based pharmacokinetic (PBPK) modeling in the pharmaceutical industry in drug development. We review PBPK models for therapeutic proteins with an emphasis on mAbs. Due to their size and similarity to endogenous antibodies, there are distinct differences between PBPK models for small molecules and mAbs. The high-level organization of a typical mAb PBPK model consists of a whole-body PBPK model with organ compartments interconnected by both blood and lymph flows. The whole-body PBPK model is coupled with tissue-level submodels used to describe key mechanisms governing mAb disposition including tissue efflux via the lymphatic system, elimination by catabolism, protection from catabolism binding to the neonatal Fc (FcRn) receptor, and nonlinear binding to specific pharmacological targets of interest. The use of PBPK modeling in the development of therapeutic proteins is still in its infancy. Further application of PBPK modeling for therapeutic proteins will help to define its developing role in drug discovery and development. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

How common is substantial weight gain after pregnancy?

Science.gov (United States)

Sumithran, Priya; Houlihan, Christine; Shub, Alexis; Churilov, Leonid; Pritchard, Natasha; Price, Sarah; Ekinci, Elif; Proietto, Joseph; Permezel, Michael

2017-11-20

Although population-based studies indicate that on average, women gain 1-2kg between pregnancies, women with obesity often attribute its development to childbearing. There is little contemporary data available regarding how commonly this occurs, particularly in women of different body mass index (BMI) categories. The aim of this study was to examine inter-pregnancy weight changes among women at a tertiary obstetric hospital in Melbourne, Australia. This was a retrospective review of data from the Birthing Outcomes System electronic record of 19,617 women aged 20 years or older, who delivered at least two consecutive singleton infants at ≥37 weeks' gestation at Mercy Hospital for Women between December 1994 and December 2015. A logistic regression model was used to assess the relationship between gain of ≥4kg/m 2 between pregnancies and maternal BMI category in the first pregnancy, adjusting for covariates of maternal age, inter-pregnancy interval, and socioeconomic status. Gain of ≥4kg/m 2 between the first two pregnancies occurred in 7.5% of normal weight women, 10.5% of overweight women, and 13.4% of women with obesity. One in five women who were normal weight in their first pregnancy increased to overweight or obese BMI categories in their second pregnancy. Substantial weight gain in relation to pregnancy affects a considerable proportion of women. Since inter-pregnancy weight gain is associated with several complications in the next pregnancy and longer term, avoiding excessive weight gain during and between pregnancies may prevent adverse health consequences in mothers and offspring. Copyright © 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Scanning the horizon for high value-add manufacturing science: Accelerating manufacturing readiness for the next generation of disruptive, high-value curative cell therapeutics.

Science.gov (United States)

Hourd, Paul; Williams, David J

2018-05-01

Since the regenerative medicine sector entered the second phase of its development (RegenMed 2.0) more than a decade ago, there is increasing recognition that current technology innovation trajectories will drive the next translational phase toward the production of disruptive, high-value curative cell and gene-based regenerative medicines. To identify the manufacturing science problems that must be addressed to permit translation of these next generation therapeutics. In this short report, a long lens look within the pluripotent stem cell therapeutic space, both embryonic and induced, is used to gain early insights on where critical technology and manufacturing challenges may emerge. This report offers a future perspective on the development and innovation that will be needed within manufacturing science to add value in the production and commercialization of the next generation of advanced cell therapies and precision medicines. Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Therapeutic genes for anti-HIV/AIDS gene therapy.

Science.gov (United States)

Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca

2013-01-01

The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.

A derating method for therapeutic applications of high intensity focused ultrasound

Science.gov (United States)

Bessonova, O. V.; Khokhlova, V. A.; Canney, M. S.; Bailey, M. R.; Crum, L. A.

2010-05-01

Current methods of determining high intensity focused ultrasound (HIFU) fields in tissue rely on extrapolation of measurements in water assuming linear wave propagation both in water and in tissue. Neglecting nonlinear propagation effects in the derating process can result in significant errors. A new method based on scaling the source amplitude is introduced to estimate focal parameters of nonlinear HIFU fields in tissue. Focal values of acoustic field parameters in absorptive tissue are obtained from a numerical solution to a KZK-type equation and are compared to those simulated for propagation in water. Focal wave-forms, peak pressures, and intensities are calculated over a wide range of source outputs and linear focusing gains. Our modeling indicates, that for the high gain sources which are typically used in therapeutic medical applications, the focal field parameters derated with our method agree well with numerical simulation in tissue. The feasibility of the derating method is demonstrated experimentally in excised bovine liver tissue.

Pulse Combustor Driven Pressure Gain Combustion for High Efficiency Gas Turbine Engines

KAUST Repository

Lisanti, Joel

2017-02-01

The gas turbine engine is an essential component of the global energy infrastructure which accounts for a significant portion of the total fossil fuel consumption in transportation and electric power generation sectors. For this reason there is significant interest in further increasing the efficiency and reducing the pollutant emissions of these devices. Conventional approaches to this goal, which include increasing the compression ratio, turbine inlet temperature, and turbine/compressor efficiency, have brought modern gas turbine engines near the limits of what may be achieved with the conventionally applied Brayton cycle. If a significant future step increase in gas turbine efficiency is to be realized some deviation from this convention is necessary. The pressure gain gas turbine concept is a well established new combustion technology that promises to provide a dramatic increase in gas turbine efficiency by replacing the isobaric heat addition process found in conventional technology with an isochoric process. The thermodynamic benefit of even a small increase in stagnation pressure across a gas turbine combustor translates to a significant increase in cycle efficiency. To date there have been a variety of methods proposed for achieving stagnation pressure gains across a gas turbine combustor and these concepts have seen a broad spectrum of levels of success. The following chapter provides an introduction to one of the proposed pressure gain methods that may be most easily realized in a practical application. This approach, known as pulse combustor driven pressure gain combustion, utilizes an acoustically resonant pulse combustor to approximate isochoric heat release and thus produce a rise in stagnation pressure.

Effect of the Holiday Season on Weight Gain: A Narrative Review.

Science.gov (United States)

Díaz-Zavala, Rolando G; Castro-Cantú, María F; Valencia, Mauro E; Álvarez-Hernández, Gerardo; Haby, Michelle M; Esparza-Romero, Julián

2017-01-01

Several studies suggest that the holiday season, starting from the last week of November to the first or second week of January, could be critical to gaining weight. This study aims to review the literature to determine the effects of the holidays on body weight. In studies of adults, a significant weight gain was consistently observed during this period (0.4 to 0.9 kg, p 0.05) during this period. Among individuals with obesity who attempt to lose weight, an increase in weight was observed (0.3 to 0.9 kg, significant in some but not in all studies), as well as increase in weight in motivated self-monitoring people (0.4 to 0.6%, p holidays (phone calls and daily mailing) appeared to prevent weight gain, but information is limited. The holiday season seems to increase body weight in adults, even in participants seeking to lose weight and in motivated self-monitoring people, whereas in children, adolescents, and college students, very few studies were found to make accurate conclusions.

Gain dynamics of quantum dot devices for dual-state operation

Energy Technology Data Exchange (ETDEWEB)

Kaptan, Y., E-mail: yuecel.kaptan@physik.tu-berlin.de; Herzog, B.; Kolarczik, M.; Owschimikow, N.; Woggon, U. [Institut für Optik und Atomare Physik, Technische Universität Berlin, Berlin (Germany); Schmeckebier, H.; Arsenijević, D.; Bimberg, D. [Institut für Festkörperphysik, Technische Universität Berlin, Berlin (Germany); Mikhelashvili, V.; Eisenstein, G. [Technion Institute of Technology, Faculty of Electrical Engineering, Haifa (Israel)

2014-06-30

Ground state gain dynamics of In(Ga)As-quantum dot excited state lasers are investigated via single-color ultrafast pump-probe spectroscopy below and above lasing threshold. Two-color pump-probe experiments are used to localize lasing and non-lasing quantum dots within the inhomogeneously broadened ground state. Single-color results yield similar gain recovery rates of the ground state for lasing and non-lasing quantum dots decreasing from 6 ps to 2 ps with increasing injection current. We find that ground state gain dynamics are influenced solely by the injection current and unaffected by laser operation of the excited state. This independence is promising for dual-state operation schemes in quantum dot based optoelectronic devices.

A gain-coefficient switched Alexandrite laser

International Nuclear Information System (INIS)

Lee, Chris J; Van der Slot, Peter J M; Boller, Klaus-J

2013-01-01

We report on a gain-coefficient switched Alexandrite laser. An electro-optic modulator is used to switch between high and low gain states by making use of the polarization dependent gain of Alexandrite. In gain-coefficient switched mode, the laser produces 85 ns pulses with a pulse energy of 240 mJ at a repetition rate of 5 Hz.

Prior exercise training blunts short-term high-fat diet-induced weight gain.

Science.gov (United States)

Snook, Laelie A; MacPherson, Rebecca E K; Monaco, Cynthia M F; Frendo-Cumbo, Scott; Castellani, Laura; Peppler, Willem T; Anderson, Zachary G; Buzelle, Samyra L; LeBlanc, Paul J; Holloway, Graham P; Wright, David C

2016-08-01

High-fat diets rapidly cause weight gain and glucose intolerance. We sought to determine whether these changes could be mitigated with prior exercise training. Male C57BL/6J mice were exercise-trained by treadmill running (1 h/day, 5 days/wk) for 4 wk. Twenty-four hours after the final bout of exercise, mice were provided with a high-fat diet (HFD; 60% kcal from lard) for 4 days, with no further exercise. In mice fed the HFD prior to exercise training, the results were blunted weight gain, reduced fat mass, and a slight attenuation in glucose intolerance that was mirrored by greater insulin-induced Akt phosphorylation in skeletal muscle compared with sedentary mice fed the HFD. When ad libitum-fed sedentary mice were compared with sedentary high-fat fed mice that were calorie restricted (-30%) to match the weight gain of the previously trained high-fat fed mice, the same attenuated impairments in glucose tolerance were found. Blunted weight gain was associated with a greater capacity to increase energy expenditure in trained compared with sedentary mice when challenged with a HFD. Although mitochondrial enzymes in white adipose tissue and UCP-1 protein content in brown adipose tissue were increased in previously exercised compared with sedentary mice fed a HFD, ex vivo mitochondrial respiration was not increased in either tissue. Our data suggest that prior exercise training attenuates high-fat diet-induced weight gain and glucose intolerance and is associated with a greater ability to increase energy expenditure in response to a high-fat diet. Copyright © 2016 the American Physiological Society.

Extended parametric gain range in photonic crystal fibers with strongly frequency-dependent field distributions.

Science.gov (United States)

Petersen, Sidsel R; Alkeskjold, Thomas T; Olausson, Christina B; Lægsgaard, Jesper

2014-08-15

The parametric gain range of a degenerate four-wave mixing process is determined in the undepleted pump regime. The gain range is considered with and without taking the mode field distributions of the four-wave mixing components into account. It is found that the mode field distributions have to be included to evaluate the parametric gain correctly in dispersion-tailored speciality fibers and that mode profile engineering can provide a way to increase the parametric gain range.

Size at birth, weight gain in infancy and childhood, and adult blood pressure in 5 low- and middle-income-country cohorts: when does weight gain matter?

Science.gov (United States)

Adair, Linda S; Martorell, Reynaldo; Stein, Aryeh D; Hallal, Pedro C; Sachdev, Harshpal S; Prabhakaran, Dorairaj; Wills, Andrew K; Norris, Shane A; Dahly, Darren L; Lee, Nanette R; Victora, Cesar G

2009-05-01

Promoting catch-up growth in malnourished children has health benefits, but recent evidence suggests that accelerated child weight gain increases adult chronic disease risk. We aimed to determine how birth weight (BW) and weight gain to midchildhood relate to blood pressure (BP) in young adults. We pooled data from birth cohorts in Brazil, Guatemala, India, the Philippines, and South Africa. We used conditional weight (CW), a residual of current weight regressed on prior weights, to represent deviations from expected weight gain from 0 to 12, 12 to 24, 24 to 48 mo, and 48 mo to adulthood. Adult BP and risk of prehypertension or hypertension (P/HTN) were modeled before and after adjustment for adult body mass index (BMI) and height. Interactions of CWs with small size-for-gestational age (SGA) at birth were tested. Higher CWs were associated with increased BP and odds of P/HTN, with coefficients proportional to the contribution of each CW to adult BMI. Adjusted for adult height and BMI, no child CW was associated with adult BP, but 1 SD of BW was related to a 0.5-mm Hg lower systolic BP and a 9% lower odds of P/HTN. BW and CW associations with systolic BP and P/HTN were not different between adults born SGA and those with normal BW, but higher CW at 48 mo was associated with higher diastolic BP in those born SGA. Greater weight gain at any age relates to elevated adult BP, but faster weight gains in infancy and young childhood do not pose a higher risk than do gains at other ages.

Association of adult weight gain and nonalcoholic fatty liver in a cross-sectional study in Wan Song Community, China

Directory of Open Access Journals (Sweden)

W.-J. Zhang

2014-02-01

Full Text Available Our objective was to examine associations of adult weight gain and nonalcoholic fatty liver disease (NAFLD. Cross-sectional interview data from 844 residents in Wan Song Community from October 2009 to April 2010 were analyzed in multivariate logistic regression models to examine odds ratios (OR and 95% confidence intervals (CI between NAFLD and weight change from age 20. Questionnaires, physical examinations, laboratory examinations, and ultrasonographic examination of the liver were carried out. Maximum rate of weight gain, body mass index, waist circumference, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, fasting blood glucose, cholesterol, triglycerides, uric acid, and alanine transaminase were higher in the NAFLD group than in the control group. HDL-C in the NAFLD group was lower than in the control group. As weight gain increased (measured as the difference between current weight and weight at age 20 years, the OR of NAFLD increased in multivariate models. NAFLD OR rose with increasing weight gain as follows: OR (95%CI for NAFLD associated with weight gain of 20+ kg compared to stable weight (change <5 kg was 4.23 (2.49-7.09. Significantly increased NAFLD OR were observed even for weight gains of 5-9.9 kg. For the “age 20 to highest lifetime weight” metric, the OR of NAFLD also increased as weight gain increased. For the “age 20 to highest lifetime weight” metric and the “age 20 to current weight” metric, insulin resistance index (HOMA-IR increased as weight gain increased (P<0.001. In a stepwise multivariate regression analysis, significant association was observed between adult weight gain and NAFLD (OR=1.027, 95%CI=1.002-1.055, P=0.025. We conclude that adult weight gain is strongly associated with NAFLD.

Study of gain-coupled distributed feedback laser based on high order surface gain-coupled gratings

Science.gov (United States)

Gao, Feng; Qin, Li; Chen, Yongyi; Jia, Peng; Chen, Chao; Cheng, LiWen; Chen, Hong; Liang, Lei; Zeng, Yugang; Zhang, Xing; Wu, Hao; Ning, Yongqiang; Wang, Lijun

2018-03-01

Single-longitudinal-mode, gain-coupled distributed feedback (DFB) lasers based on high order surface gain-coupled gratings are achieved. Periodic surface metal p-contacts with insulated grooves realize gain-coupled mechanism. To enhance gain contrast in the quantum wells without the introduction of effective index-coupled effect, groove length and depth were well designed. Our devices provided a single longitudinal mode with the maximum CW output power up to 48.8 mW/facet at 971.31 nm at 250 mA without facet coating, 3dB linewidth (39 dB). Optical bistable characteristic was observed with a threshold current difference. Experimentally, devices with different cavity lengths were contrasted on power-current and spectrum characteristics. Due to easy fabrication technique and stable performance, it provides a method of fabricating practical gain-coupled distributed feedback lasers for commercial applications.

Therapeutic kitchens for residents with dementia.

Science.gov (United States)

Marsden, J P; Meehan, R A; Calkins, M P

2001-01-01

Long-term care facilities are increasingly incorporating some sort of kitchen, often referred to as a therapeutic kitchen, for resident, staff, and family use through remodeling efforts or new construction. A study, consisting of five site visits and a questionnaire mailed to 631 facilities providing dementia care, was conducted to identify physical features that are typically included in therapeutic kitchen design and to explore how these features support daily use in relation to activities programming and food service systems. Findings indicate that universal design features should be incorporated to a greater extent and certain features are more common, reinforce homelike imagery, or enhance safety. Results also suggest that a higher number of residents participate in more recreational activities, such as baking, than they do in household chores, such as meal set-up, and therapeutic kitchens are not always linked to food service systems.

On the performance of the noise power spectrum from the gain-corrected radiography images.

Science.gov (United States)

Kim, Dong Sik; Lee, Eunae

2018-01-01

Fixed pattern noise due to nonuniform amplifier gains and scintillator sensitivity should be alleviated in radiography imaging to acquire low-noise x-ray images from detectors. Here, the noise property of the detector is usually evaluated observing the noise power spectrum (NPS). A gain-correction scheme, in which uniformly illuminated images are averaged to design a gain map, can be applied to alleviate the fixed pattern noise problem. The normalized NPS (NNPS) of the gain-corrected image decreases as the number of images for the average increases and converges to an infimum, which can be achieved if the fixed pattern noise is completely removed. If we know the NNPS infimum of the detector, then we can determine the performance of the gain-corrected images compared with the achievable lower bound. We first construct an image-formation model considering the nonuniform gain and then consider two measurement methods based on subtraction and division to estimate the NNPS infimum of the detector. In order to obtain a high-precision NNPS infimum estimate, we consider a time-averaging method. For several flat-panel radiography detectors, we constructed the NNPS infimum measurements and compared them with NNPS values of the gain-corrected images. We observed that the NNPS values of the gain-corrected images approached the NNPS infimum as the number of images for the average increased.

Medical Gains of Chondroitin Sulfate Upon Fucosylation.

Science.gov (United States)

Pomin, Vitor H

2015-01-01

Chondroitin sulfate (CS) is a glycosaminoglycan (GAG) composed of alternating N-acetyl galactosamine and glucuronic acid units within disaccharide building blocks. CS is a key functional component in proteoglycans of cartilaginous tissues. Owing to its numerous biological roles, CS is widely explored in the pharmaceutical market as nutraceutical ingredient commonly utilized against arthritis, osteoarthrosis, and sometimes osteoporosis. Tissues like shark cartilage and bovine trachea are common sources of CS. Nonetheless, a new CS type has been introduced and investigated in the last few decades in what regards its medical potentials. It is named fucosylated chondroitin sulfate (FucCS). This less common CS type is isolated exclusively from the body wall of sea cucumbers. The presence of fucosyl branching units in the holothurian FucCS gives to this unique GAG, therapeutic properties in various pathophysiological systems which are inexistent in the common CS explored in the market. Examples of these systems are coagulation, thrombosis, hemodialysis, atherosclerosis, cellular growth, angiogenesis, fibrosis, tumor growth, inflammation, viral and protozoan infections, hyperglycemia, diabetes-related pathological events and tissue damage. This report aims at describing the medical benefits gained upon fucosylation of CS. Clinical prospects of these medical benefits are also discussed herein.

Targeting Potassium Channels for Increasing Delivery of Imaging Agents and Therapeutics to Brain Tumors

OpenAIRE

Nagendra Sanyasihally Ningaraj; Divya eKhaitan

2013-01-01

Every year in the US, 20,000 new primary and nearly 200,000 metastatic brain tumor cases are reported. The cerebral microvessels/ capillaries that form the blood–brain barrier (BBB) not only protect the brain from toxic agents in the blood but also pose a significant hindrance to the delivery of small and large therapeutic molecules. Different strategies have been employed to circumvent the physiological barrier posed by blood-brain tumor barrier (BTB). Studies in our laboratory have identifi...

Obesity and the Odds of Weight Gain following Androgen Deprivation Therapy for Prostate Cancer

Directory of Open Access Journals (Sweden)

Lior Z. Braunstein

2014-01-01

Full Text Available Background. Increasing body mass index (BMI is associated with increased risk of mortality; however, quantifying weight gain in men undergoing androgen deprivation therapy (ADT for prostate cancer (PC remains unexplored. Methods. Between 1995 and 2001, 206 men were enrolled in a randomized trial evaluating the survival difference of adding 6 months of ADT to radiation therapy (RT. BMI measurements were available in 171 men comprising the study cohort. The primary endpoint was weight gain of ≥10 lbs by 6-month followup. Logistic regression analysis was performed to assess whether baseline BMI or treatment received was associated with this endpoint adjusting for known prognostic factors. Results. By the 6-month followup, 12 men gained ≥10 lbs, of which 10 (83% received RT + ADT and, of these, 7 (70% were obese at randomization. Men treated with RT as compared to RT + ADT were less likely to gain ≥10 lbs (adjusted odds ratio (AOR: 0.18 [95% CI: 0.04–0.89]; P=0.04, whereas this risk increased with increasing BMI (AOR: 1.15 [95% CI: 1.01–1.31]; P=0.04. Conclusions. Consideration should be given to avoid ADT in obese men with low- or favorable-intermediate risk PC where improved cancer control has not been observed, but shortened life expectancy from weight gain is expected.

Herbivores rescue diversity in warming tundra by modulating trait-dependent species losses and gains.

Science.gov (United States)

Kaarlejärvi, Elina; Eskelinen, Anu; Olofsson, Johan

2017-09-04

Climate warming is altering the diversity of plant communities but it remains unknown which species will be lost or gained under warming, especially considering interactions with other factors such as herbivory and nutrient availability. Here, we experimentally test effects of warming, mammalian herbivory and fertilization on tundra species richness and investigate how plant functional traits affect losses and gains. We show that herbivory reverses the impact of warming on diversity: in the presence of herbivores warming increases species richness through higher species gains and lower losses, while in the absence of herbivores warming causes higher species losses and thus decreases species richness. Herbivores promote gains of short-statured species under warming, while herbivore removal and fertilization increase losses of short-statured and resource-conservative species through light limitation. Our results demonstrate that both rarity and traits forecast species losses and gains, and mammalian herbivores are essential for preventing trait-dependent extinctions and mitigate diversity loss under warming and eutrophication.Warming can reduce plant diversity but it is unclear which species will be lost or gained under interacting global changes. Kaarlejärvi et al. manipulate temperature, herbivory and nutrients in a tundra system and find that herbivory maintains diversity under warming by reducing species losses and promoting gains.

Development of Class IIa Bacteriocins as Therapeutic Agents

OpenAIRE

Christopher T. Lohans; John C. Vederas

2012-01-01

Class IIa bacteriocins have been primarily explored as natural food preservatives, but there is much interest in exploring the application of these peptides as therapeutic antimicrobial agents. Bacteriocins of this class possess antimicrobial activity against several important human pathogens. Therefore, the therapeutic development of these bacteriocins will be reviewed. Biological and chemical modifications to both stabilize and increase the potency of bacteriocins are discussed, as well as ...

Willingness to Interact After Therapeutic Recreation in a Patient With Schizophrenia.

Science.gov (United States)

Ayumi, Kohno; Mitsunobu, Matsuda

2018-02-01

The study aim was to describe how a patient with schizophrenia who had been in a psychiatric hospital for an extended period of time changed in his desire to interact with others after participating in the therapeutic recreation program, and to interpret his inner process based on symbolic interactionism theory. Data from a patient who showed marked changes in narratives of an interview held after the program and through observation during sessions were analyzed. The patient gained a sense of willingness, including the desire to interact with others and began to act accordingly. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of Herbal Immunodulator on Body weight gain in immunosuppressed broiler birds

Directory of Open Access Journals (Sweden)

S.G. Mode

Full Text Available The herbal immunomodulator was evaluated in immunosupressed broiler birds in terms of body weight gain. The treatment with Ocimum sanctum and Emblica officinalis @ 3 gm /kg feed for 2 weeks were found to be effective immunomodulator in increasing body weight gain in broiler birds. [Vet World 2009; 2(7.000: 269-270

The diagnosis and therapeutic gain using US, CT and MRI. Submucosal tumors in stomach and duodenum

Energy Technology Data Exchange (ETDEWEB)

Miyamoto, Shinichi; Nawano, Shigeru; Tajiri, Hisao; Boku, Narikazu; Muto, Manabu; Ohtsu, Atsushi; Yoshida, Shigeaki [National Cancer Center, Kashiwa, Chiba (Japan). Hospital East; Moriyama, Noriyuki

1999-02-01

The usefulness of the ultrasonography (US), the computed tomography (CT) and the magnetic resonance imaging (MRI) was examined. The subjects were 19 patients with submucosal leiomyoma and leiomyosarcoma in the stomach and duodenum which had surgery and were histologically diagnosed in the National Cancer Center Hospital. The detectability of the primary foci was 50% (8/16) in US, and 93% (13/14) in EUS (the endoscopic ultrasonography) which makes the structure of the stomach wall and the continuity of tumors clear. CT could detect the primary foci in 94% (16/17) and was excellent to know not only the presence of the remote metastases but also the exact size and expanse of the tumors. In all cases of leiomyoma, tumors were leiomyosarcoma when the internal structure was diagnosed to be heterogeneous by both EUS and CT, or either of them. The qualitative image diagnosis is not always easy in gastrointestinal submucosal tumors, but it is important to generally diagnose by the combination with several examinations in order to select the suitable therapeutic method. (K.H.)

Dye gain gold NW array of surface plasmon polariton waveguide

Directory of Open Access Journals (Sweden)

Jun Zhu

Full Text Available Plasmon lasers can support ultrasmall mode confinement and ultrafast dynamics with device feature sizes below the diffraction limit. At present in the single visible light frequency, the optical gain method of constraint SPP on metal nanowires structure reported less. We design the gold nanowire array structure, consisting of PMMA and R6G dye molecules as gain, by 488 nm pump in the middle of the nanowires position for wide range of light, use symmetry broken overcome that momentum does not match the photonic and SPP energy conversion. Theoretical analysis shows that dyes provide coherent optical feedback, resulting in nanowires face will observe laser properties of surface plasmons. Feature analysis: the incident light and pump joint strength is greater than the sum of strength which is the incident light, pump respectively. Under the effect of dye molecules gain effective, length of SPP transmission can increase 1 µm. The results achieved in a single optical frequency of stimulated radiation, application of dye optical gain can achieve continuous gain effect. This is for the future development of plasma amplifier and the wavelength laser. Keywords: SPP, Stimulated radiation, Gold nanowires array, Dye molecules

Combined Treatment with Gonadotropin-releasing Hormone Analog and Anabolic Steroid Hormone Increased Pubertal Height Gain and Adult Height in Boys with Early Puberty for Height.

Science.gov (United States)

Tanaka, Toshiaki; Naiki, Yasuhiro; Horikawa, Reiko

2012-04-01

Twenty-one boys with a height of 135 cm or less at onset of puberty were treated with a combination of GnRH analog and anabolic steroid hormone, and their pubertal height gain and adult height were compared with those of untreated 29 boys who enter puberty below 135 cm. The mean age at the start of treatment with a GnRH analog, leuprorelin acetate depot (Leuplin(®)) was 12.3 yr, a mean of 1.3 yr after the onset of puberty, and GnRH analog was administered every 3 to 5 wk thereafter for a mean duration of 4.1 yr. The anabolic steroid hormone was started approximately 1 yr after initiation of treatment with the GnRH analog. The mean pubertal height gain from onset of puberty till adult height was significantly greater in the combination treatment group (33.9 cm) than in the untreated group (26.4 cm) (ppenis and pubic hair is promoted by the anabolic steroid hormone, no psychosocial problems arose because of delayed puberty. No clinically significant adverse events appeared. Combined treatment with GnRH analog and anabolic steroid hormone significantly increased height gain during puberty and adult height in boys who entered puberty with a short stature, since the period until epiphyseal closure was extended due to deceleration of the bone age maturation by administration of the GnRH analog and the growth rate at this time was maintained by the anabolic steroid hormone.

Association between smoking cessation and weight gain in treatment-seeking African Americans.

Science.gov (United States)

Tan, Marcia M; Okuyemi, Kolawole S; Resnicow, Ken; Dietz, Noella A; Antoni, Michael H; Webb Hooper, Monica

2018-06-01

Research has shown that African Americans gain more than average weight after smoking cessation. However, African Americans have been underrepresented in post-cessation weight gain research. The current study examined 1) the pattern of weight gain and 2) the association between smoking status and weight gain in a sample of African Americans seeking smoking cessation treatment. Data were drawn from a randomized controlled trial testing the efficacy of a 4-week culturally specific smoking cessation cognitive behavioral therapy (CBT) intervention among African American smokers (N = 342). Weight was measured and self-reported smoking status was biochemically verified at baseline, end of counseling, 3-, 6-, and 12-month follow-ups. Random effects multilevel modeling was used to examine weight gain over twelve months post CBT, and a fully unconditional model tested the pattern of weight gain over time. Smoking status was included as a time-varying factor to examine its effect on weight gain, controlling for potential confounding variables. Weight significantly increased among those who remained abstinent over 12 months post CBT [average gain of seven lbs. (three kg)]. Controlling for covariates, abstinence was predictive of the rate of weight gain for those with high weight concern. Weight gain among African American abstainers was comparable to the average post-cessation weight gain observed among the general population. It is possible that exposure to CBT (culturally specific or standard) may have mitigated excessive weight gain. Future research should assess predictors of weight gain in African American smokers to inform future smoking cessation interventions and help elucidate factors that contribute to tobacco- and obesity-related health disparities. Copyright © 2018 Elsevier Ltd. All rights reserved.

The association between gestational weight gain and risk of stillbirth: a population-based cohort study.

Science.gov (United States)

Yao, Ruofan; Park, Bo Y; Foster, Sarah E; Caughey, Aaron B

2017-10-01

To estimate the risk of stillbirth associated with excessive and inadequate weight gain during pregnancy. Retrospective cohort study using the Texas vital records database between 2006 and 2011, with 2,230,310 births (5502 stillbirths) was included for analysis. Pregnancies were categorized as adequate weight gain, excessive weight gain, inadequate weight gain, or weight loss based on the Institute of Medicine 2009 recommendations. Hazard ratios (HRs) for stillbirth were estimated for each gestational weight-gain stratum using adequate weight gain as the comparison group. The analysis was performed separately for each body mass index (BMI) class. Both inadequate weight gain and weight loss were associated with an increased risk of stillbirth for all BMI classes except the morbidly obese group. Highest risk was seen in weight-loss groups after 36 completed weeks (normal weight: HR = 18.85 [8.25-43.09]; overweight: HR = 5.87 [2.99-11.55]; obese: HR = 3.44 [2.34-5.05]). Weight loss was associated with reduced stillbirth risk in morbidly obese women between 24 and 28 weeks (HR = 0.56 [0.34-0.95]). Excess weight gain was associated with an increased risk of stillbirth among obese and morbidly obese women, with highest risk after 36 completed weeks (obese: HR = 2.00 [1.55-2.58]; morbidly obese: HR = 3.16 [2.17-4.62]). In contrast, excess weight gain was associated with reduced risk of stillbirth in normal-weight women between 24 and 28 weeks (HR = 0.57 [0.44-0.70]) and in overweight women between 29 and 33 weeks (HR = 0.62 [0.45-0.85]). Analysis for the underweight group was limited by sample size. Both excessive weight gain and inadequate weight gain were not associated with stillbirth in this group. Stillbirth risk increased with inadequate weight gain and weight loss in all BMI classes except the morbidly obese group, where weight demonstrated a protective effect. Conversely, excessive weight gain was associated with higher risk of stillbirth among

Score Gains on g-loaded Tests: No g

NARCIS (Netherlands)

te Nijenhuis, J.; van Vianen, A.E.M.; van der Flier, H.

2007-01-01

IQ scores provide the best general predictor of success in education, job training, and work. However, there are many ways in which IQ scores can be increased, for instance by means of retesting or participation in learning potential training programs. What is the nature of these score gains? Jensen

Stability in high gain plasmas in DIII-D

International Nuclear Information System (INIS)

Lazarus, E.A.; Houlberg, W.A.; Murakami, M.; Wade, M.R.

1996-10-01

Fusion power gain has been increased by a factor of 3 in DIII-D plasmas through the use of strong discharge shaping and tailoring of the pressure and current density profiles. H-mode plasmas with weak or negative central magnetic shear are found to have neoclassical ion confinement throughout most of the plasma volume. Improved MHD stability is achieved by controlling the plasma pressure profile width. The highest fusion power gain Q (ratio of fusion power to input power) in deuterium plasmas was 0.0015, which extrapolates to an equivalent Q of 0.32 in a deuterium-tritium plasma and is similar to values achieved in tokamaks of larger size and magnetic fields

Gain-switched all-fiber laser with narrow bandwidth

DEFF Research Database (Denmark)

Larsen, Casper; Giesberts, M.; Nyga, S.

2013-01-01

pulse energy is 20 μJ in a duration of 135 ns at 7 kHz. The bandwidth increases for a higher pump pulse energy and repetition rate, and this sets the limit of the output pulse energy. A single power amplifier is added to raise the peak power to the kW-level and the pulse energy to 230 μJ while keeping......Gain-switching of a CW fiber laser is a simple and cost-effective approach to generate pulses using an all-fiber system. We report on the construction of a narrow bandwidth (below 0.1 nm) gain-switched fiber laser and optimize the pulse energy and pulse duration under this constraint. The extracted...

Curcumin as potential therapeutic natural product: a nanobiotechnological perspective.

Science.gov (United States)

Shome, Soumitra; Talukdar, Anupam Das; Choudhury, Manabendra Dutta; Bhattacharya, Mrinal Kanti; Upadhyaya, Hrishikesh

2016-12-01

Nanotechnology-based drug delivery systems can resolve the poor bioavailability issue allied with curcumin. The therapeutic potential of curcumin can be enhanced by making nanocomposite preparation of curcumin with metal oxide nanoparticles, poly lactic-co-glycolic acid (PLGA) nanoparticles and solid lipid nanoparticles that increases its bioavailability in the tissue. Curcumin has manifold therapeutic effects which include antidiabetic, antihypertensive, anticancer, anti-inflammatory and antimicrobial properties. Curcumin can inhibit diabetes, heavy metal and stress-induced hypertension with its antioxidant, chelating and inhibitory effects on the pathways that lead to hypertension. Curcumin is an anticancer agent that can prevent abnormal cell proliferation. Nanocurcumin is an improved form of curcumin with enhanced therapeutic properties due to improved delivery to the diseased tissue, better internalization and reduced systemic elimination. Curcumin has multiple pharmacologic effects, but its poor bioavailability reduces its therapeutic effects. By conjugating curcumin to metal oxide nanoparticles or encapsulation in lipid nanoparticles, dendrimers, nanogels and polymeric nanoparticles, the water solubility and bioavailability of curcumin can be improved and thus increase its pharmacological effectiveness. © 2016 Royal Pharmaceutical Society.

Cyclic peptides as potential therapeutic agents for skin disorders.

Science.gov (United States)

Namjoshi, Sarika; Benson, Heather A E

2010-01-01

There is an increasing understanding of the role of peptides in normal skin function and skin disease. With this knowledge, there is significant interest in the application of peptides as therapeutics in skin disease or as cosmeceuticals to enhance skin appearance. In particular, antimicrobial peptides and those involved in inflammatory processes provide options for the development of new therapeutic directions in chronic skin conditions such as psoriasis and dermatitis. To exploit their potential, it is essential that these peptides are delivered to their site of action in active form and in sufficient quantity to provide the desired effect. Many polymers permeate the skin poorly and are vulnerable to enzymatic degradation. Synthesis of cyclic peptide derivatives can substantially alter the physicochemical characteristics of the peptide with the potential to improve its skin permeation. In addition, cyclization can stabilize the peptide structure and thereby increase its stability. This review describes the role of cyclic peptides in the skin, examples of current cyclic peptide therapeutic products, and the potential for cyclic peptides as dermatological therapeutics and cosmeceuticals.

Effect of revised IOM weight gain guidelines on perinatal outcomes.

Science.gov (United States)

Halloran, Donna R; Wall, Terry C; Guild, Camelia; Caughey, Aaron B

2011-03-01

We sought to examine perinatal outcomes in women with a body mass index (BMI) of 25 kg/m(2) comparing those whose weight gain met 2009 IOM guidelines to women meeting 1990 IOM guidelines. This is a retrospective cohort study utilizing birth records linked to hospital discharge data for all term, singleton infants born to overweight, Missouri residents (2000-2006) with a BMI of 25 kg/m(2). We excluded congenital anomalies, mothers with diabetes, hypertension, or previous cesarean delivery. Fourteen thousand nine hundred fifty-five women gained 25-35 lbs (1990 guidelines); 1.6% delivered low birth weight (LBW) infants and 1.1% delivered macrosomic infants. Eight thousand three hundred fifty women gained 15-25 lbs (2009 guidelines); 3.4% delivered LBW infants and 0.6% delivered macrosomic infants. Women who gained 15-25 lbs were 1.99 (95% CI 1.67, 2.38) times more likely to have a LBW infant and 0.59 (95% CI 0.40, 0.76) times less likely to deliver a macrosomic infant. Limiting weight gain in women with a BMI of 25 kg/m(2), per the 2009 guidelines, increases the risk of LBW deliveries and decreases the risk of macrosomia but does not reduce associated adverse perinatal outcomes. Further studies should explore the optimal weight gain to reduce these outcomes.

Receiver Gain Modulation Circuit

Science.gov (United States)

Jones, Hollis; Racette, Paul; Walker, David; Gu, Dazhen

2011-01-01

A receiver gain modulation circuit (RGMC) was developed that modulates the power gain of the output of a radiometer receiver with a test signal. As the radiometer receiver switches between calibration noise references, the test signal is mixed with the calibrated noise and thus produces an ensemble set of measurements from which ensemble statistical analysis can be used to extract statistical information about the test signal. The RGMC is an enabling technology of the ensemble detector. As a key component for achieving ensemble detection and analysis, the RGMC has broad aeronautical and space applications. The RGMC can be used to test and develop new calibration algorithms, for example, to detect gain anomalies, and/or correct for slow drifts that affect climate-quality measurements over an accelerated time scale. A generalized approach to analyzing radiometer system designs yields a mathematical treatment of noise reference measurements in calibration algorithms. By treating the measurements from the different noise references as ensemble samples of the receiver state, i.e. receiver gain, a quantitative description of the non-stationary properties of the underlying receiver fluctuations can be derived. Excellent agreement has been obtained between model calculations and radiometric measurements. The mathematical formulation is equivalent to modulating the gain of a stable receiver with an externally generated signal and is the basis for ensemble detection and analysis (EDA). The concept of generating ensemble data sets using an ensemble detector is similar to the ensemble data sets generated as part of ensemble empirical mode decomposition (EEMD) with exception of a key distinguishing factor. EEMD adds noise to the signal under study whereas EDA mixes the signal with calibrated noise. It is mixing with calibrated noise that permits the measurement of temporal-functional variability of uncertainty in the underlying process. The RGMC permits the evaluation of EDA by

Transport of nanoparticles through the blood-brain barrier for imaging and therapeutic applications

Science.gov (United States)

Shilo, Malka; Motiei, Menachem; Hana, Panet; Popovtzer, Rachela

2014-01-01

A critical problem in the treatment of neurodegenerative disorders and diseases, such as Alzheimer's and Parkinson's, is the incapability to overcome the restrictive mechanism of the blood-brain barrier (BBB) and to deliver important therapeutic agents to the brain. During the last decade, nanoparticles have gained attention as promising drug delivery agents that can transport across the BBB and increase the uptake of appropriate drugs in the brain. In this study we have developed insulin-targeted gold nanoparticles (INS-GNPs) and investigated quantitatively the amount of INS-GNPs that cross the BBB by the receptor-mediated endocytosis process. For this purpose, INS-GNPs and control GNPs were injected into the tail vein of male BALB/c mice. Major organs were then extracted and a blood sample was taken from the mice, and thereafter analyzed for gold content by flame atomic absorption spectroscopy. Results show that two hours post-intravenous injection, the amount of INS-GNPs found in mouse brains is over 5 times greater than that of the control, untargeted GNPs. Results of further experimentation on a rat model show that INS-GNPs can also serve as CT contrast agents to highlight specific brain regions in which they accumulate. Due to the fact that they can overcome the restrictive mechanism of the BBB, this approach could be a potentially valuable tool, helping to confront the great challenge of delivering important imaging and therapeutic agents to the brain for detection and treatment of neurodegenerative disorders and diseases.

Early evaluation of patient risk for substantial weight gain during olanzapine treatment for schizophrenia, schizophreniform, or schizoaffective disorder

Directory of Open Access Journals (Sweden)

Hardy Thomas A

2008-09-01

Full Text Available Abstract Background To make well informed treatment decisions for their patients, clinicians need credible information about potential risk for substantial weight gain. We therefore conducted a post-hoc analysis of clinical trial data, examining early weight gain as a predictor of later substantial weight gain. Methods Data from 669 (Study 1 and 102 (Study 2 olanzapine-treated patients diagnosed with schizophrenia, schizophreniform, or schizoaffective disorder were analyzed to identify and validate weight gain cut-offs at Weeks 1–4 that were predictive of substantial weight gain (defined as an increase of ≥ 5, 7, 10 kg or 7% of baseline weight after approximately 30 weeks of treatment. Baseline characteristics alone, baseline characteristics plus weight change from baseline to Weeks 1, 2, 3 or 4, and weight change from baseline to Weeks 1, 2, 3, or 4 alone were evaluated as predictors of substantial weight gain. Similar analyses were performed to determine BMI increase cut-offs at Weeks 1–4 of treatment that were predictive of substantial increase in BMI (1, 2 or 3 kg/m2 increase from baseline. Results At Weeks 1 and 2, predictions based on early weight gain plus baseline characteristics were more robust than those based on early weight gain alone. However, by Weeks 3 and 4, there was little difference between the operating characteristics associated with these two sets of predictors. The positive predictive values ranged from 30.1% to 73.5%, while the negative predictive values ranged from 58.1% to 89.0%. Predictions based on early BMI increase plus baseline characteristics were not uniformly more robust at any time compared to those based on early BMI increase alone. The positive predictive values ranged from 38.3% to 83.5%, while negative predictive values ranged from 42.1% to 84.7%. For analyses of both early weight gain and early BMI increase, results for the validation dataset were similar to those observed in the primary dataset

Information Gain Based Dimensionality Selection for Classifying Text Documents

Energy Technology Data Exchange (ETDEWEB)

Dumidu Wijayasekara; Milos Manic; Miles McQueen

2013-06-01

Selecting the optimal dimensions for various knowledge extraction applications is an essential component of data mining. Dimensionality selection techniques are utilized in classification applications to increase the classification accuracy and reduce the computational complexity. In text classification, where the dimensionality of the dataset is extremely high, dimensionality selection is even more important. This paper presents a novel, genetic algorithm based methodology, for dimensionality selection in text mining applications that utilizes information gain. The presented methodology uses information gain of each dimension to change the mutation probability of chromosomes dynamically. Since the information gain is calculated a priori, the computational complexity is not affected. The presented method was tested on a specific text classification problem and compared with conventional genetic algorithm based dimensionality selection. The results show an improvement of 3% in the true positives and 1.6% in the true negatives over conventional dimensionality selection methods.

Elevated CO2 stimulates marsh elevation gain, counterbalancing sea-level rise.

Science.gov (United States)

Langley, J Adam; McKee, Karen L; Cahoon, Donald R; Cherry, Julia A; Megonigal, J Patrick

2009-04-14

Tidal wetlands experiencing increased rates of sea-level rise (SLR) must increase rates of soil elevation gain to avoid permanent conversion to open water. The maximal rate of SLR that these ecosystems can tolerate depends partly on mineral sediment deposition, but the accumulation of organic matter is equally important for many wetlands. Plant productivity drives organic matter dynamics and is sensitive to global change factors, such as rising atmospheric CO(2) concentration. It remains unknown how global change will influence organic mechanisms that determine future tidal wetland viability. Here, we present experimental evidence that plant response to elevated atmospheric [CO(2)] stimulates biogenic mechanisms of elevation gain in a brackish marsh. Elevated CO(2) (ambient + 340 ppm) accelerated soil elevation gain by 3.9 mm yr(-1) in this 2-year field study, an effect mediated by stimulation of below-ground plant productivity. Further, a companion greenhouse experiment revealed that the CO(2) effect was enhanced under salinity and flooding conditions likely to accompany future SLR. Our results indicate that by stimulating biogenic contributions to marsh elevation, increases in the greenhouse gas, CO(2), may paradoxically aid some coastal wetlands in counterbalancing rising seas.

Elevated CO2 stimulates marsh elevation gain, counterbalancing sea-level rise

Science.gov (United States)

Langley, J. Adam; McKee, Karen L.; Cahoon, Donald R.; Cherry, Julia A.; Megonigal, J. Patrick

2009-01-01

Tidal wetlands experiencing increased rates of sea-level rise (SLR) must increase rates of soil elevation gain to avoid permanent conversion to open water. The maximal rate of SLR that these ecosystems can tolerate depends partly on mineral sediment deposition, but the accumulation of organic matter is equally important for many wetlands. Plant productivity drives organic matter dynamics and is sensitive to global change factors, such as rising atmospheric CO2 concentration. It remains unknown how global change will influence organic mechanisms that determine future tidal wetland viability. Here, we present experimental evidence that plant response to elevated atmospheric [CO2] stimulates biogenic mechanisms of elevation gain in a brackish marsh. Elevated CO2 (ambient + 340 ppm) accelerated soil elevation gain by 3.9 mm yr−1 in this 2-year field study, an effect mediated by stimulation of below-ground plant productivity. Further, a companion greenhouse experiment revealed that the CO2 effect was enhanced under salinity and flooding conditions likely to accompany future SLR. Our results indicate that by stimulating biogenic contributions to marsh elevation, increases in the greenhouse gas, CO2, may paradoxically aid some coastal wetlands in counterbalancing rising seas. PMID:19325121

Effect of the Holiday Season on Weight Gain: A Narrative Review

Directory of Open Access Journals (Sweden)

Rolando G. Díaz-Zavala

2017-01-01

Full Text Available Several studies suggest that the holiday season, starting from the last week of November to the first or second week of January, could be critical to gaining weight. This study aims to review the literature to determine the effects of the holidays on body weight. In studies of adults, a significant weight gain was consistently observed during this period (0.4 to 0.9 kg, p0.05 during this period. Among individuals with obesity who attempt to lose weight, an increase in weight was observed (0.3 to 0.9 kg, significant in some but not in all studies, as well as increase in weight in motivated self-monitoring people (0.4 to 0.6%, p<0.001. Programs focused on self-monitoring during the holidays (phone calls and daily mailing appeared to prevent weight gain, but information is limited. The holiday season seems to increase body weight in adults, even in participants seeking to lose weight and in motivated self-monitoring people, whereas in children, adolescents, and college students, very few studies were found to make accurate conclusions.

Structurally Based Therapeutic Evaluation: A Therapeutic and Practical Approach to Teaching Medicinal Chemistry.

Science.gov (United States)

Alsharif, Naser Z.; And Others

1997-01-01

Explains structurally based therapeutic evaluation of drugs, which uses seven therapeutic criteria in translating chemical and structural knowledge into therapeutic decision making in pharmaceutical care. In a Creighton University (Nebraska) medicinal chemistry course, students apply the approach to solve patient-related therapeutic problems in…

Exercise during pregnancy and its association with gestational weight gain.

Science.gov (United States)

Harris, Shericka T; Liu, Jihong; Wilcox, Sara; Moran, Robert; Gallagher, Alexa

2015-03-01

We examined the association between exercise during pregnancy and meeting gestational weight gain recommendations. Data came from the 2009 South Carolina Pregnancy Risk Assessment Monitoring System (n = 856). Women reported their participation in exercise/sports activities before and during pregnancy, including the number of months and types of exercise. We developed an exercise index (EI), the product of the number of months spent in exercise and average metabolic equivalents for specific exercise. The 2009 Institute of Medicine's guideline was used to categorize gestational weight gain into three classes: inadequate, adequate, and excessive. Multinomial logistic regression models were used to adjust for confounders. Over 46 % of women exceeded the recommended weight gain during pregnancy. Nearly one third (31.9 %) of women reported exercising ≥3 times a week at any time during pregnancy. Compared to women who did not report this level of exercise during pregnancy, exercising women were more likely to meet gestational weight gain recommendations (32.7 vs. 18.7 %) and had a lower odds of excessive gestational weight gain [adjusted odds ratio (AOR) 0.43, 95 % confidence interval 0.24-0.78]. Women with an EI above the median value of those women who exercised or women who exercised ≥3 times a week for 6-9 months during pregnancy had lower odds of excessive gestational weight gain (AOR for EI 0.20, 0.08-0.49; AOR for months 0.26, 0.12-0.56, respectively). Our findings support the need to promote or increase exercise during pregnancy to reduce the high proportion of women who are gaining excessive weight.

Therapeutic strategies based on glucagon-like peptide 1

DEFF Research Database (Denmark)

Deacon, Carolyn F

2004-01-01

of factors influencing its metabolic stability and pharmacokinetic/pharmacodynamic profile, have therefore been the focus of intense research in both academia and the pharmaceutical industry. Such strategies include DPP-IV-resistant GLP-1 analogs and selective enzyme inhibitors to prevent in vivo degradation...... excursions. Furthermore, via its ability to enhance satiety, GLP-1 reduces food intake, thereby limiting weight gain, and may even cause weight loss. Taken together, these actions give GLP-1 a unique profile, considered highly desirable for an antidiabetic agent, particularly since the glucose dependency...... of its antihyperglycemic effects should minimize any risk of severe hypoglycemia. However, its pharmacokinetic/pharmacodynamic profile is such that native GLP-1 is not therapeutically useful. Thus, while GLP-1 is most effective when administered continuously, single subcutaneous injections have short...

Using Copy Number Alterations to Identify New Therapeutic Targets for Bladder Carcinoma

Directory of Open Access Journals (Sweden)

Donatella Conconi

2016-02-01

Full Text Available Bladder cancer represents the ninth most widespread malignancy throughout the world. It is characterized by the presence of two different clinical and prognostic subtypes: non-muscle-invasive bladder cancers (NMIBCs and muscle-invasive bladder cancers (MIBCs. MIBCs have a poor outcome with a common progression to metastasis. Despite improvements in knowledge, treatment has not advanced significantly in recent years, with the absence of new therapeutic targets. Because of the limitations of current therapeutic options, the greater challenge will be to identify biomarkers for clinical application. For this reason, we compared our array comparative genomic hybridization (array-CGH results with those reported in literature for invasive bladder tumors and, in particular, we focused on the evaluation of copy number alterations (CNAs present in biopsies and retained in the corresponding cancer stem cell (CSC subpopulations that should be the main target of therapy. According to our data, CCNE1, MYC, MDM2 and PPARG genes could be interesting therapeutic targets for bladder CSC subpopulations. Surprisingly, HER2 copy number gains are not retained in bladder CSCs, making the gene-targeted therapy less interesting than the others. These results provide precious advice for further study on bladder therapy; however, the clinical importance of these results should be explored.

Derivation of Conditions for the Normal Gain Behavior of Conical Horns

Directory of Open Access Journals (Sweden)

Chin Yeng Tan

2007-01-01

Full Text Available Monotonically increasing gain-versus-frequency pattern is in general expected to be a characteristic of aperture antennas that include the smooth-wall conical horn. While optimum gain conical horns do naturally exhibit this behavior, nonoptimum horns need to meet certain criterion: a minimum axial length for given aperture diameter, or, alternatively, a maximum aperture diameter for the given axial length. In this paper, approximate expressions are derived to determine these parameters.

Trans-species Engineering of Glycosylated Therapeutic Proteins

DEFF Research Database (Denmark)

Yang, Zhang

important to address. Whenever glycosylation has been found to be an important PTM for function or bioactivity, human therapeutics have generally been produced in mammalian Chinese hamster ovary (CHO) cell line. Oglycosylation is one of the most complex regulated PTMs of proteins but also one of the least...... understood. Currently, mammalian cells are required for human O-glycosylation. Increasing efforts have been devoted to engineering non-mammalian cells for production of recombinant proteins with “human-like” glycosylation. Substantial success has been achieved with designed N-glycosylation in both lower......Recombinant expression of therapeutic proteins is one of the major tasks in modern biomedicine. One of the most important factors with respect to therapeutic use in human is posttranslational modifications (PTMs) of the recombinant proteins, of which protein glycosylation is by far the most...

Selection on Optimal Haploid Value Increases Genetic Gain and Preserves More Genetic Diversity Relative to Genomic Selection

OpenAIRE

Daetwyler, Hans D.; Hayden, Matthew J.; Spangenberg, German C.; Hayes, Ben J.

2015-01-01

Doubled haploids are routinely created and phenotypically selected in plant breeding programs to accelerate the breeding cycle. Genomic selection, which makes use of both phenotypes and genotypes, has been shown to further improve genetic gain through prediction of performance before or without phenotypic characterization of novel germplasm. Additional opportunities exist to combine genomic prediction methods with the creation of doubled haploids. Here we propose an extension to genomic selec...

The intercultural and interracial therapeutic relationship: challenges and recommendations.

Science.gov (United States)

Qureshi, Adil; Collazos, Francisco

2011-01-01

Although research has demonstrated that mental health services function with patients from different cultural backgrounds, a variety of culture- and race-related factors can result in services being of lower quality than that which occurs when the clinician and patient are from the same culture. The provision of culturally competent care requires many institutional and organizational adaptations that lie beyond the control of most mental health professionals. The therapeutic relationship, however, remains a key factor of mental healthcare that can be attended to by individual therapists. The therapeutic relationship plays an important role in almost every therapeutic approach, and has been increasingly recognized as representing a means to the provision of quality intercultural and interracial treatment. At the same time, a host of cultural and racial factors relating to both the patient and clinician can compromise the development of the therapeutic relationship. This paper will explore some of the key issues that complicate therapeutic contact and communication, and will outline means by which to strengthen key components of the therapeutic relationship.

Enhanced Delivery of Gold Nanoparticles with Therapeutic Potential for Targeting Human Brain Tumors

Science.gov (United States)

Etame, Arnold B.

The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non

Increased Paracrine Immunomodulatory Potential of Mesenchymal Stromal Cells in Three-Dimensional Culture

DEFF Research Database (Denmark)

Follin, Bjarke; Juhl, Morten; Cohen, Smadar

2016-01-01

Mesenchymal stromal/stem cells (MSCs) have been investigated extensively through the past years, proving to have great clinical therapeutic potential. In vitro cultivation of MSCs in three-dimensional (3D) culture systems, such as scaffolds, hydrogels, or spheroids, have recently gained attention...... for tissue engineering applications. Studies on MSC spheroids demonstrated that such cultivation increased the paracrine immunomodulatory potential of the MSCs, accompanied by phenotypic alterations. In this review, we gather results from recent experimental studies on the immunomodulatory abilities of MSCs...... when cultured as spheroids or in biomaterials like scaffolds or hydrogels compared to regular two-dimensional (2D) culture and show that alterations occurring to MSCs in spheroids also occur in MSCs in biomaterials. We provide a brief description of known mechanisms of MSC immunomodulatory capacity...

Could nutritional rehabilitation at home complement or replace centre-based therapeutic feeding programmes for severe malnutrition?

Science.gov (United States)

Gaboulaud, V; Dan-Bouzoua, N; Brasher, C; Fedida, G; Gergonne, B; Brown, V

2007-02-01

To measure the success rate of three different strategies used in Médecins Sans Frontières large-scale therapeutic nutritional rehabilitation programme in Niger, we analysed three cohorts of severely malnourished patients in terms of daily weight gain, length of stay, recovery, case fatality and defaulting. A total of 1937 children aged 6-59 months were followed prospectively from 15 August 2002 to 21 October 2003. For the three cohorts, 660 children were maintained in the therapeutic feeding centre (TFC) during the entire treatment, 937 children were initially treated at the TFC and completed treatment at home and 340 children were exclusively treated at home. For all cohorts, average time in the programme and average weight gain met the international standards (30-40 days, >8 g/kg/day). Default rates were 28.1, 16.8 and 5.6% for TFC only, TFC plus home-based and home-based alone strategies, respectively. The overall case fatality rate for the entire programme was 6.8%. Case fatality rates were 18.9% for TFC only and 1.7% for home-based alone. No deaths were recorded in children transferred to rehabilitation at home. This study suggests that satisfactory results for the treatment of severe malnutrition can be achieved using a combination of home and hospital-based strategies.

Hydrolytic gain during hydrolysis reactions : implications and correction procedures

NARCIS (Netherlands)

Marchal, L.M.; Tramper, J.

1999-01-01

Some of the structural parameters of starch (e.g. % beta- or gluco-hydrolysis) were influenced by the increase in mass during the hydrolysis reactions (hydrolytic gain). Procedures were derived to correct this apparent % of hydrolysis to actual % of hydrolysis. These analytically derived equations

Thyroid abnormalities after therapeutic external radiation

Energy Technology Data Exchange (ETDEWEB)

Hancock, S.L.; McDougall, I.R. [Stanford Univ. School of Medicine, Stanford, CA (United States); Constine, L.S. [Strong Memorial Hospital, Rochester, NY (United States)

1995-03-30

The thyroid gland is the largest pure endocrine gland in the body and one of the organs most likely to produce clinically significant abnormalities after therapeutic external radiation. Radiation doses to the thyroid that exceed approximately 26 Gy frequently produce hypothyroidism, which may be clinically overt or subclinical, as manifested by increased serum thyrotropin and normal serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may arise when the pituitary region receives doses exceeding 50 Gy with conventional, 1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk of Graves` disease or euthyroid Graves` ophthalmopathy. Silent thyroiditis, cystic degeneration, benign adenoma, and thyroid cancer have been observed after therapeutically relevant doses of external radiation. Direct or incidental thyroid irradiation increases the risk for well-differentiated, papillary, and follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest following radiation at a young age, decreases with increasing age at treatment, and increases with follow-up duration. The potentially prolonged latent period between radiation exposure and the development of thyroid dysfunction, thyroid nodularity, and thyroid cancer means that individuals who have received neck or pituitary irradiation require careful, periodic clinical and laboratory evaluation to avoid excess morbidity. 39 refs.

Thyroid abnormalities after therapeutic external radiation

International Nuclear Information System (INIS)

Hancock, Steven L.; McDougall, I. Ross; Constine, Louis S.

1995-01-01

The thyroid gland is the largest pure endocrine gland in the body and one of the organs most likely to produce clinically significant abnormalities after therapeutic external radiation. Radiation doses to the thyroid that exceed approximately 26 Gy frequently produce hypothyroidism, which may be clinically overt or subclinical, as manifested by increased serum thyrotropin and normal serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may arise when the pituitary region receives doses exceeding 50 Gy with conventional, 1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk of Graves' disease or euthyroid Graves' opthalmopathy. Silent thyroiditis, cystic degeneration, benign adenoma, and thyroid cancer have been observed after therapeutically relevant doses of external radiation. Direct or incidental thyroid irradiation increases the risk for well-differentiated, papillary, and follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest following radiation at a young age, decreases with increasing age at treatment, and increases with follow-up duration. The potentially prolonged latent period between radiation exposure and the development of thyroid dysfunction, thyroid nodularity, and thyroid cancer means that individuals who have received neck or pituitary irradiation require careful, periodic clinical and laboratory evaluation to avoid excess morbidity

Weight suppression predicts total weight gain and rate of weight gain in outpatients with anorexia nervosa.

Science.gov (United States)

Carter, Frances A; Boden, Joseph M; Jordan, Jennifer; McIntosh, Virginia V W; Bulik, Cynthia M; Joyce, Peter R

2015-11-01

The present study sought to replicate the finding of Wildes and Marcus, Behav Res Ther, 50, 266-274, 2012 that higher levels of weight suppression at pretreatment predict greater total weight gain, faster rate of weight gain, and bulimic symptoms amongst patients admitted with anorexia nervosa. Participants were 56 women with anorexia nervosa diagnosed by using strict or lenient weight criteria, who were participating in a randomized controlled psychotherapy trial (McIntosh et al., Am J Psychiatry, 162, 741-747, 2005). Thirty-five women completed outpatient treatment and post-treatment assessment. Weight suppression was the discrepancy between highest lifetime weight at adult height and weight at pretreatment assessment. Outcome variables were total weight gain, rate of weight gain, and bulimic symptoms in the month prior to post-treatment assessment [assessed using the Eating Disorders Examination (Fairburn et al., Binge-Eating: Nature, Assessment and Treatment. New York: Guilford, 1993)]. Weight suppression was positively associated with total weight gain and rate of weight gain over treatment. Regression models showed that this association could not be explained by covariates (age at onset of anorexia nervosa and treatment modality). Weight suppression was not significantly associated with bulimic symptoms in the month prior to post-treatment assessment, regardless of whether bulimic symptoms were examined as continuous or dichotomous variables. The present study reinforces the previous finding that weight suppression predicts total weight gain and rate of weight gain amongst patients being treated for anorexia nervosa. Methodological issues may explain the failure of the present study to find that weight suppression predicts bulimic symptoms. Weight suppression at pretreatment for anorexia nervosa should be assessed routinely and may inform treatment planning. © 2015 Wiley Periodicals, Inc.

Parent-Reported Bullying and Child Weight Gain between Ages 6 and 15.

Science.gov (United States)

Sutin, Angelina R; Robinson, Eric; Daly, Michael; Terracciano, Antonio

2016-12-01

Childhood bullying has long-term negative mental and physical health correlates, including weight gain and symptoms of depression. The purpose of this research is to examine whether bullying in the first year of school is associated with greater weight gain by early adolescence and whether adolescent depressive symptoms mediate this association. Data were drawn from the Longitudinal Study of Australian Children. Children (N = 3929) were measured every 2 years; BMI and waist circumference were available from ages 4 to 15. Parents reported on bullying at age 6. Children reported on their depressive symptoms at ages 12-13. Participants who weighed in the obese category at age 4 had an over 50% increased risk of being bullied in school at age 6. Being bullied at age 6 was associated with excess weight gain between ages 6 and 15, defined as either BMI or waist circumference. Depressive symptoms at age 12 partially explained the association between bullying and increases in adiposity. None of the associations varied by gender. Similar to other forms of peer victimization, bullying early in school is associated with greater weight gain through early adolescence; depressive symptom is one mechanism that contributes to this association.

Gestational Weight Gain and Overweight in Children Aged 3–6 Years

Science.gov (United States)

Guo, Lianhong; Liu, Jufen; Ye, Rongwei; Liu, Jianmeng; Zhuang, Zhixiong; Ren, Aiguo

2015-01-01

Objective To determine whether gestational weight gain (GWG) was associated with increased odds of childhood overweight after accounting for pre-pregnancy BMI. Methods In a prospective cohort study based on a premarital and perinatal health care system in China, data of 100 612 mother-child pairs were obtained. The main exposure was GWG as both a continuous and categorical variable. The outcome measure was overweight, defined by age- and sex-specific cutoff values for body mass index (BMI) in children aged 3–6 years. Results A 1-kg increase in maternal GWG was associated with an increase of 0.009 (95% confidence interval [CI]: 0.007–0.010, P children’s mean BMI; in the subgroup of pre-pregnancy overweight/obese mothers, the increase in children’s BMI was 0.028 (95% CI, 0.017–0.039, P overweight when adequate GWG was used as the reference, with an odds ratio (OR) of 1.21 (95% CI, 1.12–1.29). The risk was highest (OR 2.22; 95% CI, 1.79–2.76) in the children of mothers who were overweight/obese before pregnancy and gained excessive weight during pregnancy. Conclusions Greater maternal GWG was associated with greater offspring BMI, and the risk of overweight was doubled in children whose mothers were overweight/obese before pregnancy and gained excessive weight during pregnancy. As a result, maintenance of appropriate weight gain during pregnancy and prophylaxis of maternal overweight/obesity before pregnancy should be a strategy for preventing childhood overweight/obesity. PMID:26119288

Development of Class IIa Bacteriocins as Therapeutic Agents

Directory of Open Access Journals (Sweden)

Christopher T. Lohans

2012-01-01

Full Text Available Class IIa bacteriocins have been primarily explored as natural food preservatives, but there is much interest in exploring the application of these peptides as therapeutic antimicrobial agents. Bacteriocins of this class possess antimicrobial activity against several important human pathogens. Therefore, the therapeutic development of these bacteriocins will be reviewed. Biological and chemical modifications to both stabilize and increase the potency of bacteriocins are discussed, as well as the optimization of their production and purification. The suitability of bacteriocins as pharmaceuticals is explored through determinations of cytotoxicity, effects on the natural microbiota, and in vivo efficacy in mouse models. Recent results suggest that class IIa bacteriocins show promise as a class of therapeutic agents.

Correlates of motivation to prevent weight gain: a cross sectional survey

Directory of Open Access Journals (Sweden)

Breedveld Boudewijn

2005-03-01

Full Text Available Abstract Background This study is an application of the theory of planned behaviour (TPB with additional variables to predict the motivations to prevent weight gain. In addition, variations in measures across individuals classified into Precaution Adoption Process stages (PAPM-stages of behaviour change were investigated. Methods A cross-sectional survey among 979 non-obese Dutch adults aged 25–35 years was conducted. Multiple binary logistic regression analysis was conducted to assess the associations of Body Mass Index (BMI, demographic factors and psychosocial variables from the TPB with the intention to prevent weight gain. Differences in BMI, demographic and psychosocial factors between PAPM-stages were explored using one-way analysis of variance and chi-square tests. Results Eighty-five percent of respondents intended to prevent weight gain. Age, attitudes and risk perceptions related to weight gain were the strongest correlates of intention (age: OR = 1.12, 95%CI: 1.04–1.20; attitude OR = 7.91, 95%CI: 5.33–11.74; risk perception OR = 1.24, 95%CI: 1.11–1.38. Significant differences were detected between the PAPM-stages in almost all variables. Notably, perceived behavioural control was lowest among people who had decided to prevent weight gain. Conclusion Messages to influence attitudes towards the prevention of weight gain and risk perception may affect people who are not yet motivated to prevent weight gain. Interventions increasing people's perceived behavioural control in overcoming barriers to prevent weight gain may help people to act on their intentions.

Maternal weight gain and associations with longitudinal fetal growth in dichorionic twin pregnancies: a prospective cohort study.

Science.gov (United States)

Hinkle, Stefanie N; Hediger, Mary L; Kim, Sungduk; Albert, Paul S; Grobman, William; Newman, Roger B; Wing, Deborah A; Grewal, Jagteshwar; Zhang, Cuilin; Buck Louis, Germaine M; Grantz, Katherine L

2017-12-01

Background: Maternal metabolic demands are much greater with twin gestations; however, there are no accepted recommendations for maternal weight gain in twin pregnancies. Objective: We assessed the association of maternal weight gain and fetal growth in dichorionic twins throughout pregnancy. Design: This was a prospective US cohort study ( n = 143, 2012-2013) of dichorionic twin pregnancies with known birth outcomes followed from enrollment (11-13 wk) and for ≤6 research visits throughout gestation. Maternal prepregnancy weight was self-reported, and current weight was measured at each research visit and abstracted from prenatal records. Fetal biometry was assessed by ultrasound at each research visit. Maternal weight and twin-pair fetal size trajectories across gestation were modeled. The adjusted associations between maternal weight gain from 0 to 13, 14 to 20, 21 to 27, and 28 to 34 wk and fetal growth at the subsequent week (i.e., 14, 21, 28, and 35 wk, respectively) were estimated with the use of linear regression. Results: The mean ± SD maternal weight gain from 0 to 13, 14 to 20, 21 to 27, and 28 to 34 wk was 2.8 ± 3.0 kg, 3.9 ± 1.2 kg, 3.8 ± 1.4 kg, and 4.4 ± 2.2 kg, respectively, with a total gain of 17.7 ± 7.4 kg. Maternal weight gain from 0 to 13 wk (first trimester) was not associated with fetal size at 14 wk. Maternal weight gain from 14 to 20 and 21 to 27 wk (second trimester) was significantly associated with increased fetal weight at 21 wk [increase of 10.5 g/kg maternal weight gain (95% CI: 1.2, 19.8 g)] and 28 wk [increase of 21.3 g/kg maternal weight gain (95% CI: 0.6, 42.0 g)]. Maternal weight gain from 14 to 20 wk was associated with increased twin abdominal circumference (AC) and biparietal diameter at 21 wk. Maternal weight gain from 21 to 27 wk was associated with increased femur and humerus lengths at 28 wk. Conclusion: Maternal weight gain was associated with dichorionic twin fetal growth in the second trimester only, driven by an

Measurement of Antenna Bore-Sight Gain

Science.gov (United States)

Fortinberry, Jarrod; Shumpert, Thomas H.

2016-01-01

The absolute or free-field gain of a simple antenna can be approximated using standard antenna theory formulae or for a more accurate prediction, numerical methods may be employed to solve for antenna parameters including gain. Both of these methods will result in relatively reasonable estimates but in practice antenna gain is usually verified and documented via measurements and calibration. In this paper, a relatively simple and low-cost, yet effective means of determining the bore-sight free-field gain of a VHF/UHF antenna is proposed by using the Brewster angle relationship.

Gain scheduling using the Youla parameterization

DEFF Research Database (Denmark)

Niemann, Hans Henrik; Stoustrup, Jakob

1999-01-01

Gain scheduling controllers are considered in this paper. The gain scheduling problem where the scheduling parameter vector cannot be measured directly, but needs to be estimated is considered. An estimation of the scheduling vector has been derived by using the Youla parameterization. The use...... in connection with H_inf gain scheduling controllers....

Heavy inertial particles in turbulent flows gain energy slowly but lose it rapidly.

Science.gov (United States)

Bhatnagar, Akshay; Gupta, Anupam; Mitra, Dhrubaditya; Pandit, Rahul

2018-03-01

We present an extensive numerical study of the time irreversibility of the dynamics of heavy inertial particles in three-dimensional, statistically homogeneous, and isotropic turbulent flows. We show that the probability density function (PDF) of the increment, W(τ), of a particle's energy over a time scale τ is non-Gaussian, and skewed toward negative values. This implies that, on average, particles gain energy over a period of time that is longer than the duration over which they lose energy. We call this slow gain and fast loss. We find that the third moment of W(τ) scales as τ^{3} for small values of τ. We show that the PDF of power-input p is negatively skewed too; we use this skewness Ir as a measure of the time irreversibility and we demonstrate that it increases sharply with the Stokes number St for small St; this increase slows down at St≃1. Furthermore, we obtain the PDFs of t^{+} and t^{-}, the times over which p has, respectively, positive or negative signs, i.e., the particle gains or loses energy. We obtain from these PDFs a direct and natural quantification of the slow gain and fast loss of the energy of the particles, because these PDFs possess exponential tails from which we infer the characteristic loss and gain times t_{loss} and t_{gain}, respectively, and we obtain t_{loss}gain} for all the cases we have considered. Finally, we show that the fast loss of energy occurs with greater probability in the strain-dominated region than in the vortical one; in contrast, the slow gain in the energy of the particles is equally likely in vortical or strain-dominated regions of the flow.

Compensation of propagation loss of surface plasmon polaritons with a finite-thickness dielectric gain layer

International Nuclear Information System (INIS)

Zhang, Xin; Liu, Haitao; Zhong, Ying

2012-01-01

We theoretically study the compensation of propagation loss of surface plasmon polaritons (SPPs) with the use of a finite-thickness dielectric layer with optical gain. The impacts of the gain coefficient, the gain-layer thickness and the wavelength on the loss compensation and the field distribution of the SPP mode are systematically explored with a fully vectorial method. Abnormal behaviors for the loss compensation as the gain-layer thickness increases are found and explained. Critical values of the gain coefficient and of the corresponding gain-layer thickness for just compensating the propagation loss are provided. Our results show that as the SPP propagation loss is fully compensated with a gain coefficient at a reasonably low level, the gain layer is still thin enough to ensure a large exterior SPP field at the gain-layer/air interface, which is important for achieving a strong light–matter interaction for applications such as bio-chemical sensing. (paper)

Acceptability and effectiveness of chickpea sesame-based ready-to-use therapeutic food in malnourished HIV-positive adults

Directory of Open Access Journals (Sweden)

Paluku Bahwere

2009-03-01

Full Text Available Paluku Bahwere, Kate Sadler, Steve CollinsValid International, Oxford, United KingdomObjective: A prospective descriptive study to assess acceptability and effectiveness of a locally made ready-to-use therapeutic food (RUTF in HIV-infected chronically sick adults (CSA with mid-upper-arm circumference (MUAC <210 mm or pitting edema. Methods: Sixty-three wasted AIDS adults were prescribed 500 g representing ~2600 kcal/day of locally made RUTF for three months and routine cotrimoxazole. Weight, height, MUAC, Karnofsky score and morbidity were measured at admission and at monthly intervals. The amount of RUTF intake and acceptability were assessed monthly.Results: Ninety-five percent (60/63 of the CSA that were invited to join the study agreed to participate. Mean daily intake in these 60 patients was 300 g/person/day (~1590 Kcal and 40 g of protein. Overall, 73.3% (44/60 gained weight, BMI, and MUAC. The median weight, MUAC and BMI gains after three months were 3.0 kg, 25.4 mm, and 1.1 kg/m2, respectively. The intervention improved the physical activity performance of participants and 78.3% (47/60 regained sufficient strength to walk to the nearest health facility. Mortality at three months was 18.3% (11/60.Conclusion: Locally made RUTF was acceptable to patients and was associated with a rapid weight gain and physical activity performance. The intervention is likely to be more cost effective than nutritional support using usual food-aid commodities.Keywords: ready-to-use therapeutic food, community-based intervention, adult, supplementation, HIV, Malawi

Pregnancy weight gain by gestational age and stillbirth: a population-based cohort study.

Science.gov (United States)

Johansson, K; Hutcheon, J A; Bodnar, L M; Cnattingius, S; Stephansson, O

2017-11-21

To study the association between total and early pregnancy (gain and risk of stillbirth, stratified by early-pregnancy body mass index (BMI). Population-based cohort study. Stockholm-Gotland Region, Sweden. Pregnant women with singleton births (n = 160 560). Pregnancy weight gain was standardised into gestational age-specific z-scores. For analyses of total pregnancy weight gain, a matched design with an incidence density sampling approach was used. Findings were also contrasted with current Institute of Medicine (IOM) weight gain recommendations. Stillbirth defined as fetal death at ≥22 completed weeks of gestation. For all BMI categories, there was no statistical association between total or early pregnancy weight gain and stillbirth within the range of a weight gain z-score of -2.0 SD to +2.0 SD. Among normal-weight women, the adjusted odds ratio of stillbirth for lower (-2.0 to -1.0 SD) and higher (+1.0 to +1.9 SD) total weight gain was 0.85 (95% CI; 0.48-1.49) and 1.03 (0.60-1.77), respectively, as compared with the reference category. Further, there were no associations between total or early pregnancy weight gain and stillbirth within the range of weight gain currently recommended by the IOM. For the majority of the BMI categories, the point estimates at the extremes of weight gain values (gain and increased risks of high weight gain, but estimates were imprecise and not statistically significant. We found no associations between total or early pregnancy weight gain and stillbirth across the range of weight gain experienced by most women. There was no association between weight gain during pregnancy and stillbirth among most women. © 2017 Karolinska Institutet. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.

Immobilization and therapeutic passive stretching generate thickening and increase the expression of laminin and dystrophin in skeletal muscle

International Nuclear Information System (INIS)

Cação-Benedini, L.O.; Ribeiro, P.G.; Prado, C.M.; Chesca, D.L.; Mattiello-Sverzut, A.C.

2014-01-01

Extracellular matrix and costamere proteins transmit the concentric, isometric, and eccentric forces produced by active muscle contraction. The expression of these proteins after application of passive tension stimuli to muscle remains unknown. This study investigated the expression of laminin and dystrophin in the soleus muscle of rats immobilized with the right ankle in plantar flexion for 10 days and subsequent remobilization, either by isolated free movement in a cage or associated with passive stretching for up to 10 days. The intensity of the macrophage response was also evaluated. One hundred and twenty-eight female Wistar rats were divided into 8 groups: free for 10 days; immobilized for 10 days; immobilized/free for 1, 3, or 10 days; or immobilized/stretched/free for 1, 3, or 10 days. After the experimental procedures, muscle tissue was processed for immunofluorescence (dystrophin/laminin/CD68) and Western blot analysis (dystrophin/laminin). Immobilization increased the expression of dystrophin and laminin but did not alter the number of macrophages in the muscle. In the stretched muscle groups, there was an increase in dystrophin and the number of macrophages after 3 days compared with the other groups; dystrophin showed a discontinuous labeling pattern, and laminin was found in the intracellular space. The amount of laminin was increased in the muscles treated by immobilization followed by free movement for 10 days. In the initial stages of postimmobilization (1 and 3 days), an exacerbated macrophage response and an increase of dystrophin suggested that the therapeutic stretching technique induced additional stress in the muscle fibers and costameres

Immobilization and therapeutic passive stretching generate thickening and increase the expression of laminin and dystrophin in skeletal muscle

Energy Technology Data Exchange (ETDEWEB)

Cação-Benedini, L.O.; Ribeiro, P.G. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Medicina e Reabilitação do Aparelho Locomotor, Departamento de Biomecânica, Ribeirão Preto, SP, Brasil, Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Prado, C.M.; Chesca, D.L. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Mattiello-Sverzut, A.C. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Medicina e Reabilitação do Aparelho Locomotor, Departamento de Biomecânica, Ribeirão Preto, SP, Brasil, Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

2014-05-09

Extracellular matrix and costamere proteins transmit the concentric, isometric, and eccentric forces produced by active muscle contraction. The expression of these proteins after application of passive tension stimuli to muscle remains unknown. This study investigated the expression of laminin and dystrophin in the soleus muscle of rats immobilized with the right ankle in plantar flexion for 10 days and subsequent remobilization, either by isolated free movement in a cage or associated with passive stretching for up to 10 days. The intensity of the macrophage response was also evaluated. One hundred and twenty-eight female Wistar rats were divided into 8 groups: free for 10 days; immobilized for 10 days; immobilized/free for 1, 3, or 10 days; or immobilized/stretched/free for 1, 3, or 10 days. After the experimental procedures, muscle tissue was processed for immunofluorescence (dystrophin/laminin/CD68) and Western blot analysis (dystrophin/laminin). Immobilization increased the expression of dystrophin and laminin but did not alter the number of macrophages in the muscle. In the stretched muscle groups, there was an increase in dystrophin and the number of macrophages after 3 days compared with the other groups; dystrophin showed a discontinuous labeling pattern, and laminin was found in the intracellular space. The amount of laminin was increased in the muscles treated by immobilization followed by free movement for 10 days. In the initial stages of postimmobilization (1 and 3 days), an exacerbated macrophage response and an increase of dystrophin suggested that the therapeutic stretching technique induced additional stress in the muscle fibers and costameres.

High Gain Advanced GPS Receiver

National Research Council Canada - National Science Library

Brown, Alison; Zhang, Gengsheng

2006-01-01

NAVSYS High Gain Advanced GPS Receiver (HAGR) uses a digital beam-steering antenna array to enable up to eight GPS satellites to be tracked, each with up to 10 dBi of additional antenna gain over a conventional receiver solution...

Compensatory weight gain due to dopaminergic hypofunction: new evidence and own incidental observations

Directory of Open Access Journals (Sweden)

Bohr Iwo

2008-12-01

Full Text Available Abstract There is increasing evidence for a role of dopamine in the development of obesity. More specifically, dopaminergic hypofunction might lead to (overcompensatory food intake. Overeating and resulting weight gain may be induced by genetic predisposition for lower dopaminergic activity, but might also be a behavioral mechanism of compensating for decreased dopamine signaling after dopaminergic overstimulation, for example after smoking cessation or overconsumption of high palatable food. This hypothesis is in line with our incidental finding of increased weight gain after discontinuation of pharmaceutical dopaminergic overstimulation in rats. These findings support the crucial role of dopaminergic signaling for eating behaviors and offer an explanation for weight-gain after cessation of activities associated with high dopaminergic signaling. They further support the possibility that dopaminergic medication could be used to moderate food intake.

Determination of the STIS CCD Gain

Science.gov (United States)

Riley, Allyssa; Monroe, TalaWanda; Lockwood, Sean

2016-09-01

This report summarizes the analysis and absolute gain results of the STIS Cycle 23 special calibration program 14424 that was designed to measure the gain of amplifiers A, C and D at nominal gain settings of 1 and 4 e-/DN. We used the mean-variance technique and the results indicate a mean-variance technique.

Interactions of silica nanoparticles with therapeutics for oxidative stress attenuation in neurons

Science.gov (United States)

White-Schenk, Desiree; Shi, Riyi; Leary, James F.

2015-03-01

Oxidative stress plays a major role in many disease pathologies, notably in the central nervous system (CNS). For instance, after initial spinal cord injury, the injury site tends to increase during a secondary chemical injury process based on oxidative stress from necrotic cells and the inflammatory response. Prevention of this secondary chemical injury would represent a major advance in the treatment of people with spinal cord injuries. Few therapeutics are useful in combating such stress in the CNS due to side effects, low efficacy, or half-life. Mesoporous silica nanoparticles show promise for delivering therapeutics based on the formation of a porous network during synthesis. Ideally, they increase the circulation time of loaded therapeutics to increase the half-life while reducing overall concentrations to avoid side effects. The current study explored the use of silica nanoparticles for therapeutic delivery of anti-oxidants, in particular, the neutralization of acrolein which can lead to extensive tissue damage due to its ability to generate more and more copies of itself when it interacts with normal tissue. Both an FDA-approved therapeutic, hydralazine, and natural product, epigallocatechin gallate, were explored as antioxidants for acrolein with nanoparticles for increased efficacy and stability in neuronal cell cultures. Not only were the nanoparticles explored in neuronal cells, but also in a co-cultured in vitro model with microglial cells to study potential immune responses to near-infrared (NIRF)-labeled nanoparticles and uptake. Studies included nanoparticle toxicity, uptake, and therapeutic response using fluorescence-based techniques with both dormant and activated immune microglia co-cultured with neuronal cells.

Nonunity gain minimal-disturbance measurement

DEFF Research Database (Denmark)

Sabuncu, Metin; Mišta, L.; Fiurášek, J.

2007-01-01

We propose and experimentally demonstrate an optimal nonunity gain Gaussian scheme for partial measurement of an unknown coherent state that causes minimal disturbance of the state. The information gain and the state disturbance are quantified by the noise added to the measurement outcomes...

The Therapeutic Utility of Employment in Treating Drug Addiction: Science to Application.

Science.gov (United States)

Silverman, Kenneth; Holtyn, August F; Morrison, Reed

2016-06-01

Research on a model Therapeutic Workplace has allowed for evaluation of the use of employment in the treatment of drug addiction. Under the Therapeutic Workplace intervention, adults with histories of drug addiction are hired and paid to work. To promote drug abstinence or adherence to addiction medications, participants are required to provide drug-free urine samples or take prescribed addiction medications, respectively, to gain access to the workplace and/or to maintain their maximum rate of pay. Research has shown that the Therapeutic Workplace intervention is effective in promoting and maintaining abstinence from heroin, cocaine and alcohol and in promoting adherence to naltrexone. Three models could be used to implement and maintain employment-based reinforcement in the treatment of drug addiction: A Social Business model, a Cooperative Employer model, and a Wage Supplement model. Under all models, participants initiate abstinence in a training and abstinence initiation phase (Phase 1). Under the Social Business model, Phase 1 graduates are hired as employees in a social business and required to maintain abstinence to maintain employment and/or maximum pay. Under the Cooperative Employer model, cooperating community employers hire graduates of Phase 1 and require them to maintain abstinence to maintain employment and/or maximum pay. Under the Wage Supplement Model, graduates of Phase 1 are offered abstinence-contingent wage supplements if they maintain competitive employment in a community job. Given the severity and persistence of the problem of drug addiction and the lack of treatments that can produce lasting effects, continued development of the Therapeutic Workplace is warranted.

Essential oils, their therapeutic properties, and implication in dentistry: A review.

Science.gov (United States)

Dagli, Namrata; Dagli, Rushabh; Mahmoud, Rasha Said; Baroudi, Kusai

2015-01-01

Antibacterial treatments currently used for treatment cause several side effects, and bacterial resistance to the antibiotics is also increasing. Therefore, there is need to find better alternatives. Essential oils (EOs) have been used for treatment of various ailments since ancient times and have gained popularity over the years. Safety and efficacy of EOs have been proved by several clinical trials. This review gives an overview on the EOs, their uses, and adverse effects. A literature search was performed in the PubMed for clinical trial studies and review articles on EOs published up to February 2015. The search was performed during March 2015. The following keywords were used: "Lavender essential oil," "cinnamon oil," "clove oil," "eucalyptus oil," "peppermint oil," "lemon EOs," and "tea tree oil." Total 70 relevant articles were found in PubMed database. After screening of abstracts, 52 articles were selected to be included in the present review. On the basis of the available information, it can be concluded that EOs have the potential to be developed as preventive or therapeutic agents for various oral diseases, but further clinical trials are required to establish their safety and efficacy.

Dysfunctional Hematopoietic Stem Cell Biology: Underlying Mechanisms and Potential Therapeutic Strategies

Directory of Open Access Journals (Sweden)

Anja Geiselhart

2012-01-01

Full Text Available Fanconi anemia (FA is the most common inherited bone marrow failure syndrome. FA patients suffer to varying degrees from a heterogeneous range of developmental defects and, in addition, have an increased likelihood of developing cancer. Almost all FA patients develop a severe, progressive bone marrow failure syndrome, which impacts upon the production of all hematopoietic lineages and, hence, is thought to be driven by a defect at the level of the hematopoietic stem cell (HSC. This hypothesis would also correlate with the very high incidence of MDS and AML that is observed in FA patients. In this paper, we discuss the evidence that supports the role of dysfunctional HSC biology in driving the etiology of the disease. Furthermore, we consider the different model systems currently available to study the biology of cells defective in the FA signaling pathway and how they are informative in terms of identifying the physiologic mediators of HSC depletion and dissecting their putative mechanism of action. Finally, we ask whether the insights gained using such disease models can be translated into potential novel therapeutic strategies for the treatment of the hematologic disorders in FA patients.

Serotonin as a New Therapeutic Target for Diabetes Mellitus and Obesity

Directory of Open Access Journals (Sweden)

Chang-Myung Oh

2016-03-01

Full Text Available Serotonin (5-hydroxytryptamine [5-HT] is a monoamine that has various functions in both neuronal and non-neuronal systems. In the central nervous system, 5-HT regulates mood and feeding behaviors as a neurotransmitter. Thus, there have been many trials aimed at increasing the activity of 5-HT in the central nervous system, and some of the developed methods are already used in the clinical setting as anti-obesity drugs. Unfortunately, some drugs were withdrawn due to the development of unwanted peripheral side effects, such as valvular heart disease and pulmonary hypertension. Recent studies revealed that peripheral 5-HT plays an important role in metabolic regulation in peripheral tissues, where it suppresses adaptive thermogenesis in brown adipose tissue. Inhibition of 5-HT synthesis reduced the weight gain and improved the metabolic dysfunction in a diet-induced obesity mouse model. Genome-wide association studies also revealed genetic associations between the serotonergic system and obesity. Several genetic polymorphisms in tryptophan hydroxylase and 5-HT receptors were shown to have strong associations with obesity. These results support the clinical significance of the peripheral serotonergic system as a therapeutic target for obesity and diabetes.

Energy gains from lattice-enabled nuclear reactions

International Nuclear Information System (INIS)

Nagel, David J.

2015-01-01

The energy gain of a system is defined as the ratio of its output energy divided by the energy provided to operate the system. Most familiar systems have energy gains less than one due to various inefficiencies. By contrast, lattice-enabled nuclear reactions (LENR) offer high energy gains. Theoretical values in excess of 1000 are possible. Energy gains over 100 have already been reported. But, they have not yet been sustained for commercially significant durations. This article summarizes the current status of LENR energy gains. (author)

Motivation by potential gains and losses affects control processes via different mechanisms in the attentional network.

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Paschke, Lena M; Walter, Henrik; Steimke, Rosa; Ludwig, Vera U; Gaschler, Robert; Schubert, Torsten; Stelzel, Christine

2015-05-01

Attentional control in demanding cognitive tasks can be improved by manipulating the motivational state. Motivation to obtain gains and motivation to avoid losses both usually result in faster reaction times and stronger activation in relevant brain areas such as the prefrontal cortex, but little is known about differences in the underlying neurocognitive mechanisms of these types of motivation in an attentional control context. In the present functional magnetic resonance imaging (fMRI) study, we tested whether potential gain and loss as motivating incentives lead to overlapping or distinct neural effects in the attentional network, and whether one of these conditions is more effective than the other. A Flanker task with word stimuli as targets and distracters was performed by 115 healthy participants. Using a mixed blocked and event-related design allowed us to investigate transient and sustained motivation-related effects. Participants could either gain money (potential gain) or avoid losing money (potential loss) in different task blocks. Participants showed a congruency effect with increased reaction times for incongruent compared to congruent trials. Potential gain led to generally faster responses compared to the neutral condition and to stronger improvements than potential loss. Potential loss also led to shorter response times compared to the neutral condition, but participants improved mainly during incongruent and not during congruent trials. The event-related fMRI data revealed a main effect of congruency with increased activity in the left inferior frontal gyrus (IFG) and inferior frontal junction area (IFJ), the pre-supplementary motor area (pre-SMA), bilateral insula, intraparietal sulcus (IPS) and visual word form area (VWFA). While potential gain led to increased activity in a cluster of the IFJ and the VWFA only during incongruent trials, potential loss was linked to activity increases in these regions during incongruent and congruent trials. The

The quest for connection in interpersonal and therapeutic relationships.

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Wiseman, Hadas

2017-07-01

This paper focuses on the need for connection as a common core theme at the heart of both close relationships and therapeutic relationships and explores ways to connect these two research domains that have evolved as separate fields of study. Bowlby's attachment theory provides a strong conceptual and empirical base for linking human bonds and bonds in psychotherapy. The growing body of research intersecting attachment and psychotherapy (1980-2014) is documented, and meta-analytic studies on attachment-outcome and attachment-alliance links are highlighted. Five ways of studying attachment as a variable in psychotherapy are underscored: as moderator, as mediator, as outcome, client-therapist attachment match, and as process. By integrating conceptualizations and methods in studying relational narratives of client-therapist dyads (Core Conflictual Relationship Theme), measures of alliance, and client attachment to therapist during psychotherapy, we may discover unique client-therapist relational dances. Future fine-grained studies on how to promote core authentic relational relearning are important to clinicians, supervisors and trainers, who all share the common quest to alleviate interpersonal distress and enhance wellbeing. Directions for advancing research on interpersonal and therapeutic relationships are suggested. Learning from each other, both researchers of close relationships and of psychotherapy relationships can gain a deeper and multidimensional understanding of complex relational processes and outcomes.

Charge Gain, Voltage Gain, and Node Capacitance of the SAPHIRA Detector Pixel by Pixel

Science.gov (United States)

Pastrana, Izabella M.; Hall, Donald N. B.; Baker, Ian M.; Jacobson, Shane M.; Goebel, Sean B.

2018-01-01

The University of Hawai`i Institute for Astronomy has partnered with Leonardo (formerly Selex) in the development of HgCdTe linear mode avalanche photodiode (L-APD) SAPHIRA detectors. The SAPHIRA (Selex Avalanche Photodiode High-speed Infra-Red Array) is ideally suited for photon-starved astronomical observations, particularly near infrared (NIR) adaptive optics (AO) wave-front sensing. I have measured the stability, and linearity with current, of a 1.7-um (10% spectral bandpass) infrared light emitting diode (IR LED) used to illuminate the SAPHIRA and have then utilized this source to determine the charge gain (in e-/ADU), voltage gain (in uV/ADU), and node capacitance (in fF) for each pixel of the 320x256@24um SAPHIRA. These have previously only been averages over some sub-array. Determined from the ratio of the temporal averaged signal level to variance under constant 1.7-um LED illumination, I present the charge gain pixel-by-pixel in a 64x64 sub-array at the center of the active area of the SAPHIRA (analyzed separately as four 32x32 sub-arrays) to be about 1.6 e-/ADU (σ=0.5 e-/ADU). Additionally, the standard technique of varying the pixel reset voltage (PRV) in 10 mV increments and recording output frames for the same 64x64 subarray found the voltage gain per pixel to be about 11.7 uV/ADU (σ=0.2 uV/ADU). Finally, node capacitance was found to be approximately 23 fF (σ=6 fF) utilizing the aforementioned charge and voltage gain measurements. I further discuss the linearity measurements of the 1.7-um LED used in the charge gain characterization procedure.

Therapeutic time window and underlying therapeutic mechanism of breviscapine injection against cerebral ischemia/reperfusion injury in rats.

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Guo, Chao; Zhu, Yanrong; Weng, Yan; Wang, Shiquan; Guan, Yue; Wei, Guo; Yin, Ying; Xi, Miaomaio; Wen, Aidong

2014-01-01

Breviscapine injection is a Chinese herbal medicine standardized product extracted from Erigeron breviscapus (Vant.) Hand.-Mazz. It has been widely used for treating cardiovascular and cerebrovascular diseases. However, the therapeutic time window and the action mechanism of breviscapine are still unclear. The present study was designed to investigate the therapeutic time window and underlying therapeutic mechanism of breviscapine injection against cerebral ischemic/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2h followed by 24h of reperfusion. Experiment part 1 was used to investigate the therapeutic time window of breviscapine. Rats were injected intravenously with 50mg/kg breviscapine at different time-points of reperfusion. After 24h of reperfusion, neurologic score, infarct volume, brain water content and serum level of neuron specific enolase (NSE) were measured in a masked fashion. Part 2 was used to explore the therapeutic mechanism of breviscapine. 4-Hydroxy-2-nonenal (4-HNE), 8-hydroxyl-2'- deoxyguanosine (8-OHdG) and the antioxidant capacity of ischemia cortex were measured by ELISA and ferric-reducing antioxidant power (FRAP) assay, respectively. Immunofluorescence and western blot analysis were used to analyze the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Part 1: breviscapine injection significantly ameliorated neurologic deficit, reduced infarct volume and water content, and suppressed the levels of NSE in a time-dependent manner. Part 2: breviscapine inhibited the increased levels of 4-HNE and 8-OHdG, and enhanced the antioxidant capacity of cortex tissue. Moreover, breviscapine obviously raised the expression of Nrf2 and HO-1 proteins after 24h of reperfusion. The therapeutic time window of breviscapine injection for cerebral ischemia/reperfusion injury seemed to be within 5h after reperfusion. By up-regulating the expression of Nrf2/HO-1 pathway

Predicting the gain from deliquification measures for European wells

NARCIS (Netherlands)

Nennie, E.D.; Boer, J.P. de; Schiferli, W.

2014-01-01

Various Dutch operators have identified a need for increased application of deliquification measures in their North Sea wells. To help meet this need a Joint Industry Project (JIP) was set up to identify knowledge and experience gained in the United States on gas well deliquification and transfer

Muscle disuse caused by botulinum toxin injection leads to increased central gain of the stretch reflex in the rat

DEFF Research Database (Denmark)

Pingel, Jessica; Hultborn, Hans; Naslund-Koch, Lui

2017-01-01

Botulinum toxin (Btx) is used in children with cerebral palsy and other neurological patients to diminish spasticity and reduce the risk of development of contractures. Here, we investigated changes in the central gain of the stretch reflex circuitry in response to botulinum toxin injection...

Factors affecting pregnancy weight gain and relationships with maternal/fetal outcomes in Turkey

Science.gov (United States)

Akgun, Nilufer; Keskin, Huseyin L.; Ustuner, Isık; Pekcan, Gulden; Avsar, Ayse F.

2017-01-01

Objectives: To determine the effects of pre-pregnancy body mass index (BMI) and gestational weight gain on maternal and fetal complications, and to examine whether Turkish women achieve the recommended gestational weight gain. We also investigated the relationship between pregnancy weight gain and mode of delivery, with an examination of maternal anthropometry. Methods: A retrospective cross-sectional study was conducted on a population of 986 pregnant women between November 2011 and November 2015 at Atatürk Education and Research Hospital, Ankara, Turkey. Maternal age, BMI, monthly weight gain during pregnancy, infant birth weight, gender, and maternal and fetal adverse outcomes were evaluated. Results: The frequency of maternal complications was positively associated with elevated pre-pregnancy BMI (p0.05). The percentage of women who gained the Institute of Medicine (IOM)-recommended amount of weight was the highest in the underweight BMI group (54.1%) and the lowest in the obese BMI group (24.3%). Pregnancy weight gain exceeded IOM recommendations in the overweight (56.3%) and obese (52.5%) groups. Conclusions: While maternal weight gain during pregnancy affects neonatal body weight, higher pre-pregnancy BMI has an adverse effect on recommended weight gain during pregnancy, with increased maternal complications. PMID:28439600

Weight gain after bariatric surgery as a result of a large gastric stoma: endotherapy with sodium morrhuate may prevent the need for surgical revision.

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Catalano, Marc F; Rudic, Goran; Anderson, Alfred J; Chua, Thomas Y

2007-08-01

Obesity affects more than 30% of the U.S. population and is associated with the development of life-threatening complications. Numerous therapeutic approaches to the problem have been advocated, including low-calorie diets, anoretic drugs, behavior modifications, and exercise therapy. The only treatment proven to be effective in the long-term management of morbid obesity is surgical intervention. Complications of bariatric surgery include stomal stenosis and/or ulcer and stomal dilation (secondary to overeating). The latter complication can result in a gain of previously lost weight. To determine the effect of endoscopic injection by using a sclerosant (sodium morrhuate) to induce stomal stenosis in patients who present with stomal dilatation complicated by weight gain. Bariatric patients with a large gastric stoma were treated with sodium morrhuate stomal injection. Diameters of the stoma were followed at repeat endoscopy. Weight loss at scheduled clinic visits were compared with pretherapy weights. Twenty-eight patients (10 men, 18 women; age range, 27-58 years), after bariatric surgery with GI bypass, were referred with weight gain after initial weight loss. Weight gain was believed to be the result of a large gastric stoma. Treatment included injection of sodium morrhuate (1-2 mL circumferentially) surrounding the stoma. A total of 1 to 3 injection sessions were performed in an attempt to achieve a stoma diameter of 1.2 cm or smaller. Treatment success was defined as a decrease of stoma size to weight loss >or=75% of the weight the patient gained after establishing a steady state post bariatric surgery weight. A total of 2.3 injection sessions were performed. Successful endotherapy was achieved in 18 of 28 patients (64%). One patient developed symptoms of stomal stenosis, which required 2 separate balloon dilating sessions. No other complications were encountered. Retrospective case series. Endoscopic injection of sodium morrhuate surrounding the dilated

Comparison of Video Head Impulse Test (vHIT) Gains Between Two Commercially Available Devices and by Different Gain Analytical Methods.

Science.gov (United States)

Lee, Sang Hun; Yoo, Myung Hoon; Park, Jun Woo; Kang, Byung Chul; Yang, Chan Joo; Kang, Woo Suk; Ahn, Joong Ho; Chung, Jong Woo; Park, Hong Ju

2018-06-01

To evaluate whether video head impulse test (vHIT) gains are dependent on the measuring device and method of analysis. Prospective study. vHIT was performed in 25 healthy subjects using two devices simultaneously. vHIT gains were compared between these instruments and using five different methods of comparing position and velocity gains during head movement intervals. The two devices produced different vHIT gain results with the same method of analysis. There were also significant differences in the vHIT gains measured using different analytical methods. The gain analytic method that compares the areas under the velocity curve (AUC) of the head and eye movements during head movements showed lower vHIT gains than a method that compared the peak velocities of the head and eye movements. The former method produced the vHIT gain with the smallest standard deviation among the five procedures tested in this study. vHIT gains differ in normal subjects depending on the device and method of analysis used, suggesting that it is advisable for each device to have its own normal values. Gain calculations that compare the AUC of the head and eye movements during the head movements show the smallest variance.

Can LENR Energy Gains Exceed 1000?

Science.gov (United States)

Nagel, David J.

2011-03-01

Energy gain is defined as the energy realized from reactions divided by the energy required to produce those reactions. Low Energy Nuclear Reactions (LENR) have already been measured to significantly exceed the energy gain of 10 projected from ITER,possibly 15 years from now. Electrochemical experiments using the Pd-D system have shown energy gains exceeding 10. Gas phase experiments with the Ni-H system were reported to yield energy gains of over 100. Neither of these reports has been adequately verified or reproduced. However, the question in the title still deserves consideration. If, as thought by many, it is possible to trigger nuclear reactions that yield MeV energies with chemical energies of the order of eV, then the most optimistic expectation is that LENR gains could approach one million. Hence, the very tentative answer to the question above is yes. However, if LENR could be initiated with some energy cost, and then continue to ``burn,'' very high energy gains might be realized. Consider a match and a pile of dry logs. The phenomenon termed ``heat after death'' will be examined to see if it might be the initial evidence for nuclear ``burning.''

Characterization of transient gain x-ray lasers

International Nuclear Information System (INIS)

Dunn, J.; Osterheld, A.; Shlyaptsev, V.

1999-01-01

We have performed numerical simulations of the transient collisional excitation Ni-like Pd 4d → 4p J = 0 → 1 147 angstrom laser transition recently observed at Lawrence Livermore National Laboratory (LLNL). The high gain ∼35 cm results from the experiment are compared with detailed modeling simulations from the 1-D RADEX code in order to better understand the main physics issues affecting the measured gain and x-ray laser propagation along the plasma column. Simulations indicate that the transient gain lifetime associated with the short pulse pumping and refraction of the x-ray laser beam out of the gain region are the main detrimental effects. Gain lifetimes of ∼7 ps(1/e decay) are inferred from the smoothly changing gain experimental observations and are in good agreement with the simulations. Furthermore, the modeling results indicate the presence of a longer-lived but lower gain later in time associated with the transition from transient to quasi-steady state excitation

Emotional eating as a mediator between depression and weight gain.

Science.gov (United States)

van Strien, Tatjana; Konttinen, Hanna; Homberg, Judith R; Engels, Rutger C M E; Winkens, Laura H H

2016-05-01

Depression is often associated with weight gain but underlying mechanisms are unclear. This study assessed whether three psychological eating styles (emotional eating, external eating and restrained eating) act as mediators between depression and weight gain. We used structural equation modelling to test the hypothesized mediation models in a sample of 298 fathers and 294 mothers by assessing self-reported eating styles (Dutch Eating Behavior Questionnaire), depressive feelings (Depressive Mood List) and body mass index (BMI) at baseline and BMI after five years. In the model with emotional eating we also assessed the moderation effect of 5-HTTLPR genotype in a sub-sample of 520 Caucasians. All analyses were performed separately for the two sexes. Although the overall effect of depression on weight gain was statistically non-significant in both sexes, there was a causal chain between depression, emotional eating and weight gain in the mothers. Depressive symptoms were related to higher emotional eating and emotional eating predicted greater increases in BMI independently of depression. Moreover, the indirect effect (via emotional eating) of depression on BMI change was significant (Beta = 0.18, P = 0.026). This mediation effect was found to be independent of 5-HTTLPR genotype. No such mediation effect was found for the fathers. Further, external eating and restrained eating did not act as mediators between depression and weight gain in either sex. The finding that emotional eating acted as mediator between depression and weight gain in the mothers suggests that obesity interventions should take emotional eating into account. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Impact of Kangaroo Care on Premature Infant Weight Gain.

Science.gov (United States)

Evereklian, Melvina; Posmontier, Bobbie

Preterm births occur among 11.4% of all live infant births. Without steady weight gain, premature infants may experience lengthy hospitalizations, neurodevelopmental deficits and hospital readmissions, which can increase the financial burden on the health care system and their families. The total U.S. health-related costs linked to preterm infant deliveries are estimated at $4.33 billion. Kangaroo care is a feasible practice that can improve preterm infant weight gain. However, this intervention is utilized less often throughout the U.S. due to numerous barriers including a lack of consistent protocols, inadequate knowledge, and decreased level of confidence in demonstrating the proper kangarooing technique. An integrative review was conducted to evaluate the impact of kangaroo care on premature infant weight gain in order to educate nurses about its efficacy among preterm infants. A literature search was conducted using CINAHL, PubMed, Cochrane Reviews, ClinicalKey and Google Scholar. Large volume searches were restricted using appropriate filters and limiters. Most of the evaluated studies determined that weight gain was greater among the kangarooing premature infants. Kangaroo care is a low-tech low-cost modality that can facilitate improved preterm infant weight gain even in low-resource settings. Despite its current efficacy, kangaroo care is not widely utilized due to several barriers including an absence of standardized protocols and a lack of knowledge about its benefits. Kangaroo care can become a widespread formalized practice after nurses and parents learn about the technique and its numerous benefits for premature infants, including its association with improved weight gain. Copyright © 2017 Elsevier Inc. All rights reserved.

Gestational Weight Gain and Overweight in Children Aged 3–6 Years

Directory of Open Access Journals (Sweden)

Lianhong Guo

2015-08-01

Full Text Available Objective: To determine whether gestational weight gain (GWG was associated with increased odds of childhood overweight after accounting for pre-pregnancy BMI. Methods: In a prospective cohort study based on a premarital and perinatal health care system in China, data of 100 612 mother-child pairs were obtained. The main exposure was GWG as both a continuous and categorical variable. The outcome measure was overweight, defined by age- and sex-specific cutoff values for body mass index (BMI in children aged 3–6 years. Results: A 1-kg increase in maternal GWG was associated with an increase of 0.009 (95% confidence interval [CI]: 0.007–0.010, P < 0.001 in children’s mean BMI; in the subgroup of pre-pregnancy overweight/obese mothers, the increase in children’s BMI was 0.028 (95% CI, 0.017–0.039, P < 0.001. Excessive GWG played an important role in childhood overweight when adequate GWG was used as the reference, with an odds ratio (OR of 1.21 (95% CI, 1.12–1.29. The risk was highest (OR 2.22; 95% CI, 1.79–2.76 in the children of mothers who were overweight/obese before pregnancy and gained excessive weight during pregnancy. Conclusions: Greater maternal GWG was associated with greater offspring BMI, and the risk of overweight was doubled in children whose mothers were overweight/obese before pregnancy and gained excessive weight during pregnancy. As a result, maintenance of appropriate weight gain during pregnancy and prophylaxis of maternal overweight/obesity before pregnancy should be a strategy for preventing childhood overweight/obesity.

Divisive gain modulation of motoneurons by inhibition optimizes muscular control

DEFF Research Database (Denmark)

Vestergaard, Mikkel; Berg, Rune W.

2015-01-01

unclear whether the motoneuron gain, i.e., the slope of the transformation between synaptic input and spiking output, is also modulated to reduce variability in force. To address this issue, we use turtle hindlimb scratching as a model for fine motor control, since this behavior involves precise limb...... movement to rub the location of somatic nuisance touch. We recorded intracellularly from motoneurons in a reduced preparation where the limbs were removed to increase mechanical stability and the motor nerve activity served as a surrogate for muscle force. We found that not only is the gain of motoneurons...

X-ray application in diagnostics and therapeutics

International Nuclear Information System (INIS)

Braun, H.

1975-01-01

The lecture gives a general survey on the present possibilities of application of X-rays and radio-isotopes in medical diagnostics and therapeutics. The possibility of decreasing the radiation exposure by using image intensifiers and television is particularly indicated. The advantages of scintiscanning in diagnostics are presented by means of a series of examples. The increasing significance of telecurie equipment and particle accelerators are refered to in therapeutics. Finally, the radiation risk due to the medical application of radiation to the patient and the personnel is discussed and compared to the natural radiation exposure. (ORU/LH) [de

Dynamic excitatory and inhibitory gain modulation can produce flexible, robust and optimal decision-making.

Directory of Open Access Journals (Sweden)

Ritwik K Niyogi

Full Text Available Behavioural and neurophysiological studies in primates have increasingly shown the involvement of urgency signals during the temporal integration of sensory evidence in perceptual decision-making. Neuronal correlates of such signals have been found in the parietal cortex, and in separate studies, demonstrated attention-induced gain modulation of both excitatory and inhibitory neurons. Although previous computational models of decision-making have incorporated gain modulation, their abstract forms do not permit an understanding of the contribution of inhibitory gain modulation. Thus, the effects of co-modulating both excitatory and inhibitory neuronal gains on decision-making dynamics and behavioural performance remain unclear. In this work, we incorporate time-dependent co-modulation of the gains of both excitatory and inhibitory neurons into our previous biologically based decision circuit model. We base our computational study in the context of two classic motion-discrimination tasks performed in animals. Our model shows that by simultaneously increasing the gains of both excitatory and inhibitory neurons, a variety of the observed dynamic neuronal firing activities can be replicated. In particular, the model can exhibit winner-take-all decision-making behaviour with higher firing rates and within a significantly more robust model parameter range. It also exhibits short-tailed reaction time distributions even when operating near a dynamical bifurcation point. The model further shows that neuronal gain modulation can compensate for weaker recurrent excitation in a decision neural circuit, and support decision formation and storage. Higher neuronal gain is also suggested in the more cognitively demanding reaction time than in the fixed delay version of the task. Using the exact temporal delays from the animal experiments, fast recruitment of gain co-modulation is shown to maximize reward rate, with a timescale that is surprisingly near the

Gestational Weight Gain-for-Gestational Age Z-Score Charts Applied across U.S. Populations.

Science.gov (United States)

Leonard, Stephanie A; Hutcheon, Jennifer A; Bodnar, Lisa M; Petito, Lucia C; Abrams, Barbara

2018-03-01

Gestational weight gain may be a modifiable contributor to infant health outcomes, but the effect of gestational duration on gestational weight gain has limited the identification of optimal weight gain ranges. Recently developed z-score and percentile charts can be used to classify gestational weight gain independent of gestational duration. However, racial/ethnic variation in gestational weight gain and the possibility that optimal weight gain differs among racial/ethnic groups could affect generalizability of the z-score charts. The objectives of this study were (1) to apply the weight gain z-score charts in two different U.S. populations as an assessment of generalisability and (2) to determine whether race/ethnicity modifies the weight gain range associated with minimal risk of preterm birth. The study sample included over 4 million live, singleton births in California (2007-2012) and Pennsylvania (2003-2013). We implemented a noninferiority margin approach in stratified subgroups to determine weight gain ranges for which the adjusted predicted marginal risk of preterm birth (gestation gain between California and Pennsylvania births, and among several racial/ethnic groups in California. The optimal ranges decreased as severity of prepregnancy obesity increased in all groups. The findings support the use of weight gain z-score charts for studying gestational age-dependent outcomes in diverse U.S. populations and do not support weight gain recommendations tailored to race/ethnicity. © 2017 John Wiley & Sons Ltd.

Outrunning major weight gain: a prospective study of 8,340consistent runners during 7 years of follow-up

Energy Technology Data Exchange (ETDEWEB)

Williams, Paul T.

2006-01-06

Background: Body weight increases with aging. Short-term,longitudinal exercise training studies suggest that increasing exerciseproduces acute weight loss, but it is not clear if the maintenance oflong-term, vigorous exercise attenuates age-related weight gain inproportion to the exercise dose. Methods: Prospective study of 6,119 maleand 2,221 female runners whose running distance changed less than 5 km/wkbetween their baseline and follow-up survey 7 years later. Results: Onaverage, men who ran modest (0-24 km/wk), intermediate (24-48 km/wk) orprolonged distances (>_48 km/wk) all gained weight throughage 64,however, those who ran ?48 km/wk had one-half the average annual weightgain of those who ran<24 km/wk. Age-related weight gain, and itsreduction by running, were both greater in younger than older men. Incontrast, men s gain in waist circumference with age, and its reductionby running, were the same in older and younger men. Women increased theirbody weight and waist and hip circumferences over time, regardless ofage, which was also reduced in proportion to running distance. In bothsexes, running did not attenuate weight gain uniformly, but ratherdisproportionately prevented more extreme increases. Conclusion: Men andwomen who remain vigorously active gain less weight as they age and thereduction is in proportion to the exercise dose.

Heavy inertial particles in turbulent flows gain energy slowly but lose it rapidly

Science.gov (United States)

Bhatnagar, Akshay; Gupta, Anupam; Mitra, Dhrubaditya; Pandit, Rahul

2018-03-01

We present an extensive numerical study of the time irreversibility of the dynamics of heavy inertial particles in three-dimensional, statistically homogeneous, and isotropic turbulent flows. We show that the probability density function (PDF) of the increment, W (τ ) , of a particle's energy over a time scale τ is non-Gaussian, and skewed toward negative values. This implies that, on average, particles gain energy over a period of time that is longer than the duration over which they lose energy. We call this slow gain and fast loss. We find that the third moment of W (τ ) scales as τ3 for small values of τ . We show that the PDF of power-input p is negatively skewed too; we use this skewness Ir as a measure of the time irreversibility and we demonstrate that it increases sharply with the Stokes number St for small St; this increase slows down at St≃1 . Furthermore, we obtain the PDFs of t+ and t-, the times over which p has, respectively, positive or negative signs, i.e., the particle gains or loses energy. We obtain from these PDFs a direct and natural quantification of the slow gain and fast loss of the energy of the particles, because these PDFs possess exponential tails from which we infer the characteristic loss and gain times tloss and tgain, respectively, and we obtain tlossprobability in the strain-dominated region than in the vortical one; in contrast, the slow gain in the energy of the particles is equally likely in vortical or strain-dominated regions of the flow.

Pharmacokinetic and pharmacodynamic considerations for the next generation protein therapeutics.

Science.gov (United States)

Shah, Dhaval K

2015-10-01

Increasingly sophisticated protein engineering efforts have been undertaken lately to generate protein therapeutics with desired properties. This has resulted in the discovery of the next generation of protein therapeutics, which include: engineered antibodies, immunoconjugates, bi/multi-specific proteins, antibody mimetic novel scaffolds, and engineered ligands/receptors. These novel protein therapeutics possess unique physicochemical properties and act via a unique mechanism-of-action, which collectively makes their pharmacokinetics (PK) and pharmacodynamics (PD) different than other established biological molecules. Consequently, in order to support the discovery and development of these next generation molecules, it becomes important to understand the determinants controlling their PK/PD. This review discusses the determinants that a PK/PD scientist should consider during the design and development of next generation protein therapeutics. In addition, the role of systems PK/PD models in enabling rational development of the next generation protein therapeutics is emphasized.

Fluid biomarkers in clinical trials of Alzheimer’s disease therapeutics

Directory of Open Access Journals (Sweden)

Aaron eRitter

2015-08-01

Full Text Available With the demographic shift of the global population towards longer life expectancy, the number of people living with Alzheimer’s disease (AD has rapidly expanded and is projected to triple by the year 2050. Current treatments provide symptomatic relief but do not affect the underlying pathology of the disease. Therapies that prevent or slow the progression of the disease are urgently needed to avoid this growing public health emergency. Insights gained from decades of research have begun to unlock the pathophysiology of this complex disease and have provided targets for disease modifying therapies. In the last decade, few therapeutic agents designed to modify the underlying disease process have progressed to clinical trials and none have been brought to market. With the focus on disease modification, biomarkers promise to play an increasingly important role in clinical trials. Six biomarkers have now been included in diagnostic criteria for AD and are regularly incorporated into clinical trials. Three biomarkers are neuroimaging measures—hippocampal atrophy measured by magnetic resonance imaging (MRI, amyloid uptake as measured by Pittsburg compound B positron emission tomography (PiB PET, and decreased fluorodeoxyglucose (18F uptake as measured by positron emission tomography (FDG PET—and three are sampled from fluid sources—cerebrospinal fluid (CSF levels

Perspective on Cancer Therapeutics Utilizing Analysis of Circulating Tumor Cells

Directory of Open Access Journals (Sweden)

Keun-Yeong Jeong

2018-04-01

Full Text Available Various methods are available for cancer screening, and the methods are performed depending on the origin site of cancer. Among these methods, biopsy followed by medical imaging is the most common. After cancer progression is determined, an optimal treatment—such as surgery, chemotherapy, and/or radiation therapy—is selected. A new assay has been developed that detects circulating tumor cells (CTCs. Tracking changes in CTCs may reveal important tumoral sensitivity information or resistance patterns to specific regimens and prompt changes in therapy on a personalized basis. Characterization of CTCs at the DNA, RNA, and protein levels is important for gaining insight for clinical applications. A small number of CTCs can be analyzed to obtain genome information such as the progression of cancer including metastasis, even in a single cluster. Although many clinical studies, particularly CTC enumeration and detection of specific oncogene expression, have increased the success rate of diagnosis and predicting prognosis, there is no consensus regarding the technical approaches and various aspects of the methodology, making it difficult to standardize optimal methods for CTC analysis. However, ongoing technological advances are currently being achieved and large-scale clinical studies are being conducted. Applying CTC analysis in the clinic would be very useful for advancing diagnosis, prognosis prediction, and therapeutics.

Maternal prepregnant body mass index, duration of breastfeeding, and timing of complementary food introduction are associated with infant weight gain

DEFF Research Database (Denmark)

Baker, Jennifer Lyn; Michaelsen, Kim F; Rasmussen, Kathleen M

2004-01-01

). In this sample, prepregnant obesity (BMI > or = 30.0), short durations of breastfeeding, and earlier introduction of complementary food were associated with 0.7 kg of additional weight gain during infancy. CONCLUSIONS: Infant weight gain is associated with maternal prepregnant BMI and with an interaction between...... these associations among 3768 mother-infant dyads from the Danish National Birth Cohort. RESULTS: In multiple regression analyses, increasing maternal prepregnant BMI, decreasing durations of breastfeeding, and earlier complementary food introduction were associated with increased infant weight gain. An interaction...... was identified for short durations of breastfeeding (food introduction (associated with greater infant weight gain; however, the timing of complementary food introduction did not increase infant weight gain at longer durations of breastfeeding (> or =20 wk...

Increase in intracellular PGE2 induces apoptosis in Bax-expressing colon cancer cell

International Nuclear Information System (INIS)

Lalier, Lisenn; Pedelaborde, François; Braud, Christophe; Menanteau, Jean; M Vallette, François; Olivier, Christophe

2011-01-01

NSAIDs exhibit protective properties towards some cancers, especially colon cancer. Yet, it is not clear how they play their protective role. PGE 2 is generally shown as the only target of the NSAIDs anticancerous activity. However, PGE 2 known targets become more and more manifold, considering both the molecular pathways involved and the target cells in the tumour. The role of PGE 2 in tumour progression thus appears complex and multipurpose. To gain understanding into the role of PGE 2 in colon cancer, we focused on the activity of PGE 2 in apoptosis in colon cancer cell lines. We observed that an increase in intracellular PGE 2 induced an apoptotic cell death, which was dependent on the expression of the proapoptotic protein Bax. This increase was induced by increasing PGE 2 intracellular concentration, either by PGE 2 microinjection or by the pharmacological inhibition of PGE 2 exportation and enzymatic degradation. We present here a new sight onto PGE 2 in colon cancer cells opening the way to a new prospective therapeutic strategy in cancer, alternative to NSAIDs

Therapeutically induced changes in couple identity: the role of we-ness and interpersonal processing in relationship satisfaction.

Science.gov (United States)

Reid, David W; Dalton, E Jane; Laderoute, Kristine; Doell, Faye K; Nguyen, Thao

2006-08-01

Changes in partners' sense of self-in-relationship, which a systemic-constructivist couple therapy (SCCT) induced, led to robust improvement in satisfaction in 2 studies and a follow-up study. In each study, 13 referred couples completed measures of satisfaction, mutuality, similarities, and other-in-self construal pre-post 12 hours of SCCT. The authors reliably coded transcripts of 1st and final sessions for each partner's we-ness, the identity that each partner establishes in relationship to the other. Having met the criteria for the rigorous study of change in single group process-outcome design, changes in we-ness accompanied large posttherapy dyadic increments on all variables in each study. Therapeutic gains appeared at follow-up and correlated with increased we-ness obtained at end of therapy 2 years earlier. The authors raise theoretical implications for all types of couple therapies and explain clinical techniques.

Patterns of gestational weight gain and its association with ...

African Journals Online (AJOL)

Background: Despite the increasing global importance of gestational weight gain (GWG) and its impact on birthweight, little is known about the patterns of GWG in African populations. Objectives: To determine the pattern of GWG and its association with birthweight in Nigeria. Methods: It was a longitudinal study of 200 ...

Influence of pre-pregnancy leisure time physical activity on gestational and postpartum weight gain and birth weight - a cohort study.

Science.gov (United States)

Hegaard, Hanne Kristine; Rode, Line; Katballe, Malene Kjær; Langberg, Henning; Ottesen, Bent; Damm, Peter

2017-08-01

In order to examine the association between pre-pregnancy leisure time physical activities and gestational weight gain, postpartum weight gain and birth weight, we analysed prospectively collected data from 1827 women with singleton term pregnancies. Women were categorised in groups of sedentary women, light exercisers, moderate exercisers and competitive athletes. The results showed that sedentary women on average gained 14.1 kg during pregnancy, whereas light exercisers gained 13.7 kg, moderate exercisers gained 14.3 kg and competitive athletes 16.1 kg. Competitive athletes had an increased risk of having a gestational weight gain above Institute of Medicine (IOM) recommendations with an odds ratio of 2.60 (1.32-5.15) compared to light exercisers. However, birth weight and one year postpartum weight was similar for all four groups. Thus, although competitive athletes gain more weight than recommended during pregnancy, this may not affect birth weight or postpartum weight. Impact statement What is already known on this subjectPrevious studies have found that increased pre-pregnancy physical activity is associated with lower gestational weight gain during the last trimester, but showed no association between the pre-pregnancy level of physical activity and mean birth weight. What the results of this study addWe found that women classified as competitive exercisers had a 2.6-fold increased risk of gaining more weight than recommended compared to light exercisers. Nearly 6 out of 10 women among the competitive exercisers gained more weight than recommended by IOM. Surprisingly, this did not appear to increase birth weight or post-partum weight gain, but other adverse effects cannot be excluded. What the implications are of these findings for clinical practice and/or further researchIn the clinical practice it may be relevant to focus on and advise pre-pregnancy competitive exercisers in order to prevent excessive gestational weight gain.

Ebola virus (EBOV) infection: Therapeutic strategies.

Science.gov (United States)

De Clercq, Erik

2015-01-01

Within less than a year after its epidemic started (in December 2013) in Guinea, Ebola virus (EBOV), a member of the filoviridae, has spread over a number of West-African countries (Guinea, Sierra Leone and Liberia) and gained allures that have been unprecedented except by human immunodeficiency virus (HIV). Although EBOV is highly contagious and transmitted by direct contact with body fluids, it could be counteracted by the adequate chemoprophylactic and -therapeutic interventions: vaccines, antibodies, siRNAs (small interfering RNAs), interferons and chemical substances, i.e. neplanocin A derivatives (i.e. 3-deazaneplanocin A), BCX4430, favipiravir (T-705), endoplasmic reticulum (ER) α-glucosidase inhibitors and a variety of compounds that have been found to inhibit EBOV infection blocking viral entry or by a mode of action that still has to be resolved. Much has to be learned from the mechanism of action of the compounds active against VSV (vesicular stomatitis virus), a virus belonging to the rhabdoviridae, that in its mode of replication could be exemplary for the replication of filoviridae. Copyright © 2014 Elsevier Inc. All rights reserved.

Therapeutic Community in a California Prison: Treatment Outcomes after 5 Years

Science.gov (United States)

Zhang, Sheldon X.; Roberts, Robert E. L.; McCollister, Kathryn E.

2011-01-01

Therapeutic communities have become increasingly popular among correctional agencies with drug-involved offenders. This quasi-experimental study followed a group of inmates who participated in a prison-based therapeutic community in a California state prison, with a comparison group of matched offenders, for more than 5 years after their initial…

Olanzapine causes hypothermia, inactivity, a deranged feeding pattern and weight gain in female Wistar rats

NARCIS (Netherlands)

Evers, S. S.; Calcagnoli, F.; van Dijk, G.; Scheurink, A. J. W.

2010-01-01

Olanzapine is an a-typical antipsychotic drug antagonizing predominantly 5-HT and dopamine but also histamine muscarin and a adrenergic receptors In humans Olanzapine induces weight gain and increases the risk of type 2 diabetes The underlying mechanisms of Olanzapine-induced weight gain are unclear

Predictive Variable Gain Iterative Learning Control for PMSM

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Huimin Xu

2015-01-01

Full Text Available A predictive variable gain strategy in iterative learning control (ILC is introduced. Predictive variable gain iterative learning control is constructed to improve the performance of trajectory tracking. A scheme based on predictive variable gain iterative learning control for eliminating undesirable vibrations of PMSM system is proposed. The basic idea is that undesirable vibrations of PMSM system are eliminated from two aspects of iterative domain and time domain. The predictive method is utilized to determine the learning gain in the ILC algorithm. Compression mapping principle is used to prove the convergence of the algorithm. Simulation results demonstrate that the predictive variable gain is superior to constant gain and other variable gains.

Pump-beam-instability limits to Raman-gain-doublet ''fast-light'' pulse propagation

International Nuclear Information System (INIS)

Stenner, Michael D.; Gauthier, Daniel J.

2003-01-01

We investigate the behavior of a system for generating ''fast-light'' pulses in which a bichromatic Raman pumping beam is used to generate optical gain at two frequencies and a region of anomalous dispersion between them. It is expected that increasing the gain will increase the pulse advancement. However, as the gain increases, the pumping field becomes increasingly distorted, effectively limiting the pulse advancement. We observe as much as 12% of the input pump power converted to orthogonal polarization, broadening of the initially bichromatic pump field (25 MHz initial frequency separation) to more than 2.5 GHz, and a temporal collapse of the pump beam into an erratic train of sub-500-ps pulses. The instability is attributed to the combined effects of the cross modulation instability and stimulated Raman scattering. Extreme distortion of an injected pulse that should (absent the instability) experience an advancement of 21% of its width is observed. We conclude that the fast-light pulse advancement is limited to just a few percent of the pulse width using this pulse advancement technique. The limitation imposed by the instability is important because careful study of the information velocity in fast-light pulses requires that pulse advancement be large enough to distinguish the velocities of different pulse features. Possible methods for achieving pulse advancement by avoiding the distortion caused by the instability are discussed

Maternal thyroid function, prepregnancy obesity and gestational weight gain-The Generation R Study: A prospective cohort study.

Science.gov (United States)

Collares, Fernanda M; Korevaar, Tim I M; Hofman, Albert; Steegers, Eric A P; Peeters, Robin P; Jaddoe, Vincent W V; Gaillard, Romy

2017-12-01

Maternal prepregnancy obesity and excessive gestational weight gain are associated with pregnancy complications. Thyroid function is related to differences in body mass index (BMI) in adult populations. We examined the associations of maternal thyroid function in early pregnancy with maternal BMI and weight gain during pregnancy. In a population-based prospective cohort study among 5726 mothers, we measured maternal TSH and FT4 levels at 13.5 weeks of gestation (95% range: 9.7-17.6 weeks). Maternal weight was assessed before pregnancy and in each trimester. Higher maternal TSH levels were associated with higher prepregnancy BMI (difference: 0.18 kg/m 2 [95% CI: 0.01, 0.36] per SD increase in maternal TSH level) and higher total gestational weight gain (difference: 0.02 kg/wk [95% CI: 0.01, 0.03] per SD increase in maternal TSH level). Higher maternal FT4 levels were associated with lower prepregnancy BMI (difference: -0.44 kg/m 2 [95% CI: -0.63, -0.26] per SD increase in maternal FT4 level) and lower total gestational weight gain (difference: -0.01 kg/wk [95% CI: -0.02, -0.01] per SD increase in maternal FT4 level). The associations of maternal thyroid function with weight gain in early pregnancy were stronger than those with weight gain in mid and late-pregnancy. Maternal hypothyroidism was associated with higher prepregnancy BMI and early pregnancy weight gain, whereas opposite effects were observed for maternal hyperthyroidism (Pgain. Further studies are needed to explore maternal and foetal consequences. © 2017 John Wiley & Sons Ltd.

Weight gain - unintentional

Science.gov (United States)

... diabetes Hormone changes or medical problems can also cause unintentional weight gain. This may be due to: Cushing syndrome Underactive thyroid, or low thyroid (hypothyroidism) Polycystic ovary syndrome Menopause Pregnancy Bloating, or swelling ...

Weight Gain following Pallidal Deep Brain Stimulation: A PET Study.

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Paul Sauleau

Full Text Available The mechanisms behind weight gain following deep brain stimulation (DBS surgery seem to be multifactorial and suspected depending on the target, either the subthalamic nucleus (STN or the globus pallidus internus (GPi. Decreased energy expenditure following motor improvement and behavioral and/or metabolic changes are possible explanations. Focusing on GPi target, our objective was to analyze correlations between changes in brain metabolism (measured with PET and weight gain following GPi-DBS in patients with Parkinson's disease (PD. Body mass index was calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D-glucose PET four months before and four months after the start of GPi-DBS in 19 PD patients. Dopaminergic medication was included in the analysis to control for its possible influence on brain metabolism. Body mass index increased significantly by 0.66 ± 1.3 kg/m2 (p = 0.040. There were correlations between weight gain and changes in brain metabolism in premotor areas, including the left and right superior gyri (Brodmann area, BA 6, left superior gyrus (BA 8, the dorsolateral prefrontal cortex (right middle gyrus, BAs 9 and 46, and the left and right somatosensory association cortices (BA 7. However, we found no correlation between weight gain and metabolic changes in limbic and associative areas. Additionally, there was a trend toward a correlation between reduced dyskinesia and weight gain (r = 0.428, p = 0.067. These findings suggest that, unlike STN-DBS, motor improvement is the major contributing factor for weight gain following GPi-DBS PD, confirming the motor selectivity of this target.

α1-Proteinase inhibitor (human) in the treatment of hereditary emphysema secondary to α1-antitrypsin deficiency: number and costs of years of life gained.

Science.gov (United States)

Sclar, David Alexander; Evans, Marc A; Robison, Linda M; Skaer, Tracy L

2012-05-01

α(1)-Antitrypsin deficiency (α-ATD) is a disorder inherited in an autosomal recessive pattern, with co-dominant alleles known as the protease inhibitor system (Pi). The main function of α(1)-antitrypsin (α-AT) is to protect the lungs against a powerful elastase released from neutrophil leucocytes. α-ATD typically presents with a serum α-AT level of 80 mg/dL), with few, if any, adverse effects. The present study was designed to discern the number of years of life gained, and the expense per year of life gained, associated with use of α-AT augmentation therapy (α(1)-proteinase inhibitor [human]), relative to 'no therapeutic intervention' in persons with α-ATD. Monte Carlo simulation (MCS) was used to: (i) estimate the number of years of life gained; and (ii) estimate the health service expenditures per year of life gained for persons receiving, or not receiving, α-AT augmentation therapy. MCS afforded a decision-analytical framework parameterized with both stochastic (random) and deterministic (fixed) components, and yielded a fiscal risk-profile for each simulated cohort of interest (eight total: by sex, smoking status [non-smoker; or past use (smoker)]; and use of α-AT augmentation therapy). The stochastic components employed in the present inquiry were: (i) age-specific body weight, and height; (ii) age-specific mortality; and (iii) the probability distribution for receipt of a lung transplant, as a function of FEV(1). The deterministic components employed in the present inquiry were: (i) age in years for the simulated cohort; (ii) outlays for α-AT augmentation therapy; (iii) health service expenditures associated with receipt of a lung transplant; (iv) annual decline in FEV(1); (v) percent predicted FEV(1); (vi) initiation of α-AT augmentation therapy as a function of percent predicted FEV(1); (vii) need for a lung transplant as a function of percent predicted FEV(1); (viii) annual rate of lung infection; and (ix) mortality as a function of percent

Cycle training induces muscle hypertrophy and strength gain: strategies and mechanisms.

Science.gov (United States)

Ozaki, Hayao; Loenneke, J P; Thiebaud, R S; Abe, T

2015-03-01

Cycle training is widely performed as a major part of any exercise program seeking to improve aerobic capacity and cardiovascular health. However, the effect of cycle training on muscle size and strength gain still requires further insight, even though it is known that professional cyclists display larger muscle size compared to controls. Therefore, the purpose of this review is to discuss the effects of cycle training on muscle size and strength of the lower extremity and the possible mechanisms for increasing muscle size with cycle training. It is plausible that cycle training requires a longer period to significantly increase muscle size compared to typical resistance training due to a much slower hypertrophy rate. Cycle training induces muscle hypertrophy similarly between young and older age groups, while strength gain seems to favor older adults, which suggests that the probability for improving in muscle quality appears to be higher in older adults compared to young adults. For young adults, higher-intensity intermittent cycling may be required to achieve strength gains. It also appears that muscle hypertrophy induced by cycle training results from the positive changes in muscle protein net balance.

Persistency of Prediction Accuracy and Genetic Gain in Synthetic Populations Under Recurrent Genomic Selection

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Dominik Müller

2017-03-01

Full Text Available Recurrent selection (RS has been used in plant breeding to successively improve synthetic and other multiparental populations. Synthetics are generated from a limited number of parents ( Np , but little is known about how Np affects genomic selection (GS in RS, especially the persistency of prediction accuracy (rg , g ^ and genetic gain. Synthetics were simulated by intermating Np= 2–32 parent lines from an ancestral population with short- or long-range linkage disequilibrium (LDA and subjected to multiple cycles of GS. We determined rg , g ^ and genetic gain across 30 cycles for different training set (TS sizes, marker densities, and generations of recombination before model training. Contributions to rg , g ^ and genetic gain from pedigree relationships, as well as from cosegregation and LDA between QTL and markers, were analyzed via four scenarios differing in (i the relatedness between TS and selection candidates and (ii whether selection was based on markers or pedigree records. Persistency of rg , g ^ was high for small Np , where predominantly cosegregation contributed to rg , g ^ , but also for large Np , where LDA replaced cosegregation as the dominant information source. Together with increasing genetic variance, this compensation resulted in relatively constant long- and short-term genetic gain for increasing Np > 4, given long-range LDA in the ancestral population. Although our scenarios suggest that information from pedigree relationships contributed to rg , g ^ for only very few generations in GS, we expect a longer contribution than in pedigree BLUP, because capturing Mendelian sampling by markers reduces selective pressure on pedigree relationships. Larger TS size (NTS and higher marker density improved persistency of rg , g ^ and hence genetic gain, but additional recombinations could not increase genetic gain.

Genetic gains in wheat in Turkey: Winter wheat for dryland conditions

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Mesut Keser

2017-12-01

Full Text Available Wheat breeders in Turkey have been developing new varieties since the 1920s, but few studies have evaluated the rates of genetic improvement. This study determined wheat genetic gains by evaluating 22 winter/facultative varieties released for rainfed conditions between 1931 and 2006. The study was conducted at three locations in Turkey during 2008–2012, with a total of 21 test sites. The experimental design was a randomized complete block with four replicates in 2008 and 2009 and three replicates in 2010–2012. Regression analysis was conducted to determine genetic progress over time. Mean yield across all 21 locations was 3.34 t ha−1, but varied from 1.11 t ha−1 to 6.02 t ha−1 and was highly affected by moisture stress. Annual genetic gain was 0.50% compared to Ak-702, or 0.30% compared to the first modern landmark varieties. The genetic gains in drought-affected sites were 0.75% compared to Ak-702 and 0.66% compared to the landmark varieties. Modern varieties had both improved yield potential and tolerance to moisture stress. Rht genes and rye translocations were largely absent in the varieties studied. The number of spikes per unit area decreased by 10% over the study period, but grains spike−1 and 1000-kernel weight increased by 10%. There were no significant increases in harvest index, grain size, or spike fertility, and no significant decrease in quality over time. Future use of Rht genes and rye translocations in breeding programs may increase yield under rainfed conditions. Keywords: Genetic gain, Rainfed wheat production, Winter wheat, Yield

THE ROLE OF LAPAROSCOPY IN BLUNT ABDOMINAL TRAUMA: DIAGNOSTIC, THERAPEUTIC OR BOTH?

Science.gov (United States)

Mosai, F

2017-09-01

The use of laparoscopy in blunt abdominal trauma is gaining popularity as a useful diagnostic tool to avoid unnecessary laparotomies where there is diagnostic dilemma. But the feasibility of using laparoscopy for therapeutic intervention in these patients has been debated. Even though recent case reports seem to suggest that these patients can be managed using laparoscopy, the practice is not yet wildly adopted. A retrospective analysis of a prospectively collected data was done. All adult patients who presented with abdominal trauma and were offered laparoscopic surgery at DGMAH from 2012 to 2015 were reviewed. Data was retrieved from our departmental database and analysed using descriptive statistics. A total of 318 patients were reviewed and 35 patients had blunt abdominal trauma and were included in the study. All the patients were offered laparoscopy. The median age was 30, with 91% of our patients being males. The highest injury severity score calculated was 38. At least 77% of the patients were managed using laparoscopy. This includes 43% who had both diagnostic and therapeutic intervention and 34% had only diagnostic laparoscopy. Eight patients were converted to open surgery mainly due to active bleeding and complex injuries. We did not have any non-therapeutic laparotomies, with no documented procedure related morbidity and mortality. The positive outcomes seen from the study suggest that laparoscopy can be safe and feasible in both diagnostic and therapeutic interventions in carefully selected blunt abdominal trauma patients. A conversion to open surgery should not be regarded as a failure but rather as a sign of mature and sound clinical judgement acknowledging the limitations of laparoscopy and/or the surgeon.

Genetics and pharmacology of longevity: the road to therapeutics for healthy aging.

Science.gov (United States)

Castillo-Quan, Jorge Iván; Kinghorn, Kerri J; Bjedov, Ivana

2015-01-01

Aging can be defined as the progressive decline in tissue and organismal function and the ability to respond to stress that occurs in association with homeostatic failure and the accumulation of molecular damage. Aging is the biggest risk factor for human disease and results in a wide range of aging pathologies. Although we do not completely understand the underlying molecular basis that drives the aging process, we have gained exceptional insights into the plasticity of life span and healthspan from the use of model organisms such as the worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Single-gene mutations in key cellular pathways that regulate environmental sensing, and the response to stress, have been identified that prolong life span across evolution from yeast to mammals. These genetic manipulations also correlate with a delay in the onset of tissue and organismal dysfunction. While the molecular genetics of aging will remain a prosperous and attractive area of research in biogerontology, we are moving towards an era defined by the search for therapeutic drugs that promote healthy aging. Translational biogerontology will require incorporation of both therapeutic and pharmacological concepts. The use of model organisms will remain central to the quest for drug discovery, but as we uncover molecular processes regulated by repurposed drugs and polypharmacy, studies of pharmacodynamics and pharmacokinetics, drug-drug interactions, drug toxicity, and therapeutic index will slowly become more prevalent in aging research. As we move from genetics to pharmacology and therapeutics, studies will not only require demonstration of life span extension and an underlying molecular mechanism, but also the translational relevance for human health and disease prevention. Copyright © 2015 Elsevier Inc. All rights reserved.

CONDITIONS FOR CSR MICROBUNCHING GAIN SUPPRESSION

Energy Technology Data Exchange (ETDEWEB)

Tsai, Cheng Ying [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); Douglas, David R. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Li, Rui [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Tennant, Christopher D. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); di Mitri, Simone [Elettra–Sincrotrone Trieste, 34149 Basovizza, Trieste, Italy

2016-05-01

The coherent synchrotron radiation (CSR) of a high brightness electron beam traversing a series of dipoles, such as transport arcs, may result in phase space degradation. On one hand, the CSR can perturb electron transverse motion in dispersive regions along the beamline, causing emittance growth. On the other hand, the CSR effect on the longitudinal beam dynamics could result in microbunching gain enhancement. For transport arcs, several schemes have been proposed* to suppress the CSR-induced emittance growth. Similarly, several scenarios have been introduced** to suppress CSR-induced microbunching gain, which however mostly aim for linac-based machines. In this paper we try to provide sufficient conditions for suppression of CSR-induced microbunching gain along a transport arc, analogous to*. Several example lattices are presented, with the relevant microbunching analyses carried out by our semi-analytical Vlasov solver***. The simulation results show that lattices satisfying the proposed conditions indeed have microbunching gain suppressed. We expect this analysis can shed light on lattice design approach that could suppress the CSR-induced microbunching gain.

Shock ignition targets: gain and robustness vs ignition threshold factor

Science.gov (United States)

Atzeni, Stefano; Antonelli, Luca; Schiavi, Angelo; Picone, Silvia; Volponi, Gian Marco; Marocchino, Alberto

2017-10-01

Shock ignition is a laser direct-drive inertial confinement fusion scheme, in which the stages of compression and hot spot formation are partly separated. The hot spot is created at the end of the implosion by a converging shock driven by a final ``spike'' of the laser pulse. Several shock-ignition target concepts have been proposed and relevant gain curves computed (see, e.g.). Here, we consider both pure-DT targets and more facility-relevant targets with plastic ablator. The investigation is conducted with 1D and 2D hydrodynamic simulations. We determine ignition threshold factors ITF's (and their dependence on laser pulse parameters) by means of 1D simulations. 2D simulations indicate that robustness to long-scale perturbations increases with ITF. Gain curves (gain vs laser energy), for different ITF's, are generated using 1D simulations. Work partially supported by Sapienza Project C26A15YTMA, Sapienza 2016 (n. 257584), Eurofusion Project AWP17-ENR-IFE-CEA-01.

Mechanisms of ionizing-radiation-induced gain degradation in lateral PNP BJTs

International Nuclear Information System (INIS)

Schmidt, D.M.; Wu, A.; Schrimpf, R.D.; Pease, R.L.; Combs, W.E.

1996-01-01

The physical mechanisms for gain degradation in laterals PNP bipolar transistors are examined experimentally and through simulation. The effect of increased surface recombination velocity at the base surface is moderated by positive oxide charge

On Informatics Diagnostics and Informatics Therapeutics - Good Medical Informatics Research Is Needed Here.

Science.gov (United States)

Haux, Reinhold

2017-01-01

In the era of digitization some new procedures play an increasing role for diagnosis as well as for therapy: informatics diagnostics and informatics therapeutics. Challenges for such procedures are described. It is discussed, when research on such diagnostics and therapeutics can be regarded as good research. Examples are mentioned for informatics diagnostics and informatics therapeutics, which are based on health-enabling technologies.

Measuring learning gain: Comparing anatomy drawing screencasts and paper-based resources.

Science.gov (United States)

Pickering, James D

2017-07-01

The use of technology-enhanced learning (TEL) resources is now a common tool across a variety of healthcare programs. Despite this popular approach to curriculum delivery there remains a paucity in empirical evidence that quantifies the change in learning gain. The aim of the study was to measure the changes in learning gain observed with anatomy drawing screencasts in comparison to a traditional paper-based resource. Learning gain is a widely used term to describe the tangible changes in learning outcomes that have been achieved after a specific intervention. In regard to this study, a cohort of Year 2 medical students voluntarily participated and were randomly assigned to either a screencast or textbook group to compare changes in learning gain across resource type. Using a pre-test/post-test protocol, and a range of statistical analyses, the learning gain was calculated at three test points: immediate post-test, 1-week post-test and 4-week post-test. Results at all test points revealed a significant increase in learning gain and large effect sizes for the screencast group compared to the textbook group. Possible reasons behind the difference in learning gain are explored by comparing the instructional design of both resources. Strengths and weaknesses of the study design are also considered. This work adds to the growing area of research that supports the effective design of TEL resources which are complimentary to the cognitive theory of multimedia learning to achieve both an effective and efficient learning resource for anatomical education. Anat Sci Educ 10: 307-316. © 2016 American Association of Anatomists. © 2016 American Association of Anatomists.

Therapeutic ratio and fractionation in cancer of the lung

International Nuclear Information System (INIS)

Cox, J.D.; Bauer, M.

1988-01-01

Bronchopulmonary carcinomas have long been considered among the most frustrating problems in radiation oncology. In spite of the reasonably favorable results reported over 30 years ago with conventional X-irradiation of patients with operable carcinoma of the lung, the patients usually referred for radiation therapy with unresectable tumors permit few opportunities for successful treatment and thus lead to a general nihilism about this disease. The potential damage that can occur from radiation therapy to the normal lung can be life-threatening. Such damage was thought, erroneously, to be increased dramatically with even moderately high doses, e.g.; more than 50 Gy in 5 weeks. Therefore, few attempts were made to deliver the same high doses of radiations that would be considered mandatory for epithelial tumors of other locations such as the upper respiratory and digestive tract or the female genital tract. The therapeutic ratio was altered in an unfavorable direction with the use of small numbers of large fractions. Based on the earliest RTOG studies of carcinoma of the lung, the therapeutic ratio is at an acceptable level with 60 Gy in 30 fractions of 2.0 Gy in 6 weeks. It is encouraging that there is no evidence of an increased rate of morbidity in the hyperfractionation trials of the RTOG. The data are too preliminary with regard to therapeutic effect to know if there will truly be an increase in therapeutic ratio. It was evident that 12-24 months of follow-up are necessary before definitive answers are available

Gastric cancer stem cells: A novel therapeutic target

Science.gov (United States)

Singh, Shree Ram

2013-01-01

Gastric cancer remains one of the leading causes of global cancer mortality. Multipotent gastric stem cells have been identified in both mouse and human stomachs, and they play an essential role in the self-renewal and homeostasis of gastric mucosa. There are several environmental and genetic factors known to promote gastric cancer. In recent years, numerous in vitro and in vivo studies suggest that gastric cancer may originate from normal stem cells or bone marrow–derived mesenchymal cells, and that gastric tumors contain cancer stem cells. Cancer stem cells are believed to share a common microenvironment with normal niche, which play an important role in gastric cancer and tumor growth. This mini-review presents a brief overview of the recent developments in gastric cancer stem cell research. The knowledge gained by studying cancer stem cells in gastric mucosa will support the development of novel therapeutic strategies for gastric cancer. PMID:23583679

The teaching of therapeutic Physical Culture to asthmatic students in the university

Directory of Open Access Journals (Sweden)

Manuel Alejandro Romero-León

2016-05-01

Full Text Available The application of therapeutic physical culture asthmatic students has proved to be an excellent therapeutic method in physical rehabilitation. However, in the university students need a developer education that gives them theoretical, methodological tools. a historical analysis of the therapeutic teaching Physical Culture, in order to expose the way he has dominated his teaching was done. In addition, the elaboration of its concept in order to meet the social demand for the formation of a subject becomes heir and transmitter of a culture of physical activity that achieves deal with ailments of all kinds, increasing each time more life expectancy, the apprehension of all kinds of techniques that allows an individual to be increasingly prepared.

Assessment of weight gain during pregnancy in general prenatal care services in Brazil

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Nucci Luciana Bertoldi

2001-01-01

Full Text Available Obesity is an emerging major health risk for women around the world. In this regard, little attention has been given to pregnancy, a moment of risk not only for major weight gain in these women, but also for macrosomia in their offspring. The objective of this study is to evaluate weight gain during pregnancy. Data pertains to a cohort of pregnant women attending general prenatal care clinics in six state capitals in Brazil, from 1991 to 1995. We studied women aged 20 years and over with singleton pregnancies and no diagnosis of diabetes outside pregnancy, enrolled at approximately 20 - 28 weeks of gestation. According to the Institute of Medicine criteria, 38% (95%CI: 36-40% of the women studied gained less and 29% (95%CI: 28-31% had more than the recommended total weight gain. These proportions vary according to pre-pregnancy nutritional status. Given the increasing epidemic of obesity, the high prevalence of overweight and obesity in Brazilian women prior to pregnancy, and the lack of achievement of recommended weight gain during pregnancy, more effective means of managing weight gain during pregnancy are necessary.

ePrescribing: Reducing Costs through In-Class Therapeutic Interchange.

Science.gov (United States)

Stenner, Shane P; Chakravarthy, Rohini; Johnson, Kevin B; Miller, William L; Olson, Julie; Wickizer, Marleen; Johnson, Nate N; Ohmer, Rick; Uskavitch, David R; Bernard, Gordon R; Neal, Erin B; Lehmann, Christoph U

2016-12-14

Spending on pharmaceuticals in the US reached $373.9 billion in 2014. Therapeutic interchange offers potential medication cost savings by replacing a prescribed drug for an equally efficacious therapeutic alternative. Hard-stop therapeutic interchange recommendation alerts were developed for four medication classes (HMG-CoA reductase inhibitors, serotonin receptor agonists, intranasal steroid sprays, and proton-pump inhibitors) in an electronic prescription-writing tool for outpatient prescriptions. Using prescription data from January 2012 to June 2015, the Compliance Ratio (CR) was calculated by dividing the number of prescriptions with recommended therapeutic interchange medications by the number of prescriptions with non-recommended medications to measure effectiveness. To explore potential cost savings, prescription data and medication costs were analyzed for the 45,000 Vanderbilt Employee Health Plan members. For all medication classes, significant improvements were demonstrated - the CR improved (proton-pump inhibitors 2.8 to 5.32, nasal steroids 2.44 to 8.16, statins 2.06 to 5.51, and serotonin receptor agonists 0.8 to 1.52). Quarterly savings through the four therapeutic interchange interventions combined exceeded $200,000 with an estimated annual savings for the health plan of $800,000, or more than $17 per member. A therapeutic interchange clinical decision support tool at the point of prescribing resulted in increased compliance with recommendations for outpatient prescriptions while producing substantial cost savings to the Vanderbilt Employee Health Plan - $17.77 per member per year. Therapeutic interchange rules require rational targeting, appropriate governance, and vigilant content updates.

Small Scaffolds, Big Potential: Developing Miniature Proteins as Therapeutic Agents.

Science.gov (United States)

Holub, Justin M

2017-09-01

Preclinical Research Miniature proteins are a class of oligopeptide characterized by their short sequence lengths and ability to adopt well-folded, three-dimensional structures. Because of their biomimetic nature and synthetic tractability, miniature proteins have been used to study a range of biochemical processes including fast protein folding, signal transduction, catalysis and molecular transport. Recently, miniature proteins have been gaining traction as potential therapeutic agents because their small size and ability to fold into defined tertiary structures facilitates their development as protein-based drugs. This research overview discusses emerging developments involving the use of miniature proteins as scaffolds to design novel therapeutics for the treatment and study of human disease. Specifically, this review will explore strategies to: (i) stabilize miniature protein tertiary structure; (ii) optimize biomolecular recognition by grafting functional epitopes onto miniature protein scaffolds; and (iii) enhance cytosolic delivery of miniature proteins through the use of cationic motifs that facilitate endosomal escape. These objectives are discussed not only to address challenges in developing effective miniature protein-based drugs, but also to highlight the tremendous potential miniature proteins hold for combating and understanding human disease. Drug Dev Res 78 : 268-282, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Cellular Therapeutics for Heart Failure: Focus on Mesenchymal Stem Cells

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Amitabh C. Pandey

2017-01-01

Full Text Available Resulting from a various etiologies, the most notable remains ischemia; heart failure (HF manifests as the common end pathway of many cardiovascular processes and remains among the top causes for hospitalization and a major cause of morbidity and mortality worldwide. Current pharmacologic treatment for HF utilizes pharmacologic agents to control symptoms and slow further deterioration; however, on a cellular level, in a patient with progressive disease, fibrosis and cardiac remodeling can continue leading to end-stage heart failure. Cellular therapeutics have risen as the new hope for an improvement in the treatment of HF. Mesenchymal stem cells (MSCs have gained popularity given their propensity of promoting endogenous cellular repair of a myriad of disease processes via paracrine signaling through expression of various cytokines, chemokines, and adhesion molecules resulting in activation of signal transduction pathways. While the exact mechanism remains to be completely elucidated, this remains the primary mechanism identified to date. Recently, MSCs have been incorporated as the central focus in clinical trials investigating the role how MSCs can play in the treatment of HF. In this review, we focus on the characteristics of MSCs that give them a distinct edge as cellular therapeutics and present results of clinical trials investigating MSCs in the setting of ischemic HF.

The effects of changing exercise levels on weight and age-relatedweight gain

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Williams, Paul T.; Wood, Peter D.

2004-06-01

To determine prospectively whether physical activity canprevent age-related weight gain and whether changing levels of activityaffect body weight. DESIGN/SUBJECTS: The study consisted of 8,080 maleand 4,871 female runners who completed two questionnaires an average(+/-standard deviation (s.d.)) of 3.20+/-2.30 and 2.59+/-2.17 yearsapart, respectively, as part of the National Runners' Health Study.RESULTS: Changes in running distance were inversely related to changes inmen's and women's body mass indices (BMIs) (slope+/-standard error(s.e.): -0.015+/-0.001 and -0.009+/-0.001 kg/m(2) per Deltakm/week,respectively), waist circumferences (-0.030+/-0.002 and -0.022+/-0.005 cmper Deltakm/week, respectively) and percent changes in body weight(-0.062+/-0.003 and -0.041+/-0.003 percent per Deltakm/week,respectively, all P<0.0001). The regression slopes were significantlysteeper (more negative) in men than women for DeltaBMI and Deltapercentbody weight (P<0.0001). A longer history of running diminishedthe impact of changing running distance on men's weights. When adjustedfor Deltakm/week, years of aging in men and years of aging in women wereassociated with increases of 0.066+/-0.005 and 0.056+/-0.006 kg/m(2) inBMI, respectively, increases of 0.294+/-0.019 and 0.279+/-0.028 percentin Delta percentbody weight, respectively, and increases of 0.203+/-0.016and 0.271+/-0.033 cm in waist circumference, respectively (allP<0.0001). These regression slopes suggest that vigorous exercise mayneed to increase 4.4 km/week annually in men and 6.2 km/week annually inwomen to compensate for the expected gain in weight associated with aging(2.7 and 3.9 km/week annually when correct for the attenuation due tomeasurement error). CONCLUSIONS: Age-related weight gain occurs evenamong the most active individuals when exercise is constant.Theoretically, vigorous exercise must increase significantly with age tocompensate for the expected gain in weight associated withaging.

24 CFR 3280.507 - Comfort heat gain.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Comfort heat gain. 3280.507 Section... gain. Information necessary to calculate the home cooling load shall be provided as specified in this part. (a) Transmission heat gains. Homes complying with this section shall meet the minimum heat loss...

Psychedelics and hypnosis: Commonalities and therapeutic implications.

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Lemercier, Clément E; Terhune, Devin B

2018-06-01

Recent research on psychedelics and hypnosis demonstrates the value of both methods in the treatment of a range of psychopathologies with overlapping applications and neurophenomenological features. The potential of harnessing the power of suggestion to influence the phenomenological response to psychedelics toward more therapeutic action has remained unexplored in recent research and thereby warrants empirical attention. Here we aim to elucidate the phenomenological and neurophysiological similarities and dissimilarities between psychedelic states and hypnosis in order to revisit how contemporary knowledge may inform their conjunct usage in psychotherapy. We review recent advances in phenomenological and neurophysiological research on psychedelics and hypnosis, and we summarize early investigations on the coupling of psychedelics and hypnosis in scientific and therapeutic contexts. Results/outcomes: We highlight commonalities and differences between psychedelics and hypnosis that point to the potential efficacy of combining the two in psychotherapy. We propose multiple research paths for coupling these two phenomena at different stages in the preparation, acute phase and follow-up of psychedelic-assisted psychotherapy in order to prepare, guide and integrate the psychedelic experience with the aim of enhancing therapeutic outcomes. Harnessing the power of suggestion to modulate response to psychedelics could enhance their therapeutic efficacy by helping to increase the likelihood of positive responses, including mystical-type experiences.

Nonthermal effects of therapeutic ultrasound: the frequency resonance hypothesis.

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Johns, Lennart D

2002-07-01

To present the frequency resonance hypothesis, a possible mechanical mechanism by which treatment with non-thermal levels of ultrasound stimulates therapeutic effects. The review encompasses a 4-decade history but focuses on recent reports describing the effects of nonthermal therapeutic levels of ultrasound at the cellular and molecular levels. A search of MEDLINE from 1965 through 2000 using the terms ultrasound and therapeutic ultrasound. The literature provides a number of examples in which exposure of cells to therapeutic ultrasound under nonthermal conditions modified cellular functions. Nonthermal levels of ultrasound are reported to modulate membrane properties, alter cellular proliferation, and produce increases in proteins associated with inflammation and injury repair. Combined, these data suggest that nonthermal effects of therapeutic ultrasound can modify the inflammatory response. The concept of the absorption of ultrasonic energy by enzymatic proteins leading to changes in the enzymes activity is not novel. However, recent reports demonstrating that ultrasound affects enzyme activity and possibly gene regulation provide sufficient data to present a probable molecular mechanism of ultrasound's nonthermal therapeutic action. The frequency resonance hypothesis describes 2 possible biological mechanisms that may alter protein function as a result of the absorption of ultrasonic energy. First, absorption of mechanical energy by a protein may produce a transient conformational shift (modifying the 3-dimensional structure) and alter the protein's functional activity. Second, the resonance or shearing properties of the wave (or both) may dissociate a multimolecular complex, thereby disrupting the complex's function. This review focuses on recent studies that have reported cellular and molecular effects of therapeutic ultrasound and presents a mechanical mechanism that may lead to a better understanding of how the nonthermal effects of ultrasound may be

[Online Counselling: The prospect of a therapeutic connection].

Science.gov (United States)

Giotakos, O; Papadomarkaki, E

2016-01-01

Over the last few years, Internet has become an integral part of daily life. An abundant source of information and a principal gateway of communication between individuals, Internet has been continuously gaining considerable ground as a tool of awareness and intervention in the area of public health. With regard to the field of mental health, Internet exhibits a credible potential in facilitating dialogue not only between experts and their beneficiaries but also between stakeholders. Moreover and with regard to various aspects of public concern, it can serve as a circulation portal of educational material between students and teachers. The advent of remote support services dates back in the decade of 1970-1980. In the present time, they consist of informative guides and self-help groups or online counselling. The latter is defined as the process in which both parties, namely the therapist and the client, are involved in an oral or written conciliation through means of an internet connection, videoconferencing, live chat or e-mail exchange. The benefits of this practice - accessibility, relocation, convenience, anonymity, facilitation of face-to-face psychotherapy and low cost - could make online counseling, in specific cases, the treatment of choice. While the usage of the World Wide Web seems promising for the rectification of mental health disorders, there is some debate among experts regarding the ethical aspect of practicing psychotherapy in an interactive digital environment. Issues such as technical expertise and the tackling of related problems, difficulties in the diagnostic process, interchange of verbal and nonverbal cues, crisis management, safeguarding the therapeutic alliance, protection of personal data, age restriction, keeping boundaries in relation to the setting, the time and the dynamics of the therapeutic relationship and, finally, training and supervisory process of online therapist, are some subjects of disagreement. Relevant research reveals

New therapeutic modalities to modulate orthodontic tooth movement

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Ildeu Andrade Jr

2014-12-01

Full Text Available Modulation of orthodontic tooth movement (OTM is desirable not only to patients because it shortens treatment time, but also to orthodontists, since treatment duration is associated with increased risk of gingival inflammation, decalcification, dental caries, and root resorption. The increased focus on the biological basis of tooth movement has rendered Orthodontics a more comprehensive specialty that incorporates facets of all fields of medicine. Current knowledge raises the possibility of using new therapeutic modalities for modulation of OTM, such as corticotomy, laser therapy, vibration (low-intensity pulsed ultrasound, local injections of biomodulators and gene therapy; with the latter being applicable in the near future. They are intended to enhance or inhibit recruitment, differentiation and/or activation of bone cells, accelerate or reduce OTM, increase stability of orthodontic results, as well as assist with the prevention of root resorption. This article summarizes recent studies on each one of these therapeutic modalities, provides readers with information about how they affect OTM and points out future clinical perspectives.

Therapeutic antibodies as a treatment option for dengue fever.

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Chan, Kuan Rong; Ong, Eugenia Z; Ooi, Eng Eong

2013-11-01

Dengue fever is the most prevalent mosquito-borne viral disease globally with about 100 million cases of acute dengue annually. Severe dengue infection can result in a life-threatening illness. In the absence of either a licensed vaccine or antiviral drug against dengue, therapeutic antibodies that neutralize dengue virus (DENV) may serve as an effective medical countermeasure against severe dengue. However, therapeutic antibodies would need to effectively neutralize all four DENV serotypes. It must not induce antibody-dependent enhancement of DENV infection in monocytes/macrophages through Fc gamma receptor (FcγR)-mediated phagocytosis, which is hypothesized to increase the risk of severe dengue. Here, we review the strategies and technologies that can be adopted to develop antibodies for therapeutic applications. We also discuss the mechanism of antibody neutralization in the cells targeted by DENV that express Fc gamma receptor. These studies have provided significant insight toward the use of therapeutic antibodies as a potentially promising bulwark against dengue.

Spontaneous indices are inconsistent with arterial baroreflex gain.

Science.gov (United States)

Lipman, Ruth D; Salisbury, Julie K; Taylor, J Andrew

2003-10-01

Spontaneously occurring, parallel fluctuations in arterial pressure and heart period are frequently used as indices of baroreflex function. Despite the convenience of spontaneous indices, their relation to the arterial baroreflex remains unclear. Therefore, in 97 volunteers, we derived 5 proposed indices (sequence method, alpha-index, transfer function, low-frequency transfer function, and impulse response function), compared them with arterial baroreflex gain (by the modified Oxford pharmacologic technique), and examined their relation to carotid distensibility and respiratory sinus arrhythmia. The subjects comprised men and women (n=41) aged 25 to 86 years, 30% of whom had established coronary artery disease. Generally, the indices were correlated with each other (except alpha-index and low-frequency transfer function) and with baroreflex gain. However, the Bland-Altman method demonstrated that the spontaneous indices had limits of agreement as large as the baroreflex gain itself. Even in individuals within the lowest tertile of baroreflex gain for whom baroreflex gain appears to be the most clinically relevant, spontaneous indices failed to relate to baroreflex gain. In fact, for these individuals, there was no correlation between any index and baroreflex gain. Forward stepwise linear regression showed that all spontaneous indices and baroreflex gain were related to respiratory sinus arrhythmia, but only baroreflex gain was related to carotid distensibility. Therefore, these data suggest that spontaneous indices are inadequate estimates of gain and are inconsistent with arterial baroreflex function.

Trends and determinants of weight gains among OECD countries: an ecological study.

Science.gov (United States)

Nghiem, S; Vu, X-B; Barnett, A

2018-06-01

Obesity has become a global issue with abundant evidence to indicate that the prevalence of obesity in many nations has increased over time. The literature also reports a strong association between obesity and economic development, but the trend that obesity growth rates may converge over time has not been examined. We propose a conceptual framework and conduct an ecological analysis on the relationship between economic development and weight gain. We also test the hypothesis that weight gain converges among countries over time and examine determinants of weight gains. This is a longitudinal study of 34 Organisation for Economic Cooperation and Development (OECD) countries in the years 1980-2008 using publicly available data. We apply a dynamic economic growth model to test the hypothesis that the rate of weight gains across countries may converge over time. We also investigate the determinants of weight gains using a longitudinal regression tree analysis. We do not find evidence that the growth rates of body weight across countries converged for all countries. However, there were groups of countries in which the growth rates of body weight converge, with five groups for males and seven groups for females. The predicted growth rates of body weight peak when gross domestic product (GDP) per capita reaches US$47,000 for males and US$37,000 for females in OECD countries. National levels of consumption of sugar, fat and alcohol were the most important contributors to national weight gains. National weight gains follow an inverse U-shape curve with economic development. Excessive calorie intake is the main contributor to weight gains. Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

The therapeutic potential of truffle fungi: a patent survey

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Małgorzata Gajos

2014-12-01

Full Text Available The purpose of this article is to research and retrieve patent information regarding the therapeutic use of truffles. Truffles have a unique value as a foodstuff and impact positively on human health and well-being. They are applied in such industries as the pharmaceutical industry and the cosmetic industry. Patent documentation available in the Espacenet network and the Patentscope service were analyzed by key word and patent specifications were examined to describe state of the art and to identify scientific research trends in therapeutic applications of truffles. Medicinal properties of truffles such as the anticancer or cardiovascular effect, a reduction in blood lipids, immunological resistance and increased energy were identified. Other therapeutic benefits include sedative action, prevention of hormonal imbalances in women, pre-menopause symptom relief, senile urethritis and prostate disorders, sleep disorders and increased absorption of calcium from milk. Truffles can also be used to alleviate symptoms of milk intolerance such as diarrhoea or bloating, to ease rheumatic pains and to treat and prevent further development or recurrence of senile cataract.

Insulin detemir attenuates food intake, body weight gain and fat mass gain in diet-induced obese Sprague-Dawley rats.

Science.gov (United States)

Rojas, J M; Printz, R L; Niswender, K D

2011-07-04

Initiation and intensification of insulin therapy commonly causes weight gain, a barrier to therapy. A contrasting body of evidence indicates that insulin functions as an adiposity negative feedback signal and reduces food intake, weight gain and adiposity via action in the central nervous system. Basal insulin analogs, detemir (Det) and glargine (Glar), have been associated with less hypoglycemia compared with neutral protamine hagedorn insulin, and Det with less weight gain, especially in patients with higher body mass index (BMI). We sought to determine whether insulin therapy per se causes body weight and fat mass gain when delivered via a clinically relevant subcutaneous (SC) route in the absence of hypoglycemia and glycosuria in non-diabetic lean and diet-induced obese rats. Rats were exposed to either a low-fat diet (LFD; 13.5% fat) or high-fat diet (HFD; 60% fat), and received Det (0.5 U kg(-1)), Glar (0.2 U kg(-1)) or vehicle (Veh) SC once daily for 4 weeks. These dosages of insulin were equipotent in rats with respect to blood-glucose concentration and did not induce hypoglycemia. As predicted by current models of energy homeostasis, neither insulin Det nor Glar therapy affected food intake and weight gain in LFD rats. Det treatment significantly attenuated food intake, body weight gain and fat mass gain relative to the Glar and Veh in high-fat fed animals, mirroring observations in humans. That neither insulin group gained excess weight, suggests weight gain with SC basal insulin therapy may not be inevitable. Our data further suggest that Det possesses a unique property to attenuate the development of obesity associated with a HFD.

Gain Enhancement of Low-Profile, Electrically Small Capacitive Feed Antennas Using Stacked Meander Lines

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Kazuki Ide

2010-01-01

Full Text Available The present paper describes the gain enhancement of a small and low-profile linear antenna with capacitive feed (C-feed using three metallic layers. The antenna has very small leakage current on the outer conductor of the coaxial cable and can easily control the imaginary part of the input impedance. The gain of the stacked three-layer meander line antenna, with the meander line in the middle layer being opposite to that of the other two layers, has increased by around 7 dB compared to the single layered C-feed antenna. The antenna gain is discussed based on simulated and measured results, which demonstrates that the antenna has successfully achieved the acceptable impedance and sufficient gain for mobile terminals and RFID tags.

Investigation of effective base transit time and current gain modulation of light-emitting transistors under different ambient temperatures

Energy Technology Data Exchange (ETDEWEB)

Yang, Hao-Hsiang; Tu, Wen-Chung; Wang, Hsiao-Lun [Graduate Institute of Photonics and Optoelectronics, National Taiwan University, 1, Roosevelt Road, Sec. 4, Taipei 106, Taiwan (China); Wu, Chao-Hsin, E-mail: chaohsinwu@ntu.edu.tw [Graduate Institute of Photonics and Optoelectronics, National Taiwan University, 1, Roosevelt Road, Sec. 4, Taipei 106, Taiwan (China); Graduate Institute of Electronics Engineering, National Taiwan University, 1, Roosevelt Road, Sec. 4, Taipei106, Taiwan (China)

2014-11-03

In this report, the modulation of current gain of InGaP/GaAs light-emitting transistors under different ambient temperatures are measured and analyzed using thermionic emission model of quantum well embedded in the transistor base region. Minority carriers captured by quantum wells gain more energy at high temperatures and escape from quantum wells resulting in an increase of current gain and lower optical output, resulting in different I-V characteristics from conventional heterojunction bipolar transistors. The effect of the smaller thermionic lifetime thus reduces the effective base transit time of transistors at high temperatures. The unique current gain enhancement of 27.61% is achieved when operation temperature increase from 28 to 85 °C.

Emerging role of nanocarriers to increase the solubility and bioavailability of curcumin.

Science.gov (United States)

Mohanty, Chandana; Das, Manasi; Sahoo, Sanjeeb K

2012-11-01

Curcumin is a safe, affordable and natural bioactive molecule of turmeric (Curcuma longa). It has gained considerable attention in recent years for its multiple pharmacological activities. However, its optimum pharmaceutical potential has been limited by its lack of aqueous solubility and poor bioavailability. To mitigate the above limitations, recently various nanostructured water-soluble delivery systems were developed to increase the solubility and bioavailability of curcumin. Major reasons contributing to the low bioavailability of curcumin appear to be owing to its poor solubility, low absorption, rapid metabolism and rapid systemic elimination. The present review summarizes the strategies using curcumin in various nanocarrier delivery systems to overcome poor solubility and inconsistent bioavailability of curcumin and describes the current status and challenges for the future. The development of various drug delivery systems to deliver curcumin will certainly provide a step up towards augmenting the therapeutic activity of curcumin thereby increasing the solubility and bioavailability of curcumin. However, the future of such delivery technology will be highly dependent on the development of safe, non-toxic and non-immunogenic nanocarriers.

Gain-loss framing effects in dilemmas of trust and reciprocity

NARCIS (Netherlands)

Evans, A.M.; van Beest, I.

2017-01-01

How do trust and reciprocity decisions change when outcomes are framed in terms of potential losses (vs gains)? In two studies, with 7464 trust decisions from 359 participants and 2723 reciprocity decisions from 221 participants, we find that loss framing increases mean-level trust, but has no

Health Literacy Predicts Cardiac Knowledge Gains in Cardiac Rehabilitation Participants

Science.gov (United States)

Mattson, Colleen C.; Rawson, Katherine; Hughes, Joel W.; Waechter, Donna; Rosneck, James

2015-01-01

Objective: Health literacy is increasingly recognised as a potentially important patient characteristic related to patient education efforts. We evaluated whether health literacy would predict gains in knowledge after completion of patient education in cardiac rehabilitation. Method: This was a re-post observational analysis study design based on…

Peptide chemistry toolbox - Transforming natural peptides into peptide therapeutics.

Science.gov (United States)

Erak, Miloš; Bellmann-Sickert, Kathrin; Els-Heindl, Sylvia; Beck-Sickinger, Annette G

2018-06-01

The development of solid phase peptide synthesis has released tremendous opportunities for using synthetic peptides in medicinal applications. In the last decades, peptide therapeutics became an emerging market in pharmaceutical industry. The need for synthetic strategies in order to improve peptidic properties, such as longer half-life, higher bioavailability, increased potency and efficiency is accordingly rising. In this mini-review, we present a toolbox of modifications in peptide chemistry for overcoming the main drawbacks during the transition from natural peptides to peptide therapeutics. Modifications at the level of the peptide backbone, amino acid side chains and higher orders of structures are described. Furthermore, we are discussing the future of peptide therapeutics development and their impact on the pharmaceutical market. Copyright © 2018 Elsevier Ltd. All rights reserved.

An application of gain-scheduled control using state-space interpolation to hydroactive gas bearings

DEFF Research Database (Denmark)

Theisen, Lukas Roy Svane; Camino, Juan F.; Niemann, Hans Henrik

2016-01-01

with a gain-scheduling strategy using state-space interpolation, which avoids both the performance loss and the increase of controller order associated to the Youla parametrisation. The proposed state-space interpolation for gain-scheduling is applied for mass imbalance rejection for a controllable gas...... bearing scheduled in two parameters. Comparisons against the Youla-based scheduling demonstrate the superiority of the state-space interpolation....

Mechanistic and structural basis of bioengineered bovine Cathelicidin-5 with optimized therapeutic activity

Science.gov (United States)

Sahoo, Bikash R.; Maruyama, Kenta; Edula, Jyotheeswara R.; Tougan, Takahiro; Lin, Yuxi; Lee, Young-Ho; Horii, Toshihiro; Fujiwara, Toshimichi

2017-03-01

Peptide-drug discovery using host-defense peptides becomes promising against antibiotic-resistant pathogens and cancer cells. Here, we customized the therapeutic activity of bovine cathelicidin-5 targeting to bacteria, protozoa, and tumor cells. The membrane dependent conformational adaptability and plasticity of cathelicidin-5 is revealed by biophysical analysis and atomistic simulations over 200 μs in thymocytes, leukemia, and E. coli cell-membranes. Our understanding of energy-dependent cathelicidin-5 intrusion in heterogeneous membranes aided in designing novel loss/gain-of-function analogues. In vitro findings identified leucine-zipper to phenylalanine substitution in cathelicidin-5 (1-18) significantly enhance the antimicrobial and anticancer activity with trivial hemolytic activity. Targeted mutants of cathelicidin-5 at kink region and N-terminal truncation revealed loss-of-function. We ensured the existence of a bimodal mechanism of peptide action (membranolytic and non-membranolytic) in vitro. The melanoma mouse model in vivo study further supports the in vitro findings. This is the first structural report on cathelicidin-5 and our findings revealed potent therapeutic application of designed cathelicidin-5 analogues.

A randomized, placebo-controlled study of zonisamide to prevent olanzapine-associated weight gain.

Science.gov (United States)

McElroy, Susan L; Winstanley, Erin; Mori, Nicole; Martens, Brian; McCoy, Jessica; Moeller, Dianna; Guerdjikova, Anna I; Keck, Paul E

2012-04-01

Weight gain is commonly observed with olanzapine treatment. Zonisamide is an antiepileptic drug associated with weight loss. This study examined the effectiveness of zonisamide in preventing weight gain in 42 patients beginning olanzapine for bipolar disorder or schizophrenia. Each patient had a body mass index of 22 mg/kg or greater and was randomized to taking olanzapine with either zonisamide (n = 20) or placebo (n = 22) for 16 weeks. The primary outcome measure was change in body weight in kilograms from baseline. In the primary analysis using longitudinal regression, patients who received zonisamide had a significantly slower rate of weight gain and increase in body mass index than those who received placebo. The patients treated with zonisamide gained a mean (SD) of 0.9 (3.3) kg, whereas those treated with placebo gained a mean (SD) of 5.0 (5.5) kg; P = 0.01. None of the patients in the zonisamide group, compared with 7 patients (33%) in the placebo group, gained 7% of body weight or greater from baseline (Fisher exact test, P = 0.009). The zonisamide group, however, reported significantly more cognitive impairment as an adverse event than the placebo group (25% vs 0, respectively; P = 0.02). Zonisamide was effective for mitigating weight gain in patients with bipolar disorder or schizophrenia initiating treatment with olanzapine but was associated with cognitive impairment as an adverse event.

Implementation of nanoparticles in therapeutic radiation oncology

Science.gov (United States)

Beeler, Erik; Gabani, Prashant; Singh, Om V.

2017-05-01

Development and progress of cancer is a very complex disease process to comprehend because of the multiple changes in cellular physiology, pathology, and pathophysiology resulting from the numerous genetic changes from which cancer originates. As a result, most common treatments are not directed at the molecular level but rather at the tissue level. While personalized care is becoming an increasingly aim, the most common cancer treatments are restricted to chemotherapy, radiation, and surgery, each of which has a high likelihood of resulting in rather severe adverse side effects. For example, currently used radiation therapy does not discriminate between normal and cancerous cells and greatly relies on the external targeting of the radiation beams to specific cells and organs. Because of this, there is an immediate need for the development of new and innovative technologies that help to differentiate tumor cells and micrometastases from normal cells and facilitate the complete destruction of those cells. Recent advancements in nanoscience and nanotechnology have paved a way for the development of nanoparticles (NPs) as multifunctional carriers to deliver therapeutic radioisotopes for tumor targeted radiation therapy, to monitor their delivery, and improve the therapeutic index of radiation and tumor response to the treatment. The application of NPs in radiation therapy has aimed to improve outcomes in radiation therapy by increasing therapeutic effect in tumors and reducing toxicity on normal tissues. Because NPs possess unique properties, such as preferential accumulation in tumors and minimal uptake in normal tissues, it makes them ideal for the delivery of radiotherapy. This review provides an overview of the recent development of NPs for carrying and delivering therapeutic radioisotopes for systemic radiation treatment for a variety of cancers in radiation oncology.

Potential Gains in Reproductive-Aged Life Expectancy by Eliminating Maternal Mortality

DEFF Research Database (Denmark)

Canudas-Romo, Vladimir; Liu, L; Zimmerman, L

2014-01-01

Objective: We assessed the change over time in the contribution of maternal mortality to a life expectancy calculated between ages 15 and 49, or Reproductive-Aged Life Expectancy (RALE). Our goal was to estimate the increase in RALE in developed countries over the twentieth century and the hypoth......Objective: We assessed the change over time in the contribution of maternal mortality to a life expectancy calculated between ages 15 and 49, or Reproductive-Aged Life Expectancy (RALE). Our goal was to estimate the increase in RALE in developed countries over the twentieth century....... Findings: In developed countries, five years in RALE were gained over the twentieth century, of which approximately 10%, or half a year, was attributable to reductions in maternal mortality. In sub-Saharan African countries, the possible achievable gains fluctuate between 0.24 and 1.47 years, or 6% and 44...

Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma

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Adrian Biddle

2016-02-01

Full Text Available Cancer stem cells (CSCs drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT and mesenchymal-to-epithelial transition (MET to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC, we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44highEpCAMlow/−CD24+ cell surface marker profile. Treatment with TGFβ and retinoic acid (RA enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs.

Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma.

Science.gov (United States)

Biddle, Adrian; Gammon, Luke; Liang, Xiao; Costea, Daniela Elena; Mackenzie, Ian C

2016-02-01

Cancer stem cells (CSCs) drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC), we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44(high)EpCAM(low/-) CD24(+) cell surface marker profile. Treatment with TGFβ and retinoic acid (RA) enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER) stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs.

Intrinsic gain modulation and adaptive neural coding.

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Sungho Hong

2008-07-01

Full Text Available In many cases, the computation of a neural system can be reduced to a receptive field, or a set of linear filters, and a thresholding function, or gain curve, which determines the firing probability; this is known as a linear/nonlinear model. In some forms of sensory adaptation, these linear filters and gain curve adjust very rapidly to changes in the variance of a randomly varying driving input. An apparently similar but previously unrelated issue is the observation of gain control by background noise in cortical neurons: the slope of the firing rate versus current (f-I curve changes with the variance of background random input. Here, we show a direct correspondence between these two observations by relating variance-dependent changes in the gain of f-I curves to characteristics of the changing empirical linear/nonlinear model obtained by sampling. In the case that the underlying system is fixed, we derive relationships relating the change of the gain with respect to both mean and variance with the receptive fields derived from reverse correlation on a white noise stimulus. Using two conductance-based model neurons that display distinct gain modulation properties through a simple change in parameters, we show that coding properties of both these models quantitatively satisfy the predicted relationships. Our results describe how both variance-dependent gain modulation and adaptive neural computation result from intrinsic nonlinearity.

Gain and exposure scheduling to compensate for photorefractive neural-network weight decay

Science.gov (United States)

Goldstein, Adam A.; Petrisor, Gregory C.; Jenkins, B. Keith

1995-03-01

A gain and exposure schedule that theoretically eliminates the effect of photorefractive weight decay for the general class of outer-product neural-network learning algorithms (e.g., backpropagation, Widrow-Hoff, perceptron) is presented. This schedule compensates for photorefractive diffraction-efficiency decay by iteratively increasing the spatial-light-modulator transfer function gain and decreasing the weight-update exposure time. Simulation results for the scheduling procedure, as applied to backpropagation learning for the exclusive-OR problem, show improved learning performance compared with results for networks trained without scheduling.

IQ Gains in Argentina between 1964 and 1998

Science.gov (United States)

Flynn, James R.; Rossi-Case, Lilia

2012-01-01

The literature on IQ gains in Latin America is sparse. We estimate gains on Raven's Progressive Matrices in the city of La Plata (Argentina) between 1964 and 1998. The gains are robust at the top of the curve as well as at the bottom. Therefore, they are contrary to the hypothesis that nutrition played a major role in recent Argentine IQ gains.…

The psychology of health and addictions: therapeutic perspective

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Elisardo Becoña Iglesias

2003-06-01

Full Text Available The addiction subject is nowadays a valid one, as well as in the past century. Not only because of the increase of people that are addict, but also because of the important effects that cause on people and their environments. There are many theoretical perspectives to approach the addiction problem, but the most convenient because of its therapeutic results is the one that issupported by the psychology of health. lt is based on the integral approach to the person. This paper describes a general therapeutic scheme to work with addicts from the cognitive behaviora lperspective.

Prediction of direct and indirect genetic gains and genotypic correlations in rubber tree progenies

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Cecília Khusala Verardi

2011-09-01

Full Text Available The objective of this work was to estimate the genetic parameters, genotypic and phenotypic correlations, and direct and indirect genetic gains among and within rubber tree (Hevea brasiliensis progenies. The experiment was set up at the Municipality of Jaú, SP, Brazil. A randomized complete block design was used, with 22 treatments (progenies, 6 replicates, and 10 plants per plot at a spacing of 3x3 m. Three‑year‑old progenies were assessed for girth, rubber yield, and bark thickness by direct and indirect gains and genotypic correlations. The number of latex vessel rings showed the best correlations, correlating positively and significantly with girth and bark thickness. Selection gains among progenies were greater than within progeny for all the variables analyzed. Total gains obtained were high, especially for girth increase and rubber yield, which were 93.38 and 105.95%, respectively. Young progeny selection can maximize the expected genetic gains, reducing the rubber tree selection cycle.

Noise Induces Biased Estimation of the Correction Gain.

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Jooeun Ahn

Full Text Available The detection of an error in the motor output and the correction in the next movement are critical components of any form of motor learning. Accordingly, a variety of iterative learning models have assumed that a fraction of the error is adjusted in the next trial. This critical fraction, the correction gain, learning rate, or feedback gain, has been frequently estimated via least-square regression of the obtained data set. Such data contain not only the inevitable noise from motor execution, but also noise from measurement. It is generally assumed that this noise averages out with large data sets and does not affect the parameter estimation. This study demonstrates that this is not the case and that in the presence of noise the conventional estimate of the correction gain has a significant bias, even with the simplest model. Furthermore, this bias does not decrease with increasing length of the data set. This study reveals this limitation of current system identification methods and proposes a new method that overcomes this limitation. We derive an analytical form of the bias from a simple regression method (Yule-Walker and develop an improved identification method. This bias is discussed as one of other examples for how the dynamics of noise can introduce significant distortions in data analysis.

HD CAG-correlated gene expression changes support a simple dominant gain of function

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Jacobsen, Jessie C.; Gregory, Gillian C.; Woda, Juliana M.; Thompson, Morgan N.; Coser, Kathryn R.; Murthy, Vidya; Kohane, Isaac S.; Gusella, James F.; Seong, Ihn Sik; MacDonald, Marcy E.; Shioda, Toshi; Lee, Jong-Min

2011-01-01

Huntington's disease is initiated by the expression of a CAG repeat-encoded polyglutamine region in full-length huntingtin, with dominant effects that vary continuously with CAG size. The mechanism could involve a simple gain of function or a more complex gain of function coupled to a loss of function (e.g. dominant negative-graded loss of function). To distinguish these alternatives, we compared genome-wide gene expression changes correlated with CAG size across an allelic series of heterozygous CAG knock-in mouse embryonic stem (ES) cell lines (HdhQ20/7, HdhQ50/7, HdhQ91/7, HdhQ111/7), to genes differentially expressed between Hdhex4/5/ex4/5 huntingtin null and wild-type (HdhQ7/7) parental ES cells. The set of 73 genes whose expression varied continuously with CAG length had minimal overlap with the 754-member huntingtin-null gene set but the two were not completely unconnected. Rather, the 172 CAG length-correlated pathways and 238 huntingtin-null significant pathways clustered into 13 shared categories at the network level. A closer examination of the energy metabolism and the lipid/sterol/lipoprotein metabolism categories revealed that CAG length-correlated genes and huntingtin-null-altered genes either were different members of the same pathways or were in unique, but interconnected pathways. Thus, varying the polyglutamine size in full-length huntingtin produced gene expression changes that were distinct from, but related to, the effects of lack of huntingtin. These findings support a simple gain-of-function mechanism acting through a property of the full-length huntingtin protein and point to CAG-correlative approaches to discover its effects. Moreover, for therapeutic strategies based on huntingtin suppression, our data highlight processes that may be more sensitive to the disease trigger than to decreased huntingtin levels. PMID:21536587

Recent progress in the therapeutic applications of nanotechnology.

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Solomon, Melani; D'Souza, Gerard G M

2011-04-01

The field of pharmaceutical and medical nanotechnology has grown rapidly in recent decades and offers much promise for therapeutic advances. This review is intended to serve as a quick summary of the major areas in the therapeutic application of nanotechnology. Nanotechnology for therapeutic application falls into two broad categories of particulate systems and nanoengineered devices. Recent studies appear to focus on the development of multifunctional particles for drug delivery and imaging and the development of nanotechnology-based biosensors for diagnostic applications. Cancer treatment and diagnosis appears to be the principal focus of many of these applications, but nanotechnology is also finding application in tissue engineering and surface engineering of medical implants. Particulate drug delivery systems in general appear to be poised for increased use in the clinic, whereas nanoengineered implants and diagnostic sensors might well be the next major wave in the medical use of nanotechnology.

Cell-derived microparticles: new targets in the therapeutic management of disease.

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Roseblade, Ariane; Luk, Frederick; Rawling, Tristan; Ung, Alison; Grau, Georges E R; Bebawy, Mary

2013-01-01

Intercellular communication is essential to maintain vital physiological activities and to regulate the organism's phenotype. There are a number of ways in which cells communicate with one another. This can occur via autocrine signaling, endocrine signaling or by the transfer of molecular mediators across gap junctions. More recently communication via microvesicular shedding has gained important recognition as a significant pathway by which cells can coordinate the spread and dominance of selective traits within a population. Through this communication apparatus, cells can now acquire and secure a survival advantage, particularly in the context of malignant disease. This review aims to highlight some of the functions and implications of microparticles in physiology of various disease states, and present a novel therapeutic strategy through the regulation of microparticle production.

Welfare gains by reducing transaction costs: Linking trade and innovation policy

NARCIS (Netherlands)

Butter, den Frank A.G.; Baeten, Joost

2006-01-01

Specialisation and trade are major sources of productivity increases, and therefore of welfare gains. With reference to the Netherlands this paper discusses how (international) fragmentation of production and outsourcing may enhance productivity. In order to promote further specialisation and trade,

Pre-pregnancy BMI-specific optimal gestational weight gain for women in Japan

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Naho Morisaki

2017-09-01

Full Text Available Background: The Institute of Medicine (IOM guidelines are the most widely used guidelines on gestational weight gain; however, accumulation of evidence that body composition in Asians differs from other races has brought concern regarding whether their direct application is appropriate. We aimed to study to what extent optimal gestational weight gain among women in Japan differs by pre-pregnancy body mass index (BMI and to compare estimated optimal gestational weight gain to current Japanese and Institute of Medicine (IOM recommendations. Methods: We retrospectively studied 104,070 singleton pregnancies among nulliparous women in 2005–2011 using the Japanese national perinatal network database. In five pre-pregnancy BMI sub-groups (17.0–18.4, 18.5–19.9, 20–22.9, 23–24.9, and 25–27.4 kg/m2, we estimated the association of the rate of gestational weight gain with pregnancy outcomes (fetal growth, preterm delivery, and delivery complications using multivariate regression. Results: Weight gain rate associated with the lowest risk of adverse outcomes decreased with increasing BMI (12.2 kg, 10.9 kg, 9.9 kg, 7.7 kg, and 4.3 kg/40 weeks for the five BMI categories as described above, respectively. Current Japanese guidelines were lower than optimal gains, with the lowest risk of adverse outcomes for women with BMI below 18.5 kg/m2, and current IOM recommendations were higher than optimal gains for women with BMI over 23 kg/m2. Conclusion: Optimal weight gain during pregnancy varies largely by pre-pregnancy BMI, and defining those with BMI over 23 kg/m2 as overweight, as proposed by the World Health Organization, may be useful when applying current IOM recommendations to Japanese guidelines.

Pre-pregnancy BMI-specific optimal gestational weight gain for women in Japan.

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Morisaki, Naho; Nagata, Chie; Jwa, Seung Chik; Sago, Haruhiko; Saito, Shigeru; Oken, Emily; Fujiwara, Takeo

2017-10-01

The Institute of Medicine (IOM) guidelines are the most widely used guidelines on gestational weight gain; however, accumulation of evidence that body composition in Asians differs from other races has brought concern regarding whether their direct application is appropriate. We aimed to study to what extent optimal gestational weight gain among women in Japan differs by pre-pregnancy body mass index (BMI) and to compare estimated optimal gestational weight gain to current Japanese and Institute of Medicine (IOM) recommendations. We retrospectively studied 104,070 singleton pregnancies among nulliparous women in 2005-2011 using the Japanese national perinatal network database. In five pre-pregnancy BMI sub-groups (17.0-18.4, 18.5-19.9, 20-22.9, 23-24.9, and 25-27.4 kg/m 2 ), we estimated the association of the rate of gestational weight gain with pregnancy outcomes (fetal growth, preterm delivery, and delivery complications) using multivariate regression. Weight gain rate associated with the lowest risk of adverse outcomes decreased with increasing BMI (12.2 kg, 10.9 kg, 9.9 kg, 7.7 kg, and 4.3 kg/40 weeks) for the five BMI categories as described above, respectively. Current Japanese guidelines were lower than optimal gains, with the lowest risk of adverse outcomes for women with BMI below 18.5 kg/m 2 , and current IOM recommendations were higher than optimal gains for women with BMI over 23 kg/m 2 . Optimal weight gain during pregnancy varies largely by pre-pregnancy BMI, and defining those with BMI over 23 kg/m 2 as overweight, as proposed by the World Health Organization, may be useful when applying current IOM recommendations to Japanese guidelines. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Autophagy as a Therapeutic Target in Cardiovascular Disease

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Nemchenko, Andriy; Chiong, Mario; Turer, Aslan; Lavandero, Sergio; Hill, Joseph A.

2011-01-01

The epidemic of heart failure continues apace, and development of novel therapies with clinical efficacy has lagged. Now, important insights into the molecular circuitry of cardiovascular autophagy have raised the prospect that this cellular pathway of protein quality control may be a target of clinical relevance. Whereas basal levels of autophagy are required for cell survival, excessive levels – or perhaps distinct forms of autophagic flux – contribute to disease pathogenesis. Our challenge will be to distinguish mechanisms that drive adaptive versus maladaptive autophagy and to manipulate those pathways for therapeutic gain. Recent evidence suggests this may be possible. Here, we review the fundamental biology of autophagy and its role in a variety of forms of cardiovascular disease. We discuss ways in which this evolutionarily conserved catabolic mechanism can be manipulated, discuss studies presently underway in heart disease, and provide our perspective on where this exciting field may lead in the future. PMID:21723289

A Clinician’s Perspective on Incorporating Therapeutic Lifestyle Change into Clinical Practice

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Mark S. McIntosh

2011-02-01

Full Text Available This article describes the unique perspective of a clinician who was originally trained as an acute care specialist but in recent years had the opportunity to witness the positive impact of therapeutic lifestyle change (TLC programs in managing chronic diseases. Through experience gained from conducting a multi-center clinical trial investigating the effects of TLC program in people with metabolic syndrome, Dr. Mark S. McIntosh discusses various aspects and challenges pertinent to implementing a successful TLC program. Patients, physicians, lifestyle counselors, work places, and home environment are all critical in forming an alliance for transforming the current sick-care approach to preventive, wellness-focused approach that is far more efficient,rewarding, and financially sustainable.

Gain-of-function R225W mutation in human AMPKgamma(3 causing increased glycogen and decreased triglyceride in skeletal muscle.

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Sheila R Costford

Full Text Available BACKGROUND: AMP-activated protein kinase (AMPK is a heterotrimeric enzyme that is evolutionarily conserved from yeast to mammals and functions to maintain cellular and whole body energy homeostasis. Studies in experimental animals demonstrate that activation of AMPK in skeletal muscle protects against insulin resistance, type 2 diabetes and obesity. The regulatory gamma(3 subunit of AMPK is expressed exclusively in skeletal muscle; however, its importance in controlling overall AMPK activity is unknown. While evidence is emerging that gamma subunit mutations interfere specifically with AMP activation, there remains some controversy regarding the impact of gamma subunit mutations. Here we report the first gain-of-function mutation in the muscle-specific regulatory gamma(3 subunit in humans. METHODS AND FINDINGS: We sequenced the exons and splice junctions of the AMPK gamma(3 gene (PRKAG3 in 761 obese and 759 lean individuals, identifying 87 sequence variants including a novel R225W mutation in subjects from two unrelated families. The gamma(3 R225W mutation is homologous in location to the gamma(2R302Q mutation in patients with Wolf-Parkinson-White syndrome and to the gamma(3R225Q mutation originally linked to an increase in muscle glycogen content in purebred Hampshire Rendement Napole (RN- pigs. We demonstrate in differentiated muscle satellite cells obtained from the vastus lateralis of R225W carriers that the mutation is associated with an approximate doubling of both basal and AMP-activated AMPK activities. Moreover, subjects bearing the R225W mutation exhibit a approximately 90% increase of skeletal muscle glycogen content and a approximately 30% decrease in intramuscular triglyceride (IMTG. CONCLUSIONS: We have identified for the first time a mutation in the skeletal muscle-specific regulatory gamma(3 subunit of AMPK in humans. The gamma(3R225W mutation has significant functional effects as demonstrated by increases in basal and AMP

Therapeutic Nanodevices

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Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

Health behaviours of pregnant women and gestational weight gains – a pilot study

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Edyta Suliga

2015-10-01

Full Text Available Introduction: Abnormal weight gain during pregnancy may exert a negative effect on the development of the foetus, the course of pregnancy, and later the state of health of the mother and her baby. Due to the unfavourable health consequences of abnormal body weight gains in expectant mothers studies of the factors that determine the amount of these gains are important. Aim of the research : Evaluation of the relationship between health behaviours in pregnancy, nutritional status before pregnancy, selected socio-demographic factors, and gestational weight gain. Material and methods : The investigation included 274 women. Using a questionnaire, information was collected pertaining to the place of residence, age, body height and weight, cigarette smoking, and eating habits during pregnancy. The total weight gain during pregnancy was calculated as the difference between perinatal weight and pre-pregnancy body weight. Gestational weight gains were classified as low, recommended, or high. Results: Increased risk of high weight gain was associated with the consumption of alcoholic beverages (odds ratio (OR = 2.82, especially beer (OR = 2.72, high consumption of products supplying proteins of animal origin (OR = 2.87, and overweight before pregnancy (OR = 3.37, as well as the delivery being the mother’s first, compared to the third and subsequent childbirth (OR = 4.17. Conclusions: This study indicates that there is a need for health education among females at reproductive age in order to reduce excess weight before conception, and promotion of adequate health behaviours in pregnancy, which would allow the maintenance of normal weight gain during this period.

Studies of population inversion and gains for xuv laser development in a recombining plasma column

International Nuclear Information System (INIS)

Milchberg, H.M.

1985-01-01

An experimental study is presented of population inversions and gains in CO 2 laser produced plasmas in a number of different solid and gas targets, with and without the presence of a magnetic field. Population inversions and gains were measured in hydrogenic carbon, CVI, and in the Li-like sequence CIV, OVI, FVII, and NeVIII. The Li-like species were easily produced in gas targets and, in general, 4d-3d population inversions were seen to increase with a combination of higher target pressure and the presence of an external magnetic field. Ratios of the 4d-3d sublevel populations ranged up to approx.10, for OVI. Inversions in CIV and FVII, in cases where solid targets were used, were less sensitive to the presence of the magnetic field. Gains in the CVI 182.17 A (3-2) line were measured using solid carbon targets, and increased in the presence of a magnetic field. The effect of placing aluminum blades near the target, for plasma cooling and faster recombination, was inconclusive. In general, gains determined by measuring an on-axis enhancement of the 182.17 A line were consistent with absolute measurements of CVI excitation-level populations. Gains of 2-4 cm -1 were measured. Axially oriented carbon-fiber targets were irradiated by the CO 2 laser, and it was found that population inversions and gain resulted only when there was no magnetic field present

Therapeutic Plasma Exchange in Critically Ill Children Requiring Intensive Care.

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Cortina, Gerard; McRae, Rosemary; Chiletti, Roberto; Butt, Warwick

2018-02-01

To characterize the clinical indications, procedural safety, and outcome of critically ill children requiring therapeutic plasma exchange. Retrospective observational study based on a prospective registry. Tertiary and quaternary referral 30-bed PICU. Forty-eight critically ill children who received therapeutic plasma exchange during an 8-year period (2007-2014) were included in the study. Therapeutic plasma exchange. A total of 48 patients underwent 244 therapeutic plasma exchange sessions. Of those, therapeutic plasma exchange was performed as sole procedure in 193 (79%), in combination with continuous renal replacement therapy in 40 (16.4%) and additional extracorporeal membrane oxygenation in 11 (4.6%) sessions. The most common admission diagnoses were hematologic disorders (30%), solid organ transplantation (20%), neurologic disorders (20%), and rheumatologic disorders (15%). Complications associated with the procedure occurred in 50 (21.2%) therapeutic plasma exchange sessions. Overall, patient survival from ICU was 82%. Although patients requiring therapeutic plasma exchange alone (n = 31; 64%) had a survival rate of 97%, those with additional continuous renal replacement therapy (n = 13; 27%) and extracorporeal membrane oxygenation (n = 4; 8%) had survival rates of 69% and 50%, respectively. Factors associated with increased mortality were lower Pediatric Index of Mortality 2 score, need for mechanical ventilation, higher number of failed organs, and longer ICU stay. Our results indicate that, in specialized centers, therapeutic plasma exchange can be performed relatively safely in critically ill children, alone or in combination with continuous renal replacement therapy and extracorporeal membrane oxygenation. Outcome in children requiring therapeutic plasma exchange alone is excellent. However, survival decreases with the number of failed organs and the need for continuous renal replacement therapy and extracorporeal membrane oxygenation.

Therapeutic conflicts in emergency department patients with multimorbidity: a cross-sectional study.

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Stefan Markun

Full Text Available Patients with multimorbidity are an increasing concern in healthcare. Clinical practice guidelines, however, do not take into account potential therapeutic conflicts caused by co-occurring medical conditions. This makes therapeutic decisions complex, especially in emergency situations.The aim of this study was to identify and quantify therapeutic conflicts in emergency department patients with multimorbidity.We reviewed electronic records of all patients ≥18 years with two or more concurrent active medical conditions, admitted from the emergency department to the hospital ward of the University Hospital Zurich in January 2009. We cross-tabulated all active diagnoses with treatments recommended by guidelines for each diagnosis. Then, we identified potential therapeutic conflicts and classified them as either major or minor conflicts according to their clinical significance.166 emergency inpatients with multimorbidity were included. The mean number of active diagnoses per patient was 6.6 (SD±3.4. We identified a total of 239 therapeutic conflicts in 49% of the of the study population. In 29% of the study population major therapeutic conflicts, in 41% of the patients minor therapeutic conflicts occurred.Therapeutic conflicts are common among multimorbid patients, with one out of two experiencing minor, and one out of three experiencing major therapeutic conflicts. Clinical practice guidelines need to address frequent therapeutic conflicts in patients with co-morbid medical conditions.

Therapeutic conflicts in emergency department patients with multimorbidity: a cross-sectional study.

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Markun, Stefan; Holzer, Barbara M; Rodak, Roksana; Kaplan, Vladimir; Wagner, Claudia C; Battegay, Edouard; Zimmerli, Lukas

2014-01-01

Patients with multimorbidity are an increasing concern in healthcare. Clinical practice guidelines, however, do not take into account potential therapeutic conflicts caused by co-occurring medical conditions. This makes therapeutic decisions complex, especially in emergency situations. The aim of this study was to identify and quantify therapeutic conflicts in emergency department patients with multimorbidity. We reviewed electronic records of all patients ≥18 years with two or more concurrent active medical conditions, admitted from the emergency department to the hospital ward of the University Hospital Zurich in January 2009. We cross-tabulated all active diagnoses with treatments recommended by guidelines for each diagnosis. Then, we identified potential therapeutic conflicts and classified them as either major or minor conflicts according to their clinical significance. 166 emergency inpatients with multimorbidity were included. The mean number of active diagnoses per patient was 6.6 (SD±3.4). We identified a total of 239 therapeutic conflicts in 49% of the of the study population. In 29% of the study population major therapeutic conflicts, in 41% of the patients minor therapeutic conflicts occurred. Therapeutic conflicts are common among multimorbid patients, with one out of two experiencing minor, and one out of three experiencing major therapeutic conflicts. Clinical practice guidelines need to address frequent therapeutic conflicts in patients with co-morbid medical conditions.

Persistency of Prediction Accuracy and Genetic Gain in Synthetic Populations Under Recurrent Genomic Selection.

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Müller, Dominik; Schopp, Pascal; Melchinger, Albrecht E

2017-03-10

Recurrent selection (RS) has been used in plant breeding to successively improve synthetic and other multiparental populations. Synthetics are generated from a limited number of parents [Formula: see text] but little is known about how [Formula: see text] affects genomic selection (GS) in RS, especially the persistency of prediction accuracy ([Formula: see text]) and genetic gain. Synthetics were simulated by intermating [Formula: see text]= 2-32 parent lines from an ancestral population with short- or long-range linkage disequilibrium ([Formula: see text]) and subjected to multiple cycles of GS. We determined [Formula: see text] and genetic gain across 30 cycles for different training set ( TS ) sizes, marker densities, and generations of recombination before model training. Contributions to [Formula: see text] and genetic gain from pedigree relationships, as well as from cosegregation and [Formula: see text] between QTL and markers, were analyzed via four scenarios differing in (i) the relatedness between TS and selection candidates and (ii) whether selection was based on markers or pedigree records. Persistency of [Formula: see text] was high for small [Formula: see text] where predominantly cosegregation contributed to [Formula: see text], but also for large [Formula: see text] where [Formula: see text] replaced cosegregation as the dominant information source. Together with increasing genetic variance, this compensation resulted in relatively constant long- and short-term genetic gain for increasing [Formula: see text] > 4, given long-range LD A in the ancestral population. Although our scenarios suggest that information from pedigree relationships contributed to [Formula: see text] for only very few generations in GS, we expect a longer contribution than in pedigree BLUP, because capturing Mendelian sampling by markers reduces selective pressure on pedigree relationships. Larger TS size ([Formula: see text]) and higher marker density improved persistency of

Alternative Splicing in Breast Cancer and the Potential Development of Therapeutic Tools.

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Martínez-Montiel, Nancy; Anaya-Ruiz, Maricruz; Pérez-Santos, Martín; Martínez-Contreras, Rebeca D

2017-10-05

Alternative splicing is a key molecular mechanism now considered as a hallmark of cancer that has been associated with the expression of distinct isoforms during the onset and progression of the disease. The leading cause of cancer-related deaths in women worldwide is breast cancer, and even when the role of alternative splicing in this type of cancer has been established, the function of this mechanism in breast cancer biology is not completely decoded. In order to gain a comprehensive view of the role of alternative splicing in breast cancer biology and development, we summarize here recent findings regarding alternative splicing events that have been well documented for breast cancer evolution, considering its prognostic and therapeutic value. Moreover, we analyze how the response to endocrine and chemical therapies could be affected due to alternative splicing and differential expression of variant isoforms. With all this knowledge, it becomes clear that targeting alternative splicing represents an innovative approach for breast cancer therapeutics and the information derived from current studies could guide clinical decisions with a direct impact in the clinical advances for breast cancer patients nowadays.

Measured stimulated Raman gain in methane

International Nuclear Information System (INIS)

Lopert, R.B.

1983-01-01

This report is about the stimulated Raman effect in methane due to the nu 1 vibration. For various gas pressures between 150 torr and 30 atm, the Raman lineshape function was both experimentally measured and synthesized using a computer model. The stimulated Raman gain was measured by sending a pump laser beam provided by an argon-ion laser and a weak probe beam provided by a tunable dye laser through a cell of methane gas. The stimulated Raman effect caused some of the energy from the pump beam to be transferred to the probe beam. The intensity of the pump beam was low so the gain of the probe beam was on the order of parts per million. A two detector arrangement and a differential amplifier system that had a feedback loop to balance the detectors was constructed to measure the small gains. A detailed description of this detection system that was able to measure gains as small as 0.2 parts per million is provided

Evaluation of Therapeutics for Advanced-Stage Heart Failure and Other Severely-Debilitating or Life-Threatening Diseases.

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Prescott, J S; Andrews, P A; Baker, R W; Bogdanffy, M S; Fields, F O; Keller, D A; Lapadula, D M; Mahoney, N M; Paul, D E; Platz, S J; Reese, D M; Stoch, S A; DeGeorge, J J

2017-08-01

Severely-debilitating or life-threatening (SDLT) diseases include conditions in which life expectancy is short or quality of life is greatly diminished despite available therapies. As such, the medical context for SDLT diseases is comparable to advanced cancer and the benefit vs. risk assessment and development of SDLT disease therapeutics should be similar to that of advanced cancer therapeutics. A streamlined development approach would allow patients with SDLT conditions earlier access to therapeutics and increase the speed of progression through development. In addition, this will likely increase the SDLT disease therapeutic pipeline, directly benefiting patients and reducing the economic and societal burden of SDLT conditions. Using advanced-stage heart failure (HF) as an example that illustrates the concepts applicable to other SDLT indications, this article proposes a streamlined development paradigm for SDLT disease therapeutics and recommends development of aligned global regulatory guidance. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Macromolecular therapeutics.

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Yang, Jiyuan; Kopeček, Jindřich

2014-09-28

This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines - (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. Copyright © 2014 Elsevier B.V. All rights reserved.

Energy expenditure, spontaneous physical activity and with weight gain in kidney transplant recipients.

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Heng, Anne-Elisabeth; Montaurier, Christophe; Cano, Noël; Caillot, Nicolas; Blot, A; Meunier, Nathalie; Pereira, Bruno; Marceau, Geoffroy; Sapin, Vincent; Jouve, Christelle; Boirie, Yves; Deteix, Patrice; Morio, Beatrice

2015-06-01

Alterations in energy metabolism could trigger weight gain after renal transplantation. Nineteen transplanted non-diabetic men, 53 ± 1.6 years old, receiving calcineurin inhibitors but no corticosteroids were studied. They were compared with nine healthy men matched for height, age and lean body mass. Daily energy expenditure and its components (sleeping, basal and absorptive metabolic rates) were analyzed for 24 h in calorimetric chambers and for 4 days in free living conditions using calibrated accelerometry. Other variables known to influence energy expenditure were assessed: body composition, physical activity, 4-day food intake, drug consumption, serum C-reactive protein, interleukin-6, thyroid and parathyroid hormones, and epinephrine. Transplant recipients who gained more than 5% body weight after transplantation (n = 11, +11.0 ± 1.5 kg) were compared with those who did not (n = 8) and with the controls. Weight gain compared with non-weight gain patients and controls exhibited higher fat mass without change in lean body mass. Daily, sleeping and resting energy expenditure adjusted for lean body mass was significantly higher in non-weight gain (167.1 ± 4.2 kJ/kg/lean body mass/24 h, P controls (146.1 ± 4.6). Weight gain compared with controls and non-weight gain subjects had lower free living physical activity and a higher consumption of antihypertensive drugs and β-blockers. After kidney transplantation, weight gain patients were characterized by lower adjusted energy expenditure, reduced spontaneous physical activity but a more sedentary life style and a trend toward a higher energy intake explaining the reason they gained weight. The nWG KTR had increased resting and sleeping EE which protected them from weight gain. Such hypermetabolism was also observed in 24-h EE measurements. By comparison with the nWG patients, the WG transplant recipients were characterized by higher β-blocker consumption. These data could be helpful in the prevention of weight

Polygenic Risk, Appetite Traits, and Weight Gain in Middle Childhood

Science.gov (United States)

Steinsbekk, Silje; Belsky, Daniel; Guzey, Ismail Cuneyt; Wardle, Jane; Wichstrøm, Lars

2018-01-01

weight and fat mass more rapidly during follow-up. Each SD increase in genetic risk score was associated with a 0.22-point increase in BMI at age-4 baseline (for the intercept, unstandardized path coefficient B = 0.22 [95%CI, 0.06–0.38]; P = .008. Children with higher genetic risk scores also gained BMI points more rapidly from ages 4 to 6 years (B = 0.11 [95% CI, 0.03–0.20]; P = .01 ; β = 0.12) and from 6 to 8 years (B = 0.09 [95%CI, 0.00–0.19]; P = .05; β = 0.10), compared with their lower genetic risk peers. Children at higher genetic risk had higher levels of alleged obesogenic appetite traits than peers with lower genetic risk at age 6 years, but appetite traits did not mediate genetic associations with weight gain. The sum of the 5 indirect effects was B = −0.001 (95%CI, −0.02 –0.01); P = .86; β = 0.00. CONCLUSIONS AND RELEVANCE Genetic risk for obesity is associated with accelerated childhood weight gain. Interventions targeting childhood weight gain may provide one path to mitigating genetic risk. However, middle childhood appetite traits may not be a promising target for such interventions. Studies of early-childhood samples are needed to test whether appetite traits explain how genetic risks accelerate growth earlier in development. PMID:26830872

Maternal obesity and gestational weight gain are risk factors for infant death.

Science.gov (United States)

Bodnar, Lisa M; Siminerio, Lara L; Himes, Katherine P; Hutcheon, Jennifer A; Lash, Timothy L; Parisi, Sara M; Abrams, Barbara

2016-02-01

Assessment of the joint and independent relationships of gestational weight gain and prepregnancy body mass index (BMI) on risk of infant mortality was performed. This study used Pennsylvania linked birth-infant death records (2003-2011) from infants without anomalies born to mothers with prepregnancy BMI categorized as underweight (n = 58,973), normal weight (n = 610,118), overweight (n = 296,630), grade 1 obesity (n = 147,608), grade 2 obesity (n = 71,740), and grade 3 obesity (n = 47,277). Multivariable logistic regression models stratified by BMI category were used to estimate dose-response associations between z scores of gestational weight gain and infant death after confounder adjustment. Infant mortality risk was lowest among normal-weight women and increased with rising BMI category. For all BMI groups except for grade 3 obesity, there were U-shaped associations between gestational weight gain and risk of infant death. Weight loss and very low weight gain among women with grades 1 and 2 obesity were associated with high risks of infant mortality. However, even when gestational weight gain in women with obesity was optimized, the predicted risk of infant death remained higher than that of normal-weight women. Interventions aimed at substantially reducing preconception weight among women with obesity and avoiding very low or very high gestational weight gain may reduce risk of infant death. © 2015 The Obesity Society.

A 3-year physical activity intervention program increases the gain in bone mineral and bone width in prepubertal girls but not boys: the prospective copenhagen school child interventions study (CoSCIS).

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Hasselstrøm, H A; Karlsson, M K; Hansen, S E; Grønfeldt, V; Froberg, K; Andersen, L B

2008-10-01

The aim of this study was to evaluate the effect of increasing the amount of time spent in physical education classes on bone mineral accrual and gain in bone size in prepubertal Danish children. A total of 135 boys and 108 girls, aged 6-8 years, were included in a school-based curriculum intervention program where the usual time spent in physical education classes was doubled to four classes (180 min) per week. The control group comprised age-matched children (62 boys and 76 girls) recruited from a separate community who completed the usual Danish school curriculum of physical activity (90 min/week). Dual-energy X-ray absorptiometry was used to evaluate bone mineral content (BMC; g), bone mineral density (g/cm(2)), and bone width at the calcaneus and distal forearm before and after 3 years of intervention. Anthropometrics and Tanner stages were evaluated on the same occasions. General physical activity was measured with an accelerometer worn for 4 days. In girls, the intervention group had a 12.5% increase (P = 0.04) in distal forearm BMC and a 13.2% increase (P = 0.005) in distal forearm scanned area compared with girls in the control group. No differences were found between the intervention and control groups in boys. Increasing the frequency of physical education classes for prepubertal children is associated with a higher accrual of bone mineral and higher gain in bone size after 3 years in girls but not in boys.

Challenges of therapeutic substitution of drugs for economic reasons: focus on CVD prevention.

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Johnston, Atholl

2010-04-01

Healthcare systems throughout the world are under increasing pressure to control and minimise costs. The substitution of initially-prescribed drugs with cheaper equivalents is an obvious option which presents a rapid and visible means to reduce these costs. Whether the substitution improves patient and/or population outcomes must be appraised and this paper highlights the conditions under which therapeutic substitution may require additional thought and consideration. In this paper, some of the medical evidence and the regulatory environment for and against the three types of therapeutic substitution - generic, within-class and between-class - are discussed. This article is not an exhaustive review of the literature, but captures some of the key clinical, pharmacological, economic, policy and ethical issues regarding generic and therapeutic substitution. Search criteria of the most commonly used terms, i.e. therapeutic substitution, switching, interchange, and bioequivalence, were applied to Embase, PubMed and Google Scholar to identify relevant publications. Although population studies support therapeutic substitution in principle, there is evidence that substitution may not always result in therapeutic equivalence in individual patients, with the consequent potential for greater risks of decreased efficacy and/or increased safety concerns. Factors such as patient choice and therapeutic equivalence also play an important role in the effectiveness of the treatment and overall management of the patient. The pan-European regulatory environment provides another contradiction, encouraging widespread cost containment through reduction in drug acquisition costs, while simultaneously promoting an increased role for patients in defining and managing their own treatment. There is a strong rationale for careful management in some patients with cardiovascular disease. Treatment decisions should be transparent and based on strong clinical evidence. If not, drug substitution on

Radiation hardness of thin Low Gain Avalanche Detectors

Science.gov (United States)

Kramberger, G.; Carulla, M.; Cavallaro, E.; Cindro, V.; Flores, D.; Galloway, Z.; Grinstein, S.; Hidalgo, S.; Fadeyev, V.; Lange, J.; Mandić, I.; Medin, G.; Merlos, A.; McKinney-Martinez, F.; Mikuž, M.; Quirion, D.; Pellegrini, G.; Petek, M.; Sadrozinski, H. F.-W.; Seiden, A.; Zavrtanik, M.

2018-05-01

Low Gain Avalanche Detectors (LGAD) are based on a n++-p+-p-p++ structure where an appropriate doping of the multiplication layer (p+) leads to high enough electric fields for impact ionization. Gain factors of few tens in charge significantly improve the resolution of timing measurements, particularly for thin detectors, where the timing performance was shown to be limited by Landau fluctuations. The main obstacle for their operation is the decrease of gain with irradiation, attributed to effective acceptor removal in the gain layer. Sets of thin sensors were produced by two different producers on different substrates, with different gain layer doping profiles and thicknesses (45, 50 and 80 μm). Their performance in terms of gain/collected charge and leakage current was compared before and after irradiation with neutrons and pions up to the equivalent fluences of 5 ṡ 1015 cm-2. Transient Current Technique and charge collection measurements with LHC speed electronics were employed to characterize the detectors. The thin LGAD sensors were shown to perform much better than sensors of standard thickness (∼300 μm) and offer larger charge collection with respect to detectors without gain layer for fluences gain prolongs the beneficial performance of LGADs. Pions were found to be more damaging than neutrons at the same equivalent fluence, while no significant difference was found between different producers. At very high fluences and bias voltages the gain appears due to deep acceptors in the bulk, hence also in thin standard detectors.

Therapeutic management of radiation-induced oral mucositis

International Nuclear Information System (INIS)

Doerr, W.; Doelling-Jochem, I.; Baumann, M.; Herrmann, T.

1997-01-01

Background: Acute reactions of oral mucosa are a frequent side effect of radiotherapy, which often necessitates interruption of the treatment. Marked proliferation of tumor stem cells during treatment interruptions may occur in squamous cell carcinomata, which represent the majority of tumors in the head and neck area. Hence a fatal consequence of treatment breaks may be a significant decrease in tumor cure rates. Furthermore, marked acute responses frequently result in increased late sequelae ('consequential damage'). Therefore, amelioration of the mucosal response aiming at avoiding treatment breaks and at reduction of late reactions coul definitely increase the therapeutic success of radiation treatment. Results: A variety of prophylactic and therapeutic methods have been proposed for the management of acute radiation reactions of the oral mucosa. Frequently, their efficiacy has been established for chemotherapy or in combination with other immunosuppressive treatments. Hence, systemical rather than local effects have to be considered. Conclusions: In general, prophylaxis of oral mucositis is mainly based on dental restoration or edentation, in combination with frequent oral hygienic measures after the meals and with antiseptic mouthwashes. Intensive personal care is recommended. The necessity of a percutaneous endoscopic gastrostoma is dependent on the status of the patient and on size and localization of the treatment area, i.e. the impairment of food uptake which is to be expected. Therapeutic intervention is restricted to local or systemic treatment of pain and local application of antimycotics and antibiotics. (orig./VHE) [de

Electroacupuncture Reduces Weight Gain Induced by Rosiglitazone through PPARγ and Leptin Receptor in CNS

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Xinyue Jing

2016-01-01

Full Text Available We investigate the effect of electroacupuncture (EA on protecting the weight gain side effect of rosiglitazone (RSG in type 2 diabetes mellitus (T2DM rats and its possible mechanism in central nervous system (CNS. Our study showed that RSG (5 mg/kg significantly increased the body weight and food intake of the T2DM rats. After six-week treatment with RSG combined with EA, body weight, food intake, and the ratio of IWAT to body weight decreased significantly, whereas the ratio of BAT to body weight increased markedly. HE staining indicated that the T2DM-RSG rats had increased size of adipocytes in their IWAT, but EA treatment reduced the size of adipocytes. EA effectively reduced the lipid contents without affecting the antidiabetic effect of RSG. Furthermore, we noticed that the expression of PPARγ gene in hypothalamus was reduced by EA, while the expressions of leptin receptor and signal transducer and activator of transcription 3 (STAT3 were increased. Our results suggest that EA is an effective approach for inhibiting weight gain in T2DM rats treated by RSG. The possible mechanism might be through increased levels of leptin receptor and STAT3 and decreased PPARγ expression, by which food intake of the rats was reduced and RSG-induced weight gain was inhibited.

Ricardian Productivity Differences and the Gains from Trade

OpenAIRE

Andrei A. Levchenko; Jing Zhang

2013-01-01

This paper evaluates the role of sectoral heterogeneity in determining the gains from trade. We first show analytically that in the presence of sectoral Ricardian comparative advantage, a one- sector sufficient statistic formula that uses total trade volumes as a share of total absorption systematically understates the true gains from trade. Greater relative sectoral productivity differences lead to larger disparities between the gains implied by the one-sector formula and the true gains. Usi...

Preclinical models used for immunogenicity prediction of therapeutic proteins.

Science.gov (United States)

Brinks, Vera; Weinbuch, Daniel; Baker, Matthew; Dean, Yann; Stas, Philippe; Kostense, Stefan; Rup, Bonita; Jiskoot, Wim

2013-07-01

All therapeutic proteins are potentially immunogenic. Antibodies formed against these drugs can decrease efficacy, leading to drastically increased therapeutic costs and in rare cases to serious and sometimes life threatening side-effects. Many efforts are therefore undertaken to develop therapeutic proteins with minimal immunogenicity. For this, immunogenicity prediction of candidate drugs during early drug development is essential. Several in silico, in vitro and in vivo models are used to predict immunogenicity of drug leads, to modify potentially immunogenic properties and to continue development of drug candidates with expected low immunogenicity. Despite the extensive use of these predictive models, their actual predictive value varies. Important reasons for this uncertainty are the limited/insufficient knowledge on the immune mechanisms underlying immunogenicity of therapeutic proteins, the fact that different predictive models explore different components of the immune system and the lack of an integrated clinical validation. In this review, we discuss the predictive models in use, summarize aspects of immunogenicity that these models predict and explore the merits and the limitations of each of the models.

Subtractive, divisive and non-monotonic gain control in feedforward nets linearized by noise and delays.

Science.gov (United States)

Mejias, Jorge F; Payeur, Alexandre; Selin, Erik; Maler, Leonard; Longtin, André

2014-01-01

The control of input-to-output mappings, or gain control, is one of the main strategies used by neural networks for the processing and gating of information. Using a spiking neural network model, we studied the gain control induced by a form of inhibitory feedforward circuitry-also known as "open-loop feedback"-, which has been experimentally observed in a cerebellum-like structure in weakly electric fish. We found, both analytically and numerically, that this network displays three different regimes of gain control: subtractive, divisive, and non-monotonic. Subtractive gain control was obtained when noise is very low in the network. Also, it was possible to change from divisive to non-monotonic gain control by simply modulating the strength of the feedforward inhibition, which may be achieved via long-term synaptic plasticity. The particular case of divisive gain control has been previously observed in vivo in weakly electric fish. These gain control regimes were robust to the presence of temporal delays in the inhibitory feedforward pathway, which were found to linearize the input-to-output mappings (or f-I curves) via a novel variability-increasing mechanism. Our findings highlight the feedforward-induced gain control analyzed here as a highly versatile mechanism of information gating in the brain.

Subtractive, divisive and non-monotonic gain control in feedforward nets linearized by noise and delays

Directory of Open Access Journals (Sweden)

Jorge F Mejias

2014-02-01

Full Text Available The control of input-to-output mappings, or gain control, is one of the main strategies used by neural networks for the processing and gating of information. Using a spiking neural network model, we studied the gain control induced by a form of inhibitory feedforward circuitry — also known as ’open-loop feedback’ —, which has been experimentally observed in a cerebellum-like structure in weakly electric fish. We found, both analytically and numerically, that this network displays three different regimes of gain control: subtractive, divisive, and non-monotonic. Subtractive gain control was obtained when noise is very low in the network. Also, it was possible to change from divisive to non-monotonic gain control by simply modulating the strength of the feedforward inhibition, which may be achieved via long-term synaptic plasticity. The particular case of divisive gain control has been previously observed in vivo in weakly electric fish. These gain control regimes were robust to the presence of temporal delays in the inhibitory feedforward pathway, which were found to linearize the input-to-output mappings (or f-I curves via a novel variability-increasing mechanism. Our findings highlight the feedforward-induced gain control analyzed here as a highly versatile mechanism of information gating in the brain.

Effect of Tactile-Kinesthetic Stimulation on Weight Gaining of Preterm Infants

Directory of Open Access Journals (Sweden)

Mahdi Basiry

2009-11-01

Full Text Available Background:The quality of life and standard of health care in a society is measured  by its preterm infants' mortality rate. The popularity and credibility of alternative treatment such as touch therapy may be effective in preterm and low birth weightinfants in order to increase their survival rate.The aim of this study was to determine the effect of touch intervention on the weight gain of preterm infants who were admitted to the Neonatal Intensive Care Unite(NICU. Methods:This study was a randomized controlled trial performed in NICU of  Emamreza hospital,Mashhad,Iran,from July 2007 to November 2007. There were two groups (the control group and the case group and one response variable (weight gain.Infants in the control group received routine nursing care. Infants in the case  group,in addition to the routine care,received stroking/passive limb movement therapy  for three 15 minute sessions per day for a 10 day period.Then weight gaining was compared between the two groups .  Results:The weight gain data was analyzed by SPSS software. Over the 10 day study period, the case group gained significantly more weight compared to the control  group (p(p<0.001(.Conclusion:The data suggest that stroking/passive limb movement can be an efficientand cost effective way of enhancing growth in stable preterm infants .

Active Microwave Metamaterials Incorporating Ideal Gain Devices

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Hao Xin

2010-12-01

Full Text Available Incorporation of active devices/media such as transistors for microwave and gain media for optics may be very attractive for enabling desired low loss and broadband metamaterials. Such metamaterials can even have gain which may very well lead to new and exciting physical phenomena. We investigate microwave composite right/left-handed transmission lines (CRLH-TL incorporating ideal gain devices such as constant negative resistance. With realistic lumped element values, we have shown that the negative phase constant of this kind of transmission lines is maintained (i.e., left-handedness kept while gain can be obtained (negative attenuation constant of transmission line simultaneously. Possible implementation and challenging issues of the proposed active CRLH-TL are also discussed.

[Nuclear transfer and therapeutic cloning].

Science.gov (United States)

Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

2005-03-01

Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

Nucleus accumbens response to gains in reputation for the self relative to gains for others predicts social media use.

Science.gov (United States)

Meshi, Dar; Morawetz, Carmen; Heekeren, Hauke R

2013-01-01

Our reputation is important to us; we've experienced natural selection to care about our reputation. Recently, the neural processing of gains in reputation (positive social feedback concerning one's character) has been shown to occur in the human ventral striatum. It is still unclear, however, how individual differences in the processing of gains in reputation may lead to individual differences in real-world behavior. For example, in the real-world, one way that people currently maintain their reputation is by using social media websites, like Facebook. Furthermore, Facebook use consists of a social comparison component, where users observe others' behavior and can compare it to their own. Therefore, we hypothesized a relationship between the way the brain processes specifically self-relevant gains in reputation and one's degree of Facebook use. We recorded functional neuroimaging data while participants received gains in reputation, observed the gains in reputation of another person, or received monetary reward. We demonstrate that across participants, when responding to gains in reputation for the self, relative to observing gains for others, reward-related activity in the left nucleus accumbens predicts Facebook use. However, nucleus accumbens activity in response to monetary reward did not predict Facebook use. Finally, a control step-wise regression analysis showed that Facebook use primarily explains our results in the nucleus accumbens. Overall, our results demonstrate how individual sensitivity of the nucleus accumbens to the receipt of self-relevant social information leads to differences in real-world behavior.

Frontiers in nano-therapeutics

CERN Document Server

Tasnim, Nishat; Sai Krishna, Katla; Kalagara, Sudhakar; Narayan, Mahesh; Noveron, Juan C; Joddar, Binata

2017-01-01

This brief highlights recent research advances in the area of nano-therapeutics. Nanotechnology holds immense potential for application in a wide range of biological and engineering applications such as molecular sensors for disease diagnosis, therapeutic agents for the treatment of diseases, a vehicle for delivering therapeutics and imaging agents for theranostic applications, both in-vitro and in-vivo. The brief is grouped into the following sections namely, A) Discrete Nanosystems ; B) Anisotropic Nanoparticles; C) Nano-films/coated/layered and D) Nano-composites.

Learning to walk with an adaptive gain proportional myoelectric controller for a robotic ankle exoskeleton.

Science.gov (United States)

Koller, Jeffrey R; Jacobs, Daniel A; Ferris, Daniel P; Remy, C David

2015-11-04

Robotic ankle exoskeletons can provide assistance to users and reduce metabolic power during walking. Our research group has investigated the use of proportional myoelectric control for controlling robotic ankle exoskeletons. Previously, these controllers have relied on a constant gain to map user's muscle activity to actuation control signals. A constant gain may act as a constraint on the user, so we designed a controller that dynamically adapts the gain to the user's myoelectric amplitude. We hypothesized that an adaptive gain proportional myoelectric controller would reduce metabolic energy expenditure compared to walking with the ankle exoskeleton unpowered because users could choose their preferred control gain. We tested eight healthy subjects walking with the adaptive gain proportional myoelectric controller with bilateral ankle exoskeletons. The adaptive gain was updated each stride such that on average the user's peak muscle activity was mapped to maximal power output of the exoskeleton. All subjects participated in three identical training sessions where they walked on a treadmill for 50 minutes (30 minutes of which the exoskeleton was powered) at 1.2 ms(-1). We calculated and analyzed metabolic energy consumption, muscle recruitment, inverse kinematics, inverse dynamics, and exoskeleton mechanics. Using our controller, subjects achieved a metabolic reduction similar to that seen in previous work in about a third of the training time. The resulting controller gain was lower than that seen in previous work (β=1.50±0.14 versus a constant β=2). The adapted gain allowed users more total ankle joint power than that of unassisted walking, increasing ankle power in exchange for a decrease in hip power. Our findings indicate that humans prefer to walk with greater ankle mechanical power output than their unassisted gait when provided with an ankle exoskeleton using an adaptive controller. This suggests that robotic assistance from an exoskeleton can allow

Stacked Transformer for Driver Gain and Receive Signal Splitting

Science.gov (United States)

Driscoll, Kevin R.

2013-01-01

In a high-speed signal transmission system that uses transformer coupling, there is a need to provide increased transmitted signal strength without adding active components. This invention uses additional transformers to achieve the needed gain. The prior art uses stronger drivers (which require an IC redesign and a higher power supply voltage), or the addition of another active component (which can decrease reliability, increase power consumption, reduce the beneficial effect of serializer/deserializer preemphasis or deemphasis, and/or interfere with fault containment mechanisms), or uses a different transformer winding ratio (which requires redesign of the transformer and may not be feasible with high-speed signals that require a 1:1 winding ratio). This invention achieves the required gain by connecting the secondaries of multiple transformers in series. The primaries of these transformers are currently either connected in parallel or are connected to multiple drivers. There is also a need to split a receive signal to multiple destinations with minimal signal loss. Additional transformers can achieve the split. The prior art uses impedance-matching series resistors that cause a loss of signal. Instead of causing a loss, most instantiations of this invention would actually provide gain. Multiple transformers are used instead of multiple windings on a single transformer because multiple windings on the same transformer would require a redesign of the transformer, and may not be feasible with high-speed transformers that usually require a bifilar winding with a 1:1 ratio. This invention creates the split by connecting the primaries of multiple transformers in series. The secondary of each transformer is connected to one of the intended destinations without the use of impedance-matching series resistors.

A virtual therapeutic environment with user projective agents.

Science.gov (United States)

Ookita, S Y; Tokuda, H

2001-02-01

Today, we see the Internet as more than just an information infrastructure, but a socializing place and a safe outlet of inner feelings. Many personalities develop aside from real world life due to its anonymous environment. Virtual world interactions are bringing about new psychological illnesses ranging from netaddiction to technostress, as well as online personality disorders and conflicts in multiple identities that exist in the virtual world. Presently, there are no standard therapy models for the virtual environment. There are very few therapeutic environments, or tools especially made for virtual therapeutic environments. The goal of our research is to provide the therapy model and middleware tools for psychologists to use in virtual therapeutic environments. We propose the Cyber Therapy Model, and Projective Agents, a tool used in the therapeutic environment. To evaluate the effectiveness of the tool, we created a prototype system, called the Virtual Group Counseling System, which is a therapeutic environment that allows the user to participate in group counseling through the eyes of their Projective Agent. Projective Agents inherit the user's personality traits. During the virtual group counseling, the user's Projective Agent interacts and collaborates to recover and increase their psychological growth. The prototype system provides a simulation environment where psychologists can adjust the parameters and customize their own simulation environment. The model and tool is a first attempt toward simulating online personalities that may exist only online, and provide data for observation.

Epigenetic Mechanisms and Therapeutic Perspectives for Neurodevelopmental Disorders

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Kunio Miyake

2012-04-01

Full Text Available The number of children with mild neurodevelopmental disorders, such as autism, has been recently increasing in advanced countries. This increase is probably caused by environmental factors rather than genetic factors, because it is unlikely that genetic mutation rates suddenly increased within a short period. Epigenetics is a mechanism that regulates gene expression, depending not on the underlying DNA sequence but on the chemical modifications of DNA and histone proteins. Because mental stress can alter the epigenetic status in neuronal cells, environmental factors may alter brain function through epigenetic changes. However, one advantage of epigenetic changes is their reversibility. Therefore, diseases due to abnormal epigenetic regulation are theoretically treatable. In fact, several drugs for treating mental diseases are known to have restoring effects on aberrant epigenetic statuses, and a novel therapeutic strategy targeting gene has been developed. In this review, we discuss epigenetic mechanisms of congenital and acquired neurodevelopmental disorders, drugs with epigenetic effects, novel therapeutic strategies for epigenetic diseases, and future perspectives in epigenetic medicine.

Toward an understanding of antipsychotic drug induced weight gain - use of a rodent model

OpenAIRE

Stefanidis, Aneta

2017-01-01

Antipsychotic drug therapy is a fundamental tool in the treatment of schizophrenia and other psychoses. Recent years have seen the development of new antipsychotic compounds with an improved acute adverse effect profile; however these are often associated with weight gain and increased risk of metabolic disturbances. Olanzapine, despite its considerable adverse impact on weight gain and associated pathologies, has been recognized as the most efficacious antipsychotic drug in the treatment of ...

Therapeutic Inertia and Treatment Intensification.

Science.gov (United States)

Josiah Willock, Robina; Miller, Joseph B; Mohyi, Michelle; Abuzaanona, Ahmed; Muminovic, Meri; Levy, Phillip D

2018-01-29

This review aims to emphasize how therapeutic inertia, the failure of clinicians to intensify treatment when blood pressure rises or remains above therapeutic goals, contributes to suboptimal blood pressure control in hypertensive populations. Studies reveal that the therapeutic inertia is quite common and contributes to suboptimal blood pressure control. Quality improvement programs and standardized approaches to support antihypertensive treatment intensification are ways to combat therapeutic inertia. Furthermore, programs that utilize non-physician medical professionals such as pharmacists and nurses demonstrate promise in mitigating the effects of this important problem. Therapeutic inertia impedes antihypertensive management and requires a broad effort to reduce its effects. There is an ongoing need for renewed focus and research in this area to improve hypertension control.