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Sample records for repetitive drug exposure

  1. Dissociating mere exposure and repetition priming as a function of word type.

    Science.gov (United States)

    Butler, Laurie T; Berry, Dianne C; Helman, Shaun

    2004-07-01

    The mere exposure effect is defined as enhanced attitude toward a stimulus that has been repeatedly exposed. Repetition priming is defined as facilitated processing of a previously exposed stimulus. We conducted a direct comparison between the two phenomena to test the assumption that the mere exposure effect represents an example of repetition priming. In two experiments, having studied a set of words or nonwords, participants were given a repetition priming task (perceptual identification) or one of two mere exposure (affective liking or preference judgment) tasks. Repetition priming was obtained for both words and nonwords, but only nonwords produced a mere exposure effect. This demonstrates a key boundary for observing the mere exposure effect, one not readily accommodated by a perceptual representation systems (Tulving & Schacter, 1990) account, which assumes that both phenomena should show some sensitivity to nonwords and words.

  2. Understanding the relationship between repetition priming and mere exposure.

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    Butler, Laurie T; Berry, Dianne C

    2004-11-01

    Over the last two decades interest in implicit memory, most notably repetition priming, has grown considerably. During the same period, research has also focused on the mere exposure effect. Although the two areas have developed relatively independently, a number of studies has described the mere exposure effect as an example of implicit memory. Tacit in their comparisons is the assumption that the effect is more specifically a demonstration of repetition priming. Having noted that this assumption has attracted relatively little attention, this paper reviews current evidence and shows that it is by no means conclusive. Although some evidence is suggestive of a common underlying mechanism, even a modified repetition priming (perceptual fluency/attribution) framework cannot accommodate all of the differences between the two phenomena. Notwithstanding this, it seems likely that a version of this theoretical framework still offers the best hope of a comprehensive explanation for the mere exposure effect and its relationship to repetition priming. As such, the paper finishes by offering some initial guidance as to ways in which the perceptual fluency/attribution framework might be extended, as well as outlining important areas for future research.

  3. Upper arm elevation and repetitive shoulder movements: a general population job exposure matrix based on expert ratings and technical measurements.

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    Dalbøge, Annett; Hansson, Gert-Åke; Frost, Poul; Andersen, Johan Hviid; Heilskov-Hansen, Thomas; Svendsen, Susanne Wulff

    2016-08-01

    We recently constructed a general population job exposure matrix (JEM), The Shoulder JEM, based on expert ratings. The overall aim of this study was to convert expert-rated job exposures for upper arm elevation and repetitive shoulder movements to measurement scales. The Shoulder JEM covers all Danish occupational titles, divided into 172 job groups. For 36 of these job groups, we obtained technical measurements (inclinometry) of upper arm elevation and repetitive shoulder movements. To validate the expert-rated job exposures against the measured job exposures, we used Spearman rank correlations and the explained variance[Formula: see text] according to linear regression analyses (36 job groups). We used the linear regression equations to convert the expert-rated job exposures for all 172 job groups into predicted measured job exposures. Bland-Altman analyses were used to assess the agreement between the predicted and measured job exposures. The Spearman rank correlations were 0.63 for upper arm elevation and 0.64 for repetitive shoulder movements. The expert-rated job exposures explained 64% and 41% of the variance of the measured job exposures, respectively. The corresponding calibration equations were y=0.5%time+0.16×expert rating and y=27°/s+0.47×expert rating. The mean differences between predicted and measured job exposures were zero due to calibration; the 95% limits of agreement were ±2.9% time for upper arm elevation >90° and ±33°/s for repetitive shoulder movements. The updated Shoulder JEM can be used to present exposure-response relationships on measurement scales. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  4. P2-19: The Effect of item Repetition on Item-Context Association Depends on the Prior Exposure of Items

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    Hongmi Lee

    2012-10-01

    Full Text Available Previous studies have reported conflicting findings on whether item repetition has beneficial or detrimental effects on source memory. To reconcile such contradictions, we investigated whether the degree of pre-exposure of items can be a potential modulating factor. The experimental procedures spanned two consecutive days. On Day 1, participants were exposed to a set of unfamiliar faces. On Day 2, the same faces presented on the previous day were used again in half of the participants, whereas novel faces were used for the other half. Day 2 procedures consisted of three successive phases: item repetition, source association, and source memory test. In the item repetition phase, half of the face stimuli were repeatedly presented while participants were making male/female judgments. During the source association phase, both the repeated and the unrepeated faces appeared in one of the four locations on the screen. Finally, participants were tested on the location in which a given face was presented during the previous phase and reported the confidence of their memory. Source memory accuracy was measured as the percentage of correct non-guess trials. As results, we found a significant interaction between prior exposure and repetition. Repetition impaired source memory when the items had been pre-exposed on Day 1, while it led to greater accuracy in novel ones. These results show that pre-experimental exposure can modulate the effects of repetition on associative binding between an item and its contextual information, suggesting that pre-existing representation and novelty signal interact to form new episodic memory.

  5. Relationship to carcinogenesis of repetitive low-dose radiation exposure

    International Nuclear Information System (INIS)

    Ootsuyama, Akira

    2016-01-01

    We studied the carcinogenic effects caused by repetitive irradiation at a low dose, which has received attention in recent years, and examined the experimental methods used to evaluate radiation-induced carcinogenesis. For this experiment, we selected a mouse with as few autochthonous cancers as possible. Skin cancer was selected as the target for analysis, because it is a rare cancer in mice. Beta-rays were selected as the radiation source. The advantage of using beta-rays is weaker penetration power into tissues, thus protecting organs, such as the digestive and hematogenous organs. The benefit of our experimental method is that only skin cancer requires monitoring, and it is possible to perform long-term experiments. The back skin of mice was exposed repetitively to beta-rays three times a week until the occurrence of cancer or death, and the dose per exposure ranged from 0.5 to 11.8 Gy. With the high-dose range (2.5-11.8 Gy), the latency period and carcinogenic rate were almost the same in each experimental group. When the dose was reduced to 1-1.5 Gy, the latency period increased, but the carcinogenic rate remained. When the dose was further reduced to 0.5 Gy, skin cancer never happened, even though we continued irradiation until death of the last mouse in this group. The lifespan of 0.5 Gy group mice was the same as that of the controls. We showed that the 0.5 Gy dose did not cause cancer, even in mice exposed repetitively throughout their life span, and thus refer to 0.5 Gy as the threshold-like dose. (author)

  6. Mechanism-based drug exposure classification in pharmacoepidemiological studies

    NARCIS (Netherlands)

    Verdel, B.M.

    2010-01-01

    Mechanism-based classification of drug exposure in pharmacoepidemiological studies In pharmacoepidemiology and pharmacovigilance, the relation between drug exposure and clinical outcomes is crucial. Exposure classification in pharmacoepidemiological studies is traditionally based on

  7. Exposure to antineoplastic drugs outside the hospital environment.

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    Meijster, T; Fransman, W; Veldhof, R; Kromhout, H

    2006-10-01

    The objectives were (i) to identify occupational populations outside hospitals working with antineoplastic drugs, (ii) to determine the size of the populations 'at risk', (iii) to identify major determinants and routes of exposure outside hospitals and (iv) to estimate exposure levels and frequencies relative to levels found in hospitals. The survey consisted of two phases; (i) identification of activities with potential exposure to antineoplastic drugs by literature review, interviews, questionnaires and workplace visits, (ii) exploratory measurements of exposure and surface contamination in selected sectors. Eight sectors were identified with potential exposure to antineoplastic drugs: pharmaceutical industry, pharmacies, universities, veterinary medicine, nursing homes, home care, laundry facilities, and waste treatment. Four sectors were of primary concern: veterinary medicine, home care, nursing homes and industrial laundries. The populations potentially exposed in these sectors vary considerably (from several tens to thousands of workers), as do their levels of exposure. Exposure measurements collected in the veterinary medicine sector showed that workers are indeed exposed to antineoplastic drugs and, in some cases (on gloves after administration), levels were 15 times higher than levels measured during administration in hospitals. Workers sorting contaminated hospital laundry in industrial laundry facilities were exposed to antineoplastic drugs through inhalation. For the home care and nursing homes sectors the highest exposure levels were found when cleaning toilets and washing treated patients. These two sectors are expected to have the largest exposed population (5,000-10,000 individuals). This study has resulted in a comprehensive overview of populations with potential exposure to antineoplastic drugs. Exposure levels can potentially be high compared with the hospital environment, because exposure routes are complex and awareness of the hazard (and

  8. Repetitive exposure: Brain and reflex measures of emotion and attention

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    Ferrari, Vera; Bradley, Margaret M.; Codispoti, Maurizio; Lang, Peter J.

    2010-01-01

    Effects of massed repetition on the modulation of the late positive potential elicited during affective picture viewing were investigated in two experiments. Despite a difference in the number of repetitions across studies (from 5 to 30), results were quite similar: the late positive potential continued to be enhanced when viewing emotional, compared to neutral, pictures. On the other hand, massed repetition did prompt a reduction in the late positive potential that was most pronounced for emotional pictures. Startle probe P3 amplitude generally increased with repetition, suggesting diminished attention allocation to repeated pictures. The blink reflex, however, continued to be modulated by hedonic valence, despite massive massed repetition. Taken together, the data suggest that the amplitude of the late positive potential during picture viewing reflects both motivational significance and attention allocation. PMID:20701711

  9. Maternal hair testing for the assessment of fetal exposure to drug of abuse during early pregnancy: Comparison with testing in placental and fetal remains.

    Science.gov (United States)

    Falcon, M; Pichini, S; Joya, J; Pujadas, M; Sanchez, A; Vall, O; García Algar, O; Luna, A; de la Torre, R; Rotolo, M C; Pellegrini, M

    2012-05-10

    Drug use by pregnant women in the first trimester of pregnancy and subsequent fetal exposure during early gestation can be assessed only by repetitive/systematic maternal blood/urine analysis or segmental hair analysis. No evidence of any relationship between maternal/fetal exposure during this specific period of gestation has been demonstrated to date in a human model. To clarify drugs toxicokinetics and transplacental passage during early pregnancy, the presence of the most widely used recreational drugs of abuse and metabolites was investigated in the proximal 4cm hair segments of women undergoing voluntary termination of pregnancy (n=280) during the 12th week of gestation and the results were compared to those from placenta and fetal tissue samples in order to verify whether maternal hair testing can reflect fetal exposure and, if so, to what extent. Hair, placenta and fetal remains were analyzed by validated gas chromatography mass spectrometry assays. Eighty one positive hair samples were identified: 60 were positive for cannabis (74.1%), 28 for cocaine (34.6%), 7 for opiates (8.6%), 3 for MDMA (3.7%) and 18.5% were positive for more than one drug. The positive hair test results were confirmed in placenta/fetal tissues in 10 cases out of 60 for cannabis (16. 7%); in 7 out of 28 for cocaine (25%); and none for the 6 opiates positive cases and 3 MDMA cases, respectively. Drugs/metabolites in hair of pregnant women can be used as biomarkers of past drug use (repetitive or sporadic), although the use is not always reflected in fetal/placental tissues. There are several possible hypotheses to explain the results: (1) the use occurred before the start of pregnancy, (2) past sporadic consumption which could be measured in hair but not in fetal and placental remains because of the narrow window of drug detection in placental/fetal tissues; (3) the sensitivity of the analytical methods was not high enough for the detection of the minute amount of drugs of abuse and

  10. Effect of repetitive transcranial magnetic stimulation in drug resistant depressed patients

    International Nuclear Information System (INIS)

    Chung, Yong An; Yoo, Ie Ryung; Kang, Bong Joo; Chae, Jeong Ho; Lee, Hye Won; Moon, Hyun Jin; Kim, Sung Hoon; Sohn, Hyung Sun; Chung, Soo Kyo

    2007-01-01

    Repetitive transcranial magnetic stimulation (rTMS) has recently been clinically applied in the treatment of drug resistant depressed patients. There are mixed findings about the efficacy of rTMS on depression. Furthermore, the influence of rTMS on the physiology of the brain is not clear. We prospectively evaluated changes of regional cerebral blood flow (rCBF) between pre- and post-rTMS treatment in patients with drug resistant depression. Twelve patients with drug-resistant depression (7 male, 5 female; age range; 19∼ 52 years; mean age: 29.3 ± 9.3 years) were given rTMS on right prefrontal lobe with low frequency (1 Hz) and on left prefrontal lobe with high frequency (20 Hz), with 20-minute-duration each day for 3 weeks. Tc-99m ECD brain perfusion SPECT was obtained before and after rTMS treatment. The changes of cerebral perfusion were analyzed using statistical parametric mapping (SPM; t=3.14, uncorrected ρ < 0.01, voxel = 100). Following areas showed significant increase in rCBF after 3 weeks rTMS treatment: the cingulate gyrus, fusiform gyrus of right temporal lobe, precuneus, and left lateral globus pallidus. Significant decrement was noted in the precental and middle frontal gyrus of right frontal lobe, and fusiform gyrus of left occipital lobe. Low-frequency rTMS on the right prefrontal cortex and high-frequency rTMS on the left prefrontal cortex for 3 weeks as an add-on regimen have increased and decreased rCBF in the specific brain regions in drug-resistant depressed patients. Further analyses correlating clinical characteristics and treatment paradigm with functional imaging data may be helpful in clarifying the pathophysiology of drug-resistant patients

  11. Effect of repetitive transcranial magnetic stimulation in drug resistant depressed patients

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Yong An; Yoo, Ie Ryung; Kang, Bong Joo; Chae, Jeong Ho; Lee, Hye Won; Moon, Hyun Jin; Kim, Sung Hoon; Sohn, Hyung Sun; Chung, Soo Kyo [The Catholic University of Korea, Seoul (Korea, Republic of)

    2007-02-15

    Repetitive transcranial magnetic stimulation (rTMS) has recently been clinically applied in the treatment of drug resistant depressed patients. There are mixed findings about the efficacy of rTMS on depression. Furthermore, the influence of rTMS on the physiology of the brain is not clear. We prospectively evaluated changes of regional cerebral blood flow (rCBF) between pre- and post-rTMS treatment in patients with drug resistant depression. Twelve patients with drug-resistant depression (7 male, 5 female; age range; 19{approx} 52 years; mean age: 29.3 {+-} 9.3 years) were given rTMS on right prefrontal lobe with low frequency (1 Hz) and on left prefrontal lobe with high frequency (20 Hz), with 20-minute-duration each day for 3 weeks. Tc-99m ECD brain perfusion SPECT was obtained before and after rTMS treatment. The changes of cerebral perfusion were analyzed using statistical parametric mapping (SPM; t=3.14, uncorrected {rho} < 0.01, voxel = 100). Following areas showed significant increase in rCBF after 3 weeks rTMS treatment: the cingulate gyrus, fusiform gyrus of right temporal lobe, precuneus, and left lateral globus pallidus. Significant decrement was noted in the precental and middle frontal gyrus of right frontal lobe, and fusiform gyrus of left occipital lobe. Low-frequency rTMS on the right prefrontal cortex and high-frequency rTMS on the left prefrontal cortex for 3 weeks as an add-on regimen have increased and decreased rCBF in the specific brain regions in drug-resistant depressed patients. Further analyses correlating clinical characteristics and treatment paradigm with functional imaging data may be helpful in clarifying the pathophysiology of drug-resistant patients.

  12. Gender differences in workers with identical repetitive industrial tasks: exposure and musculoskeletal disorders.

    Science.gov (United States)

    Nordander, Catarina; Ohlsson, Kerstina; Balogh, Istvan; Hansson, Gert-Ake; Axmon, Anna; Persson, Roger; Skerfving, Staffan

    2008-08-01

    For unknown reasons, females run a higher risk than males of work-related musculoskeletal disorders. The aim of this study was to evaluate whether male and female workers, with identical repetitive work tasks, differ concerning risk of disorders, physical or psychosocial exposures. Employees in two industries were studied; one rubber manufacturing and one mechanical assembly plant. These industries were selected since in both, large groups of males and females worked side by side performing identical repetitive work tasks. Physical exposure was measured by technical equipment. Postures and movements were registered by inclinometry for the head and upper arms, and by electrogoniometry for the wrists. Muscular activity (muscular rest and %max) was registered by surface electromyography for m. trapezius and the forearm extensors (18 males and 19 females). Psychosocial work environment was evaluated by the demand-control-support model (85 males and 138 females). Musculoskeletal disorders were assessed (105 males and 172 females), by interview (last 7-days complaints), and by physical examination (diagnoses). Concerning physical exposure, females showed higher muscular activity related to maximal voluntary contractions [(%MVE); m. trapezius: females 18 (SD 9.2), males 12 (SD 4.3); forearm extensors: females 39 (SD 11), males 27 (SD 10), right side, 90th percentile]. Working postures and movements were similar between genders. Also, concerning psychosocial work environment, no significant gender differences were found. Females had higher prevalences of disorders [complaints: age-adjusted prevalence odds ratio (POR) 2.3 (95% CI 1.3-3.8) for neck/shoulders, 2.4 (1.4-4.0) for elbows/hands; diagnoses: neck/shoulder 1.9 (1.1-3.6), elbows/hands 4.1 (1.2-9.3)]. In 225 workers, PORs were adjusted for household work, personal recovery and exercise, which only slightly affected the risk estimates. In identical work tasks, females showed substantially higher muscular activity in

  13. Time-Dependent Toxic and Genotoxic Effects of Zinc Oxide Nanoparticles after Long-Term and Repetitive Exposure to Human Mesenchymal Stem Cells

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    Pascal Ickrath

    2017-12-01

    Full Text Available Zinc oxide nanoparticles (ZnO-NP are widely spread in consumer products. Data about the toxicological characteristics of ZnO-NP is still under controversial discussion. The human skin is the most important organ concerning ZnO-NP exposure. Intact skin was demonstrated to be a sufficient barrier against NPs; however, defect skin may allow NP contact to proliferating cells. Within these cells, stem cells are the most important toxicological target for NPs. The aim of this study was to evaluate the genotoxic and cytotoxic effects of ZnO-NP at low-dose concentrations after long-term and repetitive exposure to human mesenchymal stem cells (hMSC. Cytotoxic effects of ZnO-NP were measured by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT assay. Furthermore, genotoxicity was evaluated by the comet assay. For long-term observation over 6 weeks, transmission electron microscopy (TEM was applied. The results of the study indicated cytotoxic effects of ZnO-NP beginning at high concentrations of 50 μg/mL and genotoxic effects in hMSC exposed to 1 and 10 μg/mL ZnO-NP. Repetitive exposure enhanced cyto- but not genotoxicity. Intracellular NP accumulation was observed up to 6 weeks. The results suggest cytotoxic and genotoxic potential of ZnO-NP. Even low doses of ZnO-NP may induce toxic effects as a result of repetitive exposure and long-term cellular accumulation. This data should be considered before using ZnO-NP on damaged skin.

  14. Nitrogen narcosis induced by repetitive hyperbaric nitrogen oxygen mixture exposure impairs long-term cognitive function in newborn mice.

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    Bin Peng

    Full Text Available Human beings are exposed to compressed air or a nitrogen-oxygen mixture, they will produce signs and symptoms of nitrogen narcosis such as amnesia or even loss of memory, which may be disappeared once back to the normobaric environment. This study was designed to investigate the effect of nitrogen narcosis induced by repetitive hyperbaric nitrogen-oxygen mixture exposure on long-term cognitive function in newborn mice and the underlying mechanisms. The electroencephalogram frequency was decreased while the amplitude was increased in a pressure-dependent manner during 0.6, 1.2, 1.8 MPa (million pascal nitrogen-oxygen mixture exposures in adult mice. Nitrogen narcosis in postnatal days 7-9 mice but not in adult mice induced by repetitive hyperbaric exposure prolonged the latency to find the platform and decreased the number of platform-site crossovers during Morris water maze tests, and reduced the time in the center during the open field tests. An increase in the expression of cleaved caspase-3 in the hippocampus and cortex were observed immediately on the first day after hyperbaric exposure, and this lasted for seven days. Additionally, nitrogen narcosis induced loss of the dendritic spines but not of the neurons, which may mainly account for the cognitive dysfunction. Nitrogen narcosis induced long-term cognitive and emotional dysfunction in the postnatal mice but not in the adult mice, which may result from neuronal apoptosis and especially reduction of dendritic spines of neurons.

  15. Inhalation Exposure Method for Illegal Drugs.

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    Inomata, Akiko; Ogata, Akio; Tada, Yukie; Nagasawa, Akemichi; Yuzawa, Katsuhiro; Ando, Hiroshi; Kubo, Yoshikazu; Takahashi, Hiroshi; Kaihoko, Fujifumi; Tanaka, Kazuyoshi; Nakajima, Jun'ichi; Suzuki, Atsuko; Uemura, Nozomi; Moriyasu, Takako; Watanabe, Daisuke; Ishihara, Kei; Usami, Takashi; Kamei, Satoru; Kohno, Yasuaki

    2017-01-01

    We developed a new inhalation exposure method to evaluate effects of synthetic cannabimimetics that are being distributed as new, unregulated drugs in the Tokyo area. We selected the commercial product "SOUTOU" containing AB-CHMINACA and 5F-AMB as the test drug and dried marshmallow (Althaea officinalis) leaves as the negative control. A half cigarette packed with dried marshmallow leaves or SOUTOU was ignited, then mainstream smoke from each was delivered to five mice in an exposure box. After the cigarettes were fully consumed, neurobehavioral observations and a catalepsy test were performed at 15, 30 and 60 min after exposure. The effluent air from the exposure box was poured into impingers containing acetonitrile (first impinger) and dimethyl sulfoxide (second impinger). The resulting solutions were analyzed to assess decomposition of the synthetic cannabimimetics. Mice exposed to SOUTOU smoke showed many excitement behaviors and some suppressive behaviors at 15, 30 and 60 min. These clearly included cannabimimetic specific pharmacological actions. Negative control mice also showed some suppressive behaviors at 15 min but these were attenuated at later times, nearly disappearing at 60 min. In addition, the behavioral effects observed in controls were less pronounced than those in SOUTOU exposed mice. The inhalation exposure method developed in our study would be effective for determining cannabinoid specific pharmacological effects of illegal drugs, as well as for assessing the presence of active compound(s) by comparing the test substance with a negative control.

  16. Enhancement of catalase activity by repetitive low-grade H2O2 exposures protects fibroblasts from subsequent stress-induced apoptosis

    International Nuclear Information System (INIS)

    Sen, Prosenjit; Mukherjee, Sebanti; Bhaumik, Gayaram; Das, Pradeep; Ganguly, Sandipan; Choudhury, Nandini; Raha, Sanghamitra

    2003-01-01

    Exposure of Chinese hamster V79 fibroblasts to mild and repetitive H 2 O 2 doses in culture for 15 weeks produced no change in lipid peroxidation status, GSH/GSSG ratio and glutathione peroxidase activity of these cells (VST cells). In contrast, in VST cells catalase levels underwent a prominent increase which could be significantly inhibited and brought down to control levels after treatment with the catalase inhibitor 3-aminotriazole (3-AT). When control (VC) cells were exposed to UV radiation (UVC 5 J/m 2 ) or H 2 O 2 (7.5 mM, 15 min), intracellular reactive oxygen species (ROS) levels rose prominently with significant activation of caspase-3. Marked nuclear fragmentation and lower cell viability were also noted in these cells. In contrast, VST cells demonstrated a significantly lower ROS level, an absence of nuclear fragmentation and an unchanged caspase-3 activity after exposure to UVC or H 2 O 2 . Cell viability was also significantly better preserved in VST cells than VC cells after UV or H 2 O 2 exposures. Following 3-AT treatment of VST cells, UVC radiation or H 2 O 2 brought about significantly higher elevations in intracellular ROS, increases in caspase-3 activity, significantly lowered cell viability and marked nuclear fragmentation, indicating the involvement of high catalase levels in the cytoprotective effects of repetitive stress. Therefore, upregulation of the antioxidant defense after repetitive oxidative stress imparted a superior ability to cope with subsequent acute stress and escape apoptotic death and loss of viability

  17. Variable Linezolid Exposure in Intensive Care Unit Patients-Possible Role of Drug-Drug Interactions.

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    Töpper, Christoph; Steinbach, Cathérine L; Dorn, Christoph; Kratzer, Alexander; Wicha, Sebastian G; Schleibinger, Michael; Liebchen, Uwe; Kees, Frieder; Salzberger, Bernd; Kees, Martin G

    2016-10-01

    Standard doses of linezolid may not be suitable for all patient groups. Intensive care unit (ICU) patients in particular may be at risk of inadequate concentrations. This study investigated variability of drug exposure and its potential sources in this population. Plasma concentrations of linezolid were determined by high-performance liquid chromatography in a convenience sample of 20 ICU patients treated with intravenous linezolid 600 mg twice daily. Ultrafiltration applying physiological conditions (pH 7.4/37°C) was used to determine the unbound fraction. Individual pharmacokinetic (PK) parameters were estimated by population PK modeling. As measures of exposure to linezolid, area under the concentration-time curve (AUC) and trough concentrations (Cmin) were calculated and compared with published therapeutic ranges (AUC 200-400 mg*h/L, Cmin 2-10 mg/L). Coadministered inhibitors or inducers of cytochrome P450 and/or P-glycoprotein were noted. Data from 18 patients were included into the PK evaluation. Drug exposure was highly variable (median, range: AUC 185, 48-618 mg*h/L, calculated Cmin 2.92, 0.0062-18.9 mg/L), and only a minority of patients had values within the target ranges (6 and 7, respectively). AUC and Cmin were linearly correlated (R = 0.98), and classification of patients (underexposed/within therapeutic range/overexposed) according to AUC or Cmin was concordant in 15 cases. Coadministration of inhibitors was associated with a trend to higher drug exposure, whereas 3 patients treated with levothyroxine showed exceedingly low drug exposure (AUC ∼60 mg*h/L, Cmin linezolid is highly variable and difficult to predict in ICU patients, and therapeutic drug monitoring seems advisable. PK drug-drug interactions might partly be responsible and should be further investigated; protein binding appears to be stable and irrelevant.

  18. Risk of impaired cognition after prenatal exposure to psychotropic drugs

    DEFF Research Database (Denmark)

    Wibroe, M A; Mathiasen, R; Pagsberg, A K

    2017-01-01

    OBJECTIVE: Prenatal exposure to psychotropic drugs may affect the trajectories of brain development. In a register study, we investigated whether such exposure is associated with long-term impaired cognitive abilities. METHOD: Individuals born in Denmark in 1995-2008 were included. As proxies...... of a neurological/mental disorder after prenatal exposure to psychoanaleptics (primarily antidepressants) (OR: 1.86[1.24-2.78). CONCLUSION: Prenatal exposure to psychotropic drugs affects proxy outcomes of cognitive disabilities at school age. Exposure to psycholeptics carries the largest risk. The role...

  19. Embryotoxicity following repetitive maternal exposure to scorpion venom

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    BN Hmed

    2012-01-01

    Full Text Available Although it is a frequent accident in a few countries, scorpion envenomation during pregnancy remains scarcely studied. In the present study, the effects of repetitive maternal exposure to Buthus occitanus tunetanus venom are investigated and its possible embryotoxic consequences on rats. Primigravid rats received a daily intraperitoneal dose of 1 mL/kg of saline solution or 300 µg/kg of crude scorpion venom, from the 7th to the 13th day of gestation. On the 21st day, the animals were deeply anesthetized using diethyl-ether. Then, blood was collected for chemical parameter analysis. Following euthanasia, morphometric measurements were carried out. The results showed a significant increase in maternal heart and lung absolute weights following venom treatment. However, the mean placental weight per rat was significantly diminished. Furthermore, blood urea concentration was higher in exposed rats (6.97 ± 0.62 mmol/L than in those receiving saline solution (4.94 ± 0.90 mmol/L. Many organs of venom-treated rat fetuses (brain, liver, kidney and spleen were smaller than those of controls. On the contrary, fetal lungs were significantly heavier in fetuses exposed to venom (3.2 ± 0.4 g than in the others (3.0 ± 0.2 g. Subcutaneous blood clots, microphthalmia and total body and tail shortening were also observed in venom-treated fetuses. It is concluded that scorpion envenomation during pregnancy potentially causes intrauterine fetal alterations and growth impairment.

  20. Synergy Repetition Training versus Task Repetition Training in Acquiring New Skill.

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    Patel, Vrajeshri; Craig, Jamie; Schumacher, Michelle; Burns, Martin K; Florescu, Ionut; Vinjamuri, Ramana

    2017-01-01

    Traditionally, repetitive practice of a task is used to learn a new skill, exhibiting as immediately improved performance. Research suggests, however, that a more experience-based rather than exposure-based training protocol may allow for better transference of the skill to related tasks. In synergy-based motor control theory, fundamental motor skills, such as hand grasping, are represented with a synergy subspace that captures essential motor patterns. In this study, we propose that motor-skill learning through synergy-based mechanisms may provide advantages over traditional task repetition learning. A new task was designed to highlight the range of motion and dexterity of the human hand. Two separate training strategies were tested in healthy subjects: task repetition training and synergy training versus a control. All three groups showed improvements when retested on the same task. When tested on a similar, but different set of tasks, only the synergy group showed improvements in accuracy (9.27% increase) compared to the repetition (3.24% decline) and control (3.22% decline) groups. A kinematic analysis revealed that although joint angular peak velocities decreased, timing benefits stemmed from the initial feed-forward portion of the task (reaction time). Accuracy improvements may have derived from general improved coordination among the four involved fingers. These preliminary results warrant further investigation of synergy-based motor training in healthy individuals, as well as in individuals undergoing hand-based rehabilitative therapy.

  1. Enhancement of catalase activity by repetitive low-grade H{sub 2}O{sub 2} exposures protects fibroblasts from subsequent stress-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Sen, Prosenjit; Mukherjee, Sebanti; Bhaumik, Gayaram; Das, Pradeep; Ganguly, Sandipan; Choudhury, Nandini; Raha, Sanghamitra

    2003-08-28

    Exposure of Chinese hamster V79 fibroblasts to mild and repetitive H{sub 2}O{sub 2} doses in culture for 15 weeks produced no change in lipid peroxidation status, GSH/GSSG ratio and glutathione peroxidase activity of these cells (VST cells). In contrast, in VST cells catalase levels underwent a prominent increase which could be significantly inhibited and brought down to control levels after treatment with the catalase inhibitor 3-aminotriazole (3-AT). When control (VC) cells were exposed to UV radiation (UVC 5 J/m{sup 2}) or H{sub 2}O{sub 2} (7.5 mM, 15 min), intracellular reactive oxygen species (ROS) levels rose prominently with significant activation of caspase-3. Marked nuclear fragmentation and lower cell viability were also noted in these cells. In contrast, VST cells demonstrated a significantly lower ROS level, an absence of nuclear fragmentation and an unchanged caspase-3 activity after exposure to UVC or H{sub 2}O{sub 2}. Cell viability was also significantly better preserved in VST cells than VC cells after UV or H{sub 2}O{sub 2} exposures. Following 3-AT treatment of VST cells, UVC radiation or H{sub 2}O{sub 2} brought about significantly higher elevations in intracellular ROS, increases in caspase-3 activity, significantly lowered cell viability and marked nuclear fragmentation, indicating the involvement of high catalase levels in the cytoprotective effects of repetitive stress. Therefore, upregulation of the antioxidant defense after repetitive oxidative stress imparted a superior ability to cope with subsequent acute stress and escape apoptotic death and loss of viability.

  2. Repetition and the Concept of Repetition

    Directory of Open Access Journals (Sweden)

    Arne Grøn

    2013-11-01

    Full Text Available This paper offers a description of the meaning of the category of repetition. Firstly, it is pointed out that Constantin uses repetition as a concept that means the creation of epochs; the passing from Greece to Modernity is accomplished distinguishing between recollection, a concept that looks back to the past, and repetition, a concept that looks forward to future. Secondly, it is showed that the category of repetition, as a religious category, relates with what Climacus calls “ethic despair” and with what Vigilius calls “second ethics”; it is through repetition that it can be understood that sin finds its place in ethics and these shows the tension between it and dogmatics. And thirdly, it is showed that the descovery of the new category of repetition is a rediscovery of what Kierkegaard calls category of spirit; repetition has for its object the individuality, and coming to be oneself is what Kierkegaard undertands as liberty. At the end of the paper it is questioned if the category of repetition is inconsistent with the book Repetition.

  3. The impact of compulsory drug detention exposure on the avoidance of healthcare among injection drug users in Thailand.

    Science.gov (United States)

    Kerr, Thomas; Hayashi, Kanna; Ti, Lianping; Kaplan, Karyn; Suwannawong, Paisan; Wood, Evan

    2014-01-01

    Although Thailand has relied on the use of compulsory drug detention centres as a strategy to try to address problematic drug use, little is known about the effects of exposure to these centres on people who inject drugs (IDU). Therefore, we undertook this study to explore whether exposure to compulsory drug detention was associated with avoiding healthcare among Thai IDU. Using Poisson regression analyses, we examined the relationship between compulsory drug detention exposure and avoiding healthcare among participants in the Mitsampan Community Research Project based in Bangkok. 435 IDU participated in this study, including 111 (25.5%) participants who reported avoiding healthcare. In multivariate analyses, avoiding healthcare was positively associated with exposure to compulsory drug detention (adjusted prevalence ratio [APR]=1.60; 95% confidence interval [CI]: 1.16-2.21), having been refused healthcare (APR=3.46; 95% CI: 2.61-4.60), and experiencing shame associated with one's drug use (APR=1.93; 95% CI: 1.21-3.09). Exposure to compulsory drug detention was associated with avoiding healthcare among Thai IDU, suggesting that this system of detention may be contributing to the burden of preventable morbidity among IDU in this setting. Although further research is needed to confirm these findings, the results of this study reinforce previous calls to replace the system of compulsory drug detention with evidence-based public health interventions for IDU. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Timing and Duration of Drug Exposure Affects Outcomes of a Drug-Nutrient Interaction During Ontogeny

    Directory of Open Access Journals (Sweden)

    Jane Alcorn

    2010-10-01

    Full Text Available Significant drug-nutrient interactions are possible when drugs and nutrients share the same absorption and disposition mechanisms. During postnatal development, the outcomes of drug-nutrient interactions may change with postnatal age since these processes undergo ontogenesis through the postnatal period. Our study investigated the dependence of a significant drug-nutrient interaction (cefepime-carnitine on the timing and duration of drug exposure relative to postnatal age. Rat pups were administered cefepime (5 mg/kg twice daily subcutaneously according to different dosing schedules (postnatal day 1-4, 1-8, 8-11, 8-20, or 1-20. Cefepime significantly reduced serum and heart L-carnitine levels in postnatal day 1-4, 1-8 and 8-11 groups and caused severe degenerative changes in ventricular myocardium in these groups. Cefepime also altered the ontogeny of several key L-carnitine homeostasis pathways. The qualitative and quantitative changes in levels of hepatic γ-butyrobetaine hydroxylase mRNA and activity, hepatic trimethyllysine hydroxlase mRNA, intestinal organic cation/carnitine transporter (Octn mRNA, and renal Octn2 mRNA depended on when during postnatal development the cefepime exposure occurred and duration of exposure. Despite lower levels of heart L-carnitine in earlier postnatal groups, levels of carnitine palmitoyltransferase mRNA and activity, heart Octn2 mRNA and ATP levels in all treatment groups remained unchanged with cefepime exposure. However, changes in other high energy phosphate substrates were noted and reductions in the phosphocreatine/ATP ratio were found in rat pups with normal serum L-carnitine levels. In summary, our data suggest a significant drug-nutrient transport interaction in developing neonates, the nature of which depends on the timing and duration of exposure relative to postnatal age.

  5. Repetitive cryotherapy attenuates the in vitro and in vivo mononuclear cell activation response.

    Science.gov (United States)

    Lindsay, Angus; Othman, Mohd Izani; Prebble, Hannah; Davies, Sian; Gieseg, Steven P

    2016-07-01

    What is the central question of this study? Acute and repetitive cryotherapy are routinely used to accelerate postexercise recovery, although the effect on resident immune cells and repetitive exposure has largely been unexplored and neglected. What is the main finding and its importance? Using blood-derived mononuclear cells and semi-professional mixed martial artists, we show that acute and repetitive cryotherapy reduces the in vitro and in vivo T-cell and monocyte activation response whilst remaining independent of the physical performance of elite athletes. We investigated the effect of repetitive cryotherapy on the in vitro (cold exposure) and in vivo (cold water immersion) activation of blood-derived mononuclear cells following high-intensity exercise. Single and repeated cold exposure (5°C) of a mixed cell culture (T cells and monocytes) was investigated using in vitro tissue culture experimentation for total neopterin production (neopterin plus 7,8-dihydroneopterin). Fourteen elite mixed martial art fighters were also randomly assigned to either a cold water immersion (15 min at 10°C) or passive recovery protocol, which they completed three times per week during a 6 week training camp. Urine was collected and analysed for neopterin and total neopterin three times per week, and perceived soreness, fatigue, physical performance (broad jump, push-ups and pull-ups) and training performance were also assessed. Single and repetitive cold exposure significantly (P cryotherapy attenuates in vitro T-cell and monocyte activation. This may explain the disparity in in vivo neopterin and total neopterin between cold water immersion and passive recovery following repetitive exposure during a high-intensity physical impact sport that remains independent of physical performance. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

  6. Population Exposure to Phthalate-Containing Drugs

    DEFF Research Database (Denmark)

    Broe, Anne; Ennis, Zandra Nymand; Pottegård, Anton

    2017-01-01

    Phthalates are known endocrine disruptors. Not commonly recognised, phthalates are used as excipients in a number of drug formulations. We aimed to describe the sale of phthalate-containing drugs in Denmark from 2004 to 2015. National data on annual sale of medications (tablets only) were accessed...... from medstat.dk. Data from the Danish Medicines Agency on phthalate content per tablet were merged with data on total sale for each active substance and drug formulation. We used the 'defined daily dose' (DDD) as the unit of sale and calculated the total amount of phthalate (mg) dispensed per 1......,000 inhabitants. Specific tablet content was compared with the maximum daily exposure limits defined by regulatory agencies for diethylphthalate (DEP) and dibutylphthalate (DBP) of 4.0 and 0.01 mg/kg/day, respectively. Use of phthalate-containing drugs in Denmark was common. We found 154 drug products containing...

  7. [Neonatal risks of drugs exposure at the end of pregnancy].

    Science.gov (United States)

    Autret-Leca, Elisabeth; Cissoko, Hawaré; Jonville-Béra, Annie Pierre

    2011-01-01

    Foetal drugs exposure consequences depend according to the drug involved and to the length of the exposure which in the sum of length of treatment and of drug elimination (5 half life). Decisions are based upon risk evaluation and are a compromise between a risk banalisation and an excess of carefully. We described risks management for drugs used for a disease due to the pregnancy (glucocorticoïdes, antibiotics) then for drugs used for a chronic disease often preceding the pregnancy (non steroidal anti-inflammatory, serotonin recapture inhibitors, benzodiazepines, antiepileptics, conversion enzyme inhibitors/renine angiotensine antagonists, betabloquants). We also present the elements to take in account for the best drug choice at the end of pregnancy and/or for an adapted advice if the drug has been already taken: the drug itself (pharmacological effects, kinetics in neonate, toxicity marker, risk detection tool), drug amount possibly received by the neonate and literature data about neonatal manifestations due to the drug. © 2011 Société Française de Pharmacologie et de Thérapeutique.

  8. A dose-dependent relationship between exposure to a street-based drug scene and health-related harms among people who use injection drugs.

    Science.gov (United States)

    Debeck, Kora; Wood, Evan; Zhang, Ruth; Buxton, Jane; Montaner, Julio; Kerr, Thomas

    2011-08-01

    While the community impacts of drug-related street disorder have been well described, lesser attention has been given to the potential health and social implications of drug scene exposure on street-involved people who use illicit drugs. Therefore, we sought to assess the impacts of exposure to a street-based drug scene among injection drug users (IDU) in a Canadian setting. Data were derived from a prospective cohort study known as the Vancouver Injection Drug Users Study. Four categories of drug scene exposure were defined based on the numbers of hours spent on the street each day. Three generalized estimating equation (GEE) logistic regression models were constructed to identify factors associated with varying levels of drug scene exposure (2-6, 6-15, over 15 hours) during the period of December 2005 to March 2009. Among our sample of 1,486 IDU, at baseline, a total of 314 (21%) fit the criteria for high drug scene exposure (>15 hours per day). In multivariate GEE analysis, factors significantly and independently associated with high exposure included: unstable housing (adjusted odds ratio [AOR] = 9.50; 95% confidence interval [CI], 6.36-14.20); daily crack use (AOR = 2.70; 95% CI, 2.07-3.52); encounters with police (AOR = 2.11; 95% CI, 1.62-2.75); and being a victim of violence (AOR = 1.49; 95 % CI, 1.14-1.95). Regular employment (AOR = 0.50; 95% CI, 0.38-0.65), and engagement with addiction treatment (AOR = 0.58; 95% CI, 0.45-0.75) were negatively associated with high exposure. Our findings indicate that drug scene exposure is associated with markers of vulnerability and higher intensity addiction. Intensity of drug scene exposure was associated with indicators of vulnerability to harm in a dose-dependent fashion. These findings highlight opportunities for policy interventions to address exposure to street disorder in the areas of employment, housing, and addiction treatment.

  9. Repetition suppression and multi-voxel pattern similarity differentially track implicit and explicit visual memory.

    Science.gov (United States)

    Ward, Emily J; Chun, Marvin M; Kuhl, Brice A

    2013-09-11

    Repeated exposure to a visual stimulus is associated with corresponding reductions in neural activity, particularly within visual cortical areas. It has been argued that this phenomenon of repetition suppression is related to increases in processing fluency or implicit memory. However, repetition of a visual stimulus can also be considered in terms of the similarity of the pattern of neural activity elicited at each exposure--a measure that has recently been linked to explicit memory. Despite the popularity of each of these measures, direct comparisons between the two have been limited, and the extent to which they differentially (or similarly) relate to behavioral measures of memory has not been clearly established. In the present study, we compared repetition suppression and pattern similarity as predictors of both implicit and explicit memory. Using functional magnetic resonance imaging, we scanned 20 participants while they viewed and categorized repeated presentations of scenes. Repetition priming (facilitated categorization across repetitions) was used as a measure of implicit memory, and subsequent scene recognition was used as a measure of explicit memory. We found that repetition priming was predicted by repetition suppression in prefrontal, parietal, and occipitotemporal regions; however, repetition priming was not predicted by pattern similarity. In contrast, subsequent explicit memory was predicted by pattern similarity (across repetitions) in some of the same occipitotemporal regions that exhibited a relationship between priming and repetition suppression; however, explicit memory was not related to repetition suppression. This striking double dissociation indicates that repetition suppression and pattern similarity differentially track implicit and explicit learning.

  10. Maternal hair and neonatal meconium to assess gestational consumption and prenatal exposure to drugs of abuse and psychoactive drugs.

    Science.gov (United States)

    Cortes, Laura; Almeida, Laura; Sabra, Sally; Muniesa, Marta; Busardo, Francesco Paolo; Garcia-Algar, Oscar; Gomez-Roig, Maria Dolores

    2018-04-05

    In the last two decades, the consumption of drugs of abuse among women of childbearing age has experienced a significant increase and results from analyses of surveys concerning maternal intake of psychoactive prescription drugs during pregnancy indicate that the rates of intake are increasing each year. Analyses of biological matrices such as maternal hair and neonatal meconium have recently been used for assessment of gestational consumption and consequent prenatal exposure to drugs of abuse in high-risk groups of women METHODS: Maternal hair and neonatal meconium were analyzed by validated chromatographic mass spectrometric methodologies to disclose gestational use of drugs of abuse and psychoactive prescription drugs and consequent prenatal exposure in a cohort of 513 mother-newborn dyads at the Sant Joan de Déu Barcelona Hospital, Spain, during 2012- 2013. A total of 3.9% the women reported drugs of abuse or prescription psychoactive drug consumption at any time during pregnancy. The prevalence of gestational consumption and consequent prenatal exposure to drugs of abuse (e.g. cannabis, cocaine and MDMA) was 1.2% in maternal hair and 0.4% in meconium; that of psychoactive prescription drugs (e.g. venlafaxine, citalopram, fluoxetine, clomipramine) was 1.7% in maternal hair and 1.2% in meconium. The prevalence of drugs of abuse and prescription psychoactive drug consumption was lower in our specific cohort of Spanish pregnant women than in other cohorts such as those from U.S. or Denmark. Analysis of materno-fetal matrices provides a viable alternative to study prenatal exposure to these substances and develop specific social and health intervention recommendations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Simple strategy to assess linezolid exposure in patients with multi-drug-resistant and extensively-drug-resistant tuberculosis

    NARCIS (Netherlands)

    Kamp, Jasper; Bolhuis, Mathieu S.; Tiberi, Simon; Akkerman, Onno W.; Centis, Rosella; de lange, Wiel C.; Kosterink, Jos G.; van der Werf, Tjip S.; Migliori, Giovanni B.; Alffenaar, Jan-Willem C.

    Linezolid is used increasingly for the treatment of multi-drug-resistant (MDR) and extensively-drug-resistant (XDR) tuberculosis (TB). However, linezolid can cause severe adverse events, such as peripheral and optical neuropathy or thrombocytopenia related to higher drug exposure. This study aimed

  12. Cumulative exposure to phthalates from phthalate-containing drug products

    DEFF Research Database (Denmark)

    Ennis, Zandra Nymand; Broe, Anne; Pottegård, Anton

    2018-01-01

    European regulatory limit of exposure ranging between 380-1710 mg/year throughout the study period. Lithium-products constituted the majority of dibutyl phthalate exposure. Diethyl phthalate exposure, mainly caused by erythromycin, theophylline and diclofenac products, did not exceed the EMA regulatory...... to quantify annual cumulated phthalate exposure from drug products among users of phthalate-containing oral medications in Denmark throughout the period of 2004-2016. METHODS: We conducted a Danish nationwide cohort study using The Danish National Prescription Registry and an internal database held...

  13. Nitrosatable Drug Exposure during Pregnancy and Preterm and Small-for-Gestational-Age Births.

    Science.gov (United States)

    Vuong, Ann M; Shinde, Mayura U; Brender, Jean D; Shipp, Eva M; Huber, John C; Zheng, Qi; McDonald, Thomas J; Sharkey, Joseph R; Hoyt, Adrienne T; Werler, Martha M; Kelley, Katherine E; Langlois, Peter H; Canfield, Mark A

    2015-01-01

    Nitrosatable drugs react with nitrite in the stomach to form N-nitroso compounds, observed in animal models to result in adverse pregnancy outcomes, such as birth defects and reduced fetal weight. Previous studies examining prenatal exposure to medications classified as nitrosatable have reported an increased risk of preterm births (PTBs) and small-for-gestational-age (SGA) infants. Using data from mothers (controls) of babies without major birth defects from the National Birth Defects Prevention Study, prenatal nitrosatable drug usage by trimester and month of gestation was examined in relation to PTBs and SGA infants. Positive associations were observed with nitrosatable drug use and PTBs, with the strongest relationship with second trimester exposure (adjusted hazard ratio [aHR] 1.37, [95% confidence interval (CI) 1.10, 1.70]). Of the nitrosatable functional groups, secondary amines were the most notable, with a higher association among women with second (aHR 1.37, [95% CI 1.05, 1.79]) and third (aHR 1.34, [95% CI 1.02, 1.76]) trimester exposure compared with women with no prenatal nitrosatable drug use. Among SGA infants, a borderline association was noted with amide exposure during the third trimester (adjusted odds ratio 1.43 [95% confidence interval [CI] 1.00, 2.05]). Prenatal exposure to nitrosatable drugs during the second and third trimester of pregnancy, particularly secondary amines, might increase the risk of PTBs. However, prenatal exposure to nitrosatable drugs was not associated with SGA infants, with the exception of amide drugs. © 2014 John Wiley & Sons Ltd.

  14. Additive effects of repetition and predictability during comprehension: evidence from event-related potentials.

    Directory of Open Access Journals (Sweden)

    Wing-Yee Chow

    Full Text Available Previous research has shown that neural responses to words during sentence comprehension are sensitive to both lexical repetition and a word's predictability in context. While previous research has often contrasted the effects of these variables (e.g. by looking at cases in which word repetition violates sentence-level constraints, little is known about how they work in tandem. In the current study we examine how recent exposure to a word and its predictability in context combine to impact lexical semantic processing. We devise a novel paradigm that combines reading comprehension with a recognition memory task, allowing for an orthogonal manipulation of a word's predictability and its repetition status. Using event-related brain potentials (ERPs, we show that word repetition and predictability have qualitatively similar and additive effects on the N400 amplitude. We propose that prior exposure to a word and predictability impact lexical semantic processing in an additive and independent fashion.

  15. Risk of shoulder tendinitis in relation to shoulder loads in monotonous repetitive work

    DEFF Research Database (Denmark)

    Frost, P.; Bonde, J. P.; Mikkelsen, S.

    2002-01-01

    BACKGROUND: Few studies relate the occurrence of shoulder disorders to quantified ergonomic exposures. This study evaluates the hypothesis that shoulder loads in repetitive work might contribute to the occurrence of shoulder tendinitis. METHODS: This is a cross-sectional study of 1961 workers...... in repetitive work and 782 referents. Shoulder loads were quantified at task level and measures of exposures were assigned based on task distribution. Symptoms in combination with clinical criteria defined shoulder tendinitis. RESULTS: The prevalence of shoulder tendinitis was higher among exposed workers...

  16. Surface damage characteristics of CFC and tungsten with repetitive ELM-like pulsed plasma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kikuchi, Y., E-mail: ykikuchi@eng.u-hyogo.ac.jp [Graduate School of Engineering, University of Hyogo, 2167 Shosha, Himeji, 671-2280 Hyogo (Japan); Nishijima, D. [Center for Energy Research, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0417 (United States); Nakatsuka, M.; Ando, K.; Higashi, T.; Ueno, Y.; Ishihara, M.; Shoda, K.; Nagata, M. [Graduate School of Engineering, University of Hyogo, 2167 Shosha, Himeji, 671-2280 Hyogo (Japan); Kawai, T.; Ueda, Y. [Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan); Fukumoto, N. [Graduate School of Engineering, University of Hyogo, 2167 Shosha, Himeji, 671-2280 Hyogo (Japan); Doerner, R.P. [Center for Energy Research, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0417 (United States)

    2011-08-01

    Surface damage of carbon fiber composite (CFC) and tungsten (W) due to repetitive ELM-like pulsed plasma irradiation has been investigated by using a magnetized coaxial plasma gun. CX2002U CFC and stress-relieved W samples were exposed to repetitive pulsed deuterium plasmas with duration of {approx}0.5 ms, incident ion energy of {approx}30 eV, and surface absorbed energy density of {approx}0.3-0.7 MJ/m{sup 2}. Bright spots on a CFC surface during pulsed plasma exposures were clearly observed with a high-speed camera, indicating a local surface heating. No melting of a W surface was observed under a single plasma pulse exposure at energy density of {approx}0.7 MJ/m{sup 2}, although cracks were formed. Cracking of the W surface grew with repetitive pulsed plasma exposures. Subsequently, the surface melted due to localized heat absorption.

  17. Can a rapid measure of self-exposure to drugs of abuse provide dimensional information on depression comorbidity?

    Science.gov (United States)

    Butelman, Eduardo Roque; Bacciardi, Silvia; Maremmani, Angelo Giovanni Icro; Darst-Campbell, Maya; Correa da Rosa, Joel; Kreek, Mary Jeanne

    2017-09-01

    Addictions to heroin or to cocaine are associated with substantial psychiatric comorbidity, including depression. Poly-drug self-exposure (eg, to heroin, cocaine, cannabis, or alcohol) is also common, and may further affect depression comorbidity. This case-control study examined the relationship of exposure to the above drugs and depression comorbidity. Participants were recruited from methadone maintenance clinics, and from the community. Adult male and female participants (n = 1,201) were ascertained consecutively by experienced licensed clinicians. The instruments used were the SCID-I, and Kreek-McHugh-Schluger-Kellogg (KMSK) scales, which provide a rapid dimensional measure of maximal lifetime self-exposure to each of the above drugs. This measure ranges from no exposure to high unit dose, high frequency, and long duration of exposure. A multiple logistic regression with stepwise variable selection revealed that increasing exposure to heroin or to cocaine was associated greater odds of depression, with all cases and controls combined. In cases with an opioid dependence diagnosis, increasing cocaine exposure was associated with a further increase in odds of depression. However, in cases with a cocaine dependence diagnosis, increasing exposure to either cannabis or alcohol, as well as heroin, was associated with a further increase in odds of depression. This dimensional analysis of exposure to specific drugs provides insights on depression comorbidity with addictive diseases, and the impact of poly-drug exposure. A rapid analysis of exposure to drugs of abuse reveals how specific patterns of drug and poly-drug exposure are associated with increasing odds of depression. This approach detected quantitatively how different patterns of poly-drug exposure can result in increased odds of depression comorbidity, in cases diagnosed with opioid versus cocaine dependence. (Am J Addict 2017;26:632-639). © 2017 American Academy of Addiction Psychiatry.

  18. Repetitive Stress Injuries

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Repetitive Stress Injuries KidsHealth / For Teens / Repetitive Stress Injuries What's ... t had any problems since. What Are Repetitive Stress Injuries? Repetitive stress injuries (RSIs) are injuries that ...

  19. Risk factors for hand-wrist disorders in repetitive work

    DEFF Research Database (Denmark)

    Thomsen, J. F.; Mikkelsen, S.; Andersen, JH

    2007-01-01

    OBJECTIVES: To identify the risk of hand-wrist disorders related to repetitive movements, use of hand force and wrist position in repetitive monotonous work. METHODS: Using questionnaires and physical examinations, the prevalence and incidence of hand-wrist pain and possible extensor tendonitis...... (wrist pain and palpation tenderness) were determined in 3123 employees in 19 industrial settings. With the use of questionnaires and video recordings of homogenous work tasks number of wrist movements, hand force requirements and wrist position were analysed as risk factors for hand-wrist disorders......, controlling for potential personal and psychosocial confounders. All participants were re-examined three times during a follow-up period of three years. RESULTS: Force but not repetition and position was related to hand-wrist pain and possible tendonitis in the baseline analyses showing an exposure...

  20. Understanding work related musculoskeletal pain: does repetitive work cause stress symptoms?

    Science.gov (United States)

    Bonde, J P; Mikkelsen, S; Andersen, J H; Fallentin, N; Baelum, J; Svendsen, S W; Thomsen, J F; Frost, P; Kaergaard, A

    2005-01-01

    Pain in the neck and upper extremity is reported with high frequency in repetitive work. Mechanical overload of soft tissues seems a plausible mechanism, but psychological factors have received considerable attention during the past decade. If psychological factors are important for development of regional pain in repetitive work, stress symptoms would likely be on the causal path. To examine whether objective measures of repetitive monotonous work are related to occurrence and development of stress symptoms. In 1994-95, 2033 unskilled workers with continuous repetitive work and 813 workers with varied work were enrolled. Measures of repetitiveness and force requirements were quantified using video observations to obtain individual exposure estimates. Stress symptoms were recorded at baseline and after approximately one, two, and three years by the Setterlind Stress Profile Inventory. Repetitive work, task cycle time, and quantified measures of repetitive upper extremity movements including force requirements were not related to occurrence of stress symptoms at baseline or development of stress symptoms during three years of follow up. The findings do not indicate that repetitive work is associated with stress symptoms, but small effects cannot be ruled out. Thus the results question the importance of mental stress mechanisms in the causation of regional pain related to repetitive work. However, the findings should be interpreted with caution because the stress inventory has not been validated against a gold standard.

  1. The impact assessment of anticancer drug imatinib on the feeding behavior of rotifers with an integrated perspective: Exposure, post-exposure and re-exposure.

    Science.gov (United States)

    Yan, Zhengyu; Yan, Kun; He, Xingliang; Liu, Yanhua; Zhang, Jie; Lopez Torres, Oscar; Guo, Ruixin; Chen, Jianqiu

    2017-10-01

    The anticancer drugs are getting increasing attention as an emerging contaminant in the aquatic environments. In the present study, feeding behavior of the rotifer Brachionus calyciflorus under the impact of anticancer drug imatinib was evaluated. Traditional toxicological studies usually focus on dose-effect relationship at a given exposure time, while ignore the possible impact after the exposure. Thus, how the impact varied in the post-exposure and re-exposure was also considered in the present study. The feeding depression of the rotifers was attributed to the increased concentration of imatinib. Although the filtration and ingestion rate of the rotifers recovered to a certain extent after the exposure, the significant feeding inhibition still persisted even if the exposure was ended. In the re-exposure period, the feeding behavior was less depressed than those of the exposure period, which implied that rotifers might develop a tolerance to the same toxics. The activities of acetylcholine esterase (AchE) and the levels of reactive oxygen species (ROS) in rotifers were also detected. Imatinib inhibited the activities of AchE in the exposure and re-exposure while ROS levels increased significantly in the re-exposure period. Our present study provided an integrated assessment the potential environmental risks of imatinib at a new perspective. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. A comparison of the intrasubject variation in drug exposure between generic and brand-name drugs: a retrospective analysis of replicate design trials.

    Science.gov (United States)

    Yu, Yang; Teerenstra, Steven; Neef, Cees; Burger, David; Maliepaard, Marc

    2016-04-01

    The aim of the present study was to investigate whether differences in total and peak drug exposure upon generic substitution are due to differences between formulations or to intrasubject pharmacokinetic variability of the active substance. The study was designed as a retrospective reanalysis of existing studies. Nine replicate design bioequivalence studies representing six drug classes - i.e. for alendronate, atorvastatin, cyclosporin, ebastine, exemestane, mycophenolate mofetil, and ropinirole - were retrieved from the Dutch Medicines Regulatory Authority. In most studies, the intrasubject variability in total and peak drug exposure was comparable for the brand-name [in the range 0.01-0.24 for area under the concentration-time curve (AUCt ) and 0.02-0.29 for peak plasma concentration (Cmax ) on a log scale] and generic (0.01-0.23 for AUCt and 0.08-0.33 for Cmax ) drugs, and was comparable with the intrasubject variability upon switching between those drugs (0.01-0.23 for AUCt and 0.06-0.33 for Cmax ). The variance related to subject-by-formulation interaction could be considered negligible (-0.069 to 0.047 for AUCt and -0.091 to 0.02 for Cmax ). In the investigated studies, the variation in total and peak exposure seen when a patient is switched from a brand-name to a generic drug is comparable with that seen following repeated administration of the brand-name drug in the patient. Only the intrasubject variability seems to play a crucial and decisive role in the variation in drug exposure seen; no additional formulation-dependent variation in exposure is observed upon switching. Thus, our data support that, for the medicines that were included in the present investigation, from a clinical pharmacological perspective, the benefit-risk balance of a generic drug is comparable with that of the brand-name drug. © 2015 The British Pharmacological Society.

  3. Maternal characteristics associated with pregnancy exposure to FDA category C, D, and X drugs in a Canadian population.

    Science.gov (United States)

    Yang, Tubao; Walker, Mark C; Krewski, Daniel; Yang, Qiuying; Nimrod, Carl; Garner, Peter; Fraser, William; Olatunbosun, Olufemi; Wen, Shi Wu

    2008-03-01

    To estimate the frequency of exposure to prescription Food and Drug Administration (FDA) category C, D, and X drugs in pregnant women, and to analyze the maternal characteristics associated with such an exposure. A 50% random sample of women who gave a birth in Saskatchewan between January 1, 1997 and December 31, 2000 was chosen for the study. The rate of exposure to FDA category C, D, or X drugs recorded in the pharmacist database was estimated. Associations of exposure to FDA category C, D, and X drugs with maternal characteristics were evaluated using multiple logistical regression, with adjusted odds ratios (ORs) and its 95% confidence intervals (CIs) as the association measures. A total of 18 575 women were included in this study. Among them, 3604 (19.4%) had exposure to one or more FDA category C, D, and X drugs during pregnancy. Category C drugs were the most frequently used drugs (15.8%), followed by D drugs (5.2%), and X drugs (3.9%). Women with chronic health conditions had fourfold at increased risk of exposure than women without. Regardless of health status, women who were or =3, and who were on social assistance plan were at increased risk of pregnancy exposure to these drugs. About 19.4% pregnant women are exposed to FDA C, D or X drugs during pregnancy. Women with chronic diseases, younger age, increased parity, and under social assistance are at increased risk of exposure to FDA C, D, or X drugs. Copyright 2008 John Wiley & Sons, Ltd.

  4. Improvement of drug exposure data in a registration of congenital abnormalities

    DEFF Research Database (Denmark)

    de Jong van den Berg, L; Feenstra, N; Sørensen, Henrik Toft

    1999-01-01

    We examined the possibilities of improving the retrospective collection of data on drug use during pregnancy. The European Registration of Congenital Anomalies (EUROCAT) has registered information on maternal drug exposure in the northern Netherlands through a question on the notification form fo...

  5. Trends in oral drug bioavailability following bariatric surgery: examining the variable extent of impact on exposure of different drug classes.

    Science.gov (United States)

    Darwich, Adam S; Henderson, Kathryn; Burgin, Angela; Ward, Nicola; Whittam, Janet; Ammori, Basil J; Ashcroft, Darren M; Rostami-Hodjegan, Amin

    2012-11-01

    Changes to oral drug bioavailability have been observed post bariatric surgery. However, the magnitude and the direction of changes have not been assessed systematically to provide insights into the parameters governing the observed trends. Understanding these can help with dose adjustments. Analysis of drug characteristics based on a biopharmaceutical classification system is not adequate to explain observed trends in altered oral drug bioavailability following bariatric surgery, although the findings suggest solubility to play an important role. To identify the most commonly prescribed drugs in a bariatric surgery population and to assess existing evidence regarding trends in oral drug bioavailability post bariatric surgery. A retrospective audit was undertaken to document commonly prescribed drugs amongst patients undergoing bariatric surgery in an NHS hospital in the UK and to assess practice for drug administration following bariatric surgery. The available literature was examined for trends relating to drug permeability and solubility with regards to the Biopharmaceutics Classification System (BCS) and main route of elimination. No significant difference in the 'post/pre surgery oral drug exposure ratio' (ppR) was apparent between BCS class I to IV drugs, with regards to dose number (Do) or main route of elimination. Drugs classified as 'solubility limited' displayed an overall reduction as compared with 'freely soluble' compounds, as well as an unaltered and increased ppR. Clinical studies establishing guidelines for commonly prescribed drugs, and the monitoring of drugs exhibiting a narrow therapeutic window or without a readily assessed clinical endpoint, are warranted. Using mechanistically based pharmacokinetic modelling for simulating the multivariate nature of changes in drug exposure may serve as a useful tool in the further understanding of postoperative trends in oral drug exposure and in developing practical clinical guidance. © 2012 The Authors

  6. Stimulus repetition and the perception of time: the effects of prior exposure on temporal discrimination, judgment, and production.

    Directory of Open Access Journals (Sweden)

    William J Matthews

    Full Text Available It has been suggested that repeated stimuli have shorter subjective duration than novel items, perhaps because of a reduction in the neural response to repeated presentations of the same object. Five experiments investigated the effects of repetition on time perception and found further evidence that immediate repetition reduces apparent duration, consistent with the idea that subjective duration is partly based on neural coding efficiency. In addition, the experiments found (a no effect of repetition on the precision of temporal discrimination, (b that the effects of repetition disappeared when there was a modest lag between presentations, (c that, across participants, the size of the repetition effect correlated with temporal discrimination, and (d that the effects of repetition suggested by a temporal production task were the opposite of those suggested by temporal judgments. The theoretical and practical implications of these results are discussed.

  7. [The use of saliva for exposure assessments on designer drugs among adolescents].

    Science.gov (United States)

    Napierała, Marta; Tezyk, Artur; Piznal, Małgorzata; Bogusiewicz, Joanna; Florek, Ewa

    2015-01-01

    Drug use is one of the fundamental problems of the contemporary world. Due to the debilitating effects on physical and mental health and the possibility of impaired social functions, it is extremely important to assess exposure to psychoactive substances among high-risk groups. Taking into account characteristics of adolescence, one of them includes young people. To assess the exposure of young people to drugs, survey research is the most commonly use. To establish reliability of the information indicated by the students, toxicological studies could be a good manner. High-performance liquid chromatography coupled with mass spectrometry (LC-MS) is currently one of the most common techniques use for the detection and determination of psychoactive substances in biological material. In practice, an important issue in toxicological studies is the selection of a suitable biological material. Taking into account economic considerations and the method of sampling, the saliva is an increasingly used alternative material. The aim of this study was to assess the exposure of junior high school students on psychoactive substances--designer drugs, through the analysis of surveys and qualitative analysis of saliva taken from teenagers. It has been shown that surveys are a relatively quick and easy form of assessing the exposure of young people to psychoactive substances, but require verification through toxicological analysis of biological material for the presence of psychoactive substances for their reliability. Poznan secondary school students experimented with designer drugs at a similar level as respondents of nationwide survey from 2013.

  8. Trends in exposure to televised prescription drug advertising, 2003-2011.

    Science.gov (United States)

    Kornfield, Rachel; Alexander, G Caleb; Qato, Dima M; Kim, Yoonsang; Hirsch, Jan D; Emery, Sherry L

    2015-05-01

    TV accounts for more than half of pharmaceutical direct-to-consumer advertising (DTCA) spending in the U.S. The purpose of this study is to quantify average household exposure to branded and non-branded (help-seeking) televised prescription drug advertisements and describe variation over time and according to medication indication and geography. In 2013, Nielsen TV ratings were compiled for prescription pharmaceutical advertising that aired between 2003 and 2011 for the top 75 U.S. media markets. All advertisements were coded as branded or help-seeking. Advertisements were further coded for one of eight prevalent indications (allergies, arthritis, asthma, erectile dysfunction, high cholesterol, smoking cessation, depression, and sleep disorder) or as "other." Televised DTCA exposure increased from 2003 to 2007 and then declined 43% by 2011, to 111 monthly prescription drug advertisements per household. The examined indications were associated with varying amounts and patterns of exposure, with greatest declines among medications for allergies and sleep disorders. Help-seeking advertisements comprised 10% of total exposure, with substantial variation by indication. Considerations of DTCA's effects on health care should take into account the shifting concentration of advertising across indications. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  9. The Influence of Level of Processing on Advertising Repetition Effects.

    OpenAIRE

    Nordhielm, Christie L

    2002-01-01

    This research examines whether or not repetition of features of a stimulus are subject to wear-out effects that have until now only been tested for the stimulus as a whole. When consumers process features in either a shallower or deeper manner, the level of processing performed dictates the effect of repeated feature exposure on their judgments. When repeated exposures to features are processed in a shallower fashion, there is an enhancement in evaluations with no subsequent downturn, whereas...

  10. Information technology-based approaches to reducing repeat drug exposure in patients with known drug allergies.

    Science.gov (United States)

    Cresswell, Kathrin M; Sheikh, Aziz

    2008-05-01

    There is increasing interest internationally in ways of reducing the high disease burden resulting from errors in medicine management. Repeat exposure to drugs to which patients have a known allergy has been a repeatedly identified error, often with disastrous consequences. Drug allergies are immunologically mediated reactions that are characterized by specificity and recurrence on reexposure. These repeat reactions should therefore be preventable. We argue that there is insufficient attention being paid to studying and implementing system-based approaches to reducing the risk of such accidental reexposure. Drawing on recent and ongoing research, we discuss a number of information technology-based interventions that can be used to reduce the risk of recurrent exposure. Proven to be effective in this respect are interventions that provide real-time clinical decision support; also promising are interventions aiming to enhance patient recognition, such as bar coding, radiofrequency identification, and biometric technologies.

  11. Potential Exposure to Anti-Drug Advertising and Drug-Related Attitudes, Beliefs, and Behaviors among United States Youth, 1995-2006

    Science.gov (United States)

    Terry-McElrath, Yvonne M.; Emery, Sherry; Szczypka, Glen; Johnston, Lloyd D.

    2010-01-01

    Using nationally representative data from the Monitoring the Future Study on United States middle and high school students, we related exposure to anti-drug television advertising as measured by Nielsen Media Research ratings points to student self-reported drug-related outcomes from 1995-2006. Multivariate analyses controlling for key socio-demographics and accounting for the complex survey design included 337,918 cases. Results indicated that attitudes, beliefs, and behaviors regarding substance use were significantly related to such advertising exposure over the six months prior to the date youth were surveyed. However, the observed relationships varied by grade level, over time and by advertising tagline and marijuana focus. Findings differed markedly between middle and high school students across the study interval. One factor that may partially explain observed differences may be variation in the degree to which the ads focused on marijuana. Putting a concerted effort into increasing anti-drug advertising will likely increase the exposure to and recall of such ads among youth. However, the likelihood that such advertising will result in youth being less likely to use drugs seems to depend heavily on the type of advertising utilized and how it relates to different ages and characteristics of targeted youth. PMID:20961691

  12. Characterization of the multiple drug resistance phenotype expressed by tumour cells following in vitro exposure to fractionated X-irradiation

    International Nuclear Information System (INIS)

    Hill, B.T.; McClean, S.; Hosking, L.; Shellard, S.; Dempke, W.; Whelan, R.

    1992-01-01

    The major clinical problem of the emergence of drug resistant tumor cell populations is recognized in patients previously treated with antitumor drugs and with radiotherapy. It is proposed that, although radiation-induced vascular fibrosis may limit drug delivery to the tumor, exposure to radiation may 'induce' or 'select for' drug resistance. This hypothesis was examined by establishing in vitro model systems to investigate the resistance phenotype of tumor cells following exposure to X-rays. Characteristically tumor cells surviving exposure to a series of fractions of X-irradiation are shown to have consistently expressed resistance to multiple drugs, including the Vinca alkaloids and the epipodophyllotoxins. Currently this research is aimed at determining whether distinctive resistance mechanisms operate depending on whether resistance results following drug or X-ray exposure. Initial results indicate that whilst some common mechanisms operate, drug resistant tumor cells identified following exposure to X-irradiation appear to exhibit a novel multidrug resistance phenotype. (author). 13 refs., 1 tab

  13. Repetitive negative thinking and suicide: a burgeoning literature with need for further exploration.

    Science.gov (United States)

    Law, Keyne C; Tucker, Raymond P

    2017-08-24

    Extant research has found a significant overlap between various repetitive negative thinking (RNT) patterns, such as rumination and worry, across different affective disorders implicating that the process of repetitive negative thinking is likely trans-diagnostic. Furthermore, RNT patterns at the core of psychiatric disorders associated with suicide (e.g., rumination and worry) have been found to be associated with suicide even after accounting for the disorder. A synthesis of existing literature on repetitive negative thoughts suggest that following negative emotional experiences, RNTs may lead to a sense of entrapment and hopelessness that may contribute to the onset of suicidal ideation and then facilitate the transition from thinking about suicide to making a suicide attempt by increasing an individual's capability for suicide through repetitive exposure to violent thoughts and imagery associated with suicide. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Surgery for subacromial impingement syndrome in relation to intensities of occupational mechanical exposures across 10-year exposure time windows.

    Science.gov (United States)

    Dalbøge, Annett; Frost, Poul; Andersen, Johan Hviid; Svendsen, Susanne Wulff

    2018-03-01

    We aimed to identify intensities of occupational mechanical exposures (force, arm elevation and repetition) that do not entail an increased risk of surgery for subacromial impingement syndrome (SIS) even after prolonged durations of exposure. Additionally, we wanted to evaluate if exposure to hand-arm vibration (HAV) is an independent risk factor. We used data from a register-based cohort study of the entire Danish working population (n=2 374 403). During follow-up (2003-2008), 14 118 first-time events of surgery for SIS occurred. For each person, we linked register-based occupational codes (1993-2007) to a general population job exposure matrix to obtain year-by-year exposure intensities on measurement scales for force, upper arm elevation >90° and repetition and expert rated intensities of exposure to HAV. For 10-year exposure time windows, we calculated the duration of exposure at specific intensities above minimal (low, medium and high). We used a logistic regression technique equivalent to discrete survival analysis adjusting for cumulative effects of other mechanical exposures. We found indications of safe exposure intensities for repetition (median angular velocity 90° >2 min/day implied an increased risk reaching ORs of 1.7 and 1.5 after 10 years at low intensities. No associations were found for HAV. We found indications of safe exposure intensities for repetition. Any intensities of force and upper arm elevation >90° above minimal implied an increased risk across 10-year exposure time windows. No independent associations were found for HAV. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. ATTENTION FUNCTIONING IN CHILDREN WITH PRENATAL DRUG EXPOSURE.

    Science.gov (United States)

    Jaeger, Dominique A; Suchan, Boris; Schölmerich, Axel; Schneider, Dominik T; Gawehn, Nina

    2015-01-01

    Children born to drug abusers are exposed to teratogenic influences on intrauterine brain development and undergo postnatal withdrawal. We investigated the interplay of different domains and levels of attention functioning in 24 prenatally exposed and 25 nonexposed children who were 5 to 6 years old. Assessment included parent ratings and neuropsychological and electrophysiological methods. Exposed children had a higher prevalence of attention deficit hyperactivity symptoms, tended to have poorer performance in an attention test battery, and showed EEG alterations in P3 and N2c. Findings suggest long-term effects of prenatal drug exposure on specific domains and on different levels of attention functioning. © 2015 Michigan Association for Infant Mental Health.

  16. Self-reported and laboratory evaluation of late pregnancy nicotine exposure and drugs of abuse.

    Science.gov (United States)

    Hall, E S; Wexelblatt, S L; Greenberg, J M

    2016-10-01

    The objective of this study was to evaluate the prevalence of late pregnancy nicotine exposures, including secondhand smoke exposures, and to evaluate the associated risk of exposure to drugs of abuse. The study was a retrospective single-center cohort analysis of more than 18 months. We compared self-reported smoking status from vital birth records with mass spectrometry laboratory results of maternal urine using a chi-square test. Logistic regression estimated adjusted odds for detection of drugs of abuse based on nicotine detection. Compared with 8.6% self-reporting cigarette use, mass spectrometry detected high-level nicotine exposures for 16.5% of 708 women (Pdrugs of abuse, presented as adjusted odds ratios, (95% confidence interval (CI), for both low-level (5.69, CI: 2.09 to 15.46) and high-level (13.93, CI: 7.06 to 27.49) nicotine exposures. Improved measurement tactics are critically needed to capture late pregnancy primary and passive nicotine exposures from all potential sources.

  17. Prenatal drug exposure and teratological risk: one-year experience of an Italian Teratology Information Service.

    Science.gov (United States)

    De Santis, Marco; Cesari, Elena; Ligato, Maria Serena; Nobili, Elena; Straface, Gianluca; Cavaliere, Annafranca; Caruso, Alessandro

    2008-02-01

    Concern about exposure to drugs, radiation, or infection during pregnancy occur often because pregnancy is not always planned. A teratology information service offers rapid scientific counseling to all those worried about prenatal exposure. The aim of this study is to present data on the most common pharmaceutical products responsible for teratogenic risk in the one-year experience of a teratology information service in Italy. The survey was conducted among 8664 callers who contacted our Teratology Information Service in Rome between January and December 2006. Data on maternal age, gravidity, parity, maternal health status, and details of exposure (dose and timing) were collected and stored in a specific data base. Scientific counseling on prenatal exposure was given to the caller by a specialized service operator, specifying the type of risk and suggesting appropriate tests for prenatal diagnosis. Most of the people called regarding drug exposure; increased risk was present in only 5% of the pregnant women calling during pregnancy. Selective serotonin reuptake inhibitors (SSRIs) are the first category that are actually considered of increased risk to the fetus. The second category is represented by antiepileptic drugs. This experience confirms previous data that there is a high teratological risk perception among both women and physicians. The drugs estimated to present increased risk are medications used for chronic neurological diseases, mainly mood disorders and epilepsy. Preconceptional counseling for these women could be an effective strategy to prevent such exposure and to improve maternal and fetal outcome.

  18. Repetition and Translation Shifts

    Directory of Open Access Journals (Sweden)

    Simon Zupan

    2006-06-01

    Full Text Available Repetition manifests itself in different ways and at different levels of the text. The first basic type of repetition involves complete recurrences; in which a particular textual feature repeats in its entirety. The second type involves partial recurrences; in which the second repetition of the same textual feature includes certain modifications to the first occurrence. In the article; repetitive patterns in Edgar Allan Poe’s short story “The Fall of the House of Usher” and its Slovene translation; “Konec Usherjeve hiše”; are compared. The author examines different kinds of repetitive patterns. Repetitions are compared at both the micro- and macrostructural levels. As detailed analyses have shown; considerable microstructural translation shifts occur in certain types of repetitive patterns. Since these are not only occasional; sporadic phenomena; but are of a relatively high frequency; they reduce the translated text’s potential for achieving some of the gothic effects. The macrostructural textual property particularly affected by these shifts is the narrator’s experience as described by the narrative; which suffers a reduction in intensity.

  19. Data sources and methods for ascertaining human exposure to drugs.

    Science.gov (United States)

    Jones, J K; Kennedy, D L

    Estimates of population exposure based on drug use data are critical elements in the post marketing surveillance of drugs and provide a context for assessing the various risks and benefits associated with drug treatment. Such information is important in predicting morbidity and planning public health protection strategies, indepth studies, and regulatory actions. Knowledge that a population of one thousand instead of one million may potentially be exposed to a drug can help determine how a particular regulatory problem will be handled and would obviously be a major determinant in designing a case-control or cohort study. National estimates of drug use give an overview of the most commonly used drug therapies in current practice. They also furnish valuable comparison data for specific studies of drug use limited to one group of drugs, one geographic region, or one medical care setting. The FDA has access to several different national drug use data bases, each measuring a different point in the drug distribution channels. None covers the entire spectrum of drug exposures. The major "holes" in this patchwork of data bases are the inability to measure OTC drug use with any accuracy and the lack of qualitative information on drug use in hospitals. In addition, there is no patient linkage with the data. The data can only show trends in drug use. They impart no sense of the longitudinal use of drugs for individual patients. There is no direct connection between the different data bases, all of which have their own sampling frames and their own projection methodologies. The market research companies have complete control over these methodologies and they are subject to periodic changes, a situation not entirely satisfactory for epidemiologic research. Sometimes it is a struggle to keep up with these changes. Over the past two years, every one of these data bases has undergone some type of sampling or projection methodology change. One important limitation to the use of all

  20. The effect of activated charcoal on drug exposure in healthy volunteers: a meta-analysis

    DEFF Research Database (Denmark)

    Jürgens, G; Hoegberg, L C Groth; Graudal, N A

    2009-01-01

    The objective of the study was to estimate the effect of activated charcoal (AC) administered during the first 6 h after drug intake and the effect of drug properties on drug exposure. Sixty-four controlled studies were integrated in a meta-analysis. AC administered 0-5 min after administration...

  1. Comorbidity Among Depression, Conduct Disorder, and Drug Use From Adolescence to Young Adulthood: Examining the Role of Violence Exposures

    Science.gov (United States)

    Cerdá, Magdalena; Tracy, Melissa; Sánchez, Brisa N.; Galea, Sandro

    2012-01-01

    We assessed relations among depression, conduct disorder, and drug use from adolescence to young adulthood, and evaluated whether exposure to violence contributed to disorder co-occurrence. We used data from the Project on Human Development in Chicago Neighborhoods. Respondents were 12–15 years old in 1995–1997 (N = 1,517), and were reinterviewed in 1997–2000 (n = 1,315), and 2000–2002 (n = 1,210). We examined exposure to violence at ages 12–15 and 14–17, and depression, conduct disorder, and drug use at ages 14–17 and 17–20. Multivariate transition models revealed an association between prior conduct disorder and drug use, as well as a relationship between prior depression and conduct disorder. Adolescent exposure to violence was associated with higher odds of conduct disorder and drug use but not depression. Comorbid relations between conduct disorder and drug use were independent of prior exposure to violence. Although preventing adolescent exposure to violence may reduce the risk of conduct disorder and drug use by young adulthood, future research needs to investigate alternative determinants of sequential comorbidity among depression, conduct disorder, and drug use in adolescence and young adulthood. PMID:22147426

  2. Transduction of Repetitive Mechanical Stimuli by Piezo1 and Piezo2 Ion Channels

    Directory of Open Access Journals (Sweden)

    Amanda H. Lewis

    2017-06-01

    Full Text Available Several cell types experience repetitive mechanical stimuli, including vein endothelial cells during pulsating blood flow, inner ear hair cells upon sound exposure, and skin cells and their innervating dorsal root ganglion (DRG neurons when sweeping across a textured surface or touching a vibrating object. While mechanosensitive Piezo ion channels have been clearly implicated in sensing static touch, their roles in transducing repetitive stimulations are less clear. Here, we perform electrophysiological recordings of heterologously expressed mouse Piezo1 and Piezo2 responding to repetitive mechanical stimulations. We find that both channels function as pronounced frequency filters whose transduction efficiencies vary with stimulus frequency, waveform, and duration. We then use numerical simulations and human disease-related point mutations to demonstrate that channel inactivation is the molecular mechanism underlying frequency filtering and further show that frequency filtering is conserved in rapidly adapting mouse DRG neurons. Our results give insight into the potential contributions of Piezos in transducing repetitive mechanical stimuli.

  3. Efficient in vitro photodynamic inactivation of Candida albicans by repetitive light doses

    Science.gov (United States)

    Torres-Hurtado, S. A.; Ramírez Ramírez, J.; Ramos-García, R.; Ramírez-San-Juan, J. C.; Spezzia-Mazzocco, T.

    2018-02-01

    The aim of this study was to compare the effectiveness of Rose Bengal (RB) and Methylene Blue (MB) as photosensitizers (PS) in Photodynamic Inactivation (PDI) on planktonic cultures of Candida albicans, a well-known opportunistic pathogen. RB and MB at concentrations ranging from 0.5 to 60 μM and fluences of 10, 30, 45 and 60 J/cm2 were tested. The light sources consist of an array of 12 led diodes with 30 mW of optical power each; 490-540 nm (green light) to activate RB and 600 -650 nm (red light) to activate MB. We first optimize the in vitro PDI technique using a single light dose and the optimum PS concentration. The novelty of our approach consist in reducing further the PS concentration than the optimum obtained with a single light exposure and using smaller light fluence doses by using repetitive light exposures (two to three times). MB and RB were tested for repetitive exposures at concentrations ranging from 0.1 to 10 μM, with fluences of 3 to 20 J/cm2, doses well below than those reported previously. All experiments were done in triplicate with the corresponding controls; cells without treatment, light control and dark toxicity control. RB-PDI and MB-PDI significantly reduced the number of CFU/mL when compared to the control groups. The results showed that RB was more effective than MB for C. albicans inactivation. Thus, we show that is possible to reduce significantly the amount of PS and light fluence requirements using repetitive light doses of PDI in vitro.

  4. Chronic Exposure to Androgenic-Anabolic Steroids Exacerbates Axonal Injury and Microgliosis in the CHIMERA Mouse Model of Repetitive Concussion.

    Directory of Open Access Journals (Sweden)

    Dhananjay R Namjoshi

    Full Text Available Concussion is a serious health concern. Concussion in athletes is of particular interest with respect to the relationship of concussion exposure to risk of chronic traumatic encephalopathy (CTE, a neurodegenerative condition associated with altered cognitive and psychiatric functions and profound tauopathy. However, much remains to be learned about factors other than cumulative exposure that could influence concussion pathogenesis. Approximately 20% of CTE cases report a history of substance use including androgenic-anabolic steroids (AAS. How acute, chronic, or historical AAS use may affect the vulnerability of the brain to concussion is unknown. We therefore tested whether antecedent AAS exposure in young, male C57Bl/6 mice affects acute behavioral and neuropathological responses to mild traumatic brain injury (TBI induced with the CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration platform. Male C57Bl/6 mice received either vehicle or a cocktail of three AAS (testosterone, nandrolone and 17α-methyltestosterone from 8-16 weeks of age. At the end of the 7th week of treatment, mice underwent two closed-head TBI or sham procedures spaced 24 h apart using CHIMERA. Post-repetitive TBI (rTBI behavior was assessed for 7 d followed by tissue collection. AAS treatment induced the expected physiological changes including increased body weight, testicular atrophy, aggression and downregulation of brain 5-HT1B receptor expression. rTBI induced behavioral deficits, widespread axonal injury and white matter microgliosis. While AAS treatment did not worsen post-rTBI behavioral changes, AAS-treated mice exhibited significantly exacerbated axonal injury and microgliosis, indicating that AAS exposure can alter neuronal and innate immune responses to concussive TBI.

  5. Chronic Exposure to Androgenic-Anabolic Steroids Exacerbates Axonal Injury and Microgliosis in the CHIMERA Mouse Model of Repetitive Concussion.

    Science.gov (United States)

    Namjoshi, Dhananjay R; Cheng, Wai Hang; Carr, Michael; Martens, Kris M; Zareyan, Shahab; Wilkinson, Anna; McInnes, Kurt A; Cripton, Peter A; Wellington, Cheryl L

    2016-01-01

    Concussion is a serious health concern. Concussion in athletes is of particular interest with respect to the relationship of concussion exposure to risk of chronic traumatic encephalopathy (CTE), a neurodegenerative condition associated with altered cognitive and psychiatric functions and profound tauopathy. However, much remains to be learned about factors other than cumulative exposure that could influence concussion pathogenesis. Approximately 20% of CTE cases report a history of substance use including androgenic-anabolic steroids (AAS). How acute, chronic, or historical AAS use may affect the vulnerability of the brain to concussion is unknown. We therefore tested whether antecedent AAS exposure in young, male C57Bl/6 mice affects acute behavioral and neuropathological responses to mild traumatic brain injury (TBI) induced with the CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) platform. Male C57Bl/6 mice received either vehicle or a cocktail of three AAS (testosterone, nandrolone and 17α-methyltestosterone) from 8-16 weeks of age. At the end of the 7th week of treatment, mice underwent two closed-head TBI or sham procedures spaced 24 h apart using CHIMERA. Post-repetitive TBI (rTBI) behavior was assessed for 7 d followed by tissue collection. AAS treatment induced the expected physiological changes including increased body weight, testicular atrophy, aggression and downregulation of brain 5-HT1B receptor expression. rTBI induced behavioral deficits, widespread axonal injury and white matter microgliosis. While AAS treatment did not worsen post-rTBI behavioral changes, AAS-treated mice exhibited significantly exacerbated axonal injury and microgliosis, indicating that AAS exposure can alter neuronal and innate immune responses to concussive TBI.

  6. Effects of high repetition rate and beam size on hard tissue damage due to subpicosecond laser pulses

    International Nuclear Information System (INIS)

    Kim, Beop-Min; Feit, Michael D.; Rubenchik, Alexander M.; Joslin, Elizabeth J.; Eichler, Juergen; Stoller, Patrick C.; Da Silva, Luiz B.

    2000-01-01

    We report the effects of the repetition rate and the beam size on the threshold for ultrashort laser pulse induced damage in dentin. The observed results are explained as cumulative thermal effects. Our model is consistent with the experimental results and explains the dependence of the threshold on repetition rate, beam size, and exposure time. (c) 2000 American Institute of Physics

  7. Roles of repetitive sequences

    Energy Technology Data Exchange (ETDEWEB)

    Bell, G.I.

    1991-12-31

    The DNA of higher eukaryotes contains many repetitive sequences. The study of repetitive sequences is important, not only because many have important biological function, but also because they provide information on genome organization, evolution and dynamics. In this paper, I will first discuss some generic effects that repetitive sequences will have upon genome dynamics and evolution. In particular, it will be shown that repetitive sequences foster recombination among, and turnover of, the elements of a genome. I will then consider some examples of repetitive sequences, notably minisatellite sequences and telomere sequences as examples of tandem repeats, without and with respectively known function, and Alu sequences as an example of interspersed repeats. Some other examples will also be considered in less detail.

  8. Surgery for subacromial impingement syndrome in relation to intensities of occupational mechanical exposures across 10-year exposure time windows

    DEFF Research Database (Denmark)

    Dalbøge, Annett; Frost, Poul; Andersen, Johan Hviid

    2018-01-01

    OBJECTIVES: We aimed to identify intensities of occupational mechanical exposures (force, arm elevation and repetition) that do not entail an increased risk of surgery for subacromial impingement syndrome (SIS) even after prolonged durations of exposure. Additionally, we wanted to evaluate...... if exposure to hand-arm vibration (HAV) is an independent risk factor. METHODS: We used data from a register-based cohort study of the entire Danish working population (n=2 374 403). During follow-up (2003-2008), 14 118 first-time events of surgery for SIS occurred. For each person, we linked register...... of exposure at specific intensities above minimal (low, medium and high). We used a logistic regression technique equivalent to discrete survival analysis adjusting for cumulative effects of other mechanical exposures. RESULTS: We found indications of safe exposure intensities for repetition (median angular...

  9. Closed-system drug-transfer devices plus safe handling of hazardous drugs versus safe handling alone for reducing exposure to infusional hazardous drugs in healthcare staff.

    Science.gov (United States)

    Gurusamy, Kurinchi Selvan; Best, Lawrence Mj; Tanguay, Cynthia; Lennan, Elaine; Korva, Mika; Bussières, Jean-François

    2018-03-27

    Occupational exposure to hazardous drugs can decrease fertility and result in miscarriages, stillbirths, and cancers in healthcare staff. Several recommended practices aim to reduce this exposure, including protective clothing, gloves, and biological safety cabinets ('safe handling'). There is significant uncertainty as to whether using closed-system drug-transfer devices (CSTD) in addition to safe handling decreases the contamination and risk of staff exposure to infusional hazardous drugs compared to safe handling alone. To assess the effects of closed-system drug-transfer of infusional hazardous drugs plus safe handling versus safe handling alone for reducing staff exposure to infusional hazardous drugs and risk of staff contamination. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, OSH-UPDATE, CINAHL, Science Citation Index Expanded, economic evaluation databases, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov to October 2017. We included comparative studies of any study design (irrespective of language, blinding, or publication status) that compared CSTD plus safe handling versus safe handling alone for infusional hazardous drugs. Two review authors independently identified trials and extracted data. We calculated the risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CI) using both fixed-effect and random-effects models. We assessed risk of bias according to the risk of bias in non-randomised studies of interventions (ROBINS-I) tool, used an intracluster correlation coefficient of 0.10, and we assessed the quality of the evidence using GRADE. We included 23 observational cluster studies (358 hospitals) in this review. We did not find any randomised controlled trials or formal economic evaluations. In 21 studies, the people who used the intervention (CSTD plus safe handling) and control (safe handling alone) were pharmacists or pharmacy

  10. Reproductive Health Risks Associated with Occupational Exposures to Antineoplastic Drugs in Health Care Settings: A Review of the Evidence

    Science.gov (United States)

    Connor, Thomas H.; Lawson, Christina C.; Polovich, Martha; McDiarmid, Melissa A.

    2015-01-01

    Objectives Antineoplastic drugs are known reproductive and developmental toxicants. Our objective was to review the existing literature of reproductive health risks to workers who handle antineoplastic drugs. Methods A structured literature review of 18 peer-reviewed, English language publications of occupational exposure and reproductive outcomes was performed. Results While effect sizes varied with study size and population, occupational exposure to antineoplastic drugs appears to raise the risk of both congenital malformations and miscarriage. Studies of infertility and time-to-pregnancy also suggested an increased risk for sub-fertility. Conclusions Antineoplastic drugs are highly toxic in patients receiving treatment and adverse reproductive effects have been well documented in these patients. Healthcare workers with chronic, low level occupational exposure to these drugs also appear to have an increased risk of adverse reproductive outcomes. Additional precautions to prevent exposure should be considered. PMID:25153300

  11. A Nonword Repetition Task for Speakers with Misarticulations: The Syllable Repetition Task (SRT)

    Science.gov (United States)

    Shriberg, Lawrence D.; Lohmeier, Heather L.; Campbell, Thomas F.; Dollaghan, Christine A.; Green, Jordan R.; Moore, Christopher A.

    2009-01-01

    Purpose: Conceptual and methodological confounds occur when non(sense) word repetition tasks are administered to speakers who do not have the target speech sounds in their phonetic inventories or who habitually misarticulate targeted speech sounds. In this article, the authors (a) describe a nonword repetition task, the Syllable Repetition Task…

  12. Performance of repetitive tasks induces decreased grip strength and increased fibrogenic proteins in skeletal muscle: role of force and inflammation.

    Directory of Open Access Journals (Sweden)

    Samir M Abdelmagid

    Full Text Available This study elucidates exposure-response relationships between performance of repetitive tasks, grip strength declines, and fibrogenic-related protein changes in muscles, and their link to inflammation. Specifically, we examined forearm flexor digitorum muscles for changes in connective tissue growth factor (CTGF; a matrix protein associated with fibrosis, collagen type I (Col1; a matrix component, and transforming growth factor beta 1 (TGFB1; an upstream modulator of CTGF and collagen, in rats performing one of two repetitive tasks, with or without anti-inflammatory drugs.To examine the roles of force versus repetition, rats performed either a high repetition negligible force food retrieval task (HRNF, or a high repetition high force handle-pulling task (HRHF, for up to 9 weeks, with results compared to trained only (TR-NF or TR-HF and normal control rats. Grip strength declined with both tasks, with the greatest declines in 9-week HRHF rats. Quantitative PCR (qPCR analyses of HRNF muscles showed increased expression of Col1 in weeks 3-9, and CTGF in weeks 6 and 9. Immunohistochemistry confirmed PCR results, and also showed greater increases of CTGF and collagen matrix in 9-week HRHF rats than 9-week HRNF rats. ELISA, and immunohistochemistry revealed greater increases of TGFB1 in TR-HF and 6-week HRHF, compared to 6-week HRNF rats. To examine the role of inflammation, results from 6-week HRHF rats were compared to rats receiving ibuprofen or anti-TNF-α treatment in HRHF weeks 4-6. Both treatments attenuated HRHF-induced increases in CTGF and fibrosis by 6 weeks of task performance. Ibuprofen attenuated TGFB1 increases and grip strength declines, matching our prior results with anti-TNFα.Performance of highly repetitive tasks was associated with force-dependent declines in grip strength and increased fibrogenic-related proteins in flexor digitorum muscles. These changes were attenuated, at least short-term, by anti-inflammatory treatments.

  13. Analysis of Dextromethorphan and Dextrorphan in Skeletal Remains Following Differential Microclimate Exposure: Comparison of Acute vs. Repeated Drug Exposure.

    Science.gov (United States)

    Morrison, Lucas M; Unger, Kirk A; Watterson, James H

    2017-07-01

    Analysis of dextromethorphan (DXM) and its metabolite dextrorphan (DXT) in skeletal remains of rats following acute (ACU, 75 mg/kg, IP, n = 10) or three repeated (REP, 25 mg/kg, IP, n = 10, 40-min interval) doses of DXM is described. Following dosing and euthanasia, rats decomposed outdoors to skeleton in two different microclimate environments (n = 5 ACU and n = 5 REP at each site): Site A (shaded forest microenvironment) and Site B (rocky substrate exposed to direct sunlight, 600 m from Site A). Two drug-free rats at each site served as negative controls. Skeletal elements (vertebrae, ribs, pelvic girdles, femora, tibiae, skulls and scapulae) were recovered, pulverized and underwent methanolic microwave assisted extraction (MAE). Extracts were analyzed by GC-MS following clean-up by solid-phase extraction (SPE). Drug levels, expressed as mass-normalized response ratios and the ratios of DXT and DXM levels (RRDXT/RRDXM) were compared between drug exposures, microclimate sites, and across skeletal elements. DXM levels differed significantly (P < 0.05) between corresponding bone elements across exposure groups (5/7-site A; 4/7-site B), but no significant differences in DXT levels were observed between corresponding elements. RRDXT/RRDXM differed significantly (P < 0.05) between corresponding bone elements across exposure groups (6/7-site A; 5/7-site B). No significant differences were observed in levels of DXM, DXT or RRDXT/RRDXM between corresponding elements from either group between sites. When data from all bone elements was pooled, levels of DXM and RRDXT/RRDXM differed significantly between exposure groups at each site, while those of DXT did not. For both exposure groups, comparison of pooled data between sites showed no significant differences in levels of DXM, DXT or RRDXT/RRDXM. Different decomposition microclimates did not impede the discrimination of DXM exposure patterns from the analyses of DXM, DXT and RRDXT/RRDXM in bone samples. © The Author 2017

  14. Enhanced phosphorylation of cyclic AMP response element binding protein in Brain of mice following repetitive hypoxic exposure

    International Nuclear Information System (INIS)

    Gao Yanan; Gao Ge; Long Caixia; Han Song; Zu Pengyu; Fang Li; Li Junfa

    2006-01-01

    Cerebral ischemic/hypoxic preconditioning (I/HPC) is a phenomenon of endogenous protection that renders Brain tolerant to sustained ischemia/hypoxia. This profound protection induced by I/HPC makes it an attractive target for developing potential clinical therapeutic approaches. However, the molecular mechanism of I/HPC is unclear. Cyclic AMP (cAMP) response element binding protein (CREB), a selective nuclear transcriptional factor, plays a key role in the neuronal functions. Phosphorylation of CREB on Ser-133 may facilitate its transcriptional activity in response to various stresses. In the current study, we observed the changes in CREB phosphorylation (Ser-133) and protein expression in Brain of auto-hypoxia-induced HPC mice by using Western blot analysis. We found that the levels of phosphorylated CREB (Ser-133), but not protein expression of CREB, increased significantly (p < 0.05) in the hippocampus and the frontal cortex of mice after repetitive hypoxic exposure (H2-H4, n = 6 for each group), when compared to that of the normoxic (H0, n = 6) or hypoxic exposure once group (H1, n = 6). In addition, a significant enhancement (p < 0.05) of CREB phosphorylation (Ser-133) could also be found in the nuclear extracts from the whole hippocampus of hypoxic preconditioned mice (H2-H4, n = 6 for each group). These results suggest that the phosphorylation of CREB might be involved in the development of cerebral hypoxic preconditioning

  15. Adolescent Initiation of Drug Use: Effects of Prenatal Cocaine Exposure

    Science.gov (United States)

    Richardson, Gale A.; Larkby, Cynthia; Goldschmidt, Lidush; Day, Nancy L.

    2013-01-01

    Objective: To investigate the direct effects of prenatal cocaine exposure (PCE) on adolescent drug use, while controlling for other predictors of adolescent use. Method: Data are from a longitudinal study of PCE in which women and their offspring were assessed throughout childhood. Adolescents were interviewed at 15 years about their age at…

  16. Risk of shoulder tendinitis in relation to shoulder loads in monotonous repetitive work

    DEFF Research Database (Denmark)

    Frost, P.; Bonde, J. P.; Mikkelsen, S.

    2002-01-01

    BACKGROUND: Few studies relate the occurrence of shoulder disorders to quantified ergonomic exposures. This study evaluates the hypothesis that shoulder loads in repetitive work might contribute to the occurrence of shoulder tendinitis. METHODS: This is a cross-sectional study of 1961 workers...

  17. English Language Learners' Nonword Repetition Performance: The Influence of Age, L2 Vocabulary Size, Length of L2 Exposure, and L1 Phonology.

    Science.gov (United States)

    Duncan, Tamara Sorenson; Paradis, Johanne

    2016-02-01

    This study examined individual differences in English language learners' (ELLs) nonword repetition (NWR) accuracy, focusing on the effects of age, English vocabulary size, length of exposure to English, and first-language (L1) phonology. Participants were 75 typically developing ELLs (mean age 5;8 [years;months]) whose exposure to English began on average at age 4;4. Children spoke either a Chinese language or South Asian language as an L1 and were given English standardized tests for NWR and receptive vocabulary. Although the majority of ELLs scored within or above the monolingual normal range (71%), 29% scored below. Mixed logistic regression modeling revealed that a larger English vocabulary, longer English exposure, South Asian L1, and older age all had significant and positive effects on ELLs' NWR accuracy. Error analyses revealed the following L1 effect: onset consonants were produced more accurately than codas overall, but this effect was stronger for the Chinese group whose L1s have a more limited coda inventory compared with English. ELLs' NWR performance is influenced by a number of factors. Consideration of these factors is important in deciding whether monolingual norm referencing is appropriate for ELL children.

  18. Long-term repetition priming with symmetrical polygons and words.

    Science.gov (United States)

    Kersteen-Tucker, Z

    1991-01-01

    In two different tasks, subjects were asked to make lexical decisions (word or nonword) and symmetry judgments (symmetrical or nonsymmetrical) about two-dimensional polygons. In both tasks, every stimulus was repeated at one of four lags (0, 1, 4, or 8 items interposed between the first and second stimulus presentations). This paradigm, known as repetition priming, revealed comparable short-term priming (Lag 0) and long-term priming (Lags 1, 4, and 8) both for symmetrical polygons and for words. A shorter term component (Lags 0 and 1) of priming was observed for nonwords, and only very short-term priming (Lag 0) was observed for nonsymmetrical polygons. These results indicate that response facilitation accruing from repeated exposure can be observed for stimuli that have no preexisting memory representations and suggest that perceptual factors contribute to repetition-priming effects.

  19. Long-term exposure to anticholinergic and sedative drugs and cognitive and physical function in later life

    NARCIS (Netherlands)

    Wouters, H.; Hilmer, S.; Gnjidic, D.; Van Campen, J.; Teichert, M.; Van Der Meer, H.; Schaap, L.; Huisman, M.; Denig, P.; Lamoth, C.; Taxis, K.

    2017-01-01

    Introduction: Anticholinergic and sedative drugs from various therapeutic classes are frequently prescribed to older people. These drugs are known to impair cognitive and physical function in the short-term. However, long-term exposure to these drugs remains less examined. Methods: Data from the

  20. The Correlation of News Exposure About Drugs and the Anxiety Level of Parents Toward the Intensity Communication of Parents and Children About Drugs

    OpenAIRE

    Reonell Rafendi, Mochamad; Herieningsih, MS, Dra. Sri Widowati

    2016-01-01

    Drug abuse in Indonesia has increased from year to year. Not a few reports in the mass media that provide information about drugs. The majority of drug users from among teens. This condition leads to anxiety of parents in their teens in the midst of many drug cases that happened and can happen to anyone. Anxiety can encourage parents to share information to their children about the dangers and effects of drugs. The study aims to determine the correlation of news exposure about drugs and the a...

  1. Psychomotor developmental effects of prenatal exposure to psychotropic drugs: a study in EFEMERIS database.

    Science.gov (United States)

    Hurault-Delarue, Caroline; Damase-Michel, Christine; Finotto, Laurent; Guitard, Claudine; Vayssière, Christophe; Montastruc, Jean-Louis; Montastruc, François; Lacroix, Isabelle

    2016-10-01

    Little is known about neurodevelopment of children exposed to psychotropic drugs during pregnancy. The purpose of this study was to evaluate the effects of prenatal exposure to psychotropic drugs on psychomotor development in children. This observational study used the EFEMERIS database. The database records the drugs prescribed and delivered during pregnancy and the resulting outcomes. Neurodevelopment at nine and 24 months of children born to women exposed to psychotropic drugs (anxiolytics, antidepressants, neuroleptics and anti-epileptics) during the second and/or third trimesters of pregnancy was compared to children who were not exposed to these drugs. Psychomotor development of 493 children (1.5%) exposed to psychotropic drugs during pregnancy was compared to 32 303 unexposed children. Exposure to psychotropic drugs during pregnancy was associated with an increased risk of abnormal motor development at 9 months (OR = 1.3 [1.1-2.2]) and abnormal motor and mental development at 24 months (OR = 4.8 [2.1-11.0] and OR = 2.3 [1.05-4.9]). Increased risk was observed in children born to women exposed to anti-epileptic drugs, neuroleptics or antidepressants during pregnancy. This study found a higher rate of deviation from the normal developmental milestones in children born to women exposed to psychotropic drugs during pregnancy and more particularly antidepressants, neuroleptics and anti-epileptics. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  2. Report on computation of repetitive hyperbaric-hypobaric decompression tables

    Science.gov (United States)

    Edel, P. O.

    1975-01-01

    The tables were constructed specifically for NASA's simulated weightlessness training program; they provide for 8 depth ranges covering depths from 7 to 47 FSW, with exposure times of 15 to 360 minutes. These tables were based up on an 8 compartment model using tissue half-time values of 5 to 360 minutes and Workmanline M-values for control of the decompression obligation resulting from hyperbaric exposures. Supersaturation ratios of 1.55:1 to 2:1 were used for control of ascents to altitude following such repetitive dives. Adequacy of the method and the resultant tables were determined in light of past experience with decompression involving hyperbaric-hypobaric interfaces in human exposures. Using these criteria, the method showed conformity with empirically determined values. In areas where a discrepancy existed, the tables would err in the direction of safety.

  3. Haben repetitive DNA-Sequenzen biologische Funktionen?

    Science.gov (United States)

    John, Maliyakal E.; Knöchel, Walter

    1983-05-01

    By DNA reassociation kinetics it is known that the eucaryotic genome consists of non-repetitive DNA, middle-repetitive DNA and highly repetitive DNA. Whereas the majority of protein-coding genes is located on non-repetitive DNA, repetitive DNA forms a constitutive part of eucaryotic DNA and its amount in most cases equals or even substantially exceeds that of non-repetitive DNA. During the past years a large body of data on repetitive DNA has accumulated and these have prompted speculations ranging from specific roles in the regulation of gene expression to that of a selfish entity with inconsequential functions. The following article summarizes recent findings on structural, transcriptional and evolutionary aspects and, although by no means being proven, some possible biological functions are discussed.

  4. Treatment of Challenging Behavior Exhibited by Children with Prenatal Drug Exposure

    Science.gov (United States)

    Kurtz, Patricia F.; Chin, Michelle D.; Rush, Karena S.; Dixon, Dennis R.

    2008-01-01

    A large body of literature exists describing the harmful effects of prenatal drug exposure on infant and child development. However, there is a paucity of research examining strategies to ameliorate sequelae such as externalizing behavior problems. In the present study, functional analysis procedures were used to assess challenging behavior…

  5. Prenatal drug exposures sensitize noradrenergic circuits to subsequent disruption by chlorpyrifos.

    Science.gov (United States)

    Slotkin, Theodore A; Skavicus, Samantha; Seidler, Frederic J

    2015-12-02

    We examined whether nicotine or dexamethasone, common prenatal drug exposures, sensitize the developing brain to chlorpyrifos. We gave nicotine to pregnant rats throughout gestation at a dose (3mg/kg/day) producing plasma levels typical of smokers; offspring were then given chlorpyrifos on postnatal days 1-4, at a dose (1mg/kg) that produces minimally-detectable inhibition of brain cholinesterase activity. In a parallel study, we administered dexamethasone to pregnant rats on gestational days 17-19 at a standard therapeutic dose (0.2mg/kg) used in the management of preterm labor, followed by postnatal chlorpyrifos. We evaluated cerebellar noradrenergic projections, a known target for each agent, and contrasted the effects with those in the cerebral cortex. Either drug augmented the effect of chlorpyrifos, evidenced by deficits in cerebellar β-adrenergic receptors; the receptor effects were not due to increased systemic toxicity or cholinesterase inhibition, nor to altered chlorpyrifos pharmacokinetics. Further, the deficits were not secondary adaptations to presynaptic hyperinnervation/hyperactivity, as there were significant deficits in presynaptic norepinephrine levels that would serve to augment the functional consequence of receptor deficits. The pretreatments also altered development of cerebrocortical noradrenergic circuits, but with a different overall pattern, reflecting the dissimilar developmental stages of the regions at the time of exposure. However, in each case the net effects represented a change in the developmental trajectory of noradrenergic circuits, rather than simply a continuation of an initial injury. Our results point to the ability of prenatal drug exposure to create a subpopulation with heightened vulnerability to environmental neurotoxicants. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Pharmacokinetics in Drug Discovery: An Exposure-Centred Approach to Optimising and Predicting Drug Efficacy and Safety.

    Science.gov (United States)

    Reichel, Andreas; Lienau, Philip

    2016-01-01

    The role of pharmacokinetics (PK) in drug discovery is to support the optimisation of the absorption, distribution, metabolism and excretion (ADME) properties of lead compounds with the ultimate goal to attain a clinical candidate which achieves a concentration-time profile in the body that is adequate for the desired efficacy and safety profile. A thorough characterisation of the lead compounds aiming at the identification of the inherent PK liabilities also includes an early generation of PK/PD relationships linking in vitro potency and target exposure/engagement with expression of pharmacological activity (mode-of-action) and efficacy in animal studies. The chapter describes an exposure-centred approach to lead generation, lead optimisation and candidate selection and profiling that focuses on a stepwise generation of an understanding between PK/exposure and PD/efficacy relationships by capturing target exposure or surrogates thereof and cellular mode-of-action readouts in vivo. Once robust PK/PD relationship in animal PD models has been constructed, it is translated to anticipate the pharmacologically active plasma concentrations in patients and the human therapeutic dose and dosing schedule which is also based on the prediction of the PK behaviour in human as described herein. The chapter outlines how the level of confidence in the predictions increases with the level of understanding of both the PK and the PK/PD of the new chemical entities (NCE) in relation to the disease hypothesis and the ability to propose safe and efficacious doses and dosing schedules in responsive patient populations. A sound identification of potential drug metabolism and pharmacokinetics (DMPK)-related development risks allows proposing of an effective de-risking strategy for the progression of the project that is able to reduce uncertainties and to increase the probability of success during preclinical and clinical development.

  7. Posttraumatic Stress Symptoms and Nonmedical Prescription Drug Use Among College Students With Trauma Exposure.

    Science.gov (United States)

    Ham, Lindsay S; Wiersma-Mosley, Jacquelyn D; Feldner, Matthew T; Melkonian, Alexander J; Milner, Lauren A; Lewis, Sarah F

    2016-01-01

    Nonmedical prescription drug use, defined as using the drug without a prescription or in ways for which it is not prescribed, and traumatic event exposure are highly prevalent among college students. Despite evidence that posttraumatic stress symptoms could place college students at risk for nonmedical prescription drug problems, no studies have examined this relationship. This study was a preliminary examination of posttraumatic stress symptoms, lifetime nonmedical prescription drug use, hazardous use, and dependence symptoms among college students with trauma exposure. Participants were students attending a rural college in Virginia, recruited through psychology classes, flyers, LISTSERVs, and announcements at student events. All students who reported experiencing at least one traumatic event were included (N = 119); participants' mean age was 19.7 years (SD = 1.90), about half were women (n = 63, 53%), and most were Caucasian (n = 103, 87%). Nearly 60% of participants (n = 71) reported using nonmedical prescription drugs at least once during their lifetime and were more likely than those with no use to report hazardous alcohol use (p drugs. Regression analyses showed that posttraumatic stress symptom frequency was positively associated with hazardous nonmedical prescription drug use, after controlling for gender, depressive symptoms, and hazardous alcohol use (p stress symptom frequency was higher for those with any nonmedical prescription drug dependence symptoms (p drug use. Findings suggest that consideration of the types of behaviors and problems a college student is experiencing related to nonmedical prescription drug use may be more relevant to posttraumatic stress symptom frequency than dichotomous measures of nonmedical prescription drug use alone. Further, the association between the frequency of posttraumatic stress symptoms and both hazardous nonmedical prescription drug use and dependence symptoms among college students with a trauma history

  8. Repetition and lag effects in movement recognition.

    Science.gov (United States)

    Hall, C R; Buckolz, E

    1982-03-01

    Whether repetition and lag improve the recognition of movement patterns was investigated. Recognition memory was tested for one repetition, two-repetitions massed, and two-repetitions distributed with movement patterns at lags of 3, 5, 7, and 13. Recognition performance was examined both immediately afterwards and following a 48 hour delay. Both repetition and lag effects failed to be demonstrated, providing some support for the claim that memory is unaffected by repetition at a constant level of processing (Craik & Lockhart, 1972). There was, as expected, a significant decrease in recognition memory following the retention interval, but this appeared unrelated to repetition or lag.

  9. Prediction of the Maximum Number of Repetitions and Repetitions in Reserve From Barbell Velocity.

    Science.gov (United States)

    García-Ramos, Amador; Torrejón, Alejandro; Feriche, Belén; Morales-Artacho, Antonio J; Pérez-Castilla, Alejandro; Padial, Paulino; Haff, Guy Gregory

    2018-03-01

    To provide 2 general equations to estimate the maximum possible number of repetitions (XRM) from the mean velocity (MV) of the barbell and the MV associated with a given number of repetitions in reserve, as well as to determine the between-sessions reliability of the MV associated with each XRM. After determination of the bench-press 1-repetition maximum (1RM; 1.15 ± 0.21 kg/kg body mass), 21 men (age 23.0 ± 2.7 y, body mass 72.7 ± 8.3 kg, body height 1.77 ± 0.07 m) completed 4 sets of as many repetitions as possible against relative loads of 60%1RM, 70%1RM, 80%1RM, and 90%1RM over 2 separate sessions. The different loads were tested in a randomized order with 10 min of rest between them. All repetitions were performed at the maximum intended velocity. Both the general equation to predict the XRM from the fastest MV of the set (CV = 15.8-18.5%) and the general equation to predict MV associated with a given number of repetitions in reserve (CV = 14.6-28.8%) failed to provide data with acceptable between-subjects variability. However, a strong relationship (median r 2  = .984) and acceptable reliability (CV  .85) were observed between the fastest MV of the set and the XRM when considering individual data. These results indicate that generalized group equations are not acceptable methods for estimating the XRM-MV relationship or the number of repetitions in reserve. When attempting to estimate the XRM-MV relationship, one must use individualized relationships to objectively estimate the exact number of repetitions that can be performed in a training set.

  10. Parent-child drug communication: pathway from parents' ad exposure to youth's marijuana use intention.

    Science.gov (United States)

    Huansuriya, Thipnapa; Siegel, Jason T; Crano, William D

    2014-01-01

    The authors combined the 2-step flow of communication model and the theory of planned behavior to create a framework to evaluate the effectiveness of a set of advertisements from the National Youth Anti-Drug Media Campaign promoting parent-child drug communication. The sample consisted of 1,349 pairs of parents and children who responded to the first and second annual rounds of the National Survey of Parents and Youth, and 1,276 pairs from Rounds 3 and 4. Parents' exposure to the campaign reported at Round 1 was indirectly associated with youth's lowered intentions to use marijuana at Round 2. Ad exposure was associated with positive changes in parental attitudes toward drug communication and perceived social approval of antidrug communications. These two beliefs, along with perceived behavioral control, predicted parents' intentions to discuss drugs with their children. Parental intentions to discuss drugs reported at Round 1 were associated with youth's report of actual drug communication with their parents at Round 2. Frequency and breadth of the topics in parent-child drug communication were associated with less positive attitudes toward marijuana use among youth who spoke with their parents. Together, the child's attitudes toward marijuana use and perceived ability to refuse marijuana use predicted youth's intentions to use marijuana. The proposed model fit well with the data and was replicated in a parallel analysis of the data from Rounds 3 and 4. Implications for future antidrug media campaign efforts are discussed.

  11. Repetitive on-demand drug release from polymeric matrices containing a macroscopic spherical iron core.

    Science.gov (United States)

    Rovers, Stefan A; Kemmere, Maartje F; Keurentjes, Jos T F; Hoogenboom, Richard

    2017-09-15

    A system for multiple on-demand drug release has been prepared that can be activated with an alternating magnetic field as external trigger. The core/shell samples have been developed based on a macroscopic spherical iron core coated with a thermoresponsive polymer, poly(styrene-stat-butyl methacrylate), containing ibuprofen as a model drug. During exposure of the samples to the magnetic field (ON state), the release rate of ibuprofen is significantly increased, up to 35 times the release rate without the magnetic field (OFF state). Using one sample or two samples in line with the magnetic field does not influence the ON/OFF ratio of the system, showing the possibility of using multiple samples to increase and tune the drug dose. Increasing the concentration of ibuprofen in the polymer layer is shown to increase the release rate in both the ON and OFF states. Increasing the size of the iron core and, consequently, decreasing the polymer thickness, was found to only increase the release rate during exposure resulting in higher ON/OFF ratios. The developed on demand drug delivery systems represents a promising development towards on demand drug delivery implants. During my chemical engineering studies, it was only during my master thesis work that I decided to continue with PhD research as I really enjoyed doing original research. When coming to the end of my PhD research under supervision of Prof. Ulrich S. Schubert, I developed the ambition to pursue an academic career. Fortunately, I got the opportunity to stay with Prof. Schubert as project leader for the Dutch Polymer Institute (DPI). Within this position, I supervised ten researchers and was able to start developing my independent research lines. Despite that I now advise students to not stay in the same laboratory, this first position allowed me to gain some initial independence and to publish a large number of papers that has been a great benefit in my further career. After two and a half years I needed a new

  12. If you negate, you may forget: negated repetitions impair memory compared with affirmative repetitions.

    Science.gov (United States)

    Mayo, Ruth; Schul, Yaacov; Rosenthal, Meytal

    2014-08-01

    One of the most robust laws of memory is that repeated activation improves memory. Our study shows that the nature of repetition matters. Specifically, although both negated repetition and affirmative repetition improve memory compared with no repetition, negated repetition hinders memory compared with affirmative repetition. After showing participants different entities, we asked them about features of these entities, leading to either "yes" or "no" responses. Our findings show that correctly negating an incorrect feature of an entity elicits an active forgetting effect compared with correctly affirming its true features. For example, after seeing someone drink a glass of white wine, answering "no" to "was it red wine?" may lead one to greater memory loss of the individual drinking wine at all compared with answering "yes" to "was it white wine?" We find this negation-induced forgetting effect in 4 experiments that differ in (a) the meaning given for the negation, (b) the type of stimuli (visual or verbal), and (c) the memory measure (recognition or free recall). We discuss possible underlying mechanisms and offer theoretical and applied implications of the negation-induced forgetting effect in relation to other known inhibition effects. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  13. Historical cohort study of in utero exposure to uterotonic drugs and cognitive function in young adult life

    DEFF Research Database (Denmark)

    Sørensen, Henrik Toft; Steffensen, Flemming Hald; Sabroe, Svend

    1999-01-01

    Objective To examine whether in utero exposure to uterotonic drugs effects cognitive performance in draft-age men. Design Historical cohort study based on birth registry data and cognitive function measured during evaluations for military service. Subjects 4300 Danish conscripts born between 1973...... and those not exposed (n=3289), 43.1 versus 42.9 after adjustment for confounders. Conclusion Our data indicate that exposure to uterotonic drugs does not affect cognitive function 20 years later....

  14. Molecular and cellular determinants of the cyto-toxicity in combined ionizing radiations and anti-tumoral drugs exposure

    International Nuclear Information System (INIS)

    Hennequin, Ch.

    1998-01-01

    The radio-chemo-therapy combinations represent a major research way in oncology. The knowledge of the interaction mechanisms can contribute to an improvement of the clinical protocols and to a knowledge of the action processes of drugs and radiations. Three different drugs have been studied - etoposide, camptothecine and taxoids (paclitaxel, docetaxel) - on different in vitro cell descendants (V79, HeLa and SQ-20B). For etoposide, the isobolic analysis shows an additive interaction in slightly deferred exposure but a strong supra-additive interaction in concomitant exposure. A sensitization to the drug effect inside the radio-induced G2 block is also noticed. The supra-additivity in concomitant exposure is linked with the alteration of the sub-lethal lesions repair. For camptothecine, the analysis of survival curves shows a strictly additive interaction (mode II) in concomitant exposure. However, the association becomes additive at low radiation dose rates (1 Gy/h). This synergy is the result of a cyto-kinetic effect corresponding to the radio-induced accumulation of cells inside the most drug sensible compartment. With taxoids, it is shown that all kinds of interactions are possible, from a pronounced antagonism to a significant synergy. The effect depends on drugs and radiation doses and on the cells descendants. Paclitaxel and docetaxel present major differences of phase specificity: the first one targets the mitosis transition, while the second one targets the S phase. These results have permitted to precise some of the mechanisms involved in drugs and radiations synergy. In particular, it is shown that two major mechanisms, the cyto-kinetic cooperation and the alteration of DNA lesions repair, determine the effect of combined treatments on proliferating cells. (J.S.)

  15. Association between change of health care providers and pregnancy exposure to FDA category C, D and X drugs.

    Science.gov (United States)

    Yang, Jianzhou; Xie, Rihua; Krewski, Daniel; Wang, Yongjin; Walker, Mark; Cao, Wenjun; Wen, Shi Wu

    2014-01-01

    Changing health care providers frequently breaks the continuity of care, which is associated with many health care problems. The purpose of this study was to examine the association between a change of health care providers and pregnancy exposure to FDA category C, D and X drugs. A 50% random sample of women who gave a birth in Saskatchewan between January 1, 1997 and December 31, 2000 were chosen for this study. The association between the number of changes in health care providers and with pregnancy exposure to category C, D, and X drugs for those women with and without chronic diseases were evaluated using multiple logistical regression, with adjusted odds ratios (ORs) and its 95% confidence intervals (CIs) as the association measures. A total of 18 568 women were included in this study. Rates of FDA C, D, and X drug uses were 14.35%, 17.07%, 21.72%, and 31.14%, in women with no change of provider, 1-2 changes, 3-5 changes, and more than 5 changes of health care providers. An association between the number of changes of health care providers and pregnancy exposure to FDA C, D, and X drugs existed in women without chronic diseases but not in women with chronic disease. Change of health care providers is associated with pregnancy exposure to FDA category C, D and X drugs in women without chronic diseases.

  16. Penetration and delivery characteristics of repetitive microjet injection into the skin.

    Science.gov (United States)

    Römgens, Anne M; Rem-Bronneberg, Debbie; Kassies, Roel; Hijlkema, Markus; Bader, Dan L; Oomens, Cees W J; van Bruggen, Michel P B

    2016-07-28

    Drugs can be delivered transdermally using jet injectors, which can be an advantageous route compared to oral administration. However, these devices inject large volumes deep into the skin or tissues underneath the skin often causing bruising and pain. This may be prevented by injecting smaller volumes at lower depth in a repetitive way using a microjet injection device. Such a device could be used to apply drugs in a controllable and sustainable manner. However, the efficacy of microjet injection has been rarely examined. In this study, the penetration and delivery capacity was examined of a repetitive microjet injection device. Various experiments were performed on epidermal and full-thickness ex vivo human as well as ex vivo porcine skin samples. Results revealed that microjets with a velocity exceeding 90m/s penetrated an epidermal skin sample with a delivery efficiency of approximately 96%. In full-thickness human skin, the delivery efficiency drastically decreased to a value of approximately 12%. Experiments on full-thickness skin revealed that the microjets penetrated to a depth corresponding to the transition between the papillary and reticular dermis. This depth did not further increase with increasing number of microjets. In vivo studies on rats indicated that intact insulin was absorbed into the systemic circulation. Hence, the microjet injection device was able to deliver medication into the skin, although the drug delivery efficiency should be increased. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Repetitive Questioning Exasperates Caregivers

    Directory of Open Access Journals (Sweden)

    R. C. Hamdy MD

    2018-01-01

    Full Text Available Repetitive questioning is due to an impaired episodic memory and is a frequent, often presenting, problem in patients with Alzheimer’s disease (amnestic type. It is due to the patients’ difficulties learning new information, retaining it, and recalling it, and is often aggravated by a poor attention span and easy distractibility. A number of factors may trigger and maintain repetitive questioning. Caregivers should try to identify and address these triggers. In the case discussion presented, it is due to the patient’s concerns about her and her family’s safety triggered by watching a particularly violent movie aired on TV. What went wrong in the patient/caregiver interaction and how it could have been avoided or averted are explored. Also reviewed are the impact of repetitive questioning, the challenges it raises for caregivers, and some effective intervention strategies that may be useful to diffuse the angst that caregivers experience with repetitive questioning.

  18. Exposure to reactive intermediate-inducing drugs during pregnancy and the incident use of psychotropic medications among children.

    Science.gov (United States)

    Tran, Yen-Hao; Groen, Henk; Bergman, Jorieke E H; Hak, Eelko; Wilffert, Bob

    2017-03-01

    Our study aimed to investigate the association between prenatal exposure to reactive intermediate (RI)-inducing drugs and the initiation of psychotropic medications among children. We designed a cohort study using a pharmacy prescription database. Pregnant women were considered exposed when they received a prescription of RI-inducing drugs. These drugs could be either used alone (RI+/FAA-) or combined with drugs exhibiting folic acid antagonism (FAA, RI+/FAA+). The reference group included pregnant women who did not receive any RI-inducing drugs or FAA drugs. We analyzed 4116 exposed and 30 422 reference pregnancies. The hazard ratio (HR) with 95% confidence interval (CI) was 1.27 (95%CI 1.15-1.41) for pregnancies exposed to RI-inducing drugs as a whole. Considering subgroups of RI-inducing drugs, prenatal exposure to both RI+/FAA+ and RI+/FAA- was associated with the children's initiation of psychotropic medications, HRs being 1.35 (95%CI 1.10-1.66) and 1.26 (1.13-1.41), respectively. The HRs were increased with prolonged exposure to RI-inducing drugs, especially in the first and second trimesters. In a detailed examination of the psychotropics, the incidences of receiving antimigraine preparations and psychostimulants were significantly increased for the exposed children, compared with the reference children. The incidences of receiving antipsychotics and hypnotics were also higher for the exposed children; however, the HRs did not reach significance after adjustment. We found a significantly increased incident use of psychotropic medications among children prenatally exposed to RI-inducing drugs, especially during the first and second trimesters. This suggests a detrimental effect during critical periods of brain development. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  19. The risk of musculoskeletal disorders due to repetitive movements of upper limbs for workers employed in hazelnut sorting

    Directory of Open Access Journals (Sweden)

    Andrea Colantoni

    2013-09-01

    Full Text Available In the agro-industrial sector there are many activities whose urgent rhythms can cause a considerable exposure to bio-mechanical risk factors. In the hazelnut sorting, the workers are subject to several biomechanical risks, with repetitive movements, and operations that require a remarkable degree of strength. A thorough study of the workers’ exposure to repetitive manual movements has been carried out, with the aim of setting up the necessary measures to reduce the risk factors. The aim of the research is to assess the risk of work-related musculo-skeletal disorders (WMSDs due to repetitive work, for workers employed to hazelnut shells sorting. The research was carried out in an agricultural cooperative in the Viterbo’s area. For risk assessment authors used a method (Occupational Repetitive Actions “OCRA” index according to ISO 11228- 3:2009, Ergonomics - Manual handling - Part 3: Handling of low loads at high frequency which keeps into consideration several risk factors (such as repetitiveness, prehension force, posture. The risk was assessed for 16 female workers (in eight workplaces and in two different shifts through this classification: workers with experience less than 1 year, from 1 to 10 years and more than 10 years. This classification is very important for knowing if the professional experience could be considered a “prevention measure” for the risk reduction. The results show a high risk level for the right and left limb. The factors which more have contributed to reach such risk level are the great number of movements and the lack of recovering time.

  20. Developmental Neurotoxicity of Alcohol and Anesthetic Drugs Is Augmented by Co-Exposure to Caffeine

    Directory of Open Access Journals (Sweden)

    Catherine E. Creeley

    2013-07-01

    Full Text Available Anesthetic and anti-epileptic drugs used in pediatric and obstetric medicine and several drugs, including alcohol, that are abused by pregnant women, trigger widespread neuroapoptosis in the developing brain of several animal species, including non-human primates. Caffeine (CAF is often administered to premature infants to stimulate respiration, and these infants are also exposed simultaneously to anesthetic drugs for procedural sedation and/or surgical procedures. Pregnant women who abuse alcohol or other apoptogenic drugs also may heavily consume CAF. We administered CAF to infant mice alone or in combination with alcohol, phencyclidine, diazepam, midazolam, ketamine, or isoflurane, which are drugs of abuse and/or drugs frequently used in pediatric medicine, and found that CAF weakly triggers neuroapoptosis by itself and markedly potentiates the neuroapoptogenic action of each of these other drugs. Exposure of infant mice to CAF + phencyclidine resulted in long-term impairment in behavioral domains relevant to attention deficit/hyperactivity disorder, whereas exposure to CAF + diazepam resulted in long-term learning/memory impairment. At doses used in these experiments, these behavioral impairments either did not occur or were substantially less pronounced in mice exposed to CAF alone or to phencyclidine or diazepam alone. CAF currently enjoys the reputation of being highly beneficial and safe for use in neonatal medicine. Our data suggest the need to consider whether CAF may have harmful as well as beneficial effects on the developing brain, and the need for research aimed at understanding the full advantage of its beneficial effects while avoiding its potentially harmful effects.

  1. Analysis of individual drug use as a time-varying determinant of exposure in prospective population-based cohort studies

    NARCIS (Netherlands)

    B.H.Ch. Stricker (Bruno); Th. Stijnen (Theo)

    2010-01-01

    textabstractIn pharmaco-epidemiology, the use of drugs is the determinant of interest when studying exposure-outcome associations. The increased availability of computerized information about drug use on an individual basis has greatly facilitated analyses of drug effects on a population-based

  2. Computer-Related Repetitive Stress Injuries

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Computer-Related Repetitive Stress Injuries KidsHealth / For Parents / Computer-Related Repetitive Stress Injuries What's in this article? ...

  3. The role of short-term memory impairment in nonword repetition, real word repetition, and nonword decoding: A case study.

    Science.gov (United States)

    Peter, Beate

    2018-01-01

    In a companion study, adults with dyslexia and adults with a probable history of childhood apraxia of speech showed evidence of difficulty with processing sequential information during nonword repetition, multisyllabic real word repetition and nonword decoding. Results suggested that some errors arose in visual encoding during nonword reading, all levels of processing but especially short-term memory storage/retrieval during nonword repetition, and motor planning and programming during complex real word repetition. To further investigate the role of short-term memory, a participant with short-term memory impairment (MI) was recruited. MI was confirmed with poor performance during a sentence repetition and three nonword repetition tasks, all of which have a high short-term memory load, whereas typical performance was observed during tests of reading, spelling, and static verbal knowledge, all with low short-term memory loads. Experimental results show error-free performance during multisyllabic real word repetition but high counts of sequence errors, especially migrations and assimilations, during nonword repetition, supporting short-term memory as a locus of sequential processing deficit during nonword repetition. Results are also consistent with the hypothesis that during complex real word repetition, short-term memory is bypassed as the word is recognized and retrieved from long-term memory prior to producing the word.

  4. Repetitive low-frequency stimulation reduces epileptiform synchronization in limbic neuronal networks.

    Science.gov (United States)

    D'Arcangelo, G; Panuccio, G; Tancredi, V; Avoli, M

    2005-01-01

    Deep-brain electrical or transcranial magnetic stimulation may represent a therapeutic tool for controlling seizures in patients presenting with epileptic disorders resistant to antiepileptic drugs. In keeping with this clinical evidence, we have reported that repetitive electrical stimuli delivered at approximately 1 Hz in mouse hippocampus-entorhinal cortex (EC) slices depress the EC ability to generate ictal activity induced by the application of 4-aminopyridine (4AP) or Mg(2+)-free medium (Barbarosie, M., Avoli, M., 1997. CA3-driven hippocampal-entorhinal loop controls rather than sustains in vitro limbic seizures. J. Neurosci. 17, 9308-9314.). Here, we confirmed a similar control mechanism in rat brain slices analyzed with field potential recordings during 4AP (50 microM) treatment. In addition, we used intrinsic optical signal (IOS) recordings to quantify the intensity and spatial characteristics of this inhibitory influence. IOSs reflect the changes in light transmittance throughout the entire extent of the slice, and are thus reliable markers of limbic network epileptiform synchronization. First, we found that in the presence of 4AP, the IOS increases, induced by a train of electrical stimuli (10 Hz for 1 s) or by recurrent, single-shock stimulation delivered at 0.05 Hz in the deep EC layers, are reduced in intensity and area size by low-frequency (1 Hz), repetitive stimulation of the subiculum; these effects were observed in all limbic areas contained in the slice. Second, by testing the effects induced by repetitive subicular stimulation at 0.2-10 Hz, we identified maximal efficacy when repetitive stimuli are delivered at 1 Hz. Finally, we discovered that similar, but slightly less pronounced, inhibitory effects occur when repetitive stimuli at 1 Hz are delivered in the EC, suggesting that the reduction of IOSs seen during repetitive stimulation is pathway dependent as well as activity dependent. Thus, the activation of limbic networks at low frequency

  5. Trauma exposure and heavy drinking and drug use among college students: Identifying the roles of negative and positive affect lability in a daily diary study.

    Science.gov (United States)

    Weiss, Nicole H; Bold, Krysten W; Contractor, Ateka A; Sullivan, Tami P; Armeli, Stephen; Tennen, Howard

    2018-04-01

    Trauma exposure is linked to heavy drinking and drug use among college students. Extant research reveals positive associations between negative affect lability and both trauma exposure and alcohol use. This study aimed to extend past research by using daily diary methods to test whether (a) individuals with (versus without) trauma exposure experience greater negative and positive affect lability, (b) negative and positive affect lability are associated with heavy drinking and drug use, and (c) negative and positive affect lability mediate the relations between trauma exposure and heavy drinking and drug use. Participants were 1640 college students (M age=19.2, 54% female, 80% European American) who provided daily diary data for 30days via online surveys. Daily diaries assessed negative and positive affect and substance use (i.e., percent days of heavy drinking, percent days of drug use, total number of drugs used). Individuals with (versus without) a history of trauma exposure demonstrated higher levels of negative and positive affect lability. Negative, but not positive, affect lability was associated with percent days of heavy drinking, percent days of drug use, and total number of drugs used, and mediated the associations between trauma exposure and heavy drinking and drug use outcomes. Findings provide support for the underlying role of negative affect lability in the relations between trauma exposure and heavy drinking and drug use among college students, suggesting that treatments targeting negative affect lability may potentially serve to reduce heavy drinking and drug use among trauma-exposed college students. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Media Exposure and Tobacco, Illicit Drugs, and Alcohol Use among Children and Adolescents: A Systematic Review

    Science.gov (United States)

    Nunez-Smith, Marcella; Wolf, Elizabeth; Huang, Helen Mikiko; Chen, Peggy G.; Lee, Lana; Emanuel, Ezekiel J.; Gross, Cary P.

    2010-01-01

    The authors systematically reviewed 42 quantitative studies on the relationship between media exposure and tobacco, illicit drug, and alcohol use among children and adolescents. Overall, 83% of studies reported that media was associated with increased risk of smoking initiation, use of illicit drugs, and alcohol consumption. Of 30 studies…

  7. Identification of antimycotic drugs transformation products upon UV exposure

    Energy Technology Data Exchange (ETDEWEB)

    Casado, Jorge; Rodríguez, Isaac, E-mail: isaac.rodriguez@usc.es; Ramil, María; Cela, Rafael

    2015-05-30

    Highlights: • Evaluation of antimycotic drugs UV stabilities in model supports. • Simultaneous detection of precursor drugs and transformation products. • Transformation products identification from their scan, accurate MS/MS spectra. • Directed search of identified transformation products in sand and soil samples. • Preliminary toxicity estimations. - Abstract: The reactivity of three imidazolic, environmental persistent antimycotic drugs (clotrimazole, CTZ; ketoconazole, KTZ; and miconazole, MCZ) upon exposure to ultraviolet (UV) radiation is discussed. First, precursor compounds were immobilized in a silicone support which was further exposed to UV light at two different wavelengths: 254 and 365 nm. After solvent desorption, degradation kinetics of the precursor pharmaceuticals, identification of the arising transformation products (TPs) and evaluation of their time-course were investigated by liquid chromatography (LC) with quadrupole time-of-flight (QTOF) mass spectrometry (MS) detection. The three antimycotics displayed similar stabilities when exposed to 254 nm light; however, CTZ was significantly more stable than MCZ and KTZ when irradiated with the 365 nm lamp. TPs identified in silicone supports resulted from de-chlorination, cleavage, intra-molecular cyclization and hydroxylation reactions. Many of these species were also detected when exposing other solid matrices, such as sand and agricultural soil, previously spiked with target compounds, to UV light. The 50% estimated lethal concentration, calculated using the 48-h Daphnia magna test, for the two main TPs of CTZ and MCZ, at both wavelengths, were lower than those corresponding to the precursor drugs.

  8. Identification of antimycotic drugs transformation products upon UV exposure

    International Nuclear Information System (INIS)

    Casado, Jorge; Rodríguez, Isaac; Ramil, María; Cela, Rafael

    2015-01-01

    Highlights: • Evaluation of antimycotic drugs UV stabilities in model supports. • Simultaneous detection of precursor drugs and transformation products. • Transformation products identification from their scan, accurate MS/MS spectra. • Directed search of identified transformation products in sand and soil samples. • Preliminary toxicity estimations. - Abstract: The reactivity of three imidazolic, environmental persistent antimycotic drugs (clotrimazole, CTZ; ketoconazole, KTZ; and miconazole, MCZ) upon exposure to ultraviolet (UV) radiation is discussed. First, precursor compounds were immobilized in a silicone support which was further exposed to UV light at two different wavelengths: 254 and 365 nm. After solvent desorption, degradation kinetics of the precursor pharmaceuticals, identification of the arising transformation products (TPs) and evaluation of their time-course were investigated by liquid chromatography (LC) with quadrupole time-of-flight (QTOF) mass spectrometry (MS) detection. The three antimycotics displayed similar stabilities when exposed to 254 nm light; however, CTZ was significantly more stable than MCZ and KTZ when irradiated with the 365 nm lamp. TPs identified in silicone supports resulted from de-chlorination, cleavage, intra-molecular cyclization and hydroxylation reactions. Many of these species were also detected when exposing other solid matrices, such as sand and agricultural soil, previously spiked with target compounds, to UV light. The 50% estimated lethal concentration, calculated using the 48-h Daphnia magna test, for the two main TPs of CTZ and MCZ, at both wavelengths, were lower than those corresponding to the precursor drugs

  9. Illicit drug exposure in patients evaluated for alleged child abuse and neglect.

    Science.gov (United States)

    Oral, Resmiye; Bayman, Levent; Assad, Abraham; Wibbenmeyer, Lucy; Buhrow, Jakob; Austin, Andrea; Bayman, Emine O

    2011-06-01

    Substantiation of drug exposure in cases with alleged maltreatment is important to provide proper treatment and services to these children and their families. A study performed at University of Iowa Hospitals and Clinics showed that 30% of pediatric patients with burn injuries, which were due to child maltreatment, were also exposed to illicit drugs. The children presenting to the University of Iowa Hospitals and Clinics with alleged maltreatment have been tested for illicit substances since 2004. The objective of this study was to analyze the presence of illicit drug exposure in the pediatric subpopulation admitted to pediatric inpatient and outpatient units for an evaluation for abuse/neglect. The study design is a retrospective chart review. Using hospital databases, every pediatric chart with a child abuse/neglect allegation was retrieved. The association between risk factors and clinical presentation and illicit drug test result was assessed. Excel and SAS were used for statistical analysis. Institutional review board approval was obtained to conduct this study. Six hundred sixty-five charts met study inclusion criteria for child abuse/neglect allegation. Of those, 232 cases were tested for illicit drugs between 2004 and 2008 per the testing protocol. Thirty-four cases (14.7%) tested positive on a drug test. Positive test rates based on clinical presentation were 28.6% (18/63) in neglect cases, 16.1% (5/31) in cases with soft tissue injuries, 14.3% (4/28) in burn injuries, 10.0% (2/20) in cases with sexual abuse, 7.1% (2/28) in cases with fractures, and 4.8% (3/62) in abusive head trauma cases. There were long-term abuse findings in 129 children (55.6%). Logistic regression analysis revealed that positive drug testing was most significantly associated with clinical symptoms suggesting physical abuse or neglect versus sexual abuse (odds ratio [OR] = 6.70; 95% confidence interval [CI], 1.26-35.49; P = 0.026), no or public health insurance versus those with

  10. Risk factors for repetition of self-harm: a systematic review of prospective hospital-based studies.

    Directory of Open Access Journals (Sweden)

    Celine Larkin

    Full Text Available BACKGROUND: Self-harm entails high costs to individuals and society in terms of suicide risk, morbidity and healthcare expenditure. Repetition of self-harm confers yet higher risk of suicide and risk assessment of self-harm patients forms a key component of the health care management of self-harm patients. To date, there has been no systematic review published which synthesises the extensive evidence on risk factors for repetition. OBJECTIVE: This review is intended to identify risk factors for prospective repetition of self-harm after an index self-harm presentation, irrespective of suicidal intent. DATA SOURCES: PubMed, PsychInfo and Scirus were used to search for relevant publications. We included cohort studies which examining factors associated with prospective repetition among those presenting with self-harm to emergency departments. Journal articles, abstracts, letters and theses in any language published up to June 2012 were considered. Studies were quality-assessed and synthesised in narrative form. RESULTS: A total of 129 studies, including 329,001 participants, met our inclusion criteria. Some factors were studied extensively and were found to have a consistent association with repetition. These included previous self-harm, personality disorder, hopelessness, history of psychiatric treatment, schizophrenia, alcohol abuse/dependence, drug abuse/dependence, and living alone. However, the sensitivity values of these measures varied greatly across studies. Psychological risk factors and protective factors have been relatively under-researched but show emerging associations with repetition. Composite risk scales tended to have high sensitivity but poor specificity. CONCLUSIONS: Many risk factors for repetition of self-harm match risk factors for initiation of self-harm, but the most consistent evidence for increased risk of repetition comes from long-standing psychosocial vulnerabilities, rather than characteristics of an index episode

  11. Enzyme induction in neonates after fetal exposure to antiepileptic drugs

    International Nuclear Information System (INIS)

    Rating, D.; Jaeger-Roman, E.; Nau, H.; Kuhnz, W.; Helge, H.

    1983-01-01

    The 13 C-AP breath test is shown to be a convenient, noninvasive method to monitor velocity and capacity of P450-dependent AP N-demethylation in infancy and childhood. According to 13 C-AP breath tests, neonates have a very low capacity to eliminate 13 CO 2 , which is only 15 to 21% of the activity in adults. During the first year of life AP N-demethylation increases to reach its maximum at about 2 years; afterwards a slight decrease occurs. In 25 neonates exposed prenatally to different antiepileptic drugs 13 C-AP breath test was efficiently used to prove that cytochrome AP N-demethylation was considerably stimulated. After primidone/phenobarbitone, especially in combination with phenytoin, 13 C elimination reaches and even surpasses the range for older children. Valproate exposure during fetal life is not consistently followed by a significant increase in AP N-demethylation. The enzyme induction demonstrated by 13 C-AP breath test was often accompanied by accelerated metabolic clearance and shortened half-life times of transplacentally acquired antiepileptic drugs. There was good agreement between 13 C-AP breath tests and pharmacokinetic data for primidone/phenobarbitone but not for phenytoin. In contrast, in the case of phenytoin exposure during pregnancy the pharmacokinetic parameters and the 13 C breath test data will transport very different informations about enzyme induction in these neonates

  12. Pharmacotherapy in pregnancy; effect of ABC and SLC transporters on drug transport across the placenta and fetal drug exposure.

    Science.gov (United States)

    Staud, Frantisek; Cerveny, Lukas; Ceckova, Martina

    2012-11-01

    Pharmacotherapy during pregnancy is often inevitable for medical treatment of the mother, the fetus or both. The knowledge of drug transport across placenta is, therefore, an important topic to bear in mind when deciding treatment in pregnant women. Several drug transporters of the ABC and SLC families have been discovered in the placenta, such as P-glycoprotein, breast cancer resistance protein, or organic anion/cation transporters. It is thus evident that the passage of drugs across the placenta can no longer be predicted simply on the basis of their physical-chemical properties. Functional expression of placental drug transporters in the trophoblast and the possibility of drug-drug interactions must be considered to optimize pharmacotherapy during pregnancy. In this review we summarize current knowledge on the expression and function of ABC and SLC transporters in the trophoblast. Furthermore, we put this data into context with medical conditions that require maternal and/or fetal treatment during pregnancy, such as gestational diabetes, HIV infection, fetal arrhythmias and epilepsy. Proper understanding of the role of placental transporters should be of great interest not only to clinicians but also to pharmaceutical industry for future drug design and development to control the degree of fetal exposure.

  13. Assessment of Industrial Exposure to Magnetic Fields (invited paper)

    International Nuclear Information System (INIS)

    Chadwick, P.

    1999-01-01

    Magnetic field strengths produced by industrial processes can be very large, but they often exhibit a marked spatial variation. Whilst there may be the potential for exposures of workers to be high, actual exposure will be determined to a great extent by working practices. Possible metrics for epidemiological studies might be based on the temporal variability of exposure as well as maximum operator exposure or time-weighted average exposure and, whilst it might be possible to estimate these quantities from spot magnetic field strength measurements and observed working practices, this might be very difficult to achieve in practice. An alternative would be the use of a logging dosemeter: this paper describes some of the results of exposure assessments carried out in industrial environments with a modified EMDEX II magnetic field dosemeter. Magnetic fields in industrial environments often have waveforms which are not purely sinusoidal. Distortion can be introduced by the magnetic saturation of transformer and motor cores, by rectification, by poor matching between oscillator circuits and loads and when thyristors are used to control power. The resulting repetitive but non-sinusoidal magnetic field waveforms can be recorded and analysed; the spectral data may be incorporated into possible exposure metrics. It is also important to ensure that measurement instrumentation is responding appropriately in a non-sinusoidal field and this can only be done if the spectral content of the field is characterised fully. Some non-sinusoidal magnetic field waveforms cannot be expressed as a harmonic series. Specialist instrumentation and techniques are needed to assess exposure to such fields. Examples of approaches to the assessment of exposure to repetitive and non-repetitive magnetic fields are also discussed. (author)

  14. Damage threshold from large retinal spot size repetitive-pulse laser exposures.

    Science.gov (United States)

    Lund, Brian J; Lund, David J; Edsall, Peter R

    2014-10-01

    The retinal damage thresholds for large spot size, multiple-pulse exposures to a Q-switched, frequency doubled Nd:YAG laser (532 nm wavelength, 7 ns pulses) have been measured for 100 μm and 500 μm retinal irradiance diameters. The ED50, expressed as energy per pulse, varies only weakly with the number of pulses, n, for these extended spot sizes. The previously reported threshold for a multiple-pulse exposure for a 900 μm retinal spot size also shows the same weak dependence on the number of pulses. The multiple-pulse ED50 for an extended spot-size exposure does not follow the n dependence exhibited by small spot size exposures produced by a collimated beam. Curves derived by using probability-summation models provide a better fit to the data.

  15. Lipid peroxidation, detoxification capacity, and genome damage in mice after transplacental exposure to pharmaceutical drugs

    Directory of Open Access Journals (Sweden)

    D. Markovic

    2013-12-01

    Full Text Available Data on genome damage, lipid peroxidation, and levels of glutathione peroxidase (GPX in newborns after transplacental exposure to xenobiotics are rare and insufficient for risk assessment. The aim of the current study was to analyze, in an animal model, transplacental genotoxicity, lipid peroxidation, and detoxification disturbances caused by the following drugs commonly prescribed to pregnant women: paracetamol, fluconazole, 5-nitrofurantoin, and sodium valproate. Genome damage in dams and their newborn pups transplacentally exposed to these drugs was investigated using the in vivo micronucleus (MN assay. The drugs were administered to dams intraperitoneally in three consecutive daily doses between days 12 and 14 of pregnancy. The results were correlated, with detoxification capacity of the newborn pups measured by the levels of GPX in blood and lipid peroxidation in liver measured by malondialdehyde (HPLC-MDA levels. Sodium valproate and 5-nitrofurantoin significantly increased MN frequency in pregnant dams. A significant increase in the MN frequency of newborn pups was detected for all drugs tested. This paper also provides reference levels of MDA in newborn pups, according to which all drugs tested significantly lowered MDA levels of newborn pups, while blood GPX activity dropped significantly only after exposure to paracetamol. The GPX reduction reflected systemic oxidative stress, which is known to occur with paracetamol treatment. The reduction of MDA in the liver is suggested to be an unspecific metabolic reaction to the drugs that express cytotoxic, in particular hepatotoxic, effects associated with oxidative stress and lipid peroxidation.

  16. Radiation-induced changes in DNA methylation of repetitive elements in the mouse heart

    Energy Technology Data Exchange (ETDEWEB)

    Koturbash, Igor, E-mail: ikoturbash@uams.edu [Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Miousse, Isabelle R. [Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Sridharan, Vijayalakshmi [Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Nzabarushimana, Etienne; Skinner, Charles M. [Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Melnyk, Stepan B.; Pavliv, Oleksandra [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Hauer-Jensen, Martin [Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Surgical Service, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205 (United States); Nelson, Gregory A. [Departments of Basic Sciences and Radiation Medicine, Loma Linda University, Loma Linda, CA 92354 (United States); Boerma, Marjan [Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

    2016-05-15

    Highlights: • Radiation-induced dynamic changes in cardiac DNA methylation were detected. • Early LINE-1 hypomethylation was followed by hypermethylation at a later time-point. • Radiation affected one-carbon metabolism in the heart tissue. • Irradiation resulted in accumulation of satellite DNA mRNA transcripts. - Abstract: DNA methylation is a key epigenetic mechanism, needed for proper control over the expression of genetic information and silencing of repetitive elements. Exposure to ionizing radiation, aside from its strong genotoxic potential, may also affect the methylation of DNA, within the repetitive elements, in particular. In this study, we exposed C57BL/6J male mice to low absorbed mean doses of two types of space radiation—proton (0.1 Gy, 150 MeV, dose rate 0.53 ± 0.08 Gy/min), and heavy iron ions ({sup 56}Fe) (0.5 Gy, 600 MeV/n, dose rate 0.38 ± 0.06 Gy/min). Radiation-induced changes in cardiac DNA methylation associated with repetitive elements were detected. Specifically, modest hypomethylation of retrotransposon LINE-1 was observed at day 7 after irradiation with either protons or {sup 56}Fe. This was followed by LINE-1, and other retrotransposons, ERV2 and SINE B1, as well as major satellite DNA hypermethylation at day 90 after irradiation with {sup 56}Fe. These changes in DNA methylation were accompanied by alterations in the expression of DNA methylation machinery and affected the one-carbon metabolism pathway. Furthermore, loss of transposable elements expression was detected in the cardiac tissue at the 90-day time-point, paralleled by substantial accumulation of mRNA transcripts, associated with major satellites. Given that the one-carbon metabolism pathway can be modulated by dietary modifications, these findings suggest a potential strategy for the mitigation and, possibly, prevention of the negative effects exerted by ionizing radiation on the cardiovascular system. Additionally, we show that the methylation status and

  17. [Alternative biological materials to detect prenatal exposure to drugs of abuse in the third trimester of pregnancy].

    Science.gov (United States)

    García-Serra, J; Ramis, J; Simó, S; Joya, X; Pichini, S; Vall, O; García-Algar, O

    2012-11-01

    Detection of prenatal drug abuse exposure is essential to ensure an appropriate monitoring of affected children. A maternal questionnaire is not an efficient screening tool. The usefulness of maternal hair and meconium as biological materials to assess this exposure has been described in last few years. The aim of this study was to compare both these alternative biological materials for prenatal drug exposure detection in the third trimester of pregnancy, in order to assess its use as a screening tool. Between January and March 2010, samples of maternal hair and meconium from 107 mother-infant dyads were collected in Can Misses Hospital, Ibiza. The presence of opiates, cocaine, cannabis, and amphetamines, was determined in both materials, using standard chromatographic techniques. Maternal hair analysis showed a 15.9% positivity for drugs of abuse (17 cases): 11 cannabis, 7 cocaine, 1 cannabis and ecstasy, and 1 cannabis and cocaine. Only one mother reported cannabis consumption and another one, cocaine. Of the 7 cocaine positive cases in hair, 6 were confirmed in meconium analysis, while of 11 cannabis positive cases, only 3 were confirmed in meconium. Two different consumer profiles were defined: cocaine consumers and cannabis consumers (with only 2 cases of multiple drug use). The highest level of cocaine ever published was detected (1.582ng/g) in one case. This study reveals a high prevalence of drug abuse in this cohort during pregnancy. Improved screening methods may optimize prevention and monitoring of exposed infants. Maternal hair seems to be more sensitive than meconium to detect prenatal exposure to cannabis during the third trimester, so it might become a good screening tool. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  18. Exposure-response model for sibutramine and placebo: suggestion for application to long-term weight-control drug development.

    Science.gov (United States)

    Han, Seunghoon; Jeon, Sangil; Hong, Taegon; Lee, Jongtae; Bae, Soo Hyeon; Park, Wan-su; Park, Gab-jin; Youn, Sunil; Jang, Doo Yeon; Kim, Kyung-Soo; Yim, Dong-Seok

    2015-01-01

    No wholly successful weight-control drugs have been developed to date, despite the tremendous demand. We present an exposure-response model of sibutramine mesylate that can be applied during clinical development of other weight-control drugs. Additionally, we provide a model-based evaluation of sibutramine efficacy. Data from a double-blind, randomized, placebo-controlled, multicenter study were used (N=120). Subjects in the treatment arm were initially given 8.37 mg sibutramine base daily, and those who lost sibutramine, including the placebo effect, were modeled using NONMEM 7.2. An asymptotic model approaching the final body weight was chosen to describe the time course of weight loss. Extent of weight loss was described successfully using a sigmoidal exposure-response relationship of the drug with a constant placebo effect in each individual. The placebo effect was influenced by subjects' sex and baseline body mass index. Maximal weight loss was predicted to occur around 1 year after treatment initiation. The difference in mean weight loss between the sibutramine (daily 12.55 mg) and placebo groups was predicted to be 4.5% in a simulation of 1 year of treatment, with considerable overlap of prediction intervals. Our exposure-response model, which included the placebo effect, is the first example of a quantitative model that can be used to predict the efficacy of weight-control drugs. Similar approaches can help decision-making during clinical development of novel weight-loss drugs.

  19. Historical cohort study of in utero exposure to uterotonic drugs and cognitive function in young adult life

    DEFF Research Database (Denmark)

    Sørensen, Henrik Toft; Rothman, Kenneth J.; Gillman, Matthew W.

    1999-01-01

    to the central nervous system.1 Several studies have reported an association between oxytocic drugs and neonatal hyperbilirubinaemia,2 which might influence long term cognitive function.3 Little is known, however, of the long term consequences of exposure to uterotonic drugs. We investigated whether in utero...

  20. Repetitive Questioning II

    Directory of Open Access Journals (Sweden)

    R. C. Hamdy MD

    2018-02-01

    Full Text Available Repetitive questioning is a major problem for caregivers, particularly taxing if they are unable to recognize and understand the reasons why their loved one keeps asking the same question over and over again. Caregivers may be tempted to believe that the patient does not even try to remember the answer given or is just getting obnoxious. This is incorrect. Repetitive questioning is due to the underlying disease: The patient’s short term memory is impaired and he is unable to register, encode, retain and retrieve the answer. If he is concerned about a particular topic, he will keep asking the same question over and over again. To the patient each time she asks the question, it is as if she asked it for the first time. Just answering repetitive questioning by providing repeatedly the same answer is not sufficient. Caregivers should try to identify the underlying cause for this repetitive questioning. In an earlier case study, the patient was concerned about her and her family’s safety and kept asking whether the doors are locked. In this present case study, the patient does not know how to handle the awkward situation he finds himself in. He just does not know what to do. He is not able to adjust to the new unexpected situation. So he repeatedly wants to reassure himself that he is not intruding by asking the same question over and over again. We discuss how the patient’s son-in-law could have avoided this situation and averted the catastrophic ending.

  1. Early sorafenib-induced toxicity is associated with drug exposure and UGTIA9 genetic polymorphism in patients with solid tumors: a preliminary study.

    Directory of Open Access Journals (Sweden)

    Pascaline Boudou-Rouquette

    Full Text Available BACKGROUND: Identifying predictive biomarkers of drug response is of key importance to improve therapy management and drug selection in cancer therapy. To date, the influence of drug exposure and pharmacogenetic variants on sorafenib-induced toxicity remains poorly documented. The aim of this pharmacokinetic/pharmacodynamic (PK/PD study was to investigate the relationship between early toxicity and drug exposure or pharmacogenetic variants in unselected adult outpatients treated with single-agent sorafenib for advanced solid tumors. METHODS: Toxicity was recorded in 54 patients on days 15 and 30 after treatment initiation and sorafenib exposure was assessed in 51 patients. The influence of polymorphisms in CYP3A5, UGT1A9, ABCB1 and ABCG2 was examined in relation to sorafenib exposure and toxicity. Clinical characteristics, drug exposure and pharmacogenetic variants were tested univariately for association with toxicities. Candidate variables with p<0.1 were analyzed in a multivariate analysis. RESULTS: Gender was the sole parameter independently associated with sorafenib exposure (p = 0.0008. Multivariate analysis showed that increased cumulated sorafenib (AUC(cum was independently associated with any grade ≥ 3 toxicity (p = 0.037; UGT1A9 polymorphism (rs17868320 with grade ≥ 2 diarrhea (p = 0.015 and female gender with grade ≥ 2 hand-foot skin reaction (p = 0.018. Using ROC curve, the threshold AUC(cum value of 3,161 mg/L.h was associated with the highest risk to develop any grade ≥ 3 toxicity (p = 0.018. CONCLUSION: In this preliminary study, increased cumulated drug exposure and UGT1A9 polymorphism (rs17868320 identified patients at high risk for early sorafenib-induced severe toxicity. Further PK/PD studies on larger population are warranted to confirm these preliminary results.

  2. Cocaine addiction: from habits to stereotypical-repetitive behaviors and punding.

    Science.gov (United States)

    Fasano, Alfonso; Barra, Andrea; Nicosia, Paola; Rinaldi, Federica; Bria, Pietro; Bentivoglio, Anna Rita; Tonioni, Federico

    2008-07-01

    "Punding" is a stereotypical motor behavior characterized by an intense fascination with repetitive handling and examining of objects. Since its first description in amphetamine and cocaine addicts, data on punding has only derived from studies performed in patients with Parkinson's disease (PD). Punding is classifiable as the most severe form of Repetitive Reward-Seeking Behaviours (RRSB) syndromes. The aim of this study was to investigate the occurrence and phenomelogy of RRSB acutely induced by cocaine in order to determine the prevalence, severity and distinctive features discriminating "punders" from "non-punders". A consecutive sample of 50 cocaine addicts received a clinical psychiatric interview. RRSB diagnosis and severity were assessed using a modified version of a previous published questionnaire designed to identify punding in patients with PD. In the present series, 38% of the cocaine addicts met the proposed diagnostic criteria for a RRSB and 8% were considered punders. Subjects with vs. without RRSB did not differ in terms of sex ratio, age, education, occupation, predisposing habits, duration of cocaine use, hours of sleep, comorbid psychiatric disorders, and concomitant use of other drugs. These results and the observation that in the majority of cases RRSB started soon after first drug intake, strongly suggest that an underlying unknown predisposition led to the development of these behaviors. In conclusion, RRSB and punding is much more common than has been described previously and the resultant social disability is often overlooked.

  3. Emotional response to musical repetition.

    Science.gov (United States)

    Livingstone, Steven R; Palmer, Caroline; Schubert, Emery

    2012-06-01

    Two experiments examined the effects of repetition on listeners' emotional response to music. Listeners heard recordings of orchestral music that contained a large section repeated twice. The music had a symmetric phrase structure (same-length phrases) in Experiment 1 and an asymmetric phrase structure (different-length phrases) in Experiment 2, hypothesized to alter the predictability of sensitivity to musical repetition. Continuous measures of arousal and valence were compared across music that contained identical repetition, variation (related), or contrasting (unrelated) structure. Listeners' emotional arousal ratings differed most for contrasting music, moderately for variations, and least for repeating musical segments. A computational model for the detection of repeated musical segments was applied to the listeners' emotional responses. The model detected the locations of phrase boundaries from the emotional responses better than from performed tempo or physical intensity in both experiments. These findings indicate the importance of repetition in listeners' emotional response to music and in the perceptual segmentation of musical structure.

  4. Genotoxic effects induced by the exposure to an environmental mixture of illicit drugs to the zebra mussel.

    Science.gov (United States)

    Parolini, Marco; Magni, Stefano; Castiglioni, Sara; Binelli, Andrea

    2016-10-01

    Despite the growing interest on the presence of illicit drugs in freshwater ecosystems, just recently the attention has been focused on their potential toxicity towards non-target aquatic species. However, these studies largely neglected the effects induced by exposure to complex mixtures of illicit drugs, which could be different compared to those caused by single psychoactive molecules. This study was aimed at investigating the genetic damage induced by a 14-day exposure to a realistic mixture of the most common illicit drugs found in surface waters worldwide (cocaine, benzoylecgonine, amphetamine, morphine and 3,4-methylenedioxymethamphetamine) on the zebra mussel (Dreissena polymorpha). The mixture caused a significant increase of DNA fragmentation and triggered the apoptotic process and micronuclei formation in zebra mussel hemocytes, pointing out its potential genotoxicity towards this bivalve species. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Impulsive sounds change European seabass swimming patterns: Influence of pulse repetition interval

    International Nuclear Information System (INIS)

    Neo, Y.Y.; Ufkes, E.; Kastelein, R.A.; Winter, H.V.; Cate, C. ten; Slabbekoorn, H.

    2015-01-01

    Highlights: • We exposed impulsive sounds of different repetition intervals to European seabass. • Immediate behavioural changes mirrored previous indoor & outdoor studies. • Repetition intervals influenced the impacts differentially but not the recovery. • Sound temporal patterns may be more important than some standard metrics. - Abstract: Seismic shootings and offshore pile-driving are regularly performed, emitting significant amounts of noise that may negatively affect fish behaviour. The pulse repetition interval (PRI) of these impulsive sounds may vary considerably and influence the behavioural impact and recovery. Here, we tested the effect of four PRIs (0.5–4.0 s) on European seabass swimming patterns in an outdoor basin. At the onset of the sound exposures, the fish swam faster and dived deeper in tighter shoals. PRI affected the immediate and delayed behavioural changes but not the recovery time. Our study highlights that (1) the behavioural changes of captive European seabass were consistent with previous indoor and outdoor studies; (2) PRI could influence behavioural impact differentially, which may have management implications; (3) some acoustic metrics, e.g. SEL cum , may have limited predictive power to assess the strength of behavioural impacts of noise. Noise impact assessments need to consider the contribution of sound temporal structure

  6. Repetitive learning control of continuous chaotic systems

    International Nuclear Information System (INIS)

    Chen Maoyin; Shang Yun; Zhou Donghua

    2004-01-01

    Combining a shift method and the repetitive learning strategy, a repetitive learning controller is proposed to stabilize unstable periodic orbits (UPOs) within chaotic attractors in the sense of least mean square. If nonlinear parts in chaotic systems satisfy Lipschitz condition, the proposed controller can be simplified into a simple proportional repetitive learning controller

  7. Novel porcine repetitive elements

    Directory of Open Access Journals (Sweden)

    Nonneman Dan J

    2006-12-01

    Full Text Available Abstract Background Repetitive elements comprise ~45% of mammalian genomes and are increasingly known to impact genomic function by contributing to the genomic architecture, by direct regulation of gene expression and by affecting genomic size, diversity and evolution. The ubiquity and increasingly understood importance of repetitive elements contribute to the need to identify and annotate them. We set out to identify previously uncharacterized repetitive DNA in the porcine genome. Once found, we characterized the prevalence of these repeats in other mammals. Results We discovered 27 repetitive elements in 220 BACs covering 1% of the porcine genome (Comparative Vertebrate Sequencing Initiative; CVSI. These repeats varied in length from 55 to 1059 nucleotides. To estimate copy numbers, we went to an independent source of data, the BAC-end sequences (Wellcome Trust Sanger Institute, covering approximately 15% of the porcine genome. Copy numbers in BAC-ends were less than one hundred for 6 repeat elements, between 100 and 1000 for 16 and between 1,000 and 10,000 for 5. Several of the repeat elements were found in the bovine genome and we have identified two with orthologous sites, indicating that these elements were present in their common ancestor. None of the repeat elements were found in primate, rodent or dog genomes. We were unable to identify any of the replication machinery common to active transposable elements in these newly identified repeats. Conclusion The presence of both orthologous and non-orthologous sites indicates that some sites existed prior to speciation and some were generated later. The identification of low to moderate copy number repetitive DNA that is specific to artiodactyls will be critical in the assembly of livestock genomes and studies of comparative genomics.

  8. Document retrieval on repetitive string collections.

    Science.gov (United States)

    Gagie, Travis; Hartikainen, Aleksi; Karhu, Kalle; Kärkkäinen, Juha; Navarro, Gonzalo; Puglisi, Simon J; Sirén, Jouni

    2017-01-01

    Most of the fastest-growing string collections today are repetitive, that is, most of the constituent documents are similar to many others. As these collections keep growing, a key approach to handling them is to exploit their repetitiveness, which can reduce their space usage by orders of magnitude. We study the problem of indexing repetitive string collections in order to perform efficient document retrieval operations on them. Document retrieval problems are routinely solved by search engines on large natural language collections, but the techniques are less developed on generic string collections. The case of repetitive string collections is even less understood, and there are very few existing solutions. We develop two novel ideas, interleaved LCPs and precomputed document lists , that yield highly compressed indexes solving the problem of document listing (find all the documents where a string appears), top- k document retrieval (find the k documents where a string appears most often), and document counting (count the number of documents where a string appears). We also show that a classical data structure supporting the latter query becomes highly compressible on repetitive data. Finally, we show how the tools we developed can be combined to solve ranked conjunctive and disjunctive multi-term queries under the simple [Formula: see text] model of relevance. We thoroughly evaluate the resulting techniques in various real-life repetitiveness scenarios, and recommend the best choices for each case.

  9. Structure-activity studies of Wnt/β-catenin inhibition in the Niclosamide chemotype: Identification of derivatives with improved drug exposure.

    Science.gov (United States)

    Mook, Robert A; Wang, Jiangbo; Ren, Xiu-Rong; Chen, Minyong; Spasojevic, Ivan; Barak, Larry S; Lyerly, H Kim; Chen, Wei

    2015-09-01

    The Wnt signaling pathway plays a key role in regulation of organ development and tissue homeostasis. Dysregulated Wnt activity is one of the major underlying mechanisms responsible for many diseases including cancer. We previously reported the FDA-approved anthelmintic drug Niclosamide inhibits Wnt/β-catenin signaling and suppresses colon cancer cell growth in vitro and in vivo. Niclosamide is a multi-functional drug that possesses important biological activity in addition to inhibition of Wnt/β-catenin signaling. Here, we studied the SAR of Wnt signaling inhibition in the anilide and salicylamide region of Niclosamide. We found that the 4'-nitro substituent can be effectively replaced by trifluoromethyl or chlorine and that the potency of inhibition was dependent on the substitution pattern in the anilide ring. Non-anilide, N-methyl amides and reverse amide derivatives lost significant potency, while acylated salicylamide derivatives inhibited signaling with potency similar to non-acyl derivatives. Niclosamide's low systemic exposure when dosed orally may hinder its use to treat systemic disease. To overcome this limitation we identified an acyl derivative of Niclosamide, DK-520 (compound 32), that significantly increased both the plasma concentration and the duration of exposure of Niclosamide when dosed orally. The studies herein provide a medicinal chemical foundation to improve the pharmacokinetic exposure of Niclosamide and Wnt-signaling inhibitors based on the Niclosamide chemotype. The identification of novel derivatives of Niclosamide that metabolize to Niclosamide and increase its drug exposure may provide important research tools for in vivo studies and provide drug candidates for treating cancers with dysregulated Wnt signaling including drug-resistant cancers. Moreover, since Niclosamide is a multi-functional drug, new research tools such as DK520 could directly result in novel treatments against bacterial and viral infection, lupus, and metabolic

  10. Structure–activity studies of Wnt/β-catenin inhibition in the Niclosamide chemotype: Identification of derivatives with improved drug exposure

    Science.gov (United States)

    Mook, Robert A.; Wang, Jiangbo; Ren, Xiu-Rong; Chen, Minyong; Spasojevic, Ivan; Barak, Larry S.; Lyerly, H. Kim; Chen, Wei

    2015-01-01

    The Wnt signaling pathway plays a key role in regulation of organ development and tissue homeostasis. Dysregulated Wnt activity is one of the major underlying mechanisms responsible for many diseases including cancer. We previously reported the FDA-approved anthelmintic drug Niclosamide inhibits Wnt/β-catenin signaling and suppresses colon cancer cell growth in vitro and in vivo. Niclosamide is a multi-functional drug that possesses important biological activity in addition to inhibition of Wnt/β-catenin signaling. Here, we studied the SAR of Wnt signaling inhibition in the anilide and salicylamide region of Niclosamide. We found that the 4′-nitro substituent can be effectively replaced by trifluoromethyl or chlorine and that the potency of inhibition was dependent on the substitution pattern in the anilide ring. Non-anilide, N-methyl amides and reverse amide derivatives lost significant potency, while acylated salicylamide derivatives inhibited signaling with potency similar to non-acyl derivatives. Niclosamide's low systemic exposure when dosed orally may hinder its use to treat systemic disease. To overcome this limitation we identified an acyl derivative of Niclosamide, DK-520 (compound 32), that significantly increased both the plasma concentration and the duration of exposure of Niclosamide when dosed orally. The studies herein provide a medicinal chemical foundation to improve the pharmacokinetic exposure of Niclosamide and Wnt-signaling inhibitors based on the Niclosamide chemotype. The identification of novel derivatives of Niclosamide that metabolize to Niclosamide and increase its drug exposure may provide important research tools for in vivo studies and provide drug candidates for treating cancers with dysregulated Wnt signaling including drug-resistant cancers. Moreover, since Niclosamide is a multifunctional drug, new research tools such as DK520 could directly result in novel treatments against bacterial and viral infection, lupus, and metabolic

  11. REPETITIVE STRENGTH AMONG STUDENTS OF AGE 14

    Directory of Open Access Journals (Sweden)

    Besim Halilaj

    2014-06-01

    Full Text Available The study involved 82 male students of the primary school “Qamil Ilazi” in Kaçanik-Kosovo.Four movement tests, which test the repetitive strength, were conducted: 1. Pull-up, 2. Sit-Up, 3. Back extension, 4. Push-up.The main goal of this study was to verify the actual motor status, respectively the component of the repetitive strength among students of age 14 of masculine gender. In addition to verifying the actual motor status, another objective was to verify the relationship between the variables employed.Basic statistical parameters show a distribution which is not significantly different from the normal distribution, yielded highly correlative values among the repetitive strength tests. Space factorization resulted in extracting two latent squares defined as repetitive strength of arms factor, and repetitive strength of body factor.

  12. Establishment of the South-Eastern Norway Regional Health Authority Resource Center for Children with Prenatal Alcohol/Drug Exposure

    Directory of Open Access Journals (Sweden)

    Gro C. C. Løhaugen

    2015-01-01

    Full Text Available This paper presents a new initiative in the South-Eastern Health Region of Norway to establish a regional resource center focusing on services for children and adolescents aged 2–18 years with prenatal exposure to alcohol or other drugs. In Norway, the prevalence of fetal alcohol spectrum (FAS is not known but has been estimated to be between 1 and 2 children per 1000 births, while the prevalence of prenatal exposure to illicit drugs is unknown. The resource center is the first of its kind in Scandinavia and will have three main objectives: (1 provide hospital staff, community health and child welfare personnel, and special educators with information, educational courses, and seminars focused on the identification, diagnosis, and treatment of children with a history of prenatal alcohol/drug exposure; (2 provide specialized health services, such as diagnostic services and intervention planning, for children referred from hospitals in the South-Eastern Health Region of Norway; and (3 initiate multicenter studies focusing on the diagnostic process and evaluation of interventions.

  13. Dissimilarities in the metabolism of antiretroviral drugs used in HIV pre-exposure prophylaxis in colon and vagina tissues.

    Science.gov (United States)

    To, Elaine E; Hendrix, Craig W; Bumpus, Namandjé N

    2013-10-01

    Attempts to prevent HIV infection through pre-exposure prophylaxis (PrEP) include topical application of anti-HIV drugs to the mucosal sites of infection; however, a potential role for local drug metabolizing enzymes in modulating the exposure of the mucosal tissues to these drugs has yet to be explored. Here we present the first report that enzymes belonging to the cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) families of drug metabolizing enzymes are expressed and active in vaginal and colorectal tissue using biopsies collected from healthy volunteers. In doing so, we discovered that dapivirine and maraviroc, a non-nucleoside reverse transcriptase inhibitor and an entry inhibitor currently in development as microbicides for HIV PrEP, are differentially metabolized in colorectal tissue and vaginal tissue. Taken together, these data should help to guide the optimization of small molecules being developed for HIV PrEP. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Epigenetic and Transcriptional Modifications in Repetitive Elements in Petrol Station Workers Exposed to Benzene and MTBE

    Directory of Open Access Journals (Sweden)

    Federica Rota

    2018-04-01

    Full Text Available Benzene, a known human carcinogen, and methyl tert-butyl ether (MTBE, not classifiable as to its carcinogenicity, are fuel-related pollutants. This study investigated the effect of these chemicals on epigenetic and transcriptional alterations in DNA repetitive elements. In 89 petrol station workers and 90 non-occupationally exposed subjects the transcriptional activity of retrotransposons (LINE-1, Alu, the methylation on repeated-element DNA, and of H3K9 histone, were investigated in peripheral blood lymphocytes. Median work shift exposure to benzene and MTBE was 59 and 408 µg/m3 in petrol station workers, and 4 and 3.5 µg/m3, in controls. Urinary benzene (BEN-U, S-phenylmercapturic acid, and MTBE were significantly higher in workers than in controls, while trans,trans-muconic acid (tt-MA was comparable between the two groups. Increased BEN-U was associated with increased Alu-Y and Alu-J expression; moreover, increased tt-MA was associated with increased Alu-Y and Alu-J and LINE-1 (L1-5′UTR expression. Among repetitive element methylation, only L1-Pa5 was hypomethylated in petrol station workers compared to controls. While L1-Ta and Alu-YD6 methylation was not associated with benzene exposure, a negative association with urinary MTBE was observed. The methylation status of histone H3K9 was not associated with either benzene or MTBE exposure. Overall, these findings only partially support previous observations linking benzene exposure with global DNA hypomethylation.

  15. Occupational Exposure to Antineoplastic Drugs: Identification of Job Categories Potentially Exposed throughout the Hospital Medication System

    Directory of Open Access Journals (Sweden)

    Chun-Yip Hon

    2011-09-01

    Conclusion: We found drug contamination on select surfaces at every stage of the medication system, which indicates the existence of an exposure potential throughout the facility. Our results suggest that a broader range of workers are potentially exposed than has been previously examined. These results will allow us to develop a more inclusive exposure assessment encompassing all healthcare workers that are at risk throughout the hospital medication system.

  16. Hair analysis following chronic smoked-drugs-of-abuse exposure in adults and their toddler: a case report

    OpenAIRE

    Papaseit, Esther; Joya, Xavier; Velasco, Marta; Civit, Ester; Mota, Pau; Bertran, Marta; Vall, Oriol; Garcia-Algar, Oscar

    2011-01-01

    Abstract Introduction Over the past two decades, the study of chronic cocaine and crack cocaine exposure in the pediatric population has been focused on the potential adverse effects, especially in the prenatal period and early childhood. Non-invasive biological matrices have become an essential tool for the assessment of a long-term history of drug of abuse exposure. Case report We analyze the significance of different biomarker values in hair after chronic crack exposure in a two-year-old C...

  17. Safe Handling of Cytotoxic Drugs and Risks of Occupational Exposure to Nursing Staffs

    Directory of Open Access Journals (Sweden)

    Somayeh Hanafi

    2016-05-01

    Full Text Available Background: Inherent toxicity of cytotoxic drugs is the basis for their potential adverse risks from occupational exposure to the nursing staff. In Iran, chemotherapy regimens are prescribed and administered according to the world updated protocols. But little is done regarding the protective standards in this field.Methods: An observational cross-sectional survey was conducted among nurses who work in three tertiary care teaching hospitals in Tehran, Iran in 2012. All participants worked in one of the hospital wards handling cytotoxic drugs (preparation and administration. A questionnaire was used for interviewing all subjects, and observing them preparing and administering the drugs. We examined all adverse effects associated with handling of antineoplastic drugs.Results: Totally 270 adverse reactions were reported. The most frequently reported adverse effects included headache and vertigo (40 cases, hair loss (36 cases, skin rashes and itching (31 cases, and burning sensation in eyes (31 cases. In all hospital wards, the standards were met in not more than 50% of the items.Conclusion: Monitoring the personnel who are directly involved in handling of cytotoxic drugs is of great importance. Furthermore, educating the personnel in the field of standards of cytotoxic drugs handling could increase the nursing staff’s knowledge regarding these drugs’ adverse reactions.

  18. Prenatal exposure to antiepileptic drugs and dental agenesis.

    Directory of Open Access Journals (Sweden)

    Pernille E Jacobsen

    Full Text Available OBJECTIVE: The aim of the study was to investigate the association between prenatal exposure to AEDs and the risk of dental agenesis and to differentiate between the possible effects of the different drugs used. METHODS: Data on 214 exposed and 255 unexposed children, aged 12-18 years, were extracted from the Prescription Database of the Central Denmark Region and North Denmark Region and the Danish Medical Birth Registry. The children's dental charts were examined for the presence of dental agenesis. RESULTS: Overall, children exposed to AED in utero had an increased risk of developing dental agenesis, but as a group, the difference was not significant (OR = 1.7; [95% CI: 0.8-3.6]. The risk of developing dental agenesis was three-fold increased (OR = 3.1; [95% CI: 1.3-7.4] in children exposed to valproate in mono- or in poly-therapy with other AEDs than carbamazepine or oxcarbazepine. The risk was further increased (OR = 11.2; [95% CI: 2.4-51.9] in children exposed to valproate and carbamazepine or oxcarbazepine in combination. CONCLUSIONS: The present study shows that dental agenesis is a potential congenital abnormality that is related to prenatal exposure to valproate, and dental agenesis may be considered a sensitive marker for the teratogenicity of valproate.

  19. Prenatal lipopolysaccharide induces hypothalamic dopaminergic hypoactivity and autistic-like behaviors: Repetitive self-grooming and stereotypies.

    Science.gov (United States)

    Kirsten, Thiago B; Bernardi, Maria M

    2017-07-28

    Previous investigations by our group have shown that prenatal exposure to lipopolysaccharide (LPS), which mimics infection by gram-negative bacteria, induces social, cognitive, and communication deficits. For a complete screening of autistic-like behaviors, the objective of this study was to evaluate if our rat model also induces restricted and repetitive stereotyped behaviors. Thus, we studied the self-grooming microstructure. We also studied the neurochemistry of hypothalamus and frontal cortex, which are brain areas related to autism to better understand central mechanisms involved in our model. Prenatal LPS exposure on gestational day 9.5 increased the head washing episodes (frequency and time), as well as the total self-grooming. However, body grooming, paw/leg licking, tail/genital grooming, and circling behavior/tail chasing did not vary significantly among the groups. Moreover, prenatal LPS induced dopaminergic hypoactivity (HVA metabolite and turnover) in the hypothalamus. Therefore, our rat model induced restricted and repetitive stereotyped behaviors and the other main symptoms of autism experimentally studied in rodent models and also found in patients. The hypothalamic dopaminergic impairments seem to be associated with the autistic-like behaviors. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Successful Management of Repetitive Urinary Obstruction and Anuria Caused by Double J Stent Calculi Formation after Renal Transplantation

    Directory of Open Access Journals (Sweden)

    Zongyao Hao

    2014-01-01

    Full Text Available This report firstly describes an extremely rare case of repetitive double J stent calculi formation after renal transplantation caused by the antihyperparathyroidism (HPT drug calcitriol. In 2012, a woman initially presented to our hospital for anuria with lower abdominal pain. She was diagnosed with allograft hydronephrosis and double J stents obstruction by calculi formation after transplantation and treated with triplicate stents replacements in another hospital without clinical manifestations improvements. Through detailed exploration of medical history, we conclude that the abnormal calculi formation is due to the calcitriol (1,25-dihydroxyvitamin D3 administration, a drug which can increase renal tubular reabsorption of calcium for treating posttransplant HPT bone disease. After discontinuing calcitriol, the patient was stone-free and had a good recovery without severe complications during the 9-month follow-up. Our novel findings may provide an important clue and approach to managing formidable repetitive double J stent calculi formation in the clinical trial.

  1. Repetition and Emotive Communication in Music Versus Speech

    Directory of Open Access Journals (Sweden)

    Elizabeth Hellmuth eMargulis

    2013-04-01

    Full Text Available Music and speech are often placed alongside one another as comparative cases. Their relative overlaps and disassociations have been well explored (e.g. Patel, 2010. But one key attribute distinguishing these two domains has often been overlooked: the greater preponderance of repetition in music in comparison to speech. Recent fMRI studies have shown that familiarity – achieved through repetition – is a critical component of emotional engagement with music (Pereira et al., 2011. If repetition is fundamental to emotional responses to music, and repetition is a key distinguisher between the domains of music and speech, then close examination of the phenomenon of repetition might help clarify the ways that music elicits emotion differently than speech.

  2. Repetitive stress leads to impaired cognitive function that is associated with DNA hypomethylation, reduced BDNF and a dysregulated HPA axis.

    Science.gov (United States)

    Makhathini, Khayelihle B; Abboussi, Oualid; Stein, Dan J; Mabandla, Musa V; Daniels, William M U

    2017-08-01

    Exposure to repetitive stress has a negative influence on cognitive-affective functioning, with growing evidence that these effects may be mediated by a dysregulated hypothalamic-pituitary-adrenal (HPA) axis, abnormal neurotrophic factor levels and its subsequent impact on hippocampal function. However, there are few data about the effect of repetitive stressors on epigenetic changes in the hippocampus. In the present study, we examine how repetitive restrain stress (RRS) affects cognitive-affective functioning, HPA axis regulation, brain-derived neurotrophic factor (BDNF) levels, and global hippocampal DNA methylation. RRS was induced in rats by restraining the animals for 6h per day for 28 days. The novel object recognition test (NORT) was used to assess cognitive functioning and the open field test (OFT) was performed to assess anxiety-like behavior during the last week of stress. Hippocampal BDNF levels, glucocorticoid (GR) and mineralocorticoid (MR) receptor mRNA were assessed using real-time PCR and confirmed with Western blot, while ELISAs were used to determine plasma corticosterone levels and the global methylation status of the hippocampus. Animals exposed to repetitive stress demonstrated significant alterations in the NORT and OFT, had significantly increased plasma corticosterone and significantly decreased hippocampal BDNF concentrations. The expression levels of GR and MR mRNA and protein levels of these genes were significantly decreased in the stressed group compared to control animals. The global DNA methylation of the hippocampal genome of stressed animals was also significantly decreased compared to controls. The data here are consistent with previous work emphasizing the role of the HPA axis and neurotrophic factors in mediating cognitive-affective changes after exposure to repetitive stressors. Our findings, however, extend the literature by indicating that epigenetic alterations in the hippocampal genome may also play an important role in the

  3. Feature-based motion control for near-repetitive structures

    NARCIS (Netherlands)

    Best, de J.J.T.H.

    2011-01-01

    In many manufacturing processes, production steps are carried out on repetitive structures which consist of identical features placed in a repetitive pattern. In the production of these repetitive structures one or more consecutive steps are carried out on the features to create the final product.

  4. Effect of food on early drug exposure from extended-release stimulants: results from the Concerta, Adderall XR Food Evaluation (CAFE) Study.

    Science.gov (United States)

    Auiler, J F; Liu, K; Lynch, J M; Gelotte, C K

    2002-01-01

    Stimulant therapy is the mainstay of treatment for children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). Once-daily, extended-release oral formulations offer long acting control of symptoms by modifying drug delivery and absorption. In particular, consistency in early drug exposure is important for symptom control during school or work hours. Because these once-daily formulations are usually taken in the morning, the timing of the doses with breakfast is important. This study compared the effect of a high-fat breakfast on early drug exposure from a morning dose of two extended-release stimulant formulations: the osmotic-controlled OROS tablet of methylphenidate HCI (CONCERTA) and the capsule containing extended-release beads of mixed amphetamine salts (ADDERALL XR). The study had a single-dose, open-label, randomised, four-treatment, crossover design in which healthy subjects received either 36 mg CONCERTA or 20 mg ADDERALL XR in the morning after an overnight fast or a high-fat breakfast. Serial blood samples were collected over 28h to determine plasma concentrations of methylphenidate and amphetamine. The food effect on early drug exposure and the pharmacokinetic profiles up to 8 h after dosing of the two extended-release stimulants were directly compared using partial area (AUC(p4h), AUC(p6h) and AUC(p8h)) fed/fasted ratios. Amphetamine concentrations were markedly lower when the subjects had eaten breakfast, resulting in lower early drug exposures (p food, for patients with ADHD.

  5. Grade Repetition and Primary School Dropout in Uganda

    Science.gov (United States)

    Kabay, Sarah

    2016-01-01

    Research on education in low-income countries rarely focuses on grade repetition. When addressed, repetition is typically presented along with early school dropout as the "wasting" of educational resources. Simplifying grade repetition in this way often fails to recognize significant methodological concerns and also overlooks the unique…

  6. Ultrafast high-repetition imaging of fuel sprays using picosecond fiber laser.

    Science.gov (United States)

    Purwar, Harsh; Wang, Hongjie; Tang, Mincheng; Idlahcen, Saïd; Rozé, Claude; Blaisot, Jean-Bernard; Godin, Thomas; Hideur, Ammar

    2015-12-28

    Modern diesel injectors operate at very high injection pressures of about 2000 bar resulting in injection velocities as high as 700 m/s near the nozzle outlet. In order to better predict the behavior of the atomization process at such high pressures, high-resolution spray images at high repetition rates must be recorded. However, due to extremely high velocity in the near-nozzle region, high-speed cameras fail to avoid blurring of the structures in the spray images due to their exposure time. Ultrafast imaging featuring ultra-short laser pulses to freeze the motion of the spray appears as an well suited solution to overcome this limitation. However, most commercial high-energy ultrafast sources are limited to a few kHz repetition rates. In the present work, we report the development of a custom-designed picosecond fiber laser generating ∼ 20 ps pulses with an average power of 2.5 W at a repetition rate of 8.2 MHz, suitable for high-speed imaging of high-pressure fuel jets. This fiber source has been proof tested by obtaining backlight images of diesel sprays issued from a single-orifice injector at an injection pressure of 300 bar. We observed a consequent improvement in terms of image resolution compared to standard white-light illumination. In addition, the compactness and stability against perturbations of our fiber laser system makes it particularly suitable for harsh experimental conditions.

  7. Measures of anticholinergic drug exposure, serum anticholinergic activity, and all-cause postdischarge mortality in older hospitalized patients with hip fractures

    NARCIS (Netherlands)

    Mangoni, Arduino A.; van Munster, Barbara C.; Woodman, Richard J.; de Rooij, Sophia E.

    2013-01-01

    To assess possible associations between anticholinergic drug exposure and serum anticholinergic activity (SAA) and their capacities to predict all-cause mortality in older hospitalized patients. Academic medical center. Data on clinical characteristics, full medication exposure, SAA, and 4

  8. Analogous selection processes in declarative and procedural working memory: N-2 list-repetition and task-repetition costs.

    Science.gov (United States)

    Gade, Miriam; Souza, Alessandra S; Druey, Michel D; Oberauer, Klaus

    2017-01-01

    Working memory (WM) holds and manipulates representations for ongoing cognition. Oberauer (Psychology of Learning and Motivation, 51, 45-100, 2009) distinguishes between two analogous WM sub-systems: a declarative WM which handles the objects of thought, and a procedural WM which handles the representations of (cognitive) actions. Here, we assessed whether analogous effects are observed when participants switch between memory sets (declarative representations) and when they switch between task sets (procedural representations). One mechanism assumed to facilitate switching in procedural WM is the inhibition of previously used, but currently irrelevant task sets, as indexed by n-2 task-repetition costs (Mayr & Keele, Journal of Experimental Psychology: General, 129(1), 4-26, 2000). In this study we tested for an analogous effect in declarative WM. We assessed the evidence for n-2 list-repetition costs across eight experiments in which participants switched between memory lists to perform speeded classifications, mental arithmetic, or a local recognition test. N-2 list-repetition costs were obtained consistently in conditions assumed to increase interference between memory lists, and when lists formed chunks in long-term memory. Further analyses across experiments revealed a substantial contribution of episodic memory to n-2 list-repetition costs, thereby questioning the interpretation of n-2 repetition costs as reflecting inhibition. We reanalyzed the data of eight task-switching experiments, and observed that episodic memory also contributes to n-2 task-repetition costs. Taken together, these results show analogous processing principles in declarative and procedural WM, and question the relevance of inhibitory processes for efficient switching between mental sets.

  9. The Golden Ratio of Gait Harmony: Repetitive Proportions of Repetitive Gait Phases

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    Marco Iosa

    2013-01-01

    Full Text Available In nature, many physical and biological systems have structures showing harmonic properties. Some of them were found related to the irrational number known as the golden ratio that has important symmetric and harmonic properties. In this study, the spatiotemporal gait parameters of 25 healthy subjects were analyzed using a stereophotogrammetric system with 25 retroreflective markers located on their skin. The proportions of gait phases were compared with , the value of which is about 1.6180. The ratio between the entire gait cycle and stance phase resulted in 1.620 ± 0.058, that between stance and the swing phase was 1.629 ± 0.173, and that between swing and the double support phase was 1.684 ± 0.357. All these ratios did not differ significantly from each other (, , repeated measure analysis of variance or from (, resp., t-tests. The repetitive gait phases of physiological walking were found in turn in repetitive proportions with each other, revealing an intrinsic harmonic structure. Harmony could be the key for facilitating the control of repetitive walking. Harmony is a powerful unifying factor between seemingly disparate fields of nature, including human gait.

  10. Subjective duration distortions mirror neural repetition suppression.

    Science.gov (United States)

    Pariyadath, Vani; Eagleman, David M

    2012-01-01

    Subjective duration is strongly influenced by repetition and novelty, such that an oddball stimulus in a stream of repeated stimuli appears to last longer in duration in comparison. We hypothesize that this duration illusion, called the temporal oddball effect, is a result of the difference in expectation between the oddball and the repeated stimuli. Specifically, we conjecture that the repeated stimuli contract in duration as a result of increased predictability; these duration contractions, we suggest, result from decreased neural response amplitude with repetition, known as repetition suppression. Participants viewed trials consisting of lines presented at a particular orientation (standard stimuli) followed by a line presented at a different orientation (oddball stimulus). We found that the size of the oddball effect correlates with the number of repetitions of the standard stimulus as well as the amount of deviance from the oddball stimulus; both of these results are consistent with a repetition suppression hypothesis. Further, we find that the temporal oddball effect is sensitive to experimental context--that is, the size of the oddball effect for a particular experimental trial is influenced by the range of duration distortions seen in preceding trials. Our data suggest that the repetition-related duration contractions causing the oddball effect are a result of neural repetition suppression. More generally, subjective duration may reflect the prediction error associated with a stimulus and, consequently, the efficiency of encoding that stimulus. Additionally, we emphasize that experimental context effects need to be taken into consideration when designing duration-related tasks.

  11. Subjective duration distortions mirror neural repetition suppression.

    Directory of Open Access Journals (Sweden)

    Vani Pariyadath

    Full Text Available Subjective duration is strongly influenced by repetition and novelty, such that an oddball stimulus in a stream of repeated stimuli appears to last longer in duration in comparison. We hypothesize that this duration illusion, called the temporal oddball effect, is a result of the difference in expectation between the oddball and the repeated stimuli. Specifically, we conjecture that the repeated stimuli contract in duration as a result of increased predictability; these duration contractions, we suggest, result from decreased neural response amplitude with repetition, known as repetition suppression.Participants viewed trials consisting of lines presented at a particular orientation (standard stimuli followed by a line presented at a different orientation (oddball stimulus. We found that the size of the oddball effect correlates with the number of repetitions of the standard stimulus as well as the amount of deviance from the oddball stimulus; both of these results are consistent with a repetition suppression hypothesis. Further, we find that the temporal oddball effect is sensitive to experimental context--that is, the size of the oddball effect for a particular experimental trial is influenced by the range of duration distortions seen in preceding trials.Our data suggest that the repetition-related duration contractions causing the oddball effect are a result of neural repetition suppression. More generally, subjective duration may reflect the prediction error associated with a stimulus and, consequently, the efficiency of encoding that stimulus. Additionally, we emphasize that experimental context effects need to be taken into consideration when designing duration-related tasks.

  12. The Developmental Trajectory of Nonword Repetition

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    Chiat, Shula

    2006-01-01

    In line with the original presentation of nonword repetition as a measure of phonological short-term memory (Gathercole & Baddeley, 1989), the theoretical account Gathercole (2006) puts forward in her Keynote Article focuses on phonological storage as the key capacity common to nonword repetition and vocabulary acquisition. However, evidence that…

  13. Influence of the drug exposure definition on the assessment of the antipsychotic metabolic impact in patients initially treated with mood-stabilizers.

    Science.gov (United States)

    Tournier, Marie; Bégaud, Bernard; Cougnard, Audrey; Auleley, Guy-Robert; Deligne, Jean; Blum-Boisgard, Claudine; Thiébaut, Anne C M; Verdoux, Hélène

    2012-07-01

    • Metabolic disturbances represent a well-known side effect of second generation antipsychotics. However, studies comparing second generation antipsychotic drugs (SGAPs) and first generation antipsychotic drugs (FGAPs) through administrative databases have shown contrasting findings, which may be attributable to methodological differences. • The definition of antipsychotic exposure impacts on the association between antipsychotics and metabolic risk in studies carried out through administrative databases. • Considering cumulative exposure to antipsychotics or including patients exposed to an antipsychotic drug for months or years is likely to over-represent patients who tolerate the drug well with a depletion of susceptible effects. • Antipsychotic drug exposure is a time-varying determinant and episodes of no use, past use and current use should be distinguished over the study period to avoid any misclassification bias that might lead to misleading findings. To assess the influence of three definitions of antipsychotic exposure on the comparison between first generation (FGAP) and second generation (SGAP) antipsychotic drugs and 'conventional' mood stabilizers towards the risk of metabolic events using (i) a dichotomous measure (exposed/non-exposed over the follow-up), (ii) a categorical measure taking into account the chronology of exposure at the time of the metabolic event (current, recent and no use) and (iii) a continuous measure (cumulative duration). A historical fixed cohort was identified from the 2004-2006 claims database of the French health insurance programme for self-employed workers, including 3172 patients aged 18 years and over who used conventional mood stabilizers over a 3 month period. A metabolic event was defined as an incident dispensing of an anti-diabetic or lipid-lowering drug. A metabolic event occurred in 367 patients (11.6%). At least one FGAP had been prescribed in 29% of patients who did not develop a metabolic event and in

  14. Global Repetition Influences Contextual Cueing

    Science.gov (United States)

    Zang, Xuelian; Zinchenko, Artyom; Jia, Lina; Li, Hong

    2018-01-01

    Our visual system has a striking ability to improve visual search based on the learning of repeated ambient regularities, an effect named contextual cueing. Whereas most of the previous studies investigated contextual cueing effect with the same number of repeated and non-repeated search displays per block, the current study focused on whether a global repetition frequency formed by different presentation ratios between the repeated and non-repeated configurations influence contextual cueing effect. Specifically, the number of repeated and non-repeated displays presented in each block was manipulated: 12:12, 20:4, 4:20, and 4:4 in Experiments 1–4, respectively. The results revealed a significant contextual cueing effect when the global repetition frequency is high (≥1:1 ratio) in Experiments 1, 2, and 4, given that processing of repeated displays was expedited relative to non-repeated displays. Nevertheless, the contextual cueing effect reduced to a non-significant level when the repetition frequency reduced to 4:20 in Experiment 3. These results suggested that the presentation frequency of repeated relative to the non-repeated displays could influence the strength of contextual cueing. In other words, global repetition statistics could be a crucial factor to mediate contextual cueing effect. PMID:29636716

  15. Improving the ablation efficiency of excimer laser systems with higher repetition rates through enhanced debris removal and optimized spot pattern.

    Science.gov (United States)

    Arba-Mosquera, Samuel; Klinner, Thomas

    2014-03-01

    To evaluate the reasons for the required increased radiant exposure for higher-repetition-rate excimer lasers and determine experimentally possible compensations to achieve equivalent ablation profiles maintaining the same single-pulse energies and radiant exposures for laser repetition rates ranging from 430 to 1000 Hz. Schwind eye-tech-solutions GmbH and Co. KG, Kleinostheim, Germany. Experimental study. Poly(methyl methacrylate) (PMMA) plates were photoablated. The pulse laser energy was maintained during all experiments; the effects of the flow of the debris removal, the shot pattern for the correction, and precooling the PMMA plates were evaluated in terms of achieved ablation versus repetition rate. The mean ablation performance ranged from 88% to 100%; the variability between the profile measurements ranged from 1.4% to 6.2%. Increasing the laser repetition rate from 430 Hz to 1000 Hz reduced the mean ablation performance from 98% to 91% and worsened the variability from 1.9% to 4.3%. Increasing the flow of the debris removal, precooling the PMMA plates to -18°C, and adapting the shot pattern for the thermal response of PMMA to excimer ablation helped stabilize the variability. Only adapting the shot pattern for the thermal response of PMMA to excimer ablation helped stabilize the mean ablation performance. The ablation performance of higher-repetition-rate excimer lasers on PMMA improved with improvements in the debris removal systems and shot pattern. More powerful debris removal systems and smart shot patterns in terms of thermal response improved the performance of these excimer lasers. Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  16. Imbalance between abstract and concrete repetitive thinking modes in schizophrenia.

    Science.gov (United States)

    Maurage, Pierre; Philippot, Pierre; Grynberg, Delphine; Leleux, Dominique; Delatte, Benoît; Mangelinckx, Camille; Belge, Jan-Baptist; Constant, Eric

    2017-10-01

    Repetitive thoughts can be divided in two modes: abstract/analytic (decontextualized and dysfunctional) and concrete/experiential (problem-focused and adaptive). They constitute a transdiagnostic process involved in many psychopathological states but have received little attention in schizophrenia, as earlier studies only indexed increased ruminations (related to dysfunctional repetitive thoughts) without jointly exploring both modes. This study explored the two repetitive thinking modes, beyond ruminations, to determine their imbalance in schizophrenia. Thirty stabilized patients with schizophrenia and 30 matched controls completed the Repetitive Response Scale and the Mini Cambridge-Exeter Repetitive Thought Scale, both measuring repetitive thinking modes. Complementary measures related to schizophrenic symptomatology, depression and anxiety were also conducted. Compared to controls, patients with schizophrenia presented an imbalance between repetitive thinking modes, with increased abstract/analytic and reduced concrete/experiential thoughts, even after controlling for comorbidities. Schizophrenia is associated with stronger dysfunctional repetitive thoughts (i.e. abstract thinking) and impaired ability to efficiently use repetitive thinking for current problem-solving (i.e. concrete thinking). This imbalance confirms the double-faced nature of repetitive thinking modes, whose influence on schizophrenia's symptomatology should be further investigated. The present results also claim for evaluating these processes in clinical settings and for rehabilitating the balance between opposite repetitive thinking modes. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Comet assay as a human biomonitoring tool: application in occupational exposure to antineoplastic drugs

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    Carina Ladeira

    2015-05-01

    Occupational exposure to antineoplastic drugs is associated with genotoxic effects, although comet assay analyzed parameters were higher in exposed comparing with controls, were not significant. Also the study of the susceptibility biomarkers did not show statistical significant differences, the small size of our sample hampered the finding of a possible association, let alone a causality relationship.

  18. The Role of Drinking Severity on Sex Risk Behavior and HIV Exposure among Illicit Drug Users

    Science.gov (United States)

    Scherer, Michael; Trenz, Rebecca; Harrell, Paul; Mauro, Pia; Latimer, William

    2015-01-01

    Objectives The current study examined how drinking severity among injection and non-injection drug users is associated with sex risk behaviors and risk of HIV exposure. Methods The study is a secondary analysis of an investigation of risk factors among drug users in Baltimore known as the NEURO-HIV Epidemiologic Study. Participants (N = 557) completed an interview, self-reported 30-day alcohol use, lifetime injection and non-injection drug use, and provided blood samples to screen for HIV. Participants were grouped into one of three drinking severity conditions: Abstinent (no reported alcohol use in prior 30-days), Moderate Alcohol Use (≤30 drinks for females, or ≤ 60 drinks for males), or Problematic Alcohol Use (>30 drinks for females, or >60 drinks for males). Drinking severity groups were significantly different on lifetime injection drug use, heroin injection, snorting/sniffing cocaine, and smoking crack. Results Logistic regression analyses found problematic alcohol users to be more likely than alcohol abstainers to inject drugs before or during sex (AOR = 5.78; 95% CI = 2.07-16.10), and more likely than moderate alcohol users to use alcohol before/during sex (AOR = 4.96; 95% CI = 2.09-11.81), inject drugs before/during sex (AOR = 2.96; 95% CI = 1.29-6.80) and to be HIV+ among Black participants (AOR = 2.72; 95% CI = 1.14-6.49). Conclusions These results outline the necessity for research and clinical intervention among this population to reduce sex risk behaviors and potential HIV exposure, while highlighting the need to examine drinking severity as a predictor of sex risk behaviors. PMID:23617865

  19. Oral Fluid vs. Urine Analysis to Monitor Synthetic Cannabinoids and Classic Drugs Recent Exposure.

    Science.gov (United States)

    Blandino, Vincent; Wetzel, Jillian; Kim, Jiyoung; Haxhi, Petrit; Curtis, Richard; Concheiro, Marta

    2017-01-01

    Urine is a common biological sample to monitor recent drug exposure, and oral fluid is an alternative matrix of increasing interest in clinical and forensic toxicology. Limited data are available about oral fluid vs. urine drug disposition, especially for synthetic cannabinoids. To compare urine and oral fluid as biological matrices to monitor recent drug exposure among HIV-infected homeless individuals. Seventy matched urine and oral fluid samples were collected from 13 participants. Cannabis, amphetamines, benzodiazepines, cocaine and opiates were analyzed in urine by the enzyme-multipliedimmunoassay- technique and in oral fluid by liquid chromatography tandem mass spectrometry (LCMSMS). Eleven synthetic cannabinoids were analyzed in urine and in oral fluid by LC-MSMS. Five oral fluid samples were positive for AB-FUBINACA. In urine, 4 samples tested positive for synthetic cannabinoids PB-22, 5-Fluoro-PB-22, AB-FUBINACA, and metabolites UR-144 5-pentanoic acid and UR-144 4-hydroxypentyl. In only one case, oral fluid and urine results matched, both specimens being AB-FUBINACA positive. For cannabis, 40 samples tested positive in urine and 30 in oral fluid (85.7% match). For cocaine, 37 urine and 52 oral fluid samples were positive (75.7% match). Twenty-four urine samples were positive for opiates, and 25 in oral fluid (81.4% match). For benzodiazepines, 23 samples were positive in urine and 25 in oral fluid (85.7% match). These results offer new information about drugs disposition between urine and oral fluid. Oral fluid is a good alternative matrix to urine for monitoring cannabis, cocaine, opiates and benzodiazepines recent use; however, synthetic cannabinoids showed mixed results. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Repetitive thinking, executive functioning, and depressive mood in the elderly.

    Science.gov (United States)

    Philippot, Pierre; Agrigoroaei, Stefan

    2017-11-01

    Previous findings and the depressive-executive dysfunction hypothesis suggest that the established association between executive functioning and depression is accounted for by repetitive thinking. Investigating the association between executive functioning, repetitive thinking, and depressive mood, the present study empirically tested this mediational model in a sample of older adults, while focusing on both concrete and abstract repetitive thinking. This latter distinction is important given the potential protective role of concrete repetitive thinking, in contrast to the depletive effect of abstract repetitive thinking. A sample of 43 elderly volunteers, between 75 and 95 years of age, completed tests of executive functioning (the Stroop test, the Trail Making test, and the Fluency test), and questionnaires of repetitive thinking and depression. Positive correlations were observed between abstract repetitive thinking and depressive mood, and between concrete repetitive thinking and executive functioning; a negative correlation was observed between depressive mood and executive functioning. Further, mediational analysis evidenced that the relation between executive functioning and depressive mood was mediated by abstract repetitive thinking. The present data provide, for the first time, empirical support to the depressive-executive dysfunction hypothesis: the lack of executive resources would favor a mode of abstract repetitive thinking, which in turn would deplete mood. It suggests that clinical intervention targeting depression in the elderly should take into consideration repetitive thinking modes and the executive resources needed to disengage from rumination.

  1. Evaluation of lethal effect of microwave exposure on protoscolices of hydatid cyst in vitro

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    Zahra Eslamirad

    2015-10-01

    Full Text Available Objective: To investigate the lethal effect of microwave radiation on protoscolices of hydatid cyst. Methods: The protoscolices were divided in two separate groups. The first group received continuous irradiation while the second group received repetitive irradiation. According to the exposure time, the first and the second groups were divided into 8 subgroups. Non-treated protoscolices were considered as the control in each experiment. The protoscolex mortality rate was calculated, and changes in temperature difference in protoscolex suspension before and after the irradiation and the mortality rate with the increase of exposure time were recorded. Results: The results showed that microwave was able to increase the mortality rate of protoscolices in hydatid cyst. The mortality rate from 20% in 20 s of continuous exposure was increased to 100% in 50 s. Also, the differences between the mortality rates in subgroups of the first and the second groups and the control were significant (P < 0.001. Although the effect of temperature change in repetitive irradiation was not significant, non-thermal repetitive irradiation effects were obviously stronger than the thermal continuous irradiation effects. Conclusions: It seems that, microwaves especially in the repetitive mode, may be used as a supplementary measure for both treatment and prevention of hydatidosis.

  2. Persistence of a hyperthermic sign-reversal during nitrous oxide inhalation despite cue-exposure treatment with and without a drug-onset cue.

    Science.gov (United States)

    Kaiyala, Karl J; Woods, Stephen C; Ramsay, Douglas S

    2014-01-01

    We asked whether chronic tolerance and the hyperthermic sign-reversal induced by repeated 60% N 2 O exposures could be extinguished using a cue-exposure paradigm. Rats received 18 N 2 O administrations in a total calorimetry system that simultaneously measures core temperature (Tc), metabolic heat production (HP), and body heat loss (HL). Each exposure entailed a 2-h baseline period followed by a 1.5-h N 2 O exposure. The 18 drug exposures induced a robust intra-administration hyperthermia in which the initial hypothermic effect of N 2 O inverted to a significant hyperthermic sign-reversal during N 2 O inhalation due primarily to an acquired robust increase in HP. The rats were then randomized to one of three extinction procedures (n=8/procedure) over a 20-d interval: 1) a N 2 O-abstinent home-cage group (HC) that received only the usual animal care; 2) a cue-exposure group (CEXP) in which the animals were placed in the calorimeter 8 times but received no N 2 O; and 3) a drug-onset-cue group (DOC) in which animals received a brief N 2 O exposure in the calorimeter that mimicked the first 3 min of an actual 60% N 2 O trial. Following the extinction sessions, all rats received a 60% N 2 O test trial and Tc, HP and HL were assessed. The hyperthermic sign-reversal remained fully intact during the test trial, with no significant differences observed among groups in any post-baseline change in any thermal outcome. These data suggest that cue exposure may not be an efficacious strategy to reduce sign-reversals that develop with chronic drug use.

  3. Safety analysis of occupational exposure of healthcare workers to residual contaminations of cytotoxic drugs using FMECA security approach.

    Science.gov (United States)

    Le, Laetitia Minh Mai; Reitter, Delphine; He, Sophie; Bonle, Franck Té; Launois, Amélie; Martinez, Diane; Prognon, Patrice; Caudron, Eric

    2017-12-01

    Handling cytotoxic drugs is associated with chemical contamination of workplace surfaces. The potential mutagenic, teratogenic and oncogenic properties of those drugs create a risk of occupational exposure for healthcare workers, from reception of starting materials to the preparation and administration of cytotoxic therapies. The Security Failure Mode Effects and Criticality Analysis (FMECA) was used as a proactive method to assess the risks involved in the chemotherapy compounding process. FMECA was carried out by a multidisciplinary team from 2011 to 2016. Potential failure modes of the process were identified based on the Risk Priority Number (RPN) that prioritizes corrective actions. Twenty-five potential failure modes were identified. Based on RPN results, the corrective actions plan was revised annually to reduce the risk of exposure and improve practices. Since 2011, 16 specific measures were implemented successively. In six years, a cumulative RPN reduction of 626 was observed, with a decrease from 912 to 286 (-69%) despite an increase of cytotoxic compounding activity of around 23.2%. In order to anticipate and prevent occupational exposure, FMECA is a valuable tool to identify, prioritize and eliminate potential failure modes for operators involved in the cytotoxic drug preparation process before the failures occur. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Political violence exposure, adolescent school violence, and drug use: The mediating role of school support and posttraumatic stress.

    Science.gov (United States)

    Fang, Lin; Schiff, Miriam; Benbenishty, Rami

    2016-01-01

    Adolescents may engage in risk behaviors to cope with the negative psychological impacts resulting from exposure to political violence. Guided by the Deterioration Deterrence Model and General Strain Theory, the present study assessed the mediating role of school support and posttraumatic stress (PTS) on two adolescent risk behaviors (i.e., school violence and drug use) among Arab and Jewish Israeli adolescents. We analyzed data from a nationally representative survey that consisted of 4,733 Israeli high school students (54.5% females; 63.2% Jewish) following the Second Lebanon War. Structural equation modeling using weighted data bootstrapped with 2,000 iterations evaluated the mediated effects of school support and PTS. The results showed that both school support and PTS mediated the pathways from political violence exposure to school violence and drug use. However, although school support and PTS fully mediated the relationship between political violence exposure and these risk behaviors for Jewish students, school support and PTS only partially mediated the relationships for Arab students. While school support can help decrease the detrimental effect of exposure to terrorism and war, Israeli adolescents exposed to more political violence may perceive receiving less school support than those experiencing less exposure. Findings of this study provide evidence for the theorized mediated pathways between political violence exposure and adolescent risk behaviors by PTS and school support. The study serves as a basis for future research that can unpack the relationship between exposure to political violence and adolescent risk-taking behaviors. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  5. Prediction of Relative In Vivo Metabolite Exposure from In Vitro Data Using Two Model Drugs: Dextromethorphan and Omeprazole

    Science.gov (United States)

    Lutz, Justin D.

    2012-01-01

    Metabolites can have pharmacological or toxicological effects, inhibit metabolic enzymes, and be used as probes of drug-drug interactions or specific cytochrome P450 (P450) phenotypes. Thus, better understanding and prediction methods are needed to characterize metabolite exposures in vivo. This study aimed to test whether in vitro data could be used to predict and rationalize in vivo metabolite exposures using two model drugs and P450 probes: dextromethorphan and omeprazole with their primary metabolites dextrorphan, 5-hydroxyomeprazole (5OH-omeprazole), and omeprazole sulfone. Relative metabolite exposures were predicted using metabolite formation and elimination clearances. For dextrorphan, the formation clearances of dextrorphan glucuronide and 3-hydroxymorphinan from dextrorphan in human liver microsomes were used to predict metabolite (dextrorphan) clearance. For 5OH-omeprazole and omeprazole sulfone, the depletion rates of the metabolites in human hepatocytes were used to predict metabolite clearance. Dextrorphan/dextromethorphan in vivo metabolite/parent area under the plasma concentration versus time curve ratio (AUCm/AUCp) was overpredicted by 2.1-fold, whereas 5OH-omeprazole/omeprazole and omeprazole sulfone/omeprazole were predicted within 0.75- and 1.1-fold, respectively. The effect of inhibition or induction of the metabolite's formation and elimination on the AUCm/AUCp ratio was simulated. The simulations showed that unless metabolite clearance pathways are characterized, interpretation of the metabolic ratios is exceedingly difficult. This study shows that relative in vivo metabolite exposure can be predicted from in vitro data and characterization of secondary metabolism of probe metabolites is critical for interpretation of phenotypic data. PMID:22010218

  6. Directed PCR-free engineering of highly repetitive DNA sequences

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    Preissler Steffen

    2011-09-01

    Full Text Available Abstract Background Highly repetitive nucleotide sequences are commonly found in nature e.g. in telomeres, microsatellite DNA, polyadenine (poly(A tails of eukaryotic messenger RNA as well as in several inherited human disorders linked to trinucleotide repeat expansions in the genome. Therefore, studying repetitive sequences is of biological, biotechnological and medical relevance. However, cloning of such repetitive DNA sequences is challenging because specific PCR-based amplification is hampered by the lack of unique primer binding sites resulting in unspecific products. Results For the PCR-free generation of repetitive DNA sequences we used antiparallel oligonucleotides flanked by restriction sites of Type IIS endonucleases. The arrangement of recognition sites allowed for stepwise and seamless elongation of repetitive sequences. This facilitated the assembly of repetitive DNA segments and open reading frames encoding polypeptides with periodic amino acid sequences of any desired length. By this strategy we cloned a series of polyglutamine encoding sequences as well as highly repetitive polyadenine tracts. Such repetitive sequences can be used for diverse biotechnological applications. As an example, the polyglutamine sequences were expressed as His6-SUMO fusion proteins in Escherichia coli cells to study their aggregation behavior in vitro. The His6-SUMO moiety enabled affinity purification of the polyglutamine proteins, increased their solubility, and allowed controlled induction of the aggregation process. We successfully purified the fusions proteins and provide an example for their applicability in filter retardation assays. Conclusion Our seamless cloning strategy is PCR-free and allows the directed and efficient generation of highly repetitive DNA sequences of defined lengths by simple standard cloning procedures.

  7. Executive function and mental health in adopted children with a history of recreational drug exposures.

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    Brian J Piper

    Full Text Available Adoptive children are at increased risk for problematic behaviors but the origin of these individual differences in neurobehavioral function is unclear. This investigation examined whether adopted children with prenatal exposure to a wide variety of recreational drugs exhibited higher scores (i.e. more problems with executive function and psychiatric symptomology. Caregivers of children ages 5 to 18 completed an online survey with items about use of alcohol, nicotine, or methamphetamine during pregnancy followed by the Behavior Rating Inventory of Executive Function (BRIEF, N = 437 including 59 adoptive parents or the Child Behavior Checklist (CBCL, N = 549 including 54 adoptive parents. Relative to a comparison group of children raised by their biological parents, adoptive children that were polysubstance exposed during prenatal development exhibited higher rates of academic difficulties and were behind their classmates in math and reading. Adoptive children had statistically and clinically significant higher BRIEF ratings and this pattern was similar for boys and girls. CBCL ratings were significantly increased in adoptive children, particularly for Externalizing and Attention problems. Adoptive children with a history of polysubstance exposures including alcohol, nicotine, and methamphetamine are at heightened risk for difficulties with executive function as well as various psychopathologies. These findings suggest that increased monitoring to identify and implement remediation strategies may be warranted for adopted children with a history of in utero drug exposures.

  8. Lingual Kinematics during Rapid Syllable Repetition in Parkinson's Disease

    Science.gov (United States)

    Wong, Min Ney; Murdoch, Bruce E.; Whelan, Brooke-Mai

    2012-01-01

    Background: Rapid syllable repetition tasks are commonly used in the assessment of motor speech disorders. However, little is known about the articulatory kinematics during rapid syllable repetition in individuals with Parkinson's disease (PD). Aims: To investigate and compare lingual kinematics during rapid syllable repetition in dysarthric…

  9. Exposure to Rats and Rat-Associated Leptospira and Bartonella Species Among People Who Use Drugs in an Impoverished, Inner-City Neighborhood of Vancouver, Canada.

    Science.gov (United States)

    McVea, David A; Himsworth, Chelsea G; Patrick, David M; Lindsay, L Robbin; Kosoy, Michael; Kerr, Thomas

    2018-02-01

    Rat infestations are common, particularly in impoverished, inner-city neighborhoods. However, there has been little research into the nature and consequences of rat exposure in these neighborhoods, particularly in Canada. In this study, we sought to characterize exposure to rats and rat-associated Leptospira interrogans and Bartonella tribocorum, as well as risk factors associated with exposure, in residents (n = 202) of the Downtown Eastside (DTES) neighborhood of Vancouver, Canada. There was no evidence of exposure to rat-associated L. interrogans but 6/202 (3.0%) of participants were exposed to B. tribocorum, which is known to be circulating among DTES rats. We also found that frequent and close rat exposure was common among DTES residents, and that this exposure was particularly associated with injection drug use and outdoor income-generating activities (e.g., drug dealing). These risk factors may be good targets for interventions geared toward effectively reducing rat exposure.

  10. Influences on participant reporting in the World Health Organisation drugs exposure pregnancy registry; a qualitative study.

    Science.gov (United States)

    Allen, Elizabeth N; Gomes, Melba; Yevoo, Lucy; Egesah, Omar; Clerk, Christine; Byamugisha, Josaphat; Mbonye, Anthony; Were, Edwin; Mehta, Ushma; Atuyambe, Lynn M

    2014-10-31

    The World Health Organisation has designed a pregnancy registry to investigate the effect of maternal drug use on pregnancy outcomes in resource-limited settings. In this sentinel surveillance system, detailed health and drug use data are prospectively collected from the first antenatal clinic visit until delivery. Over and above other clinical records, the registry relies on accurate participant reports about the drugs they use. Qualitative methods were incorporated into a pilot registry study during 2010 and 2011 to examine barriers to women reporting these drugs and other exposures at antenatal clinics, and how they might be overcome. Twenty-seven focus group discussions were conducted in Ghana, Kenya and Uganda with a total of 208 women either enrolled in the registry or from its source communities. A question guide was designed to uncover the types of exposure data under- or inaccurately reported at antenatal clinics, the underlying reasons, and how women prefer to be asked questions. Transcripts were analysed thematically. Women said it was important for them to report everything they had used during pregnancy. However, they expressed reservations about revealing their consumption of traditional, over-the-counter medicines and alcohol to antenatal staff because of anticipated negative reactions. Some enrolled participants' improved relationship with registry staff facilitated information sharing and the registry tools helped overcome problems with recall and naming of medicines. Decisions about where women sought care, which influenced medicines used and antenatal clinic attendance, were influenced by pressure within and outside of the formal healthcare system to conform to conflicting behaviours. Conversations also reflected women's responsibilities for producing a healthy baby. Women in this study commonly take traditional medicines in pregnancy, and to a lesser extent over-the-counter medicines and alcohol. The World Health Organisation pregnancy registry

  11. Mixed Messages, Mixed Outcomes: Exposure to Direct-to-Consumer Advertising for Statin Drugs is Associated with More Frequent Visits to Fast Food Restaurants and Exercise.

    Science.gov (United States)

    Niederdeppe, Jeff; Avery, Rosemary J; Kellogg, Maxwell D; Mathios, Alan

    2017-07-01

    This study examines whether exposure to direct-to-consumer advertising (DTCAs) for statin drugs is associated with non-pharmaceutical behaviors to prevent cardiovascular disease. We focus on the relationship between statin drug DTCA exposure and the frequency of (a) visits to fast-food restaurants and (b) exercise. We combine data on the televised broadcast availability of statin drug DTCAs in large media markets in the United States with 18 waves of the Simmons National Consumer Survey (NCS; n = 120, 229) from 2001 to 2009. We find that statin drug DTCA exposure is associated, in a dose-response pattern, with modest increases in the frequency of exercise and large increases in the frequency of fast-food-restaurant visits. The relationship between statin DTCA exposure and fast-food-restaurant visits were largely consistent in direction but differed in magnitude between those without a previous diagnosis of high cholesterol and those treating high cholesterol with a statin. We conclude with a discussion of the implications of these results for future research on pharmaceutical DTCA and population health.

  12. Negative effects of item repetition on source memory.

    Science.gov (United States)

    Kim, Kyungmi; Yi, Do-Joon; Raye, Carol L; Johnson, Marcia K

    2012-08-01

    In the present study, we explored how item repetition affects source memory for new item-feature associations (picture-location or picture-color). We presented line drawings varying numbers of times in Phase 1. In Phase 2, each drawing was presented once with a critical new feature. In Phase 3, we tested memory for the new source feature of each item from Phase 2. Experiments 1 and 2 demonstrated and replicated the negative effects of item repetition on incidental source memory. Prior item repetition also had a negative effect on source memory when different source dimensions were used in Phases 1 and 2 (Experiment 3) and when participants were explicitly instructed to learn source information in Phase 2 (Experiments 4 and 5). Importantly, when the order between Phases 1 and 2 was reversed, such that item repetition occurred after the encoding of critical item-source combinations, item repetition no longer affected source memory (Experiment 6). Overall, our findings did not support predictions based on item predifferentiation, within-dimension source interference, or general interference from multiple traces of an item. Rather, the findings were consistent with the idea that prior item repetition reduces attention to subsequent presentations of the item, decreasing the likelihood that critical item-source associations will be encoded.

  13. Development of the drug for acute treatment of emergent exposure to radiation by nuclear power plant accident

    International Nuclear Information System (INIS)

    Matsumoto, Hideki

    2012-01-01

    Described is a flow of authors' studies on the drug development in the title, aiming to save the life after the emergent exposure to peri-lethal dose. Medicals with radioprotective properties have been essentially those to be given before the exposure. Authors have studied the mechanism of bystander effect of non-exposed cells where they, localizing around the directly radiation-exposed cells, acquire the radioresistance; have found that nitrogen oxide (NO) is one of mediators for the effect; and have thought to apply the NO generating agents for the drug already clinically available, such as sodium nitroprusside (SNP), isosorbide nitrate (ISDN), nicolandil (NC), nitroglycerin (NG), and nipradilol (NP). ISDN, NC, NG and NP exhibited no in vitro-toxicity in colony formation of human fibroblast AG1522 cells up to 30 micro-M whereas SNP was toxic at the level >3 micro-M due to the formation of cyanide which could be detoxicated in vivo. Actually, the 5 agents were not toxic in vivo. When male jcl/ICR mice were irradiated with lethal dose of 7.5 Gy X-ray and the 5 agents were given to make their level 30 micro-M immediately, 1, 2 and 7 days after the exposure, 3/5 animals given SNP survived. With the half lethal dose of 6.5 Gy X-ray and 50 animals, SNP was further examined in details: survival was found to be 75-85% in mice given SNP in contrast to 30-40% in the control and the life-saving effect was suggested to be due to suppression of intestinal and marrow death with the improved feature of peripheral platelet and leukocyte. Thus SNP, a drug for angina pectoris, is found radioprotective even post exposure. (T.T.)

  14. Evaluating exposure to land degradation in association with repetitive armed conflicts in North Lebanon using multi-temporal satellite data

    NARCIS (Netherlands)

    Mitri, George; Nader, Manal; van der Molen, I.; Lovett, Jonathan

    2014-01-01

    Repetitive armed conflicts may be directly and indirectly responsible for severe biophysical modification to the environment. This, in turn, makes land more susceptible to degradation. Mapping and monitoring land degradation are essential for designing and implementing post-conflict recovery plans

  15. Exposure to reactive intermediate-inducing drugs during pregnancy and the incident use of psychotropic medications among children

    NARCIS (Netherlands)

    Tran, Yen-Hao; Groen, Henk; Bergman, Jorieke E H; Hak, Eelko; Wilffert, Bob

    Purpose Our study aimed to investigate the association between prenatal exposure to reactive intermediate (RI)-inducing drugs and the initiation of psychotropic medications among children. Methods We designed a cohort study using a pharmacy prescription database. Pregnant women were considered

  16. Pre-Lexical Disorders in Repetition Conduction Aphasia

    Science.gov (United States)

    Sidiropoulos, Kyriakos; de Bleser, Ria; Ackermann, Hermann; Preilowski, Bruno

    2008-01-01

    At the level of clinical speech/language evaluation, the repetition type of conduction aphasia is characterized by repetition difficulties concomitant with reduced short-term memory capacities, in the presence of fluent spontaneous speech as well as unimpaired naming and reading abilities. It is still unsettled which dysfunctions of the…

  17. Evidence for the involvement of a nonlexical route in the repetition of familiar words: A comparison of single and dual route models of auditory repetition.

    Science.gov (United States)

    Hanley, J Richard; Dell, Gary S; Kay, Janice; Baron, Rachel

    2004-03-01

    In this paper, we attempt to simulate the picture naming and auditory repetition performance of two patients reported by Hanley, Kay, and Edwards (2002), who were matched for picture naming score but who differed significantly in their ability to repeat familiar words. In Experiment 1, we demonstrate that the model of naming and repetition put forward by Foygel and Dell (2000) is better able to accommodate this pattern of performance than the model put forward by Dell, Schwartz, Martin, Saffran, and Gagnon (1997). Nevertheless, Foygel and Dell's model underpredicted the repetition performance of both patients. In Experiment 2, we attempt to simulate their performance using a new dual route model of repetition in which Foygel and Dell's model is augmented by an additional nonlexical repetition pathway. The new model provided a more accurate fit to the real-word repetition performance of both patients. It is argued that the results provide support for dual route models of auditory repetition.

  18. Long-term repetitive sodium lauryl sulfate-induced irritation of the skin: an in vivo study.

    Science.gov (United States)

    Branco, Nara; Lee, Ivy; Zhai, Hongbo; Maibach, Howard I

    2005-11-01

    Skin may adapt to topical irritants through accommodation. This study focuses on long-term exposure to irritants and attempts to demonstrate accommodation. Sodium lauryl sulfate (SLS) induced irritant contact dermatitis at 3 concentrations (0.025% to 0.075%). Distilled water, acetone and an empty chamber served as controls. Experimental compounds were applied to forearms of 7 healthy volunteers for 24 hr before replacing by a fresh chamber for 6 non-consecutive weeks over 103 days. Possible accommodation was quantified by visual scoring (erythema and dryness) and by bioengineering parameters: transepidermal water loss (TEWL), capacitance, chromametry and laser Doppler flowmetry (LDF). Significant erythema, dryness, elevated TEWL, skin colour reflectance and LDF values occurred during the exposure periods. Upon repeat exposure, an immediate and augmented response in erythema, TEWL, skin colour reflectance and LDF developed. However, irritant skin changes were not sustained. Irritation parameters return to baseline after cessation of exposure. There was no evidence of sustained irritation or accommodation after the last exposure. Study findings do not document sustained accommodation or adaptive hyposensitivity after long-term repetitive irritant exposure under these test conditions. Alternative models should be developed to prove or disprove the accommodation hypothesis.

  19. Between-language repetition priming in antonym generation: evidence that translation-equivalent adjectives have shared conceptual representations across languages.

    Science.gov (United States)

    Taylor, Randolph S; Francis, Wendy S

    2017-03-01

    Previous literature has demonstrated conceptual repetition priming across languages in bilinguals. This between-language priming effect is taken as evidence that translation equivalents have shared conceptual representations across languages. However, the vast majority of this research has been conducted using only concrete nouns as stimuli. The present experiment examined conceptual repetition priming within and between languages in adjectives, a part of speech not previously investigated in studies of bilingual conceptual representation. The participants were 100 Spanish-English bilinguals who had regular exposure to both languages. At encoding, participants performed a shallow processing task and a deep-processing task on English and Spanish adjectives. At test, they performed an antonym-generation task in English, in which the target responses were either adjectives presented at encoding or control adjectives not previously presented. The measure of priming was the response time advantage for producing repeated adjectives relative to control adjectives. Significant repetition priming was observed both within and between languages under deep, but not shallow, encoding conditions. The results indicate that the conceptual representations of adjective translation equivalents are shared across languages.

  20. Relationship between the number of repetitions and selected percentages of one repetition maximum in free weight exercises in trained and untrained men.

    Science.gov (United States)

    Shimano, Tomoko; Kraemer, William J; Spiering, Barry A; Volek, Jeff S; Hatfield, Disa L; Silvestre, Ricardo; Vingren, Jakob L; Fragala, Maren S; Maresh, Carl M; Fleck, Steven J; Newton, Robert U; Spreuwenberg, Luuk P B; Häkkinen, Keijo

    2006-11-01

    Resistance exercise intensity is commonly prescribed as a percent of 1 repetition maximum (1RM). However, the relationship between percent 1RM and the number of repetitions allowed remains poorly studied, especially using free weight exercises. The purpose of this study was to determine the maximal number of repetitions that trained (T) and untrained (UT) men can perform during free weight exercises at various percentages of 1RM. Eight T and 8 UT men were tested for 1RM strength. Then, subjects performed 1 set to failure at 60, 80, and 90% of 1RM in the back squat, bench press, and arm curl in a randomized, balanced design. There was a significant (p squat than the bench press or arm curl at 60% 1RM for T and UT. At 80 and 90% 1RM, there were significant differences between the back squat and other exercises; however, differences were much less pronounced. No differences in number of repetitions performed at a given exercise intensity were noted between T and UT (except during bench press at 90% 1RM). In conclusion, the number of repetitions performed at a given percent of 1RM is influenced by the amount of muscle mass used during the exercise, as more repetitions can be performed during the back squat than either the bench press or arm curl. Training status of the individual has a minimal impact on the number of repetitions performed at relative exercise intensity.

  1. Understanding work related musculoskeletal pain: does repetitive work cause stress symptoms?

    DEFF Research Database (Denmark)

    Bonde, J. P.; Mikkelsen, S.; Andersen, JH

    2005-01-01

    for development of regional pain in repetitive work, stress symptoms would likely be on the causal path. AIMS: To examine whether objective measures of repetitive monotonous work are related to occurrence and development of stress symptoms. METHODS: In 1994-95, 2033 unskilled workers with continuous repetitive...... Profile Inventory. RESULTS: Repetitive work, task cycle time, and quantified measures of repetitive upper extremity movements including force requirements were not related to occurrence of stress symptoms at baseline or development of stress symptoms during three years of follow up. CONCLUSIONS......: The findings do not indicate that repetitive work is associated with stress symptoms, but small effects cannot be ruled out. Thus the results question the importance of mental stress mechanisms in the causation of regional pain related to repetitive work. However, the findings should be interpreted...

  2. Selective attention modulates neural substrates of repetition priming and "implicit" visual memory: suppressions and enhancements revealed by FMRI.

    Science.gov (United States)

    Vuilleumier, Patrik; Schwartz, Sophie; Duhoux, Stéphanie; Dolan, Raymond J; Driver, Jon

    2005-08-01

    Attention can enhance processing for relevant information and suppress this for ignored stimuli. However, some residual processing may still arise without attention. Here we presented overlapping outline objects at study, with subjects attending to those in one color but not the other. Attended objects were subsequently recognized on a surprise memory test, whereas there was complete amnesia for ignored items on such direct explicit testing; yet reliable behavioral priming effects were found on indirect testing. Event-related fMRI examined neural responses to previously attended or ignored objects, now shown alone in the same or mirror-reversed orientation as before, intermixed with new items. Repetition-related decreases in fMRI responses for objects previously attended and repeated in the same orientation were found in the right posterior fusiform, lateral occipital, and left inferior frontal cortex. More anterior fusiform regions also showed some repetition decreases for ignored objects, irrespective of orientation. View-specific repetition decreases were found in the striate cortex, particularly for previously attended items. In addition, previously ignored objects produced some fMRI response increases in the bilateral lingual gyri, relative to new objects. Selective attention at exposure can thus produce several distinct long-term effects on processing of stimuli repeated later, with neural response suppression stronger for previously attended objects, and some response enhancement for previously ignored objects, with these effects arising in different brain areas. Although repetition decreases may relate to positive priming phenomena, the repetition increases for ignored objects shown here for the first time might relate to processes that can produce "negative priming" in some behavioral studies. These results reveal quantitative and qualitative differences between neural substrates of long-term repetition effects for attended versus unattended objects.

  3. Inverted U-shaped model: How frequent repetition affects perceived risk

    OpenAIRE

    Xi Lu; Xiaofei Xie; Lu Liu

    2015-01-01

    We asked how repeated media reports on technological hazards influence an individual's risk perception. We looked for two contradictory effects, an increasing effect of repetition on perceived risk with the first few repetitions and a decreasing effect with later repetitions, leading to the inverted U-shaped pattern. In an experiment, we demonstrated the inverted U-shaped relationship between the repetition and perceived risk in the context of food risk. The finding broaden...

  4. Impaired reproduction after exposure to ADHD drugs

    DEFF Research Database (Denmark)

    Danborg, Pia Brandt; Simonsen, Anders Lykkemark; Gøtzsche, Peter C

    2017-01-01

    BACKGROUND: Few studies have reported on long-term harms caused by ADHD drugs but they are known to impair growth. OBJECTIVE: To assess whether ADHD drugs impair reproduction in mammals. METHODS: Systematic review of reproduction in studies of animals treated with ADHD drugs. DATA SOURCES: Pub....... CONCLUSION: ADHD drugs impair the reproduction in animals....

  5. Simple strategy to assess linezolid exposure in patients with multi-drug-resistant and extensively-drug-resistant tuberculosis.

    Science.gov (United States)

    Kamp, Jasper; Bolhuis, Mathieu S; Tiberi, Simon; Akkerman, Onno W; Centis, Rosella; de Lange, Wiel C; Kosterink, Jos G; van der Werf, Tjip S; Migliori, Giovanni B; Alffenaar, Jan-Willem C

    2017-06-01

    Linezolid is used increasingly for the treatment of multi-drug-resistant (MDR) and extensively-drug-resistant (XDR) tuberculosis (TB). However, linezolid can cause severe adverse events, such as peripheral and optical neuropathy or thrombocytopenia related to higher drug exposure. This study aimed to develop a population pharmacokinetic model to predict the area under the concentration curve (AUC) for linezolid using a limited number of blood samples. Data from patients with MDR-/XDR-TB who received linezolid and therapeutic drug monitoring as part of their TB treatment were used. Mw\\Pharm 3.82 (Mediware, Zuidhorn, The Netherlands) was used to develop a population pharmacokinetic model and limited sampling strategy (LSS) for linezolid. LSS was evaluated over a time span of 6 h. Blood sampling directly before linezolid administration and 2 h after linezolid administration were considered to be the most clinically relevant sampling points. The model and LSS were evaluated by analysing the correlation between AUC 12h,observed and AUC 12h,estimated . In addition, LSS was validated with an external group of patients with MDR-/XDR-TB from Sondalo, Italy. Fifty-two pharmacokinetic profiles were used to develop the model. Thirty-three profiles with a 300 mg dosing regimen and 19 profiles with a 600 mg dosing regimen were obtained. Model validation showed prediction bias of 0.1% and r 2 of 0.99. Evaluation of the most clinically relevant LSS showed prediction bias of 4.8% and r 2 of 0.97. The root mean square error corresponding to the most relevant LSS was 6.07%. The developed LSS could be used to enable concentration-guided dosing of linezolid. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  6. Prenatal drug exposure: infant and toddler outcomes.

    Science.gov (United States)

    Bandstra, Emmalee S; Morrow, Connie E; Mansoor, Elana; Accornero, Veronica H

    2010-04-01

    This manuscript provides an overview of the current scientific literature on the impact of maternal drug use, specifically opioids and cocaine, during pregnancy on the acute and long-term outcomes of infants and toddlers from birth through age 3 years. Emphasis with regard to opioids is placed on heroin and opioid substitutes used to treat opioid addiction, including methadone, which has long been regarded as the standard of care in pregnancy, and buprenorphine, which is increasingly being investigated and prescribed as an alternative to methadone. Controlled studies comparing methadone at high and low doses, as well as those comparing methadone with buprenorphine, are highlighted and the diagnosis and management of neonatal abstinence syndrome is discussed. Over the past two decades, attention of the scientific and lay communities has also been focused on the potential adverse effects of cocaine and crack cocaine, especially during the height of the cocaine epidemic in the United States. Herein, the findings are summarized from prospective studies comparing cocaine-exposed with non-cocaine-exposed infants and toddlers with respect to anthropometric growth, infant neurobehavior, visual and auditory function, and cognitive, motor, and language development. The potentially stigmatizing label of the so-called "crack baby" preceded the evidence now accumulating from well-designed prospective investigations that have revealed less severe sequelae in the majority of prenatally exposed infants than originally anticipated. In contrast to opioids, which may produce neonatal abstinence syndrome and infant neurobehavioral deficits, prenatal cocaine exposure appears to be associated with what has been described as statistically significant but subtle decrements in neurobehavioral, cognitive, and language function, especially when viewed in the context of other exposures and the caregiving environment which may mediate or moderate the effects. Whether these early findings may

  7. Translation of Syntactic Repetitions as Formal-Aesthetic Marker in Das Brot

    Directory of Open Access Journals (Sweden)

    Rosyidah

    2017-03-01

    Full Text Available Translating repetition as a formal-aesthetic marker in a literary text is a hard task and challenge for translators. The topic of this study is translation of syntactic repetition as formal-aesthetic marker in literary text. The problems examined include: (1 the syntactic repetitions in the source text and (2 the strategies to translate these repetitions carried out by the students. This is a case study with a qualitative approach which is aimed to describe the syntactic repetitions as formal aesthetic markers in the German short story Das Brot written by Wolfgang Borchert and to explain the strategies used by Indonesian students to translate the syntactic repetitions. The research data are repetitive sentences gained from the German short story and from the translated versions done by 60 students. The analysis was carried out interactively and sociosemiotically. The results show that there were repetitions at the sentence level including sentence parts, sentences and content repetition in the source text. The strategies used by the students to translate the repetitions of sentence part and sentence were exact preservation and modified preservation with reduction, implicitation and addition of extra words, avoidance with deletion, explicitation, implicitation, nominalization, and synonymy. In the meantime, content repetitions were translated using the strategy of exact preservation and preservation with modification by adding extra words and using role-based terms of address. Thus, the results lead to two new variations of modified preservation, namely preservation by adding extra words and by changing addressing terms and one new variation of avoidance that is explicitation.

  8. Grade Repetition in Queensland State Prep Classes

    Science.gov (United States)

    Anderson, Robyn

    2012-01-01

    The current study considers grade repetition rates in the early years of schooling in Queensland state schools with specific focus on the pre-schooling year, Prep. In particular, it provides empirical evidence of grade repetition in Queensland state schools along with groups of students who are more often repeated. At the same time, much of the…

  9. Visualizing stressful aspects of repetitive motion tasks and opportunities for ergonomic improvements using computer vision.

    Science.gov (United States)

    Greene, Runyu L; Azari, David P; Hu, Yu Hen; Radwin, Robert G

    2017-11-01

    Patterns of physical stress exposure are often difficult to measure, and the metrics of variation and techniques for identifying them is underdeveloped in the practice of occupational ergonomics. Computer vision has previously been used for evaluating repetitive motion tasks for hand activity level (HAL) utilizing conventional 2D videos. The approach was made practical by relaxing the need for high precision, and by adopting a semi-automatic approach for measuring spatiotemporal characteristics of the repetitive task. In this paper, a new method for visualizing task factors, using this computer vision approach, is demonstrated. After videos are made, the analyst selects a region of interest on the hand to track and the hand location and its associated kinematics are measured for every frame. The visualization method spatially deconstructs and displays the frequency, speed and duty cycle components of tasks that are part of the threshold limit value for hand activity for the purpose of identifying patterns of exposure associated with the specific job factors, as well as for suggesting task improvements. The localized variables are plotted as a heat map superimposed over the video, and displayed in the context of the task being performed. Based on the intensity of the specific variables used to calculate HAL, we can determine which task factors most contribute to HAL, and readily identify those work elements in the task that contribute more to increased risk for an injury. Work simulations and actual industrial examples are described. This method should help practitioners more readily measure and interpret temporal exposure patterns and identify potential task improvements. Copyright © 2017. Published by Elsevier Ltd.

  10. RPERT: Repetitive-Projects Evaluation and Review Technique

    Directory of Open Access Journals (Sweden)

    Remon Fayek Aziz

    2014-03-01

    Full Text Available Estimating expected completion probability of any repetitive construction project with a specified/certain duration including repetitive identical activities by using program evaluation and review technique is the most essential part in construction areas since the activities were had optimistic, most likely and pessimistic durations. This paper focuses on the calculation of expected completion probability of any repetitive construction project within a specified/certain duration (contract duration by using Line Of Balance technique (LOB in case of single or multiple number of crews integrated with Program Evaluation and Review Technique (PERT. Repetitive-Projects Evaluation and Review Technique (RPERT, which is a simplified software, will generate the expected project completion probability of a specified/certain duration (contract duration. RPERT software is designed by java programming code system to provide a number of new and unique capabilities, including: (1 Viewing the expected project completion probability according to a set of specified durations per each identical activity (optimistic time, most likely time, and pessimistic time in the analyzed project; (2 Providing seamless integration with available project time calculations. In order to provide the aforementioned capabilities of RPERT, the system is implemented and developed in four main modules: (1 A user interface module; (2 A database module; (3 A running module; and (4 A processing module. At the end, an illustrative example will be presented to demonstrate and verify the applications of proposed software (RPERT, by using probabilistic calculations for repetitive construction projects.

  11. Insufficient fluconazole exposure in pediatric cancer patients and the need for therapeutic drug monitoring in critically ill children

    NARCIS (Netherlands)

    van der Elst, Kim CM; Pereboom, Marieke; van den Heuvel, Edwin R; Kosterink, Jos G W; Scholvinck, Elisabeth H.; Alffenaar, Jan-Willem C

    2014-01-01

    Background. Fluconazole is recommended as first-line treatment in invasive candidiasis in children and infants. Although timely achievement of adequate exposure of fluconazole improves outcome, therapeutic drug monitoring is currently not recommended. Methods. We conducted a retrospective study of

  12. A proposal for a pharmacokinetic interaction significance classification system (PISCS) based on predicted drug exposure changes and its potential application to alert classifications in product labelling.

    Science.gov (United States)

    Hisaka, Akihiro; Kusama, Makiko; Ohno, Yoshiyuki; Sugiyama, Yuichi; Suzuki, Hiroshi

    2009-01-01

    Pharmacokinetic drug-drug interactions (DDIs) are one of the major causes of adverse events in pharmacotherapy, and systematic prediction of the clinical relevance of DDIs is an issue of significant clinical importance. In a previous study, total exposure changes of many substrate drugs of cytochrome P450 (CYP) 3A4 caused by coadministration of inhibitor drugs were successfully predicted by using in vivo information. In order to exploit these predictions in daily pharmacotherapy, the clinical significance of the pharmacokinetic changes needs to be carefully evaluated. The aim of the present study was to construct a pharmacokinetic interaction significance classification system (PISCS) in which the clinical significance of DDIs was considered with pharmacokinetic changes in a systematic manner. Furthermore, the classifications proposed by PISCS were compared in a detailed manner with current alert classifications in the product labelling or the summary of product characteristics used in Japan, the US and the UK. A matrix table was composed by stratifying two basic parameters of the prediction: the contribution ratio of CYP3A4 to the oral clearance of substrates (CR), and the inhibition ratio of inhibitors (IR). The total exposure increase was estimated for each cell in the table by associating CR and IR values, and the cells were categorized into nine zones according to the magnitude of the exposure increase. Then, correspondences between the DDI significance and the zones were determined for each drug group considering the observed exposure changes and the current classification in the product labelling. Substrate drugs of CYP3A4 selected from three therapeutic groups, i.e. HMG-CoA reductase inhibitors (statins), calcium-channel antagonists/blockers (CCBs) and benzodiazepines (BZPs), were analysed as representative examples. The product labelling descriptions of drugs in Japan, US and UK were obtained from the websites of each regulatory body. Among 220

  13. Head circumference at birth and exposure to tobacco, alcohol and illegal drugs during early pregnancy.

    Science.gov (United States)

    Ortega-García, Juan A; Gutierrez-Churango, Jorge E; Sánchez-Sauco, Miguel F; Martínez-Aroca, Miguel; Delgado-Marín, Juan L; Sánchez-Solis, M; Parrilla-Paricio, J J; Claudio, Luz; Martínez-Lage, Juan F

    2012-03-01

    We aimed to assess the effects of exposure to tobacco smoke, alcohol and illegal drugs during early pregnancy on the head circumference (HC) at birth of otherwise healthy neonates. A follow-up study from the first trimester of pregnancy to birth was carried out in 419 neonates. An environmental reproductive health form was used to record data of substance exposure obtained during the first obstetric visit at the end of the first trimester. A multiple linear regression model was created for this purpose. Alcohol intake during pregnancy and medical ionizing radiation exposure were the most significant predictors of HC. The mothers' alcohol consumption increased with the mothers' and fathers' education level, net family income and fathers' alcohol consumption. In contrast, maternal smoking decreased with increasing mothers' and fathers' education level and net family income. About 13% of the surveyed embryos were exposed to illegal drugs. Mild to moderate alcohol consumption diminishes the at-birth HC of theoretically healthy newborns in a linear form. There was no threshold dose. We perceived a need for increasing the awareness, and for training, of health care professionals and parents, in regard to risks of alcohol consumption and for recommending abstinence of these substances in both parents during pregnancy. It should also be remembered that medical ionizing radiation should be performed only during the first half of the cycle in fertile women. We think that our study has an important social impact as it affords data for implementing policies for promoting "healthy pregnancies".

  14. Antiretroviral Drug Activity in Macaques Infected during Pre-Exposure Prophylaxis Has a Transient Effect on Cell-Associated SHIV DNA Reservoirs.

    Directory of Open Access Journals (Sweden)

    Mian-Er Cong

    Full Text Available Pre-exposure prophylaxis (PrEP with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF is a novel HIV prevention strategy. Suboptimal PrEP adherence and HIV infection creates an opportunity for continued antiretroviral drug activity during undiagnosed infection. We previously showed that macaques infected with SHIV during PrEP with FTC/TDF display reduced acute plasma viremias and limited virus diversity. We investigated the effect of PrEP on acute SHIV DNA dynamics and on the size of the persistent virus reservoir in lymphoid tissues.Cell-associated SHIV DNA levels in PBMCs were measured in 8 macaques infected during PrEP with FTC/TDF or single-agent TAF and was compared to those seen in untreated infections (n = 10. PrEP breakthrough infections continued treatment with 1-2 weekly drug doses to model suboptimal drug exposure during undiagnosed HIV infection in humans. SHIV DNA was also measured in lymphoid tissues collected from FTC/TDF PrEP breakthroughs after 1 year of infection.Compared to untreated controls, PrEP infections had reduced plasma RNA viremias both at peak and throughout weeks 1-12 (p<0.005. SHIV DNA levels were also reduced at peak and during the first 12 weeks of infection (p<0.043 but not throughout weeks 12-20. At 1 year, SHIV DNA reservoirs in lymphoid tissues were similar in size among macaques that received PrEP or placebo.Antiviral drug activity due to PrEP limits acute SHIV replication but has only a transient effect on cell-associated SHIV DNA levels. Our model suggests that suboptimal drug exposure in persons that are taking PrEP and become infected with HIV may not be sufficient to reduce the pool of HIV-infected cells, and that treatment intensification may be needed to sustain potential virological benefits from the PrEP regimen.

  15. Subliminal mere exposure: specific, general, and diffuse effects.

    Science.gov (United States)

    Monahan, J L; Murphy, S T; Zajonc, R B

    2000-11-01

    The present research examined the possibility that repeated exposure may simultaneously produce specific and diffuse effects. In Study 1, participants were presented with 5-ms exposures of 25 stimuli each shown once (single-exposure condition) or with five repetitions of 5 stimuli (repeated-exposure condition). Participants in the repeated-exposure condition subsequently rated their own mood more positively than those in the single-exposure condition. Study 2 examined whether affect generated by subliminal repeated exposures transfers to unrelated stimuli. After a subliminal exposure phase, affective reactions to previously exposed stimuli, to new but similar stimuli, and to stimuli from a different category were obtained. Previously exposed stimuli were rated most positively and novel different stimuli least positively. All stimuli were rated more positively in the repeated-exposure condition than in the single-exposure condition. These findings suggest that affect generated by subliminal repeated exposure is sufficiently diffuse to influence ratings of unrelated stimuli and mood.

  16. Is perfectionism associated with academic burnout through repetitive negative thinking?

    Science.gov (United States)

    Garratt-Reed, David; Howell, Joel; Hayes, Lana; Boyes, Mark

    2018-01-01

    Academic burnout is prevalent among university students, although understanding of what predicts burnout is limited. This study aimed to test the direct and indirect relationship between two dimensions of perfectionism (Perfectionistic Concerns and Perfectionistic Strivings) and the three elements of Academic Burnout (Exhaustion, Inadequacy, and Cynicism) through Repetitive Negative Thinking. In a cross-sectional survey, undergraduate students ( n  = 126, M age = 23.64, 79% female) completed well-validated measures of Perfectionism, Repetitive Negative Thinking, and Academic Burnout. Perfectionistic Concerns was directly associated with all elements of burnout, as well as indirectly associated with Exhaustion and Cynicism via Repetitive Negative Thinking. Perfectionistic Strivings was directly associated with less Inadequacy and Cynicism; however, there were no indirect associations between Perfectionistic Strivings and Academic Burnout operating through Repetitive Negative Thinking. Repetitive Negative Thinking was also directly related to more burnout Exhaustion and Inadequacy, but not Cynicism. It is concluded that future research should investigate whether interventions targeting Perfectionistic Concerns and Repetitive Negative Thinking can reduce Academic Burnout in university students.

  17. Repetition code of 15 qubits

    Science.gov (United States)

    Wootton, James R.; Loss, Daniel

    2018-05-01

    The repetition code is an important primitive for the techniques of quantum error correction. Here we implement repetition codes of at most 15 qubits on the 16 qubit ibmqx3 device. Each experiment is run for a single round of syndrome measurements, achieved using the standard quantum technique of using ancilla qubits and controlled operations. The size of the final syndrome is small enough to allow for lookup table decoding using experimentally obtained data. The results show strong evidence that the logical error rate decays exponentially with code distance, as is expected and required for the development of fault-tolerant quantum computers. The results also give insight into the nature of noise in the device.

  18. Hair analysis following chronic smoked-drugs-of-abuse exposure in adults and their toddler: a case report

    Directory of Open Access Journals (Sweden)

    Papaseit Esther

    2011-12-01

    Full Text Available Abstract Introduction Over the past two decades, the study of chronic cocaine and crack cocaine exposure in the pediatric population has been focused on the potential adverse effects, especially in the prenatal period and early childhood. Non-invasive biological matrices have become an essential tool for the assessment of a long-term history of drug of abuse exposure. Case report We analyze the significance of different biomarker values in hair after chronic crack exposure in a two-year-old Caucasian girl and her parents, who are self-reported crack smokers. The level of benzoylecgonine, the principal metabolite of cocaine, was determined in segmented hair samples (0 cm to 3 cm from the scalp, and > 3 cm from the scalp following washing to exclude external contamination. Benzoylecgonine was detectable in high concentrations in the child's hair, at 1.9 ng/mg and 7.04 ng/mg, respectively. Benzoylecgonine was also present in the maternal and paternal hair samples at 7.88 ng/mg and 6.39 ng/mg, and 13.06 ng/mg and 12.97 ng/mg, respectively. Conclusion Based on the data from this case and from previously published poisoning cases, as well as on the experience of our research group, we conclude that, using similar matrices for the study of chronic drug exposure, children present with a higher cocaine concentration in hair and they experience more serious deleterious acute effects, probably due to a different and slower cocaine metabolism. Consequently, children must be not exposed to secondhand crack smoke under any circumstance.

  19. Nanosecond radar system based on repetitive pulsed relativistic BWO

    International Nuclear Information System (INIS)

    Bunkin, B.V.; Gaponov-Grekhov, A.V.; Eltchaninov, A.S.; Zagulov, F.Ya.; Korovin, S.D.; Mesyats, G.A.; Osipov, M.L.; Otlivantchik, E.A.; Petelin, M.I.; Prokhorov, A.M.

    1993-01-01

    The paper presents the results of studies of a nanosecond radar system based on repetitive pulsed relativistic BWO. A pulsed power repetitive accelerator producing electron beams of electron energy 500-700 keV and current 5 kA in pulses of duraction 10 ns with a repetition rate of 100 pps is described. The results of experiments with a high-voltage gas-filled spark gap and a cold-cathode vacuum diode under the conditions of high repetition rates are given. Also presented are the results of studies of a relativistic BWO operating with a wavelength of 3 cm. It is shown that for a high-current beam electron energy of 500-700 keV, the BWO efficiency can reach 35%, the microwave power being 10 9 W. A superconducting solenoid creating a magnetic field of 30 kOe was used for the formation and transportation of the high-current electron beam. In conclusion, the outcome of tests of a nanosecond radar station based on a pulsed power repetitive accelerator and a relativistic BWO is reported

  20. Drug use and childhood-, military- and post-military trauma exposure among women and men veterans.

    Science.gov (United States)

    Kelley, Michelle L; Brancu, Mira; Robbins, Allison T; D'Lima, Gabrielle M; Strauss, Jennifer L; Curry, John F; Fairbank, John A; Runnals, Jennifer

    2015-07-01

    The current study was undertaken to examine whether posttraumatic stress symptoms (PTSS) and depressive symptoms mediated the association between trauma exposure (combat-related trauma and non-combat traumas occurring before, during, and after military service), and drug abuse symptoms use among male and female veterans. Participants were 2304 (1851 male, 453 female) veterans who took part in a multi-site research study conducted through the Department of Veterans Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center (VISN 6 MIRECC). Path analytic models were used to determine the association between problematic past-year drug use and combat-related and non-combat trauma experienced before, during, or after the military and whether current post-traumatic stress symptoms or depressive symptoms mediated these associations. For both male and female veterans, depressive symptoms significantly mediated the effects of pre- and post-military trauma on drug abuse symptoms. Mental health providers who work with trauma-exposed Iraq and Afghanistan era veterans should assess for drug use, depressive symptoms, and life-span trauma (i.e., not only combat-related traumas) as part of a thorough trauma-based assessment for both men and women. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Dynamic, morphotype-specific Candida albicans beta-glucan exposure during infection and drug treatment.

    Directory of Open Access Journals (Sweden)

    Robert T Wheeler

    2008-12-01

    Full Text Available Candida albicans, a clinically important dimorphic fungal pathogen that can evade immune attack by masking its cell wall beta-glucan from immune recognition, mutes protective host responses mediated by the Dectin-1 beta-glucan receptor on innate immune cells. Although the ability of C. albicans to switch between a yeast- or hyphal-form is a key virulence determinant, the role of each morphotype in beta-glucan masking during infection and treatment has not been addressed. Here, we show that during infection of mice, the C. albicans beta-glucan is masked initially but becomes exposed later in several organs. At all measured stages of infection, there is no difference in beta-glucan exposure between yeast-form and hyphal cells. We have previously shown that sub-inhibitory doses of the anti-fungal drug caspofungin can expose beta-glucan in vitro, suggesting that the drug may enhance immune activity during therapy. This report shows that caspofungin also mediates beta-glucan unmasking in vivo. Surprisingly, caspofungin preferentially unmasks filamentous cells, as opposed to yeast form cells, both in vivo and in vitro. The fungicidal activity of caspofungin in vitro is also filament-biased, as corroborated using yeast-locked and hyphal-locked mutants. The uncloaking of filaments is not a general effect of anti-fungal drugs, as another anti-fungal agent does not have this effect. These results highlight the advantage of studying host-pathogen interaction in vivo and suggest new avenues for drug development.

  2. Transgenerational effects of environmental enrichment on repetitive motor behavior development.

    Science.gov (United States)

    Bechard, Allison R; Lewis, Mark H

    2016-07-01

    The favorable consequences of environmental enrichment (EE) on brain and behavior development are well documented. Much less is known, however, about transgenerational benefits of EE on non-enriched offspring. We explored whether transgenerational effects of EE might extend to the development of repetitive motor behaviors in deer mice. Repetitive motor behaviors are invariant patterns of movement that, across species, can be reduced by EE. We found that EE not only attenuated the development of repetitive behavior in dams, but also in their non-enriched offspring. Moreover, maternal behavior did not seem to mediate the transgenerational effect we found, although repetitive behavior was affected by reproductive experience. These data support a beneficial transgenerational effect of EE on repetitive behavior development and suggest a novel benefit of reproductive experience. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Single-exposure visual memory judgments are reflected in inferotemporal cortex

    Science.gov (United States)

    Meyer, Travis

    2018-01-01

    Our visual memory percepts of whether we have encountered specific objects or scenes before are hypothesized to manifest as decrements in neural responses in inferotemporal cortex (IT) with stimulus repetition. To evaluate this proposal, we recorded IT neural responses as two monkeys performed a single-exposure visual memory task designed to measure the rates of forgetting with time. We found that a weighted linear read-out of IT was a better predictor of the monkeys’ forgetting rates and reaction time patterns than a strict instantiation of the repetition suppression hypothesis, expressed as a total spike count scheme. Behavioral predictions could be attributed to visual memory signals that were reflected as repetition suppression and were intermingled with visual selectivity, but only when combined across the most sensitive neurons. PMID:29517485

  4. Electrical strength of vacuum gap at repetitive breakdown

    International Nuclear Information System (INIS)

    Dubinin, N.P.; Chistyakov, N.P.

    1983-01-01

    The investigation of repetitive pulse breakdown of vacuum space, which electrodes have been subjected to various treatment in vacuum and inert gas, is carried out. In case of electrode warm-up in vacuum up to 400 deg C as well as electronic heating up to 900 deg C the voltage in case of repetitive breakdown hasncreased approximately twice and in case of a through treatment, which is accomplished by a high-current glow discharge in inert gas, the maximum high voltage in case of the first breakdown at repetitive breakdown has decreased by 30...40%, remaining 2-3 times higher than in the first case

  5. Word and nonword repetition in patients with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Alireza Farnam

    2015-08-01

    Full Text Available Introduction: The assessment of the verbal repetition is important in the study of acquired language disorders and neuropsychology. It is helpful in differential diagnosis of aphasia subtypes, auditory breakdowns, and working memory (WM performance. Though different linguistic disorders have been identified in patients with schizophrenia, very little is known about their verbal repetition ability. Methods: The present study was conducted in the inpatient ward of Razi Psychiatric Hospital, Tabriz University of Medical Sciences, Iran, during the year 2013. Participants were: 30 patients diagnosed with schizophrenia during the maintenance phase of treatment and 30 healthy people as control group. They were asked to repeat 15 words and 15 nonwords immediately. The stimuli were 1, 2, and 3 syllabic in Turkish language. Any incorrect repetition scored 1 and correct repetitions scored 0. Lexicalization errors were compared between groups too. Results: Both groups repeated words better than nonwords. Patients showed lower ability to repeat nonwords than controls, especially in 3 syllabics. There was no significant difference in the repetition of words between groups though it was better in controls. Patients with schizophrenia made more errors in both words and nonwords and lexicalization errors were twice more. Conclusion: Lower ability to repeat nonwords (than words in patients with schizophrenia may show the involvement of phonological loop of WM. More lexicalization errors may take place because of dis-inhibition.

  6. The Effect of Parenting Stress on Child Behavior Problems in High-Risk Children with Prenatal Drug Exposure

    Science.gov (United States)

    Bagner, Daniel M.; Sheinkopf, Stephen J.; Miller-Loncar, Cynthia; LaGasse, Linda L.; Lester, Barry M.; Liu, Jing; Bauer, Charles R.; Shankaran, Seetha; Bada, Henrietta; Das, Abhik

    2009-01-01

    Objective: To examine the relationship between early parenting stress and later child behavior in a high-risk sample and measure the effect of drug exposure on the relationship between parenting stress and child behavior. Methods: A subset of child-caregiver dyads (n = 607) were selected from the Maternal Lifestyle Study (MLS), which is a large…

  7. Two discharge modes of a repetitive nanosecond pulsed helium glow discharge under sub-atmospheric pressure in the repetition frequency range of 20 to 600 kHz

    Science.gov (United States)

    Kikuchi, Yusuke; Maegawa, Takuya; Otsubo, Akira; Nishimura, Yoshimi; Nagata, Masayoshi; Yatsuzuka, Mitsuyasu

    2018-05-01

    Two discharge modes, α and γ, of a repetitive nanosecond pulsed helium glow discharge at a gas pressure of 10 kPa in the repetition frequency range from 20 to 600 kHz are reported for the first time. The pulsed glow discharge is produced in a pair of parallel plate metal electrodes without insertion of dielectrics. The α mode discharge is volumetrically produced in the electrode gap at a low-repetition frequency, whereas the γ mode discharge is localized at the cathode surface at a high-repetition frequency. At high-repetition frequency, the time interval between voltage pulses is shorter than the lifetime of the afterglow produced by the preceding discharge. Then, the γ mode discharge is maintained by a large number of secondary electrons emitted from the cathode exposed to high-density ions and metastable helium atoms in the afterglow. In the α mode discharge with a low-repetition frequency operation, primary electrons due to gas ionization dominate the ionization process. Thus, a large discharge voltage is needed for the excitation of the α mode discharge. It is established that the bifurcation of α-γ discharge mode, accompanied by a decrease in the discharge voltage, occurs at the high-repetition frequency of ∼120 kHz.

  8. Recency, repetition, and the multidimensional basis of recognition memory.

    Science.gov (United States)

    Buchsbaum, Bradley R; Lemire-Rodger, Sabrina; Bondad, Ashley; Chepesiuk, Alexander

    2015-02-25

    Recency and repetition are two factors that have large effects on human memory performance. One way of viewing the beneficial impact of these variables on recognition memory is to assume that both factors modulate a unidimensional memory trace strength. Although previous functional neuroimaging studies have indicated that recency and repetition may modulate similar brain structures, particularly in the region of the inferior parietal cortex, there is extensive behavioral evidence that human subjects can make independent and accurate recognition memory judgments about both an item's recency and its frequency. In the present study, we used fMRI to examine patterns of brain activity during recognition memory for auditory-verbal stimuli that were parametrically and orthogonally manipulated in terms of recency and number of repetitions. We found in a continuous recognition paradigm that the lateral inferior parietal cortex, a region that has previously been associated with recollective forms of memory, is highly sensitive to recency but not repetition. In a multivariate analysis of whole-brain activation patterns, we found orthogonal components that dissociated recency and repetition variables, indicating largely independent neural bases underlying these two factors. The results demonstrate that although both recency and repetition dramatically improve recognition memory performance, the neural bases for this improvement are dissociable, and thus are difficult to explain in terms of access to a unitary memory trace. Copyright © 2015 the authors 0270-6474/15/353544-11$15.00/0.

  9. Repetition of Attempted Suicide Among Immigrants in Europe

    Science.gov (United States)

    Lipsicas, Cendrine Bursztein; Mäkinen, Ilkka Henrik; Wasserman, Danuta; Apter, Alan; Kerkhof, Ad; Michel, Konrad; Renberg, Ellinor Salander; van Heeringen, Kees; Värnik, Airi; Schmidtke, Armin

    2014-01-01

    Objectives To compare frequencies of suicide attempt repetition in immigrants and local European populations, and the timing of repetition in these groups. Method: Data from 7 European countries, comprising 10 574 local and 3032 immigrant subjects, were taken from the World Health Organization European Multicentre Study on Suicidal Behaviour and the ensuing Monitoring Suicidal Behaviour in Europe (commonly referred to as MONSUE) project. The relation between immigrant status and repetition of suicide attempt within 12-months following first registered attempt was analyzed with binary logistic regression, controlling for sex, age, and method of attempt. Timing of repetition was controlled for sex, age, and the recommended type of aftercare. Results: Lower odds of repeating a suicide attempt were found in Eastern European (OR 0.50; 95% CI 0.41 to 0.61, P Europe stands in contrast to their markedly higher tendency to attempt suicide in general, possibly pointing to situational stress factors related to their suicidal crisis that are less persistent over time. Our findings also raise the possibility that suicide attempters and repeaters constitute only partially overlapping populations. PMID:25565687

  10. The development of interactive multimedia based on auditory, intellectually, repetition in repetition algorithm learning to increase learning outcome

    Science.gov (United States)

    Munir; Sutarno, H.; Aisyah, N. S.

    2018-05-01

    This research aims to find out how the development of interactive multimedia based on auditory, intellectually, and repetition can improve student learning outcomes. This interactive multimedia is developed through 5 stages. Analysis stages include the study of literature, questionnaire, interviews and observations. The design phase is done by the database design, flowchart, storyboards and repetition algorithm material while the development phase is done by the creation of web-based framework. Presentation material is adapted to the model of learning such as auditory, intellectually, repetition. Auditory points are obtained by recording the narrative material that presented by a variety of intellectual points. Multimedia as a product is validated by material and media experts. Implementation phase conducted on grade XI-TKJ2 SMKN 1 Garut. Based on index’s gain, an increasing of student learning outcomes in this study is 0.46 which is fair due to interest of student in using interactive multimedia. While the multimedia assessment earned 84.36% which is categorized as very well.

  11. Antineoplastic drugs: Occupational exposure and health risks

    OpenAIRE

    Fransman, W.

    2006-01-01

    Antineoplastic drugs are pharmaceuticals commonly used to treat cancer (and some non-neoplastic diseases), which are generally referred to as 'chemotherapy'. Oncology nurses are exposed to these drugs via the skin of hands during daily nursing activities, even when protective gloves are being used. Results of tests on bulk and surface contamination samples confirmed that patients intravenously treated with cyclophosphamide excrete the unmetabolized drug. The introduction of new guidelines and...

  12. Repetition suppression and repetition enhancement underlie auditory memory-trace formation in the human brain: an MEG study.

    Science.gov (United States)

    Recasens, Marc; Leung, Sumie; Grimm, Sabine; Nowak, Rafal; Escera, Carles

    2015-03-01

    The formation of echoic memory traces has traditionally been inferred from the enhanced responses to its deviations. The mismatch negativity (MMN), an auditory event-related potential (ERP) elicited between 100 and 250ms after sound deviation is an indirect index of regularity encoding that reflects a memory-based comparison process. Recently, repetition positivity (RP) has been described as a candidate ERP correlate of direct memory trace formation. RP consists of repetition suppression and enhancement effects occurring in different auditory components between 50 and 250ms after sound onset. However, the neuronal generators engaged in the encoding of repeated stimulus features have received little interest. This study intends to investigate the neuronal sources underlying the formation and strengthening of new memory traces by employing a roving-standard paradigm, where trains of different frequencies and different lengths are presented randomly. Source generators of repetition enhanced (RE) and suppressed (RS) activity were modeled using magnetoencephalography (MEG) in healthy subjects. Our results show that, in line with RP findings, N1m (~95-150ms) activity is suppressed with stimulus repetition. In addition, we observed the emergence of a sustained field (~230-270ms) that showed RE. Source analysis revealed neuronal generators of RS and RE located in both auditory and non-auditory areas, like the medial parietal cortex and frontal areas. The different timing and location of neural generators involved in RS and RE points to the existence of functionally separated mechanisms devoted to acoustic memory-trace formation in different auditory processing stages of the human brain. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Frequency Adaptive Repetitive Control of Grid-Tied Three-Phase PV Inverters

    DEFF Research Database (Denmark)

    Zhou, Keliang; Yang, Yongheng; Blaabjerg, Frede

    2016-01-01

    Repetitive control offers an accurate current control scheme for grid-tied converters to feed high quality sinusoidal current into the grid. However, with grid frequency being treated as a constant value, conventional repetitive controller fail to produce high quality feeding current in the prese......Repetitive control offers an accurate current control scheme for grid-tied converters to feed high quality sinusoidal current into the grid. However, with grid frequency being treated as a constant value, conventional repetitive controller fail to produce high quality feeding current...

  14. Effects of repetitive training at low altitude on erythropoiesis in 400 and 800 m runners.

    Science.gov (United States)

    Frese, F; Friedmann-Bette, B

    2010-06-01

    Classical altitude training can cause an increase in total hemoglobin mass (THM) if a minimum "dose of hypoxia" is reached (altitude >or=2,000 m, >or=3 weeks). We wanted to find out if repetitive exposure to mild hypoxia during living and training at low altitude (training camps at low altitude interspersed by 3 weeks of sea-level training and at the same time points in a control group (CG) of 5 well-trained runners. EPO, sTfR and ferritin were also repeatedly measured during the altitude training camps. Repeated measures ANOVA revealed significant increases in EPO- and sTfR-levels during both training camps and a significant decrease in ferritin indicating enhanced erythropoietic stimulation during living and training at low altitude. Furthermore, significant augmentation of THM by 5.1% occurred in the course of the 2 altitude training camps. In conclusion, repetitive living and training at low altitude leads to a hypoxia-induced increase in erythropoietic stimulation in elite 400 m and 800 m runners and, apparently, might also cause a consecutive augmentation of THM.

  15. Trust in online prescription drug information among internet users: the impact on information search behavior after exposure to direct-to-consumer advertising.

    Science.gov (United States)

    Menon, Ajit M; Deshpande, Aparna D; Perri, Matthew; Zinkhan, George M

    2002-01-01

    The proliferation of both manufacturer-controlled and independent medication-related websites has aroused concern among consumers and policy-makers concerning the trustworthiness of Web-based drug information. The authors examine consumers' trust in on-line prescription drug information and its influence on information search behavior. The study design involves a retrospective analysis of data from a 1998 national survey. The findings reveal that trust in drug information from traditional media sources such as television and newspapers transfers to the domain of the Internet. Furthermore, a greater trust in on-line prescription drug information stimulates utilization of the Internet for information search after exposure to prescription drug advertising.

  16. Measures of anticholinergic drug exposure, serum anticholinergic activity, and all-cause postdischarge mortality in older hospitalized patients with hip fractures

    NARCIS (Netherlands)

    Mangoni, Arduino A.; van Munster, Barbara C.; Woodman, Richard J.; de Rooij, Sophia E.

    Objectives: To assess possible associations between anticholinergic drug exposure and serum anticholinergic activity (SAA) and their capacities to predict all-cause mortality in older hospitalized patients. Setting: Academic medical center. Participants and Measurements: Data on clinical

  17. Postulating a dermal pathway for exposure to anti-neoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys

    NARCIS (Netherlands)

    Kromhout, H.; Hoek, F.; Uitterhoeve, R.; Huijbers, R.; Overmars, R.F.; Anzion, R.; Vermeulen, R.

    2000-01-01

    Dermal exposure to anti-neoplastic drugs has been suggested as a potentially important route of exposure of hospital workers. Three small-scale workplace surveys were carried out in several hospitals focusing on contamination by leakage from IV infusion systems; contamination by spilled urine of

  18. Association between occupational exposure levels of antineoplastic drugs and work environment in five hospitals in Japan.

    Science.gov (United States)

    Yoshida, Jin; Koda, Shigeki; Nishida, Shozo; Yoshida, Toshiaki; Miyajima, Keiko; Kumagai, Shinji

    2011-03-01

    The aim of the present study was to evaluate the measurement of contamination by antineoplastic drugs for safer handling of such drugs by medical workers. We investigated the relationship between the contamination level of antineoplastic drugs and the conditions of their handling. Air samples and wipe samples were collected from equipment in the preparation rooms of five hospitals (hospitals A-E). These samples were subjected to measurement of the amounts of cyclophosphamide (CPA), fluorouracil (5FU), gemcitabine (GEM), and platinum-containing drugs (Pt). Twenty-four-hour urine samples were collected from the pharmacists who handled or audited, the antineoplastic drugs were analyzed for CPA and Pt. Pt was detected from air samples inside BSC in hospital B. Antineoplastic drugs were detected from wipe samples of the BSC in hospitals A, B, D, and E and of other equipment in the preparation rooms in hospitals A, B, C, and D. Cyclophosphamide and 5FU were detected from wipe samples of the air-conditioner filter in hospital A, and CPA was detected from that in hospital D. Cyclophosphamide was detected from urine samples of workers in hospitals B, D, and E. The contamination level of antineoplastic drugs was suggested to be related with the amount of drugs handled, cleaning methods of the equipment, and the skill level of the technique of maintaining negative pressure inside a vial. In order to reduce the contamination and exposure to antineoplastic drugs in the hospital work environment very close to zero, comprehensive safety precautions, including adequate mixing and cleaning methods was required in addition to BSC and closed system device.

  19. Feasibility of Exposure Response Prevention to Treat Repetitive Behaviors of Children with Autism and an Intellectual Disability: A Brief Report

    Science.gov (United States)

    Boyd, Brian A.; Woodard, Cooper R.; Bodfish, James W.

    2013-01-01

    There is a lack of evidence-based behavioral therapies or pharmacotherapies to treat repetitive behaviors found in autism. Effective behavioral therapies are needed to counter any negative consequences these behaviors may have on the child's early learning and socialization. The purpose of this proof-of-principle study was to test the feasibility…

  20. Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment.

    Science.gov (United States)

    Nelson, Antoinette G; Zhang, Xiaoping; Ganapathi, Usha; Szekely, Zoltan; Flexner, Charles W; Owen, Andrew; Sinko, Patrick J

    2015-12-10

    The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today. Moving forward there are at least three high priority goals for anti-HIV drug delivery (DD) research: (1) to prevent new HIV infections from occurring, (2) to facilitate a functional cure, i.e., when HIV is present but the body controls it without drugs and (3) to eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a significant step forward in preventing the establishment of chronic HIV infection. However, the ultimate success of PrEP will depend on achieving sustained antiretroviral (ARV) tissue concentrations and will require strict patient adherence to the regimen. While first generation long acting/extended release (LA/ER) DD Systems (DDS) currently in development show considerable promise, significant DD treatment and prevention challenges persist. First, there is a critical need to improve cell specificity through targeting in order to selectively achieve efficacious drug concentrations in HIV reservoir sites to control/eradicate HIV as well as mitigate systemic side effects. In addition, approaches for reducing cellular efflux and metabolism of ARV drugs to prolong effective concentrations in target cells need to be developed. Finally, given the current understanding of HIV pathogenesis, next generation anti-HIV DDS need to address selective DD to the gut mucosa and lymph nodes. The current review focuses on the DDS technologies, critical challenges, opportunities, strategies, and approaches by which novel

  1. Generation of µW level plateau harmonics at high repetition rate.

    Science.gov (United States)

    Hädrich, S; Krebs, M; Rothhardt, J; Carstens, H; Demmler, S; Limpert, J; Tünnermann, A

    2011-09-26

    The process of high harmonic generation allows for coherent transfer of infrared laser light to the extreme ultraviolet spectral range opening a variety of applications. The low conversion efficiency of this process calls for optimization or higher repetition rate intense ultrashort pulse lasers. Here we present state-of-the-art fiber laser systems for the generation of high harmonics up to 1 MHz repetition rate. We perform measurements of the average power with a calibrated spectrometer and achieved µW harmonics between 45 nm and 61 nm (H23-H17) at a repetition rate of 50 kHz. Additionally, we show the potential for few-cycle pulses at high average power and repetition rate that may enable water-window harmonics at unprecedented repetition rate. © 2011 Optical Society of America

  2. Turkish Final Year Medical Students' Exposure to and Attitudes Concerning Drug Company Interactions: A Perspective from a Minimally Regulated Environment for Medical Students.

    Science.gov (United States)

    Beyhun, Nazim Ercument; Kolayli, Cevriye Ceyda; Can, Gamze; Topbas, Murat

    2016-01-01

    Interactions between drug companies and medical students may affect evidence-based medical practice and patient safety. The aim of this study was to assess drug company-medical student interactions in a medical faculty where limited specific national or institutional regulations apply between drug companies and medical students. The objectives of the study were to determine the exposure and attitudes of final year medical students in terms of drug company-medical student and physician interactions, to identify factors affecting those attitudes and to provide data for policymakers working on the regulation of interactions between drug companies and medical students. This anonymous questionnaire-based study of 154 medical final year medical students at the Karadeniz Technical University Medical Faculty, Trabzon, Turkey, in April and May 2015 attracted a response rate of 92.2% (n/N, 154/164). Exposure to interaction with a pharmaceutical representative was reported by 90.3% (139/154) of students, and 68.8% (106/154) reported experiencing such interaction alongside a resident. In addition, 83.7% (128/153) of students reported an interaction during internship. Furthermore, 69.9% (107/153) of students agreed that interactions influence physicians' prescription preferences, while 33.1% (51/154) thought that a medical student should never accept a gift from a drug company and 24.7% (38/154) agreed with the proposition that "drug companies should not hold activities in medical faculties". Students with rational prescription training expressed greater agreement with the statement "I am skeptical concerning the information provided by drug companies during interactions" than those who had not received such training, and this finding was supported by logistic regression [O.R.(C.I), p -3.7(1.2-11.5), p = 0.022]. Acceptance of advertisement brochures was found to significantly reduce the level of agreement with the proposition that "A physician should not accept any gift from a

  3. Turkish Final Year Medical Students' Exposure to and Attitudes Concerning Drug Company Interactions: A Perspective from a Minimally Regulated Environment for Medical Students.

    Directory of Open Access Journals (Sweden)

    Nazim Ercument Beyhun

    Full Text Available Interactions between drug companies and medical students may affect evidence-based medical practice and patient safety. The aim of this study was to assess drug company-medical student interactions in a medical faculty where limited specific national or institutional regulations apply between drug companies and medical students. The objectives of the study were to determine the exposure and attitudes of final year medical students in terms of drug company-medical student and physician interactions, to identify factors affecting those attitudes and to provide data for policymakers working on the regulation of interactions between drug companies and medical students. This anonymous questionnaire-based study of 154 medical final year medical students at the Karadeniz Technical University Medical Faculty, Trabzon, Turkey, in April and May 2015 attracted a response rate of 92.2% (n/N, 154/164. Exposure to interaction with a pharmaceutical representative was reported by 90.3% (139/154 of students, and 68.8% (106/154 reported experiencing such interaction alongside a resident. In addition, 83.7% (128/153 of students reported an interaction during internship. Furthermore, 69.9% (107/153 of students agreed that interactions influence physicians' prescription preferences, while 33.1% (51/154 thought that a medical student should never accept a gift from a drug company and 24.7% (38/154 agreed with the proposition that "drug companies should not hold activities in medical faculties". Students with rational prescription training expressed greater agreement with the statement "I am skeptical concerning the information provided by drug companies during interactions" than those who had not received such training, and this finding was supported by logistic regression [O.R.(C.I, p -3.7(1.2-11.5, p = 0.022]. Acceptance of advertisement brochures was found to significantly reduce the level of agreement with the proposition that "A physician should not accept any

  4. Turkish Final Year Medical Students’ Exposure to and Attitudes Concerning Drug Company Interactions: A Perspective from a Minimally Regulated Environment for Medical Students

    Science.gov (United States)

    Beyhun, Nazim Ercument; Kolayli, Cevriye Ceyda; Can, Gamze; Topbas, Murat

    2016-01-01

    Interactions between drug companies and medical students may affect evidence-based medical practice and patient safety. The aim of this study was to assess drug company–medical student interactions in a medical faculty where limited specific national or institutional regulations apply between drug companies and medical students. The objectives of the study were to determine the exposure and attitudes of final year medical students in terms of drug company–medical student and physician interactions, to identify factors affecting those attitudes and to provide data for policymakers working on the regulation of interactions between drug companies and medical students. This anonymous questionnaire-based study of 154 medical final year medical students at the Karadeniz Technical University Medical Faculty, Trabzon, Turkey, in April and May 2015 attracted a response rate of 92.2% (n/N, 154/164). Exposure to interaction with a pharmaceutical representative was reported by 90.3% (139/154) of students, and 68.8% (106/154) reported experiencing such interaction alongside a resident. In addition, 83.7% (128/153) of students reported an interaction during internship. Furthermore, 69.9% (107/153) of students agreed that interactions influence physicians’ prescription preferences, while 33.1% (51/154) thought that a medical student should never accept a gift from a drug company and 24.7% (38/154) agreed with the proposition that “drug companies should not hold activities in medical faculties”. Students with rational prescription training expressed greater agreement with the statement “I am skeptical concerning the information provided by drug companies during interactions” than those who had not received such training, and this finding was supported by logistic regression [O.R.(C.I), p -3.7(1.2–11.5), p = 0.022]. Acceptance of advertisement brochures was found to significantly reduce the level of agreement with the proposition that “A physician should not

  5. Autism and exergaming: effects on repetitive behaviors and cognition

    Directory of Open Access Journals (Sweden)

    Anderson-Hanley C

    2011-09-01

    Full Text Available Cay Anderson-Hanley, Kimberly Tureck, Robyn L Schneiderman Department of Psychology, Union College, Schenectady, NY, USA Abstract: Autism is a neurodevelopmental disorder that leads to impairment in social skills and delay in language development, and results in repetitive behaviors and restricted interests that impede academic and social involvement. Physical exercise has been shown to decrease repetitive behaviors in autistic children and improve cognitive function across the life-span. Exergaming combines physical and mental exercise simultaneously by linking physical activity movements to video game control and may yield better compliance with exercise. In this investigation, two pilot studies explored the potential behavioral and cognitive benefits of exergaming. In Pilot I, twelve children with autism spectrum disorders completed a control task and an acute bout of Dance Dance Revolution (DDR; in Pilot II, ten additional youths completed an acute bout of cyber cycling. Repetitive behaviors and executive function were measured before and after each activity. Repetitive behaviors significantly decreased, while performance on Digits Backwards improved following the exergaming conditions compared with the control condition. Additional research is needed to replicate these findings, and to explore the application of exergaming for the management of behavioral disturbance and to increase cognitive control in children on the autism spectrum. Keywords: autism, repetitive behaviors, exergaming, exercise, executive function

  6. Genetic Indicators of Drug Resistance in the Highly Repetitive Genome of Trichomonas vaginalis.

    Science.gov (United States)

    Bradic, Martina; Warring, Sally D; Tooley, Grace E; Scheid, Paul; Secor, William E; Land, Kirkwood M; Huang, Po-Jung; Chen, Ting-Wen; Lee, Chi-Ching; Tang, Petrus; Sullivan, Steven A; Carlton, Jane M

    2017-06-01

    Trichomonas vaginalis, the most common nonviral sexually transmitted parasite, causes ∼283 million trichomoniasis infections annually and is associated with pregnancy complications and increased risk of HIV-1 acquisition. The antimicrobial drug metronidazole is used for treatment, but in a fraction of clinical cases, the parasites can become resistant to this drug. We undertook sequencing of multiple clinical isolates and lab derived lines to identify genetic markers and mechanisms of metronidazole resistance. Reduced representation genome sequencing of ∼100 T. vaginalis clinical isolates identified 3,923 SNP markers and presence of a bipartite population structure. Linkage disequilibrium was found to decay rapidly, suggesting genome-wide recombination and the feasibility of genetic association studies in the parasite. We identified 72 SNPs associated with metronidazole resistance, and a comparison of SNPs within several lab-derived resistant lines revealed an overlap with the clinically resistant isolates. We identified SNPs in genes for which no function has yet been assigned, as well as in functionally-characterized genes relevant to drug resistance (e.g., pyruvate:ferredoxin oxidoreductase). Transcription profiles of resistant strains showed common changes in genes involved in drug activation (e.g., flavin reductase), accumulation (e.g., multidrug resistance pump), and detoxification (e.g., nitroreductase). Finally, we identified convergent genetic changes in lab-derived resistant lines of Tritrichomonas foetus, a distantly related species that causes venereal disease in cattle. Shared genetic changes within and between T. vaginalis and Tr. foetus parasites suggest conservation of the pathways through which adaptation has occurred. These findings extend our knowledge of drug resistance in the parasite, providing a panel of markers that can be used as a diagnostic tool. © The Author 2017. Published by Oxford University Press on behalf of the Society for

  7. A longitudinal investigation of perfectionism and repetitive negative thinking in perinatal depression.

    Science.gov (United States)

    Egan, Sarah J; Kane, Robert T; Winton, Karen; Eliot, Catherine; McEvoy, Peter M

    2017-10-01

    Repetitive negative thinking and perfectionism have both been proposed as processes that are related to depressive symptoms. The purpose of this study was to investigate concurrent and prospective relationships between antenatal and postnatal depression, perfectionism, and repetitive negative thinking. A longitudinal design was used and 71 women were followed from their third trimester of pregnancy to six weeks post birth. A structural equation model was tested with antenatal perfectionism predicting antenatal repetitive negative thinking, perfectionism predicting postnatal depression, and antenatal repetitive negative thinking predicting antenatal and postnatal depression. The final model provided an adequate fit to the data but the pathway from antenatal repetitive negative thinking to postnatal depression was not significant. The findings provide support for the role of perfectionism and repetitive negative thinking in the onset and maintenance of perinatal symptoms of depression. It is suggested that future research investigates the efficacy of targeting repetitive negative thinking and perfectionism in pregnancy to examine if this can reduce perinatal depression. Copyright © 2017. Published by Elsevier Ltd.

  8. Evaluation of the health effects of occupational exposure of analytic laboratory workers processing illicit drug investigation files.

    Science.gov (United States)

    Bentur, Y; Bentur, L; Rotenberg, M; Tepperberg, M; Leiba, R; Wolf, E Udi

    2013-05-01

    The Analytic Laboratory of Israel Police processes illicit drug files. In recent years, workers of this laboratory have complained of health problems. Limited information exists on the effect of occupational exposure to illicit drugs; biomonitoring was never done. To assess health effects and systemic absorption of illicit drugs in workers of the Analytic Laboratory occupationally exposed to illicit drugs. A prospective cohort study using health and occupational questionnaires, clinical assessments, and monitoring of urinary excretion of illicit drugs was conducted. The study included three blocks of one week each. At each week workers were assessed at the beginning (baseline), and the assessments were repeated at the end of the three working days. Urine specimens were analyzed for illicit drugs in an independent laboratory. Demographic, clinical, occupational, and laboratory data were subjected to descriptive analysis, and paired Student's t-test, chi-square analysis, and repeated measures model. Twenty-seven workers (age, 39.2 ± 8.3 years; 77.8% females) were included, yielding 122 paired samples. The following parameters were reduced at the end of shift compared with baseline: diastolic blood pressure (71.2 ± 11.2 and 77.2 ± 13.6 mmHg, respectively, p health complaints included headache, fatigue, and dry eyes. No illicit drug was detected in the urine specimens. It is suggested that the health concerns of the laboratory workers were not related to the absorption of illicit drugs; environmental conditions (e.g. inadequate ventilation and respirable dust) can contribute to these concerns.

  9. Concreteness of Positive, Negative, and Neutral Repetitive Thinking About the Future

    Science.gov (United States)

    Behar, Evelyn; McGowan, Sarah Kate; McLaughlin, Katie A.; Borkovec, T.D.; Goldwin, Michelle; Bjorkquist, Olivia

    2014-01-01

    Consistent with assertions that the adaptiveness of repetitive thinking is influenced by both its valence and style, Stöber (e.g., Stöber & Borkovec, 2002) has argued that worry is characterized by a reduced concreteness of thought content and that the resulting abstractness contributes to its inhibition of some aspects of anxious responding. However, extant research does not provide a direct test of Stöber’s reduced concreteness theory of worry. We sought to test Stöber’s theory and to examine the adaptiveness of repetitive worrisome thinking by randomly assigning 108 participants to engage in five consecutive periods of repetitive thinking about positively, negatively, or neutrally valenced potential future events. Results based on coding of thought data indicated that (a) repetitive thinking became increasingly less concrete as periods progressed; (b) contrary to Stöber’s theory, both negative and positive repetitive future thinking were more concrete than neutral repetitive future thinking (and did not differ from each other); and (c) abstractness of thought during negative repetitive future thinking was associated with reduced reports of imagery-based activity. Results based on self-reported affect indicated that negatively valenced repetitive future thinking was uniquely associated with initial decreases in anxious affect, followed by increased anxious affect that coincided with increased imagery-based activity. This suggests that worry is associated with a sequential mitigation of anxious meaning followed by a strengthening of anxious meaning over time. Theoretical and clinical implications of these findings are discussed. PMID:22440067

  10. Interest of the trajectory method for the evaluation of outcomes after in utero drug exposure: example of anxiolytics and hypnotics.

    Science.gov (United States)

    Hurault-Delarue, Caroline; Chouquet, Cécile; Savy, Nicolas; Lacroix, Isabelle; Beau, Anna-Belle; Montastruc, Jean-Louis; Damase-Michel, Christine

    2017-05-01

    The aim of this study was to examine the potential benefit to take into account duration and intensity of drug exposure using the recently published method based on individual drug trajectories. This approach was used to define profiles of exposure to anxiolytics/hypnotics during pregnancy and to evaluate the potential effect on newborn health. The study was performed in EFEMERIS database (54 918 mother-children pairs). An estimation of adaptation to extrauterine life was assessed using several criteria especially cardio-respiratory symptoms. A proxy variable called "neonatal pathology" was created. The occurrence of this event was studied using two approaches: The Standard Method comparing exposed and unexposed newborns, The Trajectory Method comparing the different profiles of exposure. Around 5% of newborns (n = 2768) were identified to be exposed to anxiolytics or hypnotics during pregnancy. Using the Standard Method, 6.2% of exposed newborns developed a "neonatal pathology" against 4.8% of unexposed newborns (odds ratios [OR] = 0.9[0.8-1.2], p = 0.7). With the Trajectory Method taking into account evolution of exposure during pregnancy and treatment intensity, four profiles of pregnant women were identified. A significant difference in the rates of "neonatal pathologies" was observed between profiles (p = 0.0002). Newborns of the two profiles exposed in utero to high constant level of anxiolytics or hypnotics were more at risk of developing "neonatal pathology" than unexposed newborns (OR 1  = 2.0 [1.0-3.9] and OR 2  = 7.6 [2.8-20.5]). The present study demonstrates the interest of this method based on individual drug trajectories for the evaluation of outcomes in pharmaco-epidemiological studies and more specifically during pregnancy. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Effects of repetition and temperature on Contingent Electrical Stimulation

    DEFF Research Database (Denmark)

    Castrillon, Eduardo E.; Zhou, Xinwen; Svensson, Peter

    ) activity associated with bruxism. Repetition of the electrical stimulus and skin surface temperature (ST) may affect the perception of CES and possibly also the inhibitory EMG effects.Objectives: To determine the effects of stimulus repetition and skin ST on the perception of CES.  Methods: Healthy...

  12. Post-exercise cortical depression following repetitive passive finger movement.

    Science.gov (United States)

    Otsuka, Ryohei; Sasaki, Ryoki; Tsuiki, Shota; Kojima, Sho; Onishi, Hideaki

    2017-08-24

    This study aimed to clarify the influence of range of repetitive passive finger movement on corticospinal excitability. Thirteen healthy subjects participated in this study. Passive index finger adduction-abduction movements were performed from 15° abduction to 15° adduction, 15° abduction to 0°, 0° to 15° adduction, and 15° adduction to 30° adduction, each at 15°/s for 10min on separate days. Motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation and M- and F-waves were measured before and after each repetitive passive index finger movement protocol to evaluate changes in corticospinal excitability. MEP amplitude significantly decreased after all passive movements, while F-wave amplitude, F-wave persistence, and M-wave amplitude remained stable. These results suggest that cortical excitability decreases after repetitive passive movement. However, the range of repetitive passive movement does not markedly influence the magnitude of cortical depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Pulse repetition rate multiplication by Talbot effect in a coaxial fiber

    Science.gov (United States)

    Dhingra, Nikhil; Saxena, Geetika Jain; Anand, Jyoti; Sharma, Enakshi K.

    2018-03-01

    We use a coaxial fiber, which is a cylindrical coupled waveguide structure consisting of two concentric cores, the inner rod and an outer ring core as a first order dispersive media to achieve temporal Talbot effect for pulse repetition rate multiplication (PRRM) in high bit rate optical fiber communication. It is observed that for an input Gaussian pulse train with pulse width, 2τ0=1ps at a repetition rate of 40 Gbps (repetition period, T=25ps), an output repetition rate of 640 Gbps can be achieved without significant distortion at a length of 40.92 m.

  14. Properties of water surface discharge at different pulse repetition rates

    International Nuclear Information System (INIS)

    Ruma,; Yoshihara, K.; Hosseini, S. H. R.; Sakugawa, T.; Akiyama, H.; Akiyama, M.; Lukeš, P.

    2014-01-01

    The properties of water surface discharge plasma for variety of pulse repetition rates are investigated. A magnetic pulse compression (MPC) pulsed power modulator able to deliver pulse repetition rates up to 1000 Hz, with 0.5 J per pulse energy output at 25 kV, was used as the pulsed power source. Positive pulse with a point-to-plane electrode configuration was used for the experiments. The concentration and production yield of hydrogen peroxide (H 2 O 2 ) were quantitatively measured and orange II organic dye was treated, to evaluate the chemical properties of the discharge reactor. Experimental results show that the physical and chemical properties of water surface discharge are not influenced by pulse repetition rate, very different from those observed for under water discharge. The production yield of H 2 O 2 and degradation rate per pulse of the dye did not significantly vary at different pulse repetition rates under a constant discharge mode on water surface. In addition, the solution temperature, pH, and conductivity for both water surface and underwater discharge reactors were measured to compare their plasma properties for different pulse repetition rates. The results confirm that surface discharge can be employed at high pulse repetition rates as a reliable and advantageous method for industrial and environmental decontamination applications.

  15. Word Recognition during Reading: The Interaction between Lexical Repetition and Frequency

    Science.gov (United States)

    Lowder, Matthew W.; Choi, Wonil; Gordon, Peter C.

    2013-01-01

    Memory studies utilizing long-term repetition priming have generally demonstrated that priming is greater for low-frequency words than for high-frequency words and that this effect persists if words intervene between the prime and the target. In contrast, word-recognition studies utilizing masked short-term repetition priming typically show that the magnitude of repetition priming does not differ as a function of word frequency and does not persist across intervening words. We conducted an eye-tracking while reading experiment to determine which of these patterns more closely resembles the relationship between frequency and repetition during the natural reading of a text. Frequency was manipulated using proper names that were high-frequency (e.g., Stephen) or low-frequency (e.g., Dominic). The critical name was later repeated in the sentence, or a new name was introduced. First-pass reading times and skipping rates on the critical name revealed robust repetition-by-frequency interactions such that the magnitude of the repetition-priming effect was greater for low-frequency names than for high-frequency names. In contrast, measures of later processing showed effects of repetition that did not depend on lexical frequency. These results are interpreted within a framework that conceptualizes eye-movement control as being influenced in different ways by lexical- and discourse-level factors. PMID:23283808

  16. Comorbidity Among Depression, Conduct Disorder, and Drug Use From Adolescence to Young Adulthood: Examining the Role of Violence Exposures

    OpenAIRE

    Cerdá, Magdalena; Tracy, Melissa; Sánchez, Brisa N.; Galea, Sandro

    2011-01-01

    We assessed relations among depression, conduct disorder, and drug use from adolescence to young adulthood, and evaluated whether exposure to violence contributed to disorder co-occurrence. We used data from the Project on Human Development in Chicago Neighborhoods. Respondents were 12–15 years old in 1995–1997 (N = 1,517), and were reinterviewed in 1997–2000 (n = 1,315), and 2000–2002 (n = 1,210). We examined exposure to violence at ages 12–15 and 14–17, and depression, conduct disorder, and...

  17. Evidence-Based Behavioral Interventions for Repetitive Behaviors in Autism

    Science.gov (United States)

    Boyd, Brian A.; McDonough, Stephen G.; Bodfish, James W.

    2012-01-01

    Restricted and repetitive behaviors (RRBs) are a core symptom of autism spectrum disorders (ASD). There has been an increased research emphasis on repetitive behaviors; however, this research primarily has focused on phenomenology and mechanisms. Thus, the knowledge base on interventions is lagging behind other areas of research. The literature…

  18. Repetitive sequences: the hidden diversity of heterochromatin in prochilodontid fish

    Directory of Open Access Journals (Sweden)

    Maria L. Terencio

    2015-08-01

    Full Text Available The structure and organization of repetitive elements in fish genomes are still relatively poorly understood, although most of these elements are believed to be located in heterochromatic regions. Repetitive elements are considered essential in evolutionary processes as hotspots for mutations and chromosomal rearrangements, among other functions – thus providing new genomic alternatives and regulatory sites for gene expression. The present study sought to characterize repetitive DNA sequences in the genomes of Semaprochilodus insignis (Jardine & Schomburgk, 1841 and Semaprochilodus taeniurus (Valenciennes, 1817 and identify regions of conserved syntenic blocks in this genome fraction of three species of Prochilodontidae (S. insignis, S. taeniurus, and Prochilodus lineatus (Valenciennes, 1836 by cross-FISH using Cot-1 DNA (renaturation kinetics probes. We found that the repetitive fractions of the genomes of S. insignis and S. taeniurus have significant amounts of conserved syntenic blocks in hybridization sites, but with low degrees of similarity between them and the genome of P. lineatus, especially in relation to B chromosomes. The cloning and sequencing of the repetitive genomic elements of S. insignis and S. taeniurus using Cot-1 DNA identified 48 fragments that displayed high similarity with repetitive sequences deposited in public DNA databases and classified as microsatellites, transposons, and retrotransposons. The repetitive fractions of the S. insignis and S. taeniurus genomes exhibited high degrees of conserved syntenic blocks in terms of both the structures and locations of hybridization sites, but a low degree of similarity with the syntenic blocks of the P. lineatus genome. Future comparative analyses of other prochilodontidae species will be needed to advance our understanding of the organization and evolution of the genomes in this group of fish.

  19. Hemispheric Asymmetries in Repetition Enhancement and Suppression Effects in the Newborn Brain.

    Science.gov (United States)

    Bouchon, Camillia; Nazzi, Thierry; Gervain, Judit

    2015-01-01

    The repeated presentation of stimuli typically attenuates neural responses (repetition suppression) or, less commonly, increases them (repetition enhancement) when stimuli are highly complex, degraded or presented under noisy conditions. In adult functional neuroimaging research, these repetition effects are considered as neural correlates of habituation. The development and respective functional significance of these effects in infancy remain largely unknown. This study investigates repetition effects in newborns using functional near-infrared spectroscopy, and specifically the role of stimulus complexity in evoking a repetition enhancement vs. a repetition suppression response, following up on Gervain et al. (2008). In that study, abstract rule-learning was found at birth in cortical areas specific to speech processing, as evidenced by a left-lateralized repetition enhancement of the hemodynamic response to highly variable speech sequences conforming to a repetition-based ABB artificial grammar, but not to a random ABC grammar. Here, the same paradigm was used to investigate how simpler stimuli (12 different sequences per condition as opposed to 140), and simpler presentation conditions (blocked rather than interleaved) would influence repetition effects at birth. Results revealed that the two grammars elicited different dynamics in the two hemispheres. In left fronto-temporal areas, we reproduce the early perceptual discrimination of the two grammars, with ABB giving rise to a greater response at the beginning of the experiment than ABC. In addition, the ABC grammar evoked a repetition enhancement effect over time, whereas a stable response was found for the ABB grammar. Right fronto-temporal areas showed neither initial discrimination, nor change over time to either pattern. Taken together with Gervain et al. (2008), this is the first evidence that manipulating methodological factors influences the presence or absence of neural repetition enhancement effects in

  20. Hemispheric Asymmetries in Repetition Enhancement and Suppression Effects in the Newborn Brain.

    Directory of Open Access Journals (Sweden)

    Camillia Bouchon

    Full Text Available The repeated presentation of stimuli typically attenuates neural responses (repetition suppression or, less commonly, increases them (repetition enhancement when stimuli are highly complex, degraded or presented under noisy conditions. In adult functional neuroimaging research, these repetition effects are considered as neural correlates of habituation. The development and respective functional significance of these effects in infancy remain largely unknown.This study investigates repetition effects in newborns using functional near-infrared spectroscopy, and specifically the role of stimulus complexity in evoking a repetition enhancement vs. a repetition suppression response, following up on Gervain et al. (2008. In that study, abstract rule-learning was found at birth in cortical areas specific to speech processing, as evidenced by a left-lateralized repetition enhancement of the hemodynamic response to highly variable speech sequences conforming to a repetition-based ABB artificial grammar, but not to a random ABC grammar.Here, the same paradigm was used to investigate how simpler stimuli (12 different sequences per condition as opposed to 140, and simpler presentation conditions (blocked rather than interleaved would influence repetition effects at birth.Results revealed that the two grammars elicited different dynamics in the two hemispheres. In left fronto-temporal areas, we reproduce the early perceptual discrimination of the two grammars, with ABB giving rise to a greater response at the beginning of the experiment than ABC. In addition, the ABC grammar evoked a repetition enhancement effect over time, whereas a stable response was found for the ABB grammar. Right fronto-temporal areas showed neither initial discrimination, nor change over time to either pattern.Taken together with Gervain et al. (2008, this is the first evidence that manipulating methodological factors influences the presence or absence of neural repetition enhancement

  1. The Risk of Repetition of Attempted Suicide Among Iranian Women with Psychiatric Disorders as Quantified by the Suicide Behaviors Questionnaire

    Directory of Open Access Journals (Sweden)

    Jalal Shakeri

    2015-05-01

    Full Text Available Objectives: The factors associated with repetition of attempted suicide are poorly categorized in the Iranian population. In this study, the prevalence of different psychiatric disorders among women who attempted suicide and the risk of repetition were assessed. Methods: Participants were women admitted to the Poisoning Emergency Hospital, Kermanshah University of Medical Sciences following failed suicide attempts. Psychiatric disorders were diagnosed based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV symptom checklist. Risk of repetition was evaluated using the Suicide Behaviors Questionnaire-Revised (SBQ-R. Results: About 72% of individuals had a SBQ-R score >8 and were considered to be at high risk for repeated attempted suicide. Adjustment disorders were the most common psychiatric disorders (40.8%. However, the type of psychiatric disorder was not associated with the risk of repetition (p=0.320. Marital status, educational level, employment, substance use, history of suicide among family members, and motivation were not determinant factors for repetition of suicide attempt (p=0.220, 0.880, 0.220, 0.290, 0.350 and 0.270, respectively. Younger women were associated with violent methods of attempted suicide, such as self-cutting, whereas older individuals preferred consumption of poison (p<0.001. Drug overdose was more common among single and married women whereas widows or divorcees preferred self-burning (p=0.004. Conclusion: About 72% of patients with failed suicide attempts were at high risk for repeated attempts. Age, marital status, and type of psychiatric disorder were the only determinants of suicide method. Adjustment disorders were the most common psychiatric disorders among Iranian women. However, this did not predict the risk of further attempts.

  2. A clinical repetitive transcranial magnetic stimulation service in Australia: 6 years on.

    Science.gov (United States)

    Galletly, Cherrie A; Clarke, Patrick; Carnell, Benjamin L; Gill, Shane

    2015-11-01

    There is considerable research evidence for the effectiveness of repetitive transcranial magnetic stimulation in the treatment of depression. However, there is little information about its acceptability and outcomes in clinical settings. This naturalistic study reports on a clinical repetitive transcranial magnetic stimulation service that has been running in Adelaide, South Australia (SA), for 6 years. During this time, 214 complete acute courses were provided to patients with treatment-resistant Major Depressive Disorder. Patients received either sequential bilateral or right unilateral repetitive transcranial magnetic stimulation treatment involving either 18 or 20 sessions given over 6 or 4 weeks respectively. Data included patient demographic details, duration of depression, and medication at the beginning of their repetitive transcranial magnetic stimulation course. The Hamilton Depression Rating Scale was used to assess response to repetitive transcranial magnetic stimulation. Of those undergoing a first-time acute treatment course of repetitive transcranial magnetic stimulation (N = 167), 28% achieved remission, while a further 12% met the criteria for a response to treatment. Most patients (N = 123, 77%) had previously been treated with five or more antidepressant medications, and 77 (47%) had previously received electroconvulsive therapy. Referral rates remained high over the 6 years, indicating acceptance of the treatment by referring psychiatrists. There were no significant adverse events, and the treatment was generally well tolerated. In all, 41 patients (25%) had a second course of repetitive transcranial magnetic stimulation and 6 (4%) patients had a third course; 21 patients subsequently received maintenance repetitive transcranial magnetic stimulation. This naturalistic study showed that repetitive transcranial magnetic stimulation was well accepted by both psychiatrists and patients, and has good efficacy and safety. Furthermore

  3. A repetitive elements perspective in Polycomb epigenetics.

    Directory of Open Access Journals (Sweden)

    Valentina eCasa

    2012-10-01

    Full Text Available Repetitive elements comprise over two-thirds of the human genome. For a long time, these elements have received little attention since they were considered non functional. On the contrary, recent evidence indicates that they play central roles in genome integrity, gene expression and disease. Indeed, repeats display meiotic instability associated with disease and are located within common fragile sites, which are hotspots of chromosome rearrangements in tumors. Moreover, a variety of diseases have been associated with aberrant transcription of repetitive elements. Overall this indicates that appropriate regulation of repetitive elements’ activity is fundamental.Polycomb group (PcG proteins are epigenetic regulators that are essential for the normal development of multicellular organisms. Mammalian PcG proteins are involved in fundamental processes, such as cellular memory, cell proliferation, genomic imprinting, X-inactivation, and cancer development. PcG proteins can convey their activity through long-distance interactions also on different chromosomes. This indicates that the 3D organization of PcG proteins contributes significantly to their function. However, it is still unclear how these complex mechanisms are orchestrated and which role PcG proteins play in the multi-level organization of gene regulation. Intriguingly, the greatest proportion of Polycomb-mediated chromatin modifications is located in genomic repeats and it has been suggested that they could provide a binding platform for Polycomb proteins.Here, these lines of evidence are woven together to discuss how repetitive elements could contribute to chromatin organization in the 3D nuclear space.

  4. Human skeletal muscle drug transporters determine local exposure and toxicity of statins.

    Science.gov (United States)

    Knauer, Michael J; Urquhart, Bradley L; Meyer zu Schwabedissen, Henriette E; Schwarz, Ute I; Lemke, Christopher J; Leake, Brenda F; Kim, Richard B; Tirona, Rommel G

    2010-02-05

    The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, are important drugs used in the treatment and prevention of cardiovascular disease. Although statins are well tolerated, many patients develop myopathy manifesting as muscle aches and pain. Rhabdomyolysis is a rare but severe toxicity of statins. Interindividual differences in the activities of hepatic membrane drug transporters and metabolic enzymes are known to influence statin plasma pharmacokinetics and risk for myopathy. Interestingly, little is known regarding the molecular determinants of statin distribution into skeletal muscle and its relevance to toxicity. We sought to identify statin transporters in human skeletal muscle and determine their impact on statin toxicity in vitro. We demonstrate that the uptake transporter OATP2B1 (human organic anion transporting polypeptide 2B1) and the efflux transporters, multidrug resistance-associated protein (MRP)1, MRP4, and MRP5 are expressed on the sarcolemmal membrane of human skeletal muscle fibers and that atorvastatin and rosuvastatin are substrates of these transporters when assessed using a heterologous expression system. In an in vitro model of differentiated, primary human skeletal muscle myoblast cells, we demonstrate basal membrane expression and drug efflux activity of MRP1, which contributes to reducing intracellular statin accumulation. Furthermore, we show that expression of human OATP2B1 in human skeletal muscle myoblast cells by adenoviral vectors increases intracellular accumulation and toxicity of statins and such effects were abrogated when cells overexpressed MRP1. These results identify key membrane transporters as modulators of skeletal muscle statin exposure and toxicity.

  5. Preconception care: caffeine, smoking, alcohol, drugs and other environmental chemical/radiation exposure.

    Science.gov (United States)

    Lassi, Zohra S; Imam, Ayesha M; Dean, Sohni V; Bhutta, Zulfiqar A

    2014-09-26

    As providing health education, optimizing nutrition, and managing risk factors can be effective for ensuring a healthy outcome for women and her yet un-conceived baby, external influences play a significant role as well. Alcohol, smoking, caffeine use and other similar lifestyle factors, have now become an integral part of the daily life of most men and women, who use/misuse one or more of these harmful substances regularly despite knowledge of their detrimental effects. The adverse health outcomes of these voluntary and involuntary exposures are of even greater concern in women of child bearing age where the exposure has the potential of inflicting harm to two generations. This paper is examining the available literature for the possible effects of caffeine consumption, smoking, alcohol or exposure to chemicals may have on the maternal, newborn and child health (MNCH). A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception usage of caffeine, tobacco, alcohol and other illicit drugs; and exposure to environmental chemicals and radiant on MNCH outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture. Heavy maternal preconception caffeine intake of >300 mg/d significantly increase the risk of a subsequent fetal loss by 31% (95% CI: 8-58%). On the other hand, preconception alcohol consumption leads to non-significant 30% increase in spontaneous abortion (RR 1.30; 95% CI: 0.85-1.97). Preconception counselling can lead to a significant decrease in the consumption of alcohol during the first trimester (OR 1.79; 95% CI: 1.08-2.97). Periconception smoking, on the other hand, was found to be associated with an almost 3 times increased risk of congenital heart defects (OR 2.80; 95% CI 1

  6. The roles of stimulus repetition and hemispheric activation in visual half-field asymmetries.

    Science.gov (United States)

    Sullivan, K F; McKeever, W F

    1985-10-01

    Hardyck, Tzeng, and Wang (1978, Brain and Language, 5, 56-71) hypothesized that ample repetition of a small number of stimuli is required in order to obtain VHF differences in tachistoscopic tasks. Four experiments, with varied levels of repetition, were conducted to test this hypothesis. Three experiments utilized the general task of object-picture naming and one utilized a word-naming task. Naming latencies constituted the dependent measure. The results demonstrate that for the object-naming paradigm repetition is required for RVF superiority to emerge. Repetition was found to be unnecessary for RVF superiority in the word-naming paradigm, with repetition actually reducing RVF superiority. Experiment I suggested the possibility that RVF superiority developed for the second half of the trials as a function of practice or hemispheric activation, regardless of repetition level. Subsequent experiments, better designed to assess this possibility, clearly refuted it. It was concluded that the effect of repetition depends on the processing requirements of the task. We propose that, for tasks which can be processed efficiently by one hemisphere, the effect of repetition will be to reduce VHF asymmetries; but tasks requiring substantial processing by both hemispheres will show shifts to RVF superiority as a function of repetition.

  7. Antineoplastic drugs: Occupational exposure and health risks

    NARCIS (Netherlands)

    Fransman, W.

    2006-01-01

    Antineoplastic drugs are pharmaceuticals commonly used to treat cancer (and some non-neoplastic diseases), which are generally referred to as 'chemotherapy'. Oncology nurses are exposed to these drugs via the skin of hands during daily nursing activities, even when protective gloves are being used.

  8. A feasible repetitive transcranial magnetic stimulation clinical protocol in migraine prevention.

    Science.gov (United States)

    Zardouz, Shawn; Shi, Lei; Leung, Albert

    2016-01-01

    This case series was conducted to determine the clinical feasibility of a repetitive transcranial magnetic stimulation protocol for the prevention of migraine (with and without aura). Five patients with migraines underwent five repetitive transcranial magnetic stimulation sessions separated in 1- to 2-week intervals for a period of 2 months at a single tertiary medical center. Repetitive transcranial magnetic stimulation was applied to the left motor cortex with 2000 pulses (20 trains with 1s inter-train interval) delivered per session, at a frequency of 10 Hz and 80% resting motor threshold. Pre- and post-treatment numerical rating pain scales were collected, and percent reductions in intensity, frequency, and duration were generated. An average decrease in 37.8%, 32.1%, and 31.2% were noted in the intensity, frequency, and duration of migraines post-repetitive transcranial magnetic stimulation, respectively. A mean decrease in 1.9±1.0 (numerical rating pain scale ± standard deviation; range: 0.4-2.8) in headache intensity scores was noted after the repetitive transcranial magnetic stimulation sessions. The tested repetitive transcranial magnetic stimulation protocol is a well-tolerated, safe, and effective method for migraine prevention.

  9. High-repetition-rate short-pulse gas discharge.

    Science.gov (United States)

    Tulip, J; Seguin, H; Mace, P N

    1979-09-01

    A high-average-power short-pulse gas discharge is described. This consists of a volume-preionized transverse discharge of the type used in gas lasers driven by a Blumlein energy storage circuit. The Blumlein circuit is fabricated from coaxial cable, is pulse-charged from a high-repetition-rate Marx-bank generator, and is switched by a high-repetition-rate segmented rail gap. The operation of this discharge under conditions typical of rare-gas halide lasers is described. A maximum of 900 pps was obtained, giving a power flow into the discharge of 30 kW.

  10. Local drug delivery - the early Berlin experience: single drug administration versus sustained release.

    Science.gov (United States)

    Speck, Ulrich; Scheller, Bruno; Rutsch, Wolfgang; Laule, Michael; Stangl, Verena

    2011-05-01

    Our initial investigations into restenosis inhibition by local drug delivery were prompted by reports on an improved outcome of coronary interventions, including a lower rate of target lesion revascularisation, when the intervention was performed with an ionic instead of non-ionic contrast medium. Although this was not confirmed in an animal study, the short exposure of the vessel wall to paclitaxel dissolved in contrast agent or coated on balloons proved to be efficacious. A study comparing three methods of local drug delivery to the coronary artery in pigs indicated the following order of efficacy in inhibiting neointimal proliferation: paclitaxel-coated balloons > sirolimus-eluting stents, sustained drug release > paclitaxel in contrast medium. Cell culture experiments confirmed that cell proliferation can be inhibited by very short exposure to the drug. Shorter exposure times require higher drug concentrations. Effective paclitaxel concentrations in porcine arteries are achieved when the drug is dissolved in contrast medium or coated on balloons. Paclitaxel is an exceptional drug in that it stays in the treated tissue for a long time. This may explain the long-lasting efficacy of paclitaxel-coated balloons, but does not disprove the hypothesis that the agent blocks a process initiating long-lasting excessive neointimal proliferation, which occurs early after vessel injury.

  11. Risk of single and combined exposure of birds to non-steroidal anti-inflammatory drugs and lead.

    Science.gov (United States)

    Osickova, Jitka; Skochova, Hana; Ondracek, Karel; Kral, Jiri; Damkova, Veronika; Peckova, Lucie; Pohanka, Miroslav; Vitula, Frantisek; Bandouchova, Hana; Pikula, Jiri

    2012-01-01

    Pharmaceuticals and heavy metals such as diclofenac and lead, respectively, have been identified as environmental contaminants toxic to birds and posing serious threats to declining populations of raptors worldwide. The aim of the present study was to test the hypothesis that a sublethal combination of non-steroidal anti-inflammatory drugs and lead induces more pronounced effects than single exposures in birds. A total of 40 Japanese quails (Coturnix coturnix japonica) at the age of 2 months and average weight of 180g were on a random basis divided into four experimental groups of 10 specimens (i.e., control, diclofenac, lead, and lead+diclofenac exposures). Six lead shots in the total weight of 1.5 grams were inserted into the crop on day 0 of the experiment, while a total of 5 mg/kg of diclofenac administered intramuscularly were divided into treatments on days 0 and 5. Group responses were compared using haematology and biochemistry after 10 days. There was no mortality in control and both single and combined diclofenac and lead exposure groups, nor did the birds show any clinical signs of intoxication. Univariate analyses of blood parameters yielded a decrease in haematocrit in birds exposed to both substances when compared with the control, a lower haemoglobin level of the lead-exposed group, increased activity of aspartate aminotransferase in the NSAIDs-exposed group, increased activity of alkaline phosphatase in birds exposed to a combination of diclofenac and lead, and a higher phosphorus level in the lead-exposed group. The principal component analysis revealed no multivariate pattern of responses of blood parameters and did not allow separation of exposure groups from controls when the variables and samples were projected onto a two dimensional space. Results of the present study can enhance understanding of combination toxicity of veterinary drugs and heavy metals in birds, i.e. a scenario that has become environmentally relevant in recent decades

  12. Extending Injury- and Disease-Resistant CNS Phenotypes by Repetitive Epigenetic Conditioning

    Directory of Open Access Journals (Sweden)

    Jeffrey M. Gidday

    2015-03-01

    Full Text Available Significant reductions in the extent of acute injury in the CNS can be achieved by exposure to different preconditioning stimuli, but the duration of the induced protective phenotype is typically short-lasting, and thus is deemed as limiting its clinical applicability. Extending the period over which such adaptive epigenetic changes persist – in effect, expanding conditioning’s therapeutic window – would significantly broaden the potential applications of such a treatment approach in patients. The frequency of the conditioning stimulus may hold the key. While transient (1-3 days protection against CNS ischemic injury is well established preclinically following a single preconditioning stimulus, repetitively presenting preconditioning stimuli extends the duration of ischemic tolerance by many weeks. Moreover, repetitive intermittent postconditioning enhances postischemic recovery metrics and improves long-term survival. Intermittent conditioning is also efficacious for preventing or delaying injury in preclinical models of chronic neurodegenerative disease, and for promoting long-lasting functional improvements in a number of other pathologies as well. Although the detailed mechanisms underlying these protracted kinds of neuroplasticity remain largely unstudied, accumulating empirical evidence supports the contention that all of these adaptive phenotypes are epigenetically mediated. Going forward, additional preclinical demonstrations of the ability to induce sustained beneficial phenotypes that reduce the burden of acute and chronic neurodegeneration, and experimental interrogations of the regulatory constructs responsible for these epigenetic responses, will accelerate the identification of not only efficacious, but practical, adaptive epigenetics-based treatments for individuals with neurological disease.

  13. Repetitively pulsed, double discharge TEA CO/sub 2/ laser

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, D C; James, D J; Ramsden, S A

    1975-10-01

    The design and operation of a repetitively pulsed TEA CO/sub 2/ laser is described. Average powers of up to 400 W at a repetition frequency of 200 pulses/s have been obtained. The system has also been used to provide long pulses (over 20 ..mu..s) and tunable single axial mode pulses.

  14. Modeling repetitive motions using structured light.

    Science.gov (United States)

    Xu, Yi; Aliaga, Daniel G

    2010-01-01

    Obtaining models of dynamic 3D objects is an important part of content generation for computer graphics. Numerous methods have been extended from static scenarios to model dynamic scenes. If the states or poses of the dynamic object repeat often during a sequence (but not necessarily periodically), we call such a repetitive motion. There are many objects, such as toys, machines, and humans, undergoing repetitive motions. Our key observation is that when a motion-state repeats, we can sample the scene under the same motion state again but using a different set of parameters; thus, providing more information of each motion state. This enables robustly acquiring dense 3D information difficult for objects with repetitive motions using only simple hardware. After the motion sequence, we group temporally disjoint observations of the same motion state together and produce a smooth space-time reconstruction of the scene. Effectively, the dynamic scene modeling problem is converted to a series of static scene reconstructions, which are easier to tackle. The varying sampling parameters can be, for example, structured-light patterns, illumination directions, and viewpoints resulting in different modeling techniques. Based on this observation, we present an image-based motion-state framework and demonstrate our paradigm using either a synchronized or an unsynchronized structured-light acquisition method.

  15. Body-focused repetitive behavior disorders in ICD-11

    Directory of Open Access Journals (Sweden)

    Jon E. Grant

    2014-01-01

    Full Text Available This article addresses the question of how body-focused repetitive behavior disorders (e.g., trichotillomania and skin-picking disorder should be characterized in ICD-11. The article reviews the historical nosology of the two disorders and the current approaches in DSM-5 and ICD-10. Although data are limited and mixed regarding the optimal relationship between body-focused repetitive behavior disorders and nosological categories, these conditions should be included within the obsessive-compulsive and related disorders category, as this is how most clinicians see these behaviors, and as this may optimize clinical utility. The descriptions of these disorders should largely mirror those in DSM-5, given the evidence from recent field surveys. The recommendations regarding ICD-11 and body-focused repetitive behavior disorders should promote the global identification and treatment of these conditions in primary care settings.

  16. Repetition Blindness: Out of Sight or Out of Mind?

    Science.gov (United States)

    Morris, Alison L.; Harris, Catherine L.

    2004-01-01

    Does repetition blindness represent a failure of perception or of memory? In Experiment 1, participants viewed rapid serial visual presentation (RSVP) sentences. When critical words (C1 and C2) were orthographically similar, C2 was frequently omitted from serial report; however, repetition priming for C2 on a postsentence lexical decision task was…

  17. Progress in developing repetitive pulse systems utilizing inductive energy storage

    Energy Technology Data Exchange (ETDEWEB)

    Honig, E.M.

    1983-01-01

    High-power, fast-recovery vacuum switches were used in a new repetitive counterpulse and transfer circuit to deliver a 5-kHz pulse train with a peak power of 75 MW (at 8.6 kA) to a 1-..cap omega.. load, resulting in the first demonstration of fully controlled, high-power, high-repetition-rate operation of an inductive energy-storage and transfer system with nondestructive switches. New circuits, analytical and experimental results, and feasibility of 100-kV repetitive pulse generation are discussed. A new switching concept for railgun loads is presented.

  18. Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Chaparro, M; Verreth, A; Lobaton, T

    2018-01-01

    OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs...... in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non......-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox...

  19. Studies of the impact of occupational exposure of pharmaceutical workers on the development of antimicrobial drug resistance.

    Science.gov (United States)

    Sarker, Md Moklesur Rahman; Islam, Kamrun Nahar; Huri, Hasniza Zaman; Rahman, Monzur; Imam, Hasan; Hosen, Md Biplob; Mohammad, Nur; Sarker, Md Zaidul Islam

    2014-01-01

    Pharmaceutical workers involved with the production of antimicrobial drugs are exposed to various antimicrobial chemicals in different steps of manufacturing such as grinding, sieving, compression, granulation, mixing and filling. These exposures may lead to the development of multidrug resistance (MDR) in bacteria. Scientific reports on the occupational health hazard of pharmaceutical workers involved in manufacturing antibiotics are scarce. The present study aimed to compare the degree of bacterial resistance in pharmaceutical workers in Bangladesh to that of individuals not involved in the pharmaceutical field. Twenty male workers from five local pharmaceutical companies and twenty male subjects not involved in the pharmaceutical field (non-pharmaceutical subjects) were randomly selected. Nasal fluid, mucus/cough and stool specimens were collected from each subject and were cultured separately at 37°C for 24 hours to obtain bacterial growth. The cultured species were then identified, isolated and subjected to microbial sensitivity testing against 18 different antibiotics from eight different groups by the disk diffusion method. Staphylococcus spp., Pseudomonas spp. and Escherichia coli were identified and isolated from the culture of nasal fluids, mucuses and stools, respectively. All the isolated species of bacteria exhibited significant enhancement of the degree of MDR in pharmaceutical workers compared with non-pharmaceutical subjects. Workers with a longer working history had greater degree of antibiotic resistance and vice versa. It can be certainly considered that the exposure of pharmaceutical workers to antibiotic agents resulted in a high incidence of multidrug resistance. Effective steps should be taken to minimize inherent exposure of pharmaceutical workers to antibiotics during work to prevent antimicrobial drug resistance.

  20. Prenatal exposure to ethanol during late gestation facilitates operant self-administration of the drug in 5-day-old rats.

    Science.gov (United States)

    Miranda-Morales, Roberto Sebastián; Nizhnikov, Michael E; Spear, Norman E

    2014-02-01

    Prenatal ethanol exposure modifies postnatal affinity to the drug, increasing the probability of ethanol use and abuse. The present study tested developing rats (5-day-old) in a novel operant technique to assess the degree of ethanol self-administration as a result of prenatal exposure to low ethanol doses during late gestation. On a single occasion during each of gestational days 17-20, pregnant rats were intragastrically administered ethanol 1 g/kg, or water (vehicle). On postnatal day 5, pups were tested on a novel operant conditioning procedure in which they learned to touch a sensor to obtain 0.1% saccharin, 3% ethanol, or 5% ethanol. Immediately after a 15-min training session, a 6-min extinction session was given in which operant behavior had no consequence. Pups were positioned on a smooth surface and had access to a touch-sensitive sensor. Physical contact with the sensor activated an infusion pump, which served to deliver an intraoral solution as reinforcement (Paired group). A Yoked control animal evaluated at the same time received the reinforcer when its corresponding Paired pup touched the sensor. Operant behavior to gain access to 3% ethanol was facilitated by prenatal exposure to ethanol during late gestation. In contrast, operant learning reflecting ethanol reinforcement did not occur in control animals prenatally exposed to water only. Similarly, saccharin reinforcement was not affected by prenatal ethanol exposure. These results suggest that in 5-day-old rats, prenatal exposure to a low ethanol dose facilitates operant learning reinforced by intraoral administration of a low-concentration ethanol solution. This emphasizes the importance of intrauterine experiences with ethanol in later susceptibility to drug reinforcement. The present operant conditioning technique represents an alternative tool to assess self-administration and seeking behavior during early stages of development. Published by Elsevier Inc.

  1. Repetitive laser fusion experiment and operation using a target injection system

    International Nuclear Information System (INIS)

    Nishimura, Yasuhiko; Komeda, Osamu; Mori, Yoshitaka

    2017-01-01

    Since 2008, a collaborative research project on laser fusion development based on a high-speed ignition method using repetitive laser has been carried out with several collaborative research institutes. This paper reports the current state of operation of high repetition laser fusion experiments, such as target introduction and control based on a target injection system that allows free falling under 1 Hz, using a high repetition laser driver that has been under research and development, as well as the measurement of targets that freely fall. The HAMA laser driver that enabled high repetition fusion experiments is a titanium sapphire laser using a diode-pumped solid-state laser KURE-I of green light output as a driver pump light source. In order to carry out high repetition laser fusion experiments, the target injection device allows free falling of deuterated polystyrene solid sphere targets of 1 mm in diameter under 1 Hz. The authors integrated the developed laser and injection system, and succeeded first in the world in making the nuclear fusion reaction continuously by hitting the target to be injected with laser, which is essential technology for future laser nuclear fusion reactor. In order to realize repetition laser fusion experiments, stable laser, target synchronization control, and target position measurement technologies are indispensable. (A.O.)

  2. Repetition and brain potentials when recognizing natural scenes: task and emotion differences

    Science.gov (United States)

    Bradley, Margaret M.; Codispoti, Maurizio; Karlsson, Marie; Lang, Peter J.

    2013-01-01

    Repetition has long been known to facilitate memory performance, but its effects on event-related potentials (ERPs), measured as an index of recognition memory, are less well characterized. In Experiment 1, effects of both massed and distributed repetition on old–new ERPs were assessed during an immediate recognition test that followed incidental encoding of natural scenes that also varied in emotionality. Distributed repetition at encoding enhanced both memory performance and the amplitude of an old–new ERP difference over centro-parietal sensors. To assess whether these repetition effects reflect encoding or retrieval differences, the recognition task was replaced with passive viewing of old and new pictures in Experiment 2. In the absence of an explicit recognition task, ERPs were completely unaffected by repetition at encoding, and only emotional pictures prompted a modestly enhanced old–new difference. Taken together, the data suggest that repetition facilitates retrieval processes and that, in the absence of an explicit recognition task, differences in old–new ERPs are only apparent for affective cues. PMID:22842817

  3. Exposure time independent summary statistics for assessment of drug dependent cell line growth inhibition.

    Science.gov (United States)

    Falgreen, Steffen; Laursen, Maria Bach; Bødker, Julie Støve; Kjeldsen, Malene Krag; Schmitz, Alexander; Nyegaard, Mette; Johnsen, Hans Erik; Dybkær, Karen; Bøgsted, Martin

    2014-06-05

    In vitro generated dose-response curves of human cancer cell lines are widely used to develop new therapeutics. The curves are summarised by simplified statistics that ignore the conventionally used dose-response curves' dependency on drug exposure time and growth kinetics. This may lead to suboptimal exploitation of data and biased conclusions on the potential of the drug in question. Therefore we set out to improve the dose-response assessments by eliminating the impact of time dependency. First, a mathematical model for drug induced cell growth inhibition was formulated and used to derive novel dose-response curves and improved summary statistics that are independent of time under the proposed model. Next, a statistical analysis workflow for estimating the improved statistics was suggested consisting of 1) nonlinear regression models for estimation of cell counts and doubling times, 2) isotonic regression for modelling the suggested dose-response curves, and 3) resampling based method for assessing variation of the novel summary statistics. We document that conventionally used summary statistics for dose-response experiments depend on time so that fast growing cell lines compared to slowly growing ones are considered overly sensitive. The adequacy of the mathematical model is tested for doxorubicin and found to fit real data to an acceptable degree. Dose-response data from the NCI60 drug screen were used to illustrate the time dependency and demonstrate an adjustment correcting for it. The applicability of the workflow was illustrated by simulation and application on a doxorubicin growth inhibition screen. The simulations show that under the proposed mathematical model the suggested statistical workflow results in unbiased estimates of the time independent summary statistics. Variance estimates of the novel summary statistics are used to conclude that the doxorubicin screen covers a significant diverse range of responses ensuring it is useful for biological

  4. Repetition or Reconfiguration

    DEFF Research Database (Denmark)

    Andersen, Kristina Vaarst

    , the cognitive quality of knowledge held by individual professionals is the key microfoundation for project level performance. This paper empirically tests effects of project participants with and without knowledge diversity for project level performance for projects aiming for varying degrees of repetition...... and reconfiguration. The results indicate that project performance benefits form contributions from individuals holding diverse knowledge only when projects aim for high differentiation levels. This positive association is not just moderated, it may even be reversed in the case of professionals participating in low...

  5. Visual attention to advertising : The impact of motivation and repetition

    NARCIS (Netherlands)

    Pieters, RGM; Rosbergen, E; Hartog, M; Corfman, KP; Lynch, JG

    1996-01-01

    Using eye-tracking data, we examine the impact of motivation and repetition on visual attention to advertisements differing in argument quality. Our analyses indicate that repetition leads to an overall decrease in the amount of attention. However, while at first high motivation subjects attend to

  6. Hydrophobic Drug-Loaded PEGylated Magnetic Liposomes for Drug-Controlled Release

    Science.gov (United States)

    Hardiansyah, Andri; Yang, Ming-Chien; Liu, Ting-Yu; Kuo, Chih-Yu; Huang, Li-Ying; Chan, Tzu-Yi

    2017-05-01

    Less targeted and limited solubility of hydrophobic-based drug are one of the serious obstacles in drug delivery system. Thus, new strategies to enhance the solubility of hydrophobic drug and controlled release behaviors would be developed. Herein, curcumin, a model of hydrophobic drug, has been loaded into PEGylated magnetic liposomes as a drug carrier platform for drug controlled release system. Inductive magnetic heating (hyperthermia)-stimulated drug release, in vitro cellular cytotoxicity assay of curcumin-loaded PEGylated magnetic liposomes and cellular internalization-induced by magnetic guidance would be investigated. The resultant of drug carriers could disperse homogeneously in aqueous solution, showing a superparamagnetic characteristic and could inductive magnetic heating with external high-frequency magnetic field (HFMF). In vitro curcumin release studies confirmed that the drug carriers exhibited no significant release at 37 °C, whereas exhibited rapid releasing at 45 °C. However, it would display enormous (three times higher) curcumin releasing under the HFMF exposure, compared with that without HFMF exposure at 45 °C. In vitro cytotoxicity test shows that curcumin-loaded PEGylated magnetic liposomes could efficiently kill MCF-7 cells in parallel with increasing curcumin concentration. Fluorescence microscopy observed that these drug carriers could internalize efficiently into the cellular compartment of MCF-7 cells. Thus, it would be anticipated that the novel hydrophobic drug-loaded PEGylated magnetic liposomes in combination with inductive magnetic heating are promising to apply in the combination of chemotherapy and thermotherapy for cancer therapy.

  7. Pull-production in repetitive remanufacturing

    Energy Technology Data Exchange (ETDEWEB)

    McCaskey, D.W. Jr.

    1992-09-01

    In the past, production activity control practices in most repetitive remanufacturing facilities resembled those used in intermittent production operations. These operations were characterized by large amounts of work-in-process (WIP), frequent work stoppages due to part shortages, excessive overtime, low product velocity, informal scheduling between dependent operations, low employee and management moral, and a lot of wasted time, material, labor, and space. Improvement in production activity control (PAC) methods for repetitive remanufactures has been hampered by uncertainty in: supply of incoming assets, configuration of assets, process times to refurbish assets, and yields in reclamation processes. collectively these uncertainties make shop floor operations seem uncontrollable. However, one United States Army depot has taken on the challenge. Through management supported, cross-functional teams, the Tooele Army Depot has designed and implemented pull-production systems for two of its major products, with several others to follow. This article presents a generalized version of Tooele`s pull-production system and highlights design characteristics which are specific to remanufacturing applications.

  8. Pull-production in repetitive remanufacturing

    Energy Technology Data Exchange (ETDEWEB)

    McCaskey, D.W. Jr.

    1992-09-01

    In the past, production activity control practices in most repetitive remanufacturing facilities resembled those used in intermittent production operations. These operations were characterized by large amounts of work-in-process (WIP), frequent work stoppages due to part shortages, excessive overtime, low product velocity, informal scheduling between dependent operations, low employee and management moral, and a lot of wasted time, material, labor, and space. Improvement in production activity control (PAC) methods for repetitive remanufactures has been hampered by uncertainty in: supply of incoming assets, configuration of assets, process times to refurbish assets, and yields in reclamation processes. collectively these uncertainties make shop floor operations seem uncontrollable. However, one United States Army depot has taken on the challenge. Through management supported, cross-functional teams, the Tooele Army Depot has designed and implemented pull-production systems for two of its major products, with several others to follow. This article presents a generalized version of Tooele's pull-production system and highlights design characteristics which are specific to remanufacturing applications.

  9. Active power filter for harmonic compensation using a digital dual-mode-structure repetitive control approach

    DEFF Research Database (Denmark)

    Zou, Zhixiang; Wang, Zheng; Cheng, Ming

    2012-01-01

    This paper presents an digital dual-mode-structure repetitive control approach for the single-phase shunt active power filter (APF), which aims to enhance the tracking ability and eliminate arbitrary order harmonic. The proposed repetitive control scheme blends the characteristics of both odd......-harmonic repetitive control and even-harmonic repetitive control. Moreover, the convergence rate is faster than conventional repetitive controller. Additionally, the parameters have been designed and optimized for the dual-mode structure repetitive control to improve the performance of APF system. Experimental...

  10. Paternal exposure and counselling: experience of a Teratology Information Service.

    Science.gov (United States)

    De Santis, Marco; Cesari, Elena; Cavaliere, Annafranca; Ligato, Maria Serena; Nobili, Elena; Visconti, Daniela; Caruso, Alessandro

    2008-09-01

    We describe paternal exposure and counselling in a selected population calling to an Italian Teratology Information Service (TIS). The majority of callers asked for paternal drug exposure (76%, drugs except chemotherapy) and treatment for cancer (17%, chemotherapy and/or radiotherapy). Others asked for exposure to diagnostic radiations (4%), recreational drugs (2%) and occupational chemicals (1%). Among paternal drugs neurological compounds, immunosuppressive drugs and antiviral agents were the main reasons for calling. In humans, there are no evidences of birth defects after paternal exposures, but to minimize any possible risk, counselling in men exposed to radio and chemotherapy should recommend delaying conception for at least 3 months after the end of the therapy. Male patients treated with drugs, whose teratogenic potential has been well assessed or suspected for maternal exposure, should be advised to practice effective birth control during therapy and up to one or two cycles of spermatogenesis and to avoid semen contact with vaginal walls during first trimester of pregnancy.

  11. Negative effects of item repetition on source memory

    OpenAIRE

    Kim, Kyungmi; Yi, Do-Joon; Raye, Carol L.; Johnson, Marcia K.

    2012-01-01

    In the present study, we explored how item repetition affects source memory for new item–feature associations (picture–location or picture–color). We presented line drawings varying numbers of times in Phase 1. In Phase 2, each drawing was presented once with a critical new feature. In Phase 3, we tested memory for the new source feature of each item from Phase 2. Experiments 1 and 2 demonstrated and replicated the negative effects of item repetition on incidental source memory. Prior item re...

  12. Functional dissociations in top-down control dependent neural repetition priming.

    NARCIS (Netherlands)

    Klaver, P.; Schnaidt, M.; Fell, J.; Ruhlmann, J.; Elger, C.E.; Fernandez, G.S.E.

    2007-01-01

    Little is known about the neural mechanisms underlying top-down control of repetition priming. Here, we use functional brain imaging to investigate these mechanisms. Study and repetition tasks used a natural/man-made forced choice task. In the study phase subjects were required to respond to either

  13. Effect of appreciation for Indigenous cultures and exposure to racial insults on alcohol and drug use initiation among multiethnic Argentinean youth.

    Science.gov (United States)

    Alderete, Ethel; Gregorich, Steven E; Monteban, Madalena; Kaplan, Celia P; Mejia, Raul; Livaudais-Toman, Jennifer; Pérez-Stable, Eliseo J

    2016-04-01

    This study evaluated the effect of factors reflecting appreciation of Indigenous culture and racial insults on alcohol and drug use initiation among multi-ethnic youth in Jujuy, Argentina. Students were surveyed from 27 secondary schools that were randomly selected to represent the province. A total of 3040 eligible students in 10th grade, age 14 to 18years were surveyed in 2006 and 2660 of these same students completed surveys in 11th grade in 2007. Multivariate logistic regression models assessed the effect of appreciation for Indigenous cultures and reported exposure to racial insults in 10th grade on incident current alcohol drinking in previous 30days, binge drinking (≥5 drinks at one sitting), and lifetime drug use (marijuana, inhalants or cocaine) in 11th grade among students not reporting these behaviors in 2006. In 2006, 63% of respondents reported high appreciation for Indigenous cultures and 39% had ever experienced racial insults. In 2007, incident current drinking was 24.4%, binge drinking 14.8%, and any drug use initiation was 4.1%. Exposure to racial insults increased the likelihood of binge drinking (OR=1.6; 95% CI 1.2-2.1) but was not significant for any drug use. Appreciation for Indigenous cultures reduced the risk of any drug use initiation (OR=0.5, 95% CI 0.3-0.7) but had no effect for alcohol drinking outcomes. These effects were independent of Indigenous ethnicity. Enhancing appreciation for Indigenous cultures and decreasing racial insults are achievable goals that can be incorporated into programs to prevent youth substance use. Published by Elsevier Inc.

  14. Repetitive transcranial magnetic stimulation for hallucination in schizophrenia spectrum disorders: A meta-analysis.

    Science.gov (United States)

    Zhang, Yingli; Liang, Wei; Yang, Shichang; Dai, Ping; Shen, Lijuan; Wang, Changhong

    2013-10-05

    This study assessed the efficacy and tolerability of repetitive transcranial magnetic stimulation for treatment of auditory hallucination of patients with schizophrenia spectrum disorders. Online literature retrieval was conducted using PubMed, ISI Web of Science, EMBASE, Medline and Cochrane Central Register of Controlled Trials databases from January 1985 to May 2012. Key words were "transcranial magnetic stimulation", "TMS", "repetitive transcranial magnetic stimulation", and "hallucination". Selected studies were randomized controlled trials assessing therapeutic efficacy of repetitive transcranial magnetic stimulation for hallucination in patients with schizophrenia spectrum disorders. Experimental intervention was low-frequency repetitive transcranial magnetic stimulation in left temporoparietal cortex for treatment of auditory hallucination in schizophrenia spectrum disorders. Control groups received sham stimulation. The primary outcome was total scores of Auditory Hallucinations Rating Scale, Auditory Hallucination Subscale of Psychotic Symptom Rating Scale, Positive and Negative Symptom Scale-Auditory Hallucination item, and Hallucination Change Scale. Secondary outcomes included response rate, global mental state, adverse effects and cognitive function. Seventeen studies addressing repetitive transcranial magnetic stimulation for treatment of schizophrenia spectrum disorders were screened, with controls receiving sham stimulation. All data were completely effective, involving 398 patients. Overall mean weighted effect size for repetitive transcranial magnetic stimulation versus sham stimulation was statistically significant (MD = -0.42, 95%CI: -0.64 to -0.20, P = 0.000 2). Patients receiving repetitive transcranial magnetic stimulation responded more frequently than sham stimulation (OR = 2.94, 95%CI: 1.39 to 6.24, P = 0.005). No significant differences were found between active repetitive transcranial magnetic stimulation and sham stimulation for

  15. Cellular mechanisms in drug - radiation interaction

    International Nuclear Information System (INIS)

    Trott, K.R.

    1979-01-01

    Some cytotoxic drugs, especially those belonging to the group of antibiotics and antimetabolites, sensitize the cells having survived drug treatment to the subsequent irradiation by either increasing the slope of the radiation dose response curves or by decreasing extrapolation number. Bleomycin was found to interact with radiation in L-cells and FM3A cells, but not in HeLa-cells. The data with EMT-6 cells suggest that the interaction depends on drug dose: no interaction occurred after the exposure to bleomycin which killed only 20 - 40% of the cells; yet the exposure to bleomycin which killed 90% of the cells in addition sensitized the surviving cells by the DMF of 1.3. The sensitization found 24 hr after the exposure of HeLa cells to methotrexate was due to cell synchronization. Other cytostatic drugs were found to synchronize proliferating cells even better. Therefore, the fluctuation of radiosensitivity has been commonly observed after the termination of exposure to these drugs. Preirradiation may lead to the change in drug dose response curves. The recruitment of resting cells into cycle occurs hours or days later, in some irradiated normal and malignant tissues. Since many cytostatic drugs are far more active in proliferating cells than in resting cells, the recruitment after irradiation may lead to the sudden increase in drug sensitivity, days after the irradiation. No single, simple theory seems to exist to classify and predict the cellular response to combined modality treatment. (Yamashita, S.)

  16. Autism and exergaming: effects on repetitive behaviors and cognition.

    Science.gov (United States)

    Anderson-Hanley, Cay; Tureck, Kimberly; Schneiderman, Robyn L

    2011-01-01

    Autism is a neurodevelopmental disorder that leads to impairment in social skills and delay in language development, and results in repetitive behaviors and restricted interests that impede academic and social involvement. Physical exercise has been shown to decrease repetitive behaviors in autistic children and improve cognitive function across the life-span. Exergaming combines physical and mental exercise simultaneously by linking physical activity movements to video game control and may yield better compliance with exercise. In this investigation, two pilot studies explored the potential behavioral and cognitive benefits of exergaming. In Pilot I, twelve children with autism spectrum disorders completed a control task and an acute bout of Dance Dance Revolution (DDR); in Pilot II, ten additional youths completed an acute bout of cyber cycling. Repetitive behaviors and executive function were measured before and after each activity. Repetitive behaviors significantly decreased, while performance on Digits Backwards improved following the exergaming conditions compared with the control condition. Additional research is needed to replicate these findings, and to explore the application of exergaming for the management of behavioral disturbance and to increase cognitive control in children on the autism spectrum.

  17. Autism spectrum disorders and drug addiction: Common pathways, common molecules, distinct disorders?

    Directory of Open Access Journals (Sweden)

    Patrick E. Rothwell

    2016-02-01

    Full Text Available Autism spectrum disorders (ASDs and drug addiction do not share substantial comorbidity or obvious similarities in etiology or symptomatology. It is thus surprising that a number of recent studies implicate overlapping neural circuits and molecular signaling pathways in both disorders. The purpose of this review is to highlight this emerging intersection and consider implications for understanding the pathophysiology of these seemingly distinct disorders. One area of overlap involves neural circuits and neuromodulatory systems in the striatum and basal ganglia, which play an established role in addiction and reward but are increasingly implicated in clinical and preclinical studies of ASDs. A second area of overlap relates to molecules like Fragile X mental retardation protein (FMRP and methyl CpG-binding protein-2 (MECP2, which are best known for their contribution to the pathogenesis of syndromic ASDs, but have recently been shown to regulate behavioral and neurobiological responses to addictive drug exposure. These shared pathways and molecules point to common dimensions of behavioral dysfunction, including the repetition of behavioral patterns and aberrant reward processing. The synthesis of knowledge gained through parallel investigations of ASDs and addiction may inspire the design of new therapeutic interventions to correct common elements of striatal dysfunction.

  18. Autism Spectrum Disorders and Drug Addiction: Common Pathways, Common Molecules, Distinct Disorders?

    Science.gov (United States)

    Rothwell, Patrick E

    2016-01-01

    Autism spectrum disorders (ASDs) and drug addiction do not share substantial comorbidity or obvious similarities in etiology or symptomatology. It is thus surprising that a number of recent studies implicate overlapping neural circuits and molecular signaling pathways in both disorders. The purpose of this review is to highlight this emerging intersection and consider implications for understanding the pathophysiology of these seemingly distinct disorders. One area of overlap involves neural circuits and neuromodulatory systems in the striatum and basal ganglia, which play an established role in addiction and reward but are increasingly implicated in clinical and preclinical studies of ASDs. A second area of overlap relates to molecules like Fragile X mental retardation protein (FMRP) and methyl CpG-binding protein-2 (MECP2), which are best known for their contribution to the pathogenesis of syndromic ASDs, but have recently been shown to regulate behavioral and neurobiological responses to addictive drug exposure. These shared pathways and molecules point to common dimensions of behavioral dysfunction, including the repetition of behavioral patterns and aberrant reward processing. The synthesis of knowledge gained through parallel investigations of ASDs and addiction may inspire the design of new therapeutic interventions to correct common elements of striatal dysfunction.

  19. BOLD repetition decreases in object-responsive ventral visual areas depend on spatial attention.

    Science.gov (United States)

    Eger, E; Henson, R N A; Driver, J; Dolan, R J

    2004-08-01

    Functional imaging studies of priming-related repetition phenomena have become widely used to study neural object representation. Although blood oxygenation level-dependent (BOLD) repetition decreases can sometimes be observed without awareness of repetition, any role for spatial attention in BOLD repetition effects remains largely unknown. We used fMRI in 13 healthy subjects to test whether BOLD repetition decreases for repeated objects in ventral visual cortices depend on allocation of spatial attention to the prime. Subjects performed a size-judgment task on a probe object that had been attended or ignored in a preceding prime display of 2 lateralized objects. Reaction times showed faster responses when the probe was the same object as the attended prime, independent of the view tested (identical vs. mirror image). No behavioral effect was evident from unattended primes. BOLD repetition decreases for attended primes were found in lateral occipital and fusiform regions bilaterally, which generalized across identical and mirror-image repeats. No repetition decreases were observed for ignored primes. Our results suggest a critical role for attention in achieving visual representations of objects that lead to both BOLD signal decreases and behavioral priming on repeated presentation.

  20. Considerations for Pharmacoepidemiological Studies of Drug-Cancer Associations

    DEFF Research Database (Denmark)

    Pottegård, Anton; Friis, Søren; Stürmer, Til

    2018-01-01

    and future perspectives. Aspects of data sources include assessment of complete history of drug use and data on dose and duration of drug use, allowing estimates of cumulative exposure. Outcome data from formal cancer registries are preferable, but cancer data from other sources, for example, patient......In this MiniReview, we provide general considerations for the planning and conduct of pharmacoepidemiological studies of associations between drug use and cancer development. We address data sources, study design, assessment of drug exposure, ascertainment of cancer outcomes, confounder adjustment...... or pathology registries, medical records or claims are also suitable. The two principal designs for observational studies evaluating drug-cancer associations are the cohort and case-control designs. A key challenge in studies of drug-cancer associations is the exposure assessment due to the typically long...

  1. Characterization and distribution of repetitive elements in association with genes in the human genome.

    Science.gov (United States)

    Liang, Kai-Chiang; Tseng, Joseph T; Tsai, Shaw-Jenq; Sun, H Sunny

    2015-08-01

    Repetitive elements constitute more than 50% of the human genome. Recent studies implied that the complexity of living organisms is not just a direct outcome of a number of coding sequences; the repetitive elements, which do not encode proteins, may also play a significant role. Though scattered studies showed that repetitive elements in the regulatory regions of a gene control gene expression, no systematic survey has been done to report the characterization and distribution of various types of these repetitive elements in the human genome. Sequences from 5' and 3' untranslated regions and upstream and downstream of a gene were downloaded from the Ensembl database. The repetitive elements in the neighboring of each gene were identified and classified using cross-matching implemented in the RepeatMasker. The annotation and distribution of distinct classes of repetitive elements associated with individual gene were collected to characterize genes in association with different types of repetitive elements using systems biology program. We identified a total of 1,068,400 repetitive elements which belong to 37-class families and 1235 subclasses that are associated with 33,761 genes and 57,365 transcripts. In addition, we found that the tandem repeats preferentially locate proximal to the transcription start site (TSS) of genes and the major function of these genes are involved in developmental processes. On the other hand, interspersed repetitive elements showed a tendency to be accumulated at distal region from the TSS and the function of interspersed repeat-containing genes took part in the catabolic/metabolic processes. Results from the distribution analysis were collected and used to construct a gene-based repetitive element database (GBRED; http://www.binfo.ncku.edu.tw/GBRED/index.html). A user-friendly web interface was designed to provide the information of repetitive elements associated with any particular gene(s). This is the first study focusing on the gene

  2. Repetitive Bibliographical Information in Relational Databases.

    Science.gov (United States)

    Brooks, Terrence A.

    1988-01-01

    Proposes a solution to the problem of loading repetitive bibliographic information in a microcomputer-based relational database management system. The alternative design described is based on a representational redundancy design and normalization theory. (12 references) (Author/CLB)

  3. Fragmented pictures revisited: long-term changes in repetition priming, relation to skill learning, and the role of cognitive resources.

    Science.gov (United States)

    Kennedy, Kristen M; Rodrigue, Karen M; Raz, Naftali

    2007-01-01

    Whereas age-related declines in declarative memory have been demonstrated in multiple cross-sectional and longitudinal studies, the effect of age on non-declarative manifestations of memory, such as repetition priming and perceptual skill learning, are less clear. The common assumption, based on cross-sectional studies, is that these processes are only mildly (if at all) affected by age. To investigate long-term changes in repetition priming and age-related differences in identification of fragmented pictures in a 5-year longitudinal design. Healthy adults (age 28-82 years) viewed drawings of objects presented in descending order of fragmentation. The identification threshold (IT) was the highest fragmentation level at which the object was correctly named. After a short interval, old pictures were presented again along with a set of similar but novel pictures. Five years later the participants repeated the experiment. At baseline and 5-year follow-up alike, one repeated exposure improved IT for old (priming) and new (skill acquisition) pictures. However, long-term retention of priming gains was observed only in young adults. Working memory explained a significant proportion of variance in within-occasion priming, long-term priming, and skill learning. Contrary to cross-sectional results, this longitudinal study suggests perceptual repetition priming is not an age-invariant phenomenon and advanced age and reduced availability of cognitive resources may contribute to its decline. Copyright 2007 S. Karger AG, Basel.

  4. A copper bromide vapour laser with a high pulse repetition rate

    International Nuclear Information System (INIS)

    Shiyanov, D V; Evtushenko, Gennadii S; Sukhanov, V B; Fedorov, V F

    2002-01-01

    The results of an experimental study of a copper bromide vapour laser with a discharge-channel diameter above 2.5 cm and a high pump-pulse repetition rate are presented. A TGU1-1000/25 high-power tacitron used as a switch made it possible to obtain for the first time a fairly high output radiation power for pump-pulse repetition rates exceeding 200 kHz. At a maximum pump-pulse repetition rate of 250 kHz achieved in a laser tube 2.6 cm in diameter and 76 cm long, the output power was 1.5 W. The output powers of 3 and 10.5 W were reached for pump-pulse repetition rates of 200 and 100 kHz, respectively. These characteristics were obtained without circulating a buffer gas and (or) low-concentration active impurities through the active volume. (active media. lasers)

  5. The repetition effect in building and construction works

    DEFF Research Database (Denmark)

    Gottlieb, Stefan Christoffer; Haugbølle, Kim

    are then applied on the Public Transport Authorities' main account structure of units and costs, and a method for assessing the possibilities of achieving effects of repetition for each account is described. Finally, the report summarises the core conditions necessary to take into consideration in relation......This report summarises the results from the work undertaken for the Public Transport Authority on the effect of learning and repetition in building and construction works. The results are applied by the Public Transport Authority in a new budgeting model, while the agency investigates...

  6. Nonsmoker Exposure to Secondhand Cannabis Smoke. III. Oral Fluid and Blood Drug Concentrations and Corresponding Subjective Effects.

    Science.gov (United States)

    Cone, Edward J; Bigelow, George E; Herrmann, Evan S; Mitchell, John M; LoDico, Charles; Flegel, Ronald; Vandrey, Ryan

    2015-09-01

    The increasing use of highly potent strains of cannabis prompted this new evaluation of human toxicology and subjective effects following passive exposure to cannabis smoke. The study was designed to produce extreme cannabis smoke exposure conditions tolerable to drug-free nonsmokers. Six experienced cannabis users smoked cannabis cigarettes [5.3% Δ(9)-tetrahydrocannabinol (THC) in Session 1 and 11.3% THC in Sessions 2 and 3] in a closed chamber. Six nonsmokers were seated alternately with smokers during exposure sessions of 1 h duration. Sessions 1 and 2 were conducted with no ventilation and ventilation was employed in Session 3. Oral fluid, whole blood and subjective effect measures were obtained before and at multiple time points after each session. Oral fluid was analyzed by ELISA (4 ng/mL cutoff concentration) and by LC-MS-MS (limit of quantitation) for THC (1 ng/mL) and total THCCOOH (0.02 ng/mL). Blood was analyzed by LC-MS-MS (0.5 ng/mL) for THC, 11-OH-THC and free THCCOOH. Positive tests for THC in oral fluid and blood were obtained for nonsmokers up to 3 h following exposure. Ratings of subjective effects correlated with the degree of exposure. Subjective effect measures and amounts of THC absorbed by nonsmokers (relative to smokers) indicated that extreme secondhand cannabis smoke exposure mimicked, though to a lesser extent, active cannabis smoking. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Studies of exposure of rabbits to electromagnetic pulsed fields

    International Nuclear Information System (INIS)

    Cleary, S.F.; Nickless, F.; Liu, L.M.; Hoffman, R.

    1980-01-01

    Dutch rabbits were acutely exposed to electromagnetic pulsed (EMP) fields (pulse duration 0.4 mus, field strengths of 1--2 kV/cm and pulse repetition rates in the range of 10 to 38 Hz) for periods of up to two hours. The dependent variables investigated were pentobarbital-induced sleeping time and serum chemistry (including serum triglycerides, creatine phosphokinase (CPK) isoenzymes, and sodium and potassium). Core temperature measured immediately pre-exposure and postexposure revealed no exposure-related alterations. Over the range of field strengths and pulse durations investigated no consistent, statistically significant alterations were found in the end-points investigated

  8. Contribution of fronto-striatal regions to emotional valence and repetition under cognitive conflict.

    Science.gov (United States)

    Chun, Ji-Won; Park, Hae-Jeong; Kim, Dai Jin; Kim, Eosu; Kim, Jae-Jin

    2017-07-01

    Conflict processing mediated by fronto-striatal regions may be influenced by emotional properties of stimuli. This study aimed to examine the effects of emotion repetition on cognitive control in a conflict-provoking situation. Twenty-one healthy subjects were scanned using functional magnetic resonance imaging while performing a sequential cognitive conflict task composed of emotional stimuli. The regional effects were analyzed according to the repetition or non-repetition of cognitive congruency and emotional valence between the preceding and current trials. Post-incongruence interference in error rate and reaction time was significantly smaller than post-congruence interference, particularly under repeated positive and non-repeated positive, respectively, and post-incongruence interference, compared to post-congruence interference, increased activity in the ACC, DLPFC, and striatum. ACC and DLPFC activities were significantly correlated with error rate or reaction time in some conditions, and fronto-striatal connections were related to the conflict processing heightened by negative emotion. These findings suggest that the repetition of emotional stimuli adaptively regulates cognitive control and the fronto-striatal circuit may engage in the conflict adaptation process induced by emotion repetition. Both repetition enhancement and repetition suppression of prefrontal activity may underlie the relationship between emotion and conflict adaptation. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Repetitive transcranial magnetic stimulation for hallucination in schizophrenia spectrum disorders A meta-analysis***

    Institute of Scientific and Technical Information of China (English)

    Yingli Zhang; Wei Liang; Shichang Yang; Ping Dai; Lijuan Shen; Changhong Wang

    2013-01-01

    OBJECTIVE: This study assessed the efficacy and tolerability of repetitive transcranial magnetic stimulation for treatment of auditory hal ucination of patients with schizophrenia spectrum disorders. DATA SOURCES: Online literature retrieval was conducted using PubMed, ISI Web of Science, EMBASE, Medline and Cochrane Central Register of Control ed Trials databases from January 1985 to May 2012. Key words were “transcranial magnetic stimulation”, “TMS”, “repetitive transcranial magnetic stimulation”, and “hal ucination”. STUDY SELECTION: Selected studies were randomized control ed trials assessing therapeutic ef-ficacy of repetitive transcranial magnetic stimulation for hal ucination in patients with schizophrenia spectrum disorders. Experimental intervention was low-frequency repetitive transcranial magnetic stimulation in left temporoparietal cortex for treatment of auditory hal ucination in schizophrenia spectrum disorders. Control groups received sham stimulation. MAIN OUTCOME MEASURES: The primary outcome was total scores of Auditory Hal ucinations Rating Scale, Auditory Hal ucination Subscale of Psychotic Symptom Rating Scale, Positive and Negative Symptom Scale-Auditory Hal ucination item, and Hal ucination Change Scale. Secondary outcomes included response rate, global mental state, adverse effects and cognitive function. RESULTS: Seventeen studies addressing repetitive transcranial magnetic stimulation for treatment of schizophrenia spectrum disorders were screened, with controls receiving sham stimulation. Al data were completely effective, involving 398 patients. Overal mean weighted effect size for repeti-tive transcranial magnetic stimulation versus sham stimulation was statistical y significant (MD =-0.42, 95%CI: -0.64 to -0.20, P = 0.000 2). Patients receiving repetitive transcranial magnetic stimulation responded more frequently than sham stimulation (OR = 2.94, 95%CI: 1.39 to 6.24, P =0.005). No significant differences were found

  10. Comparison of concentric and eccentric bench press repetitions to failure.

    Science.gov (United States)

    Kelly, Stephen B; Brown, Lee E; Hooker, Steven P; Swan, Pamela D; Buman, Matthew P; Alvar, Brent A; Black, Laurie E

    2015-04-01

    Eccentric muscle actions (ECC) are characterized by muscle lengthening, despite actin-myosin crossbridge formation. Muscles acting eccentrically are capable of producing higher levels of force compared with muscles acting concentrically. The purpose of this study was to determine whether ECC bench press yields greater strength than concentric (CON) as determined by 1 repetition maximum (1RM). Additionally, a comparison was made examining differences in the number of repetitions to failure at different relative intensities of 1RM. Thirty healthy men (age = 24.63 ± 5.6 years) were tested for 1RM in CON and ECC bench press and the number of repetitions completed at 60, 70, 80, and 90% 1RM. For CON repetitions, the weight was mechanically lowered to the chest, and the participant pressed it up until the elbows were fully extended. The ECC bench press consisted of lowering a barbell from a fully extended elbow position to the chest in a continuous controlled manner for 3 seconds as determined by electronic metronome. Paired t-tests showed that ECC 1RM (115.99 ± 31.08 kg) was significantly (p ≤ 0.05) greater than CON 1RM (93.56 ± 26.56 kg), and the number of repetitions completed at 90% 1RM was significantly (p ≤ 0.05) greater in ECC (7.67 ± 3.24) as compared with CON (4.57 ± 2.21). There were no significant differences in number of completed repetitions during CON and ECC bench press at 60, 70, and 80% 1RM. These data indicate that ECC actions yield increased force capabilities (∼120%) as compared with CON in the bench press and may be less prone to fatigue, especially at higher intensities. These differences suggest a need to develop unique strategies for training eccentrically.

  11. Preliminary design of a 150 kJ repetitive plasma focus for the production of 18-F

    Science.gov (United States)

    Sumini, Marco; Mostacci, Domiziano; Rocchi, Federico; Frignani, Michele; Tartari, Agostino; Angeli, Ergisto; Galaverni, Dario; Coli, Ugo; Ascione, Bernardino; Cucchi, Giorgio

    2006-06-01

    Experiments in the past five years have demonstrated production of short-lived radioisotopes with a Plasma Focus device, using the so-termed Endogenous Mode. So far radioisotope activities of only a few microcuries have been obtained from single discharges in small scale Plasma Focus machines (capacitor bank energies of approximately 7 kJ). It is expected that higher activities could be obtained with larger bank energies, operating at high pulse repetition rates, e.g. 1 Hz. However, many scientific and technological issues must be addressed for a high-energy Plasma Focus device to run at one pulse per second. Aim of this paper is to present preliminary results pertaining to the plasma, electrical, fluid-dynamical, thermal, material and mechanical design of a 150 kJ Plasma Focus, capable of a repetition rate of 1 Hz, that will be operated at 30 kV with a 350 μF capacitor bank and a maximum total current of 1.5 MA. This device will be used to breed 18-F for the synthesis of drugs used in positron-emission medical examinations, such as FDG for PET.

  12. Preliminary design of a 150 kJ repetitive plasma focus for the production of 18-F

    International Nuclear Information System (INIS)

    Sumini, Marco; Mostacci, Domiziano; Rocchi, Federico; Frignani, Michele; Tartari, Agostino; Angeli, Ergisto; Galaverni, Dario; Coli, Ugo; Ascione, Bernardino; Cucchi, Giorgio

    2006-01-01

    Experiments in the past five years have demonstrated production of short-lived radioisotopes with a Plasma Focus device, using the so-termed Endogenous Mode. So far radioisotope activities of only a few microcuries have been obtained from single discharges in small scale Plasma Focus machines (capacitor bank energies of approximately 7 kJ). It is expected that higher activities could be obtained with larger bank energies, operating at high pulse repetition rates, e.g. 1 Hz. However, many scientific and technological issues must be addressed for a high-energy Plasma Focus device to run at one pulse per second. Aim of this paper is to present preliminary results pertaining to the plasma, electrical, fluid-dynamical, thermal, material and mechanical design of a 150 kJ Plasma Focus, capable of a repetition rate of 1 Hz, that will be operated at 30 kV with a 350 μF capacitor bank and a maximum total current of 1.5 MA. This device will be used to breed 18-F for the synthesis of drugs used in positron-emission medical examinations, such as FDG for PET

  13. The intersection of stress, drug abuse and development.

    Science.gov (United States)

    Thadani, Pushpa V

    2002-01-01

    Use or abuse of licit and illicit substances is often associated with environmental stress. Current clinical evidence clearly demonstrates neurobehavioral, somatic growth and developmental deficits in children born to drug-using mothers. However, the effects of environmental stress and its interaction with prenatal drug exposure on a child's development is unknown. Studies in pregnant animals under controlled conditions show drug-induced long-term alterations in brain structures and functions of the offspring. These cytoarchitecture alterations in the brain are often associated with perturbations in neurotransmitter systems that are intimately involved in the regulation of the stress responses. Similar abnormalities have been observed in the brains of animals exposed to other adverse exogenous (e.g., environmental stress) and/or endogenous (e.g., glucocorticoids) experiences during early life. The goal of this article is to: (1) provide evidence and a perspective that common neural systems are influenced during development both by perinatal drug exposure and early stress exposure; and (2) identify gaps and encourage new research examining the effects of early stress and perinatal drug exposure, in animal models, that would elucidate how stress- and drug-induced perturbations in neural systems influence later vulnerability to abused drugs in adult offspring.

  14. Pulsed electron beam generation with fast repetitive double pulse system

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Surender Kumar; Deb, Pankaj; Shyam, Anurag, E-mail: surender80@gmail.com [Energetics and Electromagnetics Division, Bhabha Atomic Research Centre, Visakhapatnam (India); Sharma, Archana [Accelerator and Pulse Power Division, Bhabha Atomic Research Centre, Mumbai (India)

    2014-07-01

    Longer duration high voltage pulse (∼ 100 kV, 260 ns) is generated and reported using helical pulse forming line in compact geometry. The transmission line characteristics of the helical pulse forming line are also used to develop fast repetition double pulse system with very short inter pulse interval. It overcomes the limitations caused due to circuit parameters, power supplies and load characteristics for fast repetitive high voltage pulse generation. The high voltage double pulse of 100 kV, 100 ns with an inter pulse repetition interval of 30 ns is applied across the vacuum field emission diode for pulsed electron beam generation. The electron beam is generated from cathode material by application of negative high voltage (> 100 kV) across the diode by explosive electron emission process. The vacuum field emission diode is made of 40 mm diameter graphite cathode and SS mesh anode. The anode cathode gap was 6 mm and the drift tube diameter was 10 cm. The initial experimental results of pulsed electron beam generation with fast repetitive double pulse system are reported and discussed. (author)

  15. Spared behavioral repetition effects in Alzheimer's disease linked to an altered neural mechanism at posterior cortex.

    Science.gov (United States)

    Broster, Lucas S; Li, Juan; Wagner, Benjamin; Smith, Charles D; Jicha, Gregory A; Schmitt, Frederick A; Munro, Nancy; Haney, Ryan H; Jiang, Yang

    2018-02-20

    Individuals with dementia of the Alzheimer type (AD) classically show disproportionate impairment in measures of working memory, but repetition learning effects are relatively preserved. As AD affects brain regions implicated in both working memory and repetition effects, the neural basis of this discrepancy is poorly understood. We hypothesized that the posterior repetition effect could account for this discrepancy due to the milder effects of AD at visual cortex. Participants with early AD, amnestic mild cognitive impairment (MCI), and healthy controls performed a working memory task with superimposed repetition effects while electroencephalography was collected to identify possible neural mechanisms of preserved repetition effects. Participants with AD showed preserved behavioral repetition effects and a change in the posterior repetition effect. Visual cortex may play a role in maintained repetition effects in persons with early AD.

  16. Repetitive trauma and nerve compression.

    Science.gov (United States)

    Carragee, E J; Hentz, V R

    1988-01-01

    Repetitive movement of the upper extremity, whether recreational or occupational, may result in various neuropathies, the prototype of which is the median nerve neuropathic in the carpal canal. The pathophysiology of this process is incompletely understood but likely involves both mechanical and ischemic features. Experimentally increased pressures within the carpal canal produced reproducible progressive neuropathy. Changes in vibratory (threshold-type) sensibility appears to be more sensitive than two-point (innervation density-type) sensibility. The specific occupational etiologies of carpal neuropathy are obscured by methodologic and sociological difficulties, but clearly some occupations have high incidences of CTS. History and physical examination are usually sufficient for the diagnosis, but diagnostic assistance when required is available through electrophysiological testing, CT scanning, and possibly MRI. Each of these tests has limitations in both sensitivity and specificity. Treatment by usual conservative means should be combined with rest from possible provocative activities. Surgical release of the carpal canal is helpful in patients failing conservative therapy. Occupational modifications are important in both treatment and prevention of median neuropathy due to repetitive trauma.

  17. Gamma oscillations distinguish mere exposure from other likability effects.

    Science.gov (United States)

    Kongthong, Nutchakan; Minami, Tetsuto; Nakauchi, Shigeki

    2014-02-01

    Repeated exposure to neutral stimuli enhances liking for those, which is called mere exposure effect (MEE) (Zajonc, 1968). Its behavioral effects have been extensively investigated. However, the mechanism by which it is generated remains unclear. To elucidate the neural mechanism of the MEE, we recorded electroencephalograms while subjects indicated their preferences for face stimuli with and without MEE induction. According to behavioral data, participants were divided into two groups, one with, and one without MEE tendency. In participants with an MEE tendency, gamma activity (40-60 [Hz]) in the parieto-occipital area was significantly weaker for exposed faces than unexposed ones, indicating a repetition-suppression effect. Gamma activity from sites exhibiting peak repetition-suppression effects was significantly weaker in theoretically genuine MEE trials than non-MEE trials, indicating that emotion processing might influence the MEE. These results suggest that existing theories regarding mechanisms underlying the MEE, namely, fluency misattribution and apprehensiveness reduction might not be mutually exclusive. Moreover, gamma activity might be a potential indicator to distinguish the MEE from other likability effects, at least in the case of human face stimuli. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Exposure to Prescription Drugs Labeled for Risk of Adverse Effects of Suicidal Behavior or Ideation among 100 Air Force Personnel Who Died by Suicide, 2006-2009

    Science.gov (United States)

    Lavigne, Jill E.; McCarthy, Michael; Chapman, Richard; Petrilla, Allison; Knox, Kerry L.

    2012-01-01

    Prescription drugs for many indications are labeled with warnings for potential risk of suicidal ideation or behavior. Exposures to prescription drugs labeled for adverse effects of suicidal behavior or ideation among 100 Air Force personnel who died by suicide between 2006 and 2009 are described. Air Force registry data were linked to…

  19. A Drug Combination Screen Identifies Drugs Active against Amoxicillin-Induced Round Bodies of In Vitro Borrelia burgdorferi Persisters from an FDA Drug Library.

    Science.gov (United States)

    Feng, Jie; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Auwaerter, Paul G; Zhang, Ying

    2016-01-01

    Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10-20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under experimental stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that appear resistant in vitro to customary first-line antibiotics for Lyme disease. To identify more effective drugs with activity against the round body form of B. burgdorferi, we established a round body persister model induced by exposure to amoxicillin (50 μg/ml) and then screened the Food and Drug Administration drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven individual drugs scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. In this amoxicillin-induced round body model, some drug candidates such as daptomycin and clofazimine also displayed enhanced activity which was similar to a previous screen against stationary phase B. burgdorferi persisters not exposure to amoxicillin. Additional candidate drugs active against round bodies identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had the highest activity against amoxicillin-induced round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi

  20. Repetitive Elements in Mycoplasma hyopneumoniae Transcriptional Regulation.

    Directory of Open Access Journals (Sweden)

    Amanda Malvessi Cattani

    Full Text Available Transcriptional regulation, a multiple-step process, is still poorly understood in the important pig pathogen Mycoplasma hyopneumoniae. Basic motifs like promoters and terminators have already been described, but no other cis-regulatory elements have been found. DNA repeat sequences have been shown to be an interesting potential source of cis-regulatory elements. In this work, a genome-wide search for tandem and palindromic repetitive elements was performed in the intergenic regions of all coding sequences from M. hyopneumoniae strain 7448. Computational analysis demonstrated the presence of 144 tandem repeats and 1,171 palindromic elements. The DNA repeat sequences were distributed within the 5' upstream regions of 86% of transcriptional units of M. hyopneumoniae strain 7448. Comparative analysis between distinct repetitive sequences found in related mycoplasma genomes demonstrated different percentages of conservation among pathogenic and nonpathogenic strains. qPCR assays revealed differential expression among genes showing variable numbers of repetitive elements. In addition, repeats found in 206 genes already described to be differentially regulated under different culture conditions of M. hyopneumoniae strain 232 showed almost 80% conservation in relation to M. hyopneumoniae strain 7448 repeats. Altogether, these findings suggest a potential regulatory role of tandem and palindromic DNA repeats in the M. hyopneumoniae transcriptional profile.

  1. Repetitive Elements in Mycoplasma hyopneumoniae Transcriptional Regulation.

    Science.gov (United States)

    Cattani, Amanda Malvessi; Siqueira, Franciele Maboni; Guedes, Rafael Lucas Muniz; Schrank, Irene Silveira

    2016-01-01

    Transcriptional regulation, a multiple-step process, is still poorly understood in the important pig pathogen Mycoplasma hyopneumoniae. Basic motifs like promoters and terminators have already been described, but no other cis-regulatory elements have been found. DNA repeat sequences have been shown to be an interesting potential source of cis-regulatory elements. In this work, a genome-wide search for tandem and palindromic repetitive elements was performed in the intergenic regions of all coding sequences from M. hyopneumoniae strain 7448. Computational analysis demonstrated the presence of 144 tandem repeats and 1,171 palindromic elements. The DNA repeat sequences were distributed within the 5' upstream regions of 86% of transcriptional units of M. hyopneumoniae strain 7448. Comparative analysis between distinct repetitive sequences found in related mycoplasma genomes demonstrated different percentages of conservation among pathogenic and nonpathogenic strains. qPCR assays revealed differential expression among genes showing variable numbers of repetitive elements. In addition, repeats found in 206 genes already described to be differentially regulated under different culture conditions of M. hyopneumoniae strain 232 showed almost 80% conservation in relation to M. hyopneumoniae strain 7448 repeats. Altogether, these findings suggest a potential regulatory role of tandem and palindromic DNA repeats in the M. hyopneumoniae transcriptional profile.

  2. Interest of repetitive transcranial magnetic stimulation of the motor cortex in the management of refractory cancer pain in palliative care: Two case reports.

    Science.gov (United States)

    Nizard, Julien; Levesque, Amélie; Denis, Nathalie; de Chauvigny, Edwige; Lepeintre, Aurélie; Raoul, Sylvie; Labat, Jean-Jacques; Bulteau, Samuel; Maillard, Benoît; Buffenoir, Kevin; Potel, Gilles; Lefaucheur, Jean-Pascal; Nguyen, Jean Paul

    2015-06-01

    Non-drug treatments should be systematically associated to the medical analgesic treatment during the terminal phase of cancer. Patient 1, a 23-year-old woman, presented an adenocarcinoma of the rectum, with liver and lung metastases. Pain was initially treated by oral morphine and a combination of pregabalin and amitriptyline. Ketamine and intrathecal administration of morphine were both ineffective. Patient 2, a 69-year-old woman, presented a cutaneous T-cell lymphoma. She was admitted to the palliative care unit with mixed pain related to cutaneous lymphomatous infiltration. World Health Organization (WHO) step 3 analgesics had not been tolerated. Both patients received five consecutive 20-min sessions of repetitive transcranial magnetic stimulation to the right motor cortex. Patient 1 experienced a marked improvement of her pain over the days following the first repetitive transcranial magnetic stimulation session. Medical treatment was able to be rapidly decreased by about 50%, which restored an almost normal level of consciousness and lucidity. Patient 2's pain was also markedly decreased over the days following these five consecutive sessions, and repetitive transcranial magnetic stimulation also appeared to have had a beneficial effect on the patient's anxiety and mood. In the context of palliative care of cancer patients experiencing refractory pain that is difficult to control by the usual treatments, motor cortex repetitive transcranial magnetic stimulation, due to its noninvasive nature, can be used as an adjuvant therapy to improve various components of pain, including the emotional components. By reducing the doses of analgesics, repetitive transcranial magnetic stimulation decreases the severity of their adverse effects and improves the patient's quality of life. © The Author(s) 2015.

  3. A long-pulse repetitive operation magnetically insulated transmission line oscillator

    International Nuclear Information System (INIS)

    Fan, Yu-Wei; Zhong, Hui-Huang; Zhang, Jian-De; Shu, Ting; Liu, Jin Liang

    2014-01-01

    The improved magnetically insulated transmission line oscillator (MILO) is a gigawatt-class L-band high power microwave tube. It has allowed us to generate 3.1 GW pulse of 40 ns duration in the single-pulse operation and 500 MW pulse of 25 ns duration in the repetition rate operation. However, because of the severe impedance mismatch, the power conversion efficiency is only about 4% in the repetition rate operation. In order to eliminate the impedance mismatch and obtain repetitive long-pulse high-power microwave (HPM), a series of experiments are carried out and the recent progress is presented in this paper. In the single-pulse operation, when the diode voltage is 466 kV and current is 41.6 kA, the radiated microwave power is above 2.2 GW, the pulse duration is above 102 ns, the microwave frequency is about 1.74 GHz, and the power conversion efficiency is about 11.5%. In the repetition rate operation, under the condition of the diode voltage about 400 kV, beam current about 38 kA, the radiated microwave power is about 1.0 GW, the pulse duration is about 85 ns. Moreover, the radiated microwave power and the pulse duration decline little by little when the shot numbers increase gradually. The experimental results show that the impedance matching is a vital factor for HPM systems and one of the major technical challenges is to improve the cathode for the repetition rate operation MILO

  4. A long-pulse repetitive operation magnetically insulated transmission line oscillator

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Yu-Wei; Zhong, Hui-Huang; Zhang, Jian-De; Shu, Ting; Liu, Jin Liang [College of Optoelectric Science and Engineering, National University of Defense Technology, Changsha 410073 (China)

    2014-05-15

    The improved magnetically insulated transmission line oscillator (MILO) is a gigawatt-class L-band high power microwave tube. It has allowed us to generate 3.1 GW pulse of 40 ns duration in the single-pulse operation and 500 MW pulse of 25 ns duration in the repetition rate operation. However, because of the severe impedance mismatch, the power conversion efficiency is only about 4% in the repetition rate operation. In order to eliminate the impedance mismatch and obtain repetitive long-pulse high-power microwave (HPM), a series of experiments are carried out and the recent progress is presented in this paper. In the single-pulse operation, when the diode voltage is 466 kV and current is 41.6 kA, the radiated microwave power is above 2.2 GW, the pulse duration is above 102 ns, the microwave frequency is about 1.74 GHz, and the power conversion efficiency is about 11.5%. In the repetition rate operation, under the condition of the diode voltage about 400 kV, beam current about 38 kA, the radiated microwave power is about 1.0 GW, the pulse duration is about 85 ns. Moreover, the radiated microwave power and the pulse duration decline little by little when the shot numbers increase gradually. The experimental results show that the impedance matching is a vital factor for HPM systems and one of the major technical challenges is to improve the cathode for the repetition rate operation MILO.

  5. A long-pulse repetitive operation magnetically insulated transmission line oscillator.

    Science.gov (United States)

    Fan, Yu-Wei; Zhong, Hui-Huang; Zhang, Jian-De; Shu, Ting; Liu, Jin Liang

    2014-05-01

    The improved magnetically insulated transmission line oscillator (MILO) is a gigawatt-class L-band high power microwave tube. It has allowed us to generate 3.1 GW pulse of 40 ns duration in the single-pulse operation and 500 MW pulse of 25 ns duration in the repetition rate operation. However, because of the severe impedance mismatch, the power conversion efficiency is only about 4% in the repetition rate operation. In order to eliminate the impedance mismatch and obtain repetitive long-pulse high-power microwave (HPM), a series of experiments are carried out and the recent progress is presented in this paper. In the single-pulse operation, when the diode voltage is 466 kV and current is 41.6 kA, the radiated microwave power is above 2.2 GW, the pulse duration is above 102 ns, the microwave frequency is about 1.74 GHz, and the power conversion efficiency is about 11.5%. In the repetition rate operation, under the condition of the diode voltage about 400 kV, beam current about 38 kA, the radiated microwave power is about 1.0 GW, the pulse duration is about 85 ns. Moreover, the radiated microwave power and the pulse duration decline little by little when the shot numbers increase gradually. The experimental results show that the impedance matching is a vital factor for HPM systems and one of the major technical challenges is to improve the cathode for the repetition rate operation MILO.

  6. Repetitive elements in parasitic protozoa

    Directory of Open Access Journals (Sweden)

    Clayton Christine

    2010-05-01

    Full Text Available Abstract A recent paper published in BMC Genomics suggests that retrotransposition may be active in the human gut parasite Entamoeba histolytica. This adds to our knowledge of the various types of repetitive elements in parasitic protists and the potential influence of such elements on pathogenicity. See research article http://www.biomedcentral.com/1471-2164/11/321

  7. Effect of preheating on the damage to tungsten targets after repetitive ITER ELM-like heat loads

    Energy Technology Data Exchange (ETDEWEB)

    Makhlay, V A [Institute of Plasma Physics of the NSC KIPT 1, Akademicheskaya, 61108 Kharkov (Ukraine); Bandura, A N [Institute of Plasma Physics of the NSC KIPT 1, Akademicheskaya, 61108 Kharkov (Ukraine); Byrka, O V [Institute of Plasma Physics of the NSC KIPT 1, Akademicheskaya, 61108 Kharkov (Ukraine); Garkusha, I E [Institute of Plasma Physics of the NSC KIPT 1, Akademicheskaya, 61108 Kharkov (Ukraine); Chebotarev, V V [Institute of Plasma Physics of the NSC KIPT 1, Akademicheskaya, 61108 Kharkov (Ukraine); Tereshin, V I [Institute of Plasma Physics of the NSC KIPT 1, Akademicheskaya, 61108 Kharkov (Ukraine); Landman, I [Forschungszentrum Karlsruhe, IHM, 76021 Karlsruhe (Germany)

    2007-03-15

    The behaviour of a preheated tungsten target under repetitive pulsed plasma impacts of the energy density 0.75 MJ m{sup -2} with the pulse duration of 0.25 ms was studied with the quasi-stationary plasma accelerator (QSPA) Kh-50. Two identical samples of pure sintered tungsten have been exposed to numbers of pulses exceeding 100. One sample was maintained at room temperature and the other sample preheated at 650 deg. C. The experiments demonstrated that on the cold surface some macro-cracks dominate, but on the hot surface they do not develop. However, in both cases some fine meshes of micro-cracks are observed. With increasing the number of exposures, the width of the micro-cracks gradually increases, achieving 0.8-1.5 {mu}m after 100 pulses. In addition, the SEM shows some cellular structure with the cell sizes about 0.3 {mu}m, and after large numbers of exposures some blisters of sizes up to 100-150 {mu}m appear.

  8. Oxotremorine treatment reduces repetitive behaviors in BTBR T+ tf/J mice

    Directory of Open Access Journals (Sweden)

    Dionisio A. Amodeo

    2014-08-01

    Full Text Available Repetitive behaviors with restricted interests is one of the core criteria for the diagnosis of autism spectrum disorder (ASD. Current pharmacotherapies that target the dopaminergic or serotonergic systems have limited effectiveness in treating repetitive behaviors. Previous research has demonstrated that administration of muscarinic cholinergic receptor (mAChR antagonists can exacerbate motor stereotypies while mAChR agonists reduce stereotypies. The present study determined whether the mAChR agonist, oxotremorine affected repetitive behaviors in the BTBR T+ tf/J (BTBR mouse model of autism. To test the effects of oxotremorine on repetitive behaviors, marble burying and grooming behavior were measured in BTBR mice and compared to that in C57BL/6J (B6 mice. The effects of oxotremorine on locomotor activity was also measured. Thirty minutes before each test, mice received an intraperitoneal injection of saline, 0.001 mg or 0.01 mg of oxotremorine methiodide. Saline- treated BTBR mice exhibited increased marble burying and self-grooming behavior compared to that of saline-treated B6 mice. Oxotremorine significantly reduced marble burying and self-grooming behavior in BTBR mice, but had no significant effect in B6 mice. In addition, oxotremorine did not affect locomotor activity in BTBR mice, but significantly reduced locomotor activity in B6 mice at the 0.01 mg dose. These findings demonstrate that activation of mAChRs reduces repetitive behavior in the BTBR mouse and suggest that treatment with a mAChR agonist may be effective in reducing repetitive behaviors in ASD.

  9. Prevention of unnecessary pregnancy terminations by counselling women on drug, chemical, and radiation exposure during the first trimester

    International Nuclear Information System (INIS)

    Koren, G.; Pastuszak, A.

    1990-01-01

    As part of a new approach to counselling pregnant women concerned about antenatal exposure to drugs, chemicals, or radiation, we measured their tendency to terminate their pregnancy by using a visual analogue scale (VAS). Analysis of 78 cases where women had less than 50% tendency to continue pregnancy before they were advised by us reveals that 61 decided to continue their pregnancy after the consultation (57 normal, healthy infants, four miscarriages) and 17 terminated. Women who continued their pregnancy significantly changed their tendency after we discussed relevant information with them (from 34.3 +/- 2.5% to 84.5 +/- 3.3%, P less than 0.00001), whereas most of those who eventually terminated pregnancy did not change their tendency to continue pregnancy beyond the 50% mark (from 24.8 +/- 5.4% to 45.1 +/- 9.8%) (P greater than 0.1). Only two of the women who terminated their pregnancy were exposed to teratogenic drugs; however, in most other cases, other obvious reasons, unrelated to the exposure in question, were identified by the women as leading reasons for termination. An appropriate intervention in early pregnancy can prevent unnecessary pregnancy terminations by correcting misinformation and thereby decreasing the unrealistically high perception of risk by women exposed to nonteratogens

  10. Optimality based repetitive controller design for track-following servo system of optical disk drives.

    Science.gov (United States)

    Chen, Wentao; Zhang, Weidong

    2009-10-01

    In an optical disk drive servo system, to attenuate the external periodic disturbances induced by inevitable disk eccentricity, repetitive control has been used successfully. The performance of a repetitive controller greatly depends on the bandwidth of the low-pass filter included in the repetitive controller. However, owing to the plant uncertainty and system stability, it is difficult to maximize the bandwidth of the low-pass filter. In this paper, we propose an optimality based repetitive controller design method for the track-following servo system with norm-bounded uncertainties. By embedding a lead compensator in the repetitive controller, both the system gain at periodic signal's harmonics and the bandwidth of the low-pass filter are greatly increased. The optimal values of the repetitive controller's parameters are obtained by solving two optimization problems. Simulation and experimental results are provided to illustrate the effectiveness of the proposed method.

  11. Combined effect of repetitive work and cold on muscle function and fatigue.

    Science.gov (United States)

    Oksa, Juha; Ducharme, Michel B; Rintamäki, Hannu

    2002-01-01

    This study compared the effect of repetitive work in thermoneutral and cold conditions on forearm muscle electromyogram (EMG) and fatigue. We hypothesize that cold and repetitive work together cause higher EMG activity and fatigue than repetitive work only, thus creating a higher risk for overuse injuries. Eight men performed six 20-min work bouts at 25 degrees C (W-25) and at 5 degrees C while exposed to systemic (C-5) and local cooling (LC-5). The work was wrist flexion-extension exercise at 10% maximal voluntary contraction. The EMG activity of the forearm flexors and extensors was higher during C-5 (31 and 30%, respectively) and LC-5 (25 and 28%, respectively) than during W-25 (P forearm flexors at the end of W-25 was 15%. The corresponding values at the end of C-5 and LC-5 were 37% (P < 0.05 in relation to W-25) and 20%, respectively. Thus repetitive work in the cold causes higher EMG activity and fatigue than repetitive work in thermoneutral conditions.

  12. Electrophysiological Repetition Effects in Persons with Mild Cognitive Impairment depend upon Working Memory Demand.

    Science.gov (United States)

    Broster, Lucas S; Jenkins, Shonna L; Holmes, Sarah D; Edwards, Matthew G; Jicha, Gregory A; Jiang, Yang

    2018-05-07

    Forms of implicit memory, including repetition effects, are preserved relative to explicit memory in clinical Alzheimer's disease. Consequently, cognitive interventions for persons with Alzheimer's disease have been developed that leverage this fact. However, despite the clinical robustness of behavioral repetition effects, altered neural mechanisms of repetition effects are studied as biomarkers of both clinical Alzheimer's disease and pre-morbid Alzheimer's changes in the brain. We hypothesized that the clinical preservation of behavioral repetition effects results in part from concurrent operation of discrete memory systems. We developed two experiments that included probes of emotional repetition effects differing in that one included an embedded working memory task. We found that neural repetition effects manifested in patients with amnestic mild cognitive impairment, the earliest form of clinical Alzheimer's disease, during emotional working memory tasks, but they did not manifest during the task that lacked the embedded working memory manipulation. Specifically, the working memory task evoked neural repetition effects in the P600 time-window, but the same neural mechanism was only minimally implicated in the task without a working memory component. We also found that group differences in behavioral repetition effects were smaller in the experiment with a working memory task. We suggest that cross-domain cognitive challenge can expose "defunct" neural capabilities of individuals with amnestic mild cognitive impairment. Copyright © 2018. Published by Elsevier Ltd.

  13. Illusory sensation of movement induced by repetitive transcranial magnetic stimulation

    DEFF Research Database (Denmark)

    Christensen, Mark Schram; Lundbye-Jensen, Jesper; Grey, Michael James

    2010-01-01

    Human movement sense relies on both somatosensory feedback and on knowledge of the motor commands used to produce the movement. We have induced a movement illusion using repetitive transcranial magnetic stimulation over primary motor cortex and dorsal premotor cortex in the absence of limb movement...... and its associated somatosensory feedback. Afferent and efferent neural signalling was abolished in the arm with ischemic nerve block, and in the leg with spinal nerve block. Movement sensation was assessed following trains of high-frequency repetitive transcranial magnetic stimulation applied over...... premotor cortex stimulation was less affected by sensory and motor deprivation than was primary motor cortex stimulation. We propose that repetitive transcranial magnetic stimulation over dorsal premotor cortex produces a corollary discharge that is perceived as movement....

  14. Physiological responses to four hours of low-level repetitive work

    DEFF Research Database (Denmark)

    Garde, A Helene; Hansen, Åse Marie; Jensen, Bente R

    2003-01-01

    OBJECTIVES: The study investigated physiological responses to 4 hours of standardized low-level repetitive work. It was hypothesized that accumulative effects not observed after 1 hour could be found after 4 hours of repetitive work. METHODS: Ten healthy women performed intermittent (5 seconds + 5...... muscle activity during a mental reference task with low exerted force indicated attention-related muscle activity. Finally, it was indicated that repetitive work including high demands for attention is performed at the expense of the precision of the exerted force....... seconds) handgrip contractions at 10% of the maximal voluntary contraction combined with mental demands for concentration and attention. Muscle activity in the working forearm muscles, cardiovascular responses, and concentrations of biomarkers in biological fluids were recorded along with exerted force...

  15. Drug allergy passport and other documentation for patients with drug hypersensitivity - An ENDA/EAACI Drug Allergy Interest Group Position Paper

    NARCIS (Netherlands)

    Brockow, K.; Aberer, W.; Atanaskovic-Markovic, M.; Bavbek, S.; Bircher, A.; Bilo, B.; Blanca, M.; Bonadonna, P.; Burbach, G.; Calogiuri, G.; Caruso, C.; Celik, G.; Cernadas, J.; Chiriac, A.; Demoly, P.; Oude Elberink, J. N. G.; Fernandez, J.; Gomes, E.; Garvey, L. H.; Gooi, J.; Gotua, M.; Grosber, M.; Kauppi, P.; Kvedariene, V.; Laguna, J. J.; Makowska, J. S.; Mosbech, H.; Nakonechna, A.; Papadopolous, N. G.; Ring, J.; Romano, A.; Rockmann, H.; Sargur, R.; Sedlackova, L.; Sigurdardottir, S.; Schnyder, B.; Storaas, T.; Torres, M.; Zidarn, M.; Terreehorst, I.

    2016-01-01

    The strongest and best-documented risk factor for drug hypersensitivity (DH) is the history of a previous reaction. Accidental exposures to drugs may lead to severe or even fatal reactions in sensitized patients. Preventable prescription errors are common. They are often due to inadequate medical

  16. GPI-repetitive control for linear systems with parameter uncertainty / variation

    Directory of Open Access Journals (Sweden)

    John A. Cortés-Romero

    2015-01-01

    Full Text Available Robust repetitive control problems for uncertain linear systems have been considered by different approaches. This article proposes the use of Repetitive Control and Generalized Proportional Integral (GPI Control in a complementary fashion. The conditioning and coupling of these techniques has been done in a time discrete context. Repetitive control is a control technique, based on the internal model principle, which yields perfect asymptotic tracking and rejection of periodic signals. On the other hand, GPI control is established as a robust linear control system design technique that is able to reject structured time polynomial additive perturbation, in particular, parameter uncertainty that can be locally approximated by time polynomial signal. GPI control provides a suitable stability and robustness conditions for the proper Repetitive Control operation. A stability analysis is presented under the frequency response framework using plant samples for different parameter uncertainty conditions. We carry out some comparative stability analysis with other complementary control approaches that has been effective for this kind of task, enhancing a better robustness and an improved performance for the GPI case. Illustrative simulation examples are presented which validate the proposed approach.

  17. Risk of Clinically Relevant Pharmacokinetic-based Drug-drug Interactions with Drugs Approved by the U.S. Food and Drug Administration Between 2013 and 2016.

    Science.gov (United States)

    Yu, Jingjing; Zhou, Zhu; Tay-Sontheimer, Jessica; Levy, Rene H; Ragueneau-Majlessi, Isabelle

    2018-03-23

    A total of 103 drugs (including 14 combination drugs) were approved by the U.S. Food and Drug Administration from 2013 to 2016. Pharmacokinetic-based drug interaction profiles were analyzed using the University of Washington Drug Interaction Database and the clinical relevance of these observations was characterized based on information from New Drug Application reviews. CYP3A was identified as a major contributor to clinical drug-drug interactions (DDIs), involved in approximately 2/3 of all interactions. Transporters (alone or with enzymes) were found to participate in about half of all interactions, although most of these were weak-to-moderate interactions. When considered as victims, eight new molecular entities (NMEs; cobimetinib, ibrutnib, isavuconazole, ivabradine, naloxegol, paritaprevir, simeprevir, and venetoclax) were identified as sensitive substrates of CYP3A, two NMEs (pirfenidone and tasimelteon) were sensitive substrates of CYP1A2, one NME (dasabuvir) was a sensitive substrate of CYP2C8, one NME (eliglustat) was a sensitive substrate of CYP2D6, and one NME (grazoprevir) was a sensitive substrate of OATP1B1/3 (with changes in exposure greater than 5-fold when co-administered with a strong inhibitor). Interestingly, approximately 75% of identified CYP3A substrates were also substrates of P-gp. As perpetrators, most clinical DDIs involved weak-to-moderate inhibition or induction, with only two drugs (Viekira Pak and idelalisib) showing strong inhibition of CYP3A, and one NME (lumacaftor) considered as a strong CYP3A inducer. Among drugs with large changes in exposure (≥ 5-fold), whether as victim or perpetrator, the most represented therapeutic classes were antivirals and oncology drugs, suggesting a significant risk of clinical DDIs in these patient populations. The American Society for Pharmacology and Experimental Therapeutics.

  18. Exploration of verbal repetition in people with dementia using an online symptom-tracking tool.

    Science.gov (United States)

    Reeve, Emily; Molin, Pierre; Hui, Amaris; Rockwood, Kenneth

    2017-06-01

    Online tools can be used by people with dementia and their caregivers to self-identify and track troubling symptoms, such as verbal repetition. We aimed to explore verbal repetition behaviors in people with dementia. Participants were recruited via an online resource for people with dementia and their caregivers. Respondents were instructed to complete information about symptoms that are most important to them for tracking over time. In this cross-sectional study, we analyzed data pertaining to individuals with dementia who had at least three symptoms selected for tracking. Of the 3,573 participants who began a user profile, 1,707 fulfilled criteria for analysis. Verbal repetition was identified as a treatment target in 807 respondents (47.3%). Verbal repetition was more frequent in individuals with mild dementia compared to those with moderate and severe dementia (57.2% vs. 36.0% and 39.9%, p < 0.01) and in those with Alzheimer's disease versus other dementias (65.2% vs. 29.7%, p < 0.001). Repetitive questioning was the most frequent type of verbal repetition (90.5% of individuals with verbal repetition). Verbal repetition was most strongly associated with difficulties operating gadgets/appliances (OR 3.65, 95%CI: 2.82-4.72), lack of interest and/or initiative (3.52: 2.84-4.36), misplacing or losing objects (3.25: 2.64-4.01), and lack of attention and/or concentration (2.62: 2.12-3.26). Verbal repetition is a common symptom in people at all stages of dementia but is most commonly targeted for monitoring and treatment effects in its mild stage. Much research is required to further elucidate the underlying mechanisms and the effect of different treatment strategies.

  19. Quantifying repetitive speech in autism spectrum disorders and language impairment.

    Science.gov (United States)

    van Santen, Jan P H; Sproat, Richard W; Hill, Alison Presmanes

    2013-10-01

    We report on an automatic technique for quantifying two types of repetitive speech: repetitions of what the child says him/herself (self-repeats) and of what is uttered by an interlocutor (echolalia). We apply this technique to a sample of 111 children between the ages of four and eight: 42 typically developing children (TD), 19 children with specific language impairment (SLI), 25 children with autism spectrum disorders (ASD) plus language impairment (ALI), and 25 children with ASD with normal, non-impaired language (ALN). The results indicate robust differences in echolalia between the TD and ASD groups as a whole (ALN + ALI), and between TD and ALN children. There were no significant differences between ALI and SLI children for echolalia or self-repetitions. The results confirm previous findings that children with ASD repeat the language of others more than other populations of children. On the other hand, self-repetition does not appear to be significantly more frequent in ASD, nor does it matter whether the child's echolalia occurred within one (immediate) or two turns (near-immediate) of the adult's original utterance. Furthermore, non-significant differences between ALN and SLI, between TD and SLI, and between ALI and TD are suggestive that echolalia may not be specific to ALN or to ASD in general. One important innovation of this work is an objective fully automatic technique for assessing the amount of repetition in a transcript of a child's utterances. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

  20. Repetitive transcranial magnetic stimulation is effective following repeated courses in the treatment of major depressive disorder--a case report.

    Science.gov (United States)

    Dannon, Pinhas N; Grunhaus, Leon

    2003-06-01

    Repetitive transcranial magnetic stimulation (rTMS) is a relatively new treatment modality for psychiatric patients. rTMS was demonstrated to be effective in the treatment of depression. However, longitudinal outcome studies have not yet been published. Relapse rates are higher in depressed patients and most of them do not respond to the same treatment with similar success. In this report we present a patient, who experienced relapse with the various conventional drug treatments, but responded well to rTMS at three different points in time. Copyright 2003 John Wiley & Sons, Ltd.

  1. Food and Drug Administration warning on anesthesia and brain development: implications for obstetric and fetal surgery.

    Science.gov (United States)

    Olutoye, Olutoyin A; Baker, Byron Wycke; Belfort, Michael A; Olutoye, Oluyinka O

    2018-01-01

    the interval between induction of anesthesia and surgery start time will help decrease patient exposure to inhalational agents. While the Food and Drug Administration warning was based on duration and repetitive nature of exposure rather than concentration of inhalational agents, intravenous tocolytics can be considered for intraoperative use, to provide uterine relaxation for fetal surgery, in lieu of high concentrations of inhalational anesthetic agents. Practitioners should consider the type of anesthesia that will be administered and the potential risks when scheduling patients for nonobstetric and fetal surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Repetitive Behavior in Rubinstein-Taybi Syndrome: Parallels with Autism Spectrum Phenomenology

    Science.gov (United States)

    Waite, Jane; Moss, Joanna; Beck, Sarah R.; Richards, Caroline; Nelson, Lisa; Arron, Kate; Burbidge, Cheryl; Berg, Katy; Oliver, Chris

    2015-01-01

    Syndrome specific repetitive behavior profiles have been described previously. A detailed profile is absent for Rubinstein-Taybi syndrome (RTS). The Repetitive Behaviour Questionnaire and Social Communication Questionnaire were completed for children and adults with RTS (N = 87), Fragile-X (N = 196) and Down (N = 132) syndromes, and individuals…

  3. Repetitive, small-bore two-stage light gas gun

    International Nuclear Information System (INIS)

    Combs, S.K.; Foust, C.R.; Fehling, D.T.; Gouge, M.J.; Milora, S.L.

    1991-01-01

    A repetitive two-stage light gas gun for high-speed pellet injection has been developed at Oak Ridge National Laboratory. In general, applications of the two-stage light gas gun have been limited to only single shots, with a finite time (at least minutes) needed for recovery and preparation for the next shot. The new device overcomes problems associated with repetitive operation, including rapidly evacuating the propellant gases, reloading the gun breech with a new projectile, returning the piston to its initial position, and refilling the first- and second-stage gas volumes to the appropriate pressure levels. In addition, some components are subjected to and must survive severe operating conditions, which include rapid cycling to high pressures and temperatures (up to thousands of bars and thousands of kelvins) and significant mechanical shocks. Small plastic projectiles (4-mm nominal size) and helium gas have been used in the prototype device, which was equipped with a 1-m-long pump tube and a 1-m-long gun barrel, to demonstrate repetitive operation (up to 1 Hz) at relatively high pellet velocities (up to 3000 m/s). The equipment is described, and experimental results are presented. 124 refs., 6 figs., 5 tabs

  4. Effects of slow repetitive transcranial magnetic stimulation in patients with corticobasal syndrome.

    Science.gov (United States)

    Civardi, Carlo; Pisano, Fabrizio; Delconte, Carmen; Collini, Alessandra; Monaco, Francesco

    2015-06-01

    Corticobasal syndrome is characterized by asymmetric cortical sensorimotor dysfunction and parkinsonism; an altered cortical excitability has been reported. We explored with transcranial magnetic stimulation the motor cortical excitability in corticobasal syndrome, and the effects of slow repetitive transcranial magnetic stimulation. With transcranial magnetic stimulation, we studied two corticobasal syndrome patients. We determined bilaterally from the first dorsal interosseous muscle: relaxed threshold, and contralateral and ipsilateral silent period. We also evaluated the contralateral silent period after active/sham slow repetitive transcranial magnetic stimulation on the most affected side. At T0 the silent period was bilaterally short. On the most affected side, active slow repetitive transcranial magnetic stimulation induced a short lasting prolongation of the contralateral silent period. In corticobasal syndrome, transcranial magnetic stimulation showed a reduction cortical inhibitory phenomenon potentially reversed transiently by slow repetitive transcranial magnetic stimulation.

  5. Sustainment of spherical tokamak by means of repetitive injection of compact torus plasma

    International Nuclear Information System (INIS)

    Shimamura, Shin; Matsura, Ken; Takahashi, Tsutomu; Nogi, Yasuyuki

    2000-01-01

    Sustainment of spherical tokamak (S.T.) has been studied. A compact torus (C.T.) plasma was injected into confinement region by magnetized coaxial gun. For start-up and sustainment of large main spherical tokamak, single pulsed injection of small C.T. is not sufficient in many cases. C.T.plasma injection of high repetition rate is required. For this purpose magnetized coaxial gun was driven with high repetition rate current. The first injected C.T. plasma could start-up S.T. without other help. The repetitive C.T. injection grew and sustained the S.T. plasma. A CCD camera with fast gated image intensifier took a cross sectional view of S.T. during the repetitive C.T. injection. (author)

  6. PCR amplification of repetitive sequences as a possible approach in relative species quantification

    DEFF Research Database (Denmark)

    Ballin, Nicolai Zederkopff; Vogensen, Finn Kvist; Karlsson, Anders H

    2012-01-01

    Abstract Both relative and absolute quantifications are possible in species quantification when single copy genomic DNA is used. However, amplification of single copy genomic DNA does not allow a limit of detection as low as one obtained from amplification of repetitive sequences. Amplification...... of repetitive sequences is therefore frequently used in absolute quantification but problems occur in relative quantification as the number of repetitive sequences is unknown. A promising approach was developed where data from amplification of repetitive sequences were used in relative quantification of species...... to relatively quantify the amount of chicken DNA in a binary mixture of chicken DNA and pig DNA. However, the designed PCR primers lack the specificity required for regulatory species control....

  7. Design and implementation of fast charging circuit for repetitive compact torus injector

    International Nuclear Information System (INIS)

    Onchi, T.; McColl, D.; Dreval, M.; Wolfe, S.; Xiao, C.; Hirose, A.

    2014-01-01

    A novel circuit for compact torus (CT) injector operated at high repetition rates has been developed. The core technology adopted in the present work is to charge a large storage capacitor bank and quickly charge the CT capacitor bank through a stack of insulated-gate bipolar transistors (IGBTs). A system consisting of IGBTs and slow banks for the repetitive operation has been developed and installed for each discharge circuit of the University of Saskatchewan Compact Torus Injector (USCTI). A repetition rate up to 1.7 Hz and a burst of 8 CTs have been achieved

  8. Universal data compression and repetition times

    NARCIS (Netherlands)

    Willems, Frans M J

    1989-01-01

    A new universal data compression algorithm is described. This algorithm encodes L source symbols at a time. For the class of binary stationary sources, its rate does not exceed [formula omitted] [formula omitted] bits per source symbol. In our analysis, a property of repetition times turns out to be

  9. Ventral medial prefrontal cortex (vmPFC) as a target of the dorsolateral prefrontal modulation by transcranial direct current stimulation (tDCS) in drug addiction.

    Science.gov (United States)

    Nakamura-Palacios, Ester Miyuki; Lopes, Isabela Bittencourt Coutinho; Souza, Rodolpho Albuquerque; Klauss, Jaisa; Batista, Edson Kruger; Conti, Catarine Lima; Moscon, Janine Andrade; de Souza, Rodrigo Stênio Moll

    2016-10-01

    Here, we report some electrophysiologic and imaging effects of the transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) in drug addiction, notably in alcohol and crack-cocaine dependence. The low resolution electromagnetic tomography (LORETA) analysis obtained through event-related potentials (ERPs) under drug-related cues, more specifically in its P3 segment (300-500 ms) in both, alcoholics and crack-cocaine users, showed that the ventral medial prefrontal cortex (vmPFC) was the brain area with the largest change towards increasing activation under drug-related cues in those subjects that kept abstinence during and after the treatment with bilateral tDCS (2 mA, 35 cm(2), cathodal left and anodal right) over dlPFC, applied repetitively (five daily sessions). In an additional study in crack-cocaine, which showed craving decreases after repetitive bilateral tDCS, we examined data originating from diffusion tensor imaging (DTI), and we found increased DTI parameters in the left connection between vmPFC and nucleus accumbens (NAcc), such as the number of voxels, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), in tDCS-treated crack-cocaine users when compared to the sham-tDCS group. This increasing of DTI parameters was significantly correlated with craving decreasing after the repetitive tDCS. The vmPFC relates to the control of drug seeking, possibly by extinguishing this behavior. In our studies, the bilateral dlPFC tDCS reduced relapses and craving to the drug use, and increased the vmPFC activation under drug cues, which may be of a great importance in the control of drug use in drug addiction.

  10. Independent and additive repetition priming of motion direction and color in visual search.

    Science.gov (United States)

    Kristjánsson, Arni

    2009-03-01

    Priming of visual search for Gabor patch stimuli, varying in color and local drift direction, was investigated. The task relevance of each feature varied between the different experimental conditions compared. When the target defining dimension was color, a large effect of color repetition was seen as well as a smaller effect of the repetition of motion direction. The opposite priming pattern was seen when motion direction defined the target--the effect of motion direction repetition was this time larger than for color repetition. Finally, when neither was task relevant, and the target defining dimension was the spatial frequency of the Gabor patch, priming was seen for repetition of both color and motion direction, but the effects were smaller than in the previous two conditions. These results show that features do not necessarily have to be task relevant for priming to occur. There is little interaction between priming following repetition of color and motion, these two features show independent and additive priming effects, most likely reflecting that the two features are processed at separate processing sites in the nervous system, consistent with previous findings from neuropsychology & neurophysiology. The implications of the findings for theoretical accounts of priming in visual search are discussed.

  11. High-repetition-rate hydrogen chamber: Preliminary studies; Chambre a hydrogene a haut taux de repetition: Etudes preliminaires

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1967-01-01

    This report is a conclusion to the tests realised with an experimental bubbles chamber in view to study the possibilities to increase the repetition rate. The more important parameters (the evolution of the bubbles, the expansion system) are considered in a theoretical way. Then the hardware is described. To end, experimental results are compared with the first evaluations. The calculations and the experimentation are against an oscillation system for the expansion. A system with a locking is to he considered. (authors) [French] Ce rapport est une conclusion aux essais realises avec une chambre a bulles experimentale en vue d'etudier les possibilites d'accroitre les taux de repetition. Les parametres les plus importants (evolution des bulles, mecanique de la detente) sont etudies par voie theorique. Puis l'appareillage est decrit. Enfin, les resultats experimentaux sont compares aux evaluations donnees au debut. Ces calculs et cette experimentation ne sont pas en faveur d'un systeme oscillant pour la detente et il faut envisager un systeme avec verrouillage. (auteurs)

  12. Wet microcontact printing (µCP) for micro-reservoir drug delivery systems

    International Nuclear Information System (INIS)

    Lee, Hong-Pyo; Ryu, WonHyoung

    2013-01-01

    When micro-reservoir-type drug delivery systems are fabricated, loading solid drugs in drug reservoirs at microscale is often a non-trivial task. This paper presents a simple and effective solution to load a small amount of drug solution at microscale using ‘wet’ microcontact printing (µCP). In this wet µCP, a liquid solution containing drug molecules (methylene blue and tetracycline HCl) dissolved in a carrier solvent was transferred to a target surface (drug reservoir) by contact printing process. In particular, we have investigated the dependence of the quantity and morphology of transferred drug molecules on the stamp size, concentration, printing times, solvent types and surfactant concentration. It was also found that the repetition of printing using a non-volatile solvent such as polyethylene glycol (PEG) as a drug carrier material actually increased the transferred amount of drug molecules in proportion to the printing times based on asymmetric liquid bridge formation. Utilizing this wet µCP, drug delivery devices containing different quantity of drugs in micro-reservoirs were fabricated and their performance as controlled drug delivery devices was demonstrated. (paper)

  13. Examining factors that influence the effectiveness of cleaning antineoplastic drugs from drug preparation surfaces: a pilot study.

    Science.gov (United States)

    Hon, Chun-Yip; Chua, Prescillia Ps; Danyluk, Quinn; Astrakianakis, George

    2014-06-01

    Occupational exposure to antineoplastic drugs has been documented to result in various adverse health effects. Despite the implementation of control measures to minimize exposure, detectable levels of drug residual are still found on hospital work surfaces. Cleaning these surfaces is considered as one means to minimize the exposure potential. However, there are no consistent guiding principles related to cleaning of contaminated surfaces resulting in hospitals to adopt varying practices. As such, this pilot study sought to evaluate current cleaning protocols and identify those factors that were most effective in reducing contamination on drug preparation surfaces. Three cleaning variables were examined: (1) type of cleaning agent (CaviCide®, Phenokil II™, bleach and chlorhexidine), (2) application method of cleaning agent (directly onto surface or indirectly onto a wipe) and (3) use of isopropyl alcohol after cleaning agent application. Known concentrations of antineoplastic drugs (either methotrexate or cyclophosphamide) were placed on a stainless steel swatch and then, systematically, each of the three cleaning variables was tested. Surface wipes were collected and quantified using high-performance liquid chromatography-tandem mass spectrometry to determine the percent residual of drug remaining (with 100% being complete elimination of the drug). No one single cleaning agent proved to be effective in completely eliminating all drug contamination. The method of application had minimal effect on the amount of drug residual. In general, application of isopropyl alcohol after the use of cleaning agent further reduced the level of drug contamination although measureable levels of drug were still found in some cases.

  14. Iodine laser of high efficiency and fast repetition rate

    Energy Technology Data Exchange (ETDEWEB)

    Hohla, K; Witte, K J

    1976-07-01

    The scaling laws of an iodine laser of high efficiency and fast repetition rate are reported. The laser is pumped with a new kind of low pressure Hg-UV-lamps which convert 32% of the electrical input in UV-light in the absorption band of the iodine laser and which can be fired up to 100 Hz. Details of a 10 kJ/1 nsec system as dimensions, energy density, repetition rate, flow velocity, gas composition and gas pressure and the overall efficiency are given which is expected to be about 2%.

  15. Research review. Interactions between environmental chemicals and drug biotransformation in man.

    Science.gov (United States)

    Alvares, A P

    1978-01-01

    Many factors influence the metabolism of drugs in man. Besides genetic factors, environmental factors may play a significant role in explaining the variation observed in the rates of drug metabolism between different individuals. Intentional or unintentional exposure to environmental chemicals could enhance or inhibit the activity of hepatic mixed function oxidases that metabolise drugs and other foreign chemicals, as well as endogenous substrates such as steroid hormones. A major source of such exposure may be occupational. Exposure to the heavy metal, lead, has been shown to inhibit drug metabolism; whereas intensive exposure to chlorinated insecticides, and other halogenated hydrocarbons such as polychlorinated biphenyls, has been shown to enhance the metabolism of test drugs such as antipyrine and phenylbutazone. An intentional source of exposure to foreign chemicals is cigarette smoke. Cigarette smoke contains polycyclic hydrocarbons, which are known inducers of hepatic mixed function oxidases. A number of studies have shown that cigarette smoking can alter the pharmacological action and/or the metabolism of some drugs. Pharmacokinetic studies have shown that cigarette smoking decreases the bioavailability of phenacetin and increases dosage requirements of theophylline by enhancing their rate of metabolism. Data, which are not very conclusive, indicate that heavy marijuana use may have an inhibitory effect on metabolism of some drugs and an inducing effect on others such as theophylline. Dietary factors may also play a significant role in the regulation of drug metabolism. Charcoal broiling which introduces polycyclic hydrocarbons into foods has been shown to enhance the metabolism of the test drug, antipyrine, and of such commonly used drugs as phenacetin and theophylline. Such intentional or unintentional exposure to environmental chemicals which may alter the rates of drug metabolism in man indicates the importance of individualisation of drug therapy.

  16. Identification and quantification of drug-albumin adducts in serum samples from a drug exposure study in mice

    NARCIS (Netherlands)

    Switzar, L.; Kwast, L.M.; Lingeman, H.; Giera, M.; Pieters, R.H.H.; Niessen, W.M.A.

    2013-01-01

    The formation of drug-protein adducts following the bioactivation of drugs to reactive metabolites has been linked to adverse drug reactions (ADRs) and is a major complication in drug discovery and development. Identification and quantification of drug-protein adducts in vivo may lead to a better

  17. Heavy-duty high-repetition-rate generators

    NARCIS (Netherlands)

    Heesch, van E.J.M.; Yan, K.; Pemen, A.J.M.

    2002-01-01

    We present our results on high-power repetitive pulse sources for continuous operation. Two 1-10-kW systems using advanced spark gap technology and a transmission line transformer have been tested for several hundred hours at a 60-MW pulse level. High reliability and above 90% overall efficiency are

  18. The mere exposure effect depends on an odor's initial pleasantness.

    Science.gov (United States)

    Delplanque, Sylvain; Coppin, Géraldine; Bloesch, Laurène; Cayeux, Isabelle; Sander, David

    2015-01-01

    The mere exposure phenomenon refers to improvement of one's attitude toward an a priori neutral stimulus after its repeated exposure. The extent to which such a phenomenon influences evaluation of a priori emotional stimuli remains under-investigated. Here we investigated this question by presenting participants with different odors varying in a priori pleasantness during different sessions spaced over time. Participants were requested to report each odor's pleasantness, intensity, and familiarity. As expected, participants became more familiar with all stimuli after the repetition procedure. However, while neutral and mildly pleasant odors showed an increase in pleasantness ratings, unpleasant and very pleasant odors remained unaffected. Correlational analyses revealed an inverse U-shape between the magnitude of the mere exposure effect and the initial pleasantness of the odor. Consequently, the initial pleasantness of the stimuli appears to modulate the impact of repeated exposures on an individual's attitude. These data underline the limits of mere exposure effect and are discussed in light of the biological relevance of odors for individual survival.

  19. Adolescents' use of alcohol, tobacco and illicit drugs in relation to prenatal alcohol exposure: modifications by gender and ethnicity.

    Science.gov (United States)

    Pfinder, Manuela; Liebig, Stefan; Feldmann, Reinhold

    2014-01-01

    The study aimed to investigate (a) the association between low to moderate prenatal alcohol exposure (PAE) and the use of alcohol, tobacco and illicit drugs in adolescence and (b) whether the associations are modified by gender and ethnicity. The subjects of the study were 5922 children and adolescents, aged from 11 to 17 years, enrolled in the cross-sectional German Health Interview and Examination Survey for Children and Adolescents (the KiGGS study). Information on PAE is based on parental self-report questionnaires. Use of alcohol, tobacco and illicit drugs was assessed through self-report questionnaires for adolescents. Low to moderate PAE was associated with an increased risk of drinking alcohol (adjusted odds ratio (OR) 1.73, 95% confidence interval (CI) 1.34, 2.18) and also of illicit drug use (adjusted OR 1.62, 95% CI 1.23, 2.14). The associations between PAE and the use of alcohol, tobacco and illicit drugs differed according to gender and ethnicity. Gender-stratified analyses resulted in adverse effects of PAE on drinking alcohol, smoking and illicit drug use in females; however, in German males, the associations disappeared. Stronger associations between PAE and the outcome measures were found in non-Germans. Our findings indicate that low to moderate levels of maternal alcohol intake during pregnancy are a risk factor for use of alcohol, tobacco and illicit drugs by the offspring, with stronger associations in females and non-Germans.

  20. Heat accumulation during high repetition rate ultrafast laser interaction: Waveguide writing in borosilicate glass

    International Nuclear Information System (INIS)

    Zhang, Haibin; Eaton, Shane M; Li, Jianzhao; Herman, Peter R

    2007-01-01

    During high repetition rate (>200 kHz) ultrafast laser waveguide writing, visible heat modified zones surrounding the formed waveguide occur as a result of heat accumulation. The radii of the heat-modified zones increase with the laser net fluence, and were found to correlate with the formation of low-loss and cylindrically symmetric optical waveguides. A numerical thermal model based on the finite difference method is applied here to account for cumulative heating and diffusion effects. The model successfully shows that heat propagation and accumulation accurately predict the radius of the 'heat modified' zones observed in borosilicate glass waveguides formed across a wide range of laser exposure conditions. Such modelling promises better control of thermal effects for optimizing the fabrication and performance of three-dimensional optical devices in transparent materials

  1. Prevalence of prenatal exposure to substances of abuse: questionnaire versus biomarkers

    OpenAIRE

    Chiandetti, Antonella; Hernandez, Gimena; Mercadal-Hally, María; Alvarez, Airam; Andreu-Fernandez, Vicente; Navarro-Tapia, Elisabet; Bastons-Compta, Adriana; Garcia-Algar, Oscar

    2017-01-01

    Alcohol and drugs of abuse consumption in young adults, including women of childbearing age, has experienced significant increase over the past two decades. The use of questionnaires as the only measure to investigate prenatal alcohol and drugs of abuse exposure underestimates the real prevalence of exposure and could mislead to wrong conclusions. Therefore, the aim of this article was to compare reported rates of prenatal alcohol and drugs of abuse consumption with biomarkers of exposure by ...

  2. High repetition rate intense ion beam source

    International Nuclear Information System (INIS)

    Hammer, D.A.; Glidden, S.C.; Noonan, B.

    1992-01-01

    This final report describes a ≤ 150kV, 40kA, 100ns high repetition rate pulsed power system and intense ion beam source which is now in operation at Cornell University. Operation of the Magnetically-controlled Anode Plasma (MAP) ion diode at > 100Hz (burst mode for up to 10 pulse bursts) provides an initial look at repetition rate limitations of both the ion diode and beam diagnostics. The pulsed power systems are capable of ≥ 1kHz operation (up to 10 pulse bursts), but ion diode operation was limited to ∼100Hz because of diagnostic limitations. By varying MAP diode operating parameters, ion beams can be extracted at a few 10s of keV or at up to 150keV, the corresponding accelerating gap impedance ranging from about 1Ω to about 10Ω. The ability to make hundreds of test pulses per day at an average repetition rate of about 2 pulses per minute permits statistical analysis of diode operation as a function of various parameters. Most diode components have now survived more than 10 4 pulses, and the design and construction of the various pulsed power components of the MAP diode which have enabled us to reach this point are discussed. A high speed data acquisition system and companion analysis software capable of acquiring pulse data at 1ms intervals (in bursts of up to 10 pulses) and processing it in ≤ min is described

  3. MIMICRY, DIFFERENCE AND REPETITION

    Directory of Open Access Journals (Sweden)

    Marcelo Mendes de Souza

    2008-07-01

    Full Text Available This article addresses Homi K. Bhabha’s concept of mimicry in a broader context, other than that of cultural studies and post-colonial studies, bringing together other concepts, such as that of Gilles Deleuze in Difference and repetition, among other texts, and other names, such as Silviano Santiago, Jorge Luís Borges, Franz Kafka and Giorgio Agamben. As a partial conclusion, the article intends to oppose Bhabha’s freudian-marxist view to Five propositions on Psychoanalysis (1973, Gilles Deleuze’s text about Psychoanalysis published right after his book The Anti-Oedipus.

  4. Neurobehavioural Correlates of Abnormal Repetitive Behaviour

    Directory of Open Access Journals (Sweden)

    R. A. Ford

    1991-01-01

    Full Text Available Conditions in which echolalia and echopraxia occur are reviewed, followed by an attempt to elicit possible mechanisms of these phenomena. A brief description of stereotypical and perseverative behaviour and obsessional phenomena is given. It is suggested that abnormal repetitive behaviour may occur partly as a result of central dopaminergic dysfunction.

  5. Laterality of repetitive finger movement performance and clinical features of Parkinson's disease.

    Science.gov (United States)

    Stegemöller, Elizabeth; Zaman, Andrew; MacKinnon, Colum D; Tillman, Mark D; Hass, Chris J; Okun, Michael S

    2016-10-01

    Impairments in acoustically cued repetitive finger movement often emerge at rates near to and above 2Hz in persons with Parkinson's Disease (PD) in which some patients move faster (hastening) and others move slower (bradykinetic). The clinical features impacting this differential performance of repetitive finger movement remain unknown. The purpose of this study was to compare repetitive finger movement performance between the more and less affected side, and the difference in clinical ratings among performance groups. Forty-one participants diagnosed with idiopathic PD completed an acoustically cued repetitive finger movement task while "on" medication. Eighteen participants moved faster, 10 moved slower, and 13 were able to maintain the appropriate rate at rates above 2Hz. Clinical measures of laterality, disease severity, and the UPDRS were obtained. There were no significant differences between the more and less affected sides regardless of performance group. Comparison of disease severity, tremor, and rigidity among performance groups revealed no significant differences. Comparison of posture and postural instability scores revealed that the participants that demonstrated hastening had worse posture and postural instability scores. Consideration of movement rate during the clinical evaluation of repetitive finger movement may provide additional insight into varying disease features in persons with PD. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Longer repetition duration increases muscle activation and blood lactate response in matched resistance training protocols

    Directory of Open Access Journals (Sweden)

    Hugo Cesar Martins-Costa

    2016-03-01

    Full Text Available Abstract This study analyzed the effect of different repetition durations on electromyographic and blood lactate responses of the bench press exercise. Fifteen recreationally trained male volunteers completed two training protocols, matched for intensity (% one-repetition maximum; 1RM, number of sets, number of repetitions, and rest intervals. One of the protocols was performed with a repetition duration of 4 s (2 s concentric: 2 s eccentric; 2:2 protocol, whereas the second protocol had a repetition duration of 6 s (2 s concentric: 4 s eccentric; 2:4 protocol. The results showed higher normalized integrated electromyography (pectoralis major and triceps brachii for the 2:4 protocol. Blood lactate concentration was also higher in the 2:4 protocol across all sets. These results show that adding 2 s to the eccentric action in matched training protocols increases muscle activation and blood lactate response, which reinforces the notion that increasing repetition duration is an alternative load progression in resistance training.

  7. Effectiveness of Non-pharmacological Interventions on Stereotyped and Repetitive Behaviors in Preschool Children With Autism: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Hadi Zarafshan

    2017-03-01

    Full Text Available Objective: The present study aimed to review the literature on non-pharmacological interventions used to treat stereotyped and repetitive behaviors by a systematic method. Methods: Two authors independently performed a search strategy on Medline/PubMed, Scopus and PsycINFO on English articles published up to April 23, 2014 with relevant search keywords. We also reviewed the bibliographies of retrieved articles and conference proceedings to obtain additional citations and references. We used those articles that address any non-pharmacological interventions on reducing stereotyped and repetitive behaviors in preschool children with autism. Four independent reviewers screened relevant articles for inclusion criteria and assessed the quality of eligible articles with CONSORT checklist. Results: In our search, 664 relevant articles were found. After removing duplicates and screening based on title, abstract, and full text, 15 high quality studies were finally included in data analyses. The included articles were published from 1987 to 2013. Three studies were designed as A-B, two as A-B-A and reminders as A-B-A-B. The data and results of 3 clinical trials were synthesized; two of them were parallel randomized clinical trial and another one was designed as cross-over. Interventions were completely heterogeneous in case studies, including non-contingent auditory stimulation, response interruption and redirection, teaching the children to request assistance on the difficult tasks, family-implemented treatment for behavioral inflexibility with treatment approach, vocal or motor response interruption and redirection, brushing, water mist treatment, exposure response prevention, tangible reinforcement or social reinforcement, and music. Interventions in clinical trials included touch therapy, kata techniques training program, and aerobic exercise. Conclusions: The results of our review indicate that different kinds of non-pharmacological interventions can

  8. Repetitive element transcripts are elevated in the brain of C9orf72 ALS/FTLD patients.

    Science.gov (United States)

    Prudencio, Mercedes; Gonzales, Patrick K; Cook, Casey N; Gendron, Tania F; Daughrity, Lillian M; Song, Yuping; Ebbert, Mark T W; van Blitterswijk, Marka; Zhang, Yong-Jie; Jansen-West, Karen; Baker, Matthew C; DeTure, Michael; Rademakers, Rosa; Boylan, Kevin B; Dickson, Dennis W; Petrucelli, Leonard; Link, Christopher D

    2017-09-01

    Significant transcriptome alterations are detected in the brain of patients with amyotrophic lateral sclerosis (ALS), including carriers of the C9orf72 repeat expansion and C9orf72-negative sporadic cases. Recently, the expression of repetitive element transcripts has been associated with toxicity and, while increased repetitive element expression has been observed in several neurodegenerative diseases, little is known about their contribution to ALS. To assess whether aberrant expression of repetitive element sequences are observed in ALS, we analysed RNA sequencing data from C9orf72-positive and sporadic ALS cases, as well as healthy controls. Transcripts from multiple classes and subclasses of repetitive elements (LINEs, endogenous retroviruses, DNA transposons, simple repeats, etc.) were significantly increased in the frontal cortex of C9orf72 ALS patients. A large collection of patient samples, representing both C9orf72 positive and negative ALS, ALS/FTLD, and FTLD cases, was used to validate the levels of several repetitive element transcripts. These analyses confirmed that repetitive element expression was significantly increased in C9orf72-positive compared to C9orf72-negative or control cases. While previous studies suggest an important link between TDP-43 and repetitive element biology, our data indicate that TDP-43 pathology alone is insufficient to account for the observed changes in repetitive elements in ALS/FTLD. Instead, we found that repetitive element expression positively correlated with RNA polymerase II activity in postmortem brain, and pharmacologic modulation of RNA polymerase II activity altered repetitive element expression in vitro. We conclude that increased RNA polymerase II activity in ALS/FTLD may lead to increased repetitive element transcript expression, a novel pathological feature of ALS/FTLD. © The Author 2017. Published by Oxford University Press.

  9. Nonword Repetition and Vocabulary Knowledge as Predictors of Children's Phonological and Semantic Word Learning.

    Science.gov (United States)

    Adlof, Suzanne M; Patten, Hannah

    2017-03-01

    This study examined the unique and shared variance that nonword repetition and vocabulary knowledge contribute to children's ability to learn new words. Multiple measures of word learning were used to assess recall and recognition of phonological and semantic information. Fifty children, with a mean age of 8 years (range 5-12 years), completed experimental assessments of word learning and norm-referenced assessments of receptive and expressive vocabulary knowledge and nonword repetition skills. Hierarchical multiple regression analyses examined the variance in word learning that was explained by vocabulary knowledge and nonword repetition after controlling for chronological age. Together with chronological age, nonword repetition and vocabulary knowledge explained up to 44% of the variance in children's word learning. Nonword repetition was the stronger predictor of phonological recall, phonological recognition, and semantic recognition, whereas vocabulary knowledge was the stronger predictor of verbal semantic recall. These findings extend the results of past studies indicating that both nonword repetition skill and existing vocabulary knowledge are important for new word learning, but the relative influence of each predictor depends on the way word learning is measured. Suggestions for further research involving typically developing children and children with language or reading impairments are discussed.

  10. Drug allergy passport and other documentation for patients with drug hypersensitivity

    DEFF Research Database (Denmark)

    Brockow, Knut; Aberer, Werner; Atanaskovic-Markovic, M

    2016-01-01

    The strongest and best-documented risk factor for drug hypersensitivity (DH) is the history of a previous reaction. Accidental exposures to drugs may lead to severe or even fatal reactions in sensitized patients. Preventable prescription errors are common. They are often due to inadequate medical...... history or poor risk assessment of recurrence of drug reaction. Proper documentation is essential information for the doctor to make sound therapeutic decision. The European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology have formed...... a task force and developed a drug allergy passport as well as general guidelines of drug allergy documentation. A drug allergy passport, a drug allergy alert card, a certificate, and a discharge letter after medical evaluation are adequate means to document DH in a patient. They are to be handed...

  11. High-speed repetitive pellet injector prototype for magnetic confinement fusion devices

    International Nuclear Information System (INIS)

    Frattolillo, A.; Gasparotto, M.; Migliori, S.; Angelone, G.; Baldarelli, M.; Scaramuzzi, F.; Ronci, G.; Reggiori, A.; Riva, G.; Carlevaro, R.; Daminelli, G.B.

    1992-01-01

    The design of a test facility aimed at demonstrating the feasibility of high-speed repetitive acceleration of solid D 2 pellets for fusion applications, developed in a collaboration between Oak Ridge National Laboratory and ENEA Frascati, is presented. The results of tests performed at the CNPM/CNR on the piston wear in a repetitively operating two-stage gun are also reported

  12. Widespread Chromatin Accessibility at Repetitive Elements Links Stem Cells with Human Cancer

    Directory of Open Access Journals (Sweden)

    Nicholas C. Gomez

    2016-11-01

    Full Text Available Chromatin regulation is critical for differentiation and disease. However, features linking the chromatin environment of stem cells with disease remain largely unknown. We explored chromatin accessibility in embryonic and multipotent stem cells and unexpectedly identified widespread chromatin accessibility at repetitive elements. Integrating genomic and biochemical approaches, we demonstrate that these sites of increased accessibility are associated with well-positioned nucleosomes marked by distinct histone modifications. Differentiation is accompanied by chromatin remodeling at repetitive elements associated with altered expression of genes in relevant developmental pathways. Remarkably, we found that the chromatin environment of Ewing sarcoma, a mesenchymally derived tumor, is shared with primary mesenchymal stem cells (MSCs. Accessibility at repetitive elements in MSCs offers a permissive environment that is exploited by the critical oncogene responsible for this cancer. Our data demonstrate that stem cells harbor a unique chromatin landscape characterized by accessibility at repetitive elements, a feature associated with differentiation and oncogenesis.

  13. Tactile Ranschburg effects: facilitation and inhibitory repetition effects analogous to verbal memory.

    Science.gov (United States)

    Roe, Daisy; Miles, Christopher; Johnson, Andrew J

    2017-07-01

    The present paper examines the effect of within-sequence item repetitions in tactile order memory. Employing an immediate serial recall procedure, participants reconstructed a six-item sequence tapped upon their fingers by moving those fingers in the order of original stimulation. In Experiment 1a, within-sequence repetition of an item separated by two-intervening items resulted in a significant reduction in recall accuracy for that repeated item (i.e., the Ranschburg effect). In Experiment 1b, within-sequence repetition of an adjacent item resulted in significant recall facilitation for that repeated item. These effects mirror those reported for verbal stimuli (e.g., Henson, 1998a . Item repetition in short-term memory: Ranschburg repeated. Journal of Experimental Psychology: Learning, Memory, and Cognition, 24(5), 1162-1181. doi:doi.org/10.1037/0278-7393.24.5.1162). These data are the first to demonstrate the Ranschburg effect with non-verbal stimuli and suggest further cross-modal similarities in order memory.

  14. Combined impact of transient heat loads and steady-state plasma exposure on tungsten

    Energy Technology Data Exchange (ETDEWEB)

    Huber, Alexander, E-mail: A.Huber@fz-juelich.de [Forschungszentrum Jülich GmbH, Institut für Energie- und Klimaforschung, 52425 Jülich (Germany); Wirtz, Marius; Sergienko, Gennady; Steudel, Isabel [Forschungszentrum Jülich GmbH, Institut für Energie- und Klimaforschung, 52425 Jülich (Germany); Arakcheev, Aleksey; Burdakov, Aleksander [Budker Institute of Nuclear Physics (BINP), Novosibirsk 630090 (Russian Federation); Esser, Hans Guenter; Freisinger, Michaele; Kreter, Arkadi; Linke, Jochen; Linsmeier, Christian; Mertens, Philippe; Möller, Sören; Philipps, Volker; Pintsuk, Gerald; Reinhart, Michael; Schweer, Bernd [Forschungszentrum Jülich GmbH, Institut für Energie- und Klimaforschung, 52425 Jülich (Germany); Shoshin, Andrey [Budker Institute of Nuclear Physics (BINP), Novosibirsk 630090 (Russian Federation); Terra, Alexis; Unterberg, Bernhard [Forschungszentrum Jülich GmbH, Institut für Energie- und Klimaforschung, 52425 Jülich (Germany)

    2015-10-15

    Highlights: • W-samples under combined loading conditions show a lower damage threshold. • The pre-loaded W-samples show a lower damage threshold due to the D- embrittlement. • Pronounced increase of the D retention has been observed during the combined loads. • Enhanced blister formation has been observed under combined loading conditions. - Abstract: Cracking thresholds and crack patterns in tungsten targets have been studied in recent experiments after repetitive ITER-like ELM heat pulses in combination with plasma exposure in PSI-2 (Γ{sub target} = 2.5–4.0 × 10{sup 21} m{sup −2} s{sup −1}, ion energy on surface E{sub ion} = 60 eV, T{sub e} ≈ 10 eV). The heat pulses were simulated by laser irradiation. A Nd:YAG laser with energy per pulse of up to 32 J and a duration of 1 ms at the fundamental wavelength (λ = 1064 nm, repetition rate 0.5 Hz) was used to irradiate ITER-grade W samples with repetitive heat loads. In contrast to pure thermal exposure with a laser beam where the damage threshold under pure heat loads for ITER-grade W lies between 0.38 and 0.76 GW/m{sup 2}, the experiments with pre-loaded W-samples as well as under combined loading conditions show a lower damage threshold of 0.3 GW/m{sup 2}. This is probably due to deuterium embrittlement and/or a higher defect concentration in a region close to the surface due to supersaturation with deuterium. A pronounced increase in the D retention (more than a factor of five) has been observed during the combined transient heat loads and plasma exposure. Enhanced blister formation has been observed under these combined loading conditions.

  15. Combined impact of transient heat loads and steady-state plasma exposure on tungsten

    International Nuclear Information System (INIS)

    Huber, Alexander; Wirtz, Marius; Sergienko, Gennady; Steudel, Isabel; Arakcheev, Aleksey; Burdakov, Aleksander; Esser, Hans Guenter; Freisinger, Michaele; Kreter, Arkadi; Linke, Jochen; Linsmeier, Christian; Mertens, Philippe; Möller, Sören; Philipps, Volker; Pintsuk, Gerald; Reinhart, Michael; Schweer, Bernd; Shoshin, Andrey; Terra, Alexis; Unterberg, Bernhard

    2015-01-01

    Highlights: • W-samples under combined loading conditions show a lower damage threshold. • The pre-loaded W-samples show a lower damage threshold due to the D- embrittlement. • Pronounced increase of the D retention has been observed during the combined loads. • Enhanced blister formation has been observed under combined loading conditions. - Abstract: Cracking thresholds and crack patterns in tungsten targets have been studied in recent experiments after repetitive ITER-like ELM heat pulses in combination with plasma exposure in PSI-2 (Γ_t_a_r_g_e_t = 2.5–4.0 × 10"2"1 m"−"2 s"−"1, ion energy on surface E_i_o_n = 60 eV, T_e ≈ 10 eV). The heat pulses were simulated by laser irradiation. A Nd:YAG laser with energy per pulse of up to 32 J and a duration of 1 ms at the fundamental wavelength (λ = 1064 nm, repetition rate 0.5 Hz) was used to irradiate ITER-grade W samples with repetitive heat loads. In contrast to pure thermal exposure with a laser beam where the damage threshold under pure heat loads for ITER-grade W lies between 0.38 and 0.76 GW/m"2, the experiments with pre-loaded W-samples as well as under combined loading conditions show a lower damage threshold of 0.3 GW/m"2. This is probably due to deuterium embrittlement and/or a higher defect concentration in a region close to the surface due to supersaturation with deuterium. A pronounced increase in the D retention (more than a factor of five) has been observed during the combined transient heat loads and plasma exposure. Enhanced blister formation has been observed under these combined loading conditions.

  16. ReRep: Computational detection of repetitive sequences in genome survey sequences (GSS

    Directory of Open Access Journals (Sweden)

    Alves-Ferreira Marcelo

    2008-09-01

    Full Text Available Abstract Background Genome survey sequences (GSS offer a preliminary global view of a genome since, unlike ESTs, they cover coding as well as non-coding DNA and include repetitive regions of the genome. A more precise estimation of the nature, quantity and variability of repetitive sequences very early in a genome sequencing project is of considerable importance, as such data strongly influence the estimation of genome coverage, library quality and progress in scaffold construction. Also, the elimination of repetitive sequences from the initial assembly process is important to avoid errors and unnecessary complexity. Repetitive sequences are also of interest in a variety of other studies, for instance as molecular markers. Results We designed and implemented a straightforward pipeline called ReRep, which combines bioinformatics tools for identifying repetitive structures in a GSS dataset. In a case study, we first applied the pipeline to a set of 970 GSSs, sequenced in our laboratory from the human pathogen Leishmania braziliensis, the causative agent of leishmaniosis, an important public health problem in Brazil. We also verified the applicability of ReRep to new sequencing technologies using a set of 454-reads of an Escheria coli. The behaviour of several parameters in the algorithm is evaluated and suggestions are made for tuning of the analysis. Conclusion The ReRep approach for identification of repetitive elements in GSS datasets proved to be straightforward and efficient. Several potential repetitive sequences were found in a L. braziliensis GSS dataset generated in our laboratory, and further validated by the analysis of a more complete genomic dataset from the EMBL and Sanger Centre databases. ReRep also identified most of the E. coli K12 repeats prior to assembly in an example dataset obtained by automated sequencing using 454 technology. The parameters controlling the algorithm behaved consistently and may be tuned to the properties

  17. Don't Throw out the Baby with the Bathwater: Verbal Repetition, Mnemonics, and Active Learning

    Science.gov (United States)

    Saber, Jane Lee; Johnson, Richard D.

    2008-01-01

    The effectiveness of using verbal repetition and first-letter acronyms to teach a common marketing framework was examined in two experiments. In Experiment 1, 345 undergraduate students were exposed to the framework using one of four conditions: control, verbal repetition, acronym, and verbal repetition plus acronym in a traditional learning…

  18. Drug-Target Kinetics in Drug Discovery.

    Science.gov (United States)

    Tonge, Peter J

    2018-01-17

    The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure-kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug-target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug-target kinetics into predictions of drug activity.

  19. Macrophage and tumor cell responses to repetitive pulsed X-ray radiation

    Science.gov (United States)

    Buldakov, M. A.; Tretyakova, M. S.; Ryabov, V. B.; Klimov, I. A.; Kutenkov, O. P.; Kzhyshkowska, J.; Bol'shakov, M. A.; Rostov, V. V.; Cherdyntseva, N. V.

    2017-05-01

    To study a response of tumor cells and macrophages to the repetitive pulsed low-dose X-ray radiation. Methods. Tumor growth and lung metastasis of mice with an injected Lewis lung carcinoma were analysed, using C57Bl6. Monocytes were isolated from a human blood, using CD14+ magnetic beads. IL6, IL1-betta, and TNF-alpha were determined by ELISA. For macrophage phenotyping, a confocal microscopy was applied. “Sinus-150” was used for the generation of pulsed X-ray radiation (the absorbed dose was below 0.1 Gy, the pulse repetition frequency was 10 pulse/sec). The irradiation of mice by 0.1 Gy pulsed X-rays significantly inhibited the growth of primary tumor and reduced the number of metastatic colonies in the lung. Furthermore, the changes in macrophage phenotype and cytokine secretion were observed after repetitive pulsed X-ray radiation. Conclusion. Macrophages and tumor cells had a different response to a low-dose pulsed X-ray radiation. An activation of the immune system through changes of a macrophage phenotype can result in a significant antitumor effect of the low-dose repetitive pulsed X-ray radiation.

  20. Uncertainty quantification and sensitivity analysis of an arterial wall mechanics model for evaluation of vascular drug therapies.

    Science.gov (United States)

    Heusinkveld, Maarten H G; Quicken, Sjeng; Holtackers, Robert J; Huberts, Wouter; Reesink, Koen D; Delhaas, Tammo; Spronck, Bart

    2018-02-01

    Quantification of the uncertainty in constitutive model predictions describing arterial wall mechanics is vital towards non-invasive assessment of vascular drug therapies. Therefore, we perform uncertainty quantification to determine uncertainty in mechanical characteristics describing the vessel wall response upon loading. Furthermore, a global variance-based sensitivity analysis is performed to pinpoint measurements that are most rewarding to be measured more precisely. We used previously published carotid diameter-pressure and intima-media thickness (IMT) data (measured in triplicate), and Holzapfel-Gasser-Ogden models. A virtual data set containing 5000 diastolic and systolic diameter-pressure points, and IMT values was generated by adding measurement error to the average of the measured data. The model was fitted to single-exponential curves calculated from the data, obtaining distributions of constitutive parameters and constituent load bearing parameters. Additionally, we (1) simulated vascular drug treatment to assess the relevance of model uncertainty and (2) evaluated how increasing the number of measurement repetitions influences model uncertainty. We found substantial uncertainty in constitutive parameters. Simulating vascular drug treatment predicted a 6% point reduction in collagen load bearing ([Formula: see text]), approximately 50% of its uncertainty. Sensitivity analysis indicated that the uncertainty in [Formula: see text] was primarily caused by noise in distension and IMT measurements. Spread in [Formula: see text] could be decreased by 50% when increasing the number of measurement repetitions from 3 to 10. Model uncertainty, notably that in [Formula: see text], could conceal effects of vascular drug therapy. However, this uncertainty could be reduced by increasing the number of measurement repetitions of distension and wall thickness measurements used for model parameterisation.

  1. Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis.

    Science.gov (United States)

    Perry, Meghan R; Wyllie, Susan; Raab, Andrea; Feldmann, Joerg; Fairlamb, Alan H

    2013-12-03

    The Indian subcontinent is the only region where arsenic contamination of drinking water coexists with widespread resistance to antimonial drugs that are used to treat the parasitic disease visceral leishmaniasis. We have previously proposed that selection for parasite resistance within visceral leishmaniasis patients who have been exposed to trivalent arsenic results in cross-resistance to the related metalloid antimony, present in the pentavalent state as a complex in drugs such as sodium stibogluconate (Pentostam) and meglumine antimonate (Glucantime). To test this hypothesis, Leishmania donovani was serially passaged in mice exposed to arsenic in drinking water at environmentally relevant levels (10 or 100 ppm). Arsenic accumulation in organs and other tissues was proportional to the level of exposure and similar to that previously reported in human liver biopsies. After five monthly passages in mice exposed to arsenic, isolated parasites were found to be completely refractory to 500 μg · mL(-1) Pentostam compared with the control passage group (38.5 μg · mL(-1)) cultured in vitro in mouse peritoneal macrophages. Reassessment of resistant parasites following further passage for 4 mo in mice without arsenic exposure showed that resistance was stable. Treatment of infected mice with Pentostam confirmed that resistance observed in vitro also occurred in vivo. We conclude that arsenic contamination may have played a significant role in the development of Leishmania antimonial resistance in Bihar because inadequate treatment with antimonial drugs is not exclusive to India, whereas widespread antimonial resistance is.

  2. Semantic priming, not repetition priming, is to blame for false hearing.

    Science.gov (United States)

    Rogers, Chad S

    2017-08-01

    Contextual and sensory information are combined in speech perception. Conflict between the two can lead to false hearing, defined as a high-confidence misidentification of a spoken word. Rogers, Jacoby, and Sommers (Psychology and Aging, 27(1), 33-45, 2012) found that older adults are more susceptible to false hearing than are young adults, using a combination of semantic priming and repetition priming to create context. In this study, the type of context (repetition vs. sematic priming) responsible for false hearing was examined. Older and young adult participants read and listened to a list of paired associates (e.g., ROW-BOAT) and were told to remember the pairs for a later memory test. Following the memory test, participants identified words masked in noise that were preceded by a cue word in the clear. Targets were semantically associated to the cue (e.g., ROW-BOAT), unrelated to the cue (e.g., JAW-PASS), or phonologically related to a semantic associate of the cue (e.g., ROW-GOAT). How often each cue word and its paired associate were presented prior to the memory test was manipulated (0, 3, or 5 times) to test effects of repetition priming. Results showed repetitions had no effect on rates of context-based listening or false hearing. However, repetition did significantly increase sensory information as a basis for metacognitive judgments in young and older adults. This pattern suggests that semantic priming dominates as the basis for false hearing and highlights context and sensory information operating as qualitatively different bases for listening and metacognition.

  3. Storytelling and Repetitive Narratives for Design Empathy

    DEFF Research Database (Denmark)

    Fritsch, Jonas; Judice, Andrea; Soini, Katja

    2007-01-01

    study. In this paper, we show how we attained an empathic understanding through storytelling and aroused empathy to others using repetitive narratives in an experimental presentation bringing forth factual, reflective and experiential aspects of the user information. Taking as a starting point our...

  4. Neuroprotective effect of hyperbaric oxygen therapy in a juvenile rat model of repetitive mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Lei Huang

    2016-01-01

    Full Text Available Repetitive mild traumatic brain injury (rmTBI is an important medical concern for adolescent athletes that can lead to long-term disabilities. Multiple mild injuries may exacerbate tissue damage resulting in cumulative brain injury and poor functional recovery. In the present study, we investigated the increased brain vulnerability to rmTBI and the effect of hyperbaric oxygen treatment using a juvenile rat model of rmTBI. Two episodes of mild cortical controlled impact (3 days apart were induced in juvenile rats. Hyperbaric oxygen (HBO was applied 1 hour/day × 3 days at 2 atmosphere absolute consecutively, starting at 1 day after initial mild traumatic brain injury (mTBI. Neuropathology was assessed by multi-modal magnetic resonance imaging (MRI and tissue immunohistochemistry. After repetitive mTBI, there were increases in T2-weighted imaging-defined cortical lesions and susceptibility weighted imaging-defined cortical microhemorrhages, correlated with brain tissue gliosis at the site of impact. HBO treatment significantly decreased the MRI-identified abnormalities and tissue histopathology. Our findings suggest that HBO treatment improves the cumulative tissue damage in juvenile brain following rmTBI. Such therapy regimens could be considered in adolescent athletes at the risk of repeated concussions exposures.

  5. Accounting for Unobservable Exposure Time Bias Wh...

    Data.gov (United States)

    U.S. Department of Health & Human Services — Accounting for Unobservable Exposure Time Bias When Using Medicare Prescription Drug Data Unobservable exposure time is common among Medicare Part D beneficiaries,...

  6. High power, repetitive stacked Blumlein pulse generators

    Energy Technology Data Exchange (ETDEWEB)

    Davanloo, F; Borovina, D L; Korioth, J L; Krause, R K; Collins, C B [Univ. of Texas at Dallas, Richardson, TX (United States). Center for Quantum Electronics; Agee, F J [US Air Force Phillips Lab., Kirtland AFB, NM (United States); Kingsley, L E [US Army CECOM, Ft. Monmouth, NJ (United States)

    1997-12-31

    The repetitive stacked Blumlein pulse power generators developed at the University of Texas at Dallas consist of several triaxial Blumleins stacked in series at one end. The lines are charged in parallel and synchronously commuted with a single switch at the other end. In this way, relatively low charging voltages are multiplied to give a high discharge voltage across an arbitrary load. Extensive characterization of these novel pulsers have been performed over the past few years. Results indicate that they are capable of producing high power waveforms with rise times and repetition rates in the range of 0.5-50 ns and 1-300 Hz, respectively, using a conventional thyratron, spark gap, or photoconductive switch. The progress in the development and use of stacked Blumlein pulse generators is reviewed. The technology and the characteristics of these novel pulsers driving flash x-ray diodes are discussed. (author). 4 figs., 5 refs.

  7. Closed cycle high-repetition-rate pulsed HF laser

    Science.gov (United States)

    Harris, Michael R.; Morris, A. V.; Gorton, Eric K.

    1997-04-01

    The design and performance of a closed cycle high repetition rate HF laser is described. A short pulse, glow discharge is formed in a 10 SF6:1 H2 gas mixture at a total pressure of approximately 110 torr within a 15 by 0.5 by 0.5 cm3 volume. Transverse, recirculated gas flow adequate to enable repetitive operation up to 3 kHz is imposed by a centrifugal fan. The fan also forces the gas through a scrubber cell to eliminate ground state HF from the gas stream. An automated gas make-up system replenishes spent gas removed by the scrubber. Typical mean laser output powers up to 3 W can be maintained for extended periods of operation.

  8. Structurally Complex Organization of Repetitive DNAs in the Genome of Cobia (Rachycentron canadum).

    Science.gov (United States)

    Costa, Gideão W W F; Cioffi, Marcelo de B; Bertollo, Luiz A C; Molina, Wagner F

    2015-06-01

    Repetitive DNAs comprise the largest fraction of the eukaryotic genome. They include microsatellites or simple sequence repeats (SSRs), which play an important role in the chromosome differentiation among fishes. Rachycentron canadum is the only representative of the family Rachycentridae. This species has been focused on several multidisciplinary studies in view of its important potential for marine fish farming. In the present study, distinct classes of repetitive DNAs, with emphasis on SSRs, were mapped in the chromosomes of this species to improve the knowledge of its genome organization. Microsatellites exhibited a diversified distribution, both dispersed in euchromatin and clustered in the heterochromatin. The multilocus location of SSRs strengthened the heterochromatin heterogeneity in this species, as suggested by some previous studies. The colocalization of SSRs with retrotransposons and transposons pointed to a close evolutionary relationship between these repetitive sequences. A number of heterochromatic regions highlighted a greater complex organization than previously supposed, harboring a diversity of repetitive elements. In this sense, there was also evidence of colocalization of active genetic regions and different classes of repetitive DNAs in a common heterochromatic region, which offers a potential opportunity for further researches regarding the interaction of these distinct fractions in fish genomes.

  9. The algorithm for duration acceleration of repetitive projects considering the learning effect

    Science.gov (United States)

    Chen, Hongtao; Wang, Keke; Du, Yang; Wang, Liwan

    2018-03-01

    Repetitive project optimization problem is common in project scheduling. Repetitive Scheduling Method (RSM) has many irreplaceable advantages in the field of repetitive projects. As the same or similar work is repeated, the proficiency of workers will be correspondingly low to high, and workers will gain experience and improve the efficiency of operations. This is learning effect. Learning effect is one of the important factors affecting the optimization results in repetitive project scheduling. This paper analyzes the influence of the learning effect on the controlling path in RSM from two aspects: one is that the learning effect changes the controlling path, the other is that the learning effect doesn't change the controlling path. This paper proposes corresponding methods to accelerate duration for different types of critical activities and proposes the algorithm for duration acceleration based on the learning effect in RSM. And the paper chooses graphical method to identity activities' types and considers the impacts of the learning effect on duration. The method meets the requirement of duration while ensuring the lowest acceleration cost. A concrete bridge construction project is given to verify the effectiveness of the method. The results of this study will help project managers understand the impacts of the learning effect on repetitive projects, and use the learning effect to optimize project scheduling.

  10. Errors in nonword repetition: bridging short- and long-term memory.

    Science.gov (United States)

    Santos, F H; Bueno, O F A; Gathercole, S E

    2006-03-01

    According to the working memory model, the phonological loop is the component of working memory specialized in processing and manipulating limited amounts of speech-based information. The Children's Test of Nonword Repetition (CNRep) is a suitable measure of phonological short-term memory for English-speaking children, which was validated by the Brazilian Children's Test of Pseudoword Repetition (BCPR) as a Portuguese-language version. The objectives of the present study were: i) to investigate developmental aspects of the phonological memory processing by error analysis in the nonword repetition task, and ii) to examine phoneme (substitution, omission and addition) and order (migration) errors made in the BCPR by 180 normal Brazilian children of both sexes aged 4-10, from preschool to 4th grade. The dominant error was substitution [F(3,525) = 180.47; P long than in short items, was observed [F(3,519) = 108.36; P long-term memory contributes to holding memory trace. The findings were discussed in terms of distinctiveness, clustering and redintegration hypotheses.

  11. Repetitive control of an electrostatic microbridge actuator: theory and simulation

    International Nuclear Information System (INIS)

    Zhao, Haiyu; Rahn, Christopher D

    2010-01-01

    Electrostatic microactuators are used extensively in MEMS sensors, RF switches and microfluidic pumps. The high bandwidth operation required by these applications complicates the implementation of feedback controllers. This paper designs, proves stability and simulates a feedforward repetitive controller for an electrostatic microbridge. High residual stress creates tension in the microbridge that dominates bending stiffness so a pinned string model with uniform electrostatic force loading is used for model-based control. The control objective is to force the microbridge displacement to follow prescribed spatial and periodic time trajectories. Viscous damping ensures boundedness of the distributed transverse displacement in response to bounded inputs. The average displacement is measured by capacitive sensing and processed offline using a repetitive control algorithm that updates a high speed waveform generator's parameters. Simulations show that the performance depends on the amount of damping. With less than 1% damping in a representative microbridge structure, repetitive control reduces the midspan displacement overshoot by 83%

  12. Fractional laser-assisted drug uptake

    DEFF Research Database (Denmark)

    Banzhaf, Christina A; Thaysen-Petersen, Daniel; Bay, Christiane

    2017-01-01

    BACKGROUND AND OBJECTIVE: Ablative fractional laser (AFXL) is acknowledged to increase uptake of topically applied agents in skin. AFXL channels gradually close over time, which may impair this capability. The time frame for applying a drug after AFXL exposure remains to be established. The aim...... in laser-exposed and non-laser-exposed skin at 24-48 hours. CONCLUSIONS: The time frame to maintain enhanced drug delivery sustained for several hours after AFXL exposure, corresponding to channel morphology and loss of skin integrity. Lasers Surg. Med. 49:348-354, 2017. © 2016 Wiley Periodicals, Inc....

  13. Environmental contamination, product contamination and workers exposure using a robotic system for antineoplastic drug preparation.

    Science.gov (United States)

    Sessink, Paul J M; Leclercq, Gisèle M; Wouters, Dominique-Marie; Halbardier, Loïc; Hammad, Chaïma; Kassoul, Nassima

    2015-04-01

    Environmental contamination, product contamination and technicians exposure were measured following preparation of iv bags with cyclophosphamide using the robotic system CytoCare. Wipe samples were taken inside CytoCare, in the clean room environment, from vials, and prepared iv bags including ports and analysed for contamination with cyclophosphamide. Contamination with cyclophosphamide was also measured in environmental air and on the technicians hands and gloves used for handling the drugs. Exposure of the technicians to cyclophosphamide was measured by analysis of cyclophosphamide in urine. Contamination with cyclophosphamide was mainly observed inside CytoCare, before preparation, after preparation and after daily routine cleaning. Contamination outside CytoCare was incidentally found. All vials with reconstituted cyclophosphamide entering CytoCare were contaminated on the outside but vials with powdered cyclophosphamide were not contaminated on the outside. Contaminated bags entering CytoCare were also contaminated after preparation but non-contaminated bags were not contaminated after preparation. Cyclophosphamide was detected on the ports of all prepared bags. Almost all outer pairs of gloves used for preparation and daily routine cleaning were contaminated with cyclophosphamide. Cyclophosphamide was not found on the inner pairs of gloves and on the hands of the technicians. Cyclophosphamide was not detected in the stationary and personal air samples and in the urine samples of the technicians. CytoCare enables the preparation of cyclophosphamide with low levels of environmental contamination and product contamination and no measurable exposure of the technicians. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  14. [Structural plasticity associated with drugs addiction].

    Science.gov (United States)

    Zhu, Jie; Cao, Guo-fen; Dang, Yong-hui; Chen, Teng

    2011-12-01

    An essential feature of drug addiction is that an individual continues to use drug despite the threat of severely adverse physical or psychosocial consequences. Persistent changes in behavior and psychological function that occur as a function of drugs of abuse are thought to be due to the reorganization of synaptic connections (structural plasticity) in relevant brain circuits (especially the brains reward circuits). In this paper we summarized evidence that, indeed, exposure to amphetamine, cocaine, nicotine or morphine produced persistent changes in the structure of dendrites and dendritic spines on cells in relevant brain regions. We also approached the potential molecular mechanisms of these changes. It is suggested that structural plasticity associated with exposure to drugs of abuse reflects a reorganization of patterns of synaptic connectivity in these neural systems, a reorganization that alters their operation, thus contributing to some of the persistent sequela associated with drug use-including addiction.

  15. Preposition accuracy on a sentence repetition task in school age Spanish–English bilinguals*

    Science.gov (United States)

    TALIANCICH-KLINGER, CASEY L.; BEDORE, LISA M.; PEÑA, ELIZABETH D.

    2018-01-01

    Preposition knowledge is important for academic success. The goal of this project was to examine how different variables such as English input and output, Spanish preposition score, mother education level, and age of English exposure (AoEE) may have played a role in children’s preposition knowledge in English. 148 Spanish–English children between 7;0 and 9;11 produced prepositions in English and Spanish on a sentence repetition task from an experimental version of the Bilingual English Spanish Assessment Middle Extension (Peña, Bedore, Gutierrez-Clellen, Iglesias & Goldstein, in development). English input and output accounted for most of the variance in English preposition score. The importance of language-specific experiences in the development of prepositions is discussed. Competition for selection of appropriate prepositions in English and Spanish is discussed as potentially influencing low overall preposition scores in English and Spanish. PMID:28506324

  16. Considerations for effect site pharmacokinetics to estimate drug exposure: concentrations of antibiotics in the lung.

    Science.gov (United States)

    Rodvold, Keith A; Hope, William W; Boyd, Sara E

    2017-10-01

    Bronchoalveolar lavage (BAL) and microdialysis have become the most reliable and relevant methods for measuring lung concentrations of antibiotics, with the majority of BAL studies involving either healthy adult subjects or patients undergoing diagnostic bronchoscopy. Emphasis on the amount of drug that reaches the site of infection is increasingly recognized as necessary to determine whether a dose selection will translate to good clinical outcomes in the treatment of patients with pneumonia. Observed concentrations and/or parameters of exposure (e.g. area-under-the-curve) need to be incorporated with pharmacokinetic-pharmacodynamic indices so that rational dose selection can be identified for specific pathogens and types of pneumonic infection (community-acquired vs hospital-acquired bacterial pneumonia, including ventilator-associated bacterial pneumonia). Although having measured plasma or lung concentration-time data from critically ill patients to incorporate into pharmacokinetic-pharmacodynamic models is very unlikely during drug development, it is essential that altered distribution, augmented renal clearance, and renal or hepatic dysfunction should be considered. Notably, the number of published studies involving microdialysis and intrapulmonary penetration of antibiotics has been limited and mainly involve beta-lactam agents, levofloxacin, and fosfomycin. Opportunities to measure in high-resolution effect site spatial pharmacokinetics (e.g. with MALDI-MSI or PET imaging) and in vivo continuous drug concentrations (e.g. with aptamer-based probes) now exist. Going forward these studies could be incorporated into antibiotic development programs for pneumonia in order to further increase the probability of candidate success. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs.

    Science.gov (United States)

    Andreasen, Nancy C; Pressler, Marcus; Nopoulos, Peg; Miller, Del; Ho, Beng-Choon

    2010-02-01

    A standardized quantitative method for comparing dosages of different drugs is a useful tool for designing clinical trials and for examining the effects of long-term medication side effects such as tardive dyskinesia. Such a method requires establishing dose equivalents. An expert consensus group has published charts of equivalent doses for various antipsychotic medications for first- and second-generation medications. These charts were used in this study. Regression was used to compare each drug in the experts' charts to chlorpromazine and haloperidol and to create formulas for each relationship. The formulas were solved for chlorpromazine 100 mg and haloperidol 2 mg to derive new chlorpromazine and haloperidol equivalents. The formulas were incorporated into our definition of dose-years such that 100 mg/day of chlorpromazine equivalent or 2 mg/day of haloperidol equivalent taken for 1 year is equal to one dose-year. All comparisons to chlorpromazine and haloperidol were highly linear with R(2) values greater than .9. A power transformation further improved linearity. By deriving a unique formula that converts doses to chlorpromazine or haloperidol equivalents, we can compare otherwise dissimilar drugs. These equivalents can be multiplied by the time an individual has been on a given dose to derive a cumulative value measured in dose-years in the form of (chlorpromazine equivalent in mg) x (time on dose measured in years). After each dose has been converted to dose-years, the results can be summed to provide a cumulative quantitative measure of lifetime exposure. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  18. Risk for borderline ovarian tumours after exposure to fertility drugs

    DEFF Research Database (Denmark)

    Bjørnholt, Sarah Marie; Kjaer, Susanne Krüger; Nielsen, Thor Schütt Svane

    2015-01-01

    numbers. To obtain information on use of fertility drugs, hospital files and medical records of infertility-associated visits to all Danish fertility clinics were collected and supplemented with information from the Danish IVF register. We used case-cohort techniques to calculate rate ratios (RRs......STUDY QUESTION: Do fertility drugs increase the risk for borderline ovarian tumours, overall and according to histological subtype? SUMMARY ANSWER: The use of any fertility drug did not increase the overall risk for borderline ovarian tumours, but an increased risk for serous borderline ovarian...... tumours was observed after the use of progesterone. WHAT IS KNOWN ALREADY: Many epidemiological studies have addressed the connection between fertility drugs use and risk for ovarian cancer; most have found no strong association. Fewer studies have assessed the association between use of fertility drugs...

  19. Natural Rewards, Neuroplasticity, and Non-Drug Addictions

    Science.gov (United States)

    Olsen, Christopher M.

    2011-01-01

    There is a high degree of overlap between brain regions involved in processing natural rewards and drugs of abuse. “Non-drug” or “behavioral” addictions have become increasingly documented in the clinic, and pathologies include compulsive activities such as shopping, eating, exercising, sexual behavior, and gambling. Like drug addiction, non-drug addictions manifest in symptoms including craving, impaired control over the behavior, tolerance, withdrawal, and high rates of relapse. These alterations in behavior suggest that plasticity may be occurring in brain regions associated with drug addiction. In this review, I summarize data demonstrating that exposure to non-drug rewards can alter neural plasticity in regions of the brain that are affected by drugs of abuse. Research suggests that there are several similarities between neuroplasticity induced by natural and drug rewards and that, depending on the reward, repeated exposure to natural rewards might induce neuroplasticity that either promotes or counteracts addictive behavior. PMID:21459101

  20. Effects of Navigated Repetitive Transcranial Magnetic Stimulation After Stroke.

    Science.gov (United States)

    Chervyakov, Alexander V; Poydasheva, Alexandra G; Lyukmanov, Roman H; Suponeva, Natalia A; Chernikova, Ludmila A; Piradov, Michael A; Ustinova, Ksenia I

    2018-03-01

    The purpose of this study was to test the effects of navigated repetitive transcranial magnetic stimulation, delivered in different modes, on motor impairments and functional limitations after stroke. The study sample included 42 patients (58.5 ± 10.7 years; 26 males) who experienced a single unilateral stroke (1-12 months previously) in the area of the middle cerebral artery. Patients completed a course of conventional rehabilitation, together with 10 sessions of navigated repetitive transcranial magnetic stimulation or sham stimulation. Stimulation was scheduled five times a week over two consecutive weeks in an inpatient clinical setting. Patients were randomly assigned to one of four groups and received sham stimulation (n = 10), low-frequency (1-Hz) stimulation of the nonaffected hemisphere (n = 11), high-frequency (10-Hz) stimulation of the affected hemisphere (n = 13), or sequential combination of low- and high-frequency stimulations (n = 8). Participants were evaluated before and after stimulation with clinical tests, including the arm and hand section of the Fugl-Meyer Assessment Scale, modified Ashworth Scale of Muscle Spasticity, and Barthel Index of Activities of Daily Living. Participants in the three groups receiving navigated repetitive transcranial magnetic stimulation showed improvements in arm and hand functions on the Fugl-Meyer Stroke Assessment Scale. Ashworth Scale of Muscle Spasticity and Barthel Index scores were significantly reduced in groups receiving low- or high-frequency stimulation alone. Including navigated repetitive transcranial magnetic stimulation in a conventional rehabilitation program positively influenced motor and functional recovery in study participants, demonstrating the clinical potential of the method. The results of this study will be used for designing a large-scale clinical trial.

  1. A compact, repetitive accelerator for military and industrial applications

    International Nuclear Information System (INIS)

    Zutavern, F.J.; O'Malley, M.W.; Ruebush, M.H.; Rinehart, L.F.; Loubriel, G.M.; Babcock, S.R.; Denison, G.J.

    1998-04-01

    A compact, short pulse, repetitive accelerator has many useful military and commercial applications in biological counter proliferation, materials processing, radiography, and sterilization (medical instruments, waste, and food). The goal of this project was to develop and demonstrate a small, 700 kV accelerator, which can produce 7 kA particle beams with pulse lengths of 10--30 ns at rates up to 50 Hz. At reduced power levels, longer pulses or higher repetition rates (up to 10 kHz) could be achieved. Two switching technologies were tested: (1) spark gaps, which have been used to build low repetition rate accelerators for many years; and (2) high gain photoconductive semiconductor switches (PCSS), a new solid state switching technology. This plan was economical, because it used existing hardware for the accelerator, and the PCSS material and fabrication for one module was relatively inexpensive. It was research oriented, because it provided a test bed to examine the utility of other emerging switching technologies, such as magnetic switches. At full power, the accelerator will produce 700 kV and 7 kA with either the spark gap or PCSS pulser

  2. [Identification of a repetitive sequence element for DNA fingerprinting in Phytophthora sojae].

    Science.gov (United States)

    Yin, Lihua; Wang, Qinhu; Ning, Feng; Zhu, Xiaoying; Zuo, Yuhu; Shan, Weixing

    2010-04-01

    Establishment of DNA fingerprinting in Phytophthora sojae and an analysis of genetic relationship of Heilongjiang and Xinjiang populations. Bioinformatics tools were used to search repetitive sequences in P. sojae and Southern blot analysis was employed for DNA fingerprinting analysis of P. sojae populations from Heilongjiang and Xinjiang using the identified repetitive sequence. A moderately repetitive sequence was identified and designated as PS1227. Southern blot analysis indicated 34 distinct bands ranging in size from 1.5 kb-23 kb, of which 21 were polymorphic among 49 isolates examined. Analysis of single-zoospore progenies showed that the PS1227 fingerprint pattern was mitotically stable. DNA fingerprinting showed that the P. sojae isolates HP4002, SY6 and GJ0105 of Heilongjiang are genetically identical to DW303, 71228 and 71222 of Xinjiang, respectively. A moderately repetitive sequence designated PS1227 which will be useful for epidemiology and population biology studies of P. sojae was obtained, and a PS1227-based DNA fingerprinting analysis provided molecular evidence that P. sojae in Xinjiang was likely introduced from Heilongjiang.

  3. Topic Repetition in Conversations on Different Days as a Sign of Dementia.

    Science.gov (United States)

    Shinkawa, Kaoru; Yamada, Yasunori

    2018-01-01

    Detecting early signs of dementia in everyday situations becomes more and more important in a rapidly aging society. Language dysfunctions are recognized as the prominent signs of dementia. Previous computational studies characterized these language dysfunctions by using acoustic and linguistic features for detecting dementia. However, they mainly investigated language dysfunctions collected from patients during neuropsychological tests. Language dysfunctions observed during regular conversations in everyday situations received little attention. One of the dysfunctions associated with dementia which is frequently observed in regular conversations is the repetition of a topic on different days. In this study, we propose a feature to characterize topic repetition in conversations on different days. We used conversational data obtained from a daily monitoring service of eight elderly people, two of whom had dementia. Through the analysis of topic extraction with latent Dirichlet allocation, we found that the frequency of topic repetition was significantly higher in people with dementia than in the control group. The results suggest that our proposed feature for identifying topic repetition in regular conversations on different days might be used for detecting dementia.

  4. Product placement in video games: The effect of brand familiarity and repetition on consumers´ memory

    OpenAIRE

    Martí Parreño, José; Bermejo Berros, Jesús; Aldás Manzano, Joaquín

    2017-01-01

    Product placement in video games is gaining momentum as a means to target audiences in an indirect and engaging way. This research uses a 2 (high repetition vs low repetition) x 2 (high brand familiarity vs low brand familiarity) factorial design to test the effects of repetition and brand familiarity on consumers’ memory for brands placed in video games. Results suggest that consumers recall better familiar than unfamiliar brands placed in the video game and repetition increases recall for f...

  5. Genome-wide survey of repetitive DNA elements in the button mushroom Agaricus bisporus

    NARCIS (Netherlands)

    Foulongne-Oriol, M.; Murat, C.; Castanera, R.; Ramírez, L.; Sonnenberg, A.S.M.

    2013-01-01

    Repetitive DNA elements are ubiquitous constituents of eukaryotic genomes. The biological roles of these repetitive elements, supposed to impact genome organization and evolution, are not completely elucidated yet. The availability of whole genome sequence offers the opportunity to draw a picture of

  6. Reducing Repetitive Speech: Effects of Strategy Instruction.

    Science.gov (United States)

    Dipipi, Caroline M.; Jitendra, Asha K.; Miller, Judith A.

    2001-01-01

    This article describes an intervention with an 18-year-old young woman with mild mental retardation and a seizure disorder, which focused on her repetitive echolalic verbalizations. The intervention included time delay, differential reinforcement of other behaviors, and self-monitoring. Overall, the intervention was successful in facilitating…

  7. Comprehension priming as rational expectation for repetition: Evidence from syntactic processing.

    Science.gov (United States)

    Myslín, Mark; Levy, Roger

    2016-02-01

    Why do comprehenders process repeated stimuli more rapidly than novel stimuli? We consider an adaptive explanation for why such facilitation may be beneficial: priming is a consequence of expectation for repetition due to rational adaptation to the environment. If occurrences of a stimulus cluster in time, given one occurrence it is rational to expect a second occurrence closely following. Leveraging such knowledge may be particularly useful in online processing of language, where pervasive clustering may help comprehenders negotiate the considerable challenge of continual expectation update at multiple levels of linguistic structure and environmental variability. We test this account in the domain of structural priming in syntax, making use of the sentential complement-direct object (SC-DO) ambiguity. We first show that sentences containing SC continuations cluster in natural language, motivating an expectation for repetition of this structure. Second, we show that comprehenders are indeed sensitive to the syntactic clustering properties of their current environment. In a series of between-groups self-paced reading studies, we find that participants who are exposed to clusters of SC sentences subsequently process repetitions of SC structure more rapidly than participants who are exposed to the same number of SCs spaced in time, and attribute the difference to the learned degree of expectation for repetition. We model this behavior through Bayesian belief update, showing that (the optimal degree of) sensitivity to clustering properties of syntactic structures is indeed learnable through experience. Comprehension priming effects are thus consistent with rational expectation for repetition based on adaptation to the linguistic environment. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Cost Effectiveness of ‘On Demand’ Hiv Pre-Exposure Prophylaxis for Non-Injection Drug-Using Men Who Have Sex with Men in Canada

    Directory of Open Access Journals (Sweden)

    Estelle Ouellet

    2015-01-01

    Full Text Available BACKGROUND: Recent trials report the efficacy of continuous tenofovir-based pre-exposure prophylaxis (PrEP for prevention of HIV infection. The cost effectiveness of ‘on demand’ PrEP for non-injection drug-using men who have sex with men at high risk of HIV acquisition has not been evaluated.

  9. Increasing the efficacy of cue exposure treatment in preventing relapse of addictive behavior.

    Science.gov (United States)

    Havermans, Remco C; Jansen, Anita T M

    2003-07-01

    Theoretically, cue exposure treatment should be able to prevent relapse by extinguishing conditioned drug responding (e.g. cue-elicited craving). According to contemporary learning theory, though, extinction does not eliminate conditioned responding. Analogous cue exposure with response prevention (CERP) as a treatment of addictive behavior might not eliminate the learned relation between drug-related cues and drug use. This does not necessarily mean that cue exposure cannot successfully prevent relapse. Various suggestions for increasing the efficacy of cue exposure treatment are being discussed from a contemporary learning theory perspective. It is suggested that cue exposure treatment incorporating retrieval cues can be a beneficial treatment in preventing relapse of addictive behavior.

  10. Effects of methimazole and propylthiouracil exposure during pregnancy on the risk of neonatal congenital malformations: A meta-analysis

    Science.gov (United States)

    Song, Rongjing; Lin, Hepu; Chen, Yue; Zhang, Xiuying

    2017-01-01

    Objective The aim of this study was to determine the effect of exposure to different antithyroid drugs during pregnancy on the incidence of neonatal congenital malformations. Methods A meta-analysis was performed to compare the incidence of neonatal congenital malformations after exposure to different antithyroid drugs during pregnancy. Twelve studies that met the inclusion criteria were included in this meta-analysis. PubMed, Embase, and CENTRAL databases were searched from inception until January 2017. Study designs included case–control studies, prospective cohort studies, and retrospective cohort studies. Results Twelve studies involving 8028 participants with exposure to different antithyroid drugs during pregnancy were included in this study; however, only 10 studies involving 5059 participants involved exposure to different antithyroid drugs exactly during pregnancy. Our results indicated that exposure to methimazole (MMI)/carbimazole (CMZ) only during pregnancy significantly increased the risk of neonatal congenital malformations compared to no antithyroid drug exposure (OR 1.88; 95%CI 1.33 to 2.65; P = 0.0004). No differences were observed between propylthiouracil (PTU) exposure and no antithyroid drug exposure only during pregnancy (OR 0.81; 95%CI 0.58 to 1.15; P = 0.24). Exposure to MMI/CMZ only during pregnancy significantly increased the risk of neonatal congenital malformations compared to that associated with exposure to PTU (OR 1.90; 95%CI 1.30 to 2.78; P = 0.001). Conclusion For pregnant women with hyperthyroidism, exposure to MMI/CMZ significantly increased the incidence of neonatal congenital malformations compared to exposure to PTU and no antithyroid drug exposure; however, no differences were observed between PTU exposure and no antithyroid drug exposure. PMID:28671971

  11. Effects of methimazole and propylthiouracil exposure during pregnancy on the risk of neonatal congenital malformations: A meta-analysis.

    Directory of Open Access Journals (Sweden)

    Rongjing Song

    Full Text Available The aim of this study was to determine the effect of exposure to different antithyroid drugs during pregnancy on the incidence of neonatal congenital malformations.A meta-analysis was performed to compare the incidence of neonatal congenital malformations after exposure to different antithyroid drugs during pregnancy. Twelve studies that met the inclusion criteria were included in this meta-analysis. PubMed, Embase, and CENTRAL databases were searched from inception until January 2017. Study designs included case-control studies, prospective cohort studies, and retrospective cohort studies.Twelve studies involving 8028 participants with exposure to different antithyroid drugs during pregnancy were included in this study; however, only 10 studies involving 5059 participants involved exposure to different antithyroid drugs exactly during pregnancy. Our results indicated that exposure to methimazole (MMI/carbimazole (CMZ only during pregnancy significantly increased the risk of neonatal congenital malformations compared to no antithyroid drug exposure (OR 1.88; 95%CI 1.33 to 2.65; P = 0.0004. No differences were observed between propylthiouracil (PTU exposure and no antithyroid drug exposure only during pregnancy (OR 0.81; 95%CI 0.58 to 1.15; P = 0.24. Exposure to MMI/CMZ only during pregnancy significantly increased the risk of neonatal congenital malformations compared to that associated with exposure to PTU (OR 1.90; 95%CI 1.30 to 2.78; P = 0.001.For pregnant women with hyperthyroidism, exposure to MMI/CMZ significantly increased the incidence of neonatal congenital malformations compared to exposure to PTU and no antithyroid drug exposure; however, no differences were observed between PTU exposure and no antithyroid drug exposure.

  12. Radiation Exposure Alters Expression of Metabolic Enzyme Genes in Mice

    Science.gov (United States)

    Wotring, V. E.; Mangala, L. S.; Zhang, Y.; Wu, H.

    2011-01-01

    Most administered pharmaceuticals are metabolized by the liver. The health of the liver, especially the rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. Most pharmaceuticals are metabolized by the liver, and clinically-used medication doses are given with normal liver function in mind. A drug overdose can result in the case of a liver that is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism, we want to understand the effects of spaceflight on the enzymes of the liver and exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments. Additionally, it has been previous noted that pre-exposure to small radiation doses seems to confer protection against later and larger radiation doses. This protective power of pre-exposure has been called a priming effect or radioadaptation. This study is an effort to examine the drug metabolizing effects of radioadaptation mechanisms that may be triggered by early exposure to low radiation doses.

  13. Repetitive plasma opening switch for powerful high-voltage pulse generators

    International Nuclear Information System (INIS)

    Dolgachev, G.I.; Zakatov, L.P.; Nitishinskii, M.S.; Ushakov, A.G.

    1998-01-01

    Results are presented of experimental studies of plasma opening switches that serve to sharpen the pulses of inductive microsecond high-voltage pulse generators. It is demonstrated that repetitive plasma opening switches can be used to create super-powerful generators operating in a quasi-continuous regime. An erosion switching mechanism and the problem of magnetic insulation in repetitive switches are considered. Achieving super-high peak power in plasma switches makes it possible to develop new types of high-power generators of electron beams and X radiation. Possible implementations and the efficiency of these generators are discussed

  14. Repetitive Transcranial Magnetic Stimulation: a Novel Approach for Treating Oropharyngeal Dysphagia

    OpenAIRE

    Michou, Emilia; Raginis-Zborowska, Alicja; Watanabe, Masahiro; Lodhi, Taha; Hamdy, Shaheen

    2016-01-01

    In recent years, repetitive transcranial magnetic stimulation, a technique used to produce human central neurostimulation, has attracted increased interest and been applied experimentally in the treatment of dysphagia. This review presents a synopsis of the current research for the application of repetitive transcranial magnetic stimulation (rTMS) on dysphagia. Here, we review the mechanisms underlying the effects of rTMS and the results from studies on both healthy volunteers and dysphagic p...

  15. Estimating post-marketing exposure to pharmaceutical products using ex-factory distribution data.

    Science.gov (United States)

    Telfair, Tamara; Mohan, Aparna K; Shahani, Shalini; Klincewicz, Stephen; Atsma, Willem Jan; Thomas, Adrian; Fife, Daniel

    2006-10-01

    The pharmaceutical industry has an obligation to identify adverse reactions to drug products during all phases of drug development, including the post-marketing period. Estimates of population exposure to pharmaceutical products are important to the post-marketing surveillance of drugs, and provide a context for assessing the various risks and benefits, including drug safety, associated with drug treatment. This paper describes a systematic approach to estimating post-marketing drug exposure using ex-factory shipment data to estimate the quantity of medication available, and dosage information (stratified by indication or other factors as appropriate) to convert the quantity of medication to person time of exposure. Unlike the non-standardized methods often used to estimate exposure, this approach provides estimates whose calculations are explicit, documented, and consistent across products and over time. The methods can readily be carried out by an individual or small group specializing in this function, and lend themselves to automation. The present estimation approach is practical and relatively uncomplicated to implement. We believe it is a useful innovation. Copyright 2006 John Wiley & Sons, Ltd.

  16. Human exposure to power frequency magnetic fields up to 7.6 mT: An integrated EEG/fMRI study.

    Science.gov (United States)

    Modolo, Julien; Thomas, Alex W; Legros, Alexandre

    2017-09-01

    We assessed the effects of power-line frequency (60 Hz in North America) magnetic fields (MF) in humans using simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Twenty-five participants were enrolled in a pseudo-double-blind experiment involving "real" or "sham" exposure to sinusoidal 60 Hz MF exposures delivered using the gradient coil of an MRI scanner following two conditions: (i) 10 s exposures at 3 mT (10 repetitions); (ii) 2 s exposures at 7.6 mT (100 repetitions). Occipital EEG spectral power was computed in the alpha range (8-12 Hz, reportedly the most sensitive to MF exposure in the literature) with/without exposure. Brain functional activation was studied using fMRI blood oxygen level-dependent (BOLD, inversely correlated with EEG alpha power) maps. No significant effects were detected on occipital EEG alpha power during or post-exposure for any exposure condition. Consistent with EEG results, no effects were observed on fMRI BOLD maps in any brain region. Our results suggest that acute exposure (2-10 s) to 60 Hz MF from 3 to 7.6 mT (30,000 to 76,000 times higher than average public exposure levels for 60 Hz MF) does not induce detectable changes in EEG or BOLD signals. Combined with previous findings in which effects were observed on the BOLD signal after 1 h exposure to 3 mT, 60 Hz MF, this suggests that MF exposure in the low mT range (<10 mT) might require prolonged durations of exposure to induce detectable effects. Bioelectromagnetics. 38:425-435, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. [Drugs and light].

    Science.gov (United States)

    Tønnesen, H H

    1997-06-30

    The number of drugs that are found to be photochemically unstable or able to induce phototoxic side-effects is steadily increasing. It can be difficult, however, to obtain relevant information on the photoreactivity of drugs or drug products from the commonly used handbooks. This is because of lack of standard methods of evaluation or a requirement for official specifications for a given product. The author points to the main problems connected with interactions between drugs and light in vitro and in vivo. The most obvious result of exposure to light is reduced potency of the drug because of photodecomposition. Adverse effects due to the formation of photodegradation products during storage and use have also been reported. The drug substance can further cause light-induced side-effects after administration to the patient, e.g. phototoxicity and photoallergy. More data on photoreactivity are needed in order to minimize the side-effects of frequently used drugs. The article includes a list of potential photosensitizing drug substances on the Norwegian market.

  18. Fetal exposure to pimozide

    DEFF Research Database (Denmark)

    Bjarnason, Nina H; Rode, Line; Dalhoff, Kim

    2006-01-01

    Pimozide is an antidopaminergic, antipsychotic drug. Exposure during human pregnancy has not been reported previously, and recommendations on its use are based on extrapolation from other antipsychotics with antidopaminergic activity....

  19. Outcomes in spasticity after repetitive transcranial magnetic and transcranial direct current stimulations

    OpenAIRE

    Gunduz, Aysegul; Kumru, Hatice; Pascual-Leone, Alvaro

    2014-01-01

    Non-invasive brain stimulations mainly consist of repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Repetitive transcranial magnetic stimulation exhibits satisfactory outcomes in improving multiple sclerosis, stroke, spinal cord injury and cerebral palsy-induced spasticity. By contrast, transcranial direct current stimulation has only been studied in post-stroke spasticity. To better validate the efficacy of non-invasive brain stimulations in improving ...

  20. [Repetitive transcranial magnetic stimulation: A potential therapy for cognitive disorders?

    Science.gov (United States)

    Nouhaud, C; Sherrard, R M; Belmin, J

    2017-03-01

    Considering the limited effectiveness of drugs treatments in cognitive disorders, the emergence of noninvasive techniques to modify brain function is very interesting. Among these techniques, repetitive transcranial magnetic stimulation (rTMS) can modulate cortical excitability and have potential therapeutic effects on cognition and behaviour. These effects are due to physiological modifications in the stimulated cortical tissue and their associated circuits, which depend on the parameters of stimulation. The objective of this article is to specify current knowledge and efficacy of rTMS in cognitive disorders. Previous studies found very encouraging results with significant improvement of higher brain functions. Nevertheless, these few studies have limits: a few patients were enrolled, the lack of control of the mechanisms of action by brain imaging, insufficiently formalized technique and variability of cognitive tests. It is therefore necessary to perform more studies, which identify statistical significant improvement and to specify underlying mechanisms of action and the parameters of use of the rTMS to offer rTMS as a routine therapy for cognitive dysfunction. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  1. Right secondary somatosensory cortex-a promising novel target for the treatment of drug-resistant neuropathic orofacial pain with repetitive transcranial magnetic stimulation.

    Science.gov (United States)

    Lindholm, Pauliina; Lamusuo, Salla; Taiminen, Tero; Pesonen, Ullamari; Lahti, Ari; Virtanen, Arja; Forssell, Heli; Hietala, Jarmo; Hagelberg, Nora; Pertovaara, Antti; Parkkola, Riitta; Jääskeläinen, Satu

    2015-07-01

    High-frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex has analgesic effect; however, the efficacy of other cortical targets and the mode of action remain unclear. We examined the effects of rTMS in neuropathic orofacial pain, and compared 2 cortical targets against placebo. Furthermore, as dopaminergic mechanisms modulate pain responses, we assessed the influence of the functional DRD2 gene polymorphism (957C>T) and the catechol-O-methyltransferase (COMT) Val158Met polymorphism on the analgesic effect of rTMS. Sixteen patients with chronic drug-resistant neuropathic orofacial pain participated in this randomized, placebo-controlled, crossover study. Navigated high-frequency rTMS was given to the sensorimotor (S1/M1) and the right secondary somatosensory (S2) cortices. All subjects were genotyped for the DRD2 957C>T and COMT Val158Met polymorphisms. Pain, mood, and quality of life were monitored throughout the study. The numerical rating scale pain scores were significantly lower after the S2 stimulation than after the S1/M1 (P = 0.0071) or the sham (P = 0.0187) stimulations. The Brief Pain Inventory scores were also lower 3 to 5 days after the S2 stimulation than those at pretreatment baseline (P = 0.0127 for the intensity of pain and P = 0.0074 for the interference of pain) or after the S1/M1 (P = 0.001 and P = 0.0001) and sham (P = 0.0491 and P = 0.0359) stimulations. No correlations were found between the genetic polymorphisms and the analgesic effect in the present small clinical sample. The right S2 cortex is a promising new target for the treatment of neuropathic orofacial pain with high-frequency rTMS.

  2. 14-Year risk of all-cause mortality according to hypoglycaemic drug exposure in a general population.

    Directory of Open Access Journals (Sweden)

    Emilie Bérard

    Full Text Available PURPOSE: Guidelines for management of patients with type 2 diabetes mellitus recommend the use of hypoglycaemic drugs when lifestyle interventions remain insufficient for glycaemic control. Recent trials have provided worrying safety data on certain hypoglycaemic drugs. The aim of this study was to assess 14-year risk of all-cause mortality according to hypoglycaemic drug exposure at baseline, in a general population. METHODS: Our analysis was based on the observational Third French MONICA survey on cardiovascular risk factors (1995-1997. Vital status was obtained 14 years after inclusion, and assessment of determinants of mortality was based on multivariable Cox modelling. RESULTS: There were 3336 participants and 248 deaths over the 14-year period. At baseline, there were 3162 (95% non-diabetic, 46 (1% untreated type 2 diabetic and 128 (4% type 2 diabetic subjects with hypoglycaemic drug treatment (metformin alone (31%, sulfonylureas alone or in combination (49%, insulin alone or in combination (10%, or other treatments (9%. After adjustment for duration of diabetes, history of diabetes complications, area of residence (centre, age, gender, educational level, alcohol consumption, smoking, blood pressure, LDL and HDL cholesterol, which all were significant and independent determinants of mortality, the hazard ratio for all-cause mortality was 3.22 [95% confidence interval: 0.87-11.9] for untreated diabetic subjects, 2.28 [0.98-5.26] for diabetics treated with metformin alone, 1.70 [0.92-3.16] for diabetics with sulfonylureas and 4.92 [1.70-14.3] for diabetic with insulin versus non-diabetic subjects. CONCLUSIONS: Our results support the conclusion that until more evidence is provided from randomized trials, a prudent approach should be to restrain use of insulin to situations in which combinations of non-insulin agents have failed to appropriately achieve glycemic control, as it is recommended in the current guidelines for the management of

  3. The Use of Central Nervous System Active Drugs During Pregnancy

    Directory of Open Access Journals (Sweden)

    Bengt Källén

    2013-10-01

    Full Text Available CNS-active drugs are used relatively often during pregnancy. Use during early pregnancy may increase the risk of a congenital malformation; use during the later part of pregnancy may be associated with preterm birth, intrauterine growth disturbances and neonatal morbidity. There is also a possibility that drug exposure can affect brain development with long-term neuropsychological harm as a result. This paper summarizes the literature on such drugs used during pregnancy: opioids, anticonvulsants, drugs used for Parkinson’s disease, neuroleptics, sedatives and hypnotics, antidepressants, psychostimulants, and some other CNS-active drugs. In addition to an overview of the literature, data from the Swedish Medical Birth Register (1996–2011 are presented. The exposure data are either based on midwife interviews towards the end of the first trimester or on linkage with a prescribed drug register. An association between malformations and maternal use of anticonvulsants and notably valproic acid is well known from the literature and also demonstrated in the present study. Some other associations between drug exposure and outcome were found.

  4. A study of the energy absorption and exposure buildup factors of some anti-inflammatory drugs

    International Nuclear Information System (INIS)

    Ekinci, Neslihan; Kavaz, Esra; Özdemir, Yüksel

    2014-01-01

    Human radiation exposure is increasing due to radiation development in science and technology. The development of radioprotective agents is important for protecting patients from the side effects of radiotherapy and for protecting the public from unwanted irradiation. Radioprotective agents are used to reduce the damage caused by radiation in healthy tissues. There are several classes of radioprotective compounds that are under investigation. Analgesics and anti-inflammatory compounds are being considered for treating or preventing the effects of damage due to radiation exposure, or for increasing the chance of survival after exposure to a high dose of radiation. In this study, we investigated the radioprotective effects of some analgesic and anti-inflammatory compounds by evaluating buildup factors. The gamma ray energy absorption (EABF) and exposure buildup factors (EBF) were calculated to select compounds in a 0.015–15 MeV energy region up to a penetration depth of 40 mfp (mean free path). Variations of EABF and EBF with incident photon energy and penetration depth elements were also investigated. Significant variations in both EABF and EBF values were observed for several compounds at the moderate energy region. At energies below 0.15 MeV, EABF and EBF values increased with decreasing equivalent atomic number (Z eq ) of the samples. In addition, EABF and EBF were the largest for ibuprofen, aspirin, paracetamol, naproxen and ketoprofen at 0.05 and 0.06 MeV, respectively, and the EABF value was 0.1 MeV for aceclofenac. From these results, we concluded that the buildup of photons is less for aceclofenac compared to other materials. - Highlights: • Buildup factors of anti-inflammatory drugs have been calculated by a G-P fitting method. • Z eff of diclofenac was observed higher than other compounds. • It was found that buildup of photons is less for aceclofenac and diclofenac. • It would be appealing to use aceclofenac and diclofenac as radioprotective

  5. Effect of Bench Press Load Knowledge on Repetitions, Rating of Perceived Exertion, and Attentional Focus.

    Science.gov (United States)

    Beaudoin, Christina M; Cox, Zachary; Dundore, Tyler; Thomas, Tayler; Kim, Johnathon; Pillivant, Daniel

    2018-02-01

    Beaudoin, CM, Cox, Z, Dundore, T, Thomas, T, Kim, J, and Pillivant, D. Effect of bench press load knowledge on repetitions, rating of perceived exertion, and attentional focus. J Strength Cond Res 32(2): 514-519, 2018-Few studies have examined the role of the teleoanticipation during resistance training. The purpose of this study was to examine the effect of bench press (BP) load knowledge on repetitions completed, ratings of perceived exertion (RPEs), and attentional focus (% associative). Thirty-six recreationally active resistance-trained men (n = 25) and women (n = 11) participated in this study (age = 20.97 ± 1.87 years; ht = 174.12 ± 9.41 cm; and mass = 80.14 ± 14.03 kg). All subjects completed 3 testing sessions: (a) 1 repetition maximum (1RM) BP determination; (b) submaximal BP repetitions to fatigue known load (KL); and (c) submaximal BP repetitions to fatigue unknown load (UL). Known load and UL sessions were randomized and counterbalanced and both completed at 70% 1RM. An estimated weight ratio was computed using the subject's estimate of the UL weight relative to the KL weight. An independent samples t-test revealed no significant testing order difference for the estimated weight ratio. Two-way repeated-measures analysis of variances revealed no significant differences in the number of repetitions (p = 0.63), RPE (p = 0.18), or attentional focus (% associative) (p = 0.93) between the KL and UL conditions. Pearson correlations found a moderate positive association between KL repetitions completed and % associative focus when the UL was completed before the KL. Load knowledge did not influence the number of repetitions, RPE, or attentional focus while completing the BP. Further research examining the use of pacing strategies, RPE, and attentional focus during KL and UL conditions are warranted.

  6. Radiopharmaceutical drug review process

    International Nuclear Information System (INIS)

    Frankel, R.

    1985-01-01

    To ensure proper radioactive drug use (such as quality, diagnostic improvement, and minimal radioactive exposure), the Food and Drug Administration evaluates new drugs with respect to safety, effectiveness, and accuracy and adequacy of the labeling. The IND or NDA process is used for this purpose. A brief description of the process, including the Chemical Classification System and the therapeutic potential classification, is presented as it applies to radiopharmaceuticals. Also, the status of the IND or NDA review of radiopharmaceuticals is given

  7. Drug induced lung disease

    International Nuclear Information System (INIS)

    Schaefer-Prokop, Cornelia; Eisenhuber, Edith

    2010-01-01

    There is an ever increasing number of drugs that can cause lung disease. Imaging plays an important role in the diagnosis, since the clinical symptoms are mostly nonspecific. Various HRCT patterns can be correlated - though with overlaps - to lung changes caused by certain groups of drugs. Alternative diagnosis such as infection, edema or underlying lung disease has to be excluded by clinical-radiological means. Herefore is profound knowledge of the correlations of drug effects and imaging findings essential. History of drug exposure, suitable radiological findings and response to treatment (corticosteroids and stop of medication) mostly provide the base for the diagnosis. (orig.)

  8. FEMA Hazard Mitigation Assistance Severe Repetitive Loss (SRL) Data

    Data.gov (United States)

    Department of Homeland Security — This dataset contains closed and obligated projects funded under the following Hazard Mitigation Assistance (HMA) grant programs: Severe Repetitive Loss (SRL). The...

  9. FEMA Hazard Mitigation Assistance Repetitive Flood Claims (RFC) Data

    Data.gov (United States)

    Department of Homeland Security — This dataset contains closed and obligated projects funded under the following Hazard Mitigation Assistance (HMA) grant programs: Repetitive Flood Claims (RFC). The...

  10. Electrode patterning of ITO thin films by high repetition rate fiber laser

    International Nuclear Information System (INIS)

    Lin, H.K.; Hsu, W.C.

    2014-01-01

    Indium tin oxide (ITO) thin films are deposited on glass substrates using a radio frequency magnetron sputtering system. As-deposited ITO thin film was 100 nm in thickness and a transmittance of ITO film on glass substrate was 79% at 550 nm. Conductive electrodes are then patterned on the ITO films using a high repetition rate fiber laser system followed by a wet chemical etching process. The electrical, optical and structural properties of the patterned samples are evaluated by means of a four-point probe technique, spectrophotometer, X-ray diffraction (XRD), scanning electron microscopy (SEM) and atomic force microscopy (AFM). The results show that the samples annealed with a pulse repetition rate of 150 kHz or 400 kHz have a low sheet resistivity of 21 Ω/□ and a high optical transmittance of 90%. In addition, it is shown that a higher pulse repetition rate reduces both the residual stress and the surface roughness of the patterned specimens. Therefore, the present results suggest that a pulse repetition rate of 400 kHz represents the optimal processing condition for the patterning of crack-free ITO-coated glass substrates with good electrical and optical properties.

  11. Electrode patterning of ITO thin films by high repetition rate fiber laser

    Energy Technology Data Exchange (ETDEWEB)

    Lin, H.K., E-mail: HKLin@mail.npust.edu.tw; Hsu, W.C.

    2014-07-01

    Indium tin oxide (ITO) thin films are deposited on glass substrates using a radio frequency magnetron sputtering system. As-deposited ITO thin film was 100 nm in thickness and a transmittance of ITO film on glass substrate was 79% at 550 nm. Conductive electrodes are then patterned on the ITO films using a high repetition rate fiber laser system followed by a wet chemical etching process. The electrical, optical and structural properties of the patterned samples are evaluated by means of a four-point probe technique, spectrophotometer, X-ray diffraction (XRD), scanning electron microscopy (SEM) and atomic force microscopy (AFM). The results show that the samples annealed with a pulse repetition rate of 150 kHz or 400 kHz have a low sheet resistivity of 21 Ω/□ and a high optical transmittance of 90%. In addition, it is shown that a higher pulse repetition rate reduces both the residual stress and the surface roughness of the patterned specimens. Therefore, the present results suggest that a pulse repetition rate of 400 kHz represents the optimal processing condition for the patterning of crack-free ITO-coated glass substrates with good electrical and optical properties.

  12. The development of a repetition-load scheme for the eccentric-only bench press exercise.

    Science.gov (United States)

    Moir, Gavin L; Erny, Kyle F; Davis, Shala E; Guers, John J; Witmer, Chad A

    2013-01-01

    The purpose of the present study was to develop a repetition-load scheme for the eccentric-only bench press exercise. Nine resistance trained men (age: 21.6 ± 1.0 years; 1-repetition maximum [RM] bench press: 137.7 ± 30.4 kg) attended four testing sessions during a four week period. During the first session each subject's 1-RM bench press load utilizing the stretch-shortening cycle was determined. During the remaining sessions they performed eccentric-only repetitions to failure using supra-maximal loads equivalent to 110%, 120% and 130% of their 1-RM value with a constant cadence (30 reps·min(-1)). Force plates and a three dimensional motion analysis system were used during these final three sessions in order to evaluate kinematic and kinetic variables. More repetitions were completed during the 110% 1-RM condition compared to the 130% 1-RM condition (p=0.01). Mean total work (p=0.046) as well as vertical force (p=0.049), vertical work (p=0.017), and vertical power output (p=0.05) were significantly greater during the 130% 1-RM condition compared to the 110% 1-RM condition. A linear function was fitted to the number of repetitions completed under each load condition that allowed the determination of the maximum number of repetitions that could be completed under other supra-maximal loads. This linear function predicted an eccentric-only 1-RM in the bench press with a load equivalent to 164.8% 1-RM, producing a load of 227.0 ± 50.0 kg. The repetition-load scheme presented here should provide a starting point for researchers to investigate the kinematic, kinetic and metabolic responses to eccentric-only bench press workouts.

  13. Shoulder muscle fatigue during repetitive tasks as measured by electromyography and near-infrared spectroscopy.

    Science.gov (United States)

    Ferguson, Sue A; Allread, W Gary; Le, Peter; Rose, Joseph; Marras, William S

    2013-12-01

    The objective of this study was to quantify shoulder muscle fatigue during repetitive exertions similar to motions found in automobile assembly tasks. Shoulder musculoskeletal disorders (MSDs) are a common and costly problem in automotive manufacturing. Ten subjects participated in the study. There were three independent variables: shoulder angle, frequency, and force. There were two types of dependent measures: percentage change in near-infrared spectroscopy (NIRS) measures and change in electromyography (EMG) median frequency. The anterior deltoid and trapezius muscles were measured for both NIRS and EMG. Also, EMG was collected on the middle deltoid and biceps muscles. The results showed that oxygenated hemoglobin decreased significantly due to the main effects (shoulder angle, frequency, and force). The percentage change in oxygenated hemoglobin had a significant interaction attributable to force and repetition for the anterior deltoid muscle, indicating that as repetition increased, the magnitude of the differences between the forces increased. The interaction of repetition and shoulder angle was also significant for the percentage change in oxygenated hemoglobin. The median frequency decreased significantly for the main effects; however, no interactions were statistically significant. There was significant shoulder muscle fatigue as a function of shoulder angle, task frequency, and force level. Furthermore, percentage change in oxygenated hemoglobin had two statistically significant interactions, enhancing our understanding of these risk factors. Ergonomists should examine interactions of force and repetition as well as shoulder angle and repetition when evaluating the risk of shoulder MSDs.

  14. Fatigue effects upon sticking region and electromyography in a six-repetition maximum bench press.

    Science.gov (United States)

    van den Tillaar, Roland; Saeterbakken, Atle Hole

    2013-01-01

    The aim of the study was to examine the sticking region and concomitant neuromuscular activation of the prime movers during six-repetition maximum (RM) bench pressing. We hypothesised that both peak velocities would decrease and that the electromyography (EMG) of the prime movers (deltoid, major pectoralis and triceps) would increase during the pre-sticking and sticking region during the six repetitions due to fatigue. Thirteen resistance-trained males (age 22.8 ± 2.2 years, stature 1.82 ± 0.06 m, body mass 83.4 ± 7.6 kg) performed 6-RM bench presses. Barbell kinematics and EMG activity of pectoralis major, deltoid anterior, and triceps brachii during the pre-, sticking and post-sticking region of each repetition in a 6-RM bench press were analysed. For both the sticking as the post-sticking region, the time increased significantly from the first to the sixth repetition. Vertical barbell height at the start of sticking region was lower, while the height at the end of the sticking region and post-sticking region did not change during the six repetitions. It was concluded that in 6-RM bench pressing performance, the sticking region is a poor mechanical force region due to the unchanged barbell height at the end of the sticking region. Furthermore, when fatigue occurs, the pectoralis and the deltoid muscles are responsible for surpassing the sticking region as indicated by their increased activity during the pre- and sticking region during the six-repetitions bench press.

  15. Solid state pump lasers with high power and high repetition rate

    International Nuclear Information System (INIS)

    Oba, Masaki; Kato, Masaaki; Arisawa, Takashi

    1995-01-01

    We built a laser diode pumped solid state green laser (LDPSSGL) rated at high repetition rate. Two laser heads are placed in one cavity with a rotator in between to design to avoid thermal lensing and thermal birefringence effect. Although average green laser power higher than 10 W was obtained at 1 kHz repetition rate with pulse width of 20-30 nsec, the beam quality was so much deteriorated that energy efficiency was as low as 2 %. Learning from this experience that high power oscillator causes a lot of thermal distortion not only in the laser rod but also in the Q-switch device, we proceeded to built a oscillator/amplifier system. A low power oscillator has a slab type crystal in the cavity. As a result spatial distribution of laser power was extremely improved. As we expect that the high repetition rate solid state laser should be CW operated Q-switch type laser from the view point of lifetime of diode lasers, a conventional arc lamp pumped CW Q-switch green YAG laser of which the repetition rate is changeable from 1 kHz to 5 kHz and the pulse width is 250-570 nsec was also tested to obtain pumping characteristics of a dye laser as a function of power, pulse width etc., and dye laser pulse width of 100-130 nsec were obtained. (author)

  16. Controlling for Selection Effects in the Relationship between Child Behavior Problems and Exposure to Intimate Partner Violence

    Science.gov (United States)

    Emery, Clifton R.

    2011-01-01

    This article used the Project on Human Development in Chicago Neighborhoods (PHDCN) data to examine the relationship between exposure to intimate partner violence (IPV) and child behavior problems (externalizing and internalizing), truancy, grade repetition, smoking, drinking, and use of marijuana. Longitudinal data analysis was conducted on 1,816…

  17. Change in power output across a high-repetition set of bench throws and jump squats in highly trained athletes.

    Science.gov (United States)

    Baker, Daniel G; Newton, Robert U

    2007-11-01

    Athletes experienced in maximal-power and power-endurance training performed 1 set of 2 common power training exercises in an effort to determine the effects of moderately high repetitions upon power output levels throughout the set. Twenty-four and 15 athletes, respectively, performed a set of 10 repetitions in both the bench throw (BT P60) and jump squat exercise (JS P60) with a resistance of 60 kg. For both exercises, power output was highest on either the second (JS P60) or the third repetition (BT P60) and was then maintained until the fifth repetition. Significant declines in power output occurred from the sixth repetition onwards until the 10th repetition (11.2% for BT P60 and 5% for JS P60 by the 10th repetition). These findings suggest that athletes attempting to increase maximal power limit their repetitions to 2 to 5 when using resistances of 35 to 45% 1RM in these exercises.

  18. Femtosecond Ti:sapphire cryogenic amplifier with high gain and MHz repetition rate

    DEFF Research Database (Denmark)

    Dantan, Aurelien Romain; Laurat, Julien; Ourjoumtsev, Alexei

    2007-01-01

    We demonstrate high gain amplification of 160-femtosecond pulses in a compact double-pass cryogenic Ti:sapphire amplifier. The setup involves a negative GVD mirrors recompression stage, and operates with a repetition rate between 0.2 and 4 MHz with a continuous pump laser. Amplification factors a...... as high as 17 and 320 nJ Fourier-limited pulses are obtained at a 800 kHz repetition rate....

  19. Verbal Repetitions and Echolalia in Alzheimer's Discourse

    Science.gov (United States)

    Da Cruz, Fernanda Miranda

    2010-01-01

    This article reports on an investigation of echolalic repetition in Alzheimer's disease (AD). A qualitative analysis of data from spontaneous conversations with MHI, a woman with AD, is presented. The data come from the DALI Corpus, a corpus of spontaneous conversations involving subjects with AD. This study argues that echolalic effects can be…

  20. Effects of picosecond laser repetition rate on ablation of Cr12MoV cold work mold steel

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Baoye; Deng, Leimin; Liu, Peng; Zhang, Fei; Duan, Jun, E-mail: duans@hust.edu.cn; Zeng, Xiaoyan

    2017-07-01

    In this paper, the effects of pulse repetition rate on ablation efficiency and quality of Cr12MoV cold work mold steel have been studied using a picosecond (ps) pulse Nd:YVO{sub 4} laser system at λ= 1064 nm. The experimental results of area ablation on target surface reveal that laser repetition rate plays a significant role in controlling ablation efficiency and quality. Increasing the laser repetition rate, while keeping a constant mean power improves the ablation efficiency and quality. For each laser mean power, there is an optimal repetition rate to achieve a higher laser ablation efficiency with low surface roughness. A high ablation efficiency of 42.29, 44.11 and 47.52 μm{sup 3}/mJ, with surface roughness of 0.476, 0.463 and 0.706 μm could be achieved at laser repetition rate of 10 MHz, for laser mean power of 15, 17 and 19 W, respectively. Scanning electron microcopy images revels that the surface morphology evolves from rough with numerous craters, to flat without pores when we increased the laser repetition rate. The effects of laser repetition rate on the heat accumulation, plasma shield and ablation threshold were analyzed by numerical simulation, spectral analysis and multi-laser shot, respectively. The synergetic effects of laser repetition rate on laser ablation rate and machining quality were analyzed and discussed systemically in this paper.

  1. Role of drug transporters and drug accumulation in the temporal acquisition of drug resistance

    International Nuclear Information System (INIS)

    Hembruff, Stacey L; Laberge, Monique L; Villeneuve, David J; Guo, Baoqing; Veitch, Zachary; Cecchetto, Melanie; Parissenti, Amadeo M

    2008-01-01

    Anthracyclines and taxanes are commonly used in the treatment of breast cancer. However, tumor resistance to these drugs often develops, possibly due to overexpression of drug transporters. It remains unclear whether drug resistance in vitro occurs at clinically relevant doses of chemotherapy drugs and whether both the onset and magnitude of drug resistance can be temporally and causally correlated with the enhanced expression and activity of specific drug transporters. To address these issues, MCF-7 cells were selected for survival in increasing concentrations of doxorubicin (MCF-7 DOX-2 ), epirubicin (MCF-7 EPI ), paclitaxel (MCF-7 TAX-2 ), or docetaxel (MCF-7 TXT ). During selection cells were assessed for drug sensitivity, drug uptake, and the expression of various drug transporters. In all cases, resistance was only achieved when selection reached a specific threshold dose, which was well within the clinical range. A reduction in drug uptake was temporally correlated with the acquisition of drug resistance for all cell lines, but further increases in drug resistance at doses above threshold were unrelated to changes in cellular drug uptake. Elevated expression of one or more drug transporters was seen at or above the threshold dose, but the identity, number, and temporal pattern of drug transporter induction varied with the drug used as selection agent. The pan drug transporter inhibitor cyclosporin A was able to partially or completely restore drug accumulation in the drug-resistant cell lines, but had only partial to no effect on drug sensitivity. The inability of cyclosporin A to restore drug sensitivity suggests the presence of additional mechanisms of drug resistance. This study indicates that drug resistance is achieved in breast tumour cells only upon exposure to concentrations of drug at or above a specific selection dose. While changes in drug accumulation and the expression of drug transporters does occur at the threshold dose, the magnitude of

  2. Daily left prefrontal repetitive transcranial magnetic stimulation for medication-resistant burning mouth syndrome.

    Science.gov (United States)

    Umezaki, Y; Badran, B W; Gonzales, T S; George, M S

    2015-08-01

    Burning mouth syndrome (BMS) is a persistent and chronic burning sensation in the mouth in the absence of any abnormal organic findings. The pathophysiology of BMS is unclear and its treatment is not fully established. Although antidepressant medication is commonly used for treatment, there are some medication-resistant patients, and a new treatment for medication-resistant BMS is needed. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technology approved by the US Food and Drug Administration (FDA) for the treatment of depression. Recent studies have found beneficial effects of TMS for the treatment of pain. A case of BMS treated successfully with daily left prefrontal rTMS over a 2-week period is reported here. Based on this patient's clinical course and a recent pain study, the mechanism by which TMS may act to decrease the burning pain is discussed. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  3. Maximal Repetitions in Written Texts: Finite Energy Hypothesis vs. Strong Hilberg Conjecture

    Directory of Open Access Journals (Sweden)

    Łukasz Dębowski

    2015-08-01

    Full Text Available The article discusses two mutually-incompatible hypotheses about the stochastic mechanism of the generation of texts in natural language, which could be related to entropy. The first hypothesis, the finite energy hypothesis, assumes that texts are generated by a process with exponentially-decaying probabilities. This hypothesis implies a logarithmic upper bound for maximal repetition, as a function of the text length. The second hypothesis, the strong Hilberg conjecture, assumes that the topological entropy grows as a power law. This hypothesis leads to a hyperlogarithmic lower bound for maximal repetition. By a study of 35 written texts in German, English and French, it is found that the hyperlogarithmic growth of maximal repetition holds for natural language. In this way, the finite energy hypothesis is rejected, and the strong Hilberg conjecture is partly corroborated.

  4. The effect of music on repetitive disruptive vocalizations of persons with dementia.

    Science.gov (United States)

    Casby, J A; Holm, M B

    1994-10-01

    This study examined the effect of classical music and favorite music on the repetitive disruptive vocalizations of long-term-care facility (LTCF) residents with dementia of the Alzheimer's type (DAT). Three subjects diagnosed with DAT who had a history of repetitive disruptive vocalizations were selected for the study. Three single-subject withdrawal designs (ABA, ACA, and ABCA) were used to assess subjects' repetitive disruptive vocalizations during each phase: no intervention (A); relaxing, classical music (B); and favorite music (C). Classical music and favorite music significantly decreased the number of vocalizations in two of the three subjects (p < .05). These findings support a method that was effective in decreasing the disruptive vocalization pattern common in those with DAT in the least restrictive manner, as mandated by the Omnibus Budget Reconciliation Act of 1987.

  5. Multivariate prediction of spontaneous repetitive responses in ventricular myocardium exposed in vitro to simulated ischemic conditions.

    Science.gov (United States)

    Schiariti, M; Puddu, P E; Rouet, R

    1994-06-01

    Guinea-pig ventricular myocardium was partly exposed to normal Tyrode's superfusion and partly to altered conditions (using modified Tyrode's solution) set to simulate acute myocardial ischemia (PO2 80 +/- 10 mmHg; no glucose; pH 7.00 +/- 0.05; K+ 12 mM). Using a double-chamber tissue bath and standard microelectrode technique, the occurrence of spontaneous repetitive responses was investigated during simulated ischemia (occlusion) and after reperfusing the previously ischemic superfused tissue with normal Tyrode's solution (reperfusion). In 62 experiments (42 animals) the effects of: (1) duration of simulated ischemia (1321 +/- 435 s), (2) stimulation rate (1002 +/- 549 ms) and (3) number of successive simulated ischemic periods (occlusions) (1.58 +/- 0.92) on: (1) resting membrane potential, (2) action potential amplitude, (3) duration of 50 and 90% action potentials and (4) maximal upstroke velocity of action potential were studied. All variables were considered as gradients (delta) between normal and ischemic tissue. Both during occlusion and upon reperfusion, spontaneous repetitive responses were coded as single, couplets, salvos (three to nine and > 10) or total spontaneous repetitive responses (coded present when at least one of the above-mentioned types was seen). The incidence of total spontaneous repetitive responses was 31% (19/62) on occlusion and 85% (53/62) upon reperfusion. Cox's models (forced and stepwise) were used to predict multivariately the occurrence of arrhythmic events considered as both total spontaneous repetitive responses and as separate entities. These models were applicable since continuous monitoring of the experiments enabled exact timing of spontaneous repetitive response onset during both occlusion and reperfusion. In predicting reperfusion spontaneous repetitive responses, total spontaneous repetitive responses and blocks observed during the occlusion period were also considered. Total occlusion spontaneous repetitive responses

  6. Prenatal exposure to anticonvulsants and psychosexual development

    NARCIS (Netherlands)

    Dessens, A. B.; Cohen-Kettenis, P. T.; Mellenbergh, G. J.; vd Poll, N.; Koppe, J. G.; Boer, K.

    1999-01-01

    Animal studies have shown that prenatal exposure to the anticonvulsant drugs phenobarbital and phenytoin alters steroid hormone levels which consequently leads to disturbed sexual differentiation. In this study, possible sequelae of prenatal exposure to these anticonvulsants on gender development in

  7. A vacuum-sealed, gigawatt-class, repetitively pulsed high-power microwave source

    Science.gov (United States)

    Xun, Tao; Fan, Yu-wei; Yang, Han-wu; Zhang, Zi-cheng; Chen, Dong-qun; Zhang, Jian-de

    2017-06-01

    A compact L-band sealed-tube magnetically insulated transmission line oscillator (MILO) has been developed that does not require bulky external vacuum pump for repetitive operations. This device with a ceramic insulated vacuum interface, a carbon fiber array cathode, and non-evaporable getters has a base vacuum pressure in the low 10-6 Pa range. A dynamic 3-D Monte-Carlo model for the molecular flow movement and collision was setup for the MILO chamber. The pulse desorption, gas evolution, and pressure distribution were exactly simulated. In the 5 Hz repetition rate experiments, using a 600 kV diode voltage and 48 kA beam current, the average radiated microwave power for 25 shots is about 3.4 GW in 45 ns pulse duration. The maximum equilibrium pressure is below 4.0 × 10-2 Pa, and no pulse shortening limitations are observed during the repetitive test in the sealed-tube condition.

  8. Refining borders of genome-rearrangements including repetitions

    Directory of Open Access Journals (Sweden)

    JA Arjona-Medina

    2016-10-01

    Full Text Available Abstract Background DNA rearrangement events have been widely studied in comparative genomic for many years. The importance of these events resides not only in the study about relatedness among different species, but also to determine the mechanisms behind evolution. Although there are many methods to identify genome-rearrangements (GR, the refinement of their borders has become a huge challenge. Until now no accepted method exists to achieve accurate fine-tuning: i.e. the notion of breakpoint (BP is still an open issue, and despite repeated regions are vital to understand evolution they are not taken into account in most of the GR detection and refinement methods. Methods and results We propose a method to refine the borders of GR including repeated regions. Instead of removing these repetitions to facilitate computation, we take advantage of them using a consensus alignment sequence of the repeated region in between two blocks. Using the concept of identity vectors for Synteny Blocks (SB and repetitions, a Finite State Machine is designed to detect transition points in the difference between such vectors. The method does not force the BP to be a region or a point but depends on the alignment transitions within the SBs and repetitions. Conclusion The accurate definition of the borders of SB and repeated genomic regions and consequently the detection of BP might help to understand the evolutionary model of species. In this manuscript we present a new proposal for such a refinement. Features of the SBs borders and BPs are different and fit with what is expected. SBs with more diversity in annotations and BPs short and richer in DNA replication and stress response, which are strongly linked with rearrangements.

  9. Bystanders' Reactions to Witnessing Repetitive Abuse Experiences

    Science.gov (United States)

    Janson, Gregory R.; Carney, JoLynn V.; Hazler, Richard J.; Oh, Insoo

    2009-01-01

    The Impact of Event Scale-Revised (D. S. Weiss & C. R. Marmar, 1997) was used to obtain self-reported trauma levels from 587 young adults recalling childhood or adolescence experiences as witnesses to common forms of repetitive abuse defined as bullying. Mean participant scores were in a range suggesting potential need for clinical assessment…

  10. Context-Dependent Repetition Effects on Recognition Memory

    Science.gov (United States)

    Opitz, Bertram

    2010-01-01

    One widely acknowledged way to improve our memory performance is to repeatedly study the to be learned material. One aspect that has received little attention in past research regards the context sensitivity of this repetition effect, that is whether the item is repeated within the same or within different contexts. The predictions of a…

  11. Matriculation Research Report: Course Repetition Data & Analysis.

    Science.gov (United States)

    Gerda, Joe

    Due to concerns that its policy on class repetition was not promoting student success, California's College of the Canyons (CoC) undertook a project to analyze student course-taking patterns and make recommendations to modify the policy. Existing college policy did not follow Section 58161 of the State Educational Code that allows colleges to…

  12. Repetitively pulsed material testing facility

    International Nuclear Information System (INIS)

    Zucker, O.; Bostick, W.; Gullickson, R.; Long, J.; Luce, J.; Sahlin, H.

    1975-01-01

    A continuously operated, 1 pps, dense-plasma-focus device capable of delivering a minimum of 10 15 neutrons per pulse for material testing purposes is described. Moderate scaling from existing results is sufficient to provide 2 x 10 13 n/cm 2 . s to a suitable target. The average power consumption, which has become a major issue as a result of the energy crisis, is analyzed with respect to other plasma devices and is shown to be highly favorable. A novel approach to the capacitor bank and switch design allowing repetitive operation is discussed

  13. Bioanalysis for cocaine, opiates, methadone, and amphetamines exposure detection during pregnancy.

    Science.gov (United States)

    Concheiro, Marta; Lendoiro, Elena; de Castro, Ana; Gónzalez-Colmenero, Eva; Concheiro-Guisan, Ana; Peñas-Silva, Patricia; Macias-Cortiña, Manuel; Cruz-Landeira, Angelines; López-Rivadulla, Manuel

    2017-06-01

    Drug exposure during pregnancy constitutes a major legal issue and a public health concern. Drug and metabolite determination in biological matrices from mother and newborn is an objective indication of prenatal drug exposure. However, limited data are available regarding the interpretation of these analytical results in terms of window of detection and degree of exposure. We collected paired maternal hair, meconium, placenta, and umbilical cord from 727 mother-newborn dyads. We analyzed these specimens by liquid chromatography-tandem mass spectrometry for the determination of cocaine, opioids, methadone, and amphetamines, and compared the analytical results from the four different matrices. The cases were divided in non-exposure, low, and frequent exposure, based on maternal hair concentrations and segmental analysis by trimesters. For cocaine, 62 cases tested positive in hair, 9 in meconium, 6 in placenta and 7 in umbilical cord. In the case of opioids, 14 maternal hair cases were positive, 11 meconium and umbilical cord and 9 placenta samples. For methadone, 11 cases were positive in hair, 9 in meconium and 6 in placenta and umbilical cord. For amphetamines, 18 cases were positive according to maternal hair, but all meconium, placenta, and umbilical cord tested negative. Maternal hair was the most sensitive specimen to detect drug exposure during pregnancy. Meconium, placenta, and umbilical cord tested positive if hair concentrations showed frequent drug use during the whole pregnancy, especially during the third trimester. Meconium, placenta, and umbilical cord also tested positive for morphine and metabolites, if this drug was administered during labour and delivery. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Functions of repetition in the discourse of elderly speakers: The role of prosody and gesture

    OpenAIRE

    Bolly, Catherine; Gerstenberg, Annette; 14th International Pragmatics Conference (IPra), Panel session "Age and language use"

    2015-01-01

    Cognitively speaking, repetition can work as a facilitator for both the planning and the understanding of spoken language. It can work as a cohesive and interactive device or, at a higher-level function of discourse, to engage in interaction by creating interpersonal involvement: repetition always conveys altered meaning, as it has to be re-interpreted by the interlocutor “in light of the accretion, juxtaposition, or expansion” (Tannen 2007: 62). Repetition is thus useful for the building of ...

  15. Cumulative Repetition Effects across Multiple Readings of a Word: Evidence from Eye Movements

    Science.gov (United States)

    Kamienkowski, Juan E.; Carbajal, M. Julia; Bianchi, Bruno; Sigman, Mariano; Shalom, Diego E.

    2018-01-01

    When a word is read more than once, reading time generally decreases in the successive occurrences. This Repetition Effect has been used to study word encoding and memory processes in a variety of experimental measures. We studied naturally occurring repetitions of words within normal texts (stories of around 3,000 words). Using linear mixed…

  16. Fatty acid ethyl esters (FAEEs) as markers for alcohol in meconium: method validation and implementation of a screening program for prenatal drug exposure.

    Science.gov (United States)

    Hastedt, Martin; Krumbiegel, Franziska; Gapert, René; Tsokos, Michael; Hartwig, Sven

    2013-09-01

    Alcohol consumption during pregnancy is a widespread problem and can cause severe fetal damage. As the diagnosis of fetal alcohol syndrome is difficult, the implementation of a reliable marker for alcohol consumption during pregnancy into meconium drug screening programs would be invaluable. A previously published gas chromatography mass spectrometry method for the detection of fatty acid ethyl esters (FAEEs) as alcohol markers in meconium was optimized and newly validated for a sample size of 50 mg. This method was applied to 122 cases from a drug-using population. The meconium samples were also tested for common drugs of abuse. In 73 % of the cases, one or more drugs were found. Twenty percent of the samples tested positive for FAEEs at levels indicating significant alcohol exposure. Consequently, alcohol was found to be the third most frequently abused substance within the study group. This re-validated method provides an increase in testing sensitivity, is reliable and easily applicable as part of a drug screening program. It can be used as a non-invasive tool to detect high alcohol consumption in the last trimester of pregnancy. The introduction of FAEEs testing in meconium screening was found to be of particular use in a drug-using population.

  17. Measuring Glial Metabolism in Repetitive Brain Trauma and Alzheimer’s Disease

    Science.gov (United States)

    2016-09-01

    stages of repetitive brain trauma as well. Current methods of measure brain glutamate using proton spectroscopy is not specific to different cell...covering a representative range of clinical cases: a young female , young male , middle-aged male (all healthy volunteers) and a male patient with...AWARD NUMBER: W81XWH-15-1-0412 TITLE: Measuring Glial Metabolism in Repetitive Brain Trauma and Alzheimer’s Disease PRINCIPAL INVESTIGATOR

  18. A dispersion-balanced Discrete Fourier Transform of repetitive pulse sequences using temporal Talbot effect

    Science.gov (United States)

    Fernández-Pousa, Carlos R.

    2017-11-01

    We propose a processor based on the concatenation of two fractional temporal Talbot dispersive lines with balanced dispersion to perform the DFT of a repetitive electrical sequence, for its use as a controlled source of optical pulse sequences. The electrical sequence is used to impart the amplitude and phase of a coherent train of optical pulses by use of a modulator placed between the two Talbot lines. The proposal has been built on a representation of the action of fractional Talbot effect on repetitive pulse sequences and a comparison with related results and proposals. It is shown that the proposed system is reconfigurable within a few repetition periods, has the same processing rate as the input optical pulse train, and requires the same technical complexity in terms of dispersion and pulse width as the standard, passive pulse-repetition rate multipliers based on fractional Talbot effect.

  19. Repetitive transarterial chemoembolization (rTACE) of hepatocellular carcinoma: comparisons between an arterial port system and conventional angiographic technique

    International Nuclear Information System (INIS)

    Hidajat, Nico; Griesshaber, Volker; Hildebrandt, Bert; Hosten, Norbert; Schroeder, Ralf-Juergen; Felix, Roland

    2004-01-01

    Purpose: To compare the cost and radiation exposure of repetitive transarterial chemoembolization (rTACE) using percutaneously implantable port system with rTACE using conventional catheterization technique. Materials and methods: In five patients with unresectable hepatocellular carcinoma, three cycles of TACE were performed using conventional technique and six cycles using port. The cumulative cost of material and contrast agent and dose area product (DAP) were compared with the cost and DAP that would be expected if the rTACE was performed conventionally. Results: The cost of material and contrast agent was 1002.6 Euro after three cycles of TACE using conventional technique and six cycles using port, but would be 1111.8 Euro if the nine cycles were performed using conventional technique alone. The rTACE with three cycles using conventional technique and six cycles using port led to ∼63% of the cumulative DAP that would be expected in rTACE using conventional technique alone. Conclusion: In rTACE, the use of percutaneously implantable port system might enable a reduction of cost and radiation exposure

  20. The mere exposure effect depends on an odour’s initial pleasantness

    Directory of Open Access Journals (Sweden)

    Sylvain eDelplanque

    2015-07-01

    Full Text Available The mere exposure phenomenon refers to improvement of one’s attitude toward an a priori neutral stimulus after its repeated exposure. The extent to which such a phenomenon influences evaluation of a priori emotional stimuli remains under-investigated. Here we investigated this question by presenting participants with different odours varying in a priori pleasantness during different sessions spaced over time. Participants were requested to report each odour’s pleasantness, intensity, and familiarity. As expected, participants became more familiar with all stimuli after the repetition procedure. However, while neutral and mildly pleasant odours showed an increase in pleasantness ratings, unpleasant and very pleasant odours remained unaffected. Correlational analyses revealed an inverse U-shape between the magnitude of the mere exposure effect and the initial pleasantness of the odour. Consequently, the initial pleasantness of the stimuli appears to modulate the impact of repeated exposures on an individual’s attitude. These data underline the limits of mere exposure effect and are discussed in light of the biological relevance of odours for individual survival.

  1. The mere exposure effect depends on an odor’s initial pleasantness

    Science.gov (United States)

    Delplanque, Sylvain; Coppin, Géraldine; Bloesch, Laurène; Cayeux, Isabelle; Sander, David

    2015-01-01

    The mere exposure phenomenon refers to improvement of one’s attitude toward an a priori neutral stimulus after its repeated exposure. The extent to which such a phenomenon influences evaluation of a priori emotional stimuli remains under-investigated. Here we investigated this question by presenting participants with different odors varying in a priori pleasantness during different sessions spaced over time. Participants were requested to report each odor’s pleasantness, intensity, and familiarity. As expected, participants became more familiar with all stimuli after the repetition procedure. However, while neutral and mildly pleasant odors showed an increase in pleasantness ratings, unpleasant and very pleasant odors remained unaffected. Correlational analyses revealed an inverse U-shape between the magnitude of the mere exposure effect and the initial pleasantness of the odor. Consequently, the initial pleasantness of the stimuli appears to modulate the impact of repeated exposures on an individual’s attitude. These data underline the limits of mere exposure effect and are discussed in light of the biological relevance of odors for individual survival. PMID:26191021

  2. The relationship between executive functioning, central coherence, and repetitive behaviors in the high-functioning autism spectrum.

    Science.gov (United States)

    South, Mikle; Ozonoff, Sally; McMahon, William M

    2007-09-01

    This study examined the relationship between everyday repetitive behavior (primary symptoms of autism) and performance on neuropsychological tests of executive function and central coherence (secondary symptoms). It was hypothesized that the frequency and intensity of repetitive behavior would be positively correlated with laboratory measures of cognitive rigidity and weak central coherence. Participants included 19 individuals (ages 10-19) with high-functioning autism spectrum disorders (ASD group) and 18 age- and IQ-matched typically developing controls (TD group). There was partial support in the ASD group for the link between repetitive behavior and executive performance (the Wisconsin Card Sorting Task). There was no support for a link between repetitive behavior and measures of central coherence (a Gestalt Closure test and the Embedded Figures Test). Further research on repetitive behaviors in autism may benefit from a focus on narrow behavioral and cognitive constructs rather than general categories.

  3. Detecting drug-drug interactions using a database for spontaneous adverse drug reactions: an example with diuretics and non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    van Puijenbroek, E P; Egberts, A C; Heerdink, E R; Leufkens, H G

    2000-12-01

    Drug-drug interactions are relatively rarely reported to spontaneous reporting systems (SRSs) for adverse drug reactions. For this reason, the traditional approach for analysing SRS has major limitations for the detection of drug-drug interactions. We developed a method that may enable signalling of these possible interactions, which are often not explicitly reported, utilising reports of adverse drug reactions in data sets of SRS. As an example, the influence of concomitant use of diuretics and non-steroidal anti-inflammatory drugs (NSAIDs) on symptoms indicating a decreased efficacy of diuretics was examined using reports received by the Netherlands Pharmacovigilance Foundation Lareb. Reports received between 1 January 1990 and 1 January 1999 of patients older than 50 years were included in the study. Cases were defined as reports with symptoms indicating a decreased efficacy of diuretics, non-cases as all other reports. Exposure categories were the use of NSAIDs or diuretics versus the use of neither of these drugs. The influence of the combined use of both drugs was examined using logistic regression analysis. The odds ratio of the statistical interaction term of the combined use of both drugs was increased [adjusted odds ratio 2.0, 95% confidence interval (CI) 1.1-3.7], which may indicate an enhanced effect of concomitant drug use. The findings illustrate that spontaneous reporting systems have a potential for signal detection and the analysis of possible drug-drug interactions. The method described may enable a more active approach in the detection of drug-drug interactions after marketing.

  4. The pharmacist and adverse drug reaction reporting.

    Science.gov (United States)

    Pearson, K

    1982-08-01

    During premarketing trials, the number of patients exposed to a drug and the length of exposure to a drug are both limited. After marketing, many thousands, frequently millions, of patients are exposed to the drug over considerably longer periods of time, and adverse drug reactions not previously recognized appear. Because of these factors, postmarketing surveillance is extremely important. Pharmacists can contribute to drug safety and improved patient care by understanding and actively participating in the Food and Drug Administration's Spontaneous Reporting Program.

  5. Perseveration and other repetitive verbal behaviors: functional dissociations.

    Science.gov (United States)

    Christman, Sarah S; Boutsen, Frank R; Buckingham, Hugh W

    2004-11-01

    This article will review types of perseveration from a neurolinguistic perspective. During the course of the article, continuous, stuck-in-set, and recurrent perseveration will be placed in contradistinction to several other types of repetitive behaviors commonly associated with neurogenic communication disorders. These include echolalia in mixed transcortical aphasia; conduite d'approche and conduite d'ecart in fluent aphasias; lexical and nonlexical automatisms in nonfluent aphasias; palilalia in neuromotor disorders, such as Parkinson's disease (PD); and sound, syllable, word, and phrase repetitions in neurogenic stuttering. When differentiating these phenomena from perseveration, it is helpful to consider the salient factors that condition observed behaviors in individual patients, such as overall speech fluency, inventory of available utterances, nature of eliciting tasks, and propositionality of responses. Information such as communication disorder diagnosis, underlying etiology, and known sites of lesion from each patient's total clinical profile may also assist with differentiation.

  6. Task Repetition Effects on L1 Use in EFL Child Task-Based Interaction

    Science.gov (United States)

    Azkarai, Agurtzane; García Mayo, María del Pilar

    2017-01-01

    Research has shown that tasks provide second language (L2) learners with many opportunities to learn the L2. Task repetition has been claimed to benefit L2 learning since familiarity with procedure and/or content gives learners the chance to focus on more specific aspects of language. Most research on task repetition has focused on adult…

  7. The stress response in gametes and embryos after paternal chemical exposures

    International Nuclear Information System (INIS)

    Hales, Barbara F.; Aguilar-Mahecha, Adriana; Robaire, Bernard

    2005-01-01

    There is increasing concern that paternal exposure to toxic chemicals impacts negatively on progeny outcome. Exposure of male rats to a model male-mediated developmental toxicant and anticancer alkylating agent, cyclophosphamide, resulted in increased pre- and post-implantation loss, as well as in malformations. We hypothesize that the stage specificity of the effects of paternal cyclophosphamide exposure on progeny depends on the ability of germ cells to respond to stress, repair DNA or undergo apoptosis. Acute high dose exposure of male rats to cyclophosphamide increased the expression of heat shock proteins and DNA repair genes, predominantly in round spermatids. In contrast, chronic low dose treatment dramatically decreased the expression of stress response genes in pachytene spermatocytes and round spermatids, but not in elongated spermatids; this reduced ability to respond to stress may allow damage to accumulate, resulting in altered sperm function. Increased DNA damage was maximal 3 weeks after drug exposure, during spermiogenesis, a key point in sperm chromatin remodelling. Drug exposure for 9 weeks increased the frequency of spermatozoa with chromosome 4 disomy and nullisomy. DNA damage found in cyclophosphamide-exposed spermatozoa was imparted to the newly fertilized zygote. Drug-exposed spermatozoa decondensed more rapidly than control spermatozoa and male pronuclear formation was earlier. RNA synthesis was higher in 1-cell embryos sired by drug-treated fathers than in controls. Significantly, the profile of gene expression was altered in embryos sired by drug-treated males as early as the 1-cell stage. Thus, exposure of male rats to cyclophosphamide altered male germ cell quality with a consequent temporal and spatial disruption of the zygotic genome activation

  8. Genomic Organization and Physical Mapping of Tandemly Arranged Repetitive DNAs in Sterlet (Acipenser ruthenus).

    Science.gov (United States)

    Biltueva, Larisa S; Prokopov, Dimitry Y; Makunin, Alexey I; Komissarov, Alexey S; Kudryavtseva, Anna V; Lemskaya, Natalya A; Vorobieva, Nadezhda V; Serdyukova, Natalia A; Romanenko, Svetlana A; Gladkikh, Olga L; Graphodatsky, Alexander S; Trifonov, Vladimir A

    2017-01-01

    Acipenseriformes represent a phylogenetically basal clade of ray-finned fish characterized by unusual genomic traits, including paleopolyploid states of extant genomes with high chromosome numbers and slow rates of molecular evolution. Despite a high interest in this fish group, only a limited number of studies have been accomplished on the isolation and characterization of repetitive DNA, karyotype standardization is not yet complete, and sex chromosomes are still to be identified. Here, we applied next-generation sequencing and cluster analysis to characterize major fractions of sterlet (Acipenser ruthenus) repetitive DNA. Using FISH, we mapped 16 tandemly arranged sequences on sterlet chromosomes and found them to be unevenly distributed in the genome with a tendency to cluster in particular regions. Some of the satellite DNAs might be used as specific markers to identify individual chromosomes and their paralogs, resulting in the unequivocal identification of at least 18 chromosome pairs. Our results provide an insight into the characteristic genomic distribution of the most common sterlet repetitive sequences. Biased accumulation of repetitive DNAs in particular chromosomes makes them especially interesting for further search for cryptic sex chromosomes. Future studies of these sequences in other acipenserid species will provide new perspectives regarding the evolution of repetitive DNA within the genomes of this fish order. © 2017 S. Karger AG, Basel.

  9. Contrasting the Chromosomal Organization of Repetitive DNAs in Two Gryllidae Crickets with Highly Divergent Karyotypes.

    Directory of Open Access Journals (Sweden)

    Octavio M Palacios-Gimenez

    Full Text Available A large percentage of eukaryotic genomes consist of repetitive DNA that plays an important role in the organization, size and evolution. In the case of crickets, chromosomal variability has been found using classical cytogenetics, but almost no information concerning the organization of their repetitive DNAs is available. To better understand the chromosomal organization and diversification of repetitive DNAs in crickets, we studied the chromosomes of two Gryllidae species with highly divergent karyotypes, i.e., 2n(♂ = 29,X0 (Gryllus assimilis and 2n = 9, neo-X1X2Y (Eneoptera surinamensis. The analyses were performed using classical cytogenetic techniques, repetitive DNA mapping and genome-size estimation. Conserved characteristics were observed, such as the occurrence of a small number of clusters of rDNAs and U snDNAs, in contrast to the multiple clusters/dispersal of the H3 histone genes. The positions of U2 snDNA and 18S rDNA are also conserved, being intermingled within the largest autosome. The distribution and base-pair composition of the heterochromatin and repetitive DNA pools of these organisms differed, suggesting reorganization. Although the microsatellite arrays had a similar distribution pattern, being dispersed along entire chromosomes, as has been observed in some grasshopper species, a band-like pattern was also observed in the E. surinamensis chromosomes, putatively due to their amplification and clustering. In addition to these differences, the genome of E. surinamensis is approximately 2.5 times larger than that of G. assimilis, which we hypothesize is due to the amplification of repetitive DNAs. Finally, we discuss the possible involvement of repetitive DNAs in the differentiation of the neo-sex chromosomes of E. surinamensis, as has been reported in other eukaryotic groups. This study provided an opportunity to explore the evolutionary dynamics of repetitive DNAs in two non-model species and will contribute to the

  10. The interpretation of hair analysis for drugs and drug metabolites.

    Science.gov (United States)

    Cuypers, Eva; Flanagan, Robert J

    2018-02-01

    Head hair analysis for drugs and drug metabolites has been used widely with the aim of detecting exposure in the weeks or months prior to sample collection. However, inappropriate interpretation of results has likely led to serious miscarriages of justice, especially in child custody cases. The aim of this review is to assess critically what can, and perhaps more importantly, what cannot be claimed as regards the interpretation of hair test results in a given set of circumstances in order to inform future testing. We searched the PubMed database for papers published 2010-2016 using the terms "hair" and "drug" and "decontamination", the terms "hair" and "drug" and "contamination", the terms "hair" and "drug-facilitated crime", the terms "hair" and "ethyl glucuronide", and the terms "hair", "drug testing" and "analysis". Study of the reference lists of the 46 relevant papers identified 25 further relevant citations, giving a total of 71 citations. Hair samples: Drugs, drug metabolites and/or decomposition products may arise not only from deliberate drug administration, but also via deposition from a contaminated atmosphere if drug(s) have been smoked or otherwise vaporized in a confined area, transfer from contaminated surfaces via food/fingers, etc., and transfer from sweat and other secretions after a single large exposure, which could include anesthesia. Excretion in sweat of endogenous analytes such as γ-hydroxybutyric acid is a potential confounder if its use is to be investigated. Cosmetic procedures such as bleaching or heat treatment of hair may remove analytes prior to sample collection. Hair color and texture, the area of the head the sample is taken from, the growth rate of individual hairs, and how the sample has been stored, may also affect the interpretation of results. Toxicological analysis: Immunoassay results alone do not provide reliable evidence on which to base judicial decisions. Gas or liquid chromatography with mass spectrometric detection

  11. Perfluorocarbon (PFC) emulsions as potential drug carriers

    International Nuclear Information System (INIS)

    Yuhas, J.M.; Goodman, R.L.; Moore, R.E.

    1984-01-01

    PFC emulsions have excellent oxygen transporting properties and have been reported to enhance the response of murine tumors to both radiation and BCNU. While the presently available emulsions are far too toxic to the immune system to be used in cancer therapy, they can be used to investigate the overall potential of this approach. As an example, the authors have found that these emulsions can alter drug availability. The lipophilicity of both the PFC and the drug in question determine the partitioning of the drug between the organic and aqueous phases of an emulsion. In vitro, this can reduce drug effectiveness by reducing the amount of drug available to the cells. In vivo, however, this partitioning may produce sustained drug exposure, which could be of benefit in cancer therapy and other applications. In brief, as the drug is absorbed from the circulating aqueous phase, additional drug would leach from the PFC, thereby providing a sustained drug exposure similar to that obtained with liposomes. While a great deal more work will be required to evaluate the practicality of this approach, the existence of this phenomenon must be taken into account in both the design and interpretation of efficacy studies in which anesthetics, chemotherapeutics, etc are employed

  12. Effect of parallel magnetic field on repetitively unipolar nanosecond pulsed dielectric barrier discharge under different pulse repetition frequencies

    Science.gov (United States)

    Liu, Yidi; Yan, Huijie; Guo, Hongfei; Fan, Zhihui; Wang, Yuying; Wu, Yun; Ren, Chunsheng

    2018-03-01

    A magnetic field, with the direction parallel to the electric field, is applied to the repetitively unipolar positive nanosecond pulsed dielectric barrier discharge. The effect of the parallel magnetic field on the plasma generated between two parallel-plate electrodes in quiescent air is experimentally studied under different pulse repetition frequencies (PRFs). It is indicated that only the current pulse in the rising front of the voltage pulse occurs, and the value of the current is increased by the parallel magnetic field under different PRFs. The discharge uniformity is improved with the decrease in PRF, and this phenomenon is also observed in the discharge with the parallel magnetic field. By using the line-ratio technique of optical emission spectra, it is found that the average electron density and electron temperature under the considered PRFs are both increased when the parallel magnetic field is applied. The incremental degree of average electron density is basically the same under the considered PRFs, while the incremental degree of electron temperature under the higher-PRFs is larger than that under the lower-PRFs. All the above phenomena are explained by the effect of parallel magnetic field on diffusion and dissipation of electrons.

  13. Design of a low emittance and high repetition rate S-band photoinjector

    Science.gov (United States)

    Han, Jang-Hui

    2014-09-01

    As an electron beam injector of X-ray free-electron lasers (FELs), photoinjectors have been developed for the past few decades. Such an injector starting with a photocathode RF gun provides high brightness beams and therefore it is being adopted as an injector of X-ray FELs. In this paper we show how to improve photoinjector performance in terms of emittance and repetition rates by means of injector components optimization, especially with the gun. Transverse emittance at the end of an injector is reduced by optimizing the gun design, gun solenoid position, and accelerating section position. The repetition rate of an injector mainly depends on the gun. It is discussed that a repetition rate of 1 kHz at a normal-conducting S-band photoinjector is feasible by adopting a coaxial RF coupler and improving cooling-water channels surrounding the gun.

  14. Repetitive transient extraction for machinery fault diagnosis using multiscale fractional order entropy infogram

    Science.gov (United States)

    Xu, Xuefang; Qiao, Zijian; Lei, Yaguo

    2018-03-01

    The presence of repetitive transients in vibration signals is a typical symptom of local faults of rotating machinery. Infogram was developed to extract the repetitive transients from vibration signals based on Shannon entropy. Unfortunately, the Shannon entropy is maximized for random processes and unable to quantify the repetitive transients buried in heavy random noise. In addition, the vibration signals always contain multiple intrinsic oscillatory modes due to interaction and coupling effects between machine components. Under this circumstance, high values of Shannon entropy appear in several frequency bands or high value of Shannon entropy doesn't appear in the optimal frequency band, and the infogram becomes difficult to interpret. Thus, it also becomes difficult to select the optimal frequency band for extracting the repetitive transients from the whole frequency bands. To solve these problems, multiscale fractional order entropy (MSFE) infogram is proposed in this paper. With the help of MSFE infogram, the complexity and nonlinear signatures of the vibration signals can be evaluated by quantifying spectral entropy over a range of scales in fractional domain. Moreover, the similarity tolerance of MSFE infogram is helpful for assessing the regularity of signals. A simulation and two experiments concerning a locomotive bearing and a wind turbine gear are used to validate the MSFE infogram. The results demonstrate that the MSFE infogram is more robust to the heavy noise than infogram and the high value is able to only appear in the optimal frequency band for the repetitive transient extraction.

  15. Design and Development of High-Repetition-Rate Satellite Laser Ranging System

    Science.gov (United States)

    Choi, Eun-Jung; Bang, Seong-Cheol; Sung, Ki-Pyoung; Lim, Hyung-Chul; Jung, Chan-Gyu; Kim, In-Yeung; Choi, Jae-Seung

    2015-09-01

    The Accurate Ranging System for Geodetic Observation ? Mobile (ARGO-M) was successfully developed as the first Korean mobile Satellite Laser Ranging (SLR) system in 2012, and has joined in the International Laser Ranging Service (ILRS) tracking network, DAEdeoK (DAEK) station. The DAEK SLR station was approved as a validated station in April 2014, through the ILRS station ¡°data validation¡± process. The ARGO-M system is designed to enable 2 kHz laser ranging with millimeter-level precision for geodetic, remote sensing, navigation, and experimental satellites equipped with Laser Retroreflector Arrays (LRAs). In this paper, we present the design and development of a next generation high-repetition-rate SLR system for ARGO-M. The laser ranging rate up to 10 kHz is becoming an important issue in the SLR community to improve ranging precision. To implement high-repetition-rate SLR system, the High-repetition-rate SLR operation system (HSLR-10) was designed and developed using ARGO-M Range Gate Generator (A-RGG), so as to enable laser ranging from 50 Hz to 10 kHz. HSLR-10 includes both hardware controlling software and data post-processing software. This paper shows the design and development of key technologies of high-repetition-rate SLR system. The developed system was tested successfully at DAEK station and then moved to Sejong station, a new Korean SLR station, on July 1, 2015. HSLR-10 will begin normal operations at Sejong station in the near future.

  16. A relational database for personnel radiation exposure management

    International Nuclear Information System (INIS)

    David, W.; Miller, P.D.

    1993-01-01

    In-house utility personnel developed a relational data base for personnel radiation exposure management computer system during a 2 1/2 year period. The (PREM) Personnel Radiation Exposure Management System was designed to meet current Nuclear Regulatory Commission (NRC) requirements related to radiological access control, Radiation Work Permits (RWP) management, automated personnel dosimetry reporting, ALARA planning and repetitive job history dose archiving. The system has been operational for the past 18 months which includes a full refueling outage at Clinton Power Station. The Radiation Protection Department designed PREM to establish a software platform for implementing future revisions to 10CFR20 in 1993. Workers acceptance of the system has been excellent. Regulatory officials have given the system high marks as a radiological tool because of the system's ability to track the entire job from start to finish

  17. Repetitive controller for improving grid-connected photovoltaic systems

    NARCIS (Netherlands)

    Almeida, de P.M.; Duarte, J.L.; Ribeiro, P.F.; Barbosa, P.G.

    2014-01-01

    This study presents the modelling and design steps of a discrete time recursive repetitive controller (RC) to be used in a grid-connected photovoltaic (PV) system. It is shown that the linear synchronous reference frame proportional-integral controller, originally designed to control the converter's

  18. Marine Bivalve Cellular Responses to Beta Blocker Exposures ...

    Science.gov (United States)

    β blockers are prescription drugs used for medical treatment of hypertension and arrhythmias. They prevent binding of agonists such as catecholamines to β adrenoceptors. In the absence of agonist induced activation of the receptor, adenylate cyclase is not activated which in turn limits cAMP production and protein kinase A activation, preventing increases in blood pressure and arrhythmias. After being taken therapeutically, commonly prescribed β blockers may make their way to coastal habitats via discharge from waste water treatment plants (WWTP) posing a potential risk to aquatic organisms. The aim of our research is to evaluate cellular responses of three commercially important marine bivalves - Eastern oysters, blue mussels and hard clams - upon exposure to two β blocker drugs, propranolol and metoprolol, and to find molecular initiating events (MIEs) indicative of the exposure. Bivalves were obtained from Narragansett Bay (Rhode Island, USA) and acclimated in the laboratory. Following acclimation, gills and hepatopancreas (HP) tissues were harvested and separately exposed to 0, 1, 10, 100 and 1000 ng/l of each drug. Tissues were bathed in 30 parts per thousand (ppt) filtered seawater, antibiotic mix, Leibovitz nutrient media, and the test drug. Exposures were conducted for 24 hours and samples were saved for cellular biomarker assays. A lysosomal destabilization assay, which is a marker of membrane damage, was also performed at the end of each exposure.

  19. Tenofovir alafenamide (TAF) does not deplete mitochondrial DNA in human T-cell lines at intracellular concentrations exceeding clinically relevant drug exposures.

    Science.gov (United States)

    Stray, Kirsten M; Park, Yeojin; Babusis, Darius; Callebaut, Christian; Cihlar, Tomas; Ray, Adrian S; Perron, Michel

    2017-04-01

    HIV-infected patients treated with certain nucleoside reverse transcriptase inhibitors (NRTIs) have experienced adverse effects due to drug-related mitochondrial toxicity. Tenofovir alafenamide (TAF) is a novel prodrug of the NRTI tenofovir (TFV) with an improved safety profile compared to tenofovir disoproxil fumarate (TDF). Prior in vitro studies have demonstrated that the parent nucleotide TFV has no significant effects on mtDNA synthesis. This study investigated whether clinically relevant TAF and TDF exposures affect mtDNA content in human lymphocytes. First, activated or resting peripheral blood mononuclear cells (PBMCs), as well as MT-2 and Jurkat T-cell lines, were continuously treated with ddC for 10 days to establish their susceptibility to mtDNA depletion. PBMCs had low sensitivity to NRTI-mediated mtDNA depletion in vitro. In contrast, ddC treatment of rapidly dividing MT-2 and Jurkat cells resulted in a dose-dependent decrease in mtDNA. Therefore, these two T-cell lines were selected for evaluating TAF and TDF treatment effects. MT-2 and Jurkat cells were pulse-treated with TAF or TDF every 24 h for 10 days to mimic pharmacologically relevant drug exposures. Pulse treatment of cells with 3.3 μM TAF or 1.1 μM TDF for 10 days resulted in 2- to 7-fold greater steady-state intracellular TFV-diphosphate (TFV-DP) levels than those observed clinically in TAF- or TDF-treated patients. At these concentrations, no significant TAF- (106.7% and 84.1% of control; p = 0.77 and 0.12 for MT-2 and Jurkat, respectively) or TDF- (100.6% and 91.0% of control; p = 0.91 and 0.37, respectively) associated reduction in mtDNA content was observed compared with untreated control cells. This study demonstrates that, despite delivering higher intracellular levels of TFV-DP than TDF, TAF does not inhibit mtDNA synthesis in vitro at concentrations exceeding the clinically relevant intracellular drug exposures. Thus, TAF has a low potential for mitochondrial toxicity in

  20. Occupational hazards in hospitals: accidents, radiation, exposure to noxious chemicals, drug addiction and psychic problems, and assault

    Energy Technology Data Exchange (ETDEWEB)

    Gestal, J.J.

    1987-08-01

    Except for infectious diseases all the main occupational hazards affecting health workers are reviewed: accidents (explosions, fires, electrical accidents, and other sources of injury); radiation (stochastic and non-stochastic effects, protective measures, and personnel most at risk); exposure to noxious chemicals, whose effects may be either local (allergic eczema) or generalised (cancer, mutations), particular attention being paid to the hazards presented by formol, ethylene oxide, cytostatics, and anaesthetic gases; drug addiction (which is more common among health workers than the general population) and psychic problems associated with promotion, shift work, and emotional stress; and assault (various types of assault suffered by health workers, its causes, and the characterisation of the most aggressive patients).

  1. Occupational hazards in hospitals: accidents, radiation, exposure to noxious chemicals, drug addiction and psychic problems, and assault

    International Nuclear Information System (INIS)

    Gestal, J.J.

    1987-01-01

    Except for infectious diseases all the main occupational hazards affecting health workers are reviewed: accidents (explosions, fires, electrical accidents, and other sources of injury); radiation (stochastic and non-stochastic effects, protective measures, and personnel most at risk); exposure to noxious chemicals, whose effects may be either local (allergic eczema) or generalised (cancer, mutations), particular attention being paid to the hazards presented by formol, ethylene oxide, cytostatics, and anaesthetic gases; drug addiction (which is more common among health workers than the general population) and psychic problems associated with promotion, shift work, and emotional stress; and assault (various types of assault suffered by health workers, its causes, and the characterisation of the most aggressive patients). (author)

  2. [Repetitive movement of the upper limbs: results of exposure evaluation and clinical investigation during jar packaging of preserved vegetables].

    Science.gov (United States)

    Panzone, I; Carra, G; Melosi, A; Rappazzo, G; Innocenti, A

    1996-01-01

    In order to assess the prevalence of work-related musculo-skeletal disorders of the upper limbs, a total population of 29 female workers in an industrial vegetable preserving plant were examined. The average age of the workers was 41.3 years (SD = 9.2), and their average length of service was 16.7 years (SD = 7.2). Only 20% of the workers were anamnestically negative, whilst 80% had one or more disorders attributable to repetitive trauma of the upper limbs. The disorders showed no prevalence for the right side, a finding in line with the risk analysis which indicated that both limbs were equally used. The results of the risk analysis and clinical assessment confirm that high-frequency actions, combined with improper posture and a shortage of suitable recovery times, play a causal role in determining the onset of the disorders studied.

  3. Exposure to tobacco, alcohol and drugs of abuse during pregnancy. A study of prevalence among pregnant women in Malaga (Spain).

    Science.gov (United States)

    Blasco-Alonso, Marta; González-Mesa, Ernesto; Gálvez Montes, Milagros; Lozano Bravo, Isabel; Merino Galdón, Federico; Cuenca Campos, Francisco; Marín Schiaffino, Gema; Pérez Torres, Sergio; Herrera Peral, José; Bellido Estévez, Inmaculada

    2015-06-17

    The prevalence of substance abuse in women who become pregnant is similar to that of the general population, resulting in a high fetal exposure rate during the most vulnerable period regarding neurodevelopment and organogenesis. The present study was intended to assess the level of prenatal exposure to tobacco, alcohol or illicit drugs in the city of Málaga (Spain). It was designed as a cross-sectional study, and based on the anonymous self-reports of participants. A total of 451 pregnant women were recruited in the first, second or third trimester. The prevalence in each of the quarters respectively was 21.2%, 18.5% and 13.3% for smoking, 40.7%, 23.1% and 17.1% for alcohol and 4.8%, 1.9% and 1.2% for cannabis. We also found that a higher educational level was associated with a lower consumption of tobacco (RR 0.659 [0.537-0.810] p<0.0001) and greater exposure to alcohol (RR 1.87 [1.30-2.69] p<0.0007). These results, particularly in regard to alcohol intake, are sufficiently alarming to alert obstetric care providers about the need to implement preventive measures.

  4. Drug-induced trafficking of p-glycoprotein in human brain capillary endothelial cells as demonstrated by exposure to mitomycin C.

    Science.gov (United States)

    Noack, Andreas; Noack, Sandra; Hoffmann, Andrea; Maalouf, Katia; Buettner, Manuela; Couraud, Pierre-Olivier; Romero, Ignacio A; Weksler, Babette; Alms, Dana; Römermann, Kerstin; Naim, Hassan Y; Löscher, Wolfgang

    2014-01-01

    P-glycoprotein (Pgp; ABCB1/MDR1) is a major efflux transporter at the blood-brain barrier (BBB), restricting the penetration of various compounds. In other tissues, trafficking of Pgp from subcellular stores to the cell surface has been demonstrated and may constitute a rapid way of the cell to respond to toxic compounds by functional membrane insertion of the transporter. It is not known whether drug-induced Pgp trafficking also occurs in brain capillary endothelial cells that form the BBB. In this study, trafficking of Pgp was investigated in human brain capillary endothelial cells (hCMEC/D3) that were stably transfected with a doxycycline-inducible MDR1-EGFP fusion plasmid. In the presence of doxycycline, these cells exhibited a 15-fold increase in Pgp-EGFP fusion protein expression, which was associated with an increased efflux of the Pgp substrate rhodamine 123 (Rho123). The chemotherapeutic agent mitomycin C (MMC) was used to study drug-induced trafficking of Pgp. Confocal fluorescence microscopy of single hCMEC/D3-MDR1-EGFP cells revealed that Pgp redistribution from intracellular pools to the cell surface occurred within 2 h of MMC exposure. Pgp-EGFP exhibited a punctuate pattern at the cell surface compatible with concentrated regions of the fusion protein in membrane microdomains, i.e., lipid rafts, which was confirmed by Western blot analysis of biotinylated cell surface proteins in Lubrol-resistant membranes. MMC exposure also increased the functionality of Pgp as assessed in three functional assays with Pgp substrates (Rho123, eFluxx-ID Gold, calcein-AM). However, this increase occurred with some delay after the increased Pgp expression and coincided with the release of Pgp from the Lubrol-resistant membrane complexes. Disrupting rafts by depleting the membrane of cholesterol increased the functionality of Pgp. Our data present the first direct evidence of drug-induced Pgp trafficking at the human BBB and indicate that Pgp has to be released from lipid

  5. Drug-Induced Trafficking of P-Glycoprotein in Human Brain Capillary Endothelial Cells as Demonstrated by Exposure to Mitomycin C

    Science.gov (United States)

    Noack, Andreas; Noack, Sandra; Hoffmann, Andrea; Maalouf, Katia; Buettner, Manuela; Couraud, Pierre-Olivier; Romero, Ignacio A.; Weksler, Babette; Alms, Dana; Römermann, Kerstin; Naim, Hassan Y.; Löscher, Wolfgang

    2014-01-01

    P-glycoprotein (Pgp; ABCB1/MDR1) is a major efflux transporter at the blood-brain barrier (BBB), restricting the penetration of various compounds. In other tissues, trafficking of Pgp from subcellular stores to the cell surface has been demonstrated and may constitute a rapid way of the cell to respond to toxic compounds by functional membrane insertion of the transporter. It is not known whether drug-induced Pgp trafficking also occurs in brain capillary endothelial cells that form the BBB. In this study, trafficking of Pgp was investigated in human brain capillary endothelial cells (hCMEC/D3) that were stably transfected with a doxycycline-inducible MDR1-EGFP fusion plasmid. In the presence of doxycycline, these cells exhibited a 15-fold increase in Pgp-EGFP fusion protein expression, which was associated with an increased efflux of the Pgp substrate rhodamine 123 (Rho123). The chemotherapeutic agent mitomycin C (MMC) was used to study drug-induced trafficking of Pgp. Confocal fluorescence microscopy of single hCMEC/D3-MDR1-EGFP cells revealed that Pgp redistribution from intracellular pools to the cell surface occurred within 2 h of MMC exposure. Pgp-EGFP exhibited a punctuate pattern at the cell surface compatible with concentrated regions of the fusion protein in membrane microdomains, i.e., lipid rafts, which was confirmed by Western blot analysis of biotinylated cell surface proteins in Lubrol-resistant membranes. MMC exposure also increased the functionality of Pgp as assessed in three functional assays with Pgp substrates (Rho123, eFluxx-ID Gold, calcein-AM). However, this increase occurred with some delay after the increased Pgp expression and coincided with the release of Pgp from the Lubrol-resistant membrane complexes. Disrupting rafts by depleting the membrane of cholesterol increased the functionality of Pgp. Our data present the first direct evidence of drug-induced Pgp trafficking at the human BBB and indicate that Pgp has to be released from lipid

  6. Models of epidemics: when contact repetition and clustering should be included

    Directory of Open Access Journals (Sweden)

    Scholz Roland W

    2009-06-01

    Full Text Available Abstract Background The spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. Repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. However, we do not yet completely know under what conditions repetitiveness and clustering should be included for realistically modelling disease spread. Methods We compare two different types of individual-based models: One assumes random mixing without repetition of contacts, whereas the other assumes that the same contacts repeat day-by-day. The latter exists in two variants, with and without clustering. We systematically test and compare how the total size of an outbreak differs between these model types depending on the key parameters transmission probability, number of contacts per day, duration of the infectious period, different levels of clustering and varying proportions of repetitive contacts. Results The simulation runs under different parameter constellations provide the following results: The difference between both model types is highest for low numbers of contacts per day and low transmission probabilities. The number of contacts and the transmission probability have a higher influence on this difference than the duration of the infectious period. Even when only minor parts of the daily contacts are repetitive and clustered can there be relevant differences compared to a purely random mixing model. Conclusion We show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as seen in typical childhood diseases such as measles. In the case of very short infectious periods, for instance, as in Norovirus, models assuming repeating contacts will also behave

  7. Relationship between redistribution on exercise thallium-201 scintigraphy and repetitive ventricular premature beats in patients with recent myocardial infarction

    International Nuclear Information System (INIS)

    Tsuji, H.; Iwasaka, T.; Sugiura, T.; Shimada, T.; Nakamori, H.; Kimura, Y.; Inada, M.

    1991-01-01

    The relationship between myocardial ischemia detected by exercise thallium-201 scintigraphy and repetitive ventricular premature beats (VPBs) during ambulatory monitoring was evaluated in 57 patients with recent myocardial infarction. Multivariate analysis was performed to obtain the relatively important factor related to repetitive VPBs with the use of the following variables: age, redistribution, left ventricular ejection fraction, serum potassium and magnesium concentration, QRS score, left ventricular aneurysm, and the number of diseased vessels. Thirty-five patients had redistribution, but only three of them had repetitive VPBs during exercise testing. The average heart rate before 79% of 398 episodes of repetitive VPBs during ambulatory monitoring was in the range of 56 to 70/min. These data indicate that most of repetitive VPBs during ambulatory monitoring were not provoked by exercise-induced acute myocardial ischemia. However, redistribution was found to be an important factor associated with repetitive VPBs. The electrical abnormality relating to a substrate characterized by chronic reversible ischemia may explain the association between redistribution and repetitive VPBs

  8. The application of low frequency repetitive transcranial magnetic stimulation in rehabilitation of Parkinson's disease patients

    Directory of Open Access Journals (Sweden)

    WU Zhuo-hua

    2013-07-01

    Full Text Available Objective To explore the application value of low frequency repetitive transcranial magnetic stimulation (rTMS in Parkinson's disease (PD patients and electrophysiological research. Methods Fifty-six PD patients treated in the Department of Neurology of our hospital from September 2010 to September 2012 were randomly divided into 2 groups, group A (N = 28 and group B (N = 28. Patients in group A were given conventional drug treatment and rehabilitation training, while patients in group B were given low frequency rTMS on the basis of conventional drug treatment and rehabilitation training. After 3 weeks, the scores of Unified Parkinson's Disease Rating Scale (UPDRS, resting threshold (RT, cortical latent period, nerve root latent period, central motor conduction time (CMCT and the incidence of adverse reactions were compared between 2 groups. Results After intervention, the emotion, ability of daily living and motor function of patients in group B was obviously improved, and the scores of UPDRS in group B were significantly lower than that in group A (P 0.05. Conclusion The effect of low frequency rTMS in the treatment for PD is evident, safe and reliable, and with less adverse reaction. It can be used as a noninvasive physical treatment measure for PD.

  9. Radiation exposures in reprocessing facilities at the Savannah River Plant

    International Nuclear Information System (INIS)

    Hayes, G.; Caldwell, R.D.; Hall, R.M.

    1979-01-01

    Two large reprocessing facilities have been operating at the Savannah River Plant since 1955. The plant, which is near Aiken, South Carolina, is operated for the U.S. Department of Energy by the Du Pont Company. The reprocessing facilities have a work force of approximately 1,800. The major processes in the facilities are chemical separations of irradiated material, plutonium finishing, and waste management. This paper presents the annual radiation exposure for the reprocessing work force, particularly during the period 1965 through 1978. It also presents the collective and average individual annual exposures for various occupations including operators, mechanics, electricians, control laboratory technicians, and health physicists. Periodic and repetitive work activities that result in the highest radiation exposures are also described. The assimilation of radionuclides, particularly plutonium, by the work force is reviewed. Methods that have been developed to minimize the exposure of reprocessing personnel are described. The success of these methods is illustrated by experience - there has been no individual worker exposure of greater than 3.1 rems per year and only one plutonium assimilation greater than the maximum permissible body burden during the 24 years of operation of the facilities

  10. Radiation exposures in reprocessing facilities at the Savannah River Plant

    International Nuclear Information System (INIS)

    Hayes, G.; Caldwell, R.D.; Hall, R.M.

    1979-06-01

    Two large reprocessing facilities have been operating at the Savannah River Plant since 1955. The plant, which is near Aiken, South Carolina, is operated for the US Department of Energy by the Du Pont Company. The reprocessing facilities have a work force of approximately 1,800. The major processes in the facilities are chemical separations of irradiated material, plutonium finishing, and waste management. This paper presents the annual radiation exposure for the reprocessing work force, particularly during the period 1965 through 1978. It also presents the collective and average individual annual exposures for various occupations including operators, mechanics, electricians, control laboratory technicians, and health physicists. Periodic and repetitive work activities that result in the highest radiation exposures are also described. The assimilation of radionuclides, particularly plutonium, by the work force is reviewed. Methods that have been developed to minimize the exposure of reprocessing personnel are described. The success of these methods is illustrated by experience - there has been no individual worker exposure of greater than 3.1 rems per year and only one plutonium assimilation greater than the maximum permissible body burden during the 24 years of operation of the facilities

  11. Software-engineering-based model for mitigating Repetitive Strain ...

    African Journals Online (AJOL)

    The incorporation of Information and Communication Technology (ICT) in virtually all facets of human endeavours has fostered the use of computers. This has induced Repetitive Stress Injury (RSI) for continuous and persistent computer users. Proposing a software engineering model capable of enacted RSI force break ...

  12. Biopharmaceutical aspects of oral drug delivery

    NARCIS (Netherlands)

    Faassen, Werenfriedus Adrianus

    2004-01-01

    Most drugs display their therapeutic activity on specific places in the human body and should reach the systemic circulation in order to be transported towards the site of action. Irrespective of the route of administration the same sequence of steps are of relevance for the exposure to a drug:

  13. Molecular typing of Lactobacillus brevis isolates from Korean food using repetitive element-polymerase chain reaction.

    Science.gov (United States)

    Kaur, Jasmine; Sharma, Anshul; Lee, Sulhee; Park, Young-Seo

    2018-06-01

    Lactobacillus brevis is a part of a large family of lactic acid bacteria that are present in cheese, sauerkraut, sourdough, silage, cow manure, feces, and the intestinal tract of humans and rats. It finds its use in food fermentation, and so is considered a "generally regarded as safe" organism. L. brevis strains are extensively used as probiotics and hence, there is a need for identifying and characterizing these strains. For identification and discrimination of the bacterial species at the subspecific level, repetitive element-polymerase chain reaction method is a reliable genomic fingerprinting tool. The objective of the present study was to characterize 13 strains of L. brevis isolated from various fermented foods using repetitive element-polymerase chain reaction. Repetitive element-polymerase chain reaction was performed using three primer sets, REP, Enterobacterial Repetitive Intergenic Consensus (ERIC), and (GTG) 5 , which produced different fingerprinting patterns that enable us to distinguish between the closely related strains. Fingerprinting patterns generated band range in between 150 and 5000 bp with REP, 200-7500 bp with ERIC, and 250-2000 bp with (GTG) 5 primers, respectively. The Jaccard's dissimilarity matrices were used to obtain dendrograms by the unweighted neighbor-joining method using genetic dissimilarities based on repetitive element-polymerase chain reaction fingerprinting data. Repetitive element-polymerase chain reaction proved to be a rapid and easy method that can produce reliable results in L. brevis species.

  14. Decreased microvascular cerebral blood flow assessed by diffuse correlation spectroscopy after repetitive concussions in mice.

    Science.gov (United States)

    Buckley, Erin M; Miller, Benjamin F; Golinski, Julianne M; Sadeghian, Homa; McAllister, Lauren M; Vangel, Mark; Ayata, Cenk; Meehan, William P; Franceschini, Maria Angela; Whalen, Michael J

    2015-12-01

    Repetitive concussions are associated with long-term cognitive dysfunction that can be attenuated by increasing the time intervals between concussions; however, biomarkers of the safest rest interval between injuries remain undefined. We hypothesize that deranged cerebral blood flow (CBF) is a candidate biomarker for vulnerability to repetitive concussions. Using a mouse model of human concussion, we examined the effect of single and repetitive concussions on cognition and on an index of CBF (CBFi) measured with diffuse correlation spectroscopy. After a single mild concussion, CBFi was reduced by 35±4% at 4 hours (Pconcussions spaced 1 day apart, CBFi was also reduced from preinjury levels 4 hours after each concussion but had returned to preinjury levels by 72 hours after the final concussion. Interestingly, in this repetitive concussion model, lower CBFi values measured both preinjury and 4 hours after the third concussion were associated with worse performance on the Morris water maze assessed 72 hours after the final concussion. We conclude that low CBFi measured either before or early on in the evolution of injury caused by repetitive concussions could be a useful predictor of cognitive outcome.

  15. Methylation patterns of repetitive DNA sequences in germ cells of Mus musculus.

    OpenAIRE

    Sanford, J; Forrester, L; Chapman, V; Chandley, A; Hastie, N

    1984-01-01

    The major and the minor satellite sequences of Mus musculus were undermethylated in both sperm and oocyte DNAs relative to the amount of undermethylation observed in adult somatic tissue DNA. This hypomethylation was specific for satellite sequences in sperm DNA. Dispersed repetitive and low copy sequences show a high degree of methylation in sperm DNA; however, a dispersed repetitive sequence was undermethylated in oocyte DNA. This finding suggests a difference in the amount of total genomic...

  16. Scaling of black silicon processing time by high repetition rate femtosecond lasers

    Directory of Open Access Journals (Sweden)

    Nava Giorgio

    2013-11-01

    Full Text Available Surface texturing of silicon substrates is performed by femtosecond laser irradiation at high repetition rates. Various fabrication parameters are optimized in order to achieve very high absorptance in the visible region from the micro-structured silicon wafer as compared to the unstructured one. A 70-fold reduction of the processing time is demonstrated by increasing the laser repetition rate from 1 kHz to 200 kHz. Further scaling up to 1 MHz can be foreseen.

  17. Repetitively pulsed material testing facility

    International Nuclear Information System (INIS)

    Zucker, O.; Bostick, W.; Gullickson, R; Long, J.; Luce, J.; Sahlin, H.

    1975-01-01

    A continuously operated, 1 pps, dense-plasma-focus device capable of delivering a minimum of 10 15 neutrons per pulse for material testing purposes is described. Moderate scaling from existing results is sufficient to provide 2 x 10 13 n/cm 2 .s to a suitable target. The average power consumption, which has become a major issue as a result of the energy crisis, is analyzed with respect to other plasma devices and is shown to be highly favorable. A novel approach to the capacitor bank and switch design allowing repetitive operation is discussed. (U.S.)

  18. Factors affecting osteoarthritis patients' self-reported goal-directed drug information-seeking behaviors after exposure to direct-to-consumer advertising from physicians and the internet.

    Science.gov (United States)

    Liu, Yifei; Farris, Karen B; Doucette, William R

    2011-10-01

    The objective of this study was to investigate appraisal of means (ie, self-efficacy, outcome expectancy, and affect) in predicting patients' goal-directed behaviors of direct-to-consumer advertising (DTCA)-prompted drug-information search from physicians and the internet. One thousand patients were randomly selected from a nationwide sample frame of 3000 osteoarthritis patients. A self-administered survey assessed exposure to DTCA, drug-information search as goal, self-efficacy, outcome expectancy, affect, and osteoarthritis pain. After 6 weeks, another survey measured the behavior of drug-information search for respondents to the first survey. Study subjects were those who were exposed to DTCA in the previous month, and who set drug-information search as their goal. For each information source, a multiple regression analysis was conducted in which drug-information search was the dependent variable, and self-efficacy, outcome expectancy, affect, and osteoarthritis pain were the independent variables. Among 454 patients who were exposed to DTCA, 174 patients set drug-information search as their goal and were the study subjects. The regression for physicians was not statistically significant. The regression for the internet was significant, accounting for 15% of behavior variance. Self-efficacy was a strong predictor of goal-directed drug-information search from the internet. Appraisal of means was useful to predict the goal-directed behavior of DTCA-prompted drug-information search from the internet. For patients who set drug-information search as a goal, actions to promote drug-information search from the internet need to focus on self-efficacy.

  19. When the Right (Drug) Should Be Left : Prenatal Drug Exposure and Heterotaxy Syndrome

    NARCIS (Netherlands)

    van Veenendaal, Nicole R.; Kusters, Cynthia D. J.; Oostra, Roelof-Jan; Bergman, Jorieke E. H.; Cobben, Jan-Maarten

    Background: Recent studies reported an association between prenatal propylthiouracil exposure and birth defects, including abnormal arrangement across the left-right body axis, suggesting an association with heterotaxy syndrome. Methods: This case-control and case-finding study used data from 1981

  20. Repetitive nanosecond electron accelerators type URT-1 for radiation technology

    Science.gov (United States)

    Sokovnin, S. Yu.; Balezin, M. E.

    2018-03-01

    The electron accelerator URT-1М-300 for mobile installation was created for radiation disinfecting to correct drawbacks that were found the URT-1M electron accelerator operation (the accelerating voltage up to 1 МV, repetition rate up to 300 pps, electron beam size 400 × 100 mm, the pulse width about 100 ns). Accelerator configuration was changed that allowed to reduce significantly by 20% tank volume with oil where is placed the system of formation high-voltage pulses, thus the average power of the accelerator is increased by 6 times at the expense of increase in pulses repetition rate. Was created the system of the computerized monitoring parameters (output parameters and thermal mode) and remote control of the accelerator (charge voltage, pulse repetition rate), its elements and auxiliary systems (heat of the thyratron, vacuum system), the remote control panel is connected to the installation by the fiber-optical channel, what lightens the work for service personnel. For generating an electron beam up to 400 mm wide there are used metal- ceramic] and metal-dielectric cold cathodes of several emission elements (plates) with a non-uniform distribution of the electron beam current density on the output foil ± 15%. It was found that emission drop of both type of cathodes, during the operation at the high repetition rate (100 pps) is substantial at the beginning of the process, and then proceeds rather slowly that allows for continuous operation up to 40 h. Experiments showed that linear dependence of the voltage and a signal from the pin-diode remains within the range of the charge voltage 45-65 kV. Thus, voltage increases from 690 to 950 kV, and the signal from the pin-diode - from (2,8-4,6)*104 Gy/s. It allows to select electron energy quite precisely with consideration of the radiation technology requirements.

  1. Contact heat-evoked temporal summation: tonic versus repetitive-phasic stimulation.

    Science.gov (United States)

    Granot, Michal; Granovsky, Yelena; Sprecher, Elliot; Nir, Rony-Reuven; Yarnitsky, David

    2006-06-01

    Temporal summation (TS) is usually evoked by repetitive mechanical or electrical stimuli, and less commonly by tonic heat pain. The present study aimed to examine the TS induction by repetitive-phasic versus tonic heat pain stimuli. Using 27 normal volunteers, we compared the extent of summation by three calculation methods: start-to-end pain rating difference, percent change, and double-logarithmic regression of successive ratings along the stimulation. Subjects were tested twice, and the reliability of each of the paradigms was obtained. In addition, personality factors related to pain catastrophizing and anxiety level were also correlated with the psychophysical results. Both paradigms induced significant TS, with similar increases for the repetitive-phasic and the tonic paradigms, as measured on 0-100 numerical pain scale (from 52.9+/-11.7 to 80.2+/-15.5, p<0.001; and from 38.5+/-13.3 to 75.8+/-18.3, p<0.001, respectively). The extent of summation was significantly correlated between the two paradigms, when calculated by absolute change (r=0.543, p=0.004) and by regression (r=0.438, p=0.025). Session-to-session variability was similar for both paradigms, relatively large, yet not biased. As with other psychophysical parameters, this poses some limitations on TS assessment in individual patients over time. The extent of TS induced by both paradigms was found to be associated with anxiety level and pain catastrophizing. Despite some dissimilarity between the repetitive-phasic and the tonic paradigms, the many similarities suggest that the two represent a similar physiological process, even if not precisely the same. Future clinical applications of these tests will determine the clinical relevance of the TS paradigms presented in this study.

  2. Interspersion of highly repetitive DNA with single copy DNA in the genome of the red crab, Geryon quinquedens

    Energy Technology Data Exchange (ETDEWEB)

    Christie, N.T. (Univ. of Tennessee, Oak Ridge); Skinner, D.M.

    1979-02-01

    Kinetic analysis of the reassociation of 420 nucleotide (NT) long fragments has shown that essentially all of the repetitive sequences of the DNA of the red crab Geryon quinquedens are highly repetitive. There are negligible amounts of low and intermediate repetitive DNAs. Though atypical of most eukaryotes, this pattern has been observed in al other brachyurans (true crabs) studied. The major repetitive component is subdivided into short runs of 300 NT and longer runs of greater than 1200 NT while the minor component has an average sequence length of 400 NT. Both components reassociate at rates commonly observed for satellite DNAs. Unique among eukaryotes the organization of the genome includes single copy DNA contiguous to short runs (300 NT) of both repetitive components. Although patent satellites are not present, subsets of the repetitive DNA have been isolated by either restriction endonuclease digestion or by centrifugation in Ag/sup +/ or Hg/sup 2 +//Cs/sub 2/SO/sub 4/ density gradients.

  3. Residual Neurocognitive Features of Long-Term Ecstasy Users With Minimal Exposure to Other Drugs

    Science.gov (United States)

    Halpern, John H.; Sherwood, Andrea R.; Hudson, James I.; Gruber, Staci; Kozin, David; Pope, Harrison G.

    2010-01-01

    Aims In field studies assessing cognitive function in illicit ecstasy users, there are several frequent confounding factors that might plausibly bias the findings toward an overestimate of ecstasy-induced neurocognitive toxicity. We designed an investigation seeking to minimize these possible sources of bias. Design We compared illicit ecstasy users and non-users while 1) excluding individuals with significant lifetime exposure to other illicit drugs or alcohol; 2) requiring that all participants be members of the “rave” subculture; and 3) testing all participants with breath, urine, and hair samples at the time of evaluation to exclude possible surreptitious substance use. We compared groups with adjustment for age, gender, race/ethnicity, family-of-origin variables, and childhood history of conduct disorder and attention deficit hyperactivity disorder. We provide significance levels without correction for multiple comparisons. Setting Field study. Participants Fifty-two illicit ecstasy users and 59 non-users, age 18-45. Measurements Battery of 15 neuropsychological tests tapping a range of cognitive functions. Findings We found little evidence of decreased cognitive performance in ecstasy users, save for poorer strategic-self-regulation, possibly reflecting increased impulsivity. However this finding might have reflected a premorbid attribute of ecstasy users, rather than a residual neurotoxic effect of the drug. Conclusions In a study designed to minimize limitations found in many prior investigations, we failed to demonstrate marked residual cognitive effects in ecstasy users. This finding contrasts with many previous findings—including our own—and emphasizes the need for continued caution in interpreting field studies of cognitive function in illicit ecstasy users. PMID:21205042

  4. Repetitive muscle compression reduces vascular mechano-sensitivity and the hyperemic response to muscle contraction.

    Science.gov (United States)

    Messere, A; Turturici, M; Millo, G; Roatta, S

    2017-06-01

    Animal studies have shown that the rapid hyperemic response to external muscle compression undergoes inactivation upon repetitive stimulation, but this phenomenon has never been observed in humans. The aim of the present study was to determine whether 1) the vascular mechano-sensitivity underlying muscle compression-induced hyperemia is inactivated in an inter-stimulus interval (ISI)-dependent fashion upon repetitive stimulation, as suggested by animal studies, and 2) whether such inactivation also attenuates contraction-induced hyperemia. Brachial artery blood flow was measured by echo Doppler sonography in 13 healthy adults in response to 1) single and repetitive cuff muscle compression (CMC) of the forearm (20 CMCs, 1 s ISI); 2) a sequence of CMC delivered at decreasing ISI from 120 to 2 s; and 3) electrically-stimulated contraction of the forearm muscles before and after repetitive CMC. The peak amplitude of hyperemia in response to CMC normalized to baseline decreased from 2.2 ± 0.6 to 1.4 ± 0.4 after repetitive CMC and, in general, was decreased at ISI < 240 s. The peak amplitude of contraction-induced hyperemia was attenuated after as compared to before repeated CMC (1.7 ± 0.4 and 2.6 ± 0.6, respectively). Mechano-sensitivity of the vascular network can be conditioned by previous mechanical stimulation, and such preconditioning may substantially decrease contraction-induced hyperemia.

  5. Sources of Phoneme Errors in Repetition: Perseverative, Neologistic, and Lesion Patterns in Jargon Aphasia

    Directory of Open Access Journals (Sweden)

    Emma Pilkington

    2017-05-01

    Full Text Available This study examined patterns of neologistic and perseverative errors during word repetition in fluent Jargon aphasia. The principal hypotheses accounting for Jargon production indicate that poor activation of a target stimulus leads to weakly activated target phoneme segments, which are outcompeted at the phonological encoding level. Voxel-lesion symptom mapping studies of word repetition errors suggest a breakdown in the translation from auditory-phonological analysis to motor activation. Behavioral analyses of repetition data were used to analyse the target relatedness (Phonological Overlap Index: POI of neologistic errors and patterns of perseveration in 25 individuals with Jargon aphasia. Lesion-symptom analyses explored the relationship between neurological damage and jargon repetition in a group of 38 aphasia participants. Behavioral results showed that neologisms produced by 23 jargon individuals contained greater degrees of target lexico-phonological information than predicted by chance and that neologistic and perseverative production were closely associated. A significant relationship between jargon production and lesions to temporoparietal regions was identified. Region of interest regression analyses suggested that damage to the posterior superior temporal gyrus and superior temporal sulcus in combination was best predictive of a Jargon aphasia profile. Taken together, these results suggest that poor phonological encoding, secondary to impairment in sensory-motor integration, alongside impairments in self-monitoring result in jargon repetition. Insights for clinical management and future directions are discussed.

  6. The effects of exercise on cocaine self-administration, food-maintained responding, and locomotor activity in female rats: importance of the temporal relationship between physical activity and initial drug exposure.

    Science.gov (United States)

    Smith, Mark A; Witte, Maryam A

    2012-12-01

    Previous studies have reported that exercise decreases cocaine self-administration in rats with long-term access (8+ weeks) to activity wheels in the home cage. The purpose of this study was to (a) examine the importance of the temporal relationship between physical activity and initial drug exposure, (b) determine the effects of exercise on responding maintained by a nondrug reinforcer (i.e., food), and (c) investigate the effects of exercise on cocaine-induced increases in locomotor activity. To this end, female rats were obtained at weaning and divided into 4 groups: (a) EXE-SED rats were housed in exercise cages for 6 weeks and then transferred to sedentary cages after the first day of behavioral testing; (b) SED-EXE rats were housed in sedentary cages for 6 weeks and then transferred to exercise cages after the first day of behavioral testing; (c) SED-SED rats remained in sedentary cages for the duration of the study; and (d) EXE-EXE rats remained in exercise cages for the duration of the study. Relative to the sedentary group (SED-SED), exercise reduced cocaine self-administration in both groups with access to activity wheels after initial drug exposure (EXE-EXE, SED-EXE) but did not reduce cocaine self-administration in the group with access to activity wheels only before drug exposure (EXE-SED). Exercise also decreased the effects of cocaine on locomotor activity but did not reduce responding maintained by food. These data suggest that exercise may reduce cocaine use in drug-experienced individuals with no prior history of aerobic activity without decreasing other types of positively reinforced behaviors.

  7. Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse.

    Science.gov (United States)

    Korpi, Esa R; den Hollander, Bjørnar; Farooq, Usman; Vashchinkina, Elena; Rajkumar, Ramamoorthy; Nutt, David J; Hyytiä, Petri; Dawe, Gavin S

    2015-10-01

    Adaptation of the nervous system to different chemical and physiologic conditions is important for the homeostasis of brain processes and for learning and remembering appropriate responses to challenges. Although processes such as tolerance and dependence to various drugs of abuse have been known for a long time, it was recently discovered that even a single pharmacologically relevant dose of various drugs of abuse induces neuroplasticity in selected neuronal populations, such as the dopamine neurons of the ventral tegmental area, which persist long after the drug has been excreted. Prolonged (self-) administration of drugs induces gene expression, neurochemical, neurophysiological, and structural changes in many brain cell populations. These region-specific changes correlate with addiction, drug intake, and conditioned drugs effects, such as cue- or stress-induced reinstatement of drug seeking. In rodents, adolescent drug exposure often causes significantly more behavioral changes later in adulthood than a corresponding exposure in adults. Clinically the most impairing and devastating effects on the brain are produced by alcohol during fetal development. In adult recreational drug users or in medicated patients, it has been difficult to find persistent functional or behavioral changes, suggesting that heavy exposure to drugs of abuse is needed for neurotoxicity and for persistent emotional and cognitive alterations. This review describes recent advances in this important area of research, which harbors the aim of translating this knowledge to better treatments for addictions and related neuropsychiatric illnesses. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  8. Assessment of prescription opioid intentional exposures across the rural-urban continuum in the United States using both population and drug availability rates.

    Science.gov (United States)

    Le Lait, Marie-Claire; Martinez, Erin M; Severtson, Stevan G; Lavery, Sarah A; Bucher-Bartelson, Becki; Dart, Richard C

    2014-12-01

    Prescription opioid abuse and misuse are a serious problem in the U.S. today. Several studies have shown that the epidemic disproportionately affects rural areas. This paper uses three different rates to gain a more complete picture of opioid abuse in rural areas. This study examines prescription opioid intentional exposures using opioid classes tracked in the RADARS(®) System Poison Center Program. Intentional exposure rates were calculated adjusting for population and unique recipients of dispensed drug (URDD). These rates were analyzed using time (quarter) and the proportion of a three-digit zip code residing in a rural area as covariates. Additionally, the URDD per population rate was calculated to examine the proportion of the population filling prescriptions for opioids. After adjusting for population, intentional exposure cases significantly increased as the proportion of the population residing in a rural area increased. However, when adjusting for URDD, intentional exposure cases decreased with increasing rural population. The URDD per population increased as the proportion of people residing in a rural area increased. Using both population and URDD adjusted intentional exposure rates gives a more complete picture of opioid abuse in rural areas. Considering product availability can be used to develop opioid abuse prevention strategies and further the education of physicians serving rural areas about this epidemic. Copyright © 2014 John Wiley & Sons, Ltd.

  9. Interaction of Repetitively Pulsed High Energy Laser Radiation With Matter

    Science.gov (United States)

    Hugenschmidt, Manfred

    1986-10-01

    The paper is concerned with laser target interaction processes involving new methods of improving the overall energy balance. As expected theoretically, this can be achieved with high repetition rate pulsed lasers even for initially highly reflecting materials, such as metals. Experiments were performed by using a pulsed CO2 laser at mean powers up to 2 kW and repetition rates up to 100 Hz. The rates of temperature rise of aluminium for example were thereby increased by lore than a factor of 3 as compared to cw-radiation of comparable power density. Similar improvements were found for the overall absorptivities that were increased by this method by more than an order of magnitude.

  10. Repetition Suppression in the Left Inferior Frontal Gyrus Predicts Tone Learning Performance.

    Science.gov (United States)

    Asaridou, Salomi S; Takashima, Atsuko; Dediu, Dan; Hagoort, Peter; McQueen, James M

    2016-06-01

    Do individuals differ in how efficiently they process non-native sounds? To what extent do these differences relate to individual variability in sound-learning aptitude? We addressed these questions by assessing the sound-learning abilities of Dutch native speakers as they were trained on non-native tone contrasts. We used fMRI repetition suppression to the non-native tones to measure participants' neuronal processing efficiency before and after training. Although all participants improved in tone identification with training, there was large individual variability in learning performance. A repetition suppression effect to tone was found in the bilateral inferior frontal gyri (IFGs) before training. No whole-brain effect was found after training; a region-of-interest analysis, however, showed that, after training, repetition suppression to tone in the left IFG correlated positively with learning. That is, individuals who were better in learning the non-native tones showed larger repetition suppression in this area. Crucially, this was true even before training. These findings add to existing evidence that the left IFG plays an important role in sound learning and indicate that individual differences in learning aptitude stem from differences in the neuronal efficiency with which non-native sounds are processed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. [Exposure to addictogenic substances, conditioned response and treatment of the exposure with response prevention].

    Science.gov (United States)

    Khazaal, Y; Frésard, E; Zullino, D

    2007-01-01

    Exposure to drugs or related cues is associated with psycho-physiological reactivity. These responses are conditioned during periods of active consumption. Exposure with response prevention (EPR) is a treatment established for anxiety disorder and aims to reduce anxiety by an extinction of previously conditioned responses. The conditioning recognized in additive processes has led to research into EPR's therapeutic potential for treating addiction. This paper is a review of the main studies on reactivity to cues, and EPR, particularly with respect to addiction to alcohol, opiates, cocaine and tobacco. This review is based on information from the Medline database, dealing with cue reactivity, attentional bias during exposure to cues and exposure treatment for addiction in general and, in particular, for each of the aforementioned substances. Exposure to drug-related cues is clearly associated with psycho-physiological reactivity and with attentional bias. Those phenomena are associated with craving and more difficulty in maintaining abstinence. The subject's attention is thus held by a large number of drug-related environmental stimuli. These observations are linked with conditioning phenomena and suggest the possibility of treatment by EPR conditioning extinction procedures. EPR has been most widely studied for abuse and alcohol addiction. Case reports give favourable outcomes. Results from controlled studies are less clear. Studies on patients addicted to cocaine or heroine are still limited and not conclusive. Different controlled studies on EPR for nicotine addiction have not produced conclusions in favour of this treatment. Generally, the EPR procedures used vary among studies. Studies focussing particularly on the evolution of physiological responses in a laboratory setting after EPR have demonstrated reduced autonomic nervous system activity. These results do not consistently lead to a reduction in consumption behaviour and in craving when the patient is in

  12. Safety and efficacy of drugs in pregnancy.

    Science.gov (United States)

    Knoppert, David

    2011-01-01

    Although most drugs are used to treat chronic or pregnancy-induced conditions during pregnancy and lactation, very few are studied in pregnant or breastfeeding women. The information we have on drugs taken during pregnancy and lactation is usually obtained after market approval through published case reports or case series and from pregnancy exposure or retrospective birth defect registries. Furthermore, generic drugs approved for use in this vulnerable population may be approved based on results from a male trial population. This disregards the changes that can occur during pregnancy which can affect the pharmacokinetics of drugs. In an effort to improve the information provided to prescribers, in 2008 the United States Food and Drug Administration proposed a change in product labelling where information from pregnancy exposure registries would be required. As of 2009, European Medicines Agency requires additional statements on use during pregnancy within drug labelling information. In Canada, it is anticipated that the efficacy and safety of drugs in pregnancy will be included under the Drug Safety and Effectiveness Network initiative, and that this will offer a unified approach for such assessments. Pregmedic, a non-profit organization for the advancement of safe and effective use of drugs in pregnancy, has presented a number of proposals and draft guidelines to Health Canada on the inclusion of pregnant women in pharmacokinetic studies and the establishment of registries for women who take drugs during pregnancy. Pregmedic advocates for ensuring that drugs indicated for women are studied in women.

  13. Involvement of Disperse Repetitive Sequences in Wheat/Rye Genome Adjustment

    Directory of Open Access Journals (Sweden)

    Manuela Silva

    2012-07-01

    Full Text Available The union of different genomes in the same nucleus frequently results in hybrid genotypes with improved genome plasticity related to both genome remodeling events and changes in gene expression. Most modern cereal crops are polyploid species. Triticale, synthesized by the cross between wheat and rye, constitutes an excellent model to study polyploidization functional implications. We intend to attain a deeper knowledge of dispersed repetitive sequence involvement in parental genome reshuffle in triticale and in wheat-rye addition lines that have the entire wheat genome plus each rye chromosome pair. Through Random Amplified Polymorphic DNA (RAPD analysis with OPH20 10-mer primer we unraveled clear alterations corresponding to the loss of specific bands from both parental genomes. Moreover, the sequential nature of those events was revealed by the increased absence of rye-origin bands in wheat-rye addition lines in comparison with triticale. Remodeled band sequencing revealed that both repetitive and coding genome domains are affected in wheat-rye hybrid genotypes. Additionally, the amplification and sequencing of pSc20H internal segments showed that the disappearance of parental bands may result from restricted sequence alterations and unraveled the involvement of wheat/rye related repetitive sequences in genome adjustment needed for hybrid plant stabilization.

  14. Comorbid psychopathology and stress mediate the relationship between autistic traits and repetitive behaviours in adults with autism.

    Science.gov (United States)

    García-Villamisar, D; Rojahn, J

    2015-02-01

    Comorbid psychopathology and stress were considered possible mediators that may explain the relationship between some autistic traits and repetitive behaviours. The current study sought to examine the mediational effects of comorbid psychopathology, executive dysfunctions and stress in the relationship between some autistic traits and repetitive behaviours. A battery of questionnaires including measures of autistic traits, repetitive behaviours, stress, executive dysfunctions and comorbid psychopathology were administered to a sample of adults with autism and intellectual disabilities (n = 43). We found that when taken as set dimensions of comorbidity, dysexecutive functioning and stress mediated or explained the effects of autistic symptoms on repetitive behaviour. The total model explained 60% of the variation in repetitive behaviours (R = 0.60; F = 13.64, P autism, while executive functioning did not contribute to that relationship. © 2013 2013 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

  15. Comparison on different repetition rate locking methods in Er-doped fiber laser

    Science.gov (United States)

    Yang, Kangwen; Zhao, Peng; Luo, Jiang; Huang, Kun; Hao, Qiang; Zeng, Heping

    2018-05-01

    We demonstrate a systematic comparative research on the all-optical, mechanical and opto-mechanical repetition rate control methods in an Er-doped fiber laser. A piece of Yb-doped fiber, a piezoelectric transducer and an electronic polarization controller are simultaneously added in the laser cavity as different cavity length modulators. By measuring the cavity length tuning ranges, the output power fluctuations, the temporal and frequency repetition rate stability, we show that all-optical method introduces the minimal disturbances under current experimental condition.

  16. Repetition suppression in ventral visual cortex is diminished as a function of increasing autistic traits

    NARCIS (Netherlands)

    Ewbank, M.P.; Rhodes, G.; von dem Hagen, E.A.H.; Powell, T.E.; Bright, N.; Stoyanova, R.Z.; Baron-Cohen, S.; Calder, A.J.

    2015-01-01

    Repeated viewing of a stimulus causes a change in perceptual sensitivity, known as a visual aftereffect. Similarly, in neuroimaging, repetitions of the same stimulus result in a reduction in the neural response, known as repetition suppression (RS). Previous research shows that aftereffects for

  17. Repetition rate stabilization of an erbium-doped all-fiber laser via opto-mechanical control of the intracavity group velocity

    International Nuclear Information System (INIS)

    Shen, Xuling; He, Boqu; Zhao, Jian; Liu, Yang; Bai, Dongbi; Wang, Chao; Liu, Geping; Luo, Daping; Liu, Fengjiang; Li, Wenxue; Zeng, Heping; Yang, Kangwen; Hao, Qiang

    2015-01-01

    We present a method for stabilizing the repetition rate of an erbium-doped all-fiber laser by inserting an electronic polarization controller (EPC) in the fiber laser cavity. The device exhibited good integration, low cost, and convenient operation. Such a repetition rate stabilization may facilitate an all-fiber laser comb system with high integration. The repetition rate was phase-locked to a Rb reference more than 72 h with a low feedback voltage applied to one channel of the EPC. The repetition rate was 74.6 MHz. The standard deviation and the repetition rate linewidth were 1.4 and 1.7 mHz, respectively

  18. An evaluation of factors affecting duration of treatment with repetitive transcranial magnetic stimulation for depression

    Directory of Open Access Journals (Sweden)

    Roni Broder Cohen

    2007-12-01

    Full Text Available Objective: To investigate the effects of repetitive transcranialmagnetic stimulation in patients with major depression who weresubmitted to this treatment during the period from 2000 to 2006.Methods: A retrospective study with 204 patients who underwenttreatment with repetitive transcranial magnetic stimulation, collectingdata from those who experienced remission (defined as a HDRS scoreequal to or lower than 7. The patients were followed for up to 6 monthsafter treatment. Mean duration of remission for this cohort of patientswas 70.2 (± 58.4 days. Results: The only variable associated withthe duration of remission in the linear regression model was numberof repetitive transcranial magnetic stimulation sessions. Conclusion:Our findings suggest that the greater the number of sessions, the longerthe duration of repetitive transcranial magnetic stimulation effects.Consequently, future research investigating the effects of repetitivetranscranial magnetic stimulation should explore this variable in orderto maximize the therapeutic effects of this new brain stimulationtechnique.

  19. EFEKTIVITAS MODEL PEMBELAJARAN AUDITORY INTELLECTUALLY REPETITION (AIR TERHADAP PEMAHAMAN SISWA PADA KONSEP ENERGI DALAM

    Directory of Open Access Journals (Sweden)

    S. Linuwih

    2014-07-01

    Full Text Available Telah dilakukan pembelajaran fisika melalui penerapan model pembelajaran Auditory Intellectually Repetition (AIR pada pokok bahasan konsep energi dalam. Tujuan penelitian ini untuk mengetahui peningkatan pemahaman konsep siswa dan efektivitas model pembelajaran Auditory Intellectually Repetition (AIR terhadap pemahaman siswa pada konsep energi dalam. Penelitian ini menggunakan metode penelitian eksperimen kependidikan (educational experiment research, dengan rancangan pre test-post test control group design. Subjek penelitian adalah dua kelompok belajar yang terdiri atas 32 siswa (eksperimen dan 32 siswa (kontrol kelas XI IPA di SMA N 2 Ungaran tahun ajaran 2013/2014. Data dianalisis menggunakan uji gain dan uji t. Hasil penelitian menunjukkan adanya peningkatan pemahaman konsep siswa dan hasil belajar kognitif siswa. Berdasarkan hasil analisis dapat disimpulkan bahwa penerapan model pembelajaran Auditory Intellectually Repetition (AIR dalam pembelajaran fisika SMA efektif untuk meningkatkan pemahaman konsep siswa.ABSTRACTThe physics learning on concept of the internal energy was carried out through application of Auditory Intellectually Repetition (AIR learning model. This study aimed to determining the improvement of students’ concept understanding and the effectiveness of Auditory Intellectually Repetition (AIR learning model on students’ understanding of the internal energy concept. The research used educational experiment research with pre test-post test control group design. The subject of research consisted of 32 students in eksperimental group and 32 students in control group of XI IPA SMA N 2 Ungaran, academic year 2013/2014. The data were analyzed by using gain test and t test. The result showed that there was an increase of students’ concept understanding and the outcome of students’ cognitive learning. Based on the result, it can be concluded that the application of Auditory Intellectually Repetition (AIR learning model in

  20. High repetition rate burst-mode spark gap

    International Nuclear Information System (INIS)

    Faltens, A.; Reginato, L.; Hester, R.; Chesterman, A.; Cook, E.; Yokota, T.; Dexter, W.

    1978-01-01

    Results are presented on the design and testing of a pressurized gas blown spark gap switch capable of high repetition rates in a burst mode of operation. The switch parameters which have been achieved are as follows: 220-kV, 42-kA, a five pulse burst at 1-kHz, 12-ns risetime, 2-ns jitter at a pulse width of 50-ns